Search results for: Acute Inflammatory Demyelinating Polyneuropathy

Authors: Mudasir Ahmad Syed, Raashid Ahmd Wani, Mashooq Ahmad Dar, Uneeb Urwat, Riaz Ahmad Shah, Nazir Ahmad Ganai

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Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) is a primary avian pathogen responsible for severe intestinal pathology in younger chickens and economic losses. However, the Salmonella Typhimurium is also able to cause infection in humans, described by typhoid fever and acute gastro-intestinal disease. A study was conducted at days to investigate pathological, histopathological, haemato-biochemical, immunological and expression kinetics of NRAMP (natural resistance associated macrophage protein) gene family (NRAMP1 and NRAMP2) in broiler chickens following experimental infection of Salmonella Typhimurium at 0,1,3,5,7,9,11,13 and 15 days respectively. Infection was developed in birds through oral route at 2×108 CFU/ml. Clinical symptoms appeared 4 days post infection (dpi) and after one-week birds showed progressive weakness, anorexia, diarrhea and lowering of head. On postmortem examination, liver showed congestion, hemorrhage and necrotic foci on surface, while as spleen, lungs and intestines revealed congestion and hemorrhages. Histopathological alterations were principally observed in liver in second week post infection. Changes in liver comprised of congestion, areas of necrosis, reticular endothelial hyperplasia in association with mononuclear cell and heterophilic infiltration. Hematological studies confirm a significant decrease (P<0.05) in RBC count, Hb concentration and PCV. White blood cell count showed significant increase throughout the experimental study. An increase in heterophils was found up to 7dpi and a decreased pattern was observed afterwards. Initial lymphopenia followed by lymphocytosis was found in infected chicks. Biochemical studies showed a significant increase in glucose, AST and ALT concentration and a significant decrease (P<0.05) in total protein and albumin level in the infected group. Immunological studies showed higher titers of IgG in infected group as compared to control group. The real time gene expression of NRAMPI and NRAMP2 genes increased significantly (P<0.05) in infected group as compared to controls. The peak expression of NRAMP1 gene was seen in liver, spleen and caecum of infected birds at 3dpi, 5dpi and 7dpi respectively, while as peak expression of NRAMP2 gene in liver, spleen and caecum of infected chicken was seen at 9dpi, 5dpi and 9dpi respectively. This study has role in diagnostics and prognostics in the poultry industry for the detection of salmonella infections at early stages of poultry development.

Keywords: biochemistry, histopathology, NRAMP, poultry, real time expression, Salmonella Typhimurium

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Authors: Christina Drosou, Konstantina E. Kyriakopoulou, Andreas Bimpilas, Dimitrios Tsimogiannis, Magdalini C. Krokida

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Rationale: Agiorgitiko is one of the most widely-grown and commercially well-established red wine varieties in Greece. Each year viticulture industry produces a large amount of waste consisting of grape skins and seeds (pomace) during a short period. Grapes contain polyphenolic compounds which are partially transferred to wine during winemaking. Therefore, winery wastes could be an alternative cheap source for obtaining such compounds with important antioxidant activity. Specifically, red grape waste contains anthocyanins and flavonols which are characterized by multiple biological activities, including cardioprotective, anti-inflammatory, anti-carcinogenic, antiviral and antibacterial properties attributed mainly to their antioxidant activity. Ultrasound assisted extraction (UAE) is considered an effective way to recover phenolic compounds, since it combines the advantage of mechanical effect with low temperature. Moreover, green solvents can be used in order to recover extracts intended for used in the food and nutraceutical industry. Apart from the extraction, pre-treatment process like drying can play an important role on the preservation of the grape pomace and the enhancement of its antioxidant capacity. Objective: The aim of this study is to recover natural extracts from winery waste with high antioxidant capacity using green solvents so they can be exploited and utilized as enhancers in food or nutraceuticals. Methods: Agiorgitiko grape pomace was dehydrated by air drying (AD) and accelerated solar drying (ASD) in order to explore the effect of the pre-treatment on the recovery of bioactive compounds. UAE was applied in untreated and dried samples using water and water: ethanol (1:1) as solvents. The total antioxidant potential and phenolic content of the extracts was determined using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay and Folin-Ciocalteu method, respectively. Finally, the profile of anthocyanins and flavonols was specified using HPLC-DAD analysis. The efficiency of processes was determined in terms of extraction yield, antioxidant activity, phenolic content and the anthocyanins and flavovols profile. Results & Discussion: The experiments indicated that the pre-treatment was essential for the recovery of highly nutritious compounds from the pomace as long as the extracts samples showed higher phenolic content and antioxidant capacity. Water: ethanol (1:1) was considered a more effective solvent on the recovery of phenolic compounds. Moreover, ASD grape pomace extracted with the solvent system exhibited the highest antioxidant activity (IC50=0.36±0.01mg/mL) and phenolic content (TPC=172.68±0.01mgGAE/g dry extract), followed by AD and untreated pomace. The major compounds recovered were malvidin3-O-glucoside and quercetin3-O-glucoside according to the HPLC analysis. Conclusions: Winery waste can be exploited for the recovery of nutritious compounds using green solvents such as water or ethanol. The pretreatment of the pomace can significantly affect the concentration of phenolic compounds, while UAE is considered a highly effective extraction process.

Keywords: agiorgitico grape pomace, antioxidants, phenolic compounds, ultrasound assisted extraction

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Authors: Eun-Seop Kim, Eun-Ha Jang, Rana R. Kim, Sae-Byul Jang

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Objective: Preterm labor is the most common antecedent of preterm birth(PTB), which is characterized by regular uterine contraction before 37 weeks of pregnancy and cervical change. In acute preterm labor, tocolytics are administered as the first-line medication to suppress uterine contractions but rarely delay pregnancy to 37 weeks of gestation. On the other hand, according to the Korean Traditional Medicine, PTB is caused by the deficiency of Qi and unnecessary energy in the body of the mother. The aim of this study was to demonstrate the benefit of Traditional Korean Medicine as an adjuvant therapy in management of early uterine contractions and the prevention of PTB. Methods: It is a case report of a 38-year-old woman (0-0-6-0) hospitalized for irregular uterine contractions and cervical change at 33+3/7 weeks of gestation. Past history includes chemical pregnancies achieved by Artificial Rroductive Technology(ART), one stillbirth (at 7 weeks) and a laparoscopic surgery for endometriosis. After seven trials of IVF and articificial insemination, she had succeeded in conception via in-vitro fertilization (IVF) with help of Traditional Korean Medicine (TKM) treatments. Due to irregular uterine contractions and cervical changes, 2 TKM were prescribed: Gami-Dangguisan, and Antae-eum, known to nourish blood and clear away heat. 120ml of Gami-Dangguisan was given twice a day monring and evening along with same amount of Antae-eum once a day from 31 August 2013 to 28 November 2013. Tocolytics (Ritodrine) was administered as a first aid for maintenance of pregnancy. Information regarding progress until the delivery was collected during the patient’s visit. Results: On admission, the cervix of 15mm in length and cervical os with 0.5cm-dilated were observed via ultrasonography. 50% cervical effacement was also detected in physical examination. Tocolysis had been temporarily maintained. As a supportive therapy, TKM herbal preparations(gami-dangguisan and Antae-eum) were concomitantly given. As of 34+2/7 weeks of gestation, however intermittent uterine contractions appeared (5-12min) on cardiotocography and vaginal bleeding was also smeared at 34+3/7 weeks. However, enhanced tocolytics and continuous administration of herbal medicine sustained the pregnancy to term. At 37+2/7 weeks, no sign of labor with restored cervical length was confirmed. The woman gave a term birth to a healthy infant via vaginal delivery at 39+3/7 gestational weeks. Conclusions: This is the first successful case report about a preter labor patient administered with conventional tocolytic agents as well as TKM herbal decoctions, delaying delivery to term. This case deserves attention considering it is rare to maintain gestation to term only with tocolytic intervention. Our report implies the potential of herbal medicine as an adjuvant therapy for preterm labor treatment. Further studies are needed to assess the safety and efficacy of TKM herbal medicine as a therapeutic alternative for curing preterm birth.

Keywords: preterm labor, traditional Korean medicine, herbal medicine, integrative treatment, complementary and alternative medicine

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Authors: Innocent Atuhe, Babra Nalwadda, Grace Mulyowa, Annabella Habinka Ejiri

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Background: Atopic Dermatitis (AD) is one of the most prevalent and growing chronic inflammatory skin diseases in African prisons. AD care is limited in African due to a lack of information about the disease amongst primary care workers, limited access to dermatologists, lack of proper training of healthcare workers, and shortage of appropriate treatments. We designed and implemented the Prisons Telederma project based on the recommendations of the International Society of Atopic Dermatitis. We aimed at; i) increase awareness and understanding of teledermatology among prison health workers and ii) improve treatment outcomes of prisoners with atopic dermatitis through increased access to and utilization of consultant dermatologists through teledermatology in Uganda prisons. Approach: We used Store-and-forward Teledermatology (SAF-TD) to increase access to dermatologist-led care for prisoners and prison staff with AD. We conducted five days of training for prison health workers using an adapted WHO training guide on recognizing neglected tropical diseases through changes on the skin together with an adapted American Academy of Dermatology (AAD) Childhood AD Basic Dermatology Curriculum designed to help trainees develop a clinical approach to the evaluation and initial management of patients with AD. This training was followed by blended e-learning, webinars facilitated by consultant Dermatologists with local knowledge of medication and local practices, apps adjusted for pigmented skin, WhatsApp group discussions, and sharing pigmented skin AD pictures and treatment via zoom meetings. We hired a team of Ugandan Senior Consultant dermatologists to draft an iconographic atlas of the main dermatoses in pigmented African skin and shared this atlas with prison health staff for use as a job aid. We had planned to use MySkinSelfie mobile phone application to take and share skin pictures of prisoners with AD with Consultant Dermatologists, who would review the pictures and prescribe appropriate treatment. Unfortunately, the National Health Service withdrew the app from the market due to technical issues. We monitored and evaluated treatment outcomes using the Patient-Oriented Eczema Measure (POEM) tool. We held four advocacy meetings to persuade relevant stakeholders to increase supplies and availability of first-line AD treatments such as emollients in prison health facilities. Results: We have the very first iconographic atlas of the main dermatoses in pigmented African skin. We increased; i) the proportion of prison health staff with adequate knowledge of AD and teledermatology from 20% to 80%; ii) the proportion of prisoners with AD reporting improvement in disease severity (POEM scores) from 25% to 35% in one year; iii) increased proportion of prisoners with AD seen by consultant dermatologist through teledermatology from 0% to 20% in one year and iv)Increased the availability of AD recommended treatments in prisons health facilities from 5% to 10% in one year. Our study contributes to the use, evaluation, and verification of the use of teledermatology to increase access to specialist dermatology services to the most hard to reach areas and vulnerable populations such as that of prisoners.

