Investigation of Epstein-Barr virus, Cytomegalovirus, Human herpesvirus 6, and Polyoma viruses (JC virus, BK virus) among Gastric cancer patients: A cross sectional study.

Background and Aims: Gastric cancer is a significant global issue with a high death rate. This malignancy could be associated with several viral agents such as EBV, CMV, HHV-6, JCV, and BKV. Objective: Evaluation of EBV, CMV, HHV-6 ,and JCV, BKV frequency among gastric cancer patients. Methods: In this cross-sectional study, a total number of 60 gastric cancer specimens (32 male, 28 female) were retrieved from the pathology lab. Formalin-fixed paraffin-embedded tissue was used for molecular testing. DNA was extracted from samples, according to protocol, and used for PCR reaction. Polymerase chain reactions were used to assess CMV, EBV, HHV-6, JCV, and BKV frequency. Results and Conclusion: The mean age of the participants was 61 years and 53.3% (32) of the participants were Male. A total number of 5 samples (8.34%) were infected with viral agents. Four male gastric samples were infected with EBV (6.67%) and only one female sample contained the BKV genome (1.67%). Totally 8.34% of the samples were infected with EBV and BKV. The CMV, HHV-6, and JCV genome was not detected in the samples. In conclusion, the presence of two viral agents including EBV and BKV among male and female samples respectively, and the genome of other viruses were not detected.

NBS superfood: a promising adjunctive therapy in critically ill ICU patients with omicron variant of COVID-19.

This clinical trial aimed to assess the impact of Nutrition Bio-shield superfood (NBS) on clinical status among critically ill ICU patients suffering from acute respiratory distress syndrome (ARDS) due to the Omicron variant of COVID-19. A total of 400 patients with confirmed Omicron-related ARDS were randomly assigned to either the intervention group (n = 200) or the control group (n = 200). Patients in the intervention group received 1.5 g of NBS powder daily for 2 weeks in addition to standard antiviral treatment, while the control group received a placebo alongside standard antiviral therapy. Serum samples were collected from all patients in both groups, and various clinical and laboratory parameters, including ESR, CRP, D-Dimer, CPK, WBC count, lymphocyte count, and lymphocyte percentage, were measured using established methodologies. Following a 14-day intervention period, the intervention group exhibited a significant reduction in mean serum levels of CRP (15.39 vs. 48.49; P < 0.001), ESR (14.28 vs. 34.03; P < 0.001), D-Dimer (485.18 vs. 1009.13; P = 0.001), and CPK (68.93 vs. 131.48; P < 0.001) compared to the control group. Conversely, a significant increase was observed in the mean serum levels of lymphocytes (1537.06 vs. 1152.60; P < 0.001) in the intervention group after 14 days of treatment compared to the control group. The remarkable reduction in inflammatory markers and mortality rates observed with NBS supplementation alongside standard antiviral treatment underscores its crucial role in mitigating inflammation and achieving an important milestone in the fight against COVID-19.

No sign of Rotavirus co-infection in COVID-19 patients with gastrointestinal symptoms.

Background and aims: The main goal of the present study is to investigate the incidence of Rotavirus co-infection in COVID-19 patients. Methods and Results: Fecal samples of COVID-19 patients with gastrointestinal symptoms which had positive PCR- were collected from Abadan's hospital, Iran during the period December 2020 to January 2021. Samples were analyzed by RT-PCR to determine the presence of Rotavirus. Finally, the total samples size of 37 were included in this study. The mean age of patients was 48.22 years. Abdominal pain alone was detected in 48.65% of the patients. At least one gastrointestinal symptom was detected in all of the patients. Diarrhea and fever were seen in 13.51% and 59.46% of patients, respectively. Nausea and vomiting were seen in 5.41% of the patients. RT-PCR showed no infection of Rotavirus among the patients. Conclusion: Gastrointestinal symptoms related to COVID-19 are common. More studies is need among these patients groups for investigate co-infection with other fecal viral shedding carries, due to a worse prognosis and its association with disease severity.

The role of viruses in human acute appendicitis: a systematic literature review.

