The role of bacterial size, shape and surface in macrophage engulfment of uropathogenic E. coli cells.

Uropathogenic Escherichia coli (UPEC) can undergo extensive filamentation in the host during acute urinary tract infections (UTIs). It has been hypothesised that this morphological plasticity allows bacteria to avoid host immune responses such as macrophage engulfment. However, it is still unclear what properties of filaments are important in macrophage-bacteria interactions. The aim of this work was to investigate the contribution of bacterial biophysical parameters, such as cell size and shape, and physiological parameters, such as cell surface and the environment, to macrophage engulfment efficiency. Viable, reversible filaments of known lengths and volumes were produced in the UPEC strain UTI89 using a variety of methods, including exposure to cell-wall targeting antibiotics, genetic manipulation and isolation from an in vitro human bladder cell model. Quantification of the engulfment ability of macrophages using gentamicin-protection assays and fluorescence microscopy demonstrated that the ability of filaments to avoid macrophage engulfment is dependent on a combination of size (length and volume), shape, cell surface and external environmental factors. UTI89 filamentation and macrophage engulfment efficiency were also found to occur independently of the SOS-inducible filamentation genes, sulA and ymfM in both in vivo and in vitro models of infection. Compared to filaments formed via antibiotic inhibition of division, the infection-derived filaments were preferentially targeted by macrophages. With several strains of UPEC now resistant to current antibiotics, our work identifies the importance of bacterial physiological and morphological states during infection.

Mycoplasma genitalium infections among participants in a HIV pre-exposure prophylaxis program in Hanoi, Vietnam.

BACKGROUND: Mycoplasma genitalium causes a sexually transmitted infection and is also emerging as an important antimicrobial resistant pathogen. Data on M. genitalium infections among men who have sex with men (MSM) in low-resource settings are sparse. METHODS: From January to December 2022, participants in an HIV pre-exposure prophylaxis (PrEP) program in Hanoi, Vietnam were enrolled into the study. Demographic, behavioral, and clinical characteristics were collected. Self-collected urine, rectal, and pharyngeal specimens were tested for M. genitalium using the Alinity m STI Assay (Abbott Molecular, USA). Univariate and multivariate logistic regression were performed to assess for factors associated with infections. RESULTS: Among 477 participants, the median age was 25.3 years (21.7-29.6) and 92.2% (n = 440) identified as MSM; 48.6% had ≥2 sex partners and 38.1% reported condomless anal sex in the prior month. The overall prevalence of M. genitalium infection was 10.9% (52/477); 7.3% (34/464) rectal, 3.2% (15/476) urethral, and 1.9% (9/476) pharyngeal. Infections were asymptomatic in 71.2% (37/52). Among those with M. genitalium, 30.7% (16/52) were co-infected with either N. gonorrhoeae or C. trachomatis. Among those reporting rectal (n = 51) or urethral (n = 35) symptoms, but without C. trachomatis or N. gonorrhoeae co-infections, five (9.8%) had rectal infections and one (2.9%) had urethral infection. Participants with M. genitalium were more likely to be asymptomatic than participants without M. genitalium (aOR 1.93; 95% CI 1.01-3.71). CONCLUSIONS: M. genitalium infections were common among primarily MSM engaged in an HIV PrEP program in Vietnam. The prevalence was highest in rectal specimens and nearly three quarters of M. genitalium infections were asymptomatic. Testing for M. genitalium infections among those with symptoms is important to enable pathogen-directed therapy. Additional research on antimicrobial resistance and treatment strategies for M. genitalium in low-resource settings is needed.

The impacts of telemedicine on assisted reproduction: a systematic review and meta-analysis.

Telemedicine is being applied in assisted reproduction technology (ART) to provide remote consultations, monitoring and support for patients. This study aimed to evaluate the potential advantages of telemedicine in ART treatment in the form of virtual consultations. Studies in which patients were using telemedicine during ART treatment were identified from four scientific databases (PudMed, EMBASE, Scopus, Web of Science). The success of fertility treatments was compared between telemedicine and in-office care, and patient satisfaction with ART through telemedicine was assessed. Eleven studies, comprising 4697 patients, were identified. Quality assessment (Joanna Briggs Institute Critical Appraisal and revised Cochrane risk-of-bias tools) revealed an acceptable risk of bias for both randomized controlled trials and observational studies. Using a fixed-effects model, telemedicine was comparable to in-person care regarding the pregnancy rate achieved (odds ratio 1.02, 95% confidence intervals 0.83-1.26, P = 0.83). A Q-test suggested that all the included studies were homogeneous. Patients who received telemedicine during fertility treatment reported a high level of satisfaction (91%, 95% confidence intervals 80-96%). Egger's test confirmed that no publication bias was found. Telemedicine could serve as a complementary tool during fertility treatment to facilitate patients' satisfaction and overcome some practical problems without compromising treatment outcomes. Future studies should continue exploring the potential applications of telemedicine in assisted reproduction.

