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Infective native abdominal aortic aneurysms are a life-threatening condition with a high mortality rate. We report the case of a 53-year-old male patient who presented with abdominal pain and fever. Laboratory results showed an elevated white blood cell count and C-reactive protein levels. Blood cultures detected Salmonella species, and computed tomography revealed a saccular abdominal aortic aneurysm. After 14 days of preoperative antibiotic therapy, the patient underwent a successful surgical bypass from the descending thoracic aorta, through the diaphragm and muscle layers of the anterior abdominal wall, to the bilateral common femoral arteries. The patient was discharged after 30 days of hospitalization and continued antibiotic treatment for another 30 days. Follow-up clinical evaluations and imaging studies showed good recovery and no signs of infection. This case highlights the importance of combining appropriate antibiotic therapy with surgical intervention in managing infective native aortic aneurysms. In particular, an extra-anatomical approach from the descending aorta can be a viable option in selected cases of infected aortic aneurysms, providing an effective means to achieve thorough debridement and prevent future graft infections.

A 50-year-old woman was admitted to our institute because of a large tumour in her neck. This patient had been diagnosed with thyroid goitre for 5 years, but no treatment was administered. No specific medical history was noted. A large mass in the neck region was found during clinical examination, which restricted neck movement. Computed tomography revealed a diffuse, large, multinodular goitre with tracheal compression. Results from the fine-needle aspiration procedure showed benign cytology. Laboratory tests revealed normal results, including serum thyroid-stimulating hormone, free triiodothyronine, and free thyroxine levels. The patient underwent surgery for the removal of the entire thyroid tumour. The patient's postoperative period was uneventful. The patient was discharged on the 5th postoperative day. In conclusion, surgical management remains the standard treatment for giant thyroid tumours with compressive symptoms. Careful dissection and awareness of the high risk of postoperative complications in these cases are crucial for achieving good outcomes.

Surgical treatment is indicated for both symptomatic and asymptomatic bronchogenic cysts. The goal of treatment is total removal of the cyst. Percutaneous aspiration and absolute ethanol sclerotherapy is an effective, minimally invasive, and safe alternative method. We present the case of a 74-year-old woman with a symptom of persistent dry cough for 5 months. Plain and contrast-enhanced chest computed tomography revealed a large superior mediastinal cyst that could be easily accessed percutaneously. The cyst was treated by aspiration and ethanol sclerotherapy under ultrasound guidance and fluoroscopy. The patient was discharged a day later without complications. Chest CT at 6 months follow-up showed complete regression of the cyst.

Traumatic rupture of the thoracic aorta is a rare condition, with a high mortality rate. Over the last 2 decades, strategies for managing aortic injury caused by blunt chest trauma have changed substantially, resulting in significantly improved outcomes. The recent development of endovascular repair offers a less invasive alternative to conventional open repair, particularly in patients with multiple injuries. Here, we report the case of a 31-year-old man who was referred to our emergency department with blunt chest trauma following a motorcycle-truck collision. Computed tomography confirmed acute traumatic rupture of the thoracic aorta, and the patient was successfully treated with endovascular repair.

Sternal cleft is a rare congenital chest wall deformity, with a reported incidence of 1 in 100,000 live births, accounting for less than 1% of all chest wall deformities. Patients with sternal clefts can be asymptomatic; however, most cases have recurrent respiratory infections and cosmetic disfigurement. Therefore, surgical correction of this deformity is still necessary to address cosmetic issues, assuage parental concerns, and prevent repeated respiratory infections caused by paradoxical breathing patterns. Here, we report a case of complete sternal cleft associated with pectus excavatum that was successfully treated with sternal reconstruction and pectus bar insertion.

Selecting treatment options in acute arterial thrombosis of the lower extremity, which threatens limb viability, is still a challenge for vascular surgeons. Early restoration of blood flow is crucial and is conducted by surgical thrombectomies or endovascular procedures, depending on patient condition. Catheter-directed thrombolysis with or without percutaneous mechanical thrombectomy for acute limb ischemia has been widely implemented from the early 1990s. Here, we present 2 cases of acute thrombosis of below-the-knee arteries, where we successfully saved the involved limbs using catheter-directed thrombolysis and thrombus aspiration.

