Search results for: mitochondrial disorders

Authors: Tareg Belali, Mosleh Abomughaid, Muhanad Alhujaily

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HNF4a is one of the steroid hormone receptor family of transcription factors with roles in the development of the liver and the regulation of several critical metabolic pathways, such as glycolysis, drug metabolism, and apolipoproteins and blood coagulation. The transcriptional potency of HNF4a is well known due to its involvement in diabetes and other metabolic diseases. However, recently HNF4a has been discovered to be closely associated with several haematological disorders, mainly because of genetic mutations, drugs, and hepatic disorders. We review HNF4a structure and function and its role in haematological disorders. We discuss possible good therapies that are based on targeting HNF4a.

Keywords: hepatocyte nuclear factor 4 alpha, HNF4a nuclear receptor, steroid hormone receptor family of transcription factors, hematological disorders

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Authors: Zuzana Tatarkova, Ivana Pilchova, Michal Cibulka, Martin Kolisek, Peter Racay, Peter Kaplan

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Introduction: Normal functioning of mitochondria is crucial for cardiac performance. Mitochondria undergo mitophagy and biogenesis, and mitochondrial proteins are subject to extensive post-translational modifications. The state of mitochondrial homeostasis reflects overall cellular fitness and longevity. Perturbed mitochondria produce less ATP, release greater amounts of reactive molecules, and are more prone to apoptosis. Therefore mitochondrial turnover is an integral aspect of quality control in which dysfunctional mitochondria are selectively eliminated through mitophagy. Currently, the progressive deterioration of physiological functions is seen as accumulation of modified/damaged proteins with limiting regenerative ability and disturbance of such affected protein-protein communication throughout aging in myocardial cells. Methodologies: For our study was used immunohistochemistry, biochemical methods: spectrophotometry, western blotting, immunodetection as well as more sophisticated 2D electrophoresis and mass spectrometry for evaluation protein-protein interactions and specific post-translational modification. Results and Discussion: Mitochondrial stress response to reactive species was evaluated as electron transport chain (ETC) complexes, redox-active molecules, and their possible communication. Protein-protein interactions revealed a strong linkage between age and ETC protein subunits. Redox state was strongly affected in senescent mitochondria with shift in favor of more pro-oxidizing condition within cardiomyocytes. Acute myocardial ischemia and ischemia-reperfusion (IR) injury affected ETC complexes I, II and IV with no change in complex III. Ischemia induced decrease in total antioxidant capacity, MnSOD, GSH and catalase activity with recovery in some extent during reperfusion. While MnSOD protein content was higher in IR group, activity returned to 95% of control. Nitric oxide is one of the biological molecules that can out compete MnSOD for superoxide and produce peroxynitrite. This process is faster than dismutation and led to the 10-fold higher production of nitrotyrosine after IR injury in adult with higher protection in senescent ones. 2D protein profiling revealed 140 mitochondrial proteins, 12 of them with significant changes after IR injury and 36 individual nitrotyrosine-modified proteins further identified by mass spectrometry. Linking these two groups, 5 proteins were altered after IR as well as nitrated, but only one showed massive nitration per lowering content of protein after IR injury in adult. Conclusions: Senescent cells have greater proportion of protein content, which might be modulated by several post-translational modifications. If these protein modifications are connected to functional consequences and protein-protein interactions are revealed, link may lead to the solution. Assume all together, dysfunctional proteostasis can play a causative role and restoration of protein homeostasis machinery is protective against aging and possibly age-related disorders. This work was supported by the project VEGA 1/0018/18 and by project 'Competence Center for Research and Development in the field of Diagnostics and Therapy of Oncological diseases', ITMS: 26220220153, co-financed from EU sources.

Keywords: aging heart, mitochondria, proteomics, redox state

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Authors: Blessing Ojeme, Frederick Quinn, Russell Karls, Shannon Quinn

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The detection and segmentation of mitochondria from fluorescence microscopy are crucial for understanding the complex structure of the nervous system. However, the constant fission and fusion of mitochondria and image distortion in the background make the task of detection and segmentation challenging. In the literature, a number of open-source software tools and artificial intelligence (AI) methods have been described for analyzing mitochondrial images, achieving remarkable classification and quantitation results. However, the availability of combined expertise in the medical field and AI required to utilize these tools poses a challenge to its full adoption and use in clinical settings. Motivated by the advantages of automated methods in terms of good performance, minimum detection time, ease of implementation, and cross-platform compatibility, this study proposes a fully automated framework for the detection and segmentation of mitochondria using both image shape information and descriptive statistics. Using the low-cost, open-source python and openCV library, the algorithms are implemented in three stages: pre-processing, image binarization, and coarse-to-fine segmentation. The proposed model is validated using the mitochondrial fluorescence dataset. Ground truth labels generated using a Lab kit were also used to evaluate the performance of our detection and segmentation model. The study produces good detection and segmentation results and reports the challenges encountered during the image analysis of mitochondrial morphology from the fluorescence mitochondrial dataset. A discussion on the methods and future perspectives of fully automated frameworks conclude the paper.

Keywords: 2D, binarization, CLAHE, detection, fluorescence microscopy, mitochondria, segmentation

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Authors: Andrew Anis Fakhrey Mosaad

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Introduction: There are many different types of sleep disorders, each with serious implications for a person's health and a large financial burden on society. Method: This review offers a framework based on the International Classification of Sleep Disorders to aid in the diagnosis and treatment of sleep disorders. Differentiating between primary and secondary insomnia is covered, along with pharmacological and nonpharmacological therapy options. Common abnormalities of the circadian rhythm are mentioned along with their therapies, such as light therapy and chronotherapy. This article discusses the identification and management of periodic limb movement disorder and restless legs syndrome. The therapy of upper airway resistance syndrome and obstructive sleep apnea are the main topics of discussion. Conclusion: The range of narcolepsy symptoms and results, as well as diagnostic procedures and treatment, are discussed. The causes, outcomes, and treatments of many types of insomnias, such as sleep terrors, somnambulism, and rapid eye movement (REM) behavior sleep disorders, are discussed.