Tracking modifications to implementation strategies: a case study from SNaP - a hybrid type III randomized controlled trial to scale up integrated systems navigation and psychosocial counseling for PWID with HIV in Vietnam.

INTRODUCTION: Evaluation of implementation strategies is core to implementation trials, but implementation strategies often deviate from the original plan to adjust to the real-world conditions. The optimal approach to track modifications to implementation strategies is unclear, especially in low-resource settings. Using data from an implementation trial for people who inject drugs (PWID) with HIV in Vietnam, we describe the tracking of implementation strategy modifications and present findings of this process. METHODS: SNaP (Systems Navigation and Psychosocial Counseling) is a hybrid type-III effectiveness-implementation randomized controlled trial aiming to scale up the evidence-based intervention, integrated systems navigation and psychosocial counseling, for PWID with HIV in Vietnam. Forty-two HIV testing sites were randomized 1:1 to a standard or tailored arm. While the standard arm (SA) received a uniform package of strategies, implementation strategies for the tailored arm (TA) were tailored to address specific needs of each site. The central research team also met monthly with the TA to document how their tailored strategies were implemented over time. Five components were involved in the tracking process: describing the planned strategies; tracking strategy use; monitoring barriers and solutions; describing modifications; and identifying and describing any additional strategies. RESULTS: Our approach allowed us to closely track the modifications to implementation strategies in the tailored arms every month. TA sites originally identified 27 implementation strategies prior to implementation. During implementation, five strategies were dropped by four sites and two new strategies were added to twelve sites. Modifications of five strategies occurred at four sites to accommodate their changing needs and resources. Difficulties related to the COVID-19 pandemic, low number of participants recruited, high workload at the clinic, lack of resources for HIV testing and high staff turnover were among barriers of implementing the strategies. A few challenges to tracking modifications were noted, including the considerable amount of time and efforts needed as well as the lack of motivation from site staff to track and keep written documentations of modifications. CONCLUSIONS: We demonstrated the feasibility of a systematic approach to tracking implementation strategies for a large-scale implementation trial in a low-resource setting. This process could be further enhanced and replicated in similar settings to balance the rigor and feasibility of implementation strategy tracking. Our findings can serve as additional guidelines for future researchers planning to report and track modifications to implementation strategies in large, complex trials. TRIAL REGISTRATION: clinicaltrials.gov ID: NCT03952520 (first posted 2019-05-16).

Surgical complications in neuromuscular scoliosis surgery: systematic review and meta-analysis of the last ten years.

PURPOSE: Surgical correction of neuromuscular scoliosis is often a challenging and extensive procedure. Due to this complexity and the high disease burden that these patients carry, per and post-operative complications are not uncommon. The purpose of this study was to systematically review and describe the pooled rates of postoperative complications and analyze risk factors for complications in neuromuscular scoliosis surgery described in the literature in the last ten years. METHODS: A systematic review of the English literature across multiple databases was conducted using search criteria (neuromuscular scoliosis AND complications) and using PRISMA guidelines (Jan 2012-July 2022). Studies with less than 30 patients and follow-up of < 2 years were excluded. Data extraction and meta-analysis were performed using random mode effect. Statistical analysis was conducted using OpenMeta software. Meta-regression analysis was used to detect risk factors (surgical approach, intraoperative time, intraoperative blood loss, preoperative Cobb angle and patient diagnosis) associated with each complication group. Confidence interval (CI) was set at 95%. RESULTS: Twenty-two studies met the inclusion criteria involving 2155 patients. The level of evidence among studies were III (9) and IV (13). The most common primary diagnosis was cerebral palsy (43%) followed by Duchenne muscle dystrophy (20%), myelomeningocele (7.4%), spinal muscle atrophy (7.1%), Rett syndrome (< 2%) and combined other pathologies (20.2%). The pooled incidence rate of wound complications was the highest, amongst all complications, at 13.3% (CI 10.838 to 16.861); closely followed by respiratory complications (11.8%;CI 5.7 to 19.7). Implant failure occurred in 7.1% cases (CI 6.418 to 11.465), gastrointestinal complications was 5.2%; CI 2.4 to 8), pseudarthrosis in (4.6%;CI 2.2 to 6.9) and neurological deficit in 2.9% (CI 1.989 to 6.086). The pooled rate of revision surgery was (9.6%; CI 6.2 to 12.9). Heterogeneity was assessed using I2 test which results were moderately heterogeneous. Meta-regression analysis revealed that the diagnosis of myelomeningocele or Duchenne muscle dystrophy or spinal muscle atrophy were strongly associated with wound and respiratory complications (p = 0.007 and p = 0.005, respectively). CONCLUSION: Wound-related (13.3%) and respiratory complications (11.8%) remain the most common complications among studies after corrective surgery for neuromuscular scoliosis. Both are significantly associated with Duchenne muscle dystrophy, spinal muscle atrophy and myelomeningocele.

