RESUMO
The kinetics of sulfur transfer from titanocene (poly)sulfides (RCp2TiS5, Cp2TiS4CMe2, Cp2Ti(SAr)2, Cp2TiCl(SAr)) to sulfenyl chlorides (S2Cl2, RSCl) have been investigated by a combination of stopped-flow UV-Vis/NMR reaction monitoring, titration assays, numerical kinetic modelling and KS-DFT calculations. The reactions are rapid, proceeding to completion over timescales of milliseconds to minutes, via a sequence of two S-S bond-forming steps (k 1, k 2). The archetypical polysulfides Cp2TiS5 (1a) and Cp2TiS4C(Me2) (2a) react with disulfur dichloride (S2Cl2) through rate-limiting intermolecular S-S bond formation (k 1) followed by a rapid intramolecular cyclization (k 2, with k 2 â« k 1 [RSCl]). The monofunctional sulfenyl chlorides (RSCl) studied herein react in two intermolecular S-S bond forming steps proceeding at similar rates (k 1 ≈ k 2). Reactions of titanocene bisthiophenolates, Cp2Ti(SAr)2 (5), with both mono- and di-functional sulfenyl chlorides result in rapid accumulation of the monothiophenolate, Cp2TiCl(SAr) (6) (k 1 > k 2). Across the range of reactants studied, the rates are relatively insensitive to changes in temperature and in the electronics of the sulfenyl chloride, moderately sensitive to the electronics of the titanocene (poly)sulfide (ρ (Ti-(SAr)) ≈ -2.0), and highly sensitive to the solvent polarity, with non-polar solvents (CS2, CCl4) leading to the slowest rates. The combined sensitivities are the result of a concerted, polarized and late transition state for the rate-limiting S-S bond forming step, accompanied by a large entropic penalty. Each substitution step {[Ti]-SR' + Cl-SR â [Ti]-Cl + RS-SR'} proceeds via titanium-assisted Cl-S cleavage to generate a transient pentacoordinate complex, Cl-[Cp2TiX]-S(R')-SR, which then undergoes rapid Ti-S dissociation.
RESUMO
The prevalence of thyroid dysfunction is increasing, often leading to unfavorable alterations in lipid profiles. Dyslipidemia is a risk factor for cardiovascular disease. The present study aimed to assess the prevalence of thyroid dysfunction and examine its effects on serum lipid profiles among Jordanians. A total of 228 subjects were recruited and divided into two groups: patients with thyroid dysfunction (n=178, mean age=52.6±9.8 years) and a control group (n=50, mean age=51.7±9.2 years). Serum thyroid-stimulating hormone, free thyroxine 4, free triiodothyronine 3, total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein and triglycerides (TG) were measured. Results showed that thyroid dysfunction was diagnosed in 75% of participants, with an increased frequency among females. The prevalence of overt hypothyroidism was 17.4%, subclinical hypothyroidism was 43.8%, overt hyperthyroidism was 18.4% and subclinical hyperthyroidism was 20.4%. There was a significant association between hypothyroidism and elevated TC (>200 mg/dl), LDL (>130 mg/dl) and TG (>200 mg/dl; P<0.05). Among the hypothyroid patients, 48.4% had hypercholesterolemia and 32.3% had hypertriglyceridemia. In conclusion, public screening and education are necessary to combat thyroid dysfunction. There is a notable link between thyroid dysfunction and lipid abnormalities, necessitating regular monitoring for dyslipidemia and cardiovascular disease in affected patients.
RESUMO
Faces are a crucial environmental trigger. They communicate information about several key features, including identity. However, the 2019 coronavirus pandemic (COVID-19) significantly affected how we process faces. To prevent viral spread, many governments ordered citizens to wear masks in public. In this research, we focus on identifying individuals from images or videos by comparing facial features, identifying a person's biometrics, and reducing the weaknesses of person recognition technology, for example when a person does not look directly at the camera, the lighting is poor, or the person has effectively covered their face. Consequently, we propose a hybrid approach of detecting either a person with or without a mask, a person who covers large parts of their face, and a person based on their gait via deep and machine learning algorithms. The experimental results are excellent compared to the current face and gait detectors. We achieved success of between 97% and 100% in the detection of face and gait based on F1 score, precision, and recall. Compared to the baseline CNN system, our approach achieves extremely high recognition accuracy.
