Search results for: clinical symptoms

Authors: R. Raudonis, L. Raudonė, V. Janulis, P. Viškelis

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Pharmacological and clinical studies demonstrated that phenolic compounds particularly flavonoids and phenolic acids are responsible for a wide spectrum of therapeutic activities. Flavonoids and phenolic acids are regarded as natural antioxidants that play an important role in protecting cells from oxidative stress. Qualitatively prepared dry extracts possess high stability and concentration of bio active compounds, facility of standardization and quality control. The aim of this work was to determine the phenolic and antioxidant profiles of Hippophaë rhamnoides L., Betula pendula Roth., Tilia cordata Mill., Sorbus aucuparia L. leaves dry extracts and to identify markers of antioxidant activity. Extracts were analyzed using high-performance liquid chromatography (HPLC) with FRAP post-column assay. Dry extracts are versatile forms possessing wide area of applications, final product ensure consistent phytochemical and functional properties. Seven flavonoids: rutin, hyperoside, isorhamnetin 3-O-rutinoside, isorhamnetin 3-O-glucoside, quercetin, kaempferol, isorhamnetin were identified in dry extract of Hippophaë rhamnoides L. leaves. Predominant compounds were flavonol glycosides which were chosen as markers for quantitative control of dry extracts. Chlorogenic acid, hyperoside, rutin, quercetin, isorhamnetin were prevailing compounds in Betula pendula Roth. leaves extract, whereas strongest ferric reducing activity was determined for chlorogenic acid and hyperoside. Notable amounts of protocatechuic acid and flavonol glycosides, rutin, hyperoside, quercitrin, isoquercitrin were identified in the chromatographic profile of Tilia cordata Mill. Neochlorogenic and chlorogenic acids were significantly dominant compounds in antioxidant profile in dry extract of Sorbus aucuparia L. leaves. Predominant compounds of antioxidant profiles could be proposed as functional markers of quality of phenolic rich raw materials. Dry extracts could be further used for manufacturing of pharmaceutical and nutraceuticals.

Keywords: dry extract, FRAP, antioxidant activity, phenolic

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Authors: Grace McCambridge, Alanna Keady, Madhur Agrawal, Dequina Nicholas Alvarado, Barbara Nikolajczyk, Leena Panneerseelan-Bharath

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Age is a non-modifiable risk factor for the inflammation that underlies pathologies such as type 2 diabetes mellitus (T2DM). Inflammation, as indicated by circulating cytokines, rises in aging, but mechanisms that promote this ‘inflammaging’ remain poorly defined. Furthermore, downstream consequences of inflammaging, including the development of an inflammatory profile that predicts comorbidities like T2DM, remain speculative. We tested the possibility that natural aging-associated changes in autophagy, a process that is compromised in both aging and T2DM, regulates inflammatory profiles in older subjects. Our data showed that circulating CD4⁺ T cells from older compared to younger subjects have (i) defects in autophagy; (ii) higher mitochondria accumulation; (iii) a failure to metabolically shift from oxidative phosphorylation to anaerobic glycolysis upon αCD3/CD28 activation; (iv) more reactive oxygen species (ROS) accumulation; and (v) a cytokine profile that recapitulates the Th17 profile that predicts T2DM. ROS scavenging in cells from older subjects restored mitochondrial mass and membrane potential (indicators of improved autophagy) and reduced Th17 cytokines to amounts made by T cells from younger subjects. Knock-down of the autophagy protein Atg3 in T cells from younger subjects increased mitochondrial accumulation and Th17 cytokines. To begin translating these findings to clinical practice, we showed that physiological concentrations of the diabetes drug metformin (100 µM) added in vitro enhanced autophagy, prevented mitochondria and ROS accumulation, increased anaerobic glycolysis, and decreased Th17 cytokines in activated CD4⁺ T cells from older subjects. Metformin therefore improves autophagy and multiple downstream pro-inflammatory mechanisms CD4⁺ T cells from older subjects. We conclude that autophagy improvement ameliorates the development of a T2DM-predictive Th17 profile in aging, and thus holds promise for delay or prevention of aging-associated metabolic decline.

Keywords: autophagy, mitochondrial turnover, ROS, glycolysis

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Authors: Amadou Wurry Jallow, Adama N. S. Bah, Karamo Bah, Shih-Ye Wang, Kuo-Chung Chu, Chien-Yeh Hsu

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Chronic kidney disease (CKD) is a major public health challenge with high prevalence, rising incidence, and serious adverse consequences. Developing effective risk prediction models is a cost-effective approach to predicting and preventing complications of chronic kidney disease (CKD). This study aimed to develop an accurate machine learning model that can dynamically identify individuals at risk of CKD using various kinds of diagnostic data, with or without laboratory data, at different follow-up points. Creatinine is a key component used to predict CKD. These models will enable affordable and effective screening for CKD even with incomplete patient data, such as the absence of creatinine testing. This retrospective cohort study included data on 19,429 adults provided by a private research institute and screening laboratory in Taiwan, gathered between 2001 and 2015. Univariate Cox proportional hazard regression analyses were performed to determine the variables with high prognostic values for predicting CKD. We then identified interacting variables and grouped them according to diagnostic data categories. Our models used three types of data gathered at three points in time: non-laboratory, laboratory, and metabolic indices data. Next, we used subgroups of variables within each category to train two machine learning models (Random Forest and XGBoost). Our machine learning models can dynamically discriminate individuals at risk for developing CKD. All the models performed well using all three kinds of data, with or without laboratory data. Using only non-laboratory-based data (such as age, sex, body mass index (BMI), and waist circumference), both models predict chronic kidney disease as accurately as models using laboratory and metabolic indices data. Our machine learning models have demonstrated the use of different categories of diagnostic data for CKD prediction, with or without laboratory data. The machine learning models are simple to use and flexible because they work even with incomplete data and can be applied in any clinical setting, including settings where laboratory data is difficult to obtain.

Keywords: chronic kidney disease, glomerular filtration rate, creatinine, novel metabolic indices, machine learning, risk prediction

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Authors: Syeda Hira, Muhammad Gulfraz

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Background: Liver diseases cause serious health issues. Plants contain active compounds that significantly help in the treatment of various diseases. Ficus carica is traditionally used for the treatment of liver diseases. The purpose of the present study was the isolation and identification of active components from F.carica leaves which are responsible for hepatoprotective activity. Methods: The study was designed to identify the most active hepatoprotective sub-fraction from ethyl acetate fraction of Ficus carica by in vitro study and evaluation of its in vivo hepatoprotective effect in animal models. Ethyl acetate fraction was subjected to column, and a total of eight sub-fractions were obtained. In vitro, the hepatoprotective effect of all sub-fractions was determined on HepG2 cell lines. Toxicity was induced by CCl₄ (Carbon tetrachloride), and silymarin was used as a positive control. On the basis of the results, the most active sub-fraction was subjected to LC-MS and FT-IR analysis for the identification of bioactive compounds. In vivo, the hepatoprotective effect was determined in mice. Toxicity was induced by CCl₄; at the end of the experiment, biochemical parameters such as ALT, AST, ALP, bilirubin, and total protein were estimated in serum. Histopathology of liver tissues was also done. Results: Sub-fraction FVI exhibited significant (P<0.05) hepatoprotective activity as compared to other sub-fractions, which was almost similar to the standard drug silymarin. Six known bioactive compounds were identified from this sub-fraction after LC-MS analysis. In vivo, the hepatoprotective activity of sub-fraction FVI was evaluated in CCl₄-induced toxicated mice. Administration of CCl₄ significantly increased level of ALT (Alanine transaminase), AST (Aspartate aminotransferase), ALP (Alkaline phosphatase), and bilirubin and decreased the total protein. Treatment with sub-fraction FVI significantly (p<0.05) reversed the level of these biomarkers toward normal at both doses of 25 mg/kg and 50 mg/kg. Conclusion: Our findings confirmed the hepatoprotective effect of ethyl acetate fraction of F.carica. It could be a good candidate for the development of a natural hepatoprotective drug; pre-clinical investigation on ethyl acetate fraction is recommended.

