ABSTRACT
Previous studies reporting the association between gut microbiota dysbiosis and maternal obesity were mostly confined at the phylum level or at postpartum period. This study aimed to investigate the dynamic changes in gut microbial communities associated with maternal obesity at different time points of pregnancy. We performed 16S rRNA gene V3-V4 amplicon sequencing on stool samples from 110 women in all three trimesters and 1-month postpartum. Maternal gut microbial communities associated with maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) were explored. The influence of maternal obesity on gut microbiota trajectories was determined based on longitudinal shifts in community clusters across the trimesters. The richness index of alpha diversity decreased with the progression of pregnancy, particularly in women with excessive GWG. The evenness index in 2nd trimester was found inversely associated with GWG. Various taxonomic differences in 1st trimester were associated with excessive GWG, whereas limited taxonomic differences in 2nd and 3rd trimesters were associated with pre-pregnancy BMI or GWG. Meanwhile, the gut microbiota trajectory with especially depleted genus Faecalibacterium in 1st trimester was associated with excessive GWG (adjusted odds ratio 5.7, 95% confidence interval 1.2-28.1). Moreover, the longitudinal abundances of genus Lachnospiraceae ND3007 group across gestations were depleted in women with overweight/obese pre-pregnancy BMI, while genus Bifidobacterium enriched in women with excessive GWG. Our study shows that dysbiosis of the gut microbiota in early pregnancy may have a significant impact on excess GWG. The abundance of the genus Faecalibacterium in 1st trimester may be a potential risk factor. Clinical trial number: NCT03785093 (https://classic.clinicaltrials.gov/ct2/show/NCT03785093).
Subject(s)
Body Mass Index , Dysbiosis , Feces , Gastrointestinal Microbiome , Gestational Weight Gain , RNA, Ribosomal, 16S , Humans , Female , Pregnancy , Adult , Feces/microbiology , RNA, Ribosomal, 16S/genetics , Dysbiosis/microbiology , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Obesity/microbiology , Young Adult , Obesity, Maternal , Faecalibacterium/geneticsABSTRACT
Subject(s)
Tuberculosis , Humans , Taiwan/epidemiology , Male , Tuberculosis/epidemiology , Tuberculosis/drug therapy , Disease Notification/statistics & numerical data , Female , Middle Aged , Adult , Aged , Young Adult , Registries , Adolescent , National Health Programs , Child , Child, Preschool , Databases, Factual , InfantABSTRACT
Freshwater systems in cold regions, including the Laurentian Great Lakes, are threatened by both eutrophication and salinization, due to excess nitrogen (N), phosphorus (P) and chloride (Cl-) delivered in agricultural and urban runoff. However, identifying the relative contribution of urban vs. agricultural development to water quality impairment is challenging in watersheds with mixed land cover, which typify most developed regions. In this study, a self-organizing map (SOM) analysis was used to evaluate the contributions of various forms of land cover to water quality impairment in southern Ontario, a population-dense, yet highly agricultural region in the Laurentian Great Lakes basin where urban expansion and agricultural intensification have been associated with continued water quality impairment. Watersheds were classified into eight spatial clusters, representing four categories of agriculture, one urban, one natural, and two mixed land use clusters. All four agricultural clusters had high nitrate-N concentrations, but levels were especially high in watersheds with extensive corn and soybean cultivation, where exceedances of the 3 mg L-1 water quality objective dramatically increased above a threshold of |â¼30 % watershed row crop cover. Maximum P concentrations also occurred in the most heavily tile-drained cash crop watersheds, but associations between P and land use were not as clear as for N. The most urbanized watersheds had the highest Cl- concentrations and expansions in urban area were mostly at the expense of surrounding agricultural land cover, which may drive intensification of remaining agricultural lands. Expansions in tile-drained corn and soybean area, often at the expense of mixed, lower intensity agriculture are not unique to this area and suggest that river nitrate-N levels will continue to increase in the future. The SOM approach provides a powerful means of simplifying heterogeneous land cover characteristics that can be associated with water quality patterns and identify problem areas to target management.