Knowledge and attitudes of medical and pharmacy university students regarding monkeypox: a multicenter, cross-sectional study in Vietnam.

BACKGROUND: In May 2022, monkeypox (mpox) suddenly reappeared and rapidly spread worldwide. This global outbreak was a public health emergency of international concern. This study investigated Vietnamese medical and pharmacy university students' knowledge and attitudes towards mpox. METHODS: This online cross-section survey was administered among students in four universities using a convenience sampling method. A semi-structured questionnaire was shared among students via a Google Forms link (quick-response code) in university amphitheaters at recess. Frequency (percentage) and mean (standard division) were used for descriptive statistics. Univariate and multivariate linear regression analyses were conducted to identify factors associated with students' mpox knowledge and attitudes. A p-value < 0.001 was considered statistical significance. RESULTS: A total of 1,848 students participated in this study (including 1,030 medical students and 818 pharmacy students). Their common sources for seeking mpox/health information included the Internet (89.7%) and mass media (64.2%). Students' average knowledge and attitude scores were 11.542 ± 3.910 (range: 0-23) and 30.301 ± 3.738 (range: 9-45), respectively. The average knowledge score of pharmacy students (12.139 ± 3.545) was significantly higher than that of medical students (11.067 ± 4.118) (p < 0.001). The average attitude score of the former (30.454 ± 3.787) was comparatively higher than that of the latter (30.181 ± 3.696), but this difference was insignificant (p = 0.111). Factors significantly associated with students' mpox knowledge and/or attitudes were their sex, age, year of study, residence, major, grade point average, type of university, seeking mpox information in the past, and using reliable sources to seek health information (p < 0.001). A positive correlation existed between students' knowledge and attitude scores (p < 0.001). CONCLUSIONS: Students' knowledge about mpox was relatively poor, while their attitudes were comparatively positive. Universities and relevant authorities should focus on the above factors and use multiple platforms and channels of communication to guarantee that trustworthy information about mpox can reach as many students as possible.

Investigation of Urinary Metabolites of Organophosphate Esters in Hanoi, Vietnam: Assessment Exposure and Estimated Daily Intake.

In recent years, organophosphate esters (OPEs) have become one of the most common additives in various consumer products worldwide, therefore the exposure and impact of OPEs on human health are drawing a lot of attention. In this study, three metabolites of OPEs including bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPhP) and diethyl phosphate (DEP) were investigated in first-morning void urine samples taken from a population (age range: 3-76 years old) in Hanoi, Vietnam. The most dominant urinary OPE metabolite was DEP with the geometric mean of specific gravity adjust (SG-adjusted) concentration were 1960 ng mL-1 and detected frequency (DF) of 98%. Followed by DPhP (8.01 ng mL-1, DF: 100%) and BDCIPP (2.18 ng mL-1, DF: 51%). The results indicated that gender and age might have associations with the OPE metabolites variation in urine samples. The levels of OPE metabolites in urine samples from females were slightly higher than in males. An increase in age seems to have an association with a decrease in DPhP levels in urine. Exposure doses of parent OPEs were evaluated from the unadjusted urinary concentration of corresponding OPE metabolite. The estimated exposure doses of triethyl phosphate (TEP) (mean: 534,000 ng kg-1 d-1) were significantly higher than its corresponding reference dose, suggesting the high potential risk from the current exposure doses of TEP to human health. The results of this work provided the initial information on the occurrence of three OPE metabolites in urine from Hanoi, Vietnam and estimated exposure dose of corresponding parent OPEs.

