Medical Principles and Practice最新文献

Aging is an inevitable life process which is accelerated by lifestyle and environmental factors. It is an irreversible accretion of molecular and cellular damage associated with changes in the body composition and deterioration in physiological functions. Each cell (other than stem cells), reaches the limit of its ability to replicate, known as cellular or replicative senescence and consequently, the organs lose their physiological functions resulting in overall impairment. Other factors that promote aging include smoking, alcohol, UV rays, sleep habits, food, stress, sedentary life style and genetic abnormalities. These stress factors, can alter our endogenous clock (the circadian rhythm) and the microbial commensals. As a result of effect of these stressors, the microorganisms that generally support human physiological processes become baleful. The disturbance of natural physiology instigates many age-related pathologies, such as cardiovascular diseases, chronic obstructive pulmonary disorder, cerebrovascular diseases, opportunistic infections, high blood pressure, cancer, diabetes, kidney diseases, dementia, and Alzheimer's disease. The present review covers the three most essential processes of the circadian clock; the circadian gene mechanism and regulation, the mitotic clock (which plays a vital role in the telomere's attrition) and gut microbiota and their metabolome that drive aging and lead to age-related pathologies. In conclusion, maintaining a synchronized circadian rhythm, a healthy gut microbiome and telomere integrity is essential for mitigating the effects of aging and promoting longevity. The interplay among these factors underscores the importance of lifestyle choices in enhancing overall health and lifespan.

Objective: The problem of hospital cross-infection due to contamination of disinfectants has been recognized elsewhere. The passage of bacteria through diluted disinfectants may not only bring about phenotypic changes in their antibiograms but also changes in phage susceptibility patterns. Contact with disinfectants in sublethal concentrations allows survival and multiplication of bacteria.

Methods and materials: Serial passage, through disinfectants at subminimal inhibitory concentrations, induced antibiotic resistance in 18% of derived phenotypic variants of fifty strains of Pseudomonas aeruginosa which were isolated from diarrheal stools of infants in children's hospital.

Results: A proportion of these strains became susceptible to an increased number of antibiotics. The present study revealed that all the isolates were resistant to tetracycline and carbenicillin and 40% of these isolates became sensitive to both antibiotics after exposure to disinfectants. The exposure to disinfectants induced neomycin resistance among two isolates. The resistance patterns were three before disinfectants exposure which increased to be nine different patterns after exposure. No antibiotic resistance was transferred between P. aeruginosa and Escherichia coli K12 as a recipient strain.

Conclusions: Almost 50% of the isolates tested became sensitive to tetracycline, carbenicillin and co-trimoxazole after exposure to disinfectants. The resistance patterns among the 50 isolates were three which changed to be nine different patterns after exposure to disinfectants. Unjustifiable use of disinfectants might give a chance for survival and multiplication of pathogenic bacteria to develop new resistance patterns to antibiotics in use with a short time. These new resistance variants of bacteria which multiply in hospital environment could lead to serious epidemic conflicts particularly the epidemiological reporting and management.

Objectives: This pilot retrospective case-control study questioned whether systemic statin use causes pulp calcification using cone-beam computed tomography images from the patients prescribed oral statins and comparing those of healthy individuals.

Subjects and methods: CBCT scans of 54 patients, including 27 age- and sex-matched patients for the study and control groups, were analysed using Mimics Innovation Suite software. The study included patients using statins regularly for at least 1 year. Only intact teeth with opposing teeth were selected for the study group and matched with the control group. Dental crown and pulp chamber volumes were calculated and proportioned. The data were analysed with chi-square and Shapiro-Wilk tests to assess normal distribution, followed by Mann-Whitney U test if necessary.

Results: Statistical analysis showed no difference between the study and control groups (p = 0.505). Statin use duration did not cause statistically significant difference in terms of the reduction of pulp chamber volume (p = 0.141).

Conclusion: Within the limitations of the study, systemic statin use did not cause dental pulp calcification. The results suggest, oral administration of the statin drugs is not an unfavourable condition for dental practice. Further studies with larger numbers of patients are needed to support this conclusion.