Keywords: teledermatology, prisoners, reaching, un-reachable

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Authors: Isabela S. Gonçalves, Vitor G. P. Lima, Tiago M. B. Campos, Marcos Jacobovitz, Luana M. R. Vasconcellos, Ivone R. Oliveira

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Periodontitis is an infectious disease of multifactorial origin, which originates from a periodontogenic bacterial biofilm that colonizes the surfaces of the teeth, resulting in an inflammatory reaction to microbial aggression. In the absence of adequate treatment, it can lead to the gradual destruction of the periodontal ligaments, cementum and alveolar bone. In guided tissue/bone regeneration therapy (GTR/GBR), a barrier membrane is placed between the fibrous tissues and the bone defect to prevent unwanted incursions of fibrous tissues into the bone defect, thus allowing the regeneration of quality bone. Currently, there are a significant number of biodegradable barrier membranes available on the market. However, a very common problem is that the membranes are not bioactive/osteogenic, that is, they are incapable of inducing a favorable osteogenic response and integration with the host tissue, resulting in many cases in displacement/expulsion of the membrane, requiring a new surgical procedure and replacement of the implant. Aiming to improve the bioactive and osteogenic properties of the membrane, this work evaluated the production of membranes that integrate the biocompatibility of the hydrophilic synthetic polymer (polyvinyl alcohol - PVA) with the osteogenic effects of chlorinated bioactive glasses (BG58S-Cl), using the electrospinning equipment (AeroSpinner L1.0 from Areka) which allows the execution of spinning by high voltage and/or blowing in solution and with a high production rate, enabling development on an industrial scale. In the formulation of bioactive glasses, the replacement of nitrates by chlorinated molecules has shown to be a promising alternative, since the chloride ion is naturally present in the body and, with its presence in the bioactive glass, the biocompatibility of the material increases. Thus, in this work, chlorinated bioactive glasses were synthesized by the sol-gel route using the compounds tetraethyl orthosilicate (TEOS), calcium chloride dihydrate and monobasic ammonium phosphate with pH adjustments with 37% HCl (1.5 or 2.5) and different calcination temperatures (500, 600 and 700 °C) were evaluated. The BG-58S-Cl powders obtained were characterized by pH, conductivity and zeta potential x time curves and by SEM/FEG, FTIR-ATR and Raman tests. The material produced under the selected conditions was evaluated in relation to the milling procedure, obtaining particles suitable for incorporation into PVA polymer solutions to be electrospun (D50 = 22 µm). Membranes were produced and evaluated regarding the influence of the crosslinking agent content as well as the crosslinking treatment temperature (3, 5 and 10 wt% citric acid) and (130 or 175 oC) and were characterized by SEM/FEG, FTIR, TG and DSC. From the optimization of the crosslinking conditions, membranes were prepared by adding BG58S-Cl powder (5 and 10 wt%) to the PVA solutions and were characterized by SEM-FEG, DSC, bioactivity in SBF and behavior in cell culture (cell viability, total protein content, alkaline phosphatase, mineralization nodules). The micrographs showed homogeneity of the distribution of BG58S-Cl particles throughout the sample, favoring cell differentiation.

Keywords: barrier membranes, chlorinated bioactive glasses, polyvinyl alcohol, tissue regeneration.

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Authors: Bassma A. Abdelhaleem, Mamdouh A. Abdulrhman, Nagwa I. Mohamed

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Malnutrition in children is an increasing problem worldwide which may result in both short and long-term irreversible negative health outcomes. Severe Acute Malnutrition (SAM) affects more than 18 million children each year, mostly living in low-income settings. SAM contributes to 45% of all deaths in children less than five years of age. Honey is a natural sweetener, containing mainly monosaccharides (up to 80%), disaccharides (3–5%), water (17–20%), and a wide range of minor constituents such as vitamins, minerals, proteins, amino acids, enzymes, and phytochemicals, mainly phenolic acids, and flavonoids. Honey has been used in many cultures around the world due to its known nutritional and medicinal benefits including the treatment of hypercholesterolemia. Despite its use since ancient times yet little is known about its potential benefits for malnourished children. Honey has the potential to be an affordable solution for malnourished low-income children as it is nutrient-dense and calorie dense food, easily absorbed, highly palatable, enhances appetite, and boosts immunity. This study assessed the effect of clover honey supplementation on the anthropometric measurements and lipid profile of malnourished infants and children. A prospective interventional clinical trial was conducted between November 2019 to November 2020, on 40 malnourished infants and children divided into two groups: Group A (20 children; 11 males and 9 females) received honey in a dose of 1.75ml/kg/dose, twice weekly for 12 weeks and Group B (20 children; 6 males and 14 females) received placebo. Written informed consent was obtained for parents/guardians. Patients were recruited from the Pediatric Nutrition Clinic at Ain Shams University. Anthropometric measurements (weight, height, body mass index, head circumference, and mid-arm circumference) and fasting serum cholesterol levels were measured at baseline and after 3 months. The 3-month honey consumption had a statistically highly significant effect on increasing weight, height, and body mass index and lowering fasting serum cholesterol levels in primary malnourished infants and children. Weight, height, body mass index, and fasting serum cholesterol level before honey consumption were (9.49 ± 2.03, 81.45 ± 8.31, 14.24 ± 2.15, 178.00 ± 20.91) and after 3 months of honey consumption were (10.91 ± 2.11, 84.80 ± 8.23, 15.07 ± 2.05, 162.45 ± 19.73) respectively with P-value < 0.01. Our results showed a significant desirable effect of honey consumption on changes in nutritional status based on weight, height, and body mass index, and has a favourable effect on lowering fasting serum cholesterol levels. These results propose the use of honey as an affordable solution to improve malnutrition, particularly in low-income countries. However, further research needs to weigh benefits against potential harms including the risk of botulinum toxin that is historically associated with honey consumption in early childhood.

Keywords: clinical trial, dyslipidemia, honey, malnutrition

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Authors: Rosemary Saunders, Courtney Glass, Karla Seaman, Karen Gullick, Julie Andrew, Anne Wilkinson, Ashwini Davray

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Current literature demonstrates that most Australians receive end-of-life care in a hospital setting, despite most hoping to die within their own home. The necessity for high quality end-of-life care has been emphasised by the Australian Commission on Safety and Quality in Health Care and the National Safety and Quality in Health Services Standards depict the requirement for comprehensive care at the end of life (Action 5.20), reinforcing the obligation for continual organisational assessment to determine if these standards are suitably achieved. Limited research exploring clinical staff perspectives of end-of-life care delivery has been conducted within an Australian private health context. This study aimed to investigate clinical staff member perceptions of end-of-life care delivery at a private hospital in Western Australia. The study comprised of a multi-faceted mixed-methods methodology, part of a larger study. Data was obtained from clinical staff utilising surveys and focus groups. A total of 133 questionnaires were completed by clinical staff, including registered nurses (61.4%), enrolled nurses (22.7%), allied health professionals (9.9%), non-palliative care consultants (3.8%) and junior doctors (2.2%). A total of 14.7% of respondents were palliative care ward staff members. Additionally, seven staff focus groups were conducted with physicians (n=3), nurses (n=26) and allied health professionals including social workers (n=1), dietitians (n=2), physiotherapists (n=5) and speech pathologists (n=3). Key findings from the surveys highlighted that the majority of staff agreed it was part of their role to talk to doctors about the care of patients who they thought may be dying, and recognised the importance of communication, appropriate training and support for clinical staff to provide quality end-of-life care. Thematic analysis of the qualitative data generated three key themes: creating the setting which highlighted the importance of adequate resourcing and conducive physical environments for end-of-life care and to support staff and families; planning and care delivery which emphasised the necessity for collaboration between staff, families and patients to develop care plans and treatment directives; and collaborating in end-of-life care, with effective communication and teamwork leading to achievable care delivery expectations. These findings contribute to health professionals better understanding of end-of-life care provision and the importance of collaborating with patients and families in care delivery. It is crucial that health care providers implement strategies to overcome gaps in care, so quality end-of-life care is provided. Findings from this study have been translated into practice, with the development and implementation of resources, training opportunities, support networks and guidelines for the delivery of quality end-of-life care.

Keywords: clinical staff, end-of-life care, mixed-methods, private hospital.