Shift from a Zero-COVID strategy to a New-normal strategy for controlling SARS-COV-2 infections in Vietnam.

The aim of this study is to analyse the changing patterns in the transmission of COVID-19 in relation to changes in Vietnamese governmental policies, based on epidemiological data and policy actions in a large Vietnamese province, Bac Ninh, in 2021. Data on confirmed cases from January to December 2021 were collected, together with policy documents. There were three distinct periods of the COVID-19 pandemic in Bac Ninh province during 2021. During the first period, referred to as the 'Zero-COVID' period (01/04-07/04/2021), there was a low population vaccination rate, with less than 25% of the population receiving its first vaccine dose. Measures implemented during this period focused on domestic movement restrictions, mask mandates, and screening efforts to control the spread of the virus. The subsequent period, referred to as the 'Transition' period (07/05-10/22/2021), witnessed a significant increase in population vaccination coverage, with 80% of the population receiving their first vaccine dose. During this period, several days passed without any reported COVID-19 cases in the community. The local government implemented measures to manage domestic actions and reduce the time spent in quarantine, and encouraged home quarantining for the close contacts of cases with COVID-19. Finally, the 'New-normal' stage (10/23-12/31/2021), during which the population vaccination coverage with a second vaccine dose increased to 70%, and most of the mandates for the prevention and control of COVID-19 were reduced. In conclusion, this study highlights the importance of governmental policies in managing and controlling the transmission of COVID-19 and provides insights for developing realistic and context-specific strategies in similar settings.

Constructing and validating an occupational job strain index based on five Norwegian nationwide surveys of living conditions on work environment.

BACKGROUND: It has been claimed that Nordic register data are a "goldmine" for research. However, one limitation is the lack of information on working conditions. Job exposure matrices (JEMs) are one solution to this problem. Thus, the three aims of this study were (i) to investigate the reliability of an occupation-based psychosocial JEM, i.e., a Job Strain Index (job strain or JSI abbreviated), (ii) to examine the construct and criterion-related validity of this measure of job strain (iii) and assesses the concurrent and the predictive validity of an occupation-based Job Strain Index for use in analyses of Norwegian register data. METHOD: The study utilized five waves of the nationwide Norway Survey of Living Conditions in the Work Environment with a total sample of 43,977 individuals and register data with a total sample of 1,589,535 individuals. Job strain was composed of items belonging to the two dimensions of Karasek's DC model, job demands and job control (1979). The reliability of the JSI and its dimensions and components were investigated by measuring the degree of agreement (Cohen's kappa), sensitivity, specificity, and internal consistency (Cronbach's alpha). Construct validity was assessed by confirmatory factor analysis, and criterion-related validity was measured by concurrent validity and predictive validity. The selected concurrent criteria were self-reported survey information on long-term sick absence, anxiety, depression, and sleeping difficulty. The predictive criteria were register information on receipt of disability benefits, mortality, and long-term sick leave. RESULTS: Agreement between individual and occupation-based job strain and components was fair to poor. The sensitivity and specificity of occupation-based job strain and its components varied from acceptable to low. The consistency of the items comprising job demand and job control was clearly acceptable. Regarding concurrent validity, significant associations between (both individual and occupational) job strain, and long-term sick leave and sleeping difficulty were observed for both genders. Occupation-based job strain indicated an elevated risk for anxiety and depression among men, but not among women. As for predictive reliability, significant associations between occupation-based job strain and all three health outcomes were observed for both men and women. CONCLUSION: Our occupation-based JSI serves as a reliable and valid indicator of psychosocial job exposure that can be used in analyses of Norwegian register data where individual information on such conditions is missing.

Drug Harm Reduction in Vietnam: A Review of Stakeholders' Perspectives and Implications for Future Interventions.

