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Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by significant metabolic disruptions, including weight loss and hypermetabolism in both patients and animal models. Leptin, an adipose-derived hormone, displays altered levels in ALS. Genetically reducing leptin levels (Lepob/+) to maintain body weight improved motor performance and extended survival in female SOD1G93A mice, although the exact molecular mechanisms behind these effects remain elusive. Here, we corroborated the sexual dimorphism in circulating leptin levels in ALS patients and in SOD1G93A mice. We reproduced a previous strategy to generate a genetically deficient leptin SOD1G93A mice (SOD1G93ALepob/+) and studied the transcriptomic profile in the subcutaneous adipose tissue and the spinal cord. We found that leptin deficiency reduced the inflammation pathways activated by the SOD1G93A mutation in the adipose tissue, but not in the spinal cord. These findings emphasize the importance of considering sex-specific approaches in metabolic therapies and highlight the role of leptin in the systemic modulation of ALS by regulating immune responses outside the central nervous system.

Hard and semi-hard cheeses are popular dairy products in Egypt, but they may convey a health risk for consumers due to their poor hygienic quality and safety. One of the common problems that consumers face when buying these cheeses from the Egyptian market is the bad odour that shortly develops after purchase even though they are refrigerated. This problem may indicate a high bacterial count in the cheese or the presence of undesirable microorganisms. Therefore, the current study aimed to assess the hygienic quality and safety of some retailed cheese sold in Egyptian markets. One hundred hard and semi-hard cheese samples locally manufactured (including 34 Ras, 33 Cheddar, and 33 Gouda) were analyzed for their microbiological and chemical quality. The results indicated that the Ras cheese samples had the highest bacterial counts, salt, and fat content, while the Cheddar cheese samples had the highest acidity, moisture content and the lowest microbial load. The Gouda cheese samples had the lowest fat/total solids ratio and a variable bacterial count. Forty-five Staphylococcus aureus strains were isolated from the cheese samples; 25 of them were coagulase-positive. The antibiotic susceptibility of twenty isolates was phenotypically and genotypically evaluated. All isolates were resistant to Cefixime, Oxacillin, and Metronidazole, while sensitive to Amoxicillin/Clavulanic Acid and Linezolid. The resistance to other antibiotics varied among the isolates. The antibiotic resistance genes were detected by polymerase chain reaction (PCR). The obtained results indicate that the hard and semi-hard cheeses sold in many markets were poor in hygienic quality and safety and posed a health risk for consumers due to the presence of multidrug-resistant Staphylococcus species. Ras cheese was the worst cheese type in most quality and safety parameters.

TDP-43 pathology is found in several neurodegenerative disorders, collectively referred to as “TDP-43 proteinopathies”. Aggregates of TDP-43 are present in the brains and spinal cords of >97% of amyotrophic lateral sclerosis (ALS), and in brains of ∼50% of frontotemporal dementia (FTD) patients. While mutations in the TDP-43 gene (TARDBP) are usually associated with ALS, many clinical reports have linked these mutations to cognitive impairments and/or FTD, but also to other neurodegenerative disorders including Parkinsonism (PD) or progressive supranuclear palsy (PSP). TDP-43 is a ubiquitously expressed, highly conserved RNA-binding protein that is involved in many cellular processes, mainly RNA metabolism. To investigate systemic pathological mechanisms in TDP-43 proteinopathies, aiming to capture the pleiotropic effects of TDP-43 mutations, we have further characterised a mouse model carrying a point mutation (M323K) within the endogenous Tardbp gene. Homozygous mutant mice developed cognitive and behavioural deficits as early as 3 months of age. This was coupled with significant brain structural abnormalities, mainly in the cortex, hippocampus, and white matter fibres, together with progressive cortical interneuron degeneration and neuroinflammation. At the motor level, progressive phenotypes appeared around 6 months of age. Thus, cognitive phenotypes appeared to be of a developmental origin with a mild associated progressive neurodegeneration, while the motor and neuromuscular phenotypes seemed neurodegenerative, underlined by a progressive loss of upper and lower motor neurons as well as distal denervation. This is accompanied by progressive elevated TDP-43 protein and mRNA levels in cortex and spinal cord of homozygous mutant mice from 3 months of age, together with increased cytoplasmic TDP-43 mislocalisation in cortex, hippocampus, hypothalamus, and spinal cord at 12 months of age. In conclusion, we find that Tardbp M323K homozygous mutant mice model many aspects of human TDP-43 proteinopathies, evidencing a dual role for TDP-43 in brain morphogenesis as well as in the maintenance of the motor system, making them an ideal in vivo model system to study the complex biology of TDP-43.

