Murine typhus is a common cause of acute febrile illness in Bandung, Indonesia.

Murine typhus (MT), an infection caused by the gram-negative bacteria Rickettsia typhi (R. typhi), is a significant cause of acute febrile illness (AFI) in Southeast Asia but is rarely reported in Indonesia. The current study aimed to describe the clinical characteristics of MT cases in Bandung, West Java. Non-confirmed AFI cases (n = 176) from a prospective cohort study of whom paired serum samples (acute (T1), midterm (T2), or convalescent (T3)) were available were screened using MT serology. IgG against R. typhi was detected in the T2 or T3 samples using an in-house ELISA. Positive IgG samples were further screened for the presence of IgM. If both IgM and IgG were positive, the endpoint titer of T1, T2, or T3 was determined. In cases with a fourfold increase in titer, real-time PCR of T1 samples was performed to detect R. typhi DNA. In total, 71/176 (40.3%) patients tested positive for IgG antibody, and 26 AFI cases were confirmed as MT (23 cases by PCR, 3 cases by fourfold titer increased IgG or IgM titer). The most common clinical symptoms in the confirmed cases were headache (80%), arthralgia (73%), malaise (69%), and myalgia (54%). In these cases, the presumptive clinical diagnoses were typhoid fever (43.2%), dengue (38.5%), and leptospirosis (19.2%). MT was not considered in any of the patients, and no patients received doxycycline. These findings confirmed that MT is an important cause of AFI in Indonesia. MT should be included in the differential diagnosis of AFI, and empirical treatment with doxycycline should be considered.

Exercise-Induced Autophagy Ameliorates Motor Symptoms Progressivity in Parkinson's Disease Through Alpha-Synuclein Degradation: A Review.

This study reviews the molecular mechanism of exercise-induced autophagy/mitophagy and its possible mechanism in delaying motor symptoms progressivity in Parkinson's disease (PD). Relevant articles obtained from PubMed and EBSCOhost were reviewed. After analyzing the articles, it was found that autophagy can be induced by exercise and can possibly be activated through the AMPK-ULK1 pathway. Mitophagy can also be induced by exercise and can possibly be activated through PINK1/Parkin pathway and AMPK-dependent pathway. Moreover, exercise-induced autophagy can decrease the accumulation of toxic α-synuclein aggregates in PD and therefore can delay motor symptoms progressivity.

The Role of Gut Dysbiosis in the Pathophysiology of Tinnitus: A Literature Review.

INTRODUCTION: For years, tinnitus has become a prevalent symptom in the ENT department. However, the mechanism underlying tinnitus remains unclear. There is increasing evidence that tinnitus is related to an abnormal central gain in the central auditory system and increased neuroinflammatory mediators. On the other hand, recent studies have shown that gut dysbiosis plays a crucial role in brain function, and gut dysbiosis contributes to several neurological diseases. Hence, giving insight into its possible involvement in tinnitus. AIMS: This study evaluated the potential role of gut microbiota dysbiosis in the path mechanism of tinnitus, mainly through its effect on neurotransmitter production and neuroinflammation induction. METHODS: This study uses a literature review approach, inclusive only of experimental studies in the recent five years discussing gut dysbiosis, neurotransmitter, neuroinflammation, and tinnitus signaling. RESULTS: From 22 relevant literature, we found that gut dysbiosis impacts neurotransmitter production such as GABA and 5-HT and contributes to the neuroinflammatory process by increasing pro-inflammatory cytokines and activated microglia. These altered neurotransmitter profiles and triggered pro-inflammatory mediators were also found in tinnitus. CONCLUSION: Gut microbiota dysbiosis is likely to underlie tinnitus's pathomechanism by altering neurotransmitter production and activating the neuroinflammatory response in the brain.

Type, Intensity, and Duration of Exercise as Regulator of Gut Microbiome Profile.

ABSTRACT: Gut microbiome profile is related to individual health. In metabolic syndrome, there is a change in the gut microbiome profile, indicated by an increase in the ratio of Firmicutes to Bacteroidetes. Many studies have been conducted to determine the effect of exercise on modifying the gut microbiome profile. The effectiveness of exercise is influenced by its type, intensity, and duration. Aerobic training decreases splanchnic blood flow and shortens intestinal transit time. High-intensity exercise improves mitochondrial function and increases the essential bacteria in lactate metabolism and urease production. Meanwhile, exercise duration affects the hypothalamic-pituitary-adrenal axis. All of these mechanisms are related to each other in producing the effect of exercise on the gut microbiome profile.

Importance of gut microbiome regulation for the prevention and recovery process after SARS-CoV-2 respiratory viral infection (Review).