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Authors: Md. S. Sabuz

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Bangladesh, a South Asian developing country, has achieved a remarkable breakthrough in health indicators during the last four decades despite immense income inequality. This phenomenon results in the mystical exclusion of marginalized people from obtaining health care facilities. However, the persistence of exclusion of the disadvantaged remains troubling. Exclusion occurs from occupational inferiority, pay and wage differences, educational backwardness, gender disparity to urban-rural complexity and eliminate the unprivileged from seeking and availing the health services. Evidence from Bangladesh shows that many sick people prefer to die at home without securing medical services because in previous times they were not treated well, not because the medical facilities were inadequate or antediluvian but the socio-economic class allows them to receive obdurate treatment. Furthermore, government and policymakers have given enormous emphasis on infrastructural development and achieving health indicators instead of ensuring quality services and inclusiveness of people from all spheres. Therefore, it is high time to address the issues concerning this and highlight the impact of economic status on health status in a sociological perspective. The objective of this study is to consider ways of assessing and exploring the impact of economic status for instance: occupational status, pay and wage variable, on health status in the context of Bangladesh. The hypotheses are that there are a significant number of factors affecting economic status which are impactful for health status eventually, but acute income inequality is a prominent factor. Illiteracy, gender disparity, remoteness, incredibility on services, superior costs, superstition etc. are the dominant indicators behind the economic factors influencing the health status. The chosen methodologies are a qualitative and quantitative approaches to accomplish the research objectives. Secondary sources of data will be used to conduct the study. Surveys will be conducted on the people who have ever been through the health care facilities and people from the different socio-economic and cultural backgrounds. Focus group discussions will be conducted to acquire the data from different cultural and regional citizens. The findings show that 48% of people who are from disadvantaged communities have been deprived of proper health care facilities. The general reasons behind this are the higher cost of medicines and other equipment. A significant number of people are unaware of the appropriate facilities. It was found that the socio-economic variables are the main influential factors that work as the driving force for both economic dimension and health status. Above all regional variables and gender, dimensions have an enormous effect on determining the health status of an individual or community. Amidst many positive achievements for example decrease in the child mortality rate, an increase in the immunization programs of the child etc., the inclusiveness of all classes of people in health care facilities has been overshadowed in Bangladesh. However, this phenomenon along with the socio-economic and cultural phenomena significantly demolishes the quality and inclusiveness of the health status of people.

Keywords: cultural context of health, economic status, gender and health, rural health care

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Authors: Kennedy Zinn, Chris Anderson

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Chronic Covid syndrome (CCS) is a condition in which individuals who test positive for Covid-19 experience persistent symptoms after recovering from the virus. CCS affects every organ system, including the central nervous system. Neurological “long-haul” symptoms last from a few weeks to several months and include brain fog, chronic fatigue, dyspnea, mood dysregulation, and headaches. Data suggest that 10-30% of individuals testing positive for Covid-19 develop CCS. Current literature indicates a decreased quality of life in persistent symptoms. CCS is a pervasive and pernicious COVID-19 sequelae. More research is needed to understand risk factors, impact, and possible interventions. Research frequently cites cytokine storming as noteworthy etiology in CCS. Cytokine storming is a malfunctional immune response and facilitates multidimensional interconnected physiological responses. The most prominent responses include abnormal blood flow, hypoxia/hypoxemia, inflammation, and endothelial damage. Neurological impairments and pathogenesis in CCS parallel that of traumatic brain injury (TBI). Both exhibit impairments in memory, cognition, mood, sustained attention, and chronic fatigue. Evidence suggests abnormal blood flow, inflammation, and hypoxemia as shared causal factors. Cytokine storming is also typical in mTBI. The shared characteristics in symptoms and etiology suggest potential parallel routes of investigation that allow for better understanding of CCS. Research on the effect of altitude in mTBI varies. Literature finds decreased rates of concussions at higher altitudes. Other studies suggest that at a higher altitude, pre-existing mTBI symptoms are exacerbated. This may mean that in CCS, the geographical location where individuals live and the location where individuals experienced acute Covid-19 symptoms may influence the severity and risk of developing CCS. It also suggests that clinics which treat mTBI patients could also provide benefits for those with CCS. This study aims to examine the relationships between altitude and CCS as a risk factor and investigate the longevity and severity of symptoms in different altitudes. Existing patient data from a concussion clinic using fMRI scans and self-reported symptoms will be used for approximately 30 individuals with CCS symptoms. The association between acclimated altitude and CCS severity will be analyzed. Patients will be classified into low, medium, and high altitude groups and compared for differences on fMRI severity scores and self-reported measures. It is anticipated that individuals living in lower altitudes are at higher risk of developing more severe neuropsychological symptoms in CCS. It is also anticipated that a treatment approach for mTBI will also be beneficial to those with CCS.

Keywords: altitude, chronic covid syndrome, concussion, covid brain, EPIC treatment, fMRI, traumatic brain injury

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Authors: John Farr Rothrock

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Although migraine traditionally has been assumed to convey a relative decrease in libido, sexual activity and sexual performance, recent data have suggested that the female migraine population is far from homogenous in this regard. We sought to determine the levels of libido, sexual activity and sexual performance in the female migraine patient population both generally and according to clinical phenotype. In this single-blind study, a consecutive series of sexually active new female patients ages 25-55 initially presenting to a university-based headache clinic and having a >1 year history of migraine were asked to complete anonymously a survey assessing their sexual histories generally and as they related to their headache disorder and the 19-item Female Sexual Function Index (FSFI). To serve as 2 separate control groups, 100 sexually active females with no history of migraine and 100 female migraineurs from the general (non-clinic) population but matched for age, marital status, educational background and socioeconomic status completed a similar survey. Over a period of 3 months, 188 consecutive migraine patients were invited to participate. Twenty declined, and 28 of the remaining 160 potential subjects failed to meet the inclusion criterion utilized for “sexually active” (ie, heterosexual intercourse at a frequency of > once per month in each of the preceding 6 months). In all groups younger age (p<.005), higher educational level attained (p<.05) and higher socioeconomic status (p<.025) correlated with a higher monthly frequency of intercourse and a higher likelihood of intercourse resulting in orgasm. Relative to the 100 control subjects with no history of migraine, the two migraine groups (total n=232) reported a lower monthly frequency of intercourse and recorded a lower FSFI score (both p<.025), but the contribution to this difference came primarily from the chronic migraine (CM) subgroup (n=92). Patients with low frequency episodic migraine (LFEM) and mid frequency episodic migraine (MFEM) reported a higher FSFI score, higher monthly frequency of intercourse, higher likelihood of intercourse resulting in orgasm and higher likelihood of multiple active sex partners than controls. All migraine subgroups reported a decreased likelihood of engaging in intercourse during an active migraine attack, but relative to the CM subgroup (8/92=9%), a higher proportion of patients in the LFEM (12/49=25%), MFEM (14/67=21%) and high frequency episodic migraine (HFEM: 6/14=43%) subgroups reported utilizing intercourse - and orgasm specifically - as a means of potentially terminating a migraine attack. In the clinic vs no-clinic groups there were no significant differences in the dependent variables assessed. Research subjects with LFEM and MFEM may report a level of libido, frequency of intercourse and likelihood of orgasm-associated intercourse that exceeds what is reported by age-matched controls free of migraine. Many patients with LFEM, MFEM and HFEM appear to utilize intercourse/orgasm as a means to potentially terminate an acute migraine attack.

Keywords: migraine, female, libido, sexual activity, phenotype

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Authors: Lina Paola Orozco Marin, Yuliet Montoya Osorio, John Bustamante Osorno

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Ischemic events can culminate in acute myocardial infarction by irreversible cardiac lesions that cannot be restored due to the limited regenerative capacity of the heart. Cell therapy seeks to replace these injured or necrotic cells by transplanting healthy and functional cells. The therapeutic alternatives proposed by tissue engineering and cardiovascular regenerative medicine are the use of biomaterials to mimic the native extracellular medium, which is full of proteins, proteoglycans, and glycoproteins. The selected biomaterials must provide structural support to the encapsulated cells to avoid their migration and death in the host tissue. In this context, the present research work focused on developing a natural thermosensitive hydrogel, its physical and chemical characterization, and the determination of its biocompatibility in vitro. The hydrogel was developed by mixing hydrolyzed bovine and porcine collagen at 2% w/v, chitosan at 2.5% w/v, and beta-glycerolphosphate at 8.5% w/w and 10.5% w/w in magnetic stirring at 4°C. Once obtained, the thermosensitivity and gelation time were determined, incubating the samples at 37°C and evaluating them through the inverted tube method. The morphological characterization of the hydrogels was carried out through scanning electron microscopy. Chemical characterization was carried out employing infrared spectroscopy. The biocompatibility was determined using the MTT cytotoxicity test according to the ISO 10993-5 standard for the hydrogel’s precursors using the fetal human ventricular cardiomyocytes cell line RL-14. The RL-14 cells were also seeded on the top of the hydrogels, and the supernatants were subculture at different periods to their observation under a bright field microscope. Four types of thermosensitive hydrogels were obtained, which differ in their composition and concentration, called A1 (chitosan/bovine collagen/beta-glycerolphosphate 8.5%w/w), A2 (chitosan/porcine collagen/beta-glycerolphosphate 8.5%), B1 (chitosan/bovine collagen/beta-glycerolphosphate 10.5%) and B2 (chitosan/porcine collagen/beta-glycerolphosphate 10.5%). A1 and A2 had a gelation time of 40 minutes, and B1 and B2 had a gelation time of 30 minutes at 37°C. Electron micrographs revealed a three-dimensional internal structure with interconnected pores for the four types of hydrogels. This facilitates the exchange of nutrients, oxygen, and the exit of metabolites, allowing to preserve a microenvironment suitable for cell proliferation. In the infrared spectra, it was possible to observe the interaction that occurs between the amides of polymeric compounds with the phosphate groups of beta-glycerolphosphate. Finally, the biocompatibility tests indicated that cells in contact with the hydrogel or with each of its precursors are not affected in their proliferation capacity for a period of 16 days. These results show the potential of the hydrogel to increase the cell survival rate in the cardiac cell therapies under investigation. Moreover, the results lay the foundations for its characterization and biological evaluation in both in vitro and in vivo models.