Keywords: diagnosis, treatment, sleep disorders, insomnia

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Authors: H. Imad, Y. Cheah, O. Aamera

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The aims of this research are to study the mitochondrial non-coding region by using the Sanger sequencing technique and establish the degree of variation characteristics of a fragment. FTA® Technology (FTA™ paper DNA extraction) utilized to extract DNA. A portion of a non-coding region encompassing positions 37 to 340 amplified in accordance with the Anderson reference sequence. PCR products purified by EZ-10 spin column then sequenced and detected by using the ABI 3730xL DNA Analyzer. New polymorphic positions 57, 63, and 101 are described may in future be suitable sources for identification purpose. The data obtained can be used to identify variable nucleotide positions characterized by frequent occurrence most promising for identification variants.

Keywords: encompassing nucleotide positions 37 to 340, HVII, Iraq, mitochondrial DNA, polymorphism, frequency

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Authors: Bosiacki Mateusz, Anna Lubkowska, Dariusz Chlubek, Irena Baranowska-Bosiacka

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Exposure to cold temperatures can be considered a stressor that can lead to adaptive responses. The present study hypothesized the possibility of a positive effect of cold water exercise on mitochondrial biogenesis and muscle energy metabolism in aging rats. The purpose of this study was to evaluate the effects of cold water exercise on energy status, purine compounds, and mitochondrial biogenesis in the muscles of aging rats as indicators of the effects of cold water exercise and their usefulness in monitoring adaptive changes. The study was conducted on 64 aging rats of both sexes, 15 months old at the time of the experiment. The rats (male and female separately) were randomly assigned to the following study groups: control, sedentary animals; 5°C groups animals - training swimming in cold water at 5°C; 36°C groups - animals training swimming in water at thermal comfort temperature. The study was conducted with the approval of the Local Ethical Committee for Animal Experiments. The animals in the experiment were subjected to swimming training for 9 weeks. During the first week of the study, the duration of the first swimming training was 2 minutes (on the first day), increasing daily by 0.5 minutes up to 4 minutes on the fifth day of the first week. From the second to the eighth week, the swimming training was 4 minutes per day, five days a week. At the end of the study, forty-eight hours after the last swim training, the animals were dissected. In the skeletal muscle tissue of the thighs of the rats, we determined the concentrations of ATP, ADP, AMP, Ado (HPLC), PGC-1a protein expression (Western blot), PGC1A, Mfn1, Mfn2, Opa1, and Drp1 gene expression (qRT PCR). The study showed that swimming in water at a thermally comfortable temperature improved the energy metabolism of the aging rat muscles by increasing the metabolic rate (increase in ATP, ADP, TAN, AEC) and enhancing mitochondrial fusion (increase in mRNA expression of regulatory proteins Mfn1 and Mfn2). Cold water swimming improved muscle energy metabolism in aging rats by increasing the rate of muscle energy metabolism (increase in ATP, ADP, TAN, AEC concentrations) and enhancing mitochondrial biogenesis and dynamics (increase in the mRNA expression of proteins of fusion-regulating factors – Mfn1, Mfn2, and Opa1, and the factor regulating mitochondrial fission – Drp1). The concentration of high-energy compounds and the expression of proteins regulating mitochondrial dynamics in the muscle may be a useful indicator in monitoring adaptive changes occurring in aging muscles under the influence of exercise in cold water. It represents a short-term adaptation to changing environmental conditions and has a beneficial effect on maintaining the bioenergetic capacity of muscles in the long term. Conclusion: exercise in cold water can exert positive effects on energy metabolism, biogenesis and dynamics of mitochondria in aging rat muscles. Enhancement of mitochondrial dynamics under cold water exercise conditions can improve mitochondrial function and optimize the bioenergetic capacity of mitochondria in aging rat muscles.

Keywords: cold water immersion, adaptive responses, muscle energy metabolism, aging

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Authors: Ipek Sensu

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Comorbid Axis I disorders are highly common for suicidal borderline personality disorder (BPD) patients, especially substance use disorder and anxiety disorders. Since interpersonal dysfunction is one of the core symptoms in BPD, the purpose of the current study is to examine perceived criticism and anxiety disorders and also substance abuse disorders (SUD) for women with borderline personality disorder (BPD) who attempt suicide at least once in their lifetime. In the current study, it was suggested that the perceived criticism from others and being upset by criticism differ between suicidal women with BPD with comorbidity of anxiety disorders and SUD (separately) and suicidal women with BPD without anxiety disorders and without SUD (separately). The participants in this study included ninety-nine women who have already been diagnosed with borderline personality disorder and also have had at least two episodes of deliberate self-harm, in other words, suicide attempts and/or non-suicidal self-injury (NSSI) in the last five years and at least one episode in the 8-week period before joining the research study and at least one suicide attempt in the previous year. Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) and Social History Interview (SHI) were conducted to determine the comorbid axis I disorders and level of perceived criticism. As a result of the independent sample t-tests, the first hypothesis was rejected, in other words, women with BPD and a comorbid anxiety disorder did not show significantly higher levels of ‘criticized by others’, compared to women with BPD alone. However, the levels of ‘upset at criticism’ were significantly different between suicidal women with BPD with or without any anxiety disorders, which is the second hypothesis. In addition, the third hypothesis was also accepted; this means, women with BPD who had any substance use dependence would show significantly higher levels of 'criticized by others' compared to women with BPD alone. Finally, the fourth hypothesis was partly accepted: that is, women with BPD with alcohol dependence had significantly higher levels of ‘how upset when they expose to criticism’, compared to those without alcohol dependence. Limitations, implications, and directions for future research are discussed.

Keywords: anxiety disorders, borderline personality disorders, perceived criticism, substance use disorders

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Authors: Marek Halenár, Eva Tvrdá, Tomáš Slanina, Ľubomír Ondruška, Eduard Kolesár, Peter Massányi, Adriana Kolesárová

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The present in vitro study was designed to reveal whether amygdalin (AMG) is able to cause changes to the motility, viability and mitochondrial activity of rabbit spermatozoa. New Zealand White rabbits (n = 10) aged four months were used in the study. Semen samples were collected from each animal and used for the in vitro incubation. The samples were divided into five equal parts and diluted with saline supplemented with 0, 0.5, 1, 2.5 and 5 mg/mL AMG. At times 0h, 3h and 5h spermatozoa motion parameters were assessed using the SpermVision™ computer-aided sperm analysis (CASA) system, cell viability was examined with the metabolic activity (MTT) assay, and the eosin-nigrosin staining technique was used to evaluate the viability of rabbit spermatozoa. All AMG concentrations exhibited stimulating effects on the spermatozoa activity, as shown by a significant preservation of the motility (P<0.05 with respect to 0.5 mg/mL and 1 mg/mL AMG; Time 5 h) and mitochondrial activity (P< 0.05 in case of 0.5 mg/mL AMG; P< 0.01 in case of 1 mg/mL AMG; P < 0.001 with respect to 2.5 mg/mL and 5 mg/mL AMG; Time 5 h). None of the AMG doses supplemented had any significant impact of the spermatozoa viability. In conclusion, the data revealed that short-term co-incubation of spermatozoa with AMG may result in a higher preservation of the sperm structural integrity and functional activity.

