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Acrylamide (AA) is a carcinogenic compound that affects people due to its frequent use in laboratories and industry as well as the high-temperature cooking of foods with high hydrocarbon content. AA is known to cause severe reproductive abnormalities. The main aim of this study is to evaluate the protective effect of rutin (RU), a phytoactive compound, against AA-induced reproductive toxicity in female rats. Initially, rats were exposed to AA (40 mg/kg for 10 days). Therapy of RU was given after AA intoxication consecutively for 3 days. After 24 h of the last treatment, all the animals were sacrificed. The study evaluated reproductive hormones, oxidative stress markers, membrane-bound enzymes, DNA damage, histological findings, and an in silico approach to determine the protective efficacy of RU. The results indicated that RU significantly protected against inflammation, oxidative stress, and DNA damage induced by AA, likely due to its antioxidant properties.
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Acrilamida , Dano ao DNA , Inflamação , Estresse Oxidativo , Rutina , Animais , Rutina/farmacologia , Feminino , Estresse Oxidativo/efeitos dos fármacos , Acrilamida/toxicidade , Dano ao DNA/efeitos dos fármacos , Ratos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologia , Ratos Wistar , Simulação por Computador , Antioxidantes/farmacologia , Antioxidantes/metabolismoRESUMO
Barley stripe or yellow rust (BYR) caused by Puccinia striiformis f. sp. hordei (Psh) is a significant constraint to barley production. The disease is best controlled by genetic resistance, which is considered the most economical and sustainable component of integrated disease management. In this study, we assessed the diversity of resistance to Psh in a panel of international barley genotypes (n = 266) under multiple disease environments (Ecuador, India, and Mexico) using genome-wide association studies (GWASs). Four quantitative trait loci (QTLs) (three on chromosome 1H and one on 7H) associated with resistance to Psh were identified. The QTLs were validated by mapping resistance to Psh in five biparental populations, which detected key genomic regions on chromosomes 1H (populations Pompadour/Zhoungdamei, Pompadour/Zug161, and CI9214/Baudin), 3H (Ricardo/Gus), and 7H (Fumai8/Baronesse). The QTL RpshQ.GWA.1H.1 detected by GWAS and RpshQ.Bau.1H detected using biparental mapping populations co-located were the most consistent and stable across environments and are likely the same resistance region. RpshQ.Bau.1H was saturated using population CI9214/Baudin by enriching the target region, which placed the resistance locus between 7.9 and 8.1 Mbp (flanked by markers sun_B1H_03, 0.7 cM proximal to Rpsh_1H and sun_B1H_KASP_02, 3.2 cM distal on 1HS) in the Morex reference genome v.2. A Kompetitive Allele Specific PCR (KASP) marker sun_B1H_KASP_01 that co-segregated for RpshQ.Bau.1H was developed. The marker was validated on 50 Australian barley cultivars, showing well-defined allelic discrimination and presence in six genotypes (Baudin, Fathom, Flagship, Grout, Sakurastar, and Shepherd). This marker can be used for reliable marker-assisted selection and pyramiding of resistance to Psh and in diversifying the genetic base of resistance to stripe rust.
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BACKGROUND: Laparoscopic cholecystectomy (LC) is the standard of care for symptomatic gall stone disease. A good scoring system is necessary to standardize the reporting. Our aim was to develop and validate an objective scoring system, the Surgical Cholecystectomy Score (SCS) to grade the difficulty of LC. METHODS: The study was conducted in a single surgical unit at a tertiary care hospital in two phases from January 2017 to April 2021. Retrospective data was analysed and the difficulty of each procedure was graded according to the modified Nassar's scoring system. Significant preoperative and intraoperative data obtained was given a weightage score. In phase II, these scores were validated on a prospective cohort. Each procedure was classified either as easy, moderately difficult or difficult. STATISTICAL ANALYSIS: A univariate analysis was performed on the data followed by a multivariate regression analysis. Bidirectional stepwise selection was done to select the most significant variables. The Beta /Schneeweiss scoring system was used to generate a rounded risk score. RESULTS: Data of 800 patients was retrieved and graded. 10 intraoperative parameters were found to be significant. Each variable was assigned a rounded risk score. The final SCS range for intraoperative parameters was 0-15. The scoring system was validated on a cohort of 249 LC. In the final scoring, cut off SCS of > 8 was found to correlate with difficult procedures. Score of < 2 was equivalent to easy LC. A score between 2 and 8 indicated moderate difficulty. The area under ROC curve was 0.98 and 0.92 for the intraoperative score indicating that the score was an excellent measure of the difficulty level of LCs. CONCLUSION: The scoring system developed in this study has shown an excellent correlation with the difficulty of LC. It needs to be validated in different cohorts and across multiple centers further.
