Acute leukemias constitute some of the most common malignant disorders. Despite significant progress made in the treatment of these disorders, their etiology remains unknown. A large and diverse group of genetic and environmental variables have been proposed. The role of a variety of factors, including pre-existing and acquired genetic mutations, exposure to radiation and various chemicals during pre-conception, pregnancy and throughout life have been explored. The effects of inherited genetic variations and disorders, pre-existing diseases, infectious agents, hobbies, occupations, prior treatments and a host of other factors have been proposed, but none is universally applicable to all cases. Variation in the incidence and prognosis based on the age, sex, race, type of the disease, geographic area of residence and other factors are intriguing, but remains unexplained. Advances in genomic profiling, including genome‐wide gene expression, DNA copy number, and single nucleotide polymorphism [SNP] genotype may shed some light on the role of genetics in these disparities. Separate two-hit hypothesis for the development of acute myeloblastic and lymphoblastic leukemia have been proposed. The latter combines genetics and infection factors resulting in leukemogenesis. A number of pre- and post-natal environmental conditions and exposure to infections, including a mycovirus infected Aspergillus flavus, have been suggested. The exact nature, timing, sequence of the events and mechanisms resulting in occurrence of leukemia requires further investigations. This review summarizes some of the above factors and the direction for future research on the etiology of acute leukemias.

Down Syndrome (DS) is a chromosomal disorder due to the presence of an additional chromosome 21 that causes intellectual deficit and physical anomalies and predisposes patients to develop infections throughout their lives. Pneumonias are more serious in patients with DS, requiring hospitalization, and represent an important cause of mortality in this population. Cytomegalovirus (CMV) causes widespread and serious infections in immunocompromised individuals, affecting the respiratory tract and, causing interstitial pneumonia, is associated with a high mortality rate. However, CMV-induced pneumonia is not reported in DS patients. The prevalence and severity of CMV respiratory infections in subjects with DS is unknown. This case describes a 50-year-old female patient suffering from DS who developed extensive bilateral pneumonia with severe respiratory failure which required hospitalization in intensive care, intubation and mechanical ventilation after approximately 10 days of empiric antibiotic and anitimycotic therapy for fever, cough and dyspnea. The patient was diagnosed with CMV pneumonia and recovered after treatment with Ganciclovir. To the best of our knowledge, this is the first reported case of CMV pneumonia in a patient with DS. This case aims to highlight that CMV pneumonia in individuals with DS can be a life-threatening condition. It also clarifies the importance of early diagnosis of infections from opportunistic pathogens such as CMV to ensure timely and efficient treatment.

Classifications of AAFD/PCFD have evolved with an increased understanding of the pathology involved. A review of classification systems helps identify deficiencies and respective contributions to the evolution in understanding the classification of AAFD. Using multiple electronic database searches (Medline, PubMed) and Google search, original papers classifying AAFD were identified. Nine original articles were identified that met the inclusion criteria. Johnson's original classification and multiple variants provided a significant leap in understanding and communicating the pathology but remained tibialis posterior tendon focussed. Drawbacks of these classifications include the implication of causality, linearity of progression through stages, an over-simplification of stage 2 deformity and a failure to understand multiple tendons react, not just tibialis posterior. Later classifications, such as the PCFD classification, are deformity-centric. Early instability in non-cavus feet and all stages of cavus feet can present pain and instability with minor/no deformity. These may not be captured in deformity-based classifications biased to planus feet.' The authors developed the 'Triple Classification' (TC) understanding that primary pathology is a progressive ligament failure/instability that presents as tendon reactivity, deformity, and painful impingement. There is a variable manifestation dependent on starting foot morphology. This review has identified deficiencies within classification systems used in AAFD/PCFD and, as a result, was used to help develop a more comprehensive 'Triple classification'. Advantages of the TC include representing foot types with no deformity, defining complex secondary instabilities, delinking of foot types, tendon reactivity/ligament instability and deformity to represent these independently in a more comprehensive classification system.

Brugada Syndrome is a cardiac channelopathy closely related to lethal arrhythmias and sudden death in people without underlying structural pathology. The diagnosis is usually assumed with electrocardiographic patterns strictly limited to the right precordial leads, V1 or V2; but this is not so at all. In our article, we describe the clinical case of a patient with a novel and different electrocardiographic presentation: the typical diagnostic pattern was presented in a lower lead of the electrocardiogram, and next to it, another pattern was presented in a contiguous lead. In addition, we propose the possible association of a structural pathology (non-compaction cardiomyopathy) with Brugada Syndrome, since both share a possible common genetic origin in the SCN5A gene.

Rett syndrome (RTT) is a rare disease and one of the most abundant causes for intellectual disa-bilities in females. Single mutations in the gene coding for methyl-CpG-binding protein 2 (MECP2), are responsible for the disease. MeCP2 regulates gene expression as a transcriptional regulator as well as through epigenetic imprinting and chromatin condensation. Consequently, numerous biological pathways on multiple levels are influenced however, the exact molecular pathways from genotype to phenotype are currently not fully elucidated. Treatment of RTT is purely symptomatic where no curative options for RTT have yet to reach the clinic. The paucity of this is mainly due to an incomplete understanding of the underlying pathophysiology of the dis-order with no clinically useful common disease drivers, biomarkers or therapeutic targets being identified. With the premise of identifying universal and robust disease drivers and therapeutic targets, here we interrogated a range of RTT transcriptomic studies spanning different species, models and MECP2 mutations. A meta-analysis using RNA sequencing data from brains of RTT mouse models human post-mortem brain tissue and patient-derived induced pluripotent stem cells (iPSC) neurons was performed using Weighted Gene Correlation Network Analysis (WGC-NA). This study identified a module of genes common to all datasets with the following ten hub genes driving the expression ATRX, ADCY7, ADCY9, SOD1, CACNA1A, PLCG1, CCT5, RPS9, BDNF and MECP2. Here we discuss the potential benefits of these genes as therapeutic targets.

A Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease of unknown aetiology under growing interest now in view of the increasingly recognized post-COVID syndrome as a new entity with similar clinical presentation. We performed the first cross-sectional study of ME/CFS in community population in Russia and then described and compared some clinical and pathophysiological characteristics of ME/CFS and post-COVID syndrome as neuroimmune disorders. Of the cohort of 76 individuals who suggested themselves suffering from ME/CFS 56 subsequently were confirmed as having CFS/ME according to ≥1 of the 4 most commonly used case definition. Of the cohort of 14 individuals with post-COVID-19 syndrome 14 met diagnostic criteria for ME/CFS. The prevalence of clinically expressed and subclinical anxiety and depression in ME / CFS and post-COVID ME/CFS did not differ significantly from that in healthy individuals. Severity of anxiety / depressive symptoms did not correlate with the severity of fatigue neigther in ME / CFS nor in post-COVID ME/CFS, but the positive correlation was found between the severity of fatigue and 20 other symptoms of ME / CFS related to the domains of “post-exertional exhaustion”, “immune dysfunction”, “sleep disturbances”, "dysfunction of the autonomic nervous system", "neurological sensory / motor disorders" and "pain syndromes". Immunological abnormalities were identified in 12/12 patients with ME / CFS according to the results of laboratory testing. The prevalence of postural orthostatic tachycardia assessed by the active standing test was 37.5% in ME / CFS and 75.0% in post-COVID ME/CFS (the latter was higher than in healthy controls, p = 0.02) There was a more pronounced increase in heart rate starting from the 6th minute of the test in post-COVID ME/CFS compared with the control group. Assessment of the functional characteristics of microcirculation by laser doppler flowmetry revealed obvious and very similar changes in ME/CFS and post-COVID ME/CFS compared to the healthy controls. The identified pattern corresponded to the hyperemic form of microcirculation disorders, usually observed in acute inflammatory processes or in deficiency of systemic vasoconstriction influences.

Meier–Gorlin syndrome (MGS) is a rare genetic developmental disorder that causes primordial proportional dwarfism, microtia, absent or hypoplastic patellae and other skeletal anomalies. Overlapping skeletal symptoms make MGS difficult to diagnose clinically. We describe a 3-year-old boy with short stature, recurrent respiratory infections, short-rib dysplasia, tower head and facial dysmorphisms who was admitted to the Tomsk Genetic Clinic to verify a clinical diagnosis of Jeune syndrome. Clinical Exome sequencing revealed two variants (compound heterozygosity) in the ORC6 gene: c.2T>C(p.Met1Thr) and c.449+5G>A. In silico analysis showed the pathogenicity of these two mutations and predicted a decrease in donor splicing site strength for c.449+5G>A. An in vitro minigene assay demonstrated that variant c.449+5G>A causes a complete skipping of exon 4 in ORC6 gene. The parents asked for urgent prenatal testing for MGS for the next pregnancy, but it ended in a miscarriage. Thus, this case report may help to prevent MGS misdiagnosis in the future. We also performed in silico and functional analyses of ORC6 mutations and developed a restriction fragment length polymorphism and haplotype-based short-tandem-repeat assay for prenatal genetic testing for MGS. These findings should elucidate MGS aetiology and improve the quality of genetic counselling for affected families.

Hantavirus cardiopulmonary syndrome (HCPS) is characterized by capillary leak, pulmonary edema (PE) and shock that leads to death in up to 40% of patients. Treatment is supportive, including mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO). Hemodynamic monitoring is critical to titrate therapy and to decide ECMO support. Transpulmonary thermodilution (TPTD) provides hemodynamic and PE data that has not been systematically used to understand HCPS pathophysiology. We identified 11 HCPS patients monitored with TPTD; 5 on MV, 3 on ECMO. We analyzed 133 measurements to describe the hemodynamic pattern and its association to PE. The main findings were reduced stroke volume, global ejection fraction (GEF) and preload parameters associated to increased extravascular lung water and pulmonary vascular permeability compatible with hypovolemia, myocardial dysfunction and increased permeability PE. Lung water correlated positively with heart rate (HR, r=0.20) and negatively with mean arterial pressure (r=-0.27) and GEF (r=-0.36), suggesting that PE is linked to hemodynamic impairment. Pulmonary vascular permeability correlated positively with HR (r=0.31) and negatively with cardiac index (r=-0.49), end-diastolic volume (r=-0.48) and GEF (r=-0.40), suggesting that capillary leak contributes to hypovolemia and systolic dysfunction. In conclusion, TPTD data suggests that in HCPS patients, increased permeability leads to PE, hypovolemia and circulatory impairment.

This report is a narrative of a certified nurse working on a long-term rehabilitation ward for patients with dementia in Japan during the early phase of the COVID-19 pandemic. During this time visitation restrictions had been implemented to prevent the spread of COVID-19 causing psychological distress for patients and their families which nurses had to cope with . The nurse was interviewed twice September–October 2020. The recordings were transcribed verbatim and analysed thematically. Three themes were identified relating to changes in care in response to the pandemic which nurses had to adapt to: the risk of collapse of family members’ roles, anxiety caused by patients forgetting family members and family memories and increased disorientation. During the pandemic, nursing care needs to adapt, ensuring that family attachments and ties continue and minimizing the disruption caused by the pandemic, while ensuring that everyone remains Covid-safe.

On March 2020 strict measures took place in Finland to limit the COVID -19 pandemic. A majority of the Finnish COVID -19 –patients have been located in the southern Finland and consequently cared for in the HUS Helsinki University Hospital. During the ongoing pandemic, HUS personnel’s psychological symptoms are followed via an electronic survey, which also delivers information on psychosocial support services. The baseline survey in June 2020 was sent to 25494 HUS employees out of whom 4804 (19%) answered; altogether 62.4% of the respondents were nursing staff and 8.9% medical doctors. While the follow-up continues for a year and a half, this report shares the sociodemographic characteristics of the respondents and the first results of psychological symptoms from the baseline survey. Out of those who were directly involved in pandemic patients` care, 43.4% reported potentially traumatic COVID-19 pandemic-related experiences vs. 21.8% among the other (p < 0.001). While over a half of the personnel was symptomless, a group of respondents reported pandemic work –related traumatic events and concurrent depressive, insomnia and anxiety symptoms. This highlights the need to ensure appropriate psychosocial support services to all traumatized personnel and PTEs were present especially among nursing staff.

Autoimmune limbic encephalitis (LE) is a rare, but devastating complication of allogeneic hem-atopoietic stem cell transplantation (HSCT). There is currently limited evidence describing the risk factors, laboratory features, and underlying mechanisms of this neurologic adverse event. We retrospectively reviewed available clinical, imaging, and laboratory data from adult patients with hematological malignancies who underwent haploidentical HSCT with cyclophosphamide (PTCy) at Chungnam National University Hospital from June 2016 to May 2020. Patients who developed LE were compared to those who did not based on clinical assessment, serum inflam-matory biomarkers, and reconstitution of various T cell populations. Of 35 patients, four devel-oped LE. There were no differences in patient demographics, donor demographics, or treatment conditions between patients that did and did not develop LE. Overall, patients with LE had worse clinical outcomes and overall survival than those without. In addition, they tended to have higher markers of systemic inflammation in the early post-transplant period, including fever, C-reactive protein (CRP), and cytokines. Remarkably, baseline interleukin-6 levels before HSCT were found to be higher in patients who developed LE than those who did not. In addition, analysis of T cell subsets showed impaired expansion of CD25+FOXP3+ regulatory T (Treg) cells in LE compared to non-LE patients despite appropriate reconstitution of the total CD4+ T cell population. Patients that developed LE within the first 30 days of HSCT were likely to have high serum IL-6 among other inflammatory cytokines coupled with suppression of regulatory T cell differentiation. Further work is needed on the mechanisms underlying impaired Treg expansion following HSCT and potential therapies.

Pregnant women (PW) are at a higher risk of diseases and hospitalization from viral respiratory infections, specially influenza, due to cardiopulmonary and immunological changes. This study assessed the impact of viral respiratory infections on PW hospitalized with severe acute respiratory infection (SARI). It´s a cross-sectional study with 42 PW and 85 non-pregnant women (NPW) admitted with SARI to two tertiary hospital between January 2015 and December 2019. The rate of virus prevalence, SARI hospitalization, length of hospital stay, oxygen supplementation, intensive care unit (ICU) admission, and death were comparable between PW and NPW. Multivariate analysis showed that PW had a higher rate of viral SARI hospitalizations (OR = 2.37; 95% CI =1.02 - 5.48) compared to NPW, with influenza virus being the most prevalent (aOR =7.58; 95% CI =1.53 - 37.66). Length of hospital stay (aOR = 0.83; 95% CI = 0.73 – 0.95) and admission to the ICU (aOR=0.028; 95% CI=0.004 - 0.25) were lower in PW compared to hospitalized NPW. Respiratory viruses had a greater impact on the frequency of SARI in the group of PW. Although PW had a higher rate of influenza SARI, they had a better outcome than NPW due to the treatment they received.