Subject(s)
Glaucoma , Optic Disk , Humans , Optic Disk/blood supply , Retina , Glaucoma/etiology , Choroid/blood supplyABSTRACT
Objective: Knee osteoarthritis (OA) is a complex disease with heterogeneous representations. Although it is modifiable to prevention and early treatment, there still lacks a reliable and accurate prognostic tool. Hence, we aim to develop a quantitative and self-administrable knee replacement (KR) risk stratification system for knee osteoarthritis (KOA) patients with clinical features. Method: A total of 14 baseline features were extracted from 9592 cases in the Osteoarthritis Initiative (OAI) cohort. A survival model was constructed using the Random Survival Forests algorithm. The prediction performance was evaluated with the concordance index (C-index) and average receiver operating characteristic curve (AUC). A three-class KR risk stratification system was built to differentiate three distinct KR-free survival groups. Thereafter, Shapley Additive Explanations (SHAP) was introduced for model explanation. Results: KR incidence was accurately predicted by the model with a C-index of 0.770 (±0.0215) and an average AUC of 0.807 (±0.0181) with 14 clinical features. Three distinct survival groups were observed from the ten-point KR risk stratification system with a four-year KR rate of 0.79%, 5.78%, and 16.2% from the low, medium, and high-risk groups respectively. KR is mainly caused by pain medication use, age, surgery history, diabetes, and a high body mass index, as revealed by SHAP. Conclusion: A self-administrable and interpretable KR survival model was developed, underscoring a KR risk scoring system to stratify KOA patients. It will encourage regular self-assessments within the community and facilitate personalised healthcare for both primary and secondary prevention of KOA.
ABSTRACT
INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused extensive disruption of public health worldwide. There were reports of COVID-19 patients having multiple complications. This study investigated COVID-19 from a genetic perspective. METHODS: We conducted RNA sequencing (RNA-Seq) analysis of respiratory tract samples from 24 patients with COVID-19. Eight patients receiving mechanical ventilation or extracorporeal membrane oxygenation were regarded as severe cases; the remaining 16 patients were regarded as non-severe cases. After quality control, statistical analyses were performed by logistic regression and the Kolmogorov-Smirnov test to identify genes associated with disease severity. RESULTS: Six genes were associated with COVID-19 severity in both statistical tests, namely RPL15, BACE1-AS, CEPT1, EIF4G1, TMEM91, and TBCK. Among these genes, RPL15 and EIF4G1 played roles in the regulation of mRNA translation. Gene ontology analysis showed that the differentially expressed genes were mainly involved in nervous system diseases. CONCLUSION: RNA sequencing analysis showed that severe acute respiratory syndrome coronavirus 2 infection is associated with the overexpression of genes involved in nervous system disorders.
Subject(s)
COVID-19 , Humans , COVID-19/genetics , Amyloid Precursor Protein Secretases , SARS-CoV-2/genetics , Hong Kong/epidemiology , Aspartic Acid Endopeptidases , Sequence Analysis, RNASubject(s)
COVID-19 , Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/surgery , Pandemics , Exercise TherapyABSTRACT
PURPOSE: We sought to compare females and males for the risk of reoperation following different inguinal hernia repair approaches (open, laparoscopic, and robotic). METHODS: We conducted a retrospective cohort study including all patients aged ≥ 18 who underwent first inguinal hernia repair with mesh within a US integrated healthcare system (2010-2020). Data were obtained from the system's integrated electronic health record. Multiple Cox proportional-hazards regression was used to evaluate the association between sex and risk for ipsilateral reoperation during follow-up. Analysis was stratified by surgical approach (open, laparoscopic, and robotic). RESULTS: The study cohort was comprised of 110,805 patients who underwent 131,626 inguinal hernia repairs with mesh, 10,079 (7.7%) repairs were in females. After adjustment for confounders, females had a higher risk of reoperation than males following open groin hernia repair (hazard ratio [HR] = 1.98, 95% CI 1.74-2.25), but a lower reoperation risk following laparoscopic repair (HR = 0.70, 95% CI 0.51-0.97). The crude 5-year cumulative reoperation probability following robotic repair was 2.8% in males and no reoperations were observed for females. Of females who had a reoperation, 10.3% (39/378) were for a femoral hernia, while only 0.6% (18/3110) were for femoral hernias in males. CONCLUSION: In a large multi-center cohort of mesh-based inguinal hernia repair patients, we found a higher risk for reoperation in females after an open repair approach compared to males. Lower risk was observed for females through a minimally invasive approach (laparoscopic or robotic) and may be due to the ability to identify an occult femoral hernia through these approaches.
