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The interplay between lipid metabolism and immune response in macrophages plays a pivotal role in various infectious diseases, notably tuberculosis (TB). Herein, we illuminate the modulatory effect of heat-killed Mycobacterium tuberculosis (HKMT) on macrophage lipid metabolism and its implications on the inflammatory cascade. Our findings demonstrate that HKMT potently activates the lipid scavenger receptor, CD36, instigating lipid accumulation. While CD36 inhibition mitigated lipid increase, it unexpectedly exacerbated the inflammatory response. Intriguingly, this paradoxical effect was linked to an upregulation of PPARδ. Functional analyses employing PPARδ modulation revealed its central role in regulating both lipid dynamics and inflammation, suggesting it as a potential therapeutic target. Moreover, primary monocytic cells from diabetic individuals, a demographic at amplified risk of TB, exhibited heightened PPARδ expression and inflammation, further underscoring its pathological relevance. Targeting PPARδ in these cells effectively dampened the inflammatory response, offering a promising therapeutic avenue against TB.
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BACKGROUND: Out-of-pocket (OOP) payment is one of many countries' main financing options for health care. High OOP payments push them into financial catastrophe and the resultant impoverishment. The infrastructure, society, culture, economic condition, political structure, and every element of the physical and social environment influence the intensity of financial catastrophes in health expenditure. Hence, the incidence of Catastrophic Health Expenditure (CHE) must be studied more intensively, specifically from regional aspects. This systematic review aims to make a socio-ecological synthesis of the predictors of CHE. METHOD: We retrieved data from Scopus and Web of Science. This review followed PRISMA guidelines. The interest outcomes of the included literature were the incidence and the determinants of CHE. This review analyzed the predictors in light of the socio-ecological model. RESULTS: Out of 1436 screened documents, fifty-one met the inclusion criteria. The selected studies were quantitative. The studies analyzed the socioeconomic determinants from the demand side, primarily focused on general health care, while few were disease-specific and focused on utilized care. The included studies analyzed the interpersonal, relational, and institutional predictors more intensively. In contrast, the community and policy-level predictors are scarce. Moreover, neither of the studies analyzed the supply-side predictors. Each CHE incidence has different reasons and different outcomes. We must go with those case-specific studies. Without the supply-side response, it is difficult to find any effective solution to combat CHE. CONCLUSION: Financial protection against CHE is one of the targets of sustainable development goal 3 and a tool to achieve universal health coverage. Each country has to formulate its policy and enact laws that consider its requirements to preserve health rights. That is why the community and policy-level predictors must be studied more intensively. Proper screening of the cause of CHE, especially from the perspective of the health care provider's perspective is required to identify the individual, organizational, community, and policy-level barriers in healthcare delivery.
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Enfermedad Catastrófica , Gastos en Salud , Humanos , Gastos en Salud/estadística & datos numéricos , Enfermedad Catastrófica/economía , Factores Socioeconómicos , Financiación Personal/estadística & datos numéricosRESUMEN
This study investigates the well-being effect of international migration and remittance on human and gender development in selected South Asian countries. The study has adopted panel regression analysis using secondary data from the World Development Indicators and United Nations Development Programme. This database contains information on seven South Asian countries from 1995 to 2020. The study simultaneously applied the Levin-Lin-Chu, Breitung and IM-Pesaran unit root tests to check the stationarity of data. After satisfying the condition, econometric models such as Fixed and Random Effects were executed. Pesaran's test of cross-sectional independence, the Westerlund test for cointegration and VIF tests were performed in order to check the robustness of the results. As a post-diagnostic tool, the Hausman test suggests that the Fixed Effect models are appropriate for each estimation. The results demonstrate that personal remittance positively and significantly affects human and gender development. Similarly, international migration significantly influences human development while negatively affecting gender development. The study suggests that these countries should prioritize attaining higher remittances by sending more international migrants. Similarly, the provision of cheaper formal channels for remitting money and giving incentives can be effective for higher remittance inflow. Moreover, negotiation at the government-to-government level can effectively expand the international labour market of the selected countries.
