Search results for: cardiovascular disorder

Authors: Christina Largent, Tazley Hobbs

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Objective: A literature review was performed to examine the existing research on COVID-19 lockdown as it relates to ADHD child/adolescent individuals, media use, and impact on educational performance/learning. It was surmised that with the COVID-19 shut-down and transition to remote learning, a less structured learning environment, increased screen time, in addition to potential difficulty accessing school resources would impair ADHD individuals’ performance and learning. A resulting increase in the number of youths diagnosed and treated for ADHD would be expected. As of yet, there has been little to no published data on the incidence of ADHD as it relates to COVID-19 outside of reports from several nonprofit agencies such as CHADD (Children and Adults with Attention-Deficit/Hyperactivity Disorder ), who reported an increased number of calls to their helpline, The New York based Child Mind Institute, who reported an increased number of appointments to discuss medications, and research released from Athenahealth showing an increase in the number of patients receiving new diagnosis of ADHD and new prescriptions for ADHD medications. Methods: A literature search for articles published between 2020 and 2021 from Pubmed, Google Scholar, PsychInfo, was performed. Search phrases and keywords included “covid, adhd, child, impact, remote learning, media, screen”. Results: Studies primarily utilized parental reports, with very few from the perspective of the ADHD individuals themselves. Most findings thus far show that with the COVID-19 quarantine and transition to online learning, ADHD individuals’ experienced decreased ability to keep focused or adhere to the daily routine, as well as increased inattention-related problems, such as careless mistakes or lack of completion in homework, which in turn translated into overall more difficulty with remote learning. To add further injury, one study showed (just on evaluation of two different sites within the US) that school based services for these individuals decreased with the shift to online-learning. Increased screen time, television, social media, and gaming were noted amongst ADHD individuals. One study further differentiated the degree of digital media, identifying individuals with “problematic “ or “non-problematic” use. ADHD children with problematic digital media use suffered from more severe core symptoms of ADHD, negative emotions, executive function deficits, damage to family environment, pressure from life events, and a lower motivation to learn. Conclusions and Future Considerations: Studies found not only was online learning difficult for ADHD individuals but it, in addition to greater use of digital media, was associated with worsening ADHD symptoms impairing schoolwork, in addition to secondary findings of worsening mood and behavior. Currently, data on the number of new ADHD cases, in addition to data on the prescription and usage of stimulants during COVID-19, has not been well documented or studied; this would be well-warranted out of concern for over diagnosing or over-prescribing our youth. It would also be well-worth studying how reversible or long-lasting these negative impacts may be.

Keywords: COVID-19, remote learning, media use, ADHD, child, adolescent

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Authors: T. Schilirò, S. Bonetta, S. Bonetta, E. Ceretti, D. Feretti, I. Zerbini, V. Romanazzi, S. Levorato, T. Salvatori, S. Vannini, M. Verani, C. Pignata, F. Bagordo, G. Gilli, S. Bonizzoni, A. Bonetti, E. Carraro, U. Gelatti

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Air pollution is one of the most important worldwide health concern. In the last years, in both the US and Europe, new directives and regulations supporting more restrictive pollution limits were published. However, the early effects of air pollution occur, especially for the urban population. Several epidemiological and toxicological studies have documented the remarkable effect of particulate matter (PM) in increasing morbidity and mortality for cardiovascular disease, lung cancer and natural cause mortality. The finest fractions of PM (PM with aerodynamic diameter <2.5 µm and less) play a major role in causing chronic diseases. The International Agency for Research on Cancer (IARC) has recently classified air pollution and fine PM as carcinogenic to human (1 Group). The structure and composition of PM influence the biological properties of particles. The chemical composition varies with season and region of sampling, photochemical-meteorological conditions and sources of emissions. The aim of the MAPEC (Monitoring Air Pollution Effects on Children for supporting public health policy) study is to evaluate the associations between air pollution and biomarkers of early biological effects in oral mucosa cells of 6-8 year old children recruited from first grade schools. The study was performed in five Italian towns (Brescia, Torino, Lecce, Perugia and Pisa) characterized by different levels of airborne PM (PM10 annual average from 44 µg/m3 measured in Torino to 20 µg/m3 measured in Lecce). Two to five schools for each town were chosen to evaluate the variability of pollution within the same town. Child exposure to urban air pollution was evaluated by collecting ultrafine PM (PM0.5) in the school area, on the same day of biological sampling. PM samples were collected for 72h using a high-volume gravimetric air sampler and glass fiber filters in two different seasons (winter and spring). Gravimetric analysis of the collected filters was performed; PM0.5 organic extracts were chemically analyzed (PAH, Nitro-PAH) and tested on A549 by the Comet assay and Micronucleus test and on Salmonella strains (TA100, TA98, TA98NR and YG1021) by Ames test. Results showed that PM0.5 represents a high variable PM10 percentage (range 19.6-63%). PM10 concentration were generally lower than 50µg/m3 (EU daily limit). All PM0.5 extracts showed a mutagenic effect with TA98 strain (net revertant/m3 range 0.3-1.5) and suggested the presence of indirect mutagens, while lower effect was observed with TA100 strain. The results with the TA98NR and YG1021 strains showed the presence of nitroaromatic compounds as confirmed by the chemical analysis. No genotoxic or oxidative effect of PM0.5 extracts was observed using the comet assay (with/without Fpg enzyme) and micronucleus test except for some sporadic samples. The low biological effect observed could be related to the low level of air pollution observed in this winter sampling associated to a high atmospheric instability. For a greater understanding of the relationship between PM size, composition and biological effects the results obtained in this study suggest to investigate the biological effect of the other PM fractions and in particular of the PM0.5-1 fraction.

Keywords: airborne PM, ames test, comet assay, micronucleus test

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Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche

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It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.

Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells

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Authors: C. Sancho Salvatierra, J. M. Martinez Nieto, R. García Gonzalez-Gordon, M. I. Martinez Bellido

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Introduction: Nature could act as an asset for human health protecting against possible diseases and promoting the state of both physical and mental health. Goals: This paper aims to determine which natural elements present evidence that show positive influence on human health, on which particular aspects and how. It also aims to determine the best biomarkers to measure such influence. Method: A systematic literature review was carried out. First, a general free text search was performed in databases, such as Scopus, PubMed or PsychInfo. Secondly, a specific search was performed combining keywords in order of increasing complexity. Also the Snowballing technique was used and it was consulted in the CSIC’s (The Spanish National Research Council). Databases: Of the 130 articles obtained and reviewed, 80 referred to natural elements that influenced health. These 80 articles were classified and tabulated according to the nature elements found, the health aspects studied, the health measurement parameters used and the measurement techniques used. In this classification the results of the studies were codified according to whether they were positive, negative or neutral both for the elements of nature and for the aspects of health studied. Finally, the results of the 80 selected studies were summarized and categorized according to the elements of nature that showed the greatest positive influence on health and the biomarkers that had shown greater reliability to measure said influence. Results: Of the 80 articles studied, 24 (30.0%) were reviews and 56 (70.0%) were original research articles. Among the 24 reviews, 18 (75%) found positive results of natural elements on health, and 6 (25%) both positive and negative effects. Of the 56 original articles, 47 (83.9%) showed positive results, 3 (5.4%) both positive and negative, 4 (7.1%) negative effects, and 2 (3.6%) found no effects. The results reflect positive effects of different elements of nature on the following pathologies: diabetes, high blood pressure, stress, attention deficit hyperactivity disorder, psychotic, anxiety and affective disorders. They also show positive effects on the following areas: immune system, social interaction, recovery after illness, mood, decreased aggressiveness, concentrated attention, cognitive performance, restful sleep, vitality and sense of well-being. Among the elements of nature studied, those that show the greatest positive influence on health are forest immersion, natural views, daylight, outdoor physical activity, active transport, vegetation biodiversity, natural sounds and the green residences. As for the biomarkers used that show greater reliability to measure the effects of natural elements are the levels of cortisol (both in blood and saliva), vitamin D levels, serotonin and melatonin, blood pressure, heart rate, muscle tension and skin conductance. Conclusions: Nature is an asset for health, well-being and quality of life. Awareness programs, education and health promotion are needed based on the elements that nature brings us, which in turn generate proactive attitudes in the population towards the protection and conservation of nature. The studies related to this subject in Spain are very scarce. Aknowledgements. This study has been promoted and partially financed by the Environmental Foundation Jaime González-Gordon.

Keywords: health, green areas, nature, well-being

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Authors: Asma Ben Hmidene, Mizuho Hanaki, Kazuma Murakami, Kazuhiro Irie, Hiroko Isoda, Hideyuki Shigemori

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Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are characterized as a peripheral metabolic disorder and a degenerative disease of the central nervous system, respectively. It is now widely recognized that T2DM and AD share many pathophysiological features including glucose metabolism, increased oxidative stress and amyloid aggregation. Amyloid beta (Aβ) is the components of the amyloid deposits in the AD brain and while the component of the amyloidogenic peptide deposit in the pancreatic islets of Langerhans is identified as human islet amyloid polypeptide (hIAPP). These two proteins are originated from the amyloid precursor protein and have a high sequence similarity. Although the amino acid sequences of amyloidogenic proteins are diverse, they all adopt a similar structure in aggregates called cross-beta-spine. Add at that, extensive studies in the past years have found that like Aβ1-42, IAPP forms early intermediate assemblies as spherical oligomers, implicating that these oligomers possess a common folding pattern or conformation. These similarities can be used in the search for effective pharmacotherapy for DM, since potent therapeutic agents such as antioxidants with a catechol moiety, proved to inhibit Aβ aggregation, may play a key role in the inhibit the aggregation of hIAPP treatment of patients with DM. Tamarix gallica is one of the halophyte species having a powerful antioxidant system. Although it was traditionally used for the treatment of various liver metabolic disorders, there is no report about the use of this plant for the treatment or prevention of T2DM and AD. Therefore, the aim of this work is to investigate their protective effect towards T2DM and AD by isolation and identification of α-glucosidase inhibitors, with antioxidant potential, that play an important role in the glucose metabolism in diabetic patient, as well as, the polymerization of hIAPP and Aβ aggregation inhibitors. Structure-activity relationship study was conducted for both assays. And as for α-glucosidase inhibitors, their mechanism of action and their synergistic potential when applied with a very low concentration of acarbose were also suggesting that they can be used not only as α-glucosidase inhibitors but also be combined with established α-glucosidase inhibitors to reduce their adverse effect. The antioxidant potential of the purified substances was evaluated by DPPH and SOD assays. Th-T assay using 42-mer amyloid β-protein (Aβ42) for AD and hIAPP which is a 37-residue peptide secreted by the pancreatic β –cells for T2DM and Transmission electronic microscopy (TEM) were conducted to evaluate the amyloid aggragation of the actives substances. For α-glucosidase, p-NPG and glucose oxidase assays were performed for determining the inhibition potential and structure-activity relationship study. The Enzyme kinetic protocol was used to study the mechanism of action. From this research, it was concluded that polyphenols playing a role in the glucose metabolism and oxidative stress can also inhibit the amyloid aggregation, and that substances with a catechol and glucuronide moieties inhibiting amyloid-β aggregation, might be used to inhibit the aggregation of hIAPP.