Subject(s)
Delivery of Health Care, Integrated , Hernia, Femoral , Hernia, Inguinal , Adult , Male , Humans , Female , Reoperation , Cohort Studies , Retrospective Studies , Hernia, Inguinal/surgery , Hernia, Inguinal/etiology , Hernia, Femoral/surgery , Surgical Mesh/adverse effects , Herniorrhaphy/adverse effects , RecurrenceABSTRACT
Urban green waste and food waste are often used as bulking agents to prepare home compost in combination with animal manure in urban horticulture and community gardening. Although it is known that antimicrobial resistance genes (ARGs) persist in home compost, their origins have not been determined. In addition, the factors contributing to ARGs persistence remain unclear. In this study, we aim to (i) characterize the changes in the microbiome and antimicrobial resistome during the composting process of home compost using metagenomics shotgun sequencing, (ii) identify the source of the ARGs persisted in home compost using SourceTracker, and (iii) elucidate the collective effect of compost microbiome and environmental factors, including the physicochemical properties and antibiotics concentration of home compost, in contributing to ARG persistence using Procrustes analysis, co-occurrence network analysis, variation partitioning analysis, and structural equation modeling. SourceTracker analysis indicated that urban green waste bulking agent was the major source of the persisting ARGs in home compost instead of animal manure. Procrustes analysis and co-occurrence network analysis revealed a strong association between microbiome and antimicrobial resistome. Variation partitioning analysis and structural equation modeling suggested that physicochemical properties shaped the antimicrobial resistome directly and indirectly by influencing the microbiome. Our results indicated that the persistence of ARGs in home compost might be due to the succession of microbial species from the urban green waste bulking agent, and the physicochemical properties might have defined the compost environment to shape the microbiome in the compost, thus, in turn, the persisting antimicrobial resistome.
Subject(s)
Composting , Oxazolidinones , Refuse Disposal , Animals , Anti-Bacterial Agents/pharmacology , Drug Resistance, Bacterial/genetics , Manure/analysis , Food , Genes, BacterialABSTRACT
PURPOSE: Inguinal hernia repair is one of the most common operations performed globally. Identification of risk factors that contribute to hernia recurrence following an index inguinal hernia repair, especially those that are modifiable, is of paramount importance. Therefore, we sought to investigate risk factors for reoperation following index inguinal hernia repair. METHODS: 125,133 patients aged ≥ 18 years who underwent their first inguinal hernia repair with mesh within a large US integrated healthcare system were identified for a cohort study (2010-2020). Laparoscopic, robotic, and open procedures were included. The system's integrated electronic health record was used to obtain data on demographics, patient characteristics, surgical characteristics, and reoperations. The association of these characteristics with ipsilateral reoperation during follow-up was modeled using Cox proportional-hazards regression. Risk factors were selected into the final model by stepwise regression with Akaike Information Criteria, which quantifies the amount of information lost if a factor is left out of the model. Factors associated with reoperation with p < 0.05 were considered statistically significant. RESULTS: The cumulative incidence of reoperation at 5-year follow-up was 2.4% (95% CI 2.3-2.5). Increasing age, female gender, increasing body mass index, White race, chronic pulmonary disease, diabetes, drug abuse, peripheral vascular disease, and bilateral procedures all associated with a higher risk for reoperation during follow-up. CONCLUSION: This study identifies several risk factors associated with reoperation following inguinal hernia repair. These risk factors may serve as targets for optimization protocols prior to elective inguinal hernia repair, with the goal of reducing reoperation risk.