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Países en Desarrollo , Emigración e Inmigración , Humanos , Demografía , Dinámica Poblacional , Estudios TransversalesRESUMEN
BACKGROUND: Organ transplantation is an effective therapy for end-stage organ failure. However, there is a large gap between the need for and the supply of donor organs. OBJECTIVES: This study aimed to assess nursing students' knowledge and attitudes about organ donation. MATERIALS AND METHODS: This is a descriptive cross-sectional design study. The study was conducted at four faculties of nursing, which were Baghdad, Misan, Tikrit, and Kirkuk in Iraq. The three tools included are as follows: I: Socio-Demographic Questionnaire; II: Organ-Tissue Donation and Transplantation Knowledge Scale (ODTKS); and III: Organ Donation Attitude Scale (ODAS). RESULTS: More than two-thirds (71%) of the studied students have an accepted level of knowledge, while 70% of the studied students had a positive attitude toward organ donation and transplantation. There were statistically significant differences (P- value <0.05) between socio-demographic characteristics and knowledge level regarding gender, marital status, and academic year. Also, there were significant differences between socio-demographic characteristics and students' attitude levels regarding gender and academic year. CONCLUSION: More than two-thirds of students had a good and fair level of knowledge and a positive attitude toward organ donation and transplantation. Providing lectures within the curriculum is needed for students to raise their knowledge and attitude about organ transplantation and donation.
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The repair of mandibular defects is a challenging clinical problem, and associated infections often hinder the treatment, leading to failure in bone regeneration. Herein, a multifunctional platform is designed against the shortages of existing therapies for infected bone deficiency. 2D Ti3C2 MXene and berberine (BBR) are effectively loaded into 3D printing biphasic calcium phosphate (BCP) scaffolds. The prepared composite scaffolds take the feature of the excellent photothermal capacity of Ti3C2 as an antibacterial, mediating NIR-responsive BBR release under laser stimuli. Meanwhile, the sustained release of BBR enhances its antibacterial effect and further accelerates the bone healing process. Importantly, the integration of Ti3C2 improves the mechanical properties of the 3D scaffolds, which are beneficial for new bone formation. Their remarkable biomedical performances in vitro and in vivo present the outstanding antibacterial and osteogenic properties of the Ti3C2-BBR functionalized BCP scaffolds. The synergistic therapy makes it highly promising for repairing infected bone defects and provides insights into a wide range of applications of 2D nanosheets in biomedicine.
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Berberina , Hidroxiapatitas , Nitritos , Andamios del Tejido , Elementos de Transición , Berberina/farmacología , Regeneración Ósea , Antibacterianos/farmacología , Impresión TridimensionalRESUMEN
Diaphragmatic injuries, particularly on the right side, are a rare yet challenging clinical scenario, especially when associated with other injuries. We present the case of a 38-year-old male patient who sustained a fall from a significant height, resulting in blunt abdominal trauma, chest injuries, right-side diaphragmatic injury, a grade 4 liver injury, and fractures of the right ribs, right femur, and pelvis. The patient also suffered a lung laceration with hemopneumothorax. The clinical team managed these injuries through a video-assisted thoracoscopy, laparotomy, and primary repair of the diaphragmatic rupture. The postoperative course was complicated by a low-output bile leak and infection of the orthopedic surgical wound, but these were effectively managed, and the patient showed a steady recovery. This case underscores the complexity of managing traumatic injuries that span multiple body regions and systems, requiring a coordinated, multidisciplinary approach. It also highlights the critical role of timely intervention and appropriate surgical strategies in the successful recovery of patients from complex traumas.
