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A key element of women's empowerment is the ability to participate in household decision-making. This study presents the qualitative results from the Shonjibon Cash and Counselling Trial baseline process evaluation with the aim of exploring the status of women's decision-making at the trial's outset and to facilitate the exploration of any changes in women's empowerment over the course of the trial. Between January and March 2021, we conducted forty-one in-depth interviews with pregnant women in rural Bangladesh. The research team translated, transcribed, coded, and discussed the interviews. We used thematic analysis to examine women's experience and perceptions on household decision-making. The key findings that emerged; women jointly participated in financial decision-making with their husbands; men made the final decision regarding seeking healthcare, and women solely made choices regarding infant and young child feeding. Our findings revealed that women felt that they needed to discuss their plans to go outside the house with their husbands, many perceived a lack of importance in the community towards women's participation in decision-making. This study documents current contextual information on the status of women's involvement in household decision-making and intrahousehold power dynamics at the start of the Shonjibon Cash and Counselling Trial.
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In this study, three different univariate municipal solid waste (MSW) disposal rate forecast models (SARIMA, Holt-Winters, Prophet) were examined using different testing periods in four North American cities with different socioeconomic conditions. A review of the literature suggests that the selected models are able to handle seasonality in a time series; however, their ability to handle outliers is not well understood. The Prophet model generally outperformed the Holt-Winters model and the SARIMA model. The MAPE and R2 of the Prophet model during pre-COVID-19 were 4.3-22.2% and 0.71-0.93, respectively. All three models showed satisfactory predictive results, especially during the pre-COVID-19 testing period. COVID-19 lockdowns and the associated regulatory measures appear to have affected MSW disposal behaviors, and all the univariate models failed to fully capture the abrupt changes in waste disposal behaviors. Modeling errors were largely attributed to data noise in seasonality and the unprecedented event of COVID-19 lockdowns. Overall, the modeling errors of the Prophet model were evenly distributed, with minimum modeling biases. The Prophet model also appeared to be versatile and successfully captured MSW disposal rates from 3000 to 39,000 tons/month. The study highlights the potential benefits of the use of univariate models in waste forecast.
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COVID-19 , Ciudades , Eliminación de Residuos , COVID-19/epidemiología , América del Norte , Residuos Sólidos , Humanos , Modelos Teóricos , SARS-CoV-2RESUMEN
Electronic waste recycling companies have proliferated in many countries due to valuable materials present in end-of-life electronic and electrical equipment. This article examined the business characteristics and management performance of Electronic Products Recycling Association (EPRA), a Canadian nationwide electronic product stewardship organization. The organization's annual performance reports, from 2012 to 2020, for nine Canadian provinces in which it currently operates were aggregated and analyzed. Temporal analysis using regression and Mann-Kendall tests were employed, and five characteristics of EPRA's business were analyzed, including e-waste products collected, number of drop-off locations, efforts to build public awareness, operating expenses, and growth of e-waste stewardship. Results show a decline in the amount of e-waste collected across the provinces, except in New Brunswick, which started its program in 2017. The Mann-Kendall test revealed declining temporal trends in most provinces. Although the collection/drop off sites and stewardship organizations increased astronomically over the study period in Canada, the amounts of e-waste collected decreased. We found that public awareness generally did not increase the amount of e-waste collected, and these campaigns only appeared to be effective in jurisdictions with good accessibility of e-waste recycling. Processing cost accounted for the majority of the e-waste management budget in Canada, and different factors affected the financial success of the stewards differently.
