SIRT2 inhibition protects against cardiac hypertrophy and ischemic injury.

Sirtuins (SIRT) exhibit deacetylation or ADP-ribosyltransferase activity and regulate a wide range of cellular processes in the nucleus, mitochondria, and cytoplasm. The role of the only sirtuin that resides in the cytoplasm, SIRT2, in the development of ischemic injury and cardiac hypertrophy is not known. In this paper, we show that the hearts of mice with deletion of Sirt2 (Sirt2-/-) display improved cardiac function after ischemia-reperfusion (I/R) and pressure overload (PO), suggesting that SIRT2 exerts maladaptive effects in the heart in response to stress. Similar results were obtained in mice with cardiomyocyte-specific Sirt2 deletion. Mechanistic studies suggest that SIRT2 modulates cellular levels and activity of nuclear factor (erythroid-derived 2)-like 2 (NRF2), which results in reduced expression of antioxidant proteins. Deletion of Nrf2 in the hearts of Sirt2-/- mice reversed protection after PO. Finally, treatment of mouse hearts with a specific SIRT2 inhibitor reduced cardiac size and attenuates cardiac hypertrophy in response to PO. These data indicate that SIRT2 has detrimental effects in the heart and plays a role in cardiac response to injury and the progression of cardiac hypertrophy, which makes this protein a unique member of the SIRT family. Additionally, our studies provide a novel approach for treatment of cardiac hypertrophy and injury by targeting SIRT2 pharmacologically, providing a novel avenue for the treatment of these disorders.

COVID-19 Pandemic Experiences in Pediatric Intensive Care Unit: An Iranian Referral Hospital-Based Study.

Introduction: In late February 2020, after we had informed about the presence of some cases of COVID-19 in Iran and its rapid spread throughout the country, we decided to make the necessary arrangements for patients with critical conditions in Pediatric Intensive Care Unit (PICU) at Children's Medical Center. There are a little data on critically ill children with COVID-19 infection with ICU requirements. The aim of this study was to describe clinical characteristics, laboratory parameters, treatment, and outcomes of the pediatrics population infected by SARS-CoV-2 admitted to PICU. Materials and Methods: This study was performed between February 2020 and May 2020 in the COVID PICU of the Children's Medical Center Hospital in Tehran, Iran. Patients were evaluated in terms of demographic categories, primary symptoms and signs at presentation, underlying disease, SARS-CoV-2 RT-PCR test result, laboratory findings at PICU admission, chest X-ray (CXR) and lung CT findings, and treatment. Moreover, the need to noninvasive ventilation (NIV) or mechanical ventilation, the length of hospital stay in the PICU, and outcomes were assessed. Results: In total, 99 patients were admitted to COVID PICU, 42.4% (42 patients) were males, and 66 patients had positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction (RT-PCR). There was no statistically significant difference in the frequency of clinical signs and symptoms (except for fever) among patients with positive SARS-CoV-2 RT-PCR and negative ones. Among all admitted patients, the presence of underlying diseases was noticed in 81 (82%) patients. Of 99 patients, 34 patients were treated with NIV during their admission. Furthermore, 35 patients were intubated and treated with mechanical ventilation. Unfortunately, 11 out of 35 mechanically ventilated patients (31%) passed away. Conclusion: No laboratory and radiological findings in children infected with COVID-19 were diagnostic in cases with COVID-19 admitted to PICU. There are higher risks of severe COVID-19, PICU admission, and mortality in children with comorbidities.

Renal Involvement in a Child with COVID-19 Infection and its Management with CRRT.

Novel Coronavirus disease (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) presenting mainly as an acute respiratory illness with interstitial and alveolar pneumonia. It can also affect multiple organs such as the kidney, heart, intestinal tract, blood, and nervous system. We report a 10-year-old boy presenting with severe cough, tachypnea, retraction and respiratory distress, fever, myalgia, oliguria, and anuria thereafter. He had no history of diarrhea, vomiting, or a runny nose. Laboratory findings include leukopenia and lymphopenia. CRP, ESR, and procalcitonin levels were high, but serum LDH was normal. RT-PCR test was positive. In the initial days of admission, he needed mechanical ventilation support due to ARDS and received antiviral drugs, renal replacement therapy, hemoperfusion, and other necessary supportive cares. Thirty-five days later, he weaned from the ventilator and discharged from hospital. Two weeks later, COVID-19 specific IgG was found in serologic test.

Current Treatments and Therapeutic Options for COVID-19 Patients: A Systematic Review.