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The genus Prototheca is an extremely unusual group of achlorophyllic, obligately heterotrophic algae. Six species have been identified as pathogens of vertebrates, including cattle and humans. In cattle, P. bovis is the main infectious pathogen and is associated with bovine mastitis. In contrast, human infections typically involve P. wickerhamii and are associated with a spectrum of varying clinical presentations. Prototheca spp. enter the host from the environment and are therefore likely to be initially recognized by cells of the innate immune system. However, little is known about the nature of the interaction between Prototheca spp. and host phagocytes. In the present study, we adopt a live-cell imaging approach to investigate these interactions over time. Using environmental and clinical strains, we show that P. bovis cells are readily internalized and processed by macrophages, whereas these immune cells struggle to internalize P. wickerhamii. Serum opsonization of P. wickerhamii only marginally improves phagocytosis, suggesting that this species (but not P. bovis) may have evolved mechanisms to evade phagocytosis. Furthermore, we show that inhibition of the kinases Syk or PI3K, which are both critical for innate immune signaling, drastically reduces the uptake of P. bovis. Finally, we show that genetic ablation of MyD88, a signaling adaptor critical for Toll-like receptor signaling, has little impact on uptake but significantly prolongs phagosome maturation once P. bovis is internalized. Together, our data suggest that these two pathogenic Prototheca spp. have very different host-pathogen interactions which have potential therapeutic implications for the treatment of human and animal disease.
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Prototheca , Humanos , Femenino , Animales , Bovinos , Prototheca/genética , Fagocitosis , Macrófagos , Fagocitos , Transducción de SeñalRESUMEN
Osteoporosis is a common disease, especially among the elderly. This study aimed to comprehensively examine the roles of immune microenvironment in osteoporosis pathogenesis. Expression profiles of GSE35959, GSE7158, and GSE13850 datasets were used to analyze differential expression and identify hub genes related to immune features. Based on the single-cell RNA sequencing (scRNA-seq) data of an osteoporosis patient, different cell types were classified and the relation between immune environment and osteoporosis was explored. Twelve hub genes significantly associated with immune features were selected and 11 subgroups were defined using scRNA-seq data. The expression of two hub genes (CDKN1A and TEFM) was greatly altered during the transformation from mesenchymal stem cells (MSCs) to osteoblasts. Chemokines and chemokine receptors were differentially enriched in different cell types. CXCL12 was high-expressed in MSCs. This study emphasized that immune microenvironment played a critical role in the pathogenesis of osteoporosis. Chemokines and chemokine receptors can modify cell development and affect the interactions among different cell types, leading to unbalanced bone remodeling.
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Osteoporosis , Humanos , Anciano , Células Cultivadas , Osteoporosis/genética , Quimiocinas/genética , Receptores de Quimiocina/genética , Análisis de Secuencia de ARNRESUMEN
Phototherapy, which generally refers to photothermal therapy (PTT) and photodynamic therapy (PDT), has received significant attention over the past few years since it is non-invasive, has effective selectivity, and has few side effects. As a result, it has become a promising alternative to traditional clinical treatments. At present, two-dimensional materials (2D materials) have proven to be at the forefront of the development of advanced nanomaterials due to their ultrathin structures and fascinating optical properties. As a result, much work has been put into developing phototherapy platforms based on 2D materials. This review summarizes the current developments in 2D materials beyond graphene for phototherapy, focusing on the novel approaches of PTT and PDT. New methods are being developed to go above and beyond conventional treatment to fully use the potential of 2D materials. Additionally, the efficacy of cutting-edge phototherapy is assessed, and the existing difficulties and future prospects of 2D materials for phototherapy are covered.