(1) Background: Asthma and Chronic Obstructive Pulmonary Disease (COPD ) are major global health issues, impacting morbidity, mortality, and healthcare costs. Despite the proven benefits of pharmacist involvement in managing these conditions, their potential in hospitals remains underused. This study aimed to identify patients at high risk of rehospitalisation post-exacerbation of asthma or COPD, to target pharmaceutical interventions. (2) Methods: Data from the University Hospital for January-December 2019 on adult admissions for asthma/COPD were analyzed, focusing on demographics, hospitalization, and clinical outcomes. (3) Results: Among the 140 patients enrolled, a significant majority (91%) underwent adjustments in their treatment regimens during their hospital stay, and nearly 59% faced readmission within six months. A survival analysis highlighted a notable disparity in the rates of rehospitalisation-free survival between patients with asthma and those with COPD, identifying COPD patients as having a higher susceptibility to rehospitalisation. (4) Conclusion: The study found COPD pa-tients at greater risk but didn't specify a priority profile, suggesting the necessity for broad, cus-tomized interventions to improve outcomes and reduce healthcare strain.

The objective of this study was to investigate the impact of athletes' respiratory muscle strength, as assessed through maximal inspiratory (MIP) and expiratory pressure (MEP), on aerobic endurance, as indicated by maximal oxygen consump-tion (Max VO2) kinetics. Respiratory muscle strength was assessed using a digital spirometer (Pony FX Cosmed, Italy), while maximal oxygen utilization capacity was measured using a breath-by-breath automatic portable gas analysis system (Cosmed K5, Italy). Statistical analysis was conducted utilizing SPSS 22.0. Based on the standardized regression coefficients (β), it was found that MEP (mean ± SD: 130.95 ± 42.82) and inspiratory diaphragmatic circumference values significantly influenced ventilatory equivalent (VE), oxygen consumption (VO2), and carbon dioxide pro-duction (VCO2). Conversely, the remaining predictor variables did not exhibit a sig-nificant effect on VE (mean ± SD: 134.80 ± 36.69), VO2 (mean ± SD: 3877.52 ± 868.47 ml), and VCO2 (mean ± SD: 4301.27 ± 1001.07 ml). In contrast, measurements of chest circumference (mean ± SD: 91.40 ± 10.72 cm), MEP, and diaphragmatic cir-cumference during inspiration (mean ± SD: 95.20 ± 10.21 cm) were found to signifi-cantly impact Max VO2 (mean ± SD: 58.52 ± 10.74 ml/kg/min), while the other pre-dictor variables did not demonstrate a significant effect on Max VO2. Conclusively, the study revealed that measured values of diaphragmatic circumference during inspiration and MEP exerted a notable influence on Max VO2, VE, VO2, and VCO2. Our findings underscore the importance of considering respiratory muscle strength in assessing and enhancing athletes' aerobic performance. These insights contribute to a deeper understanding of the interplay between respiratory function and exercise capacity, offering potential avenues for optimizing training regimens and perfor-mance outcomes in athletic contexts.

Ethoxyquin (EQ) is used as a synthetic antioxidant mainly in animal food, but it has also been reported to have neuroprotective properties by diminishing the peripheral neuropa-thy resulting from anti-cancer chemotherapy in animal models. However, EQ has not been thoroughly evaluated in humans and its use is under debate. The objective of this work was to examine the effect of EQ on primary fibroblasts derived from controls and patients with confirmed mitochondrial dysfunction. To this end, we incubated primary fibroblasts from patients with mitochondrial respiratory chain complex 1 (C1) deficiency, cyto-chrome-c-oxidase (COX) deficiency and genetic form of Parkinson’s disease (PD). Alt-hough EQ did not alter ATP production it significantly increased oxygen consumption and improved energy status in C1 and COX cells while decreasing ROS production in COX, PD and control cells and maintaining mitochondrial content. These effects could possibly be attributed to the antioxidant and chaperone-modulating properties of EQ and to induced SOD2 expression in some cells. Our results indicate that EQ has the potential to improve some mitochondrial functions. Still, caution should be exerted since overdose of this com-pound affected cell growth.

Respiratory allergic diseases, affect over 500 million people globally and pose a substantial burden in terms of morbidity, mortality, and healthcare costs. Restrictive factors such as geographical disparities, infectious pandemics, limitations in resource, and shortage of allergy specialists in underserved areas, impede effective management. Moreover, the well-established suboptimal adherence in patients with respiratory allergies, contribute further to the accelerated loss of disease control. Telemedicine encompasses real-time visits, store-and-forward options triage, and computer-based technologies for establishing and efficient doctor-patient communication. Recent advances in digital technology, including designated applications, informative materials, digital examination devices, wearables, digital inhalers, and integrated platforms, facilitate personalized and evidence-based care delivery. The integration of telemonitoring in respiratory allergy care has shown beneficial effects in disease control, adherence, and quality of life. While the COVID-19 pandemic accelerated the adoption of telemedicine, certain concerns regarding technical requirements, platform quality, safety, reimbursement, and regulatory considerations remain unresolved. Challenges in telemonitoring implementation further include ensuring effective doctor-patient collaboration, addressing privacy concerns, and establishing cost-effective models. The integration of artificial intelligence (AI) in telemonitoring applications holds promise for data analysis, pattern recognition, and personalized treatment plans. Striking the balance between AI-enabled insights and human expertise is crucial for optimizing the benefits of telemonitoring. This overview reports the up- to- date telemedicine approaches in managing patients with respiratory allergies. While telemonitoring exhibits potential in enhancing patient care and healthcare delivery, critical considerations have to be addressed in order to ensure the successful integration of telemonitoring into the healthcare landscape.

Objective: To determine if higher weight-to-length z-scores after 32 weeks of gestation are associated with higher Pulmonary Scores (PS) in preterm infants requiring respiratory support using a prospective observational study. Methods: Infants born <30 weeks, with a post-menstrual age (PMA) of 30-33 weeks were enrolled. Weight, infant’s length, and head circumference were measured weekly. Data on calories/kg/d, protein g/kg/d, weight for length percentiles, z-scores, and BMI at 33 through 40 weeks PMA were collected. PS was calculated. Results: We analyzed 91 infants. The mean gestational age was 26.9 ± 1.7 weeks. There was a significant association between PS and W/L z scores(p<0.0001). For every one-unit increase in W/L z-scores, PS increased by 0.063. There was a significant association between PS and W/L percentiles (p = 0.0017) as well as BMI (p = <0.0001). For every unit increase in W/L percentiles, PS increased by 0.002, and for a unit increase in BMI, PS increased by 0.04. The association remained significant after postnatal steroids, sex, corrected, and birth gestational ages were included in the regression analysis. Nutrition did not affect anthropometric measurements. Conclusion: Our study is the first to demonstrate that higher BMI and W/L may adversely affect respiratory severity in infants.

(1) Background: Respiratory infections are a major public health problem worldwide, with potentially serious consequences. Indeed, these infections remain one of the main causes of morbidity and mortality in children under 5 years old in developing countries. Etiological information on respiratory infections is crucial for prevention and case management strategies. This systematic review aims to describe the etiology of respiratory infections reported in studies carried out in sub-Saharan African countries; (2) Methods: Using PubMed, HINARI and Google scholar search engines, a systematic search was carried out to identify published articles on the etiology of viral and/or bacterial respiratory infections in sub-Saharan Africa in patients of all ages. We have only considered data from sub-Saharan Africa. Papers published from 2010 to 2021, in English or French have been included in this review; (3) Results: After reviewing 115 articles reporting studies carried out in the African continent, only 32 articles were selected of which, studies were conducted in 15 sub-Saharan African countries, including 6/32 (18.75%) in Cameroon. Twenty (62.5%) were cross-sectional studies, and twenty-four (75%) were hospital-based investigations. In these studies, RT-PCR and culture methods were respectively used for viruses and bacteria investigations. Respiratory syncytial virus was the most frequently identified, with prevalence ranging from 0.6% to 59%, followed by rhinovirus (9.3% -73%), influenza virus (flu) A/B (0.9%-69.1%), and human adenovirus (0.9% - 30.8%). Streptococcus pneumoniae (14.2% - 96%), followed by Haemophilus influenzae type b (2.5% - 54%), and Klebsiella pneumoniae (1.4% - 49.9%) were the most frequently detected bacteria; (4) Conclusions: This review has reported that many pathogens, mainly viruses, are associated with acute respiratory infections in sub-Saharan Africa in both children and adults. Unfortunately, the limited geographical distribution of data across sub-Saharan Africa does not allow most of countries to develop an effective strategy for the prevention and treatment of respiratory infections.

Respiratory syncytial virus (RSV) is a common respiratory virus that can cause mild to severe illness in people of all ages. The most common symptoms of an RSV infection are cough, runny nose, and fever. However, RSV can also cause more serious complications, such as tracheobronchitis, bronchiolitis, pneumonia, and apnea. RSV is especially dangerous for infants, young children, and older adults. RSV is a seasonal virus, with peak incidence in the winter months. The virus spreads through respiratory droplets produced when an infected person coughs or sneezes. The virus can also be spread through contact with contaminated surfaces. Treatment is aimed at relieving symptoms and preventing complications. This review will provide an overview of the medical significance, virology, pathogenesis, immunity, epidemiology, symptoms, risk factors, and complications associated with RSV, and the diagnosis and management of RSV infections.

Background: Children suffering from COVID-19 constitute about 10% of the entire population infected with the virus. In most of them, we observe asymptomatic or mild course; however, about 1% of affected children require a stay in the pediatric intensive care unit (PICU) due to the severe life-threatening course. The risk of respiratory failure, as in adults, is associated with the coexistence of concomitant diseases. The aim of our study was to analyze patients admitted to PICUs due to severe course of SARS-CoV-19 infection. Methods: A retrospective multi-center study, the analysis covered all children with a confirmed diagnosis of SARS-CoV-2 virus infection, who were admitted to PICUs, in the period from November 2020 to August 2021. We studied epidemiological and laboratory parameters, and the endpoint – survival or death. Results: The study analyzed 45 patients (0.075% of all children hospitalized in Poland due to COVID-19 at that time). Mortality calculated in the entire study group was 40% (n=18). Statistically significant differences between the compared groups (survived and died) concerned the parameters of the respiratory system, Lung Injury Score and Pediatric Sequential Organ Failure Assessment . A significant correlation between disease severity and the patient's prognosis was shown by the liver function parameter AST (p=0.028). Analyzing patients requiring mechanical ventilation and assuming survival as the primary outcome, a significantly higher oxygen index on the first day of hospitalization, lower pSOFA scores and lower AST levels (p: 0.007; 0.043; 0.020; 0.005; 0.039, respectively) were found. Conclusions: As in adults, children with comorbidities are most frequently at risk of severe SARS-CoV-2 infection. Increasing symptoms of respiratory failure, the need for mechanical ventilation and persistently high values of aspartate aminotransferase are indicators of poor prognosis.

The practice of physical activity is an effective non-pharmacological strategy for preventing and treating chronic diseases. A large body of evidence has contributed to establishing a positive correlation between a physically active lifestyle and health benefits, including enhanced vaccination responses, lower numbers of senescent T-cells, increased T-cell proliferative capacity, lower levels of inflammatory cytokines, and improved neutrophil and macrophage function. While females are generally thought to exert more robust immune responses than males in response to a variety of challenges, and both male and female sex hormones have been suggested as mediators of immune function, research on this topic has not always been designed with a sex-specific lens. The goal of this review is to summarize the available experimental and clinical evidence linking exercise and immune function in male and female subjects, with an emphasis on sex differences and sex-specific mechanisms. Overall, the available evidence indicates that moderate exercise and physical activity improves immune function in both sexes, whereas prolonged and high-intensity exercise temporarily impairs immune responses at a higher degree in females. A role of male and female sex hormones in these sex-specific effects is also discussed.

Under the pressure of fluoroquinolones, Pasteurella multocida (PM) can easily develop resistance to fluoroquinolones mediated by QRDR target mutation. It is imperative to find new drug resistance inhibitor targets to combat the rapid development of drug resistance. In order to overcome these problems, we sequenced the transcriptome of PM with different levels of resistance to ENR(0.03 μg/mL; 8 μg/mL; 32μg/Ml, Enrofloxacin). The results showed that with the increase of resistance to fluoroquinolones, the expression of satP gene was significantly up-regulated. The satP gene deletion strain and replenishment strain were constructed, and their drug resistance and tolerance were determined. The results showed that the deletion of satP gene did not affect the resistance of PM to fluoroquinolones, rather affected the time when PM developed resistance to fluoroquinolones. After 10 generations of drug induction, the MIC (minimum inhibitory concentration) of fluoroquinolones for wild strain was 64 μg/mL, while the MIC for satP gene deletion strain was only 8 μg/mL. The MDK99 test (time to kill 99% bacteria),agar diffusion test and mutation frequency test showed that the tolerance of satP gene deletion strain was significantly lower than that of wild strain. At the same time, the virulence of gene deletion strain and wild strain was tested, and about 400 times decreased virulence was observed for satP gene deletion strain. The mouse infection model confirmed that mice infected with satP gene deletion strains were more likely to be treated with ENR than mice infected with wild-type bovine PM strains. The results show that satP has potential to be a target of fluoroquinolone resistance inhibitors.

The study aimed to evaluate the association between the changes in ventilatory variables (tidal volume (Vt), respiratory rate (RR), and lung ventilation (VE)) and deoxygenation of m.intescostales (∆SmO2-m.intercostales) during a maximal incremental exercise in nineteen male competitive marathon runners. The ventilatory variables and oxygen-consumption (VO2) were recorded breath-by-breath by exhaled gas analysis. A near-infrared spectroscopy device (MOXY) located in the right-hemithorax allowed recording SmO2-m.intercostales. To explore changes in oxygen levels in muscles with high demand during exercise, a second MOXY records SmO2-m.vastus laterallis. The triphasic model of exercise intensity was used for evaluating changes in SmO2 in both muscle groups. We found that ∆SmO2-m.intercostales correlated with VO2-peak (r=0.65; p=0.002) and the increase of VE (r=0.78; p=0.001), RR (r=0.54; p=0.001), but not Vt (p=0.210). The interaction of factors (muscles X exercise-phases) in SmO2 expressed as an arbitrary unit (a.u) was significant (p=0.005). At VT1 were no difference (p=0.177), but SmO2-m.intercostales was higher at VT1 (p&lt;0.001) and VO2-peak (p&lt;0.001). In competitive marathon runners, the m.intercostales deoxygenation during incremental exercise is directly associated with the aerobic capacity and increased lung ventilation and respiratory rate, but not tidal volume. Besides, it shows less deoxygenation than m.vastus laterallis at intensities above the aerobic ventilatory threshold.

The objective of this study was to describe the overall pattern of morbidity and mortality of children seen at the Thai Binh Pediatric Hospital in Vietnam, with a focus on infectious diseases. A retrospective review of hospitalisation records was conducted from 1 January 2015 to 31 December 2019. Data were obtained from a total of 113,999 records. The median age of patients was 18 months, with 83.98% of patients aged <5 years. Infectious diseases accounted for 61.0% of all cases. The most prevalent diseases were lower respiratory tract infections (32.8%), followed by gastrointestinal infections (13.3%) and confirmed influenza (5.4%). Most infections were not microbiologically documented. A total of 81.4% patients received at least one antibiotic. Most patients (97.0%) were hospitalised for less than 15 days. Regarding outcomes, 87.8% patients were discharged home with a favourable outcome. 12.0% were transferred to the Vietnam National Children’s Hospital because their condition had worsened and 0.1% died. In total, infectious diseases accounted for 40.4% of deaths, followed by neonatal disorders (34.6%). Our data serves a basis for the identification of needs for diagnostic tools and for future evaluation of the effect of the targeted implementation of such facilities. Point-of-care tests, including real-time PCR assays to identify common pathogens should be implemented for more accurate diagnosis and more appropriate antibiotic use.

