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Alzheimer's disease (AD) is a complex neurodegenerative disorder that develops over decades. AD brain proteomics reveals vast alterations in protein levels and numerous altered biologic pathways. Here, we compare AD brain proteome and network changes with the brain proteomes of amyloid ß (Aß)-depositing mice to identify conserved and divergent protein networks with the conserved networks identifying an Aß amyloid responsome. Proteins in the most conserved network (M42) accumulate in plaques, cerebrovascular amyloid (CAA), and/or dystrophic neuronal processes, and overexpression of two M42 proteins, midkine (Mdk) and pleiotrophin (PTN), increases the accumulation of Aß in plaques and CAA. M42 proteins bind amyloid fibrils in vitro, and MDK and PTN co-accumulate with cardiac transthyretin amyloid. M42 proteins appear intimately linked to amyloid deposition and can regulate amyloid deposition, suggesting that they are pathology modifiers and thus putative therapeutic targets. We posit that amyloid-scaffolded accumulation of numerous M42+ proteins is a central mechanism mediating downstream pathophysiology in AD.
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BACKGROUND: Bad breath (halitosis) is a common problem affecting psycho-social wellbeing of young people. We aimed to explore the extent of self-perceived halitosis and associated factors among university students in Dhaka, Bangladesh. METHODS: A cross-sectional study was conducted among university students from November 2021 to April 2022. Six private and two public universities were approached. A total of 318 participants were conveniently selected for the study. A self-administered questionnaire was used for data collection. Students unwilling to participate were excluded. Multivariable logistic regression analysis was used to examine factors associated with halitosis. Statistical analysis was conducted using Stata Version 17. RESULTS: A total of 55.97% of students had self-perceived halitosis, with females (74.53%) having a significantly higher proportion than males (36.94%) (p < 0.001). A significantly higher proportion of halitosis was found among participants who were overweight ( 61%), had obesity (60.77%), smoked cigarette (46.79%), consumed alcohol (71.43%), lacked exercise (66.29%), were on unhealthy diet (57.35%), consumed coffee/tea (61.35%), breathed through mouth (64.60%), brushed tooth infrequently (85.71%), changed toothbrush after 6 months (77.42%), did not use toothpaste (94.74%), did not use/ sometimes used fluoride toothpaste (75.76%), lacked dental floss use (60.85%), did not use toothpick (62.87%), did chew or sometimes chewed sugar-free chewing gum (75.82%), did not clear / cleaned tongue sometimes (76.14%), did use mouth freshener regularly or occasionally (64.97%), did not use or used mouthwash sometimes (58.87%) were also associated with higher self-perceived halitosis (p < 0.05 for all). Students with gum bleeding, swollen gums, dry mouth, dental caries, food accumulation, and tooth sensitivity had a significantly (p < 0.05 for all) higher proportion of self-perceived halitosis (76.85%, 81.82%, 72.50%, 67.78%, 64.13% and 67.40%, respectively) compared to those without this problem. Being female (OR = 5.04; 95% CI: 2.01-12.62; p < 0.001), alcohol consumers (OR 7.35; 95% CI: 1.77-30.50; p = 0.006); not using sugar free chewing gum (OR = 0.25; 95% CI: 0.10-0.58; p = 0.001), lack of tongue cleaning (OR 4.62; 95% CI: 2.16-9.84; p < 0.001), and gum bleeding (OR = 7.43; 95% CI: 3.00-18.35; p < 0.001) were independently associated with halitosis on multivariable regression. CONCLUSION: This study reveals a high proportion of self-perceived halitosis and relevant factors. There should be more public education on the causes of halitosis and potential management approaches.