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The C-type lectin receptors (CLRs) Dectin-1 and Dectin-2 are involved in several innate immune responses and are expressed mainly in dendritic cells, monocytes, and macrophages. Dectin-1 activation exacerbates obesity, inflammation, and insulin resistance/type 2 diabetes (T2D). However, the role of Dectin-2 is not clear in T2D. This study aims to evaluate the expression and function of Dectin-2 in peripheral blood mononuclear cells (PBMCs) isolated from diabetic patients and non-diabetic controls. Flow-cytometry and qRT-PCR were performed to evaluate the expression of Dectin-2 in different leukocyte subpopulations isolated from T2D patients (n = 10) and matched non-diabetic controls (n = 11). The functional activity of Dectin-2 was identified in PBMCs. CRP, IL-1ß, and TNF-α concentrations were determined by ELISA. siRNA transfection and Western blotting were performed to assess p-Syk and p-NF-kB expression. siRNA transfection was performed to knock down the gene of interest. Our results show that Dectin-2 expression was the highest in monocytes compared with other leukocyte subpopulations. The expression of Dectin-2 was significantly increased in the monocytes of T2D patients compared with non-diabetic controls. Dectin-2 expression positively correlated with markers of glucose homeostasis, including HOMA-IR and HbA1c. The expression of inflammatory markers was elevated in the PBMCs of T2D patients. Interestingly, SOCS3, a negative regulator of inflammation, was expressed significantly lowlier in the PBMCs of T2D patients. Moreover, SOCS3 expression was negatively correlated with Dectin-2 expression level. The further analysis of inflammatory signaling pathways showed a persistent activation of the Dectin-2-Syk-NFkB pathway that was instigated by the diminished expression of SOCS3. Dectin-2 activation failed to induce SOCS3 expression and suppress subsequent inflammatory responses in the PBMCs of diabetic patients. siRNA-mediated knockdown of SOCS3 in PBMCs displayed a similar inflammatory phenotype to diabetic PBMCs when exposed to Dectin-2 ligands. Altogether, our findings suggest that elevated Dectin-2 and its relationship with SOCS3 could be involved in the abnormal immune response observed in T2D patients.
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Diabetes Mellitus Tipo 2 , Lectinas Tipo C , Leucocitos Mononucleares , Proteína 3 Supresora de la Señalización de Citocinas , Biomarcadores/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Inflamación/metabolismo , Leucocitos Mononucleares/metabolismo , FN-kappa B/metabolismo , ARN Interferente Pequeño/metabolismo , Proteína 3 Supresora de la Señalización de Citocinas/metabolismoRESUMEN
Smart biomaterials have been rapidly advancing ever since the concept of tissue engineering was proposed. Interacting with human cells, smart biomaterials can play a key role in novel tissue morphogenesis. Various aspects of biomaterials utilized in or being sought for the goal of encouraging bone regeneration, skin graft engineering, and nerve conduits are discussed in this review. Beginning with bone, this study summarizes all the available bioceramics and materials along with their properties used singly or in conjunction with each other to create scaffolds for bone tissue engineering. A quick overview of the skin-based nanocomposite biomaterials possessing antibacterial properties for wound healing is outlined along with skin regeneration therapies using infrared radiation, electrospinning, and piezoelectricity, which aid in wound healing. Furthermore, a brief overview of bioengineered artificial skin grafts made of various natural and synthetic polymers has been presented. Finally, by examining the interactions between natural and synthetic-based biomaterials and the biological environment, their strengths and drawbacks for constructing peripheral nerve conduits are highlighted. The description of the preclinical outcome of nerve regeneration in injury healed with various natural-based conduits receives special attention. The organic and synthetic worlds collide at the interface of nanomaterials and biological systems, producing a new scientific field including nanomaterial design for tissue engineering.