1) Background: Respiratory tract infections (RTI) has been known to be a significant health concern for mortality and morbidity since many years. This study was aimed at determining the prevalence of bacterial pathogen causing upper respiratory tract (URTIs) and the susceptibility patterns to frequently used antibiotics among patients attending Abusetta hospital in Tripoli district; 2) Methods: A total of 1,110 throat swabs were collected between Jan, 2011 to December, 2014 and inoculated onto Blood agar, MacCkonkey agar and Chocolate agar then incubated at 37 oC for 24 hours. Bacterial pathogens were determined by bacteriological culture methods and antibiotic susceptibility of the isolates was identified following Clinical Laboratory Standard Institute guidelines (CLSI); 3) Results: Of the 1,110 respiratory samples tested, 71.1% (n = 789) of specimens were positive cultures with the dominant bacterial pathogens being streptococcus pneumonia 43.3% (n = 342), followed by pseudomonas aeruginosa 22.8% (n = 180), staphylococcus aurous 13.8% (n = 109), Escherichia Coli 6.9% (n = 55), Enterobacter spp 6.2% (n = 49), Citrobacter 4.5% (n = 36), and Klebsiella 2.2% (n = 18). Most isolates exhibited resistance against the commonly used antibiotics and to at least one antibiotic; and 4) Conclusions: The level of antibiotic resistance in this study is alarming and brings to light the timely and suitable diagnosis of the common bacteria causes of URTIs and proper antibiotic administration based on susceptibility test.

There is an ongoing global pandemic of human respiratory syncytial virus (RSV) infection that results in substantial annual morbidity and mortality. In Australia, RSV is the major cause of acute lower respiratory tract infections (ALRI). Nevertheless, little is known about the extent and origins of genetic diversity of RSV in Australia, nor the factors that shape this diversity. We conducted a genome-scale analysis of RSV infections in New South Wales (NSW). RSV genomes were successfully sequenced for 144 specimens collected between 2010-2016. Of these, 64 belonged to the RSVA and 80 to the RSVB subtype. Phylogenetic analysis revealed a wide diversity of RSV lineages within NSW and that both subtypes evolved rapidly in a strongly clock-like manner, with mean rates of approximately 6-8 x 10^-4 nucleotide substitutions per site per year. There was only weak evidence for geographic clustering of sequences, indicative of fluid patterns of transmission within the infected population, and no evidence of any clustering by patient age such that viruses in the same lineages circulate through the entire host population. Importantly, we show that both subtypes circulated concurrently in NSW with multiple introductions into the Australian population in each year, and only limited evidence for multi-year persistence.

The study aimed to estimate the prevalence of respiratory symptoms and to assess respiratory health risks associated with Particulate Matter (PM) exposure among the residents of Windhoek, Namibia. Objectives: To measure particulate pollution concentration in Windhoek through monitoring of particulate matter concentration and to identify any associations between particulate pollution, individual location and respiratory health among the Windhoek resident’s. Methods: an adapted standardized self-administered questionnaire was used to collect respiratory health related data as well as previous exposure, while PM monitoring was done using ASTM D1739 reference method. Results: A high prevalence was observed for cough (43%), breathlessness (25%), and Asthma (11.2%). PM was found to be a significant risk factor for episode of cough and phlegm, while high PM exposure category had increased odds ratio for episode of phlegm and cough (OR: 2.5, 95% CI: 0.8-8.0). No association was observed between location and respiratory health outcomes. Conclusion: The study found high levels of PM concentration across all Windhoek suburbs which were above the German, American and EPA. Enactment of legislation relating to the control and monitoring of PM related emissions at point of generation is required at country and city level.

Wolfram syndrome 1 (WS1) is an uncommon autosomal recessive neurological disorder that is characterized by diabetes insipidus, early-onset non-autoimmune diabetes mellitus, optic atrophy, and deafness (DIDMOAD). Other clinical manifestations are neuropsychiatric symptoms, urinary tract alterations, and endocrinological disorders. The rapid clinical course of WS1 results in death by the age of 30. Severe brain atrophy leads to central respiratory failure, which is the main cause of death in WS1 patients. Mutations in the WFS1 gene, located on chromosome 4p16, account for approximately 90% of WS1 cases. The gene produces wolframin, a transmembrane glycoprotein widely distributed and highly expressed in retinal, neural, and muscular tissues. Wolframin plays a crucial role in the regulation of apoptosis, insulin signaling, and ER calcium homeostasis, as well as the ER stress response. WS1 has been designated as a neurodegenerative and neurodevelopmental disorder due to the numerous abnormalities in the ER stress-mediated system. WS1 is a devastating neurodegenerative disease that affects patients and their families. Early diagnosis and recognition of the initial clinical signs may slow the disease's progression and improve symptomatology. Moreover, it is critical to provide genetic counseling to the patient's relatives in order to reduce the risk of transmitting WS1. Regrettably, there are currently no specific drugs for the therapy of this fatal disease. A better understanding of the etiology of WS1 will make possible the development of new therapeutic approaches that may enhance the life expectancy of patients. This review will examine the pathogenetic mechanisms, development, and progression of neuropsychiatric diseases commonly associated with WS1. A thorough understanding of WS1's neurophysiopathology is critical for achieving the goal of improving patients' quality of life and life expectancy.

(1) Background: LUS has emerged as a simple, rapid and non-invasive method for the dynamic assessment of pulmonary congestion, a major prognostic factor and a therapeutic target in AHF. (2) Methods: In the single-center prospective observational study, 42 patients hospitalized for AHF in the post-emergency polyvalent medicine department of CHU Grenoble were successively included between May 2021 and July 2022. Clinical examination, LUS and electrolyte panel results were collected daily. Vital status was assessed 30 days after the last LUS. The primary endpoint was the evolution of the number of B-lines according to the dose of diuretic administered ; (3) Results: We performed 188 LUS. Our patients were elderly (85.8 [SD 8.1]) and comorbid. The median number of B-lines decreased from 17 at admission to 7 in the middle of the hospital stay, then stagnated until discharge. Simultaneously, the median dose of diuretics, initially stable at a maximum of 40 mg/d IV, decreased to 20mg/d IV by the end of hospital stay. Patients with CKD had a higher mean number of B-lines at entry (24.2 [SD 11.6]) compared to those without CKD (8.2 [SD 8.8]). However, the evolution of B-lines number was independent of creatinine levels. 30-day all-causes mortality was significantly related to the number of B-lines at discharge (15.2 [SD 10.1] in deceased patients versus 3.9 [SD 5.4] in living patients, p

Background/Objectives: Infectious Endocarditis often requires surgical intervention, with postoperative acute kidney injury (AKI) posing a significant concern. This retrospective study aimed to investigate AKI incidence, its impact on short-term mortality, and identify modifiable factors in patients with endocarditis scheduled for valve surgery. Methods: This single center study enrolled 130 consecutive endocarditis patients from 2013 to 2021 undergoing valve surgery. Creatinine levels were monitored pre- and postoperatively, and AKI was defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patient demographics, comorbidities, procedural details, and complications were recorded. Primary outcomes included AKI incidence, the relevance of creatinine levels for AKI detection, and the association of AKI with 30-, 60- and 180-day mortality. Modifiable factors contributing to AKI were explored as secondary outcomes. Results: Postoperatively, 35.4% developed AKI. The highest creatinine elevation occurred on the 2nd postoperative day. Best predictive value for AKI was a creatinine level of 1.35 mg/dl on the 2nd day (AUC: 0.901; sensitivity: 0.89, specificity: 0.79). Elevated creatinine levels on the 2nd day were robust predictors for short-term mortality at 30, 60 and 180 days postoperatively (AUC ranging from 0.708 to 0.789). CK-MB levels at 24 hours postoperatively and minimum hemoglobin during surgery were identified as independent predictors for AKI in logistic regression. Conclusions: This study highlights the crucial role of creatinine levels in predicting short-term mortality in surgical endocarditis patients. A specific threshold (1.35 mg/dl) provides a practical marker for risk stratification, offering insights for refining perioperative strategies and optimizing outcomes in this challenging patient population.

The KOSovan Acute Coronary Syndrome (KOS-ACS) Registry is established as a prospective, continuous, nationwide, web-based registry that is operated online. The KOS-ACS registry is designed with the following objectives: 1) to obtain data on the demographic, clinical, and laboratory characteristics of ACS patients treated in Kosovo; 2) to create a national database with information on health care in ACS patients treated in Kosovo; 3) to identify the national features of associations between ACS characteristics and clinical outcomes, including mortality, complications, length of hospital stay, and quality of clinical care; and 4) to propose a practical guide for improving the quality and efficiency of ACS treatment in Kosovo. The Kosovo Society of Cardiology and University of Prishtina will be responsible for the development of the KOS-ACS registry and centralized data analysis at the national level. The KOS-ACS Registry will enroll all patients admitted, at any of the registered clinical centers, with the diagnosis of ACS and who will be clinically managed at any of the Kosovo hospitals. Data on patient demographics, clinical characteristics, previous and hospital drug treatment, and reperfusion therapy will be collected. The type of ACS (Unstable angina, NSTEMI or STEMI) will also be clearly defined. The time from first medical contact to balloon inflation (FMC-to-balloon) and door-to-ballon time will be registered. In-hospital death and complications will be registered. Data on post-hospital primary outcome (MACE: cardiac death, all-cause mortality, hospitalization, stroke, need for coronary revascularization) of patients, at 30 days and 1 year, will be included in the Registry.

Heart failure is a global major healthcare problem with millions of hospitalizations annually and with a very high mortality. There is an increased interest in finding new and reliable biomarkers for the diagnostication, prognostication and therapeutical guidance of patients hospitalized for acute heart failure. There is data to sustain the role of CA 125, a worldwide used marker of ovarian cancer, in patients with heart failure. Several studies have shown links between CA 125 levels and congestion seen in acute heart failure, high mortality and readmission rates at 6 months follow up after discharge from acute heart failure and also a role of CA 125 in the guidance of heart failure therapy. There are also clinical trials that showed that several particularities of CA 125 make it even better than NTpro BNP ( a classical and more utilised marker of heart failure) in several scenarios of acute heart failure.

There is evidence that kidney involvement is frequently observed in COVID-19 patients, and can manifest as mild proteinuria to advancing acute kidney injury (AKI). One of the mechanisms is microvascular and macrovascular thrombosis caused by the hypercoagulation phase of the disease. Thromboelastography (TEG) is a valuable examination to detect significant hemostatic abnormalities, including the hypercoagulable state. This study analyzed the coagulation profiles, including TEG parameters, in COVID-19 patients who developed AKI compared to those who did not during their intensive care unit (ICU) stay, to identify predictors of AKI. Our single-center cohort retrospective study involved adult patients of COVID-19 in the ICU of Sardjito Hospital in Yogyakarta, Indonesia between May and September 2021. Patients were divided into two groups of AKI and non-AKI based on 2012 KDIGO definition and the elaboration by Indonesian Society of Nephrology. Variables showing a significant difference in the two groups were then analyzed using univariate and multivariate binary logistic regression. A total of 60 COVID-19 patients were included in the study, and 35% of them developed AKI. Compared to non-AKI patients, those with AKI exhibited a greater prevalence of diabetes mellitus (66.7% versus 35.9%, P = 0.023), higher D-Dimer levels (970 versus 685 ng/mL, P = 0.045), and higher values in TEG parameters of maximum amplitude/MA (74.6 versus 65.9 mm, P = 0.001) and coagulation index/CI (2.3 versus 1.0, P = 0.033). TEG parameter of MA emerged as the sole significant predictor for the development of AKI (OR, 6.33; 95% CI, 1.56 to 25.64). Our study validated the kidney involvement of COVID-19 infection, and showed that diabetes mellitus, high D-Dimer levels, and hypercoagulability serve as prominent risk factors in the development of AKI. Furthermore, TEG parameter of MA exceeding 70 mm is the single independent significant predictor of AKI.

Background Research in the subject of the influence of SARS-CoV-2 mechanisms on human’s homeostasis remains actual problem. Particular interest is the study of pathomorphological changes in the appendix in children with COVID-19. Objectives Aim of the study: morphological and molecular biological evaluation of the appendix in children of different age groups with COVID-19. Methods Groups were formed on the basis of anamnestic, clinical and morphological data: I (n = 42; aged 2 to 18 years, average - 10.8 years) – with an established clinical diagnosis: coronavirus infection (COVID-19; PCR+); II (n = 55; aged 2 to 18 years, average - 9.7 years) – with a confirmed clinical diagnosis of acute appendicitis; collected before the onset of the COVID-19 pandemic in 2017-2019; III (n = 38; aged 2 to 18 years, average - 10.3 years) - control group. Histological and immunohistochemical studies were conducted using primary antibodies to CD3, CD4, CD68, CD163, CD20, CD138 and to pro-inflammatory (IL-1, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines. Results In most samples of appendix in children with COVID-19 were discovered signs of destructive phlegmonous-ulcerative and gangrenous appendicitis. An increase in CD3+, CD4+, CD68+, CD163+, CD20+ CD138+ immunocompetent cells was found in the appendix of children with COVID-19. As well, there is an increase in pro-inflammatory (IL-1, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines. Conclusions The aforementioned pathological and immunohistochemical changes were more pronounced in the group of children aged 6-12 years (childhood).

In this work, we tried to emphasize whole transcriptome expression changes in the Wistar rats brainstem two hours after acute stress. Most of the genes were upregulated. We detected massive shift of neuropeptides Crh, Trh,Cga, Tshb, Uts2b, Tac4, Lep and neuropeptide receptors Hcrtr1, Sstr5, Bdkrb2, Crhr2 signaling, as well as Glutamate Grin3b, Grm2 and GABA Gpr156, Acetylcholine Chrm4,Chrne, Adreno- Adra2b receptors expression uprising. Intensive increase in expression of intermediate filaments Krt83/Krt86/Krt80/Krt84/Krt87/Krt4/Krt76 and motor proteins Myo7a, Klc3 was detected. Remarkably, at this time we also observed signs of microglia activation. Both expression of anti-inflammatory cytokines Il13, Ccl24 and proinflammatory cytokin’s receptors Il9r, Il12rb1, Tnfrsf14, Tnfrsf13c, Tnfrsf25, Tnfrsf1b were increased. In the Wnt signaling pathway, we have seen increased expression of ligands-receptors Wnt1, Wnt11, Ror2, and also negative regulators Notum, Sfrp5, Sost. Also we conducted cDNA libraries normalization with duplex specific nuclease and compared results. On the basis of our RNAseq data, we chose reference genes for RT-qPCR best suitable for experiments with acute stress.

