Medical Principles and Practice最新文献

Objective: Clostridioides difficile is a major cause of healthcare-associated diarrhea worldwide. For years, metronidazole and vancomycin were considered the standard treatment for C. difficile infection (CDI). However, they are increasingly being associated with treatment failure and recurrence. In this study we investigated the in vitro activity of dalbavancin and fourteen other antimicrobials against 155 toxigenic C. difficile isolates originating from patients with C. difficile-associated diarrhea.

Materials and methods: Antimicrobial susceptibility was evaluated by the MIC Test Strip and the results were interpreted using both the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial susceptibility Testing (EUCAST) breakpoints.

Results: C. difficile isolates were fully susceptible to metronidazole, vancomycin, amoxicillin/ clavulanate, piperacillin/tazobactam, and tigecycline. All isolates were dalbavancin susceptible by the CLSI breakpoint (≤ 0.25 μg/ml) compared with 97.4% susceptibility by the EUCAST breakpoint (≤ 0.125 μg/ml). Dalbavancin demonstrated significantly lower MIC50 and MIC90 values compared to vancomycin (0.047 vs. 0.38 and 0.125 vs. 0.5, respectively, p < 0.001). Resistance rates to penicillin, ampicilin, cefoxitin, imipenem, meropenem, clindamycin, moxifloxacin, chloramphenicol, and tetracycline were 20%, 14.2% , 100%, 75.5%, 0.6%, 51%, 36.1%, 3.2%, and 14.8%, respectively. Multidrug-resistant (MDR) phenotypes were detected among 41.3% of the isolates.

Conclusion: Dalbavancin exhibited potent activity against the isolates tested. As C. difficile is an important healthcare-associated pathogen, continued surveillance is required to monitor for development of resistance.

Background & Purpose A new discriminatory system for evaluating the quality of pharmaceuticals is described in this paper as the Pharmaceutical Polygon Fingerprint Matrix system (PharmP-FM). To assess the quality of various pharmaceutical formulations and dosage forms, PharmP-FM uses both qualitative and quantitative fingerprinting techniques. The system expands on the SeDeM expert system, which was initially created to evaluate the suitability of powder for direct compression. PharmP-FM creates a graphical representation of the product's pharmaceutical quality using a set of input parameters. The Performance Index (PI), Normalized Parameter Index (NPI), and Formulation Index (FI) are among the system's output parameters. Methods To evaluate PharmP-FM's performance, the paper examines its application in assessing batch-to-batch variability of weight loss supplement capsules and the quality of multisource brand products of levothyroxine tablets. The findings demonstrate PharmP-FM's capability to identify variations in pharmaceutical quality across these products. Results & Conclusion This paper concludes that PharmP-FM exhibits potential promise as a pharmaceutical quality assessment tool. Its user-friendly nature and adaptability to different formulations and dosage forms make it a versatile discriminatory system. Additionally, PharmP-FM is an open-ended and scalable system that can incorporate additional parameters and accommodate products of varying complexities. The study's results strongly suggest its potential as a potential tool for pharmaceutical quality assessment.

Objectives: Oral healthcare professionals play a crucial role in guiding patients toward evidence-based choices among the many available oral rinses. In this study, we explored how specific oral rinse formulations affect the viability and modulate critical virulence traits of the opportunistic fungal pathogen Candida albicans.

Materials and methods: We assessed the effects of these oral rinses on the production of germ tube, production of phospholipase and hemolysin, as well as biofilm formation.

Results: We found that oral rinses containing cetylpyridinium chloride (CPC) and chlorhexidine (CHX) showed the greatest fungicidal activity with the lowest MFCs (0.38% and 0.78%, respectively). Oral rinses based on zinc chloride and sodium fluoride with Miswak bark extract (MIS) or essential oils (EO) had much lower fungicidal activity (8-16 times lower) compared to CHX and CPC. However, they had a significantly greater impact on the virulence traits of C. albicans. They reduced germ tube production by 86% - 89% (versus 42% for CHX and 29% for CPC), completely inhibited phospholipase and hemolysin production, and together with the CPC-based oral rinse, exerted the greatest reductions in biofilm formation across all tested concentrations. This was in contrast to both the controls and CHX, which had a minimal effect on biofilm formation.