Keywords: cardiac cell therapy, cardiac ischemia, natural polymers, thermosensitive hydrogel

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Authors: Jatinder Pal Singh, Harpreet Singh, Gagandeep Singh Digra, Mandeep Kaur Sidhu, Pawan Kumar

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Introduction: Ganglion cyst is a benign condition in which there is a cystic lesion in relation to a joint or a tendon sheath arising from myxoid degeneration of fibrous connective tissue. These can be unilocular or multilocular. In rare cases, there may be multiple ganglion cysts, known as cystic ganglionosis. They can occur at any age but are commonly seen in adults. Clinically they may be asymptomatic or present as swelling or mass effect in adjacent structures. These are common in extremities such as hands and feet. Case Presentation: 11-year-old female child presented with slowly progressive painless swelling of her right hand since the age of 4. Antenatal and perinatal history was unremarkable. Her family history was negative. She denies fever, malaise, morning stiffness, weight loss, fatigue, restriction of joint movements, or any sensory and motor deficit. Lab parameters were negative for inflammatory or infectious etiology. No other joint or extremity involvement was present. On physical examination, the swelling was present on the dorsum and palmer aspect of the right hand and wrist. They were non-tender on palpation without any motor or sensory deficit. MRI hand revealed multiple well-defined fluid signal intensity cystic appearing lesions in periarticular/intraarticular locations in relation to distal radio-ulnar, radio-carpal, intercarpal, carpometacarpal, metacarpophalangeal and interphalangeal joints as well as peritendinous location around flexor tendons more so in the region of wrist, palm, 1st and 5th digit and along extensor tendons in the region of wrist, largest one noted along flexor pollicis longus tendon in thenar region and along 1st digit measuring approx. 4.6 x 1.2 x 1.2 centimeter. Pressure erosions and bone remodelling were noted in the bases of the 2nd to 5th metacarpals, capitate, trapezoid, the distal shaft of 1st metacarpal, and proximal phalanx of 1st digit. Marrow edema was noted in the base and proximal shaft of the 4th metacarpal and proximal shaft of the 3rd metacarpal – likely stress or pressure related. The patient was advised of aspiration, but the family refused the procedure. Therefore the patient was kept on conservative treatment. Conclusion: Cystic ganglionosis is a rare condition with very few cases reported in the medical literature. Its prevalence and association are not known because of the rarity of this condition. It should be considered as an important differential in patients presenting with soft tissue swelling in extremities. Treatment option includes conservative management, aspiration, and surgery. Aspiration has a high recurrence rate. Although surgery has a low recurrence rate, it carries a high rate of complications. Imaging with MRI is essential for confirmation of the cystic nature of lesions and their relation with the joint capsules or tendons. This helps in differentiating from other soft tissue lesions and presurgical planning.

Keywords: radiology, rare, cystic ganglionosis, child

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Authors: Chang Liu, Hanwen Zhang, Vikash Sharma, Don Eliseo Lucerno-Prisno III, Emmanuel Yujuico, Maulik Chokshi, Prashanthi Krishnakumar, Bach Xuan Tran, Giang Thu Vu, Kamilla Anna Pinter, Shenglan Tang

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Background and Aims: Globally, many health systems focus on hospital-based healthcare models targeting acute care and disease treatment, which are not effective in addressing the challenges of ageing populations, chronic conditions, multi-morbidities, and increasingly unhealthy lifestyles. Recently, integrated care programs on chronic diseases have been developed, piloted, and implemented to meet such challenges. However, integrated care programs in the Asia-Pacific region vary in the levels of integration from linkage to coordination to full integration. This study aims to identify and analyze existing cases of integrated care in the Asia-Pacific region and identify the facilitators and barriers in order to improve existing cases and inform future cases. Methods: The study is a comparative study, with a combination approach of desk-based research and key informant interviews. The selected countries included in this study represent a good mix of lower-middle income countries (the Philippines, India, Vietnam, and Fiji), upper-middle income country (China), and high-income country (Singapore) in the Asia-Pacific region. Existing integrated care programs were identified through the scoping review approach. Trigger, history, general design, beneficiaries, and objectors were summarized with barriers and facilitators of integrated care based on key informant interviews. Representative case(s) in each country were selected and comprehensively analyzed through deep-dive case studies. Results: A total of 87 existing integrated care programs on chronic diseases were found in all countries, with 44 in China, 21 in Singapore, 12 in India, 5 in Vietnam, 4 in the Philippines, and 1 in Fiji. 9 representative cases of integrated care were selected for in-depth description and analysis, with 2 in China, the Philippines, and Vietnam, and 1 in Singapore, India, and Fiji. Population aging and the rising chronic disease burden have been identified as key drivers for almost all the six countries. Among the six countries, Singapore has the longest history of integrated care, followed by Fiji, the Philippines, and China, while India and Vietnam have a shorter history of integrated care. Incentives, technologies, education, and performance evaluation would be crucial for developing strategies for implementing future programs and improve already existing programs. Conclusion: Integrated care is important for addressing challenges surrounding the delivery of long-term care. To date, there is an increasing trend of integrated care programs on chronic diseases in the Asia-Pacific region, and all six countries in our study set integrated care as a direction for their health systems transformation.

Keywords: integrated healthcare, integrated care delivery, chronic diseases, Asia-Pacific region

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Authors: Tatsiana Ihnatovich, Darya Nizheharodava, Mikalai Halabarodzka, Tatsiana Savitskaya, Marina Zafranskaya

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Liver fibrosis is a complex of histological changes resulting from chronic liver disease accompanied by an excessive production and deposition of extracellular matrix components in the hepatic parenchyma. Liver fibrosis is a serious medical and social problem. Hepatic stellate cells (HSCs) make a significant contribution to the extracellular matrix deposition due to liver injury. Mesenchymal stem cells (MSCs) have a pronounced anti-inflammatory, regenerative and immunomodulatory effect; they are able to differentiate into hepatocytes and induce apoptosis of activated HSCs that opens the prospect of their use for preventing the excessive fibro-formation and the development of liver cirrhosis. The aim of the study is to evaluate the effect of MSCs therapy on the expression of fibrogenesis markers genes in liver tissue and HSCs cultures of rats with experimental liver cirrhosis (ELC). Materials and methods: ELC was induced by the common bile duct ligation (CBDL) in female Wistar rats (n = 19) with an average body weight of 250 (220 ÷ 270) g. Animals from the control group (n = 10) were sham-operated. On the 56th day after the CBDL, the rats of the experimental (n = 12) and the control (n = 5) groups received intraportal MSCs in concentration of 1×106 cells/animal (previously obtained from rat’s bone marrow) or saline, respectively. The animals were taken out of the experiment on the 21st day. HSCs were isolated by sequential liver perfusion in situ with following disaggregation, enzymatic treatment and centrifugation of cell suspension on a two-stage density gradient. The expression of collagen type I (Col1a1) and type III (Col3a1), matrix metalloproteinase type 2 (MMP2) and type 9 (MMP9), tissue inhibitor of matrix metalloproteinases type 1 (TIMP1), transforming growth factor β type 1 (TGFβ1) and type 3 (TGFβ3) was determined by real-time polymerase chain reaction. Statistical analysis was performed using Statistica 10.0. Results: In ELC rats compared to sham-operated animals, a significant increase of all studied markers expression was observed. The administration of MSCs led to a significant decrease of all detectable markers in the experimental group compared to rats without cell therapy. In ELC rats, an increased MMP9/TIMP1 ratio after cell therapy was also detected. The infusion of MSCs in the sham-operated animals did not lead to any changes. In the HSCs from ELC animals, the expression of Col1a1 and Col3a1 exceeded the similar parameters of the control group (p <0.05) and statistically decreased after the MSCs administration. The correlation between Col3a1 (Rs = 0.51, p <0.05), TGFβ1 (Rs = 0.6, p <0.01), and TGFβ3 (Rs = 0.75, p <0.001) expression in HSCs cultures and liver tissue has been found. Conclusion: Intraportal administration of MSCs to rats with ELC leads to a decreased Col1a1 and Col3a1, MMP2 and MMP9, TIMP1, TGFβ1 and TGFβ3 expression. The correlation between the expression of Col3a1, TGFβ1 and TGFβ3 in liver tissue and in HSCs cultures indicates the involvement of activated HSCs in the fibrogenesis that allows considering HSCs to be the main cell therapy target in ELC.

Keywords: cell therapy, experimental liver cirrhosis, hepatic stellate cells, mesenchymal stem cells

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Authors: Al. Tsertsvadze. L. Ebralidze, I. Matchutadze. D. Berashvili, A. Bakuridze

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Peatlands are landscape elements, they are formed over a very long period by physical, chemical, biologic, and geologic processes. In the moderate zone of Caucasus, the Kolkheti lowlands are distinguished by the diversity of relictual plants, a high degree of endemism, orographic, climate, landscape, and other characteristics of high levels of biodiversity. The unique properties of the Kolkheti region lead to the formation of special, so-called, endemic peat peloids. The composition and properties of peloids strongly depend on peat-forming plants. Peat is considered a unique complex of raw materials, which can be used in different fields of the industry: agriculture, metallurgy, energy, biotechnology, chemical industry, health care. They are formed in permanent wetland areas. As a result of decay, higher plants remain in the anaerobic area, with the participation of microorganisms. Peat mass absorbs soil and groundwater. Peloids are predominantly rich with humic substances, which are characterized by high biological activity. Humic acids stimulate enzymatic activity, regenerative processes, and have anti-inflammatory activity. Objects of the research were Kolkheti peat peloids (Ispani, Anaklia, Churia, Chirukhi, Peranga) possessing different formation phases. Due to specific physical and chemical properties of research objects, the aim of the research was to develop analytical methods in order to study the chemical composition of the objects. The research was held using modern instrumental methods of analysis: Ultraviolet-visible spectroscopy and Infrared spectroscopy, Scanning Electron Microscopy, Centrifuge, dry oven, Ultraturax, pH meter, fluorescence spectrometer, Gas chromatography-mass spectrometry (GC-MS/MS), Gas chromatography. Based on the research ration between organic and inorganic substances, the spectrum of micro and macro elements, also the content of minerals was determined. The content of organic nitrogen was determined using the Kjeldahl method. The total composition of amino acids was studied by a spectrophotometric method using standard solutions of glutamic and aspartic acids. Fatty acid was determined using GC (Gas chromatography). Based on the obtained results, we can conclude that the method is valid to identify fatty acids in the research objects. The content of organic substances in the research objects was held using GC-MS. Using modern instrumental methods of analysis, the chemical composition of research objects was studied. Each research object is predominantly reached with a broad spectrum of organic (fatty acids, amino acids, carbocyclic and heterocyclic compounds, organic acids and their esters, steroids) and inorganic (micro and macro elements, minerals) substances. Modified methods used in the presented research may be utilized for the evaluation of cosmetological balneological and pharmaceutical means prepared on the base of Kolkheti's Sphagnum Peat Peloids.

