فهرست مطالب

Journal of Advances in Medical and Biomedical Research
Volume:31 Issue: 144, Jan-Feb 2023

  • تاریخ انتشار: 1401/11/08
  • تعداد عناوین: 15
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  • Nasrin Amiri Dashatan, Marzieh Ashrafmansouri, Mehdi Koushki, Nayebali Ahmadi* Pages 1-13
    Background and Objective

     Leishmaniasis is among the seven more significant tropical diseases, and it is a major global health issue with a wide range of clinical symptoms and potentially lethal consequences. Resveratrol and its derivatives have been shown to have anti-Leishmanial properties. This study aimed to use a meta-analysis of relevant papers to determine the leishmanicidal impact of resveratrol and its derivatives.

    Materials and Methods

     A comprehensive search method was used to query the electronic databases of PubMed, ScienceDirect, Embase, ISI Web of Science, and Scopus up until June 2021. The articles that met the inclusion criteria were chosen. Random-effects models were used to calculate mean differences in IC50 (concentration corresponding to a 50% reduction in Leishmania) for each outcome. The Newcastle-Ottawa Scale was used to assess the quality of the evidence. To assess heterogeneity and the stability of the pooled data, sensitivity and subgroup analyses were performed. The Egger's and Begg's tests were used to assess publication bias.

    Results

     In the meta-analysis, nine studies were considered. Resveratrol (RSV) and its derivatives significantly reduced survivability in Leishmania promastigote [24.02 mg/ml; (95% CI 17.1, 30.8); P<0.05; I2 = 99.8%; P Heterogeneity = 0.00] and amastigote [18.3 mg/ml; (95% CI 13.5, 23.2); P<0.05; I2 = 99.6%; P Heterogeneity= 0.00]. The meta-analysis revealed a considerable publication bias. Sensitivity analyses revealed that the effect magnitude was similar, but the heterogeneity was reduced. According to subgroup analysis, the pooled effect sizes of leishmanicidal resveratrol and its derivatives were altered by the kind of stilbenes and Leishmania species.

    Conclusion

     According to the findings of this meta-analysis, RSV and its derivatives could be a possible therapeutic option for leishmaniasis. However, more research is needed to confirm and employ this chemical against Leishmania.

    Keywords: Resveratrol, Stilbenes derivatives, Leishmania, Leishmaniasis, Meta-analysis
  • Zahra Nasehi, MohammadEsmaeil Shahaboddin, Sadegh Jafarnejad* Pages 14-24
    Background and Objective

     It has been reported that allopathic drugs do not have significant effects on diabetes treatment. In contemporary literature, much attention has been given to the potential use of traditional medicines, including medicinal plants, in the treatment of metabolic abnormalities. Indeed, the effect of Securigera securidaca, as a medicinal agent, in alleviating the complications of diabetes has received marked attention, particularly in animal models. The aim of this review is to clarify the S.securidaca therapeutic effects in diabetes mellitus treatment based on animal research.

    Materials and Methods

     PubMed, Google Scholar, and the Web of Science were searched, from inception to January 2020 to investigate the effects of S.securidaca on diabetes in animal models. Each article was critically rewired for its methodological quality using the CAMARADE tool.

    Results

     Thirteen articles were reviewed and some positive effects of S.securidaca were observed in alloxan and Streptozotocin-induced diabetic animals. With a closer look at the mechanisms, S.securidaca is comparable with current antidiabetic drugs. The results of animal trials indicated hypoglycemic effects of S.securidaca in animal models.

    Conclusion

     Remedies like S.securidaca could count as a treatment option for diabetic patients, alongside current antidiabetic medications, yet with fewer side-effects.

    Keywords: Securidaca, Diabetes Mellitus, Hypoglycemic Agents, Herbal Medicine
  • Amin Rezaei, Seyed Sirvan Hosseini, Shahryar Khosravi, Mohammadreza Kosarimoghadam, Behnam Amirpour Najafabadi, Mohammad Karim Golnari* Pages 25-31
    Background and Objective

     Cerebral palsy is a non-progressive disorder of posture and motor status caused by various factors and can cause childhood disabilities and abnormalities like flat foot deformity. Kinesio Taping is a typical technique that helps relieve pain, relax muscles, and increase proprioception. The purpose of this study was to evaluate the effectiveness of Kinesio Taping on the plantar arch index in children with diplegic cerebral palsy.

