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Data scarcity hinders global conservation initiatives, and there is a pressing demand for spatially detailed soil and species data to restore human-altered tropical forests. We, therefore, aimed to generate foundational soil environment and habitat suitability data and high-resolution soil maps to aid restoration efforts in a critical ecosystem of the threatened Indo-Burma Biodiversity Hotspot region, i.e., Tarap Hill Reserve (THR) in Bangladesh. Using multiple soil depths and vegetation data, we answered three major questions. (QI) How do spatial distribution and the relationships between soil physicochemical properties (i.e., pH, sand, silt, and clay percentages, organic carbon, and nutrients - N, P, K, Ca, Mg, Fe, and Zn) vary from surface to deeper soils (top 1 m)? (QII) How do different forest management interventions, i.e., old-growth forests (OGF), mixed plantations (MXP), and mono-specific plantations (MOP), influence soil properties, nutrients, and carbon in different soil depths? (QIII) Which spatial interpolation methods are best suited for making more accurate soil property predictions at different depths? Our analyses reveal decreasing availability of critical nutrients like N, P, Mg, and Fe from surface to subsurface soils, while pH, soil organic carbon, and clay content increased with depth. Several soil properties showed significant interactions, although the strength of the interactions changed from surface to deeper soils. Besides, forest management interventions significantly influenced soil functionality by having higher nutrient availability and soil organic carbon in OGF than MXP and MOP. Predictive performances of the deterministic and geostatistical interpolation methods varied for different soil properties in different soil depths, and soil maps revealed substantial heterogeneity in the distribution of soil properties across space and along depths. This study represents a pioneering step in data-driven tropical forest restoration, and our novel findings and high-resolution soil maps could guide future studies focusing on species habitat preferences, restoration ecology, and spatial conservation planning in the Indo-Burma Biodiversity Hotspot region and elsewhere in the tropics.
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Surfactants can reduce the interfacial surface tension between two immiscible liquids making them a desirable component for various industrial applications. However, the toxic nature of chemical surfactants brought immense attention towards biosurfactants. Being biodegradable, biosurfactants are eco-friendly and considered safer for different commercial uses. This study focused on the production of biosurfactant from an oil-degrading bacteria and its functional efficacy for prospective industrial applications. Here, a promising oil-tolerant strain, Bacillus velezensis S2 was isolated from oil contaminated sites which showed >50% degradation of convoluted crude oil within 28 days in comparison to a control. The isolate was then found to produce an excellent surface-active compound with an emulsification index of 67.30 ± 0.8% and could reduce the surface tension up to 36.86 ± 0.36 mN m-1. It also manifested a critical micelle concentration of 45 mg L-1 while reducing the surface tension from 72 to 30 mN m-1. When extracting biosurfactant from isolated bacteria, ethyl acetate extraction showed 1.5 times greater efficacy than chloroform : methanol extraction. The purified biosurfactant was characterized using TLC, 1H NMR, 13C NMR, FTIR, elemental analyses and spectrophotometric techniques leading to its identification as a rhamnolipid. The stability of produced biosurfactant at higher temperature (up to 180 °C) was determined by thermal analysis, endorsing its application in high temperature reservoir conditions. Additionally, the extracted biosurfactant showed excellent foaming efficacy with insignificant antibacterial and cytotoxic responses, which indicates their potential application in cleaning and cosmetics industries. Thus, the present study outlines a bi-functional novel isolate Bacillus velezensis S2 which could play a significant role in oil remediation from the environment as well as serve as a potential source of non-toxic and eco-friendly biosurfactants for various industrial applications.
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SUMMARYThe success of the Severe Acute Respiratory Syndrome Coronavirus 2 mRNA vaccines to lessen/prevent severe COVID-19 opened new opportunities to develop RNA vaccines to fight other infectious agents. HIV-1 is a lentivirus that integrates into the host cell genome and persists for the lifetime of infected cells. Multiple mechanisms of immune evasion have posed significant obstacles to the development of an effective HIV-1 vaccine over the last four decades since the identification of HIV-1. Recently, attempts to address some of these challenges have led to multiple studies that manufactured, optimized, and tested, in different animal models, mRNA-based HIV-1 vaccines. Several clinical trials have also been initiated or are planned to start soon. Here, we review the current strategies applied to HIV-1 mRNA vaccines, discuss different targeting approaches, summarize the latest findings, and offer insights into the challenges and future of HIV-1 mRNA vaccines.