Assuntos
COVID-19 , Aprendizado de Máquina , Redes Neurais de Computação , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Aprendizado Profundo , Algoritmos , SARS-CoV-2/isolamento & purificação , Face , Marcha/fisiologia , Identificação Biométrica/métodosRESUMO
OBJECTIVES: This aimed to develop a blueprint for an effective community pharmacy Hepatitis C virus (HCV) testing service by producing a consensus statement. STUDY DESIGN: This was a modified Delphi process. METHODS: We recruited a heterogenous panel of experts (who had been involved in the setup or delivery of a community pharmacy HCV testing service) by purposive and chain referral methods. We had three rounds of a modified Delphi process. The first was a series of questions with free text responses and was analysed using thematic analysis, and the second and third were statements for the respondents to rate using a 7-point Likert scale. Consensus was predefined in a published protocol, and the results were reviewed by a public and patient involvement panel before the statement was finalised. RESULTS: We had 24 participants, including community and hospital-based pharmacists, local pharmaceutical committee members, charity representatives (Hepatitis C Trust), local clinical service lead, nurse specialists and doctors. The response rate of the first, second and third rounds were 100%, 96% and 88%, respectively. After the third round, we had 60 statements that reached consensus. We discussed the accepted statements with a patient and public involvement group. We used these statements to produce the I-COPTIC statement and a graphical summary. CONCLUSIONS: We developed a blueprint for the design of a gold standard community pharmacy HCV testing service. We believe this will support the successful implementation of community pharmacy testing for HCV. Community pharmacy testing is an important service to help achieve and maintain HCV elimination.
Assuntos
Serviços Comunitários de Farmácia , Consenso , Técnica Delphi , Hepatite C , Humanos , Hepatite C/diagnóstico , Serviços Comunitários de Farmácia/organização & administração , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Farmácias/organização & administraçãoRESUMO
Cholangiocarcinoma (CCA) remains a devastating malignancy and a significant challenge to treat. The majority of CCA patients are diagnosed at an advanced stage, making the disease incurable in most cases. The advent of high-throughput genetic sequencing has significantly improved our understanding of the molecular biology underpinning cancer. The identification of 'druggable' genetic aberrations and the development of novel targeted therapies against them is opening up new treatment strategies. Currently, 3 targeted therapies are approved for use in CCA; Ivosidenib in patients with IDH1 mutations and Infigratinib/Pemigatinib in those with FGFR2 fusions. As our understanding of the biology underpinning CCA continues to improve it is highly likely that additional targeted therapies will become available in the near future. This is important, as it is thought up to 40 % of CCA patients harbour a potentially actionable mutation. In this review we provide an overview of the molecular pathogenesis of CCA and highlight currently available and potential future targeted treatments.
RESUMO
Angiogenesis is important for tissue during normal physiological processes as well as in a number of diseases, including cancer. Drug resistance is one of the largest difficulties to antiangiogenesis therapy. Due to their lower cytotoxicity and stronger pharmacological advantage, phytochemical anticancer medications have a number of advantages over chemical chemotherapeutic drugs. In the current study, the effectiveness of AuNPs, AuNPs-GAL, and free galangin as an antiangiogenesis agent was evaluated. Different physicochemical and molecular approaches have been used including the characterization, cytotoxicity, scratch wound healing assay, and gene expression of VEGF and ERKI in MCF-7 and MDA-MB-231 human breast cancer cell line. Results obtained from MTT assay show cell growth reduction in a time- and dose-dependent aspect; also, in comparison to individual treatment, a synergistic impact was indicated. CAM assay results demonstrated galangin-gold nanoparticle capacity to suppress angiogenesis in chick embryo. Additionally, altering VEGF and ERKI gene expression was recorded. Taken together, all the results can conclude that galangin-conjugated gold nanoparticles can be a promising antiangiogenesis supplemental drug in breast cancer treatment.
