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•Drivers of low-diversity dysbiosis include antibiotics, host genetics, physiology.•Dysbiosis results in shifts in microbial composition and function.•Dysbiosis results in shifts in ...microbial composition and function.
Dysbiosis, an imbalance in microbial communities, is linked with disease when this imbalance disturbs microbiota functions essential for maintaining health or introduces processes that promote disease. Dysbiosis in disease is predicted when microbiota differ compositionally from a healthy control population, but only truly defined when these differences are mechanistically related to adverse phenotypes. For the human gut microbiota, dysbiosis varies across diseases. One common manifestation is replacement of the complex community of anaerobes typical of the healthy adult gut microbiome with a community of lower overall microbial diversity and increased facultative anaerobes. Here we review diseases in which low-diversity dysbiosis has been observed and mechanistically linked with disease, with a particular focus on liver disease, inflammatory bowel disease, and Clostridium difficile infection.
Bisphenol A (BPA), a high production chemical commonly found in plastics, has drawn great attention from researchers due to the substance's potential toxicity. Using data from three National Health ...and Nutrition Examination Survey (NHANES) cycles, we explored the consistency and robustness of BPA's reported effects on coronary heart disease and diabetes.
We report the use of three different statistical models in the analysis of BPA: (1) logistic regression, (2) log-linear regression, and (3) dose-response logistic regression. In each variation, confounders were added in six blocks to account for demographics, urinary creatinine, source of BPA exposure, healthy behaviours, and phthalate exposure. Results were sensitive to the variations in functional form of our statistical models, but no single model yielded consistent results across NHANES cycles. Reported ORs were also found to be sensitive to inclusion/exclusion criteria. Further, observed effects, which were most pronounced in NHANES 2003-04, could not be explained away by confounding.
Limitations in the NHANES data and a poor understanding of the mode of action of BPA have made it difficult to develop informative statistical models. Given the sensitivity of effect estimates to functional form, researchers should report results using multiple specifications with different assumptions about BPA measurement, thus allowing for the identification of potential discrepancies in the data.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
People with opioid use disorder are vulnerable to disruptions in access to addiction treatment and social support during the COVID-19 pandemic. Our study objective was to understand changes in ...emergency department (ED) utilization following a nonfatal opioid overdose during COVID-19 compared to historical controls in 6 healthcare systems across the United States.
Opioid overdoses were retrospectively identified among adult visits to 25 EDs in Alabama, Colorado, Connecticut, North Carolina, Massachusetts, and Rhode Island from January 2018 to December 2020. Overdose visit counts and rates per 100 all-cause ED visits during the COVID-19 pandemic were compared with the levels predicted based on 2018 and 2019 visits using graphical analysis and an epidemiologic outbreak detection cumulative sum algorithm.
Overdose visit counts increased by 10.5% (n=3486; 95% confidence interval CI 4.18% to 17.0%) in 2020 compared with the counts in 2018 and 2019 (n=3020 and n=3285, respectively), despite a 14% decline in all-cause ED visits. Opioid overdose rates increased by 28.5% (95% CI 23.3% to 34.0%) from 0.25 per 100 ED visits in 2018 to 2019 to 0.32 per 100 ED visits in 2020. Although all 6 studied health care systems experienced overdose ED visit rates more than the 95th percentile prediction in 6 or more weeks of 2020 (compared with 2.6 weeks as expected by chance), 2 health care systems experienced sustained outbreaks during the COVID-19 pandemic.
Despite decreases in ED visits for other medical emergencies, the numbers and rates of opioid overdose-related ED visits in 6 health care systems increased during 2020, suggesting a widespread increase in opioid-related complications during the COVID-19 pandemic. Expanded community- and hospital-based interventions are needed to support people with opioid use disorder and save lives during the COVID-19 pandemic.
Over 35 million falls occur in older adults annually and are associated with increased emergency department (ED) revisits and 1-year mortality. Despite associations between medications and falls, the ...prevalence of fall risk-increasing drugs remains high. Our objective was to implement an ED-based medication reconciliation for patients presenting after falls and determine whether an intervention targeting high-risk medications was related to decreased future falls.