Objectives: Inflammatory bowel diseases which are characterized by endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) signaling pathway are commonly treated with 5-amino salicylic acid (5-ASA). The objective of this study was to investigate the role of 5-amino salicylic acid in the UPR-signaling pathway in experimental colitis.

Materials and methods: Colitis was induced in male Sprague-Dawley rats by intrarectal instillation of trinitrobenzene sulfonic acid. Animals received 5-amino salicylic acid (100 mg/kg body weight) 2 h before the induction of colitis and repeated daily until day 7. The animals were sacrificed on day 7 and tissues were collected for analysis.

Results: The expression of protein kinase R (PKR)-like ER kinase (PERK), a mediator of UPR signaling increased significantly (p < 0.05), while inositol-requiring enzyme type-1 (IRE1) and the CCAAT/enhancer-binding homologous protein (CHOP) remained unaltered in the inflamed colon. The expression of glucose-regulated protein-78, activator of transcription factor-4, and phosphorylated-eukaryotic initiation factor-2α (eIF2αP) increased (p < 0.05) in the inflamed colon. However, the levels of eIF2α protein and mRNA expression remained unchanged. Myeloperoxidase activity, colon weight, and infiltration of inflammatory cells increased significantly (p < 0.05) in the submucosa whereas the body weight decreased. These changes were significantly inhibited by 5-amino salicylate treatment.

Conclusion: These findings suggest that the anti-inflammatory properties of 5-amino salicylic acid are mediated through the inhibition of the PERK signaling pathway.

Objective: In this study, we have mapped the relative importance of well-defined recombinantly expressed Mycobacterium tuberculosis antigens in the T cell recognition repertoire of latently infected individuals not progressing to active disease.

Materials and methods: Peripheral blood mononuclear cells from healthy latently infected long term non-progressors were screened for antigen-induced proliferation and Th1 cytokine, Interferon- (IFN-γ) responses.

Results: The panel of antigens tested showed a clear spectrum of responsiveness and lead to the identification of a subgroup of frequently recognized antigens (MPT59, CFP7, CFP10, CFP21, TB37.6 /PPE68, ESAT-6, MPT51, and DnaK) with a high cellular response level as measured in both proliferation and IFN-γ assays. Among a subgroup of antigens also screened for responses in tuberculosis patients, CFP21 was identified as differentially recognized in non-progressors. For both cellular assays, we found a positive correlation between responder frequency and magnitude of response. A significant correlation between the level of antigen-specific proliferation and INF-γ secretion was also observed.

Conclusion: We have identified a defined set of M. tuberculosis antigens frequently recognized by T cells at a high response level from latently infected long term non-progressors which warrant further investigation for a potential role in immune regulation and protection against progression to active disease.

Antimicrobial resistance (AMR) is a global health crisis that has already claimed millions of lives and is projected to affect millions more unless urgent action is taken. Effective control of AMR requires the correct choice and dosage of antibiotics, as well as robust surveillance and research. Understanding the mechanisms of antibiotic action and the emergence of resistance phenotypes along with their genotypes is essential. This knowledge, combined with insights into resistance prevalence and spread, empowers clinicians to propose alternative therapies. Nitrofurantoin, a 70-year-old antibiotic, remains effective for the treatment of uncomplicated lower UTIs. Preventing emergence and spread of nitrofurantoin-resistant superbugs would preserve the efficacy of this antibiotic which is crucial for ongoing and future AMR efforts. Nitrofurantoin resistance evolves slowly, leading to low prevalence compared to other antibiotics. However, it is often linked with extensive drug resistance, complicating treatment outcomes. Even a minor percentage of nitrofurantoin-resistant bacteria can cause significant clinical challenges due to irreversible evolution. While detailed study of these mechanisms can guide the development of strategies to combat nitrofurantoin resistance, early detection of resistant infections is critical for saving lives. The current review aimed to provide a comprehensive analysis of nitrofurantoin's mechanisms of action, resistance evolution, prevalence, and resistance prediction. Our goal is to offer valuable insights for researchers and clinicians to enhance nitrofurantoin use and address the challenges posed by AMR.

