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1.
Ann Med Surg (Lond) ; 86(4): 1933-1941, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38576948

RESUMO

Background and aims: Increased use of digital devices in the modern era has led to the development of digital eye strain (DES) or computer vision syndrome in their users. This can result in the development of various ocular and visual symptoms among them. In this study, the authors aimed to view the prevalence of digital eye strain among radiology physicians in Pakistan and their associated risk factors. Materials and methods: A cross-sectional study was conducted to evaluate occupational DES among radiology physicians in Pakistan. The data collection was done using the convenience sampling technique, and the data were analyzed using IBM SPSS for Windows, Version 25.0. Results: Out of the 247 respondents, 33.6% were males and 66.4% were females. 41.7% of them were between 30 and 40 years of age and 51.8% of them were radiology residents. 52.2% of the participants had a refractive error and were using a corrective lens. The majority of the radiologists in our study (84.2%) preferred picture archiving and communication system (PACS) over films and 82.2% of them reported having breaks of less than 15 min. Major symptoms reported by the participants were tired or heavy eyes (69.6%) and headache (69.3%). The proportion of developing DES was higher in females [P=0.001, adjusted odds ratio (aOR)=2.94], radiology residents (P=0.031, aOR=3.29), and working hours of more than 4 h per day (P<0.001, aOR=0.04). Conclusion: With recent advances in the field of radiology in Pakistan, the frequency of developing DES among radiologists is increasing. Being a female, having long working hours, and having noticeable flickers on the digital screens were among the significant factors in developing DES among radiologists.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38563867

RESUMO

BACKGROUND: Vasomotor symptoms (VMS), such as hot flashes and night sweats, are highly prevalent and burdensome for women experiencing menopausal transition. Fezolinetant, a selective neurokinin 3 receptor (NK3R) antagonist, is a potential therapeutic option for mitigating VMS. OBJECTIVES: Our aim is to assess the efficacy and evaluate the safety profile of fezolinetant compared with placebo in post-menopausal women suffering from VMS, by pooling all the relevant data and reflecting the most current evidence. SEARCH STRATEGY/SELECTION CRITERIA: An extensive literature search was performed in the PubMed, Medline and Cochrane Library databases from inception until June 2023 to identify relevant trials. DATA COLLECTION AND ANALYSIS: Mean differences (MDs) and 95% confidence intervals (CIs) were calculated for continuous outcomes. Risk ratios (RRs) were calculated for dichotomous outcomes. All statistical analyses were performed using R Statistical Software. MAIN RESULTS: A total of six randomized controlled trials were added. For the frequency of daily VMS, the combined pooled result favored the fezolinetant group over placebo (MD -2.38, 95% CI -2.64 to -2.12; P < 0.001, I2 = 0%). For the severity of daily VMS, fezolinetant was again found to be superior to the placebo group (MD -0.40, 95% CI -0.51 to -0.29; P < 0.001, I2 = 70%). Fezolinetant (120 mg) consistently demonstrated a significant reduction in the severity of daily moderate/severe VMS compared with other doses at both 4 and 12 weeks. Patient-reported outcomes (PROs) of Greene Climacteric Scale (GCS), PROMIS the Sleep Disturbance Short Form 8b and Menopause-Specific Quality of Life (MENQoL) scores indicated significant improvement with fezolinetant. No significant difference in efficacy of fezolinetant at 4 and 12 weeks were observed in any outcome. As for safety, no significant differences in the treatment emergent adverse events at 12 weeks were found between fezolinetant and placebo. CONCLUSIONS: Our study significantly favors fezolinetant over placebo regarding the primary efficacy outcomes of daily moderate to severe VMS frequency and severity, including PROs, while both the groups are comparable in terms of treatment emergent adverse events. Further studies are needed to confirm these findings.

