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Introduction: The dysbiosis of vaginal microbiota is recognized as a potential underlying factor contributing to infertility in women. This study aimed to compare the vaginal microbiomes of infertile and fertile women to investigate their relationship with infertility. Methods: Metagenomic analysis was conducted on samples from 5 infertile and 5 fertile individuals using both amplicon 16S and metagenomics shotgun sequencing methods. Results and discussion: In the infertile group, the bacterial community was primarily represented by three major bacterial genera: Lactobacillus (79.42%), Gardnerella (12.56%) and Prevotella (3.33%), whereas, the fertile group exhibited a more diverse composition with over 8 major bacterial genera, accompanied by significantly reduced abundance of Lactobacillus (48.79%) and Gardnerella (6.98%). At the species level, higher abundances of L. iners, L. gasseri and G. vaginalis were observed in the infertile group. Regarding the microbiome composition, only one fertile and two infertile subjects exhibited the healthiest Community State Types, CST-1, while CST-3 was observed among two infertile and one fertile subject, and CST-4 in three other fertile and one infertile subject. Overall, alpha diversity metrics indicated greater diversity and lower species richness in the control (fertile) group, while the infertile group displayed the opposite trend. However, beta-diversity analysis did not show distinct clustering of samples associated with any specific group; instead, it demonstrated CST-type specific clustering. Shotgun metagenomics further confirmed the dominance of Firmicutes, with a greater abundance of Lactobacillus species in the infertile group. Specifically, L. iners and G. vaginalis were identified as the most dominant and highly abundant in the infertile group. Fungi were only identified in the control group, dominated by Penicillium citrinum (62.5%). Metagenome-assembled genomes (MAGs) corroborated read-based taxonomic profiling, with the taxon L. johnsonii identified exclusively in disease samples. MAG identities shared by both groups include Shamonda orthobunyavirus, L. crispatus, Human endogenous retrovirus K113, L. iners, and G. vaginalis. Interestingly, the healthy microbiomes sequenced in this study contained two clusters, Penicillium and Staphylococcus haemolyticus, not found in the public dataset. In conclusion, this study suggests that lower species diversity with a higher abundance of L. iners, L. gasseri and G. vaginalis, may contribute to female infertility in our study datasets. However, larger sample sizes are necessary to further evaluate such association.
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Bacterias , Infertilidad Femenina , Metagenómica , Microbiota , Vagina , Humanos , Femenino , Vagina/microbiología , Metagenómica/métodos , Infertilidad Femenina/microbiología , Adulto , Microbiota/genética , Bangladesh , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , ARN Ribosómico 16S/genética , Metagenoma , Adulto Joven , Lactobacillus/aislamiento & purificación , Lactobacillus/genética , Lactobacillus/clasificación , Disbiosis/microbiología , FilogeniaRESUMEN
Nowadays, perovskite materials are well known for electronics and optoelectronics applications. We have investigated a potential candidate for those applications to compare the applicability in optoelectronics, photorefractive and photovoltaic (PV) devices. The systematic comparative study of the structural, electronic, optical, mechanical, and thermodynamic properties of pure BaTiO3 and Ca doped BaTiO3 (Ba1-xCaxTiO3 where x = 0.125, 0.25, 0.375, 0.500, 0.625) perovskite have been carried out using first-principles and density-functional-theory calculations as recently this material was mostly experimented. The measured structural parameters from the geometrically optimized structure of cubic BT ceramic compared with the other theoretical values. A crystal phase transition occurs when doping content x = 0.25. The electronic band structure shows that the nature of the bandgap is changed from indirect bandgap to direct bandgap energy at G-point after doping the Ca atom into BaTiO3 (BT) crystal. Doping of Ca into BT has led to bandstructure modification including conduction band (CB) shifting toward the higher energy level. Electronic properties have been reported to examine the contribution of different orbitals to the CB and to the valance band (VB). This study investigated the modification of optical properties such as absorption, reflectivity, refractive index, extinction coefficient, conductivity, dielectric function and loss function at the energy range from 0 to 30 eV. The prominent absorption peak and optical energy were observed at the UV light energy region. Based on the optical behavior of the material this theoretical research suggests that the doped BT solution is a suitable candidate for photorefractive and optoelectronic devices. Different elastic constants reveal mechanical stability and the existence of the covalent bond of those compounds. Debye temperature increases with doping content. Hence modification of BaTiO3 crystal by Ca atom significantly develop various properties that led it to multifunctional applications.
