Search results for: fragile X syndrome

Authors: Lakmini Wijesooriya, Vicki Chalker, Jessica Day, Priyantha Perera, N. P. Sunil-Chandra

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M. pneumoniae has been identified as an etiology for exacerbation of asthma (EQA), although viruses play a major role in EOA. M. pneumoniae infection is treated empirically with macrolides, and its antibiotic sensitivity is not detected routinely. Characterization of the organism by genotyping and determination of macrolide resistance is important epidemiologically as it guides the empiric antibiotic treatment. To date, there is no such characterization of M. pneumoniae performed in Sri Lanka. The present study describes the characterization of M. pneumoniae detected from a child with EOA following a screening of 100 children with EOA. Of the hundred children with EOA, M. pneumoniae was identified only in one child by Real-Time polymerase chain reaction (PCR) test for identifying the community-acquired respiratory distress syndrome (CARDS) toxin nucleotide sequences. The M. pneumoniae identified from this patient underwent detection of macrolide resistance via conventional PCR, amplifying and sequencing the region of the 23S rDNA gene that contains single nucleotide polymorphisms that confer resistance. Genotyping of the isolate was performed via nested Multilocus Sequence Typing (MLST) in which eight (8) housekeeping genes (ppa, pgm, gyrB, gmk, glyA, atpA, arcC, and adk) were amplified via nested PCR followed by gene sequencing and analysis. As per MLST analysis, the M. pneumoniae was identified as sequence type 14 (ST14), and no mutations that confer resistance were detected. Resistance to macrolides in M. pneumoniae is an increasing problem globally. Establishing surveillance systems is the key to informing local prescriptions. In the absence of local surveillance data, antibiotics are started empirically. If the relevant microbiological samples are not obtained before antibiotic therapy, as in most occasions in children, the course of antibiotic is completed without a microbiological diagnosis. This happens more frequently in therapy for M. pneumoniae which is treated with a macrolide in most patients. Hence, it is important to understand the macrolide sensitivity of M. pneumoniae in the setting. The M. pneumoniae detected in the present study was macrolide sensitive. Further studies are needed to examine a larger dataset in Sri Lanka to determine macrolide resistance levels to inform the use of macrolides in children with EOA. The MLST type varies in different geographical settings, and it also provides a clue to the existence of macrolide resistance. The present study enhances the database of the global distribution of different genotypes of M. pneumoniae as this is the first such characterization performed with the increased number of samples to determine macrolide resistance level in Sri Lanka. M. pneumoniae detected from a child with exacerbation of asthma in Sri Lanka was characterized as ST14 by MLST and no mutations that confer resistance were detected.

Keywords: mycoplasma pneumoniae, Sri Lanka, characterization, macrolide resistance

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Authors: Steven G. Sclan

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Background: Since December 2019, the world has been afflicted by the spread of the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2), which is responsible for the condition referred to as Covid-19. The illness has had a cataclysmic impact on the political, social, economic, and overall well-being of the population of the entire globe. While Covid-19 has had a substantial universal fatality impact, it may have an even greater effect on the socioeconomic, medical well-being, and healthcare planning for remaining societies. Significance: As these numbers illustrate, many more persons survive the infection than die from it, and many of those patients have noted ongoing, persistent symptoms after successfully enduring the acute phase of the illness. Recognition and understanding of these symptoms are crucial for developing and arranging efficacious models of care for all patients (whether or not having been hospitalized) surviving acute covid illness and plagued by post-acute symptoms. Furthermore, regarding Covid infection in children (< 18 y/o), although it may be that Covid “+” children are not major vectors of infective transmission, it now appears that many more children than initially thought are carrying the virus without accompanying obvious symptomatic expression. It seems reasonable to wonder whether viral effects occur in children – those children who are Covid “+” and now asymptomatic – and if, over time, they might also experience similar symptoms. An even more significant question is whether Covid “+” asymptomatic children might manifest increased multiple health problems as they grow – i.e., developmental complications (e.g., physical/medical, metabolic, neurobehavioral, etc.) – in comparison to children who had been consistently Covid “ - ” during the pandemic. Topics Addressed and Theoretical Importance: This review is important because of the description of both quantitative and qualitative methods for clinical and biomedical research. Topics reviewed will consider the importance of well-designed, comprehensive (i.e., quantitative and qualitative methods) longitudinal studies of Post Covid-19 symptoms in both adults and children. Also reviewed will be general characteristics of longitudinal studies and a presentation of a model for a proposed study. Also discussed will be the benefit of longitudinal studies for the development of efficacious interventions and for the establishment of cogent, practical, and efficacious community healthcare service planning for post-acute covid patients. Conclusion: Results of multi-dimensional, longitudinal studies will have important theoretical implications. These studies will help to improve our understanding of the pathophysiology of long COVID and will aid in the identification of potential targets for treatment. Such studies can also provide valuable insights into the long-term impact of COVID-19 on public health and socioeconomics.

Keywords: COVID-19, post-COVID-19, long COVID, longitudinal research, quantitative research, qualitative research

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Authors: Nadia Arikat, Katharine Blain

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During the worst of the COVID pandemic, only essential treatment was provided for patients needing urgent care. With the prolonged extent of the pandemic, there has been a return to more routine referrals for paediatric dentistry advice and treatment for specialist conditions. However, some of these patients and/or their carers may have significant medical issues meaning that attending in-person appointments carries additional risks. This poses an ethical dilemma for clinicians. This project looks at how a secure video conferencing platform (“Near Me”) has been used to assess the need and urgency for in-person new patient visits, particularly for patients and families with additional risks. “Near Me” is a secure online video consulting service used by NHS Scotland. In deciding whether to bring a new patient to the hospital for an appointment, the clinical condition of the teeth together with the urgency for treatment need to be assessed. This is not always apparent from the referral letter. In addition, it is important to judge the risks to the patients and carers of such visits, particularly if they have medical issues. The use and effectiveness of “Near Me” consultations to help decide whether vulnerable paediatric patients should have in-person appointments will be illustrated and discussed using two families: one where the child is medically compromised (Alagille syndrome with previous liver transplant), and the other where there is a medically compromised parent (undergoing chemotherapy and a bone marrow transplant). In both cases, it was necessary to take into consideration the risks and moral implications of requesting that they attend the dental hospital during a pandemic. The option of remote consultation allowed further clinical information to be evaluated and the families take part in the decision-making process about whether and when such visits should be scheduled. These cases will demonstrate how medically compromised patients (or patients with vulnerable carers), could have their dental needs assessed in a socially distanced manner by video consultation. Together, the clinician and the patient’s family can weigh up the risks, with regards to COVID-19, of attending for in-person appointments against the benefit of having treatment. This is particularly important for new paediatric patients who have not yet had a formal assessment. The limitations of this technology will also be discussed. It is limited by internet availability, the strength of the connection, the video quality and families owning a device which allows video calls. For those from a lower socio-economic background or living in some rural areas, this may not be possible or limit its usefulness. For the two patients discussed in this project, where the urgency of their dental condition was unclear, video consultation proved beneficial in deciding an appropriate outcome and preventing unnecessary exposure of vulnerable people to a hospital environment during a pandemic, demonstrating the usefulness of such technology when it is used appropriately.

Keywords: COVID-19, paediatrics, triage, video consultations

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Authors: Mohit Kumar, Beklashwar Salona, Shiv Murti, Mukesh Singh

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We report here a case of five-months old male baby, born as second child of non-consanguineous parents with no considerable history of genetic abnormality which was referred to our cytogenetic laboratory for chromosomal analysis. Physical dysmorphic facial features including mongoloid face, cleft palate, simian crease, and developmental delay were observed. We present this case with unique balanced autosomal translocation of t(3;10)(p21;p13). The risk of phenotypic abnormalities based on de novo balanced translocation was estimated to be 7%. The association of balanced chromosomal rearrangement with Down syndrome features such as multiple congenital anomalies, facial dysmorphism and congenital heart anomalies are very rare in a 5-months old male child. Trisomy-21 is not uncommon in chromosomal abnormality with the birth defect and balanced translocations are frequently observed in patients with secondary infertility or recurrent spontaneous abortion (RSA). Two ml heparinized peripheral blood cells cultured in RPMI-1640 for 72 hours supplemented with 20% fetal bovine serum, phytohemagglutinin (PHA), and antibiotics were used for chromosomal analysis. A total 30 metaphases images were captured using Olympus-BX51 microscope and analyzed using Bio-view karyotyping software through GTG-banding (G bands by trypsin and Giemsa) according to International System for Human Cytogenetic Nomenclature 2016. The results showed balanced translocation between short arm of chromosome # 3 and short arm of chromosome # 10. The karyotype of the child was found to be 46,XY,t(3;10)(p21; p13). Chromosomal abnormalities are one of the major causes of birth defect in new born babies. Also, balanced translocations are frequently observed in patients with secondary infertility or recurrent spontaneous abortion. The index case presented with dysmorphic facial features and had a balanced translocation 46,XY,t(3;10)(p21;p13). This translocation with break points at (p21; p13) has not been reported in the literature in a child with facial dysmorphism. To the best of our knowledge, this is the first report of novel balanced translocation t(3;10) with break points in a child with dysmorphic features. We found balanced chromosomal translocation instead of any trisomy or unbalanced aberrations along with some phenotypic abnormalities. Therefore, we suggest that such novel balanced translocation with abnormal phenotype should be reported in order to enable the pathologist, pediatrician, and gynecologist to have a better insight into the intricacies of chromosomal abnormalities and their associated phenotypic features. We hypothesized that dysmorphic features as seen in this case may be the result of change in the pattern of genes located at the breakpoint area in balanced translocations or may be due to deletion or mutation of genes located on the p-arm of chromosome # 3 and p-arm of chromosome # 10.

