Gut microbiota in neurological diseases: Melatonin plays an important regulatory role.

Melatonin is a highly conserved molecule produced in the human pineal gland as a hormone. It is known for its essential biological effects, such as antioxidant activity, circadian rhythm regulator, and immunomodulatory effects. The gut is one of the primary known sources of melatonin. The gut microbiota helps produce melatonin from tryptophan, and melatonin has been shown to have a beneficial effect on gut barrier function and microbial population. Dysbiosis of the intestinal microbiota is associated with bacterial imbalance and decreased beneficial microbial metabolites, including melatonin. In this way, low melatonin levels may be related to several human diseases. Melatonin has shown both preventive and therapeutic effects against various conditions, including neurological diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. This review was aimed to discuss the role of melatonin in the body, and to describe the possible relationship between gut microbiota and melatonin production, as well as the potential therapeutic effects of melatonin on neurological diseases.

New-onset lung sarcoidosis, an adverse event by COVID-19 or a sign of convalescence; a case report.

Key Clinical Message: Sarcoidosis is a systemic inflammatory disease able to affect any organ within the body. Sarcoidosis may be the body's secondary response to COVID-19 infection and a sign of rehabilitation. Early response to the treatments reinforces this hypothesis. The majority of sarcoidosis patients require immunosuppressive therapies, including corticosteroids. Abstract: Most studies so far have focused on the management of COVID-19 in patients suffering from sarcoidosis. Nevertheless, the current report aims to present a COVID-19-induced sarcoidosis case. Sarcoidosis is a systemic inflammatory disease with granulomas. Still, its etiology is unknown. It often affects the lungs and lymph nodes. A previously healthy 47-year-old female was referred with the following chief complaints: atypical chest pain, dry cough, and dyspnea on exertion within a month after COVID-19 infection. Accordingly, a chest computed tomography revealed multiple conglomerated lymphadenopathies in the thoracic inlet, mediastinum, and hila. A core-needle biopsy from the nodes revealed non-necrotizing granulomatous inflammation, sarcoidal type. The sarcoidosis diagnosis was proposed and confirmed by a negative purified protein derivative (PPD) test. Accordingly, prednisolone was prescribed. All symptoms were relieved. A control lung HRCT was taken 6 months later, showing the lesions had disappeared. In conclusion, sarcoidosis may be the body's secondary response to COVID-19 infection and a sign of disease convalescence.

Association of systemic complications with mortality in coronavirus disease of 2019: A cohort study on intensive care unit patients.

Background: Since the beginning of the coronavirus disease of 2019 (COVID-19) pandemic, concerns raised by the growing number of deaths worldwide. Acute respiratory distress syndrome (ARDS) and extrapulmonary complications can correlate with prognosis in COVID-19 patients. This study evaluated the association of systemic complications with mortality in severely affected COVID-19 patients. Materials and Methods: This retrospective study was done on 51 intensive care unit (ICU)-admitted COVID-19 adult patients who were admitted to the ICU ward of Khorshid hospital, affiliated with Isfahan University of Medical Sciences. Only the patients who had a definite hospitalization outcome (dead vs. survivors) were included in the study. Daily clinical and paraclinical records were used to diagnose in-hospital complications in these patients. Results: The sample was comprised of 37 males (72.5%) and 14 females (27.4%). The median age of patients was 63 years (Min: 20, Max: 84), with the mortality rate of 47.1%. In total, 70.6% of patients had at least one coexisting disorder. Chronic kidney disease was associated with the worse outcome (29.16% of dead patients against 3.70 of survived ones). Mechanical ventilation was used in 58.8% of patients. Patients who had received invasive ventilation were more likely to die (87.50% of dead patients against 7.40 of survivors), Complications including sepsis and secondary infections (odds ratio: 8.05, confidence interval: 2.11-30.63) was the strongest predictors of mortality. Conclusion: Complications including sepsis and secondary infections can increase the risk of death in ICU-admitted COVID-19 patients. Therefore, it is substantial that the physicians consider preventing or controlling these complications.

Age-Dependent Clinical Features and Prognosis of COVID-19 Patients.

Background: The clinical and paraclinical symptoms of COVID-19 differ across age groups. This study investigated the differences between these parameters and their outcomes in young, middle-aged, and elderly patients admitted to a COVID-19 referral center. Materials and Methods: This retrospective study encompassed patients with COVID-19 hospitalized at Khorshid Hospital (Isfahan, Iran) during February 23 to April 30, 2020. The patients' predisposing conditions, clinical and paraclinical findings, and outcomes were compared among three young, middle-aged, and elderly groups. Results: Of the 1185 hospitalized patients with suspected COVID-19, 1065 were discharged or died at the end of the study. Among these 1065 patients, 654 patients with the mean age of 57.7 years had positive PCR results or typical CT scans and were included in the study, of whom 77 (11.8%), 353 (54%), and 234 (34.2%) patients were assigned into the young, middle-aged, and elderly groups, respectively. There was no statistically significant difference among the three groups regarding the prevalence of clinical symptoms. Moreover, CRP, ESR, WBC, BUN, Cr, and lymphocytes were higher in the elderly group. The ground-glass opacity (GGO) (24.1%), GGO-consolidation (27.4%), and consolidation (10.3%) were the most common CT scan findings in the young, middle-aged, and elderly groups, respectively. Fifty-three patients (8.1%) died, and the mortality rates were 10.36%, 7.27%, and 3.8% in the elderly, middle-aged, and young groups, respectively. Conclusion: COVID 19 symptoms do not depend on age; however, paraclinical findings differ across young, middle-aged, and elderly patients.