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Visceral leishmaniasis is a potentially fatal disease caused by the parasitic protists, Leishmania donovani and L. infantum. Current treatments remain unsuitable due to cost, the need for hospitalization, variable efficacy against different species, toxicity and emerging resistance. Herein, we report the SAR exploration of the novel hit 4-Fluoro-N-(5-(4-methoxyphenyl)-1-methyl-1H-imidazole-2-yl)benzamide [1] previously identified from a high throughput screen against Trypanosoma brucei, Trypanosoma cruzi and Leishmania donovani. An extensive and informative set of analogues were synthesized incorporating key modifications around the scaffold resulting in improved potency, whilst the majority of compounds maintained low cytotoxicity against human THP-1 macrophages that are target cells for these pathogens. New lead compounds identified within this study also maintained desirable physicochemical properties, improved metabolic stability in vitro and displayed no significant mitotoxicity against HepG2 cell lines. This compound class warrants continued investigation towards development as a novel treatment for Visceral Leishmaniasis.
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Antiprotozoarios , Leishmania donovani , Leishmaniasis Visceral , Trypanosoma cruzi , Antiprotozoarios/química , Humanos , Imidazoles/uso terapéutico , Leishmaniasis Visceral/tratamiento farmacológicoRESUMEN
Influenza virus is a major cause of death on a global scale. Seasonal vaccines have been developed to combat influenza; however, they are not always highly effective. One strategy to develop a more broadly active influenza vaccine is the use of multiple rounds of layered consensus buildings to generate recombinant antigens, termed computationally optimized broadly reactive antigen (COBRA). Immunization with the COBRA hemagglutinin (HA) can elicit broad protection against multiple strains of a single influenza subtype (e.g., H1N1). We formulated a COBRA H1 HA with a stimulator of interferon genes agonist cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) into a nasal gel for vaccination against influenza. The gel formulation was designed to increase mucoadhesion and nasal retention of the antigen and adjuvant to promote a strong mucosal response. It consisted of a Schiff base-crosslinked hydrogel between branched polyethyleneimine and oxidized dextran. Following a prime-boost-boost schedule, an intranasal gel containing cGAMP and model antigen ovalbumin (OVA) led to the faster generation of serum IgG, IgG1, and IgG2c and significantly greater serum IgG1 levels on day 42 compared to soluble controls. Additionally, OVA-specific IgA was detected in nasal, vaginal, and fecal samples for all groups, except the vehicle control. When the COBRA HA was given intranasally in a prime-boost schedule, the mice receiving the gel containing the COBRA and cGAMP had significantly higher serum IgG and IgG2c at day 41 compared to all groups, and only this group had IgA levels above the background in vaginal, nasal, and fecal samples. Overall, this study indicates the utility of an intranasal gel for the delivery of COBRAs for the generation of serum and mucosal humoral responses.
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Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Infecciones por Orthomyxoviridae , Animales , Anticuerpos Antivirales , Femenino , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Humanos , Inmunoglobulina A , Inmunoglobulina G , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/prevención & control , Ratones , Infecciones por Orthomyxoviridae/prevención & controlRESUMEN
OBJECTIVES: The contingent valuation (CV) method elicits willingness to pay (WTP) for calculating the value of statistical life (VSL). CV approaches for assessing VSL are uncommon in many low and middle-income countries (LMICs). Between 2008 and 2018 only 44 articles utilized WTP in a health-related field and of these only 5 (11%) utilized CV to assess the WTP for a mortality risk reduction. We elicit WTP estimates and compute VSL using the CV method in Bangladesh. METHODS: The pilot study was primarily aimed at developing best practice guidelines for CV studies in LMICs to get more robust WTP estimates. To this end, we explored three methodological a) Varying the name of the intervention, keeping all other characteristics constant; b) varying the effectiveness of the health intervention and c) offering an overnight period to think about the WTP scenario. The survey was administered 413 randomly selected participants. VSL was for a 1/3000 mortality risk reduction. RESULTS: We had more males (54%) than females (46%) and the mean annual self-reported income was $5,683.36. Mean VSL is $11,339.70 with a median of $10,413. The ratio of child: adult WTP is approximately 1 by both gender and age category. The vaccine intervention had the largest amount of $0 WTP and protest responses (52% and 58% respectively). 93% of the participants were able to describe (teach-back) the vaccine effectiveness using their own family as an example. CONCLUSION: Our study provides empirical evidence on how to better generate CV surveys to produce more robust WTP estimates.