Keywords: Ficus carica, hepatoprotective, CCl₄, bioactive compounds, liver markers

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Authors: F. Polito, M. Cucinotta, A. Conti, C. Lo Giudice, C. Tomasello, F. Angileri, D. La Torre, M. Aguennouz

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Glioblastoma multiforme (GBM) is the most aggressive form of brain tumors, with an extremely poor prognosis. Telomeres lenght is associated with tumor progression in several type of human cancers and telomere elongation is a common molecular feature of advanced malignancies. Among the telomeric shelterin proteins PTOP is required for telomeric protein complex assembly, telomerase recruitment and activity, and telomere length regulation through a PTOP-telomerase interaction. Previous studies suggest that PTOP upregulation is involved in radioresistance and telomere lengthening in colorectal cancer cells. Moreover, in human osteosarcoma cells PTOP deletion led to telomere shortening, increased apoptosis and radiation sensitivity enhancement. However, to date, little is known about the role of PTOP in progression of glioma cancers. In light of this background aim of the study is to investigate the expression of PTOP in different grades of human glioma and its correlation with the pathological grade of gliomas, grades of malignancy, proliferative activity and apoptosis. Fifteen Low Grade Astrocytomas (LGA), 18 Anaplastic Astrocytomas (AA) and 26 Glioblastoma Multiforme (GBM) samples were analyzed. Three samples of normal brain tissue (NBT) were used as controls. The expression levels of PTOP, h-TERT, BIRC1 and cyclin D1 were determined by real time PCR and/or western blot. Results obtained shows that PTOP expression in glioma tissues is tightly correlated with clinical grade ( p < 0.01 ). No correlation was found between PTOP expression and other clinicopathologic parameters. The expression of PTOP was positively correlated with the expression of hTERT and TERF1. Furthermore PTOP positively correlates with cyclin D1 and negatively correlates with the expression of BIRC1. Our findings indicate that PTOP might play key role in the progression of glioma regulating telomerase activity and likely through regulation of cell cycle and apoptosis. In conclusion results obtained prompted us to speculate that PTOP might represents a potential molecular bio marker and a therapeutic target for the treatment of glioblastoma tumors.

Keywords: glioblastoma, PTOP, telomere, brain tumors

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Authors: Michelle R. Sullivan

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Positive romantic relationships and marriages offer a buffer against a host of physical and emotional difficulties. Conversely, poor relationship quality and marital discord can have deleterious consequences for individuals and families. Research has described non-monogamy, infidelity, and consensual non-monogamy, as both consequential and causal of relationship difficulty, or as a unique way a couple strives to make a relationship work. Much research on consensual non-monogamy has built on feminist theory and critique. To the author’s best knowledge, to date, no studies have examined the predictive relationship between individual and relationship characteristics and expectations of non-monogamy. The current longitudinal study: 1) estimated the prevalence of expectations of partner non-monogamy and 2) evaluated whether gender, sexual identity, age, education, how a couple met, and relationship quality were predictive expectations of partner non-monogamy. This study utilized the publically available longitudinal dataset, How Couples Meet and Stay Together. Adults aged 18- to 98-years old (n=4002) were surveyed by phone over 5 waves from 2009-2014. Demographics and how a couple met were gathered through self-report in Wave 1, and relationship quality and expectations of partner non-monogamy were gathered through self-report in Waves 4 and 5 (n=1047). The prevalence of expectations of partner non-monogamy (encompassing both infidelity and consensual non-monogamy) was 4.8%. Logistic regression models indicated that sexual identity, gender, education, and relationship quality were significantly predictive of expectations of partner non-monogamy. Specifically, male gender, lower education, identifying as lesbian, gay, or bisexual, and a lower relationship quality scores were predictive of expectations of partner non-monogamy. Male gender was not predictive of expectations of partner non-monogamy in the follow up logistic regression model. Age and whether a couple met online were not associated with expectations of partner non-monogamy. Clinical implications include awareness of the increased likelihood of lesbian, gay, and bisexual individuals to have an expectation of non-monogamy and the sequelae of relationship dissatisfaction that may be related. Future research directions could differentiate between non-monogamy subtypes and the person and relationship variables that lead to the likelihood of consensual non-monogamy and infidelity as separate constructs, as well as explore the relationship between predicting partner behavior and actual partner behavioral outcomes.

Keywords: open relationship, polyamory, infidelity, relationship satisfaction

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Authors: Hung-Chieh Chen, Kuo-Hui Wang, Tsu-Lin Yeh

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Proteomics represent the performance of genomic complement proteins and the protein level on functional genomics. This study adopted proteomic strategies for comparing serum proteins among three groups: elite sprinter (sprint runner group, SR), long-distance runners (long-distance runner group, LDR), and the untrained control group (control group, CON). Purposes: This study aims to identify elite sprinters and long-distance runners’ serum protein and to provide a comparison of their serum proteome’ composition. Methods: Serum protein fractionations that separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and analyzed by a quantitative nano-LC-MS/MS-based proteomic profiling. The one-way analysis of variance (ANOVA) and Scheffe post hoc comparison (α= 0.05) was used to determine whether there is any significant difference in each protein level among the three groups. Results: (1) After analyzing the 307 identified proteins, there were 26 unique proteins in the SR group, and 18 unique proteins in the LDR group. (2) For the LDR group, 7 coagulation function-associated proteins’ expression levels were investigated: vitronectin, serum paraoxonase/arylesterase 1, fibulin-1, complement C3, vitamin K-dependent protein, inter-alpha-trypsin inhibitor heavy chain H3 and von Willebrand factor, and the findings show the seven coagulation function-associated proteins were significantly lower than the group of SR. (3) Comparing to the group of SR, this study found that the LDR group’s expression levels of the 2 antioxidant proteins (afamin and glutathione peroxidase 3) were also significantly lower. (4) The LDR group’s expression levels of seven immune function-related proteins (Ig gamma-3 chain C region, Ig lambda-like polypeptide 5, clusterin, complement C1s subcomponent, complement factor B, complement C4-A, complement C1q subcomponent subunit A) were also significantly lower than the group of SR. Conclusion: This study identified the potential serum protein markers for elite sprinters and long-distance runners. The changes in the regulation of coagulation, antioxidant, or immune function-specific proteins may also provide further clinical applications for these two different track athletes.

Keywords: biomarkers, coagulation, immune response, oxidative stress

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Authors: Peggy M. Randon, Lisa Randon

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Introduction: The post-COVID-19 era has presented unique challenges for addressing complex mental health issues, particularly due to exacerbated stress, increased social isolation, and disrupted continuity of care. This article outlines relevant health disparities and policy implications within the context of the United States while maintaining international relevance. Methods: A comprehensive literature review (including studies, reports, and policy documents) was conducted to examine concerns related to childhood-onset schizophrenia and the impact on patients and their families. Qualitative and quantitative data were synthesized to provide insights into the complex etiology of schizophrenia, the effects of the pandemic, and the challenges faced by socioeconomically disadvantaged populations. Case studies were employed to illustrate real-world examples and areas requiring policy reform. Results: Early intervention in childhood is crucial for preventing or mitigating the long-term impact of complex psychotic disorders, particularly schizophrenia. A comprehensive understanding of the genetic, environmental, and physiological factors contributing to the development of schizophrenia is essential. The COVID-19 pandemic worsened symptoms and disrupted treatment for many adolescent patients with schizophrenia, emphasizing the need for adaptive interventions and the utilization of virtual platforms. Health disparities, including stigma, financial constraints, and language or cultural barriers, further limit access to care, especially for socioeconomically disadvantaged populations. Policy implications: Current US health policies inadequately support patients with schizophrenia. The limited availability of longitudinal care, insufficient resources for families, and stigmatization represent ongoing policy challenges. Addressing these issues necessitates increased research funding, improved access to affordable treatment plans, and cultural competency training for healthcare providers. Public awareness campaigns are crucial to promote knowledge, awareness, and acceptance of mental health disorders. Conclusion: The unique challenges faced by children and families in the US affected by schizophrenia and other psychotic disorders have yet to be adequately addressed on institutional and systemic levels. The relevance of findings to an international audience is emphasized by examining the complex factors contributing to the onset of psychotic disorders and their global policy implications. The broad impact of the COVID-19 pandemic on mental health underscores the need for adaptive interventions and global responses. Addressing policy challenges, improving access to care, and reducing the stigma associated with mental health disorders are crucial steps toward enhancing the lives of adolescents and young adults with schizophrenia and their family members. The implementation of virtual platforms can help overcome barriers and ensure equitable access to support and resources for all patients, enabling them to lead healthy and fulfilling lives.