Conclusion: By inhibiting the virulence factors the oral rinse can have a crippling effect on C. albicans, weakening this opportunistic pathogen and hindering its potential to cause infection.

Alzheimer's disease (AD) is the most common cause of neurodegenerative impairment in elderly people. Clinical characteristics include short-term memory loss, confusion, hallucination, agitation, and behavioural disturbance. Owing to evolving research in biomarkers AD can be discovered at early onset, but the disease is currently considered a continuum, which suggests that pharmacotherapy is most efficacious in the preclinical phase, possibly 15 - 20 years before discernible onset. Present developments in AD therapy aim to respond to this understanding and go beyond the drug families that relieve clinical symptoms. Another important factor in this development is the emergence of precision medicine that aims to tailor treatment to specific patients or patient subgroups. This relatively new platform would categorize AD patients on the basis of parameters like clinical aspects, brain imaging, genetic profiling, clinical genetics and epidemiological factors. This review enlarges on recent progress in the design and clinical use of antisense molecules, antibodies, antioxidants, small molecules and gene editing to stop AD progress and possibly reverse the disease on the basis of relevant biomarkers.

Objectives: Atypical femoral fracture (AFF) is an atypical low-energy subtrochanteric and diaphyseal femoral fracture. Even if bone fusion is achieved in patients with AFF, the risk of AFF in the contralateral femur must be considered. This study aimed to investigate the factors affecting complete AFF in the contralateral femur and conservatively treated incomplete AFF.

Subject and methods: Radiographs of 111 femurs in 104 AFF cases were examined, and the femurs were classified as follows: 85 contralateral femurs with complete AFF; 18 contralateral femurs with incomplete AFF; 8 femurs with incomplete AFF without surgical treatment. Various patients' clinical data were collected, and we investigated the factors affecting the second complete AFF.

Results: Complete fractures occurred in 10 (9.7%) of 103 femurs without incomplete AFF at the first visit and in 3 (37.5%) of 8 femurs with incomplete AFF. The Kaplan-Meier curve revealed that lateral cortical bone thickening and thigh pain were associated with significantly poorer prognoses (p = 0.026 and p = 0.013, respectively). Multivariate analyses revealed that eldecalcitol usage after AFF onset (p = 0.0094) and previous use of bisphosphonate or denosumab (p = 0.0126) were protective factors for second complete AFF and that the presence of thigh pain (p = 0.0134) was a risk factor for second complete AFF.

Conclusions: Eldecalcitol administration after bone union of first AFF may prevent AFF recurrence. In addition, painful incomplete AFF has a high risk of developing a complete fracture.

Objective: Workers in the healthcare sector are exposed to a multitude of bacterial genera. The location of their work contributes significantly to shaping personal microbiomes. In this study, we investigated the role of the workspace on the nasal bacteriome of staff working in a healthcare-associated research facility.

Methods: The anterior nares of 10 staff working in different laboratories on the ground and first floor of the research facility were aseptically swabbed. Genomic DNA from each sample was used to amplify the V3 and V4 regions of the 16S rRNA gene. The amplified products were sequenced using the MiSeq sequencer (Illumina). Operational taxonomic units were filtered through MG-RAST v.3.6. Taxonomic profiling and visualizations were performed in MicrobiomeAnalyst v2.0.

Results: The Wilcoxson Sum test at median abundances (p < 0.05) indicated that seven taxa (Micromonosporaceae, Micromonospora, Lactobacillaceae, Lactobacillus, Betaproteobacteria, Burkholderiales, Pectobacterium) were significantly diverse between ground-floor and first-floor workers. The analysis of similarity coefficient was 0.412 (p < 0.03) between the ground and the first-floor workers. Random forest analysis predicted 15 features that were significantly different (p < 0.05) in individuals working in different laboratories. Species richness and evenness also differed according to the placement of individuals in respective laboratories.

Conclusion: These findings add to the knowledge that the healthcare support staff are at a speculated occupational risk. A slight shift in the abundances of bacterial genera and species might lead to unwanted consequences. Continual monitoring is thus warranted.

