Silver nanoparticles alter the dimerization of Aß42 studied by REMD simulations.

The aggregation of amyloid beta (Aß) peptides is associated with the development of Alzheimer's disease (AD). However, there has been a growing belief that the oligomerization of Aß species in different environments has a neurotoxic effect on the patient's brain, causing damage. It is necessary to comprehend the compositions of Aß oligomers in order to develop medications that may effectively inhibit these neurotoxic forms that affect the nervous system of AD patients. Thus, dissociation or inhibition of Aß aggregation may be able to prevent AD. To date, the search for traditional agents and biomolecules has largely been unsuccessful. In this context, nanoparticles have emerged as potential candidates to directly inhibit the formation of Aß oligomers. The oligomerization of the dimeric Aß peptides with or without the influence of a silver nanoparticle was thus investigated using temperature replica-exchange molecular dynamics (REMD) simulations. The physical insights into the dimeric Aß oligomerization were clarified by analyzing intermolecular contact maps, the free energy landscape of the dimeric oligomer, secondary structure terms, etc. The difference in obtained metrics between Aß with or without a silver nanoparticle provides a picture of the influence of silver nanoparticles on the oligomerization process. The underlying mechanisms that are involved in altering Aß oligomerization will be discussed. The obtained results may play an important role in searching for Aß inhibitor pathways.

Real space iterative reconstruction for vector tomography (RESIRE-V).

Tomography has had an important impact on the physical, biological, and medical sciences. To date, most tomographic applications have been focused on 3D scalar reconstructions. However, in some crucial applications, vector tomography is required to reconstruct 3D vector fields such as the electric and magnetic fields. Over the years, several vector tomography methods have been developed. Here, we present the mathematical foundation and algorithmic implementation of REal Space Iterative REconstruction for Vector tomography, termed RESIRE-V. RESIRE-V uses multiple tilt series of projections and iterates between the projections and a 3D reconstruction. Each iteration consists of a forward step using the Radon transform and a backward step using its transpose, then updates the object via gradient descent. Incorporating with a 3D support constraint, the algorithm iteratively minimizes an error metric, defined as the difference between the measured and calculated projections. The algorithm can also be used to refine the tilt angles and further improve the 3D reconstruction. To validate RESIRE-V, we first apply it to a simulated data set of the 3D magnetization vector field, consisting of two orthogonal tilt series, each with a missing wedge. Our quantitative analysis shows that the three components of the reconstructed magnetization vector field agree well with the ground-truth counterparts. We then use RESIRE-V to reconstruct the 3D magnetization vector field of a ferromagnetic meta-lattice consisting of three tilt series. Our 3D vector reconstruction reveals the existence of topological magnetic defects with positive and negative charges. We expect that RESIRE-V can be incorporated into different imaging modalities as a general vector tomography method. To make the algorithm accessible to a broad user community, we have made our RESIRE-V MATLAB source codes and the data freely available at https://github.com/minhpham0309/RESIRE-V .

Outcomes of balloon angioplasty and stent placement for iliac artery lesions classified as TASC II A, B: a single-center study.

Background: Iliac artery stenosis or occlusion is a critical condition that can severely impact a patient's quality of life. The effectiveness of balloon angioplasty and intraluminal stenting for the treatment of iliac artery lesions classified as TASC II A and B was evaluated in this single-center prospective study. Methods: Conducted between October 2016 and September 2020 at Cho Ray Hospital's Vascular Surgery Department, this prospective study involved PAD patients categorized by TASC II A and B classifications who underwent endovascular intervention. Intervention outcomes were assessed peri-procedure and during short-term and mid-term follow-ups. Results: Of the total of 133 patients, 34.6% underwent balloon angioplasty, while 65.4% received stenting. The immediate technical success rate was 97.7%, while the clinical success rate was 62.4%. Complications were minimal, with major limb amputation reported in 1.5% of the cases. There was a significant improvement in Rutherford classification and ABI at short-term follow-up, with a patency rate of 90.2%. The mid-term post-intervention follow-up yielded similar results with an 86.1% patency rate. The mortality rates associated with arterial occlusion were 2.3% during short-term follow-up and 1.7% during mid-term follow-up. Conclusion: Balloon angioplasty and stent placement are effective and safe interventions for TASC II A and B iliac artery occlusions with favorable short and mid-term outcomes. Further, multi-center studies with larger sample sizes are recommended for more comprehensive conclusions, including long-term follow-up assessment.

