Search results for: psychosomatic disorders

Authors: Ange Weinrabe, James Tran, Ian B. Hickie

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Risk-taking behaviour is common during youth. In the time between adolescence and early adulthood, young people (aged 15-25 years) are more vulnerable to mood disorders, such as anxiety and depression. What impact does an emerging mood disorder have on decision-making in youth at critical decision points in their lives? In this article, we explore the impact of risk and ambiguity on youth decision-making in a clinical setting using a well-known economic experiment. At two time points, separated by six to eight weeks, we measured risky and ambiguous choices concurrently with findings from three psychological questionnaires, the 10-item Kessler Psychological Distress Scale (K10), the 17-item Quick Inventory of Depressive Symptomatology Adolescent Version (QIDS-A17), and the 12-item Somatic and Psychological Health Report (SPHERE-12), for young help seekers aged 16-25 (n=30, mean age 19.22 years, 19 males). When first arriving for care, we found that 50% (n=15) of participants experienced severe anxiety (K10 ≥ 30) and were severely depressed (QIDS-A17 ≥ 16). In Session 2, taking attrition rates into account (n=5), we found that 44% (n=11) remained severe across the full battery of questionnaires. When applying multiple regression analyses of the pooled sample of observations (N=55), across both sessions, we found that participants who rated severely anxious avoided making risky decisions. We suggest there is some statistically significant (although weak) (p=0.09) relation between risk and severe anxiety scores as measured by K10. Our findings may support working with novel tools with which to evaluate youth experiencing an emerging mood disorder and their cognitive capacities influencing decision-making.

Keywords: anxiety, decision-making, risk, adolescence

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Authors: Hamzeh Awad

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Disability is considered to be a worldwide complex phenomenon which rising at a phenomenal rate and caused by many different factors. Chronic diseases such as cardiovascular disease and diabetes can lead to mobility disability in particular and disability in general. The ICF is an integrative bio-psycho-social model of functioning and disability and considered by the World Health Organization (WHO) to be a reference for disability classification using its categories and core set to classify disorder’s functional limitations. Specialist programs at Sultan Bin Abdul Aziz Humanitarian City (SBAHC) are providing both inpatient and outpatient services have started to implement the ICF and use it as a problem solving tool in Rehab. Diabetes is leading contributing factor for disability and considered epidemic in several Gulf countries including the Kingdom of Saudi Arabia (KSA), where its prevalence continues to increase dramatically. Metabolic disorders, mainly diabetes are not well covered in Rehab field. The purpose of this study is present to research and clinical rehabilitation field of DREAM and ICF as a framework in clinical and research setting in Rehab service. Also, shed the light on using the ICF as problem solving tool at SBAHC. There are synergies between disability causes and wider public health priorities in relation to both chronic disease and disability prevention. Therefore, there is a need for strong advocacy and understanding of the role of ICF as a reference in Rehab settings in Middle East if we wish to seize the opportunity to reverse current trends of acquired disability in the region.

Keywords: international classification of functioning, disability and health (ICF), prototype, rehabilitation and diabetes

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Authors: Khadija Rafi, Neha Jamil, Laiba Khalid, Meerub Nawaz, Mahwish Farooq

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Speech articulation is a complex process to produce intelligible sounds with the help of precise movements of various structures within the vocal tract. All these structures in the vocal tract are named as articulators, which comprise lips, teeth, tongue, and palate. These articulators work together to produce a range of distinct phonemes, which happen to be the basis of language. It starts with the airstream from the lungs passing through the trachea and into oral and nasal cavities. When the air passes through the mouth, the tongue and the muscles around it form such coordination it creates certain sounds. It can be seen when the tongue is placed in different positions- sometimes near the alveolar ridge, soft palate, roof of the mouth or the back of the teeth which end up creating unique qualities of each phoneme. We can articulate vowels with open vocal tracts, but the height and position of the tongue is different every time depending upon each vowel, while consonants can be pronounced when we create obstructions in the airflow. For instance, the alphabet ‘b’ is a plosive and can be produced only by briefly closing the lips. Articulation disorders can not only affect communication but can also be a hurdle in speech production. To improve articulation skills for such individuals, doctors often recommend speech therapy, which involves various kinds of exercises like jaw exercises and tongue twisters. However, this disorder is more common in children who are going through developmental articulation issues right after birth, but in adults, it can be caused by injury, neurological conditions, or other speech-related disorders. In short, speech articulation is an essential aspect of productive communication, which also includes coordination of the specific articulators to produce different intelligible sounds, which are a vital part of spoken language.

Keywords: linguistics, speech articulation, speech therapy, language learning

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Authors: Irina M. Kolesnikova, Andrey M. Gaponov, Sergey A. Roumiantsev, Tatiana V. Grigoryeva, Dilyara R. Khusnutdinova, Dilyara R. Kamaldinova, Alexander V. Shestopalov

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Background. Obese patients have unequal risks of metabolic disorders. It is accepted to distinguish between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). MUHO patients have a high risk of metabolic disorders, insulin resistance, and diabetes mellitus. Among the other things, the gut microbiota also contributes to the development of metabolic disorders in obesity. Obesity is accompanied by significant changes in the gut microbial community. In turn, bacterial translocation from the intestine is the basis for the blood microbiome formation. The aim was to study the features of the blood microbiome in patients with various metabolic types of obesity. Patients, materials, methods. The study included 116 healthy donors and 101 obese patients. Depending on the metabolic type of obesity, the obese patients were divided into subgroups with MHO (n=36) and MUHO (n=53). Quantitative and qualitative assessment of the blood microbiome was based on metagenomic analysis. Blood samples were used to isolate DNA and perform sequencing of the variable v3-v4 region of the 16S rRNA gene. Alpha diversity indices (Simpson index, Shannon index, Chao1 index, phylogenetic diversity, the number of observed operational taxonomic units) were calculated. Moreover, we compared taxa (phyla, classes, orders, and families) in terms of isolation frequency and the taxon share in the total bacterial DNA pool between different patient groups. Results. In patients with MHO, the characteristics of the alpha-diversity of the blood microbiome were like those of healthy donors. However, MUHO was associated with an increase in all diversity indices. The main phyla of the blood microbiome were Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. Cyanobacteria, TM7, Thermi, Verrucomicrobia, Chloroflexi, Acidobacteria, Planctomycetes, Gemmatimonadetes, and Tenericutes were found to be less significant phyla of the blood microbiome. Phyla Acidobacteria, TM7, and Verrucomicrobia were more often isolated in blood samples of patients with MUHO compared with healthy donors. Obese patients had a decrease in some taxonomic ranks (Bacilli, Caulobacteraceae, Barnesiellaceae, Rikenellaceae, Williamsiaceae). These changes appear to be related to the increased diversity of the blood microbiome observed in obesity. An increase of Lachnospiraceae, Succinivibrionaceae, Prevotellaceae, and S24-7 was noted for MUHO patients, which, apparently, is explained by a magnification in intestinal permeability. Conclusion. Blood microbiome differs in obese patients and healthy donors at class, order, and family levels. Moreover, the nature of the changes is determined by the metabolic type of obesity. MUHO linked to increased diversity of the blood microbiome. This appears to be due to increased microbial translocation from the intestine and non-intestinal sources.