Objectives. To determine how harm reduction should be applied in low-resource countries such as Vietnam by exploring the perspectives of people who use drugs (PWUD), health care professionals, and policymakers regarding methadone treatment and harm reduction strategies. Methods. We conducted 2 qualitative studies in Vietnam between 2016 and 2021. We interviewed 62 PWUD and 22 experts in drug policy development and drug treatment programs, conducted observations at methadone clinics and harm reduction program meetings, and analyzed drug policy documents. Results. PWUD considered methadone treatment only as a transition to a drug-free life. Policymakers deemed harm reduction ineffective and continued to enforce arrest and incarceration of PWUD. Drug intervention programs are not yet geared to providing specialized services. Effective communication strategies and information on evidence-based harm reduction models are inadequate to help policymakers make the right decisions. Conclusions. Harm reduction principles have not been fully adopted in Vietnam. A harm reduction strategy based on a more humanistic approach that goes beyond a biomedicalized approach is urgently needed in Vietnam and other countries in the Global South. (Am J Public Health. 2022;112(S2):S182-S190. https://doi.org/10.2105/AJPH.2022.306764).

Stigma experienced by people living with HIV who are on methadone maintenance treatment and have symptoms of common mental disorders in Hanoi, Vietnam: a qualitative study.

BACKGROUND: Stigma around human immunodeficiency virus (HIV), injection drug use (IDU), and mental health disorders can be co-occurring and have different impacts on the well-being of people living with HIV (PWH) who use drugs and have mental health disorders. This stigma can come from society, health professionals, and internalized stigma. A person who has more than one health condition can experience overlapping health-related stigma and levels of stigma which can prevent them from receiving necessary support and healthcare, serving to intensify their experience with stigma. This study investigates HIV, drug use, and mental health stigmas in three dimensions (social, internalized, and professional) around PWH on methadone maintenance treatment (MMT) who have common mental disorders (CMDs) including depression, anxiety, and stress-related disorders in Hanoi, Vietnam.Please check and confirm whether corresponding author's email id is correctly identified.The cooresponding author's email is correct METHODS: We conducted semi-structured, in-depth interviews (IDIs) (n = 21) and two focus group discussions (FGDs) (n = 10) with PWH receiving MMT who have CMD symptoms, their family members, clinic health care providers, and clinic directors. We applied thematic analysis using NVIVO software version 12.0, with themes based on IDI and FGD guides and emergent themes from interview transcripts. RESULTS: The study found evidence of different stigmas towards HIV, IDU, and CMDs from the community, family, health care providers, and participants themselves. Community and family members were physically and emotionally distant from patients due to societal stigma around illicit drug use and fears of acquiring HIV. Participants often conflated stigmas around drug use and HIV, referring to these stigmas interchangeably. The internalized stigma around having HIV and injecting drugs made PWH on MMT hesitant to seek support for CMDs. These stigmas compounded to negatively impact participants' health. CONCLUSIONS: Strategies to reduce stigma affecting PWH on MMT should concurrently address stigmas around HIV, drug addiction, and mental health. Future studies could explore approaches to address internalized stigma to improve self-esteem, mental health, and capacities to cope with stigma for PWH on MMT. TRIAL REGISTRATION: NCT04790201, available at clinicaltrials.gov.

Selection of Candida albicans trisomy during oropharyngeal infection results in a commensal-like phenotype.

When the fungus Candida albicans proliferates in the oropharyngeal cavity during experimental oropharyngeal candidiasis (OPC), it undergoes large-scale genome changes at a much higher frequency than when it grows in vitro. Previously, we identified a specific whole chromosome amplification, trisomy of Chr6 (Chr6x3), that was highly overrepresented among strains recovered from the tongues of mice with OPC. To determine the functional significance of this trisomy, we assessed the virulence of two Chr6 trisomic strains and a Chr5 trisomic strain in the mouse model of OPC. We also analyzed the expression of virulence-associated traits in vitro. All three trisomic strains exhibited characteristics of a commensal during OPC in mice. They achieved the same oral fungal burden as the diploid progenitor strain but caused significantly less weight loss and elicited a significantly lower inflammatory host response. In vitro, all three trisomic strains had reduced capacity to adhere to and invade oral epithelial cells and increased susceptibility to neutrophil killing. Whole genome sequencing of pre- and post-infection isolates found that the trisomies were usually maintained. Most post-infection isolates also contained de novo point mutations, but these were not conserved. While in vitro growth assays did not reveal phenotypes specific to de novo point mutations, they did reveal novel phenotypes specific to each lineage. These data reveal that during OPC, clones that are trisomic for Chr5 or Chr6 are selected and they facilitate a commensal-like phenotype.

Understanding Vietnam's drug policy for amphetamine-type stimulants misuse.