Keywords: balanced translocation, karyotyping, phenotypic abnormalities, facial dimorphisms

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Authors: Dr. Jenit Gandhi, Dr. Manojith SS, Dr. Nakul GV, Dr. Sharath Honnani, Dr. Shaurav Ghosh, Dr. Neel Shetty, Dr. Nagabhushan JS, Dr. Manish Joshi

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Introduction: Acute pancreatitis is an inflammatory condition of the pancreas which begins in pancreatic acinar cells and triggers local inflammation that may progress to systemic inflammatory response (SIRS) and causing distant organ involvement and its function and ending up with multiple organ dysfunction syndromes (MODS). Aim: A comparative study in acute pancreatitis to find out the effectiveness of early addition of Ulinastatin to current standard care in Indian subjects . Methodology: A current prospective observational study is done during study period of 1year (Dec 2018 –Dec 2019) duration to evaluate the effect of early addition of Ulinastatin to the current standard treatment and its efficacy to reduce the early complication, analgesic requirement and duration of hospital stay in patients with Acute Pancreatitis. Results: In the control group 25 were males and 05 were females. In the test group 18 were males and 12 females. Majority was in the age group between 30 - 70 yrs of age with >50% in the 30-50yrs age group in both test and control groups. The VAS was median grade 3 in control group as compared to median grade 2 in test group , the pain was more in the initial 2 days in test group compared to 4 days in test group , the analgesic requirement was used for more in control group (median 6) to test group( median 3 days ). On follow up after 5 days for a period of 2 weeks none of the patients in the test group developed any complication. Where as in the control group 8 patients developed pleural effusion, 04-Pseudopancreatic cyst, 02 – patient developed portal vein and splenic vein thrombosis, 02 patients – ventilator with ARDS which were treated symptomatically whereas in test group 02 patient developed pleural effusions and 01 pseudo pancreatic cyst with splenic artery aneurysm, 01 – patient with AKI and MODS symptomatically treated. The duration of hospital stay for a median period of 4 days (2 – 7 days) in test group and 7 days (4 -10 days) in control group. All patients were able to return to normal work on an average of 5days compared 8days in control group, the difference was significant. Conclusion:The study concluded that early addition of Ulinastatin to current standard treatment of acute Pancreatitis is effective in reducing pain, early complication and duration of hospital stay in Indian subject

Keywords: Ulinastatin, VAS – visual analogue score , AKI – acute kidney injury , ARDS – acute respiratory distress syndrome

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Authors: Veenapani Rajeev Verma

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Context: Assessing facility readiness is paramount as it can indicate capacity of facilities to provide essential care for resilience to health challenges. In the context of decentralization, estimation of supply side readiness indices at sub national level is imperative for effective evidence based policy but remains a colossal challenge due to lack of dependable and representative data sources. Setting: District Poonch of Jammu and Kashmir was selected for this study. It is remote, rural district with unprecedented topographical barriers and is identified as high priority by government. It is also a fragile area as is bounded by Line of Control with Pakistan bearing the brunt of cease fire violations, military skirmishes and sporadic militant attacks. Hilly geographical terrain, rudimentary/absence of road network and impoverishment are quintessential to this area. Objectives: Objective of the study is to a) Evaluate the service readiness of health facilities and create a concise index subsuming plethora of discrete indicators and b) Ascertain supply side barriers in service provisioning via stakeholder’s analysis. Study also strives to expand analytical domain unravelling context and area specific intricacies associated with service delivery. Methodology: Mixed method approach was employed to triangulate quantitative analysis with qualitative nuances. Facility survey encompassing 90 Subcentres, 44 Primary health centres, 3 Community health centres and 1 District hospital was conducted to gauge general service availability and service specific availability (depth of coverage). Compendium of checklist was designed using Indian Public Health Standards (IPHS) in form of standard core questionnaire and scorecard generated for each facility. Information was collected across dimensions of amenities, equipment, medicines, laboratory and infection control protocols as proposed in WHO’s Service Availability and Readiness Assesment (SARA). Two stage polychoric principal component analysis employed to generate a parsimonious index by coalescing an array of tracer indicators. OLS regression method used to determine factors explaining composite index generated from PCA. Stakeholder analysis was conducted to discern qualitative information. Myriad of techniques like observations, key informant interviews and focus group discussions using semi structured questionnaires on both leaders and laggards were administered for critical stakeholder’s analysis. Results: General readiness score of health facilities was found to be 0.48. Results indicated poorest readiness for subcentres and PHC’s (first point of contact) with composite score of 0.47 and 0.41 respectively. For primary care facilities; principal component was characterized by basic newborn care as well as preparedness for delivery. Results revealed availability of equipment and surgical preparedness having lowest score (0.46 and 0.47) for facilities providing secondary care. Presence of contractual staff, more than 1 hr walk to facility, facilities in zone A (most vulnerable) to cross border shelling and facilities inaccessible due to snowfall and thick jungles was negatively associated with readiness index. Nonchalant staff attitude, unavailability of staff quarters, leakages and constraint in supply chain of drugs and consumables were other impediments identified. Conclusions/Policy Implications: It is pertinent to first strengthen primary care facilities in this setting. Complex dimensions such as geographic barriers, user and provider behavior is not under precinct of this methodology.

Keywords: effective coverage, principal component analysis, readiness index, universal health coverage

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Authors: Babarina Maria, Andropova Margarita

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Introduction: Hypoparathyroidism (HypoPT) is a rare endocrine disorder with an estimated prevalence of 0.25 per 1000 individuals. The most common cause of HypoPT is the loss of active parathyroid tissue following thyroid or parathyroid surgery. Sometimes permanent postoperative HypoPT occures, manifested by hypocalcemia in combination with low levels of PTH during 6 months or more after surgery. Cognitive impairments in patients with hypocalcemia due to chronic HypoPT are observed, and this can lead to problems and challenges in everyday living: memory loss and impaired concentration, that may be the cause of poor compliance. Clinical case: Patient K., 66 years old, underwent thyroidectomy in 2013 (at the age of 55) because of papillary thyroid cancer T1NxMx, histopathology findings confirmed the diagnosis. 5 years after the surgery, she was followed up on an outpatient basis, TSH levelsonly were monitored, and the dose of levothyroxine was adjusted. In 2018 due to, increasing complaints include tingling and cramps in the arms and legs, memory loss, sleep disorder, fatigue, anxiety, hair loss, muscle pain, tachycardia, positive Chvostek, and Trousseau signs were diagnosed during examination, also in blood analyses: total Ca 1.86 mmol/l (2.15-2.55), Ca++ 0.96 mmol/l (1.12-1.3), P 1.55 mmol/l (0.74-1.52), Mg 0.79 mmol/l (0.66-1.07) - chronic postoperative HypoPT was diagnosed. Therapy was initiated: alfacalcidol 0.5 mcg per day, calcium carbonate 2000 mg per day, cholecalciferol 1000 IU per day, magnesium orotate 3000 mg per day. During the case follow-up, hypocalcemia, hyperphosphatemia persisted, hypercalciuria15.7 mmol/day (2.5-6.5) was diagnosed. Dietary recommendations were given because of the high content of phosphorus rich foods, and therapy was adjusted: the dose of alfacalcidol was increased to 2.5 mcg per day, and the dose of calcium carbonate was reduced to 1500 mg per day. As part of the screening for complications of hypoPT, data for cataracts, Fahr syndrome, nephrocalcinosis, and kidney stone disease were not obtained. However, HypoPT compensation was not achieved, and therefore hydrochlorothiazide 25 mg was initiated, the dose of alfacalcidol was increased to 3 mcg per day, calcium carbonate to 3000 mg per day, magnesium orotate and cholecalciferol were continued at the same doses. Therapeutic goals were achieved: calcium phosphate product <4.4 mmol2/l2, there were no episodes of hypercalcemia, twenty-four-hour urinary calcium excretion was significantly reduced. Conclusion: Timely prescription, careful explanation of drugs usage rules, and monitoring and maintaining blood and urine parameters within the target contribute to the prevention of HypoPT complications development and life-threatening events.

Keywords: hypoparathyroidism, hypocalcemia, hyperphosphatemia, hypercalciuria

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Authors: Neha Batra Bali, Monika Tomar, Vinay Gupta

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A reagentless biosensor for detection of urea based on ZnO-CuO composite thin film is presented in following work. Biosensors have immense potential for varied applications ranging from environmental to clinical testing, health care, and cell analysis. Immense growth in the field of biosensors is due to the huge requirement in today’s world to develop techniques which are both cost effective and accurate for prevention of disease manifestation. The human body comprises of numerous biomolecules which in their optimum levels are essential for functioning. However mismanaged levels of these biomolecules result in major health issues. Urea is one of the key biomolecules of interest. Its estimation is of paramount significance not only for healthcare sector but also from environmental perspectives. If level of urea in human blood/serum is abnormal, i.e., above or below physiological range (15-40mg/dl)), it may lead to diseases like renal failure, hepatic failure, nephritic syndrome, cachexia, urinary tract obstruction, dehydration, shock, burns and gastrointestinal, etc. Various metal nanoparticles, conducting polymer, metal oxide thin films, etc. have been exploited to act as matrix to immobilize urease to fabricate urea biosensor. Amongst them, Zinc Oxide (ZnO), a semiconductor metal oxide with a wide band gap is of immense interest as an efficient matrix in biosensors by virtue of its natural abundance, biocompatibility, good electron communication feature and high isoelectric point (9.5). In spite of being such an attractive candidate, ZnO does not possess a redox couple of its own which necessitates the use of electroactive mediators for electron transfer between the enzyme and the electrode, thereby causing hindrance in realization of integrated and implantable biosensor. In the present work, an effort has been made to fabricate a matrix based on ZnO-CuO composite prepared by pulsed laser deposition (PLD) technique in order to incorporate redox properties in ZnO matrix and to utilize the same for reagentless biosensing applications. The prepared bioelectrode Urs/(ZnO-CuO)/ITO/glass exhibits high sensitivity (70µAmM⁻¹cm⁻²) for detection of urea (5-200 mg/dl) with high stability (shelf life ˃ 10 weeks) and good selectivity (interference ˂ 4%). The enhanced sensing response obtained for composite matrix is attributed to the efficient electron exchange between ZnO-CuO matrix and immobilized enzymes, and subsequently fast transfer of generated electrons to the electrode via matrix. The response is encouraging for fabricating reagentless urea biosensor based on ZnO-CuO matrix.