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Residuos Electrónicos , Reciclaje , Administración de Residuos , Reciclaje/métodos , Canadá , Administración de Residuos/métodosRESUMEN
The NS2B/NS3 protease is highly conserved among various proteases of the Zika virus, making it an important therapeutic target for developing broad-spectrum antiviral drugs. The NS2B/NS3 protease is a crucial enzyme in the replication cycle of Zika virus and plays a significant role in viral maturation and assembly. Inhibiting the activity of this protease can potentially prevent viral replication, making it an attractive target for developing therapies against Zika virus infection. This work screens 429 antiviral peptides in comparison with substrate peptide against the NS2B/NS3 of Zika virus using molecular docking and molecular dynamics (MD) simulation. Based on the docking screening, MD simulation conducted for the best four peptides including AVP0239, AVP0642, AVP0660, and AVP2044, could be effective against NS2B/NS3. These results were compared with the control substrate peptide. Further analysis indicates that AVP0642 and AVP2044 are the most promising candidates. The interaction analysis showed that the catalytic site residues including His51, Asp75, Ser135 and other non-catalytic residues such as Asp129, Asp83, and Asp79 contribute substantial interactions. Hydrogen bonds (41%) and hydrophobic interactions (33%) are observed as the prominent non-covalent interaction prompting the peptide-protein complex formation. Furthermore, the structure-activity relationship (SAR) illustrates that positively charged (Lys, Arg) residues in the peptides dominate the interactions. This study provides the basis for developing novel peptide-based protease inhibitors for Zika virus.
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ABSTRACT Introduction: Hypogonadism is one of the most frequent complications in transfusion-dependent thalassemia patients and early recognition and treatment is the core element in restoring impaired gonadal function. Despite the high burden of disease, relevant studies are scarcely addressing the gonadal function of such patients in Bangladesh. The pattern of gonadal function in transfusion-dependent thalassemia patients must be characterized before planning a generalized management plan. Moreover, since iron overload is a key reason behind hypogonadism in thalassemia patients, investigating the role of serum ferritin level as a diagnostic tool for hypongadism was also an aim of this study. Methods: This cross-sectional study was conducted at the Department of Transfusion Medicine of the Bangabandhu Sheikh Mujib Medical University. According to the inclusion and exclusion criteria, a total of 94 patients were enrolled in this study. A detailed history and thorough clinical examination were carried out in each patient and recorded using a pretested structured questionnaire. In addition, the laboratory assessment of serum ferritin, luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol in serum were also performed. The data were analyzed using the STATA (v.16). Results: The mean age of the patients with transfusion-dependent thalassemia was 18.81 ± 4.65 (SD), with 53.3% of the patients being male. The overall prevalence of hypogonadism was 35.11%, 18.1% being normogonadotropic, 11.7% being hypogonadotropic and 5.3% being hypergonadotropic. The serum ferritin level was significantly higher (p < 0.001) in patients with hypogonadism (Eugonadal: 2,174.79 (± 749.12) ng/ml; Hypogonadal: 3,572.59 (± 1,199.49) ng/ml). The area under the receiver operating characteristic (ROC) curve of serum ferritin was high (0.83) and the p-value was highly significant (< 0.001). Conclusion: Therefore, the serum ferritin level and gonadal hormone analysis of transfusion-dependent thalassemia patients can be considered a screening tool for assessing gonadal function and early detection and prevention of hypogonadism.
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There is currently a lack of studies on residential waste collection during COVID-19 in North America. SARIMA models were developed to predict residential waste collection rates (RWCR) across four North American jurisdictions before and during the pandemic. Unlike waste disposal rates, RWCR is relatively less sensitive to the changes in COVID-19 regulatory policies and administrative measures, making RWCR more appropriate for cross-jurisdictional comparisons. It is hypothesized that the use of RWCR in forecasting models will help us to better understand the residential waste generation behaviors in North America. Both SARIMA models performed satisfactorily in predicting Regina's RWCR. The SARIMA DCV model's performance is noticeably better during COVID-19, with a 15.7% lower RMSE than that of the benchmark model (SARIMA BCV). The skewness of overprediction ratios was noticeably different between jurisdictions, and modeling errors were generally lower in less populated cities. Conflicting behavioral changes might have altered the residential waste generation characteristics and recycling behaviors differently across the jurisdictions. Overall, SARIMA DCV performed better in the Canadian jurisdiction than in U.S. jurisdictions, likely due to the model's bias on a less variable input dataset. The use of RWCR in forecasting models helps us to better understand the residential waste generation behaviors in North America and better prepare us for a future global pandemic.