BACKGROUND: There have been debates about the human appendix function, and while previous research suggested it might be a vestigial organ with no functional significance, recent studies have pointed out that it might have an important role in the immune system. Acute appendicitis (AA) is a common cause of emergency abdominal surgery in the world. Some epidemiologic investigations have found an association between appendicitis and viral infections. In this study, we have reviewed systematically articles to discover viral infections that cause appendicitis and find any possible correlations between the two. METHODS: This systematic review was performed by searching among electronic databases including Web of Science, PubMed, Scopus, and EMBASE on viruses and appendicitis topics. RESULTS: Conducted search leads to 983 results in all databases after the duplicate removal and screening by title, abstract, and full-text based on inclusion criteria lead to 19 studies. There were several assays to detect the viruses, which are thought to be AA causative agents. RT-PCR and immunoassays were the mainstay methods to detect the probable cause. CONCLUSION: Investigations suggested that some viruses including measles virus (MV), influenza virus, dengue fever virus (DFV), human immunodeficiency virus (HIV), human herpesviruses, rotavirus, and adenovirus are associated with acute appendicitis. Despite the available reports, the specific mechanisms behind the relationship between acute appendicitis and viral infections are yet to be understood. Therefore, further investigations are necessary to find out the pathogenesis and pathophysiology of viral complications in appendicitis.

Investigation of the biofilm formation in extra-intestinal pathogenic Escherichia coli ST131 strains and its correlation with the presence of fimH, afa, and kpsMSTII genes.

Escherichia coli sequence type 131 (ST131) is a multidrug-resistant strain with the global dissemination. Biofilm formation-related factors include the most important virulence factors in extra-intestinal pathogenic E. coli (ExPEC) ST131 strains causing infections with treatment-limited subjects. This study aims to investigate the biofilm formation ability and its correlation with the presence of fimH, afa, and kpsMSTII genes in clinical isolates of ExPEC ST131. In this regard, the prevalence and characteristics of these strains collected and evaluated. The results revealed strong, moderate, and weak attachment abilities related to biofilm formation attributes in 45%, 20%, and 35% of strains, respectively. In the meantime, the frequency of the fimH, afa, and kpsMSTII genes among the isolates was observed as follows: fimH positive: 65%; afa positive: 55%; and kpsMSTII positive: 85%. The results convey a significant different of biofilm formation ability between clinical E. coli ST131 and non-ST131 isolates. Furthermore, while 45% of ST131 isolates produced strong biofilms, only 2% of non-ST131 isolates showed the ability to form strong biofilms. The attending of fimH, afa, and kpsMSTII genes in the majority of ST131 strains demonstrated a key role leading to biofilm formation. These findings suggested the application of fimH, afa, and kpsMSTII gene suppressors for treating biofilm infections caused by drug-resistant ST131 strains.

Partial sequence conservation of SARS-CoV-2 NSP-2, NSP-12, and Spike in stool samples from Abadan, Iran.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the clinical manifestations of the virus have undergone many changes. Recently, there have been many reports on gastrointestinal symptoms in COVID-19 patients. This study is aimed to perform a detailed phylogenetic study and assessment of different SNVs in the RNA genome of viruses isolated from fecal samples of patients with COVID-19 who have gastrointestinal symptoms, which can help better understand viral pathogenesis. In the present study, 20 fecal samples were collected by written consent from COVID-19 patients. According to the manufacturer's protocol, virus nucleic acid was extracted from stool samples and the SARS-CoV-2 genome presence in stool samples was confirmed by RT-PCR assay. Three viral genes, S, nsp12, and nsp2, were amplified using the reverse transcription polymerase chain reaction (RT-PCR) method and specific primers. Multiple sequencing alignment (MSA) was performed in the CLC word bench, and a phylogenetic tree was generated by MEGA X based on the neighbor-joining method. Of all cases, 11 (55%) were males. The mean age of the patients was 33.6 years. Diabetes (70%) and blood pressure (55%) were the most prevalent comorbidities. All 20 patients were positive for SARS-CoV-2 infection in respiratory samples. Molecular analysis investigation among 20 stool samples revealed that the SARS-CoV-2 genome was found among 10 stool samples; only three samples were used for sequencing. The polymorphism and phylogenetic analysis in SARS-CoV-2 showed great similarity among all of the evaluated genes with the Wuhan reference sequence and all of the current variants of concern (VOCs). The current study represents a great similarity in polymorphism and phylogenetic analysis of the SARS-CoV-2 isolates with the Wuhan reference sequence and all of the current VOC in the particular evaluated partial sequences of S, nsp12, and nsp2.