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Halitosis , Estudiantes , Humanos , Halitosis/psicología , Halitosis/etiología , Halitosis/epidemiología , Femenino , Masculino , Bangladesh/epidemiología , Estudios Transversales , Universidades , Adulto Joven , Estudiantes/estadística & datos numéricos , Estudiantes/psicología , Autoimagen , Encuestas y Cuestionarios , Adulto , Factores de Riesgo , AdolescenteRESUMEN
Background: Vaccination against Human papillomavirus (HPV) is recommended to avoid HPV infections and its associated diseases, including cervical cancer. However, there is no awareness study among Bangladeshi population. Hence, this nationwide study was conducted to explore HPV vaccine awareness and its determinants among parents of eligible adolescent girls. Methods: This study was conducted among the parents of daughters aged 9-15 years from 42 out of 64 randomly selected districts of Bangladesh between June 28 to August 2, 2023. A multistage sampling method was used to enroll 2151 study participants from all eight divisions of Bangladesh. A semi-structured questionnaire was used for face-to-face interviews in this study. The statistical software Stata (Version 17) was used for statistical analyses. Results: The average age of the participants was 38.18 (±5.86) years. Only 22.32 % of the participants were aware of the HPV vaccine. Every additional year of age increased the likelihood of being aware of the HPV vaccine by 3 % (AOR: 1.03; 95%CI: 1.00-1.06). Participants residing in the urban area had 3.56 times higher odds of awareness than rural and semi-urban people. Businessmen and housewives had 60 % (AOR: 0.40; 95 % CI: 0.22-0.69) and 77 % (AOR: 0.23; 95 % CI: 0.16-0.33) lower odds in comparison to job holders. The lower-income group exhibited significantly higher odds of awareness (AOR: 0.25, 95%CI: 0.16-0.39) compared to the middle and the higher-income group. Participants who never went through routine health check-ups had 77 % lower odds of being aware than those who availed of regular routine check-ups (AOR: 0.23; 95%CI: 0.16-0.34). Conclusion: Awareness of the HPV vaccine among the general population of Bangladesh is very low. Age, residence, occupation, monthly income, and routine medical check-ups were associated with HPV vaccine awareness. A nationwide awareness campaign would increase this awareness level among the Bangladeshi population, especially among the parents of daughters.
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We report a highly significant correlation in brain proteome changes between Alzheimers disease (AD) and CRND8 APP695NL/F transgenic mice. However, integrating protein changes observed in the CRND8 mice with co-expression networks derived from human AD, reveals both conserved and divergent module changes. For the most highly conserved module (M42, matrisome) we find many proteins accumulate in plaques, cerebrovascular amyloid (CAA), dystrophic processes, or a combination thereof. Overexpression of two M42 proteins, midkine (Mdk) and pleiotrophin (PTN), in CRND8 mice brains leads to increased accumulation of A ß ; in plaques and in CAA; further, recombinant MDK and PTN enhance A ß ; aggregation into amyloid. Multiple M42 proteins, annotated as heparan sulfate binding proteins, bind to fibrillar A ß 42 and a non-human amyloid fibril in vitro. Supporting this binding data, MDK and PTN co-accumulate with transthyretin (TTR) amyloid in the heart and islet amyloid polypeptide (IAPP) amyloid in the pancreas. Our findings establish several critical insights. Proteomic changes in modules observed in human AD brains define an A ß ; amyloid responsome that is well conserved from mouse model to human. Further, distinct amyloid structures may serve as scaffolds, facilitating the co-accumulation of proteins with signaling functions. We hypothesize that this co-accumulation may contribute to downstream pathological sequalae. Overall, this contextualized understanding of proteomic changes and their interplay with amyloid deposition provides valuable insights into the complexity of AD pathogenesis and potential biomarkers and therapeutic targets.
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BACKGROUND: The global outbreak of COVID-19 has created unprecedented havoc among health care workers, resulting in significant psychological strains like insomnia. This study aimed to analyze insomnia prevalence and job stressors among Bangladeshi health care workers in COVID-19 units. METHODOLOGY: We conducted this cross-sectional study to assess insomnia severity from January to March 2021 among 454 health care workers working in multiple hospitals in Dhaka city with active COVID-dedicated units. We selected 25 hospitals conveniently. We used a structured questionnaire for face-to-face interviews containing sociodemographic variables and job stressors. The severity of insomnia was measured by the Insomnia Severity Scale (ISS). The scale has seven items to evaluate the rate of insomnia, which was categorized as the absence of Insomnia (0-7); sub-threshold Insomnia (8-14); moderate clinical Insomnia (15-21); and severe clinical Insomnia (22-28). To identify clinical insomnia, a cut-off value of 15 was decided primarily. A cut-off score of 15 was initially proposed for identifying clinical insomnia. We performed a chi-square test and adjusted logistic regression to explore the association of different independent variables with clinically significant insomnia using the software SPSS version 25.0. RESULTS: 61.5% of our study participants were females. 44.9% were doctors, 33.9% were nurses, and 21.1% were other health care workers. Insomnia was more dominant among doctors and nurses (16.2% and 13.6%, respectively) than others (4.2%). We found clinically significant insomnia was associated with several job stressors (p < 0.05). In binary logistic regression, having sick leave (OR = 0.248, 95% CI = 0.116, 0.532) and being entitled to risk allowance (OR = 0.367, 95% CI = 0.124.1.081) showed lower odds of developing Insomnia. Previously diagnosed with COVID-19-positive health care workers had an OR of 2.596 (95% CI = 1.248, 5.399), pointing at negative experiences influencing insomnia. In addition, we observed that any training on risk and hazard increased the chances of suffering from Insomnia (OR = 1.923, 95% CI = 0.934, 3.958). CONCLUSION: It is evident from the findings that the volatile existence and ambiguity of COVID-19 have induced significant adverse psychological effects and subsequently directed our HCWs toward disturbed sleep and insomnia. The study recommends the imperativeness to formulate and implement collaborative interventions to help HCWs cope with this crisis and mitigate the mental stresses they experience during the pandemic.