Black Americans suppress emotions when prejudice is believed to stem from shared ignorance.

Past research examining lay theories of the origins of prejudice has focused on white Americans and has not considered how Black Americans' lay theories of prejudice may impact emotion regulation following discrimination. Across three samples of Black Americans (N = 419), the present research examined relationships between endorsement of two lay theories of prejudice origins (1, beliefs that prejudice stems from shared social ignorance and 2, that prejudice stems from malice). Stronger beliefs that prejudice stems from shared ignorance were associated with greater expression suppression following experiences of racial discrimination (studies 1b and 2), which was, in turn, associated with psychological distress (study 2). By centering the beliefs and experiences of Black Americans in response to discrimination events, the present research has implications for understanding how emotion regulation following racial discrimination is impacted by marginalized groups' conceptualizations of prejudice. Future research should investigate how these factors impact health disparities.

Towards universal health coverage in Vietnam: a mixed-method case study of enrolling people with tuberculosis into social health insurance.

BACKGROUND: Vietnam's primary mechanism of achieving sustainable funding for universal health coverage (UHC) and financial protection has been through its social health insurance (SHI) scheme. Steady progress towards access has been made and by 2020, over 90% of the population were enrolled in SHI. In 2022, as part of a larger transition towards the increased domestic financing of healthcare, tuberculosis (TB) services were integrated into SHI. This change required people with TB to use SHI for treatment at district-level facilities or to pay out of pocket for services. This study was conducted in preparation for this transition. It aimed to understand more about uninsured people with TB, assess the feasibility of enrolling them into SHI, and identify the barriers they faced in this process. METHODS: A mixed-method case study was conducted using a convergent parallel design between November 2018 and January 2022 in ten districts of Hanoi and Ho Chi Minh City, Vietnam. Quantitative data were collected through a pilot intervention that aimed to facilitate SHI enrollment for uninsured individuals with TB. Descriptive statistics were calculated. Qualitative interviews were conducted with 34 participants, who were purposively sampled for maximum variation. Qualitative data were analyzed through an inductive approach and themes were identified through framework analysis. Quantitative and qualitative data sources were triangulated. RESULTS: We attempted to enroll 115 uninsured people with TB into SHI; 76.5% were able to enroll. On average, it took 34.5 days to obtain a SHI card and it cost USD 66 per household. The themes indicated that a lack of knowledge, high costs for annual premiums, and the household-based registration requirement were barriers to SHI enrollment. Participants indicated that alternative enrolment mechanisms and greater procedural flexibility, particularly for undocumented people, is required to achieve full population coverage with SHI in urban centers. CONCLUSIONS: Significant addressable barriers to SHI enrolment for people affected by TB were identified. A quarter of individuals remained unable to enroll after receiving enhanced support due to lack of required documentation. The experience gained during this health financing transition is relevant for other middle-income countries as they address the provision of financial protection for the treatment of infectious diseases.

Mitigation of caffeine micropollutants in wastewater through Ag-doped ZnO photocatalyst: mechanism and environmental impacts.