4.
Front Nutr ; 11: 1344986, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585617

RESUMO

The lentil (Lens culinaris Medikus ssp. Culinaris) is a self-pollinating, diploid (2n = 2X = 14) crop with a genome size of 4 Gbp. The present study was conducted to provide a database for the evaluation of lentil antioxidant capacity, nutritional quality, and biochemical attributes. For these purposes, lentil germplasm, including 100 exotic and local genotypes from different agro-climatic zones of Pakistan, was collected. Significant variation (p < 0.05) was found among the genotypes under investigation using the Tukey HSD test. Ascorbate peroxidase was highest in ALTINOPARK (2,465 Units/g s. wt.), catalase in LPP 12110 (5,595 Units/g s. wt.), superoxide dismutase in LPP 12105 (296.75 Units/g s. wt.), and peroxidase in NIAB Masoor 2002 (3,170 Units/g s. wt.). Furthermore, NLM 15016 had a maximum total antioxidant capacity of 15.763 mg/g s. wt. The maximum values of total soluble sugars (83.93 mg/g. s. wt.) and non-reducing sugars (74.79 mg/g. s. wt.) were noticed in NLM 15015. The highest reducing sugars were detected in ILL 8006 (45.68 mg/g. s. wt.) ascorbic acid in LPP 12182 (706 µg/g s. wt.), total phenolic content in NLI 17003 (54,600 µM/g s. wt.), and tannins in NLI 17057 (24,563 µM/g s. wt.). The highest chlorophyll a (236.12 µg/g s. wt.), chlorophyll b (317 µg/g s. wt.), total chlorophyll (552.58 µg/g s. wt.), and lycopene (10.881 µg/g s. wt.) were found in NLH 12097. Maximum total carotenoids were revealed in the local approved variety Markaz 2009 (17.89 µg/g s. wt.). Principal component analysis (PCA), correlation analysis (Pearson's test), and agglomerative hierarchical clustering (AHC) were performed to detect the extent of variation in genotypes. In cluster analysis, all genotypes were categorized into three clusters. Cluster II genotypes showed remarkable divergence with cluster III. According to PCA, the contribution of PC-I regarding tested nutritional parameters toward variability was the highest (39.75%) and indicated positive factor loading for the tested nutritional and biochemical parameters. In conclusion, genotype X 2011S 33-34-32 can be used by the food industry in making pasta, multigrain bread, and snacking foods due to its high protein content for meat alternative seekers. Identified genotypes with high nutritional attributes can be utilized to improve quality parameters in the respective lentil breeding lines.

5.
Int J Biol Macromol ; 266(Pt 2): 131393, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38582476

RESUMO

Biocomposites developed using natural fibers serve as a sustainable alternative to synthetic composite materials. However, narrowing the performance gap between synthetic composites and biocomposites requires serious efforts. A promising approach is the modification of natural fibers using various chemical treatments. This paper investigates the potential of tannic acid (TA) treatment as a sustainable approach to enhance mechanical performance and reduce moisture absorption of flax fabric-reinforced biocomposites. The methodology involves the treatment of flax woven fabric with tannic acid, a naturally occurring polyphenolic compound, followed by the fabrication of biocomposite using a green epoxy matrix. The variables studied during treatment are TA concentration and processing time. Characterization of untreated and treated flax fabric and its composites was done using various analytical techniques such as FTIR spectroscopy, moisture absorption and mechanical testing (tensile strength, flexural strength, and impact resistance). FTIR spectroscopy of TA-treated flax confirmed attachment of aromatic rings and carbon double bond formation, thus serving for properties enhancement. The mechanical characterization of composites showed that properties are enhanced up to an optimum limit of concentration and processing time i.e., 1 % concentration and 30 min of processing. Moisture absorption of the TA-treated composite also reduced significantly as compared to untreated composites. These findings contribute towards the advancement in sustainable biocomposites and pave the way for their utilization in various applications.