The effect of Nutrition Bio-shield superfood (NBS) on disease severity and laboratory biomarkers in patients with COVID-19: A randomized clinical trial.

BACKGROUND: Nutrition Bio-shield Superfood (NBS) is an organic and viable herbal supplement that could improve the function of the immune system. The present study aims to determine the effect of NBS on disease severity and laboratory biomarkers in patients with COVID-19. METHODS: This current study was a randomized, comparative, parallel two-arm and single-blind clinical trial study performed in Tehran, Iran. In total, 70 patients with COVID-19 were included in the present study and assigned to two groups including 1) intervention group (n = 35) and 2) control group (n = 35). All patients included in the intervention group received 4.5 gr daily rate of NBS superfood, three times the daily rate of 1.5 gr for 14 days. In contrast, patients included in the control group received a placebo three times a day for 14 days. The measurement of laboratory parameters including CRP, ESR, D-Dimer, LDH, CPK, SGOT, SGPT, ALP, FBG, WBC count, PLT, and lymphocyte count was performed using standard kits and methods. Moreover, all serum samples were tested to determine the levels of IL-6 and TNF-ɑ using specific commercially available ELISA kits according to the instructions of the manufacturer. RESULTS: A significant decrease in the mean serum level of several variables including CRP (p < 0.001), ESR (p < 0.001), D- Dimer (p = 0.001), LDH (p < 0.001), SGOT (p = 0.002), SGPT (p = 0.019), ALP (p < 0.001), WBC count (p < 0.001), body temperature (p = 0.013), IL-6 (p < 0.001), and TNF-α (p < 0.001) was seen 14 days after intervention from baseline in the intervention group than control group. In contrast, in the intervention group, the significant increase from baseline of lymphocyte percentage (p < 0.001) and oxygen saturation (p < 0.001) was seen 14 days after receiving NBS superfood than the control group. CONCLUSION: Results showed that the use of NBS superfood had various beneficial effects on COVID-19 disease severity. These results suggest that NBS superfood can be used as an effective natural supplement in the treatment process of COVID-19 disease.

Identification and molecular characterization of penicillin-nonsusceptible Streptococcus pneumoniae isolates recovered from invasive infections in a pre-pneumococcal vaccine era.

BACKGROUND: Given the significant role of penicillin-nonsusceptible Streptococcus pneumoniae in inducing severe infectious diseases, identifying serotypes and genotypes that can mediate antimicrobial resistance has become a pillar of treatment strategies. This study aims to determine the correlation between the minimum inhibitory concentration of antimicrobial agents and amino acid mutations in penicillin-binding proteins. Moreover, molecular serotyping and multiple-locus variable number tandem repeat analysis typing were first-ever performed to characterize the invasive penicillin-nonsusceptible S. pneumoniae isolates in Iran. METHODS: Of 149 isolates, antimicrobial susceptibility tests were performed against penicillin, ceftriaxone, and cefotaxime by the MIC Test Strip, and sequence analysis of the pbp genes was performed through PCR-sequencing method. All penicillin-nonsusceptible S. pneumoniae isolates were serotyped and genotyped by sequential multiplex PCR and multiple-locus variable-number tandem repeat analysis, respectively. RESULTS: Among pneumococcal isolates, 53 isolates were classified as penicillin-nonsusceptible S. pneumoniae, of which 38 (71.7%) and 15 (28.3%) were resistant and intermediate to penicillin, respectively. Furthermore, ceftriaxone- and cefotaxime-nonsusceptible pneumococci constituted 33 (62.2%) and 29 cases (54.7%), respectively. Of note, there were 8 and 41 different serotypes and multiple-locus variable-number tandem repeat analysis types, respectively. CONCLUSIONS: Due to the increasing resistance to antimicrobial agents, the most efficient approach to preventing pneumococcal infection mortality as vaccine-preventable diseases is focusing on wide-spectrum vaccination. Based on our findings, the 13-valent pneumococcal conjugate vaccine could considerably reduce the incidence of invasive pneumococcal diseases due to the high rate of serotype coverage.

Human Herpesvirus 6 Infection and Risk of Chronic Fatigue Syndrome: A Systematic Review and Meta-Analysis.