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Nanocompuestos , Ingeniería de Tejidos , Antibacterianos , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/uso terapéutico , Humanos , PolímerosRESUMEN
Recently, cardiac arrhythmia recognition from electrocardiography (ECG) with deep learning approaches is becoming popular in clinical diagnosis systems due to its good prognosis findings, where expert data preprocessing and feature engineering are not usually required. But a lightweight and effective deep model is highly demanded to face the challenges of deploying the model in real-life applications and diagnosis accurately. In this work, two effective and lightweight deep learning models named Deep-SR and Deep-NSR are proposed to recognize ECG beats, which are based on two-dimensional convolution neural networks (2D CNNs) while using different structural regularizations. First, 97720 ECG beats extracted from all records of a benchmark MIT-BIH arrhythmia dataset have been transformed into 2D RGB (red, green, and blue) images that act as the inputs to the proposed 2D CNN models. Then, the optimization of the proposed models is performed through the proper initialization of model layers, on-the-fly augmentation, regularization techniques, Adam optimizer, and weighted random sampler. Finally, the performance of the proposed models is evaluated by a stratified 5-fold cross-validation strategy along with callback features. The obtained overall accuracy of recognizing normal beat and three arrhythmias (V-ventricular ectopic, S-supraventricular ectopic, and F-fusion) based on the Association for the Advancement of Medical Instrumentation (AAMI) is 99.93%, and 99.96% for the proposed Deep-SR model and Deep-NSR model, which demonstrate that the effectiveness of the proposed models has surpassed the state-of-the-art models and also expresses the higher model generalization. The received results with model size suggest that the proposed CNN models especially Deep-NSR could be more useful in wearable devices such as medical vests, bracelets for long-term monitoring of cardiac conditions, and in telemedicine to accurate diagnose the arrhythmia from ECG automatically. As a result, medical costs of patients and work pressure on physicians in medicals and clinics would be reduced effectively.
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Algoritmos , Complejos Prematuros Ventriculares , Electrocardiografía , Frecuencia Cardíaca , Humanos , Redes Neurales de la Computación , Procesamiento de Señales Asistido por ComputadorRESUMEN
Atherosclerosis is a chronic degenerative disorder characterized by lipid-dense plaques and low-grade inflammation affecting arterial walls. Foamy macrophages are important in the formation of atherosclerotic plaques and the induction of low-grade inflammation. The presence of lipid-laden macrophages has occurred in infections caused by opportunistic pathogens. Candida albicans is the major cause of candidiasis in immunocompromised patients, including those with diabetes mellitus. However, the role played by C. albicans in macrophage foaming and the associated inflammation is poorly understood. We investigated whether C. albicans induces foaming along with inflammation in macrophages and, if so, by which mechanism(s). We incubated THP-1 macrophages with heat-killed C. albicans (HKCA). HKCA-induced lipid accumulation in macrophages along with increased expression of inflammatory markers, including CD11b and CD11c or expression and secretion of IL-1ß. HKCA also increased the expression of PPARγ, CD36, and FABP4 in macrophages. Mechanistically, we found that the foamy and inflammatory macrophage phenotype induced by HKCA requires FABP4 because disruption of FABP4 in macrophages either by chemical inhibitor BMS309404 or small interfering RNA (siRNA) abrogated foam cell formation and expression of inflammatory markers CD11b, CD11c, and IL-1ß. Furthermore, HKCA-treated macrophages displayed high expression and secretion of MMP-9. Inhibition of FABP4 resulted in suppression of HCKA-induced MMP-9 production. Overall, our results demonstrate that C. albicans induces foam cell formation, inflammation, and MMP-9 expression in macrophages via the upregulation of FABP4, which may constitute a novel therapeutic target for treating C. albicans-induced atherosclerosis.