Objective: The cannabinoid receptor-2 agonist AM1241 exhibits notable cardioprotective effects against myocardial infarction, positioning it as a promising therapeutic candidate for cardiovascular disease. This study explores AM1241's protective role in myocardial ischemia-reperfusion (IR) injury and its association with the Nrf2/HO-1 pathway.

Methods: In an established Sprague-Dawley rat IR model, AM1241's impact on cardiac injury was assessed through echocardiography, 2,3,5-triphenyl tetrazolium chloride staining, and histological analysis. H9c2 cells underwent hypoxia-reoxygenation, with AM1241's influence on cell viability determined by the CCK-8 assay. Reactive oxygen species (ROS) production was measured using the DCFH-DA assay, and Nrf2 and HO-1 protein expressions were evaluated through immunofluorescence and Western blot.

Results: Myocardial ischemia-reperfusion injury (MIRI) increased infarct size, inflammatory cell presence, oxidative and nitrosative stress, impaired cardiac function, and elevated apoptosis rates. AM1241 mitigated these effects, enhancing cell viability, reducing ROS production, and upregulating Nrf2 and HO-1 expression. The antioxidant effect of AM1241 was inhibited by ML385 intervention.

Conclusions: AM1241 attenuates oxidative stress, alleviates MIRI, and activates the Nrf2/HO-1 signaling pathway, underscoring its potential as a therapeutic strategy for MIRI.

Avascular necrosis of femoral head (AVNFH) is a debilitating disease of the young, affecting the quality of life significantly and eventually leading to total hip replacement surgery. The disease is diagnosed clinico-radiologically and MRI is the investigation of choice to diagnose the early stages of the disease. There is neither an early biomarker for detection nor is there a permanent cure for the disease and most of the patients are managed with various combinations of surgical and medical management protocols. In this review, we comprehensively address the etiopathogenesis, clinical characteristics, therapeutic procedures, bone characteristics, histopathology, multi-omic studies, finite element modeling, and systems analysis that has been performed in AVNFH. The etiology includes various factors that compromise the blood supply to the femoral head which also includes contributions by environmental and genetic factors. Multi-omic analysis has shown an association of deregulated pathways with the disease. The cell types involved include mesenchymal stem cells, osteoblasts, osteoclasts, endothelial and immune cells. Biochemical, hematological, histopathology, IHC, and other bone remodeling and degradation marker studies have been performed. A systems analysis using multi-omic data sets from published literature was carried out, the relevance of which is discussed to delineate potential mechanisms in etiopathogenesis, diagnosis, and effective management of this debilitating disease.

Objective: Investigating the relationship between physical activity (PA) and depressive symptoms is a vital field of research globally. Nonetheless, this association remains unexplored in the context of older Palestinian adults, highlighting the need for additional research on this population. Therefore, this study aimed to examine the association between PA and depressive symptoms among older Palestinian adults.

Subjects and methods: A cross-sectional study was conducted in the West Bank/Palestine with 266 participants. Data were collected using a PA socio-cultural adapted questionnaire (PA-SCAQ), the EuroQuol-5Dimensions-5Levels measure, and the Geriatric depression scale (GDS-15). Independent sample t tests and ANOVA tests were used to investigate mean differences in PA and GDS-15 scores between groups. Furthermore, multiple linear regression analysis was used to examine the relationship between study variables and the impact of the independent variable (PA level) on depressive symptoms.

Results: The mean age of the participants was 65.01 ± 8.02 years (range: 55-86), women 51.9%. Lower levels of PA and higher depressive symptoms were recorded among women, participants ≥65 years, and with recorded diagnosed disease (p < 0.05). The regression analysis showed a negative significant correlation between PA and GDS-15 scores (β = -0.235, p < 0.001), when controlling for age (model 2), and for age and sex (model 3), significant associations were recorded, respectively (β = 0.192, p = 0.002), and (β = 0.14, p = 0.015).

Conclusion: Participants who recorded higher depressive symptoms had a lower level of PA; regular moderate-intensity aerobic exercises can contribute to prevent depression symptoms in older adults.