BackgroundSmoking is a common problem in university students worldwide. Smoking is one of the most dangerous social phenomena and has a significant impact on public health. This study investigated the beliefs and attitudes of medical students toward smoking in Sudan.MethodsA cross-sectional study was conducted among medical students at Al Neelain University, Sudan, from March to June 2022 using a web-based questionnaire. The questionnaire consisted of eight items on demographic characteristics and 13 on the beliefs and attitudes toward smoking. Other data included smoking status, smoking habits, the number of cigarettes smoked per day, and smoking duration. Data analysis was performed descriptively, and chi-square test and logistic regression were conducted using SPSS version 24. Statistical significance was set at 0.05.ResultsA total of 336 students participated in this study, and the smoking prevalence was 48.8% (41.1% in men and 7.7% in women). In total, 76.8% reported smoking daily at a rate of 5–10 cigarettes per day. In terms of students’ beliefs about smoking, 86.8% disagreed with selling cigarettes at the university. Of the respondents, 68.4% did not approve smoking on campus. There was a relationship between smoking habits and the age group of 22–25 years, which was the highest smoking category among students (p-value = 0.01).ConclusionThe prevalence of cigarette smoking among medical students is disturbing, particularly as they are future doctors. There is a need to include plans to reduce smoking among students that can be incorporated into courses and special programs.

Abstract Background Composition of gut microbiota has recently been suggested as a key factor persuading the pathogenesis of numerous human diseases including hepatic cirrhosis. Objective To evaluate the potential impact of Lactobacillus acidophilus and Bifidobacterium bifidum microbiota on the progression of hepatic histopathological changes among patients with non-cirrhotic chronic hepatitis C (HCV) infection with different viral load. Additionally, to assess fecal composition of Lactobacillus acidophilus ATCC-4356 and Bifidobacterium bifidum ATCC-11863 microbiota genotypes Material and methods This study was carried out on 40 non-cirrhotic chronically infected HCV patients, and 10 healthy-controls. Liver biopsy and HCV genomic viral load were assessed for all patients after full clinical examination. Lactobacillus acidophilus ATCC-4356 and Bifidobacterium bifidum ATCC-11863 microbiota were assessed in all fecal samples using PCR assay, after counting total lactic acid bacteria. Results There was a significantly higher difference between the count of both total lactic acid and Lactobacillus acidophilus of healthy controls compared to patients (P-value 1, there were no statistically significant differences with both the serum level of hepatitis C viremia (P = 0.850 and 0.977 respectively) and the score of fibrosis (P = 0.246 and 0.260 respectively). Genotypic analysis for the composition of the studied microbiota revealed that diversity was higher in healthy controls compared to patients. Conclusions The progression of hepatic fibrosis in HCV chronically infected patients seems to be plausible based on finding the altered Lactobacillus acidophilus and Bifidobacterium bifidum gut microbiota composition. Thus, modulation of these microbiota seems to be a promising target for prevention and control of HCV infection.

Summary: Amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) is a fatal neurodegenerative disorder, and continued innovation is needed for improved understanding and for developing therapeutics. We have created next-generation genomically humanized knockin mouse models, by replacing the mouse genomic region of Sod1, Tardbp (TDP-43), and Fus, with their human orthologs, preserving human protein biochemistry and splicing with exons and introns intact. We establish a new standard of large knockin allele quality control, demonstrating the utility of indirect capture for enrichment of a genomic region of interest followed by Oxford Nanopore sequencing. Extensive analysis shows that homozygous humanized animals only express human protein at endogenous levels. Characterization of humanized FUS animals showed that they are phenotypically normal throughout their lifespan. These humanized strains are vital for preclinical assessment of interventions and serve as templates for the addition of coding or non-coding human ALS/FTD mutations to dissect disease pathomechanisms, in a physiological context.