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Autoimmune diseases are driven largely by a pathogenic cytokine milieu produced by aberrantly activated lymphocytes. Many cytokines, including interferon gamma (IFN-γ), utilize the JAK/STAT pathway for signal propagation. Suppressor of Cytokine Signaling-1 (SOCS1) is an inducible, intracellular protein that regulates IFN-γ signaling by dampening JAK/STAT signaling. Using Fas deficient, MRL/MpJ-Faslpr/J (MRL/lpr) mice, which develop lupus-like disease spontaneously, we tested the hypothesis that a peptide mimic of the SOCS1 kinase inhibitory region (SOCS1-KIR) would inhibit lymphocyte activation and modulate lupus-associated pathologies. Consistent with in vitro studies, SOCS1-KIR intraperitoneal administration reduced the frequency, activation, and cytokine production of memory CD8+ and CD4+ T lymphocytes within the peripheral blood, spleen, and lymph nodes. In addition, SOCS1-KIR administration reduced lymphadenopathy, severity of skin lesions, autoantibody production, and modestly reduced kidney pathology. On a cellular level, peritoneal SOCS1-KIR administration enhanced Foxp3 expression in total splenic and follicular regulatory T cells, reduced the effector memory/naïve T lymphocyte ratio for both CD4+ and CD8+ cells, and reduced the frequency of GL7+ germinal center enriched B cells. Together, these data show that SOCS1-KIR treatment reduced auto-reactive lymphocyte effector functions and suggest that therapeutic targeting of the SOCS1 pathway through peptide administration may have efficacy in mitigating autoimmune pathologies.
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Enfermedades Autoinmunes/tratamiento farmacológico , Factores de Transcripción Forkhead/genética , Lupus Eritematoso Sistémico/tratamiento farmacológico , Péptidos/farmacología , Proteína 1 Supresora de la Señalización de Citocinas/genética , Animales , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Linfocitos B/efectos de los fármacos , Biomimética , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD8-positivos/efectos de los fármacos , Citocinas/genética , Interferón gamma/genética , Quinasas Janus/genética , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/inmunología , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/inmunología , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Ratones Endogámicos MRL lpr , Péptidos/síntesis química , Factores de Transcripción STAT/genética , Bazo/efectos de los fármacos , Bazo/inmunología , Proteína 1 Supresora de la Señalización de Citocinas/farmacología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Receptor fas/genéticaRESUMEN
PURPOSE: To compare reduction in intraocular pressure (IOP) and IOP-lowering medication in eyes undergoing excisional goniotomy with Kahook Dual Blade (KDB) vs iStent microbypass implantation, both combined with phacoemulsification, in eyes with mild to moderate open-angle glaucoma (OAG). SETTING: Nine practices in the United States. DESIGN: Prospective, randomized, active-controlled, parallel-group clinical trial. METHODS: Eyes were randomized to KDB-Phaco or iStent-Phaco group. Demographics, corrected distance visual acuity, IOP, IOP-lowering medications, and adverse events were collected at baseline and at day 1, week 1, and months 1, 3, 6, and 12 postoperatively. The primary outcome measure was the proportion of eyes at 12 months with IOP reduction of 20% or greater or IOP medication reduction of 1 or more compared with baseline. RESULTS: For this study, 164 eyes of 164 patients were analyzed (82 in each group). Mean IOP was reduced at 12 months compared with baseline from 18.5 (standard of error 0.4) to 15.4 (0.4) mm Hg in the KDB-Phaco group and from 18.5 (0.3) to 16.1 (0.4) mm Hg in the iStent-Phaco group (P = .24). Mean IOP-lowering medications were reduced from 1.3 (0.1) to 0.3 (0.1) in the KDB-Phaco group and from 1.4 (0.1) to 0.4 (0.1) in the iStent-Phaco group (P = .17). Among study completers, the primary outcome was attained in 74 (93.7%) of 79 patients of KDB-Phaco eyes and 65 (83.3%) of 78 patients of iStent-Phaco eyes (P = .04). Both procedures had similar safety profiles. CONCLUSIONS: Both procedures lowered both IOP and the need for IOP-lowering medications effectively and safely in eyes with mild to moderate OAG and cataract. Significantly, more KDB-Phaco eyes than iStent-Phaco eyes met the primary outcome of 20% or greater IOP reduction or 1 or more medication reduction at 12 months.