Keywords: biosensor, reagentless, urea, ZnO-CuO composite

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Authors: Fani Sakellariadou

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The Blue Economy includes all marine-based and marine-related activities. They correspond to established, emerging as well as unborn ocean-based industries. Seabed mining is an emerging marine-based activity; its operations depend particularly on cutting-edge science and technology. The 21st century will face a crisis in resources as a consequence of the world’s population growth and the rising standard of living. The natural capital stored in the global ocean is decisive for it to provide a wide range of sustainable ecosystem services. Seabed mineral deposits were identified as having a high potential for critical elements and base metals. They have a crucial role in the fast evolution of green technologies. The major categories of marine mineral deposits are deep-sea deposits, including cobalt-rich ferromanganese crusts, polymetallic nodules, phosphorites, and deep-sea muds, as well as shallow-water deposits including marine placers. Seabed mining operations may take place within continental shelf areas of nation-states. In international waters, the International Seabed Authority (ISA) has entered into 15-year contracts for deep-seabed exploration with 21 contractors. These contracts are for polymetallic nodules (18 contracts), polymetallic sulfides (7 contracts), and cobalt-rich ferromanganese crusts (5 contracts). Exploration areas are located in the Clarion-Clipperton Zone, the Indian Ocean, the Mid Atlantic Ridge, the South Atlantic Ocean, and the Pacific Ocean. Potential environmental impacts of deep-sea mining include habitat alteration, sediment disturbance, plume discharge, toxic compounds release, light and noise generation, and air emissions. They could cause burial and smothering of benthic species, health problems for marine species, biodiversity loss, reduced photosynthetic mechanism, behavior change and masking acoustic communication for mammals and fish, heavy metals bioaccumulation up the food web, decrease of the content of dissolved oxygen, and climate change. An important concern related to deep-sea mining is our knowledge gap regarding deep-sea bio-communities. The ecological consequences that will be caused in the remote, unique, fragile, and little-understood deep-sea ecosystems and inhabitants are still largely unknown. The blue economy conceptualizes oceans as developing spaces supplying socio-economic benefits for current and future generations but also protecting, supporting, and restoring biodiversity and ecological productivity. In that sense, people should apply holistic management and make an assessment of marine mining impacts on ecosystem services, including the categories of provisioning, regulating, supporting, and cultural services. The variety in environmental parameters, the range in sea depth, the diversity in the characteristics of marine species, and the possible proximity to other existing maritime industries cause a span of marine mining impact the ability of ecosystems to support people and nature. In conclusion, the use of the untapped potential of the global ocean demands a liable and sustainable attitude. Moreover, there is a need to change our lifestyle and move beyond the philosophy of single-use. Living in a throw-away society based on a linear approach to resource consumption, humans are putting too much pressure on the natural environment. Applying modern, sustainable and eco-friendly approaches according to the principle of circular economy, a substantial amount of natural resource savings will be achieved. Acknowledgement: This work is part of the MAREE project, financially supported by the Division VI of IUPAC. This work has been partly supported by the University of Piraeus Research Center.

Keywords: blue economy, deep-sea mining, ecosystem services, environmental impacts

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Authors: I. M. Salama, R. N. Miftahof

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A functional element of the myenteric nervous plexus is a morphologically distinct ganglion. Composed of sensory, inter- and motor neurons and arranged via synapses in neuronal circuits, their task is to decipher and integrate spike coded information within the plexus into regulatory output signals. The stability of signal processing in response to a wide range of internal/external perturbations depends on the plasticity of individual neurons. Any aberrations in this inherent property may lead to instability with the development of a dynamics chaos and can be manifested as pathological conditions, such as intestinal dysrhythmia, irritable bowel syndrome. The aim of this study is to investigate patterns of signal transduction within a two-neuronal chain - a ganglion - under normal physiological and structurally altered states. The ganglion contains the primary sensory (AH-type) and motor (S-type) neurons linked through a cholinergic dendro somatic synapse. The neurons have distinguished electrophysiological characteristics including levels of the resting and threshold membrane potentials and spiking activity. These are results of ionic channel dynamics namely: Na+, K+, Ca++- activated K+, Ca++ and Cl-. Mechanical stretches of various intensities and frequencies are applied at the receptive field of the AH-neuron generate a cascade of electrochemical events along the chain. At low frequencies, ν < 0.3 Hz, neurons demonstrate strong connectivity and coherent firing. The AH-neuron shows phasic bursting with spike frequency adaptation while the S-neuron responds with tonic bursts. At high frequency, ν > 0.5 Hz, the pattern of electrical activity changes to rebound and mixed mode bursting, respectively, indicating ganglionic loss of plasticity and adaptability. A simultaneous increase in neuronal conductivity for Na+, K+ and Ca++ ions results in tonic mixed spiking of the sensory neuron and class 2 excitability of the motor neuron. Although the signal transduction along the chain remains stable the synchrony in firing pattern is not maintained and the number of discharges of the S-type neuron is significantly reduced. A concomitant increase in Ca++- activated K+ and a decrease in K+ in conductivities re-establishes weak connectivity between the two neurons and converts their firing pattern to a bistable mode. It is thus demonstrated that neuronal plasticity and adaptability have a stabilizing effect on the dynamics of signal processing in the ganglion. Functional modulations of neuronal ion channel permeability, achieved in vivo and in vitro pharmacologically, can improve connectivity between neurons. These findings are consistent with experimental electrophysiological recordings from myenteric ganglia in intestinal dysrhythmia and suggest possible pathophysiological mechanisms.

Keywords: neuronal chain, signal transduction, plasticity, stability

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Authors: Jannis Kountouras, Nikolaos Kapetanakis, Stergios A. Polyzos, Apostolis Papaeftymiou, Panagiotis Katsinelos, Ioannis Venizelos, Christina Nikolaidou, Christos Zavos, Iordanis Romiopoulos, Elena Tsiaousi, Evangelos Kazakos, Michael Doulberis

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Background & Aims: Helicobacter pylori infection (Hp-I) has been recognized as a substantial risk agent involved in gastrointestinal (GI) tract oncogenesis by stimulating cancer stem cells (CSCs), oncogenes, immune surveillance processes, and triggering GI microbiota dysbiosis. We aimed to investigate the possible involvement of active Hp-I in the sequence: chronic inflammation–adenoma–colorectal cancer (CRC) development. Methods: Four pillars were investigated: (i) endoscopic and conventional histological examinations of patients with CRC, colorectal adenomas (CRA) versus controls to detect the presence of active Hp-I; (ii) immunohistochemical determination of the presence of Hp; expression of CD44, an indicator of CSCs and/or bone marrow-derived stem cells (BMDSCs); expressions of oncogene Ki67 and anti-apoptotic Bcl-2 protein; (iii) expression of CD45, indicator of immune surveillance locally (assessing mainly T and B lymphocytes locally); and (iv) correlation of the studied parameters with the presence or absence of Hp-I. Results: Among 50 patients with CRC, 25 with CRA, and 10 controls, a significantly higher presence of Hp-I in the CRA (68%) and CRC group (84%) were found compared with controls (30%). The presence of Hp-I with accompanying immunohistochemical expression of CD44 in biopsy specimens was revealed in a high proportion of patients with CRA associated with moderate/severe dysplasia (88%) and CRC patients with moderate/severe degree of malignancy (91%). Comparable results were also obtained for Ki67, Bcl-2, and CD45 immunohistochemical expressions. Concluding Remarks: Hp-I seems to be involved in the sequence: CRA – dysplasia – CRC, similarly to the upper GI tract oncogenesis, by several pathways such as the following: Beyond Hp-I associated insulin resistance, the major underlying mechanism responsible for the metabolic syndrome (MetS) that increase the risk of colorectal neoplasms, as implied by other Hp-I related MetS pathologies, such as non-alcoholic fatty liver disease and upper GI cancer, the disturbance of the normal GI microbiota (i.e., dysbiosis) and the formation of an irritative biofilm could contribute to a perpetual inflammatory upper GIT and colon mucosal damage, stimulating CSCs or recruiting BMDSCs and affecting oncogenes and immune surveillance processes. Further large-scale relative studies with a pathophysiological perspective are necessary to demonstrate in-depth this relationship.