Keywords: modern analytical methods, natural resources, peat, chemistry

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Authors: Garima Singh

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Objectives: Behavioral Crisis Center (BCC) is a community solution to a community problem. There has been an exponential increase in the incidence and prevalence of mental health crises around the world. The effects of the crisis negatively impact our patients and their families and strain the law enforcement and emergency room. The goal of the multi-disciplinary care model is to break the crisis cycle and provide 24-7 rapid access to an acre and crisis stabilization. We initiated our first BCC care center in 2020 in the midst of the COVID pandemic and have seen a remarkable improvement in patient ‘care and positive financial outcome. Background: Mental illnesses are common in the United States. Nearly one in five U.S. adults live with a mental illness (52.9 million in 2020). This number represented 21.0% of all U.S. adults. To address some of these challenges and help our community, In May 2020, we opened our first Behavioral crisis center (BCC). Since then, we have served more than 2500 patients and is the first southwest Missouri’s first 24/7 facility for crisis–level behavioral health and substance use needs. It has been proven to be a more effective place than emergency departments, jails, or local law enforcement. Methods: BCC was started in 2020 to serve the unmet need of the community and provide access to behavioral health and substance use services identified in the community. Funding was possible with significant investment from the county and Missouri Foundation for Health, with contributions from medical partners. It is a multi-disciplinary care center consisting of Physicians, nurse practitioners, nurses, behavioral technicians, peer support specialists, clinical intake specialists, and clinical coordinators and hospitality specialists. The center provides services including psychiatry care, outpatient therapy, community support services, primary care, peer support and engagement. It is connected to a residential treatment facility for substance use treatment for continuity of care and bridging the gap, which has resulted in the completion of treatment and better outcomes. Results: BCC has proven to be a great resource to the community and the Missouri Health Coalition is providing funding to replicate the model in other regions and work on a similar model for children and adolescents. Overall, 29% of the patients seen at BCC are stabilized and discharged with outpatient care. 50% needed acute stabilization in a hospital setting and 21% required long-term admission, mostly for substance use treatment. The local emergency room had a 42% reduction in behavioral health encounters compared to the previous 3 years. Also, by a quick transfer to BCC, the average stay in ER was reduced by 10 hours and time to follow up behavioral health assessment decreased by an average of 4 hours. Uninsured patients are also provided Medicaid application assistance which has benefited 55% of individuals receiving care at BCC. Conclusions: BCC is impacting community health and improving access to quality care and substance use treatment. It is a great investment for our patients and families.

Keywords: BCC, behvaioral health, community health care, addiction treatment

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Authors: Leo Nnamdi Ozurumba-Dwight

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Single-cell genomic analytical systems have proved to be a platform to isolate bulk cells into selected single cells for genomic, proteomic, and related metabolomic studies. This is enabling systematic investigations of the level of heterogeneity in a diverse and wide pool of cell populations. Single cell technologies, embracing techniques such as high parameter flow cytometry, single-cell sequencing, and high-resolution images are playing vital roles in these investigations on messenger ribonucleic acid (mRNA) molecules and related gene expressions in tracking the nature and course of disease conditions. This entails targeted molecular investigations on unit cells that help us understand cell behavoiur and expressions, which can be examined for their health implications on the health state of patients. One of the vital good sides of single-cell RNA sequencing (scRNA seq) is its probing capacity to detect deranged or abnormal cell populations present within homogenously perceived pooled cells, which would have evaded cursory screening on the pooled cell populations of biological samples obtained as part of diagnostic procedures. Despite conduction of just single-cell transcriptome analysis, scRNAseq now permits comparison of the transcriptome of the individual cells, which can be evaluated for gene expressional patterns that depict areas of heterogeneity with pharmaceutical drug discovery and clinical treatment applications. It is vital to strictly work through the tools of investigations from wet lab to bioinformatics and computational tooled analyses. In the precise steps for scRNAseq, it is critical to do thorough and effective isolation of viable single cells from the tissues of interest using dependable techniques (such as FACS) before proceeding to lysis, as this enhances the appropriate picking of quality mRNA molecules for subsequent sequencing (such as by the use of Polymerase Chain Reaction machine). Interestingly, scRNAseq can be deployed to analyze various types of biological samples such as embryos, nervous systems, tumour cells, stem cells, lymphocytes, and haematopoietic cells. In haematopoietic cells, it can be used to stratify acute myeloid leukemia patterns in patients, sorting them out into cohorts that enable re-modeling of treatment regimens based on stratified presentations. In immunotherapy, it can furnish specialist clinician-immunologist with tools to re-model treatment for each patient, an attribute of precision medicine. Finally, the good predictive attribute of scRNAseq can help reduce the cost of treatment for patients, thus attracting more patients who would have otherwise been discouraged from seeking quality clinical consultation help due to perceived high cost. This is a positive paradigm shift for patients’ attitudes primed towards seeking treatment.

Keywords: immunotherapy, transcriptome, re-modeling, mRNA, scRNA-seq

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Authors: N. G. Klivleyeva, T. I. Glebova, G. V. Lukmanova, S. B. Bayseit, S. Z. Taubaeva, M. K. Kalkozhaeva

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The role of viral diseases in the general infectious disease incidence increases every year and requires special attention to the problem of interpreting the etiology of infectious agents. Influenza and acute respiratory viral infections are one of the most pressing public health issues. In the period 2012-2014, collection of 419 nasal swabs and 150 blood sera has been carried out in the patient care institutions of the various Kazakhstan regions from patients with symptoms of ARVI and pneumonia. Primary identification of biosamples for the presence of influenza viral antigens in enzyme immunoassay on nitrocellulose membrane gave positive results in 125 swabs (29.8%). Biosample screening in immunofluorescence test revealed the presence of influenza viral antigens against A/H1 in 63 samples (15.0%), A/H3 – in 70 samples (16.7%) and type B – in 9 samples (2.1%). As a result of primary infection, and successive passages in chick embryos and MDCK cell cultures, 38 HAAg were isolated from 419 samples with a clear cytopathic effect and hemagglutination titre in MDCK cell culture within 1:2-1:4, in CE - 1:8-1:256. The infectivity of isolates in chicken embryos were 3.5-6.5 lg EID50/0.2, in MDCK cell culture – 2.5-6.5 lg PFU/ml. Identification of 28 isolates was carried out in inhibition reactions of hemagglutinating activity and neuraminidase activity, showed their belonging to the influenza virus: 26 strains to A/H1N1, one - to A/H3N2, and one - to type B. Serological examination of blood sera for the presence of specific antibodies being an indirect evidence of the performed isolation and contributing to the timely interpretation of the disease etiology in the epidemics takes an important place in the comprehensive study of influenza viruses circulating among people. Serological analyzes were carried out in HAI assay using a kit consisting of 12 reference strains obtained from the WHO centre for reference and research on Influenza (CDC, Atlanta, USA) and three Kazakhstan (A/Almaty/347/09 (H1N1v), A/Almaty/462/11 (H3N2) and B/Almaty/414/10) human influenza viruses that are stored in the laboratory collection. The results of serological analysis of 150 blood sera showed that antihaemagglutinins against the A/H3N2 virus serosubtype were found in 46 samples (49.4%) out of 93 sera collected in 2012-2013. The antibody titres were within 1:160-1:320. 19 sera (20.4%) were seropositive against influenza A/H1N1 virus, the antibodies were observed in titres of 1:20-1:40. Six sera (6.4%) were positive against the influenza A/H1N1+A/H3N2 virus (mixed infection); the antibodies were recorded in titres of 1:20-1:40. Antihaemagglutinins against influenza type B virus were detected only in five sera (5.4%). The results of analysis of 57 sera collected in 2014 showed that antihaemagglutinins against A/H3N2 virus subtype were detected in 32 blood sera (56.1%) in titres of 1:160-1:640. Ten sera (17.5%) were seropositive against A/H1N1 virus; antihaemagglutinins against influenza type B virus were not detected. Therefore, virological and serological studies have shown that in Kazakhstan, as well as in the world, the influenza viruses A/H1N1, A/H3N2 and influenza B viruses were actively circulating during the epidemic seasons in 2012-2014.

Keywords: influenza, MDCK cell, serological analysis, virus

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Authors: Meless Gebrie Bore, Lin Perry, Xiaoyue Xu, Andargachew Kassa, Marilyn Cruickshank

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Background: Adolescents living with HIV (ALHIV) in Ethiopia face significant health challenges, particularly related to nutrition, which is essential for optimizing antiretroviral therapy (ART) outcomes. This population is vulnerable to nutritional deficiencies due to increased energy demands and the adverse effects of HIV, alongside rapid growth and low socio-economic status. Despite advances in ART, research on nutritional care for ALHIV in Ethiopia is limited. Integrated nutritional interventions are critical for improving health outcomes, yet comprehensive guidance is lacking. This study aimed to evaluate healthcare workers' practices in ART clinics, assess the nutritional status of ALHIV, and provide recommendations for enhancing nutritional care. Method: Cross-sectional surveys were conducted, recruiting 44 healthcare professionals and 384 ALHIV across ten public hospitals in Addis Ababa and Oromia regions. Participants were selected using purposive sampling for healthcare workers and proportionate random sampling for ALHIV engaged in ART services. Data was collected using a pre-tested structured questionnaire with quantitative and qualitative components facilitated by trained healthcare workers through the Kobo Toolbox program. Results: Findings revealed that while most healthcare workers conducted basic nutritional assessments, more sensitive methods were rarely used. Only 36.4% assessed dietary intake and 27.3% evaluated food security. Nutrition counseling was limited, with only 38.6% providing such services regularly. Health Care worker participants expressed dissatisfaction with the integration of nutrition services due to a lack of training and resources. Nutritional assessments revealed that 24.2% of ALHIV were classified as thin, 21.7% as stunted, and 34.9% as malnourished based on mid-upper arm circumference, with 19.4% experiencing severe acute malnutrition. These results highlight the urgent need and opportunities to improve nutritional support tailored to ALHIV-specific needs. Conclusion and Recommendations: Study findings identified evidence of substantial nutritional deficits and critical gaps in nutritional care for ALHIV in Ethiopian ART clinics. While basic assessment and counseling were generally practiced, limited use of more sensitive methods and inadequate integration of nutrition services hindered care effectiveness. To improve health outcomes, it is essential to enhance training for healthcare workers, develop standardized nutrition guidelines, and allocate resources effectively. Conducting further research with large, diverse samples and integrating comprehensive nutritional care alongside ART services will enable better matching of the nutritional needs of this vulnerable population.