Abstract: Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully un-derstood and causal treatment options are not available. Recently we demonstrated that Hepa-ranase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that As-pirin has inhibitory effect on Hpa. Another compound, which possesses a mild pan-creato-protective effect against AP, is Trehalose, a common disaccharide. We hypothesize that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhib-itors of Hpa, may exert pancreato-protective effect better than each drug alone. Thus, the current study examines the pancreato-protective effects of Aspirin, Trehalose, PG545 and SST0001 in ex-perimental model of AP induced by Cerulein in wild-type (WT) and Hpa over-expressing (Hpa-Tg) mice. Cerulein-induced AP in WT mice was associated with significant rises in the se-rum levels of Lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in heparanase transgenic (Hpa-Tg) mice vs wild-type (WT) mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti-Hpa drug combinations constitute a novel therapy for this common orphan disease.

The definition of Early Cholecystectomy (EC) is still debatable. This paper aims to find whether the timing of EC affects outcomes. This is a multicentric prospective observational study including patients with acute calculous cholecystitis (ACC) who had cholecystectomy within ten days from the onset of symptoms. Kruskall-Wallis test, Fisher’s Exact test and Spearman rank correlation were used for statistical analysis. The patients were divided into three groups depending on the timing of the operation: 0-3 days, 4-7 days, or 8-10 days from the onset of symptoms. 1117 patients were studied over a year. The time from the onset of symptoms to EC did not affect the postoperative complications and mortality, the conversion and the reintervention rate. It was a significant risk factor for intraoperative complications (0-3 days, 2.8%; 4-7 days, 5.6%; 8-10 days, 7.9%; p=0.01) and subtotal cholecystectomies (0-3 days, 2.7%; 4-7 days, 5.6%; 8-10 days, 10.9%; p&lt;0.001). ACC is an evolutive inflammatory process and, as the days go by, the local and systemic inflammation increases which makes surgery more complex and difficult with higher risk of intraoperative complications. We recommend performing EC for ACC as soon as possible within the first ten days of the onset of symptoms.

In this study, a case of acute cattle death was investigated. The pathogen was identified, and its molecular characteristics and vector were analysed. This study provides a reference for the prevention and control of babesiosis and the healthy breeding of cattle. In this study, unengorged and engorged Rhipicephalus microplus ticks were collected from the Chongqing area. The unengorged ticks were cultured on cattle under laboratory conditions, and the engorged ticks were cultured to lay eggs. In the process, the cattle suddenly died at 12 days from the bite of an unengorged R. microplus tick. In addition, the larvae hatched from R. microplus eggs, which were cultured on the other cattle, and the experimental cattle died in approximately 14 days. Blood was collected from a second dying and stored at 4 ℃ for one week. Two millilitres of anticoagulated blood was injected subcutaneously into the third cow without piriformis infection. On the fourth day, the body temperature rose to 41 ℃ with slight lymphadenopathy. On the fifth day, the cow suddenly fell and died approximately 4 hours later. DNA was extracted from the blood of all dead cattle and amplified by PCR with piriformis universal primers. The results showed that the cattle were infected with Babesia bovis. The phylogenetic tree based on 18S rRNA showed that the Chongqing strain of B. bovis, which caused the death of cattle, was closely related to the Yunnan strain in China and had the same taxonomic status as the Spanish strain. This case report will draw people's attention to B. bovis once again, and positive control measures should be taken to reduce the losses of farmers to achieve the goal of healthy breeding.

Excessive intake of fluoride, one of the trace elements to maintain health, leads to liver injury. Tetramethylpyrazine (TMP) is a kind of traditional Chinese medicine monomer with good antioxidant and hepatoprotective function. The aim of this study was to investigate the effect of TMP on liver injury induced by acute fluorosis. A total of 60 1-month-old male Institute of Cancer Research mice without carriage of pathogenic bacteria were selected. All mice were fed adaptively for one week, and then randomly divided into 5 groups: control (K) group, model (F) group, low-dose (LT) group, medium-dose (MT) group and high-dose (HT) group. The control and model group were given distilled water, while 40 mg/kg (LT), 80 mg/kg (MT) and 160 mg/kg (HT) TMP were fed by gavage for two weeks with the maximum gavage volume of mice is 0.2ml/10g/d. Except for the control group, all groups were given fluoride (35 mg/kg) by intraperitoneal injection on the last day of the experiment. The results of this study showed that compared with the model group, TMP alleviated the pathological changes of liver induced by fluoride and improved the ultrastructure of liver cells; TMP significantly decreased the levels of ALT, AST and MDA (P <0.05), and increased the levels of T-AOC, T-SOD and GSH (P <0.05). The results of mRNA detection showed that TMP significantly increased the mRNA expression levels of Nrf2, HO-1, CAT, GSH-Px and SOD in liver compared with model group (P <0.05). In conclusion, TMP can inhibit oxidative stress by activating Nrf2 pathway and alleviate liver injury induced by fluoride.

Abstract: COVID-19 Long Haulers, an estimated 3% to 12% of people infected globally with coronavirus having latter devasting symptoms 12 weeks after the initial infection is on the rise. We conducted a collaborative study with the long covid patient organization in Greece in order to estimate the prevalence, symptoms and problems that adult long haulers experience and then propose a management plan for these patients. Symptoms were obtained from 208 patients using unstructured qualitative free text entries in an anonymized online questionnaire. The majority of respondents (68.8%) were not hospitalized and had been diagnosed more than six months ago with lingering symptoms (66,8%). Eighteen different symptoms (fatigue, tachycardia, shortness of breath, parosmia etc) were mentioned in both hospitalized and community patients. Interestingly, patients with initial mild symptoms suffer from the same persistent symptoms as those who were hospitalized. Awareness of long covid sequelae seems to be low even among medical doctors. Treatment options incorporating targeted rehabilitation programs are either not available or still excluded from the management plan of long covid patients. Since long COVID is a multi-systemic entity, we propose a holistic interventional approach using a multidisciplinary medical team in order to securely and effectively diagnose and treat these specific patients. Academic and medical community must collaborate with long covid patients’ organizations so as to provide personalized medicine.

Epigenetic alterations have contributed greatly to human carcinogenesis. Conventional epigenetic studies have been predominantly focused on DNA methylation, histone modifications and chromatin remodelling. However, recently, RNA modification (m6A-methylation) also termed ‘epitranscriptomics’ has emerged as a new layer of epigenetic regulation due to its diverse role in various biological processes. In this review, we have summarized the therapeutic potential of m6A-modifiers in controlling haematological disorders especially acute myeloid leukemia (AML). It is a type of blood cancer affecting specific subsets of blood-forming hematopoietic stem/progenitor cells (HSPCs) which proliferate rapidly and acquire self-renewable capacities with impaired terminal cell-differentiation and apoptosis leading to abnormal accumulation of white blood cells, and thus an alternative therapeutic approach is required urgently. Here, we have described how RNA m6A-modification machineries EEE (Editor/writer: Mettl3, Mettl14; Eraser/remover: FTO, ALKBH5 and Effector/reader: YTHDF-1/2) could be reformed into potential druggable candidate or as RNA modifying drug (RMD) to treat leukemia. Moreover, we have shed-light on the role of microRNA and suppressor of cytokine signalling (SOCS/CISH) in increasing anti-tumor immunity towards leukemia. We anticipate, our investigation will provide a fundamental knowledge in nurturing the potential of RNA modifiers in discovering novel therapeutics or immunotherapeutic procedures.

Introduction: Decompensated heart failure (HF) is a complex and debilitating syndrome, which constitutes a severe emergency condition with high morbidity and mortality. The kidneys play fundamental roles in the pathophysiology of HF and, in the context of decompensations, acute kidney injury (AKI) has a bilateral cause-and-effect relationship, which can significantly worsen prognosis. However, the interaction between AKI and decompensated HF is poorly understood. Objective: This study aimed to assess the occurrence of AKI in patients hospitalized due to decompensated HF and to analyze its prognostic impact during hospitalization. Methods: Prospective single-center observational study that included patients hospitalized due to decompensated HF in a tertiary-level teaching hospital, conducted between July 2017 and January 2020. Patients who developed AKI during hospitalization were compared with those who did not develop it, until hospital discharge or death. AKI was defined as a serum creatinine increase greater than or equal to 0.3 mg/dl in 48 hours, a 1.5-fold increase in baseline creatinine in seven days or urinary volume <0.5 ml/kg/h during six hours, according to the Acute Kidney Injury Network (AKIN) criteria. The endpoints analyzed were death, need for invasive mechanical ventilation (IMV) and length of hospital stay. The Wilcoxon, Mann-Whitney and unpaired student t tests were used. Results: Ninety-nine patients were included, with a mean age of 65.4 ± 14 years, of which 47 (47.5%) were male and 52 (52.5%) were female. Reduced ejection fraction was observed in 77.8% of patients, whilst 22.2% had a diagnosis of HF with preserved EF. The decompensation clinical classifications were: dry and warm = 7 (7.1%), wet and warm = 72 (72.7%), wet and cold = 15 (15.1%) and dry and cold = 5 (5.1%). The average left ventricular ejection fraction was 38.3% ± 15. AKI ocurred in 22 patients (22.2%). Comparison between patients who evolved with and without AKI showed higher mortality (36.4% vs 10.4%, p = 0.004) and the need for IMV (54.5% vs 13%, p = 0.0001) in the first group. There was no significant difference regarding the length of in-hospital stay (22.9 ± 19 vs 18.8 ± 16 days, p = 0.26). Conclusions: The occurrence of AKI was frequent in patients with decompensated HF requiring hospitalization, affecting approximately one out of five patients. This complication was significantly associated with increased mortality and the need for IMV during hospitalization.

The study evaluates the toxic effects of acute and sub-acute oral administration of methanol extracts of Geophila obvallata in rats. During acute study, a dose of 1600, 2900 and 5000 mg/kg bw of extract was orally administered to rats. Rats were observed for signs of toxicity for two weeks. During sub-acute study (28 days), the extract, at doses of 100, 500 and 1000 mg/kg bw were administered orally to rats while control rats were given only tap water. At the end of the study, samples were collected for analyses. In acute toxicity studies, the extract did not induce death after single dose administration. Hence, the LD50 was estimated above 5000mg/kg. The results of sub-acute toxicity study show that no significant changes were observed in the body weights, organ weights, kidney function and organ histology. There were significant changes in hematology and biochemical indices investigated at elevated doses of 500 and 1000 mg/kg bw compared to the control. GOE may be considered non-toxic at a dose of 100 mg/kg with promising applications in drug therapy.

There are presently more than 18 known aflatoxins (>18) most of which have been insufficiently studied for their incidence, health-risk, and mechanisms of toxicity to allow effective intervention and control means that would significantly and sustainably reduce their incidence and adverse effects on health and economy. Among these, aflatoxin B1 (AFB1) has by far been the most studied; and yet, many aspects of the range and mechanisms of the diseases it causes remain to be elucidated. Its mutagenicity, tumorigenicity, and carcinogenicity, which are the best known still suffer from many limitations regarding the relative contribution of the oxidative stress and the reactive epoxide derivative (Aflatoxin-exo 8,9-epoxide) in the induction of the diseases, as well as its metabolic and synthesis pathways. Additionally, despite the well-established additive effects for carcinogenicity between AFB1 and other risk factors, e.g., hepatitis viruses B and C, and the algal hepatotoxic microcystins, the mechanisms of this synergy remain unclear. This study reviews the most recent advances in the mechanisms of toxicity of aflatoxins and the adverse health effects that they cause in humans and animals.

The Sars-Cov-2 pandemic led to several needed containing measures that conditioned the onset of depressive, anxiety and post-traumatic stress symptoms in population. These symptoms, espe-cially if not diagnosed and treated, can also occur in patients undergoing surgery with high im-pact on people’s lives, like hysterectomy. To evaluate the post-surgical distress and anx-ious-depressive symptoms following hysterectomy for benign disease focusing on the impact of COVID-19 pandemic. The prospective observational cohort study included patients undergoing hysterectomy for benign disease. Psychologic evaluation through social-demographic question-naires was obtained before surgery (T1), postoperatively (T2), and 3 months after surgery (T3). The HADS (Hospital Anxiety and Depression Scale) was used to evaluate anxious-depressive symptoms and the PCL-5 (Post-traumatic Stress Disorder Checklist for DSM-5) compared the on-set of post-surgical distress and anxiety and depressive symptoms. The pre-COVID-19 pan-demic period was compared to the post-COVID-19 pandemic phase. Patients treated after COVID-19 pandemic showed higher depressive symptoms rate compared to those treated before (p-value=0.02); conversely, pre-COVID-19 patients were more prone to develop a PTSD (p-value=0.04). A significative association between the occurrence PTSD and anxiety-depressive symptoms registered at T2 a (p-value=0.007) and T3 (p-value

Background: Evaluation of nutrition programs is essential to guarantee the effectiveness of community-based management of acute malnutrition (CMAM). Methods: The Rainbow Project Supplementary Feeding Programs (SFPs) in Zambia were evaluated between years 2015-17, following implementation of new recommendations based on previous evaluations (years 2012-14). Outcomes of the program were compared with International Standards and with those of 2012-14. Cox proportional risk regression analysis was performed to identify predictors of mortality and defaulting. Results: Data for 900 under age 5 years malnourished children (48.8% male; mean age 19.7months ±9.9) were analyzed. Rainbow 2015-17 program outcomes met International Standards, for general malnutrition or stratified moderate acute malnutrition (MAM) and severe acute malnutrition (SAM). When comparing with 2012-14 outcomes, better performance was noted: mortality rates were reduced by half (5.6% vs 3.1%, p = 0.01; for SAM: 12.4% vs 6.7%, p = 0.006), with significant improvement in average weight gain and mean length of stay (p<0.001), and increased awareness of HIV status (+30%; p < 0.001). HIV infection (5.5; 1.9–15.9), WAZ < −3 at baseline (4.6; 1.3–16.1) and kwashiorkor (3.5; 1.2–9.5) remained the major predictors of mortality. Conclusion: The effectiveness of the Rainbow SFPs for child malnutrition treatment and prevention in Zambia has significantly improved after evaluation and implementation activities, with impressive outcomes which resulted in a 50% reduction in mortality.

Hamman’s syndrome is a rare condition that mostly affects young males, often with a predisposition of asthma. It includes the presence of free air in the mediastinum and subcutaneous emfysema with no other underlying cause such as trauma or infection. It occurs spontanously and often in association with prolonged valsalva manouvre. This might explain why there are some cases of Hamman syndrome among young females giving birth. Here we present a case report of a 24-year- old primigravida with Hamman’s syndrome. She presented with symptoms a few hours after an uncomplicated vaginal delivery at 40+1 pregnancy week. The symptoms resolved spontanously after a few days of observation. We also give a systemic review of reported cases since 2000 to provide overview on pathomechanism, symptoms, diagnostics, treatment and management of this condition. Hamman’s syndrome is a rare, usually benign, but potentially serious complication that can occur during the second stage of labour. Diagnostics include inquiring about typical symptoms, clinical examination and chest x-ray or CT scan. Treatment is usually conservative with oxygen, bronchodilators and pain relief. The reccurence rate is low and there is no contraindication to vaginal delivery in future pregnancies. However, it is suggested that physicians and midwives be cautious and consider low threshold for instrumental delivery or caesarean section to avoid excessive valsalva manoeuvre.