Keywords: α-glucosidase inhibitors, amyloid aggregation inhibition, mechanism of action, polyphenols, structure activity relationship, synergistic potential, tamarix gallica

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Authors: Alok Bapatla, Pamela Lutting, Mariastella Serrano

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Background: Irritable Bowel Syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain associated with altered bowel habits in the absence of an underlying organic cause. Although the exact etiology of IBS is not fully understood, one of the leading theories postulates a pathology within the Brain-Gut Axis that leads to an overall increase in gastrointestinal sensitivity and pejorative changes in gastrointestinal motility. Research and clinical practice have shown that Gut Directed Hypnotherapy (GDH) has a beneficial clinical role in improving Mind-Gut control and thereby comorbid conditions such as anxiety, abdominal pain, constipation, and diarrhea. Aims: This study presents a 17-year old male with underlying anxiety and a one-year history of IBS-Constipation Predominant Subtype (IBS-C), who has demonstrated impressive improvement of symptoms following GDH treatment following refractory trials with medications including bisacodyl, senna, docusate, magnesium citrate, lubiprostone, linaclotide. Method: The patient was referred to a licensed clinical psychologist specializing in clinical hypnosis and cognitive-behavioral therapy (CBT), who implemented “The Standardized Hypnosis Protocol for IBS” developed by Dr. Olafur S. Palsson, Psy.D at the University of North Carolina at Chapel Hill. The hypnotherapy protocol consisted of a total of seven weekly 45-minute sessions supplemented with a 20-minute audio recording to be listened to once daily. Outcome variables included the GAD-7, PHQ-9 and DCI-2, as well as self-ratings (ranging 0-10) for pain (intensity and frequency), emotional distress about IBS symptoms, and overall emotional distress. All variables were measured at intake prior to administration of the hypnosis protocol and at the conclusion of the hypnosis treatment. A retrospective IBS Questionnaire (IBS Severity Scoring System) was also completed at the conclusion of the GDH treatment for pre-and post-test ratings of clinical symptoms. Results: The patient showed improvement in all outcome variables and self-ratings, including abdominal pain intensity, frequency of abdominal pain episodes, emotional distress relating to gut issues, depression, and anxiety. The IBS Questionnaire showed a significant improvement from a severity score of 400 (defined as severe) prior to GDH intervention compared to 55 (defined as complete resolution) at four months after the last session. IBS Questionnaire subset questions that showed a significant score improvement included abdominal pain intensity, days of pain experienced per 10 days, satisfaction with bowel habits, and overall interference of life affected by IBS symptoms. Conclusion: This case supports the existing research literature that GDH has a significantly beneficial role in improving symptoms in patients with IBS. Emphasis is placed on the numerical results of the IBS Questionnaire scoring, which reflects a patient who initially suffered from severe IBS with failed response to multiple medications, who subsequently showed full and sustained resolution

Keywords: pediatrics, constipation, irritable bowel syndrome, hypnotherapy, gut-directed hypnosis

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Authors: A. Calabrese, V. F. Uricchio, D. di Noia, S. Favale, C. Caiati, G. P. Maggi, G. Donvito, D. Diacono, S. Tangaro, A. Italiano, E. Riezzo, M. Zippitelli, M. Toriello, E. Celiberti, D. Festa, A. Colaianni

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Climate change has a severe impact on human health. There is a vast literature demonstrating temperature increase is causally related to cardiovascular problem and represents a high risk for human health, but there are not study that improve a solution. In this work, it is studied how the clime influenced the human parameter through the analysis of climatic conditions in an area of the Apulia Region: Capurso Municipality. At the same time, medical personnel involved identified a set of variables useful to define an index describing health condition. These scientific studies are the base of an innovative alert system, IPPOCRATE, whose aim is to asses climate risk and share information to population at risk to support prevention and mitigation actions. IPPOCRATE is an e-health system, it is designed to provide technological support to analysis of health risk related to climate and provide tools for prevention and management of critical events. It is the first integrated system of prevention of human risk caused by climate change. IPPOCRATE calculates risk weighting meteorological data with the vulnerability of monitored subjects and uses mobile and cloud technologies to acquire and share information on different data channels. It is composed of four components: Multichannel Hub. Multichannel Hub is the ICT infrastructure used to feed IPPOCRATE cloud with a different type of data coming from remote monitoring devices, or imported from meteorological databases. Such data are ingested, transformed and elaborated in order to be dispatched towards mobile app and VoIP phone systems. IPPOCRATE Multichannel Hub uses open communication protocols to create a set of APIs useful to interface IPPOCRATE with 3rd party applications. Internally, it uses non-relational paradigm to create flexible and highly scalable database. WeHeart and Smart Application The wearable device WeHeart is equipped with sensors designed to measure following biometric variables: heart rate, systolic blood pressure and diastolic blood pressure, blood oxygen saturation, body temperature and blood glucose for diabetic subjects. WeHeart is designed to be easy of use and non-invasive. For data acquisition, users need only to wear it and connect it to Smart Application by Bluetooth protocol. Easy Box was designed to take advantage from new technologies related to e-health care. EasyBox allows user to fully exploit all IPPOCRATE features. Its name, Easy Box, reveals its purpose of container for various devices that may be included depending on user needs. Territorial Registry is the IPPOCRATE web module reserved to medical personnel for monitoring, research and analysis activities. Territorial Registry allows to access to all information gathered by IPPOCRATE using GIS system in order to execute spatial analysis combining geographical data (climatological information and monitored data) with information regarding the clinical history of users and their personal details. Territorial Registry was designed for different type of users: control rooms managed by wide area health facilities, single health care center or single doctor. Territorial registry manages such hierarchy diversifying the access to system functionalities. IPPOCRATE is the first e-Health system focused on climate risk prevention.

Keywords: climate change, health risk, new technological system

Procedia PDF Downloads 836

Authors: Samuel Escandón, María J. Peñaherrera-Vélez, Signe Vargas-Rosvik, Carlos Jerves Córdova, Ximena Vélez-Calvo, Angélica Ochoa-Avilés

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Overweight and obesity are considered risk factors in childhood for developing nutrition-related non-communicable diseases (NCDs), such as diabetes, cardiovascular diseases, and cancer. In Ecuador, 35.4% of 5- to 11-year-olds and 29.6% of 12- to 19-year-olds are overweight or obese. Globally, unhealthy food environments characterized by high consumption of processed/ultra-processed food and rapid urbanization are highly related to the increasing nutrition-related non-communicable diseases. The evidence shows that in low- and middle-income countries (LMICs), fiscal policies and regulatory measures significantly reduce unhealthy food environments, achieving substantial advances in health. However, in some LMICs, little is known about the impact of governments' action to implement healthy food-environment policies. This study aimed to generate evidence on the state of implementation of public policy focused on food environments for the prevention of overweight and obesity in children and adolescents in Ecuador compared to global best practices and to target key recommendations for reinforcing the current strategies. After adapting the INFORMAS' Healthy Food Environment Policy Index (Food‐EPI) to the Ecuadorian context, the Policy and Infrastructure support components were assessed. Individual online interviews were performed using fifty-one indicators to analyze the level of implementation of policies directly or indirectly related to preventing overweight and obesity in children and adolescents compared to international best practices. Additionally, a participatory workshop was conducted to identify the critical indicators and generate recommendations to reinforce or improve the political action around them. In total, 17 government and non-government experts were consulted. From 51 assessed indicators, only the one corresponding to the nutritional information and ingredients labelling registered an implementation level higher than 60% (67%) compared to the best international practices. Among the 17 indicators determined as priorities by the participants, those corresponding to the provision of local products in school meals and the limitation of unhealthy-products promotion in traditional and digital media had the lowest level of implementation (34% and 11%, respectively) compared to global best practices. The participants identified more barriers (e.g., lack of continuity of effective policies across government administrations) than facilitators (e.g., growing interest from the Ministry of Environment because of the eating-behavior environmental impact) for Ecuador to move closer to the best international practices. Finally, within the participants' recommendations, we highlight the need for policy-evaluation systems, information transparency on the impact of the policies, transformation of successful strategies into laws or regulations to make them mandatory, and regulation of power and influence from the food industry (conflicts of interest). Actions focused on promoting a more active role of society in the stages of policy formation and achieving more articulated actions between the different government levels/institutions for implementing the policy are necessary to generate a noteworthy impact on preventing overweight and obesity in children and adolescents. Including systems for internal evaluation of existing strategies to strengthen successful actions, create policies to fill existing gaps and reform policies that do not generate significant impact should be a priority for the Ecuadorian government to improve the country's food environments.