Surgical treatment of abdominal aortic aneurysm in patients with a transplanted kidney is true a challenge. Conventional open repair of the aneurysm requires aortic cross-clamping. Therefore, it can pose a risk of ischemic injury to the transplanted kidney. Endovascular repair, which limits the duration of interruption of blood flow to the transplanted kidney, is a suitable alternative for repair of abdominal aortic aneurysm, if feasible anatomically. Here, we present a case of a 62-year-old woman who was transferred to our hospital because of abdominal pain and had a history of renal transplant 14 years ago. Computed tomography confirmed a large infrarenal fusiform abdominal aortic aneurysm 6 cm in maximal diameter and another 4 cm fusiform aneurysm in the left common iliac artery. We successfully performed endovascular aneurysm repair combined with femoro-femoral bypass. The postoperative course was uneventful, and the patient was discharged on the 5th postoperative day.

Venous malformation is considered the most common congenital vascular anomaly. The most common region is the head and neck region involving the lips. Venous malformation of the lips always leads to cosmetic and functional issues. A multidisciplinary approach is recommended in the treatment of this malformation. In this report, we describe two cases of large venous malformation in the lower lip that were successfully treated by percutaneous sclerotherapy followed by plastic surgery. In our two-case presentation, sclerotherapy was performed prior to plastic surgery to improve the efficiency and reduce excessive bleeding, which resulted in significantly improved appearance and physical function. Keywords: Venous malformation, Sclerotherapy, Plastic surgery

Objective: Environmental factors that drive obesity are often studied individually, whereas obesogenic environments are likely to consist of multiple factors from food and physical activity (PA) environments. This study aimed to compose and describe a comprehensive, theory‐based, expert‐informed index to quantify obesogenicity for all neighborhoods in the Netherlands. Methods: The Obesogenic Built Environment CharacterisTics (OBCT) index consists of 17 components. The index was calculated as an average of componential scores across both food and PA environments and was scaled from 0 to 100. The index was visualized and summarized with sensitivity analysis for weighting methods. Results: The OBCT index for all 12,821 neighborhoods was right‐skewed, with a median of 44.6 (IQR = 10.1). Obesogenicity was lower in more urbanized neighborhoods except for the extremely urbanized neighborhoods (>2500 addresses/km2), where obesogenicity was highest. The overall OBCT index score was moderately correlated with the food environment (Spearman ρ = 0.55, p <0.05) and with the PA environment (ρ = 0.38, p <0.05). Hierarchical weighting increased index correlations with the PA environment but decreased correlations with the food environment. Conclusions: The novel OBCT index and its comprehensive environmental scores are potentially useful tools to quantify obesogenicity of neighborhoods. [ABSTRACT FROM AUTHOR]