Keywords: Helicobacter pylori, colorectal cancer, colorectal adenomas, gastrointestinal oncogenesis

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Authors: B. T. Naveen Kumar, Anuj Tyagi, Niraj Kumar Singh, Visanu Boonyawiwat, A. H. Shanthanagouda, Orawan Boodde, K. M. Shankar, Prakash Patil, Shubhkaramjeet Kaur

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Early mortality syndrome (EMS)/Acute Hepatopancreatic Necrosis Disease (AHPND) has emerged as a major obstacle for the shrimp farming around the world. It is caused by a strain of Vibrio parahaemolyticus. The possible preventive and control measure is, early and rapid detection of the pathogen in the broodstock, post-larvae and monitoring the shrimp during the culture period. Polymerase chain reaction (PCR) based early detection methods are good, but they are costly, time taking and requires a sophisticated laboratory. The present study was conducted to develop a simple, sensitive and rapid diagnostic farmer level kit for the reliable detection of AHPND in shrimp. A panel of monoclonal antibodies (MAbs) were raised against the recombinant Pir B protein (rPirB). First, an immunodot was developed by using MAbs G3B8 and Mab G3H2 which showed specific reactivity to purified r-PirB protein with no cross-reactivity to other shrimp bacterial pathogens (AHPND free Vibrio parahaemolyticus (Indian strains), V. anguillarum, WSSV, Aeromonas hydrophila, and Aphanomyces invadans). Immunodot developed using Mab G3B8 is more sensitive than that with the Mab G3H2. However, immunodot takes almost 2.5 hours to complete with several hands-on steps. Therefore, the flow-through assay (FTA) was developed by using a plastic cassette containing the nitrocellulose membrane with absorbing pads below. The sample was dotted in the test zone on the nitrocellulose membrane followed by continuos addition of five solutions in the order of i) blocking buffer (BSA) ii) primary antibody (MAb) iii) washing Solution iv) secondary antibody and v) chromogen substrate (TMB) clear purple dots against a white background were considered as positive reactions. The FTA developed using MAbG3B8 is more sensitive than that with MAb G3H2. In FTA the two MAbs showed specific reactivity to purified r-PirB protein and not to other shrimp bacterial pathogens. The FTA is simple to farmer/field level, sensitive and rapid requiring only 8-10 min for completion. Tests can be developed to kits, which will be ideal for use in biosecurity, for the first line of screening (at the port or pond site) and during monitoring and surveillance programmes overall for the good management practices to reduce the risk of the disease.

Keywords: acute hepatopancreatic necrosis disease, AHPND, flow-through assay, FTA, farmer level, immunodot, pond site, shrimp

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Authors: Nursyafiq Ali Shibramulisi, Nor Farah Fauzi, Nur Azniza Zawin Anuar, Nurul Atikah Azmi, Janice Hew Pei Fang

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Background: Work related musculoskeletal disorders (WRMD) among dental personnel have been underestimated and under-reported worldwide and specifically in Malaysia. The problem will arise and progress slowly over time, as it results from accumulated injury throughout the period of work. Several risk factors, such as repetitive movement, static posture, vibration, and adapting poor working postures, have been identified to be contributing to WRMSD in dental practices. Dental personnel is at higher risk of getting this problem as it is their working nature and core business. This would cause pain and dysfunction syndrome among them and result in absence from work and substandard services to their patients. Methodology: A cross-sectional study involving 19 government dental clinics in Perak was done over the period of 3 months. Those who met the criteria were selected to participate in this study. Malay version of the Self-Reported Nordic Musculoskeletal Discomfort Form was used to identify the prevalence of WRMSD, while the intensity of pain in the respective regions was evaluated using a 10-point scale according to ‘Pain as The 5ᵗʰ Vital Sign’ by MOH Malaysia and later on were analyzed using SPSS version 25. Descriptive statistics, including mean and SD and median and IQR, were used for numerical data. Categorical data were described by percentage. Pearson’s Chi-Square Test and Spearman’s Correlation were used to find the association between the prevalence of WRMSD and other socio-demographic data. Results: 159 dentists, 73 dental therapists, 26 dental lab technicians, 81 dental surgery assistants, and 23 dental attendants participated in this study. The mean age for the participants was 34.9±7.4 and their mean years of service was 9.97±7.5. Most of them were female (78.5%), Malay (71.3%), married (69.6%) and right-handed (90.1%). The highest prevalence of WRMSD was neck (58.0%), followed by shoulder (48.1%), upper back (42.0%), lower back (40.6%), hand/wrist (31.5%), feet (21.3%), knee (12.2%), thigh 7.7%) and lastly elbow (6.9%). Most of those who reported having neck pain scaled their pain experiences at 2 out of 10 (19.5%), while for those who suffered upper back discomfort, most of them scaled their pain experience at 6 out of 10 (17.8%). It was found that there was a significant relationship between age and pain at neck (p=0.007), elbow (p=0.027), lower back (p=0.032), thigh (p=0.039), knee (p=0.001) and feet (p=0.000) regions. Job position also had been found to be having a significant relationship with pain experienced at the lower back (p=0.018), thigh (p=0.011), knee, and feet (p=0.000). Conclusion: The prevalence of WRMSD among dental personnel in Perak was found to be high. Age and job position were found to be having a significant relationship with pain experienced in several regions. Intervention programs should be planned and conducted to prevent and reduce the occurrence of WRMSD, as all harmful or unergonomic practices should be avoided at all costs.

Keywords: WRMSD, ergonomic, dentistry, dental

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Authors: Jacob Dangerfield, Jacob Pollard, Jennifer DeCou

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Introduction: Burnout, anxiety, and depression are three conditions that are prevalent in medical providers. This is especially the case in the field of anesthesia, which has a high number of providers suffering from burnout and burnout syndrome. A major contributor to this issue is isolation in the workplace, with a perceived lack of peer support as a major risk factor for burnout. Two organizational interventions that can be done to help improve this issue are small group sessions and providing affordable mental health services. Per American College of Graduate Medical Education (ACGME) Guidelines, these affordable mental health services are a requirement of all residency programs, but for a variety of reasons, many residents do not access them. As physicians, we are often not good at asking for help. With this in mind, we hypothesized that carrying out small group resiliency sessions facilitated by Graduate Medical Education (GME) Wellness Counselors would improve both resident peer support as well as the likelihood that a resident will reach out to GME Wellness in a time of need. Methods: We held small group resiliency sessions with the GME Wellness Mental Health Professionals during protected didactic time. These sessions were small groups, including the members of one’s class (i.e., first-year residents on their own), and were facilitated by 1-2 mental health professionals. After these sessions, we surveyed residents who attended using a short Google Forms survey and using a 5-point Likert Scale, asked residents about some outcomes from the session. A “strongly agree” or “agree” was considered a positive response. Results: Results from our survey showed that the resident sessions had multiple positive outcomes. This survey was sent to 29 residents, and we had a 62% response rate. We found out through this survey that these small group sessions had a perceived positive impact on resident personal well-being, increased perceived peer support from classmates, and made residents more likely to reach out to GME Wellness in the future. Perceived positive impact on well-being was found in 83% of resident respondents, improved perceived peer support in 83% of respondents, and 78% of resident respondents stated that this session increased their likelihood of reaching out to mental health professionals. Conclusions: Through this study, we can conclude that our hypothesis was correct in that Small Group Resiliency Sessions that are facilitated by GME Wellness Counselors improve both resident peer support as well as the likelihood a resident reaches out to these mental health professionals in time of need. We believe these findings are very important as they address two important factors that can aid in decreasing a provider’s risk of experiencing burnout. Through this simple means, we believe other residency programs can help the well-being of their residents, and together, we can decrease the number of cases of burnout in anesthesia.

Keywords: anesthesiology, burnout, wellness, depression, residents, trainees, mental health

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Authors: Gustavo Axel Elizalde-Velázquez

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Metformin is the first line of oral therapy to treat type II diabetes and is also employed as a treatment for other indications, such as polycystic ovary syndrome, cancer, and COVID-19. Recent data suggest it is the aspirin of the 21st century due to its antioxidant and anti-aging effects. However, increasingly current articles indicate its long-term consumption generates mitochondrial impairment. Up to date, it is known metformin increases the biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription, but further information related to brain damage after its consumption is missing. Bearing in mind the above, this work aimed to establish whether or not chronic exposure to metformin may alter swimming behavior and induce neurotoxicity in Danio rerio adults. For this purpose, 250 Danio rerio grown-ups were assigned to six tanks of 50 L of capacity. Four of the six systems contained 50 fish, while the remaining two had 25 fish (≈1 male:1 female ratio). Every system with 50 fish was allocated one of the three metformin treatment concentrations (1, 20, and 40 μg/L), with one system as the control treatment. Systems with 25 fish, on the other hand, were used as positive controls for acetylcholinesterase (10 μg/L of Atrazine) and oxidative stress (3 μg/L of Atrazine). After four months of exposure, a mean of 32 fish (S.D. ± 2) per group of MET treatment survived, which were used for the evaluation of behavior with the Novel Tank test. Moreover, after the behavioral assessment, we aimed to collect the blood and brains of all fish from all treatment groups. For blood collection, fish were anesthetized with an MS-222 solution (150 mg/L), while for brain gathering, fish were euthanized using the hypothermic shock method (2–4 °C). Blood was employed to determine CASP3 activity and the percentage of apoptotic cells with the TUNEL assay, and brains were used to evaluate acetylcholinesterase activity, oxidative damage, and gene expression. After chronic exposure, MET-exposed fish exhibited less swimming activity when compared to control fish. Moreover, compared with the control group, MET significantly inhibited the activity of AChE and induced oxidative damage in the brain of fish. Concerning gene expression, MET significantly upregulated the expression of Nrf1, Nrf2, BAX, p53, BACE1, APP, PSEN1, and downregulated CASP3 and CASP9. Although MET did not overexpress the CASP3 gene, we saw a meaningful rise in the activity of this enzyme in the blood of fish exposed to MET compared to the control group, which we then confirmed by a high number of apoptotic cells in the TUNEL assay. To the best of our understanding, this is the first study that delivers evidence of oxidative impairment, apoptosis, AChE alteration, and overexpression of B- amyloid-related genes in the brain of fish exposed to metformin.