Keywords: children and adolescents, food-EPI, food policies, healthy food environment

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Authors: Laurence Weinberg, Dominic Walpole, Dong-Kyu Lee, Michael D’Silva, Jian W. Chan, Lachlan F. Miles, Bradley Carp, Adam Wells, Tuck S. Ngun, Siven Seevanayagam, George Matalanis, Ziauddin Ansari, Rinaldo Bellomo, Michael Yii

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Background: There have been multiple recent advancements in the selection, optimization and management of cardiac surgical patients. However, there is limited data regarding the outcomes of nonagenarians undergoing cardiac surgery, despite this vulnerable cohort increasingly receiving these interventions. This study describes the patient characteristics, management and outcomes of a group of nonagenarians undergoing cardiac surgery in the context of contemporary peri-operative care. Methods: A retrospective observational study was conducted of patients 90 to 99 years of age (i.e., nonagenarians) who had undergone cardiac surgery requiring a classic median sternotomy (i.e., open-heart surgery). All operative indications were included. Patients who underwent minimally invasive surgery, transcatheter aortic valve implantation and thoracic aorta surgery were excluded. Data were collected from four hospitals in Victoria, Australia, over an 8-year period (January 2012 – December 2019). The primary objective was to assess six-month mortality in nonagenarians undergoing open-heart surgery and to evaluate the incidence and severity of postoperative complications using the Clavien-Dindo classification system. The secondary objective was to provide a detailed description of the characteristics and peri-operative management of this group. Results: A total of 12,358 adult patients underwent cardiac surgery at the study centers during the observation period, of whom 18 nonagenarians (0.15%) fulfilled the inclusion criteria. The median (IQR) [min-max] age was 91 years (90.0:91.8) [90-94] and 14 patients (78%) were men. Cardiovascular comorbidities, polypharmacy and frailty, were common. The median (IQR) predicted in-hospital mortality by EuroSCORE II was 6.1% (4.1-14.5). All patients were optimized preoperatively by a multidisciplinary team of surgeons, cardiologists, geriatricians and anesthetists. All index surgeries were performed on cardiopulmonary bypass. Isolated coronary artery bypass grafting (CABG) and CABG with aortic valve replacement were the most common surgeries being performed in four and five patients, respectively. Half the study group underwent surgery involving two or more major procedures (e.g. CABG and valve replacement). Surgery was undertaken emergently in 44% of patients. All patients except one experienced at least one postoperative complication. The most common complications were acute kidney injury (72%), new atrial fibrillation (44%) and delirium (39%). The highest Clavien-Dindo complication grade was IIIb occurring once each in three patients. Clavien-Dindo grade IIIa complications occurred in only one patient. The median (IQR) postoperative length of stay was 11.6 days (9.8:17.6). One patient was discharged home and all others to an inpatient rehabilitation facility. Three patients had an unplanned readmission within 30 days of discharge. All patients had follow-up to at least six months after surgery and mortality over this period was zero. The median (IQR) duration of follow-up was 11.3 months (6.0:26.4) and there were no cases of mortality observed within the available follow-up records. Conclusion: In this group of nonagenarians undergoing cardiac surgery, postoperative six-month mortality was zero. Complications were common but generally of low severity. These findings support carefully selected nonagenarian patients being offered cardiac surgery in the context of contemporary, multidisciplinary perioperative care. Further, studies are needed to assess longer-term mortality and functional and quality of life outcomes in this vulnerable surgical cohort.

Keywords: cardiac surgery, mortality, nonagenarians, postoperative complications

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Authors: Wondale Getinet Alemu, Lillian Mwanri, Clemence Due, Telake Azale, Anna Ziersch

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Background: Mental illness is one of the most severe, chronic, and disabling public health problems that affect patients' Quality of life (QoL). Improving the QoL for people with mental illness is one of the most critical steps in stopping disease progression and avoiding complications of mental illness. Therefore, we aimed to assess the QoL and its determinants in patients with mental illness in outpatient clinics in Northwest Ethiopia in 2023. Methods: A facility-based cross-sectional study was conducted among people with mental illness in an outpatient clinic in Ethiopia. The sampling interval was decided by dividing the total number of study participants who had a follow-up appointment during the data collection period (2400) by the total sample size of 638, with the starting point selected by lottery method. The interviewer-administered WHOQOL BREF-26 tool was used to measure the QoL of people with mental illness. The domains and Health-Related Quality of Life (HRQoL) were identified. The indirect and direct effects of variables were calculated using structural equation modeling with SPSS-28 and Amos-28 software. A p-value of < 0.05 and a 95% CI were used to evaluate statistical significance. Results: A total of 636 (99.7%) participants responded and completed the WHOQOL-BREF questionnaire. The mean score of overall HRQoL of people with mental illness in the outpatient clinic was (49.6 ± 10 Sd). The highest QoL was found in the physical health domain (50.67 ±9.5 Sd), and the lowest mean QoL was found in the psychological health domain (48.41±10 Sd). Rural residents, drug nonadherence, suicidal ideation, not getting counseling, moderate or severe subjective severity, the family does not participate in patient care, and a family history of mental illness had an indirect negative effect on HRQoL. Alcohol use and psychological health domain had a direct positive effect on QoL. Furthermore, objective severity of illness, having low self-esteem, and having a history of mental illness in the family had both direct and indirect effects on QoL. Furthermore, sociodemographic factors (residence, educational status, marital status), social support-related factors (self-esteem, family not participating in patient care), substance use factors (alcohol use, tobacco use,) and clinical factors (objective and subjective severity of illness, not getting counseling, suicidal ideation, number of episodes, comorbid illness, family history of mental illness, poor drug adherence) directly and indirectly affected QoL. Conclusions: In this study, the QoL of people with mental illness was poor, with the psychological health domain being the most affected. Sociodemographic factors, social support-related factors, drug use factors, and clinical factors directly and indirectly, affect QoL through the mediator variables of physical health domains, psychological health domains, social relation health domains, and environmental health domains. In order to improve the QoL of people with mental illnesses, we recommend that emphasis be given to addressing the scourge of mental health, including the development of policy and practice drivers that address the above-identified factors.

Keywords: quality of life, mental wellbeing, mental illness, mental disorder, Ethiopia

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Authors: Andreea Campu, Ilinica Muresan, Simona Cainap, Simion Astilean, Monica Focsan

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Acute myocardial infarction (AMI) is the most severe cardiovascular disease, which has threatened human lives for decades, thus a continuous interest is directed towards the detection of cardiac biomarkers such as cardiac troponin I (cTnI) in order to predict risk and, implicitly, fulfill the early diagnosis requirements in AMI settings. Microfluidics is a major technology involved in the development of efficient sensing devices with real-time fast responses and on-site applicability. Microfluidic devices have gathered a lot of attention recently due to their advantageous features such as high sensitivity and specificity, miniaturization and portability, ease-of-use, low-cost, facile fabrication, and reduced sample manipulation. The integration of gold nanoparticles into the structure of microfluidic sensors has led to the development of highly effective detection systems, considering the unique properties of the metallic nanostructures, specifically the Localized Surface Plasmon Resonance (LSPR), which makes them highly sensitive to their microenvironment. In this scientific context, herein, we propose the implementation of a novel detection device, which successfully combines the efficiency of gold bipyramids (AuBPs) as signal transducers and thermal generators with the sample-driven advantages of the microfluidic channels into a miniaturized, portable, low-cost, specific, and sensitive test for the dual LSPR-thermographic cTnI detection. Specifically, AuBPs with longitudinal LSPR response at 830 nm were chemically synthesized using the seed-mediated growth approach and characterized in terms of optical and morphological properties. Further, the colloidal AuBPs were deposited onto pre-treated silanized glass substrates thus, a uniform nanoparticle coverage of the substrate was obtained and confirmed by extinction measurements showing a 43 nm blue-shift of the LSPR response as a consequence of the refractive index change. The as-obtained plasmonic substrate was then integrated into a microfluidic “Y”-shaped polydimethylsiloxane (PDMS) channel, fabricated using a Laser Cutter system. Both plasmonic and microfluidic elements were plasma treated in order to achieve a permanent bond. The as-developed microfluidic plasmonic chip was further coupled to an automated syringe pump system. The proposed biosensing protocol implicates the successive injection inside the microfluidic channel as follows: p-aminothiophenol and glutaraldehyde, to achieve a covalent bond between the metallic surface and cTnI antibody, anti-cTnI, as a recognition element, and target cTnI biomarker. The successful functionalization and capture of cTnI was monitored by LSPR detection thus, after each step, a red-shift of the optical response was recorded. Furthermore, as an innovative detection technique, thermal determinations were made after each injection by exposing the microfluidic plasmonic chip to 785 nm laser excitation, considering that the AuBPs exhibit high light-to-heat conversion performances. By the analysis of the thermographic images, thermal curves were obtained, showing a decrease in the thermal efficiency after the anti-cTnI-cTnI reaction was realized. Thus, we developed a microfluidic plasmonic chip able to operate as both LSPR and thermal sensor for the detection of the cardiac troponin I biomarker, leading thus to the progress of diagnostic devices.

Keywords: gold nanobipyramids, microfluidic device, localized surface plasmon resonance detection, thermographic detection

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Authors: Harpa Ragnarsdóttir, Magnús Kjartan Gíslason, Kristín Briem, Guðný Lilja Oddsdóttir

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Introduction: Whiplash-Associated Disorder (WAD) is a health problem characterized by motor, neurological and psychosocial symptoms, stressing the need for a multimodal treatment approach. To achieve individualized multimodal approach, prognostic factors need to be identified early using validated patient-reported and objective outcome measures. The aim of this study is to demonstrate the degree of association between patient-reported and clinical outcome measures of WAD patients in the subacute phase. Methods: Individuals (n=41) with subacute (≥1, ≤3 months) WAD (I-II), medium to high-risk symptoms, or neck pain rating ≥ 4/10 on the Visual Analog Scale (VAS) were examined. Outcome measures included measurements for movement control (Butterfly test) and cervical active range of motion (cAROM) using the NeckSmart system, a computer system using an inertial measurement unit (IMU) that connects to a computer. The IMU sensor is placed on the participant’s head, who receives visual feedback about the movement of the head. Patient-reported neck disability, pain intensity, general health, self-perceived handicap, central sensitization, and difficulties due to dizziness were measured using questionnaires. Excel and R statistical software were used for statistical analyses. Results: Forty-one participants, 15 males (37%), 26 females (63%), mean (SD) age 36.8 (±12.7), underwent data collection. Mean amplitude accuracy (AA) (SD) in the Butterfly test for easy, medium, and difficult paths were 2.4mm (0.9), 4.4mm (1.8), and 6.8mm (2.7), respectively. Mean cAROM (SD) for flexion, extension, left-, and right rotation were 46.3° (18.5), 48.8° (17.8), 58.2° (14.3), and 58.9° (15.0), respectively. Mean scores on the Neck Disability Index (NDI), VAS, Dizziness Handicap Inventory (DHI), Central Sensitization Inventory (CSI), and 36-Item Short Form Survey RAND version (RAND) were 43% (17.4), 7 (1.7), 37 (25.4), 51 (17.5), and 39.2 (17.7) respectively. Females showed significantly greater deviation for AA compared to males for easy and medium Butterfly paths (p<0.05). Statistically significant moderate to strong positive correlation was found between the DHI and easy (r=0.6, p=0.05), medium (r=0.5, p=0.05)) and difficult (r=0.5, p<0.05) Butterfly paths, between the total RAND score and all cAROMs (r between 0.4-0.7, p≤0.05) except flexion (r=0.4, p=0.7), and between the NDI score and CSI (r=0.7, p<0.01), VAS (r=0.5, p<0.01), and DHI (r=0.7, p<0.01) scores respectively. Discussion: All patient-reported and objective measures were found to be outside the reference range. Results suggest females have worse movement control in the neck in the subacute WAD phase. However, no statistical difference based on gender was found in patient-reported measures. Suggesting females might have worse movement control than males in general in this phase. The correlation found between DHI and the Butterfly test can be explained because the DHI measures proprioceptive symptoms like dizziness and eye movement disorders that can affect the outcome of movement control tests. A correlation was found between the total RAND score and cAROM, suggesting that a reduced range of motion affects the quality of life. Significance: The NeckSmart system can detect abnormalities in cAROM, fine movement control, and kinesthesia of the neck. Results suggest females have worse movement control than males. Results show a moderate to a high correlation between several patient-reported and objective measurements.