Keywords: amygdalin, CASA, mitochondrial activity, motility, rabbits, spermatozoa, viability

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Authors: Zakieh Piri, Shahla Damanabi, Peyman Rezaii Hachesoo

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Introduction: Healthcare organizations like other organizations suffer from a number of disorders such as Business Sponsor Disorder, Business Acceptance Disorder, Cultural/Political Disorder, Data Disorder, etc. As quality in healthcare care mostly depends on the quality of data, we aimed to identify data disorders and its symptoms in two teaching hospitals. Methods: Using a self-constructed questionnaire, we asked 20 questions in related to quality and usability of patient data stored in patient records. Research population consisted of 150 managers, physicians, nurses, medical record staff who were working at the time of study. We also asked their views about the symptoms and treatments for any data disorders they mentioned in the questionnaire. Using qualitative methods we analyzed the answers. Results: After classifying the answers, we found six main data disorders: incomplete data, missed data, late data, blurred data, manipulated data, illegible data. The majority of participants believed in their important roles in treatment of data disorders while others believed in health system problems. Discussion: As clinicians have important roles in producing of data, they can easily identify symptoms and disorders of patient data. Health information managers can also play important roles in early detection of data disorders by proactively monitoring and periodic check-ups of data.

Keywords: data disorders, quality, healthcare, treatment

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Authors: Alberto Hananel

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The aim of this work is to modelize the occlusion of a person with temporomandibular disorders as an evolutionary equation and approach its solution by the construction and characterizing of discrete variational splines. To formulate the problem, certain boundary conditions have been considered. After showing the existence and the uniqueness of the solution of such a problem, a convergence result of a discrete variational evolutionary spline is shown. A stress analysis of the occlusion of a human jaw with temporomandibular disorders by finite elements is carried out in FreeFem++ in order to prove the validity of the presented method.

Keywords: approximation, evolutionary PDE, Finite Element Method, temporomandibular disorders, variational spline

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Authors: Suliman Khan, Rabeea Siddique, Mengzhou Xue

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Background: Patients with neurological disorders often display altered circadian rhythms. The disrupted circadian rhythms through chronic jetlag or shiftwork are thought to increase the risk and severity of human disease, including cancer, psychiatric, and related brain diseases. In this study, we investigated the impact of shiftwork or chronic jetlag (CJL) like conditions on mice’s brains. Transcriptome profiling based on RNA sequencing revealed that genes associated with serious neurological disorders were differentially expressed in the nucleus accumbens (NAc) and prefrontal cortex (PFC). According to the qPCR analysis, several key regulatory genes associated with neurological disorders were significantly altered in the NAc, PFC, hypothalamus, hippocampus, and striatum. Serotonin levels and the expression levels of serotonin transporters and receptors were significantly altered in mice treated with CJL. Overall, these results indicate that CJL may increase the risk of neurological disorders by disrupting the key regulatory genes, biological functions, serotonin, and corticosterone. These molecular linkages can further be studied to investigate the mechanism underlying CJL or shiftwork-mediated neurological disorders in order to develop treatment strategies.

Keywords: chronic jetlag, molecular profiles, brain disorders, circadian rhythms

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Authors: N. V. Kazmiruk, Y. R. Nartsissov

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Phosphate activated glutaminase (GA, E.C. 3.5.1.2) plays a key role in glutamine/glutamate homeostasis in mammalian brain, catalyzing the hydrolytic deamidation of glutamine to glutamate and ammonium ions. GA is mainly localized in mitochondria, where it has the catalytically active form on the inner mitochondrial membrane (IMM) and the other soluble form, which is supposed to be dormant. At present time, the exact localization of the membrane glutaminase active site remains a controversial and an unresolved issue. The first hypothesis called c-side localization suggests that the catalytic site of GA faces the inter-membrane space and products of the deamidation reaction have immediate access to cytosolic metabolism. According to the alternative m-side localization hypothesis, GA orients to the matrix, making glutamate and ammonium available for the tricarboxylic acid cycle metabolism in mitochondria directly. In our study, we used a multi-compartment kinetic approach to simulate metabolism of glutamate and glutamine in the astrocytic cytosol and mitochondria. We used physiologically important ratio between the concentrations of glutamine inside the matrix of mitochondria [Glnₘᵢₜ] and glutamine in the cytosol [Glncyt] as a marker for precise functioning of the system. Since this ratio directly depends on the mitochondrial glutamine carrier (MGC) flow parameters, key observation was to investigate the dependence of the [Glnmit]/[Glncyt] ratio on the maximal velocity of MGC at different initial concentrations of mitochondrial glutamate. Another important task was to observe the similar dependence at different inhibition constants of the soluble GA. The simulation results confirmed the experimental c-side localization hypothesis, in which the glutaminase active site faces the outer surface of the IMM. Moreover, in the case of such localization of the enzyme, a 3-fold decrease in ammonium production was predicted.