INTRODUCTION: Chronic fatigue syndrome (CFS) is a neurological disease that is accompanied by excessive fatigue or tiredness. There are several reports confirming the association between human herpesvirus 6 (HHV-6) infection and CFS illness. This systematic review and meta-analysis was performed to integrate the information of published studies with regard to this association until May 2021. METHODS: The literature search was based on keywords including "chronic fatigue syndrome and HHV 6," "chronic fatigue syndrome and HHV-6," "chronic fatigue syndrome and HHV6," "chronic fatigue syndrome and Herpes virus 6," and "chronic fatigue syndrome and Herpesvirus6" in MEDLINE (PubMed), Web of Science, and EMBASE. RESULTS: The literature search identified 17 studies to be included in the systematic review and 11 studies in meta-analysis. The symmetry funnel plot and Egger's test (p value = 0.2) identified no publication bias among studies. Moreover, the low level of I2 revealed homogeneity across studies. DISCUSSION: In conclusion, the association between the HHV-6 infection and CFS incidence was substantiated. However, the results of this study also suggest that further comprehensive studies are needed to solidify the association between HHV-6 and CFS. Future studies should consider additional factors that may have affected the significance of such a correlation.

A multicenter retrospective study of clinical features, laboratory characteristics, and outcomes of 166 hospitalized children with coronavirus disease 2019 (COVID-19): A preliminary report from Iranian Network for Research in Viral Diseases (INRVD).

BACKGROUND: The objectives of this study were to analyze the clinical features and laboratory profiles and risk factors associated with critical illness of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: One hundred and sixty-six coronavirus disease 2019 (COVID-19) Iranian pediatric patients were recruited through a collaborative research network between March and May 2020. Demographics, clinical, laboratory, and radiological results were obtained from patient files. RESULTS: Of 166 patients, 102 (61%) and 64 (39%) were males and females, respectively. Ninety-six (57.8%) and 70 (42.2%), had moderate and severe conditions, respectively. Thirty (18%) of patients died. The common symptoms were fever (73%), cough (54%), and shortness of breath, headache decrease in neutrophil and platelet counts; increase values in lactate dehydrogenase, decrease in the blood pH and HCO3 were significantly associated with the disease severity. 54% and 56% of patients showed abnormal radiographic appearance in Chest X-ray and in chest computed tomography scan, respectively. Sixty-one (36.7%) of patients were referred to intensive care unit (ICU). The coexistence of comorbidity was the main factor associated with ICU admission, shock, arrhythmia, acute kidney injury, acute respiratory distress syndrome, acute cardiac injury, and death. CONCLUSIONS: We describe a higher than previously recognized rate of COVID-19 mortality in Iranian pediatric patients. Epidemiological factors, such as the relatively high case fatality rate in the country and the presence of underlying diseases were the main factors for the high death rate.

Clinical Symptoms and Types of Samples Are Critical Factors for the Molecular Diagnosis of Symptomatic COVID-19 Patients: A Systematic Literature Review.

BACKGROUND: Currently, a novel coronavirus found in 2019 known as SARS-CoV-2 is the etiological agent of the COVID-19 pandemic. Various parameters including clinical manifestations and molecular evaluation can affect the accuracy of diagnosis. This review aims to discuss the various clinical symptoms and molecular evaluation results in COVID-19 patients, to point out the importance of onset symptoms, type, and timing of the sampling, besides the methods that are used for detection of SARS-CoV-2. METHODS: A systematic literature review of current articles in the Web of Science, PubMed, Scopus, and EMBASE was conducted according to the PRISMA guideline. RESULTS: Of the 12946 patients evaluated in this investigation, 7643 were confirmed to be COVID-19 positive by molecular techniques, particularly the RT-PCR/qPCR combined technique (qRT-PCR). In most of the studies, all of the enrolled cases had 100% positive results for molecular evaluation. Among the COVID-19 patients who were identified as such by positive PCR results, most of them showed fever or cough as the primary clinical signs. Less common symptoms observed in clinically confirmed cases were hemoptysis, bloody sputum, mental disorders, and nasal congestion. The most common clinical samples for PCR-confirmed COVID-19 patients were obtained from throat, oropharyngeal, and nasopharyngeal swabs, while tears and conjunctival secretions seem to be the least common clinical samples for COVID-19 diagnosis among studies. Also, different conserved SARS-CoV-2 gene sequences could be targeted for qRT-PCR detection. The suggested molecular assay being used by most laboratories for the detection of SARS-CoV-2 is qRT-PCR. CONCLUSION: There is a worldwide concern on the COVID-19 pandemic and a lack of well-managed global control. Hence, it is crucial to update the molecular diagnostics protocols for handling the situation. This is possible by understanding the available advances in assays for the detection of the SARS-CoV-2 infection. Good sampling procedure and using samples with enough viral loads, also considering the onset symptoms, may reduce the qRT-PCR false-negative results in symptomatic COVID-19 patients. Selection of the most efficient primer-probe for target genes and samples containing enough viral loads to search for the existence of SARS-CoV-2 helps detecting the virus on time using qRT-PCR.