Since the start of COVID-19 pandemic the Republic of Djibouti, in the horn of Africa, has experienced two epidemic waves of the virus between April and August 2020 and between February and May 2021. By May 2021, COVID-19 had affected 1.18% of the Djiboutian population and caused 152 deaths. Djibouti hosts several foreign military bases which makes it a potential hot-spot for the introduction of different SARS-CoV-2 strains. We genotyped fifty three viruses that have spread during the two epidemic waves. Next, using spike sequencing of twenty-eight strains and whole genome sequencing of thirteen strains, we found that Nexstrain clades 20A and 20B with a typically European D614G substitution in the spike and a frequent P2633L substitution in nsp16 were the dominant viruses during the first epidemic wave, while the clade 20H South African variants spread during the second wave characterized by an increase in the number of severe forms of COVID-19.

The study was carried out at Faculty of Agriculture, Ain Shams University to assess the effect of two of algae species (Arthrospira platensis and Nannochloropsis gaditana) on growth performance of monosex tilapia fish (Oreochromis niloticus), fish were fed on a basal diet supplemented with 0,3,5,7% of each algae. To perform seven experimental treatments were assigned in three replicates each. The experiment was designated as follows: (T1) control (without algae), (T2) basal diet supplemented with 3% spirulina (spiru 3), (T3) basal diet supplemented with 5% spirulina (spiru 5), (T4) basal diet supplemented with 7% spirulina (spiru 7), (T5) basal diet supplemented with 3% Nannochloropsis (nanno 3), (T6) basal diet supplemented with 5% Nannochloropsis (nanno 5) and (T7) basal diet supplemented with 7% Nannochloropsis (nanno 7). Experimental tanks were a part of closed recirculating system, where almost constant environmental conditions were kept throughout the experimental period. Twenty-one quadrate fiber glass tanks with 108-liter water capacity were stocked with 15 fish per tank. The individual initial body weight (2.7 g) was recorded at the beginning of the experiment. All fish in each tank was weighed every two weeks during the whole experimental period. The fish were fed the experimental diet for 95 days Results indicated that nanno 5 treatment had higher significant trend (P

There is an increasing interest in the study of the relation between alterations in systemic lipid metabolism and neurodegenerative disorders, in particular in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). In ALS these alterations are well described and evident not only with the progression of the disease but also years before diagnosis. Still, there are some discrepancies in findings relating to the causal nature of lipid metabolic alterations, partly due to the great clinical heterogeneity in ALS. ALS presentation is within a disorder spectrum with Frontotemporal Dementia (FTD), and many patients present mixed forms of ALS and FTD, thus increasing the variability. Lipid metabolic and other systemic metabolic alterations have not been well studied in FTD, or in ALS–FTD mixed forms, as has been in pure ALS. With the recent development in lipidomics and the integration with other -omics platforms, there is now emerging data that not only facilitates the identification of biomarkers but also enables understanding of the underlying pathological mechanisms. Here, we reviewed the recent literature to compile lipid metabolic alterations in ALS, FTD, and intermediate mixed forms, with a view to appraising key commonalities or differences within the spectrum.

Abstract Background In the demanding environment of the neonatal intensive care unit (NICU), quality nursing care hinges on effective teamwork and communication among nurses. However, this requirement for close cooperation can expose nurses to significant levels of moral distress. This study aims to explore the connection between the quality of teamwork and the experience of moral distress among NICU nurses. Methods Employing a cross-sectional, multicenter descriptive correlational design, this study surveyed female NICU nurses across the cities of Khorramabad and Semnan. Census sampling was utilized over five months, from July to November 2023, resulting in the participation of 190 nurses. Tools for data collection included demographic questionnaires, the Team-STEPPS Teamwork Perception Questionnaire (T-TPQ), and the Moral Distress Scale-Revised (MDS-R) for nurses. Results The findings revealed an average teamwork score of 3.73 ± 0.78, denoting an acceptable level, and an average moral distress score of 91.2 ± 56.7, indicating a low level. In multiple linear regression, marital status showed a direct positive correlation (β = 38.5, SE (β) = 9.3, p

Abstract In recent decades, emerging data have highlighted the critical role of extracellular vesicles (EVs), especially (exosomes) Exos, in the progression and development of several cancer types. These nano-sized vesicles are released by different cell lineages within the cancer niche and maintain a suitable platform for the interchange of various signaling molecules in a paracrine manner. Based on several studies, Exos can transfer oncogenic factors to other cells, and alter the activity of immune cells, and tumor microenvironment, leading to the expansion of tumor cells and metastasis to the remote sites. It has been indicated that the cell-to-cell crosstalk is so complicated and a wide array of factors are involved in this process. How and by which mechanisms Exos can regulate the behavior of tumor cells and non-cancer cells is at the center of debate. Here, we scrutinize the molecular mechanisms involved in the oncogenic behavior of Exos released by different cell lineages of tumor parenchyma. Besides, tumoricidal properties of Exos from various stem cell (SC) types are discussed in detail.