Keywords: AChE inhibition, CASP3 activity, NovelTank test, oxidative damage, TUNEL assay

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Authors: Satria B. Mahathma, Asri Hendrawati

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Background: Diabetes mellitus (DM) is a metabolic disorder syndrome characterized by chronic hyperglycemia. The number of people with diabetes rose from 108 million in 1980 to 422 million in 2014. In general, almost 90% of the prevalence of DM is type 2 DM which marked by insulin resistance and decreased receptor sensitivity. Aside from conventional antidiabetic therapy, the utilization of medicinal plants as alternative medicine has beneficial effects in diabetic patients. Flavonoid contents in radish leaves such as quercetin, pelargonidin, and kaempferol are thought to have antidiabetic activity on decreasing blood glucose levels by tricyclic nucleotide modulation of pancreatic beta cells and ameliorating insulin resistance. This study aimed to determine the effect of variant concentration of radish leaves ethanol extract on blood glucose levels in diabetic rats. Method: This study used pretest-posttest control group design by using 16 male Wistar rats which were induced type-2 diabetic by streptozotocin 60 mg/kg BW-nicotinamide 120 mg/kg BW intraperitoneally. Rats who had developed type-2 DM later divided randomly into 4 groups; negative control received placebo, positive control received glibenclamide 5 mg/kg BW/day, rats intervention I and intervention II received 100% and 50% of radish leaves ethanol extract, respectively. Treatments were administered orally for four weeks. The blood glucose levels were measured using the Enzymatic Colorimetric Test “GOD-PAP”. Data were analyzed by the dependent t-test for pretest-posttest intervention difference and one-way ANOVA followed by post hoc test to determine the significant difference of each treatment to obtain the significant data. Result: The result revealed that intervention group had lower blood glucose levels mean than control group which the lowest was intervention II group (negative control: 540,9 ± 191,7 mg/dl, positive control: 494, 97 ± 64,91 mg/dl, intervention I: 301,92 ± 165,70 mg/dl, and intervention II group: 276,1 ± 139,02 mg/dl. Intervention II group had the highest antidiabetic activity, followed by the intervention I group with the amount of decrease in blood glucose levels were -151,85 ± 77,43 mg/dl and -11,08 ± 186,62 mg/dl, however negative and positive control group didn’t have antidiabetic activity. The dependent t-test result showed there is a significant difference in decreasing blood glucose levels in the intervention II pretest-posttest intervention (p=0,03) while the other group didn’t. Data analyzed by one-way ANOVA also revealed the intervention II group significantly declined blood glucose levels compared to the negative and positive control group (p = 0,033 and p=0,032, respectively). Conclusion: There is a significant effect of radish leaves ethanol extract on blood glucose levels in streptozotocin-nicotinamide-induced diabetic rats with the optimal therapeutic effect at a concentration of 50%.

Keywords: blood glucose levels, medicinal plant, radish leaves, type-2 diabetes mellitus

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Authors: Vanessa Bennemann, Gabriela Laste, Márcia Inês Goettert

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The gestational period is a phase in which the pregnant woman undergoes constant physiological and hormonal changes, which are part of the woman’s biological cycle, the development of the fetus, childbirth, and lactation. These are factors of response to the immunological adaptation of the human reproductive process that is directly related to the pregnancy’s well-being and development. Although most pregnancies occur without complications, about 15% of pregnant women will develop potentially fatal complications, implying maternal and fetal risk. Therefore, requiring specialized care for high-risk pregnant women (HRPW) with obstetric interventions for the survival of the mother and/or fetus. Among the risk factors that characterize HRPW are the women's age, gestational diabetes mellitus (GDM), autoimmune diseases, infectious diseases such as syphilis and HIV, hypertension (SAH), preeclampsia, eclampsia, HELLP syndrome, uterine contraction abnormalities, and premature placental detachment (PPD), thyroid disorders, among others. Thus, pregnancy has an impact on the thyroid gland causing changes in the functioning of the mother's thyroid gland, altering the thyroid hormone (TH) profiles and production as pregnancy progresses. Considering, throughout the gestational period, the interpretation of the results of the tests to evaluate the thyroid functioning depends on the stage in which the pregnancy is. Thyroid disorders are directly related to adverse obstetric outcomes and in child development. Therefore, the adequate release of TH is important for a pregnancy without complications and optimal fetal growth and development. Objective: Investigate the physiological effects caused by thyroid disorders in the gestational period. Methods: A search for articles indexed in PubMed, Scielo, and MDPI databases, was performed using the term “AND”, with the descriptors: Pregnancy, Thyroid. With several combinations that included: Melatonin, Thyroidopathy, Inflammatory processes, Cytokines, Anti-inflammatory, Antioxidant, High-risk pregnancy. Subsequently, the screening was performed through the analysis of titles and/or abstracts. The criteria were: including clinical studies in general, randomized or not, in the period of 10 years prior to the research, in the English literature; excluded: experimental studies, case reports, research in the development phase. Results: In the preliminary results, a total of studies (n=183) were found, (n=57) excluded, such as studies of cancer, diabetes, obesity, and skin diseases. Conclusion: To date, it has been identified that thyroid diseases can impair the fetus’s brain development. Further research is suggested on this matter to identify new substances that may have a potential therapeutic effect to aid the gestational period with thyroid diseases.

Keywords: pregnancy, thyroid, melatonin, high-risk pregnancy

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Authors: Anshu Gupta, Charu Gupta

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Background: Adolescence is the transitional period between puberty and adulthood. It is marked by immense turmoil in emotional and behavioral spheres. Adolescents are at risk of an array of behavioral and emotional problems, resulting in social, academic and vocational function impairments. Conflicts in the family and inability of the parents to cope with the changing demands of an adolescent have a negative impact on the overall development of the child. This augers ill for the individual’s future, resulting in depression, delinquency and suicides among other problems. Aim: The aim of the study was to compare the prevalence of behavioral and emotional problems in school going adolescents aged 13 to 15 years residing in Ludhiana city. Method: A total of 1380 school children in the age group of 13 to 15 years were assessed by the adolescent health screening questionnaire (FAPS) and Youth Self-Report (2001) questionnaire. Statistical significance was ascertained by t-test, chi-square test (x²) and ANOVA, as appropriate. Results: A considerably high prevalence of behavioral and emotional problems was found in school going adolescents (26.5%), more in girls (31.7%) than in boys (24.4%). In case of boys, the maximum problem was in the 13 year age group, i.e., 28.2%, followed by a significant decline by the age of 14 years, i.e., 24.2% and 15 years, i.e., 19.6%. In case of girls also, the maximum problem was in the 13 year age group, i.e., 32.4% followed by a marginal decline in the 14 years i.e., 31.8% and 15 year age group, i.e., 30.2%. Demographic factors were non contributory. Internalizing syndrome (22.4%) was the most common problem followed by the neither internalizing nor externalizing (17.6%) group. In internalizing group, most (26.5%) of the students were observed to be anxious/ depressed. Social problem was observed to be the most frequent (10.6%) among neither internalizing nor externalizing group. Aggressive behavior was the commonest (8.4%) among externalizing group. Internalizing problems, mainly anxiety and depression, were commoner in females (30.6%) than males (24.6%). More boys (16%) than girls (13.4%) were reported to suffer from externalizing disorders. A critical review of the data showed that most of the adolescents had poor knowledge about reproductive health. Almost 36% reported that the source of their information on sexual and reproductive health being friends and the electronic media. There was a high percentage of adolescents who reported being worried about sexual abuse (20.2%) with majority of them being girls (93.6%) reflecting poorly on the social setup in the country. About 41% of adolescents reported being concerned about body weight and most of them being girls (92.4%). Up to 14.5% reported having thoughts of using alcohol or drugs perhaps due to the easy availability of substances of abuse in this part of the country. 12.8% (mostly girls) reported suicidal thoughts. Summary/conclusion: There is a high prevalence of emotional and behavioral problems among school-going adolescents. Resolution of these problems during adolescence is essential for attaining a healthy adulthood. The need of the hour is to spread awareness among caregivers and formulation of effective management strategies including school mental health programme.

Keywords: adolescence, behavioral, emotional, internalizing problem

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Authors: Mustafa M. Donma, Orkide Donma

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The examination of both serum lipid fractions and body’s lipid composition are quite informative during the evaluation of obesity stages. Within this context, alterations in lipid parameters are commonly observed. The variations in the fat distribution of the body are also noteworthy. Total cholesterol (TC), triglycerides (TRG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C) are considered as the basic lipid fractions. Fat deposited in trunk and extremities may give considerable amount of information and different messages during discrete health states. Ratios are also derived from distinct fat distribution in these areas. Trunk-to-leg fat ratio (TLFR) and trunk-to-appendicular fat ratio (TAFR) are the most recently introduced ratios. In this study, lipid fractions and TLFR, as well as TAFR, were evaluated, and the distinctions among healthy, obese (OB), and morbid obese (MO) groups were investigated. Three groups [normal body mass index (N-BMI), OB, MO] were constituted from a population aged 6 to 18 years. Ages and sexes of the groups were matched. The study protocol was approved by the Non-interventional Ethics Committee of Tekirdag Namik Kemal University. Written informed consent forms were obtained from the parents of the participants. Anthropometric measurements (height, weight, waist circumference, hip circumference, head circumference, neck circumference) were obtained and recorded during the physical examination. Body mass index values were calculated. Total, trunk, leg, and arm fat mass values were obtained by TANITA Bioelectrical Impedance Analysis. These values were used to calculate TLFR and TAFR. Systolic (SBP) and diastolic blood pressures (DBP) were measured. Routine biochemical tests including TC, TRG, LDL-C, HDL-C, and insulin were performed. Data were evaluated using SPSS software. p value smaller than 0.05 was accepted as statistically significant. There was no difference among the age values and gender ratios of the groups. Any statistically significant difference was not observed in terms of DBP, TLFR as well as serum lipid fractions. Higher SBP values were measured both in OB and MO children than those with N-BMI. TAFR showed a significant difference between N-BMI and OB groups. Statistically significant increases were detected between insulin values of N-BMI group and OB as well as MO groups. There were bivariate correlations between LDL and TLFR (r=0.396; p=0.037) as well as TAFR values (r=0.413; p=0.029) in MO group. When adjusted for SBP and DBP, partial correlations were calculated as (r=0.421; p=0.032) and (r=0.438; p=0.025) for LDL-TLFR as well as LDL-TAFR, respectively. Much stronger partial correlations were obtained for the same couples (r=0.475; p=0.019 and r=0.473; p=0.020, respectively) upon controlling for TRG and HDL-C. Much stronger partial correlations observed in MO children emphasize the potential transition from morbid obesity to metabolic syndrome. These findings have concluded that LDL-C may be suggested as a discriminating parameter between OB and MO children.