Keywords: whiplash associated disorders, car-collision, neck, trauma, subacute

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Authors: Majed Al Otaibi, Melissa Lessard-Beaudoin, Amel Loudghi, Raphael Chouinard-Watkins, Melanie Plourde, Frederic Calon, C. Alexandre Castellano, Stephen Cunnane, Helene Payette, Pierrette Gaudreau, Denis Gris, Rona K. Graham

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Introduction: Alzheimer disease (AD) is a chronic disorder that affects millions of individuals worldwide. Symptoms include memory dysfunction, and also alterations in attention, planning, language and overall cognitive function. Olfactory dysfunction is a common symptom of several neurological disorders including AD. Studying the mechanisms underlying the olfactory dysfunction may therefore lead to the discovery of potential biomarkers and/or treatments for neurodegenerative diseases. Objectives: To determine if olfactory dysfunction predicts future cognitive impairment in the aging population and to characterize the olfactory system in a murine model expressing a genetic factor of AD. Method: For the human study, quantitative olfactory tests (UPSIT and OMT) have been done on 93 subjects (aged 80 to 94 years) from the Quebec Longitudinal Study on Nutrition and Successful Aging (NuAge) cohort accepting to participate in the ORCA secondary study. The telephone Modified Mini Mental State examination (t-MMSE) was used to assess cognition levels, and an olfactory self-report was also collected. In a separate cohort, olfactory cortical volume was calculated using MRI results from healthy old adults (n=25) and patients with AD (n=18) using the AAL single-subject atlas and performed with the PNEURO tool (PMOD 3.7). For the murine study, we are using Western blotting, RT-PCR and immunohistochemistry. Result: Human Study: Based on the self-report, 81% of the participants claimed to not suffer from any problem with olfaction. However, based on the UPSIT, 94% of those subjects showed a poor olfactory performance and different forms of microsmia. Moreover, the results confirm that olfactory function declines with age. We also detected a significant decrease in olfactory cortical volume in AD individuals compared to controls. Murine study: Preliminary data demonstrate there is a significant decrease in expression levels of the proform of caspase-3 and the caspase substrate STK3, in the olfactory bulb of mice expressing human APOE4 compared with controls. In addition, there is a significant decrease in the expression level of the caspase-9 proform and caspase-8 active fragment. Analysis of the mature neuron marker, NeuN, shows decreased expression levels of both isoforms. The data also suggest that Iba-1 immunostaining is increased in the olfactory bulb of APOE4 mice compared to wild type mice. Conclusions: The activation of caspase-3 may be the cause of the decreased levels of STK3 through caspase cleavage and may play role in the inflammation observed. In the clinical study, our results suggest that seniors are unaware of their olfactory function status and therefore it is not sufficient to measure olfaction using the self-report in the elderly. Studying olfactory function and cognitive performance in the aging population will help to discover biomarkers in the early stage of the AD.

Keywords: Alzheimer's disease, APOE4, cognition, caspase, brain atrophy, neurodegenerative, olfactory dysfunction

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Authors: Catherine S. Fichten, Tali Heiman, Mary Jorgensen, Mai Nhu Nguyen, Rhonda Amsel, Dorit Olenik-Shemesh

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The study examined Canadian and Israeli students' perceptions related to their intention to graduate from their program of studies. Canada and Israel are dissimilar in many ways that affect education, including language and alphabet. In addition, the postsecondary education systems differ. For example, in some parts of Canada (e.g., in Quebec, Canada’s 2nd largest province), students matriculate after 11 years of high school; in Israel, this typically occurs after 12 years. In addition, Quebec students attend two compulsory years of junior college before enrolling in a three-year university Bachelor program; in Israel students enroll in a three-year Bachelor program directly after matriculation. In addition, Israeli students typically enroll in the army shortly after high school graduation; in Canada, this is not the case. What the two countries do have in common is concern about the success of postsecondary students with disabilities. The present study was based on Ajzen’s Theory of Planned Behavior (TPB); the model suggests that behavior is influenced by Intention to carry it out. This, in turn, is predicted by the following correlated variables: Perceived Behavioral Control (i.e., ease or difficulty enacting the behavior - in this case graduation), Subjective Norms (i.e., perceived social/peer pressure from individuals important in the student’s life), and Attitude (i.e., positive or negative evaluation of graduation). A questionnaire was developed to test the TPB in previous Canadian studies and administered to 845 Canadian college students (755 nondisabled, 90 with LD/ADHD) who had completed at least one semester of studies) and to 660 Israeli university students enrolled in a Bachelor’s program (537 nondisabled, 123 with LD/ADHD). Because Israeli students were older than Canadian students we covaried age in SPSS-based ANOVA comparisons and included it in regression equations. Because females typically have better academic outcomes than males, gender was included in all analyses. ANOVA results indicate only a significant gender effect for Intention to graduate, with females having higher scores. Four stepwise regressions were conducted, with Intention to graduate as the predicted variable, and Gender and the three TPB predictors as independent variables (separate analyses for Israeli and Canadian samples with and without LD/ADHD). Results show that for samples with LD/ADHD, although Gender and Age were not significant predictors, the TPB predictors were, with all three TPB predictors being significant for the Canadian sample (i.e., Perceived Behavioral Control, Subjective Norms, Attitude, R2=.595), and two of the three (i.e., Perceived Behavioral Control, Subjective Norms) for the Israeli sample (R2=.528). For nondisabled students, the results for both countries show that all three TPB predictors were significant along with Gender: R2=.443 for Canada and R2=.332 for Israel; age was not significant. Our findings show that despite vast differences between our Canadian and Israeli samples, Intention to graduate was related to the three TPB predictors. This suggests that our TPB measure is valid for diverse samples and countries that it can be used as a quick, inexpensive way to predict graduation rates, and that strengthening the three predictor variables may result in higher graduation rates.

Keywords: disability, higher education, students, theory of planned behavior

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Authors: Dina Farran, Mark Ashworth, Fiona Gaughran

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Atrial fibrillation (AF), the most prevalent cardiac arrhythmia, is associated with an increased risk of stroke, contributing to heart failure and death. In this project, we aim to improve patient safety by screening for stroke risk among people with AF and co-morbid mental illness. To do so, we started by conducting a systematic review and meta-analysis on prevalence, management, and outcomes of AF in people with Serious Mental Illness (SMI) versus the general population. We then evaluated oral anticoagulation (OAC) prescription trends in people with AF and co-morbid SMI in King’s College Hospital. We also evaluated the association between mental illness severity and OAC prescription in eligible patients in South London and Maudsley (SLaM) NHS Foundation Trust. Next, we implemented an electronic clinical decision support system (eCDSS) consisting of a visual prompt on patient electronic Personal Health Records to screen for AF-related stroke risk in three Mental Health of Older Adults wards at SLaM. Finally, we assessed the feasibility and acceptability of the eCDSS by qualitatively investigating clinicians’ perspectives of the potential usefulness of the eCDSS (pre-intervention) and their experiences and their views regarding its impact on clinicians and patients (post-intervention). The systematic review showed that people with SMI had low reported rates of AF. AF patients with SMI were less likely to receive OAC than the general population. When receiving warfarin, people with SMI, particularly bipolar disorder, experienced poor anticoagulation control compared to the general population. Meta-analysis showed that SMI was not significantly associated with an increased risk of stroke or major bleeding when adjusting for underlying risk factors. The main findings of the first observational study were that among AF patients having a high stroke risk, those with co-morbid SMI were less likely than non-SMI to be prescribed any OAC, particularly warfarin. After 2019, there was no significant difference between the two groups. In the second observational study, patients with AF and co-morbid SMI were less likely to be prescribed any OAC compared to those with dementia, substance use disorders, or common mental disorders, adjusting for age, sex, stroke, and bleeding risk scores. Among AF patients with co-morbid SMI, warfarin was less likely to be prescribed to those having alcohol or substance dependency, serious self-injury, hallucinations or delusions, and activities of daily living impairment. In the intervention, clinicians were asked to confirm the presence of AF, clinically assess stroke and bleeding risks, record risk scores in clinical notes, and refer patients at high risk of stroke to OAC clinics. Clinicians reported many potential benefits for the eCDSS, including improving clinical effectiveness, better identification of patients at risk, safer and more comprehensive care, consistency in decision making and saving time. Identified potential risks included rigidity in decision-making, overreliance, reduced critical thinking, false positive recommendations, annoyance, and increased workload. This study presents a unique opportunity to quantify AF patients with mental illness who are at high risk of severe outcomes using electronic health records. This has the potential to improve health outcomes and, therefore patients' quality of life.