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COVID-19 , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Trastornos del Inicio y del Mantenimiento del Sueño , Femenino , Humanos , Masculino , Bangladesh , Estudios Transversales , Personal de SaludRESUMEN
Obesity is associated with an imbalance of micro-and macro-nutrients, gut dysbiosis, and a "leaky" gut phenomenon. Polyphenols, such as curcumin, resveratrol, and anthocyanins may alleviate the systemic effects of obesity, potentially by improving gut microbiota, intestinal barrier integrity (IBI), and zinc homeostasis. The essential micronutrient zinc plays a crucial role in the regulation of enzymatic processes, including inflammation, maintenance of the microbial ecology, and intestinal barrier integrity. In this review, we focus on IBI- which prevents intestinal lipopolysaccharide (LPS) leakage - as a critical player in polyphenol-mediated protective effects against obesity-associated white adipose tissue (WAT) inflammation. This occurs through mechanisms that block the movement of the bacterial endotoxin LPS across the gut barrier. Available research suggests that polyphenols reduce WAT and systemic inflammation via crosstalk with inflammatory NF-κB, the mammalian target of rapamycin (mTOR) signaling and zinc homeostasis.
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Microbioma Gastrointestinal , Humanos , Polifenoles/farmacología , Lipopolisacáridos/farmacología , Antocianinas/farmacología , Obesidad/microbiología , Inflamación/tratamiento farmacológico , Antiinflamatorios/farmacología , Homeostasis , Zinc/farmacología , Disbiosis/microbiologíaRESUMEN
The plant-derived polyphenol curcumin alleviates the inflammatory and metabolic effects of obesity, in part, by reducing adipose tissue inflammation. We hypothesized that the benefits of curcumin supplementation on diet-induced obesity and systemic inflammation in mice occur through downregulation of white adipose tissue (WAT) inflammation. The hypothesis was tested in adipose tissue from high-fat diet-induced obese mice supplemented with or without curcumin and in 3T3-L1 adipocytes treated with or without curcumin. Male B6 mice were fed a high-fat diet (HFD, 45% kcal fat) with or without 0.4% (w/w) curcumin supplementation (HFC). Metabolic changes in these mice have been previously reported. Here, we determined the serum levels of the curcumin metabolites tetrahydrocurcumin (THC) and curcumin-O-glucuronide (COG) using mass spectrometry. Moreover, we determined interleukin 6 (IL-6) levels and proteomic changes in LPS-stimulated 3T3-L1 adipocytes treated with or without curcumin by using immunoassays and mass spectrometry, respectively, to gain further insight into any altered processes. We detected both curcumin metabolites, THC and COG, in serum samples from the curcumin-fed mice. Both curcumin and its metabolites reduced LPS-induced adipocyte IL-6 secretion and mRNA levels. Proteomic analyses indicated that curcumin upregulated EIF2 and mTOR signaling pathways. Overall, curcumin exerted anti-inflammatory effects in adipocytes, in part by reducing IL-6, and these effects may be linked to the upregulation of the mTOR signaling pathway, warranting additional mechanistic studies on the effects of curcumin and its metabolites on metabolic health.
