RESUMO
This study was designed to assess the possibility of using bacteriophage-encoded endolysins for controlling planktonic and biofilm cells. The endolysins, LysEP114 and LysEP135, were obtained from plasmid vectors containing the endolysin genes derived from Escherichia coli phages. The high identity (>96 %) was observed between LysEP114 and LysEP135. LysEP114 and LysEP135 were characterized by pH, thermal, and lactic acid stability, lytic spectrum, antibacterial activity, and biofilm eradication. The molecular masses of LysEP114 and LysEP135 were 18.2 kDa, identified as muramidases. LysEP114 and LysEP135 showed high lytic activity against the outer membrane-permeabilized E. coli KCCM 40405 at below 37 °C, between pH 5 to 11, and below 70 mM of lactic acid. LysEP114 and LysEP135 showed the broad rang of lytic activity against E. coli KACC 10115, S. Typhimurium KCCM 40253, S. Typhimurium CCARM 8009, tetracycline-resistant S. Typhimurium, polymyxin B-resistant S. Typhimurium, chloramphenicol-resistant S. Typhimurium, K. pneumoniae ATCC 23357, K. pneumoniae CCARM 10237, and Shigella boydii KACC 10792. LysEP114 and LysEP135 effectively reduced the numbers of planktonic E. coli KCCM by 1.7 and 2.1 log, respectively, when treated with 50 mM lactic acid. The numbers of biofilm cells were reduced from 7.3 to 4.1 log CFU/ml and 2.2 log CFU/ml, respectively, when treated with LysEP114- and LysEP135 in the presence of 50 mM lactic acid. The results suggest that the endolysins in combination with lactic acid could be potential alternative therapeutic agents for controlling planktonic and biofilm cells.
Assuntos
Antibacterianos , Biofilmes , Endopeptidases , Escherichia coli , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Endopeptidases/farmacologia , Endopeptidases/genética , Endopeptidases/metabolismo , Antibacterianos/farmacologia , Concentração de Íons de Hidrogênio , Plâncton/efeitos dos fármacos , Plâncton/virologia , Colífagos/genética , Colífagos/fisiologia , Ácido Láctico/farmacologia , Bacteriófagos/genética , Temperatura , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Proteínas Virais/genética , Proteínas Virais/farmacologia , Proteínas Virais/metabolismoRESUMO
Although low estrogen is considered to suppress uterine endometrial carcinoma, the most cases occur in the postmenopausal stage. After menopause, the production of androgen level also declines. Therefore, to resolve the above enigma, we hypothesize that the postmenopausal decline of androgen is a trigger of its progression. In the present study, to validate this hypothesis, we examine the pathological roles of androgen/AR by analyzing clinical data, culturing endometrioid cancer cell lines, and using murine models. Clinical data show that androgen receptor (AR) expression and serum dihydrotestosterone (DHT) are associated with lower disease-free survival (DFS). DHT suppresses malignant behaviors in AR-transfected human endometrial cancer cells (ECC). In ovariectomized Ptenff/PRcre/+ mice, DHT decreases the proliferation of spontaneously developed murine ECC. In AR-transfected human ECC and Ptenff/PRcre/+ mice, DHT suppresses FOXP4 expression. FOXP4-overexpressed human ECC increases, while FOXP4-knocked-down ECC shows decreased malignant behaviors. DHT/AR-mediated ECC suppression is restored by FOXP4 overexpression. The high FOXP4 expression is significantly correlated with low postoperative DFS. These findings indicate that the androgen/AR system suppresses the malignant activity of endometrial carcinoma and that downstream FOXP4 is another target molecule. These findings will also impact developments in clinical approaches to elderly health.