Subject(s)
Delivery of Health Care, Integrated , Hernia, Inguinal , Laparoscopy , Humans , Female , Reoperation , Hernia, Inguinal/surgery , Hernia, Inguinal/etiology , Cohort Studies , Herniorrhaphy/adverse effects , Herniorrhaphy/methods , Recurrence , Risk Factors , Laparoscopy/methods , Surgical Mesh/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgeryABSTRACT
INTRODUCTION: Pre-exposure prophylaxis (PrEP) persistence among men who have sex with men (MSM) in real world clinical settings for HIV prevention is suboptimal. New longer-acting formulations of PrEP are becoming available, including injectables, subdermal implants, and other oral medications. These longer-acting formulations have the potential to improve retention among those who have challenges remaining adherent to daily oral PrEP. METHODS: We interviewed 49 MSM who had initiated but discontinued oral PrEP at three diverse clinics across the United States. We examined participants' perspectives about long-acting PrEP formulations and how long-acting options could affect PrEP use using thematic analysis. RESULTS: Participants were not very knowledgeable about long-acting formulations of PrEP but were open to learning about them and considering use. Participants were concerned about safety and efficacy of products given that they were still newer and/or in development. Finally, participants had clear preferences for oral pills, injectables, and then subdermal implants and were most interested in options that reduced the number of visits to the clinic. CONCLUSION: Long-acting formulations of PrEP are acceptable to MSM with suboptimal PrEP persistence and have the potential to improve PrEP persistence. However, many felt they needed more information on safety, efficacy, and use to consider these options. As these long-acting formulations are implemented, public health campaigns and clinical interventions to encourage may maximize uptake particularly among those who are not currently adherent to daily oral PrEP.
Subject(s)
Pre-Exposure Prophylaxis , Sexual and Gender Minorities , Male , United States , Humans , Homosexuality, Male , Ambulatory Care Facilities , EmotionsABSTRACT
INTRODUCTION: This study investigated the awareness, perceptions, and acceptance of human papillomavirus (HPV) vaccination for children among parents in Hong Kong. It also explored factors associated with, and differences in, vaccine acceptance and hesitancy between parents of girls and boys. METHODS: Parents of boys or girls in Primary 5 to 6 were invited to participate in an online survey through an established health and lifestyle e-platform. RESULTS: Overall, 851 parents completed the survey: 419 (49.2%) had daughters, 348 (40.9%) had sons, and 84 (9.9%) had children of both genders. Parents who enrolled their children into the Childhood Immunisation Programme were more likely to accept HPV vaccination (79.7% vs 33.7%, odds ratio [OR]=7.70; 95% confidence interval [CI]=5.39-11.01; P<0.001); parents of girls were more likely to accept than parents of boys (86.0% vs 71.8%, OR=2.40; 95% CI=1.67-3.46; P<0.001). Among parents of girls and boys, the main reasons for HPV vaccination acceptance were prevention of cancers (girls: 68.8% and boys: 68.7%), prevention of sexually transmitted diseases (girls: 67.3% and boys: 68.3%), and optimal timing before initiation of sexual activity (girls: 62.8% and boys: 59.8%). Vaccine hesitancy was mainly associated with concerns about serious side-effects (girls: 66.7% and boys: 68.0%) and the belief that their children were too young (girls: 60.0% and boys: 54.0%). CONCLUSION: Parents in Hong Kong are hesitant about HPV vaccination for their sons. This barrier could be removed by providing information to correct vaccine safety misconceptions and offering a gender-neutral vaccination programme through the school-based Childhood Immunisation Programme.