Background: Active transportation (AT) and free play (FP) are the primary ways in which children engage in unstructured physical activity in cities, with independent mobility (IM) gaining increased attention as a potential precursor of AT and FP. However, current trends show that children are engaging in less FP and AT, and have less IM, than previous generations and it is not well understood how these practices, and their interrelatedness, differ by neighbourhood-level socio-economic stats (SES) and municipal contexts Objectives: This study aims to address the gaps in knowledge by quantifying, comparing, and correlating IM, AT, and FP practices in high and low-SES neighbourhoods within and across the cities of Montreal and Kingston, Canada Methods: 584 questionnaires were distributed among children in grades 1 to 5, living in low- and high-SES neighbourhoods of these two citiesResultsEngagement in the three practices was low in every study neighbourhood, though all three practices were higher in high-SES compared to low-SES neighbourhoods in both cities. Levels of FP were higher in Kingston compared to Montreal, while AT was higher in Montreal than in Kingston Conclusion: This study revealed social inequalities in all three of these practices based on socioeconomic status and city. Since IM is likely a precursor to both independent FP and AT, more research is warranted into how our cities can become more conducive to IM in children, particularly in low SES neighbourhoods where children have less freedom of movement independently and otherwise.

Spinal cord injury (SCI) is a debilitating condition that results in impaired sensory and motor function due to the limited self-regenerative ability of the spinal cord. To address this issue, combination therapy has been proposed as an effective treatment strategy for SCI regeneration. In this study, Platelet-Rich Plasma (PRP)-derived exosomes loaded with dexamethasone were utilized in a mouse model of SCI compression. PRP-derived exosomes loaded with dexamethasone (Dex) were prepared using ultracentrifugation and sonication methods and were administered to the mice via intravenous injection. Following a four-week duration, behavioral assessments were administered to assess functional recuperation, and diverse metrics encompassing the expression of genes associated with apoptosis and antiapoptosis, serum cytokine concentrations and tissue sampling were subjected to thorough examination. The results of this study demonstrated that mice treated with PRP-derived exosomes loaded with Dex (ExoDex) exhibited altered levels of TNF-α and IL-10, along with decreased Bax and increased Bcl2 expression in comparison to the model group. Furthermore, intravenously injected ExoDex reduced the size of the lesion site, lymphocyte infiltration, vacuolation, cavity size and tissue disorganization while also improving locomotor recovery. We propose that the utilization of exosome-loaded Dex therapy holds potential as a promising and clinically relevant approach for injured spinal cord repair. However, further extensive research is warranted in this domain to validate and substantiate the outcomes presented in this study.

Abstract In the present work, Silver nanoparticles (AgNPs) were fabricated through the dandelion flower hydroalcoholic extract, and their properties were characterized by FTIR, XRD, UV visible, SEM, and EDX. The results demonstrated that the average diameter of the green fabricated AgNPs is 45–55 nm (G-AgNPs). The antioxidant, antimicrobial, antidiabetic, and photocatalytic properties of G-AgNPs were compared with two commercially available different diameter sizes (20 and 80–100 nm) of AgNPs (C-AgNPs1- and C-AgNPs2, respectively). The sample's capacity for antioxidants was evaluated by DPPH free radical scavenging method. The consequences showed that G-AgNPs have higher radical scavenging activity (47.8%) than C-AgNPs2 (39.49%) and C-AgNPs1 (33.91%). To investigate the photocatalytic property, methylene blue dye was used. The results displayed that G-AgNPs is an effective photo-catalyst compared to C-AgNPs2 and C-AgNPs1, which respectively have an inhibition potential of 75.22, 51.94, and 56.65%. Also, the antimicrobial capacity of nanoparticles was assayed against, the gram-negative Escherichia coli and gram-positive Staphylococcus aureus bacteria. The results indicated that G-AgNPs could effectively inhibit the growth of both bacteria, compared to C-AgNPs1 and C-AgNPs2. Finally, G-AgNPs exhibited a considerable α-glucosidase enzyme inhibitory effect (88.37%) in comparison with C-AgNPs1 (61.7%) and C-AgNPs2 (50.5%).