Assuntos
Androgênios , Neoplasias do Endométrio , Fatores de Transcrição Forkhead , Receptores Androgênicos , Feminino , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/genética , Humanos , Animais , Camundongos , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Receptores Androgênicos/metabolismo , Receptores Androgênicos/genética , Androgênios/metabolismo , Linhagem Celular Tumoral , Di-Hidrotestosterona/metabolismo , Di-Hidrotestosterona/farmacologia , Regulação Neoplásica da Expressão Gênica , Pessoa de Meia-Idade , Proliferação de CélulasRESUMO
BACKGROUND: Menstrual health is essential for gender equity and the well-being of women and girls. Qualitative research has described the burden of poor menstrual health on health and education; however, these impacts have not been quantified, curtailing investment. The Adolescent Menstrual Experiences and Health Cohort (AMEHC) Study aims to describe menstrual health and its trajectories across adolescence, and quantify the relationships between menstrual health and girls' health and education in Khulna, Bangladesh. METHODS AND ANALYSIS: AMEHC is a prospective longitudinal cohort of 2016 adolescent girls recruited at the commencement of class 6 (secondary school, mean age=12) across 101 schools selected through a proportional random sampling approach. Each year, the cohort will be asked to complete a survey capturing (1) girls' menstrual health and experiences, (2) support for menstrual health, and (3) health and education outcomes. Survey questions were refined through qualitative research, cognitive interviews and pilot survey in the year preceding the cohort. Girls' guardians will be surveyed at baseline and wave 2 to capture their perspectives and household demographics. Annual assessments will capture schools' water, sanitation and hygiene, and support for menstruation and collect data on participants' education, including school attendance and performance (in maths, literacy). Cohort enrolment and baseline survey commenced in February 2023. Follow-up waves are scheduled for 2024, 2025 and 2026, with plans for extension. A nested subcohort will follow 406 post-menarche girls at 2-month intervals throughout 2023 (May, August, October) to describe changes across menstrual periods. This protocol outlines a priori hypotheses regarding the impacts of menstrual health to be tested through the cohort. ETHICS AND DISSEMINATION: AMEHC has ethical approval from the Alfred Hospital Ethics Committee (369/22) and BRAC James P Grant School of Public Health Institutional Review Board (IRB-06 July 22-024). Study materials and outputs will be available open access through peer-reviewed publication and study web pages.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Menstruação , Feminino , Adolescente , Humanos , Criança , Menstruação/psicologia , Bangladesh/epidemiologia , Estudos Prospectivos , MenarcaRESUMO
Extreme weather events in South and Southeast Asia exert profound psychosocial impacts, amplifying the prevalence of mental illness. Despite their substantial consequences, there is a dearth of research and representation in the current literature. We conducted a systematic review of observational studies published between January 1, 2000, and January 20, 2024, to examine the impact of extreme weather events on the mental health of the South and Southeast Asian population. Quality assessment of the included studies was conducted using the Newcastle-Ottawa Scale (NOS) quality appraisal checklist. The search retrieved 70 studies that met the inclusion criteria and were included in our review. Most were from India (n = 22), and most used a cross-sectional study design (n = 55). Poor mental health outcomes were associated with six types of extreme weather events: floods, storm surges, typhoons, cyclones, extreme heat, and riverbank erosion. Most studies (n = 41) reported short-term outcome measurements. Findings included outcomes with predictable symptomatology, including post-traumatic stress disorder, depression, anxiety, general psychological distress, emotional distress and suicide. Limited studies on long-term effects showed higher mental disorders after floods and typhoons, while cyclone-exposed individuals had more short-term distress. Notably, the review identified over 50 risk factors influencing mental health outcomes, categorized into six classes: demographic, economic, health, disaster exposure, psychological, and community factors. However, the quantitative evidence linking extreme weather events to mental health was limited due to a lack of longitudinal data, lack of control groups, and the absence of objective exposure measurements. The review found some compelling evidence linking extreme weather events to adverse mental health in the South and Southeast Asia region. Future research should focus on longitudinal study design to identify the specific stressors and climatic factors influencing the relationship between climate extremes and mental health in this region.
Assuntos
Clima Extremo , Saúde Mental , Humanos , Saúde Mental/estatística & dados numéricos , Sudeste Asiático/epidemiologia , Transtornos Mentais/epidemiologia , Estudos Observacionais como AssuntoRESUMO
BACKGROUND: The lack of menstrual hygiene management (MHM) information and facilities in schools is a major contributor to adolescent girls' school absenteeism in low- and middle-income countries like Bangladesh. OBJECTIVES: This paper examines the changes over time in school MHM facilities, knowledge and perceptions among adolescent girls, in relation to school absenteeism between 2014 and 2018 in Bangladesh. METHODS: We examined changes in MHM and school absenteeism among schoolgirls using nationally representative data from the Bangladesh National Hygiene Baseline Survey 2014 and National Hygiene Survey 2018. Given the repetitive nature of our data and its clustering within participants, our method included performing descriptive analysis, bivariate analysis, and multivariate Generalised Estimating Equation (GEE) modelling to analyse these changes. RESULTS: Results showed that adolescent girls' menstruation-related absenteeism decreased between 2014 and 2018. Percentage of adolescents who missed school decreased from 25% to 14% (PD: -11; CI: -16 to -6.1), while the average number of missed days reduced from 2.8 to 2.5 (PD: -0.33; CI: -0.57 to -0.10). In the GEE model, we found that living in rural areas (coef: -5.6; CI: -10.06 to -1.14), parental restrictions on going outside (coef: 4.47; CI: 0.75 to 8.2), education levels of girls (coef: -9.48; CI: -14.17 to -4.79), girl's belief that menstruation affects school performance (coef: 23.32; CI: 19.71 to 26.93), and using old cloths (coef: -4.2; CI: -7.6 to -0.79) were significantly associated with higher absenteeism. However, participant's age, type of school, knowledge of menstruation before menarche, receiving information regarding MHM, separate place for changing absorbents, and separate latrine and urine facility were not significantly associated with the changes in absenteeism over time. CONCLUSION: This paper emphasised the associations between changes in school absenteeism, parental restrictions on students, students' education levels, and menstruation-related misperceptions. Ongoing research, policy reviews, and targeted interventions to improve MHM perceptions among girls are required to provide long-term benefits for adolescent girls in Bangladesh.