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Hemofilia A , Humanos , Hemofilia A/epidemiología , Hemofilia A/terapia , Pakistán , Factor VIIIRESUMEN
Biochar is the thermal degradation product of biomass generated in an oxygen-limited environment under different pyrolysis conditions. Biochar characteristics are functions of the feedstock material and pyrolysis temperature. Depending on pyrolysis conditions biochar concentrates varying quantities of recalcitrant and labile carbon along with nutrients which in turn affect soil physiochemical properties and microbial processes. Biochar in soil balances carbon content encourages nitrogen fixation and solubilize phosphorus along with enhancing soil enzyme activity. It serves as a microhabitat for microorganisms present in soil thus influences the diversity, composition, and distribution of soil microbial communities by affecting their intra- and interspecific communication. This review provides an overview of the current knowledge about biochar characteristics, its interactions with soil, and associated biota and its role in soil remediation. In addition, this paper also discussed the factors affecting the capacity of biochar to adsorb organic pollutants following different mechanisms. Being an effective adsorbent due its high specific surface area, large porosity, and numerous surface functional groups biochar has been explored extensively in field of environment to remediate contaminated soils.
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Lumpy skin disease (LSD) is a viral disease that affects farm animals including water buffalo. It is caused by the contagious LSD virus, a member of the Poxiviridae family's Capripox genus. Skin sores are thought to be the most common site of infection since the virus may live for lengthy periods in lesions or scabs. The first clinical indications of LSD were described in Zambia, in 1929. Pakistan has also been afflicted by LSD, with a high number of animals infected at many cattle ranches in Karachi, 190,000 cases of LSD have been reported nationwide, with greater than 7500 deaths attributable to the illness. LSD has a huge influence on Pakistan's economic status, resulting in the loss of cattle and a decrease in milk output. The Ministry of Research and National Food Safety in Pakistan has formed a working group to create a framework for controlling the spread of LSD in cattle and buffalo. Official and private veterinarians, both field and slaughterhouse, veterinary students, farmers, cattle merchants, cattle truck drivers, and artificial inseminators should all participate in awareness efforts.
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Enfermedades de los Bovinos , Dermatosis Nodular Contagiosa , Virus de la Dermatosis Nodular Contagiosa , Bovinos , Animales , Dermatosis Nodular Contagiosa/epidemiología , Pakistán/epidemiología , Leche , Animales Domésticos , Búfalos , Enfermedades de los Bovinos/epidemiologíaRESUMEN
Glioblastoma Multiforme (GBM) is a debilitating type of brain cancer with a high mortality rate. Despite current treatment options such as surgery, radiotherapy, and the use of temozolomide and bevacizumab, it is considered incurable. Various methods, such as drug repositioning, have been used to increase the number of available treatments. Drug repositioning is the use of FDA-approved drugs to treat other diseases. This is possible because the drugs used for this purpose have polypharmacological effects. This means that these medications can bind to multiple targets, resulting in multiple mechanisms of action. Antipsychotics are one type of drug used to treat GBM. Antipsychotics are a broad class of drugs that can be further subdivided into typical and atypical classes. Typical antipsychotics include chlorpromazine, trifluoperazine, and pimozide. This class of antipsychotics was developed early on and primarily works on dopamine D2 receptors, though it can also work on others. Olanzapine and Quetiapine are examples of atypical antipsychotics, a category that was created later. These medications have a high affinity for serotonin receptors such as 5- HT2, but they can also act on dopamine and H1 receptors. Antipsychotic medications, in the case of GBM, also have other effects that can affect multiple pathways due to their polypharmacological effects. These include NF-B suppression, cyclin deregulation, and -catenin phosphorylation, among others. This review will delve deeper into the polypharmacological, the multiple effects of antipsychotics in the treatment of GBM, and an outlook for the field's future progression.