COVID-19 associated central nervous system manifestations, mental and neurological symptoms: a systematic review and meta-analysis.

The ongoing pandemic of Coronavirus disease 2019 (COVID-19) has infected more than 27 million confirmed cases and 8,90,000 deaths all around the world. Verity of viral infections can infect the nervous system; these viral infections can present a wide range of manifestation. The aim of the current study was to systematically review the COVID-19 associated central nervous system manifestations, mental and neurological symptoms. For that we conducted a comprehensive systematic literature review of four online databases, including Web of Science, PubMed, Scopus and Embase. All relevant articles that reported psychiatric/psychological symptoms or disorders in COVID-19 without considering time and language restrictions were assessed. All the study procedures were performed based on the PRISMA criteria. Due to the screening, 14 studies were included. The current study result indicated that, the pooled prevalence of CNS or mental associated disorders with 95% CI was 50.68% (6.68-93.88). The most prevalence symptoms were hyposmia/anosmia/olfactory dysfunction (number of study: 10) with 36.20% (14.99-60.51). Only one study reported numbness/paresthesia and dysphonia. Pooled prevalence of numbness/paresthesia and dysphonia was 5.83% (2.17-12.25) and 2.39% (10.75-14.22). The pooled prevalence of depression and anxiety was 3.52% (2.62-4.54) and 13.92% (9.44-19.08). Our findings demonstrate that COVID-19 has a certain relation with neurological symptoms. The hypsomia, anosmia or olfactory dysfunction was most frequent symptom. Other symptoms were headache or dizziness, dysgeusia or ageusia, dysphonia and fatigue. Depression, anxiety, and confusion were less frequent symptoms.

Identification of dysregulated pathways underlying HTLV-1-associated myelopathy/tropical spastic paraparesis through co-expression network analysis.

Human T cell lymphotropic virus-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a pathogen-caused disease which is associated with the progressive neurological disorder. HAM/TSP affects the expression level of several proteins and dysregulates some biological pathways. To identify the interaction patterns among expressed genes in HAM/TSP patients, weighted gene co-expression network analysis (WGCNA) was applied. Three microarray datasets regarding HAM/TSP were merged, and the co-expression network was constructed among genes. A total of 38 modules were identified. Three preserved modules in HAM/TSP in comparison to the healthy subjects which also had the most connected proteins and enriched in the biological pathways were selected. These modules were enriched in pathways related to immune systems, cell cycle, viral infection, and neuronal systems. Moreover, the involvement of novel immunological-related proteins including C1QB, GBP5, PSME1, SERPING1, and UBE2C; neurological-related proteins including TUBA4A, TUBB8, and TP63; and also proteins including TRPC6, PRKG2, OPRD1, PRKACA, and TUBB4A involved in the cGMP-PKG signaling pathway, thyroid hormone synthesis, and recruitment of mitotic centrosome proteins and complexes were found. Therefore, tracing these proteins and the identified modules can shed light on the pathogenesis mechanism of HAM/TSP and help to find potential therapeutic targets. However, further experimental validation should be performed to confirm the proposed functional players.

Trend in Prevalence of Hepatitis B Virus Infection Among Blood Donor Individuals: An Eleven-year of Experience in Lorestan, Iran.

