Clinical phenotypes and constipation severity in Parkinson’s disease: Relation to Prevotella species

Background: The gut microbiome is speculated to play a crucial role in its pathogenesis of Parkinson’s disease as a triggering factor. Recent hypotheses suggested that Prevotella species regulate gut permeability, exert a neuroprotective effect, and interestingly, has been suspected to be deficient in PD patients, and so may play a role in this disease. Aim: This study was designed to compare between PD patients and their healthy controls as regards relative Prevotella abundance, prevalence of Prevotella-dominant Enterotype, and constipation severity. Also, to correlate Prevotella changes with the clinical phenotypes and  severity of motor and non-motor symptoms of PD. Methods: Twenty-five PD cases were enrolled in this study and cross-matched to 25 healthy subjects representing the control group. Overall NMS severity was assessed using the Non-Motor Symptoms Scale (NMSS). Quantitative SYBR green Real Time PCR was performed for the identification and quantitation of Prevotella in stool. Results: Prevotella relative abundance was 4-fold decreased in cases when compared to controls with PIGD phenotype showing the lowest abundance, however the difference was not statistically significance. Prevotella-dominant Enterotype was less presented in cases compared to controls, the result was statistically significant. Severe and very severe constipation grades presented 64% of cases group Vs 12% of control group. There was statistically significant positive correlation between total constipation score and UPDRS total score and motor symptoms phenotypes. Conclusion: Relative low Prevotella abundance in PD patients appears to be related to severe phenotypes of the disease; PIGD and mixed phenotypes. Severe constipation was more presented in PD cases which may be considered  as a preclinical biomarker for PD

Homicide drop in seven European countries: General or specific across countries and crime types?

This study examines homicide trends in seven European countries – Denmark, Estonia, Finland, the Netherlands, Scotland, Sweden and Switzerland – all of which manifested a substantial drop in homicide mortality between 1990 and 2016. By using data from the European Homicide Monitor, a coding scheme created to enable cross-country comparisons, combined with the national cause-of-death statistics, we explore generality versus specificity of the homicide drop. We examine changes in the demographic structure of victims and offenders and disaggregate homicides by different subtypes of lethal incidents, such as family-related homicides referring to conflicts between family members, and criminal milieu homicides occurring in the context of robberies, gang-related conflicts or organised crime. Results point to the generality of the drop: in most of the countries studied, the declining trend included all homicide types. The overall decline in homicide mortality was driven mostly by the decline in male victimisation and offending. In most of the countries, the gender distribution of victims and offenders changed only slightly during the study period, whereas the development of the distribution of homicide types manifested greater diversity. Our findings illustrate the benefits of disaggregated analyses in comparative homicide research

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Trends and predictors of antimicrobial resistance among patients with urinary tract infections at a tertiary hospital facility in Alexandria, Egypt: a retrospective record-based classification and regression tree analysis

Abstract Background The incidence of Antimicrobial Resistance (AMR) in uropathogens varies between countries and over time. We aim to study the patterns and potential predictors of AMR among patients with UTIs admitted to the Urology Department at Alexandria University Hospital. Methods An observational retrospective record-based study was conducted on all patients admitted to the Urology department from October 2018 to October 2020. Data collected from patients’ records included: demographic data, diagnosis on admission, history of chronic diseases, duration of hospital stay, insertion of a urinary catheter, duration of the catheter in days, history of the use of antibiotics in the previous three months, and history of urinary tract operations. If UTI was documented, we abstracted data about urine culture, use of antibiotics, results of urine cultures, type of organism isolated, and sensitivity to antibiotics. We conducted a multivariable logistic regression model. We performed Classification and Regression Tree Analysis (CART) for predicting risk factors associated with drug resistance among patients with UTI. Data were analyzed using SPSS statistical package, Version 28.0, and R software (2022). Results This study encompassed 469 patients with UTIs. The most commonly isolated bacterium was Escherichia coli, followed by Klebsiella pneumoniae. Multidrug resistance (MDR) was found in 67.7% (149/220) of patients with hospital-acquired UTIs and in 49.4% (83/168) of patients with community-acquired UTIs. Risk factors independently associated with antimicrobial resistance according to logistic regression analysis were the use of antibiotics within three months (AOR = 5.2, 95% CI 2.19–12.31), hospital-acquired UTI (AOR = 5.7, 95% CI 3.06–10.76), diabetes mellitus (AOR = 3.8, 95% CI 1.24–11.84), age over 60 years (AOR = 2.9, 95% CI 1.27–6.72), and recurrent UTI (AOR = 2.6, 95% CI 1.08–6.20). Classification and regression tree (CART) analysis revealed that antibiotic use in the previous three months was the most significant predictor for developing drug resistance. Conclusion The study concluded a high level of antimicrobial resistance as well as significant MDR predictors among hospitalized patients with UTIs. It is vital to assess resistance patterns in our hospitals frequently to improve rational antibiotic treatment as well as to sustain antimicrobial stewardship programs and a rational strategy in the use of antibiotics. Empirical therapy for UTI treatment should be tailored to the potential pathogens’ susceptibility to ensure optimal treatment. Strategic antibiotic use is essential to prevent further AMR increases. Further research should focus on suggesting new biological systems or designed drugs to combat the resistance of UTI pathogens

