Circulating brain-derived neurotrophic factor as a potential biomarker in stroke: a systematic review and meta-analysis.

BACKGROUND: Stroke, an acute cerebrovascular event, is a leading cause of disability, placing a significant psycho-socioeconomic burden worldwide. The adaptation and reorganization process following any neuronal damage is regarded as neuroplasticity. Among many factors believed to attribute to this process, Brain-derived Neurotrophic Factor (BDNF) is a neurotrophin coordinating neuroplasticity after various neurological disorders such as stroke. METHODS: We conducted a systematic search in the main electronic medical databases in January 2021. Primarily we want to compare BDNF levels between patients with stroke and healthy controls (HC). Additional aims included investigation of (1) longitudinal changes in the BDNF levels post-stroke, (2) effects of physical training, (3) repeated transcranial magnetic stimulation (rTMS), and presence of depression on BDNF levels in patients with stroke. RESULTS: Among 6243 reviewed records from PubMed, Web of Science, and Scopus, 62 studies were eligible for inclusion in our systematic review. Subjects with stroke, n = 1856, showed lower BDNF levels compared to HC, n = 1191 (SMD [95%CI] = - 1.04 [- 1.49 to - 0.58]). No significant difference was detected in the level of BDNF through time points past stroke. BDNF levels were lower in the patients with depression compared to non-depressed subjects (SMD [95%CI] = - 0.60 [- 1.10 to - 0.10]). Physical training had an immediate positive effect on the BDNF levels and not statistically significant effect in the long term; SMD [95%CI] = 0.49 [0.09 to 0.88]) and SMD [95%CI] = 0.02 [- 0.43 to 0.47]). Lastly, rTMS showed no effect on the level of BDNF with 0.00 SMD. CONCLUSIONS: Our study confirms that stroke significantly decreases the level of BDNF in various domains such as cognition, affect, and motor function. As BDNF is the major representative of neuroplasticity within nervous system, it is believed that stroke has a significant impact on the CNS regeneration, which is permanent if left untreated. This effect is intensified with coexisting conditions such as depression which further decrease the BDNF level but the net impact yet needs to be discovered. We also conclude that exercise and some interventions such as different medications could effectively reverse the damage but further studies are crucial to reach the exact modality and dosage for their optimal effect.

Novel G6PC3 Mutations in Patients with Congenital Neutropenia: Case Reports and Review of the Literature.

BACKGROUND: Severe congenital neutropenia (SCN4) caused by mutations in glucose-6- phosphatase catalytic subunit 3 (G6PC3) is characterized by recurrent infections due to severe neutropenia, may be accompanied by other extra-hematopoietic manifestations; including structural heart defects, urogenital abnormalities, prominent superficial venous markings, growth retention, and inflammatory bowel diseases with rare incidence. The homozygous or compound heterozygous mutations of G6PC3 are responsible for most cases of autosomal recessive SCN4. Herein, we present two cases of SCN4 affected by novel mutations in the G6PC3, in addition to a summarized list of variants in G6PC3 gene that are reported as pathogenic and related to the SCN4 phenotype. CASE PRESENTATION: Herein, we present two cases of SCN4; the first case was a three-months old boy with severe neutropenia and prior history of hospitalization due to umbilical separation, umbilical herniation, omphalitis, and pyelonephritis; and the second case was an eight-year-old with a history of neutropenia, recurrent and severe episodes of intractable diarrhea, refractory rectovaginal and rectoperineal fistula, congenital inguinal hernia, and ASD type 2. Whole exome sequencing was performed for both cases, which revealed two novel homozygous missense mutations in G6PC3 that were predicted to be deleterious; c.337G>A, p. Gly113Arg in the first case and c.479C>T; P. Ser160Leu in the second case. To our knowledge, both of these two mutations have not been reported in the G6PDC3 gene. CONCLUSION: In patients with severe neutropenia with varying extra hematopoietic syndrome, mutation of G6PC3 should be suspected after ruling out other mutations related to neutropenia. This study pointed toward novel G6PC3 mutations that should be considered in order to diagnose patients with severe congenital neutropenia.

Exploration of the Epidemiological and Emotional Impact of Quarantine and Isolation During the COVID-19 Pandemic.

Starting in December 2019 in Wuhan Municipal Health Commission, the coronavirus disease 2019 (COVID-19) has crossed the borders forming a pandemic in 2020. The absence of pharmacological interventions has pushed governments to apply different sets of old, non-pharmacological interventions, which are, though temporary, helpful to prevent further pandemic propagation. In the context of COVID-19, research confirms that quarantine is useful, mainly if applied early and if combined with other public health measures. However, the efficacy of quarantine and isolation is limited in many ways, ranging from legal issues and suspension of economic activities to mental health considerations. This chapter is an exploration of (i) epidemiological impact of isolation and quarantine; (ii) emotional impact of isolation and quarantine; and (iii) the possible effect of culture on quarantine experience.