RESUMO
INTRODUCTION: Systemic therapy can result in disappearance of colorectal liver metastases in up to 40% of patients. This might be an overestimation caused by suboptimal imaging modalities. The aim of this study was to investigate the use of imaging modalities and the incidence, management and outcome of patients with disappearing liver metastases (DLMs). METHODS: This was a retrospective study of consecutive patients treated for colorectal liver metastases at a high volume hepatobiliary centre between January 2013 and January 2015 after receiving induction or neoadjuvant systemic therapy. Main outcomes were use of imaging modalities, incidence, management and longterm outcome of patients with DLMs. RESULTS: Of 158 patients included, 32 (20%) had 110 DLMs. Most patients (88%) had initial diagnostic imaging with contrast enhanced-CT, primovist-MR and FDG-PET and 94% of patients with DLMs were restaged using primovist-MR. Patients with DLMs had significantly smaller metastases and the median initial size of DLMs was 10 mm (range 5-61). In the per lesion analysis, recurrence after "watch & wait" for DLMs occurred in 36%, while in 19 of 20 resected DLMs no viable tumour cells were found. Median overall (51 vs. 28 months, p < 0.05) and progression free survival (10 vs. 3 months, p = 0.003) were significantly longer for patients with DLMs. CONCLUSION: Even state-of-the-art imaging and restaging cannot solve problems associated with DLMs. Regrowth of these lesions occurs in approximately a third of the lesions. Patients with DLMs have better survival.
Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/secundário , Fluordesoxiglucose F18 , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is a chronic functional bowel disorder. Many adults worldwide have symptoms associated with IBS and are responsible for most gastroenterology visits. The aim of this study is to illustrate and analyze the prevalence of IBS among the general population in Makkah Al-Mukarramah city using the Rome IV criteria in relation to psychiatric disorders. METHODOLOGY: This was a cross-sectional study conducted on Makkah citizens. The study excluded all residents in Makkah without Saudi nationality or below the age of 18. The survey was created using Google forms and shared randomly on social media. The sample size was calculated using the OpenEpi website v3.0. The online questionnaire is composed of three sections: sociodemographic data, Rome IV criteria with the Bristol Stool Scale, and lastly the Depression, Anxiety, and Stress Scale 21 (DASS-21) score for stress, anxiety, and depression. Data were analyzed using SPSS software for Windows V.23, and odds ratio (OR) with 95% confidence intervals (95% CI) was obtained for selected risk factors using logistic regression. RESULTS: Nine hundred and twenty-one individuals from Makkah city completed the survey. The overall IBS prevalence was 20.19%. The commonest subtypes of IBS were IBS-M followed by IBS-C (53.8% and 22%, respectively). In the multiple regression analysis, stress (P = <0.001, OR = 2.473) was statistically significantly associated with IBS. CONCLUSION: In this study, the prevalence of IBS among Makkah citizens is high. Stress was found to be a major risk factor for IBS.
RESUMO
The synthesis, chemical and biological characterization of seven Ru(II) polypyridyl complexes containing acetylacetonate (acac) ligands are reported. Electronic absorption spectra were determined and electrochemical potentials consistent with Ru(III/II) couples ranging from +0.60 to +0.73 V vs Ag/AgCl were measured. A series of complexes were screened against MDA-MB-231, DU-145, and MCF-10A cell lines to evaluate their cytotoxicities in cancer and normal cell lines. Although most complexes were either nontoxic or equipotent in cancer cells and normal cell lines, compound 1, [Ru(dpqy)(acac)(py)](PF6), where dqpy is 2,6-di(quinolin-2-yl)pyridine, showed up to 2.5:1.0 selectivity for cancer as compared to normal cells, along with nanomolar EC50 values in MDA-MB-231 cells. Lipophilicity, determined as the octanol/water partition coefficient, logâ¯Po/w, ranged from -0.33 (0.06) to 1.15 (0.10) for the complexes. Although cytotoxicity was not correlated with electrochemical potentials, a moderate linear correlation between lipophilicity and toxicities was observed. Cell death mechanism studies indicated that several of the Ru-acac compounds, including 1, induce apoptosis in MDA-MB-231 cells.