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Vacunas contra el SIDA , Infecciones por VIH , VIH-1 , Humanos , VIH-1/inmunología , VIH-1/genética , Vacunas contra el SIDA/inmunología , Infecciones por VIH/prevención & control , Infecciones por VIH/inmunología , Animales , Vacunas de ARNm , ARN Mensajero/genética , ARN Mensajero/inmunología , Vacunas Sintéticas/inmunología , SARS-CoV-2/inmunología , SARS-CoV-2/genética , COVID-19/prevención & control , COVID-19/inmunologíaRESUMEN
An effective HIV-1 vaccine is still not available, and most vaccine efficacy trials conducted over the years resulted in no significant overall protection. Here we highlight several insights gained from these trials as well as emerging questions that may be important for further guidance to advance current research directions.
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Vacunas contra el SIDA , Infecciones por VIH , VIH-1 , Inmunización Pasiva , Humanos , Vacunas contra el SIDA/administración & dosificación , Vacunas contra el SIDA/inmunología , Ensayos Clínicos como Asunto , Anticuerpos Anti-VIH/inmunología , Infecciones por VIH/prevención & control , Infecciones por VIH/inmunología , VIH-1/inmunología , Inmunización Pasiva/métodos , Eficacia de las VacunasRESUMEN
Background and aim: N-acetyl-p-benzoquinoneimine (NAPQI), a toxic byproduct of paracetamol (Acetaminophen, APAP), can accumulate and cause liver damage by depleting glutathione and forming protein adducts in the mitochondria. These adducts disrupt the respiratory chain, increasing superoxide production and reducing ATP. The goal of this study was to provide computational proof that succinate dehydrogenase (SDH), a subunit of complex II in the mitochondrial respiratory chain, is a favorable binding partner for NAPQI in this regard. Method: Molecular docking, molecular dynamics simulation, protein-protein interaction networks (PPI), and KEGG metabolic pathway analysis were employed to identify binding characteristics, interaction partners, and their associations with metabolic pathways. A lipid membrane was added to the experimental apparatus to mimic the natural cellular environment of SDH. This modification made it possible to develop a context for investigating the role and interactions of SDH within a cellular ecosystem that was more realistic and biologically relevant. Result: The molecular binding affinity score for APAP and NAPQI with SDH was predicted -6.5 and -6.7 kcal/mol, respectively. Furthermore, RMSD, RMSF, and Rog from the molecular dynamics simulations study revealed that NAPQI has slightly higher stability and compactness compared to APAP at 100 ns timeframe with mitochondrial SDH. Conclusion: This study serves to predict the mechanistic process of paracetamol toxicity by using different computational approaches. In addition, this study will provide information about the drug target against APAP hepatotoxicity.
