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1.
Eur J Case Rep Intern Med ; 11(7): 004619, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38984175

RESUMO

Introduction: Renal squamous cell carcinoma (SCC) is a neoplasm with an extremely rare occurrence compared to other renal malignancies. The classic presentation includes a palpable mass and flank pain; however, the presentation is seldom non-specific. Our study describes the significance of programmed death ligand-1 (PD-L1) expression in renal cancer and its association with clinical outcomes, alongside available treatment options. Case description: An 80-year-old female with a history of hypertension and cerebral aneurysm presented with right flank pain and blood in urine and was diagnosed with pyelonephritis and left renal mass/phlegmon. A biopsy revealed SCC of the kidney with metastasis to the lung and aortocaval lymph node. Positron emission tomography (PET) scan confirmed malignancy in the kidney and lung. Treatment with pemrolizumab and carboplatin plus paclitaxel was initiated but poorly tolerated as the haemoglobin dropped rapidly. Conclusion: SCC poses a diagnostic challenge due to its rarity and non-specific symptoms, often leading to advanced stage diagnosis. PD-L1 expression is pivotal in assessing tumour aggressiveness and prognosis. PD-L1 inhibitors offer promise, but their efficacy in renal SCC warrants further investigation. Radical nephrectomy and systemic chemotherapy show potential in advanced cases, necessitating vigilant management of treatment-related side effects. This case emphasises the need for ongoing research to refine therapeutic approaches and enhance outcomes in renal SCC patients. LEARNING POINTS: PD-L1 expression is pivotal in assessing tumour aggressiveness and prognosis of renal cell carcinoma.PD-L1 inhibitors hold promise as a therapeutic intervention in renal squamous cancer.Radical nephrectomy and systemic chemotherapy show potential in managing advanced renal cancer.

2.
Medicine (Baltimore) ; 103(26): e38724, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38941403

RESUMO

This retrospective study aims to explore the sex disparity in dual antiplatelet therapy (DAPT) noncompliance among left main stem percutaneous coronary intervention (PCI) patients with drug-eluting stent (DES) and identify predictors associated with non-adherence. Data were collected from the medical records of 1585 patients, including 1104 males and 481 females, who underwent left main stem PCI with DES. Baseline characteristics, angiographic features, and DAPT compliance rates at 1 month and 12 months were analyzed. Univariate logistic regression was used to identify predictors of DAPT noncompliance. The overall DAPT noncompliance rate at 1 month was 8.5%, increasing to 15.5% at 12 months. Females exhibited slightly higher noncompliance rates than males at both 1 month (15.6% vs 14.5%) and 12 months (28.1% vs 19.0%), although the difference was not statistically significant. Smoking status showed a modest impact on non-adherence, with current smokers exhibiting a lower noncompliance rate (14.9% at 1 month). Prior coronary artery disease history was associated with increased noncompliance at 12 months (18.9%). Angiographic characteristics, including lesion location and Syntax score, had no consistent association with DAPT noncompliance. This study highlights sex disparity in DAPT noncompliance among patients undergoing left main stem PCI with DES. Comorbidities, socioeconomic status, smoking status, and prior coronary artery disease history were identified as predictors of non-adherence.


Assuntos
Stents Farmacológicos , Adesão à Medicação , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Humanos , Masculino , Feminino , Intervenção Coronária Percutânea/estatística & dados numéricos , Intervenção Coronária Percutânea/métodos , Estudos Retrospectivos , Pessoa de Meia-Idade , Stents Farmacológicos/estatística & dados numéricos , Fatores Sexuais , Idoso , Adesão à Medicação/estatística & dados numéricos , Inibidores da Agregação Plaquetária/uso terapêutico , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/terapia , Terapia Antiplaquetária Dupla/métodos , Fatores de Risco , Angiografia Coronária/estatística & dados numéricos
3.
Clin Appl Thromb Hemost ; 30: 10760296241261364, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38870350