Keywords: blood microbiome, blood bacterial DNA, obesity, metabolically healthy obesity, metabolically unhealthy obesity

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Authors: Arslan Masood Pirzada, Muhammad Naeem, Hafiz Haider Ali, Muhammad Latif, Aown Sammar Raza, Asad Hussain Bukhari, Muhammad Saqib, Muhammad Ijaz

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Cyperus rotundus (Cyperaceae), a medicinal herb, is being traditionally used as a home remedy for the treatment of various clinical conditions like diarrhea, diabetic, pyretic, inflammation, malaria, and for treating stomach and bowel disorders. Its current status is one of the most widespread, troublesome, and economically damaging agronomic weeds, growing wildly in various tropical and sub-tropical regions of the world. Tuber and rhizomes of Cyperus rotundus possess a higher concentration of active ingredients in the form of essential oils, phenolic acids, ascorbic acids and flavonoids, responsible for its remedial properties. Exploitation of any medicinal plant application depends on the crucial and comprehensive information about the therapeutic potential of a plant. Researchers have evaluated and characterized the significance of Cyperus rotundus as an anti-androgenic, anti-bacterial, anti-cancerous, anti-convulsant, anti-diabetic, anti-diarrheal, anti-genotoxic, anti-inflammatory, anti-lipidemic, anti-malarial, anti-mutagenic, anti-obesity, anti-oxidant, anti-uropathogenic, hepato-, cardio-, neuroprotective, and nootropic agent. This paper comprises a broad review to summarize the current state of knowledge about chemical constituents, potential economic uses and therapeutic aspects of Cyperus rotundus that will aid in the development of bioethanol and modern herbal medicine through latest technologies that will promote the ability of this plant in the cure of many clinical disorders.

Keywords: purple nutsedge, chemical composition, economic uses, therapeutic values, future directions

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Authors: Olga Santesteban, Glorisa Canino, Hector R. Bird, Cristiane S. Duarte

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Objective: To address whether harsh discipline is associated with disruptive behavior disorders (DBD) in Puerto Rican children over time. Background: Both cross-sectional and longitudinal studies report that rates of DBD vary by gender, age and other demographics, being more frequent among boys, later in life and among those who live in urban areas. Also, the literature supports the direct, positive association between harsh discipline and externalizing behaviors. Nevertheless, scholars have underscored the important role of race and ethnicity in understanding discipline effects on children. The impact of harsh discipline in a Puerto Rican population remains to be studied. Methods: Sample: This is a secondary analysis of the Boricua Youth Study which assessed yearly (3 times) Puerto Rican children aged 5-15 in two different sites: San Juan (Puerto Rico) and the South Bronx (NY), N=2951. Participants that did not have scores of harsh discipline in the 3 waves were excluded for this analysis (N=2091). Main Measures: a) Harsh Discipline (Parent report) was measured using 6 items from the “Parental Discipline Scale” that measures various forms of punishment, including physical and verbal abuse, and withholding affection; b) Disruptive Behavior Disorder (Parent report): Parent version of the Diagnostic Interview Schedule for Children-IV (DISC-IV) was used to asses children’s conduct disorders; c) Demographic factors: Child gender, child age, family income, marital status; d) Parental factors: parental psychopathology, parental monitoring, familism, parent support; e) Children characteristics: Controlling for any diagnostic at wave 1 (internalizing or externalizing). Data Analysis: Logistic regression was carried out relating the likelihood of DBD to harsh discipline along waves controlling for potential confounders as demographics, child and parent characteristics. Results: There were no significant differences in harsh discipline by site in wave 1 and wave 2 but there was a significant difference in wave 3. Also, there were no significant differences in DBD by site in wave 1 and wave 2 but there was a significant difference in wave 3. There was a significant difference of discipline by gender and age in all the waves. We calculated unadjusted (OR) and adjusted (AOD) and 95% confidence intervals (95%CI) showing the relation between harsh discipline at wave 1 and the presence of child disruptive behavior disorder at wave 3 for both South Bronx and Puerto Rico. There was an association between harsh discipline and the likelihood of having DBD in The Bronx (AOR=1.76; 95%CI=1.13-2.74, p.013) and in Puerto Rico (AOR=2.17; 95%CI=1.28-3.67, p.004) having controlled for demographic, parental and individual factors. Conclusions: Context may be an important differential factor shaping the potential risk of harsh discipline toward DBD for Puerto Rican children.

Keywords: disruptive behavior disorders, harsh discipline, puerto rican, psychological education

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Authors: F. Ruiz-Navarro, M. Matzner, G. Kobinia

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Background: Cerebral palsy (CP) encompasses the largest group of childhood movement disorders, the patterns and severity varies widely. Today, the management focuses only on a rehabilitation therapy that tries to secure the functions remained and prevents complications. However the treatments are not aimed to cure the disease. Stem cells (SCs) transplant via intrathecal is a new approach to the disease. Method: Our aim was to performed a pilot study under the condition of unproven treatment on clinical practice to assessed the safety and efficacy of Neuron Point-of-care Stem cell Therapy (N-POCST), an ambulatory procedure of autologous bone marrow derived SCs (BM-SCs) harvested from the posterior superior iliac crest undergo an on-site cell separation for intrathecal infusion via lumbar puncture. Results: 82 patients were treated in a period of 28 months, with a follow-up after 6 months. They had a mean age of 6,2 years old and male predominance (65,9%). Our preliminary results show that: A. No patient had any major side effects, B. Only 20% presented mild headache due to LP, C. 53% of the patients had an improvement in spasticity, D. 61% improved the coordination abilities, 23% improved the motor function, 15% improved the speech, 23% reduced the number of convulsive events with the same doses or less doses of anti-convulsive medication and 94% of the patients report a subjective general improvement. Conclusions: These results support previous worldwide publications that described the safety and effectiveness of autologous BM-SCs transplant for patients wit CP.

Keywords: autologous transplant, cerebral palsy, point of care, childhood movement disorders

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Authors: Linta Koka

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Aim: The way people with severe mental disorders deal with self-stigma and how it affects their self-esteem is a problem that has gained much attention in recent years. The primary aim of this study was to empirically explore the link between self-stigma and self-esteem of individuals with the presence of a mental illness, offering a novel perspective by exploring the same variables amongst a sample without a mental illness. Methods: This study utilized a cross-sectional study. Participants with (N=85) and without (N=75) a mental health issue were included from Darlingdon's Mind organization. Participants completed two scales, one of Self-Stigma of Mental Illness Scale and one of Self-Esteem, following some demographics questions. Results: According to the primary hypothesis, self-stigma significantly correlates with self-esteem in the clinical population. Furthermore, gender and ethnicity, above all the demographics, positively correlates to the relationship of self-stigma with self-esteem in people who endure a mental health issue. Limitations: A significant limitation is that of the size of the sample of participants conducted in this study. The clinical population was limited to 85 participants, and the control group consisted of 76 participants. Since the sample was not representative. The small size used did not allow any comparisons between the group with mental illness and the control group. There was a restricted time to approach the participants since the online survey was released by the end of May. Conclusions: Individuals suffering from mental illnesses may internalize stigmatizing stereotypes on an explicit level. Efforts should be made to lessen the harmful impact stigma may have on mentally ill people, such as worsening symptoms or delays in receiving care. Further study is needed within this small research topic to improve awareness and regulate mental health among the general population. Undoubtedly, people with mental disorders are stigmatized; therefore, more research is required to explore all factors contributing to mentally ill patients' devaluation.