    Materials and Methods

     This randomized clinical trial study was performed on 20 children with spastic diplegic cerebral palsy aged 2 to 6 years in Zanjan-Iran rehabilitation centers. The children were examined in separate intervention and control groups. In the control group, common flat foot exercises were performed. In contrast, in the intervention group, the Kinesio Taping method was used in addition to the mentioned exercises, and finally, the data were analyzed. Paired samples T-Test and Independent T-Test were used to determine the effect of Kinesio Taping in reducing flat feet.

    Results

     After statistical analysis, it was found that, although both groups showed significant results in their plantar arch indexes, the intervention group's results seemed more effective (p<0.05).

    Conclusion

     Kinesio taping can be a safe, inexpensive, and accessible method to manage flat feet complications in children with diplegic cerebral palsy.

    Keywords: Flatfoot, Kinesio Taping, Cerebral palsy
  • Soleiman Gharanjik, Morteza Motedayen, Reza Hasanzadeh Makoui, Nima Motamed, Minoo Emami, Armin Bordbar, MohammadReza Jamshidi, Reza Madadi* Pages 32-39
    Background and Objective

     Acute myocardial infarction (MI) is caused due to coronary artery occlusion and divided into two forms of ST-elevation (STEMI) and non-ST-elevation (NSTEMI) myocardial infarction. This study aimed to determine the success rate of treatment with primary PCI (percutaneous coronary intervention) versus thrombolysis in the establishment of perfusion and to evaluate the short-term complications caused by each method.

    Materials and Methods

     In this prospective cohort study, 90 patients were selected for primary PCI treatment and 90 patients for thrombolytic treatment. Clinical data and basic demographic characteristics of the patients and cardiovascular risk factors were recorded. The success rate of coronary reperfusion by primary PCI and thrombolytic therapy was then determined by angiography and 90-minute ECG with resolution or improvement of chest pain. All patients were examined for any serious complications such as cerebrovascular accidents, shock, and heart failure for 30 days after treatment. Data were analyzed using SPSS ver. 20.

    Results

     In the primary PCI group, 75.6% of the patients were males, and 24.4% were females, but in the thrombolytic group, 76.6% and 23.3% of the cases were males and females, respectively. The mean door-to-balloon time for PCI was 63.60 ± 23.92 and was 53.70 ±21.52 min in the thrombolytic group. Thrombolysis in myocardial infarction (TIMI) flow grade III and TIMI-II were the most frequent in primary PCI and thrombolytic groups, respectively. The odds ratio (OD) of mechanical MI and major arrhythmia in patients received the primary PCI compared to those received thrombolytic therapy was 0.24 and 0.66, respectively. Also, the OD of mortality in the primary PCI group was 2.12.

    Conclusion

     Our findings suggest that in STEMI patients, the chances of short-term complications such as post-MI mechanical complications, major arrhythmia, and bleeding requiring blood transfusion were lower in patients who were treated with primary PCI than those who received thrombolytic treatment. Also, the average hospitalization in CCU and hospital in the primary PCI group was lower than the thrombolytic group.

    Keywords: Primary PCI, Thrombolytic, Fibrinolysis, ST-Elevation Myocardial Infarction (STEMI)
  • Hamidreza Mehdizadeh, Zahra Bahari, Shahin Zekriamir, Hassan Shahriary, MohammadJavad Behzadnia* Pages 40-45
    Background and Objective

     Patients suffering from cardiac arrest (CA) have poor prognosis and survival. The association of pre-arrest comorbidity with unsuccessful resuscitation in patients with CA is far from clear. The aim of the present study was to investigate the association between pre-existing comorbidity and unsuccessful resuscitation following CA in Iranian patients.

    Materials and Methods

     Data of all the patients with CA (1320 patients) who were admitted to Baqiyatallah Hospital (Tehran, Iran), and underwent cardiopulmonary resuscitation (CPR) from 2018 to 2020 were retrospectively reviewed. We analyzed the association of comorbidity data with the mortality rate and unsuccessful CPR.