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Colecistectomia Laparoscópica , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Idoso , Cálculos Biliares/cirurgia , Estudos Prospectivos , Medição de RiscoRESUMO
Introduction: Traumatic hemothorax is accounted for about 20% of traumatic chest injuries. Although majority can be managed with the timely placement of intercostal tube (ICT) drainage, the remaining pose a challenge owing to high complication rates associated with retained hemothorax. Although various treatment modalities including intrapleural instillation of fibrinolytics, radioimage guided drainage, VATS guided evacuation and thoractomy do exist to address the retained hemothorax, but indications along with timing to employ a specific treatment option is still unclear and ambiguous. Methods: Patient with residual hemothorax (>200 mL) on ultrasonography after 48 h of indwelling ICT was randomized into either early video-assisted thoracic surgery (VATS) or conventional approach cohort. Early VATS cohort was subjected to video-assisted thoracoscopic evacuation of undrained blood along with normal saline irrigation and ICT placement. The conventional cohort underwent intrapleural thrombolytic instillation for 3 consecutive days. The outcome measures were the duration of indwelling ICT, removal rate of tube thoracostomy, length of hospital stay, duration of intensive care unit (ICU) monitoring, need for mechanical ventilation, incidence of pulmonary and pleural complications, and requirement of additional intervention to address undrained hemothorax and mortality rate. Results: The early VATS cohort had shorter length of hospital stay (7.50 ± 0.85 vs. 9.50 ± 3.03, P = 0.060), reduced duration of indwelling ICT (6.70 ± 1.25 vs. 8.30 ± 2.91, P = 0.127) with higher rate of tube thoracostomy removal (70% vs. 30%, P = 0.003) and lesser need of additional interventions (0% vs. 30%, P = 0.105). Thoracotomy (3 patients) and image-guided drainage (4 patients) were additional interventions to address retained hemothorax in the conventional cohort. However, similar length of ventilator assistance (0.7 ± 0.48 vs. 0.60 ± 1.08, P = 0.791) and prolonged ICU monitoring (1.30 ± 1.06 vs. 0.90 ± 1.45, P = 0.490) was observed in early VATS cohort. Both the cohorts had no mortality. Conclusion: VATS-guided early evacuation of traumatic hemothorax is associated with shorter length of hospital stay along with abbreviated indwelling ICT duration, reduced incidence of complications, lesser readmissions, and improved rate of tube thoracostomy removal. However, the duration of ventilator requirement, ICU stay, and mortality remain unchanged.
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No licensed vaccine exists for the lethal plague and yersiniosis. Therefore, a combination of recombinant YopE and LcrV antigens of Yersinia pestis was evaluated for its vaccine potential in a mouse model. YopE and LcrV in formulation with alum imparted a robust humoral immune response, with isotyping profiles leaning towards the IgG1 and IgG2b subclasses. It was also observed that a significantly enhanced expression of IFN-γ, TNF-α, IL-6, IL-2, and IL-1ß from the splenic cells of vaccinated mice, as well as YopE and LcrV-explicit IFN-γ eliciting T-cells. The cocktail of YopE + LcrV formulation conferred complete protection against 100 LD50Y. pestis infection, while individually, LcrV and YopE provided 80 % and 60 % protection, respectively. Similarly, the YopE + LcrV vaccinated animal group had significantly lower colony forming unit (CFU) counts in the spleen and blood compared to the groups administered with YopE or LcrV alone when challenged with Yersinia pseudotuberculosis and Yersinia enterocolitica. Histopathologic evidence reinforces these results, indicating the YopE + LcrV formulation provided superior protection against acute lung injury as early as day 3 post-challenge. In conclusion, the alum-adjuvanted YopE + LcrV is a promising vaccine formulation, eliciting a robust antibody response including a milieu of pro-inflammatory cytokines and T-cell effector functions that contribute to the protective immunity against Yersinia infections. YopE and LcrV, conserved across all three human-pathogenic Yersinia species, provide cross-protection. Therefore, our current vaccine (YopE + LcrV) targets all three pathogens: Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica. However, the efficacy should be tested in other higher mammalian models.