RESUMO

OBJECTIVE: To examine the effectiveness of rivaroxaban compared to enoxaparin in patients diagnosed with cancer and venous thromboembolism. METHODS: A search of Pub Med, Scopus, and Google Scholar, from inception through April 2023 was conducted. Articles comparing rivaroxaban with enoxaparin in patients with cancer and VTE/PE/DVT were included. Review Manager Version 5.2 was utilised for the analysis of the following outcomes; VTE, PE, DVT, major bleeding, and mortality. RESULTS: A total of 8 articles and 2276 patients were included in the final analysis. Pooled analysis showed that rivaroxaban had a statistically insignificant reduced association with VTE occurrence (RR:0.83, 95% CI:0.58-1.18, P:0.3) as well as a statically insignificant reduction in major bleeding (RR:0.79, 95% CI:0.53-1.18, P:0.25). Analysis showcased that there was an insignificant reduction of mortality rivaroxaban as compared to enoxaparin (RR:0.74, 95% CI: 0.46-1.20, P:0.23). CONCLUSION: Rivaroxaban can serve as a viable alternative to enoxaparin, with no appreciable drawbacks, for preventing and managing VTE in patients with malignancy.


Assuntos
Enoxaparina , Neoplasias , Rivaroxabana , Tromboembolia Venosa , Humanos , Anticoagulantes/uso terapêutico , Enoxaparina/uso terapêutico , Hemorragia/induzido quimicamente , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Recidiva , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/tratamento farmacológico
4.
Cureus ; 16(5): e59742, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38841035

RESUMO

Dermatofibrosarcoma protuberans (DFSP) is a low- to intermediate-grade dermal soft tissue malignant tumor (sarcoma) with a high local recurrence rate but low metastatic potential. DFSP is characterized by uniform spindle cell fascicles arranged classically in a storiform pattern and by CD34 immunoreactivity. On gross examination, DFSP usually manifests as a white or yellow soft tissue mass with a smooth outer surface and poor circumscription. In this study, we report a case of DFSP with fibrosarcomatous transformation, a rare but well-known phenomenon encountered in DFSP that is correlated with an increased risk of adverse outcomes in patients with DFSP. A 45-year-old male presented with a progressively enlarging lump on his left shoulder, initially suspected of being a lipoma but diagnosed as a fibrosarcomatous transformation of DFSP. Surgical resection was performed, with the subsequent identification of metastatic sarcoma in pulmonary nodules. Robotic-assisted thoracoscopy excised the nodules, confirming metastatic sarcoma with aggressive behavior. Despite negative adjuvant treatment plans, the patient remains under surveillance with imaging, showing no recurrence in recent scans. Continued follow-up with medical and surgical oncology is planned. DFSP is a rare soft tissue sarcoma characterized by indolent growth and low metastatic potential, except in fibrosarcomatous transformation cases. Molecularly, DFSP is defined by a COL1A1-PDGFB fusion transcript that is targetable with imatinib therapy. Treatment involves wide surgical resection, with adjuvant radiation therapy in select cases. Radiation therapy may be employed in cases with close or positive margins, while conventional chemotherapy has limited utility. Multidisciplinary collaboration is crucial for optimal management. Overall, this case underscores the challenges in diagnosing and managing aggressive sarcomas like fibrosarcomatous DFSP, emphasizing the importance of vigilant surveillance and multidisciplinary collaboration in optimizing patient outcomes. Further research is needed to understand the mechanisms underlying fibrosarcomatous transformation and to explore novel therapeutic avenues for this challenging malignancy.

5.
Curr Probl Cardiol ; 49(7): 102607, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38697333

RESUMO

INTRODUCTION: Rheumatoid Arthritis (RA) is a risk enhancing factor for cardiovascular diseases (CVD). However, data regarding the magnitude and trends of RA associated CVD-related mortality in the United States (U.S) remains scarce. METHODS: A retrospective analysis was conducted using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) dataset. We extracted age-adjusted mortality rates (AAMR) per 100,000 persons and calculated the annual percentage change (APC) through Joinpoint regression. The outcomes were stratified to discern temporal, sex-based, racial, and geographic patterns in RA-associated CVD mortality. RESULTS: Between 1999 and 2020, 128,058 deaths related to CVD in RA patients aged 25 and above were recorded. The AAMR decreased from 3.50 in 1999 to 2.79 in 2020. However, sex disparities persisted, with females consistently experiencing a higher AAMR (3.35) compared to males (1.74). Non-Hispanic (NH) American Indian/Alaska Native had the highest AAMR (4.44) followed by NH White (2.83), NH Black or African American (2.47) and Hispanic or Latino (2.13), while NH Asian/Pacific Islander had the lowest AAMR (1.28). Geographically, the Midwestern region had the highest AAMR (3.12), while the Northeast had the lowest (2.19) with micropolitan (3.47) and nonmetropolitan (3.37) areas exhibiting higher AAMRs compared to large metropolitans (2.28). Notably, states with the highest AAMRs included North Dakota, South Dakota, Vermont, Minnesota and Wyoming. CONCLUSION: Recent trends reveal an upward incline in RA-associated CVD-related mortality with profound disparities related to sex, race, geography and regions. Redressing these disparities necessitates the implementation of targeted population level interventions.