Background: Auriculotherapy is a widely used approach for alleviating discomfort in patients experiencing pain, itchiness, sleep disturbances, and heightened anxiety. This method is also applicable to patients dealing with significant burn scars, who often encounter similar symptoms. Employed as an adjuvant therapy, auriculotherapy demonstrates potential in mitigating these clinical manifestations among individuals with major burn scars. These symptoms are known to be influenced by the autonomic nervous system. Objectives: Despite the absence of current data elucidating the impact of auriculotherapy on the autonomic nervous system, we embarked on an analysis of our heart rate variability (HRV) data to evaluate autonomic system functionality before and after the administration of auriculotherapy. Methods: Paired-samples t-tests and linear regression analysis of HRV variables and correlations with TBSA before and after auriculotherapy of a cohort of 31 survivors from 2016 Formosa Color Dust Explosion was carried out. Results: Significant change of specific HRV variables were found before and after auriculotherapy, and significantly negative correlations was revealed between TBSA and pre-SD prior to auriculotherapy. Conclusion: Our study showed that auriculotherapy may, at least in part, restore the equilibrium of autonomic nervous system and improve HRV parameters.

(1) Background: Metabolic syndrome is a strong predictor of cardiovascular disease thus the objective of the study was to verify the prevalence of metabolic syndrome in farmers, as well as to verify the association with sociodemographic, work and lifestyle factors. (2) Methods: Cross-sectional, observational study, carried out with 790 individuals. For the diagnosis of metabolic syndrome, the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) and International Diabetes Federation (IDF) criteria were used. Pearson's chi-square test and binary logistic regression were used to verify factors associated with metabolic syndrome (3) Results: The prevalence of MS according to the IDF criteria was 16.3% overall, with 9.7% of women (95% CI: 6.66–16.16) and 6.6% of men (95% CI: 5.17–11.97). According to the NCEP/ATP III criterion, it was 12.3% overall, with 7.5% corresponding to women (95% CI: 6.62 – 13.13) and 4.8% to men (95% CI: 3.5 – 8.70). With regard to the conditions that make up metabolic syndrome, it was found that high density lipoprotein, high blood pressure and high waist circumference were the most prevalent. (4) Conclusions: The prevalence of metabolic syndrome is considerable in the population when compared to other regions, both rural and urban, in Brazil.

Osmotic demyelination syndrome (ODS) is an acute demyelinating disorder characterized by the loss of myelin in the center of the basis pons which is defined as central pontine myelinolysis (CPM) and demyelination process in locations outside the pons which is defined as extrapontine myelinolysis (EPM). ODS including CPM and EPM is mainly caused by the rapid correction of hyponatremia. However, there are several reports of ODS in medical condition such as malnutrition, alcoholism, liver transplantation, malignancy, sepsis, electrolyte imbalance including hypernatremia, hypokalemia, hypophosphatemia, and chronic illness. Rarely, ODS was reported in patients with hyperammonemia or hyperbilirubinemia without sodium fluctuations. The symptoms usually correspond to the lesion site and EPM precedes CPM. Because ODS may be irreversible, prevention is more important. Here, we report a case of ODS secondary to the hyperammonemia and hyperbilirubinemia, as it can have unfavorable prognosis.

It is important to be familiar with the presentation of Turner syndrome and to understand the common causes of death associated with the disease. Using the autopsy case as an example, this case report will outline the classic presentation of Turner syndrome, go over its physiology, epidemiology, pathogenesis and explain the cause of death in this particular case while also highlighting other common causes of death/risk factors within Turner syndrome. Differential diagnosis and mimicking disease processes will also be discussed. This report will also highlight the molecular tests used for the diagnosis of Turner syndrome, discuss developments using in situ hybridization, and discuss why this method is best for the determination of Turner syndrome over conventional karyotyping.

Introduction: VULTO-VAN SILFHOUT-DE VRIES SYNDROME (VSVS;OMIM#615828) is an extremely rare hereditary disease associated with impaired intellectual development and speech, delayed psychomotor development and behavioral anomalies, including autistic behavioral traits and poor eye contact. To date, 27 patients with VSVS have been reported in the world literature. Materials and Methods: We describe a 23y.o. male patient with autism spectrum disorder (ASD) who was admitted to the gastroenterological hospital with signs of pseudomembranous colitis. ASD was first noted in the patient at the age of 2.5y.o. Later he developed epileptic seizers and prominent growth retardation. Prior to the hospitalization he was excluded chromosomal aberrations, Martin-Bell syndrome, aminoacidopathies/aminoacidurias associated with ASD. Whole genome sequencing was prescribed to the patient at 23y.o. Results: The patient appeared to be a heterozygous carrier of “de novo” variant c.662C>T (p.S221L) in ex 4 of the DEAF1 gene. c.662C> T had not been previously described in genomic databases. According to the ACMG criteria this missense variant was considered to be pathogenic. VSVS was diagnosed in the patient. Conclusions: The phenotype of the patient is very similar to the data presented in the world literature. However, growth retardation and cachexia, not previously described in the articles, are of interest.

Gilbert Syndrome, is a benign condition characterized by persistent indirect hyperbilirubinemia due to reduced UDP-glucuronyltransferase enzyme activity. Its coexistence with other clinical disorders has important clinical and pharmacological implications. GS is known to coexist with many hemolytic conditions and may lead to diagnostic difficulty and also increased incidence of gallstones. UGT1A1 gene has been shown to be involved in the conjugation of various physiologically important endogenous and exogenous compounds, so individuals with Gilbert mutation (the variant allele UGT1A1*28) have an increased risk of toxicity of various drugs and endogenous compounds like irinotecan, steroid hormones, implicated in various human carcinoma like colorectal and breast carcinoma. Deferiprone (DFP) is an orally available chelator used in the management of iron overload in patients with Transfusion Dependent Thalassemia (TDT). In this study, fifteen out of 275 patients with TDT, had a deferiprone-induced joint deformity. Among these fifteen patients with joint deformity, eleven patients (four patients were homozygous for TA 7 repeats and seven were heterozygous for TA7 repeats) had associated gilbert mutation. Therefore, we hypothesize that patients of TDT who had underlying Gilbert mutation might have decreased enzymatic activity of UGTIA6, which metabolizes the DFP, leading to more prominent adverse effects related to DFP.

Inflammation is known to be risk factors for metabolic diseases. The purpose of this study was to develop a Food-based Index of Dietary Inflammatory Potential (FBDI) and conduct its validation assessment. This study analyzed raw data from Korean Genome and Epidemiology Study 2012–2014 data of 17,771 people. We carried out the correlation analysis between 51 food groups and hs-CRP. The FBDI was developed by multiple regression method with hs-CRP and selected 17 food group. For the validation of FBDI, 7795 people in the 6th Korea National Health and Nutrition Examination Survey (KNHAES) was used. Binary logistic regression analysis was used for risk analysis of metabolic syndrome and FBDI. The FBDI model included that 7 were composed of anti-inflammatory food groups and 3 of inflammatory food groups. The FBDI was calculated by multiplying the intake of food group by β coefficients. KNHAES were included in the validation of FBDI. The risk of metabolic syndrome was found to be 2.152 times higher in the group with the highest FBDI than in the group with the lowest one (95% Cl:1.458–3.178, p for trend = 0.000). This study developed FBDI reflecting food intake for Koreans, which showed a significant relationship with the risk of metabolic syndrome.

Proposed fundamental laws of biology and a model of health and disease underscore the importance of the lymphatic system. The lymphatics are responsible for two of the laws of biology and the fulcrum of health and disease balancing proliferation with regeneration through the immune system. It is responsible for protection from the environment and repair of senile and damaged tissue. Life is constantly bombarded by forces that increase entropy. Lymphatics provide negative entropy to maintain health. Lymphatics help maintain cellular homeostasis removing products of metabolism. Using these principles, the role of lymphatics is investigated in salt sensitivity hypertension, cardiorenal system, the new pillar of heart failure and kidney disease - Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors, and brain diseases. The realization of organ lymphatics in maintenance of health and disease opens the avenue to new therapeutics. This is the unrealized potential of lymphatic study.

Development of the central nervous system (CNS) depends on accurate spatiotemporal control of signalling pathways and transcription programs. Forkhead Box G1 (FOXG1) is one of the master regulators that plays fundamental roles in forebrain development, from the timing of neurogenesis to the patterning of the cerebral cortex. Mutations in the FOXG1 gene cause a rare neurodevelopmental disorder called FOXG1 syndrome, also known as congenital form of Rett syndrome. Patients presenting with FOXG1 syndrome manifest a spectrum of phenotypes ranging from severe cognitive dysfunction and microcephaly to social withdrawal and communication deficits with varying severities. To develop and improve therapeutic interventions, there has been considerable progress towards unravelling the multi-faceted functions of FOXG1 in neurodevelopment and pathogenesis of FOXG1 syndrome. Moreover, recent advances in genome editing and stem cell technologies, as well as increased yield of information from high throughput omics opened promising and important new avenues in FOXG1 research. In this review, we provide a summary of clinical features and emerging molecular mechanisms underlying FOXG1 syndrome, and explore disease-modelling approaches in animals and human-based systems to highlight prospects of research and possible clinical interventions.

Mechanical ventilation is a life-saving treatment for critically ill patients who are struggling to breathe independently due to injury or disease. Globally, large numbers of Individuals have always required mechanical ventilation per year. The Covid-19 pandemic elevated the significance of the mechanical ventilation which have played a significant role in sustaining Covid 19 infected critically ill patients who could not breathe on their own. The pandemic drew the attention of the world to the shortage of ventilators globally.This research work presents the formulation of a detailed Port Hamiltonian model of a mechanical ventilator integrated to the human respiratory system. The interconnection and coupling conditions for the various subsystem within the mechanical ventilator and the coupling between the mechanical ventilator and the human respiratory system is also presented.A structure preservation discretization is provided along side numerical simulations and results. The obtained results are found to be comparable to results presented in literature.The future work will include the design of suitable controllers for system.

Viral tropism is most commonly linked to receptor use, but host cell protease use can be a notable factor in susceptibility to infection. Here we review the use of host cell proteases by human viruses, focusing on those with primarily respiratory tropism, particularly SARS-CoV-2. We first describe the various classes of proteases present in the respiratory tract, as well as elsewhere in the body, and incorporate the targeting of these proteases as therapeutic drugs for use in humans. Host cell proteases are also linked to the systemic spread of viruses and play important roles outside of the respiratory tract; therefore, we address how proteases affect viruses across the spectrum of infections that can occur in humans, intending to understand the extrapulmonary spread of SARS-CoV-2.

Neurologic symptoms associated with Long COVID result from the persistent infection of SARS-CoV-2 in the nasal neuroepithelial cells, leading to inflammation in the central nervous sys-tem (CNS). As of today, there is no evidence that vaccines or medications can clear the persistent viral infection in the olfactory mucosa. Recently published clinical data demonstrate that only 5% of Long COVID anosmia patients have fully recovered during the past 2 years and 10.4% of COVID patients are still symptomatic 18 months post infection. Our group demonstrated that ep-igallocatechin-3-gallate-monopalmitate (EC16m) nanoformulations possess strong antiviral activ-ity against human coronavirus, suggesting this green tea-derived compound in nanoparticle for-mulations could be developed as an intranasally delivered new drug targeting the persistent SARS-CoV-2 infection, as well as inflammation and oxidative stress in the CNS, leading to resto-ration of neurologic functions. The objective of the current study is to evaluate the mucociliary safety of the EC16m nasal nanoformulations and the efficacy against human coronavirus. Meth-ods: nanoparticle size and Zeta potential were measured using the ZetaView Nanoparticle Tracking Analysis system; mucociliary safety was determined using MucilAir Human Nasal Epi-thelium Model; contact antiviral activity and post-infection inhibition against OC43 viral strain were assessed by TCID50 assay for cytopathic effect on MRC-5 cells. Results: the saline-based EC16 mucoadhesive nanoformulations containing 0.005 to 0.02% w/v EC16m have no significant difference in comparison to saline (0.9% NaCl) on tissue integrity, cytotoxicity, and cilia beat fre-quency. A 5-minute contact inactivated 99.9% of the β-coronavirus OC43. OC43 viral replication was inhibited by >99% after infected MAR-5 cells were treated with one of the formulations. Con-clusion: the saline-based novel EC16m mucoadhesive nasal nanoformulations rapidly inactivated human coronavirus with mucociliary safety measurements comparable to saline, a solution widely used for nasal applications.

The study aimed to determine the effect of heat stress (HS) on reproductive parameters [calving to first service (CTFS) and first service conception rate (FSCR)] and general physiological responses [rectal temperature (RT) and respiratory rate (RR)] in tropical Holstein Friesian dairy cows raised in Ratchaburi province, Thailand. Cows were divided into a moderate HS (n = 22) and a mild HS (n = 22) group. Cycling cows were detected and injected with PGF2α at the beginning of the experimental period. Reproductive and physiological parameters were recorded. The average temperature humidity indices experienced by the cows were 80.67 ± 0.79 and 77.81 ± 1.09 for the moderate and mild HS groups, respectively. Cows showed significantly lower RT and RR in the mild (38.47 ± 0.21°C and 41.04 ± 4.55 bpm, respectively) than in the moderate HS group (38.87 ± 0.15°C and 51.17 ± 10.52 bpm). Under mild HS, cows showed a better response to injection of PGF2α than those under moderate HS. The percentage of cows that ovulated after being induced by PGF2α and showed estrus signs was higher in the mild than the moderate HS groups (54.55% versus 18.18%). Furthermore, the FSCR of cows under mild HS tended to be higher than in the moderate HS group (54.55 % and 42.11%, respectively), while the average CTFS interval was significantly shorter under mild than moderate HS (69.47 ± 18.18 and 84.60 ± 27.68, respectively). These results indicate that HS impairs reproductive performance in cross-bred Holstein cows, especially in moderate HS conditions.

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in cattle raised in North America. At the feedlot, cattle are subject to metaphylactic treatment with macrolides to prevent BRD, a practice that may promote antimicrobial resistance and has resulted in an urgent need for novel strategies. Mannheimia haemolytica is one of the major bacterial agents of BRD. The inhibitory effects of two amphipathic, α-helical (PRW4, WRL3) and one β-sheet (WK2) antimicrobial peptides were evaluated against multidrug-resistant (MDR) M. haemolytica isolated from Alberta feedlots. WK2 was not cytotoxic against bovine turbinate (BT) cells by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. All three peptides inhibited M. haemolytica, with WK2, being the most efficacious against multiple isolates. At 8-16 µg/ml, WK2 was bactericidal against Mh 330 in broth and at 32 µg/ml in the presence of BT cells, reduced the population by 3 logs CFU/ml without causing cytotoxic effects. The membrane integrity of Mh 330 was examined using NPN (1-N-phenylnaphthylamine), and ONPG (o-Nitrophenyl β-D-galactopyranoside) with both the inner and outer membranes being compromised. Thus, WK2 may be a viable alternative to the use of macrolides as part of BRD prevention and treatment strategies.