Subject(s)
Papillomavirus Infections , Papillomavirus Vaccines , Child , Humans , Male , Female , Hong Kong , Papillomavirus Infections/prevention & control , Human Papillomavirus Viruses , Patient Acceptance of Health Care , Health Knowledge, Attitudes, Practice , Parents , VaccinationABSTRACT
BACKGROUND: Atezolizumab intravenous (IV) is approved for the treatment of various solid tumours. To improve treatment convenience and health care efficiencies, a coformulation of atezolizumab and recombinant human hyaluronidase PH20 was developed for subcutaneous (SC) use. Part 2 of IMscin001 (NCT03735121) was a randomised phase III, open-label, multicentre, noninferiority study comparing the drug exposure of atezolizumab SC with atezolizumab IV. PATIENTS AND METHODS: Eligible patients with locally advanced/metastatic non-small-cell lung cancer were randomised 2 : 1 to receive atezolizumab SC (1875 mg; n = 247) or IV (1200 mg; n = 124) every 3 weeks. The co-primary endpoints were cycle 1 observed trough serum concentration (Ctrough) and model-predicted area under the curve from days 0 to 21 (AUC0-21 d). The secondary endpoints were steady-state exposure, efficacy, safety, and immunogenicity. Exposure following atezolizumab SC was then compared with historical atezolizumab IV values across approved indications. RESULTS: The study met both of its co-primary endpoints: cycle 1 observed Ctrough {SC: 89 µg/ml [coefficient of variation (CV): 43%] versus IV: 85 µg/ml (CV: 33%); geometric mean ratio (GMR), 1.05 [90% confidence interval (CI) 0.88-1.24]} and model-predicted AUC0-21 d [SC: 2907 µg d/ml (CV: 32%) versus IV: 3328 µg d/ml (CV: 20%); GMR, 0.87 (90% CI 0.83-0.92)]. Progression-free survival [hazard ratio 1.08 (95% CI 0.82-1.41)], objective response rate (SC: 12% versus IV: 10%), and incidence of anti-atezolizumab antibodies (SC: 19.5% versus IV: 13.9%) were similar between arms. No new safety concerns were identified. Ctrough and AUC0-21 d for atezolizumab SC were consistent with the other approved atezolizumab IV indications. CONCLUSIONS: Compared with IV, atezolizumab SC demonstrated noninferior drug exposure at cycle 1. Efficacy, safety, and immunogenicity were similar between arms and consistent with the known profile for atezolizumab IV. Similar drug exposure and clinical outcomes following SC and IV administration support the use of atezolizumab SC as an alternative to atezolizumab IV.
Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Antineoplastic Agents/therapeutic use , Lung Neoplasms/drug therapy , Administration, Intravenous , Infusions, Intravenous , Antineoplastic Combined Chemotherapy Protocols/adverse effectsABSTRACT
BACKGROUND: Total knee arthroplasty (TKA) is a cost-effective procedure, but it is also associated with substantial postoperative pain. The present study aimed to compare pain relief and functional recovery after TKA among groups that received intravenous corticosteroids, periarticular corticosteroids, or a combination of both. METHODS: This randomized, double-blinded clinical trial in a local institution in Hong Kong recruited 178 patients who underwent primary unilateral TKA. Six of these patients were excluded because of changes in surgical technique; 4, because of their hepatitis B status; 2, because of a history of peptic ulcer; and 2, because they declined to participate in the study. Patients were randomized 1:1:1:1 to receive placebo (P), intravenous corticosteroids (IVS), periarticular corticosteroids (PAS), or a combination of intravenous and periarticular corticosteroids (IVSPAS). RESULTS: The pain scores at rest were significantly lower in the IVSPAS group than in the P group over the first 48 hours (p = 0.034) and 72 hours (p = 0.043) postoperatively. The pain scores during movement were also significantly lower in the IVS and IVSPAS groups than in the P group over the first 24, 48, and 72 hours (p ≤ 0.023 for all). The flexion range of the operatively treated knee was significantly better in the IVSPAS group than in the P group on postoperative day 3 (p = 0.027). Quadriceps power was also greater in the IVSPAS group than in the P group on postoperative days 2 (p = 0.005) and 3 (p = 0.007). Patients in the IVSPAS group were able to walk significantly further than patients in the P group in the first 3 postoperative days (p ≤ 0.003). Patients in the IVSPAS group also had a higher score on the Elderly Mobility Scale than those in the P group (p = 0.036). CONCLUSIONS: IVS and IVSPAS yielded similar pain relief, but IVSPAS yielded a larger number of rehabilitation parameters that were significantly better than those in the P group. This study provides new insights into pain management and postoperative rehabilitation following TKA. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.