    Results

     In the present study, 794 (60.2%) patients were female. Most CAs occurred in the hospital (1289). The case fatality rate (CFR) of CA was 69.92%. Additionally, of the 1320 patients, CPR was unsuccessful in 1271 (96.3%) patients. Our data analysis revealed that gender had no significant relationship with the mortality rate and unsuccessful CPR. However, age was significantly associated with mortality, but not with unsuccessful CPR. CA, respiratory distress, and impaired consciousness were significantly associated with mortality. Furthermore, cardiomyopathy, coronary artery bypass grafting (CABG), renal disease (P=0.032), and poisoning had a significant correlation with mortality. In addition, CABG and congestive heart failure (CHF) were significantly correlated with the unsuccessful CPR.

    Conclusion

     The present study suggested that CABG and CHF had a significant relationship with unsuccessful resuscitation. Furthermore, cardiomyopathy, CABG, renal disease, and poisoning were significantly associated with mortality.

    Keywords: Cardiac arrest, CPR, Comorbidity
  • Zhaleh Karimi Moghaddam, Samaneh Karimkhanilouei, Golnaz Asaadi Tehrani* Pages 46-56
    Background and Objective

     Breast cancer is the second leading cause of cancer-related death in women. Better individualized treatment needs novel prognostic predictors. X-ray repair cross complementing XRCC5 and XRCC6 are coding genes of the Ku protein complex (key components of the non-homologous end-joining [NHEJ] pathway), which could serve as prognostic factors in breast cancer. Hence, in this study, the association of XRCC5 (coding the Ku70 subunit) and XRCC6 (coding the Ku80 subunit) single polymorphisms with the risk of metastatic breast cancer was assessed.

    Materials and Methods

     This study included 30 breast cancer patients and 30 age-matched healthy women. Tetra-Arms polymerase chain reaction (PCR) and high-resolution melt (HRM) real-time PCR were performed to determine XRCC5 (variable number tandem repeat [VNTR] polymorphism, rs6147172) and XRCC6 (rs132793) polymorphisms, respectively. Demographical and clinical tumor status was recorded for all women. Allele frequencies and related genotypes were identified.

    Results

     Our results indicated that 34% of patients receiving chemotherapy had metastases in other organs, mostly in the lung. The frequencies of 0R/0R, 1R/1R, 2R/2R, and 1R/R genotypes in the XRCC5 gene were 6.6%, 63.3%, 6.6%, and 23.3%, respectively. No significant association was found between XRCC5 and metastatic breast cancer (P = 0.426). In addition, the XRCC5 polymorphism was associated with progesterone (P = 0.068), as well as the time interval between chemotherapy and relapse (P = 0.069). The frequency of AA, GG, and AG genotypes in XRCC6 were 0%, 33.3%, and 66.7%, respectively. The XRCC6 polymorphism was associated with cancer metastasis. There was a significant relationship between age (P = 0.048) and family history (P = 0.020) with cancer incidence. A significant association was observed between the XRCC6 polymorphism with human epithelial receptor 2 (HER2; P = 0.070) and radiotherapy sessions (P = 0.007).

    Conclusion

     We speculate that the genetic variation of the XRCC6 gene (rs132793 SNP) might be considered as a diagnostic biomarker in breast cancer, but further studies are necessary to confirm the results.

    Keywords: Breast cancer, Metastasis, Polymorphism, XRCC5, XRCC6
  • Iraj Shahramian, Pouya Ostadrahimi, Mahboobeh Sheikh, Somayeh Nazari, Hadi Mirzarie, Abdolvahab Moradi, Alireza Aminisefat, Ali Bazi, Feteme Parooie*, Masoud Tahani Pages 57-63
    Background and Objective

     Since the distribution of HBV genotypes in patients with hepatitis B indicates the predominant genotypes in specific geographical area, this study aimed to investigate the prevalence of S gene mutations in high-risk children with maternal HBV in southeastern Iran.

    Materials and Methods

     This cross-sectional prospective study was performed from March 2019 to March 2020. We studied 26 patients infected with hepatitis B virus through vertical route. Serological markers of HBV were tested for HBs Ag, anti-HBs, HBe Ag, anti-HBe, and anti-HBc through ELISA. HBV-positive DNA-HBV samples were examined by nested PCR. The correlation between categorical variables was estimated using Spearmen correlation coefficient.  All statistical analyses were performed using SPSS version 22 software.