Summary: Heterojunction nanostructure construction and morphology engineering are considered to be effective approaches to improve photocatalytic performance. Herein, ternary hierarchical hollow structures consisting of cobalt-aluminum-layered double hydroxide (CoAl-LDH) nanoplates grown on hollow carbon nitride spheres (HCNS) and decorated with N-doped carbon quantum dots (NCQDs) were prepared using a templating method and a subsequent solvothermal process. The obtained HCNS@LDH/NCQD composites presented an improved performance in photocatalytic degradation of tetracycline and inactivation of E. coli compared with pure HCNS and LDH under visible light illumination. The enhanced photocatalytic activity of the designed photocatalyst could be attributed to the following reasons: (1) A special hollow structure provides more active sites and has multiple capabilities of light reflection by helping with a high specific surface area that improves the harvesting efficiency of solar light and (2) the strong synergistic effect among the constituents, which promotes separation and transfer of charge carriers and broadens the photo-response range.

BackgroundThe substantial increasing trend of binge drinking is a global alarm. Our aim was to undertake a systematic review and meta-analysis of cross-sectional studies to explore the association of current smoking with binge drinking among adults.MethodsWe systematically searched Web of Knowledge; PubMed; Scopus; Embase and Ovid (MEDLINE, EMBASE, PsycARTICLES, PsycINFO, PsycEXTRA, and PsycTests) (from inception to 27 May 2020) databases to identify cross-sectional studies of the association between current smoking and binge drinking. Study screening, data extraction, and methodological quality assessment were all carried out by two independent authors. Adjusted odds ratio (AOR) was pooled with 95% confidence intervals (CI) using random effects model in the meta-analysis, followed by the investigation of the heterogeneity via Q-test and I2 statistic. We assessed publication bias using a funnel plot, the Egger’s, and Begg’s tests.ResultsWe identified 3,171 studies and included nine cross-sectional studies with 64,516 participants. A significant association was found between current smoking and binge drinking among both genders (AOR = 2.97; 95% CI = 1.98 to 4.45; I2 = 90.5%). Subgroup analysis showed that this association among women, men, Caucasians, and Asians/Africans were (AOR = 3.68; 95% CI = 1.03 to 13.18; I2 = 98.9%), (AOR = 2.53; 95% CI = 1.87 to 3.42; I2 = 73.1%), (AOR = 1.36; 95% CI: 1.01–1.83, I2 = 47.4%), and (AOR = 3.93; 95% CI: 2.99–5.17, I2 = 61.3%), respectively. There was no evidence of publication bias.ConclusionCurrent smoking is associated with binge drinking and can be used for identifying and screening binge drinkers. Moreover, this association is stronger among men, and Asians/Africans. This meta-analysis estimation was limited to English-language studies, and the full text of about 3.5% of reports for retrieval was not found, then generalization of the results should be done with caution.

Background and Objective: Heavy metal (HM) pollution of settled dust on the interior surfaces of elementary schools may affect the health of young students; hence, the health risk of such pollution should be assessed. Therefore, the aims of this study were to measure the content of heavy metals in the settled dust in the indoor of elementary schools in Bandar Abbas and to assess the attributed health risks. Materials and Methods: In this study, dust samples were collected from the interior surfaces of elementary schools in Bandar Abbas. Settled dust samples were digested using aqua regia solution and then their metals contents were measured using ICP-OES. To assess the health risk attributed to this pollution, daily intake doses through ingestion, inhalation and skin absorption routes were estimated. Then, non-carcinogenic and carcinogenic risks were calculated considering the daily intake doses and toxicity factors. Results: The average concentrations of arsenic, cadmium, cobalt, chromium, nickel and lead in settled dust were 5.45, 0.58, 11.44, 69.72, 83.95 and 66.72 mg/kg, respectively. The non-carcinogenic risk level for all metals was below threshold, while the carcinogenic risk level for arsenic (2.18×10-6) exceeded the threshold. Conclusion: This study showed that the settled dust in elementary schools of Bandar Abbas is polluted with various levels of heavy metals. Health risk assessment showed that the exposure to dust containing heavy metals in the elementary schools of Bandar Abbas does not pose significant non-carcinogenic risk, but the carcinogenic risk of As exceeded the threshold limit and should be considered.