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported to affect organs other than the lungs, including the liver, brain, kidneys and intestine, and gastrointestinal symptoms, such as nausea, vomiting, diarrhea and abdominal discomfort, have also been reported. Thus, SARS-CoV-2 could potentially directly or indirectly regulate the gut microbiome profile and its homeostasis. The abundance of Coprobacillus, Clostridium ramosum and Clostridium are associated with the severity of COVID-19, and Firmicutes, Bacteriodetes, Proteobacteria and Actinobacteria are also related to COVID-19 infection. The four phyla are correlated with the severity of COVID-19 infection in patients. The modulation of factors that control the physiological growth of the gut microbiome will determine the proportionate ratio of microbiome types (profile). Taken together, gut microbiome profile alterations in COVID-19 patients may have a cross effect with the modulation of cytokine levels in COVID-19 infection. With these findings, several factors that regulate gut microbiome homeostasis may support the degree of the clinical symptoms and hasten the recovery process after COVID-19 infection.

A phase III, observer-blind, randomized, placebo-controlled study of the efficacy, safety, and immunogenicity of SARS-CoV-2 inactivated vaccine in healthy adults aged 18-59 years: An interim analysis in Indonesia.

BACKGROUND: The WHO declared COVID-19 a pandemic on March 11th, 2020. This serious outbreak and the precipitously increasing numbers of deaths worldwide necessitated the urgent need to develop an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. The development of COVID-19 vaccines has moved quickly. In this study, we assessed the efficacy, safety, and immunogenicity of an inactivated (SARS-CoV-2) vaccine. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to evaluate the efficacy, immunogenicity, and safety of an inactivated SARS-CoV-2 vaccine and its lot-to-lot consistency. A total of 1620 healthy adults aged 18-59 years were randomly assigned to receive 2 injections of the trial vaccine or placebo on a day 0 and 14 schedule. This article was based on an interim report completed within 3 months following the last dose of study vaccine. The interim analysis includes safety and immunogenicity data for 540 participants in the immunogenicity subset and an efficacy analysis of the 1620 subjects. For the safety evaluation, solicited and unsolicited adverse events were collected after the first and second vaccination within 14 and 28 days, respectively. Blood samples were collected for an antibody assay before and 14 days following the second dose. RESULTS: Most of the adverse reactions were in the solicited category and were mild in severity. Pain at the injection site was the most frequently reported symptom. Antibody IgG titer determined by enzyme-linked immunosorbent assay was 97.48% for the seroconversion rate. Using a neutralization assay, the seroconversion rate was 87.15%. The efficacy in preventing symptomatic confirmed cases of COVID-19 occurring at least 14 days after the second dose of vaccine using an incidence rate was 65.30%. CONCLUSIONS: From the 3-month interim analysis, the vaccine exhibited a 65.30% efficacy at preventing COVID-19 illness with favorable safety and immunogenicity profiles.

High Proportion of Oxacillin-Susceptible mecA-Positive Staphylococcus aureus Isolates from Post-Viral Acute Rhinosinusitis Patients.

<b>Background and Objective:</b> Detection of methicillin-resistant<i> S. aureus</i> have become a challenge in the presence of oxacillin-susceptible and <i>mecA</i>-positive <i>S. aureus </i>(OS-MRSA), concerning the misidentification events and therapeutic implications. This study aims to identify the OS-MRSA in clinical isolates of Post-viral acute rhinosinusitis, which, hopefully, can interfere with the therapeutic strategy. <b>Materials and Methods:</b> There were 60 patients diagnosed with Post-viral acute rhinosinusitis, recruited from an Ear, Nose and Throat (ENT) outpatient clinic. <i>Staphylococcus aureus</i> isolates were identified from the culture and were then tested for antibiotics susceptibility using a Kirby-Bauer disc diffusion test. The <i>mecA</i>, <i>mecC</i> and <i>blaZ</i> genes were determined using the Polymerase Chain Reaction (PCR) method. <b>Results:</b> <i>Staphylococcus aureus </i>was identified in 20 of the 60 samples from the patients (33.3%; 95% CI: 21.0-45.6). Of the 20 isolates, 19 isolates (95%) had a positive <i>mecA</i> gene, 19 (95%) had a positive <i>mecC</i> gene and 20 (100.0%) had a positive <i>blaZ </i>gene. The majority of the <i>mecA</i>-positive <i>S. aureus</i> showed an oxacillin-susceptible (85%) and 3 isolates (15.0%) were oxacillin-resistant toward the <i>S. aureus</i>. <b>Conclusion:</b> There was a high proportion of Oxacillin/cefoxitin-Susceptible <i>mecA</i>-positive <i>S. aureus</i> in the study population that indicate phenotypic susceptibility to antibiotics does not always indicate the absence of genes that carry resistant traits, thus allowing misidentification if the only phenotypic examination is carried out.