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Antipsicóticos , Glioblastoma , Humanos , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Glioblastoma/tratamiento farmacológico , Fumarato de Quetiapina , Dopamina , Receptores de Serotonina/metabolismoRESUMEN
The oviduct provides optimum physiological and biochemical milieu essential for successful fertilization, early embryo development and facilitates functional maturation of spermatozoa. A study has revealed that spermatozoa alters the gene expression in bovine oviductal epithelial cells (BOECs) remotely via bio-active particles, thus acting as a cue to the oviduct prior to their arrival. However, very little attention has been paid to the question of whether spermatozoa could alter the cargo of extracellular vesicles (EVs) derived from BOECs. Therefore, the aim of this study was to investigate the alterations in small non-coding RNAs in EVs cargo derived from BOECs when incubated with spermatozoa in contact and non-contact co-culture models. After 4 h of incubation the EVs were isolated from the conditioned media, followed by small non-coding sequencing of the BOEC derived EVs. Our results revealed that EVs from both co-culture models contained distinct cargo in form of miRNA, fragmented mRNA versus control. The pathway enrichment analysis revealed that EV miRNA from direct co-culture were involved in the biological processes associated with phagocytosis, macroautophagy, placenta development, cellular responses to TNF and FGF. The mRNA fragments also varied within the different groups and mapped to the exonic regions of the transcriptome providing vital insights regarding the changes in cellular transcriptome on the arrival of spermatozoa. The findings of this study suggest that spermatozoa, in contact as well as remotely, alter the EV cargo of female reproductive tract epithelial cells which might be playing an essential role in pre and post-fertilization events.
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Hepatitis C virus (HCV) infection is a major public health concern, and almost two million people are infected per year globally. This is occurred by the diverse spectrum of viral genotypes, which are directly associated with chronic liver disease (fibrosis, and cirrhosis). Indeed, the viral genome encodes three principal proteins as sequentially core, E1, and E2. Both E1 and E2 proteins play a crucial role in the attachment of the host system, but E2 plays a more fundamental role in attachment. The researchers have found the "E2-CD81 complex" at the entry site, and therefore, CD81 is the key receptor for HCV entrance in both humans, and chimpanzees. So, the researchers are trying to block the host CD81 receptor and halt the virus entry within the cellular system via plant-derived compounds. Perhaps that is why the current research protocol is designed to perform an in silico analysis of the flavonoid compounds for targeting the tetraspanin CD81 receptor of hepatocytes. To find out the best flavonoid compounds from our library, web-based tools (Swiss ADME, pKCSM), as well as computerized tools like the PyRx, PyMOL, BIOVIA Discovery Studio Visualizer, Ligplot+ V2.2, and YASARA were employed. For molecular docking studies, the flavonoid compounds docked with the targeted CD81 protein, and herein, the best-outperformed compounds are Taxifolin, Myricetin, Puerarin, Quercetin, and (-)-Epicatechin, and outstanding binding affinities are sequentially - 7.5, - 7.9, - 8.2, - 8.4, and - 8.5 kcal/mol, respectively. These compounds have possessed more interactions with the targeted protein. To validate the post docking data, we analyzed both 100 ns molecular dynamic simulation, and MM-PBSA via the YASARA simulator, and finally finds the more significant outcomes. It is concluded that in the future, these compounds may become one of the most important alternative antiviral agents in the fight against HCV infection. It is suggested that further in vivo, and in vitro research studies should be done to support the conclusions of this in silico research workflow.