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BACKGROUND: Thoracic trauma frequently includes a pneumothorax, hemothorax, or hemopneumothorax, which may necessitate an Intercostal drainage (ICD) for air and fluid evacuation to improve breathing and circulatory function. It is a simple and life-saving procedure; nevertheless, it carries morbidity, even after its removal. Efforts have been made continuously to shorten the duration of ICD, but mostly in non-trauma patients. In this study, we evaluated the impact of negative pleural suction over the duration of ICD. METHODS: This study was a prospective randomized controlled interventional trial conducted at Level 1 Trauma Centre. Thoracic trauma patients with ICD, who met the inclusion criteria (sample size 70) were randomized into two groups, the first group with negative pleural suction up to -20 cm H2O, and the second group as conventional, i.e. ICD connected to underwater seal container only. The primary objective was to compare the duration of ICDs and the secondary objectives were the length of hospital stay and various complications of thoracic trauma. RESULTS: Duration of ICD was measured in median days with minimum & maximum days. For the negative suction group, it was 4 days (2-16 days); for the conventional group, it was also 4 days (2-17 days). There was also no significant difference among both groups in length of hospital stay. CONCLUSION: The beneficial effect of negative pleural suction to ICD could not be demonstrated over the duration of ICD and hospital stay. In both groups, there was no significant difference in complication rates like recurrent pneumothorax, retained hemothorax, persistent air leak, and empyema. LEVEL OF EVIDENCE: Therapeutic Study, Level II TRIAL REGISTRATION: This trial was registered with the Clinical Trial Registry of India (CTRI) with registration no. REF/2020/11/038403.
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Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-beta plaques and neurofibrillary tangles in the brain, leading to synaptic dysfunction and cognitive decline. Healthy synapses are the crucial for normal brain function, memory restoration and other neurophysiological function. Synapse loss and synaptic dysfunction are two primary events that occur during AD initiation. Synapse lifecycle and/or synapse turnover is divided into five key stages and several sub-stages such as synapse formation, synapse assembly, synapse maturation, synapse transmission and synapse termination. In normal state, the synapse turnover is regulated by various biological and molecular factors for a healthy neurotransmission. In AD, the different stages of synapse turnover are affected by AD-related toxic proteins. MicroRNAs (miRNAs) have emerged as critical regulators of gene expression and have been implicated in various neurological diseases, including AD. Deregulation of miRNAs modulate the synaptic proteins and affect the synapse turnover at different stages. In this review, we discussed the key milestones of synapse turnover and how they are affected in AD. Further, we discussed the involvement of miRNAs in synaptic turnover, focusing specifically on their role in AD pathogenesis. We also emphasized the regulatory mechanisms by which miRNAs modulate the synaptic turnover stages in AD. Current studies will help to understand the synaptic life-cycle and role of miRNAs in each stage that is deregulated in AD, further allowing for a better understanding of the pathogenesis of devastating disease.
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Doença de Alzheimer , MicroRNAs , Sinapses , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Humanos , Sinapses/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , AnimaisRESUMO
Interfacial failure in carbon fiber-reinforced epoxy (CFRE) laminates is a prominent mode of failure, attracting significant research attention. The large surface-energy mismatch between carbon fiber (CF) and epoxy results in a weaker interface. This study presents a facile yet effective method for enhancing the interfacial adhesion between CF and epoxy with self-healable interfaces. Two variants of a designer sizing agent, poly(ether imide) (PEI), were synthesized, one without a self-healing property termed BO, and the second one by incorporating disulfide metathesis in one of its monomers that renders self-healing properties at the interface-mediated by network reconfiguration, termed BA. 0.25 wt % of CF was found to be the optimum amount of BO and BA sizing agents. The surface free energy of CF drastically increased and became quite close to the surface energy of epoxy after the deposition of both sizing agents and the higher surface roughness. The improved surface wettability, presence of functional groups, and mechanical interlocking worked in tandem to strengthen the interface. The interlaminar shear strength (ILSS) and flexural strength (FS) of CFRE laminate sized with BO consequently increased by 35% and 22% and of CFRE laminate sized with BA increased by 26% and 19%, respectively. Fractography analysis revealed outstanding bonding between epoxy and PEI-CF, indicating that matrix fracture is the predominant mode of failure. The self-healable interfaces due to the preinstalled disulfide metathesis in the sizing agent resulted in 51% self-healing efficiency in ILSS for BA-sized CFRE laminate. Interestingly, the functional properties, deicing, and EMI shielding effectiveness were not compromised by modification of the interface with this designer sizing agent. This study opens new avenues for interfacial modification to improve the mechanical properties while retaining the key functional properties of the laminates.