This was an observational prospective cohort study at a single site in the United States. Adults 65 years and older presenting to the ED after falls had a pharmacist review their medicines. Pharmacists made recommendations to taper, stop, or discuss medications with the primary clinician. At 3, 6, and 12 months, we recorded the number of fall-related return ED visits and determined if recommended medication changes had been implemented. We compared the rate of return visits of patients who had followed the medication change recommendations and those who received recommendations but had no change in their medications using chi-square tests.
A total of 577 patients (mean age 81 years, 63.6% female) were enrolled of 1509 potentially eligible patients. High-risk medications were identified in 310 patients (53.7%) who received medication recommendations. High-risk medications were associated with repeat fall-related visits at 12 months (risk difference 8.1% 95% confidence interval 0.97-15.0). A total of 134 (43%) patients on high-risk medications had evidence of medication modification. At 12 months, there was no statistically significant difference in return fall visits between patients who had modifications to medications compared with those who had not implemented changes (p = 0.551).
Our findings identified opportunities for medication optimization in over half of emergency visits for falls and demonstrated that medication counseling in the ED is feasible. However, evaluation of the effect on future falls was limited.
Even a simple sensory stimulus can elicit distinct innate behaviors and sequences. During sensorimotor decisions, competitive interactions among neurons that promote distinct behaviors must ensure ...the selection and maintenance of one behavior, while suppressing others. The circuit implementation of these competitive interactions is still an open question. By combining comprehensive electron microscopy reconstruction of inhibitory interneuron networks, modeling, electrophysiology, and behavioral studies, we determined the circuit mechanisms that contribute to the Drosophila larval sensorimotor decision to startle, explore, or perform a sequence of the two in response to a mechanosensory stimulus. Together, these studies reveal that, early in sensory processing, (1) reciprocally connected feedforward inhibitory interneurons implement behavioral choice, (2) local feedback disinhibition provides positive feedback that consolidates and maintains the chosen behavior, and (3) lateral disinhibition promotes sequence transitions. The combination of these interconnected circuit motifs can implement both behavior selection and the serial organization of behaviors into a sequence.
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•Mechanical stimuli in Drosophila larvae evoke hunch, bend, or a sequence of the two•Reciprocally connected feedforward inhibitory interneurons mediate behavioral choice•Feedback disinhibition biases behavioral choice and prevents sequence reversals•Lateral disinhibition promotes sequence transitions
Neural circuits for behavioral choice and sequences are revealed by combining EM reconstruction of neuronal networks, electrophysioloy, modeling and optogenetic manipulation.
Patients with heart failure (HF) often suffer from multimorbidity. Rapid assessment of multimorbidity is important for minimizing the risk of harmful drug-disease and drug-drug interactions. We ...assessed the accuracy of using the electronic health record (EHR) problem list to identify comorbid conditions among patients with chronic HF in the emergency department (ED). A retrospective chart review study was performed on a random sample of 200 patients age ≥65 years with a diagnosis of HF presenting to an academic ED in 2019. We assessed participant chronic conditions using: (1) structured chart review (gold standard) and (2) an EHR-based algorithm using the problem list. Chronic conditions were classified into 37 disease domains using the Agency for Healthcare Research Quality's Elixhauser Comorbidity Software. For each disease domain, we report the sensitivity, specificity, positive predictive value, and negative predictive of using an EHR-based algorithm. We calculated the intra-class correlation coefficient (ICC) to assess overall agreement on Elixhauser domain count between chart review and problem list. Patients with HF had a mean of 5.4 chronic conditions (SD 2.1) in the chart review and a mean of 4.1 chronic conditions (SD 2.1) in the EHR-based problem list. The five most prevalent domains were uncomplicated hypertension (90%), obesity (42%), chronic pulmonary disease (38%), deficiency anemias (33%), and diabetes with chronic complications (30.5%). The positive predictive value and negative predictive value of using the EHR-based problem list was greater than 90% for 24/37 and 32/37 disease domains, respectively. The EHR-based problem list correctly identified 3.7 domains per patient and misclassified 2.0 domains per patient. Overall, the ICC in comparing Elixhauser domain count was 0.77 (95% CI: 0.71-0.82). The EHR-based problem list captures multimorbidity with moderate-to-good accuracy in patient with HF in the ED.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Given that randomized trials exploring adjuvant chemotherapy for bladder cancer have been underpowered and/or terminated prematurely, yielding inconsistent results and creating an evidence gap, we ...sought to compare the effectiveness of cystectomy versus cystectomy plus adjuvant chemotherapy in real-world patients.