A one-year hospital-based prospective COVID-19 open-cohort in the Eastern Mediterranean region: The Khorshid COVID Cohort (KCC) study.

The COVID-19 is rapidly scattering worldwide, and the number of cases in the Eastern Mediterranean Region is rising. Thus, there is a need for immediate targeted actions. We designed a longitudinal study in a hot outbreak zone to analyze the serial findings between infected patients for detecting temporal changes from February 2020. In a hospital-based open-cohort study, patients are followed from admission until one year from their discharge (the 1st, 4th, 12th weeks, and the first year). The patient recruitment phase finished at the end of August 2020, and the follow-up continues by the end of August 2021. The measurements included demographic, socio-economics, symptoms, health service diagnosis and treatment, contact history, and psychological variables. The signs improvement, death, length of stay in hospital were considered primary, and impaired pulmonary function and psychotic disorders were considered main secondary outcomes. Moreover, clinical symptoms and respiratory functions are being determined in such follow-ups. Among the first 600 COVID-19 cases, 490 patients with complete information (39% female; the average age of 57±15 years) were analyzed. Seven percent of these patients died. The three main leading causes of admission were: fever (77%), dry cough (73%), and fatigue (69%). The most prevalent comorbidities between COVID-19 patients were hypertension (35%), diabetes (28%), and ischemic heart disease (14%). The percentage of primary composite endpoints (PCEP), defined as death, the use of mechanical ventilation, or admission to an intensive care unit was 18%. The Cox Proportional-Hazards Model for PCEP indicated the following significant risk factors: Oxygen saturation < 80% (HR = 6.3; [CI 95%: 2.5,15.5]), lymphopenia (HR = 3.5; [CI 95%: 2.2,5.5]), Oxygen saturation 80%-90% (HR = 2.5; [CI 95%: 1.1,5.8]), and thrombocytopenia (HR = 1.6; [CI 95%: 1.1,2.5]). This long-term prospective Cohort may support healthcare professionals in the management of resources following this pandemic.

Isolation and Molecular Identification of Leishmania spp. Agents in Patients with Cutaneous Leishmaniasis in Yazd Province, Endemic Region of Central Iran.

BACKGROUND: Cutaneous Leishmaniasis (CL) is a major health problem in many parts of Iran. Many methods have been introduced for detection and identification of Cutaneous Leishmaniasis. The purpose of this study was isolation and molecular identification of Leishmania spp. agents in patients with CL from endemic region of central Iran. In this study, one of the main loci of central Iran named Yazd will be assessed CL identification using PCR-RFLP. METHODS: For this cross-sectional study, sampling was done from 372 suspicious patients with CL who referred to Health Centers of Yazd Province from 2016 to 2017. After collection samples of patients, DNA extraction was done from samples on slides. Genus detection was done using specific primers by PCR. RFLP analysis was done for species identification. RESULTS: Out of 372 samples, 159 samples were positive using PCR based method. Out of 159 samples, 87 (54.7%) L. major and 72 (45.3%) L. tropica were identified using RFLP analysis. The number of lesions in each patient was different but 119 (74.8%) patients showed the number of 1-3 lesions, and more lesions (more than 10 lesions) was showed in 4 (2.5%) person. CONCLUSION: The CL found in Yazd province resulted from L. major and L. tropica as the agents of rural and urban types, respectively. The prevalence of L. major and L. tropica was almost the same. This indicated that control programs could be designed for treatment and vector and reservoir control.

Sequestration inside the yeast vacuole may enhance Helicobacter pylori survival against stressful condition.

Vacuole of eukaryotic cells, beyond intracellular digestion plays additional roles such as storage of nutrients that provide favorable conditions for bacterial survival. In this study, occurrence of H. pylori inside the vacuole of Candida yeast was studied and the role of vacuolating cytotoxin A (VacA) in constructing the vacuole was discussed. One gastric Candida yeast was used for Live/Dead stain and fluorescence in situ hybridization (FISH) with universal bacterial probe. Yeast total DNA was used for amplification of full-length bacterial 16S rDNA as well as H. pylori-specific 16S rDNA and vacA alleles. Vacuoles were isolated from yeast cells and stained with fluorescent yeast vacuole membrane marker MDY-64. DNA extracted from vacuoles was used for amplification of H. pylori-specific 16S rDNA. Fluorescent microscopy showed occurrence of viable bacteria inside the vacuole of intact Candida yeast cells. FISH showed intracellular bacteria as fluorescent spots inside the vacuole of mother and daughter yeast cells, suggesting bacterial transmission to next generations of yeast. Sequencing of amplified products of bacterial 16S rDNA and amplification of H. pylori 16S rDNA and vacA confirmed the identity of intracellular bacteria as H. pylori. Isolated vacuoles were stained with membrane-specific marker and H. pylori 16S rDNA was amplified from their DNA content. Results of this study suggest yeast vacuole as a specialized niche for H. pylori. It appears that sequestration inside the vacuole may enhance bacterial survival.