Keywords: self-stigma, mental illness, self-esteem, clinical population, non-clinical population

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Authors: Velvizhi Dharmalingam, Rajalaksmi Ramalingam, Rekha Prabhu, Ilavarasan Raju

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Background: The use of herbal products for various therapeutic regimens has increased tremendously in the developing countries. Elaeocarpus ganitrus(Rudraksha) is a broad-leaved tree, belonging to the family Elaeocarpaceae found in tropical and subtropical areas. It is popular in an indigenous system of medicine like Ayurveda, Siddha, and Unani. According to Ayurvedic medicine, Rudraksha is used in the managing of blood pressure, asthma, mental disorders, diabetes, gynaecological disorders, neurological disorders such as epilepsy and liver diseases. Objectives: The present study aimed to study the physicochemical parameters of Elaeocarpus ganitrus(fruits) and identify the phenolic compounds (gallic acid, ellagic acid, and chebulinic acid). To estimate the microbial load and the antibacterial activity of extract of Elaeocarpus ganitrus for selective pathogens. Methodology: The dried powdered fruit of Elaeocarpus ganitrus was performed the physicochemical parameters (such as Loss on drying, Alcohol soluble extractive, Water soluble extractive, Total ash and Acid insoluble ash) and pH was measured. The dried coarse powdered fruit of Elaeocarpus ganitrus was extracted successively with hexane, chloroform, ethylacetate and aqueous alcohol by cold percolation method. Identification of phenolic compounds (gallic acid, ellagic acid, chebulinic acid) was done by HPTLC method and confirmed by co-TLC using different solvent system.The successive extracts of Elaeocarpus ganitrus and standards (like gallic acid, ellagic acid, and chebulinic acid) was approximately weighed and made up with alcohol. HPTLC (CAMAG) analysis was performed on a TLC over silica gel 60F254 precoated aluminium plate, layer thickness 0.2 mm (E.Merck, Germany) by using ATS4, Visualizer and Scanner with wavelength at 254 nm, 366 nm and derivatized with different reagents. The microbial load such as total bacterial count, total fungal count, Enterobacteria, Escherichia coli, Salmonella species, Staphylococcus aureus and Pseudomonas aeruginosa by serial dilution method and antibacterial activity of was measured by Kirby bauer method for selective pathogens. Results: The physicochemical parameter of Elaeocarpus ganitrus was studied for standardization of crude drug. Among all the successive extracts were identified with phenolic compounds and Elaeocarpus ganitrus extract having potent antibacterial activity against gram-positive and gram-negative bacteria.

Keywords: antimicrobial activity, Elaeocarpus ganitrus, HPTLC, phenolic compounds

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Authors: Sulemana Saibu, Moses Ikpeme

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Background: The severity of the COVID-19 pandemic, brought on by the SARS-CoV-2 coronavirus, has been unprecedented since the 1918 influenza pandemic. SARS-CoV-2 cases of CNS and peripheral nervous system disease, including neurodegenerative disorders and chronic immune-mediated diseases, may be anticipated based on knowledge of past coronaviruses, particularly those that caused the severe acute respiratory syndrome and Middle East respiratory syndrome outbreaks. Although respiratory symptoms are the most common clinical presentation, neurological symptoms are becoming increasingly recognized, raising concerns about their potential role in causing Parkinson's disease, Multiple sclerosis, and Narcolepsy. This systematic review aims to summarize the current evidence by exploring the association between COVID-19 infection and how it may overlap with etiological mechanisms resulting in Narcolepsy, Parkinson's disease, and Multiple sclerosis. Methods: A systematic search was conducted using electronic databases ((PubMed/MedLine, Embase, PsycINFO, ScieLO, Web of Science, ProQuest (Biotechnology, Virology, and AIDS), Scopus, and CINAHL)) to identify studies published between January 2020 and December 2022 that investigated the association between COVID-19 and Parkinson's disease, multiple sclerosis, and Narcolepsy. Per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the review was performed and reported. Study quality was assessed using the Critical Appraisal Skills Programme Checklist and the Joanna Briggs Institute Critical appraisal tools. Results: A total of 21 studies out of 1025 met the inclusion criteria, including 8 studies reporting Parkinson's disease, 11 on multiple sclerosis, and 2 on Narcolepsy. In COVID-19 individuals compared to the general population, Narcolepsy, Parkinson's disease, and multiple sclerosis were shown to have a higher incidence. The findings imply that COVID-19 may worsen the signs or induce multiple sclerosis and Parkinson's disease and may raise the risk of developing Narcolepsy. Further research is required to confirm these connections because the available data is insufficient. Conclusion: According to the existing data, COVID-19 may raise the risk of Narcolepsy and have a causative relationship with Parkinson's disease, multiple sclerosis, and other diseases. More study is required to confirm these correlations and pinpoint probable mechanisms behind these interactions. Clinicians should be aware of how COVID-19 may affect various neurological illnesses and should treat patients who are affected accordingly.

Keywords: COVID-19, parkinson’s disease, multiple sclerosis, narcolepsy, neurological disorders, sars-cov-2, neurodegenerative disorders, chronic immune-mediated diseases

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Authors: Farid Rezaei, Zahra Reza Soltani, Behrouz Tavana, Afsaneh Dadarkhah, Masoume Bahrami Asl, S. Alireza Mirghasemi

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Introduction: Fibromyalgia is a syndrome comprised of a group of symptoms. The primary symptom of fibromyalgia is pain propagation is associated by Secondary symptoms include fatigue, cognitive disorders, sleep disorders and hypersensitivity to painful stimuli. Recent studies have shown that there is a direct relationship between fibromyalgia and certain changes in brain activity. Aim: The aim of this study is determining the effect of tDCS in pain and quality of life in patients with fibromyalgia. Method: 68 patients with fibromyalgia who had inclusion criterias were randomly divided into two groups of case and control. Groups were matched in terms of gender, age, education, duration of pain and PMS. Patient groups treated with tDCS device manufacture by Enraf company made in Netherlands (M1 anodal stimulation, 2 mA constant current, 20 minutes, for 10 sessions (3 days a week)). Also the protocol was done for control group, in sham mode of tDCS device that had no current, for 10 sessions of 20 minutes. Before treatment, immediately after the end of 10 sessions treatment (short-term) and 10 week later (long-term effect), pain intensity questionnaires (VAS) and quality of life in fibromyalgia patients questionnaire was completed by the patient. Results: Pain intensity were significantly lower in the treatment group than the sham group 2 weeks and 10 weeks after treatment than before treatment (P < 0.001). Although the quality of life of patients 2 weeks after treatment showed no significant change, but ten weeks after treatment were more than sham group (P < 0.0001). Conclusion: Our results suggest that tDCS is a safe and effective in treating fibromyalgia patients and an important effect in reducing pain and increasing quality of their life.