6.
J Coll Physicians Surg Pak ; 34(4): 480-483, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38576294

RESUMO

OBJECTIVE: To analyse the frequency, risk factors, and clinical symptoms of acute graft-versus-host disease (aGvHD) in patients with beta-thalassemia major after allogeneic haematopoietic stem cell transplantation (HSCT). STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Clinical Haematology, Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, from January 2017 to December 2021. METHODOLOGY: Data were obtained from patients diagnosed with bone and tissue malignancies (BTM) who had undergone haematopoietic stem cell transplantation (HSCT) and experienced aGVHD. Patients who experienced initial graft failure and individuals who underwent subsequent bone marrow transplantation were excluded. RESULTS: Total of 117 patients diagnosed with BTM underwent fully matched HSCT, including 76 (65%) males, and 41 (35%) females. The median age of the patients undergoing transplantation was 7.34±7.32 years and the donors' median age was 7.6±9.85 years. Among the donors, 53 (45.3%) were males and 64 (54.7%) were females. Gender disparity was observed in 46 (39.3%) instances as a female donor matched with a male recipient. A total of 106 individuals underwent bone marrow harvest (BMH); with 5 (4.3%) patients receiving peripheral blood stem cells (PBSC) and 6 (5.2%) patients receiving both BMH and PBSC. Acute GvHD was observed in 50 (42.7%) patients, including 30 (60%) males and 20 (40%) females. Grade I GvHD occurred in 32 (27.3%) individuals, Grade II GvHD in 16 (13.7%) patients, and Grade III GvHD in one (0.8%) patient. It had no statistically significant association with recipient/donor age, gender disparity, the source of the graft source, the dose of stem cells, or the presence of thymoglobulin (TG). CONCLUSION: Acute GvHD was observed in high frequency in Beta-thalassemia patients receiving morrow harvesting proportional to their gender distribution. Associated factors were GvHD prophylaxis measure, mucositis and, CMV reactivation. KEY WORDS: Beta thalassemia major patients, Acute graft versus host disease, Allogeneic haematopoietic stem cell.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Talassemia beta , Humanos , Masculino , Feminino , Criança , Adolescente , Recém-Nascido , Lactente , Pré-Escolar , Talassemia beta/complicações , Talassemia beta/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Medula Óssea/efeitos adversos , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Paquistão/epidemiologia , Estudos Retrospectivos
7.
Sci Rep ; 14(1): 7292, 2024 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538691

RESUMO

Glioblastoma multiforme (GBM) IDH-wildtype is the most prevalent brain malignancy in adults. However, molecular mechanisms, which leads to GBM have not been completely elucidated. Granulocyte colony-stimulating factor (GCSF), Granulocyte colony-stimulating factor receptor GCSFR, and Signal transducers and activators of transcription 3 (STAT3) have been involved in the occurrence and development of various cancers, but their role in GBM is little known. Herein, we have investigated the gene and protein expression of GCSF, GCSFR, and STAT3 in 21 tissue biopsy samples and also in tumor associated normal tissue (TANT) samples derived from glioblastoma patients, which revealed significantly differential expression of these genes. To validate our findings, we performed a comprehensive integrated analysis of transcriptomic and proteomic profiling of respective genes by retrieving GBM RNA-sequence data from Genome Atlas Databases. GO and KEGG analysis revealed enrichment in disease-related pathways, such as JAK/STAT pathway activation, which were associated with GBM progression. We further performed computational docking analysis of potential drug candidate Nisin against GCSF, and the results were validated in vitro through cytotoxic activity assay using a human glioblastoma cell line SF-767 in a dose-dependent manner. Our comprehensive analysis reveals that GCSF augments glioma progression, and its blockade with anticancer bacteriocin peptide Nisin can potentially inhibit the growth and metastasis of GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Nisina , Adulto , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Nisina/metabolismo , Janus Quinases/metabolismo , Proteômica , Transdução de Sinais , Fatores de Transcrição STAT/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Fator Estimulador de Colônias de Granulócitos/metabolismo , Regulação Neoplásica da Expressão Gênica
8.
Curr Probl Cardiol ; 49(6): 102530, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38518844