Micropollutants, such as caffeine (M-CF), pose a significant threat to ecosystems and human health through water and food sources. The utilization of metal oxide-based photocatalysts has proven to be an effective treatment method for the removal of organic pollutants. This study explores the efficacy of Ag-doped ZnO (Ag/ZnO) for removing M-CF from wastewater. The characterization of Ag/ZnO underscores the crucial role of band gap energy in the photocatalytic degradation process. This parameter influences the separation of electrons and holes (e-/h+) and the generation of reactive radicals. Under solar light, Ag/ZnO demonstrated markedly superior photocatalytic activity, achieving an impressive degradation efficiency of approximately 93.4%, in stark contrast to the 53.2% occurred by ZnO. Moreover, Ag/ZnO exhibited a remarkable degradation efficiency of M-CF in wastewater, reaching 83.5%. A key advantage of Ag/ZnO lies in its potential for recovery and reuse in subsequent treatments, contributing to a reduction in operational costs for industrial wastewater treatment. Impressively, even after five cycles, Ag/ZnO maintained a noteworthy photodegradation rate of M-CF at 78.6%. These results strongly suggest that Ag/ZnO presents a promising solution for the removal of micropollutants in wastewater, with potential scalability for industrial and large-scale applications.

Association of the minimal cyclophosphamide equivalent dose and outcome of microdissection testicular sperm extraction in patients with persistent azoospermia after chemotherapy.

Objective: To investigate whether the minimal cyclophosphamide equivalent dose (mCED), a novel approach for estimating alkylating agent exposure, is associated with the sperm retrieval rates by microdissection testicular sperm extraction (mTESE) in azoospermic postchemotherapy cancer survivors. Design: A retrospective cohort study conducted between 2002 and 2017. Setting: An academic medical center. Patients: A total of 28 azoospermic postchemotherapy cancer survivors who underwent mTESE. Interventions: Chemotherapy exposure and mCED calculation. Main Outcome Measures: The primary outcome was the association between the mCED and sperm retrieval rate using mTESE. The mCED value for each patient's regimen received was estimated using the lowest recommended dosing regimen from the range of recommended doses at the time of administration. Results: Spermatozoa were successfully retrieved in 11 (39.3%) of the patients. Age at the time of receiving chemotherapy and mCED were significant factors associated with sperm retrieval. An mCED of <4,000 mg/m2 had a higher sperm retrieval rate (10/14, 71.4%) than an mCED of >4,000 mg/m2 (0/8, 0). The hormone levels were not significantly different when comparing patients with and without successful sperm retrieval. Seminoma, nonseminomatous germ cell tumor, and acute lymphoblastic leukemia had favorable sperm retrieval rates-100% (2/2), 66.7% (2/3), and 66.7% (2/3), respectively-although the numbers of patients in each group were small. Conclusion: Among this cohort of patients with cancer who required chemotherapy regimens, successful sperm retrieval by mTESE was only noted among cancer survivors receiving an mCED of <4,000 mg/m2.

Factors Influencing the Outcome of Patients with Primary Ewing Sarcoma of the Sacrum.

Background: Ewing sarcoma (EwS) is a rare and highly malignant bone tumor primarily affecting children, adolescents, and young adults. The pelvis, trunk, and lower extremities are the most common sites, while EwS of the sacrum as a primary site is very rare, and only few studies focusing on this location are published. Due to the anatomical condition, local treatment is challenging in sacral malignancies. We analyzed factors that might influence the outcome of patients suffering from sacral EwS. Methods: We retrospectively analyzed data of the GPOH EURO-E.W.I.N.G 99 trial and the EWING 2008 trial, with a cohort of 124 patients with localized or metastatic sacral EwS. The study endpoints were overall survival (OS) and event-free survival (EFS). OS and EFS were calculated using the Kaplan-Meier method, and univariate comparisons were estimated using the log-rank test. Hazard ratios (HRs) with respective 95% confidence intervals (CIs) were estimated in a multivariable Cox regression model. Results: The presence of metastases (3y-EFS: 0.33 vs. 0.68; P < 0.001; HR = 3.4, 95% CI 1.7 to 6.6; 3y-OS: 0.48 vs. 0.85; P < 0.001; HR = 4.23, 95% CI 1.8 to 9.7), large tumor volume (≥200 ml) (3y-EFS: 0.36 vs. 0.69; P=0.02; HR = 2.1, 95% CI 1.1 to 4.0; 3y-OS: 0.42 vs. 0.73; P=0.04; HR = 2.1, 95% CI 1.03 to 4.5), and age ≥18 years (3y-EFS: 0.41 vs. 0.60; P=0.02; HR = 2.6, 95% CI 1.3 to 5.2; 3y-OS: 0.294 vs. 0.59; P=0.01; HR = 2.92, 95% CI 1.29 to 6.6) were revealed as adverse prognostic factors. Conclusion: Young age seems to positively influence patients` survival, especially in patients with primary metastatic disease. In this context, our results support other studies, stating that older age has a negative impact on survival. Tumor volume, metastases, and the type of local therapy modality have an impact on the outcome of sacral EwS. Level of evidence: Level 2. This trial is registered with NCT00020566 and NCT00987636.