In the realm of cement production, clinker-producing factories emerge as both energy and material-intensive entities, emitting a substantial array of primary pollutants into the environment compared to their non-clinker producing counterparts. Our study delves into Ethiopian clinker-producing cement factories, unraveling the concentration of primary pollutants and their repercussions on neighboring communities. Venturing beyond mere statistics, we meticulously measured particulate matter (PM2.5 and PM10) and gaseous emissions (CO2, N2O, SO2) at various units within the cement factories and in nearby residential areas. The findings reveal an ambient air quality riddled with concern; PM2.5 levels ranged from 137 to 814 μg/m3, PM10 from 195 to 886 μg/m3 within the cement factories, and PM2.5 (113 to 196 μg/m3) and PM10 (125 to 453 μg/m3) in the adjacent village. Alarmingly, these particulate matter emissions exceeded the limits set by Ethiopian ambient air quality guidelines (150 μg/m3). Unraveling the health implications, respiratory diseases were notably high among individuals aged 25 to 60, followed closely by those aged 6 to 24. In contrast, the age groups 0–5 and > 61 exhibited lesser susceptibility, as infants and the elderly spent more time at home, thus reducing exposure to emissions. Our study underscores the urgent need for legal measures, calling for the establishment of buffer zones between cement factories and settlements. This proactive step, if enforced, holds the promise of mitigating cement particulate emissions and safeguarding the well-being of communities residing in proximity to these industrial giants.

Increasing evidence supports the direct healing effects of forests, partly attributed to the exposure to plant-emitted monoterpenes available in the forest atmosphere. The potential benefits on respiratory functions from inhaling monoterpenes have gained attention, especially due to the global rise in respiratory diseases. This study involved 42 asthmatic adolescents attending a summer rehabilitation camp at an Altitude Pediatric Asthma Center within a densely forested area in the Eastern Italian Alps. Volatile organic compound measurements indicated a pristine atmosphere, enabling modeling of continuous hourly monoterpenes concentration. Monoterpene concentration exposure and total inhaled dose were assessed over a 14-day stay, during which spirometry, lung oscillometry, and fractional exhaled nitric oxide were measured. Statistically significant correlations were observed between modifications in lung function parameters among asthmatic adolescents and monoterpenes exposure. These findings suggest a potential localized airway effect specific to monoterpenes. This pilot cohort study might pave the way for further investigations into the therapeutic effects of forest monoterpenes on lung function tests, asthma, and the broader healing potential of forest environments.

The last decade the impulse-radio ultra-wideband (IR-UWB) radar sensors have tended to substitute the gold standard, polysomnography (PSG), for the acquisition of the primary vital signs of the human body. However, the main drawback of the radar sensor is its sensitivity to the environmental noise and body motion. In this work, we aim to investigate whether radar sensor recordings of the chest and heart motion can be accurate substitutes to the PSG chest and heartbeat signals measurements. In terms of this scientific issue, we develop an innovative pipeline of handling the radar-based recordings, which includes: (a) the motion detection, (b) the extraction of the respiration, heartbeat and activity vital signs and (c) the estimation of the respiratory and heartbeat rates, i.e., the RR and HR, respectively. Our experimental results, applying our proposed methodology to 5 subjects during their sleep, showed that the radar sensor’s measurements can be comparative to the those producted by the PSG. Moreover, the corresponding RR and HR frequencies were proven to have Pearson’s correlation, between the radar and the PSG, greater than 0.9 and 0.78, respectively. Finally, the relative errors between the PSG, and the radar-based RR and HR rates were proven to be less than 6% and 10%, respectively.

The hypothesis that health status is the highest-ranking concept, followed by respiratory symptoms and dyspnea as the lowest-ranking concepts in subjects with chronic obstructive pulmonary disease (COPD) was tested in a real clinical setting with 157 subjects with stable COPD. Spearman's rank correlation coefficients for scores of health status using the COPD assessment test (CAT), respiratory symptoms using the COPD Evaluating Respiratory Symptoms (E-RS) and dyspnea using the Dyspnoea-12 (D-12) between any two were 0.6 to 0.7. Upon categorizing the patients as "abnormal" or "normal" according to the threshold, it was found that 30 patients (19.1%) had dyspnea, respiratory symptoms, and impaired the health status. Dyspnea was considered an important part of respiratory symptoms though seven patients had dyspnea but no respiratory symptoms. There were 10 patients who had respiratory symptoms without dyspnea but without health status problems. Furthermore, there were six patients who had both dyspnea and respiratory symptoms but whose health status was classified as fine. Thus, the hypothesis was correct in approximately 85% of cases.

Severe respiratory syncytial virus (RSV) infections in early life have been linked to the development of chronic airway disease. RSV is a potent inducer of reactive oxygen species (ROS) which contributes to inflammation and enhanced clinical disease. NF-E2-related factor 2 (Nrf2) is an evolutionary conserved redox-responsive protein that helps to protect cells and whole organisms from oxidative stress and injury. The role of Nrf2 in the context of viral-mediated chronic lung injury is not known. Herein, we show that RSV experimental infection of adult Nrf2 deficient BALB/c mice (Nrf2-/-; Nrf2 KO) is characterized by enhanced disease, increased inflammatory cell recruitment to the bronchoalveolar compartment, and a more robust upregulation of innate and inflammatory genes and proteins, compared to wild type Nrf2+/+ competent mice (WT). These events that occur at very early time points, lead to increased peak RSV replication in Nrf2 KO compared to WT mice (day 5). To evaluate longitudinal changes of the lung architecture, mice were scanned weekly by high-resolution micro-computed tomography (micro-CT) imaging up to 28 days after initial viral inoculation. Based on micro-CT qualitative 2D imaging and quantitative reconstructed histogram-based analysis of lung volume and density, we found that RSV infected Nrf2 KO mice developed significantly greater and prolonged fibrosis compared to WT mice. Results of this study underscore the critical role of Nrf2-mediated protection from oxidative injury not only in acute pathogenesis of RSV infection, but also in its long-term consequences of chronic airway injury.

The effective detection of viruses in aircraft wastewater is crucial to establish surveillance programs for monitoring virus spread via aircraft passengers. This study aimed to compare the performance of two virus concentration workflows, adsorption-extraction (AE) and Nanotrap® Microbiome A Particles (NMAP), in detecting the prevalence and concentrations of 15 endogenous viruses in aircraft lavatory wastewater samples. The viruses tested include two indicator viruses, four enteric viruses, and nine respiratory viruses. The results showed that cross-assembly phage (crAssphage), human polyomavirus (HPyV), rhinovirus A (RhV A), and rhinovirus B (RhV B) were detected in all wastewater samples using both workflows. However, enterovirus (EV), human norovirus (HNoV GII), human adenovirus (HAdV), bocavirus (BoV), parechovirus (PeV), epstein-barr virus (EBV), influenza A virus (IAV), and respiratory syncytial virus B (RsV B) were infrequently detected by both workflows, and hepatitis A virus (HAV), influenza B virus (IBV), and respiratory syncytial virus B (RsV A) were not detected in any samples. The NMAP workflow had greater detection rates of EV, PeV, and RsV B than the AE workflow, while the AE workflow had greater detection rates of HAdV, BoV, and EBV than the NMAP workflow. The concentration of each virus was also analyzed, and the results showed that CrAssphage had the highest mean concentration (6.76 log₁₀ GC/12.5 mL) followed by HPyV (5.46 log₁₀ GC/12.5 mL using the AE workflow, while the mean concentrations of enteric and respiratory viruses ranged from 2.48 to 3.63 log₁₀ GC/12.5 mL. Using the NMAP workflow, the mean concentration of crAssphage was 5.18 log₁₀ GC/12.5 mL and the mean concentration of HPyV was 4.20 log₁₀ GC/12.5 mL, while mean concentrations of enteric and respiratory viruses ranged from 2.55 to 3.74 log₁₀ GC/12.5 mL. The mean concentrations of CrAssphage, HPyV, RhV A, and RhV B between the two workflows were statistically significant (p < 0.05). In summary, the present study provides valuable insights into the performance of virus concentration workflows in detecting and quantifying different viruses in aircraft lavatory wastewater samples. The findings can aid in the selection of an appropriate concentration workflow for virus surveillance studies and contribute to the development of efficient and reliable virus detection methods.

In Kawasaki disease (KD), convulsions are rare and mostly attributed to latent and coexisting encephalitis/encephalopathy due to KD itself. Therefore, we retrospectively investigated concomitant viral infections in patients with KD. Between January 2012 and December 2020, among 523 patients with KD, 7 (1.53%), 1 (0.19%), 6 and 1 (1.15% and 0.19%) were positive for adenovirus (AdV-Ag), respiratory syncytial virus (RSV-Ag), and influenza A or B (Flu A-Ag or Flu B-Ag) antigens, respectively. Among them, two were positive for both AdV-Ag and FluA-Ag. Seven patients with KD (1.3%) presented febrile convulsions, and only one was diagnosed with encephalitis/encephalopathy. Between January 2021 and August 2022, 57 patients with KD were newly diagnosed among whom FilmArray® respiratory panel (FARP) was applied on 24 patients, and 14 (58.3%) were positive for at least one virus. During the same period, 32 out of 45 patients (71.1%) with febrile convulsions examined using the FARP were positive for at least one virus. The trend of viruses in patients with KD and febrile convulsion reflected the regional epidemic viral infection. Respiratory virus detected at a much higher rate using the FARP suggests that most convulsions in patients with KD might be related to concomitant viral infection. The possible involvement and association of concomitant respiratory viral infections in patients with KD with prognosis or encephalopathy/encephalitis remain to be investigated.

Viral respiratory infections are recognized risk factors for the loss of control of allergic asthma and the induction of exacerbations, both in adults and children. Severe asthma is more susceptible to virus-induced asthma exacerbations, especially in the presence of high IgE levels. In the course of immune responses to viruses, an initial activation of innate immunity typically occurs and the production of type I and III interferons is essential in the control of viral spread. However, the Th2 inflammatory environment still appears to be protective against viral infections in general and in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections as well. As for now, literature data, although very limited and preliminary, show that severe asthma patients treated with biologics don’t have an increased risk of SARS-CoV-2 infection or progression to severe forms compared to the non-asthmatic population. Omalizumab, an anti-IgE monoclonal antibody, exerts a profound cellular effect, which is able to stabilize the effector cells becoming much more efficient from the point of view of innate immunity in contrasting respiratory viral infections. In addition to the antiviral effect, clinical efficacy and safety of this biological allows a great improvement in the management of asthma.

Pesticide exposure is a growing concern for public health. Although Brazil is the world's largest consumer of pesticides, few studies addressed the health effects among farmers. This study aimed to evaluate whether pesticide exposure is associated with respiratory outcomes among rural workers and relatives in Brazil during the crop and off-seasons. 82 family farmers were interviewed about occupational history and respiratory symptoms, and cholinesterase tests were conducted in the crop-season. Spirometry was performed during the crop and off-season. Respiratory outcomes were compared between seasons and multiple regressions were conducted to search for associations with exposure indicators. Participants were occupationally and environmentally exposed to multiple pesticides from an early age. During the crop and off-season, respectively, they presented a prevalence of 40% and 30.7% for cough, 30.7% and 24% for nasal allergies, and 24% and 17.3% for chest tightness. Significant relations between spirometry impairments and exposure indicators were found both during the crop and off-season. These findings provide complementary evidence about the association of pesticide exposure with adverse respiratory effects among family farmers in Brazil. This situation requires special attention as it may increase the risk of pulmonary dysfunctions, and the morbidity and mortality burden associated with these diseases.

The review aims to examine how well numerical indicators of business bankruptcy can predict outcomes. The paper examines ten critical studies that concentrate on statistical models for bankruptcy predictions utilizing PRISMA criteria. The findings highlight the usefulness of numerical indicators in indicating financial hardship, particularly cash flow ratios. In order to connect theoretical knowledge with real-world corporate strategy applications, the study ends by reaffirming the importance of these indicators in strategic decision-making.

Fragile X syndrome (FXS) is caused by the full mutation in the FMR1 gene on the Xq27.3 chromosome region. It is the most common monogenic cause of Autism Spectrum Disorder (ASD) and inherited intellectual disability (ID). Besides ASD, ID and other issues, individuals with FXS may exhibit sleep problems and impairment of circadian rhythm (CR). The Drosophila melanogaster models of FXS, such as dFMR1B55, present excellent model for research in the FXS field. During this study, sleep pattern and CR in dFMR1B55 mutants were analyzed, using a new platform based on continuous high-resolution videography in integration with a highly-customized version of software. This methodology provides more sensitive results, which could be crucial for all further research in this model of fruit flies. The study revealed that dFMR1 B55 male mutants can be considered weak rhythmic flies rather than totally arrhythmic, and present a good alternative animal model of genetic disorder, which includes impairment of CR and sleep behavior. The combination of videography and software used in the current study should be recommended as a gold-standard methodology for such further research.

Furthermore, the nasal congestion typical of rhinitis can contribute to upper airway obstruction and sleep-disordered breathing. A vicious circle is created between asthma and sleep-disordered breathing: uncontrolled asthma and sleep-disordered breathing can worsen each other. In children with genetic obesity, despite alterations in the immune system, fewer allergies are found compared to the general population. The causes of this reduced allergenicity are unclear but probably involve genetic, immunological, and environmental factors. Further studies are needed to understand the mechanisms. The study emphasizes the importance of jointly evaluating and managing allergies, obesity, and sleep-disordered breathing in children, considering their close interconnection.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents unexplained and sudden deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for prolonged QTc or Long QT Syndrome (LQTS) should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiogram (ECG) could identify congenital heart defects (CHD) early, especially those not detected at birth. Infants with prolonged QT intervals typically undergo genetic analysis for Long QT Syndrome; (2) Methods: The study involved infants aged 20-40 days, born clinically healthy, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHD identified immediately after birth, as well as those who underwent ECG or echocardiogram for other clinical or historical indications, were excluded from the study. The data were analyzed using SPSS version 22.0; (3) Results: Of the 42,200 infants involved, 2,245 were enrolled, with 39.9% being males. Subsequently, 164 children (37.8% males) with prolonged QT intervals underwent further diagnostic investigations. Genetic mutations were identified in 11 out of 18 tested children. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Medications used included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%; (4) Conclusions: The screening has proven effective in early diagnosing Long QT Syndrome and other cardiac rhythm anomalies, with additional benefits in detecting mutations and/or QTc prolongations in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

(1) Background: The stylohyoid syndrome, known as classical Eagle Syndrome (cES), is characterized by calcificatication of the stylohyoid chain with numerous nonspecific symptoms, mainly pain. This study introduces Minimally Invasive Cervical Styloidectomy (MICS). (2) Methods: MICS was performed on sixty-five patients diagnosed with classical Eagle syndrome. Patients underwent meticulous differential diagnosis. Surgical plans were established based on the findings from neck angioCT. (3) Results: The healing process was uneventful without significant complications. The overall success rate was 97.0%, with a follow-up of a minimum of six months. In one case, the surgery did not yield the desired improvement. In one case, a partial relapse of symptoms was observed. (4) Conclusions: MICS is a straightforward and efficient surgical treatment technique for stylohyoid syndrome.