RESUMO

Rheumatic Heart Disease (RHD) remains a leading cause of cardiovascular death (CVD) globally. Mitral Valve repair (MVP) and mitral valve replacement (MVR) are the two most commonly and successfully used techniques to treat the disease. MVP is associated with reduced post-operative complications compared to MVR; however, it carries the risk of valvular fibrosis and scarring. Given the lack of recommendations, inconsistent findings, and paucity of pathophysiological evidence at present, we aimed to conduct a meta-analysis and systematically review the available literature to determine the efficacy and safety of MVP compared to MVR in improving clinical outcomes among patients with RHD. A comprehensive literature search was conducted on MEDLINE (PubMed), Cochrane Central and Scopus from inception till September 2023. The primary objective was early mortality defined as any cause-related death occurring 30 days following surgery. Secondary outcomes included long-term survival defined as the time duration between hospital discharge and all-cause death. Infectious endocarditis, thromboembolic events (including stroke, brain infarction, peripheral embolism, valve thrombosis, and transient ischemic attack), and haemorrhagic events (any serious bleeding event that required hospitalisation, resulted in death, resulted in permanent injury, or required blood transfusion) were all considered as post- operative complications. Additionally aggregated Kaplan-Meier curves were reconstructed for long term survival, freedom from reoperation, and freedom from valve-related adverse events by merging the reconstructed individual patient data (IPD) from each individual study. A significant decrease in early mortality with MV repair strategy versus MV replacement [RR 0.63; P = 0.003) irrespective of mechanical or bioprosthetic valves was noted. The results reported significantly higher long-term survival in patients undergoing MVP versus MVR (HR 0.53; P = 0.0009). Reconstructed Kaplan-Meier curves showed that the long term survival rates at 4, 8, and 12 years were 88.6, 82.0, 74.6 %, in the MVR group and 91.7, 86.8, 81.0 %, in the MVP group, respectively. MVP showed statistically significant reduction in early mortality, adverse vascular events, and better long-term survival outcomes compared to the MVR strategy in this analysis.

9.
Cont Lens Anterior Eye ; : 102148, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38514290

RESUMO

PURPOSE: Demodex blepharitis, often overlooked in ocular surface disease, involves Demodex mites, prevalent ectoparasites on human skin. Current treatments may not effectively eliminate these mites, prompting a need for targeted therapies. Lotilaner, an antiparasitic agent, shows promise. This systematic review and meta-analysis assesses 0.25% lotilaner ophthalmic solution's efficacy in reducing Demodex mite populations and its impact on ocular surface inflammation in Demodex blepharitis patients. METHODS: A comprehensive literature search was performed in the PubMed and Cochrane Library databases from inception until February 2024 to identify relevant trials investigating the use of lotilaner in patients with Demodex blepharitis. The included studies were assessed for quality, and a meta-analysis was conducted to determine the overall treatment effects of lotilaner. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated for binary variables. All statistical analyses were performed using the R Statistical Software. RESULTS: Five studies met the inclusion criteria and were included in this systematic review and meta-analysis. Lotilaner demonstrated significant efficacy in Collarette Cure [OR = 6.64; 95 % CI 3.78 to 11.04; p < 0.00001, I2 = 62 %] %], clinically meaningful collarette reduction [OR = 6.21; 95 % CI 3.67 to 10.49; p < 0.00001, I2 = 90 %], and achieving at least 1-grade collarette improvement [OR = 5.12; 95 % CI (2.96 to 8.88); p < 0.00001, I2 = 90 %] compared to the placebo group. The treatment also resulted in mite eradication [OR = 6.18; 95 % CI 4.67 to 6.18; p < 0.00001, I2 = 34 %], reduction in mite density [OR = 9.37; 95 % CI 5.36 to 16.36; p < 0.00001, I2 = 84 %], and erythema cure [OR = 2.29; 95 % CI 2.24 to 3.39; p < 0.00001, I2 = 5 %] and composite cure [OR = 7.05; 95 % CI 3.66 13. 61; p < 0.00001, I2 = 11 %]. The study suggests that lotilaner is a promising therapeutic option for collarette and associated symptoms, but the high heterogeneity in some outcomes and limited long-term data warrant further research to confirm its effectiveness and safety. CONCLUSION: This systematic review and meta-analysis provides robust evidence supporting the efficacy of 0.25% lotilaner ophthalmic solution in treating Demodex blepharitis. Approval of this targeted therapy represents a significant milestone in ophthalmology and offers a promising treatment option for patients with Demodex blepharitis. Eye care professionals should consider the potential benefits of lotilaner in managing and alleviating the symptoms associated with Demodex infestations on the eyelids. Further research and long-term follow-up studies are warranted to assess the safety and effectiveness of lotilaner in treating Demodex blepharitis.