BACKGROUND: Hepatitis B virus is one of the transfusion transmissible infections. Despite the availability of hepatitis B virus (HBV) vaccine and screening tests but still danger of virus transmission via blood transfusion is high in some regions. The objective of this study was to determine the trend of seroprevalence of hepatitis B in over an 11-year period (2005-2015). METHODS: In this study, 355,083 blood donors were estimated for hepatitis B surface antigen (HBs Ag) seropositivity during 2005-2015 who referred to blood infusion centers of Lorestan province. Third-generation ELISA method was used to detect HBs Ag. RESULTS: The prevalence of HBs Ag in blood donors was 0.29% (1017). It was decreased steadily from 2005 to 2015 (0.68% to 0.12%) but increased in 2008 year. The trend prevalence of HBs Ag seropositivity significantly decreased over the study period (P < 0.001). The decline in HBV infection rates was more prominent in regular and repeated donor's groups compared to people who donated blood for the first time (P < 0.001). CONCLUSIONS: The result of present study was indicated, Lorestan city in west of Iran can be classified as a low-income region because the low prevalence of HBs Ag in blood donors. Also the prevalence of HBs Ag in first-time donors was higher than other groups.

Integron types, antimicrobial resistance genes, virulence gene profile, alginate production and biofilm formation in Iranian cystic fibrosis Pseudomonas aeruginosa isolates.

Cystic fibrosis (CF) patients commonly suffer from continuous and recurrent lung infections caused by Pseudomonas aeruginosa, the dominant pathogen in CF airways. This study aimed to determine the integron types, gene cassettes, virulence determinants, ß-lactam resistance genes, biofilm formation and alginate production in P. aeruginosa isolated from Iranian CF patients. A total of 143 P. aeruginosa isolates were obtained from CF patients. Susceptibility of isolates to different antimicrobials was evaluated by disc diffusion method. ESBL, MBL and KPC production was assessed. Congo red agar and tissue culture plates were used for evaluation of biofilm formation. Alginate production was determined using the Carbazole assay. Integrase genes, resistance determinants (ESBLs, MBLs and KPC) and genes encoding virulence factors were evaluated by PCR. All isolates were susceptible to colistin, piperacillin-tazobactam and ticarcillin; 8.4% of isolates were considered as MDR phenotype. Out of 6.3% IPM-resistant isolates, prevalence of virulence genes was as follows: lasB (100%) and plcB (100%), plcH (96.5%). Biofilm formation and alginate production ability were found in 54.5% of isolates. The prevalence of the alginate-encoding genes was 92.3%, 86.7% and 67.1% for algD, algU and algL genes, respectively. PpyR, pslA and pelA genes were detected in 98.6%, 89.5% and 57.3% of the isolates, respectively. The high prevalence of colonization in CF lungs may increase the pathogenicity of P. aeruginosa due to their adhesion and protective properties caused by biofilm- and alginate-production. LasB, plcB, plcH, exoS, toxA, algD, ppyR and pslA genes were predominant in CF P. aeruginosa strains.

Prevalence of Gram-negative bacteria in ventilator-associated pneumonia in neonatal intensive care units: a systematic review and meta-analysis protocol.

INTRODUCTION: Ventilator-associated pneumonia (VAP) is a common and potentially lethal problem among mechanically ventilated neonates in neonatal intensive care units (NICUs). The main pathogenic bacteria of VAP in NICUs are Gram-negative pathogens, which show a general decline in sensitivities to commonly used antibiotics, but their true prevalence is not known. METHODS AND ANALYSIS: We aim to provide a systematic review of studies measuring the prevalence of Gram-negative bacteria in VAP in NICUs. We will search PubMed, SCOPUS, EMBASE and the ISI Web of Science, as well as the Google Scholar search engine with no restriction on language. Full copies of articles will be identified by a defined search strategy and will be considered for inclusion against predefined criteria. Study selection and data extraction will be performed by 2 independent reviewers. Statistical analysis will include the identification of data sources and documentation of estimates, as well as the application of the random-effects and fixed-effects meta-analysis models. This will allow us to aggregate prevalence estimates and account for between-study variability in calculating the overall pooled estimates and 95% CI for the prevalence of Gram-negative bacteria in VAP in NICUs. Heterogeneity will be evaluated using the I2 and χ2 statistical tests to determine the extent of variation in effect estimates due to heterogeneity rather than chance. Publication bias and data synthesis will be assessed by funnel plots and Begg's and Egger's tests using STATA software V.13. This systematic review protocol was prepared according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocols (PRISMA-P) 2015 Statement. ETHICS AND DISSEMINATION: No ethical issues are predicted. These findings will be published in a peer-reviewed journal and presented at national and international conferences. TRIAL REGISTRATION NUMBER: CRD42016036048.