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Curcumina , Glucurónidos , Animales , Ratones , Curcumina/farmacología , Interleucina-6/genética , Lipopolisacáridos , Proteómica , Adipocitos , Tejido Adiposo Blanco , Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Serina-Treonina Quinasas TOR , Obesidad/tratamiento farmacológicoRESUMEN
Oral health is a critical component of human health but is sometimes forgotten, particularly during humanitarian crises. This research aimed to ascertain the state of oral health among Rohingya refugees living in one of the largest refugee camps and evaluate their knowledge and practice of oral health. A multicenter cross-sectional survey was conducted among 477 participants from July to September 2021 using a structured questionnaire. There were 34 Rohingya camps and out of those 14 camps were accessible for data collection. The study participants were between 18-82 years residing in the refugee camps under Cox's Bazar. The majority of participants (53.88%) were female and between the ages of 25 and 45. Around 46.12% of respondents did not have basic oral health knowledge, while 53.67% were in need of dental care. Nearly half of the participants demonstrated poor oral health practices. Participants' age and educational level were positively associated with oral health knowledge (p = 0.02 and p<0.001). Furthermore, the knowledge level was positively associated with oral health practice (p = .025). Participants with a history of teeth pain and discomfort in the last 12 months were ten times more likely to seek treatment (OR = 9.93, CI: 5.591-17.64). The study indicated a growing demand for dental care among Rohingya refugees staying in Bangladesh. To reduce the severity of oral health issues, use of minimally invasive restorative procedures can be suggested in camps. New oral health promotion campaigns should be emphasized and proper education, ideally in their original language, can be beneficial.
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Refugiados , Adulto , Bangladesh , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Salud Bucal , Campos de RefugiadosRESUMEN
SCOPE: Obesity prevalence continues to increase and contribute to metabolic diseases, potentially by driving systemic inflammation. Curcumin is an anti-inflammatory spice with claimed health benefits. However, mechanisms by which curcumin may reduce obesity-associated inflammation are poorly understood; thus, it is hypothesized that benefits of curcumin consumption may occur through reduced white adipose tissue (WAT) inflammation and/or beneficial changes in gut bacteria. METHODS AND RESULTS: Male B6 mice are fed high-fat diets (HFD, 45% kcal fat) or HFD supplemented with 0.4% (w/w) curcumin (HFC) for 14 weeks. Curcumin supplementation significantly reduces adiposity and total macrophage infiltration in WAT, compared to HFD group, consistent with reduced mRNA levels of M1 (Cd80, Cd38, Cd11c) and M2 (Arginase-1) macrophage markers. Moreover, curcumin supplementation reduces expression of other key pro-inflammatory genes, such as NF-κB p65 subunit (p65), Stat1, Tlr4, and Il6, in WAT (p < 0.05). Using microbial 16S RNA sequencing, it is demonstrated that the relative abundance of the Lactococcus, Parasutterella, and Turicibacter genera are increased in the HFC group versus HFD. CONCLUSIONS: Curcumin exerts protective metabolic effects in dietary obesity, in part through downregulation of adipose tissue inflammation, which may be mediated by alterations in composition of gut microbiota, and metabolism of curcumin into curcumin-O-glucuronide.
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Curcumina , Microbioma Gastrointestinal , Tejido Adiposo/metabolismo , Tejido Adiposo Blanco/metabolismo , Animales , Curcumina/metabolismo , Curcumina/farmacología , Dieta Alta en Grasa/efectos adversos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/inducido químicamente , Obesidad/etiologíaRESUMEN
The influence of diet on the gut microbiota is an emerging research area with significant impact on human health and disease. However, the effects of beef, the most consumed red meat in the United States, on gut microbial profile are not well studied. Following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols, the objective of this systematic review was to conduct a rigorous and thorough review of the current scientific literature regarding the effects of beef protein and the resulting bioactivity of beef protein and amino acids on the gut microbiota, with the goal of identifying gaps in the literature and guiding future research priorities. Utilizing MEDLINE Complete, PubMed, ScienceDirect, Scopus, and Google Scholar databases, we conducted searches including terms and combinations of the following: animal protein, amino acid, beef, bioactive compounds, diet, health, microbiome, peptide, processed beef, and protein. We identified 131 articles, from which 15 were included in our review. The effects of beef on mouse and rat models were mostly consistent for the bacterial phylum level. Short-term (1-4-wk) beef intakes had little to no effect on microbial profiles in humans. Most studies utilized high beef feeding (240-380 g/d), and no study examined recommended amounts of protein [â¼3.71 oz/d (105 g/d) meats, poultry, and eggs, or â¼26 oz/week (737 g/wk) from these food sources] according to US dietary guidelines. Additionally, the majority of animal and human studies with adverse findings examined the impact of beef in the context of a diet high in fat or sugar. In conclusion, an extensive gap exists in the literature regarding beef and the microbiota. More studies are necessary to elucidate the role of the microbiota following the consumption of beef, especially in interaction with other dietary compounds, and how beef preparation, processing, and cooking methods differentially influence the biological effects of beef on human health.