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Rheumatoid arthritis (RA) is the most common inflammatory polyarthritis in Bangladesh. Bangladesh Rheumatology Society (BRS) proposes these management recommendations to treat the considerable burden of RA in the resource-constrained situation based on the best current evidence combined with societal challenges and opportunities. BRS formed a task force (TF) comprising four rheumatologists. The TF searched for all available literature, including updated American College of Rheumatology (ACR), European Alliance of Associations for Rheumatology (EULAR), and Asia-Pacific League of Associations for Rheumatology (APLAR) and several other guidelines, and systematic literature reviews until October 2023, and then a steering committee was formed, which included rheumatologists and internists. We followed the EULAR standard operating procedures to categorize levels of evidence and grading of recommendations. This recommendation has two parts -- general (diagnosis of RA, nomenclature of disease-modifying anti-rheumatic drugs [DMARDs], disease activity indices) and management portion. The TF agreed on four overarching principles and 12 recommendations. Overarching principles deal with early diagnosis and disease activity monitoring. Recommendations 1-5 discuss using glucocorticoids, NSAIDs, and conventional synthetic DMARDs (csDMARD). Recommendations 6-9 stretch the use of targeted synthetic DMARDs (tsDMARDs) and biological DMARDs (bDMARDs). The suggested DMARD therapy includes initiation with methotrexate (MTX) or another csDMARD (in case of contraindication to MTX) in the first phase and the addition of a tsDMARD in the second phase, switching to an alternative tsDMARDs or bDMARDs in the subsequent phases. The TF included the Padua prediction score for the thromboembolism risk estimation. Recommendations 10-12 cover infection screening, vaccination, and DMARD tapering. Bangladesh has a higher prevalence of RA. This recommendation will serve as a tool to treat this high burden of patients with RA scientifically and more effectively.
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Saltwater intrusion in the coastal areas of Bangladesh is a prevalent phenomenon. However, it is not conducive to activities such as irrigation, navigation, fish spawning and shelter, and industrial usage. The present study analyzed 45 water samples collected from 15 locations in coastal areas during three seasons: monsoon, pre-monsoon, and post-monsoon. The aim was to comprehend the seasonal variation in physicochemical parameters, including water temperature, pH, electrical conductivity (EC), salinity, total dissolved solids (TDS), hardness, and concentrations of Na+, K+, Mg2+, Ca2+, Fe2+, HCO3-, PO43-, SO42-, and Cl-. Additionally, parameters essential for agriculture, such as soluble sodium percentage (SSP), sodium absorption ratio (SAR), magnesium absorption ratio (MAR), residual sodium carbonate (RSC), Kelly's ratio (KR), and permeability index (PI), were examined. Their respective values were found to be 63%, 16.83 mg/L, 34.92 mg/L, 145.44 mg/L, 1.28 mg/L, and 89.29%. The integrated water quality index was determined using entropy theory and principal component analysis (PCA). The resulting entropy water quality index (EWQI) and SAR of 49.56% and 63%, respectively, indicated that the samples are suitable for drinking but unsuitable for irrigation. These findings can assist policymakers in implementing the Bangladesh Deltaplan-2100, focusing on sustainable land management, fish cultivation, agricultural production, environmental preservation, water resource management, and environmental protection in the deltaic areas of Bangladesh. This research contributes to a deeper understanding of seasonal variations in the hydrochemistry and water quality of coastal rivers, aiding in the comprehension of salinity intrusion origins, mechanisms, and causes.
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Agua Potable , Agua Subterránea , Contaminantes Químicos del Agua , Calidad del Agua , Monitoreo del Ambiente/métodos , Ríos , Bangladesh , Sodio/análisis , Contaminantes Químicos del Agua/análisis , Agua Subterránea/análisis , Agua Potable/análisis , IndiaRESUMEN
The mitogen-activated protein kinase (MAPK) signaling pathway, particularly the p38 MAPK and ERK1/2, has been implicated in the pathogenesis of Parkinson's disease (PD). Recent studies have shown that MAPK signaling pathway can influence the expression of matrix metalloproteinase 9 (MMP-9), known for its involvement in various physiological and pathological processes, including neurodegenerative diseases. This study explores the modulation of MMP-9 expression via the MAPK/ERK signaling cascade and its potential therapeutic implications in the context of PD-associated motor dysfunction. Here, tolperisone hydrochloride (TL), a muscle relaxant that blocks voltage-gated sodium and calcium channels, was used as a treatment to observe its effect on MAPK signaling and MMP-9 expression. Rotenone (RT) exposure in mice resulted in a significant reduction in substantia nigra and primary motor cortex neurons, which were further evidenced by impairments in motor function. When TL was administered, neuron count was restored (89.0 ± 4.78 vs 117.0 ± 4.46/mm2), and most of the motor dysfunction was alleviated. Mechanistically, TL reduced the protein expression of phospho-p38MAPK (1.06 fold vs 1.00 fold) and phospho-ERK1/2 (1.16 fold vs 1.02 fold), leading to the inhibition of MAPK signaling, as well as reduced MMP-9 concentrations (2.76 ± 0.10 vs 1.94 ± 0.10â¯ng/mL) in the process of rescuing RT-induced neuronal cell death and motor dysfunction. Computational analysis further revealed TL's potential inhibitory properties against MMP-9 along with N and L-type calcium channels. These findings shed light on TL's neuroprotective effects via MMP-9 inhibition and MAPK signaling downregulation, offering potential therapeutic avenues for PD-associated motor dysfunction.