Keywords: glutamate metabolism, glutaminase, kinetic approach, mitochondrial membrane, multi-compartment modeling

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Authors: Makhosi Buthelezi

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Mitochondrial DNA cytochrome c oxidase I (COI) gene analyses linked the South African groundnut leaf miner (GLM) to the Australian soya bean moth Aproaerema simplexella (Walker) and Indian Aproaerema modicella (Deventer). Thus, the genetic relatedness of GLM, A. simplexela, and A. modicella was examined by performing mitochondrial and nuclear (COI, cytochrome oxidase subunit II (COII), mitochondrial cytochrome b (CYTB), nuclear ribosomal 28S (28S) and intergenic spacer elongation factor-1 alpha ( EF-1 ALPHA) on 44 specimens collected from South Africa, four from Mozambique, and three each from single locations in India and Australia. Phylogenetic analyses were conducted using the Maximum Parsimony (MP) and Neighbour-Joining (NJ) methods. All of the datasets of the five DNA gene regions that were sequenced were also analyzed using the Basic Local Alignment Search Tool (BLAST) to find the closest matches for inclusion in the phylogenetic trees as outgroups and for purposes of information. In the phylogenetic trees for COI, COII, cytb and EF-1 ALPHA, a similar pattern was observed in the way that the sequences assembled into different groups; i.e., some sequences of A. simplexella from Australia were grouped separately from the others, but some Australian sequences grouped with those of the GLM from South Africa, India, and Mozambique. In the phylogenetic tree for 28S, all sequences from South Africa, Australia, India, and Mozambique grouped together and formed one group. For COI, genetic pairwise distance ranged from 0.97 to 3.60 %, for COII it ranged from 0.19% to 2.32%, for cytb it ranged from 0.25 to 9.77% and for EF-1 ALPHA it ranged 0.48 to 6.99%. Results of this study indicate that these populations are genetically related and presumably constitute a single species. Thus, further molecular and morphological studies need to be undertaken in order to resolve this apparent conundrum on the taxonomy of these populations.

Keywords: aproaerema modicella, aproaerema simplexella, mitochondrial DNA, nuclear DNA

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Authors: David G. Maxinez, Andrés Ferreyra Ramírez, Liliana Castillo Sánchez, Nancy Adán Mendoza, Carlos Aviles Cruz

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This research describes the use of fuzzy logic in detection, assessment, analysis and evaluation of children with behavioral disorders. It shows how to acquire and analyze ambiguous, vague and full of uncertainty data coming from the input variables to get an accurate assessment result for each of the typologies presented by children with behavior problems. Behavior disorders analyzed in this paper are: hyperactivity (H), attention deficit with hyperactivity (DAH), conduct disorder (TD) and attention deficit (AD).

Keywords: alteration, behavior, centroid, detection, disorders, economic, fuzzy logic, hyperactivity, impulsivity, social

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Authors: Debasmita Dubey, Rajesh Kumar Meher, Smruti Pragya Samal, Pradeep Kumar Naik

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Background: To determine antioxidant properties and anticancer activity by ROS and mitochondrial transmembrane potential mediated apoptosis against MCF7, MDA-MB-231, cell line. Methods: Leaf sample was extracted using methanol by microwave digestion technique. The antioxidant properties of the methanolic extract were determined by a DPPH scavenging assay. In vitro anticancer activity, mitochondrial transmembrane potential, apoptosis activity and DNA fragmentation study, as well as intracellular ROS activity of most potential leaf extract, were also determined by using the MDA-MB-231cell line. In vivo animal toxicity study was carried out using mice model. Results: Methanolic leaf extract has shown the highest antioxidant, as well as anticancer activity, is based on the assay conducted. For the identification of active phytochemicals from methanolic extract, High-resolution mass spectroscopy-LCMS was used. In vitro cytotoxicity study against MCF-7 and MDA-MB-231 cell line and IC 50 value was found to be 37.5µg/ml. From histopathological studies, no toxicity in liver and kidney tissue was identified. Conclusion: This plant tuber can be used as a regular diet to reduce the chance of breast cancer. Further, more studies should be conducted to isolate and identify the responsible compound.

Keywords: human breast adenocarcinoma, ROS, mitochondrial transmembrane, apoptosis

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Authors: Abeer Mohammed, Nevein Mustafa Elashery, Mona Hassan Abdel Aal, Ereny Wilson Nagib

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The Aim of the current study is to investigate nutrition role in the management of psychiatric disorders. Research Design: A quasi- experimental research design was utilized for this study. Setting The study was conducted at outpatient clinic at Institute of Psychiatry affiliated to Ain Shams University hospitals, using a convenient sample of 50 psychiatric patients with depression, schizophrenia, bipolar disorders, and obsessive compulsive disorders. Tools: data were collected through; first, an interview questionnaire covering socio-demographic characteristics, second, nutrition assessment tools Third, nutrition risk assessment. Fourth, nutrition management program Results showed that there were highly statistically significant improvements in modified nutritional supplements for patients with depression, schizophrenia, bipolar disorders, and obsessive compulsive disorders' patients after conducting the nutrition management program. Regarding psychiatric patients’ knowledge about healthy food, healthy nutritional habits, and patients’ awareness & readiness for change, there were highly statistically significant improvements. Concerning signs and symptoms of psychiatric disorders, there were highly statistically significant improvements for depression, schizophrenia, bipolar disorders, and obsessive-compulsive patients after conducting the management program. In conclusion, the nutrition management program was effective in improving symptoms associated with, depression, schizophrenia, bipolar disorders, and obsessive compulsive disorders. The study recommended that nurses should have more contribution in counseling psychiatric patients, and their families about healthy diet and healthy habits. Further research should recommend studying the effectiveness of herbs on enhancing mental health for psychiatric patients.

Keywords: nutrition, role, management, psychiatric disorders

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Authors: Anna Höfer, Johannes Herrmann, Patrick Meybohm, Christopher Lotz