Staphylococcus aureus Pneumonia in Can Tho, Vietnam: Clinical Characteristics, Antimicrobial Resistance Profile and Risk Factors of Mortality.

INTRODUCTION: Staphylococcus aureus (S. aureus) is an important pathogen in both community-acquired and hospital-acquired pneumonia. S. aureus pneumonia has a high mortality rate and serious complications. Resistance to multiple antibiotics is a major challenge in the treatment of S. aureus pneumonia. Understanding the antibiotic resistance profile of S. aureus and the risk factors for mortality can help optimize antibiotic regimens and improve patient outcomes in S. aureus pneumonia. METHODS: A prospective cohort study of 118 patients diagnosed with S. aureus pneumonia between May 2021 and June 2023 was conducted, with a 30-day follow-up period. Demographic information, comorbidities, Charlson Comorbidity Index, clinical characteristics, outcomes, and complications were collected for each enrolled case. The data were processed and analyzed using R version 3.6.2. RESULTS: S. aureus pneumonia has a 30-day mortality rate of approximately 50%, with complication rates of 22% for acute respiratory distress syndrome (ARDS), 26.3% for septic shock, and 14.4% for acute kidney injury (AKI). Among patients with methicillin-resistant S. aureus (MRSA) pneumonia treated with vancomycin (n = 40), those with a vancomycin minimum inhibitory concentration (MIC) ≤ 1 had significantly higher cumulative survival at day 30 compared to those with MIC ≥ 2 (log-rank test p = 0.04). The prevalence of MRSA among S. aureus isolates was 84.7%. Hemoptysis, methicillin resistance, acidosis (pH < 7.35), and meeting the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) criteria for severe pneumonia were significantly associated with mortality in a multivariate Cox regression model based on the adaptive least absolute shrinkage and selection operator (LASSO). CONCLUSIONS: S. aureus pneumonia is a severe clinical condition with high mortality and complication rates. MRSA has a high prevalence in Can Tho City, Vietnam. Hemoptysis, methicillin resistance, acidosis (pH < 7.35), and meeting the IDSA/ATS criteria for severe pneumonia are risk factors for mortality in S. aureus pneumonia.

Lymph node harvesting after laparoscopic complete mesocolic excision colectomy in colon cancer with practical application of glacial acid, absolute ethanol, water, and formaldehyde solution: A prospective cohort study.