In this observational cross-sectional study, we investigated the relationship between combined obesogenic neighbourhood characteristics and various cardiovascular disease risk factors in adults, including BMI, systolic blood pressure, and blood lipids, as well as the prevalence of overweight/obesity, hypertension, and dyslipidaemia. We conducted a large-scale pooled analysis, comprising data from five Dutch cohort studies (n = 183,871). Neighbourhood obesogenicity was defined according to the Obesogenic Built-environmental CharacterisTics (OBCT) index. The index was calculated for 1000m circular buffers around participants' home addresses. For each cohort, the association between the OBCT index and prevalence of overweight/obesity, hypertension and dyslipidaemia was analysed using robust Poisson regression models. Associations with continuous measures of BMI, systolic blood pressure, LDL-cholesterol, HDL-cholesterol, and triglycerides were analysed using linear regression. All models were adjusted for age, sex, education level and area-level socio-economic status. Cohort-specific estimates were pooled using random-effects meta-analyses. The pooled results show that a 10 point higher OBCT index score was significantly associated with a 0.17 higher BMI (95%CI: 0.10 to 0.24), a 0.01 higher LDL-cholesterol (95% CI: 0.01 to 0.02), a 0.01 lower HDL cholesterol (95% CI: −0.02 to −0.01), and non-significantly associated with a 0.36 mmHg higher systolic blood pressure (95%CI: −0.14 to 0.65). A 10 point higher OBCT index score was also associated with a higher prevalence of overweight/obesity (PR = 1.03; 95% CI: 1.02 to 1.05), obesity (PR = 1.04; 95% CI: 1.01 to 1.08) and hypertension (PR = 1.02; 95% CI: 1.00 to 1.04), but not with dyslipidaemia. This large-scale pooled analysis of five Dutch cohort studies shows that higher neighbourhood obesogenicity, as measured by the OBCT index, was associated with higher BMI, higher prevalence of overweight/obesity, obesity, and hypertension. These findings highlight the importance of considering the obesogenic environment as a potential determinant of cardiovascular health. • Our study adds value to the existing evidence by considering combined exposure to obesogenic environmental factors. • We used the Obesogenic Built-environmental CharacterisTics (OBCT) index to combine various exposures based on theory and evidence. • We found that a higher OBCT index score is associated with higher BMI, prevalence of overweight/obesity, and hypertension. • The results also show minimal associations with blood lipids, and a potential relationship with systolic blood pressure. • This study highlights the potential use of the OBCT index in identifying areas at risk for CVD risk factors. [ABSTRACT FROM AUTHOR]

Background: In this study, we determined the impact of the COVID-19 pandemic on Western Sydney patients with substance use disorders (SUD) by comparing emergency department (ED) admission rates before and after the onset of the COVID-19 pandemic and before the rollout of COVID-19 vaccination. Methods: ED admission data for patients with SUD were retrieved from the local electronic medical record (eMR) on the hospital central database. ED data collected from 25 January to 25 July 2019 (before the COVID-19 pandemic) were compared with data from 25 January to 25 July 2020 (early pandemic). ED admission reasons were categorised based on the presenting complaints and ED diagnoses. Results: Despite an overall reduction in ED admissions during the early pandemic, compared to the pre-pandemic period, admissions for patients with SUD increased significantly (1.7% to 3.4%, p < 0.01). ED admission rates related to infection (0.05% to 0.12%, p < 0.01), local infection (0.02% to 0.05%, p < 0.01), trauma (0.06% to 0.12%, p < 0.01), alcohol (0.01% to 0.03%, p < 0.05), and other issues (0.06% to 0.10%, p < 0.05) increased significantly among Indigenous patients with SUD. ED admission rates related to drugs (0.12% to 0.39%, p < 0.01), infection (0.21% to 0.34%, p < 0.01), local infection (0.07% to 0.18%, p < 0.01), gastrointestinal (0.15% to 0.23%, p < 0.05), trauma (0.14% to 0.25%, p < 0.01), alcohol (0.36% to 0.74%, p < 0.01), and 'other' issues (0.47% to 0.91%, p < 0.01) increased significantly among non-Indigenous patients with SUD. Four cases of COVID-19 were reported among these patients. Conclusions: There was an increase in ED admissions for patients with SUD in the initial six months of the COVID-19 pandemic (before vaccine rollout), mainly for drugs, systemic infection, local infection, trauma, and alcohol-related reasons. Now that most people in New South Wales have been vaccinated against COVID-19, a further study is needed to quantify the effect of the pandemic on patients with SUD in the post-vaccine era. [ABSTRACT FROM AUTHOR]