We conducted an observational study to compare the effectiveness of adjuvant chemotherapy versus observation postcystectomy in patients with pathologic T3-4 and/or pathologic node-positive bladder cancer using the National Cancer Data Base. We compared overall survival using propensity score (-adjusted, -stratified, -weighted, and -matched) analyses based on patient-, facility-, and tumor-level characteristics. A sensitivity analysis was performed to examine the impact of performance status.
A total of 5,653 patients met study inclusion criteria; 23% received adjuvant chemotherapy postcystectomy. Chemotherapy-treated patients were younger and more likely to have private insurance, live in areas with a higher median income and higher percentage of high school-educated residents, and have lymph node involvement and positive surgical margins (P < .05 for all comparisons). Stratified analyses adjusted for propensity score demonstrated an improvement in overall survival with adjuvant chemotherapy (hazard ratio, 0.70; 95% CI, 0.64 to 0.76), and similar results were achieved with propensity score matching and weighting. The association between adjuvant chemotherapy and improved survival was consistent in subset analyses and was robust to the effects of poor performance status.
In this observational study, adjuvant chemotherapy was associated with improved survival in patients with locally advanced bladder cancer. Although neoadjuvant chemotherapy remains the preferred approach based on level I evidence, these data lend further support for the use of adjuvant chemotherapy in patients with locally advanced bladder cancer postcystectomy who did not receive chemotherapy preoperatively.
Leishmania species are sand fly-transmitted protozoan parasites that cause leishmaniasis, neglected tropical diseases that affect millions of people. Leishmania amastigotes must overcome a variety of ...host defenses, including reactive oxygen species (ROS) produced by the NADPH oxidase. Leishmania species encode three superoxide dismutases (SODs): the mitochondrial SODA and two glycosomal SODs (SODB1 and SODB2). SODs are metalloenzymes that function in antioxidant defense by converting superoxide to oxygen and hydrogen peroxide. Here, we investigated a role for SODB1 in Leishmania infection of macrophages and virulence in mice. We found that a single allele deletion of SODB1 (SODB1/Δsodb1) had minimal effects on the replication of axenically-grown L. major promastigotes or differentiation to infective metacyclic promastigotes. Disruption of a single SODB1 allele also did not affect L. donovani differentiation to amastigotes induced axenically, or the replication of axenically-grown L. donovani promastigotes and amastigotes. In contrast, the persistence of SODB1/Δsodb1 L. major in WT macrophages was impaired, and the development of cutaneous lesions in SODB1/Δsodb1 L. major-infected C57BL/6 and BALB/c mice was strongly reduced. The reduced disease severity in mice was associated with reduced burdens of SODB1/Δsodb1 L. major parasites in the foot at late, but not early times post-inoculation, as well as an impaired capacity to disseminate from the site of inoculation. Collectively, these data suggest that SODB1 is critical for L. major persistence in macrophages and virulence in mice.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•A historical perspective on associations between ABO blood type and bacteria.•Mechanisms that drive relationships between host blood type and commensal and pathogenic ...bacteria.•Review of conflicting evidence for an influence of host blood type on the intestinal microbiome.•How this knowledge may inform the development of microbiome-targeted intervention strategies.
The complex communities of microbes that constitute the human microbiome are influenced by host and environmental factors. Here, we address how a fundamental aspect of human biology, blood type, contributes to shaping this microscopic ecosystem. Although this question remains largely unexplored, we glean insights from decades of work describing relationships between pathogens and blood type. The bacterial strategies, molecular mechanisms, and host responses that shaped those relationships may parallel those that characterize how blood type and commensals interact. Understanding these nuanced interactions will expand our capacity to analyze and manipulate the human microbiome.
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