10.
PLoS One ; 19(3): e0298414, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38483918

RESUMO

ß-glucan is a well-documented feed additive for its potent immunostimulatory properties in many farmed fish species. This study examined how it can also be a promising growth promoter, modulate antioxidant enzyme activities, and act as an anti-stress agent in striped catfish (Pangasianodon hypophthalmus). A 12-week feeding experiment was untaken to determine the effects of dietary ß-glucan supplementation at graded levels (0, 0.5, 1.0, and 1.5 g kg-1). Measured indicators suggest that a dietary inclusion level of 1.5 g kg-1 ß-glucan gave the highest positive responses: weight gain (120.10 g fish-1), survival (98.30%), and lower FCR (1.70) (P<0.05). Whole body proximate analysis had only revealed that crude protein was significantly affected by the dietary inclusion of ß-glucan (P<0.05), with the highest protein content (19.70%) being in fish that were fed with 1.5 g kg-1 ß-glucan. Although other inclusion levels (i.e., 0.5 and 1 g kg-1) of ß-glucan did not enhance body protein content (P>0.05). The assessment of fatty acid composition in muscle, liver, and adipose tissues showed modifications with the inclusion of ß-glucan. Antioxidative-related enzyme activities (inc. catalase, glutathione peroxidase, and superoxide dismutase) that were measured in the liver had higher levels when fed with ß-glucan inclusion diets (P<0.05). Following the feed trial, fish were subjected to crowding stress treatment. It was subsequently found that catfish fed with ß-glucan-based diet groups had lower levels of blood stress-related indicators compared to the control group with no dietary ß-glucan. The use of 1.5 g kg-1 of dietary ß-glucan resulted in the lowest measured levels of cortisol (43.13 ng mL-1) and glucose (50.16 mg dL-1). This study has demonstrated that the dietary inclusion of ß-glucan can have functional benefits beyond the immunological enhancements in striped catfish. Furthermore, its use can increase production levels and mitigate the stress associated with intensive farming practices.


Assuntos
Peixes-Gato , beta-Glucanas , Animais , beta-Glucanas/farmacologia , Suplementos Nutricionais/análise , Dieta/veterinária , Antioxidantes/farmacologia , Ração Animal/análise
11.
PLoS One ; 19(3): e0299195, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38483972

RESUMO

A 90-day study was conducted to investigate the effects of substituting sunflower oil (SFO) for fish oil (FO) on various parameters in Labeo rohita (initial weight 18.21 ± 0.22 g). Five experimental diets with different levels of SFO (up to 7%) substitution for FO (0%, 25%, 50%, 75%, and 100%) were formulated, ensuring equal levels of nitrogen and lipids. The results indicated that even with 100% substitution of SFO with FO, there were no significant differences (P>0.05) were observed in growth performance. The survival rate (SR), hepato-somatic index (HSI), and viscero-somatic index (VSI) as well as whole-body composition were also nonsignificant by SFO substitution. However, the fatty acid profiles in both muscle and liver were influenced (P<0.05) by dietary substitution. Saturated fats (SFA) decreased, while monounsaturated fats (MUFA), and linoleic acid (LA) increased (P<0.05). On the other hand, the contribution of linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) decreased (P<0.05) as the amount of SFO in the diet increased. Hematology parameters, including red blood cells (RBCs), hemoglobin (Hb), and hematocrit (Hct), were not affected. Globulin (GLO) levels decreased significantly (P<0.05), while alanine transaminase (ALT) and aspartate transaminase (AST) activity showed nonsignificant increases (P>0.05). Total protein (TP) increased (P<0.05) at 100% SFO inclusion in the diet, and albumin (ALB) levels increased (P<0.05) at 75% and 100% SFO inclusion in the diet. Cholesterol (CHOL), triacylglycerol (TG), and high-density lipids (HDL) were not significantly affected (P>0.05), while low-density lipids (LDL) were significantly increased (P<0.05) compared to the control group. Cortisol (CORT) and glucose (GLU) levels showed nonsignificant (P>0.05) changes. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities in the liver and serum were not significantly (P>0.05) affected, while malondialdehyde (MDA) status was significantly (P<0.05) reduced. In conclusion, the fatty acid profile of the muscle and liver of fish was modified by the diets, and FO can be substituted with SFO up to 100% for L. rohita, which is beneficial for growth and immunity while marinating the lipid contents in fish. Our study revealed that fully replacing fish oil with SFO shows promise in fully replacing FO without compromising the growth and overall health status of the fish.