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Parkinson's Disease (PD) occurs as a result of the progressive loss of dopaminergic neurons within the substantia nigra causing motor and non-motor symptoms and has become more prevalent within the last several decades. With mitochondria being essential to cellular survival, mitochondrial dysfunction contributes to the disease progression by increasing neuron loss through (1) insufficient ATP production and (2) reactive oxygen species generation. MicroRNAs (miRNAs) are small molecules located throughout cells that regulate gene expression, particularly mitochondrial function. Through their own dysregulation, miRNAs offset the delicate balance of mitochondrial function by altering or dysregulating the expression of proteins, increasing neuroinflammation, increasing retention of toxic substances, limiting the removal of reactive oxygen species, and preventing mitophagy. Improper mitochondrial function places cells at increased risk of apoptosis, a major concern in individuals with PD due to their reduced number of dopaminergic neurons. This article has identified the 17 most promising mitochondrial associated miRNAs within PD: hsa-miR-4639-5p, miR-376a, miR-205, miR-421, miR-34b/c, miR-150, miR-7, miR-132, miR-17-5p, miR-20a, miR-93, miR-106, miR-181, miR-193b, miR-128, miR-181a, and miR-124-3p. These miRNAs alter mitochondrial function and synaptic energy by impeding normal gene expression when up or downregulated. However, there is limited research regarding mitochondria-localized miRNAs that are typically seen in other diseases. Mitochondria-localized miRNA may have a greater impact on mitochondrial dysfunction due to their proximity. Further research is needed to determine the location of these miRNAs and to better understand their regulatory capabilities on mitochondrial and synaptic function within PD.
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INTRODUCTION: Surgical stabilization of rib fractures (SSRF) using standard rib plating systems has become a norm in developed countries. However, the procedure has not garnered much interest in low-middle-income countries, primarily because of the cost. METHODS: This was a single-center pilot randomized trial. Patients with severe rib fractures were randomized into two groups: SSRF and nonoperative management. SSRF arm patients underwent surgical fixation in addition to the tenets of nonoperative management. Low-cost materials like stainless steel wires and braided polyester sutures were used for fracture fixation. The primary outcome was to assess the duration of hospital stay. RESULTS: Twenty-two patients were randomized, 11 in each arm. Per-protocol analysis showed that the SSRF arm had significantly reduced duration of hospital stay (22.6 ± 19.1 d versus 7.9 ± 5.7 d, P value 0.031), serial pain scores at 48 h and 5 d (median score 5, IQR (3-6) versus median score 7, IQR (6.5-8), P value 0.004 at 48 h and median score 2 IQR (2-3) versus median score 7 IQR (4.5-7) P value 0.0005 at 5 d), significantly reduced need for injectable opioids (9.9 ± 3.8 mg versus 4.4 ± 3.4 mg, P value 0.003) and significantly more ventilator-free days (19.9 ± 8.7 d versus 26.4 ± 3.2 d, P value 0.04). There were no statistically significant differences in the total duration of ICU stay (median number of days 2, IQR 1-4.5 versus median number of days 7, IQR 1-14, P value 0.958), need for tracheostomy (36.4% versus 0%, P value 0.155), and pulmonary and pleural complications. CONCLUSIONS: SSRF with low-cost materials may provide benefits similar to standard rib plating systems and can be used safely in resource-poor settings.
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Fixação Interna de Fraturas , Tempo de Internação , Fraturas das Costelas , Humanos , Projetos Piloto , Fraturas das Costelas/cirurgia , Fraturas das Costelas/economia , Fraturas das Costelas/terapia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Tempo de Internação/estatística & dados numéricos , Tempo de Internação/economia , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/economia , Fixação Interna de Fraturas/métodos , Poliésteres/economia , Suturas/economia , Fios Ortopédicos/economia , Resultado do Tratamento , Idoso , Placas Ósseas/economia , Aço Inoxidável/economiaRESUMO
Leishmaniasis, a debilitating disease caused by protozoan parasites of the genus Leishmania and transmitted by the bite of a female sandfly, continues to present significant challenges despite ongoing research and collaboration in vaccine development. The intricate interaction between the parasite's life cycle stages and the host's immunological response, namely the promastigote and amastigote forms, adds complexity to vaccine design. The quest for a potent vaccine against Leishmaniasis demands a comprehensive understanding of the immune mechanisms that confer long-lasting protection, which necessitates extensive research efforts. In this pursuit, innovative approaches such as reverse vaccinology and computer-aided design offer promising avenues for unraveling the intricacies of host-pathogen interactions and identifying effective vaccine candidates. However, numerous obstacles, including limited treatment options, the need for sustained antigenic presence, and the prevalence of co-infections, particularly with HIV, impede progress. Nevertheless, through persistent research endeavours and collaborative initiatives, the goal of developing a highly efficacious vaccine against Leishmaniasis can be achieved, offering hope through the latest Omics data development with immunoinformatics approaches for effective vaccine design for the prevention of this disease.