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Inhibidores de la Metaloproteinasa de la Matriz , Enfermedad de Parkinson , Tolperisona , Animales , Masculino , Ratones , Regulación hacia Abajo/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Metaloproteinasa 9 de la Matriz/metabolismo , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Ratones Endogámicos C57BL , Actividad Motora/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Rotenona/farmacología , Tolperisona/farmacocinética , Tolperisona/uso terapéuticoRESUMEN
The envelope glycoprotein (Env) trimer on the surface of human immunodeficiency virus type I (HIV-1) mediates viral entry into host CD4+ T cells and is the sole target of neutralizing antibodies. Broadly neutralizing antibodies (bnAbs) that target gp120 V3-glycan of HIV-1 Env trimer are potent and block the entry of diverse HIV-1 strains. Most V3-glycan bnAbs interact, to a different extent, with a glycan attached to N332, but Asn at this position is not absolutely conserved or required for HIV-1 entry based on the prevalence of N332 in different circulating HIV-1 strains from diverse clades. Here, we studied the effects of amino acid changes at position 332 of HIV-1AD8 Envs on HIV-1 sensitivity to antibodies, cold exposure, and soluble CD4. We further investigated how these changes affect Env function and HIV-1 infectivity in vitro. Our results suggest robust tolerability of HIV-1AD8 Env N332 to changes, with specific changes that resulted in extended exposure of gp120 V3 loop, which is typically concealed in most primary HIV-1 isolates. Viral evolution leading to Asn at position 332 of HIVAD8 Envs is supported by the selection advantage of high levels of cell-cell fusion, transmission, and infectivity with high levels of cell surface expression and slightly higher gp120 shedding than most N332 variants. Thus, tolerance of HIV-1AD8 Envs to different amino acids at position 332 provides increased flexibility to respond to changing conditions/environments and evade the immune system. Modeling studies of the distance between N332 glycan and specific bnAbs were in agreement with N332 glycan dependency on bnAb neutralization. Overall, our studies provide insights into the contribution of specific amino acids at position 332 to Env antigenicity, stability on ice, and conformational states. IMPORTANCE: Glycan attached to amino acid asparagine at position 332 of HIV-1 envelope glycoproteins is a main target of a subset of broadly neutralizing antibodies that block HIV-1 infection. Here, we defined the contribution of different amino acids at this position to Env antigenicity, stability on ice, and conformational states.
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Infecciones por VIH , Seropositividad para VIH , VIH-1 , Humanos , Aminoácidos , Anticuerpos Neutralizantes , Anticuerpos ampliamente neutralizantes , Productos del Gen env del Virus de la Inmunodeficiencia Humana , Glicoproteínas , Anticuerpos Anti-VIH , Proteína gp120 de Envoltorio del VIH/genética , Hielo , PolisacáridosRESUMEN
ABSTRACT: Histiocytic disorders mostly occur as de-novo nodal or extranodal benign masses with rare secondary malignant transformation. A 10-year-old female presented with 10-cm cervical swelling since 9 months associated with fever. Computed tomography revealed left cervical lymphadenopathy and bilateral lung nodules. Lymph node excision biopsy showed effacement of architecture by atypical histiocytes with marked nuclear pleomorphism and frequent mitosis. Focal areas showed mature histiocytes with emperipolesis. The cells were immunopositive for CD68, CD163, and S100 (focal), whereas they were negative for Langerin and CD1a. The Ki67 proliferative index was 30%. A diagnosis of histiocytic sarcoma in a background of Rosai-Dorfman disease was made.