Keywords: atrial fibrillation, stroke, mental health conditions, electronic clinical decision support systems

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Authors: Omaymah Al-Otoom, Rajesh Mehta

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Introduction: Migration is an established risk factor in the development of schizophrenia and other forms of psychosis. The exposure to different social adversities, including social isolation, discrimination, and economic stress, is thought to contribute to elevated rates of psychosis in immigrants and their children. We present a case of resistant schizophrenia in an immigrant adolescent. Case: The patient is a 15-year-old male immigrant. In October 2021, the patient was admitted for irritability, suicidal ideations, and hallucinations. He was treated with Fluoxetine 10 mg daily for irritability. In November 2021, he presented with similar manifestations. Fluoxetine was discontinued, and Risperidone 1 mg at bedtime was started for psychotic symptoms. In March 2022, he presented with commanding auditory hallucinations (voices telling him that people were going to kill his father). Risperidone was gradually increased to 2.5 mg twice daily for hallucinations. The outpatient provider discontinued Risperidone and started Olanzapine 7.5 mg and Lurasidone 40 mg daily. In August 2022, he presented with worsening paranoia due to medication non-adherence. The patient had limited improvement on medications. In October 2022, the patient presented to the ED for visual hallucinations and aggression towards the family. His medications were Olanzapine 10 mg daily, Lurasidone 60 mg daily, and Haloperidol 2.5 mg twice daily. In the ED, he received multiple as-needed medications and was placed in seclusion for his aggressive behavior. The patient showed a positive response to a higher dose of Olanzapine and decreased dose of Lurasidone. The patient was discharged home in stable condition. Two days after discharge, he was brought for bizarre behavior, visual hallucinations, and homicidal ideations at school. Due to concerns for potential antipsychotic side effects and poor response, Lurasidone and Olanzapine were discontinued, and he was discharged home on Haloperidol 5 mg in the morning and 15 mg in the evening. Clozapine treatment was recommended on an outpatient basis. He has no family history of psychotic disorders. He has no history of substance use. A medical workup was done, the electroencephalogram was normal, and the urine toxicology was negative. Discussion: Our patient was on three antipsychotics at some point with no improvement in his psychotic symptoms, which qualifies as treatment-resistant schizophrenia (TRP). It is well recognized that migrants are at higher risk of different psychiatric disorders, including posttraumatic stress disorder, affective disorders, schizophrenia, and psychosis. This is thought to be related to higher exposure to traumatic life events compared to the general population. In addition, migrants are more likely to experience poverty, separation from family members, and discrimination which could contribute to mental health issues. In one study, they found that people who migrated before the age of 18 had twice the risk of psychotic disorders compared to the native-born population. It is unclear whether migration increases the risk of treatment resistance. In a Canadian study, neither ethnicity nor migrant status was associated with treatment resistance; however, this study was limited by its small sample size. There is a need to implement psychiatric prevention strategies and outreach programs through research to mitigate the risk of mental health disorders among immigrants.

Keywords: psychosis, immigrant, adolescent, treatment resistant schizophrenia

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Authors: Xiaoqing Peng, Aijing Luo, Yang Chen

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Background: Cyberchondria, as an "emerging risk" accompanied by the information era, is a new abnormal pattern characterized by excessive or repeated online searches for health-related information and escalating health anxiety, which endangers people's physical and mental health and poses a huge threat to public health. Objective: To explore and discuss the research status, hotspots and trends of Cyberchondria. Methods: Based on a total of 77 articles regarding "Cyberchondria" extracted from Web of Science from the beginning till October 2019, the literature trends, countries, institutions, hotspots are analyzed by bibliometric analysis, the concept definition of Cyberchondria, instruments, relevant factors, treatment and intervention are discussed as well. Results: Since "Cyberchondria" was put forward for the first time in 2001, the last two decades witnessed a noticeable increase in the amount of literature, especially during 2014-2019, it quadrupled dramatically at 62 compared with that before 2014 only at 15, which shows that Cyberchondria has become a new theme and hot topic in recent years. The United States was the most active contributor with the largest publication (23), followed by England (11) and Australia (11), while the leading institutions were Baylor University(7) and University of Sydney(7), followed by Florida State University(4) and University of Manchester(4). The WoS categories "Psychiatry/Psychology " and "Computer/ Information Science "were the areas of greatest influence. The concept definition of Cyberchondria is not completely unified in the world, but it is generally considered as an abnormal behavioral pattern and emotional state and has been invoked to refer to the anxiety-amplifying effects of online health-related searches. The first and the most frequently cited scale for measuring the severity of Cyberchondria called “The Cyberchondria Severity Scale (CSS) ”was developed in 2014, which conceptualized Cyberchondria as a multidimensional construct consisting of compulsion, distress, excessiveness, reassurance, and mistrust of medical professionals which was proved to be not necessary for this construct later. Since then, the Brazilian, German, Turkish, Polish and Chinese versions were subsequently developed, improved and culturally adjusted, while CSS was optimized to a simplified version (CSS-12) in 2019, all of which should be worthy of further verification. The hotspots of Cyberchondria mainly focuses on relevant factors as follows: intolerance of uncertainty, anxiety sensitivity, obsessive-compulsive disorder, internet addition, abnormal illness behavior, Whiteley index, problematic internet use, trying to make clear the role played by “associated factors” and “anxiety-amplifying factors” in the development of Cyberchondria, to better understand the aetiological links and pathways in the relationships between hypochondriasis, health anxiety and online health-related searches. Although the treatment and intervention of Cyberchondria are still in the initial stage of exploration, there are kinds of meaningful attempts to seek effective strategies from different aspects such as online psychological treatment, network technology management, health information literacy improvement and public health service. Conclusion: Research on Cyberchondria is in its infancy but should be deserved more attention. A conceptual consensus on Cyberchondria, a refined assessment tool, prospective studies conducted in various populations, targeted treatments for it would be the main research direction in the near future.

Keywords: cyberchondria, hypochondriasis, health anxiety, online health-related searches

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Authors: Tamar Lin, Nufar Buchshtab, Yifat Elharar, Julian Nicenboim, Rotem Edgar, Iddo Weiner, Lior Zelcbuch, Ariel Cohen, Sharon Kredo-Russo, Inbar Gahali-Sass, Naomi Zak, Sailaja Puttagunta, Merav Bassan

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Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder that is characterized by dry skin and flares of eczematous lesions and intense pruritus. Multiple lines of evidence suggest that AD is associated with increased colonization by Staphylococcus aureus, which contributes to disease pathogenesis through the release of virulence factors that affect both keratinocytes and immune cells, leading to disruption of the skin barrier and immune cell dysfunction. The aim of the current study is to develop a bacteriophage-based product that specifically targets S. aureus. Methods: For the discovery of phage, environmental samples were screened on 118 S. aureus strains isolated from skin samples, followed by multiple enrichment steps. Natural phages were isolated, subjected to Next-generation Sequencing (NGS), and analyzed using proprietary bioinformatics tools for undesirable genes (toxins, antibiotic resistance genes, lysogeny potential), taxonomic classification, and purity. Phage host range was determined by an efficiency of plating (EOP) value above 0.1 and the ability of the cocktail to completely lyse liquid bacterial culture under different growth conditions (e.g., temperature, bacterial stage). Results: Sequencing analysis demonstrated that the 118 S. aureus clinical strains were distributed across the phylogenetic tree of all available Refseq S. aureus (~10,750 strains). Screening environmental samples on the S. aureus isolates resulted in the isolation of 50 lytic phages from different genera, including Silviavirus, Kayvirus, Podoviridae, and a novel unidentified phage. NGS sequencing confirmed the absence of toxic elements in the phages’ genomes. The host range of the individual phages, as measured by the efficiency of plating (EOP), ranged between 41% (48/118) to 79% (93/118). Host range studies in liquid culture revealed that a subset of the phages can infect a broad range of S. aureus strains in different metabolic states, including stationary state. Combining the single-phage EOP results of selected phages resulted in a broad host range cocktail which infected 92% (109/118) of the strains. When tested in vitro in a liquid infection assay, clearance was achieved in 87% (103/118) of the strains, with no evidence of phage resistance throughout the study (24 hours). A S. aureus host was identified that can be used for the production of all the phages in the cocktail at high titers suitable for large-scale manufacturing. This host was validated for the absence of contaminating prophages using advanced NGS methods combined with multiple production cycles. The phages are produced under optimized scale-up conditions and are being used for the development of a topical formulation (BX005) that may be administered to subjects with atopic dermatitis. Conclusions: A cocktail of natural phages targeting S. aureus was effective in reducing bacterial burden across multiple assays. Phage products may offer safe and effective steroid-sparing options for atopic dermatitis.

Keywords: atopic dermatitis, bacteriophage cocktail, host range, Staphylococcus aureus

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Authors: Ina Filkobski, Eran Shor

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This article explores how newspapers cover murder of women by family members and intimate partners. Three major Israeli newspapers were compared in order to analyse the coverage of Jewish and Arab victims and culprits and to examine whether and in what ways the media contribute to the construction of symbolic boundaries between minority and dominant social groups. A sample of some 459 articles that were published between 2013 and 2015 was studied using a systematic qualitative content analysis. Our findings suggest that the treatment of murder cases by the media varies according to the ethnicity of both victims and culprits. The murder of Jews by family members or intimate partners was framed as a shocking and unusual event, a result of the individual personality or pathology of the culprit. Conversely, when Arabs were the killers, murders were often explained by focusing on the culture of the ethnic group, described as traditional, violent, and patriarchal. In two-thirds of the cases in which Arabs were involved, so-called ‘honor killing’ or other cultural explanations were proposed as the motive for the murder. This was often the case even before a suspect was detected, while police investigation was at its very early stages, and often despite forceful denials from victims’ families. In case of Jewish culprits, more than half of the articles in our sample suggested mental disorder to explain the acts and cultural explanations were almost entirely absent. Beyond the emphasis on psychological vs. cultural explanations, newspaper articles also tend to provide much more detail about Jewish culprits than about Arabs. Such detailed examinations convey a desire to make sense of the event by understanding the supposedly unique and unorthodox nature of the killer. The detailed accounts were usually absent from the reports on Arab killers. Thus, even if reports do not explicitly offer cultural motivations for the murder, the fact that reports often remain laconic leaves people to draw their own conclusions, which would then be likely based on existing cognitive scripts and previous reports on family murders among Arabs. Such treatment contributes to the notion that Arab and Muslim cultures, religions, and nationalities are essentially misogynistic and adhere to norms of honor and shame that are radically different from those of modern societies, such as the Jewish-Israeli one. Murder within the family is one of the most dramatic occurrences in the social world, and in societies that see themselves as modern it is a taboo; an ultimate signifier of danger. We suggest that representations of murder provide a valuable prism for examining the construction of group boundaries. Our analysis, therefore, contributes to the scholarly effort to understand the creation and reinforcement of symbolic boundaries between ‘society’ and its ‘others’ by systematically tracing the media constructions of ‘otherness’. While our analysis focuses on Israel, studies on the United States, Canada, and various European countries with ethnically and racially heterogeneous populations, make it clear that the stigmatisation and exclusion of visible, religious, and language minorities are not unique to the Israeli case.