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Enfermedades Prevenibles por Vacunación , Vacunas , Adulto , Bangladesh , Niño , Femenino , Humanos , Renta , Masculino , Proyectos Piloto , Encuestas y Cuestionarios , Enfermedades Prevenibles por Vacunación/economíaRESUMEN
OBJECTIVE: We estimated the cost-effectiveness of home fortification with micronutrient powder delivered in a sales-based programme in reducing the prevalence of Fe deficiency anaemia among children 6-59 months in Bangladesh. DESIGN: Cross-sectional interviews with local and central-level programme staff and document reviews were conducted. Using an activity-based costing approach, we estimated start-up and implementation costs of the programme. The incremental cost per anaemia case averted and disability-adjusted life years (DALY) averted were estimated by comparing the home fortification programme and no intervention scenarios. SETTING: The home fortification programme was implemented in 164 upazilas (sub-districts) in Bangladesh. PARTICIPANTS: Caregivers of child 6-59 months and BRAC staff members including community health workers were the participants for this study. RESULTS: The home fortification programme had an estimated total start-up cost of 35·46 million BDT (456 thousand USD) and implementation cost of 1111·63 million BDT (14·12 million USD). The incremental cost per Fe deficiency anaemia case averted and per DALY averted was estimated to be 1749 BDT (22·2 USD) and 12 558 BDT (159·3 USD), respectively. Considering per capita gross domestic product (1516·5 USD) as the cost-effectiveness threshold, the home fortification programme was highly cost-effective. The programme coverage and costs for nutritional counselling of the beneficiary were influential parameters for cost per DALY averted in the one-way sensitivity analysis. CONCLUSIONS: The market-based home fortification programme was a highly cost-effective mechanism for delivering micronutrients to a large number of children in Bangladesh. The policymakers should consider funding and sustaining large-scale sales-based micronutrient home fortification efforts assuming the clear population-level need and potential to benefit persists.
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Micronutrientes , Bangladesh/epidemiología , Niño , Análisis Costo-Beneficio , Estudios Transversales , Humanos , PolvosRESUMEN
While highly active antiretroviral therapy (HAART) has significantly reduced mortality rates in patients with human immunodeficiency virus type 1 (HIV-1), its efficacy may be impeded by emergence of drug resistance caused by lack of patient adherence. A therapeutic strategy that requires infrequent drug administration as a result of sustained release of antiretroviral drugs would put less burden on the patient. Long-acting antiretroviral prodrugs for HIV therapy were synthesized through modification of the active drugs, emtricitabine (FTC) and elvitegravir (EVG), with docosahexaenoic acid (DHA) in one-step, one-pot, high-yielding reactions. The in vitro drug release profiles of these synthetic conjugates demonstrated sustained and controlled release of the active drug over a period of 3-4â¯weeks attributable to the hydrolysis of the chemical linker in conjunction with the hydrophilicity of the parent drug. Both conjugates exhibited superior antiviral activities in tissue culture models of HIV replication as compared to those of the free drugs, strengthening their role as potent prodrugs for HIV therapy. Pharmacokinetic analysis in CD1 mice further confirmed the long-acting aspect of these conjugates with released drug concentrations in plasma detected at their respective IC90/IC95 values over a period of 2â¯weeks and discernable amounts of active drug even at 6â¯weeks. Our findings suggest that the injectable small molecule conjugates could be used as long-acting controlled release of FTC and EVG in attempts to mitigate adherence-related HIV resistance.