Assuntos
ApoptoseRESUMO
BACKGROUND: Diabetes mellitus (DM) is a well-known risk factor for Non-alcoholic fatty liver disease (NAFLD). Patients with type 2 DM (T2DM) who have NAFLD are at a higher risk of developing advanced stages of liver disease, including fibrosis, cirrhosis, and hepatocellular carcinoma compared to non-diabetic patients. This study aimed to estimate the prevalence of NAFLD among patients with T2DM, using hepatic ultrasonographic changes combined with derangement of hepatic transaminases level. MATERIALS AND METHODS: This cross-sectional study was conducted at the National Center for Diabetes, Endocrinology and Genetics (NCDEG) in Amman, Jordan. A total of 408 patients with T2DM and 90 non-diabetic subjects were included in this study. Body mass index (BMI), waist circumference, glycosylated hemoglobin (HbA1c), lipid parameters and abdominal ultrasonography were measured. RESULTS: Using the ultrasonographic criteria for the diagnosis of NAFLD, the prevalence of NAFLD was 80.4 % and 53.3 % among diabetic and non-diabetic participants, respectively. Among the diabetic participants, 25 %, 40.4 %, and 15 % had mild, moderate, and severe grades of steatosis, respectively. On the other hand, 24.4 %, 21.1 %, and 7.8 % of the non-diabetic participants had mild, moderate, and severe grades of steatosis, respectively. Diabetic patients between 25 and 45 years of age, patients with overweight or obesity, patients with increased waist circumference were significantly at higher risk of having NAFLD. High TG, lower HDL, elevated AST and ALT, and using sulfonylureas and metformin versus using metformin only were significantly associated with increased odds of having NAFLD. CONCLUSIONS: NAFLD is highly prevalent among patients with T2DM. Overweight or obesity, abnormal cholesterol levels and treatment with sulfonylureas were significantly associated with NAFLD.
RESUMO
INTRODUCTION: Hyperglycemia is associated with an elevated level of reactive nitrogen species (RNS) that leads to nitrosative stress and exacerbates the progression of diabetic complications. METHODS: Present study was aimed to evaluate the therapeutic effects of essential oils (EOs) on increased serum levels of nitric oxide (NO) in diabetogenic rats. Diabetogenic rats were treated with EOs separately and/or in combination at the dose of 100 mg/kg, orally for one month. Blood sampling was done at the 1st, 15th and 30th day of the treatment period to investigate the effect of treatment on biomarkers of diabetic complications. RESULTS: In diabetogenic rats, serum levels of NO, malondialdehyde (MDA) and pro-inflammatory cytokines were significantly increased when compared with that of the control group. Whereas, diabetogenic rats treated with EOs decreased serum levels of NO, MDA and pro-inflammatory cytokines up to a significant extent when compared with that diabetogenic rats treated with the standard antidiabetic drug. Moreover, EOs also increased insulin sensitivity in peripheral tissues and insulin secretion from ß-cells of pancreatic islets more efficiently when compared with that of diabetogenic rats. Additionally, it was also found that EOs improved lipid profile and normal functions of kidney and liver as compared to that of diabetogenic rats. CONCLUSION: Findings of this study indicate that EOs may reduce pro-inflammatory cytokine levels by modulating the expression of NO. EOs may also ameliorate the nitrosative stress and maintain glucose homeostasis that are major culprits of diabetic complications.
Assuntos
Citocinas/antagonistas & inibidores , Diabetes Mellitus Experimental/tratamento farmacológico , Mediadores da Inflamação/antagonistas & inibidores , Óxido Nítrico/antagonistas & inibidores , Óleos Voláteis/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Aloxano , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Citocinas/sangue , Diabetes Mellitus Experimental/sangue , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Mediadores da Inflamação/sangue , Masculino , Óxido Nítrico/sangue , Óleos Voláteis/farmacologia , Estresse Oxidativo/fisiologia , Ratos , Ratos WistarRESUMO
OBJECTIVES: Salmonella enterica serovar Paratyphi A, the causative pathogen of enteric fever, is a major public-health concern affecting millions of people around the world. We conducted whole-genome sequencing and analysis of a novel macrolide-resistant Salmonella Paratyphi A strain isolated from Karachi, Pakistan. METHODS: Genomic DNA of Salmonella Paratyphi A strain JRCGR-AK14 was sequenced on a MiSeq platform. Read quality was evaluated and paired-end reads were assembled into contigs and scaffolds. The quality of contigs and scaffolds was evaluated and assembled contigs were annotated. Virulence genes, antimicrobial resistance genes (ARGs), tRNAs, rRNAs, coding sequences and clustered regularly interspaced short palindromic repeats (CRISPRs) were identified. ARGs and mutations in quinolone-resistance determining regions (QRDRs) were identified by Antimicrobial Resistance Identification By Assembly (ARIBA) and ResFinder. Known and unknow mutations in the QRDRs were predicted. RESULTS: The genome of Salmonella Paratyphi A was calculated at 4529866 bp with 4381 genes and 1088 hypothetical proteins. Several putative genes coding for multidrug efflux pumps were identified. In addition, gene mutations conferring resistance to nitrofurantoin (e.g. marA, mdsC, Escherichia coli soxS), pulvomycin (e.g. H-NS, cpxA, E. coli EF-Tu) and fosfomycin (CRP, kdpE, E. coli glpT) were also identified. Several ARGs along with the mobile genetic element transposon Tn10 were also identified. It is evident from the results that diverse redundant mechanisms are involved in regulation of drug resistance in this strain. CONCLUSION: The current findings provide valuable data for understanding the multidrug resistance and pathogenic characteristics of clinical Salmonella Paratyphi A isolates.