INTRODUCTION: The emergence of widespread amphetamine-type stimulants (ATSs) usage has created significant challenges for drug control and treatment policies in Southeast Asian countries. This study analyses the development of drug policies and examines current treatment program constraints in Vietnam to deal with ATS misuse. The aim was to gain insights that may be useful for national and international drug-related policy development and revision. METHODS: A desk review of national policy documents and 22 in-depth key informant interviews were conducted from 2019 to 2021. Thematic content analysis was employed to identify key themes and their connections. RESULTS: Analysis identified Vietnam's 30-year history of developing policies and formulating strategies to reduce supply, demand, and harm from illicit drugs. With the increasing number of people who use ATS (PWUA), Vietnam has recently promoted harsh policy and law enforcement to deter drug use and supply. This policy trend prevails in many Asian countries. The three main constraints in dealing with ATS misuse emerged from punitive and restrictive drug policies. First, the general public believed that Centre-based compulsory treatment (CCT) is the only appropriate treatment for all types of illicit drug addiction despite its low-quality service provision. The rigid drug policy has led to social persuasion with impractical expectations for CCT effectiveness. Second, the emphasis on punishment and detention has hampered new drug treatment service development in Vietnam. CCT has become monopolistic in the context of impoverished services. Third, people who use drugs tend to hide their needs and avoid formal treatment and support services, resulting in declined social coherence. CONCLUSION: While new drugs are constantly evolving, the current law enforcement approach potentially constrains expertise to adopt effective treatment services. This study suggests that the top-down policing mechanism presently hinders the development of an appropriate intervention strategy for ATS misuse and diminishes social support to service providers.

How has the COVID-19 epidemic affected the risk behaviors of people who inject drugs in a city with high harm reduction service coverage in Vietnam? A qualitative investigation.

INTRODUCTION: The COVID-19 outbreak disproportionally affects vulnerable populations including people who inject drugs (PWID). Social distancing and stay-at-home orders might result in a lack of access to medical and social services, poorer mental health, and financial precariousness, and thus, increases in HIV and HCV risk behaviors. This article explores how the HIV/HCV risk behaviors of PWID in Haiphong, a city with high harm reduction service coverage in Vietnam, changed during the early phase of the COVID-19 pandemic, and what shaped such changes, using the risk environment framework. METHOD: We conducted three focus group discussions with peer outreach workers in May 2020 at the very end of the first lockdown, and 30 in-depth interviews with PWID between September and October 2020, after the second wave of infection in Vietnam. Discussions and interviews centered on the impact of the COVID-19 pandemic on their lives, and how their drug use and sexual behaviors changed as a result of the pandemic. RESULTS: The national shutdown of nonessential businesses due to the COVID-19 epidemic caused substantial economic challenges to participants, who mostly were in a precarious financial situation before the start of the epidemic. Unsafe injection is no longer an issue among our sample of PWID in Haiphong thanks to a combination of different factors, including high awareness of injection-related HIV/HCV risk and the availability of methadone treatment. However, group methamphetamine use as a means to cope with the boredom and stress related to COVID-19 was common during the lockdown. Sharing of smoking equipment was a standard practice. Female sex workers, especially those who were active heroin users, suffered most from COVID-related financial pressure and may have engaged in unsafe sex. CONCLUSION: While unsafe drug injection might no longer be an issue, group methamphetamine use and unsafe sex were the two most worrisome HIV/HCV risk behaviors of PWID in Haiphong during the social distancing and lockdown periods. These elevated risks could continue beyond the enforced lockdown periods, given PWID in general, and PWID who are also sex workers in particular, have been disproportionately affected during the global crisis.

SARS-CoV-2 coronavirus in water and wastewater: A critical review about presence and concern.

The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in water and wastewater has recently been reported. According to the updated literature, the stools and masks of the patients diagnosed with coronavirus disease (COVID-19) were considered as the primary route of coronavirus transmission into water and wastewater. Most coronavirus types which attack human (possible for SARS-CoV-2) are often inactivated rapidly in water (i.e., the survival of human coronavirus 229E in water being 7 day at 23 °C). However, the survival period of coronavirus in water environments strongly depends on temperature, property of water, concentration of suspended solids and organic matter, solution pH, and dose of disinfectant used. The World Health Organization has stated that the current disinfection process of drinking water could effectively inactivate most of the bacterial and viral communities present in water, especially SARS-CoV-2 (more sensitive to disinfectant like free chlorine). A recent study confirmed that SARS-CoV-2 RNA was detected in inflow wastewater (but not detected in outflow one). Although the existence of SARS-CoV-2 in water influents has been confirmed, an important question is whether it can survive or infect after the disinfection process of drinking water. To date, only one study confirmed that the infectivity of SARS-CoV-2 in water for people was null based on the absence of cytopathic effect (CPE) in infectivity tests. Therefore, further studies should focus on the survival of SARS-CoV-2 in water and wastewater under different operational conditions (i.e., temperature and water matrix) and whether the transmission from COVID-19-contaminated water to human is an emerging concern. Although paper-based devices have been suggested for detecting the traces of SARS-CoV-2 in water, the protocols and appropriate devices should be developed soon. Wastewater and sewage workers should follow the procedures for safety precaution against SARS-CoV-2 exposure.