Objectives: Quality of surgery has recently become an essential topic in the prognosis of colon cancer. Complete mesocolic excision for colon cancer has recently gained popularity with high-quality surgery. Patient specimens after complete mesocolic excision with central vessel ligation procedures have an integrity of the mesocolon and the yield of three fields of lymph node harvest. We apply the glacial acid, absolute ethanol, water, and formaldehyde solution to each specimen based on the Japanese classification of lymph node groups and station numbers. We aim to identify the distribution and status of lymph node metastasis according to each tumor site and some pathological characteristics related to this disease. Methods: A prospective cohort study was performed on 45 laparoscopic complete mesocolic excision surgery patients. Results: 2791 lymph nodes were harvested after complete mesocolic excision surgery. The average number was 62.0 ± 22.3 nodes. The mean tumor size (in the largest dimension) was 4.2 ± 1.8 cm. The average length of the resected bowel segments was 29.1 ± 7.7 cm. There are 63 (2.3%) node metastases in 2791 lymph nodes, in which 17/45 (37.8%) patients had pN(+). The minimum positive node size was 1 mm. The positive pericolic lymph nodes (station 1) accounted for the highest rate, with 53 nodes (1.9%). The number of lymph nodes in young age ⩽60 is more significant than in older. The results were similar, with a more significant node retrieval in the group with a tumor size >4.5 cm and specimen length >25 cm. The number of lymph nodes in lower tumor invasive (pT1,3) was smaller than pT4. Our research shows that the cecum, ascending, and descending colon had greater nodes than others, with a mean number of 78.6, 74.2, and 71.3, respectively. Conclusions: The metastasis and harvested lymph nodes accounted for the highest rate of colon cancer in station 1 and the lowest rate in station 3. The number of retrieved lymph nodes was significantly associated with tumor location, size, specimen length, and patient age.

Surgical Complications in Papillary Thyroid Cancer Patients with Cervical Lymph Node Metastases.

Background: The reported complication rates of neck dissection are not specific patients with papillary thyroid cancer` with metastatic lymph nodes. This study aimed to describe the complication profile of neck dissection and the effect of concurrent lateral neck dissection on complication rates. Methods: This single-center prospective cohort study analyzed the data of 52 patients who underwent a total thyroidectomy and therapeutic lymph node dissection between March 2021 and March 2023. The clinicopathologic characteristics of patients and surgical complications were analyzed. Results: The transient recurrent laryngeal nerve palsy (RLNP) and hypoparathyroidism rates were 55.8% and 51.9%, respectively. The chyle leakage rate was 5.8%. Tracheostomy was performed on 1 patient (1.9%). Patients with transient RLNP had more retrieved lymph nodes than patients without RLNP (5.5 ± 2.7 vs 3.9 ± 1.5, P = .013). The rates of transient RLNP and hypoparathyroidism were higher in the total thyroidectomy with central and lateral neck dissection group than the total thyroidectomy with central neck dissection group (62.2% vs 14.3%, P = .035 and 57.8% vs 14.3%, P = .046). Multivariate analysis showed that the increased number of retrieved lymph nodes in the central compartment and the addition of lateral neck dissection were independent risk factors for transient RLNP, with odds ratio (OR) (95% confidence interval) of 0.72 (0.53-0.98) and 9.42 (1.02-87.34). Conclusion: The rates of transient RLNP and hypoparathyroidism after lymph node dissection in patients with papillary thyroid cancer with metastatic lymph nodes were high, and a greater number of retrieved lymph nodes in the central neck and the addition of lateral neck dissection were predictors for transient RLNP. These data may be used to discuss preoperatively with patients and make surgeons more cautious and meticulous during surgery to minimize complications.

Antiproliferative in Vitro Evaluation of Terpenic Amines Synthesized via a Rhodium-catalyzed Hydroaminomethylation.

Terpene-derived alkaloids show a variety of biological activities, including antioxidant, anti-inflammatory, antimicrobial and cytotoxicity effects. In this work, homologated monoterpene amines have been prepared via a rhodium-catalyzed hydroaminomethylation of biomass-based alkenes, such as (R)-limonene, linalool, myrcene and camphene, in combination with secondary amines of aliphatic and aromatic nature, namely morpholine and N-methylaniline, leading to highly chemo- and regioselective processes. The as-prepared amines were obtained in 50-99 % overall yields, and in vitro tested on a human colon cancer cell line (HCT-116) to evaluate their cytotoxic potential. The lead compound of the series (3 a) showed cytotoxicity in the micromolar range (IC50 52.46 µM) via the induction of cell death by apoptosis, paving the way towards further structure-activity relationship studies.

Halophilic lactic acid bacteria - Play a vital role in the fermented food industry.