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Hepacivirus , Hepatitis C , Humanos , Hepacivirus/genética , Hepacivirus/metabolismo , Simulación del Acoplamiento Molecular , Hepatitis C/tratamiento farmacológico , Hepatitis C/genética , Hepatitis C/metabolismo , Hepatocitos/metabolismo , Flavonoides/farmacología , Flavonoides/metabolismo , Tetraspanina 28/genética , Tetraspanina 28/metabolismo , Tetraspanina 28/farmacologíaRESUMEN
SARS-CoV-2 is the foremost culprit of the novel coronavirus disease 2019 (nCoV-19 and/or simply COVID-19) and poses a threat to the continued life of humans on the planet and create pandemic issue globally. The 3-chymotrypsin-like protease (MPRO or 3CLPRO) is the crucial protease enzyme of SARS-CoV-2, which directly involves the processing and release of translated non-structural proteins (nsps), and therefore involves the development of virus pathogenesis along with outbreak the forecasting of COVID-19 symptoms. Moreover, SARS-CoV-2 infections can be inhibited by plant-derived chemicals like amentoflavone derivatives, which could be used to develop an anti-COVID-19 drug. Our research study is designed to conduct an in silico analysis on derivatives of amentoflavone (isoginkgetin, putraflavone, 4''''''-methylamentoflavone, bilobetin, ginkgetin, sotetsuflavone, sequoiaflavone, heveaflavone, kayaflavone, and sciadopitysin) for targeting the non-structural protein of SARS-CoV-2, and subsequently further validate to confirm their antiviral ability. To conduct all the in silico experiments with the derivatives of amentoflavone against the MPRO protein, both computerized tools and online servers were applied; notably the software used is UCSF Chimera (version 1.14), PyRx, PyMoL, BIOVIA Discovery Studio tool (version 4.5), YASARA (dynamics simulator), and Cytoscape. Besides, as part of the online tools, the SwissDME and pKCSM were employed. The research study was proposed to implement molecular docking investigations utilizing compounds that were found to be effective against the viral primary protease (MPRO). MPRO protein interacted strongly with 10 amentoflavone derivatives. Every time, amentoflavone compounds outperformed the FDA-approved antiviral medicine that is currently underused in COVID-19 in terms of binding affinity (- 8.9, - 9.4, - 9.7, - 9.1, - 9.3, - 9.0, - 9.7, - 9.3, - 8.8, and - 9.0 kcal/mol, respectively). The best-selected derivatives of amentoflavone also possessed potential results in 100 ns molecular dynamic simulation (MDS) validation. It is conceivable that based on our in silico research these selected amentoflavone derivatives more precisely 4''''''-methylamentoflavone, ginkgetin, and sequoiaflavone have potential for serving as promising lead drugs against SARS-CoV-2 infection. In consequence, it is recommended that additional in vitro as well as in vivo research studies have to be conducted to support the conclusions of this current research study.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/metabolismo , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Farmacología en Red , Inhibidores de Proteasas/química , Proteínas no Estructurales Virales , Antivirales/química , Péptido Hidrolasas/metabolismoRESUMEN
Glioblastoma (GB) are aggressive tumors that obstruct normal brain function. While the skull cannot expand in response to cancer growth, the growing pressure in the brain is generally the first sign. It can produce more frequent headaches, unexplained nausea or vomiting, blurred peripheral vision, double vision, a loss of feeling or movement in an arm or leg, and difficulty speaking and concentrating; all depend on the tumor's location. GB can also cause vascular thrombi, damaging endothelial cells and leading to red blood cell leakage. Latest studies have revealed the role of single nucleotide polymorphisms (SNPs) in developing and spreading cancers such as GB and breast cancer. Many discovered SNPs are associated with GB, particularly in great abundance in the promoter region, creating polygenetic vulnerability to glioma. This study aims to compile a list of some of the most frequent and significant SNPs implicated with GB formation and proliferation.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/genética , Glioblastoma/patología , Células Endoteliales/patología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Encéfalo/patologíaRESUMEN
Diabetic retinopathy is one of the withering disorders that has been making the lives of patients miserable. Arising as a result of chronic high blood sugar levels in diabetes patients, retinopathy has become a major reason causing permanent blindness, retinal detachment, vitreous humor, rage, or glaucoma among patients. Angiogenesis being the major culprit behind the development of this condition is the growth of new blood vessels from the earlier ones existing. The abnormal growth and poor development of blood vessels also lead to aggravation of the conditions, with vascular endothelial growth factor (VEGF) playing a major role in the process. Various anti-angiogenic therapies or anti-VEGF therapies are being explored for the treatment of this condition. 4 widely explored drugs being-Bevacizumab, pegaptanib sodium, ranibizumab, and aflibercept. The review article tries to summarize studies illustrating the efficacy of these drugs in the treatment of diabetic retinopathy along with some of the herbal therapeutic paradigms displaying anti-angiogenic action that is being used to treat this condition.