Keywords: children, lipid parameters, obesity, trunk-to-leg fat ratio, trunk-to-appendicular fat ratio

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Authors: Walter Vera-Ortega, Idoia Busnadiego, Sam J. Wilson

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Introduction: Human Immunodeficiency Virus type 1 (HIV-1) is responsible for the acquired immunodeficiency syndrome (AIDS), a leading cause of death worldwide infecting millions of people each year. Despite intensive research in vaccine development, therapies against HIV-1 infection are not curative, and the huge genetic variability of HIV-1 challenges to drug development. Current animal models for HIV-1 research present important limitations, impairing the progress of in vivo approaches. Macaques require a CD8+ depletion to progress to AIDS, and the maintenance cost is high. Mice are a cheaper alternative but need to be 'humanized,' and breeding is not possible. The development of an HIV-1 clone able to replicate in mice is a challenging proposal. The lack of human co-factors in mice impedes the function of the HIV-1 accessory proteins, Tat and Rev, hampering HIV-1 replication. However, Tat and Rev function can be replaced by constitutive/chimeric promoters, codon-optimized proteins and the constitutive transport element (CTE), generating a novel HIV-1 clone able to replicate in mice without disrupting the amino acid sequence of the virus. By minimally manipulating the genomic 'identity' of the virus, we propose the generation of an HIV-1 clone able to replicate in mice to assist in antiviral drug development. Methods: i) Plasmid construction: The chimeric promoters and CTE copies were cloned by PCR using lentiviral vectors as templates (pCGSW and pSIV-MPCG). Tat mutants were generated from replication competent HIV-1 plasmids (NHG and NL4-3). ii) Infectivity assays: Retroviral vectors were generated by transfection of human 293T cells and murine NIH 3T3 cells. Virus titre was determined by flow cytometry measuring GFP expression. Human B-cells (AA-2) and Hela cells (TZMbl) were used for infectivity assays. iii) Protein analysis: Tat protein expression was determined by TZMbl assay and HIV-1 capsid by western blot. Results: We have determined that NIH 3T3 cells are able to generate HIV-1 particles. However, they are not infectious, and further analysis needs to be performed. Codon-optimized HIV-1 constructs are efficiently made in 293T cells in a Tat and Rev independent manner and capable of packaging a competent genome in trans. CSGW is capable of generating infectious particles in the absence of Tat and Rev in human cells when 4 copies of the CTE are placed preceding the 3’LTR. HIV-1 Tat mutant clones encoding different promoters are functional during the first cycle of replication when Tat is added in trans. Conclusion: Our findings suggest that the development of an HIV-1 Tat-Rev independent clone is challenging but achievable aim. However, further investigations need to be developed prior presenting our HIV-1 clone as a candidate model for research.

Keywords: codon-optimized, constitutive transport element, HIV-1, long terminal repeats, research model

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Authors: Nathaniel Oladimeji Dixon, Adekemi Dorcas Fadun

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Educational managers have observed a downward trend in the administrative effectiveness of non-teaching staff in federal universities in South-west Nigeria. This is evident in the low-quality service delivery of administrators and unaccomplished institutional goals and missions of higher education. Scholars have thus indicated the need for the deployment and adoption of a practice that encourages information collection and sharing among stakeholders with a view to improving service delivery and outcomes. This study examined the extent to which knowledge management correlated with the administrative effectiveness of non-teaching staff in federal universities in South-west Nigeria. The study adopted the survey design. Three federal universities (the University of Ibadan, Federal University of Agriculture, Abeokuta, and Obafemi Awolowo University) were purposively selected because administrative ineffectiveness was more pronounced among non-teaching staff in government-owned universities, and these federal universities were long established. The proportional and stratified random sampling was adopted to select 1156 non-teaching staff across the three universities along the three existing layers of the non-teaching staff: secretarial (senior=311; junior=224), non-secretarial (senior=147; junior=241) and technicians (senior=130; junior=103). Knowledge Management Practices Questionnaire with four sub-scales: knowledge creation (α=0.72), knowledge utilization (α=0.76), knowledge sharing (α=0.79) and knowledge transfer (α=0.83); and Administrative Effectiveness Questionnaire with four sub-scales: communication (α=0.84), decision implementation (α=0.75), service delivery (α=0.81) and interpersonal relationship (α=0.78) were used for data collection. Data were analyzed using descriptive statistics, Pearson product-moment correlation and multiple regression at 0.05 level of significance, while qualitative data were content analyzed. About 59.8% of the non-teaching staff exhibited a low level of knowledge management. The indices of administrative effectiveness of non-teaching staff were rated as follows: service delivery (82.0%), communication (78.0%), decision implementation (71.0%) and interpersonal relationship (68.0%). Knowledge management had significant relationships with the indices of administrative effectiveness: service delivery (r=0.82), communication (r=0.81), decision implementation (r=0.80) and interpersonal relationship (r=0.47). Knowledge management had a significant joint prediction on administrative effectiveness (F (4;1151)= 0.79, R=0.86), accounting for 73.0% of its variance. Knowledge sharing (β=0.38), knowledge transfer (β=0.26), knowledge utilization (β=0.22), and knowledge creation (β=0.06) had relatively significant contributions to administrative effectiveness. Lack of team spirit and withdrawal syndrome is the major perceived constraints to knowledge management practices among the non-teaching staff. Knowledge management positively influenced the administrative effectiveness of the non-teaching staff in federal universities in South-west Nigeria. There is a need to ensure that the non-teaching staff imbibe team spirit and embrace teamwork with a view to eliminating their withdrawal syndromes. Besides, knowledge management practices should be deployed into the administrative procedures of the university system.

Keywords: knowledge management, administrative effectiveness of non-teaching staff, federal universities in the south-west of nigeria., knowledge creation, knowledge utilization, effective communication, decision implementation

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Authors: Mohamed Abo El Nasr, Mohamed Shoeib, Abdelhamid Abdelkhalik, Amro Serag

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Background: Early assessment of severity of chest trauma, either blunt or penetrating is of critical importance in prediction of patient outcome. Different trauma scoring systems are widely available and are based on anatomical or physiological parameters to expect patient morbidity or mortality. Up till now, there is no ideal, universally accepted trauma score that could be applied in all trauma centers and is suitable for assessment of severity of chest trauma patients. Aim: Our aim was to compare various trauma scoring systems regarding their predictability of morbidity and mortality in chest trauma patients. Patients and Methods: This study was a prospective study including 400 patients with chest trauma who were managed at Tanta University Emergency Hospital, Egypt during a period of 2 years (March 2014 until March 2016). The patients were divided into 2 groups according to the mode of trauma: blunt or penetrating. The collected data included age, sex, hemodynamic status on admission, intrathoracic injuries, and associated extra-thoracic injuries. The patients outcome including mortality, need of thoracotomy, need for ICU admission, need for mechanical ventilation, length of hospital stay and the development of acute respiratory distress syndrome were also recorded. The relevant data were used to calculate the following trauma scores: 1. Anatomical scores including abbreviated injury scale (AIS), Injury severity score (ISS), New injury severity score (NISS) and Chest wall injury scale (CWIS). 2. Physiological scores including revised trauma score (RTS), Acute physiology and chronic health evaluation II (APACHE II) score. 3. Combined score including Trauma and injury severity score (TRISS ) and 4. Chest-Specific score Thoracic trauma severity score (TTSS). All these scores were analyzed statistically to detect their sensitivity, specificity and compared regarding their predictive power of mortality and morbidity in blunt and penetrating chest trauma patients. Results: The incidence of mortality was 3.75% (15/400). Eleven patients (11/230) died in blunt chest trauma group, while (4/170) patients died in penetrating trauma group. The mortality rate increased more than three folds to reach 13% (13/100) in patients with severe chest trauma (ISS of >16). The physiological scores APACHE II and RTS had the highest predictive value for mortality in both blunt and penetrating chest injuries. The physiological score APACHE II followed by the combined score TRISS were more predictive for intensive care admission in penetrating injuries while RTS was more predictive in blunt trauma. Also, RTS had a higher predictive value for expectation of need for mechanical ventilation followed by the combined score TRISS. APACHE II score was more predictive for the need of thoracotomy in penetrating injuries and the Chest-Specific score TTSS was higher in blunt injuries. The anatomical score ISS and TTSS score were more predictive for prolonged hospital stay in penetrating and blunt injuries respectively. Conclusion: Trauma scores including physiological parameters have a higher predictive power for mortality in both blunt and penetrating chest trauma. They are more suitable for assessment of injury severity and prediction of patients outcome.

Keywords: chest trauma, trauma scores, blunt injuries, penetrating injuries

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Authors: Wu Liching

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Aim This case aims to discuss the pathogenesis, clinical manifestations and medical treatment of strokes caused by mitochondrial gene mutations. Methods Diagnosis of ischemic stroke caused by mitochondrial gene defect by means of "next-generation sequencing mitochondrial DNA gene variation detection", imaging examination, neurological examination, and medical history; this study took samples from the neurology ward of a medical center in northern Taiwan cases diagnosed with acute cerebral infarction as the research objects. Result This case is a 49-year-old married woman with a rare disease, mitochondrial gene mutation inducing ischemic stroke. She has severe hearing impairment and needs to use hearing aids, and has a history of diabetes. During the patient’s hospitalization, the blood test showed that serum Lactate: 7.72 mmol/L, Lactate (CSF) 5.9 mmol/L. Through the collection of relevant medical history, neurological evaluation showed changes in consciousness and cognition, slow response in language expression, and brain magnetic resonance imaging examination showed subacute bilateral temporal lobe infarction, which was an atypical type of stroke. The lineage DNA gene has m.3243A>G known pathogenic mutation point, and its heteroplasmic level is 24.6%. This pathogenic point is located in MITOMAP and recorded as Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) , Leigh Syndrome and other disease-related pathogenic loci, this mutation is located in ClinVar and recorded as Pathogenic (dbSNP: rs199474657), so it is diagnosed as a case of stroke caused by a rare disease mitochondrial gene mutation. After medical treatment, there was no more seizure during hospitalization. After interventional rehabilitation, the patient's limb weakness, poor language function, and cognitive impairment have all improved significantly. Conclusion Mitochondrial disorders can also be associated with abnormalities in psychological, neurological, cerebral cortical function, and autonomic functions, as well as problems with internal medical diseases. Therefore, the differential diagnoses cover a wide range and are not easy to be diagnosed. After neurological evaluation, medical history collection, imaging and rare disease serological examination, atypical ischemic stroke caused by rare mitochondrial gene mutation was diagnosed. We hope that through this case, the diagnosis of rare disease mitochondrial gene variation leading to cerebral infarction will be more familiar to clinical medical staff, and this case report may help to improve the clinical diagnosis and treatment for patients with similar clinical symptoms in the future.