Protease-activated receptor-2 in endosomes signals persistent pain of irritable bowel syndrome.

Once activated at the surface of cells, G protein-coupled receptors (GPCRs) redistribute to endosomes, where they can continue to signal. Whether GPCRs in endosomes generate signals that contribute to human disease is unknown. We evaluated endosomal signaling of protease-activated receptor-2 (PAR2), which has been proposed to mediate pain in patients with irritable bowel syndrome (IBS). Trypsin, elastase, and cathepsin S, which are activated in the colonic mucosa of patients with IBS and in experimental animals with colitis, caused persistent PAR2-dependent hyperexcitability of nociceptors, sensitization of colonic afferent neurons to mechanical stimuli, and somatic mechanical allodynia. Inhibitors of clathrin- and dynamin-dependent endocytosis and of mitogen-activated protein kinase kinase-1 prevented trypsin-induced hyperexcitability, sensitization, and allodynia. However, they did not affect elastase- or cathepsin S-induced hyperexcitability, sensitization, or allodynia. Trypsin stimulated endocytosis of PAR2, which signaled from endosomes to activate extracellular signal-regulated kinase. Elastase and cathepsin S did not stimulate endocytosis of PAR2, which signaled from the plasma membrane to activate adenylyl cyclase. Biopsies of colonic mucosa from IBS patients released proteases that induced persistent PAR2-dependent hyperexcitability of nociceptors, and PAR2 association with ß-arrestins, which mediate endocytosis. Conjugation to cholestanol promoted delivery and retention of antagonists in endosomes containing PAR2 A cholestanol-conjugated PAR2 antagonist prevented persistent trypsin- and IBS protease-induced hyperexcitability of nociceptors. The results reveal that PAR2 signaling from endosomes underlies the persistent hyperexcitability of nociceptors that mediates chronic pain of IBS. Endosomally targeted PAR2 antagonists are potential therapies for IBS pain. GPCRs in endosomes transmit signals that contribute to human diseases.

Assessment of the Impact of Pharmacist-led Transitions of Care Services in a Primary Health Center.

Background: The impact of pharmacist-led transition of care services with collaborative drug therapy management has shown to improve patients' outcomes and decrease health costs. Compelling statistics show higher readmission rates for under-insured patients compared with insured patients at primary health care clinics. Methods: This is a single center, prospective, cohort study designed to examine team-based collaborative drug therapy management and its effect on therapeutic outcomes of under-insured patients with target chronic diseases managed in a primary health center. Targeted chronic diseases included dyslipidemia, diabetes, hypertension, anticoagulation disorders, chronic obstructive pulmonary disease, and heart failure. The primary outcome measures included percentage of time in therapeutic international normalized ratio (INR) and percentage of patients at targeted goals of blood pressure, lipids, and hemoglobin A1c (HbA1c). Secondary outcomes included reduced emergency department visits, number of patient encounters, hospital readmissions within 30 days of discharge, and disease exacerbation rates. Results: Patients were at INR goal 58% of the time compared with 52% at baseline (P = .66). There was a 9% improvement in mean HbA1c in the intervention group when compared with baseline (9.6% vs 10.9%, P = .03). With pharmacist intervention, 73.8% of the patients had their blood pressure at goal compared with 50% at baseline (P = .14). A limited number of patients were readmitted for different reasons, including uncontrolled disease states. Conclusions: The pharmacist-physician collaborative drug therapy management led to improved blood pressure control, average HbA1c, and time in therapeutic INR range. A decrease in health care utilization was also identified.

Decreased Cephalosporin Susceptibility of Oropharyngeal Neisseria Species in Antibiotic-using Men Who Have Sex With Men in Hanoi, Vietnam.

