Animal models of multiple sclerosis: Focus on experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a chronic, progressive disorder of the central nervous system (CNS) that affects more than two million people worldwide. Several animal models resemble MS pathology; the most employed are experimental autoimmune encephalomyelitis (EAE) and toxin- and/or virus-induced demyelination. In this review we will summarize our knowledge on the utility of different animal models in MS research. Although animal models cannot replicate the complexity and heterogeneity of the MS pathology, they have proved to be useful for the development of several drugs approved for treatment of MS patients. This review focuses on EAE because it represents both clinical and pathological features of MS. During the past decades, EAE has been effective in illuminating various pathological processes that occur during MS, including inflammation, CNS penetration, demyelination, axonopathy, and neuron loss mediated by immune cells."This is the peer reviewed version of the following article: Bjelobaba I, Begovic-Kupresanin V, Pekovic S, Lavrnja I. Animal models of multiple sclerosis: Focus on experimental autoimmune encephalomyelitis. J Neurosci Res. 2018, which has been published in final form at [https://doi.org/10.1002/jnr.24224]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

Healthcare associated Clostridioides difficile infection in adult surgical and medical patients hospitalized in tertiary hospital in Belgrade, Serbia: a seven years prospective cohort study

Introduction: Clostridioides difficile (C. difficile) infection (CDI) is one of the most common healthcare-associated (HA) infections in contemporary medicine. The risk factors (RFs) for HA CDI in medical and surgical patients are poorly investigated in countries with a limited resource healthcare system. Therefore, the aim of the study was to investigate differences in patients’ characteristics, factors related to healthcare and outcomes associated with HA CDI in surgical and medical patients in tertiary healthcare centre in Serbia. Materials and Methods: A prospective cohort study was conducted including adult patients diagnosed with initial episode of HA CDI, first recurrence of disease, readmission to hospital, while deaths within 30 days of CDI diagnosis and in-hospital mortality were also recorded. Patients hospitalized for any non-surgical illness, who developed initial HA CDI were assigned to medical group, whereas those who developed initial HA CDI after surgical procedures were in surgical group. The data on patients’ characteristics and factors related to healthcare were collected, too. Results: During 7-year period, from 553 patients undergoing in-hospital treatment and diagnosed with CDI, 268 (48.5%) and 285 (51.5%) were surgical and medical patients, respectively. Age ≥ 65 years, use of proton pump inhibitors, chemotherapy and fluoroquinolones were positively associated with being in medical group, whereas admission to intensive care unit and use of second- and third-generation cephalosporins were positively associated with being in surgical group. Conclusions: Based on obtained results, including significant differences in 30-day mortality and in-hospital mortality, it can be concluded that medical patient were more endangered with HA CDI than surgical ones

Vaccine Effectiveness against SARS-CoV-2 Infection during the Circulation of Alpha, Delta, or Omicron Variants: A Retrospective Cohort Study in a Tertiary Hospital in Serbia

The COVID-19 pandemic prompted rapid vaccine development and deployment worldwide. Despite widespread vaccination efforts, understanding the effectiveness of vaccines in hospitalized patients remains a critical concern. This retrospective cohort study, conducted at a tertiary healthcare centre in Serbia, tracked patients hospitalized during different waves of COVID-19 variants—Alpha, Delta, and Omicron. Data collection included demographics, comorbidities, symptoms, and vaccination status. Among 3593 patients, those with prior exposure to COVID-19 cases or hospital treatment showed higher positivity rates. Symptom prevalence varied across waves, with coughs persisting. Patients without chronic diseases were more frequent among those testing negative. Vaccine effectiveness varied, with Sinopharm demonstrating a 45.6% effectiveness initially and Pfizer-BioNTech showing an effectiveness of up to 74.8% within 0–84 days after the second dose. Mixed-dose strategies, notably Sinopharm as a primary dose followed by a Pfizer-BioNTech booster, suggested increased protection. Despite substantial vaccination availability, a significant portion of hospitalized patients remained unvaccinated. This study underscores the dynamic nature of vaccine effectiveness and advocates for booster strategies to address evolving challenges in combating COVID-19, particularly in hospitalized patients

Association between Antibiotic Use and Hospital-Onset <i>Clostridioides difficile</i> Infection in University Tertiary Hospital in Serbia, 2011–2021: An Ecological Analysis