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Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Sarcoma Histiocítico , Histiocitosis Sinusal , Inmunohistoquímica , Tomografía Computarizada por Rayos X , Humanos , Femenino , Sarcoma Histiocítico/diagnóstico , Sarcoma Histiocítico/patología , Histiocitosis Sinusal/diagnóstico , Histiocitosis Sinusal/patología , Niño , Antígenos CD/análisis , Proteínas S100/análisis , Histiocitos/patología , Ganglios Linfáticos/patología , Biopsia , Histocitoquímica , Transformación Celular Neoplásica , Microscopía , Receptores de Superficie Celular/genética , Linfadenopatía/patología , Molécula CD68RESUMEN
Exosomes are nanometric membrane vesicles of late endosomal origin that are released by most, if not all, cell types as a sophisticated means of intercellular communication. They play an essential role in the movement of materials and information between cells, transport a variety of proteins, lipids, RNA, and other vital data, and over time, they become an essential part of the drug delivery system and a marker for the early detection of many diseases. Dendritic cells have generated interest in cancer immunotherapy due to their ability to initiate and modify effective immune responses. Apart from their cytokine release and direct interactions with other cell types, DCs also emit nanovesicles, such as exosomes, that contribute to their overall activity. Numerous studies have demonstrated exosomes to mediate and regulate immune responses against cancers. Dendritic cell-derived exosomes (DCs) have attracted a lot of attention as immunotherapeutic anti-cancer treatments since it was found that they contain functional MHC-peptide complexes along with a variety of other immune-stimulating components that together enable immune cell-dependent tumor rejection. By enhancing tumor and immunosuppressive immune cells or changing a pro-inflammatory milieu to inhibit tumor advancement, exosomes generated from dendritic cells can initiate and support tumor growth. This study reviewed the immunogenicity of dendritic cell-derived exosomes and strategies for expanding their immunogenic potential as novel and effective anti-cancer therapies.
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Exosomas , Neoplasias , Humanos , Exosomas/genética , Células Dendríticas , Neoplasias/patología , Inmunidad , InmunoterapiaRESUMEN
OBJECTIVE: This scoping review investigated the existing literature and identified the evidence gaps related to diagnosis and management in children aged 2-18 years presenting to hospitals with a co-diagnosis of asthma and community-acquired pneumonia. DATA SOURCES: We designed a scoping review following Arksey and O'Malley's scoping review framework and PRISMA extension for a scoping review. We searched literature using five electronic databases: PubMed, CINAHL, Scopus, Web of Science, and Embase from 2003 to June 2023. RESULTS: A total of 1599 abstracts with titles were screened and 12 abstracts were selected for full review. Separate guidelines including Modified Global Initiative for Asthma (GINA) guidelines; modified Integrated Management of Childhood Illness (IMCI) guidelines; and a consensus guideline developed by the Pediatric Infectious Diseases Society (PIDS) and Infectious Diseases Society of America (IDSA) were used for diagnosing asthma and CAP individually. Chest X-rays were used in 83.3% (10/12) of studies to establish the co-diagnosis of asthma-CAP in children. Variations were observed in using different laboratory investigations across the studies. Infectious etiologies were detected in five (41.7%) studies. In 75% (9/12) of studies, children with asthma-CAP co-diagnosis were treated with antimicrobials, however, bacterial etiology was not reported in 44.4% (4/9) of the studies. CONCLUSIONS: Our scoping review suggests that chest X-rays are commonly used to establish the co-diagnosis of asthma-CAP and antibiotics are often used without laboratory confirmation of a bacterial etiology. Clinical practice guidelines for the management of asthma and pneumonia in children who present with co-diagnosis may standardize clinical care and reduce variation.