Assuntos
Artrite Reumatoide , Doenças Cardiovasculares , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artrite Reumatoide/mortalidade , Artrite Reumatoide/epidemiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
6.
Chin J Cancer Res ; 36(2): 195-214, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38751441

RESUMO

Hepatocellular carcinoma (HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers; the most prominent is circulating tumor DNA (ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction (PCR) [emulsion PCR (ePCR), digital PCR (dPCR), and bead, emulsion, amplification, magnetic (BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection, treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations (either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1; 2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF; 3) DNA methylation (RASSF1A, SEPT9, KMT2C and CCNA2); 4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1; and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful results. Still, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification.

7.
Eur J Case Rep Intern Med ; 11(3): 004339, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455694

RESUMO

Introduction: During treatment for malignant lymphoma, cytopenia can develop for several reasons. This can range from mild cytopenias leading to infection and bleeding to full-blown drug-induced aplastic anaemia. While aplastic anaemia affects individuals of all genders and ages, here, we describe aplastic anaemia after chemotherapy exposure to bendamustine in a 65-year-old female with non-Hodgkin's lymphoma. Case description: A 65-year-old woman with recurrent indolent marginal zone lymphoma and post-chemotherapy with bendamustine and rituximab, presented with a neutropenic fever and was admitted with a leading diagnosis of sepsis. In the previous two weeks, the patient required regular transfusions of packed red blood cells and platelets and maintained a daily ZARXIO® regimen. Laboratory results revealed pancytopenia, and broad-spectrum antibiotics (cefepime/vancomycin) were given. The patient was subsequently admitted to the hospital under the care of the haematology/oncology team and was ultimately diagnosed with aplastic anaemia, likely as a consequence of bendamustine chemoimmunotherapy. She elicited a positive response to the triple immunosuppressive therapy (IST) regimen (two immunotherapeutic agents plus one anti-thymocyte globulin (ATG), after which her cell counts returned to normal. Conclusions: This case underscores the importance of recognising haematologic complications linked to bendamustine and advocates for further research to increase the understanding among healthcare professionals of drug-induced aplastic anaemia. Bendamustine can cause severe autoimmune haemolytic anaemia and aplastic anaemia and may require multiple transfusions and a multidrug regimen for treatment. The use of ATG as a therapeutic intervention is appropriate because it has been effective in treating aplastic anaemia. LEARNING POINTS: Bendamustine can cause severe autoimmune haemolytic anaemia and aplastic anaemia, a side effect which has rarely been reported but is of significant clinical importance.Drug-induced aplastic anaemia is a complex, potentially devastating consequence of treating blood cancers and is a relatively unexplored area that requires further understanding.Anti-thymocyte globulin is effective in treating bendamustine-induced aplastic anaemia as it degrades lymphocytes that destroy the bone marrow.