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Diabetes Mellitus , Retinopatía Diabética , Humanos , Retinopatía Diabética/tratamiento farmacológico , Inhibidores de la Angiogénesis/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , Ranibizumab/uso terapéutico , Desarrollo de Medicamentos , Proteínas Recombinantes de Fusión/uso terapéutico , Diabetes Mellitus/tratamiento farmacológicoRESUMEN
INTRODUCTION: Hypogonadism is one of the most frequent complications in transfusion-dependent thalassemia patients and early recognition and treatment is the core element in restoring impaired gonadal function. Despite the high burden of disease, relevant studies are scarcely addressing the gonadal function of such patients in Bangladesh. The pattern of gonadal function in transfusion-dependent thalassemia patients must be characterized before planning a generalized management plan. Moreover, since iron overload is a key reason behind hypogonadism in thalassemia patients, investigating the role of serum ferritin level as a diagnostic tool for hypongadism was also an aim of this study. METHODS: This cross-sectional study was conducted at the Department of Transfusion Medicine of the Bangabandhu Sheikh Mujib Medical University. According to the inclusion and exclusion criteria, a total of 94 patients were enrolled in this study. A detailed history and thorough clinical examination were carried out in each patient and recorded using a pretested structured questionnaire. In addition, the laboratory assessment of serum ferritin, luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol in serum were also performed. The data were analyzed using the STATA (v.16). RESULTS: The mean age of the patients with transfusion-dependent thalassemia was 18.81 ± 4.65 (SD), with 53.3% of the patients being male. The overall prevalence of hypogonadism was 35.11%, 18.1% being normogonadotropic, 11.7% being hypogonadotropic and 5.3% being hypergonadotropic. The serum ferritin level was significantly higher (p < 0.001) in patients with hypogonadism (Eugonadal: 2,174.79 (± 749.12) ng/ml; Hypogonadal: 3,572.59 (± 1,199.49) ng/ml). The area under the receiver operating characteristic (ROC) curve of serum ferritin was high (0.83) and the p-value was highly significant (< 0.001). CONCLUSION: Therefore, the serum ferritin level and gonadal hormone analysis of transfusion-dependent thalassemia patients can be considered a screening tool for assessing gonadal function and early detection and prevention of hypogonadism.
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Robotic surgery has applications in many medical specialties, including urology, general surgery, and surgical oncology. In the context of a widespread resource and personnel shortage in Low- and Middle-Income Countries (LMICs), the use of robotics in surgery may help to reduce physician burnout, surgical site infections, and hospital stays. However, a lack of haptic feedback and potential socioeconomic factors such as high implementation costs and a lack of trained personnel may limit its accessibility and application. Specific improvements focused on improved financial and technical support to LMICs can help improve access and have the potential to transform the surgical experience for both surgeons and patients in LMICs. This review focuses on the evolution of robotic surgery, with an emphasis on challenges and recommendations to facilitate wider implementation and improved patient outcomes.