ABSTRACT：Background: Diagnosing rhabdomyolysis has usually defined at least five or ten times the upper limit creatine kinase level; but it is conservative for Exertional rhabdomyolysis. The aim was to analysis the biomarkers during a military operation in an extreme environment with high physical demand. Material and Methods: Seventeen male military personnel (age: 27.83 ± 2.96 years; weight: 76.31 ± 7.67 kg; and height 174.92 ± 5.91 cm) participated for this investigation. The creatine kinase (CK); blood urea nitrogen (BUN); creatinine (Cr); sodium (Na); potassium (K); aspartate amino transferase (AST) and alanine amino transferase (ALT) were analyzed. Urine specific gravity (USG) the hydration status was monitored. The Generalized Linear Models for repeated measures and the Friedman’s two-way test were used to comparative moments. Results: The BUN; Cr; Na; and K mean values showed a nonsignificant. The statistical significance of the test was found in CK and AST. There was considerable variability of CK between subjects during the operation. The moderate correlation between CK and Cr was found during study. Conclusion: Elevated CK levels after the operation were characterized as physiological pattern. These results reinforce that CK values are not predictors of renal function in activities with intense and continuous physical demand

Background: Boronic acids form di-ester bonds with cis-hydroxyl groups in carbohydrates. The formation of these adducts could impair the physical and chemical properties of the precursors, even their biological activity. Methods: Two carbohydrate-derivatives from D-fructose and D-arabinose and phenylboronic acid were synthesized in a straightforward one-step procedure and chemically characterized by spectroscopy and X-ray diffraction crystallography. Also, an acute toxicity test was performed to determine their Lethal Dose50 (LD50) by using the Lorke’s method. Results: Analytical chemistry assays confirmed adducts by the generation of the diester bonds with a β-D-pyranose of carbohydrates, including signals corresponding to the formation of new bonds, like the stretching of B-O bonds. The NMR spectra yielded information about the stereoselectivity in the synthesis reaction by the finding of just one signal in the range for the anomeric carbon in the 13C NMR spectra of both adducts. The acute toxicity tests showed that LD50 value for both compounds is 1265 mg/kg, while Effective Dose 50 for sedation is 531 mg/kg. However, differences were in the onset and lapse of sedation. Conclusions: These adducts are bioactive and highly safe agents. Further biological evaluation is desirable to explore medical purposes.

Background: Breast cancer and other neoplasms like acute lymphocytic leukemia pose a serious threat to public health worldwide. Treatment for malignancies including acute lymphocytic leukemia and breast cancer requires enzymes that break down L-glutamine. An amidohydrolase called L-glutaminase can be an effective chemotherapeutic tool for treating various cancers. Methods: On mineral L-glutamine agar selective medium (MGA), a few bacterial isolates were examined in the current investigation to see if they produced L-glutaminase. However, the most effective positive bacterial isolates generating L-glutaminase were identified using morphological and biochemical testing. Molecular detection using the direct Southern blotting approach was also used to determine the main positive isolate that produces L-glutaminase. L-glutaminase synthesis by bacteria was evaluated for its characteristics. Using an MTT test, the anticancer activity was evaluated. Results: exclusive bacterial isolates that used L-glutamine as their sole source of metabolic nitrogen exhibited favorable growth on MGA. PH 7.4 and a temperature of 37 0C were the ideal environmental and physiological conditions for developing positive bacterial isolates. From the soil samples taken from various soil conditions in Egypt, the morphological and biochemical analyses showed that Bacillus cereus 14579 was the main positive bacterial generating L-glutaminase isolate. At a pH of 7.4 and a temperature of 37 °C, the following activators—KCL, ZnSO4, FeSO4, K2HPO4, and MgSO4—provided the high-grade circumstances for characterizing L-glutaminase synthesis. Bacillus cereus-produced L-glutaminase has shown excellent bioavailability and effectiveness as an anticancer therapy. The yield [productivity] was 5.2 U/ml during the original manufacture from MGA, but it increased to 42.96 U/ ml by bacterial recombinant DNA manufacturing. The molecular mass of L-glutaminase was roughly 37 KDa. L-glutaminase was purified, yielding final enzyme recovery of 55 1.23%, total activity 12,990± 19.76 ( U), specific activity 384.66± 8.92( U/ mg of protein), and purification fold 2± 2.99. Furthermore, the L-glutaminase activity was raised by 19%, 23%, 15%, and 9%, respectively, by the enzymatic activators Mn2+, K+, Na+, and Fe3+. It demonstrated strong DPPH scavenging activity (IC50 = 61 μg/ mL) and anticancer activity( IC50 = 40.72, 9.7, 7.39, 20.61, 51.28, and 11.55 μg/ mL, respectively) against human liver (HepG-2), colon ( HCT-116), breast ( MCF-7), lung( A-549), lymphocytic( CCL-120), and cervical( Hela) cancer cell lines. A stronger affinity for its substrate was shown by the kinetic parameters of Km and Vmax, which were 13.2 10-5 M and 119.86 μmol/ ml/ min, respectively. Conclusion: Acute lymphocytic leukemia and breast cancer are examples of auxotrophic malignancies for which L-glutamine serves as the only metabolic source, and L-glutaminase generated by Bacillus cereus was an appropriate enzyme in the therapy of these diseases.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding children are scarce. The purpose of our study is to explore the risk factor for AKD and impact of AKD following an acute kidney injury (AKI) episode in children on mortality and new-onset CKD. Methods: We retrospectively evaluated 736 children with ages between 2 and 18 years old with AKI admitted in a tertiary care hospital from the west Romania over a 9 years period. Results: AKD incidence following AKI was 17%. Patients that developed AKD were older, with higher baseline serum creatinine values, urea, C reactive protein and lower proteins, haemoglobin and sodium. They were more often exposed to sepsis, critical illness and nephrotoxic medications and presented certain susceptibilities like CKD, neoplasia, anemia, heart failure, arterial hypertension, stem cell transplant and female gender. AKI causes that increased the risk of AKD were intrinsic ones. AKD increased the overall mortality by three times. The factors that independently increased the risk of evolution towards CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: AKD is an independent risk factor for mortality and new-onset CKD in children.

Alterations in the composition and diversity, metabolism, and products of the microbiome, and of the gut microbiome (GM), have been shown to be closely associated with the onset and progression of many human diseases, including cancer (i.e. hematological neoplasms). Acute lymphoblastic leukemia (ALL) is the most common form of childhood malignancy. Affected cases present typical alterations of GM, followed by inflammation, which contribute to its progression, response to therapy, as well as possible relapses. Recent evidence also reports that GM influences the development and functions of the newborn's hematopoietic system through the process of developmental programming during fetal life, as well as its susceptibility to the onset of onco-hematological pathologies, namely ALL. Furthermore, in children with ALL, GM has been found to vary in composition, variety, and functions during the clinical stages of ALL, and such variation may influence and predict the complications and prognosis of ALL after chemotherapy treatment or stem cell hematopoietic transplant. Here, we suggest some therapeutic strategies, which can be applied at two levels of intervention to recover the microbiome, and consequently prevent/delay ALL or arrest its progression.

OBJECTIVES: To assess the predictive value of serum trypsin and Trypsinogen Activation Peptide (TAP) for the severity of AP by means of a single center cohort study as well as a systematic review of the current literature. METHODS: The literature search was conducted using Medline (PubMed), EMBASE and the Cochrane Central Register. A total of 142 patients with acute pancreatitis (AP) were included in the cohort study and parameters of the revised Atlanta criteria of 2012 and the APACHE II were assessed. RESULTS: The review showed promising results for the predictive value of serum trypsinogen-2, but conflicting results for serum TAP and trypsin. In the cohort study, patients were observed for 4 days after diagnosis of AP: 9 patients had severe AP, 35 patients had moderate AP and 81 patients had mild AP. The ratio of the geometric mean of severe vs mild AP for trypsin was 0.72 (95% CI: 0.51-1.00), p=0.053 and for TAP 0.74 (95% CI: 0.54-1.01), p=0.055 respectively. CONCLUSION: The cohort study showed an inverse correlation of serum levels of TAP and trypsin with severity of AP. Serum TAP and trypsin have an inferior predictive value of severity of AP compared to the clinical APACHE II score.

Background: Limited data exist on postoperative acute kidney injury (AKI) in patients underwent esophageal cancer surgery. The purpose of the study was to evaluate the incidence, risk factors and consequences of postoperative acute kidney after esophagectomy. Methods: This was a retrospective cohort study. The study was conducted in a tertiary specialized cancer center in Italy. All patients undergoing elective esophageal cancer surgery between 2016 and 2021 were included in the study. AKI was defined according to Kidney Disease: Improving Global Outcomes criteria (both serum creatinine and urine output), within 48 hours after surgery. Preoperative and intraoperative data were registered. We also collected data concerning progression of AKI, need for kidney replacement therapy, mortality, medical (pulmonary, cardiovascular, septic) and surgical complications within 30 days from surgery, as well as length of hospital stay. Results: Incidence of postoperative AKI was 32%. The independent risk factors were body mass index and the invasive surgical approach. Persistent AKI accounted for 15% of the cases and it was associated with increased risk of major cardiovascular events (odds ratio 4.14, 95% CI 1.05-15.8, p-value 0.036), pulmonary complications (OR 3.67, 95% CI 1.04-14.9, p-value 0.050) and increased length of hospital stay (AME 7.2, 0.5-13.9, p-value 0.035). Conclusions: Postoperative AKI is common after esophageal cancer surgery. BMI and totally invasive surgical approach are independent risk factors. Persistent AKI lasting more than 48 hours increased the risk for cardiovascular and pulmonary complications, with prolonged length of hospital stay.

Although acute heart failure (AHF) is a common disease associated with significant symptoms, morbidity and mortality, the diagnosis, risk stratification and treatment of patients with hypertensive acute heart failure (H-AHF) still remain a challenge in modern medicine. Despite great progress in diagnostic and therapeutic modalities, this disease is still accompanied by a high rate of both in-hospital (from 3.8% to 11%) and one-year mortality (from 20% to 36%). Considering the high rate of re-hospitalization (22% to 30% in the first three months), the treatment of this disease represents a major financial blow to the health system of each country. This disease is characterized by heterogeneity in precipitating factors, clinical presentation, therapeutic modalities and prognosis. Since heart decompensation usually occurs quickly (within a few hours) in patients with H-AHF, establishing a rapid diagnosis is of vital importance. In addition to establishing the diagnosis of heart failure itself, it is necessary to see the underlying cause that led to it, especially if it is de novo heart failure. Given that hypertension is a precipitating factor of AHF and in up to 11% of AHF patients, strict control of arterial blood pressure is necessary until target values are reached in order to prevent the occurrence of H-AHF, which is still accompanied by a high rate of both early and long-term mortality.

Acute myeloid leukemia (AML) is an aggressive malignancy characterized by rapid growth and uncontrolled proliferation of undifferentiated myeloid cells. Metabolic reprogramming is commonly observed in the bone marrow of AML patients, as leukemia cells require increased ATP supply to support disease progression. In this study, we examined the potential role of mesothelin as a metabolic modulator in myeloid cells in AML. Mesothelin is a well-known marker of solid tumors that promotes cancer cell proliferation and survival. We initially analyzed alterations in mesothelin expression in the myeloblast subpopulations, defined as SSC-Alow/CD45dim, obtained from bone marrow of AML patients using flow cytometry. Our results showed overexpression of mesothelin in 34.8% of AML patients. Subsequently, metabolic changes in leukemia cells were evaluated by comparing the oxygen consumption rates (OCR) of bone marrow samples derived from adult AML patients. Notably, higher OCR was observed in the mesothelin-positive compared to the mesothelin-low and non-expressing groups. Treatment with recombinant human mesothelin protein enhanced OCR and increased the mRNA expression of glycolytic enzymes and mitochondrial complex II in KG1α AML cells. Notably, siRNA targeting mesothelin in KG1α cells led to reduction of glycolysis-related gene expression but had no effect on the mitochondrial complex gene. The collective results demonstrate that mesothelin induces metabolic changes in leukemia cells, facilitating acquisition of a rapid supply of ATP for proliferation in AML. Therefore, targeting of mesothelin presents a potentially promising approach for mitigating the progression of AML through inhibition of glycolysis and mitochondrial respiration in myeloid cells.

Methotrexate (MTX), a structurally related substance to folic acid, is an important chemotherapeutic agent used for decades in the treatment of pediatric acute lymphoblastic leukemia (ALL) and other types of cancer as non Hodgkin lymphomas and osteosarcomas. Despite the successful outcomes observed, the primary drawback is the variability in the pharmacokinetics and pharmacodynamics between patients. The main adverse events related to its use are mainly nephrotoxicity, mucositis and myelosuppression especially when used in high doses. The potential adverse reactions and toxicities associated with MTX are a cause for concern and may lead to dose reduction or treatment interruption. Genetic variants in MTX transport genes have been linked to toxicity. Pharmacogenetic studies conducted in the past focused on single nucleotide polymorphisms (SNPs) in the coding and 5′-regulatory regions of genes. Recent studies have demonstrated a significant role of miRNAs in the transport and metabolism of drugs, and in the regulation of target genes. The last few years, the number of annotated miRNAs is continually rising, as well as the studies of miRNA polymorphisms and MTX toxicity. Therefore, the objective of the present study is to investigate the role of miRNA variants related to MTX adverse effects.

Idiosyncratic drug induced liver injury (DILI) is an unpredictable reaction of exposed individual on a certain drug, and the drug-induced autoimmune hepatitis (DIAIH) presents a DILI phenotype that mimics idiopathic autoimmune hepatitis (AIH) when considering the clinical, biochemical, serological and histological parameters. We present a case of a 48-year-old male that was hospitalized due to severe hepatocellular liver injury two months after the self-treatment with the muscle-building dietary supplement based on arginine-alpha-ketoglutarate, L-citrulline, L tyrosine, creatine malate and beet extract. His immunology panel was positive with increased IgG levels, and the radiologic methods showed no signs of chronic liver disease. He underwent corticosteroid treatment with adequate response. After the therapy withdrawal, a clinical relapse occurred. Seven months after the initial presentation liver MR suggested the initial cirrhotic changes of the right liver lobe. Liver biopsy revealed abundant lymphoplasmacytic infiltrate with piecemeal necrosis and grade 2 fibrosis. He responded well on the corticosteroid treatment again, and was further treated with low dose prednisone without additional relapses. Several years later, further management confirmed presence of liver cirrhosis with no histological or biochemical signs of the disease activity. DIAIH is a DILI phenotype difficult to distinguish from idiopathic AIH despite a wide armamentarium of diagnostic methods. Regular patient monitoring and clinical open-mindedness with the adjustment of therapeutic approaches according to the disease course are more important than strict labelling of the disease.

Acute kidney injury (AKI) is a clinical syndrome where a rapid decrease in kidney function and/or urine output is observed, which may result in the imbalance of water, electrolyte and acid base, and is associated with poor prognosis and prolonged hospitalization. Therefore, early diagnosis and treatment to avoid the severe AKI stage is important. While several biomarkers, such as urinary L-FABP and NGAL, can be clinically useful, there is still no gold standard for early detection of AKI and there are limited therapeutic options against AKI. miRNAs are non-coding and single-stranded RNAs that silence their target genes in the post-transcriptional process and are involved in a wide range of biological processes. Recent accumulated evidence has revealed that miRNAs may be potential biomarkers and therapeutic targets for AKI. In this review article, we summarize the current knowledge about miRNAs as promising biomarkers and potential therapeutic targets for AKI, as well as the challenges in their clinical use.