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Mitochondria are pivotal for energy supply and regulation of cellular functions. Deficiencies of mitochondrial metabolism have been implicated in diverse stressful conditions including infections. Platelets are key mediators for thrombo-inflammation during development and resolution of acute respiratory distress syndrome (ARDS). Previous data point to an exhausted platelet phenotype in critically-ill patients with coronavirus 19 disease (COVID-19) impacting the course of disease. The objective of this work was to characterize platelet mitochondrial metabolism in patients suffering from COVID-19 ARDSA longitudinal analysis of platelet mitochondrial metabolism in 24 patients with COVID-19 induced ARDS compared to 35 healthy controls (ctrl) was performed. Blood samples were analyzed at two time points (t1=day 1; t2=day 5-7 after study inclusion). The activity of mitochondrial citrate synthase was photometrically measured. The impact of oxidative stress on mitochondrial permeability was assessed by a photometric calcium-induced swelling assay and the activity of superoxide dismutase (SOD) by a SOD assay kit. The amount of protein carbonylation and the activity of mitochondria complexes I-IV were photometrically determined. Levels of interleukins (IL)-1α, IL-1β and tumor necrosis factor (TNF-) α were measured by a Multiplex assay kit. Median age was 54 years, 63 % were male and BMI was 29.8 kg/m2. SOFA (12; IQR: 10-15) and APACHE II (27; IQR: 24-30) indicated critical illness. Median Murray Score was 3.4 (IQR: 2.8-3.4), 21/24 (88%) required mechanical ventilation and V-V ECMO support in 14/24 (58%). Platelet counts in ARDS did not change during ICU stay (t1: 212 vs. t2: 209 x109/L). However, mean platelet volume (MPV) significantly increased (t1: 10.6 vs. t2: 11.9 fL; p<0.0001). Citrate synthase activity showed no significant differences between ctrl and ARDS patients. Calcium induced swelling was more pronounced in patients at t1 compared to t2 and to ctrl (50µM; t1: 0.006 vs. ctrl: 0.016 ΔOD; p=0.001). The amount of protein carbonylation as marker for irreversible proteomic modification constantly increased during ICU stay and compared to ctrl., without reaching significance. In parallel, superoxid dismutase activity gradually declined during ICU treatment vs. ctrl (t2: - 29 vs. ctrl.: - 17 %; p=0.0464). Complex I analysis revealed significantly stronger activity in ARDS vs. ctrl. (t1: 0.633 vs. ctrl.: 0.415 ΔOD; p=0.0086). There were no significant differences in complex II, III or IV activity in platelets from ARDS patients compared to ctrl. IL-18 constantly increased during the observation period without reaching significance. IL-1α and TNF-α did not differ from ctrl. However, IL-1β levels were significantly elevated in ARDS (t1: 16.8; t2: 16.6 vs. ctrl.: 12.4 pg/mL; p1=0.0335, p2=0.0032). This study reveals new insights in platelet mitochondrial metabolism during COVID-19 caused ARDS. it data point towards enhanced platelet activity with a pronounced turnover rate. We found increased activity of mitochondria complex I and evidence for enhanced oxidative stress. In parallel, protective mechanisms against oxidative stress were narrowed with elevated levels of IL-1β likely causing a pro-apoptotic environment. These mechanisms may contribute to platelet exhaustion in ARDS.

Keywords: acute respiratory distress syndrome (ARDS), coronavirus 19 disease (COVID-19), oxidative stress, platelet mitochondrial metabolism

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Authors: Berihun Dachew, Abdullah Mamun, Joemer Maravilla, Rosa Alati

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Background: Hypertensive disorders of pregnancy are a major cause of maternal and childhood morbidity and mortality worldwide. However, its effect on offspring mental and behavioural disorders is unclear. Aims:The aim of this study was to provide the best scientific evidence regarding the association between hypertensive disorders of pregnancy and offspring mental and behavioural problems. Methods: We systematically searched Scopus, PubMed, Cochrane, EMBASE, CINAH and PsycINFO databases. A total of 23 studies (11 included in meta-analysis) were identified. A qualitative analysis was conducted by summarizing, comparing, and contrasting the abstracted data for all included studies. For quantitative analysis, relative risk (RR) with 95% confidence interval (95% CI) was used as pooled effect size. Heterogeneity was assessed by measuring Cochran’s Q and I2 test statistics. Results: Of the 23 studies included in this review, 15 studies found that hypertensive disorders of pregnancy had a negative impact for at least one mental or behavioural problem. The pooled effect of 11 studies included in the meta-analysis showed that preeclampsia was associated with increased risk of offspring schizophrenia (RR=1.37; 95% CI, 1.08-1.72). Conclusions: Intrauterine exposure to pre-eclampsia increased the risk of schizophrenia among offspring. However, we found inconclusive finding on the effect of hypertensive disorders of pregnancy and other mental and behavioural problems. Further high quality, large sample, mother child cohort studies are needed to further progress this area of research.

Keywords: behavioural disorders, hypertensive disorders of pregnancy, mental disorders, offspring

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Authors: Seema Singh Parmar, Shweta Chauhan

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Aims & Objectives: To evaluate the presence of various psychiatric disorders in patients reporting with a headache as the only symptom. Methodology: 200 patients with the chief complain of a headache who visited the psychiatric OPD of a tertiary care were investigated. Out of them 50 who had pure psychiatric illness without any other neurological disease were investigated, and their diagnosis was made. Independent sample t-tests were applied to generate results. Results: The most common psychiatric diagnosis seen in the sample was Depression (64%) out of which 47% showed features of Depression with anxious distress. Other psychiatric disorders seen were Generalized Anxiety Disorder, Panic Attacks, Somatic Symptom Disorder and Obsessive Compulsive Disorder. For pure psychiatry, headache related illnesses female to male ratio was 1.64. Conclusion: The increasing frequency of psychiatric disorders among patients who only visit the doctor seeking treat a headache shows the need for better identification of psychiatric disorders because proper diagnosis and target of psychiatric treatment shall give complete relief to the patient’s symptomatology.

Keywords: anxiety disorders, depression, headache, panic attacks

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Authors: Hsien Hua Kuo, Wen Chun Lin, Chia Chi Hsu, Hsien Wen Kuo

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Objective: Despite the high prevalence of musculoskeletal disorders (MSDs) among nurses, which has been consistently observed in the studies of Western countries, very little information regarding intensity of workload and work-related quality of life (WRQOL) related to MSDs among nurses is available in Taiwan. The objective of this study is to investigate the factors affecting musculoskeletal disorders in nurses from a hospital. Methods: 550 nurses from a hospital in Taoyuan were interviewed using a modified standardized Nordic Musculoskeletal (NMQ) questionnaire which contained the demographic information, workplace condition and musculoskeletal disorders. Results: Response rate of nurses were 92.5% from a teaching hospital. Based on medical diagnosis by physician, neck of musculoskeletal disorders had the highest percentage in nine body portions. The higher percentage of musculoskeletal disorders in nurses found from wards of internal and surgery. Severity and symptoms of musculoskeletal disorders diagnosed by self-reported questionnaire significantly correlated with WRQOL, job satisfaction and intensity of workload among nurses based on the logistic regression model. Conclusion: The severity and symptoms of musculoskeletal disorders among nurses showed a dose-dependent with WRQOL and workload. When work characteristics in hospital were modified, the severity of musculoskeletal disorders among nurses will be decreased and alleviated. Comment: Multifaceted ergonomic intervention programme to reduce the prevalence of MSDs among nurses was by encouraging nurses to do more physical activity which will make them more flexible and increase their strength. Therefore, the head nurse should encourage nurses to regularly physical activity and to modify unfitting ergonomic environment in order to reduce the prevalence of MSDs.