    Results

     Our study showed that no S gene mutation occurred in studied children. However, 4 (15.4%) of the children were HBe Ag positive, while the frequency of positive HBe antibody positive in the serum of children was 18 (69.2%).

    Conclusion

     In general, since different types of Pre-S / S variants are predominantly identified in patients with chronic HBV that can affect the progression of liver disease, it is therefore necessary to evaluate the types of Pre-S / S variants regularly in HBV. Carriers should be identified to help discover people at higher risk for liver disease. Our study, as a single center study in southeastern Iran, indicated no mutation in this gene in hepatitis B patients.

    Keywords: Mutation, Hepatitis B, HBV, Children
  • Mahvash Ghorbani, Alireza Mahmoudian*, Seyyed Meysam Abtahi Froushani, Abdolghaffar Ownagh, Amir Tokmahchi Pages 64-72
    Background and Objective

     Ulcerative colitis (UC) is an unknown recurrent intestinal disease and a common cause of gastrointestinal disorders, which may lead to colorectal cancer if not diagnosed and treated in a timely manner. The beneficial effects of several probiotics in diseases like inflammatory bowel disease (IBD) have been investigated, although their mechanisms have not been yet fully understood. In this study, we investigated the possible association between the changes in the levels of the expression of miRNAs and the anti-inflammatory activity of the L. acidophilus as a probiotic model in Wistar rats suffering the acid-induced UC.

    Materials and Methods

     Twenty rats were randomly divided into four groups. To induce colitis, the rats were briefly anesthetized, and 1 ml of acetic acid (4%) was injected into their rectum using a Foley catheter, as explained previously.  L. acidophilus was given orally (3×108 CCU/ml) for 10 days. The rats were monitored daily for clinical signs for 10 days. Following euthanasia, the macroscopic and microscopic pathological lesions in the intestinal tissues were examined. Additionally, the total RNA from specimens were extracted, and the expression levels of mRNAs for cytokines, including TNFα, IL-1β, IL-6, IL-10, IFN-γ, and the expression levels of miR-1, miR-155, miR-let7d, and miR-99a were determined using the qPCR method.

    Results

     The clinical signs and pathological damages induced by acid were ameliorated in the rats receiving L. acidophilus compared with rats that did not receive it, as evidenced by improved clinical signs and results of immunohistochemistry and chemical assays. miRNAs, including miR-1, miR-99, miR-Let7d and miR-155 and changes in the expression of mRNAs, including TNFα, IL-1β, IL-6, IL-10 and IFN-γ were significant. Changes in the amount of myeloperoxidase, nitrite oxide, and malondialdehyde were also significant (P ≤ 0.05). In pathological examination, immune cell infiltration and COX2 were different in colitis and treatment groups.

    Conclusion

     Therapeutic use of probiotics ameliorated UC by significantly changing the levels of miR-1, miR-99, miR-Let7d and miR-155.

    Keywords: Lactobacillus acidophilus, MicroRNA, Ulcerative colitis
  • Fariba Mahmoodpoor, Seyed Hojjat Hosseini, Elham Ahmadian, Mohammadreza Ardalan, Koorosh Kamali, Sepideh Zununi Vahed, Saeed Sardari, Narjes Khavasi* Pages 73-79
    Background and Objective

     Increment in cancer prevalence and subsequent need for chemotherapy leads to distinct kidney-related diseases such as acute kidney injury (AKI). Cisplatin is a common chemotherapeutic agent that has been used in many cancers; however, it can damage renal cells. Capparis spinosa is an important therapeutic plant in Persian medicine that encompasses high amounts of bioactive antioxidant components. The current study aimed to evaluate the nephroprotective effects of Capparis spinosa seed hydroalcoholic extract (CSSE) against cisplatin-induced nephrotoxicity in vivo through histopathological evaluation.

    Materials and Methods

     Forty Sprague Dawley rats weighing within the range of 230±20 gr were randomly divided into eight groups including sham, a single-dose cisplatin intraperitoneally (IP) injected group (7 mg/kg), toxic dose CSSE (200 mg/kg) group, and groups with cisplatin 7mg/kg IP and different doses of CSSE. Histopathological changes in the kidney tissues were quantified by the image-J program and analyzed by statistical methods.