Background Evaluating progress towards hepatitis C virus (HCV) elimination is critical. This study estimated prevalence of current HCV infection and HCV treatment uptake among people who inject drugs (PWID) in Australia. Methods The Enhancing Treatment of Hepatitis C in Opioid Substitution Settings Engage is an observational study of PWID attending drug treatment clinics and needle and syringe programs (NSPs). Participants completed a questionnaire including self-reported treatment history and underwent point-of-care HCV RNA testing (Xpert HCV Viral Load Fingerstick; Cepheid). Results Between May 2018 and September 2019, 1443 participants were enrolled (64% injected drugs in the last month, 74% receiving opioid agonist therapy [OAT]). HCV infection status was uninfected (28%), spontaneous clearance (16%), treatment-induced clearance (32%), and current infection (24%). Current HCV was more likely among people who were homeless (adjusted odds ratio, 1.47; 95% confidence interval, 1.00–2.16), incarcerated in the previous year (2.04; 1.38–3.02), and those injecting drugs daily or more (2.26; 1.43–2.42). Among those with previous chronic or current HCV, 66% (n = 520/788) reported HCV treatment. In adjusted analysis, HCV treatment was lower among females (.68;.48–.95), participants who were homeless (.59;.38–.96), and those injecting daily or more (.51;.31–.89). People aged ≥45 years (1.46; 1.06–2.01) and people receiving OAT (2.62; 1.52–4.51) were more likely to report HCV treatment. Conclusions Unrestricted direct-acting antiviral therapy access in Australia has yielded high treatment uptake among PWID attending drug treatment and NSPs, with a marked decline in HCV prevalence. To achieve elimination, PWID with greater marginalization may require additional support and tailored strategies to enhance treatment. [ABSTRACT FROM AUTHOR]

• AAA is frequently associated with CAD in elderly patients. • The optimal management of CAD associated with AAA in an octogenarian is a challenge. • Combined CABG and EVAR is a promising way to improve the therapeutic efficiency. Coronary artery disease (CAD) is commonly associated with abdominal aortic aneurysms (AAAs) in elderly patients. When severe CAD requiring coronary artery bypass grafting (CABG) is associated with an impending AAA in a high-risk patient, the options for the suitable timing of CABG and AAA repair strategy (one-stage or two-stage) are still being debated. An 87-year-old man with non-ST-segment elevation myocardial infarction and a giant abdominal aortic aneurysm was transferred to our centre. Coronary angiography revealed triple-vessel coronary disease, and computed tomography confirmed a giant infrarenal fusiform abdominal aortic aneurysm 9 cm in maximal diameter. We simultaneously performed endovascular aneurysm repair prior to on-pump beating-heart coronary artery bypass grafting. The postoperative course was uneventful, and the patient was discharged on the 15th postoperative day. Combined endovascular aneurysm repair and on-pump beating heart coronary artery bypass grafting in a one-stage operation is a promising strategy to improve therapeutic efficiency in octogenarians. More studies are needed to compare the efficacy and safety of one-stage and two-stage operations to treat concomitant coronary artery disease and aortovascular pathology in the high-risk octogenarian patients. [ABSTRACT FROM AUTHOR]

This article examines the sets for “Art" and Le dieu du carnage by Yasmina Reza. It examines the roles of objects onstage and analyzes the relationship that the protagonists have with them. It shows that male and female characters who compete in debates throughout these pieces end up resembling each other and blending together. Although male superiority seems to prevail in “Art", with the fall of the curtain at the end of Le dieu du carnage, the characters become agendered. [ABSTRACT FROM AUTHOR]

Bacterial regulatory RNAs have been extensively studied for over a decade, and are progressively being integrated into the complex genetic regulatory network. Transcriptomic arrays, recent deep-sequencing data and bioinformatics suggest that bacterial genomes produce hundreds of regulatory RNAs. However, while some have been authenticated, the existence of the others varies according to strains and growth conditions, and their detection fluctuates with the methodologies used for data acquisition and interpretation. For example, several small RNA (sRNA) candidates are now known to be parts of UTR transcripts. Accurate annotation of regulatory RNAs is a complex task essential for molecular and functional studies. We defined bona fide sRNAs as those that (i) likely act in trans and (ii) are not expressed from the opposite strand of a coding gene. Using published data and our own RNA-seq data, we reviewed hundreds of Staphylococcus aureus putative regulatory RNAs using the DETR'PROK computational pipeline and visual inspection of expression data, addressing the question of which transcriptional signals correspond to sRNAs. We conclude that the model strain HG003, a NCTC8325 derivative commonly used for S. aureus genetic regulation studies, has only about 50 bona fide sRNAs, indicating that these RNAs are less numerous than commonly stated. Among them, about half are associated to the S. aureus sp. core genome and a quarter are possibly expressed in other Staphylococci. We hypothesize on their features and regulation using bioinformatic approaches. [ABSTRACT FROM AUTHOR]