Keywords: musculoskeletal disorders, nurse, WRQOL, job satisfaction

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Authors: Denis Nono, Catherine Abbo, Thomas Wenzel

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Introduction: The study explored socio-cultural perspectives of childhood disorders and its implications for health seeking. Emphasis was on exploring local understanding and perceptions and how these ideas affect health seeking. Study aim: To explore the socio-cultural perspectives of neuro-developmental disorders and its implications on health seeking behaviour. Methods: The methods used in this study included key informant interviews conducted with health professionals. Parents of the children aged (6-15 years) with neuro-developmental disorders were recruited from the hospital to participate in focus group discussion, participant observation and individual in-depth interviews. Results: The study found out that stigma extended from children to parents and caregivers who were also shunned by community members. Participants described their children as “a gift from God” others described them as “a test from God”. The communities perceive the disorders as a spiritual infliction and always insisted that the children be taken for Acholi cultural and traditional rituals to cleanse children and they believed that mental illness has spiritual linkages. Conclusion: This study gives unique insights into the perceptions of neuro-developmental disorders and health seeking behavior in Gulu District and neighboring communities. The results showed that communities linked disorders to spiritual affliction, misunderstandings between families, bewitching, and other supernatural forces. Some of the participants highly recommended biomedical approaches to prevention, management and control of the disorders.

Keywords: ethnography, health seeking, neuro-developmental disorders, socio-cultural

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Authors: Maisa Haj-Tas, Jehad Alaraifi

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The significance of the study: This retrospective study examined the speech and language profiles of patients who received clinical services at the University of Jordan Hearing and Speech Clinic (UJ-HSC) from 2009 to 2014. The UJ-HSC clinic is located in the capital Amman and was established in the late 1990s. It is the first hearing and speech clinic in Jordan and one of first speech and hearing clinics in the Middle East. This clinic provides services to an annual average of 2000 patients who are diagnosed with different communication disorders. Examining the speech and language profiles of patients in this clinic could provide an insight about the most common disorders seen in patients who attend similar clinics in Jordan. It could also provide information about community awareness of the role of speech therapists in the management of speech and language disorders. Methodology: The researchers examined the clinical records of 1140 patients (797 males and 343 females) who received clinical services at the UJ-HSC between the years 2009 and 2014 for the purpose of data analysis for this study. The main variables examined in the study were disorder type and gender. Participants were divided into four age groups: children, adolescents, adults, and older adults. The examined disorders were classified as either speech disorders, language disorders, or dysphagia (i.e., swallowing problems). The disorders were further classified as childhood language impairments, articulation disorders, stuttering, cluttering, voice disorders, aphasia, and dysphagia. Results: The results indicated that the prevalence for language disorders was the highest (50.7%) followed by speech disorders (48.3%), and dysphagia (0.9%). The majority of patients who were seen at the JU-HSC were diagnosed with childhood language impairments (47.3%) followed consecutively by articulation disorders (21.1%), stuttering (16.3%), voice disorders (12.1%), aphasia (2.2%), dysphagia (0.9%), and cluttering (0.2%). As for gender, the majority of patients seen at the clinic were males in all disorders except for voice disorders and cluttering. Discussion: The results of the present study indicate that the majority of examined patients were diagnosed with childhood language impairments. Based on this result, the researchers suggest that there seems to be a high prevalence of childhood language impairments among children in Jordan compared to other types of speech and language disorders. The researchers also suggest that there is a need for further examination of the actual prevalence data on speech and language disorders in Jordan. The fact that many of the children seen at the UJ-HSC were brought to the clinic either as a result of parental concern or teacher referral indicates that there seems to an increased awareness among parents and teachers about the services speech pathologists can provide about assessment and treatment of childhood speech and language disorders. The small percentage of other disorders (i.e., stuttering, cluttering, dysphasia, aphasia, and voice disorders) seen at the UJ-HSC may indicate a little awareness by the local community about the role of speech pathologists in the assessment and treatment of these disorders.

Keywords: clinic, disorders, language, profile, speech

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Authors: Linghua Kong, Xinxia Chen, Mika Gissler, Catharina Lavebratt

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Background: Prenatal exposure to preeclampsia has been associated with an increased risk of offspring attention-deficit/hyperactivity disorders (ADHD), autism spectrum disorder (ASD), and intellectual disability. However, little is known about the association between prenatal exposure to severe preeclampsia and neurodevelopmental and psychiatric disorders in offspring. Objective: This study aimed to assess the risk of maternal preeclampsia combined with perinatal problems, specifically low birth weight and prematurity, on offspring neuropsychiatric disorders. Methods: All singleton live births in Finland between 1996 and 2014 (n=1 012 723) were followed up in nation-wide registries until 2018. Main exposures included pre-eclampsia, small for gestational age, and delivery before 34 gestational weeks. Offspring neurodevelopmental and psychiatric disorders (ICD-10 codes) were examined as outcomes variables. Offspring birth year, sex, maternal age at delivery, parity, marital status at birth, mother's country of birth, maternal smoking, maternal gestational diabetes, maternal use of psychotropic medication during pregnancy, and maternal systemic inflammatory diseases were used as covariates. Risks for neurodevelopmental and psychiatric disorders were estimated using Cox proportional hazards modeling. Results: Of the 1 012 723 offspring, 25 901 (2.6%) were exposed to preeclampsia, and 93 281 (9.2%) were diagnosed with a neuropsychiatric disorder. Compared to births unexposed to preeclampsia, small for gestational age or delivery before 34 gestational weeks, those exposed to preeclampsia only had a 21% increase in the likelihood of any neuropsychiatric disorders after adjusting for potential confounding (adjusted HR=1.21, 95% CI: 1.15-1.26), while exposure to preeclampsia combined with small for gestational age or delivery before 34 gestational weeks had a more than twofold increased risk of having a child with neuropsychiatric disorders (adjusted HR=2.16, 95% CI: 2.02-2.32). The adjusted HR for neuropsychiatric disorders in offspring with small for gestational age or delivery before 34 gestational weeks only was 1.79 (95% CI: 1.73-1.83). In addition, the risk estimate in offspring exposed to both preeclampsia and perinatal problems was greater than those only exposed to preeclampsia for having personality disorders (adjusted HR=1.66; 95% CI: 1.07-2.57), intellectual disabilities (adjusted HR=3.47; 95% CI: 2.86-4.22), specific developmental disorders (adjusted HR=2.91; 95% CI: 2.69-3.15), ASD (adjusted HR=1.75; 95% CI: 1.42-2.17), ADHD and conduct disorders (adjusted HR=2.00; 95%CI: 1.76-2.27), and other behavioral and emotional disorders (adjusted HR=2.09; 95% CI: 1.84-2.37). Conclusion: In utero exposure to severe preeclampsia increased the risk of several neurodevelopmental and psychiatric disorders in offspring. Our findings are relevant to women with hypertensive disorders with regard to pregnancy consultation and management and may yield effective clues for the prevention of neurodevelopmental and psychiatric disorders in childhood.