Keywords: fibromyalgia, tDCS, quality of life, VAS score

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Authors: Aneal Khan, Elleine Allapitan, Desmond Koo, Katherine-Ann Piedalue, Shaneel Pathak, Utkarsh Subnis

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Background: Disease management of metabolic, genetic disorders is long-term and can be cumbersome to patients and caregivers. Patient-Reported Outcome Measures (PROMs) have been a useful tool in capturing patient perspectives to help enhance treatment compliance and engagement with health care providers, reduce utilization of emergency services, and increase satisfaction with their treatment choices. Currently, however, PROMs are collected during infrequent and decontextualized clinic visits, which makes translation of patient experiences challenging over time. The GRIT study aims to evaluate a digital health journal application called Zamplo that provides a personalized health diary to record self-reported health outcomes accurately and efficiently in patients with metabolic, genetic disorders. Methods: This is a randomized controlled trial (RCT) (1:1) that assesses the efficacy of Zamplo to increase patient activation (primary outcome), improve healthcare satisfaction and confidence to manage medications (secondary outcomes), and reduce costs to the healthcare system (exploratory). Using standardized online surveys, assessments will be collected at baseline, 1 month, 3 months, 6 months, and 12 months. Outcomes will be compared between patients who were given access to the application versus those with no access. Results: Seventy-seven patients were recruited as of November 30, 2021. Recruitment for the study commenced in November 2020 with a target of n=150 patients. The accrual rate was 50% from those eligible and invited for the study, with the majority of patients having Fabry disease (n=48) and the remaining having Pompe disease and mitochondrial disease. Real-time clinical responses, such as pain, are being measured and correlated to disease-modifying therapies, supportive treatments like pain medications, and lifestyle interventions. Engagement with the application, along with compliance metrics of surveys and journal entries, are being analyzed. An interim analysis of the engagement data along with preliminary findings from this pilot RCT, and qualitative patient feedback will be presented. Conclusions: The digital self-care journal provides a unique approach to disease management, allowing patients direct access to their progress and actively participating in their care. Findings from the study can help serve the virtual care needs of patients with metabolic, genetic disorders in North America and the world over.

Keywords: eHealth, mobile health, rare disease, patient outcomes, quality of life (QoL), pain, Fabry disease, Pompe disease

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Authors: Dinesh K. S., D. R. C. V. Jayadevan

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Autism is the most prevalent of a subset of the disorders organized under the umbrella of pervasive developmental disorders. After the publication of Andrew Wakefield's paper in lancet, many critiques deny this connection even without looking in to the matter. The British Medical Journal even put an editorial regarding this issue. BMJ 2010; 340:c1807. But ayurveda has ample of evidences to believe this connectivity. Dysbiosis, yeast growth of the gut, nutritional deficiencies, enzyme deficiencies, essential fatty acid deficiencies, Gastro esophageal reflux disease, indigestion, inflammatory bowel, chronic constipation & its cascade are few of them to note. The purpose of this paper is to present the observed changes in the behavioural symptoms of autistic babies after a gut management protocol which is a usual programme of our autism treatment plan especially after dysbiotic changes after antibiotic administration. Is there any correlation between changes (if significant) in gut symptoms and behavioral problems of autistic babies especially after a dysbiosis induced by antibiotics. Retrospective analysis of the case sheets of autistic patients admitted in Vaidyaratnam P.S.Varier Ayurveda College hospital, kottakkal,kerala, india from September 2010 are taken for the data processing. Autistic patients are used to come to this hospital as a part of their usual course of treatment. We investigated 40 cases diagnosed as autistic by clinical psychologists from different institutions who had dysbiosis induced by antibiotics. Significant change in gut symptoms before and after treatment p<0.05 in most of its components Significant change in behavioral symptoms before and after treatments p<0.05 in most of the components Correlation between gut symptoms change and behavioral symptoms changes after treatment is + 0.86. Conclusion : Selected Polyherbal Ayurveda treatment has significant role to play to make changes abnormal behaviors in autistic babies and has a positive correlation with changes in gut symptoms induced by dysbiosis of antibiotic intake.

Keywords: ayurveda, autism, dysbiosis, antibiotic

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Authors: B. Sadek, N. Khan, Shreesh K. Ojha, Adel Sadeq, D. Lazewska, K. Kiec-Kononowicz

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The involvement of Histamine H3 receptors (H3Rs) in memory and the potential role of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., Alzheimer disease (AD) is well established. Therefore, the memory-enhancing effects of the H3R antagonist DL77 on MK801-induced cognitive deficits were evaluated in passive avoidance paradigm (PAP) and novel object recognition (NOR) tasks in adult male rats, applying donepezil (DOZ) as a reference drug. Animals pretreated with acute systemic administration of DL77 (2.5, 5, and 10 mg/kg, i.p.) were significantly ameliorated in regard to MK801-induced memory deficits in PAP. The ameliorative effect of most effective dose of DL77 (5 mg/kg, i.p.) was abrogated when animals were pretreated with a co-injection with the H3R agonist R-(α)-methylhistamine (RAMH, 10 mg/kg, i.p.). Moreover, and in the NOR paradigm, DL77 (5 mg/kg, i.p.) reversed MK801-induced deficits long-term memory (LTM), and the DL77-provided procognitive effect was comparable to that of reference drug DOZ, and was reversed when animals were co-injected with RAMH (10 mg/kg, i.p.). However, DL77(5 mg/kg, i.p.) failed to alter short-term memory (STM) impairment in NOR test. Furthermore, DL77 (5 mg/kg) failed to induce any alterations of anxiety and locomotor behaviors of animals naive to elevated-plus maze (EPM), indicating that the ameliorative effects observed in PAP or NOR tests were not associated to alterations in emotions or in natural locomotion of tested animals. These results reveal the potential contribution of H3Rs in modulating CNS neurotransmission systems associated with neurodegenerative disorders, e.g., AD.

Keywords: histamine H3 receptor, antagonist, learning and memory, Alzheimer's disease, neurodegeneration, passive avoidance paradigm, novel object recognition, behavioral research

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Authors: J. Raub, H. Schillok, L. Kaupe, C. Jung-Sievers, G. Pitschel-Walz, M. Bühner, J. Gensichen, F. D. Pokal-Gruppe

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Introduction: In Germany, depression ranks among the top ten diseases with the highest disease burden and often occurs with comorbidities. Collaborative Care (CC), a concept developed in the United States for the primary care management of chronic diseases, has been identified as an efficient model for the treatment of depression in general medicine. A recent meta-analysis highlights research gaps regarding CC in patients with psychiatric multimorbidity. The highest prevalence of psychiatric comorbidities in depression is observed in anxiety disorders, post-traumatic stress disorder (PTSD), and substance use disorders. Methods: We conducted a literature search following the PRISMA guidelines with three components: Collaborative Care, Depression and randomized controlled trial on the common databases. We focused on the examination of psychiatric comorbidities in depression, specifically Posttraumatic Stress Disorder (PTSD) and Substance Use Disorder (SUD). Results: During the screening process, we identified nine relevant articles related to PTSD, the number of articles related to Substance Use Disorder (SUD) was ten. We examined a total of 8,634 individuals. Our literature review did not reveal any overall significant superiority of the Collaborative Care model compared to Usual Care in patients with depression with comorbid Substance Use Disorder (SUD) or Posttraumatic Stress Disorder (PTSD). Discussion: Five studies demonstrate a faster and statistically significant improvement in depression outcomes among patients with Substance Use Disorder (SUD) and Posttraumatic Stress Disorder (PTSD). Currently, several randomized controlled trials on the topic of Collaborative Care in depression with psychiatric comorbidity are ongoing, such as miCare, Claro and COMET.