Assuntos
Higiene , Menstruação , Feminino , Adolescente , Humanos , Absenteísmo , Conhecimentos, Atitudes e Prática em Saúde , MenarcaRESUMO
Messenger RNA (mRNA) vaccines against infectious diseases and for anticancer immunotherapy have garnered considerable attention. Currently, mRNA vaccines encapsulated in lipid nanoparticles are administrated via intramuscular injection using a needle. However, such administration is associated with pain, needle phobia, and lack of patient compliance. Furthermore, side effects such as fever and anaphylaxis associated with the lipid nanoparticle components are also serious problems. Therefore, noninvasive, painless administration of mRNA vaccines that do not contain other problematic components is highly desirable. Antigen-presenting cells reside in the epidermis and dermis, making the skin an attractive vaccination site. Iontophoresis (ItP) uses weak electric current applied to the skin surface and offers a noninvasive permeation technology that enables intradermal delivery of hydrophilic and ionic substances. ItP-mediated intradermal delivery of biological macromolecules has also been studied. Herein, we review the literature on the use of ItP technology for intradermal delivery of naked mRNA vaccines which is expected to overcome the challenges associated with mRNA vaccination. In addition to the physical mechanism, we discuss novel biological mechanisms of iontophoresis, particularly ItP-mediated opening of the skin barriers and the intracellular uptake pathway, and how the combined mechanisms can allow for effective intradermal delivery of mRNA vaccines.
RESUMO
INTRODUCTION: The vaccination against coronavirus disease 2019 (COVID-19) has been identified as a promising strategy to reduce the severity of the pandemic. Despite the safe and effective COVID-19 vaccines, bringing socioeconomically disadvantaged people under vaccination coverage has been challenging for developing countries like Bangladesh. Therefore, this study explored the determinants of vaccine acceptance among urban slum residents of Bangladesh using the Health Belief Model (HBM) and Theory of Planned Behavior (TPB). METHODS: A face-to-face survey of 400 urban slum dwellers in two large cities in Bangladesh was conducted between July 5 to August 5, 2021. The questionnaire included vaccine acceptance, socio-demographics, health-related characteristics, trust in health authorities, reasons for vaccine hesitancy, and dimensions of HBM and TPB frameworks. Hierarchical logistic regression was performed to evaluate the association between these characteristics and vaccination acceptance. RESULTS: Around 82% (n = 327) of respondents were willing to accept the COVID-19 vaccine. In a fully adjusted model, respondents with secondary level education had higher intention (OR = 46.93, 95%CI = 1.21-1807.90, p < 0. 05) to accept COVID-19 vaccine. Respondents with bad (OR = 0.11, 95%CI = 0.01-0.35, p<0.05) or very bad (OR = 0.01, 95%CI = 0.01-0.35, p<0.05) health conditions were less interested in the COVID-19 vaccination. In regard to HBM dimensions, greater perceived susceptibility (OR = 1.75, 95% CI = 1.12-2.75, p < 0.05), and perceived benefits (OR = 3.28, 95% CI = 1.17-6.00, p < 0.001) were associated with a greater willingness to get vaccinated. In regard to TPB, higher self-efficacy in preventing illness without the vaccine increased the desire to get vaccinated (OR = 1.55, 95% CI = 1.02-2.37, p < 0.05). Fear of unknown side effects, religious beliefs, contraindications to vaccination, and insufficient information on the vaccine were the main reasons for vaccine hesitancy. CONCLUSIONS: These findings offer valuable insights for policymakers in Bangladesh to design targeted interventions that address vaccine hesitancy and increase vaccination acceptability among socially disadvantaged individuals in urban areas. Strategies should focus on providing accurate and accessible information about the vaccine, communicating its positive impact effectively, engaging with religious leaders to address misconceptions, and tailoring vaccination campaigns to meet the unique needs of different demographic groups.