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BACKGROUND: High-fidelity visualization of anatomical organs is crucial for neurosurgical education, simulation, and planning. This becomes much more important for minimally invasive neurosurgical procedures. Realistic anatomical visualization can allow resident surgeons to learn visual cues and orient themselves with the complex 3-dimensional (3D) anatomy. Achieving full fidelity in 3D medical visualization is an active area of research; however, the prior reviews focus on the application area and lack the underlying technical principles. Accordingly, the present study attempts to bridge this gap by providing a narrative review of the techniques used for 3D visualization. METHODS: We conducted a literature review on 3D medical visualization technology from 2018 to 2023 using the PubMed and Google Scholar search engines. The cross-referenced manuscripts were extensively studied to find literature that discusses technology relevant to 3D medical visualization. We also compiled and ran software applications that were accessible to us in order to better understand them. RESULTS: We present the underlying fundamental technology used in 3D medical visualization in the context of neurosurgical education, simulation, and planning. Further, we discuss and categorize a few important applications based on the 3D visualization techniques they use. CONCLUSIONS: The visualization of virtual human organs has not yet achieved a level of realism close to reality. This gap is largely due to the interdisciplinary nature of this research, population diversity, and validation complexities. With the advancements in computational resources and automation of 3D visualization pipelines, next-gen applications may offer enhanced medical 3D visualization fidelity.
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Imageamento Tridimensional , Neurocirurgia , Procedimentos Neurocirúrgicos , Humanos , Imageamento Tridimensional/métodos , Procedimentos Neurocirúrgicos/educação , Procedimentos Neurocirúrgicos/métodos , Neurocirurgia/educação , Simulação por ComputadorRESUMO
JOURNAL/nrgr/04.03/01300535-202412000-00026/figure1/v/2024-04-08T165401Z/r/image-tiff Gamma-aminobutyric acid (GABA)ergic neurons, the most abundant inhibitory neurons in the human brain, have been found to be reduced in many neurological disorders, including Alzheimer's disease and Alzheimer's disease-related dementia. Our previous study identified the upregulation of microRNA-502-3p (miR-502-3p) and downregulation of GABA type A receptor subunit α-1 in Alzheimer's disease synapses. This study investigated a new molecular relationship between miR-502-3p and GABAergic synapse function. In vitro studies were performed using the mouse hippocampal neuronal cell line HT22 and miR-502-3p agomiRs and antagomiRs. In silico analysis identified multiple binding sites of miR-502-3p at GABA type A receptor subunit α-1 mRNA. Luciferase assay confirmed that miR-502-3p targets the GABA type A receptor subunit α-1 gene and suppresses the luciferase activity. Furthermore, quantitative reverse transcription-polymerase chain reaction, miRNA in situ hybridization, immunoblotting, and immunostaining analysis confirmed that overexpression of miR-502-3p reduced the GABA type A receptor subunit α-1 level, while suppression of miR-502-3p increased the level of GABA type A receptor subunit α-1 protein. Notably, as a result of the overexpression of miR-502-3p, cell viability was found to be reduced, and the population of necrotic cells was found to be increased. The whole cell patch-clamp analysis of human-GABA receptor A-α1/ß3/γ2L human embryonic kidney (HEK) recombinant cell line also showed that overexpression of miR-502-3p reduced the GABA current and overall GABA function, suggesting a negative correlation between miR-502-3p levels and GABAergic synapse function. Additionally, the levels of proteins associated with Alzheimer's disease were high with miR-502-3p overexpression and reduced with miR-502-3p suppression. The present study provides insight into the molecular mechanism of regulation of GABAergic synapses by miR-502-3p. We propose that micro-RNA, in particular miR-502-3p, could be a potential therapeutic target to modulate GABAergic synapse function in neurological disorders, including Alzheimer's disease and Alzheimer's disease-related dementia.