Keywords: childhood, schizophrenia, policy, United, States, health, disparities

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Authors: M. Yaqoob, C. S. O’Neill, S. Faraj, C. L. O’Neill

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This paper presents the preliminary findings from a study exploring nurse’s contributions to end of life decisions and to the care of dying patients in ICU units in the Kingdom of Bahrain. The process of dying is complex as medical clinicians are frequently unable to say with certainty when death will occur. It is generally accepted that end of life care begins when it is possible to know that death is imminent. Nurses do not make medical treatment decisions when caring for a dying patient. There are, however, many other types of decisions made when a patient is approaching the end of life and nurses are either formally or informally part of these decision making processes. This study explored nurses care practices at the end of life, in two ICU units in large hospitals in the Kingdom of Bahrain. The research design was a grounded theory approach. Ten nurses participated, six of whom were Bahraini nationals and four were Indian. A core category death avoidance talk was supported by three major subcategories, degrees of involvement in decision making; signalling and creating an awareness of death; care shifting from dying patients to family. Despite nurses asserting that they carried out the orders of doctors and had no role in decision making processes at end of life this study showed that there were degrees of nurse involvement. Doctors frequently discussed the patient’s clinical condition with nurses and also sought information regarding the family. Information about the family was of particular relevance if the doctor was considering a DNR order, which the nurses equated with dying. Families were not always informed when a DNR decision was made. When families were not informed the nurses engaged in sophisticated rituals signalling and creating awareness to family members that the death of their loved one was near. This process also involved a subtle shifting of care from the dying patient to the family. This seminar paper will focus particularly on how nurses signal and create an awareness of death in an ICU setting. The findings suggest that despite the avoidance of death talk in the ICU nurses indirectly convey and create an awareness that death is near to family members.

Keywords: decision making, dying patients, end of life, intensive care unit

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Authors: Kai Pai Huang

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Background: There are several types of plasma cell neoplasms including multiple myeloma, plasmacytoma, lymphoplasmacytic lymphoma, and monoclonal gammopathy of undetermined significance (MGUS) are found in our lab. Today, we want to compare with two cases using the method of capillary electrophoresis. Method: Serum is prepared and electrophoresis is performed at alkaline PH in a capillary using the Sebia® Capillary 2. Albumin and globulins are detected by the detector which is located in the cathode of the capillary and the signals are transformed to peaks. Serum was treated with beta-mercaptoethanol which reducing the polymerized immunoglobulin to monomer immunoglobulin to clarify two M-protein are secreted from the same plasma cell clone in bone marrow. Result: Case 1: A 78-year-old female presenting dysuria, oliguria and leg edema for several months. Laboratory data showed proteinuria, leukocytosis, results of high serum IgA and lambda light chain. A renal biopsy found amyloid fibrils in the glomerular mesangial area. Serum protein electrophoresis shows a major monoclonal peak in the β region and minor small peak in gamma region, and the immunotyping studies for serum showed two IgA/λ type. Case 2: A 55-year-old male presenting abdominal distension and low back pain for more than one month. Laboratory data showed T12 T8 compression fracture, results of high serum IgM and kappa light chain. Bone marrow aspiration showed the cells from the bone marrow are B cells with monotypic kappa chain expression. Bone marrow biopsy found this is lymphoplasmacytic lymphoma (Waldenstrom macroglobulin). Serum protein electrophoresis shows a monoclonal peak in the β region and the immunotyping studies for serum showed IgM/κ type. Conclusion: Plasma cell neoplasm can be diagnosed by many examinations. Among them, using capillary electrophoresis by a lab can separate several types of gammopathy and the quantification of a monoclonal peak can be used to evaluate the patients’ prognosis or treatment.

Keywords: plasma cell neoplasm, capillary electrophoresis, serum protein electrophoresis, immunotyping

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Authors: Suharni Mohamad Suharni Mohamad, Nurul Izzati Hamzan Nurul Izzati Hamzan, Norhayu Abdul Rahman Norhayu Abdul Rahman, Siti Suraiya Md Noor Siti Suraiya Md Noor

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Human papillomavirus (HPV) is an important risk factor for development of oral cancer. HPV16 is the most common type found in HPV-positive squamous cell carcinoma. In the present study, we established a real-time loop-mediated isothermal amplification (real-time LAMP) for detection of HPV16. A set of six primers was specially designed to recognize eight distinct sequences of HPV16-E6. Detection and quantification was achieved by real-time monitoring using a real-time turbidimeter based on threshold time required for turbidity in the LAMP reaction. LAMP reagents (MgSO4, dNTPs, Bst polymerase concentrations) and various incubation times and temperatures were optimized. The sensitivity was determined using 10-fold serial dilutions of HPV16 standard strain. The specificity of was evaluated using other HPV genotypes. The optimized method was established with specifically designed primers by real-time detection in approximately 30 min at 65°C. The limit of detection of HPV16 using the LAMP assay was 10 pg/ml that could be detected in 30 min. The LAMP assay was 10 times more sensitive than the conventional PCR in detecting HPV16. No cross-reactivity with other HPV genotypes was observed. This quantitative real-time LAMP assay may improve diagnostic potential for the detection and quantification of HPV16 in clinical samples and epidemiological studies due to its rapidity, simplicity, high sensitivity and specificity. This assay will be further evaluated with HPV DNAs of saliva from patients with oral squamous cell carcinoma. Acknowledgement: This study was financially supported by the ScienceFund Grant, Ministry of Science, Technology and Innovation (305/PPSG/6113219).

Keywords: Oral Squamous Cell Carcinoma (OSCC), Human Papillomavirus 16 (HPV16), Loop-Mediated Isothermal Amplification (LAMP), rapid detection

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Authors: Jolanta Uszko, Tomasz Wloch, Aneta Pirowska, Roman Nowobilski

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Introduction: Phantom phenomena are often reported by subjects who have undergone limb amputation. Mostly, patients feel the amputated part of the limb as if it was still attached to the body. Two types of phantom phenomena: painless (phantom sensation) and painful (phantom pain) were described. Triggers of phantom sensations and phantom pain, as well as fully effective treatment, have not been clearly described yet. Purpose: To assess the influence of psychosocial factors and some clinical conditions on the occurrence of phantom phenomena in amputee athletes. Subjects: 21 men (age: 31 years, SD = 7.5 years) after lower or upper extremity amputation, who regularly performed high-intensity sports (Amp Football Team Players) were included to the study. Method and equipment: In the research, the following method and tools were used: Questionnaire [Pirowska] adapted for athletes with disabilities, Numerical Rating Scale (NRS) - for phantom pain assessment, McGill Pain Assessment Questionnaire (short version), Beck's Depression Inventory (BDI), State Trait Anxiety Inventory (STAI): X-1 and X-2, shortened version of The World Health Organization Quality of Life (WHOQOLBREFF). Results: In the study group, the lower leg amputations with traumatic etiology were predominant. Phantom sensations were present in all subjects. Half of the respondents claimed to experience phantom sensations at least once a day, paroxysmally. There was a prevalence of phantom sensations characterized as incomplete, immobile limb. Phantom pain was reported by over 85% of respondents. The nature of phantom pain was frequently described as stabbing, squeezing, shooting, pulsing, tiring. There was a significant correlation between phantom pain intensity and anxiety, quality of life, depressive tendencies, perception of phantom pain as the obstacle in daily functioning and intensity of the limb pain before amputation. Conclusions: The etiology of phantom phenomena is complex. Psychological factors seem to have a significant influence on the intensity of the phantom pain. Particular attention should be paid to patients who complain about persistent limb pain before the amputation. These are patients with an increased risk of the phantom pain of relatively high intensity.