Assuntos
Ácidos Graxos , Óleos de Peixe , Óleos de Peixe/farmacologia , Ácidos Graxos/metabolismo , Antioxidantes/metabolismo , Óleo de Girassol , Estudos de Viabilidade , Óleos de Plantas/farmacologia , Dieta , Fígado/metabolismo , Composição Corporal , Biomarcadores/metabolismo
12.
East Mediterr Health J ; 30(1): 46-52, 2024 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-38415335

RESUMO

Background: In Pakistan, where the burden of communicable diseases remains high, the private sector accounts for 62% of health care provision. Aim: To describe the role of the private sector in communicable disease management in Pakistan and inform a more effective engagement towards achieving Universal Health Coverage. Methods: We searched the literature and available documents on policies, regulations and experiences in private health sector engagement in Pakistan. We interviewed policy level experts regarding the formulation of national health policies and plans and a sample of private providers using a structured questionnaire to assess their awareness of and engagement in communicable disease programmes. Results: Published reports described initiatives to engage the private sector in improving coverage for a package of care and programme-specific initiatives. Pakistan did not have a national policy for structural engagement, and regulations were limited. Policy level experts interviewed perceived the private sector as market-driven and poorly regulated. Thirty-nine percent of private sector providers interviewed were aware or had been trained in procedures or guidelines, and 23% of them had had their performance monitored by government. Conclusion: We recommend that the Ministry of Health provide overall vision for the operations of the public and private health sectors so that both sectors can complement each other towards the achievement of Universal Health Coverage, including for communicable diseases.


Assuntos
Doenças Transmissíveis , Setor Privado , Humanos , Paquistão , Imunização , Vacinação , Doenças Transmissíveis/epidemiologia
13.
Int J Cancer ; 154(11): 1987-1998, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38319157

RESUMO

Approximately 5% of colorectal cancers (CRCs) have a gain-of-function mutation in the GNAS gene, which leads to the activation of cAMP-dependent signaling pathways and associates with poor prognosis. We investigated the effect of an activating GNAS mutation in CRC cell lines on gene expression and cell proliferation in vitro, and tumor growth in vivo. GNAS-mutated (GNASmt) HCT116 cells showed stimulated synthesis of cAMP as compared to parental (Par) cells. The most upregulated gene in the GNASmt cells was cAMP-hydrolyzing phosphodiesterase 4D (PDE4D) as detected by RNA sequencing. To further validate our finding, we analyzed PDE4D expression in a set of human CRC tumors (n = 35) and demonstrated overexpression in GNAS mutant CRC tumors as compared to GNAS wild-type tumors. The GNASmt HCT116 cells proliferated more slowly than the Par cells. PDE4 inhibitor Ro 20-1724 and PDE4D subtype selective inhibitor GEBR-7b further suppressed the proliferation of GNASmt cells without an effect on Par cells. The growth inhibitory effect of these inhibitors was also seen in the intrinsically GNAS-mutated SK-CO-1 CRC cell line having high levels of cAMP synthesis and PDE4D expression. In vivo, GNASmt HCT116 cells formed smaller tumors than the Par cells in nude mice. In conclusion, our findings demonstrate that GNAS mutation results in the growth suppression of CRC cells. Moreover, the GNAS mutation-induced overexpression of PDE4D provides a potential avenue to impede the proliferation of CRC cells through the use of PDE4 inhibitors.