Keywords: Depression, primary care, collaborative care, PTSD, Substance use Disorder

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Authors: Rachel Dolan

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Background: Over two thirds of women in prison in England are mothers, and estimates suggest between 100 and 200 women per year give birth during imprisonment. There are currently six mother and baby units (MBUs) in prisons in England which admit women and babies up to the age of 18 months. Although there are only 65 places available, and despite positive impacts, they are rarely full. Mental illness may influence the number of admissions, as may interpretation of admission criteria. They are the only current alternative to separation for imprisoned mothers and their babies. Aims: To identify the factors that affect the decision to apply for/be offered a place in a prison MBU; to measure the impact of a placement upon maternal mental health and wellbeing; To measure the Initial outcomes for mother and child. Methods: A mixed methods approach - 100 pregnant women in English prisons are currently being recruited from prisons in England. Quantitative measures will establish the prevalence of mental disorder, personality disorder, substance misuse and quality of life. Qualitative interviews will document the experiences of pregnancy and motherhood in prison. Results: Preliminary quantitative findings suggest the most prevalent mental disorders are anxiety and depression and approximately half the participants meet the criteria for one or more personality disorders. The majority of participants to date have been offered a place in a prison MBU, and those in a prison with an MBU prior to applying are more likely to be admitted. Those with a previous history of childcare issues, who are known to social services are less likely to be offered a place. Qualitative findings suggest that many women are often hungry and uncomfortable during pregnancy, many have feelings of guilt about having a child in prison and that feelings of anxiety and worry are exacerbated by lack of information.

Keywords: mothers, prison, mother and baby units, mental health

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Authors: Kadhim Alabady

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Background: Autism poses a particularly large public health challenge and an inspiring lifelong challenge for many families; it is a lifelong challenge of a different kind. Purpose: Therefore, it is important to understand what the key challenges are and how to improve the lives of children who are affected with autism in Dubai. Method: In order to carry out this research we have used a qualitative methodology. We performed structured in–depth interviews and focus groups with mental health professionals working at: Al Jalila hospital (AJH), Dubai Autism Centre (DAC), Dubai Rehabilitation Centre for Disabilities, Latifa hospital, Private Sector Healthcare (PSH). In addition to that, we conducted quantitative approach to estimate ASD prevalence or incidence data due to lack of registry. ASD estimates are based on research from national and international documents. This approach was applied to increase the validity of the findings by using a variety of data collection techniques in order to explore issues that might not be highlighted through one method alone. Key findings: Autism is the most common of the Pervasive Developmental Disorders. Dubai Autism Center estimates it affects 1 in 146 births (0.68%). If we apply these estimates to the total number of births in Dubai for 2014, it is predicted there would be approximately 199 children (of which 58 were Nationals and 141 were Non–Nationals) suffering from autism at some stage. 16.4% of children (through their families) seek help for ASD assessment between the age group 6–18+. It is critical to understand and address factors for seeking late–stage diagnosis, as ASD can be diagnosed much earlier and how many of these later presenters are actually diagnosed with ASD. Autism spectrum disorder (ASD) is a public health concern in Dubai. Families do not consult GPs for early diagnosis for a variety of reasons including cultural reasons. Recommendations: Effective school health strategies is needed and implemented by nurses who are qualified and experienced in identifying children with ASD. There is a need for the DAC to identify and develop a closer link with neurologists specializing in Autism, to work alongside and for referrals. Autism can be attributed to many factors, some of those are neurological. Currently, when families need their child to see a neurologist they have to go independently and search through the many that are available in Dubai and who are not necessarily specialists in Autism. Training of GP’s to aid early diagnosis of Autism and increase awareness. Since not all GP’s are trained to make such assessments increasing awareness about where to send families for a complete assessment and the necessary support. There is an urgent need for an adult autism center for when the children leave the safe environment of the school at 18 years. These individuals require a day center or suitable job training/placements where appropriate. There is a need for further studies to cover the needs of people with an Autism Spectrum Disorder (ASD).

Keywords: autism spectrum disorder, autism, pervasive developmental disorders, incidence

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Authors: Soumaya Mrabet, Imen Akkari, Amira Atig, Elhem Ben Jazia

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Introduction: Primary biliary cirrhosis (PBC) is a cholestatic cholangitis of unknown etiology. It is frequently associated with autoimmune diseases, which explains their systematic screening. The aim of our study was to determine the prevalence and the type of autoimmune disorders associated with PBC and to assess their impact on the prognosis of the disease. Material and methods: It is a retrospective study over a period of 16 years (2000-2015) including all patients followed for PBC. In all these patients we have systematically researched: dysthyroidism (thyroid balance, antithyroid autoantibodies), type 1 diabetes, dry syndrome (ophthalmologic examination, Schirmer test and lip biopsy in case of Presence of suggestive clinical signs), celiac disease(celiac disease serology and duodenal biopsies) and dermatological involvement (clinical examination). Results: Fifty-one patients (50 women and one men) followed for PBC were collected. The Mean age was 54 years (37-77 years). Among these patients, 30 patients(58.8%) had at least one autoimmune disease associated with PBC. The discovery of these autoimmune diseases preceded the diagnosis of PBC in 8 cases (26.6%) and was concomitant, through systematic screening, in the remaining cases. Autoimmune hepatitis was found in 12 patients (40%), defining thus an overlap syndrome. Other diseases were Hashimoto's thyroiditis (n = 10), dry syndrome (n = 7), Gougerot Sjogren syndrome (n=6), celiac disease (n = 3), insulin-dependent diabetes (n = 1), scleroderma (n = 1), rheumatoid arthritis (n = 1), Biermer Anemia (n=1) and Systemic erythematosus lupus (n=1). The two groups of patients with PBC with or without associated autoimmune disorders were comparable for bilirubin levels, Child-Pugh score, and response to treatment. Conclusion: In our series, the prevalence of autoimmune diseases in PBC was 58.8%. These diseases were dominated by autoimmune hepatitis and Hashimoto's thyroiditis. Even if their association does not seem to alter the prognosis, screening should be systematic in order to institute an early and adequate management.

Keywords: autoimmune diseases, autoimmune hepatitis, primary biliary cirrhosis, prognosis

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Authors: Aanh Eduardo Dimate-Garcia, Diana Carolina Rodriguez-Romero, Edna Yuliana Gonzalez Rincon, Diana Marcela Pardo Lopez, Yessica Garibello Cubillos

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Musculoskeletal disorders (MD) are the new epidemic of chronic diseases, are multifactorial and affect the different productive sectors. Although there are multiple instruments to evaluate the static and dynamic load, the method of repetitive occupational action (OCRA) seems to be an attractive option. Objective: It is aimed to analyze the use of the OCRA method and the prevalence of MD in workers of various productive sectors according to the literature (2007-2018). Materials and Methods: A literature review (following the PRISMA statement) of studies aimed at assessing the level of biomechanical risk (OCRA) and the prevalence of MD in the databases Scielo, Science Direct, Scopus, ProQuest, Gale, PubMed, Lilacs and Ebsco was realized; 7 studies met the selection criteria; the majority are quantitative (cross section). Results: it was evidenced (gardening and flower-growers) in this review that 79% of the conditions related to the task require physical requirements and involve repetitive movements. In addition, of the high appearance of DM in the high-low back, upper and lower extremities that are produced by the frequency of the activities carried out (footwear production). Likewise, there was evidence of 'very high risks' of developing MD (salmon industry) and a medium index (OCRA) for repetitive movements that require special care (U-Assembly line). Conclusions: the review showed the limited use of the OCRA method for the detection of MD in workers from different sectors, and this method can be used for the detection of biomechanical risk and the appearance of MD.