    Results

     Cisplatin-induced glomerular and tubular injuries in the kidney tissue. A single-dose cisplatin decreased the glomerular area and Bowman's capsule area, increased Bowman's space, and induced tubular loss of brush borders, tubular dilatation, tubular cast formation and tubular necrosis. All of the changes were reversed by CSSE significantly.

    Conclusion

     Post-CSSE (50 and 100 mg/kg) treatment could protect against cisplatin-induced nephrotoxicity in vivo. More clinical studies are needed to confirm its protective effects on the prevention of kidney injury in chemotherapy receiving patients.

    Keywords: Capparis spinosa, Persian Medicine, Pathology, Acute kidney injury, Cisplatin. Cancer
  • Azar Hosseini, Leila Ziaee, Arezoo Rajabian, MohammadTaher Boroushaki* Pages 80-85
    Background and Objective

     Aging is a natural phenomenon which can cause changes in most organs and cells. Numerous mechanisms including oxidative stress and free radical generation is involved in the progression of the aging process. Pomegranate seed oil (PSO), has different therapeutic properties including anti-oxidant and anti-inflammatory effects. In this research, the effect of PSO against D-galactose-induced aging is investigated.

    Materials and Methods

     D-galactose, 500 mg/kg, injected subcutaneously (S.C.) to induce aging in rats. Animals in treatment groups received PSO, 0.4 and 0.8 ml/kg intraperitoneally (i.p.). After 42 days, behavioral test was evaluated by passive avoidance (PA). Then animals killed, blood samples collected by cardiac puncture, and brain and liver removed. Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) measured in serum. Malondialdehyde (MDA) and thiol contents of brain and liver homogenized tissue samples were determined.

    Results

     D-galactose increased lipid-peroxidation in liver and brain tissues as well as elevation of ALT, AST, but the level of thiol contents decreased in homogenized tissues. Both doses of PSO attenuated d-galactose-induced injury in liver and brain by decreasing ALT, AST, MDA and elevation of thiol content. The PA test showed that PSO increased the latency time to enter the dark chamber compared to the control group.

    Conclusion

     PSO decreased D-galactose-induced aging in rats via prevention of oxidative stress. This effect may be related to the presence of various compounds and their anti-oxidant properties, which is found in PSO.

    Keywords: Aging, Lipid peroxidation, Oxidative stress, Punica granatum
  • Parisa Azadfar, Zahra Noormohammadi*, Maryam Noroozian, Akram Eidi, Pejman Mortazavi Pages 86-92
    Background and Objective

     Dysregulation of long-term expression of non-coding RNAs (lncRNAs) has a potential role in progressive brain disorders such as Alzheimer's disease. This study aimed to analyze the apoptosis and expression of 51A and NAT-Rad18 lncRNAs and their target genes in brain tissue and peripheral blood mononuclear cells (PBMCs) of the rat model of AD, before and after memantine treatment.

    Materials and Methods

     Twenty-eight male Wistar rats were divided into four groups: 1. Normal control (n = 4), 2. Sham-operated (n = 4), 3. Alzheimer's control (n = 10), and 4. The experimental group (n = 10) was treated with memantine. The qPCR and TUNEL tests were used to detect the lncRNAs expression and apoptosis.

    Results

     Sorl1 gene was reduced in brain tissue of Alzheimer’s control (p = 0.016) and PBMCs of Alzheimer's control and experimental groups (p = 0.002 and p = 0.001 respectively). The expression of NAT-Rad18 and Rad18 genes increased in brain tissue of Alzheimer's control group (p = 0.002 and p = 0.04 respectively) while reduced in PBMCs of Alzheimer's control and experimental groups (p = 0.005 and p = 0.045 for NAT-Rad18, p = 0.01 and p = 0.006 for Rad18).

    Conclusion

     ROC curve analysis showed 100% sensitivity and 85.7% specificity for the Sorl1 gene with 0.911 under the curve area and 100% sensitivity and 100% specificity for NAT-Rad18 and Rad18, separately with one under the curve area. Decreased expression in Sorl1, NAT-Rad18, and Rad18 genes can be used as blood biomarkers for diagnosis independently. However, studies on Alzheimer's patients are needed.