Keywords: amputation, phantom pain, phantom sensations, adaptive sports

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Authors: Boris Bajer, Andrea Havranova, Miroslav Vlcek, Richard Imrich, Adela Penesova

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Lifestyle interventions can prevent the deterioration of impaired glucose tolerance to manifest type 2 diabetes, and also prevent cardiovascular diseases, as it showed many studies (the Finnish Diabetes Prevention Study, Diabetes Prevention Program (DPP), . the China Da Qing Diabetes Prevention Study, etc.) Therefore the aim of our study was to compare the effect of intensified lifestyle intervention on cardiometabolic parameters. Methods: It is an ongoing randomized interventional clinical study (NCT02325804) focused on the reduction of body weight/fat. Intervention: hypocaloric diet (30% restriction of calories) and physical activity 150 minutes/week. Before and after 8 weeks of intervention all patients underwent complete medical examination (measurement of physical fitness, resting metabolic rate (RMR), body composition analysis, oral glucose tolerance test, parameters of lipid metabolism, and other cardiometabolic risk factors. Results: So far 39 patients finished the intervention. The average reduction of body weight was 6,8 + 4,9 kg (0-15 kg; p=0,0006), accompanied with significant reduction of body fat percentage (p ≤ 0,0001), amount of fat mass (p=0,03), waist circumference (p=0.02). Amount of lean mass and RMR remained unchanged. Heart rate (p=0,02), systolic and diastolic blood pressure was reduced (p=0,01 p=0,02 resp.) as well as insulin sensitivity was improved. Lipid parameters also changed - cholesterol, LDL decreased (p=0,05, p=0,04 resp.), while triglycerides showed tendency to decrease (p=0,055). Liver function improved, alanine aminotrasnferase (ALT) were reduced (p=0,01). Physical fitness significantly improved (as measure VO2 max (p=0,02). Conclusion: Results of our study are in line with previous results about the beneficial effect of intensive lifestyle changes on the reduction of cardiometabolic risk factors and improvement of liver function. Supported by grants APVV 15-0228; VEGA 2/0161/16

Keywords: obesity, weight loss, diet lipids, blood pressure, liver enzymes

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Authors: I-Hui Hsieh, Yu-Hsuan Hu

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The powerful effect of music is often associated with changes in physiological responses such as heart rate and respiration. Previous studies demonstrate that Mayer waves of blood pressure, the spontaneous rhythm occurring at 0.1 Hz, corresponds to a progressive crescendo of the musical phrase. However, music contain dynamic changes in temporal and spectral features. As such, it remains unclear which aspects of musical structures optimally affect synchronization of cardiovascular rhythms. This study investigates the independent contribution of spectral pattern, temporal pattern, and dissonance level on synchronization of cardiovascular rhythms. The regularity of acoustical patterns occurring at a periodic rhythm of 0.1 Hz is hypothesized to elicit the strongest coherence of cardiovascular rhythms. Music excerpts taken from twelve pieces of Western classical repertoire were modulated to contain varying degrees of pattern regularity of the acoustic envelope structure. Three levels of dissonance were manipulated by varying the harmonic structure of the accompanying chords. Electrocardiogram and photoplethysmography signals were recorded for 5 minutes of baseline and simultaneously while participants listen to music excerpts randomly presented over headphones in a sitting position. Participants were asked to indicate the pleasantness of each music excerpt by adjusting via a slider presented on screen. Analysis of the Fourier spectral power of blood pressure around 0.1 Hz showed a significant difference between music excerpts characterized by spectral and temporal pattern regularity compared to the same content in random pattern. Phase coherence between heart rate and blood pressure increased significantly during listening to spectrally-regular phrases compared to its matched control phrases. The degree of dissonance of the accompanying chord sequence correlated with level of coherence between heart rate and blood pressure. Results suggest that low-level auditory features of music can entrain coherence of autonomic physiological variables. These findings have potential implications for using music as a clinical and therapeutic intervention for regulating cardiovascular functions.

Keywords: cardiovascular rhythms, coherence, dissonance, pattern regularity

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Authors: Cenza Rhoda, Falone Sunda, Elvis Kidzeru, Nonhlanhla P. Khumalo, Afolake Arowolo

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Introduction: The human FAM111B gene mutations are associated with POIKTMP, a rare multi-organ fibrosing disease. Recent studies also reported the overexpression of FAM111B in specific cancers. However, the role of FAM111B in these pathologies, particularly fibrosarcoma, remains unknown. Materials and Methods: FAM111B RNA expression in some cancer cell lines was assessed in silico and validated in vitro in these cell lines and skin fibroblasts derived from the South African family member affected by POIKTMP with the heterozygous FAM111B gene mutation: NM_198947.4: c.1861T>G (p. Tyr621Asp or Y621D) by qPCR and western blot. The cellular function of FAM111B was also studied in HT1080 using various cell-based functional assays and a simple and cost-effective PCR-RFLP method for genotyping/screening FAM111B gene mutations described. Results: Expression studies showed upregulated FAM111B mRNA and protein in the cancer cells. High FAM111B expression with robust nuclear localization occurred in HT1080. Additionally, expression data and cell-based assays indicated that FAM111B led to the upregulation of cell migration and decreased cell apoptosis and cell proliferation modulation. FAM111B Y621D mutation showed similar effects on cell migration but minimal impact on cell apoptosis. FAM111B mRNA and protein expression were markedly downregulated (p ≤ 0.05) in the patient's skin-derived fibroblasts. Lastly, the PCR-RFLP method successfully genotyped FAM111B Y621D gene mutation. Discussion: FAM111B is a cancer-associated nuclear protein: Its modulation by mutations may enhance cell migration and proliferation and decrease apoptosis, as seen in cancers and POIKTMP/fibrosis, thus representing a viable therapeutic target in these disorders. Furthermore, the PCR-RFLP method could prove a valuable tool for FAM111B mutation validation or screening in resource-constrained laboratories.