Bacteria optimize their fitness in response to a changing environment by tight regulation of gene expression. Regulation can be controlled at both transcriptional and post-transcriptional levels via key players such as sigma factors, regulatory proteins and regulatory RNAs. The identification of phenotypes associated with gene deletions is the established method for finding gene functions but may require testing many conditions for each studied mutant. As regulatory RNAs often contribute to fine-tuning gene expression, phenotypes associated with their inactivation are often weak and difficult to detect. Nevertheless, minor phenotypes conferring modest advantages, may allow bacteria to emerge after some generations under selective pressure. A strategy employing DNA barcodes can be used to perform competition experiments between mutants and to monitor fitness associated with mutations in different growth conditions. We combined this strategy with deep sequencing to study regulatory RNAs in Staphylococcus aureus , a major opportunistic pathogen. [ABSTRACT FROM AUTHOR]

Sternal cleft is a rare congenital chest wall deformity, with a reported incidence of 1 in 100,000 live births, accounting for less than 1% of all chest wall deformities. Patients with sternal clefts can be asymptomatic; however, most cases have recurrent respiratory infections and cosmetic disfigurement. Therefore, surgical correction of this deformity is still necessary to address cosmetic issues, assuage parental concerns, and prevent repeated respiratory infections caused by paradoxical breathing patterns. Here, we report a case of complete sternal cleft associated with pectus excavatum that was successfully treated with sternal reconstruction and pectus bar insertion. [ABSTRACT FROM AUTHOR]

In all three kingdoms of life, RNA is not only involved in the expression of genetic information, but also carries out extremely diverse cellular functions. This versatility is essentially due to the fact that RNA molecules can exploit the power of base pairing to allow them to fold into a wide variety of structures through which they can perform diverse roles, but also to selectively target and bind to other nucleic acids. This is true in particular for bacterial small regulatory RNAs that act by imperfect base-pairing with target mRNAs, and thereby control their expression through different mechanisms. Here we outline an overview of in vivo and in vitro approaches that are currently used to gain mechanistic insights into how these sRNAs control gene expression in bacteria. [ABSTRACT FROM AUTHOR]