Assuntos
Farmacorresistência Bacteriana , Macrolídeos/farmacologia , Salmonella paratyphi A/genética , Sequenciamento Completo do Genoma/métodos , Adolescente , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Feminino , Genoma Bacteriano , Humanos , Testes de Sensibilidade Microbiana , Mutação , Paquistão , Salmonella paratyphi A/efeitos dos fármacos , Salmonella paratyphi A/isolamento & purificação , Fatores de Virulência/genéticaRESUMO
Ladakh is the high altitude (11,184 ft above sea level) cold desert region in the state of Jammu & Kashmir (India), where winter temperature goes below - 35 °C. A total of 37 faecal samples were collected from local Changthangi and Russian merino sheep of the Leh region of Ladakh, having the history of diarrhoea and emaciation, followed by death. Of the 37 samples collected, 20 (54.05%) showed presence of Cryptosporidium sp. infection on faecal smear examination after Ziehl-Neelsen staining. The number of samples positive for Cryptosporidium sp. infection on faecal smear examination was 7 and 13 for Russian Merino and local Changthangi sheep, respectively. The occurrence of Cryptosporidium sp. infection was similar in both sexes, 11/20 (55%) in females and 9/20 (45%) for males. The Age-wise occurrence of Cryptosporidium sp. infection in different age groups was found to be: 50% in less than 2 year age group and 50% in more than 2 year age group. To the best of our knowledge, this is the first report of Cryptosporidium sp. infection in adult sheep from India. The survival of the parasite at such freezing temperature gives the insight about its cold-resistant nature.
RESUMO
As part of its mission to promote the best surgical care for cancer patients, the European Society of Surgical Oncology (ESSO) has been developing multiple programmes for clinical research along with its educational portfolio. This position paper describes the different research activities of the Society over the past decade and an action plan for the upcoming five years to lead innovative and high quality surgical oncology research. ESSO proposes to consider pragmatic research methodologies as a complement to randomised clinical trials (RCT), advocates for increased funding and operational support in conducting research and aims to enable young surgeons to be active in research and establish partnerships for translational research activities.
Assuntos
Pesquisa Biomédica/tendências , Ensaios Clínicos como Assunto , Assistência à Saúde Culturalmente Competente , Projetos de Pesquisa/tendências , Oncologia Cirúrgica/tendências , Europa (Continente) , Humanos , Sociedades MédicasRESUMO
INTRODUCTION: Enhanced recovery after surgery (ERAS) for peri-hilar cholangiocarcinoma (pCCA) has not been described in the literature. This study examined patients undergoing pCCA resection within a standard post hepatectomy ERAS pathway to define achievable targets suitable for these patients. METHODS: Patients undergoing pCCA resection at University Hospital Aintree (January 2009-October 2017) were identified. Achievement of key ERAS outcomes was assessed. Patients were stratified on incidence of major complications and pre-operative cardiopulmonary exercise testing. Chi Square and Mann Whitney analyses were undertaken as appropriate. Achievable ERAS targets were derived from patients who did not develop a major complication. RESULTS: 46 patients underwent resection with enhanced recovery. Median age 65 (24 male: 22 female). Key ERAS outcomes in patients who did not experience major complications are described as medians (interquartile range): length of stay 8 days (6-13), duration critical care 2 days (2-4), inotropes 6â¯h (0-24), epidural 3 days (3-4), early mobilization day 1 (1-2), full mobilization day 3 (3-4), urinary catheter removal day 4 (3-5), NGT removal day 1 (1-2) and restoration oral nutrition day 2 (2-4). Patients deemed high risk pre-operatively or those who developed major complications post-operatively required significantly longer critical care (pâ¯=â¯0.008 and pâ¯=â¯0.002 respectively). Other ERAS targets remained achievable in similar timeframes. CONCLUSIONS: ERAS for pCCA is achievable. Applicable ERAS standards are defined which take into account minor complications. High risk patients and those with major complications can be appropriately managed in an ERAS pathway, though there is increased need for critical care support.