Keywords: FAM111B, POIKTMP, cancer, fibrosis, PCR-RFLP

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Authors: Ammar Asma, Bouafia Nabiha, Ghammam Rim, Ezzi Olfa, Ben Cheikh Asma, Mahjoub Mohamed, Helali Radhia, Sma Nesrine, Chouchène Imed, Boussarsar Hamadi, Njah Mansour

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Background: Central venous catheter associated infections (CVC-AI) are among the serious hospital-acquired infections. The aims of this study are to determine the incidence of CVC-AI, and their risk factors among patients followed in a Tunisian medical intensive care unit (ICU). Materials / Methods: A prospective cohort study conducted between September 15th, 2015 and November 15th, 2016 in an 8-bed medical ICU including all patients admitted for more than 48h. CVC-AI were defined according to CDC of ATLANTA criteria. The enrollment was based on clinical and laboratory diagnosis of CVC-AI. For all subjects, age, sex, underlying diseases, SAPS II score, ICU length of stay, exposure to CVC (number of CVC placed, site of insertion and duration catheterization) were recorded. Risk factors were analyzed by conditional stepwise logistic regression. The p-value of < 0.05 was considered significant. Results: Among 192 eligible patients, 144 patients (75%) had a central venous catheter. Twenty-eight patients (19.4%) had developed CVC-AI with density rate incidence 20.02/1000 CVC-days. Among these infections, 60.7% (n=17) were systemic CVC-AI (with negative blood culture), and 35.7% (n=10) were bloodstream CVC-AI. The mean SAPS II of patients with CVC-AI was 32.76 14.48; their mean Charlson index was 1.77 1.55, their mean duration of catheterization was 15.46 10.81 days and the mean duration of one central line was 5.8+/-3.72 days. Gram-negative bacteria was determined in 53.5 % of CVC-AI (n= 15) dominated by multi-drug resistant Acinetobacter baumani (n=7). Staphylococci were isolated in 3 CVC-AI. Fourteen (50%) patients with CVC-AI died. Univariate analysis identified men (p=0.034), the referral from another hospital department (p=0.03), tobacco (p=0.006), duration of sedation (p=0.003) and the duration of catheterization (p=0), as possible risk factors of CVC-AI. Multivariate analysis showed that independent factors of CVC-AI were, male sex; OR= 5.73, IC 95% [2; 16.46], p=0.001, Ramsay score; OR= 1.57, IC 95% [1.036; 2.38], p=0.033, and duration of catheterization; OR=1.093, IC 95% [1.035; 1.15], p=0.001. Conclusion: In a monocenter cohort, CVC-AI had a high density and is associated with poor outcome. Identifying the risk factors is necessary to find solutions for this major health problem.

Keywords: central venous catheter associated infection, intensive care unit, prospective cohort studies, risk factors

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Authors: Inigo de Miguel Beriain

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Genetic data of deceased persons are of great interest for both biomedical research and clinical use. This is due to several reasons. On the one hand, many of our diseases have a genetic component; on the other hand, we share genes with a good part of our biological family. Therefore, it would be possible to improve our response considerably to these pathologies if we could use these data. Unfortunately, at the present moment, the status of data on the deceased is far from being satisfactorily resolved by the EU data protection regulation. Indeed, the General Data Protection Regulation has explicitly excluded these data from the category of personal data. This decision has given rise to a fragmented legal framework on this issue. Consequently, each EU member state offers very different solutions. For instance, Denmark considers the data as personal data of the deceased person for a set period of time while some others, such as Spain, do not consider this data as such, but have introduced some specifically focused regulations on this type of data and their access by relatives. This is an extremely dysfunctional scenario from multiple angles, not least of which is scientific cooperation at the EU level. This contribution attempts to outline a solution to this dilemma through an alternative proposal. Its main hypothesis is that, in reality, health data are, in a sense, a rara avis within data in general because they do not refer to one person but to several. Hence, it is possible to think that all of them can be considered data subjects (although not all of them can exercise the corresponding rights in the same way). When the person from whom the data were obtained dies, the data remain as personal data of his or her biological relatives. Hence, the general regime provided for in the GDPR may apply to them. As these are personal data, we could go back to thinking in terms of a general prohibition of data processing, with the exceptions provided for in Article 9.2 and on the legal bases included in Article 6. This may be complicated in practice, given that, since we are dealing with data that refer to several data subjects, it may be complex to refer to some of these bases, such as consent. Furthermore, there are theoretical arguments that may oppose this hypothesis. In this contribution, it is shown, however, that none of these objections is of sufficient substance to delegitimize the argument exposed. Therefore, the conclusion of this contribution is that we can indeed build a general framework on the processing of personal data of deceased persons in the context of the GDPR. This would constitute a considerable improvement over the current regulatory framework, although it is true that some clarifications will be necessary for its practical application.

Keywords: collective data conceptual issues, data from deceased people, genetic data protection issues, GDPR and deceased people

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Authors: Vidhya Venugopal, Jeremiah Chinnadurai, Rebekah A. I. Lucas, Tord Kjellstrom, Bruno Lemke

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Introduction: The effects of climate change (CC) are largely discussed across the globe in terms of impacts on the environment and the general population, but the impacts on workers remain largely unexplored. The predicted rise in temperatures and heat events in the CC scenario have health implications on millions of workers in physically exerting jobs. The current health and productivity risks associated with heat exposures are characterized, future risk estimates as temperature rises and recommendations towards developing protective and preventive occupational health and safety guidelines for India are discussed. Methodology: Cross-sectional studies were conducted in several occupational sectors with workers engaged in moderate to heavy labor (n=1580). Quantitative data on heat exposures (WBGT°C), physiological heat strain indicators viz., Core temperature (CBT), Urine specific gravity (USG), Sweat rate (SwR) and qualitative data on heat-related health symptoms and productivity losses were collected. Data were analyzed for associations between heat exposures, health and productivity outcomes related to heat stress. Findings: Heat conditions exceeded the Threshold Limit Value (TLV) for safe manual work in 66% of the workers across several sectors (Avg.WBGT of 28.7°C±3.1°C). Widespread concerns about heat-related health outcomes (86%) were prevalent among workers exposed to high TLVs, with excessive sweating, fatigue and tiredness being commonly reported by workers. The heat stress indicators, core temperature (14%), Sweat rate (8%) and USG (9%), were above normal levels in the study population. A significant association was found between rise in Core Temperatures and WBGT exposures (p=0.000179) Elevated USG and SwR in the worker population indicate moderate dehydration, with potential risks of developing heat-related illnesses. In a steel industry with high heat exposures, an alarming 9% prevalence of kidney/urogenital anomalies was observed in a young workforce. Heat exposures above TLVs were associated with significantly increased odds of various adverse health outcomes (OR=2.43, 95% CI 1.88 to 3.13, p-value = <0.0001) and productivity losses (OR=1.79, 95% CI 1.32 to 2.4, p-value = 0.0002). Rough estimates for the number of workers who would be subjected to higher than TLV levels in the various RCP scenarios are RCP2.6 =79%, RCP4.5 & RCP6 = 81% and at RCP 8.5 = 85%. Rising temperatures due to CC has the capacity to further reduce already compromised health and productivity by subjecting the workers to increased heat exposures in the RCP scenarios are of concern for the country’s occupational health and economy. Conclusion: The findings of this study clearly identify that health protection from hot weather will become increasingly necessary in the Indian subcontinent and understanding the various adaptation techniques needs urgent attention. Further research with a multi-targeted approach to develop strategies for implementing interventions to protect the millions of workers is imperative. Approaches to include health aspects of climate change within sectoral and climate change specific policies should be encouraged, via a number of mechanisms, such as the “Health in All Policies” approach to avert adverse health and productivity consequences as climate change proceeds.

Keywords: heat stress, occupational health, productivity loss, heat strain, adverse health outcomes

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Authors: Marjan Moradi fard, Hossein Rassi, Masoud Houshmand

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Aim: Breast cancer is one of the most common cancers affecting the morbidity and mortality of Iranian women. This disease is a result of collective alterations of oncogenes and tumor suppressor genes. Studies have produced conflicting results concerning the role of p53 codon 72 polymorphism (G>C) and miR-146a rs2910164 polymorphism (G>C) on the risk of several cancers; therefore, a research was performed to estimate the association between the p53 codon 72 polymorphism and miR-146a rs2910164 polymorphism in breast cancer. Methods and Materials: A total of 45 archival breast cancer samples from Khatam hospital and 40 healthy samples were collected. Verification of each cancer reported in a relative was sought through the pathology reports of the hospital records. Then, DNA extracted from all samples by standard methods and p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes were analyzed using multiplex PCR. The tubules, mitotic activity, necrosis, polymorphism and grade of breast cancer were staged by Nottingham histological grading and immunohistochemical staining of the sections from the paraffin wax embedded tissues for the expression of ER, PR and p53 was carried out using a standard method. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Successful DNA extraction was assessed by PCR amplification of b-actin gene (99 bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of breast cancer in the study population. In this study, we established that tumors of p53 GG genotype and miR-146a rs2910164 CC genotype exhibited higher mitotic activity, higher polymorphism, lower necrosis, lower tubules, higher ER- and PR-negatives and lower TP53-positives than the other genotypes. Conclusion: The present study provided preliminary evidence that a p53 GG genotype may effect breast cancer risk in the study population, interacting synergistically with miR-146a rs2910164 CC genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with clinical parameters can serve as major risk factors in the early identification of breast cancers.