Keywords: checklist, cumulative trauma disorders, musculoskeletal diseases, repetitive movements

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Authors: Edward Poluyi, Eghosa Morgan, Charles Poluyi, Chibuikem Ikwuegbuenyi, Grace Imaguezegie

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Background: Current epidemiological studies have examined the associations between moderate and severe traumatic brain injury (TBI) and their risks of developing neurodegenerative diseases. Concussion, also known as mild TBI (mTBI), is however quite distinct from moderate or severe TBIs. Only few studies in this burgeoning area have examined concussion—especially repetitive episodes—and neurodegenerative diseases. Thus, no definite relationship has been established between them. Objectives : This review will discuss the available literature linking concussion and amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD). Materials and Methods: Given the complexity of this subject, a realistic review methodology was selected which includes clarifying the scope and developing a theoretical framework, developing a search strategy, selection and appraisal, data extraction, and synthesis. A detailed literature matrix was set out in order to get relevant and recent findings on this topic. Results: Presently, there is no objective clinical test for the diagnosis of concussion because the features are less obvious on physical examination. Absence of an objective test in diagnosing concussion sometimes leads to skepticism when confirming the presence or absence of concussion. Intriguingly, several possible explanations have been proposed in the pathological mechanisms that lead to the development of some neurodegenerative disorders (such as ALS and AD) and concussion but the two major events are deposition of tau proteins (abnormal microtubule proteins) and neuroinflammation, which ranges from glutamate excitotoxicity pathways and inflammatory pathways (which leads to a rise in the metabolic demands of microglia cells and neurons), to mitochondrial function via the oxidative pathways.

Keywords: amyotrophic lateral sclerosis, Alzheimer's disease, mild traumatic brain injury, neurodegeneration

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Authors: Myriam Rousseau, Marie-Hélène Poulin, Suzie McKinnon, Jacinthe Bourassa

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Context: There is a growing demand for effective training programs for parents of children with autism spectrum disorders. While traditional in-person training is effective, it can be difficult for some parents to participate due to distance, time, and cost. Telepractice, a form of distance education, could be a viable alternative to address these challenges. Research objective: The objective of this study is to explore the experiences of parents of children with autism who participated in a training program offered by telepractice in order to document: 1) the experience of parents who participated in a program telepractice training program for autistic children, 2) parental satisfaction with the telepractice modality, and 3) potential benefits of using telepractice to deliver training programs to parents of autistic children. Method: This study followed a qualitative research design, and Braun and Clarke's six-step procedure was used for the thematic analysis of the comments provided by parents. Data were collected through individual interviews with parents who participated in the project. The analysis focused on identifying patterns and themes in the comments in order to better understand parents' experiences with the telepractice modality. Results: The study revealed that parents were generally satisfied with the telepractice modality, as it was easy to use and enabled a better balance between work and family. This modality also enabled parents to share and receive mutual support. Despite the positive results, it is still relevant to offer training in different modalities to meet the different needs of parents. Conclusion: The study shows that parents of children with autism are generally satisfied with telepractice as a training modality. The results suggest that telepractice can be an effective alternative to traditional face-to-face training. The study highlights the importance of taking parents' needs and preferences into account when designing and implementing training programs.

Keywords: parents, children, training, telepractice

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Authors: Anukriti Verma, Bhawna Rathi, Shivani Sharda

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Reactive Arthritis (ReA) is a disorder that causes inflammation in joints due to certain infections at distant sites in the body. ReA begins with stiffness, pain, and inflammation in these areas especially the ankles, knees, and hips. It gradually causes several complications such as conjunctivitis in the eyes, skin lesions in hand, feet and nails and ulcers in the mouth. Nowadays the diagnosis of ReA is based upon a differential diagnosis pattern. The parameters for differentiating ReA from other similar disorders include physical examination, history of the patient and a high index of suspicion. There are no standard lab tests or markers available for ReA hence the early diagnosis of ReA becomes difficult and the chronicity of disease increases with time. It is reported that enteric disorders such as Inflammatory Bowel Disease (IBD) that is inflammation in gastrointestinal tract namely Crohn’s Disease (CD) and Ulcerative Colitis (UC) are reported to be linked with ReA. Several microorganisms are found such as Campylobacter, Salmonella, Shigella and Yersinia causing IBD leading to ReA. The aim of our study was to perform the in-silico analysis in order to find interactions between microorganisms and human host causing IBD leading to ReA. A systems biology approach for metabolic network reconstruction and simulation was used to find the essential genes of the reported microorganisms. Interactomics study was used to find the interactions between the pathogen genes and human host. Genes such as nhaA (pathogen), dpyD (human), nagK (human) and kynU (human) were obtained that were analysed further using the functional, pathway and network analysis. These genes can be used as putative drug targets and biomarkers in future for early diagnosis, prevention, and treatment of IBD leading to ReA.

Keywords: drug targets, inflammatory bowel disease, reactive arthritis, systems biology

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Authors: Ayşe Defne Öz, Özlem Bozkurt

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Alzheimer's Disease (AD) is counted as one of the most important global health problems and the main cause of dementia. The term dementia refers to a wide spectrum of disorders characterized by global, chronic, and generally irreversible cognitive deterioration. It is estimated that %60 % to 80 of the cases of dementia are because of AD. Alzheimer's is a slowly progressive brain disease. The reason for AD is unknown to the author's best knowledge, yet it is one of the topics that is most researched. AD shows the histopathologically abnormal accumulation of the protein beta-amyloid (plague) outside neurons and twisted strands of the protein tau (tangles) inside neurons in the brain. These changes are accompanied by damage to the brain tissue and the death of neurons. AD causes people to have difficulty remembering names or conversations. Some of the later symptoms are difficulty in talking and walking. Alzheimer's Disease is elevated by the illness and mortality of COVID-19. COVID-19 has affected many lives globally and had profound effects on human lives. COVID-19 is caused by SARS-CoV-2, which is a virus that attacks the respiratory and central nervous system and has neuroinvasive potential. More than %80 of COVID-19 patients have ageusia or anosmia, representing the pathognomic features of the disease. Patients with dementia are frail, and with the COVID-19 pandemic, including isolation, cognitive decline may exacerbate. Furthermore, patients with AD can be unable to follow the directions, such as covering their mouth and nose while coughing and can live in nursing homes which makes them more open to being infected. As COVID-19 is highly infectious and its management requires isolation and quarantine, the need for caregivers for AD management conflicts with that of COVID-19 and adds an extra burden on AD patients, caregivers, families, society, and the economy. Due to the entry of SARS-CoV-2 into the central nervous system, inflammation caused by COVID-19, prolonged hospitalization, and delirium, it has been reported that COVID-19 causes many neurological disorders and predisposition to AD.