Assuntos
Cromograninas , Neoplasias Colorretais , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4 , Subunidades alfa Gs de Proteínas de Ligação ao GTP , Animais , Humanos , Camundongos , Cromograninas/genética , Cromograninas/metabolismo , Neoplasias Colorretais/genética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Células HCT116 , Camundongos Nus , Mutação , Inibidores da Fosfodiesterase 4/farmacologia
14.
J Clin Anesth ; 94: 111425, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38412619

RESUMO

BACKGROUND: Ciprofol, a newer entrant with similarities to propofol, has shown promise with a potentially improved safety profile, making it an attractive alternative for induction of general anesthesia. This meta-analysis aimed to assess the safety and efficacy of ciprofol compared with propofol during general anesthesia induction. METHODS: A comprehensive literature search was conducted using PubMed, Clinical Trial.gov, and Cochrane Library databases from inception to July 2023 to identify relevant studies. All statistical analyses were conducted using R statistical software version 4.1.2. RESULTS: Thirteen Randomized Controlled Trials (RCTs) encompassing a total of 1998 participants, were included in our analysis. The pooled analysis indicated that Ciprofol was associated with a notably lower incidence of pain upon injection [RR: 0.15; 95% CI: 0.10 to 0.23; I^2 = 43%, p < 0.0000001] and was non-inferior to propofol in terms of anesthesia success rate [RR: 1.00; 95% CI: 0.99 to 1.01; I^2 = 0%; p = 0.43]. In terms of safety, the incidence of hypotension was significantly lower in the ciprofol group [RR:0.82; 95% CI:0.68 to 0.98; I^2 = 48%; p = 0.03]. However, no statistically significant differences were found for postoperative hypertension, bradycardia, or tachycardia. CONCLUSION: In conclusion, Ciprofol is not inferior to Propofol in terms of its effectiveness in general anesthesia. Ciprofol emerges as a valuable alternative sedative with fewer side effects, especially reduced injection pain, when compared to Propofol. SUMMARY: Propofol, frequently utilized as an anesthetic, provides swift onset and quick recovery. However, it has drawbacks such as a narrow effective dosage range and a high occurrence of adverse effects, particularly pain upon injection. Ciprofol, a more recent drug with propofol-like properties, has demonstrated promise and may have an improved safety profile, making it a compelling alternative for inducing general anesthesia. This meta-analysis compared the safety and effectiveness of Ciprofol with Propofol for general anesthesia induction in a range of medical procedures, encompassing thirteen Randomized Controlled Trials (RCTs) and 1998 individuals. The pooled analysis indicated that Ciprofol was associated with a notably lower incidence of pain upon injection [RR: 0.15; 95% CI: 0.10 to 0.23; I^2 = 43%, p < 0.0000001] and was non-inferior to propofol in terms of anesthesia success rate [RR: 1.00; 95% CI: 0.99 to 1.01; I^2 = 0%; p = 0.43]. In terms of safety, the incidence of hypotension was significantly lower in the ciprofol group [RR:0.82; 95% CI:0.68 to 0.98; I^2 = 48%; p = 0.03]. However, no statistically significant differences were found for hypertension, bradycardia, or tachycardia. In conclusion, ciprofol is equally effective at inducing and maintaining general anesthesia as propofol. When compared to propofol, ciprofol is a better alternative sedative for operations including fiberoptic bronchoscopy, gynecological procedures, gastrointestinal endoscopic procedures, and elective surgeries because it has less adverse effects, most notably less painful injections.