INTRODUCTION: COVID-19 is the third rising epidemic in the 21st century that quickly turned into a worldwide pandemic. Many clinical studies have been achieved to investigate treatments to confront COVID-19. Therefore, we conducted a systematic review to describe the recent treatment strategies to treat COVID-19 patients. METHODS: A systematic search was performed in the databases of PubMed, Scopus, Embase, Science direct, Up to date, and Web of Science using the keywords of Coronavirus, COVID-19, SARS-CoV-2, Novel Coronavirus, 2019-nCoV, Treatment, Medicine, Therapy, Intervention, Drug, Medications, and Cure. All the relevant articles were collected from December 2019 to July 2020. RESULTS: We included 58 studies including 38 articles (eleven reviews, ten editorial documents, three case reports, one mix method, one cohort study), and 19 published clinical trials. Review of studies showed that Lopinavir/Ritonavir (n=16), Remdesivir (n=13), Convalescent plasma (n=11), Chloroquine (n=11), Ribavirin (n=9), Hydroxychloroquine sulfate (n=8), Traditional Chinese Medicine (TCM) (n=8), and Arbidol (n=7), were the most frequently therapies used to treat COVID-19 patients. CONCLUSION: In the absence of definitive treatment protocols, recently proposed approaches have appeared to be an effective therapy for accelerating the recovery of COVID-19 patients. Some of these treatments may have been in the early stages of testing. However, future preclinical and clinical trials are warranted to validate findings.

Improving SDS-PAGE method for monoclonal antibodies: The advantages of Tris-Acetate over Tris-Glycine SDS-PAGE system and comparison with CE-SDS method.

Present study compares two different buffer systems for the electrophoretic separation of the IgG1 and IgG2 Monoclonal Antibodies using SDS-PAGE method. A modified Tris-acetate system was shown to be superior for separation of these proteins in a 6-20% gradient gel as compared with the traditionally used Tris-glycine method. This modified Tris-acetate buffer system showed sharper bands, more accurate determination of molecular weight, higher resolution, and better estimation of sub-fragments with closer results to those obtained by Capillary Gel Electrophoresis. Also in a parallel experiment, effect of IgG deglycosylation by PNGase-F enzyme was investigated and revealed no significant improvement on the SDS-PAGE results.

Epidemiology of HIV in Iran.

Iran has been one of the active countries fighting against HIV/AIDS in the Middle East during the last decades. Moreover, there is a strong push to strengthen the national health management system concerning HIV prevention and control. In Iran, HIV disease has its unique features, from changes in modes of transmission to improvement in treatment and care programs, which can make it a good case for closer scrutiny. The present review describes the HIV epidemic in Iran from the first case diagnosed until prevention among different groups at risk and co-infections. Not only we addressed the key populations and community-based attempts to overcome HIV-related issues in clinics, but we also elaborated on the efforts and trends in society and the actual behaviors related to HIV/AIDS. Being located in the Middle East and North Africa (MENA) region, given the countryspecific characteristics, and despite all the national efforts along with other countries in this region, Iran still needs to take extra measures to reduce HIV transmission, especially in health education. Although Iran is one of the pioneers in implementing applicable and appropriate policies in the MENA region, including harm reduction services to reduce HIV incidence, people with substance use disorder continue to be the majority of those living with HIV in the country. Similar to other countries in this region, the HIV prevention and control programs aim at 90-90-90 targets to eliminate HIV infection and reduce the transmission, especially the mother-to-child transmission and among other key populations.

HIV and risk behaviors among visitors of inmates at the Great Tehran Prison, Iran, 2018.

OBJECTIVES: The objective of the present study was to determine the prevalence of HIV and risk behaviors among the inmates' visitors at the Great Tehran Prison in 2018.This population is more likely to be infected with HIV due to their relationship with inmates. However, they have not been prioritized to the other populations in comparison to inmates who are usually prioritized over others. METHOD: Using a convenient sampling method, we recruited inmates' visitorsat the Great Tehran Prison in 2018. An anonymous questionnaire collected information on the participant's demographic characteristics, relationship withinmate, imprisonment history, drug-related risk behaviors, and HIV-related risk behaviors.Rapid HIV blood test detected HIV positive people. To examine the association between risk behaviors and HIV infection, we used a multivariate logistic regression model to calculate the adjusted Odds Ratio (OR)(adjusted Odds ratio of 23.140, 95% CI OD: 1.994-268.5). RESULTS: 1131 visitors were asked to participate in the study; out of which 1120 consented (99%).Out of the 1120 participants, 55.2% were female, and the majority (72.4%) aged older than 35 years. Of those who had a sexual partner, 50% did not usea condom in the last 6 months. Overall, HIV prevalence was 0.4% in the inmate visitors, but it was significantly higher among those with a history of drug injection(p=0.003). CONCLUSION: Our findings indicated that overall the HIV prevalence is low amonginmates' visitors; Subgroups with a history of injection have high HIV prevalence which needs to beprioritized for HIV screening and treatment.