Keywords: adolescents living with HIV(ALHIV), antiretroviral therapy (ART), HIV, Ethiopia, malnutrition, nutritional support, stunting, thinness

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Authors: Mihail Simion Beldean-Galea, Virginia Coman, Florina Copaciu, Mihaela Vlassa, Radu Mihaiescu, Adina Croitoru, Viorel Arghius, Modest Gertsiuk, Mikola Gertsiuk

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Taking into consideration the huge number of chemicals released into environment compartments a proper environmental risk assessment is difficult to predict due to the gap of legislation and improper toxicological assessment of chemicals compounds. In Romania as well as in many other countries from Europe, the chemical status of the water body is characterized taking into consideration the Water Framework Directive (WFD) and the substances listed in Annex X. This Annex includes 45 substances from different classes of organic compounds and heavy metals for which AA-EQS and MAC-EQS have been established. For other compounds which are not included in Annex X, different methodologies to prioritize chemicals for risk assessment and monitoring has been proposed. These methodologies take into account Predicted No-Effect Concentrations (PNECs) of different classes of chemicals compounds available from existing risk assessments or from read-across models for acute toxicity to the standard test organisms such as Daphnia magna and Selenastrum capricornutum. Our work presents the monitoring results of 30 priority substances including polyaromatic hydrocarbons, pesticides, halogenated compounds, plasticizers and heavy metals and other 34 substances from different classes of pesticides and pharmaceuticals which are not included on the list of priority substances, performed in the Upper Tisza River Watershed from Romania and Ukraine. The obtained monitoring data were used for the establishment of the list of more relevant pollutants in the studied area and to establish the potential river basin specific pollutants. For this purpose, two indicators such as the Frequency of exceedance and Extent of exceedance of Predicted no-Effect Concentration (PNEC) were evaluated. These two indicators are based on maximum environmental concentrations (MECs) of priority substances and for other pollutants is use statistically based averages of obtained measured concentration compared to the lowest PNEC thresholds. From the obtained results it can be concluded that polyaromatic hydrocarbon such as Fluoranthene, Benzo[a]pyrene, Benzo[b]fluorathene, benzo[k]fluoranthene, Benzo(g.h.i)perylene, Indeno(1.2.3-cd)-pyrene, heavy metals such as Cadmium, Lead and Nickel can be considered as river basin specific pollutants, their concentration exceeding the Annual Average EQS concentration. Other compounds such as estrone, estriol, 174-β estradiol, naproxen or some antibiotics (Penicillin G, Tetracycline or Ceftazidime) should be taken into account for a long monitoring, in some cases their concentration exceeding PNEC. Acknowledgements: This work is performed in the frame of NATO SfP Programme, Project no. 984440.

Keywords: prioritization, river basin specific pollutants, Tisza River, water framework directive

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Authors: Tarek Saadawi, Rosario Gennaro, Jonathan Akeley

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There is rapidly growing demand for professionals to fill positions in Cybersecurity. This is recognized as a national priority both by government agencies and the private sector. Cybersecurity is a very wide technical area which encompasses all measures that can be taken in an electronic system to prevent criminal or unauthorized use of data and resources. This requires defending computers, servers, networks, and their users from any kind of malicious attacks. The need to address this challenge has been recognized globally but is particularly acute in the New York metropolitan area, home to some of the largest financial institutions in the world, which are prime targets of cyberattacks. In New York State alone, there are currently around 57,000 jobs in the Cybersecurity industry, with more than 23,000 unfilled positions. The Cybersecurity Program at City College is a collaboration between the Departments of Computer Science and Electrical Engineering. In Fall 2020, The City College of New York matriculated its first students in theCybersecurity Master of Science program. The program was designed to fill gaps in the previous offerings and evolved out ofan established partnership with Facebook on Cybersecurity Education. City College has designed a program where courses, curricula, syllabi, materials, labs, etc., are developed in cooperation and coordination with industry whenever possible, ensuring that students graduating from the program will have the necessary background to seamlessly segue into industry jobs. The Cybersecurity Program has created multiple pathways for prospective students to obtain the necessary prerequisites to apply in order to build a more diverse student population. The program can also be pursued on a part-time basis which makes it available to working professionals. Since City College’s Cybersecurity M.S. program was established to equip students with the advanced technical skills needed to thrive in a high-demand, rapidly-evolving field, it incorporates a range of pedagogical formats. From its outset, the Cybersecurity program has sought to provide both the theoretical foundations necessary for meaningful work in the field along with labs and applied learning projects aligned with skillsets required by industry. The efforts have involved collaboration with outside organizations and with visiting professors designing new courses on topics such as Adversarial AI, Data Privacy, Secure Cloud Computing, and blockchain. Although the program was initially designed with a single asynchronous course in the curriculum with the rest of the classes designed to be offered in-person, the advent of the COVID-19 pandemic necessitated a move to fullyonline learning. The shift to online learning has provided lessons for future development by providing examples of some inherent advantages to the medium in addition to its drawbacks. This talk will address the structure of the newly-implemented Cybersecurity Master’s Program and discuss the innovations, challenges, and possible future directions.

Keywords: cybersecurity, new york, city college, graduate degree, master of science

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Authors: Modi Alsubaie, Chris Dickens, Barnaby Dunn, Andy Gibson, Obioha Ukoumunned, Alison Evans, Rachael Vicary, Manish Gandhi, Willem Kuyken

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Background: Depression co-occurs in 20% of people with cardiovascular disorders, can persist for years and predicts worse physical health outcomes. While psychosocial treatments have been shown to effectively treat acute depression in those with comorbid cardiovascular disorders, to date there has been no evaluation of approaches aiming to prevent relapse and treat residual depression symptoms in this group. Therefore, the current study aimed to examine the feasibility and acceptability of a randomised controlled trial design evaluating an adapted version of mindfulness-based cognitive therapy (MBCT) designed specifically for people with co-morbid depression and cardiovascular disorders. Methods: A 3-arm feasibility randomised controlled trial was conducted, comparing MBCT adapted for people with cardiovascular disorders plus treatment as usual (TAU), mindfulness-based stress reduction (MBSR) plus TAU, and TAU alone. Participants completed a set of self-report measures of depression severity, anxiety, quality of life, illness perceptions, mindfulness, self-compassion and affect and had their blood pressure taken immediately before, immediately after, and three months following the intervention. Those in the adapted-MBCT arm additionally underwent a qualitative interview to gather their views about the adapted intervention. Results: 3400 potentially eligible participants were approached when attending an outpatient appointment at a cardiology clinic or via a GP letter following a case note search. 242 (7.1%) were interested in taking part, 59 (1.7%) were screened as being suitable, and 33 (<1%) were eventually randomised to the three groups. The sample was heterogeneous in terms of whether they reported current depression or had a history of depression and the time since the onset of cardiovascular disease (one to 25 years). Of 11 participants randomised to adapted MBCT seven completed the full course, levels of home mindfulness practice were high, and positive qualitative feedback about the intervention was given. Twenty-nine out of 33 participants randomised completed all the assessment measures at all three-time points. With regards to the primary outcome (depression), five out of the seven people who completed the adapted MBCT and three out of five under MBSR showed significant clinical change, while in TAU no one showed any clinical change at the three-month follow-up. Conclusions: The adapted MBCT intervention was feasible and acceptable to participants. However, aspects of the trial design were not feasible. In particular, low recruitment rates were achieved, and there was a high withdrawal rate between screening and randomisation. Moreover, the heterogeneity in the sample was high meaning the adapted intervention was unlikely to be well tailored to all participants needs. This suggests that if the decision is made to move to a definitive trial, study recruitment procedures will need to be revised to more successfully recruit a target sample that optimally matches the adapted intervention.

Keywords: mindfulness-based cognitive therapy (MBCT), depression, cardiovascular disorders, feasibility, acceptability

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Authors: Heba Kamal Mohamed

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Introduction: Tramadol is a weak -opioid receptor agonist with an analgesic effect because of the inhibition of uptake of norepinephrine and serotonin. Nowadays, tramadol hydrochloride is frequently used as a pain reliever. Tramadol is recommended for the management of acute and chronic pain of moderate to severe intensity associated with a variety of diseases or problems, including osteoarthritis, diabetic neuropathy, neuropathic pain, and even perioperative pain in human patients. In obstetrics and gynecology, tramadol is used extensively to treat postoperative pain. Aim of the study: This study was undertaken to investigate the histological (light and electron microscopic) and immunohistochemical effects of long term tramadol treatment on the ovary of adult rats and the possible recovery after tramadol withdrawal. Design: Experimental study. Materials and methods: Thirty adult female albino rats were used in this study. They were classified into three main groups (10 rats each). Group I served as the control group. Group II, rats were subcutaneously injected with tramadol 40 mg/kg three times per week for 8 weeks. Group III, rats were subcutaneously injected with tramadol 40 mg/kg three times per week for 8 weeks then were kept for another 8 weeks without treatment for recovery. At the end of the experiment rats were sacrificed and bilateral oophorectomy was carried out; the ovaries were processed for histological study (light and electron microscopic) and immunohistochemical reaction for caspase-3 (apoptotic protein). Results: Examination of the ovary of tramadol-treated rats (group II) revealed many atretic ovarian follicles, some follicles showed detachment of the oocyte from surrounding granulosa cells and others showed loss of the oocyte. Many follicles revealed degenerated vacuolated oocytes and vacuolated theca folliculi cells. Granulosa cells appeared shrunken, disrupted and loosely attached with vacuolated cytoplasm and pyknotic nuclei. Some follicles showed separation of granulosa cells from the theca folliculi layer. The ultrastructural study revealed the presence of granulosa cells with electron dense indented nuclei, damaged mitochondria and granular vacuolated cytoplasm. Other cells showed accumulation of large amount of lipid droplets in their cytoplasm. Some follicles revealed rarifaction of the cytoplasm of oocytes and absent zona pellucida. Moreover, apoptotic changes were detected by immunohistochemical staining in the form of increased staining intensity to caspase-3 (apoptotic protein). With Masson's Trichrome stain, there was an increased collagen fibre deposition in the ovarian cortical stroma. The wall of blood vessels appeared thickened. In the withdrawal group (group III), there was a little improvement in the histological and immunohistochemical changes. Conclusion: Tramadol had serious deleterious effects on ovarian structure. Thus, it should be used with caution, especially when a long term treatment is indicated. Withdrawal of tramadol led to a little improvement in the structural impairment of the ovary.