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Asma , Enfermedades Transmisibles , Infecciones Comunitarias Adquiridas , Neumonía , Niño , Humanos , Asma/diagnóstico , Asma/tratamiento farmacológico , Neumonía/diagnóstico , Neumonía/tratamiento farmacológico , Antibacterianos/uso terapéutico , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Enfermedades Transmisibles/tratamiento farmacológicoRESUMEN
The envelope glycoprotein (Env) trimer on the surface of human immunodeficiency virus type I (HIV-1) mediates viral entry into host CD4+ T cells and is the sole target of neutralizing antibodies. Broadly neutralizing antibodies (bnAbs) that target gp120 V3-glycan of HIV-1 Env trimer are potent and block the entry of diverse HIV-1 strains. Most V3-glycan bnAbs interact, to a different extent, with a glycan attached to N332 but Asn at this position is not absolutely conserved or required for HIV-1 entry based on prevalence of N332 in different circulating HIV-1 strains from diverse clades. Here, we studied the effects of amino acid changes at position 332 of HIV-1AD8 Envs on HIV-1 sensitivity to antibodies, cold exposure, and soluble CD4. We further investigated how these changes affect Env function and HIV-1 infectivity in vitro. Our results suggest robust tolerability of HIV-1AD8 Env N332 to changes with specific changes that resulted in extended exposure of gp120 V3 loop, which is typically concealed in most primary HIV-1 isolates. Viral evolution leading to Asn at position 332 of HIVAD8 Envs is supported by the selection advantage of high levels of cell-cell fusion, transmission, and infectivity even though cell surface expression levels are lower than most N332 variants. Thus, tolerance of HIV-1AD8 Envs to different amino acids at position 332 provides increased flexibility to respond to changing conditions/environments and to evade the immune system. Modeling studies of the distance between N332 glycan and specific bnAbs was in agreement with N332 glycan dependency on bnAb neutralization. Overall, our studies provide insights into the contribution of specific amino acids at position 332 to Env antigenicity, stability on ice, and conformational states.
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OBJECTIVE: To measure the severity of allergic rhinitis (AR) and different types of headaches in patients with septal deviation before and after septoplasty. METHODS: This multicentre, prospective, longitudinal, observational study enrolled patients with deviated nasal septum, nasal symptoms and headaches associated with persistent AR lasting at least 2 months without resolution. The nasal obstruction evaluation (NOSE) scale, immunoglobulin-E (Ig-E) levels and visual analogue scale (VAS) for headache pain severity were evaluated before and after septoplasty using Wilcoxon signed-rank test. RESULTS: A total of 196 patients were enrolled in the study (102 males; 94 females). A total of 134 patients (68%) were diagnosed with severe AR and 166 (85%) experienced headaches with AR. The majority (100 of 166 patients; 60%) had sinusoidal headaches, while 25% (42 of 166 patients) reported a combination of sinusoidal headache and migraine and 14% (24 of 166 patients) experienced migraines. A comparison of preoperative and postoperative Ig-E levels, NOSE and VAS scores demonstrated that septoplasty significantly improved AR symptoms and headaches. Although there were significant improvements in headaches overall post-septoplasty, only the sinusoidal components improved, while migraine remained unaffected. CONCLUSION: Septoplasty improved AR and sinusoidal headaches in patients with septal deviation, but migraines remained unaffected.