A series of tetra- O -acetyl-α-d-glucopyranosyl thioureas 8a-l of substituted 2-aminopyrimidines 4a-l have been designed and synthesized. The latter were prepared from corresponding chalcones 3a-l of p -bromoacetophenone and appropriate substituted benzaldehydes by their reaction with guanidine. The target thiourea compounds 8a-l exhibited significant inhibitory activity in vitro against enzymes that were related to type 2 diabetes mellitus, including α-amylase, α-glucosidase, DPP-4, and PTP1B. Amongst these thioureas, compound 8k with an ortho -methoxy group was the most potential enzyme inhibitor against α-amylase with an IC 50 value of 9.72 ± 0.34 μM. Its meta -isomer 8j was the strongest inhibitor against α-glucosidase with IC 50 = 9.73 ± 0.72 μM. In the inhibition against DPP-4, compound 8f with a para -bromo substituent exhibited the strongest activity with an IC 50 value of 2.53 ± 0.03 nM. In the inhibition against PTP1B, compound 8h with a para -isopropyl substituent had the strongest inhibitory activity with an IC 50 value of 2.74 ± 0.03 μM. The enzyme kinetics of the most active compounds, including 8j, 8f and 8h against α-glucosidase, DPP-4, and PTP1B, respectively, were studied. The obtained results showed that 8j was a competitive α-glucosidase inhibitor with an inhibitory constant K I value of 9.31 μM. Compound 8f was a non-competitive inhibitor for DDP-4 with an inhibitory constant K I value of 12.57 μM. Compound 8h was also a non-competitive inhibitor for DDP-4 with an inhibitory constant K I value of 12.41 μM. The cytotoxicity of the most active compounds, including 8f and 8k (against α-amylase), 8i and 8j (against α-glucosidase), 8a, 8f, and 8g (against DPP-4), and 8d, 8f, and 8h (against PTP1B) was screened. The obtained cytotoxicity showed that all tested inhibitors were noncytotoxic to human normal cell line 3T3. Induced fit docking simulations of all synthesized compounds 8a-l were performed on four enzymes 4W93 (for α-amylase), 3TOP (for α-glucosidase), 3W2T (for DPP-4), and 1NNY (for PTP1B). Key interactions of each of these ligands with residues in the active pocket of each studied enzyme have been shown., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A series of sulfonyl thioureas 6a-q containing a benzo[d]thiazole ring with an ester functional group was synthesized from corresponding substituted 2-aminobenzo[d]thiazoles 3a-q and p-toluenesulfonyl isothiocyanate. They had remarkable inhibitory activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase (MAO)-A, and MAO-B. Among thioureas, several compounds had notable activity in the order of 6k > 6 h > 6c (AChE), 6j > 6g > 6k (BChE), 6k > 6g > 6f (MAO-A), and 6i > 6k > 6h (MAO-B). Compound 6k was an inhibitor of interest due to its potent or good activity against all studied enzymes, with IC 50 values of 0.027 ± 0.008 μM (AChE), 0.043 ± 0.004 μM (BChE), 0.353 ± 0.01 μM (MAO-A), and 0.716 ± 0.02 μM (MAO-B). This inhibitory capacity was comparable to that of the reference drugs for each enzyme. Kinetic studies of two compounds with potential activity, 6k (against AChE) and 6j (against BChE), had shown that both 6k and 6j followed competitive-type enzyme inhibition, with K i constants of 24.49 and 12.16 nM, respectively. Induced fit docking studies for enzymes 4EY7, 7BO4, 2BXR, and 2BYB showed active interactions between sulfonyl thioureas of benzo[d]thiazoles and the residues in the active pocket with ligands 6k, 6i, and 6j, respectively. The stability of the ligand-protein complexes while each ligand entered the active site of each enzyme (4EY7, 7BO4, 2BXR, or 2BYB) was confirmed by molecular dynamics simulations., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

Background: Hepatitis C virus (HCV) infection can now be cured with well-tolerated direct-acting antiviral (DAA) therapy. However, a potential barrier to HCV elimination is the emergence of resistance-associated substitutions (RASs) that reduce the efficacy of antiviral drugs, but real-world studies assessing the clinical impact of RASs are limited. Here, an analysis of the impact of RASs on retreatment outcomes for different salvage regimens in patients nationally who failed first-line DAA therapy is reported., Methods: We collected data from 363 Australian patients who failed first-line DAA therapy, including: age, sex, fibrosis stage, HCV genotype, NS3/NS5A/NS5B RASs, details of failed first-line regimen, subsequent salvage regimens, and treatment outcome., Results: Of 240 patients who were initially retreated as per protocol, 210 (87.5%) achieved sustained virologic response (SVR) and 30 (12.5%) relapsed or did not respond. The SVR rate for salvage regimens that included sofosbuvir/velpatasvir/voxilaprevir was 94.3% (n = 140), sofosbuvir/velpatasvir 75.0% (n = 52), elbasvir/grazoprevir 81.6% (n = 38), and glecaprevir/pibrentasvir 84.6% (n = 13). NS5A RASs were present in 71.0% (n = 210) of patients who achieved SVR and in 66.7% (n = 30) of patients who subsequently relapsed. NS3 RASs were detected in 20 patients (20%) in the SVR group and 1 patient in the relapse group. NS5B RASs were observed in only 3 patients. Cirrhosis was a predictor of relapse after retreatment, as was previous treatment with sofosbuvir/velpatasvir., Conclusions: In our cohort, the SVR rate for sofosbuvir/velpatasvir/voxilaprevir was higher than with other salvage regimens. The presence of NS5A, NS5B, or NS3 RASs did not appear to negatively influence retreatment outcomes., Competing Interests: Potential conflicts of interest. M.W.D. advises, is on the speakers’ bureau for Gilead, AbbVie, GSK, and Merck, and has received grants from Gilead and AbbVie. J.G. advises, is on the speakers’ bureau for, and received grants from Gilead; he advises and is on the speakers’ bureau for AbbVie and MSD. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Current evidence on neighborhood walkability and active commuting focuses on residential rather than workplace environment. This cross-sectional study investigated whether higher workplace walkability (WW) was associated with commute walking, both independently and together with residential walkability, using data from 6769 respondents of the 2017 Dutch national travel survey. In a fully adjusted logistic regression model, 10% increase in WW was associated with 32% higher odds of commute walking (Odds ratio (OR): 1.31, 95% Confidence Interval (CI: 1.27-1.36). The estimates were stronger in rural dwellers than urban residents, (OR rural 1.49, 95%CI: 1.34-1.64 vs OR highly . urban 1.19, 95%CI: 1.13-1.26). In participants with both high residential walkability and WW, we observed 215% higher odds (OR 3.15, 95% CI: 2.48-3.99) of commute walking compared to those with low walkability in both. Our study indicated the importance and complementary nature of walkable residence and workplace in contribution to physical activity of working individuals through active commuting., (© 2023 The Authors. Published by Elsevier Ltd.)