Keywords: comparative study of media coverege of minority and majority groups, construction of symbolic group boundaries, murder of women by family members and intimate partners, Israel, Jews, Arabs

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Authors: Marielle Leijten, Catherine Meulemans, Sven De Maeyer, Luuk Van Waes

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For the diagnosis of Alzheimer's disease (AD), a large variety of neuropsychological tests are available. In some of these tests, linguistic processing - both oral and written - is an important factor. Language disturbances might serve as a strong indicator for an underlying neurodegenerative disorder like AD. However, the current diagnostic instruments for language assessment mainly focus on product measures, such as text length or number of errors, ignoring the importance of the process that leads to written or spoken language production. In this study, it is our aim to describe and test differences between cognitive and impaired elderly on the basis of a selection of writing process variables (inter- and intrapersonal characteristics). These process variables are mainly related to pause times, because the number, length, and location of pauses have proven to be an important indicator of the cognitive complexity of a process. Method: Participants that were enrolled in our research were chosen on the basis of a number of basic criteria necessary to collect reliable writing process data. Furthermore, we opted to match the thirteen cognitively impaired patients (8 MCI and 5 AD) with thirteen cognitively healthy elderly. At the start of the experiment, participants were each given a number of tests, such as the Mini-Mental State Examination test (MMSE), the Geriatric Depression Scale (GDS), the forward and backward digit span and the Edinburgh Handedness Inventory (EHI). Also, a questionnaire was used to collect socio-demographic information (age, gender, eduction) of the subjects as well as more details on their level of computer literacy. The tests and questionnaire were followed by two typing tasks and two picture description tasks. For the typing tasks participants had to copy (type) characters, words and sentences from a screen, whereas the picture description tasks each consisted of an image they had to describe in a few sentences. Both the typing and the picture description tasks were logged with Inputlog, a keystroke logging tool that allows us to log and time stamp keystroke activity to reconstruct and describe text production processes. The main rationale behind keystroke logging is that writing fluency and flow reveal traces of the underlying cognitive processes. This explains the analytical focus on pause (length, number, distribution, location, etc.) and revision (number, type, operation, embeddedness, location, etc.) characteristics. As in speech, pause times are seen as indexical of cognitive effort. Results. Preliminary analysis already showed some promising results concerning pause times before, within and after words. For all variables, mixed effects models were used that included participants as a random effect and MMSE scores, GDS scores and word categories (such as determiners and nouns) as a fixed effect. For pause times before and after words cognitively impaired patients paused longer than healthy elderly. These variables did not show an interaction effect between the group participants (cognitively impaired or healthy elderly) belonged to and word categories. However, pause times within words did show an interaction effect, which indicates pause times within certain word categories differ significantly between patients and healthy elderly.

Keywords: Alzheimer's disease, keystroke logging, matching, writing process

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Authors: Dirk Bruland, Paulo Pinheiro, Ullrich Bauer

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Introduction: Over 3 million children, about one quarter of all students, experience at least one parent with mental disorder in Germany every year. Children of mentally-ill parents are at considerably higher risk of developing serious mental health problems. The different burden patterns and coping attempts often become manifest in children's school lives. In this context, schools can have an important protective function, but can also create risk potentials. In reference to Jorm, pupil-related teachers’ mental health literacy (Teacher-MHL) includes the ability to recognize change behaviour, the knowledge of risk factors, the implementation of first aid intervention, and seeking professional help (teacher as gatekeeper). Although teachers’ knowledge and increased awareness of this topic is essential, the literature provides little information on the extent of teachers' abilities. As part of a German-wide research consortium on health literacy, this project, launched in March for 3 years, will conduct evidence-based mental health literacy research. The primary objective is to measure Teacher-MHL in the context of pupil-related psychosocial factors at primary and secondary schools (grades 5 & 6), while also focussing on children’s social living conditions. Methods: (1) A systematic literature review in different databases to identify papers with regard to Teacher-MHL (completed). (2) Based on these results, an interview guide was developed. This research step includes a qualitative pre-study to inductively survey the general profiles of teachers (n=24). The evaluation will be presented on the conference. (3) These findings will be translated into a quantitative teacher survey (n=2500) in order to assess the extent of socio-analytical skills of teachers as well as in relation to institutional and individual characteristics. (4) Based on results 1 – 3, developing a training program for teachers. Results: The review highlights a lack of information for Teacher-MHL and their skills, especially related to high-risk-groups like children of mentally ill parents. The literature is limited to a few studies only. According to these, teacher are not good at identifying burdened children and if they identify those children they do not know how to handle the situations in school. They are not sufficiently trained to deal with these children, especially there are great uncertainties in dealing with the teaching situation. Institutional means and resources are missing as well. Such a mismatch can result in insufficient support and use of opportunities for children at risk. First impressions from the interviews confirm these results and allow a greater insight in the everyday school-life according to critical life events in families. Conclusions: For the first time schools will be addressed as a setting where children are especially "accessible" for measures of health promotion. Addressing Teacher-MHL gives reason to expect high effectiveness. Targeting professionals' abilities for dealing with this high-risk-group leads to a discharge for teacher themselves to handle those situations and increases school health promotion. In view of the fact that only 10-30% of such high-risk families accept offers of therapy and assistance, this will be the first primary preventive and health-promoting approach to protect the health of a yet unaffected, but particularly burdened, high-risk group.

Keywords: children of mentally ill parents, health promotion, mental health literacy, school

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Authors: Melina Kopke, Jelle Van Dijk

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Persons with cognitive disabilities, such as Autism Spectrum Disorder (ASD) are often dependent on some form of professional support. Recent transformations in Dutch healthcare have spurred institutions to apply new, empowering methods and tools to enable their clients to cope (more) independently in daily life. Assistive Technologies (ATs) seem promising as empowering tools. While ATs can, functionally speaking, help people to perform certain activities without human assistance, we hold that, from a design-theoretical perspective, such technologies often fail to empower in a deeper sense. Most technologies serve either to prescribe or to monitor users’ actions, which in some sense objectifies them, rather than strengthening their agency. This paper proposes that theories of embodied interaction could help formulating a design vision in which interactive assistive devices augment, rather than replace, human agency and thereby add to a persons’ empowerment in daily life settings. It aims to close the gap between empowerment theory and the opportunities provided by assistive technologies, by showing how embodiment and empowerment theory can be applied in practice in the design of new, interactive assistive devices. Taking a Research-through-Design approach, we conducted a case study of designing to support independently living people with ASD with structuring daily activities. In three iterations we interlaced design action, active involvement and prototype evaluations with future end-users and healthcare professionals, and theoretical reflection. Our co-design sessions revealed the issue of handling daily activities being multidimensional. Not having the ability to self-manage one’s daily life has immense consequences on one’s self-image, and also has major effects on the relationship with professional caregivers. Over the course of the project relevant theoretical principles of both embodiment and empowerment theory together with user-insights, informed our design decisions. This resulted in a system of wireless light units that users can program as a reminder for tasks, but also to record and reflect on their actions. The iterative process helped to gradually refine and reframe our growing understanding of what it concretely means for a technology to empower a person in daily life. Drawing on the case study insights we propose a set of concrete design principles that together form what we call the embodied empowerment design framework. The framework includes four main principles: Enabling ‘reflection-in-action’; making information ‘publicly available’ in order to enable co-reflection and social coupling; enabling the implementation of shared reflections into an ‘endurable-external feedback loop’ embedded in the persons familiar ’lifeworld’; and nudging situated actions with self-created action-affordances. In essence, the framework aims for the self-development of a suitable routine, or ‘situated practice’, by building on a growing shared insight of what works for the person. The framework, we propose, may serve as a starting point for AT designers to create truly empowering interactive products. In a set of follow-up projects involving the participation of persons with ASD, Intellectual Disabilities, Dementia and Acquired Brain Injury, the framework will be applied, evaluated and further refined.

Keywords: assistive technology, design, embodiment, empowerment

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Authors: Priyanka Mokashi, Aparna Khanna, Nancy Pandita

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Diabetes mellitus is a chronic metabolic disorder which will be the 7th leading cause of death by 2030. The current line of treatment for the diabetes mellitus is oral antidiabetic drugs (biguanides, sulfonylureas, meglitinides, thiazolidinediones and alpha-glycosidase inhibitors) and insulin therapy depending upon the type 1 or type 2 diabetes mellitus. But, these treatments have their disadvantages, ranging from the developing of resistance to the drugs and adverse effects caused by them. Alternative to these synthetic agents, natural products provides a new insight for the development of more efficient and safe drugs due to their therapeutic values. Enicostema littorale blume (A. Raynal) is a traditional Indian plant belongs to the Gentianaceae family. It is widely distributed in Asia, Africa, and South America. There are few reports on Swrtiamarin, major component of this plant for its antidiabetic activity. However, the antidiabetic activity of flavonoids from E. littorale and their mechanism of action have not yet been elucidated. Flavonoids have a positive relationship with disease prevention and can act on various molecular targets and regulate different signaling pathways in pancreatic β-cells, adipocytes, hepatocytes and skeletal myofibers. They may exert beneficial effects in diabetes by (i) improving hyperglycemia through regulation of glucose metabolism in hepatocytes; (ii) enhancing insulin secretion and reducing apoptosis and promoting proliferation of pancreatic β-cells; (iii) increasing glucose uptake in hepatocytes, skeletal muscle and white adipose tissue (iv) reducing insulin resistance, inflammation and oxidative stress. Therefore, we have isolated four flavonoid rich fractions, Fraction A (FA), Fraction B (FB), Fraction C (FC), Fraction D (FD) from crude alcoholic hot (AH) extract from E. littorale, identified by LC/MS. Total eight flavonoids were identified on the basis of fragmentation pattern. Flavonoid FA showed the presence of swertisin, isovitexin, and saponarin; FB showed genkwanin, quercetin, isovitexin, FC showed apigenin, swertisin, quercetin, 5-O-glucosylswertisin and 5-O-glucosylisoswertisin whereas FD showed the presence of swertisin. Further, these fractions were assessed for their antidiabetic activity on stimulating glucose uptake in insulin-resistant HepG2 cell line model (IR/HepG2). The results showed that FD containing C-glycoside Swertisin has significantly increased the glucose uptake rate of IR/HepG2 cells at the concentration of 10 µg/ml as compared to positive control Metformin (0.5mM) which was determined by glucose oxidase- peroxidase method. It has been reported that enhancement of glucose uptake of cells occurs due the translocation of Glut4 vesicles to cell membrane through IR/IRS1/AKT pathway. Therefore, we have studied expressions of three genes IRS1, AKT and Glut4 by real-time PCR to evaluate whether they follow the same pathway or not. It was seen that the glucose uptake rate has increased in FD treated IR/HepG2 cells due to the activation of insulin receptor substrate-1 (IRS1) followed by protein kinase B (AKT) through phosphoinositide 3-kinase (PI3K) leading to translocation of Glut 4 vesicles to cell membrane, thereby enhancing glucose uptake and insulin sensitivity of insulin resistant HepG2 cells. Hence, the up-regulation indicated the mechanism of action through which FD (Swertisin) acts as antidiabetic candidate in the treatment of type 2 diabetes mellitus.