Turbulent Drag Reduction by a Near Wall Surface Tension Active Interface.

In this work we study the turbulence modulation in a viscosity-stratified two-phase flow using Direct Numerical Simulation (DNS) of turbulence and the Phase Field Method (PFM) to simulate the interfacial phenomena. Specifically we consider the case of two immiscible fluid layers driven in a closed rectangular channel by an imposed mean pressure gradient. The present problem, which may mimic the behaviour of an oil flowing under a thin layer of different oil, thickness ratio h2/h1 = 9, is described by three main flow parameters: the shear Reynolds number Reτ (which quantifies the importance of inertia compared to viscous effects), the Weber number We (which quantifies surface tension effects) and the viscosity ratio λ = ν1/ν2 between the two fluids. For this first study, the density ratio of the two fluid layers is the same (ρ2 = ρ1), we keep Reτ and We constant, but we consider three different values for the viscosity ratio: λ = 1, λ = 0.875 and λ = 0.75. Compared to a single phase flow at the same shear Reynolds number (Reτ = 100), in the two phase flow case we observe a decrease of the wall-shear stress and a strong turbulence modulation in particular in the proximity of the interface. Interestingly, we observe that the modulation of turbulence by the liquid-liquid interface extends up to the top wall (i.e. the closest to the interface) and produces local shear stress inversions and flow recirculation regions. The observed results depend primarily on the interface deformability and on the viscosity ratio between the two fluids (λ).

Effect of Aerobic Exercise on Morphine Self-administration and Pain Modulation in Rats.

BACKGROUND: Exercise reverses retention deficit induced by morphine. The present study investigated the effect of aerobic exercise on tolerance to morphine usage and pain modulation. MATERIALS AND METHODS: Male Wistar rats were divided into four groups as follows: (1) saline group (S), (2) morphine group (M), (3) saline + exercise (S + E), and (4) morphine + exercise group (M + E). The rats were initially trained to receive small pellets of food by pressing an active lever in the self-administration apparatus. The tail-flick and hot-plate tests were used for pain assessment. To perform the experiment, the jugular vein was exposed and cannulated. After recovery, the animals were placed in the self-administration apparatus and allowed to self-administer morphine in 2 h sessions over 11 consecutive days. RESULTS: The morphine group was found to record a higher number of active lever pressings than did the saline one while this parameter decreased in the morphine + exercise group compared with the morphine one. Moreover, the morphine + exercise exhibited lowered pain sensitivity as evidenced to have reduced morphine use in the hot plate test. CONCLUSION: The exercise might be suggested to reduce using of morphine and modulate pain probably through the release of endogenous opioid.

Usefulness of Danaparoid sodium in patients with Heparin-induced thrombocytopenia after cardiac surgery.

OBJECTIVE: Thrombocytopenia is a common problem in cardiovascular surgery patients. However, heparin-induced thrombocytopenia (HIT) is a rare but life-threatening complication of prophylaxis or treatment with heparin. Prompt management of HIT with an alternative anticoagulant is necessary due to the extreme risk of thrombotic complications. Therefore, we evaluated the effects of danaparoid in the treatment of HIT in patients with cardiac surgery who are at moderate to high risk of HIT. METHODS: A prospective observational study involving 418 postcardiac surgery patients who received unfractionated heparin and low-molecular weight heparin was conducted in an educational tertiary cardiac care hospital in Iran. All patients were assessed for HIT type II based on thrombocytopenia and pretest clinical scoring system, the "4T's" score. HIT patients were treated with 1500-2500 units intravenous bolus danaparoid sodium followed by 200-400 units/h for a mean of 5 days. Successful response to danaparoid therapy, defined as augmentation in platelet count and improvement of thrombotic events was assessed in all patients treated with danaparoid. FINDINGS: According to pretest clinical score (4T's), the probability of HIT was high in 14 (3.3%) patients and intermediate in three ones (0.7%). 15 patients with HIT were treated with danaparoid. One death occurred in danaparoid-treated group due to persistent thrombocytopenia. The rest of patients were treated successfully with danaparoid without any major thrombotic complication. CONCLUSION: According to our data and the previous studies', HIT can be managed prosperously with danaparoid in postcardiac surgery patients. However, with the absence of any increase in platelet count after 3-5 days of danaparoid therapy and/or the occurrence of a new thrombotic event, danaparoid cross-reactivity with heparin should be suspected.