    Keywords: Alzheimer’s disease, Rat, Biomarker, lncRNA, Memantine
  • Samrad Mehrabi, Alireza Salehi*, Hossein Molavi Vardanjani, Ali Kooshki, Fereshteh Mehrabi Pages 93-99
    Background and Objective

     Chronic obstructive pulmonary disease (COPD) is a common disease that causes 6% of deaths, 90% of which occur in low- and middle-income countries. Improving these patients' quality of life (QOL) is one of the primary treatment goals. The St. George's Respiratory Questionnaire (SGRQ) is used to measure the health status of patients with respiratory problems. This research aimed to assess the health status of patients with COPD after validating the Persian version of this questionnaire.

    Materials and Methods

     The study was performed from Feb to Oct 2016 in Shiraz, Iran. First, the Persian version of the questionnaire was validated using a back-translation technique by two translators, supervised by two researchers, and finally approved by two pulmonologists. The test-retest method was used to investigate the questionnaire's reliability. The questionnaire was used to assess the health status of 158 COPD patients with FEV1/FVC ratio≤ 0.7 or FEV1<80%, without exacerbation, cardiac disease, or recent hospitalization.

    Results

     The reliabilities of the first part (questions 1-7) and second part (questions 8-14) of the questionnaire was 0.64 and 0.90, respectively. The current health was good, fair, poor, and very poor in 7.6%, 22.2%, 44.9%, 22.8%, and 2.5% of the patients, respectively. The mean± standard deviation (SD) scores calculated for symptoms, activity, and impact were 54.216±23.725, 41.477±24.996, and 37.482±26.390, and the total score was 133.176±69.284.

    Conclusion

     The Persian version of the SGRQ-C was valid and reliable. The patients with COPD at our center had a good health status.

    Keywords: Pulmonary Disease, Chronic Obstructive, Quality of Life, St. George Respiratory Questionnaire
  • Seyed Hashem Sezavar, Mahboubeh Pazoki*, Nehzat Akiash, Farzad Dashti, Pegah Joghataie Pages 100-102

    Partial muscular inter-ventricular septal defect (VSD) or Pacman heart is a rare congenital or occasionally acquired anomaly. Concurrent Pacman heart and Shone's complex are extremely rare and have never been reported until now. We described a 37-year-old male patient with congenital Pacman heart, flail mitral valve (FMV), and a history of multiple congenital anomalies, including subvalvular aortic stenosis, bicuspid aortic valve (AV), and coarctation of the aorta compatible with the incomplete form of Shone's complex. Cardiac surgery was not necessary to perform for this anomaly due to the absence of a left-to-right shunt through this partial defect.

    Keywords: Flail mitral leaflet, Congenital heart defects, Bicuspid aortic valve
  • Maryam Arfaatabar, Ghasem Azimi, Ensieh Masoorian, Sareh Bagheri-Josheghani, Maryam Ghobahi, MohammadReza Pourmand* Pages 103-106

    Legionella pneumophila is a thin, aerobic, Gram-negative, pathogenic bacillus and the leading cause of Legionnaires’ disease (LD) in human, especially those with high risk conditions including immune system disorders or chronic lung diseases. The mortality rate of LD has been reported to be 60% or higher in inappropriately treated cases. Investigating the prevalence of L. pneumophila and identifying contaminated sources in hospital settings are essential steps that should be taken to control the disease and evaluate the efficacy of interventional strategies. Currently, the culture method is considered as the “gold standard” for detection of L. pneumophila and  LD diagnosis. In this case report of severe LD in Iran, we studied a 60-year-old male patient with underlying chronic obstructive pulmonary disease (COPD). We also presented the clinical and pathophysiological features of LD as well as its diagnostic and therapeutic methods. The importance of early diagnosis of L. pneumophila infection in patients with COPD is also highlighted.

    Keywords: Legionella pneumophila, Chronic obstructive pulmonary disease, Legionnaires' disease, Pneumonia, Iran
  • Nader Agakhani, Fariba Hosseinzadegan* Pages 107-108

    The health-care system should be ready to deal with a large number of COVID-19 patients who may require critical care. Patients with severe consequences should have well-rehearsed and structured protocols for quick identification, isolation, triage, and care plans. The higher incidence of metabolic syndrome combined with COVID-19 shows that concurrence of these two disorders, as well as the therapeutic and care issues they cause, should be thoroughly investigated to improve defense against disease along its course and more caution and special supportive care should be taken to avoid future problems.

    Keywords: COVID-19 -Metabolic syndrome-pandemic