8.
Inorg Chem ; 63(12): 5623-5633, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38471143

RESUMO

Recently emerging perovskite nanocrystals (PNCs) are very attractive fluorescence nanomaterials due to their very narrow emission peak, tunable wavelength, and extremely high quantum yield, but their chemosensing, biosensing and bioimaging applications suffer from the poor stability of ordinary PNCs in aqueous media, especially in biological matrices. Recently developed water-stable 2D CsPb2Br5-encapsulated 3D CsPbBr3 PNCs (i.e., CsPbBr3/CsPb2Br5 PNCs) show extremely stable light emission in pure water, but their fluorescence is seriously quenched in aqueous media containing biological molecules due to their chemical reactions. In this work, we used a facile method to encapsulate pure water-stable CsPbBr3/CsPb2Br5 PNCs in water with SiO2 and polyethylene glycol hexadecyl ether (Brij58) into a new kind of biological environment-stable PNCs (CsPbBr3/CsPb2Br5@SiO2-Brij58). The synthesis of the target PNCs can be accomplished in a fast, easy, and green way. The obtained CsPbBr3/CsPb2Br5@SiO2-Brij58 PNCs maintain strong fluorescence emission for a long time, all in pH 7.4 PBS, BSA, and minimum essential medium, exhibiting excellent biological environment stability. Moreover, the developed biological environment-stable PNCs show good biocompatibility and have been successfully used in cell imaging. Overall, the work provides an easy, low-cost, and efficient application of PNCs in bioimaging.


Assuntos
Compostos de Cálcio , Nanopartículas , Óxidos , Titânio , Água , Cetomacrogol , Dióxido de Silício
10.
Eur J Case Rep Intern Med ; 11(2): 004265, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38352806

RESUMO

A nuclear protein in testis (NUT) midline carcinoma arises from squamous cells and is often located in the head, neck, and lungs. This report focuses on the negative p63 mutation and older age at the diagnosis of a NUT carcinoma, which has significant prognostic implications. A 62-year-old patient presented initially with a three-year history of recurring frontal headaches, intermittent nasal bleeding, and a sensation of a nasal cavity mass. An incisional biopsy revealed a poorly differentiated NUT carcinoma in the left maxillary sinus. A functional endoscopic sinus surgery was performed, but the cancer recurred. As a result, a total maxillectomy was performed, and the patient was declared cancer-free with no evidence of residual disease. This is a rare instance of a p63-negative midline NUT cell carcinoma (NCC) in an elderly patient, which could potentially contribute to a more favourable prognosis and longer survival compared to other reported cases. LEARNING POINTS: Molecular analysis of a NUT carcinoma and age at diagnosis may serve as a potential means for predicting patient prognosis in cases of midline NCC.Each patient should receive careful monitoring and a personalised treatment strategy based on their molecular studies. Surgical resection, along with a combination of radiotherapy and chemotherapy, has the potential to improve overall survival rates.In line with the commonly observed relationship between increased p63 mutation and poorer survival rates, a negative p63 expression in squamous cell carcinomas may indicate a more favorable prognosis. This hypothesis highlights the importance of further research to validate these findings.

11.
J Pak Med Assoc ; 74(1): 99-104, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38219173

RESUMO

Objective: To determine the association between internet use and anxiety among people during the coronavirus disease- 2019 pandemic. METHODS: The cross-sectional study was conducted across Pakistan from January 14 to February 21, 2021, which was the active phase of the coronavirus disease-2019 pandemic in Pakistan. The participants were aged at least 13 years having internet access regardless of gender or their location across Pakistan. The anonymous web-based survey was conducted using a questionnaire generated on Google Forms and disseminated through various social media platforms and WhatsApp groups. Anxiety symptoms were screened using the Depression, Anxiety and Stress Scale-21, while the Young Internet Addiction Test was used to evaluate symptoms of internet addiction. Data was analysed using STATA 16. RESULTS: Of the 1,145 subjects, 686(60%) were females and 459(40%) were males. A total of 257(22.5%) participants were found to have extremely severe anxiety and internet usage pattern was significantly associated with the level of anxiety (p<0.05). Age, gender, social class and marital status were not significantly different (p>0.05), while family income and area of living were significantly different (p<0.05) in terms of anxiety levels. The odd of addictive internet use was 10.2 (95% confidence interval: 5.7-18.5) times greater in extreme anxiety individuals compared to individuals having no anxiety after controlling for other sociodemographic, health-related, behavioural and environmental factors during the pandemic. Conclusion: A significant association of anxiety was found with internet addiction during the coronavirus disease-2019 pandemic.