Some substituted thioureas (6a-i) containing a 1,3,4-thiadiazole ring were synthesized by the reaction of the corresponding substituted 2-amino-1,3,4-thiadiazoles 3a-i with p -toluenesulfonyl isocyanate in a one-pot procedure. The antibacterial and antifungal activities of these sulfonyl thioureas were estimated using a minimum inhibitory concentration protocol. Almost all the thioureas exhibited remarkable antimicrobial activity. Amongst the studied compounds, thioureas 6a, 6c, 6h, and 6i were better inhibitors against the bacterium S. aureus , with MIC values of 0.78-3.125 μg mL -1 . These compounds were also tested for their inhibition against S. aureus enzymes, including enzymes of DNA gyrase, DNA topoisomerase IV (Topo IV), and dihydrofolate reductase. Amongst the compounds, 6h was a strong inhibitor, with IC 50 values of 1.22, 53.78, and 0.23, respectively. Induced fit docking calculations were performed to observe the binding efficiency and steric interactions of these compounds. The obtained results showed that compound 6h was compatible with the active sites of S. aureus DNA gyrase 2XCS. This ligand interacted with residues ASP1083 (chain D), MET1121 (chain B), ARG1122 (chain D), and also with HOH2035, HOH2089, HOH2110, HOH2162. Molecular dynamics simulation in a water solvent system showed that the active interactions with residues ASP083 and MET1121 (chain B), along with ASP1083, MET1121, and ARG1122 (chain D), played an important role in stabilizing complex 6h/2XCS in the active pocket., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Some substituted glucose-conjugated thioureas containing 1,3-thiazole ring, 4a-h, were synthesized by the reaction of the corresponding substituted 2-amino-4-phenyl-1,3-thiazoles 2a-h with 2,3,4,6-tetra- O -acetyl-β-d-glucopyranosyl isocyanate. The antibacterial and antifungal activities of these thiazole-containing thioureas were estimated using a minimum inhibitory concentration protocol. Among these compounds, 4c, 4g, and 4h were better inhibitors with MIC = 0.78-3.125 μg mL -1 . These three compounds were also tested for their ability to inhibit S. aureus enzymes, including DNA gyrase, DNA topoisomerase IV (Topo IV), and dihydrofolate reductase, and compound 4h was found to be a strong inhibitor with IC 50 = 1.25 ± 0.12, 67.28 ± 1.21, and 0.13 ± 0.05 μM, respectively. Induced-fit docking and MM-GBSA calculations were performed to observe the binding efficiencies and steric interactions of these compounds. The obtained results showed that compound 4h is compatible with the active site of S. aureus DNA gyrase 2XCS with four H-bond interactions with residues Ala1118, Met1121, and F:DC11 and also three interactions with F:DG10 (two interactions) and F:DC11 (one interaction). Molecular dynamics simulation in a water solvent system showed that ligand 4h had active interactions with enzyme 2XCS through residues Ala1083, Glu1088, Ala1118, Gly1117, and Met1121., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