Halophilic lactic acid bacteria have been widely found in various high-salt fermented foods. The distribution of these species in salt-fermented foods contributes significantly to the development of the product's flavor. Besides, these bacteria also have the ability to biosynthesize bioactive components which potentially apply to different areas. In this review, insights into the metabolic properties, salt stress responses, and potential applications of these bacteria have been have been elucidated. The purpose of this review highlights the important role of halophilic lactic acid bacteria in improving the quality and safety of salt-fermented products and explores the potential application of these bacteria.

Effectiveness of care bundles for prevention and treatment of postpartum hemorrhage: a systematic review.

OBJECTIVE: Care bundles are a promising approach to reducing postpartum hemorrhage-related morbidity and mortality. We assessed the effectiveness and safety of care bundles for postpartum hemorrhage prevention and/or treatment. DATA SOURCES: We searched MEDLINE, Embase, Cochrane CENTRAL, Maternity and Infant Care Database, and Global Index Medicus (inception to June 9, 2023) and ClinicalTrials.gov and the International Clinical Trials Registry Platform (last 5 years) using a phased search strategy, combining terms for postpartum hemorrhage and care bundles. STUDY ELIGIBILITY CRITERIA: Peer-reviewed studies evaluating postpartum hemorrhage-related care bundles were included. Care bundles were defined as interventions comprising ≥3 components implemented collectively, concurrently, or in rapid succession. Randomized and nonrandomized controlled trials, interrupted time series, and before-after studies (controlled or uncontrolled) were eligible. METHODS: Risk of bias was assessed using RoB 2 (randomized trials) and ROBINS-I (nonrandomized studies). For controlled studies, we reported risk ratios for dichotomous outcomes and mean differences for continuous outcomes, with certainty of evidence determined using GRADE. For uncontrolled studies, we used effect direction tables and summarized results narratively. RESULTS: Twenty-two studies were included for analysis. For prevention-only bundles (2 studies), low-certainty evidence suggests possible benefits in reducing blood loss, duration of hospitalization, and intensive care unit stay, and maternal well-being. For treatment-only bundles (9 studies), high-certainty evidence shows that the E-MOTIVE intervention reduced risks of composite severe morbidity (risk ratio, 0.40; 95% confidence interval, 0.32-0.50) and blood transfusion for bleeding, postpartum hemorrhage, severe postpartum hemorrhage, and mean blood loss. One nonrandomized trial and 7 uncontrolled studies suggest that other postpartum hemorrhage treatment bundles might reduce blood loss and severe postpartum hemorrhage, but this is uncertain. For combined prevention/treatment bundles (11 studies), low-certainty evidence shows that the California Maternal Quality Care Collaborative care bundle may reduce severe maternal morbidity (risk ratio, 0.64; 95% confidence interval, 0.57-0.72). Ten uncontrolled studies variably showed possible benefits, no effects, or harms for other bundle types. Nearly all uncontrolled studies did not use suitable statistical methods for single-group pretest-posttest comparisons and should thus be interpreted with caution. CONCLUSION: The E-MOTIVE intervention improves postpartum hemorrhage-related outcomes among women delivering vaginally, and the California Maternal Quality Care Collaborative bundle may reduce severe maternal morbidity. Other bundle designs warrant further effectiveness research before implementation is contemplated.

Macromolecular Cargo Encapsulation via In Vitro Assembly of Two-Component Protein Nanoparticles.

Self-assembling protein nanoparticles are a promising class of materials for targeted drug delivery. Here, the use of a computationally designed, two-component, icosahedral protein nanoparticle is reported to encapsulate multiple macromolecular cargoes via simple and controlled self-assembly in vitro. Single-stranded RNA molecules between 200 and 2500 nucleotides in length are encapsulated and protected from enzymatic degradation for up to a month with length-dependent decay rates. Immunogenicity studies of nanoparticles packaging synthetic polymers carrying a small-molecule TLR7/8 agonist show that co-delivery of antigen and adjuvant results in a more than 20-fold increase in humoral immune responses while minimizing systemic cytokine secretion associated with free adjuvant. Coupled with the precise control over nanoparticle structure offered by computational design, robust and versatile encapsulation via in vitro assembly opens the door to a new generation of cargo-loaded protein nanoparticles that can combine the therapeutic effects of multiple drug classes.