Keywords: tramadol, ovary, withdrawal, rats

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Authors: Tatjana Kadifkova Panovska, Svetlana Kulevanova, Blagica Jovanova

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Biological systems possess the ability to neutralize the excess of reactive oxygen species (ROS) and to protect cells from destructive alterations. However, many pathological conditions (cardiovascular diseases, autoimmune disorders, cancer) are associated with inflammatory processes that generate an excessive amount of reactive oxygen species (ROS) that shift the balance between endogenous antioxidant systems and free oxygen radicals in favor of the latter, leading to oxidative stress. Therefore, an additional source of natural compounds with antioxidant properties that will reduce the amount of ROS in cells is much needed despite their broad utilization; many plant species remain largely unexplored. Therefore, the purpose of the present study is to investigate the antioxidant activity of twenty-five selected medicinal and aromatic plant species. The antioxidant activity of the ethanol extracts was evaluated with in vitro assays: 2,2’-diphenyl-1-pycryl-hydrazyl (DPPH), ferric reducing antioxidant power (FRAP), non-site-specific- (NSSOH) and site-specific hydroxyl radical-2-deoxy-D-ribose degradation (SSOH) assays. The Folin-Ciocalteu method and AlCl3 method were performed to determine total phenolic content (TPC) and total flavonoid content (TFC). All examined plant extracts manifested antioxidant activity to a different extent. Cinnamomum verum J.Presl bark and Ocimum basilicum L. Herba demonstrated strong radical scavenging activity and reducing power with the DPPH and FRAP assay, respectively. Additionally, significant hydroxyl scavenging potential and metal chelating properties were observed using the NSSOH and SSOH assays. Furthermore, significant variations were determined in the total polyphenolic content (TPC) and total flavonoid content (TFC), with Cinnamomum verum and Ocimum basilicum showing the highest amount of total polyphenols. The considerably strong radical scavenging activity, hydroxyl scavenging potential and reducing power for the species mentioned above suggest of a presence of highly bioactive phytochemical compounds, predominantly polyphenols. Since flavonoids are the most abundant group of polyphenols that possess a large number of available reactive OH groups in their structure, it is considered that they are the main contributors to the radical scavenging properties of the examined plant extracts. This observation is supported by the positive correlation between the radical scavenging activity and the total polyphenolic and flavonoid content obtained in the current research. The observations from the current research nominate Cinnamomum verum bark and Ocimum basilicum herba as potential sources of bioactive compounds that could be utilized as antioxidative additives in the food and pharmaceutical industries. Moreover, the present study will help the researchers as basic data for future research in exploiting the hidden potential of these important plants that have not been explored so far.

Keywords: ethanol extracts, radical scavenging activity, reducing power, total polyphenols.

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Authors: Anna Demian, Levi Howard, L. Ng, Leslie Simon, Mark Dragon, A. Desai, Timothy Devlantes, W. David Freeman

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Introduction: Out-of-hospital cardiac arrest (OHCA) can carry a high mortality. For survivors, the most common complication is hypoxic-ischemic brain injury (HIBI). Rarely, lumbosacral spinal cord and/or other spinal cord artery ischemia can occur due to anatomic variation and variable mean arterial pressure after the return of spontaneous circulation. We present a case of an OHCA survivor who later woke up with bilateral leg weakness with preserved sensation (ASIA grade B, L2 level). Methods: We describe a clinical, radiographic, and laboratory presentation, as well as a National Library of Medicine (NLM) search engine methodology, characterizing incidence/prevalence of this entity is discussed. A 70-year-old male, a longtime smoker, and alcohol user, suddenly collapsed at a bar surrounded by friends. He had complained of chest pain before collapsing. 911 was called. EMS arrived, and the patient was in pulseless electrical activity (PEA), cardiopulmonary resuscitation (CPR) was initiated, and the patient was intubated, and a LUCAS device was applied for continuous, high-quality CPR in the field by EMS. In the ED, central lines were placed, and thrombolysis was administered for a suspected Pulmonary Embolism (PE). It was a prolonged code that lasted 90 minutes. The code continued with the eventual return of spontaneous circulation. The patient was placed on an epinephrine and norepinephrine drip to maintain blood pressure. ECHO was performed and showed a “D-shaped” ventricle worrisome for PE as well as an ejection fraction around 30%. A CT with PE protocol was performed and confirmed bilateral PE. Results: The patient woke up 24 hours later, following commands, and was extubated. He was found paraplegic below L2 with preserved sensation, with hypotonia and areflexia consistent with “spinal shock” or anterior spinal cord syndrome. MRI thoracic and lumbar spine showed a conus medullaris level spinal cord infarction. The patient was given IV steroids upon initial discovery of cord infarct. NLM search using “cardiac arrest” and “spinal cord infarction” revealed 57 results, with only 8 review articles. Risk factors include age, atherosclerotic disease, and intraaortic balloon pump placement. AoA (Artery of Adamkiewicz) anatomic variation along with existing atherosclerotic factors and low perfusion were also known risk factors. Conclusion: Acute paraplegia from anterior spinal cord infarction of the AoA territory after cardiac arrest is rare. Larger prospective, multicenter trials are needed to examine potential interventions of hypothermia, lumbar drains, which are sometimes used in aortic surgery to reduce ischemia and/or other neuroprotectants.

Keywords: cardiac arrest, spinal cord infarction, artery of Adamkiewicz, paraplegia

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Authors: Koteswara Rao Pagolu, Raghava Rao Tamanam

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The present study was aimed to find out the prevalence of DD's in Visakhapatnam, one of the north coastal districts of Andhra Pradesh, India during a span of five years. A cross-sectional investigation was held at District early intervention center (DEIC), Visakhapatnam from 2016 to 2020. To identify the pattern and trend of different DD's including seasonal variations, a retrospective analysis of the health center's inpatient database for the past 5 years was done. Male and female children aged 2 months-18 years are included in the study with the prior permission of the concerned medical officer. The screening tool developed by the Ministry of health and family welfare, India, was used for the study. Among 26,423 cases, children with birth defects are 962, 2229 with deficiencies, 7516 with diseases, and 15716 with disabilities were admitted during the study period. From birth defects, congenital deafness occurred in large numbers with 22.66%, and neural tube defect observed in a small number of cases with 0.83% during the period. From the side of deficiencies, severe acute malnutrition has mostly occurred (66.80 %) and a small number of children were affected with goiter (1.70%). Among the diseases, dental carriers (67.97%) are mostly found and these cases were at peak during the years 2016 and 2019. From disabilities, children with vision impairment (20.55%) have mostly approached the center. Over the past 5 years, the admission rate of down's syndrome and congenital deafness cases showed a rising trend up to 2019 and then declined. Hearing impairment, motor delay, and learning disorder showed a steep rise and gradual decline trend, whereas severe anemia, vitamin-D deficiency, otitis media, reactive airway disease, and attention deficit hyperactivity disorder showed a declining trend. However, congenital heart diseases, dental caries, and vision impairment admission rates showed a zigzag pattern over the past 5 years. This center had inadequate diagnostic facilities related to genetic disease management. For advanced confirmation, the cases are referred to a district government hospital or private diagnostic laboratories in the city for genetic tests. Information regarding the overall burden and pattern of admissions in the health center is obtained by the review of DEIC records. Through this study, it is observed that the incidence of birth defects, as well as genetic disease burden, is high in the Visakhapatnam district. Hence there is a need for strengthening of management services for these diseases in this region.

Keywords: child health screening, developmental delays, district early intervention center, genetic disease management, infrastructural facility, Visakhapatnam district

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Authors: Farrah Putri Salmanida, Mei-Li Wu, Rika Wahyuningtyas, Wen-Bin Chung, Hso-Chi Chaung, Ko-Tung Chang

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Within the field of immunotherapy, oncolytic virotherapy (OVT) employs dual approaches that directly eliminate tumor cells while preserving healthy ones and indirectly reprogram the tumor microenvironment (TME) to elicit antitumor responses. Within the TME, tumor associated macrophages (TAMs) manifest characteristics akin to those of anti-inflammatory M2 macrophages, thus earning the designation of M2-like TAMs. In prior research, two antigens denoted as A1 (g6Ld10T) and A3 (ORF6L5), derived from a complete sequence of ORF5 with partial sequence of ORF6 in Porcine Reproductive and Respiratory Syndrome Virus Genotype 2 (PRRSV-2), demonstrated the capacity to repolarize M2-type porcine alveolar macrophages (PAMs) into M1 phenotypes. In this study, we sought for utilizing OVT strategies by introducing A1 or A3 on TAMs to endow them with the anti-tumor traits of M1 macrophages while retaining their capacity to target cancer cells. Upon exposing human THP-1-derived M2 macrophages to a cross-species test with 2 µg/ml of either A1 or A3 for 24 hours, real time PCR revealed that A3, but not A1, treated cells exhibited upregulated gene expressions of M1 markers (CCR7, IL-1ß, CCL2, Cox2, CD80). These cells reacted to virus-derived antigen, as evidenced by increased expression of pattern-recognition receptors TLR3, TLR7, and TLR9, subsequently providing feedback in the form of type I interferon responses like IFNAR1, IFN-ß, IRF3, IRF7, OAS1, Mx1, and ISG15. Through an MTT assay, only after 15 µg/ml of A3 treatment could the cell viability decrease, with a predicted IC50 of 16.96 µg/ml. Interestingly, A3 caused dose-dependent toxicity to a rat C6 glial cancer cell line even at doses as low as 2.5 µg/ml and reached its IC50 at 9.419 µg/ml. Using Annexin V/7AAD staining and PCR test, we deduced that a significant proportion of C6 cells were undergoing the early apoptosis phase predominantly through the intrinsic apoptosis cascade involving Bcl-2 family proteins. Following this stage, we conducted a test on A3’s repolarization ability, which revealed a significant rise in M1 gene expression markers, such as TNF, CD80, and IL-1ß, in M2-like TAMs generated in vitro from murine RAW264.7 macrophages grown with conditioned medium of 4T1 breast cancer cells. This was corroborated by the results of transcriptome analysis, which revealed that the primary subset among the top 10 to top 30 significantly upregulated differentially expressed genes (DEGs) dominantly consisted of M1 macrophages profiles, including Ccl3, Ccl4, Csf3, TNF, Bcl6b, Stc1, and Dusp2. Our findings unveiled the remarkable potential of the PRRSV-derived antigen A3 to repolarize macrophages while also being capable of selectively inducing apoptosis in cancerous cells. While further in vivo study is needed for A3, it holds promise as an adjuvant by its dual effects in cancer therapy modalities.