Assuntos
COVID-19 , Masculino , Feminino , Humanos , COVID-19/epidemiologia , Pandemias , Uso da Internet , Estudos Transversais , Paquistão/epidemiologia , Ansiedade/epidemiologia , Internet , Depressão
12.
Artigo em Inglês | MEDLINE | ID: mdl-38188891

RESUMO

Ensifentrine is a novel inhalational phosphodiesterase (PDE)3 and PDE4 inhibitor which improves bronchodilation and decreases inflammatory markers by acting locally on the bronchial tissue, with minimal systemic effects. Both preclinical and clinical trials have demonstrated benefits of this therapy, including improvement in lung function and reduction in exacerbations. This therapy is currently under review by the US Food and Drug Administration with a decision expected in 2024.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Estados Unidos , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Isoquinolinas , Pirimidinonas , Brônquios
13.
Curr Probl Cardiol ; 49(1 Pt A): 102018, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37544620

RESUMO

Altitude-related venous thrombosis (ARVT) is a condition of growing concern among individuals engaged in high-altitude travel and activities. This updated review explores the epidemiology, pathophysiological mechanisms, clinical presentations, and management of ARVT based on a thematic analysis and synthesis of the existing literature. ARVT's multifactorial etiology involves the interplay of hypobaric hypoxia and endothelial dysfunction, creating a procoagulant state and increasing the risk of thrombosis. Common clinical manifestations include pain, swelling, and redness in the extremities, necessitating accurate and timely diagnosis, particularly in remote settings. Thromboprophylaxis during high-altitude travel and activities plays a crucial role in reducing the risk of ARVT, while anticoagulation remains the mainstay of management. Further research is needed to optimize preventive and treatment strategies, enhancing patient outcomes and safety in high-altitude environments.


Assuntos
Cardiopatias , Tromboembolia Venosa , Trombose Venosa , Humanos , Altitude , Anticoagulantes/uso terapêutico , Fatores de Risco , Tromboembolia Venosa/etiologia , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia , Trombose Venosa/prevenção & controle
14.
Sci Rep ; 13(1): 22179, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38092868

RESUMO

Eco-friendly and cost-effective catalysts with multiple active sites, large surface area, high stability and catalytic activity are highly desired for efficient water splitting as a sustainable green energy source. Within this line, a facile synthetic approach based on solventless thermolysis was employed for the simple and tunable synthesis of Ni1-xMgxFe2O4 (0 ≤ x ≤ 1) nanosheets. The characterization of nanosheets (via p-XRD, EDX, SEM, TEM, HRTEM, and SAED) revealed that the pristine ferrites (NiFe2O4 and MgFe2O4), and their solid solutions maintain the same cubic symmetry throughout the composition regulation. Elucidation of the electrochemical performance of the nanoferrite solid solutions showed that by tuning the local chemical environment of Ni in NiFe2O4 via Mg substitution, the intrinsic catalytic activity was enhanced. Evidently, the optimized Ni0.4Mg0.6Fe2O4 catalyst showed drastically enhanced HER activity with a much lower overpotential of 121 mV compared to the pristine NiFe2O4 catalyst. Moreover, Ni0.2Mg0.8Fe2O4 catalyst exhibited the best OER performance with a low overpotential of 284 mV at 10 mA/cm2 in 1 M KOH. This enhanced electrocatalytic activity could be due to improved electronic conductivity caused by the partial substitution of Ni2+ by Mg2+ in the NiFe2O4 matrix as well as the synergistic effect in the Mg-substituted NiFe2O4. Our results suggest a feasible route for developing earth-abundant metal oxide-based electrocatalysts for future water electrolysis applications.

15.
Pak J Med Sci ; 39(6): 1742-1746, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37936734

RESUMO

Objectives: To identify the latest trends in the clinical picture and severity of the disease, which will help better understand and manage dengue. Methodology: It was a cross-sectional, hospital-based study performed in the tertiary care hospitals of Punjab from August 21 to December 2022, in which serologically and polymerase chain reaction (PCR) confirmed patients with dengue infection, were enrolled. Demographic and clinical variables were recorded on a pre-tested Performa, processed and presented in frequency and percentages, and graphs were generated. Mean and standard deviation was used to present continuous variables. Results: Out of a total of 580 patients, 472 were diagnosed with Dengue Fever (DF) and 108 with Dengue Hemorrhagic Fever (DHF). About 79.31% of the patients were male and 20.69% were females. The mean age of patients was 32.5±9 years. Among the clinical features the percentage of high-grade fever, body aches, and vomiting were the highest. The liver function profile showed that serum bilirubin, Serum aspartate transaminase (AST), serum alanine transaminase (ALT,) and alkaline phosphatase (ALP) levels were markedly raised. Conclusion: This study showed that with time the trends in the presentation of dengue are slowly shifting, which will help us better manage the disease burden in the future.