BACKGROUND: Neisseria gonorrhoeae (NG) infections are a global health burden. NG resistance to cephalosporins, which is increasingly reported, is an imminent threat to public health. Many hypothesize that commensal Neisseria species are an important reservoir for genetic material conferring antimicrobial resistance in NG; however, clinical data are lacking. METHODS: Men who have sex with men (MSM) in Hanoi, Vietnam, completed a questionnaire regarding antibiotic use. We collected pharyngeal specimens, cultured Neisseria species, and measured minimum inhibitory concentrations (MICs) to ciprofloxacin, cefixime, ceftriaxone, and cefpodoxime. Using MIC criteria for antimicrobial susceptibility in NG, we categorized the Neisseria species and compared mean MIC levels between different antibiotic user groups. RESULTS: Of 207 participants, 38% used at least 1 antibiotic in the past 6 months; 52% without a prescription. A median of 1 Neisseria species was cultured from each participant (range, 1-4) with 10 different Neisseria species identified overall. The proportion of Neisseria with reduced susceptibility to ciprofloxacin was 93%, cefpodoxime 84%, cefixime 31%, and ceftriaxone 28%. Antibiotic use within the past month was strongly associated with Neisseria species having increased MICs to cefixime, ceftriaxone, and cefpodoxime (mean MIC ratios of 6.27, 4.11, and 7.70, respectively), compared with those who used antibiotics between 1 and 6 months prior (P < .05, all comparisons). CONCLUSIONS: MSM in our study often used antibiotics without a prescription. At least 1 commensal Neisseria species colonized all men. Recent use of any antibiotics may select for oropharyngeal Neisseria species with antimicrobial resistance. The normal flora of the oropharynx may be an important source of antimicrobial resistance in Neisseria gonorrhoeae.

Third-degree burn mouse treatment using recombinant human fibroblast growth factor 2.

Fibroblast growth factor 2 (FGF-2) is a multifunctional protein that has major roles in wound healing, tissue repair, and regeneration. This therapeutic protein is widely used for burn treatment because it can stimulate cell proliferation and differentiation, angiogenesis, and extracellular matrix remodeling. In this study, we developed a simple method using a controlled heated brass rod to create a homogenous third-degree burn murine model and evaluated the treatment using recombinant human FGF-2 (rhFGF-2). The results indicated that the wound area was 0.83 ± 0.05 cm2 and wound depth was 573.42 ± 147.82 µm. Mice treated with rhFGF-2 showed higher rates of wound closure, granulation tissue formation, angiogenesis, and re-epithelialization than that of phosphate-buffered saline (PBS)-treated group. In conclusion, our lab-made rhFGF-2 could be a potentially therapeutic protein for burn treatment as well as a bioequivalent drug for other commercial applications using FGF-2.

Dynamic contrast-enhanced MRI of brown and beige adipose tissues.

PURPOSE: The vascular blood flow in brown adipose tissue (BAT) is important for handling triglyceride clearance, increased blood flow and oxygenation. We used dynamic contrast-enhanced (DCE)-MRI and fat fraction (FF) imaging for investigating vascular perfusion kinetics in brown and beige adipose tissues with cold exposure or treatment with ß3-adrenergic agonist. METHODS: FF imaging and DCE-MRI using gadolinium-diethylenetriaminepentaacetic acid were performed in interscapular BAT (iBAT) and beige tissues using male Wister rats (n = 38). Imaging was performed at thermoneutral condition and with either cold exposure, treatment with pharmacological agent CL-316,243, or saline. DCE-MRI and FF data were co-registered to enhance the understanding of metabolic activity. RESULTS: Uptake of contrast agent in activated iBAT and beige tissues were significantly (P < .05) higher than nonactivated iBAT. The Ktrans and kep increased significantly in iBAT and beige tissues after treatment with either cold exposure or ß3-adrenergic agonist. The FF decreased in activated iBAT and beige tissues. The Ktrans and FF from iBAT and beige tissues were inversely correlated (r = 0.97; r = 0.94). Significant increase in vascular endothelial growth factor expression and Ktrans in activated iBAT and beige tissues were in agreement with the increased vasculature and vascular perfusion kinetics. The iBAT and beige tissues were validated by measuring molecular markers. CONCLUSION: Increased Ktrans and decreased FF in iBAT and beige tissues were in agreement with the vascular perfusion kinetics facilitating the clearance of free fatty acids. The methodology can be extended for the screening of browning agents.