Keywords: low birth weight, neurodevelopmental disorders, preeclampsia, prematurity, psychiatric disorders

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Authors: Sanjay Saraf

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The oral cavity can be the site for early manifestations of mucocutaneous disorders (MD) or the only site for occurrence of these disorders. It can also exhibit oral lesions with simultaneous associated skin lesions. The MD involving the oral mucosa commonly presents with signs such as ulcers, vesicles and bullae. The unique environment of the oral cavity may modify these signs of the disease, thereby making the clinical diagnosis an arduous task. In addition to the unique environment of oral cavity, the overlapping of the signs of various mucocutaneous disorders, also makes the clinical diagnosis more intricate. The aim of this review is to present the oral signs of dermatological disorders having common oral involvement and emphasize their importance in early detection of the systemic disorders. The aim is also to highlight the necessity of oral examination by a dermatologist while examining the skin lesions. Prior to the oral examination, it must be imperative for the dermatologists and the dental clinicians to have the knowledge of oral anatomy. It is also important to know the impact of various diseases on oral mucosa, and the characteristic features of various oral mucocutaneous lesions. An initial clinical oral examination is may help in the early diagnosis of the MD. Failure to identify the oral manifestations may reduce the likelihood of early treatment and lead to more serious problems. This paper reviews the oral manifestations of immune mediated dermatological disorders with common oral manifestations.

Keywords: dermatological investigations, genodermatosis, histological features, oral examination

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Authors: Ryan D. Martinus

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Inflammation of the endothelium is an important process leading to diabetic atherosclerosis. However, the molecular mechanisms by which diabetes contributes to endothelial inflammation remain to be established. Using In-vitro cultured Human cells and Hsp60 specific ELISA assays, we show that Hsp60 is not only induced in Human monocyte cells under hyperglycaemic conditions but that the Hsp60 is also secreted from these cells. Furthermore, we also demonstrate that the Hsp60 secreted from these monocyte cells is also able to activate Toll-like receptor-4 (TLR4) from Human endothelial cells. This suggests that a potential link may exist between the hyperglycaemia-induced expression of Hsp60 in monocyte cells and vascular inflammation. Circulating levels of Hsp60 due to mitochondrial stress in diabetes patients could, therefore, be an important modulator of inflammation in endothelial cells and thus contribute to the increased incidences of atherosclerosis in diabetes mellitus.

Keywords: mitochondria, Hsp60, inflammation, diabetes mellitus

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Authors: Maria Luisa Barcena De Arellano, Sofya Pozdniakova, Pavelas Karkacas, Anja Kuhl, Istvan Baczko, Yury Ladilov, Vera Regitz-Zagrosek

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Introduction: Aging is associated with deterioration of the physiological function, leading to systemic inflammation and mitochondrial dysfunction that promote the development of cardiovascular diseases. Sex differences in aging-related cardiovascular diseases have been postulated. However, their precise mechanisms remain unclear. In the current study, we aimed to investigate the sex difference in the age-related alteration in Sirt1-AMPK signaling and its relation to the mitochondrial biogenesis and inflammation. Methods: Male and female human non-disease lateral left ventricular wall tissue (young (17–40 years; n= 7 male and 7 female) and old (50–68 years; n= 9 male and 8 female)) were used. qRT-PCR, western blot and immunohistochemistry assays were performed for expression analyses of Sirt1, AMPK, pAMPK, ac-Ku70, TFAM, PGC-1α, Sirt3, SOD2 and catalase. CD68 was used as a marker for macrophages and the ratio of IL-12:IL10 (pro-inflammatory phenotype (high IL-12/low IL-10) and anti-inflammatory phenotype (low IL-12/high IL-10) was used to examine the inflammatory stage in the heart. Results: Sirt1 expression was significantly higher in young females compared to young males, whereas in aged hearts Sirt1 expression was significantly downregulated in females, but not in males. In line with the Sirt1 downregulation in aged females, acetylation of nuclear Ku70, a direct target of Sirt1, in aged female hearts was significantly elevated. The activity of AMPK was significantly decreased in aged individuals, however no sex differences in the AMPK expression or activity were found in young or old individuals. The expression of mitochondrial proteins TOM40, SOD2 and Sirt3 was significantly higher in young females compared to young males, while in aged female hearts SOD2 and TOM40 were downregulated. In addition, the expression of catalase, a key cytosolic and mitochondrial anti-oxidative enzyme was significantly higher in young females and this female sex benefit was lost in aged hearts. In addition, the number of cardiac macrophages was significantly increased in old female, but not in male hearts. Consistently, the pro-inflammatory shift in old females was further confirmed by differences in the IL12/IL10 ratio in young female cardiac tissue in a favour of the anti-inflammatory mediator IL-10 (ratio 1:4) compared to young males (ratio 1:1). The anti-inflammatory environment in the heart was lost in aged females (ratio 1:1). Conclusion: Aging leads to the significant downregulation of Sirt1 expression and elevated acetylation of Ku70 in female, but not in male hearts. Furthermore, a beneficial upregulation of mitochondrial and anti-oxidative proteins in young females is lost with aging. Moreover, the malfunctions in the expression of Sirt1 and mitochondrial proteins in aged female hearts is accompanied by a significant pro-inflammatory shift. The study provides a molecular basis for the increased incidence of cardiovascular diseases in old women.