Keywords: E. littorale, glucose transporter, glucose uptake rate, insulin resistance

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Authors: Elena Bellini, Daniele Mugnaini, Michele Boschetto

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People with an Autistic Spectrum Disorder and an Intellectual Disability who need to attend a Hospital Emergency Waiting Room frequently present high levels of discomfort and challenging behaviors due to stress-related hyperarousal, sensory sensitivity, novelty-anxiety, communication and self-regulation difficulties. Increased agitation and acting out also disturb the diagnostic and therapeutic processes, and the emergency room climate. Architectural design disciplines aimed at reducing distress in hospitals or creating autism-friendly environments are called for to find effective answers to this particular need. A growing number of researchers are considering the physical environment as an important point of intervention for people with autism. It has been shown that providing the right setting can help enhance confidence and self-esteem and can have a profound impact on their health and wellbeing. Environmental psychology has evaluated the perceived quality of care, looking at the design of hospital rooms, paths and circulation, waiting rooms, services and devices. Furthermore, many studies have investigated the influence of the hospital environment on patients, in terms of stress-reduction and therapeutic intervention’ speed, but also on health professionals and their work. Several services around the world are organizing autism-friendly hospital environments which involve the architecture and the specific staff training. In Italy, the association Spes contra spem has promoted and published, in 2013, the ‘Chart of disabled people in the hospital’. It stipulates that disabled people should have equal rights to accessible and high-quality care. There are a few Italian examples of therapeutic programmes for autistic people as the Dama project in Milan and the recent experience of Children and Autism Foundation in Pordenone. Careggi’s Emergency Waiting Room in Florence has been built to satisfy this challenge. This project of research comes from a collaboration between the technical staff of Careggi Hospital, the Center for autism PAMAPI and some architects expert in the sensory environment. The methodology of focus group involved architects, psychologists and professionals through a transdisciplinary research, centered on the links between the spatial characteristics and clinical state of people with ASD. The relationship between architectural space and quality of life is studied to pay maximum attention to users’ needs and to support the medical staff in their work by a specific program of training. The result of this research is a sum of criteria used to design the emergency waiting room, that will be illustrated. A protected room, with a clear space design, maximizes comprehension and predictability. The multisensory environment is thought to help sensory integration and relaxation. Visual communication through Ipad allows an anticipated understanding of medical procedures, and a specific technological system supports requests, choices and self-determination in order to fit sensory stimulation to personal preferences, especially for hypo and hypersensitive people. All these characteristics should ensure a better regulation of the arousal, less behavior problems, improving treatment accessibility, safety, and effectiveness. First results about patient-satisfaction levels will be presented.

Keywords: accessibility of care, autism-friendly architecture, personalized therapeutic process, sensory environment

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Authors: M. Shahab Uddin, Pennung Warnitchai

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Currently more than half of the world’s populations are living in cities, and the number and sizes of cities are growing faster than ever. Cities rely on the effective functioning of complex and interdependent critical infrastructures networks to provide public services, enhance the quality of life, and save the community from hazards and disasters. In contrast, complex connectivity and interdependency among the urban critical infrastructures bring management challenges and make the urban system prone to the domino effect. Unplanned rapid growth, increased connectivity, and interdependency among the infrastructures, resource scarcity, and many other socio-political factors are affecting the typical state of an urban system and making it susceptible to numerous sorts of diversion. In addition to internal vulnerabilities, urban systems are consistently facing external threats from natural and manmade hazards. Cities are not just complex, interdependent system, but also makeup hubs of the economy, politics, culture, education, etc. For survival and sustainability, complex urban systems in the current world need to manage their vulnerabilities and hazardous incidents more wisely and more interactively. Coordinated management in such systems makes for huge potential when it comes to absorbing negative effects in case some of its components were to function improperly. On the other hand, ineffective management during a similar situation of overall disorder from hazards devastation may make the system more fragile and push the system to an ultimate collapse. Following the quantum, the current research hypothesizes that a hazardous event starts its journey as an emergency, and the system’s internal vulnerability and response capacity determine its destination. Connectivity and interdependency among the urban critical infrastructures during this stage may transform its vulnerabilities into dynamic damaging force. An emergency may turn into a disaster in the absence of effective management; similarly, mismanagement or lack of management may lead the situation towards a catastrophe. Situation awareness and factual decision-making is the key to win a battle. The current research proposed a contextual decision support system for an urban critical infrastructure system while integrating three different models: 1) Damage cascade model which demonstrates damage propagation among the infrastructures through their connectivity and interdependency, 2) Restoration model, a dynamic restoration process of individual infrastructure, which is based on facility damage state and overall disruptions in surrounding support environment, and 3) Optimization model that ensures optimized utilization and distribution of available resources in and among the facilities. All three models are tightly connected, mutually interdependent, and together can assess the situation and forecast the dynamic outputs of every input. Moreover, this integrated model will hold disaster managers and decision makers responsible when it comes to checking all the alternative decision before any implementation, and support to produce maximum possible outputs from the available limited inputs. This proposed model will not only support to reduce the extent of damage cascade but will ensure priority restoration and optimize resource utilization through adaptive and collaborative management. Complex systems predictably fail but in unpredictable ways. System understanding, situation awareness, and factual decisions may significantly help urban system to survive and sustain.

Keywords: disaster prevention, decision support system, emergency response, urban critical infrastructure system

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Authors: Patricia Shirley Almeida Prado, Liz Brito, Selma Paixão Argollo, Gracie Moreira, Leticia Matos Sobrinho

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Diffuse idiopathic skeletal hyperostosis (DISH) is a degenerative bone disease also known as Forestier´s disease and ankylosing hyperostosis of the spine is characterized by a tendency toward ossification of half the anterior longitudinal spinal ligament without intervertebral disc disease. DISH is not considered to be osteoarthritis, although the two conditions commonly occur together. Diagnostic criteria include fusion of at least four vertebrae by bony bridges arising from the anterolateral aspect of the vertebral bodies. These vertebral bodies have a 'dripping candle wax' appearance, also can be seen periosteal new bone formation on the anterior surface of the vertebral bodies and there is no ankylosis at zygoapophyseal facet joint. Clinically, patients with DISH tend to be asymptomatic some patients mention moderate pain and stiffness in upper back. This disease is more common in man, uncommon in patients younger than 50 years and rare in patients under 40 years old. In modern populations, DISH is found in association with obesity, (type II) diabetes; abnormal vitamin A metabolism and also associated with higher levels of serum uric acid. There is also some association between the increase of risk of stroke or other cerebrovascular disease. The DISH condition can be confused with Heterotopic Ossification, what is the bone formation in the soft tissues as the result of trauma, wounding, surgery, burnings, prolonged immobility and some central nervous system disorder. All these conditions have been described extensively as myositis ossificans which can be confused with the fibrodysplasia (myositis) ossificans progressive. As in the DISH symptomatology it can be asymptomatic or extensive enough to impair joint function. A third confusion osteoarthritis disease that can bring confusion are the enthesopathies that occur in the entire skeleton being common on the ischial tuberosities, iliac crests, patellae, and calcaneus. Ankylosis of the sacroiliac joint by bony bridges may also be found. CASE 1: this case is skeletal remains presenting skull, some vertebrae and scapulae. This case remains unidentified and due to lack of bone remains. Sex, age and ancestry profile was compromised, however the DISH pathognomonic findings and diagnostic helps to estimate sex and age characteristics. Moreover to presenting DISH these skeletal remains also showed some bone alterations and non-metrics as fusion of the first vertebrae with occipital bone, maxillae and palatine torus and scapular foramen on the right scapulae. CASE 2: this skeleton remains shows an extensive bone heterotopic ossification on the great trochanter area of left femur, right fibula showed a healed fracture in its body however in its inteosseous crest there is an extensive bone growth, also in the Ilium at the region of inferior gluteal line can be observed some pronounced bone growth and the skull presented a pronounced mandibular, maxillary and palatine torus. Despite all these pronounced heterotopic ossification the whole skeleton presents moderate bone overgrowth that is not linked with aging, since the skeleton belongs to a young unidentified individual. The appropriate osteopathological diagnosis support the human identification process through medical reports and also assist with epidemiological data that can strengthen vulnerable anthropological estimates.

Keywords: bone disease, DISH, human identification, human remains

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Authors: Agnes Simone

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A 52-year-old male with unknown psychiatric and medical history was brought to the Psychiatric Emergency Room by ambulance directly from jail. He had been detained for three weeks for possession of a firearm while intoxicated. On initial evaluation, the patient was unable to provide a reliable history. He presented with odd jerking movements of his extremities and catatonic features, including mutism and stupor. His vital signs were stable. Patient was transferred to the medical emergency department for work-up of altered mental status. Due to suspicion for opioid overdose, the patient was given naloxone (Narcan) with no improvement. Laboratory work-up included complete blood count, comprehensive metabolic panel, thyroid stimulating hormone, vitamin B12, folate, magnesium, rapid plasma reagin, HIV, blood alcohol level, aspirin, and Tylenol blood levels, urine drug screen, and urinalysis, which were all negative. CT head and chest X-Ray were also negative. With this negative work-up, the medical team concluded there was no organic etiology and requested inpatient psychiatric admission. Upon re-evaluation by psychiatry, it was evident that the patient continued to have an altered mental status. Of note, the medical team did not include substance withdrawal in the differential diagnosis due to stable vital signs and a negative urine drug screen. The psychiatry team decided to check California's prescription drug monitoring program (CURES) and discovered that the patient was prescribed benzodiazepine alprazolam (Xanax) 2mg BID, a sedative-hypnotic, and hydrocodone/acetaminophen 10mg/325mg (Norco) QID, an opioid. After a thorough chart review, his daughter's contact information was found, and she confirmed his benzodiazepine and opioid use, with recent escalation and misuse. It was determined that the patient was experiencing alprazolam withdrawal, given this collateral information, his current symptoms, negative urine drug screen, and recent abrupt discontinuation of medications while incarcerated. After admission to the medical unit and two doses of alprazolam 2mg, the patient's mental status, alertness, and orientation improved, but he had no memory of the events that led to his hospitalization. He was discharged with a limited supply of alprazolam and a close follow-up to arrange a taper. Accompanying this case report, a qualitative review of presentations with alprazolam withdrawal was completed. This case and the review highlights: (1) Alprazolam withdrawal can occur at low doses and within just one week of use. (2) Alprazolam withdrawal can present without any vital sign instability. (3) Alprazolam withdrawal does not respond to short-acting benzodiazepines but does respond to certain long-acting benzodiazepines due to its unique chemical structure. (4) Alprazolam withdrawal is distinct from and more severe than other benzodiazepine withdrawals. This case highlights (1) the importance of physician utilization of drug-monitoring programs. This case, in particular, relied on California's drug monitoring program. (2) The importance of obtaining collateral information, especially in cases in which the patient is unable to provide a reliable history. (3) The importance of including substance intoxication and withdrawal in the differential diagnosis even when there is a negative urine drug screen. Toxidrome of withdrawal can be delayed. (4) The importance of discussing addiction and withdrawal risks of medications with patients.