In this study, the click chemistry between N-propargyl derivatives of substituted 4H-pyrano[2,3-d]pyrimidines and tetra-O-acetyl-α-d-glucopyranosyl azide carried out under catalytic conditions using catalyst CuI@Montmorillonite and additive N,N-diisopropylethylamine (DIPEA). The yields of obtained hybrid compounds having 4H-pyrano[2,3-d]pyrimidine connected to 1H-1,2,3-triazole rings were about 85-94 %. All these synthesized hybrid compounds were examined for in vitro α-amylase (with IC 50 values in the range of 103.63±1.13 μM to 295.45±1.11 μM) and α-glucosidase (with IC 50 values in the range of 45.63±1.14 μM to 184.52±1.15) inhibitory activity. Amongst this series, ethyl ester 8m showed the best inhibitory activity against α-amylase with IC 50 of 103.63±1.13 μM, while ethyl ester 8t exhibited the highest activity against α-glucosidase with IC 50 of 45.63±1.14 μM. The kinetics of the inhibition of compound 8t showed the competitive α-glucosidase inhibitor property of this compound. Furthermore, the most potent compounds had any cytotoxicity against human normal cells. Induced fit docking and molecular dynamics simulation calculations indicated that the inhibition potential compounds 8m and 8t had the active interactions with the residues in receptors of corresponding tested enzymes. The calculated binding free energy from MM-GBSA approach showed that the major energy components contributed to the active binding of these studied inhibitors, including Coulomb, lipophilic and van der Waals energy. Further, 300 ns MD simulation showed that studied ligand-protein complexes were stable and indicated the structural observations into mode of binding in these complexes., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

This study evaluated HCV treatment initiation among people who inject drugs (PWID) following an intervention of campaign days involving peer connection, point-of-care HCV RNA testing, and linkage to nursing support. ETHOS Engage is an observational cohort study of PWID attending 25 drug treatment clinics and needle and syringe programs in Australia (May 2018-September 2019). Point-of-care results were provided to the nurse, facilitating confirmatory testing and treatment. The study aimed to evaluate treatment uptake and factors associated with treatment at 24 months post-enrolment. There were 317 people with current HCV infection and eligible for treatment (median age 43, 65% male, 15% homeless, 69% receiving opioid agonist treatment, 70% injected in last month). Overall, 15% (47/317), 27% (85/317), 38% (120/317), and 49% (155/317) of people with current HCV infection had initiated treatment at 3-, 6-, 12-, and 24-months following testing, respectively. Homelessness (adjusted hazard ratio (aHR): 0.40; 95% confidence interval: 0.23, 0.71) and incarceration in the past 12 months (vs. never, aHR:0.46; 0.28, 0.76) were associated with decreased treatment initiation in the 24 months post-enrolment. This testing campaign intervention facilitated HCV treatment uptake among PWID. Further interventions are needed to achieve HCV elimination among people experiencing homelessness or incarceration.

In this work, reduced graphene oxide/double-walled carbon nanotubes/octahedral-Fe 3 O 4 /chitosan composite material modified screen-printed gold electrodes (rGO/DWCNTs/Oct-Fe 3 O 4 /Cs/SPAuE) under inhibition of urease enzyme was developed for the determination of glyphosate (GLY). The electrochemical behaviors of GLY on these electrodes were evaluated by square wave voltammetry (SWV). With the electroactive surface area is 1.7 times higher than that of bare SPAuE, the rGO/DWCNTs/Oct-Fe 3 O 4 /Cs/SPAuE for detection of GLY shows a low detection limit (LOD) of ~ 0.08 ppb in a large concentration range of 0.1-1000 ppb. Moreover, it is also successfully applied to the determination of GLY in river water samples with recoveries and relative standard deviations (RSDs) from 98.7% to 106.9% and from 0.79% to 0.87%, respectively. The developed composite will probably provide an universal electrochemical sensing platform that is very promising for environmental monitoring.