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Glaucoma de Ángulo Abierto , Trabeculectomía , Glaucoma de Ángulo Abierto/cirugía , Humanos , Presión Intraocular , Estudios Prospectivos , Estudios Retrospectivos , Stents , Malla TrabecularRESUMEN
Phagocytosis is a receptor-mediated process critical to innate immune clearance of pathogens. It proceeds in a regulated sequence of stages: (a) migration of phagocytes towards pathogens, (b) recognition of PAMPs and binding through PRRs, (c) engulfment and internalisation into phagosomes, (d) phagosome maturation, and (e) killing of pathogen or host cells. However, little is known about the role that individual receptors play in these discrete stages in the recognition of fungal cells. In a previous study, we found that dectin-2 deficiency impacted some but not all stages of macrophage-mediated phagocytosis of Candida glabrata. Because the C-type lectin receptor dectin-2 critically requires coupling to the FcRγ chain for signalling, we hypothesised that this coupling may be important for regulating phagocytosis of fungal cargo. We therefore examined how deficiency in FcRγ itself or two receptors to which it couples (dectin-2 and mincle) impacts phagocytosis of six fungal organisms representing three different fungal taxa. Our data show that deficiency in these proteins impairs murine bone marrow-derived macrophage migration, engulfment, and phagosome maturation, but not macrophage survival. Therefore, FcRγ engagement with selective C-type lectin receptors (CLRs) critically affects the spatio-temporal dynamics of fungal phagocytosis.
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Hongos/inmunología , Fagocitosis , Receptores de Reconocimiento de Patrones/inmunología , Animales , Candida/inmunología , Movimiento Celular , Lectinas Tipo C/inmunología , Lectinas Tipo C/metabolismo , Macrófagos/citología , Malassezia/inmunología , Proteínas de la Membrana/inmunología , Proteínas de la Membrana/metabolismo , Ratones , Mucor/inmunología , Unión Proteica , Receptores Fc/inmunología , Receptores Fc/metabolismo , Receptores de Reconocimiento de Patrones/metabolismo , Saccharomyces/inmunologíaRESUMEN
A study was conducted to analyze the dairy farming sector of Bangladesh from an economic viewpoint. Primary data was collected from smallholder dairy farms using survey questionnaires. A Cobb-Douglas production function and multiple regression models were estimated to analyze farm milk productivity and gross margin of the dairy farms. Surveyed dairy farms owned on an average 3.07 milking cows comprising 0.37 indigenous and 2.70 crossbred cows. Average milk productivity was 7.80 liter per cow per day, in which indigenous cow milk productivity was 1.9 1iter per day and crossbred cow milk productivity was 6.48 liter per cow per day. The study found that average daily milk production of small, medium, and large dairy farms were 5.45, 32.50, and 59.83 liter, respectively. Average monthly revenue and cost of milk production were US$ 79 and US$ 21 per cow, resulting in the average net return of US$ 58 per cow per month. Both quantitative estimation and t test results indicated a positive and statistically significant relationship between farm size and milk productivity and gross margin. The study findings also indicate that crossbred cows are providing higher economic benefits to the dairy farmers compared to the indigenous breeds. Despite being smallholder and subsistence, dairy farming shows potential for increasing returns to scale, and hence, there is a scope for further growth of the sector.
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Industria Lechera/economía , Granjas/economía , Animales , Bangladesh , Bovinos , Costos y Análisis de Costo , Industria Lechera/métodos , Industria Lechera/estadística & datos numéricos , Agricultores , Granjas/estadística & datos numéricos , Femenino , Masculino , Leche/economíaRESUMEN
In the published version of this paper the author Neus Baena's name was incorrectly given as Neus Baena Diez. This has now been corrected in both the HTML and PDF versions of the paper.