Keywords: breast cancer, miR-146a rs2910164 polymorphism, p53 codon 72 polymorphism, tumors, pathology reports

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Authors: Mustafa M. Donma, Orkide Donma

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Metabolic syndrome (MetS) is a disease associated with obesity. It is a complicated clinical problem possibly affecting body composition as well as macrominerals. These parameters gain further attention, particularly in the pediatric population. The aim of this study is to investigate the amount of discrete body composition fractions in groups that differ in the severity of obesity. Also, the possible associations with calcium (Ca), phosphorus (P), magnesium (Mg) will be examined. The study population was divided into four groups. Twenty-eight, 29, 34, and 34 children were involved in Group 1 (healthy), 2 (obese), 3 (morbid obese), and 4 (MetS), respectively. Institutional Ethical Committee approved the study protocol. Informed consent forms were obtained from the participants. The classification of obese groups was performed based upon the recommendations of the World Health Organization. Metabolic syndrome components were defined. Serum Ca, P, Mg concentrations were measured. Within the scope of body composition, fat mass, fat-free mass, protein mass, mineral mass were determined by a body composition monitor using bioelectrical impedance analysis technology. Weight, height, waist circumference, hip circumference, head circumference, and neck circumference values were recorded. Body mass index, diagnostic obesity notation model assessment index, fat mass index, and fat-free mass index values were calculated. Data were statistically evaluated and interpreted. There was no statistically significant difference among the groups in terms of Ca and P concentrations. Magnesium concentrations differed between Group 1 and Group 4. Strong negative correlations were detected between P as well as Mg and fat mass index as well as diagnostic obesity notation model assessment index in Group 4, the group, which comprised morbid obese children with MetS. This study emphasized unique associations of P and Mg minerals with diagnostic obesity notation model assessment index and fat mass index during the evaluation of morbid obese children with MetS. It was also concluded that diagnostic obesity notation model assessment index and fat mass index were more proper indices in comparison with body mass index and fat-free mass index for the purpose of defining body composition in children.

Keywords: children, fat mass, fat-free mass, macrominerals, obesity

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Authors: Swarkar Sharma, Ekta Rai, Ankit Mahajan, Parvinder Kumar, Manoj K Dhar, Sushil Razdan, Kumarasamy Thangaraj, Carol Wise, Shiro Ikegawa M.D., K.K. Pandita M.D.

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Rare disorders are poorly understood hence, remain uncharacterized or patients are misdiagnosed and get poor medical attention. A rare mysterious skeletal disorder that remained unidentified for decades and rendered many people physically challenged and disabled for life has been reported in an isolated remote village ‘Arai’ of Poonch district of Jammu and Kashmir. This village is located deep in mountains and the population residing in the region is highly consanguineous. In our survey of the region, 70 affected people were reported, showing similar phenotype, in the village with a population of approximately 5000 individuals. We were able to collect samples from two multi generational extended families from the village. Through Whole Exome sequencing (WES), we identified a rare variation NM_003880.3:c.156C>A NP_003871.1:p.Cys52Ter, which results in introduction of premature stop codon in WISP3 gene. We found this variation perfectly segregating with the disease in one of the family. However, this variation was absent in other family. Interestingly, a novel splice site mutation at position c.643+1G>A of WISP3 gene, perfectly segregating with the disease was observed in the second family. Thus, exploiting WES and putting different evidences together (familial histories and genetic data, clinical features, radiological and biochemical tests and findings), the disease has finally been diagnosed as a very rare recessive hereditary skeletal disease “Progressive Pseudorheumatoid Arthropathy of Childhood” (PPAC) also known as “Spondyloepiphyseal Dysplasia Tarda with Progressive Arthropathy” (SEDT-PA). This genetic characterization and identification of the disease causing mutations will aid in genetic counseling, critically required to curb this rare disorder and to prevent its appearance in future generations in the population. Further, understanding of the role of WISP3 gene the biological pathways should help in developing treatment for the disorder.

Keywords: whole exome sequencing, Next Generation Sequencing, rare disorders

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Authors: Umamaheswari Shanmugam, Silvia Ronchi

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Software, artificial intelligence, and machine learning can improve healthcare through innovative and advanced technologies that can use the large amount and variety of data generated during healthcare services every day; one of the significant advantages of these new technologies is the ability to get experience and knowledge from real-world use and to improve their performance continuously. Healthcare systems and institutions can significantly benefit because the use of advanced technologies improves the efficiency and efficacy of healthcare. Software-defined as a medical device, is stand-alone software that is intended to be used for patients for one or more of these specific medical intended uses: - diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of a disease, any other health conditions, replacing or modifying any part of a physiological or pathological process–manage the received information from in vitro specimens derived from the human samples (body) and without principal main action of its principal intended use by pharmacological, immunological or metabolic definition. Software qualified as medical devices must comply with the general safety and performance requirements applicable to medical devices. These requirements are necessary to ensure high performance and quality and protect patients' safety. The evolution and the continuous improvement of software used in healthcare must consider the increase in regulatory requirements, which are becoming more complex in each market. The gap between these advanced technologies and the new regulations is the biggest challenge for medical device manufacturers. Regulatory requirements can be considered a market barrier, as they can delay or obstacle the device's approval. Still, they are necessary to ensure performance, quality, and safety. At the same time, they can be a business opportunity if the manufacturer can define the appropriate regulatory strategy in advance. The abstract will provide an overview of the current regulatory framework, the evolution of the international requirements, and the standards applicable to medical device software in the potential market all over the world.

Keywords: artificial intelligence, machine learning, SaMD, regulatory, clinical evaluation, classification, international requirements, MDR, 510k, PMA, IMDRF, cyber security, health care systems

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Authors: Ayman K. El Essawy, Amal M. Hosny, Hala M. Abu Shady

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The rapid detection of TB and drug resistance, both optimizes treatment and improves outcomes. In the current study, respiratory specimens were collected from 155 patients. Conventional susceptibility testing and MIC determination were performed for rifampicin (RIF) and isoniazid (INH). Genotype MTBDRplus assay, which is a molecular genetic assay based on the DNA-STRIP technology and specific gene sequencing with primers for rpoB, KatG, and mab-inhA genes were used to detect mutations associated with resistance to rifampicin and isoniazid. In comparison to other categories, most of rifampicin resistant (61.5%) and isoniazid resistant isolates (47.1%) were from patients relapsed in treatment. The genotypic profile (using Genotype MTBDRplus assay) of multi-drug resistant (MDR) isolates showed missing of katG wild type 1 (WT1) band and appearance of mutation band katG MUT2. For isoniazid mono-resistant isolates, 80% showed katG MUT1, 20% showed katG MUT1, and inhA MUT1, 20% showed only inhA MUT1. Accordingly, 100% of isoniazid resistant strains were detected by this assay. Out of 17 resistant strains, 16 had mutation bands for katG distinguished high resistance to isoniazid. The assay could clearly detect rifampicin resistance among 66.7% of MDR isolates that showed mutation band rpoB MUT3 while 33.3% of them were considered as unknown. One mono-resistant rifampicin isolate did not show rifampicin mutation bands by Genotype MTBDRplus assay, but it showed an unexpected mutation in Codon 531 of rpoB by DNA sequence analysis. Rifampicin resistance in this strain could be associated with a mutation in codon 531 of rpoB (based on molecular sequencing), and Genotype MTBDRplus assay could not detect the associated mutation. If the results of Genotype MTBDRplus assay and sequencing were combined, this strain shows hetero-resistance pattern. Gene sequencing of eight selected isolates, previously tested by Genotype MTBDRplus assay, could detect resistance mutations mainly in codon 315 (katG gene), position -15 in inhA promotes gene for isoniazid resistance and codon 531 (rpoB gene) for rifampicin resistance. Genotyping techniques allow distinguishing between recurrent cases of reinfection or reactivation and supports epidemiological studies.