Keywords: cancer cell apoptosis, interferon responses, macrophage repolarization, recombinant protein

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Authors: Raj Chandran, Saul Datwyler, Jaime Marino, Daniel West, Karla Grasso, Adam Buss, Hina Syed, Zina Al Sahouri, Jennifer Yen, Krista Caudle, Beth McQuiston

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The Alinity i TBI test is Therapeutic Goods Administration (TGA) registered and is a panel of in vitro diagnostic chemiluminescent microparticle immunoassays for the measurement of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) in plasma and serum. The Alinity i TBI performance was evaluated in a multi-center pivotal study to demonstrate the capability to assist in determining the need for a CT scan of the head in adult subjects (age 18+) presenting with suspected mild TBI (traumatic brain injury) with a Glasgow Coma Scale score of 13 to 15. TBI has been recognized as an important cause of death and disability and is a growing public health problem. An estimated 69 million people globally experience a TBI annually1. Blood-based biomarkers such as glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) have shown utility to predict acute traumatic intracranial injury on head CT scans after TBI. A pivotal study using prospectively collected archived (frozen) plasma specimens was conducted to establish the clinical performance of the TBI test on the Alinity i system. The specimens were originally collected in a prospective, multi-center clinical study. Testing of the specimens was performed at three clinical sites in the United States. Performance characteristics such as detection limits, imprecision, linearity, measuring interval, expected values, and interferences were established following Clinical and Laboratory Standards Institute (CLSI) guidance. Of the 1899 mild TBI subjects, 120 had positive head CT scan results; 116 of the 120 specimens had a positive TBI interpretation (Sensitivity 96.7%; 95% CI: 91.7%, 98.7%). Of the 1779 subjects with negative CT scan results, 713 had a negative TBI interpretation (Specificity 40.1%; 95% CI: 37.8, 42.4). The negative predictive value (NPV) of the test was 99.4% (713/717, 95% CI: 98.6%, 99.8%). The analytical measuring interval (AMI) extends from the limit of quantitation (LoQ) to the upper LoQ and is determined by the range that demonstrates acceptable performance for linearity, imprecision, and bias. The AMI is 6.1 to 42,000 pg/mL for GFAP and 26.3 to 25,000 pg/mL for UCH-L1. Overall, within-laboratory imprecision (20 day) ranged from 3.7 to 5.9% CV for GFAP and 3.0 to 6.0% CV for UCH-L1, when including lot and instrument variances. The Alinity i TBI clinical performance results demonstrated high sensitivity and high NPV, supporting the utility to assist in determining the need for a head CT scan in subjects presenting to the emergency department with suspected mild TBI. The GFAP and UCH-L1 assays show robust analytical performance across a broad concentration range of GFAP and UCH-L1 and may serve as a valuable tool to help evaluate TBI patients across the spectrum of mild to severe injury.

Keywords: biomarker, diagnostic, neurology, TBI

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Authors: Dmitriy Babenko, Sergey Yegorov, Ilya Korshukov, Aidana Sultanbekova, Valentina Barkhanskaya, Tatiana Bashirova, Yerzhan Zhunusov, Yevgeniya Li, Viktoriya Parakhina, Svetlana Kolesnichenko, Yeldar Baiken, Aruzhan Pralieva, Zhibek Zhumadilova, Matthew S. Miller, Gonzalo H. Hortelano, Anar Turmuhambetova, Antonella E. Chesca, Irina Kadyrova

Abstract:

Introduction: The rapidly evolving COVID-19 pandemic, along with the re-emergence of pathogens causing acute respiratory infections (ARI), has necessitated the development of novel diagnostic tools to differentiate various causes of ARI. MALDI-MS, due to its wide usage and affordability, has been proposed as a potential instrument for diagnosing SARS-CoV-2 versus non-SARS-CoV-2 ARI. The aim of this study was to investigate the potential of MALDI-MS in conjunction with a machine learning model to accurately distinguish between symptomatic infections caused by SARS-CoV-2 and non-SARS-CoV-2 during both the early and later phases of the pandemic. Furthermore, this study aimed to analyze mass spectrometry (MS) data obtained from nasal swabs of healthy individuals. Methods: We gathered mass spectra from 252 samples, comprising 108 SARS-CoV-2-positive samples obtained in 2020 (Covid 2020), 7 SARS-CoV- 2-positive samples obtained in 2023 (Covid 2023), 71 samples from symptomatic individuals without SARS-CoV-2 (Control non-Covid ARVI), and 66 samples from healthy individuals (Control healthy). All the samples were subjected to RT-PCR testing. For data analysis, we employed the caret R package to train and test seven machine-learning algorithms: C5.0, KNN, NB, RF, SVM-L, SVM-R, and XGBoost. We conducted a training process using a five-fold (outer) nested repeated (five times) ten-fold (inner) cross-validation with a randomized stratified splitting approach. Results: In this study, we utilized the Covid 2020 dataset as a case group and the non-Covid ARVI dataset as a control group to train and test various machine learning (ML) models. Among these models, XGBoost and SVM-R demonstrated the highest performance, with accuracy values of 0.97 [0.93, 0.97] and 0.95 [0.95; 0.97], specificity values of 0.86 [0.71; 0.93] and 0.86 [0.79; 0.87], and sensitivity values of 0.984 [0.984; 1.000] and 1.000 [0.968; 1.000], respectively. When examining the Covid 2023 dataset, the Naive Bayes model achieved the highest classification accuracy of 43%, while XGBoost and SVM-R achieved accuracies of 14%. For the healthy control dataset, the accuracy of the models ranged from 0.27 [0.24; 0.32] for k-nearest neighbors to 0.44 [0.41; 0.45] for the Support Vector Machine with a radial basis function kernel. Conclusion: Therefore, ML models trained on MALDI MS of nasopharyngeal swabs obtained from patients with Covid during the initial phase of the pandemic, as well as symptomatic non-Covid individuals, showed excellent classification performance, which aligns with the results of previous studies. However, when applied to swabs from healthy individuals and a limited sample of patients with Covid in the late phase of the pandemic, ML models exhibited lower classification accuracy.

Keywords: SARS-CoV-2, MALDI-TOF MS, ML models, nasopharyngeal swabs, classification

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Authors: Horia Păunescu

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Purpose: The study aimed to assess the depressant or antidepressant effects of several Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in mice: the selective cyclooxygenase-2 (COX-2) inhibitor meloxicam, and the non-selective COX-1 and COX-2 inhibitors lornoxicam, sodium metamizole, and ketorolac. The current literature data regarding such effects of these agents are scarce. Materials and methods: The study was carried out on NMRI mice weighing 20-35 g, kept in a standard laboratory environment. The study was approved by the Ethics Committee of the University of Medicine and Pharmacy „Carol Davila”, Bucharest. The study agents were injected intraperitoneally, 10 mL/kg body weight (bw) 1 hour before the assessment of the locomotor activity by cage testing (n=10 mice/ group) and 2 hours before the forced swimming tests (n=15). The study agents were dissolved in normal saline (meloxicam, sodium metamizole), ethanol 11.8% v/v in normal saline (ketorolac), or water (lornoxicam), respectively. Negative and positive control agents were also given (amitryptilline in the forced swimming test). The cage floor used in the locomotor activity assessment was divided into 20 equal 10 cm squares. The forced swimming test involved partial immersion of the mice in cylinders (15/9cm height/diameter) filled with water (10 cm depth at 28C), where they were left for 6 minutes. The cage endpoint used in the locomotor activity assessment was the number of treaded squares. Four endpoints were used in the forced swimming test (immobility latency for the entire 6 minutes, and immobility, swimming, and climbing scores for the final 4 minutes of the swimming session), recorded by an observer that was "blinded" to the experimental design. The statistical analysis used the Levene test for variance homogeneity, ANOVA and post-hoc analysis as appropriate, Tukey or Tamhane tests.Results: No statistically significant increase or decrease in the number of treaded squares was seen in the locomotor activity assessment of any mice group. In the forced swimming test, amitryptilline showed an antidepressant effect in each experiment, at the 10 mg/kg bw dosage. Sodium metamizole was depressant at 100 mg/kg bw (increased the immobility score, p=0.049, Tamhane test), but not in lower dosages as well (25 and 50 mg/kg bw). Ketorolac showed an antidepressant effect at the intermediate dosage of 5 mg/kg bw, but not so in the dosages of 2.5 and 10 mg/kg bw, respectively (increased the swimming score, p=0.012, Tamhane test). Meloxicam and lornoxicam did not alter the forced swimming endpoints at any dosage level. Discussion: 1) Certain NSAIDs caused changes in the forced swimming patterns without interfering with locomotion. 2) Sodium metamizole showed a depressant effect, whereas ketorolac proved antidepressant. Conclusion: NSAID-induced mood changes are not class effects of these agents and apparently are independent of the type of inhibited cyclooxygenase (COX-1 or COX-2). Disclosure: This paper was co-financed from the European Social Fund, through the Sectorial Operational Programme Human Resources Development 2007-2013, project number POSDRU /159 /1.5 /S /138907 "Excellence in scientific interdisciplinary research, doctoral and postdoctoral, in the economic, social and medical fields -EXCELIS", coordinator The Bucharest University of Economic Studies.

Keywords: antidepressant, depressant, forced swim, NSAIDs

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