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PURPOSE: We delineate the clinical spectrum and describe the histology in arterial tortuosity syndrome (ATS), a rare connective tissue disorder characterized by tortuosity of the large and medium-sized arteries, caused by mutations in SLC2A10. METHODS: We retrospectively characterized 40 novel ATS families (50 patients) and reviewed the 52 previously reported patients. We performed histology and electron microscopy (EM) on skin and vascular biopsies and evaluated TGF-ß signaling with immunohistochemistry for pSMAD2 and CTGF. RESULTS: Stenoses, tortuosity, and aneurysm formation are widespread occurrences. Severe but rare vascular complications include early and aggressive aortic root aneurysms, neonatal intracranial bleeding, ischemic stroke, and gastric perforation. Thus far, no reports unequivocally document vascular dissections or ruptures. Of note, diaphragmatic hernia and infant respiratory distress syndrome (IRDS) are frequently observed. Skin and vascular biopsies show fragmented elastic fibers (EF) and increased collagen deposition. EM of skin EF shows a fragmented elastin core and a peripheral mantle of microfibrils of random directionality. Skin and end-stage diseased vascular tissue do not indicate increased TGF-ß signaling. CONCLUSION: Our findings warrant attention for IRDS and diaphragmatic hernia, close monitoring of the aortic root early in life, and extensive vascular imaging afterwards. EM on skin biopsies shows disease-specific abnormalities.
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Arterias/anomalías , Proteínas Facilitadoras del Transporte de la Glucosa/genética , Hernia Diafragmática/genética , Inestabilidad de la Articulación/genética , Síndrome de Dificultad Respiratoria del Recién Nacido/genética , Enfermedades Cutáneas Genéticas/genética , Malformaciones Vasculares/genética , Adolescente , Adulto , Aorta/diagnóstico por imagen , Aorta/fisiopatología , Arterias/diagnóstico por imagen , Arterias/fisiopatología , Biopsia , Niño , Preescolar , Factor de Crecimiento del Tejido Conjuntivo/genética , Femenino , Hernia Diafragmática/fisiopatología , Humanos , Lactante , Inestabilidad de la Articulación/epidemiología , Inestabilidad de la Articulación/fisiopatología , Masculino , Mutación , Linaje , Síndrome de Dificultad Respiratoria del Recién Nacido/fisiopatología , Piel/patología , Enfermedades Cutáneas Genéticas/epidemiología , Enfermedades Cutáneas Genéticas/fisiopatología , Proteína Smad2/genética , Factor de Crecimiento Transformador beta/genética , Malformaciones Vasculares/epidemiología , Malformaciones Vasculares/fisiopatologíaRESUMEN
The Ypd1 phosphorelay protein is a central constituent of fungal two-component signal transduction pathways. Inhibition of Ypd1 in Saccharomyces cerevisiae and Cryptococcus neoformans is lethal due to the sustained activation of the 'p38-related' Hog1 stress-activated protein kinase (SAPK). As two-component signalling proteins are not found in animals, Ypd1 is considered to be a prime antifungal target. However, a major fungal pathogen of humans, Candida albicans, can survive the concomitant sustained activation of Hog1 that occurs in cells lacking YPD1. Here we show that the sustained activation of Hog1 upon Ypd1 loss is mediated through the Ssk1 response regulator. Moreover, we present evidence that C. albicans survives SAPK activation in the short-term, following Ypd1 loss, by triggering the induction of protein tyrosine phosphatase-encoding genes which prevent the accumulation of lethal levels of phosphorylated Hog1. In addition, our studies reveal an unpredicted, reversible, mechanism that acts to substantially reduce the levels of phosphorylated Hog1 in ypd1Δ cells following long-term sustained SAPK activation. Indeed, over time, ypd1Δ cells become phenotypically indistinguishable from wild-type cells. Importantly, we also find that drug-induced down-regulation of YPD1 expression actually enhances the virulence of C. albicans in two distinct animal infection models. Investigating the underlying causes of this increased virulence, revealed that drug-mediated repression of YPD1 expression promotes hyphal growth both within murine kidneys, and following phagocytosis, thus increasing the efficacy by which C. albicans kills macrophages. Taken together, these findings challenge the targeting of Ypd1 proteins as a general antifungal strategy and reveal novel cellular adaptation mechanisms to sustained SAPK activation.