Keywords: M. tuberculosis, rpoB, KatG, inhA, genotype MTBDRplus

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Authors: Sena Park

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Background: The concurrent presentation with colorectal cancer in the inguinal hernia has been extremely rare. Due to its rarity, its presentation may lead to diagnostic and therapeutic dilemmas. We aim to review all the reported cases on colorectal cancer incarcerated in the inguinal hernia in the last 20 years, and discuss the operative approaches. Methods: We identified all case reports on colorectal cancer within inguinal hernia using PUBMED (2002-2022) and MEDLINE (2002-2022). The search strategy included the following keywords: colorectal cancer (title/abstract) AND inguinal hernia (title/abstract) OR incarceration (title/abstract). The search did not include letters, book chapters, systemic reviews, meta-analysis and editorials. Results: In the last 20 years, a total of 19 cases on colorectal cancer within the inguinal hernia were identified. The age of the patients ranged between 48 and 89. Majority of the patients were male (95%). Most commonly involved part of the large intestine was sigmoid colon (79%). Of all the cases, 79 percent of patients received open procedure and 21 percent had laparoscopic procedure. Discussion: Inguinal hernias are common with an incidence of approximately 1.7 percent. Colorectal cancer is the one of the leading causes of cancer-related mortality worldwide. However, their concurrent presentation has been extremely rare. In the last 20 years, 19 cases on concurrent presentation of colorectal cancer and inguinal hernia have been reported. Most patients who had open procedures had two incisions of groin incision and a midline laparotomy. There were 4 cases where the oncological resection was performed laparoscopically. The advantages of laparoscopic resection include reduced blood lost, reduced post-operative pain, reduced length of hospital stay and similar number of lymph nodes taken. From the review of the cases in the last 20 years, both open and laparoscopic approaches seemed to be safe and achieve adequate oncological resections. Conclusion: This is a brief overview of reported cases of colorectal cancer presenting with inguinal hernia concurrently. Due to its rarity, there are no current guidelines on operative approach in clinical practice. The experience in the last 20 years supports both open and laparoscopic approach.

Keywords: colorectal cancer, inguinal hernia, incarceration, operative approach

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Authors: Recep Kesli, Gulsah Asik, Cengiz Demir, Onur Turkyilmaz

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Objective: Stenotrophomonas maltophilia (S. maltophilia) has recently emerged as an important nosocomial microorganism. Treatment of invasive infections caused by this organism is problematic because this microorganism is usually resistant to a wide range of commonly used antimicrobials. We aimed to evaluate clinical isolates of S. maltophilia in respect to sampling sites and antimicrobial resistant. Method: During a two years period (October 2013 and September 2015) eighteen samples collected from the intensive care unit (ICU) patients hospitalized in Afyon Kocatepe University, ANS Practice and Research Hospital. Identification of the bacteria was determined by conventional methods and automated identification system-VITEK 2 (bio-Mérieux, Marcy l’toile, France). Antibacterial resistance tests were performed by Kirby Bauer disc (Oxoid, England) diffusion method following the recommendations of CLSI. Results: Eighteen S. maltophilia strains were identified as the causative agents of different infections. The main type of infection was lower respiratory tract infection (83,4 %); three patients (16,6 %) had bloodstream infection. While, none of the 18 S. maltophilia strains were found to be resistant against to trimethoprim sulfametaxasole (TMP-SXT) and levofloxacine, eight strains 66.6 % were found to be resistant against ceftazidim. Conclusion: The isolation of S.maltophilia starains resistant to TMP-SXT is vital. In order to prevent or minimize infections due to S. maltophilia such precuations should be utilized: Avoidance of inappropriate antibiotic use, prolonged implementation of foreign devices, reinforcement of hand hygiene practices and the application of appropriate infection control practices. Microbiology laboratories also may play important roles in controlling S. maltophilia infections by monitoring the prevalence, continuously, the provision of local antibiotic resistance paterns data and the performance of synergistic studies also may help to guide appropirate antimicrobial therapy choices.

Keywords: Stenotrophomonas maltophilia, trimethoprim-sulfamethoxazole, antimicrobial resistance, Stenotrophomonas spp.

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Authors: Reema K. AlEssa, Sahar Alshomer, Abdullah Alfaleh, Sultan ALkhenaizan, Mohammed Albalwi

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Ichthyosis is a disorder of abnormal keratinization, characterized by excessive scaling, and consists of more than twenty subtypes varied in severity, mode of inheritance, and the genes involved. There is insufficient data in the literature about the epidemiology and characteristics of ichthyosis locally. Our aim is to identify the histopathological features and genetic profile of ichthyosis. Method: It is an observational retrospective case series study conducted in March 2020, included all patients who were diagnosed with Ichthyosis and confirmed by histological and molecular findings over the last 20 years in King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. Molecular analysis was performed by testing genomic DNA and checking genetic variations using the AmpliSeq panel. All disease-causing variants were checked against HGMD, ClinVar, Genome Aggregation Database (gnomAD), and Exome Aggregation Consortium (ExAC) databases. Result: A total of 60 cases of Ichthyosis were identified with a mean age of 13 ± 9.2. There is an almost equal distribution between female patients 29 (48%) and males 31 (52%). The majority of them were Saudis, 94%. More than half of patients presented with general scaling 33 (55%), followed by dryness and coarse skin 19 (31.6%) and hyperlinearity 5 (8.33%). Family history and history of consanguinity were seen in 26 (43.3% ), 13 (22%), respectively. History of colloidal babies was found in 6 (10%) cases of ichthyosis. The most frequent genes were ALOX12B, ALOXE3, CERS3, CYP4F22, DOLK, FLG2, GJB2, PNPLA1, SLC27A4, SPINK5, STS, SUMF1, TGM1, TGM5, VPS33B. Most frequent variations were detected in CYP4F22 in 16 cases (26.6%) followed by ALOXE3 6 (10%) and STS 6 (10%) then TGM1 5 (8.3) and ALOX12B 5 (8.3). The analysis of molecular genetic identified 23 different genetic variations in the genes of ichthyosis, of which 13 were novel mutations. Homozygous mutations were detected in the majority of ichthyosis cases, 54 (90%), and only 1 case was heterozygous. Few cases, 4 (6.6%) had an unknown type of ichthyosis with a negative genetic result. Conclusion: 13 novel mutations were discovered. Also, about half of ichthyosis patients had a positive history of consanguinity.