Keywords: Alzheimer's disease, COVID-19, dementia, SARS-CoV-2

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Authors: Engy S. El-Kayal, Mohamed M. S. Arafa

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There are various causes of ankle pain including traumatic and non-traumatic causes. Various imaging techniques are available for assessment of AP. MRI is considered to be the imaging modality of choice for ankle joint evaluation with an advantage of its high spatial resolution, multiplanar capability, hence its ability to visualize small complex anatomical structures around the ankle. However, the high costs and the relatively limited availability of MRI systems, as well as the relatively long duration of the examination all are considered disadvantages of MRI examination. Therefore there is a need for a more rapid and less expensive examination modality with good diagnostic accuracy to fulfill this gap. HRU has become increasingly important in the assessment of ankle disorders, with advantages of being fast, reliable, of low cost and readily available. US can visualize detailed anatomical structures and assess tendinous and ligamentous integrity. The aim of this study was to compare the diagnostic accuracy of HRU with MRI in the assessment of patients with AP. We included forty patients complaining of AP. All patients were subjected to real-time HRU and MRI of the affected ankle. Results of both techniques were compared to surgical and arthroscopic findings. All patients were examined according to a defined protocol that includes imaging the tendon tears or tendinitis, muscle tears, masses, or fluid collection, ligament sprain or tears, inflammation or fluid effusion within the joint or bursa, bone and cartilage lesions, erosions and osteophytes. Analysis of the results showed that the mean age of patients was 38 years. The study comprised of 24 women (60%) and 16 men (40%). The accuracy of HRU in detecting causes of AP was 85%, while the accuracy of MRI in the detection of causes of AP was 87.5%. In conclusions: HRU and MRI are two complementary tools of investigation with the former will be used as a primary tool of investigation and the latter will be used to confirm the diagnosis and the extent of the lesion especially when surgical interference is planned.

Keywords: ankle pain (AP), high-resolution ultrasound (HRU), magnetic resonance imaging (MRI) ultrasonography (US)

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Authors: Wafa Al Jabri

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Background: In Middle Eastern Countries (MECs), there is a high prevalence of genetic blood disorders (GBDs), particularly sickle cell disease and thalassemia. The GBDs are considered a major public health concern that place a huge burden to individuals, families, communities, and health care systems. The high rates of consanguineous marriages, along with the unacceptable termination of at-risk pregnancy in MECs, reduce the possible solutions to control the high prevalence of GBDs. Since the early 1970s, most of MECs have started introducing premarital screening services (PSS) as a preventive measure to identify the asymptomatic carriers of GBDs and to provide genetic counseling to help couples plan for healthy families; yet, the success rate of PSS is very low. Purpose: This paper aims to highlight the factors that affect the success of PSS in MECs. Methods: An integrative review of articles located in CINAHL, PubMed, SCOPUS, and MedLine was carried out using the following terms: “premarital screening,” “success,” “effectiveness,” and “ genetic blood disorders”. Second, a hand search of the reference lists and Google searches were conducted to find studies that did not exist in the primary database searches. Only studies which are conducted in MECs and published after 2010 were included. Studies that were not published in English were excluded. Results: Eighteen articles were included in the review. The results showed that PSS in most of the MECs was successful in achieving its objective of identifying high-risk marriages; however, the service failed to meet its ultimate goal of reducing the prevalence of GBDs. Various factors seem to hinder the success of PSS, including poor public awareness, late timing of the screening, culture and social stigma, lack of prenatal diagnosis services and therapeutic abortion, emotional factors, religious beliefs, and lack of genetic counseling services. However, poor public awareness, late timing of the screening, religious misbeliefs, and the lack of adequate counseling services were the most common barriers identified. Conclusion and Implications: The review help in providing a framework for an effective preventive measure to reduce the prevalence of GBDs in MECS. This framework focuses primarily in overcoming the identified barriers by providing effective health education programs in collaboration with religious leaders, offering the screening test to young adults at an earlier stage, and tailoring the genetic counseling to consider people’s values, beliefs, and preferences.

Keywords: premarital screening, middle east, genetic blood disorders, factors

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Authors: Monika Dmitrzak-Weglarz, Aleksandra Rajewska-Rager, Maria Skibinska, Natalia Lepczynska, Piotr Sibilski, Joanna Pawlak, Pawel Kapelski, Joanna Hauser

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Epidermal growth factor (EGF) is a well-known neurotrophic factor that involves in neuronal growth and synaptic plasticity. The proteomic research provided in order to identify novel candidate biological markers for mood disorders focused on elevated EGF serum level in patients during depression episode. However, the EGF association with mood disorder spectrum among adolescents and young adults has not been studied extensively. In this study, we aim to investigate the serum levels of EGF in adolescents and young adults during hypo/manic, depressive episodes and in remission compared to healthy control group. In our study, we involved 80 patients aged 12-24 years in 2-year follow-up study with a primary diagnosis of mood disorder spectrum, and 35 healthy volunteers matched by age and gender. Diagnoses were established according to DSM-IV-TR criteria using structured clinical interviews: K-SADS for child and adolescents, and SCID for young adults. Clinical and biological evaluations were made at baseline and euthymic mood (at 3th or 6th month of treatment and after 1 and 2 years). The Young Mania Rating Scale and Hamilton Rating Scale for Depression were used for assessment. The study protocols were approved by the relevant ethics committee. Serum protein concentration was determined by Enzyme-Linked Immunosorbent Assays (ELISA) method. Human EGF (cat. no DY 236) DuoSet ELISA kit was used (R&D Systems). Serum EGF levels were analysed with following variables: age, age under 18 and above 18 years old, sex, family history of affective disorders, drug-free vs. medicated. Shapiro-Wilk test was used to test the normality of the data. The homogeneity of variance was calculated with Levene’s test. EGF levels showed non-normal distribution and the homogeneity of variance was violated. Non-parametric tests: Mann-Whitney U test, Kruskall-Wallis ANOVA, Friedman’s ANOVA, Wilcoxon signed rank test, Spearman correlation coefficient was applied in the analyses The statistical significance level was set at p<0.05. Elevated EGF level at baseline (p=0.001) and at month 24 (p=0.02) was detected in study subjects compared with controls. Increased EGF level in women at month 12 (p=0.02) compared to men in study group have been observed. Using Wilcoxon signed rank test differences in EGF levels were detected: decrease from baseline to month 3 (p=0.014) and increase comparing: month 3 vs. 24 (p=0.013); month 6 vs. 12 (p=0.021) and vs. 24 (p=0.008). EGF level at baseline was negatively correlated with depression and mania occurrence at 24 months. EGF level at 24 months was positively correlated with depression and mania occurrence at 12 months. No other correlations of EGF levels with clinical and demographical variables have been detected. The findings of the present study indicate that EGF serum level is significantly elevated in the study group of patients compared to the controls. We also observed fluctuations in EGF levels during two years of disease observation. EGF seems to be useful as an early marker for prediction of diagnosis, course of illness and treatment response in young patients during first episode od mood disorders, which requires further investigation. Grant was founded by National Science Center in Poland no 2011/03/D/NZ5/06146.

Keywords: biological marker, epidermal growth factor, mood disorders, prediction

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Authors: André Furtado, Rafael Mineiro, Isabel Gonçalves, Cecília Santos, Telma Quintela

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The development of therapies for central nervous system (CNS) disorders is one of the biggest challenges of current pharmacology, given the unique features of brain barriers, which limit drug delivery. Efflux transporters (ABC transporters) expressed at the blood-cerebrospinal fluid barrier (BCSFB), are the main obstacles for the delivery of therapeutic compounds into the CNS, compromising the effective treatment of brain cancer, brain metastasis from peripheral cancers, or even neurodegenerative disorders. It is thus extremely important to understand the regulation of these transporters for reducing their expression while treating a brain disorder or choosing the most appropriate conditions for drug administration. Based on the fact that the BCSFB have fine-tuned biological rhythms, studying the circadian variation of drug transport processes is critical for choosing the most appropriate time of the day for drug administration. In our study, using an in vitro model of the BCSFB, we characterized the circadian transport profile of methotrexate (MTX) and donepezil (DNPZ), two drugs involved in the treatment of cancer and Alzheimer’s Disease symptoms, respectively. We found that MTX is transported across the basal and apical membranes of the BCSFB in a circadian way. The circadian pattern of an ABC transporter, Abcc4, might be partially responsible for MTX circadian transport. Furthermore, regarding the DNPZ transport study, we observed that the regulation of Abcg2 expression by the circadian rhythm will impact the circadian-dependent transport of DNPZ across the BCSFB. Overall, our results will contribute to the current knowledge on brain pharmacoresistance at the BCSFB by disclosing how circadian rhythms control drug delivery to the brain, setting the grounds for a potential application of chronotherapy to brain diseases to enhance the efficacy of medications and minimize their side effects.