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Trastornos Migrañosos , Obstrucción Nasal , Rinitis Alérgica , Masculino , Femenino , Humanos , Estudios Prospectivos , Resultado del Tratamiento , Tabique Nasal/cirugía , Rinitis Alérgica/complicaciones , Rinitis Alérgica/cirugía , Obstrucción Nasal/cirugía , Obstrucción Nasal/complicaciones , Obstrucción Nasal/diagnóstico , Cefalea/etiología , Trastornos Migrañosos/complicaciones , Trastornos Migrañosos/cirugíaRESUMEN
Acne vulgaris (AV) is a psychosomatic disorder and can negatively affect individuals, especially in terms of psychological well-being, self-esteem, and quality of life (QoL). The current study aimed to investigate the association between AV and psychological health, as well as the influence of acne and psychological distress in predicting patients' self-esteem and QoL. This cross-sectional study included 150 patients clinically diagnosed with AV. The severity of acne was measured using GAGS, and following that, patients were instructed to complete the following forms: DASS-21, RSES, CADI, DLQI, and WHOQoL. Female AV patients had significantly higher depression (p = 0.003, t = 3.025) and anxiety (p < 0.001, t = 3.683). Pearson's correlation analysis indicated a strong, positive, and significant correlation between having acne and experiencing depression (r = 0.630), anxiety (r = 0.661), and stress (r = 0.758) (p < 0.001). Multiple regression analysis suggested acne and associated psychological distress had a significant and negative impact on the patient's self-esteem and quality of life. This study highlights the multifaceted consequences of AV and the need to manage its psychological distress. It emphasizes the need for holistic patient care that addresses acne's physical and emotional aspects, with the ultimate goal of enhancing well-being and QoL.
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Acné Vulgar , Distrés Psicológico , Humanos , Femenino , Calidad de Vida/psicología , Estudios Transversales , Índice de Severidad de la EnfermedadRESUMEN
An effective human immunodeficiency virus type I (HIV-1) vaccine that robustly elicits broadly neutralizing antibodies (bnAbs) against HIV-1 envelope glycoproteins (Envs) to block viral entry is still not available. Thus, identifying triggers for elicitation of different types of anti-HIV-1 Env antibodies by vaccination could provide further guidance for immunogen design and vaccine development. Here, we studied the immune response to HIV-1 Env immunogens in rabbits. We show that sequential immunizations with conformation-specific Env immunogens can elicit low titer but broad neutralization responses against heterologous, neutralization-resistant (tier 2/3) transmitted/founder (T/F) HIV-1 strains. More importantly, an mRNA vaccine candidate that could mediate the presentation of a cytoplasmic tail-deleted (ΔCT) HIV-1AD8 Env immunogen on virus-like particles significantly increased the neutralization response. This strategy shifted the type of elicited antibodies, decreasing the level of binding to soluble Envs while significantly increasing their overall viral neutralization activity. The breadth and potency of neutralizing response against heterologous, T/F HIV-1 strains significantly increased in a subset of rabbits. Efficient neutralization activity was associated with high cellular immune responses specific to HIV-1 Envs. These results help to understand the immune response to different immunization schemes and will allow developing new approaches to selectively manipulate the type of humoral immune response by specific vaccination.
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AIMS: Dysregulation of PI3K/Akt/GSK3ß signaling has been implicated in various neurological disorders, including autism spectrum disorder (ASD). G protein-coupled receptor 55 (GPR55) has recently emerged as a potential regulator of this signaling cascade. This study explores the intricate modulation of the PI3K/Akt/GSK3ß signaling cascade via GPR55 activation and its potential therapeutic implications in the context of autism-associated neuronal impairments. MAIN METHODS: Valproic acid (VPA) was administered on embryonic day 12 (E12) to induce ASD, and lysophosphatidylinositol (LPI), a GPR55 agonist, was used prenatally to modulate the receptor activity. Golgi-cox staining was performed to observe neuronal morphology, and Hematoxylin and eosin (H and E) staining was carried out to quantify damaged neurons. Enzyme-linked immunosorbent assay (ELISA) was implemented to identify molecular mediators involved in neuroprotection. KEY FINDINGS: Prenatal VPA exposure resulted in significant abnormalities in synaptic development, which were further evidenced by impairments in social interaction and cognitive function. When LPI was administered, most of the synaptic abnormalities were alleviated, as reflected by higher neuron and dendritic spine count. LPI treatment also reduced cytoplasmic cytochrome c concentration and related neuronal cell death. Mechanistically, GPR55 activation by LPI increases the expression of phospho-Akt and phospho-GSK3ß, leading to the activation of this signaling in the process of rescuing synaptic abnormalities and mitochondria-mediated neuronal apoptosis. SIGNIFICANCE: The observed therapeutic effects of GPR55 activation shed light on its significance as a prospective target for ameliorating mitochondrial dysfunction and dendritic spine loss, offering novel prospects for developing targeted interventions to alleviate the neuropathological causes of ASD.