Additional file 1 of Trends and predictors of antimicrobial resistance among patients with urinary tract infections at a tertiary hospital facility in Alexandria, Egypt: a retrospective record-based classification and regression tree analysis

Supplementary Material

Optimization of tolerability and efficacy of the novel dual amylin and calcitonin receptor agonist KBP-089 through dose escalation and combination with a GLP-1 analog

Amylin and GLP-1 agonism induce a well-known anorexic effect at dose initiation, which is managed by dose escalation. In this study we investigated how to optimize tolerability while maintaining efficacy of a novel, highly potent dual amylin and calcitonin receptor agonist (DACRA), KBP-089. Furthermore, we tested the GLP-1 add-on potential of KBP-089 in high-fat diet (HFD)-fed rats. KBP-089 potently activated both the amylin and calcitonin receptors in vitro and demonstrated a prolonged receptor activation as well as a potent reduction of acute food intake. HFD rats dosed every day or every second day obtained equal weight loss at study end, albeit with an uneven reduction in both food intake and body weight in rats dosed every second day. In a 4-fold dose escalation, KBP-089 induced a transient reduction in food intake at every escalation step, with reducing magnitude over time, and the following treatment with 2.5, 10, and 40 µg/kg resulted in an ~15% vehicle-corrected weight loss, a corresponding reduction in adipose tissue (AT), and, in all treatment groups, improved oral glucose tolerance ( P &lt; 0.01). Twofold and linear escalations suppressed body weight evenly with no significant reduction in food intake at either escalation step. KBP-089 (1.25 µg/kg) and liraglutide (50 µg/kg) reduced 24-h food intake by 29% and 37% compared with vehicle, respectively; however, when they were combined, 24-h food intake was reduced by 87%. Chronically, KBP-089 (1.25 µg/kg) and liraglutide (50 µg/kg) lowered body weight 8% and 2% in HFD rats, respectively, whereas the combination resulted in a 12% body weight reduction. Moreover, the combination improved glucose tolerance ( P &lt; 0.05). In conclusion, DACRAs act complementarily with GLP-1 on food intake and body weight. Furthermore, on escalation, KBP-089 was well tolerated and induced and sustained a significant weight loss and a reduction in AT in lean and HFD rats, underscoring the potential of KBP-089 as an anti-obesity agent. </jats:p

Homicide drop in seven European countries : general or specific across countries and crime types?

This study examines homicide trends in seven European countries – Denmark, Estonia, Finland, the Netherlands, Scotland, Sweden and Switzerland – all of which manifested a substantial drop in homicide mortality between 1990 and 2016. By using data from the European Homicide Monitor, a coding scheme created to enable cross-country comparisons, combined with the national cause-of-death statistics, we explore generality versus specificity of the homicide drop. We examine changes in the demographic structure of victims and offenders and disaggregate homicides by different subtypes of lethal incidents, such as family-related homicides referring to conflicts between family members, and criminal milieu homicides occurring in the context of robberies, gang-related conflicts or organised crime. Results point to the generality of the drop: in most of the countries studied, the declining trend included all homicide types. The overall decline in homicide mortality was driven mostly by the decline in male victimisation and offending. In most of the countries, the gender distribution of victims and offenders changed only slightly during the study period, whereas the development of the distribution of homicide types manifested greater diversity. Our findings illustrate the benefits of disaggregated analyses in comparative homicide research.This study examines homicide trends in seven European countries – Denmark, Estonia, Finland, the Netherlands, Scotland, Sweden and Switzerland – all of which manifested a substantial drop in homicide mortality between 1990 and 2016. By using data from the European Homicide Monitor, a coding scheme created to enable cross-country comparisons, combined with the national cause-of-death statistics, we explore generality versus specificity of the homicide drop. We examine changes in the demographic structure of victims and offenders and disaggregate homicides by different subtypes of lethal incidents, such as family-related homicides referring to conflicts between family members, and criminal milieu homicides occurring in the context of robberies, gang-related conflicts or organised crime. Results point to the generality of the drop: in most of the countries studied, the declining trend included all homicide types. The overall decline in homicide mortality was driven mostly by the decline in male victimisation and offending. In most of the countries, the gender distribution of victims and offenders changed only slightly during the study period, whereas the development of the distribution of homicide types manifested greater diversity. Our findings illustrate the benefits of disaggregated analyses in comparative homicide research.Peer reviewe