16.
J Infect Public Health ; 16(12): 1971-1981, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37879150

RESUMO

BACKGROUND: Genomic characterization of the dengue virus (DENV) is useful for understanding its molecular evolution, transmission, pathogenicity and infectivity. The DENV genomic RNA encodes three structural proteins, capsid (C) envelope (E) and membrane (M) proteins mediating viral entry and assembly during host infection. The current study aims to explore the DENV serotypes and mutations in the E and M proteins. METHODS: Twenty-three samples of DENV-positive patients were processed and selected for whole genome sequencing (WGS) from the Punjab Province of Pakistan. RESULTS: Among the 23 WGS, 19 samples showed numerous mutations (BioProject ID PRJNA943555). DENV1 and DENV2 are the most prevalent serotypes. A total of 179 mutations were detected in the E protein, in which K203E, T88A, I114L, and I293T are novel. The I270L, T272A, S273L, and T277A were found in the "kl" ß-hairpin (aa 270-279). The M protein harbors 74 mutations, of which 24 were novel. Three prominent complementary regions in the prM and E protein complex formations include R6, E46, D47, D63, and D65 on 'pr' peptide, and E84, K64, and H244, K247 on E, remain conserved except R6C. To our knowledge, it is the first comprehensive study of mutations in structural proteins. CONCLUSION: Genomic epidemiology is critical for analyzing emerging mutations and designing new policies therapeutic efforts for future outbreaks.


Assuntos
Vírus da Dengue , Dengue , Humanos , Vírus da Dengue/genética , Anticorpos Antivirais , Mutação , Dengue/epidemiologia , Genoma Viral
17.
Front Pharmacol ; 14: 1265440, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37745070

RESUMO

Cancer has remained one of the leading causes of death worldwide, with a lack of effective treatment. The intrinsic shortcomings of conventional therapeutics regarding tumor specificity and non-specific toxicity prompt us to look for alternative therapeutics to mitigate these limitations. In this regard, we developed multifunctional bimetallic (FeCo) bi-MIL-88B-FC MOFs modified with folic acid-conjugated chitosan (FC) as drug delivery systems (DDS) for targeted delivery of 5-Fluorouracil (5-FU). The bi-MIL-88B nanocarriers were characterized through various techniques, including powder X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray, thermogravimetric analysis, and Fourier transform infrared spectroscopy. Interestingly, 5-FU@bi-MIL-88B-FC showed slower release of 5-FU due to a gated effect phenomenon endowed by FC surface coating compared to un-modified 5-FU@bi-MIL-88B. The pH-responsive drug release was observed, with 58% of the loaded 5-FU released in cancer cells mimicking pH (5.2) compared to only 24.9% released under physiological pH (5.4). The in vitro cytotoxicity and cellular internalization experiments revealed the superiority of 5-FU@bi-MIL-88B-FC as a highly potent targeted DDS against folate receptor (FR) positive SW480 cancer cells. Moreover, due to the presence of Fe and Co in the structure, bi-MIL-88B exhibited peroxidase-like activity for chemodynamic therapy. Based on the results, 5-FU@bi-MIL-88B-FC could serve as promising candidate for smart DDS by sustained drug release and selective targeting.