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Trastorno del Espectro Autista , Receptores Acoplados a Proteínas G , Humanos , Trastorno del Espectro Autista/tratamiento farmacológico , Glucógeno Sintasa Quinasa 3 beta , Lisofosfolípidos/metabolismo , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Receptores Acoplados a Proteínas G/metabolismo , Ácido Valproico/farmacologíaRESUMEN
Hemochromatosis is a genetic disorder characterized by excessive absorption and accumulation of iron in the body. It is one of the most common inherited disorders. The excess iron deposition can cause damage to various organs, including the liver, heart, pancreas, and joints. If left untreated, hemochromatosis can lead to serious complications such as cirrhosis, diabetes, heart failure, and increased risk of certain cancers. Iron overload in hemochromatosis significantly affects the cardiovascular system, leading to morbidity and mortality. This article reviews the current literature describing the pathogenesis and various cardiovascular manifestations of hemochromatosis, including dilated cardiomyopathy, conduction abnormalities, heart failure, cardiac fibrosis, myocardial infarction, and valvular heart disease. This article aims to provide a detailed understanding of the cardiovascular manifestations associated with hemochromatosis and their underlying mechanisms through a review of current literature in publicly available databases.
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Concentration, source, ecological and health risks of sixteen polycyclic aromatic hydrocarbons (PAHs) were estimated for water and sediment samples of two urban rivers namely Buriganga River (BR) and Dhaleswari River (DR). The mean concentration of ∑PAHs in BR water and sediment were 9619.2 ngL-1 and 351.6 ngg-1, respectively. Furthermore, the average PAH concentrations detected in DR water and sediment were 1979.1 ngL-1 and 792.9 ngg-1, respectively. The composition profile showed that 3-ring PAHs were dominant in the water matrix; however, 5-ring PAHs were prevalent in the sediment samples of both rivers. Sources apportion study of PAHs indicated that mixed combustion and petroleum sources are responsible for PAHs contamination in the rivers. Ecological risk study of water suggested that the aquatic lives of both rivers are threatened by Fla, BbF, BkF, DahA, and IcdP, as presented above the threshold level. Comparison with sediment quality guidelines (SQGs) indicated that adverse effects might cause occasionally in the sediment ecosystem in DR at certain sampling sites for Nap, Acy, Fl, Phe, Ant, Pyr, Chr, BaP, and DahA. On the other hand, the presence of Nap, Acy and DahA might occasionally cause adverse biological effects in the BR sediment ecosystem. Estimated hazard quotient (HI > 1) and carcinogenic risk (CRtotal > 10-4) values indicated that local inhabitants living in the vicinity of the rivers are prone to high health risks.
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In this study, a carbon-based adsorbent was developed from waste newspaper through pyrolysis at 800 °C to evaluate the removal efficiency of polycyclic aromatic hydrocarbons (Benzo[ghi]perylene (BghiP) and Indeno [1,2,3-cd] pyrene (IP)) from wastewater. The surface area of the developed adsorbent was estimated at 509.247m2g-1 which allowed the adsorption of the PAHs from wastewater. The maximum adsorption capacity was estimated at 138.436 µg g-1 and 228.705 µg g-1 for BghiP and IP, respectively and the highest removal efficiency was observed at pH 2. Around 91% removal efficiency was observed at pH 7 for both pollutants. Experimental adsorption data were fit for pseudo-second-order kinetics and Langmuir isotherm models, which demonstrate electrostatic interaction, monolayered deposition, hydrogen bonding, and π-π interaction between adsorbate and adsorbent which play a significant role in adsorption. The regeneration study described that the developed adsorbent could be able to intake 52.75% BghiP and 48.073% IP until the 8th and 6th cycles, respectively. The removal efficiency of the adsorbent in the real sample was also evaluated. This study will provide a method to convert waste material into adsorbent and will remove PAHs from wastewater as a function of pollutant mitigation and waste management.