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Background: Alopecia Areata (AA) is found to be the most prevalent autoimmune disorder amongst the general population. It was observed that AA patients are at a significantly higher risk of developing obstructive sleep apnea and non-apneic insomnia than patients without AA. On the contrary, patients with identified sleep disorders were found to be more prone to developing AA as compared to the patients without sleep disorders. This study, therefore, validated the hypothesis of a bidirectional association between AA and sleep disorders. Aims: In this systematic review, our primary aim is to assess the prevalence of sleep disorders in Alopecia Areata patients while also assessing the inverse relationship between the two disorders. Methods: A literature search of MEDLINE, Google Scholar and Cochrane CENTRAL was performed from their inception to April 2022. Articles were selected for inclusion if they met the following eligibility criteria: (a) Studies enrolling patients having alopecia areata to assess the sleep quality. (b) Studies assessing the risks of alopecia areata in individuals with sleep disorder (c) Studies evaluating the bidirectional association between alopecia areata and sleep quality. Case reports, commentaries, and editorials were excluded. The outcomes of recruited studies were qualitatively synthesised and study findings are summarized in the results section and tabulated in summary tables. Results: Our search on electronic databases yielded 1562 articles. After abstract screening and full text review, 5 cross sectional and 3 cohort studies are included in this systematic review. Cases with PSQI scores higher than 5 and 6 were found to be in greater numbers amongst the AA patient population when compared to the control population (p < 0.001). Moreover, studies showed that patients with sleep disorders were greatly predisposed to develop subsequent AA as compared to patients without sleep disorders (aHR 4.70; 95% CI 3.99-5.54) (P < 0.0001). Conclusion: The findings from our results display a significant bi-directional cause-effect relation between AA and sleep disorders. However, more large-scale observational studies on this subject are required to further validate our findings.
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Alzheimer's disease (AD) is the most common neurodegenerative disorder in the world, affecting an estimated 50 million individuals. The nerve cells become impaired and die due to the formation of amyloid-beta (Aß) plaques and neurofibrillary tangles (NFTs). Dementia is one of the most common symptoms seen in people with AD. Genes, lifestyle, mitochondrial dysfunction, oxidative stress, obesity, infections, and head injuries are some of the factors that can contribute to the development and progression of AD. There are just a few FDA-approved treatments without side effects in the market, and their efficacy is restricted due to their narrow target in the etiology of AD. Therefore, our aim is to identify a safe and potent treatment for Alzheimer's disease. We chose the ursolic acid (UA) and its similar compounds as a compounds' library. And the ChEMBL database was adopted to obtain the active and inactive chemicals against Keap1. The best Quantitative structure-activity relationship (QSAR) model was created by evaluating standard machine learning techniques, and the best model has the lowest RMSE and greatest R2 (Random Forest Regressor). We chose pIC50 of 6.5 as threshold, where the top five potent medicines (DB06841, DB04310, DB11784, DB12730, and DB12677) with the highest predicted pIC50 (7.091184, 6.900866, 6.800155, 6.768965, and 6.756439) based on QSAR analysis. Furthermore, the top five medicines utilize as ligand molecules were docked in Keap1's binding region. The structural stability of the nominated medications was then evaluated using molecular dynamics simulations, RMSD, RMSF, Rg, and hydrogen bonding. All models are stable at 20 ns during simulation, with no major fluctuations observed. Finally, the top five medications are shown as prospective inhibitors of Keap1 and are the most promising to battle AD.
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Generalized Anxiety Disorder (GAD) is a prevalent condition and a significant cause of mental disability and poor quality of life. People with GAD have chronic worrying, restlessness, and discrimination from the general public; Little is known about the stigmatizing attitudes toward people with GAD among Syrian students. The questionnaires contained demographic data about age, gender, social status, personal stigma toward GAD scale, perceived stigma toward GAD scale, social distance with those with GAD, the participants' usual source of their knowledge about GAD, helpful interventions, and supporting information. A total of 1,370 replies were collected, but only 1,358 were used for analysis as 12 participants declined to complete the survey. About 44.1% of participants agreed that people with GAD could snap out of the problem, most of them being females (32.4% of the total population). Compared to medical students, more non-medical students (7.1% of the total population) believed that anxiety is a sign of personal weakness. This study demonstrated that Syrian college students showed a high level of stigmatizing and socially distancing attitudes toward people with GAD, particularly female and non-medical students.