Assuntos
Anestesia Geral , Anestésicos Intravenosos , Propofol , Humanos , Bradicardia/induzido quimicamente , Hipertensão/induzido quimicamente , Hipotensão/induzido quimicamente , Dor , Propofol/efeitos adversos , Propofol/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Taquicardia/induzido quimicamente , Anestésicos Intravenosos/efeitos adversos , Anestésicos Intravenosos/uso terapêutico
15.
Vaccine X ; 17: 100452, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38328274

RESUMO

Influenza virus has presented a considerable healthcare challenge during the past years, particularly in vulnerable groups with compromised immune systems. Therapeutics and vaccination have always been in research annals since the spread of influenza. Efforts have been going on to develop an antiviral therapeutic approach that could assist in better disease management and reduce the overall disease complexity, resistance development, and fatality rates. On the other hand, vaccination presents a chance for effective, long-term, cost-benefit, and preventive response against the morbidity and mortality associated with the influenza. However, the issues of resistance development, strain mutation, antigenic variability, and inability to cure wide-spectrum and large-scale strains of the virus by available vaccines remain there. The article gathers the updated data for the therapeutics and available influenza vaccines, their mechanism of action, shortcomings, and trials under clinical experimentation. A methodological approach has been adopted to identify the prospective therapeutics and available vaccines approved and within the clinical trials against the influenza virus. Review contains influenza therapeutics, including traditional and novel antiviral drugs and inhibitor therapies against influenza virus as well as research trials based on newer drug combinations and latest technologies such as nanotechnology and organic and plant-based natural products. Most recent development of influenza vaccine has been discussed including some updates on traditional vaccination protocols and discussion on next-generation and upgraded novel technologies. This review will help the readers to understand the righteous approach for dealing with influenza virus infection and for deducing futuristic approaches for novel therapeutic and vaccine trials against Influenza.

16.
Am J Surg ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38336575

RESUMO

Despite the life-saving nature of colorectal surgeries, patients often experience intra and post-operative problems, especially pain and discomfort. This meta-analysis aimed to evaluate the effectiveness of erector spinae plane block (ESP block) in postoperative pain management for patients undergoing colorectal surgeries. A comprehensive systematic literature search was conducted in PubMed and Cochrane Library databases from inception until December 2023. Eight studies were deemed appropriate for inclusion. The pooled analysis demonstrated a significant decrease with the ESP block compared to the control group in postoperative opioid consumption [MD â€‹= â€‹-15.96 â€‹mg; 95 â€‹% CI (-28.74 to -3.18); p â€‹= â€‹0.014, I2 â€‹= â€‹87 â€‹%], intraoperative opioid consumption [MD â€‹= â€‹-35.51 â€‹mg; 95 â€‹% CI (-62.63 to -8.40); p â€‹= â€‹0.010, I2 â€‹= â€‹87 â€‹%], pain scores [MD â€‹= â€‹-0.94; 95 â€‹% CI (-1.27 to -0.60); p â€‹< â€‹0.000001, I2 â€‹= â€‹86 â€‹%], with a significantly shorter duration of hospital stay [MD â€‹= â€‹-1.25 days; 95 â€‹% CI (-2.02 to -0.48); p â€‹= â€‹0.002, I2 â€‹= â€‹23 â€‹%]. This meta-analysis support the use of erector spinae plane block (ESP) for postoperative pain management in colorectal surgeries. ESP shows significant reductions in opioid consumption, pain scores and hospital stay.

17.
Clin Kidney J ; 17(2): sfad226, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38327281

RESUMO

Chronic changes on kidney biopsy specimens include increasing amounts of arteriosclerosis, glomerulosclerosis, interstitial fibrosis and tubular atrophy, enlarged nephron size, and reduced nephron number. These chronic changes are difficult to accurately assess by visual inspection but are reasonably quantified using morphometry. This review describes the various patient populations that have undergone morphometric analysis of kidney biopsies. The common approaches to morphometric analysis are described. The chronic kidney disease outcomes associated with various chronic changes by morphometry are also summarized. Morphometry enriches the characterization of chronicity on a kidney biopsy and this can supplement the pathologist's diagnosis. Artificial intelligence image processing tools are needed to automate the annotations needed for practical morphometric analysis of kidney biopsy specimens in routine clinical care.

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