Keywords: inflammation, mitochondrial dysfunction, aging, Sirt1-AMPK axis

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Authors: Diana C. El Assal, Fatima Monteiro, Caroline May, Peter Barbuti, Silvia Bolognin, Averina Nicolae, Hulda Haraldsdottir, Lemmer R. P. El Assal, Swagatika Sahoo, Longfei Mao, Jens Schwamborn, Rejko Kruger, Ines Thiele, Kathrin Marcus, Ronan M. T. Fleming

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Degeneration of substantia nigra pars compacta dopaminergic neurons is one of the hallmarks of Parkinson's disease. These neurons have a highly complex axonal arborisation and a high energy demand, so any reduction in ATP synthesis could lead to an imbalance between supply and demand, thereby impeding normal neuronal bioenergetic requirements. Synaptic mitochondria exhibit increased vulnerability to dysfunction in Parkinson's disease. After biogenesis in and transport from the cell body, synaptic mitochondria become highly dependent upon oxidative phosphorylation. We applied a systems biochemistry approach to identify the metabolic pathways used by neuronal mitochondria for energy generation. The mitochondrial component of an existing manual reconstruction of human metabolism was extended with manual curation of the biochemical literature and specialised using omics data from Parkinson's disease patients and controls, to generate reconstructions of synaptic and somal mitochondrial metabolism. These reconstructions were converted into stoichiometrically- and fluxconsistent constraint-based computational models. These models predict that Parkinson's disease is accompanied by an increase in the rate of glycolysis and a decrease in the rate of oxidative phosphorylation within synaptic mitochondria. This is consistent with independent experimental reports of a compensatory switching of bioenergetic pathways in the putamen of post-mortem Parkinson's disease patients. Ongoing work, in the context of the SysMedPD project is aimed at computational prediction of mitochondrial drug targets to slow the progression of neurodegeneration in the subset of Parkinson's disease patients with overt mitochondrial dysfunction.

Keywords: bioenergetics, mitochondria, Parkinson's disease, systems biochemistry

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Authors: Phan Minh Trang, Joacim Rocklöv, Kim Bao Giang, Gunnar Kullgren, Maria Nilsson

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There are recent studies from high income countries reporting an association between heat waves and hospital admissions for mental health disorders. It is not previously studied if such relations exist in sub-tropical and tropical low- and middle-income countries. In this study from Vietnam, the assumption was that hospital admissions for mental disorders may be triggered, or exacerbated, by heat exposure and heat waves. A database from Hanoi Mental Hospital with mental disorders diagnosed by the International Classification of Diseases 10, spanning over five years, was used to estimate the heatwave-related impacts on admissions for mental disorders. The relationship was analysed by a Negative Binomial regression model accounting for year, month, and days of week. The focus of the study was heat-wave events with periods of three or seven consecutive days above the threshold of 35oC daily maximum temperature. The preliminary study results indicated that heat-waves increased the risks for hospital admission for mental disorders (F00-79) from heat-waves of three and seven days with relative risks (RRs) of 1.16 (1.01–1.33) and 1.42 (1.02–1.99) respectively, when compared with non-heat-wave periods. Heatwave-related admissions for mental disorders increased statistically significantly among men, among residents in rural communities and in elderly. Moreover, cases for organic mental disorders including symptomatic illnesses (F0-9) and mental retardation (F70-79) raised in high risks during heat waves. The findings are novel studying a sub-tropical middle-income city, facing rapid urbanisation and epidemiological and demographic transitions.

Keywords: mental disorders, admissions for F0-9 or F70-79, maximum temperature, heat waves

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Authors: Ogbonnaya O. Iroanya, Samson T. Fakorede, Osamudiamen J. Edosa, Hadiat A. Azeez

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The human mitochondrial DNA (mtDNA) is about 17 kbp circular DNA fragments found within the mitochondria together with smaller fragments of 1200 bp known as the control region. Knowledge of variation within populations has been employed in forensic and molecular anthropology studies. The study was aimed at investigating the polymorphic nature of the two hypervariable segments (HVS) of the mtDNA, i.e., HVS1 and HVS2, and to determine the haplogroup distribution among individuals resident in Lagos, Southwestern Nigeria. Peripheral blood samples were obtained from sixty individuals who are not related maternally, followed by DNA extraction and amplification of the extracted DNA using primers specific for the regions under investigation. DNA amplicons were sequenced, and sequenced data were aligned and compared to the revised Cambridge Reference Sequence (rCRS) GenBank Accession number: NC_012920.1) using BioEdit software. Results obtained showed 61 and 52 polymorphic nucleotide positions for HVS1 and HVS2, respectively. While a total of three indels mutation were recorded for HVS1, there were seven for HVS2. Also, transition mutations predominate nucleotide change observed in the study. Genetic diversity (GD) values for HVS1 and HVS2 were estimated to be 84.21 and 90.4%, respectively, while random match probability was 0.17% for HVS1 and 0.89% for HVS2. The study also revealed mixed haplogroups specific to the African (L1-L3) and the Eurasians (U and H) lineages. New polymorphic sites obtained from the study are promising for human identification purposes.

Keywords: hypervariable region, indels, mitochondrial DNA, polymorphism, random match probability

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Authors: A. G. Margaryan

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Aims and Objectives: Assessment of health status and detection disorders of external respiration functions (ERF) during preventative medical examination among physicians of Armenia. Subjects and Methods: Overall, fifty-nine physicians (17 men and 42 women) were examined and spirometry was carried out. The average age of the physicians was 50 years old. The studies were conducted on the Micromedical MicroLab 3500 Spirometer. Results: 25.4% among 59 examined physicians are overweight; 22.0% of them suffer from obesity. Two physicians are currently smokers. About half of the examined physicians (50.8%) at the time of examination were diagnosed with some diseases and had different health-related problems (excluding the problems related to vision and hearing). FVC was 2.94±0.1, FEV1 – 2.64±0.1, PEF – 329.7±19.9, and FEV₁%/FVC – 89.7±1.3. Pathological changes of ERF are identified in 23 (39.0%) cases. 28.8% of physicians had first degree of restrictive disorders, 3.4% – first degree of combined obstructive/ restrictive disorders, 6.8% – second degree of combined obstructive/ restrictive disorders. Only three physicians with disorders of the ERF were diagnosed with chronic bronchitis and bronchial asthma. There were no statistically significant changes in ERF depending on the severity of obesity (P> 0.05). Conclusion: The study showed the prevalence of ERF among physicians, observing mainly mild and moderate changes in ERF parameters.

Keywords: Armenia, external respiration function, health status, physicians

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