This ecological study is the largest to date examining the association between rates of antibiotic use (AU) and hospital-onset (HO) Clostridioides difficile infection (CDI) in a tertiary university hospital in Serbia. There was no clear trend in the incidence of HO-CDI over time. Total utilization of antibacterials for systemic use increased from 38.57 DDD/100 bed-days (BD) in 2011 to 56.39 DDD/100 BD in 2021. The most commonly used antibiotics were third-generation cephalosporins, especially ceftriaxone, with maximum consumption in 2021 (19.14 DDD/100 BD). The share of the Access group in the total utilization of antibiotics ranged from 29.95% to 42.96% during the observed period. The utilization of the Reserve group of antibiotics indicated a statistically significant increasing trend (p = 0.034). A statistically significant difference in the consumption of medium-risk antibiotics from 2011 to 2021 was shown for penicillins and a combination of sulfamethoxazole and trimethoprim. The consumption of cefotaxime showed a statistically significant negative association with the rate of HO-CDI (r = −0.647; p = 0.031). Ampicillin and the combination of amoxicilline with clavulanic acid have shown a negative statistically significant correlation with the ID of HO-CDI (r = −0.773 and r = −0.821, respectively). Moreover, there was a statistically significant negative correlation between consumption of “medium-risk antibiotics” and the rate of HO-CDI (r = −0.677). The next challenging step for the hospital multidisciplinary team for antimicrobials is to modify the antibiotic list according to the Access, Watch, and Reserve classification, in such a way that at least 60% of the AU should be from the Access group, according to the World Health Organization recommendation

Healthcare associated Clostridioides difficile infection in adult surgical and medical patients hospitalized in tertiary hospital in Belgrade, Serbia: A seven years prospective cohort study

Introduction: Clostridioides difficile (C. difficile) infection (CDI) is one of the most common healthcare-associated (HA) infections in contemporary medicine. The risk factors (RFs) for HA CDI in medical and surgical patients are poorly investigated in countries with a limited resource healthcare system. Therefore, the aim of the study was to investigate differences in patients’ characteristics, factors related to healthcare and outcomes associated with HA CDI in surgical and medical patients in tertiary healthcare centre in Serbia. Materials and Methods: A prospective cohort study was conducted including adult patients diagnosed with initial episode of HA CDI, first recurrence of disease, readmission to hospital, while deaths within 30 days of CDI diagnosis and in-hospital mortality were also recorded. Patients hospitalized for any non-surgical illness, who developed initial HA CDI were assigned to medical group, whereas those who developed initial HA CDI after surgical procedures were in surgical group. The data on patients’ characteristics and factors related to healthcare were collected, too. Results: During 7-year period, from 553 patients undergoing in-hospital treatment and diagnosed with CDI, 268 (48.5%) and 285 (51.5%) were surgical and medical patients, respectively. Age ≥ 65 years, use of proton pump inhibitors, chemotherapy and fluoroquinolones were positively associated with being in medical group, whereas admission to intensive care unit and use of second- and third-generation cephalosporins were positively associated with being in surgical group. Conclusions: Based on obtained results, including significant differences in 30-day mortality and in-hospital mortality, it can be concluded that medical patient were more endangered with HA CDI than surgical ones

The influence of early antibiotic therapy on the clinical manifestations in patients with early Lyme disease

Introduction/Objective. Lyme borreliosis is a multisystem infectious disease caused by Borrelia burgdorferi spirochetes transmitted by the bite of an infected tick. The disease manifestations are very different, with the skin, joints, heart, and nervous systems being most often affected. The aim of this study was to find out whether there are significant differences in the appearance of symptoms and signs of the disease between the subjects who did / did not receive prophylactic, early antibiotic therapy, after the tick bite in patients diagnosed with the early phase of Lyme borreliosis. Methods. The study was carried out on 2,070 patients, who were treated or examined at the Clinic for Infectious and Tropical Diseases in the 1989–2004 period. The patients were divided into group А (n = 591), in which they were given early antibiotic therapy, and group B (n = 1,479), in which they were not. The antibiotic therapy was used within five days of a tick bite in patients with a probable infection, who, at the time, did not have any symptoms or signs. The applied antibiotics included cephalosporins, macrolides, tetracyclines, semisynthetic penicillins, repeatedly for seven or 14 days, or benzathine benzylpenicillin once only. Results. The disease developed in a statistically significantly larger number of patients who were not given early antibiotic therapy (537/1,479) than in those who received the therapy (10/951), i.e. the ratio was 36.3% vs. 1.7%. We concluded that only two antibiotics were sufficient for optimal prevention: doxycycline and ampicillin, administered for seven days. The applied antibiotics showed a high statistically significant efficacy, ranging from 93.7% (cephalosporins) to 99.4% (macrolides). Conclusion. The application of early antibiotic therapy after a tick bite was effective in preventing the early phase of Lyme borreliosis, while in the case of infection it prevented the development of extracutaneous manifestations