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Fármacos Anti-VIH/administración & dosificación , Ácidos Docosahexaenoicos/administración & dosificación , Emtricitabina/administración & dosificación , Profármacos/administración & dosificación , Quinolonas/administración & dosificación , Animales , Fármacos Anti-VIH/química , Fármacos Anti-VIH/farmacocinética , Línea Celular , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Ácidos Docosahexaenoicos/química , Ácidos Docosahexaenoicos/farmacocinética , Liberación de Fármacos , Emtricitabina/química , Emtricitabina/farmacocinética , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Inyecciones Intramusculares , Ratones , Profármacos/química , Profármacos/farmacocinética , Quinolonas/química , Quinolonas/farmacocinéticaRESUMEN
INTRODUCTION: Leptin is now known to be an important hormone affecting intrauterine fetal growth. Since growth of fetus is also affected by the glycemic status of the mother. Serum leptin of infant is influenced by the maternal diabetic state. Investigation of cord blood leptin in babies of DM (Diabetes Mellitus) and GDM (Gestational Diabetes Mellitus) mothers (controlled blood glucose levels) may provide some indication about involvement of genetic factor in the development of leptin abnormalities in fetus. AIM: The study was taken to investigate whether cord blood insulin, c-peptide and leptin levels correlate with birth weight in offspring of DM mother. METHODS: Blood was drawn from umbilical cord of 30 babies from GDM mothers (GDM-babies), 45 babies from Type 2 DM Mothers (DM-babies), and 30 babies from ND (Nondiabetic) mothers (ND-babies) of term pregnancy. Weight, blood glucose, placenta, serum leptin and c-peptide of the babies were measured. RESULTS: Birth weight of GDM and DM babies were significantly higher compared to ND-babies. Glucose level in GDM babies was significantly higher than ND and DM babies. Leptin levels in GDM babies were significantly higher than that of ND and DM babies. Serum c-peptide in GDM babies was significantly higher than DM and ND babies. However, there was no significant difference in leptin-glucose ratio among the three groups. Irrespective of degree of hyperglycemia leptin is a major determinant of fetal growth. CONCLUSIONS: DM mother produces different insulinemic and leptinemic responses in the fetus indicating a possible genetic involvement.
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Diabetes Mellitus Tipo 2/sangre , Diabetes Gestacional/sangre , Insulina/sangre , Leptina/sangre , Atención Terciaria de Salud , Bangladesh/epidemiología , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiología , Femenino , Sangre Fetal/metabolismo , Humanos , Recién Nacido , Masculino , Embarazo , Atención Terciaria de Salud/métodosRESUMEN
BACKGROUND: Insulin resistance has been proposed to be the most likely phenotypic trait that could represent a genetic link between low birth weight and type 2 diabetes, especially in Southeast Asia. Insulin resistance can persist for many years, even decades, before the manifestation of overt diabetes. There have been many studies suggesting a strong genetic basis in the etiology of type 2 diabetes mellitus. There is also ample evidence providing a link with low birth weight and type 2 diabetes in later life. Hence, parental insulin sensitivity could well serve as a representation of the offspring's future insulin resistance state. Association between maternal insulin sensitivity and the incidence of type 2 diabetes mellitus in low birth weight babies is confounded by many factors and hence, has limited value in the determination of any genetic origin of the disease. Therefore, the present study was done to investigate the relationship between paternal insulin sensitivity and the growth parameters of the foetus to determine a genetic link between poor early growth and the increased risk of type 2 diabetes mellitus in later life. MATERIALS AND METHODS: The study was performed on 30 healthy fathers and their babies born from nondiabetic mothers. Each father underwent a low-dose short insulin tolerance test (ITT) as a measure of insulin sensitivity. Placental weight was recorded and a blood sample was collected from the placental side of the umbilical cord at birth for measurement of insulin. Measurement of birth weight, length, and head circumference were recorded and ponderal index was calculated from the formula: weight (kg)/ length (cm)(3). Individual parameters of insulin resistance syndrome were measured in the fathers. RESULTS: The degree of insulin sensitivity, K(m) (constant for insulin tolerance test) did not correlate with the fetal growth parameters (Ponderal Index r = 0.031, P = 0.870; weight of baby r = 0.010, P = 0.959; length of baby r = 0.087, P = 0.464; head circumference r = 0.280, P = 0.142) or with the fathers' anthropometric measures: body mass index (BMI), blood pressure, fasting glucose, insulin, and lipid profiles. CONCLUSION: The data suggest that the mechanism linking insulin resistance with low birth weight is not a genetically determined defect.