Human placenta-derived mesenchymal stem cells transplantation in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 (phase I clinical trial): safety profile assessment.

BACKGROUND: High morbidity and mortality rates of the COVID-19 pandemic have made it a global health priority. Acute respiratory distress syndrome (ARDS) is one of the most important causes of death in COVID-19 patients. Mesenchymal stem cells have been the subject of many clinical trials for the treatment of ARDS because of their immunomodulatory, anti-inflammatory, and regenerative potentials. The aim of this phase I clinical trial was the safety assessment of allogeneic placenta-derived mesenchymal stem cells (PL-MSCs) intravenous injection in patients with ARDS induced by COVID-19. METHODS: We enrolled 20 patients suffering from ARDS caused by COVID-19 who had been admitted to the intensive care unit. PL-MSCs were isolated and propagated using a xeno-free/GMP compliant protocol. Each patient in the treatment group (N = 10) received standard treatment and a single dose of 1 × 106 cells/kg PL-MSCs intravenously. The control groups (N = 10) only received the standard treatment. Clinical signs and laboratory tests were evaluated in all participants at the baseline and during 28 days follow-ups. RESULTS: No adverse events were observed in the PL-MSC group. Mean length of hospitalization, serum oxygen saturation, and other clinical and laboratory parameters were not significantly different in the two groups (p > 0.05). CONCLUSION: Our results demonstrated that intravenous administration of PL-MSCs in patients with COVID-19 related ARDS is safe and feasible. Further studies whit higher cell doses and repeated injections are needed to evaluate the efficacy of this treatment modality. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT); IRCT20200621047859N4. Registered 1 March 2021, https://en.irct.ir/trial/52947 .

Predictors of short-term mortality after acute stroke in East Azerbaijan province, 2014.

Introduction: Stroke is one of the important causes of death and disability in Iran. This study aimed to examine the factors influencing the short-term mortality of stroke in Northwest of Iran. Methods: Study population were all patients with confirming the diagnosis of the first-ever stroke who were hospitalized in two referral teaching hospitals from October 2013 to March 2015. They were followed up to 30 days after onset of stroke. A neurology year three resident was responsible for extracting the clinical data and assessment of stroke severity on admission using National Institute of Health Stroke Scale (NIHSS), and information about risk factors and socio-demographic factors were collected using face to face interview. Data were analysed using Cox proportional regression by STATA software version 14. Results: A total of 1036 consecutive patients with first-ever stroke were included in this study. Of them, 228 patients (22%) died within 30 days after stroke accordance. Advanced age was significantly associated with a hazard for early mortality (HR=1.05 95% CI 1.09-1.04), the inverse was true for education level; mortality decreased as the education level increased; it was 25.7 percent among illiterate and 14.3 among patients with higher education. The NIHSS score on admission for 30-days mortality and hemorrhagic stroke were associated with HR=1.11 (95% CI 1.09-1.13) and HR= 1.65 (95% CI 1.15-2.36) respectively. Conclusion: Advanced age, stroke subtype and high NIHSS score are the independent predictors of early mortality in this study. This provides important implications for the clinicians to target the high-risk patients for the specific therapies and management strategies.

Effects of A 4-Week Aerobic Exercise on Lipid Profile and Expression of LXRα in Rat Liver.

OBJECTIVE: Liver X receptors (LXRs) are ligand-activated transcription factors of the nuclear hormonal receptor superfamily which modulate the expression of genes involved in cholesterol homeostasis. Hence, further unraveling of the molecular function of this gene may be helpful in preventing cardiovascular diseases. MATERIALS AND METHODS: This experimental intervention study included twelve adult Wistar male rats (12-14 weeks old, 200-220 g) which were divided into the control (n=6) and training (n=6) groups. The training group received exercise on a motor-driven treadmill at 28 meters/minute (0% grade) for 60 minutes a day, 5 days a week for 4 weeks. Rats were sacrificed 24 hours after the last session of exercise. A portion of the liver was excised, immediately washed in ice-cold saline and frozen in liquid nitrogen for extraction of total RNA. Plasma was collected for high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and triglycerides (TG) measurements. All variables were compared by independent t test. RESULTS: A significant increase in LXRα transcript level was observed in trained rats (P<0.01). Plasma HDL-C concentration was also significantly higher (P<0.01) in trained rats. There was a significant decrease in the concentrations of LDL-C (P<0.01) and TC (P<0.02), and the ratios of TC/HDL-C (P<0.001) and LDL/HDL-C (P<0.002) in trained rats. However, the TG concentration was unchanged (P>0.05). CONCLUSION: We found that endurance training induces significant elevation in LXRα gene expression and plasma HDL-C concentration resulting in depletion of the cellular cholesterol. Therefore, it seems that a contributor to the positive effects of exercise in cardiovascular disease prevention is through the expression of LXRα, which is a key step in reverse cholesterol transport.