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Carbon fiber-reinforced epoxy (CFRE) laminates have attracted significant attention as a structural material specifically in the aerospace industry. In recent times, various strategies have been developed to modify the carbon fiber (CF) surface as the interface between the epoxy matrix and CFs plays a pivotal role in determining the overall performance of CFRE laminates. In the present work, graphene oxide (GO) was used to tag a polyetherimide (PEI, termed BA) containing exchangeable bonds and was employed as a sizing agent to improve the interfacial adhesion between CFs and epoxy. This unique GO-tagged-BA sizing agent termed BAGO significantly enhanced the mechanical properties of CFRE laminates by promoting stronger interactions between CFs and the epoxy matrix. The successful synthesis of BAGO was verified by Fourier-transform infrared spectroscopy. Additionally, the partial reduction of GO owing to this tagging with BA was further confirmed by X-ray diffraction and Raman spectroscopy, and the thermal stability of this unique sizing agent was evaluated using thermogravimetric analysis. The amount of GO in BAGO was optimized as 0.25 wt% of BA termed 0.25-BAGO. The 0.25-BAGO sizing agent resulted in a significant increase in surface roughness, from 15 nm to 140 nm, and surface energy, from 13.2 to 34.7 mN m-1 of CF. The laminates prepared from 0.25-BAGO exhibited a remarkable 40% increase in flexural strength (FS) and a 35% increase in interlaminar shear strength (ILSS) due to interfacial strengthening between epoxy and CFs. In addition, these laminates exhibited a self-healing efficiency of 51% in ILSS due to the presence of dynamic disulfide bonds in BAGO. Interestingly, the laminates with 0.25-BAGO exhibited enhanced Joule heating and enhanced deicing, though the EMI shielding efficiency slightly declined.
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INTRODUCTION: Our aim was to perform a systematic review and meta-analysis for the association of neck circumference (NC) in polycystic ovary syndrome (PCOS) patients as compared to non-PCOS controls. METHODS: Primarily the PubMed/MEDLINE database and others such as SCOPUS, Google Scholar, Cochrane Library, were searched up to November 15, 2023 for observational studies comparing NC in PCOS versus non-PCOS women. The mean and SD values of NC and other covariates in PCOS and control groups were extracted by two independent reviewers, and the quality and risk of bias assessment was done using Newcastle-Ottawa Scale. The meta-analysis employed combined standardized mean differences (SMD) with 95% confidence intervals (CI) to compare NC between PCOS patients and controls. The heterogeneity and validity were addressed by subgroup, meta-regression, and sensitivity analyses. We conducted a Bootstrapped meta-analysis using 1,000 and 10,000 simulations to test the accuracy of the obtained results. The certainty of evidence was assessed by the GRADE approach. RESULTS: Our meta-analysis included 9 observational studies. The PCOS patients showed significantly higher NC values than the non-PCOS controls (SMD: 0.66, 95% CI: 0.41-0.91, p < 0.0001). In the bootstrap meta-analysis, the accuracy of the observed findings was proved (SMD = 0.66, 95% CI = 0.42-0.91) for the NC outcome. No publication bias was detected in the funnel plot analysis using Begg's and Egger's tests. The 95% prediction interval of 0.036-1.28 suggests that the true outcomes of the studies are generally in the same direction as the estimated average outcome. The sensitivity analysis provided the robustness of the outcome, and no single study was overly influential on the pooled estimate. CONCLUSION: This meta-analysis provides accurate evidence for significantly higher NC values in PCOS as compared to non-PCOS controls. There is no sufficient evidence on the diagnostic accuracy measures for NC in PCOS. Hence, further research on its diagnostic utility in PCOS is needed.