Drug resistance patterns in HIV patients with virologic failure in Iran.

We reviewed the medical charts of 1,700 patients diagnosed with HIV who referred to a central HIV clinic in Tehran between 2004 and 2017. Participants who had a viral load of > 200 copies/mL after six months or more on antiretroviral therapy (ART) were grouped as virologic failure (VF). We assessed the demographic characteristics, diagnosis date, first ART regimen, and resistance to various ART drugs. Out of 1,700 patients, 72 (4.2%) had a treatment failure. Among those with treatment failure, 51.3% were on zidovudine + lamivudine + efavirenz, 13.9% were on tenofovir + lamivudine + lopinavir/ritonavir, and 12.5% were on tenofovir + emtricitabine + efavirenz. In patients with treatment failure, the highest resistance was to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) combination (44.4%). In these patients, resistance to tenofovir (one of the NRTIs) was 29.1%. The highest treatment failure was observed among patients treated with nevirapine (NVP) and efavirenz (EFV)-based regimen. Our findings suggest that protease inhibitors should be considered as first-line drugs in ART regimens in VF patients in Iran.

Levofloxacin Versus Ceftriaxone and Azithromycin Combination in the Treatment of Community Acquired Pneumonia in Hospitalized Patients.

BACKGROUND: In Asia, an estimated one million deaths are caused by communityacquired pneumonia (CAP) each year. Despite the high mortality in elderly people, a large number of CAP patients have been treated and survived with optimal life expectancy. A few studies have been done on adult CAP therapeutic approaches in Asia. Moreover, differences have been noted between these studies and European data. We aimed to investigate the efficacy of oral Levofloxacin (TAVANEX), 750 mg, once daily for five days versus parenteral Ceftriaxone 1gr BD, plus oral Azithromycin (250 mg, once daily) for seven to ten days (standard regimen) in CAP treatment. MATERIALS AND METHODS: We conducted a prospective randomized trial among 150 patients with CAP in Qaem Hospital of Alborz city from December 2016 to June 2017. A group of CAP patients were randomized in two treatment groups. One group was treated with oral Levofloxacin (TAVANEX), 750 mg, once daily for five days and the other group with parenteral Ceftriaxone 1gr BD plus oral Azithromycin (250 mg, once daily) for seven to ten days (standard regimen). The efficacy and side effects of the assigned drugs were compared between two groups. The probability level for statistical significance was set at P ≤ 0.05. RESULTS: The body temperature (P value=0.09), WBC count (P value=0.15), respiratory sounds (P value=0.18) and admission duration (P value=0.15) showed no significant differences after treatment between two groups. There was no report of hospital mortality, clinical deterioration and antibiotic escalation during hospital admission in both groups of study. In standard regimen group, only two (2.7%) patients had skin rash while in Levofloxacin group one case (1.3%) had skin rash, two patients (2.7%) had gastrointestinal problems and three (4%) patients showed central nervous system (CNS) complications. In both groups, the reticulonodular pattern was more frequently observed in Chest X-ray. Although standard regimen group (n=27, 36%) showed more consolidation than patients in Levofloxacin group (n=22, 29.3%), and the ground glass pattern was observed more in Levofloxacin group. CONCLUSION: We concluded that monotherapy with oral Levofloxacin was as effective as treatment with Ceftriaxone plus Azithromycin combination in patients with CAP who required hospitalization.

Cinnarizine versus Topiramate in Prophylaxis of Migraines among Children and Adolescents: A Randomized, Double-Blind Clinical Trial.

OBJECTIVE: Migraines, a common health problem in children and adolescents, still do not have an FDA approved preventive treatment for patients under the age of 18 years. This study compares and contrasts the efficacy and safety of cinnarizine and topiramate in preventing pediatric migraines. MATERIALS & METHODS: In this randomized, double-blind clinical trial 44 migrainous (from 4-15 years of age) were equally allocated to receive cinnarizine or topiramate. The primary efficacy measure was monthly migraine frequency. Secondary efficacy measures were monthly migraine intensity and ≥ 50% responder rate. Efficacy measures were recorded at the baseline and at 4, 8, and 12 weeks of treatment. RESULTS: During the double-blind phase of the study, monthly migraine frequency and intensity were significantly decreased in both the cinnarizine and topiramate groups when compared to the baseline. However, at the end of the study, the cinnarizine group exhibits a significant decrease from the baseline in the mean monthly migraine intensity when compared to the topiramate group (4.7 vs. 3, respectively; 95% CI = -0.8 to -3.2). CONCLUSION: No significant difference between cinnarizine and topiramate was found for the prevention of pediatric migraines. Both treatments were well tolerated.