Concurrent atypical diffused tuberculosis and macrorhabdosis in a canary (Serinus canaria).

A dead canary from a mixed species zoological garden was presented for diagnostic necropsy. Cachexia with prominent atrophy of pectoral muscles, yellowish brown discoloration of the liver and kidney, dark brown to black intestinal contents and moderate proventricular dilatation with some degree of catarrhal gastritis were the significant macroscopic findings. Parenchymatous organs like the liver, the spleen, the lung and the kidneys were extremely affected by massive diffuse necrosis and heavy infiltration of mononuclear inflammatory cells, histopathologically. Many giant bacilli resembling Macrorrhabdus ornithogaster were seen microscopically in the wet smear of the isthmus mucosa. Ghost-like unstained bacilli were revealed in the Giemsa stained contact smears of the liver and spleen. No typical mycobacterial granulomatous lesion was found in different tissues, but in Ziehl-Neelsen stained thin layer histologic sections from the liver, spleen, lung and kidney, numerous acid fast organisms were diffusely distributed. The case was diagnosed an atypical avian tuberculosis with concurrent macrorhabdosis. Mycobacterium sp. are capable of giving rise to a progressive disease in humans, especially in immunocompromised individuals. Cases of avian tuberculosis might be overlooked for lack of pathognomonic lesions suggestive of mycobacteriosis.

Electrodiagnostic evaluation of peripheral nervous system changes in patients with multiple sclerosis.

BACKGROUND: There is supportive evidence that multiple sclerosis (MS) could potentially affect the peripheral nervous system. We assessed peripheral sensory and motor nerve involvement in patients with MS by a nerve conduction velocity test. METHODS: We studied 75 patients who had a relapsing-remitting or secondary progressive pattern. We measured amplitude, latency, conduction velocity, Hoffmann reflex (H-Reflex), and F-Waves. RESULTS: The amplitude of the right tibial, right proneal, left tibial, left proneal, and left median motor nerves was less than the mean for the normal population. Right ulnar sensory conduction in the patients showed an amplitude that was less than that of the normal population; there was no significant change in the amplitude of other sensory nerves. Latencies of the right and left median and right proneal motor nerves and left ulnar sensory nerves were statistically less than that of the normal population. Mean motor conduction velocity and F-wave conduction did not differ significantly from the normal population. H-reflex latencies of the right and left lower limbs were significantly more prolonged than those of the normal population. CONCLUSION: Our results suggest possible peripheral motor nerve abnormalities in MS patients, especially with the amplitude of the motor nerves; however, our results do not demonstrate any significant difference among the nerve conduction velocity parameters of sensory nerves between MS patients and the normal population.

Endurance training enhances LXRα gene expression in Wistar male rats.

Liver X receptor α (LXRα) is a member of the ligand-activated transcription factor of nuclear hormonal receptor superfamily, whose activation leads to modulation in the expression of genes involved in cholesterol homeostasis including ATP-binding cassette transporter A1 (ABCA1), which plays a crucial role in plasma high-density lipoprotein cholesterol (HDL-C) remodeling. The purpose of this study was to investigate whether endurance training enhanced the expression level of liver LXRα gene. Twelve adult male Wistar rats (200-220 g) were divided into control and training groups. Training group received exercise on a motor-driven treadmill at 28 m/min (0 % grade) for 60 min/day, 5 days/week for 8 weeks. Twenty-four hours after the last exercise session, the rats were killed and blood was taken from the right ventricle of each rat. Plasma was collected for HDL-C, low-density lipoprotein cholesterol (LDL-C), TC and TG measurements. Furthermore, a portion of the liver of each rat was excised and washed in ice-cold saline and frozen in liquid nitrogen for assessment of LXRα and ABCA1 mRNA levels. Data indicated significant increase in both LXRα and ABCA1 mRNA levels in trained rats, compared to control rats. Plasma HDL-C concentration was significantly higher (P < 0.001) in trained rats at the end of treadmill exercise. However, there was a significant decrease in LDL-C (P < 0.003), TG, TC concentration, TC/HDL-C and LDL/HDL-C ratios in trained rats compared with those in the control group (P < 0.001). In conclusion, we found that endurance training induced significant elevation in LXRα gene expression, which correlated with enhanced levels of ABCA1 mRNA and plasma HDL-C concentration.