Keywords: acute stroke, MELAS, lactic acidosis, mitochondrial disorders

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Authors: Nadia Noor, Farida Faisal

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Horizontal hostility has been identified as a special type of workplace violence and refers to the aggressive behavior inflicted by women towards other women due to gender issues or towards minority group members due to minority issues. Many women, while they want eagerly to succeed and invest invigorated efforts to achieve success, harbor negative feelings for other women to succeed in their career. This phenomenon has been known as Horizontal Violence, Horizontal Hostility, Lateral Violence, Indirect Aggression, or The Tall Poppy Syndrome in Australian culture. Tall Poppy is referred to as a visibly successful individual who attracts envy or hostility due to distinctive characteristics. Therefore, horizontal hostility provides theoretical foundation to examine fierce competition among females than males for their limited access to top level management positions. In Pakistan, gender discrimination persists due to male dominance in the society and women do not enjoy basic equality rights in all aspects of life. They are oppressed at social and organizational level. As Government has been trying to enhance women participation through providing more employment opportunities, provision of peaceful workplace is mandatory that will enable aspiring females to achieve objectives of career success. This research study will help to understand antecedents, dimensions and outcomes of horizontal hostility that hinder career success of competitive females. The present paper is a review paper and various forms of horizontal hostility have been discussed in detail. Different psychological and organizational level drivers of horizontal hostility have been explored through literature. Psychological drivers include oppression, lack of empowerment, learned helplessness and low self-esteem. Organizational level drivers include sticky floor, glass ceiling, toxic work environment and leadership role. Horizontal hostility among working women results in psychological and physical outcomes including stress, low motivation, poor job performance and intention to leave. The study recommends provision of healthy and peaceful work environment that will enable competent women to achieve objectives of career success. In this regard, concrete actions and effective steps are required to promote gender equality at social and organizational level. The need is to ensure the enforcement of legal frameworks by government agencies in order to provide healthy working environment to women by reducing harassment and violence against them. Organizations must eradicate drivers of horizontal hostility and provide women peaceful work environment. In order to develop coping skills, training and mentoring must be provided to them.

Keywords: gender discrimination, glass ceiling, horizontal hostility, oppression

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Authors: Ioannis Panagiotopoulos, Aristidis Anastasakis, Konstantinos Toutouzas, Ioannis Iakovou, Charalampos Vlachopoulos, Vasilis Voudris, Georgios Tziomalos, Konstantinos Tsioufis, Efstathios Kastritis, Alexandros Briassoulis, Kimon Stamatelopoulos, Alexios Antonopoulos, Paraskevi Exadaktylou, Evanthia Giannoula, Anastasia Katinioti, Maria Kalantzi, Evangelos Leontiadis, Eftychia Smparouni, Ioannis Malakos, Nikolaos Aravanis, Argyrios Doumas, Maria Koutelou

Abstract:

Introduction: Cardiac amyloidosis from Transthyretin (ATTR-CA) is an infiltrative disease characterized by the deposition of pathological transthyretin complexes in the myocardium. This study describes the characteristics of patients diagnosed with ATTR-CA from 2019 until present at the Nuclear Medicine Department of Onassis Cardiac Surgery Center and AHEPA Hospital. These centers have extensive experience in amyloidosis and modern technological equipment for its diagnosis. Materials and Methods: Records of consecutive patients (N=73) diagnosed with any type of amyloidosis were collected, analyzed, and prospectively followed. The diagnosis of amyloidosis was made using specific myocardial scintigraphy with Tc-99m DPD. Demographic characteristics, including age, gender, marital status, height, and weight, were collected in a database. Clinical characteristics, such as amyloidosis type (ATTR and AL), serum biomarkers (BNP, troponin), electrocardiographic findings, ultrasound findings, NYHA class, aortic valve replacement, device implants, and medication history, were also collected. Some of the most significant results are presented. Results: A total of 73 cases (86% male) were diagnosed with amyloidosis over four years. The mean age at diagnosis was 82 years, and the main symptom was dyspnea. Most patients suffered from ATTR-CA (65 vs. 8 with AL). Out of all the ATTR-CA patients, 61 were diagnosed with wild-type and 2 with two rare mutations. Twenty-eight patients had systemic amyloidosis with extracardiac involvement, and 32 patients had a history of bilateral carpal tunnel syndrome. Four patients had already developed polyneuropathy, and the diagnosis was confirmed by DPD scintigraphy, which is known for its high sensitivity. Among patients with isolated cardiac involvement, only 6 had left ventricular ejection fraction below 40%. The majority of ATTR patients underwent tafamidis treatment immediately after diagnosis. Conclusion: In conclusion, the experiences shared by the two centers and the continuous exchange of information provide valuable insights into the diagnosis and management of cardiac amyloidosis. Clinical suspicion of amyloidosis and early diagnostic approach are crucial, given the availability of non-invasive techniques. Cardiac scintigraphy with DPD can confirm the presence of the disease without the need for a biopsy. The ultimate goal still remains continuous education and awareness of clinical cardiologists so that this systemic and treatable disease can be diagnosed and certified promptly and treatment can begin as soon as possible.

Keywords: amyloidosis, diagnosis, myocardial scintigraphy, Tc-99m DPD, transthyretin

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Authors: John W. Travis

Abstract:

There is an epidemic of couples separating after a child is born into a family, generally with the father leaving emotionally or physically in the first few years after birth. This separation creates high levels of stress for both parents, especially the primary parent, leaving her (or him) less available to the infant for healthy attachment and nurturing. The deterioration of the couple’s bond leaves parents increasingly under-resourced, and the dependent child in a compromised environment, with an increased likelihood of developing an attachment disorder. Objectives: To understand the dynamics of a couple, once the additional and extensive demands of a newborn are added to a nuclear family structure, and to identify effective ways to support all members of the family to thrive. Qualitative studies interviewed men, women, and couples after pregnancy and the early years as a family, regarding key destructive factors, as well as effective tools for the couple to retain a strong bond. In-depth analysis of a few cases, including the author’s own experience, reveal deeper insights about subtle factors, replicated in wider studies. Using a self-assessment survey, many fathers report feeling abandoned, due to the close bond of the mother-baby unit, and in turn, withdrawing themselves, leaving the mother without support and closeness to resource her for the baby. Fathers report various types of abandonment, from his partner to his mother, with whom he did not experience adequate connection as a child. The study identified a key destructive factor to be unrecognized wounding from childhood that was carried into the relationship. The study culminated in the naming of Male Postpartum Abandonment Syndrome (MPAS), describing the epidemic in industrialized cultures with the nuclear family as the primary configuration. A growing family system often collapses without a minimum number of adult caregivers per infant, approximately four per infant (3.87), which allows for proper healing and caretaking. In cases with no additional family or community beyond one or two parents, the layers of abandonment and trauma result in the deterioration of a couple’s relationship and ultimately the family structure. The solution includes engaging community in support of new families. The study identified (and recommends) specific resources to assist couples in recognizing and healing trauma and disconnection at multiple levels. Recommendations include wider awareness and availability of resources for healing childhood wounds and greater community-building efforts to support couples for the whole family to thrive.

Keywords: abandonment, attachment, community building, family and marital functioning, healing childhood wounds, infant wellness, intimacy, marital satisfaction, relationship quality, relationship satisfaction

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Authors: Bill D. Geis

Abstract:

Suicide wrongful death forensic cases are the fastest rising tort in mental health law. It is estimated that suicide-related cases have accounted for 15% of U.S. malpractice claims since 2006. Most suicide-related personal injury claims fall into the legal category of “wrongful death.” Though mental health experts may be called on to address a range of forensic questions in wrongful death cases, the central consultation that most experts provide is about the negligence element—specifically, the issue of whether the clinician met the clinical standard of care in assessing, treating, and managing the deceased person’s mental health care. Standards of care, varying from U.S. state to state, are broad and address what a reasonable clinician might do in a similar circumstance. This fact leaves the issue of the suicide standard of care, in each case, up to forensic experts to put forth a reasoned estimate of what the standard of care should have been in the specific case under litigation. Because the general state guidelines for standard of care are broad, forensic experts are readily retained to provide scientific and clinical opinions about whether or not a clinician met the standard of care in their suicide assessment, treatment, and management of the case. In the past and in much of current practice, the assessment of suicide has centered on the elicitation of verbalized suicide ideation. Research in recent years, however, has indicated that the majority of persons who end their lives do not say they are suicidal at their last medical or psychiatric contact. Near-term risk assessment—that goes beyond verbalized suicide ideation—is needed. Our previous research employed structural equation modeling to predict lethal suicide risk--eight negative thought patterns (feeling like a burden on others, hopelessness, self-hatred, etc.) mediated by nine transdiagnostic clinical factors (mental torment, insomnia, substance abuse, PTSD intrusions, etc.) were combined to predict acute lethal suicide risk. This structural equation model, the Lethal Suicide Risk Pattern (LSRP), Acute model, had excellent goodness-of-fit [χ2(df) = 94.25(47)***, CFI = .98, RMSEA = .05, .90CI = .03-.06, p(RMSEA = .05) = .63. AIC = 340.25, ***p < .001.]. A further SEQ analysis was completed for this paper, adding a measure of Acute Suicide Ideation to the previous SEQ. Acceptable prediction model fit was no longer achieved [χ2(df) = 3.571, CFI > .953, RMSEA = .075, .90% CI = .065-.085, AIC = 529.550].This finding suggests that, in this additional study, immediate verbalized suicide ideation information was unhelpful in the assessment of lethal risk. The LSRP and other dynamic, near-term risk models (such as the Acute Suicide Affective Disorder Model and the Suicide Crisis Syndrome Model)—going beyond elicited suicide ideation—need to be incorporated into current clinical suicide assessment training. Without this training, the standard of care for suicide assessment is out of sync with current research—an emerging dilemma for the forensic evaluation of suicide wrongful death cases.