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Pescoço , Síndrome do Ovário Policístico , Síndrome do Ovário Policístico/patologia , Humanos , Feminino , Pescoço/anatomia & histologia , Pescoço/patologia , Abordagem GRADERESUMO
Diabetic foot (DF) represents a severe complication of diabetes mellitus, imposing substantial psychological and economic burdens on affected individuals. This investigation sought to assess the therapeutic efficacy of stem cell interventions in the management of DF complications. A comprehensive systematic search across PubMed, Embase, CINAHL, Scopus, and the Cochrane library databases was conducted to identify pertinent studies for meta-analysis. Outcome measures encompassed ulcer or wound healing rates, amputation rates, angiogenesis, ankle-brachial index (ABI), and pain-free walking distance. Dichotomous outcomes were expressed as risk differences (RDs) with 95% confidence intervals (CIs), while continuous data were articulated as standardized mean differences (SMDs) with corresponding 95% CIs. Statistical analyses were executed using RevMan 5.3 and Open Meta, with bootstrapped meta-analysis conducted through OpenMEE software. A total of 20 studies, comprising 24 arms and involving 1304 participants, were incorporated into the meta-analysis. The findings revealed that stem cell therapy exhibited superior efficacy compared to conventional interventions in terms of ulcer or wound healing rate [RD = 0.36 (0.28, 0.43)], pain-free walking distance [SMD = 1.27 (0.89, 1.65)], ABI [SMD = 0.61 (0.33, 0.88)], and new vessel development [RD = 0.48 (0.23, 0.78)], while concurrently reducing the amputation rate significantly [RD = -0.19 (-0.25, -0.12)]. Furthermore, no statistically significant difference in adverse events was observed [RD -0.07 (-0.16, 0.02)]. The Grading of Recommendations, Assessment, Development, and Evaluation assessment indicated varying levels of evidence certainty, ranging from very low to moderate, for different outcomes. Bootstrapping analysis substantiated the precision of the results. The meta-analysis underscores the significant superiority of stem cell therapy over conventional approaches in treating DF complications. Future investigations should prioritize large-scale, randomized, double-blind, placebo-controlled, multicenter trials, incorporating rigorous long-term follow-up protocols. These studies are essential for elucidating the optimal cell types and therapeutic parameters that contribute to the most effective treatment strategies for DF management.
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Introduction: Sarcoidosis is an idiopathic systemic granulomatous disorder that can affect multiple organs, including rare extrapulmonary sites like the premaxilla. This case report presents a rare occurrence of premaxillary sarcoidosis, a condition scarcely reported in medical literature. Case Report: The patient, a 62-year-old male, presented with a progressively enlarging painless swelling on the right cheek over a three-year period. Despite multiple Fine Needle Aspiration Cytology (FNAC) examinations yielding no conclusive diagnosis, a contrast-enhanced computed tomographic (CT) scan revealed an ill-defined lesion in the premaxillary soft tissue. Biopsy and subsequent excision procedures confirmed the presence of non-caseating granulomas with asteroid bodies, indicative of sarcoidosis. With no systemic involvement and complete excision of the disease, further treatment was not necessary. Conclusion: This case highlights the challenges in diagnosing premaxillary (Extrapulmonary Sarcoidosis) sarcoidosis due to its rarity and resemblance to other dental and maxillofacial conditions and granulomatous lesions. Accurate diagnosis requires a high index of suspicion, multidisciplinary approach, involving clinical assessment, histopathological analysis, and imaging modalities. By deepening our understanding of these uncommon presentations, this report aims to enhance clinical awareness and contribute to improved patient outcomes.
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Immediate control of excessive bleeding and prevention of infections are of utmost importance in the management of wounds. Cryogels have emerged as promising materials for the rapid release of medication and achieving hemostasis. However, their quick release properties pose the challenge of exposing patients to high concentrations of drugs. In this study, hybrid nanocomposites were developed to address this issue by combining poly(vinyl alcohol) and κ-carrageenan with whitlockite nanoapatite (WNA) particles and ciprofloxacin, aiming to achieve rapid hemostasis and sustained antibacterial effects. A physically cross-linked cryogel was obtained by subjecting a blend of poly(vinyl alcohol) and κ-carrageenan to successive freezing-thawing cycles, followed by the addition of WNA. Furthermore, ciprofloxacin was introduced into the cryogel matrix for subsequent evaluation of its wound healing properties. The resulting gel system exhibited a 3D microporous structure and demonstrated excellent swelling, low cytotoxicity, and outstanding mechanical properties. These characteristics were evaluated through analytical and rheological experiments. The nanocomposite cryogel with 4% whitlockite showed extended drug release of 71.21 ± 3.5% over 21 days and antibacterial activity with a considerable growth inhibition zone (4.19 ± 3.55 cm). Experiments on a rat model demonstrated a rapid hemostasis property of cryogels within an average of 83 ± 4 s and accelerated the process of wound healing with 96.34% contraction compared to the standard, which exhibited only â¼78% after 14 days. The histopathological analysis revealed that the process of epidermal re-epithelialization took around 14 days following the skin incision. The cryogel loaded with WNAs and ciprofloxacin holds great potential for strategic utilization in wound management applications as an effective material for hemostasis and anti-infection purposes.