Proprotein convertases 1 and 2 (PC1 and PC2) are expressed in neurally differentiated rat bone marrow stromal stem cells (BMSCs).

Neural-like cells derived from bone marrow stromal stem cells (BMSCs) have potential usefulness in cell therapy of degenerative or traumatic diseases of the central nervous system (CNS). The functional recovery mediated by these cells, however, depends on the secretion of neurotrophins (NTs) and their cognate receptors, as the main regulators of neural survival and death. The function of NTs is further modulated by proprotein convertase (PC) enzymes which function in converting proproteins (including proNTs) into their functional end products. Accordingly, failure in converting proprotein forms of NTs into their mature forms may lead to neuronal cell death. In the present study, we have investigated the expression profile of PCs before and during neural differentiation of rat BMSCs by RT-PCR. Our results show that major members of the PC family functioning in the constitutive secretory pathway (furin, PACE4 and PC7/LPC) are highly expressed in both undifferentiated and neurally differentiated BMSCs. In contrast, while PC1/PC3 and PC2 (specific to neural and endocrine cells) are absent in undifferentiated BMSCs, their expression is initiated upon the induction of differentiation. In conclusion, our results suggest that neurally differentiated BMSCs have acquired the functional machinery to process the precursor forms of proteins in both the constitutive and regulated pathways.

Early effects of burning rice farm residues on respiratory symptoms of villagers in suburbs of Isfahan, Iran.

Villagers residing in areas with rice farms are exposed to smoke from burning of agricultural waste that may affect respiratory health. To assess respiratory effects of this smoke-induced air pollution, a cross-sectional study has been conducted in three randomly selected villages of Isfahan rural areas. A physician-administered health questionnaire was completed for 433 male and 561 female villagers aged 1-80 years, followed by physical examinations and spirometry in symptomatic cases, before and after a rice burning episode in October 2000. Total particulate and respirable particulate maters (PM 10 was doubled during burning episode. Prevalence rates for respiratory symptoms before smoke were: recent asthma attacks (7.7%), using asthma medications (3%), sleep disturbed by dyspnea and cough (7.4%), exercise-induced cough (13.3%), which increased to 9.5, 7.1, 9.3 and 17%, respectively. Mean initial values (as percent of prediction) for; FEV1, FEV1/FVC, PEFR, and FEF25-75 were: 85.9 +/- 22.7, 81.7 +/- 8, 86.2 +/- 26.2 and 60 +/- 26.4, respectively. The mentioned values decreased to to 83.2 +/- 19.5, 76.5 +/- 10.3, 85.5 +/- 21.1 and 54.3 +/- 26.4, respectively. All of the clinical and spirometric changes were statistically significant. Study findings suggest increased respiratory morbidity associated with rice burning episodes among all people living in the area.

Indoor women jobs and pulmonary risks in rural areas of Isfahan, Iran, 2000.

The prevalence rate of chronic airway's diseases in women and associated risk factors in developing countries are not well clarified. We evaluated the role of indoor duties in the prevalence of asthma, chronic bronchitis, and related symptoms among females in Isfahan suburbs. In three randomly selected villages, 561 responder females (response rate=95.25%) were evaluated through medical interview and physical examinations. Symptoms, signs, occupational and smoking histories, indoor and farming duties, possible outdoor jobs, housing and farming conditions were assessed. The observed respiratory morbidities were: current asthma (11.2%), history of asthma (1.3%), using asthma medications in life (15.2%), chronic bronchitis (3.4%), exercise-induced dyspnea and/or cough (16.2%), and frequent night coughs and/or dyspnea (15.3%). Age, childhood pulmonary infection, bread baking, carpet weaving and using biomass fuels were significant risk factors for all the pulmonary morbidities (P<0.05 to <0.001). Poultry feeding, using kerosene and gas fuels, were less strong risk factors for asthma and chronic bronchitis, respectively Only seven women were current or ex-smokers. Indoor respirable particulate matters were two to four folds more concentrated than outdoors. Women doing indoor jobs in Iran are potential risk factors for development of chronic obstructive pulmonary disease.