Fitness trade-offs of multidrug efflux pumps in Escherichia coli K-12 in acid or base, and with aromatic phytochemicals.

Multidrug efflux pumps are the frontline defense mechanisms of Gram-negative bacteria, yet little is known of their relative fitness trade-offs under gut conditions such as low pH and the presence of antimicrobial food molecules. Low pH contributes to the proton-motive force (PMF) that drives most efflux pumps. We show how the PMF-dependent pumps AcrAB-TolC, MdtEF-TolC, and EmrAB-TolC undergo selection at low pH and in the presence of membrane-permeant phytochemicals. Competition assays were performed by flow cytometry of co-cultured Escherichia coli K-12 strains possessing or lacking a given pump complex. All three pumps showed negative selection under conditions that deplete PMF (pH 5.5 with carbonyl cyanide 3-chlorophenylhydrazone or at pH 8.0). At pH 5.5, selection against AcrAB-TolC was increased by aromatic acids, alcohols, and related phytochemicals such as methyl salicylate. The degree of fitness cost for AcrA was correlated with the phytochemical's lipophilicity (logP). Methyl salicylate and salicylamide selected strongly against AcrA, without genetic induction of drug resistance regulons. MdtEF-TolC and EmrAB-TolC each had a fitness cost at pH 5.5, but salicylate or benzoate made the fitness contribution positive. Pump fitness effects were not explained by gene expression (measured by digital PCR). Between pH 5.5 and 8.0, acrA and emrA were upregulated in the log phase, whereas mdtE expression was upregulated in the transition-to-stationary phase and at pH 5.5 in the log phase. Methyl salicylate did not affect pump gene expression. Our results suggest that lipophilic non-acidic molecules select against a major efflux pump without inducing antibiotic resistance regulons.IMPORTANCEFor drugs that are administered orally, we need to understand how ingested phytochemicals modulate drug resistance in our gut microbiome. Bacteria maintain low-level resistance by proton-motive force (PMF)-driven pumps that efflux many different antibiotics and cell waste products. These pumps play a key role in bacterial defense by conferring resistance to antimicrobial agents at first exposure while providing time for a pathogen to evolve resistance to higher levels of the antibiotic exposed. Nevertheless, efflux pumps confer energetic costs due to gene expression and pump energy expense. The bacterial PMF includes the transmembrane pH difference (ΔpH), which may be depleted by permeant acids and membrane disruptors. Understanding the fitness costs of efflux pumps may enable us to develop resistance breakers, that is, molecules that work together with antibiotics to potentiate their effect. Non-acidic aromatic molecules have the advantage that they avoid the Mar-dependent induction of regulons conferring other forms of drug resistance. We show that different pumps have distinct selection criteria, and we identified non-acidic aromatic molecules as promising candidates for drug resistance breakers.

Vision-Based Assistance for Vocal Fold Identification in Laryngoscopy with Knowledge Distillation.

Laryngoscopy images play a vital role in merging computer vision and otorhinolaryngology research. However, limited studies offer laryngeal datasets for comparative evaluation. Hence, this study introduces a novel dataset focusing on vocal fold images. Additionally, we propose a lightweight network utilizing knowledge distillation, with our student model achieving around 98.4% accuracy-comparable to the original EfficientNetB1 while reducing model weights by up to 88%. We also present an AI-assisted smartphone solution, enabling a portable and intelligent laryngoscopy system that aids laryngoscopists in efficiently targeting vocal fold areas for observation and diagnosis. To sum up, our contribution includes a laryngeal image dataset and a compressed version of the efficient model, suitable for handheld laryngoscopy devices.