Maternal Dexamethasone Exposure Induces Sex-Specific Changes in Histomorphology and Redox Homeostasis of Rat Placenta

As the mediator between the mother and fetus, the placenta allows the most appropriate environment and optimal fetal growth. The placenta of one sex sometimes has a greater ability over the other to respond to and protect against possible maternal insults. Here, we characterized sex differences in the placenta’s morphological features and antioxidant status following dexamethasone (Dx) exposure. Pregnant rats were exposed to Dx or saline. The placenta was histologically and stereologically analyzed. The activity of the antioxidant enzymes, lipid peroxides (TBARS), superoxide anion and nitric oxide (NO) was measured. The decrease in placental zone volumes was more pronounced (p p p < 0.05) antioxidant enzyme activities, enhanced TBARS and NO concentration indicate that Dx exposure triggered oxidative stress in the placenta of both fetal sexes, albeit stronger in the placenta of female fetuses. In conclusion, maternal Dx treatment reduced the size and volume of placental zones, altered placental histomorphology, decreased cell proliferation and triggered oxidative stress; however, the placentas of female fetuses exerted more significant responses to the treatment effects. The reduced placental size most probably reduced the transport of nutrients and oxygen, thus resulting in the reduced weight of fetuses, similar in both sexes. The lesser ability of the male placenta to detect and react to maternal exposure to environmental challenges may lead to long-standing health effects

Clinical manifestations, therapy and outcome of pandemic influenza a (H1N1) 2009 in hospitalized patients

Background/Aim. Increasing number of epidemiological and clinical studies to date showed that the pandemic influenza A (H1N1) 2009, by its characteristics, significantly differs from infection caused by seasonal influenza. Therefore, the information about clinical spectrum of manifestations, risk factors for severe form of the disease, treatment and outcome in patients with novel flu are still collected. Methods. A total of 98 patients (mean age 32 ± 15 years, range 14-88 years) with the signs and symptoms of novel influenza were treated in the Clinic for Infectious and Tropical Diseases, Military Medical Academy. There were 74 (75.5%) patients with suspected influenza A (H1N1) 2009, 10 (10.2%) with the likelihood and 14 (14.3%) with the confirmed influenza. In all the patients we registered the basic demographic data, risk factors for severe disease, symptoms and signs of influenza, laboratory tests and chest radiography. We analyzed antiviral therapy use and disease outcome (survived, died). Results. The average time from the beginning of influenza A (H1N1) to the admission in hospital was 3 days (0-16 days) and from the moment of hospitalization to the Intensive Care Unit (ICU) admission was 2 days (0-5 days). There were 49 (50.0%) patients, 20-29 years of age and 5 (5.1%) patients older than 65. A total of 21 (21.4%) patients were with underlying disease, 18 (18.4%) were obese, 19 (19.4%) were cigarette smokers. All of the patients had fever, 81 (82.6%) cough, while dyspnea and diarrhea were registered in ¼ of the patients. In more than 75% of the patients laboratory tests were within normal limits. The realtime polymerase chain reaction (PCR) test for identification of influenza A (H1N1) 2009 was positive in 14 (77.8%), while pneumonia was verified in 30 (30.7%) of the patients. Six (6.1%) patients, mean age of 45 ± 14 years (31-59 years) were admitted to the ICU, of whom five (5.1%) had Adult Respiratory Distress Syndrome (ARDS). Risk factors were registered more frequently in the patients with acute respiratory failure (14.2% vs 4.9%, p &lt; 0.05). A total of 67 (68.4%) patients received oseltamivir, 89 (90.1%) was applied to antibiotics and 64 (65.3%) were treated with a combined therapy. Antiviral therapy was applied to 43 (43.3%) patients in the first 48 hours from the onset of the disease, of whom only one (3.4%) developed ARDS. Fatal outcome was noted in 2.0% of the patients (2 of 98 patients) and in 33.3% of the patients treated in the ICU. Conclusion. Novel influenza A (H1N1) is most commonly manifested as a mild acute respiratory disease, which usually affects young healthy adults. A small number of the patients develop severe illness with acute respiratory failure and death. Patients seem to have benefit from antiviral therapy especially in first 48 hours