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Fosfatos de Cálcio , Criogéis , Álcool de Polivinil , Humanos , Ratos , Animais , Criogéis/química , Álcool de Polivinil/farmacologia , Carragenina/química , Cicatrização , Ciprofloxacina , Antibacterianos/farmacologia , Antibacterianos/química , Hemostasia , EtanolRESUMO
Several converging lines of evidence from our group support a potential role of RLIP76 (AKA Rlip) in neurodegenerative disorders, including Alzheimer's Disease (AD). However, the role of Rlip in Alzheimer's and other neurodegenerative diseases is not well understood. The purpose of the present study is to determine the role of Rlip in the brains of AD patients and control subjects. To achieve our goals, we used frozen tissues and formalin-fixed paraffin-embedded postmortem brains from AD patients of different Braak stages and age-matched control subjects. Our immunohistology and immunoblotting blotting analysis revealed that expression of Rlip protein gradually and significantly decreased (p = 0.0001) with AD progression, being lowest in Braak stage IV-V. Rlip was colocalized with Amyloid beta (Aß) and phosphorylated tau (p-Tau) as observed by IHC staining and co-immunoprecipitation studies. Lipid peroxidation (4-HNE generation) and H2O2 production were significantly higher (p = 0.004 and 0.0001 respectively) in AD patients compared to controls, and this was accompanied by lower ATP production in AD (p = 0.0009). Oxidative DNA damage was measured by 8-Hydroxyguanosine (8-OHdG) in tissue lysates by ELISA and COMET assay. AD 8-OHdG levels were significantly higher (p = 0.0001) compared to controls. COMET assay was performed in brain cells, isolated from frozen postmortem samples. The control samples showed minimal DNA in comets representing few DNA strand breaks (<20 %), (score-0-1). However, the AD group showed an average of 50 % to 65 % of DNA in comet tails (score-4-5) indicating numerous DNA strand breaks. The difference between the two groups was significant (p = 0.001), as analyzed by Open Comet by ImageJ. Elevated DNA damage was further examined by western blot analysis for phosphorylated histone variant H2AX (γH2AX). Induction of γH2AX was very significant (p < 0.0001) and confirmed the presence of double-strand breaks in DNA. Overall, our results indicate an important role for Rlip in maintaining neuronal health and homeostasis by suppressing cellular oxidative stress and DNA damage. Based on our findings, we cautiously conclude that Rlip is a promising therapeutic target for Alzheimer's disease.
Assuntos
Doença de Alzheimer , Doenças Mitocondriais , Humanos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Autopsia , Encéfalo/metabolismo , DNA/metabolismo , Peróxido de Hidrogênio/metabolismo , Doenças Mitocondriais/metabolismo , Estresse Oxidativo/fisiologiaRESUMO
Genome-wide association studies (GWAS) are one of the best ways to look into the connection between single-nucleotide polymorphisms (SNPs) and the phenotypic performance. This study aimed to identify the genetic variants that significantly affect the important reproduction traits in Vrindavani cattle using genome-wide SNP chip array data. In this study, 96 randomly chosen Vrindavani cows were genotyped using the Illumina Bovine50K BeadChip platform. A linear regression model of the genome-wide association study was fitted in the PLINK program between genome-wide SNP markers and reproduction traits, including age at first calving (AFC), inter-calving period (ICP), dry days (DD), and service period (SP) across the first three lactations. Information on different QTLs and genes, overlapping or adjacent to genomic coordinates of significant SNPs, was also mined from relevant databases in order to identify the biological pathways associated with reproductive traits in bovine. The Bonferroni correction resulted in total 39 SNP markers present on different chromosomes being identified that significantly affected the variation in AFC (6 SNPs), ICP (7 SNPs), DD (9 SNPs), and SP (17 SNPs). Novel potential candidate genes associated with reproductive traits that were identified using the GWAS methodology included UMPS, ITGB5, ADAM2, UPK1B, TEX55, bta-mir-708, TMPO, TDRD5, MAPRE2, PTER, AP3B1, DPP8, PLAT, TXN2, NDUFAF1, TGFA, DTNA, RSU1, KCNQ1, ADAM32, and CHST8. The significant SNPs and genes associated with the reproductive traits and the enriched genes may be exploited as candidate biomarkers in animal improvement programs, especially for improved reproduction performance in bovines.