Electrocardiographic and genetic characteristics in first degree relatives of hypertrophic cardiomyopathy probands: A descriptive cross-sectional study from Vietnam.

Objectives: In order to study the phenotype-genotype relationship and to better understand the early consequences of the mutation, we would report the spectrum of electrocardiographic and genetic features in the relatives of hypertrophic cardiomyopathy (HCM) patients. Methods: Participants underwent a comprehensive clinical assessment, electrocardiography, standardized and echocardiography and genetic testing. In probands, next-generation sequencing was performed using the gene panel associated with HCM, while in relatives, Sanger sequencing was used to screen for mutations identified in their individual probands. Results: A total of 84 participants were included in this study. The interventricular septal and posterior wall thickness was highest in the G+/LVH+ group, followed by the G+/LVH- group, and was lowest in G-/LVH- group. Compared to the normal control group, the pathologic Q wave was statistically more prevalent in the G+/LVH- group. The prevalence of repolarization abnormalities and major abnormalities was highest in the G+/LVH+ group, followed by the G+/LVH- group, and lowest in G-/LVH- group. Conclusion: Our results suggested that sarcomere mutations have early consequences on myocardial biology. These findings suggest the possibility of implementing a mutation carrier detection model within families affected by HCM, where ECG could play a central role when combined with other relevant clinical factors. Longitudinal studies on a cohort of G+/LVH- patients are required.

Prevalence of violence victimisation and poly-victimisation among female sex workers in Haiphong, Viet Nam: A cross-sectional study.

This cross-sectional study is the first to describe the prevalence of violence and poly-victimisation among 310 female sex workers (FSWs) who were cisgender in Haiphong, Viet Nam. An adapted version of the WHO-Multi-Country Study on Violence against Women Survey Instrument was administered to assess physical, sexual, economic and emotional forms of violence perpetrated by an intimate partner, paying partner/client, and/or others (e.g. relatives, police, strangers and other FSWs) during adulthood. The ACE-Q scale was administered to assess adverse childhood experiences (ACEs) before age 18 years. Our findings showed that FSWs are exposed to high rates of multiple forms of violence by multiple perpetrators. For any male client-perpetrated violence (CPV), lifetime prevalence was 70.0%, with 12-month prevalence 61.3%. Lifetime prevalence of male intimate partner violence (IPV) was 62.1%, and the 12-month prevalence was 58.2%. Lifetime and prior 12-month prevalence of physical and/or sexual violence by other perpetrators (OPV) was 18.1% and 14.2%, respectively. Sixty-five percent of FSWs reported at least one type of ACE. Overall, 21.6 percent of FSWs reported having experienced all three forms of violence (IPV, CPV and OPV) in their lifetime. Policy and programme recommendations for screening and prevention of violence are needed in this setting.

Unique case of vascularization: superficial brachial artery and radial persistent median artery.

During a routine cadaveric dissection of a 93-year-old male donor, unique arterial variations were observed in the right upper extremity. This rare arterial branching pattern began at the third part of the axillary artery (AA), where it gave off a large superficial brachial artery (SBA) before bifurcating into the subscapular artery and a common stem. The common stem then gave off a division for the anterior and posterior circumflex humeral arteries, before continuing as a small brachial artery (BA). The BA terminated as a muscular branch to the brachialis muscle. The SBA bifurcated into a large radial artery (RA) and small ulnar artery (UA) in the cubital fossa. The UA branching pattern was atypical, giving off only muscular branches in the forearm and a deep UA before contributing to the superficial palmar arch (SPA). The RA provided the radial recurrent artery and a common trunk (CT) proximally before continuing its course to the hand. The CT from the RA gave off a branch that divided into anterior and posterior ulnar recurrent arteries, as well as muscular branches, before it bifurcated into the persistent median artery (PMA) and the common interosseous artery. The PMA anastomosed with the UA before entering the carpal tunnel and contributed to the SPA. This case presents a unique combination of arterial variations in the upper extremity and is clinically and pathologically relevant.