Keywords: addiction risk of benzodiazepines, alprazolam withdrawal, altered mental status, benzodiazepines, drug monitoring programs, sedative-hypnotics, substance use disorder

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Authors: Gagandeep Singh Digra, Pawan Kumar, Mandeep Kaur Sidhu

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INTRODUCTION: Chronic Progressive External Ophthalmoplegia (CPEO), also known as Progressive External Ophthalmoplegia (PEO), is a type of eye disorder characterized by a loss of the muscle functions involved in eye and eyelid movement. CPEO can be caused by mutations in mitochondrial DNA. It typically manifests in young adults with bilateral and progressive ptosis as the most common presentation but can also present with difficulty swallowing (dysphagia) and general weakness of the skeletal muscles (myopathy), particularly in the neck, arms, or legs. CASE PRESENTATION: This is a case discussion of 3 cousins who presented to our clinic. A 23-year-old male with past surgical history (PSH) of ptosis repair 2 years ago presented with a chief complaint of nasal intonation for 1.5 years associated with difficulty swallowing. The patient also complained of nasal regurgitation of liquids. He denied any headaches, fever, seizures, weakness of arms or legs, urinary complaints or changes in bowel habits. Physical Examination was positive for facial muscle weakness, including an inability to lift eyebrows (Frontalis), inability to close eyes tightly (Orbicularis Oculi), corneal reflex absent bilaterally, difficulty clenching jaw (Masseter muscle), difficulty smiling (Zygomaticus major), inability to elevate upper lip (Zygomaticus minor). Another cousin of the first patient, a 25-year-old male with no past medical history, presented with complaints of nasal intonation for 2 years associated with difficulty swallowing. He denied a history of nasal regurgitation, headaches, fever, seizures, weakness, urinary complaints or changes in bowel habits. Physical Examination showed facial muscle weakness of the Frontalis muscle, Orbicularis Oculi muscle, Masseter Muscle, Zygomaticus Major, Zygomaticus Minor and absent corneal reflexes. A 28-year-old male, a cousin of the first two patients, presented with chief complaints of ptosis and nasal intonation for the last 8 years. He also complained of difficulty swallowing and nasal regurgitation of liquids. His physical examination showed facial muscle weakness, including frontalis muscle (inability to lift eyebrows), Orbicularis Oculi (inability to close eyes tightly), absent corneal reflexes bilaterally, Zygomaticus Major (difficulty smiling), and Zygomaticus Minor (inability to elevate upper lip). MRI brain and visual field of all the patients were normal. Differential diagnoses, including Grave’s disease, Myasthenia Gravis and Glioma, were ruled out. Due to financial reasons, muscle biopsy could not be pursued. Pedigree analysis revealed only males were affected, likely due to maternal inheritance, so the clinical diagnosis of CPEO was made. The patients underwent symptomatic management, including ptosis surgical correction for the third patient. CONCLUSION: Chronic Progressive External Ophthalmoplegia (CPEO), a rare case entity, occurs in young adults as a manifestation of mitochondrial myopathy. There are three modes of transmission- maternal transmission associated with mitochondrial point mutations, autosomal recessive, and autosomal dominant. CPEO can sometimes be difficult to diagnose, especially in asymmetric presentation. Therefore, it is crucial to keep it in differential diagnosis to avoid delay in diagnosis.

Keywords: neurology, chronic, progressive, ophthalmoplegia

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Authors: Salam N. Abdo, Orien L. Tulp, George P. Einstein

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The purpose of this exploratory study was to gather the insights into psoriasis etiology, treatment, and patient experience, for developing psoriasis and psoriatic arthritis diagnostic test. Data collection methods consisted of a comprehensive meta-analysis of relevant studies and psoriasis patient survey. Established meta-analysis guidelines were used for the selection and qualitative comparative analysis of psoriasis and psoriatic arthritis research studies. Only studies that clearly discussed psoriasis etiology, treatment, and patient experience were reviewed and analyzed, to establish a qualitative data base for the study. Using the insights gained from meta-analysis, an existing psoriasis patient survey was modified and administered to collect additional data as well as triangulate the results. The hypothesis is that specific types of psoriatic disease have specific etiology and pathophysiologic pattern. The following etiology categories were identified: bacterial, environmental/microbial, genetic, immune, infectious, trauma/stress, and viral. Additional results, obtained from meta-analysis and confirmed by patient survey, were the common age of onset (early to mid-20s) and type of psoriasis (plaque; mild; symmetrical; scalp, chest, and extremities, specifically elbows and knees). Almost 70% of patients reported no prescription drug use due to severe side effects and prohibitive cost. These results will guide the development of psoriasis and psoriatic arthritis diagnostic test. The significant number of medical publications classified psoriatic arthritis disease as inflammatory of an unknown etiology. Thus numerous meta-analyses struggle to report any meaningful conclusions since no definitive results have been reported to date. Therefore, return to the basics is an essential step to any future meaningful results. To date, medical literature supports the fact that psoriatic disease in its current classification could be misidentifying subcategories, which in turn hinders the success of studies conducted to date. Moreover, there has been an enormous commercial support to pursue various immune-modulation therapies, thus following a narrow hypothesis/mechanism of action that is yet to yield resolution of disease state. Recurrence and complications may be considered unacceptable in a significant number of these studies. The aim of the ongoing study is to focus on a narrow subgroup of patient population, as identified by this exploratory study via meta-analysis and patient survey, and conduct an exhaustive work up, aiming at mechanism of action and causality before proposing a cure or therapeutic modality. Remission in psoriasis has been achieved and documented in medical literature, such as immune-modulation, phototherapy, various over-the-counter agents, including salts and tar. However, there is no psoriasis and psoriatic arthritis diagnostic test to date, to guide the diagnosis and treatment of this debilitating and, thus far, incurable disease. Because psoriasis affects approximately 2% of population, the results of this study may affect the treatment and improve the quality of life of a significant number of psoriasis patients, potentially millions of patients in the United States alone and many more millions worldwide.

Keywords: biologics, early diagnosis, etiology, immune disease, immune modulation therapy, inflammation skin disorder, phototherapy, plaque psoriasis, psoriasis, psoriasis classification, psoriasis disease marker, psoriasis diagnostic test, psoriasis marker, psoriasis mechanism of action, psoriasis treatment, psoriatic arthritis, psoriatic disease, psoriatic disease marker, psoriatic patient experience, psoriatic patient quality of life, remission, salt therapy, targeted immune therapy

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Authors: C. Bel, J. Nevado, F. Ciceri, M. Ropacki, T. Hoffmann, P. Lapunzina, C. Buesa

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Background: The Phelan-McDermid syndrome (PMS) is a genetic disorder caused by the deletion of the terminal region of chromosome 22 or mutation of the SHANK3 gene. Shank3 disruption in mice leads to dysfunction of synaptic transmission, which can be restored by epigenetic regulation with both Lysine Specific Demethylase 1 (LSD1) inhibitors. PMS subjects result in a variable degree of intellectual disability, delay or absence of speech, autistic spectrum disorders symptoms, low muscle tone, motor delays and epilepsy. Vafidemstat is an LSD1 inhibitor in Phase II clinical development with a well-established and favorable safety profile, and data supporting the restoration of memory and cognition defects as well as reduction of agitation and aggression in several animal models and clinical studies. Therefore, vafidemstat has the potential to become a first-in-class precision medicine approach to treat PMS patients. Aims: The goal of this research is to perform an observational trial to psychometrically characterize individuals carrying deletions in SHANK3 and build a foundation for subsequent precision psychiatry clinical trials with vafidemstat. Methodology: This study is characterizing the clinical profile of 20 to 40 subjects, > 16-year-old, with genotypically confirmed PMS diagnosis. Subjects will complete a battery of neuropsychological scales, including the Repetitive Behavior Questionnaire (RBQ), Vineland Adaptive Behavior Scales, Escala de Observación para el Diagnostico del Autismo (Autism Diagnostic Observational Scale) (ADOS)-2, the Battelle Developmental Inventory and the Behavior Problems Inventory (BPI). Results: By March 2021, 19 patients have been enrolled. Unsupervised hierarchical clustering of the results obtained so far identifies 3 groups of patients, characterized by different profiles of cognitive and behavioral scores. The first cluster is characterized by low Battelle age, high ADOS and low Vineland, RBQ and BPI scores. Low Vineland, RBQ and BPI scores are also detected in the second cluster, which in contrast has high Battelle age and low ADOS scores. The third cluster is somewhat in the middle for the Battelle, Vineland and ADOS scores while displaying the highest levels of aggression (high BPI) and repeated behaviors (high RBQ). In line with the observation that female patients are generally affected by milder forms of autistic symptoms, no male patients are present in the second cluster. Dividing the results by gender highlights that male patients in the third cluster are characterized by a higher frequency of aggression, whereas female patients from the same cluster display a tendency toward higher repetitive behavior. Finally, statistically significant differences in deletion sizes are detected comparing the three clusters (also after correcting for gender), and deletion size appears to be positively correlated with ADOS and negatively correlated with Vineland A and C scores. No correlation is detected between deletion size and the BPI and RBQ scores. Conclusions: Precision medicine may open a new way to understand and treat Central Nervous System disorders. Epigenetic dysregulation has been proposed to be an important mechanism in the pathogenesis of schizophrenia and autism. Vafidemstat holds exciting therapeutic potential in PMS, and this study will provide data regarding the optimal endpoints for a future clinical study to explore vafidemstat ability to treat shank3-associated psychiatric disorders.

Keywords: autism, epigenetics, LSD1, personalized medicine

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