Objective: Implantable cardioverter defibrillators (ICDs) are the standard treatment for patients with reduced left ventricular ejection fraction (LVEF ≤35%) to reduce the risk of sudden cardiac death. Loop diuretics can cause electrolyte imbalances, leading to an increased incidence of ICD shocks. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have shown cardiovascular benefits in patients with heart failure (HF), but their effects on ventricular arrhythmias and ICD shocks, particularly in patients receiving different doses of loop diuretics, are not fully understood. This study evaluated the effects of furosemide dose and SGLT2i use on ICD shocks in HF patients with reduced left ventricular ejection fraction (HFrEF).

Materials and methods: HFrEF patients using oral furosemide and undergoing ICD implantation in our clinic were followed for 12 months to monitor ICD shocks for ventricular arrhythmias. They were grouped according to daily oral furosemide dose and SGLT2i use.

Results: Out of 175 patients, the use of high-dose furosemide (>80 mg/day) was significantly higher in the ICD shock group compared to the non-shock group (38.8% vs. 16.7%, p = 0.001), while the use of SGLT2i was lower (19.4% vs. 45.4%, p < 0.001). ICD shocks occurred in 67.6% of patients on high-dose furosemide without SGLT2i and 30.0% with SGLT2i (p < 0.001). Multivariate analysis identified the absence of SGLT2i as an independent predictor of ICD shocks.

Conclusions: SGLT2i was associated with reduced ventricular arrhythmias and ICD shocks in HF patients, even when high doses of furosemide were used. The absence of SGLT2i in HF treatment was an independent predictor of ICD shocks.

Objectives: The study aimed to assess the relationship between the Fit fOR The Aged (FORTA) score - a classification system designed to evaluate medication appropriateness in older adults - and several negative outcomes, including impaired cognitive performance, functional status, adverse clinical events, and all-cause mortality at 3, 6, and 12 months after hospital discharge.

Methods: This retrospective study utilized data from the ELICADHE cohort, a cluster-randomized trial conducted across 20 Italian internal medicine and geriatric wards. The study included patients aged 75 and older with complete FORTA score assessments. Demographics, medication history, and comorbidities were collected. The FORTA classification system assessed medication appropriateness. FORTA scores were calculated and FORTA score cut-offs (3 and 5) were applied. Statistical analyses included descriptive statistics, survival analysis with Cox regression, logistic regression, and negative-binomial regression using SAS 9.4 and RStudio 12.1. Ethical approval was obtained.

Results: Of the 506 patients included, 171 (33.8%) were fully assessable with complete FORTA scores. The study found no significant association between higher FORTA scores and impaired cognitive performance, functional status, or mortality. Additionally, no clear relationship was observed between FORTA scores and adverse clinical events or mortality. The analysis indicated that age was a significant factor associated with mortality and adverse clinical events.

Conclusion: The study did not find a significant relationship between the FORTA score and negative outcomes in older patients discharged from internal medicine and geriatric wards. Further research is needed to define specific FORTA score cut-off values and expand the criteria to improve medication assessment in this population.

Objective: We aimed to investigate the relationship between advanced glycation end product (AGE) levels in patients with saphenous vein graft (SVG) failure and in patients without SVG failure.

Subjects and methods: In our study, 55 patients with a history of previous coronary artery bypass grafting (CABG) surgery, who subsequently underwent coronary angiography for any reason and were found to have either SVG occlusion or significant lesions, were included as study patients. Additionally, 55 patients who have had CABG surgery without SVG failure for at least 1 year served as the control group. AGE values of the patients were measured using the skin autofluorescence method.

Results: In our study results, we observed a significant difference in AGE levels between the two groups of patients with similar demographic characteristics (SVG failure groups AGE 3.2 [2.8-3.6] vs. control groups AGE 2.4 [2.1-2.7] p < 0.001). In the receiver operating characteristic curve analysis, we determined the ability of AGE levels to detect SVG failure with an area under the curve of 0.869. We found that in patients with AGE >3, it could detect SVG failure with a sensitivity of 70.9% and a specificity of 87.3%.

Conclusions: Our results demonstrate that AGE levels can predict SVG failure risk inexpensively, easily, and quickly.