Background and Objectives: The current study aimed to determine the impact of fasciotomy on mortality and morbidity in children and adults with crush-related AKI following the 2023 Kahramanmaraş earthquakes. Materials and Methods: The study included individuals who had suffered crush injuries after the 2023 Kahramanmaraş earthquakes and were identified as having acute kidney injury (AKI). Patients with AKI were divided into two groups based on age: those under 18 years and those over 18 years. A comparative analysis was conducted between the mortality and morbidity rates of patients who underwent fasciotomy and those who did not. Disseminated intravascular coagulopathy (DIC), sepsis, and adult respiratory distress syndrome (ARDS) have all been identified as contributors to morbidity. Results: The study was conducted with a total of 40 patients (21 males and 19 females) aged between four and 83 years. A total of 21 patients underwent fasciotomy and the patients underwent varying numbers of fasciotomy, ranging from zero to 11. The mortality rate was 12.5%, corresponding to five adult patients. No instances of mortality were reported in the paediatric cohort. The application of fasciotomy in instances of crush-induced AKI did not result in elevated levels of mortality in either the paediatric or adult demographic. Within the adult population, a substantial difference in the duration of dialysis was observed between individuals who underwent fasciotomy and those who did not. A statistically significant increase in the number of fasciotomy incisions was observed in patients diagnosed with sepsis compared with those without sepsis. The study found a significant positive correlation between the number of fasciotomy incisions and dialysis days. Conclusions: Neither adult nor paediatric patients with crush-induced AKI showed an increased risk of death after fasciotomy. The number of fasciotomy incisions significantly correlated with the development of sepsis. Despite experiencing delays in hospital admission for paediatric patients, the incidence of both crush syndrome and mortality rates among children remained relatively low.

Acute promyelocytic leukemia (APL) currently represents one of the malignant hemopathies with the best therapeutic responses following the introduction of all-trans retinoic acid (ATRA) and later of arsenic trioxide (ATO) treatment. As a result, patients with APL achieve long-term responses in a large proportion after first-line therapy, so that performing hematopoietic stem cell transplant as consolidation of first complete remission is no longer necessary. Even in the case of relapses, most patients obtain a new remission thanks to the therapy with ATO and ATRA, but to maintain it, a consolidation treatment as effective as possible is necessary. The experience accumulated from studies published in the last two decades shows the effectiveness of hematopoietic stem cell transplantation (HSCT) in improving the evolution of patients who achieve a new complete re-mission. Thus, the recommendations of expert groups indicate transplantation as consolidation therapy in patients with a second complete remission with the mention of the use of autologous HSCT in cases with complete molecular remission and allogeneic HSCT for patients with the persistence of minimal residual disease or early relapse. However, there is a variety of contro-versial aspects related to the role of HSCT in APL, from obtaining outcome data almost exclusively from retrospective studies and historical analyzes to questions related to the type of transplanta-tion, the impact of minimal residual disease, conditioning regimens, or the role of other thera-peutic options. All these questions justify the performance of controlled prospective studies in the following years.

Laminitis is considered as an important underlying cause of lameness diseases, yet its specific pathogenesis remains unclear. Autophagy is an intracellular degradation mechanism that controls recycling of membrane-associated integrin and may aid in the progression of metabolic diseases. But the significance of autophagy for initiation and development of laminitis is unknown. The present study aimed to explore autophagy activity in the laminar tissue of dairy cows with oligofructose-induced laminitis. Twelve healthy non-pregnant Holstein cows were randomly divided to 2 groups of 6 cows each, entitled the control group and the oligofructose overload group (OF group), respectively. At 0 h, cows in OF group were gavaged with oligofructose (17 g/kg BW) dissolved in warm deionized water (20 mL/kg BW) through oral rumen tube, and dairy cows in control group were gavaged with the same volume of deionized water by the same method. At -72 h before perfusion as well as 0 h, 6 h, 12 h, 18 h, 24 h, 36 h, 48 h, 60 h, and 72 h after perfusion, clinical evaluations in both groups were monitored. After 72 h, laminar tissues of dairy cows in both groups were collected to examine genes and proteins. We found the significantly higher (P<0.05) levels of mRNA ATG5, ATG12, and Becilin1, but P62 and mTOR were extensively lower (P<0.01) in the laminar tissue of the OF group than the control group. Protein expression level of Becilin-1 was higher significantly (P<0.05), and the protein expression level of LC3II was lower significantly (P<0.05) in OF group than control group. However, the expression of P62 reduced (P>0.05) non-significantly in OF group than control group. The distribution of Beclin1 protein in laminar tissue increased (P<0.01) significantly, and distribution of P62 protein decreased (P<0.05) significantly in OF group than control group. In conclusion, laminar tissue damage occurred during the onset of laminitis, which promoted the occurrence of autophagy, and confirmed that autophagy was involved in the regulation and pathogenesis of laminitis in dairy cows.

Alginate extraction is from seaweed, and lignin separation is from by-product corn (stalks and leaves). Alginate/lignin is a synthetic polymer rich in biological activity of great interest. Antioxidant activities of alginate/lignin were evaluated, such as total antioxidant activity, reducing power activity, DPPH free radical scavenging activity, and α – glucosidase inhibition activity. The test of anticancer activity was on four cell lines (Hep G2, fibroblast, MCF-7, and NCI H460). Determination of physical-chemistry characteristics of alginate/lignin was through FTIR, DSC, SEM_EDS, SEM_EDS mapping, XRD, XRF, and 1H-NMR. A study of acute toxicity of alginate/lignin was on Swiss albino mice. The results showed alginate/lignin possessed antioxidant activity such as total antioxidant activity, reducing power activity, especially, α – glucosidase inhibition activity, and no free radical scavenging activity. Alginate/lignin did not be typical in cancer cell lines. Alginate/lignin existed in a thermally stable regular spherical shape in the investigated thermal region. Some specific functional groups of alginate and lignin did not exist in alginate/lignin crystal. Elements such as C, O, Na, and S were popular in the alginate/lignin structure. LD0 and LD100 of alginate/lignin in mice were 3.91 g/kg and 9.77 g/kg, respectively. Alginate/lignin is the potential for application as pharmaceutical materials, functional foods, and supporting diabetes treatment.

Epstein-Barr virus (EBV) is a widely disseminated herpesvirus for which antibodies have been demonstrated in over 90% of adults worldwide. After subclinical primary EBV infections, as well as after infectious mononucleosis, the virus can be shed in saliva for a prolonged period of time. Diseases and disorders that can induce EBV salivary shedding include mental disorders and sex, connective tissue disease, multiple sclerosis, systemic lupus erythematosus, malaria and HIV infection. As the occurrence of EBV in saliva during acute infectious diseases has not been systematically researched so far, this pilot cross-sectional study aimed to investigate the possible relationship between acute infectious diseases and salivary shedding of EBV. A total of 40 patients with acute infectious diseases was enrolled, along with 41 adults free of acute infections. Peripheral venous blood samples for serodiagnosis and saliva samples for EBV PCR testing were collected from both groups. The most common acute infectious disease was COVID-19 pneumonia, followed by haemorrhagic fever with renal syndrome. Crude proportions of people with positive serological test results and those with saliva viral shedding were similar in the two groups. The presented preliminary data does not indicate acute infectious conditions as a marked “contributor” in increasing salivary EBV shedding.

Abstract: The purpose of this review is to summarize recent knowledge on the main processes that occur during wound healing, including the responses of various cell types and the molecular mechanisms involved. Particular attention is also dedicated to new therapies often involved in the resolution of wounds, whether acute or chronic. Awareness of these dynamics is important for the various professional figures who are confronted with these kinds of problem daily. However, the study of the healing mechanisms has yet to be defined in detail, in fact there are alterations of variously coordinated events which lead to a delayed resolution or, as in the case of keloids, to pathological states consisting in the excessive formation of scars with consequences yet to be seen. to define. Therefore, it is necessary to know the most feasible approaches and the most effective therapies.

Though there has been a decline in the number of new cases of viral hepatitis-induced acute liver failure in Europe and the United States of America, viral hepatitis still remains the leading cause of acute liver failure in Asia-Pacific and South America. However, the epidemiology of viral-hepatitis-induced acute liver failure in sub-Saharan Africa-the world epicenter of viral hepatitis-is unclear. The aim of this review was to collate data on the incidence, prevalence, specific etiologic agents, features/diagnosis, treatment and prognosis of viral-induced acute liver failure in sub-Saharan Africa. One hundred and forty-seven cases of viral-induced acute liver failure were recorded in 11 studies conducted in six countries between 1981-2020. Etiological agents were: Hepatitis viruses A, B, C, and E, as well as Adenovirus, Enterovirus, Parvovirus, Herpes Simplex Virus (HSV) and EBV. HAV was the most frequent in paediatric subjects: (11/16) 69% and (19/30) 63%. HBV was the only etiological agent in the study that only included adults. HEV (genotype 2 in one study) contracted amidst hepatitis E outbreaks was the most commonly reported cause of ALF in pregnant women. Treatment was mainly supportive, and liver transplantation reported only in South Africa. Where reported, case fatality rates were high. In conclusion, viral-hepatitis induced acute liver failure is largely understudied in sub-Saharan Africa. The few available data are consistent with literature from the other parts of the world regarding aetiologic agents. Liver transplantation is not available in most sub-Saharan African countries, and short-term case fatality rates of individuals with acute liver failure could outstrip current rates from the other world regions.

Acute lymphoblastic leukemia is the most common malignancy in children and is characterized by numerous genetic and epigenetic abnormalities. Epigenetic mechanisms, which involve DNA methylations and histone modifications, result in the heritable silencing of genes without a change in their coding sequence. Emerging studies are increasing our understanding of the epigenetic role of leukemogenesis and have demonstrated the potential of DNA methylations and histone modifications as a biomarker for lineage and subtypes classification, predicting relapse, and disease progression in ALL. Epigenetic abnormalities are relatively reversible when treated with some small molecule-based agents compared to genetic alterations. In this review, we conclude the genetic and epigenetic characteristics in ALL and discuss the future role of DNA methylation and histone modifications in predicting relapse, finally focus on the individual and precision therapy targeting epigenetic alterations.

Background: Acute ischemic stroke is among the main causes of mortality worldwide; a rapid and opportune diagnosis is crucial to improve a patient's outcome. MicroRNAs are quite useful for a rapid and accurate diagnosis.Methods: We perform both structural networks approach and a meta-analysis (using a random-effect model to evaluate the heterogeneity and risk bias, according to the PRISMA statement) to analyze the feasibility to develop a microRNA-based biomarker panel for an opportune AIS diagnosis. Results: Structural networks identify a set of eight miRNAs (miR-16, miR-124-3p, miR-484, miR-15a, miR-4454, miR-107, miR-125b-5p and miR-320b) as preliminary microRNA-based biomarker panel, from these only three microRNAs are significantly associated with the main risk factors of AIS, (miR-107: hypertension, 95% CI 9.74-53.24 p<0.0001, type 2 Diabetes mellitus, 95% CI 2.18-19.26); p=0.0008; miR-16 hypertension, 95% CI 1.26-3.56 p=0.0046, smoking, 95% CI 1.07-3.54 p=0.0277; and miR-15a hypertension, 95% CI 1.26-3.56 p=0.0046; smoking, 95% CI 1.07-3.54 p=0.0277). However, the meta-analysis reveals that data is highly heterogeneous and biased; and only microRNAs isolated from plasma samples and further processed in microarrays are the most reliable to distinguish AIS patients.Conclusions: Together our results show that although there are some miRNAs that seem to be associated with AIS, we are still far to develop a miRNA-based biomarker for AIS diagnosis and it is necessary to harmonize the protocols, results and include more populations for further studies otherwise we will remain throwing punches in the dark.

The MLL gene is a site of frequent rearrangement in acute leukemia with multiple fusion partners, but MLL-SEPT6 rearrangement is rare in clinical leukemia practice, and only 13 cases have been reported. We describe the case of an acute myelogenous leukemia child with MLL-SEPT6 rearrangement whose age of onset and accompanying gene mutations differs from previous reports. Considering the poor prognosis of leukemia children with MLL-SEPT6 rearrangement and the unsatisfactory results of existing treatments, the study of this case may provide new theories for diagnosis and treatment of MLL-SEPT6-associated childhood acute leukemia.

Physical activity is considered a promising preventive intervention to reduce the risk of developing Alzheimer’s disease (AD). However, the positive effect of exercise therapy has not been proven conclusively yet, likely due to confounding factors such as varying activity regimens and life or disease stages. To examine the impact of different routines of physical exercise in the early disease stages, we subjected young 5xFAD and wild-type mice to 1-day (acute) and 30-day (chronic) voluntary wheel running and compared them with age-matched sedentary controls. We observed a significant increase in brain lactate levels in acutely trained 5xFAD mice relative to all other experimental groups. Subsequent brain RNA-seq analysis did not reveal major differences in transcriptomic regulation between training durations in 5xFAD mice. In contrast, acute training yielded substantial gene expression changes in wild-type animals relative to their chronically trained and sedentary counterparts. The comparison of 5xFAD and wild-type mice showed the highest transcriptional differences in the chronic and sedentary groups, whereas acute training was associated with much fewer differentially expressed genes. In conclusion, our results suggest that different training durations did not affect the global transcriptome of 3-month-old 5xFAD mice, whereas acute running seemed to induce a similar transcriptional stress state in wild-type animals as already known for 5xFAD mice.

Background: Treatment at stabilization center is an important intervention to avert the huge burden of mortality for children with complicated severe acute malnutrition (SAM). Recent reviews indicated a wide range in recovery rate (34-88%) due to several context-specific factors. This study aimed to estimate time to recovery and to determine predictors of time to recovery among children aged 6-59 month with severe acute malnutrition. Method: Retrospective cohort study was used among 375 children aged 6-59 months admitted in Jimma university medical center, from September 2015 to September 2017. Kaplan Meir estimate and survival curve was used to compare the time to recovery using log-rank test among different characteristics. Cox Proportional Hazard Model was used to identify significant predictors of time to recovery. Results: Median time of recovery for cohort of SAM children’s was 19 days (95%CI: 17.95-20.05). Independent predictors of time to recovery were: Play stimulation, vaccination status, Tuberculosis, malaria, use of amoxicillin, deworming and shock. Conclusion: The findings of this study showed that the average length of stay on treatment and median time for recovery are within the sphere standard. Psychosocial stimulation, appropriate provision of routine medication and management of medical co-morbidity are needed to promote fast recovery.

Novel coronavirus infection is a recent infective agent that causes severe potentially fatal pneumonia. The clinical presentation includes asymptomatic infection, severe pneumonia, and acute respiratory failure. Data pertaining to the clinical presentation of solid organ transplant recipients are scarce. Two cases of novel coronavirus infection in two recipients of renal transplant with variable clinical presentations and outcomes are reported. The first patient presented with progressive respiratory symptoms, acute renal failure, and passed away, whereas the second one, although presented with respiratory tract symptoms and hypoxemia remained stable and exhibited an excellent clinical recovery despite recent reception of thymoglobulin induction. This paper reports rare cases of novel coronavirus infection in renal transplant recipients. For an enhanced insight of the novel coronavirus infection and acute kidney injury on the clinical presentation, severity, and outcome in solid organ transplant recipients, further investigations are required.