18.
Heliyon ; 9(7): e18033, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37483772

RESUMO

Traumatic brain injury (TBI) is the major and leading cause of mortality and an alarming public health challenge. TBI leads to permanent cognitive, motor, sensory and psychotic disabilities. Patients suffering from the various and long-term repercussions of TBI currently have limited therapy choices. The current research work was designed to evaluate the beneficial and neuroprotective role of Troxerutin (Trox) (a natural flavonoid) in a closed brain injury mouse model. The male BALB/c 8-weeks old mice (n꞊150) were randomly distributed in three experimental groups. Control group of mice (n꞊50), TBI group (n꞊50) and Trox pre-treated mice group (Trox + TBI, n꞊50). The mice in Trox + TBI were pre-treated with Trox (150 mg/kg, 7 days) before TBI. The weight-drop mechanism was used to induce mild-moderate injury in mice in both the groups. Our results showed that the mice pre-treated with troxerutin significantly improved neurological severity score, blood glucose level, food intake and brain edema as compared to the mice in the TBI group. Furthermore, compared to the TBI group, the mice treated with troxerutin improved cognitive behavior as evaluated by Open field test, Shallow Water Maze and Y-Maze, decreased brain-infarct volume and blood-brain barrier (BBB) permeability, significantly decreased Reactive Oxygen Species (ROS), improved neuronal morphology and survival in the brain regions such as cortex and hippocampus. In summary, our data provided evidence that pre-treatment with troxerutin improved neurological functions, decreased the BBB permeability, improved behavior, reduced ROS and increased neuronal survival in the weight-drop close head traumatic injury mouse model.

19.
Inorg Chem ; 62(21): 8379-8388, 2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37191662

RESUMO

The electrochemical conversion of oxygen to water is a crucial process required for renewable energy production, whereas its first two-electron step produces a versatile chemical and oxidant─hydrogen peroxide. Improving performance and widening the limited selection of the potential catalysts for this reaction is a step toward the implementation of clean-energy technologies. As silver is known as one of the most effective catalysts of oxygen reduction reaction (ORR), we have designed a suitable molecular precursor pathway for the selective synthesis of metallic (Ag), intermetallic (Ag3Sb), and binary or ternary metal sulfide (Ag2S and AgSbS2) nanomaterials by judicious control of reaction conditions. The decomposition of xanthate precursors under different reaction conditions in colloidal synthesis indicates that carbon-sulfur bond cleavage yields the respective metal sulfide nanomaterials. This is not the case in the presence of trioctylphosphine when the metal-sulfur bond is broken. The synthesized nanomaterials were applied as catalysts of oxygen reduction at the liquid-liquid and solid-liquid interfaces. Ag exhibits the best performance for electrochemical oxygen reduction, whereas the electrocatalytic performance of Ag and Ag3Sb is comparable for peroxide reduction in an alkaline medium. Scanning electrochemical microscopy (SECM) analysis indicates that a flexible 2-electron to 4-electron ORR pathway has been achieved by transforming metallic Ag into intermetallic Ag3Sb.

20.
J Pak Med Assoc ; 73(3): 723-727, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36932799

RESUMO

Epilepsy is the third most common neurological disease in the world associated with a high frequency in the paediatric age group. This study aims to evaluate the prevalence, types and aetiologies of epilepsy within the Pakistani population. A retrospective review of the charts of all patients, below the age of 18 years, presenting with epilepsy to the Department of Neurology at The Children's Hospital and Institute of Child Health, Lahore, from January 2016 to December 2020, was carried out. Analysis was performed using SPSS Version 26. A p value of <0.05 was considered statistically significant. A total of 1,097 patients were studied, of which 644 (58.8%) were males and 451 (41.2%) females. a vast majority, i.e. 1,021 (96.1%), of the study participants, belonged to the province of Punjab. Afebrile seizures [n=798 (72.7%)] were more commonly reported than febrile seizures [n=299 (27.3%)]. Among seizure types, generalised seizures were the most common type of seizure reported in 520 (49.8%) patients. Refractory seizures were the least common type reported in 3 (0.3%) patients. Aetiology was mostly idiopathic [n=540 (49.2)], followed by congenital [n=228 (20.8%)]. The most frequently reported duration of seizure was between one and three minutes [n=116 (42.3%)]. The most common ictal features seen were a combination of up-rolling of eyes and frothing from the mouth [n=206 (34.9%)]. Results from this study can be used by health care providers to better formulate therapeutic interventions for a timely diagnosis and effective treatment of epilepsy.


Assuntos
Epilepsias Parciais , Epilepsia Generalizada , Epilepsia , Masculino , Feminino , Humanos , Criança , Adolescente , Anticonvulsivantes/uso terapêutico , Paquistão/epidemiologia , Epilepsias Parciais/tratamento farmacológico , Centros de Atenção Terciária , Epilepsia Generalizada/tratamento farmacológico , Epilepsia/epidemiologia , Epilepsia/tratamento farmacológico , Convulsões/epidemiologia , Convulsões/etiologia , Convulsões/tratamento farmacológico
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