Keywords: ichthyosis, genetic profile, molecular characterization, congenital ichthyosis

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Authors: Uliana N. Tumanova, Viacheslav M. Lyapin, Vladimir G. Bychenko, Alexandr I. Shchegolev, Gennady T. Sukhikh

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It is well known that the gas formed as a result of postmortem decomposition of tissues can be detected already 24-48 hours after death. In addition, the conditions of keeping and storage of the corpse (temperature and humidity of the environment) significantly determine the rate of occurrence and development of posthumous changes. The presence of sepsis is accompanied by faster postmortem decomposition and decay of the organs and tissues of the body. The presence of gas in the vessels and cavities can be revealed fully at postmortem CT. Radiologists must certainly report on the detection of intraorganic or intravascular gas, wich was detected at postmortem CT, to forensic experts or pathologists before the autopsy. This gas can not be detected during autopsy, but it can be very important for establishing a diagnosis. To explore the possibility of postmortem CT for the evaluation of gas accumulations in the newborns' vessels, who died from congenital sepsis. Researched of 44 newborns bodies (25 male and 19 female sex, at the age from 6 hours to 27 days) after 6 - 12 hours of death. The bodies were stored in the refrigerator at a temperature of +4°C in the supine position. Grouped 12 bodies of newborns that died from congenital sepsis. The control group consisted of 32 bodies of newborns that died without signs of sepsis. Postmortem CT examination was performed at the GEMINI TF TOF16 device, before the autopsy. The localizations of gas accumulations in the vessels were determined on the CT tomograms. The sepsis diagnosis was on the basis of clinical and laboratory data and autopsy results. Gases in the vessels were detected in 33.3% of cases in the group with sepsis, and in the control group - in 34.4%. A group with sepsis most often the gas localized in the heart and liver vessels - 50% each, of observations number with the detected gas in the vessels. In the heart cavities, aorta and mesenteric vessels - 25% each. In control most often gas was detected in the liver (63.6%) and abdominal cavity (54.5%) vessels. In 45.5% the gas localized in the cavities, and in 36.4% in the vessels of the heart. In the cerebral vessels and in the aorta gas was detected in 27.3% and 9.1%, respectively. Postmortem CT has high diagnostic capabilities to detect free gas in vessels. Postmortem changes in newborns that died from sepsis do not affect intravascular gas production within 6-12 hours. Radiation methods should be used as a supplement to the autopsy, including as a kind of ‘guide’, with the indication to the forensic medical expert of certain changes identified during CT studies, for better definition of pathological processes during the autopsy. Postmortem CT can be recommend as a first stage of autopsy.

Keywords: congenital sepsis, gas, newborn, postmortem CT

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Authors: Amany Ragab, Nashwa Khairat Abousamra, Omayma Saleh, Asmaa Higazy

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Insulin resistance syndrome has been shown to be associated with many coagulation and fibrinolytic proteins and these associations suggest that some coagulation and fibrinolytic proteins have a role in atherothrombotic disorders. This study was conducted to determine the levels of some of the haemostatic parameters in subjects having metabolic syndrome and to correlate these values with the anthropometric and metabolic variables associated with this syndrome. The study included 46 obese non diabetic subjects of whom 28 subjects(group1) fulfilled the ATP III criteria of the metabolic syndrome and 18 subjects (group2) did not have metabolic syndrome as well as 14 lean subjects (group 3) of matched age and sex as a control group. Clinical and laboratory evaluation of the study groups stressed on anthropometric measurements (weight, height, body mass index, waist circumference, and sagittal abdominal diameter), blood pressure, and laboratory measurements of fasting plasma glucose, fasting insulin, serum lipids, tissue plasminogen activator (t-PA), antithrombin III activity (ATIII), protein C and von Willebrand factor (vWf) antigen. There was significant increase in the concentrations of t-PA and vWf antigens in subjects having metabolic syndrome (group 1) in comparison to the other groups while there were non-significant changes in the levels of protein C antigen and AT III activity. Both t-PA and vWf showed significant correlation with HOMA-IR as a measure of insulin sensitivity. The t-PA showed also significant correlation with most of the variables of metabolic syndrome including waist circumference, BMI, systolic blood pressure, fasting plasma glucose, fasting insulin, and HDL cholesterol. On the other hand, vWf showed significant correlations with fasting plasma glucose, fasting insulin and sagital abdominal diameter, with non-significant correlations with the other variables. Haemostatic and fibrinolytic parameters should be included in the features and characterization of the insulin resistance syndrome. t-PA and vWf antigens concentrations were increased in subjects with metabolic syndrome and correlated with the HOMA-IR measure of insulin sensitivity. Taking into consideration that both t-PA and vWf are mainly released from vascular endothelium, these findings could be an indicator of endothelial dysfunction in that group of subjects.

Keywords: insulin resistance, obesity, metabolic syndrome, coagulation

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Authors: Elżbieta Turska

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Introduction: One of the most difficult times in a person’s life is adolescence. The experiences in this period may shape the future life of this person to a large extent. This is the reason why many young people experience sadness, dejection, hopelessness, sense of worthlessness, as well as losing interest in various activities and social relationships, all of which are often classified as mood disorders. As many as 15-40% adolescents experience depressed moods and for most of them they resolve and are not carried into adulthood. However, (5-6%) of those affected by mood disorders develop the depressive syndrome and as many as (1-3%) develop full-blown clinical depression. Materials: A large questionnaire was given to 2508 students, aged 13–16 years old, and one of its parts was the Burns checklist, i.e. the standard test for identifying depressed mood. The questionnaire asked about many aspects of the student’s life, it included a total of 53 questions, most of which had subquestions. It is important to note that the data suffered from many problems, the most important of which were missing data and collinearity. Aim: In order to identify the correlates of mood disorders we built predictive models which were then trained and validated. Our aim was not to be able to predict which students suffer from mood disorders but rather to explore the factors influencing mood disorders. Methods: The problems with data described above practically excluded using all classical statistical methods. For this reason, we attempted to use the following Artificial Intelligence (AI) methods: classification trees with surrogate variables, random forests and xgboost. All analyses were carried out with the use of the mlr package for the R programming language. Resuts: The predictive model built by classification trees algorithm outperformed the other algorithms by a large margin. As a result, we were able to rank the variables (questions and subquestions from the questionnaire) from the most to least influential as far as protection against mood disorder is concerned. Thirteen out of twenty most important variables reflect the relationships with parents. This seems to be a really significant result both from the cognitive point of view and also from the practical point of view, i.e. as far as interventions to correct mood disorders are concerned.

Keywords: mood disorders, adolescents, family, artificial intelligence

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Authors: Christopher S. Perez, Kendal C. Boyd

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global suicide rates have decreased in recent decades, rates in the United States have increased by 35.2 percent since 1999.American Indians and Alaska Natives (AI/AN) have the highest rates of suicide in the U.S., with approximately 22 suicides per 100,000 people as of 2019. AI/AN have experienced significant historical trauma resulting in disproportionate rates of substance abuse and mental disorders. This literature review aimed to identify the demographic and clinical risk and protective factors for American Indians and Alaska Natives and provide an overview of suicidality in this population. The literature reflected varying definitions of suicidality depending on region, with some AI/AN tribesconceptualizing suicide through a spiritual framework, while others defined suicide in the biomedical sense. Furthermore, AI/AN adults and adolescents experienced higher rates of suicidal ideation when compared to other racial groups. Religious preference, sexual orientation, prior suicidal behavior, psychiatric admission, history of abuse, substance abuse, family history of mental illness, family history of substance abuse, family history of suicidal behaviors, domestic violence, and trauma were discussed as factors related to suicidality. Recommendations included increasing access to and utilization of mental health and medical services, culturally adapting suicide prevention programs to AI/AN communities, increasing support for LGBTQ+ AI/AN, providing opportunities that reinforce ethnic identity, and post-hospitalization follow-up care. The following databases were utilized to obtain peer-reviewed articles for this literature review: Complementary Index, Academic Search Premier, Science Direct, PsycInfo, Social Sciences Citation Index, PsycArticles, PubMed, EbscoHost, and PsycBooks. Articles that examined Native populations outside of the United States did not cite a primary source and/or were published before 1990 were excluded.

Keywords: alaska native, american indian, protective factors, risk factors, suicidality, suicide

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