Keywords: forensic evaluation, standard of care, suicide, suicide assessment, wrongful death

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Authors: Caroline Lavratti, Pedro Dal Lago, Gustavo Reinaldo, Gilson Dorneles, Andreia Bard, Laira Fuhr, Daniela Pochmann, Alessandra Peres, Luciane Wagner, Viviane Elsner

Abstract:

Approximately 1% of the world's population is affected by schizophrenia (SZ), a chronic and debilitating neurodevelopmental disorder. Among possible factors, reduced levels of Brain-derived neurotrophic factor (BDNF) has been recognized in physiopathogenesis and course of SZ. In this context, peripheral BDNF levels have been used as a biomarker in several clinical studies, since this neurotrophin is able to cross the blood-brain barrier in a bi-directional manner and seems to present a strong correlation with the central nervous system fluid levels. The patients with SZ usually adopts a sedentary lifestyle, which has been partly associated with the increase in obesity incidence rates, metabolic syndrome, type 2 diabetes and coronary heart disease. On the other hand, exercise, a non-invasive and low cost intervention, has been considered an important additional therapeutic option for this population, promoting benefits to physical and mental health. To our knowledge, few studies have been pointed out that the positive effects of exercise in SZ patients are mediated, at least in part, to enhanced levels of BDNF after training. However, these studies are focused on evaluating the effect of single bouts of exercise of chronic interventions, data concerning the short- and long-term exercise outcomes on BDNF are scarce. Therefore, this study aimed to evaluate the effect of a concurrent exercise protocol (CEP) on plasma BDNF levels of SZ patients in different time-points. Material and Methods: This study was approved by the Research Ethics Committee of the Centro Universitário Metodista do IPA (no 1.243.680/2015). The participants (n=15) were subbmited to the CEP during 90 days, 3 times a week for 60 minutes each session. In order to evaluate the short and long-term effects of exercise, blood samples were collected pre, 30, 60 and 90 days after the intervention began. Plasma BDNF levels were determined with the ELISA method, from Sigma-Aldrich commercial kit (catalog number RAB0026) according to manufacturer's instructions. Results: A remarkable increase on plasma BDNF levels at 90 days after training compared to baseline (p=0.006) and 30 days (p=0.007) values were observed. Conclusion: Our data are in agreement with several studies that show significant enhancement on BDNF levels in response to different exercise protocols in SZ individuals. We might suggest that BDNF upregulation after training in SZ patients acts in a dose-dependent manner, being more pronounced in response to chronic exposure. Acknowledgments: This work was supported by Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS)/Brazil.

Keywords: exercise, BDNF, schizophrenia, time-points

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Authors: Fidelis E. Uwumiro, Chimaobi O. Nwevo, Favour O. Osemwota, Victory O. Okpujie, Emeka S. Obi, Omamuyovbi F. Nwoagbe, Ejiroghene Tejere, Joycelyn Adjei-Mensah, Christopher N. Ekeh, Charles T. Ogbodo

Abstract:

Several risk factors associated with cardiovascular events have been identified as specific to Chronic Kidney Disease (CKD). This study endeavors to validate these CKD-specific risk factors using up-to-date national-level data, thereby highlighting the crucial significance of confirming the validity and generalizability of findings obtained from previous studies conducted on smaller patient populations. The study utilized the nationwide inpatient sample database to identify adult hospitalizations for CKD from 2016 to 2020, employing validated ICD-10-CM/PCS codes. A comprehensive literature review was conducted to identify both traditional and CKD-specific risk factors associated with cardiovascular events. Risk factors and cardiovascular events were defined using a combination of ICD-10-CM/PCS codes and statistical commands. Only risk factors with specific ICD-10 codes and hospitalizations with complete data were included in the study. Cardiovascular events of interest included cardiac arrhythmias, sudden cardiac death, acute heart failure, and acute coronary syndromes. Univariate and multivariate regression models were employed to evaluate the association between chronic kidney disease-specific risk factors and cardiovascular events while adjusting for the impact of traditional CV risk factors such as old age, hypertension, diabetes, hypercholesterolemia, inactivity, and smoking. A total of 690,375 hospitalizations for CKD were included in the analysis. The study population was predominantly male (375,564, 54.4%) and primarily received care at urban teaching hospitals (512,258, 74.2%). The mean age of the study population was 61 years (SD 0.1), and 86.7% (598,555) had a CCI of 3 or more. At least one traditional risk factor for CV events was present in 84.1% of all hospitalizations (580,605), while 65.4% (451,505) included at least one CKD-specific risk factor for CV events. The incidence of CV events in the study was as follows: acute coronary syndromes (41,422; 6%), sudden cardiac death (13,807; 2%), heart failure (404,560; 58.6%), and cardiac arrhythmias (124,267; 18%). 91.7% (113,912) of all cardiac arrhythmias were atrial fibrillations. Significant odds of cardiovascular events on multivariate analyses included: malnutrition (aOR: 1.09; 95% CI: 1.06–1.13; p<0.001), post-dialytic hypotension (aOR: 1.34; 95% CI: 1.26–1.42; p<0.001), thrombophilia (aOR: 1.46; 95% CI: 1.29–1.65; p<0.001), sleep disorder (aOR: 1.17; 95% CI: 1.09–1.25; p<0.001), and post-renal transplant immunosuppressive therapy (aOR: 1.39; 95% CI: 1.26–1.53; p<0.001). The study validated malnutrition, post-dialytic hypotension, thrombophilia, sleep disorders, and post-renal transplant immunosuppressive therapy, highlighting their association with increased risk for cardiovascular events in CKD patients. No significant association was observed between uremic syndrome, hyperhomocysteinemia, hyperuricemia, hypertriglyceridemia, leptin levels, carnitine deficiency, anemia, and the odds of experiencing cardiovascular events.

Keywords: cardiovascular events, cardiovascular risk factors in CKD, chronic kidney disease, nationwide inpatient sample

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Authors: Shiamaa Eltantawy, Gihan Sobhy, Alif Alaam

Abstract:

Wilson disease, or hepatolenticular degeneration, is an autosomal recessive disease that results in excess copper buildup in the body. It primarily affects the liver and basal ganglia of the brain, but it can affect other organ systems. Musculoskeletal abnormalities, including premature osteoarthritis, skeletal deformity, and pathological bone fractures, can occasionally be found in WD patients with a hepatic or neurologic type. The aim was to assess the prevalence of osteoporosis and osteopenia in Wilson’s disease patients. This case-control study was conducted on ninety children recruited from the inpatient ward and outpatient clinic of the Paediatric Hepatology, Gastroenterology, and Nutrition department of the National Liver Institute at Menofia University, aged from 1 to 18 years. Males were 49, and females were 41. Children were divided into three groups: (Group I) consisted of thirty patients with WD; (Group II) consisted of thirty patients with chronic liver disease other than WD; (Group III) consisted of thirty age- and sex-matched healthy The exclusion criteria were patients with hyperparathyroidism, hyperthyroidism, renal failure, Cushing's syndrome, and patients on certain drugs such as chemotherapy, anticonvulsants, or steroids. All patients were subjected to the following: 1- Full history-taking and clinical examination. 2-Laboratory investigations: (FBC,ALT,AST,serum albumin, total protein, total serum bilirubin,direct bilirubin,alkaline phosphatase, prothrombin time, serum critine,parathyroid hormone, serum calcium, serum phosphrus). 3-Bone mineral density (BMD, gm/cm2) values were measured by dual-energy X-ray absorptiometry (DEXA). The results revealed that there was a highly statistically significant difference between the three groups regarding the DEXA scan, and there was no statistically significant difference between groups I and II, but the WD group had the lowest bone mineral density. The WD group had a large number of cases of osteopenia and osteoporosis, but there was no statistically significant difference with the group II mean, while a high statistically significant difference was found when compared to group III. In the WD group, there were 20 patients with osteopenia, 4 patients with osteoporosis, and 6 patients who were normal. The percentages were 66.7%, 13.3%, and 20%, respectively. Therefore, the largest number of cases in the WD group had osteopenia. There was no statistically significant difference found between WD patients on different treatment regimens regarding DEXA scan results (Z-Score). There was no statistically significant difference found between patients in the WD group (normal, osteopenic, or osteoporotic) regarding phosphorus (mg/dL), but there was a highly statistically significant difference found between them regarding ionised Ca (mmol/L). Therefore, there was a decrease in bone mineral density when the Ca level was decreased. In summary, Wilson disease is associated with bone demineralization. The largest number of cases in the WD group in our study had osteopenia (66.7%). Different treatment regimens (zinc monotherapy, Artamin, and zinc) as well as different laboratory parameters have no effect on bone mineralization in WD cases. Decreased ionised Ca is associated with low BMD in WD patients. Children with WD should be investigated for BMD.

Keywords: wilson disease, Bone mineral density, liver disease, osteoporosis

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