Keywords: blood-cerebrospinal fluid barrier, ABC transporters, drug transport, chronotherapy

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Authors: Shruti Govindarajan

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In-utero gene editing with CRISPR-Cas9 opens up new possibilities for treating genetic disorders during pregnancy while still in mother’s womb. By targeting genetic mutations in the early stages of fetal development, this approach could potentially prevent severe conditions—like cystic fibrosis, sickle cell anemia, and muscular dystrophy—from causing harm. CRISPR-Cas9, which allows precise DNA edits, could be delivered into fetal cells through vectors such as adeno-associated viruses (AAVs) or nanoparticles, correcting disease-causing mutations and possibly offering lifelong relief from these disorders. For families facing severe genetic diagnoses, in-utero gene editing could provide a transformative option. However, technical challenges remain, including ensuring that gene editing only targets the intended cells and verifying long-term safety. Ethical considerations are also at the forefront of this technology. The editing of a fetus's genes brings up difficult questions about consent, especially since these genetic changes will affect the child’s entire life without their input. There's also concern over possible unintended side effects, or changes passed down to future generations. Moreover, if used beyond therapeutic purposes, this technology could be misused for ‘enhancements,’ like selecting for certain physical or cognitive traits, raising concerns about inequality and social pressures. In this way, in-utero gene editing brings both exciting potential and complex moral questions. As research progresses, addressing these scientific and ethical concerns will be key to ensuring that this technology is used responsibly, prioritizing safety, fairness, and a focus on alleviating genetic disease. A cautious and inclusive approach, along with clear regulations, will be essential to realizing the benefits of in-utero gene editing while protecting against unintended consequences.

Keywords: in-utero gene editing, CRISPR, bioethics, genetic disorder

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Authors: Peng Guo

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Objective To investigate the clinical characteristics and changes of video-polysomnography (v-PSG) in Parkinson disease (PD) patients accompanied with cognitive impairment. Methods Three hundred and ninety-four patients with PD were enrolled in Beijing Tiantan Hospital, according to CI level, the patients were divided into PD without cognitive impairment (PD-NCI), PD with mild cognitive impairment (PD-MCI), and PD with dementia (PDD) group. Collect patient's demographic data, including gender, onset age, education level and duration. The cognitive function of PD patients was evaluated by Montreal cognitive assessment (MoCA) scale, and the overall cognitive function and cognitive domains of the three groups were compared.Using v-PSG to assess the sleep status of patients. Correlation analysis of MoCA Scale and v-PSG results in PD-CI group. Results 1. In 394 cases of PD, 94 cases (23.86%) in PD-NCI group , 177 cases(44.92%) in PD-MCI group , 123 cases (31.22%) in PDD group. 2.There was no significant difference in gender, age of onset, education level and duration in PD-NCI group, PD-MCI group and PDD group （P＞0.05）. 3. The total score of MoCA scale in PD-NCI group, PD-MCI group and PDD group decreased one by one. In PD-NCI group, PD-MCI group and PDD group, the scores of each cognitive domain in MoCA scale decreased significantly（P<0.05）. 4.Compared with the PD-MCI group, PDD group had lower total sleep time, lower sleep efficiency （P<0.05）. Compared with PD-NCI group, PDD group had lower total sleep time and lower sleep efficiency （P<0.05）.5. The sleep efficiency of PD-CI patients is positively correlated with the total score of MoCA scale, visual spatial function, executive function, delayed recall and attention score（P<0.05). Conclusions The incidence of CI in PD patients was high; The cognitive function and cognitive domains of PD-CI patients were significantly impaired; In patients with PD-CI, total sleep time decreased, sleep efficiency decreased, and it was related to overall cognitive function and partial cognitive impairment.

Keywords: Parkinson disease, cognitive impairment, clinical characteristics, sleep disorders, video-polysomnography

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Authors: Y. Z. Gad

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Disorders of Sex Development (DSD) are defined as congenital conditions in which development of chromosomal, gonadal or anatomical sex is atypical. The DSD are relatively prevalent in Egypt. In spite of that, the relative rarity of the individual disease types or their molecular pathologies frequently resulted in reporting on single or few cases. This augmented the challenging nature of phenotype-genotype correlation in this disease group and its utilization in the management of such medical emergency. Through critical assessment of the published DSD reports, the current review aims at analyzing the clinical characteristics of the various DSD forms in relation to the underlying molecular pathologies. A systematic literature search was done in Pubmed, using relevant keywords (Egypt versus DSD, genital ambiguity or ambiguous genitalia, the old terms of 'intersex, hermaphroditism and pseudohermaphroditism', and a list of the DSD entities and their related genes). The search yielded 24 reports of molecular data in Egyptian patients presenting with ambiguous genitalia. However, only 21 publications fulfilled the criteria of inclusion of detailed clinical descriptions and definitive molecular diagnoses of individual patients. Curation of the data yielded a total of 53 cases that were ascertained from 40 families. Fifty-one patients present with ambiguous genitalia only while 2 had multiple congenital anomalies. Parental consanguinity was noted in 60% of cases. Sex of rearing at initial presentation was female in 75% and 60% in 46,XY and 46,XX DSD cases, respectively. The external genital phenotype in 2/3 of the 46,XY DSD cases showed moderate undermasculinization [Quigley scores 3 & 4] and 1/3 had severe presentations [scores 5 & 6]. For 46,XX subjects, 1 had severe virilization of the external genitalia while 8 had moderate phenotype. Hormonal data were inconclusive or contradictory to final diagnosis in a forth of cases. Collectively, 31 families [31/40, 77.5%] with 46,XY DSD had molecular defects in the genes, 5 alpha reductase 2 (SRD5A2) [12/31], 17 beta-hydroxysteroid dehydrogenase 3 [8/31], androgen receptor [7/31], Steroidogenic factor 1 [2/31], luteinizing hormone receptor [1/31], and fibroblast growth factor receptor 1 [1/31]. In a multiethnic study, 9 families afflicted with 46,XX DSD due to 11 beta hydroxylase (CYP11B1) deficiency were documented. Two recurrent mutations, G34R and N160D, in SRD5A2 were present, respectively, in 42 and 17% of cases. Similarly, 4 recurrent mutations resulted in 89% of the CYP11B1 presentations. In conclusion, this analysis highlights the importance of autosomal recessive inheritance and inbreeding among DSD presentations, the importance of founder effect in at least 2 disorders, the difficulties in relating the genotype with the indeterminate genital phenotype, the under-reporting of some DSD subtypes, and the notion that the reported mutational profiles among Egyptian DSD cases are relatively different from those reported in other ethnic groups.

Keywords: disorders of sex development, genital ambiguity, mutation, molecular diagnosis, Egypt

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