Novel Mutations of the TYMP Gene in Mitochondrial Neurogastrointestinal Encephalomyopathy: Case Series and Literature Review.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a multi-system disorder caused by several homozygous or compound heterozygous mutations, mostly in the nuclear gene of TYMP. Our current knowledge on the underlying pathology of the disease is derived through the study of about 200 cases of different ethnicities. Clinical presentations include severe cachexia, weakness, ptosis, diplopia, abdominal cramps or digestive tract disorders, hearing impairment, and paresthesia.Herein, we aim to present five novel mutations of the nuclear gene of TYMP in six Iranian patients diagnosed with MNGIE. In our population, age at the time of diagnosis was 18 to 49 years, while the onset of the symptoms varied from 13 to 20 years. We detected two pathogenic non-frameshift nonsense premature stop codon mutations (c.1013C > A, and c.130C > T), one variant of uncertain significance (VUS) non-frameshift missense mutation (c.345G > T), one likely pathogenic frameshift insertion (c.801_802insCGCG), and one likely benign homozygous non-frameshift deletion (c.1176_1187del) from two siblings. Our findings also confirm the autosomal recessive inheritance pattern of MNGIE in the Iranian population. The lack of knowledge in the area of nuclear gene-modifier genes shadows the genotype-phenotype relationships of MNGIE.

Novel BTK mutation in X-linked agammaglobulinemia: Report of a 17-year-old male

Introduction and objectives: X-linked agammaglobulinemia (XLA), the first known primary immunodeficiency, is caused by rare mutations in Bruton’s tyrosine kinase (BTK) gene. Mutations in the BTK gene lead to a failure in the development and maturation of B-cell linage. A decreased number of B-cells results in agammaglobulinemia and increased susceptibility to a variety of infections. Therefore, patients with XLA usually manifest with repetitive bacterial infections, such as upper respiratory tract infections, septic arthritis, osteomyelitis, and urinary tract infections, since their infancy. Patients We report a 17-year-old Iranian boy with XLA, referred to us with a history of severe and recurrent episodes of bacterial infections for a period of six years. Results Genetic analysis using the whole Exome sequencing revealed a hemizygous missense mutation in the BTK gene (c.428 A > T, p.His143Leu). Conclusion To our knowledge, c.428 A > T has not been reported in the BTK gene (AU)

Novel BTK mutation in X-linked agammaglobulinemia: Report of a 17-year-old male.

INTRODUCTION AND OBJECTIVES: X-linked agammaglobulinemia (XLA), the first known primary immunodeficiency, is caused by rare mutations in Bruton's tyrosine kinase (BTK) gene. Mutations in the BTK gene lead to a failure in the development and maturation of B-cell linage. A decreased number of B-cells results in agammaglobulinemia and increased susceptibility to a variety of infections. Therefore, patients with XLA usually manifest with repetitive bacterial infections, such as upper respiratory tract infections, septic arthritis, osteomyelitis, and urinary tract infections, since their infancy. PATIENTS: We report a 17-year-old Iranian boy with XLA, referred to us with a history of severe and recurrent episodes of bacterial infections for a period of six years. RESULTS: Genetic analysis using the whole Exome sequencing revealed a hemizygous missense mutation in the BTK gene (c.428 A > T, p.His143Leu). CONCLUSION: To our knowledge, c.428 A > T has not been reported in the BTK gene.

Persian adaptation of Edinburgh Cognitive and Behavioural Screen (ECAS).

Objectives: To adapt the Edinburgh Cognitive and Behavioral screen (ECAS) English version into Persian. Methods: The ECAS test was adapted and implemented to 30 ALS patients and 31 healthy volunteers in Tehran, Iran. The ECAS results were compared to MoCA and ALS-FRS-r, the other standard tools to determine whether the translated version is reliable and valid in the new language. In addition, the patients' caregivers were interviewed for behavioral and psychiatric changes. Results: The Persian version of ECAS revealed high internal consistency (α = 0.791), alongside the strong correlation of ECAS and its subscales with MoCA and ALS-FRS. Moreover, Persian ECAS discriminated against the patients and the healthy population well. Sensitivity analysis revealed promising results of Persian ECAS with an area under the curve of 0.871 in ROC curve analysis. Cognitive impairment was observed in 43.33% of patients. Conclusion: The Persian version of the ECAS, exclusively designed for the Iranian population, is the first screening tool to assess multiple neuropsychological functions, which provides a rapid and inclusive screen of cognitive and behavioral impairments specifically in ALS patients.

A Reliable Prognostic Marker for Liver Dysfunction in COVID-19 Infection.

BACKGROUND In December 2019, COVID-19 emerged from China and spread to become a pandemic, killing over 1,350,000 up to November 18, 2020. Some patients with COVID-19 have abnormal liver function tests. We aimed to determine the clinical significance of liver chemistries in patients with COVID-19. METHODS We performed a cross-sectional study of 1044 consecutive patients with confirmed COVID-19 in two referral hospitals in Tehran, Iran, from February to April 2020. All cases were diagnosed by clinical criteria and confirmed by characteristic changes in the spiral chest computed tomography (CT) and nucleic acid testing of the nasopharyngeal samples. We evaluated the association between abnormal liver enzymes or function tests and survival, intensive care unit (ICU) admission and fatty liver changes in CT scans. RESULTS The mean age was 61.01 ± 16.77 years, and 57.68% were male. Of 495 patients with elevated alanine transaminase (ALT) levels, 194 had chest CT scans, in which fatty liver disease was seen in 38.1%. 41 patients (21.13%) had moderate to severe, and 33 (17.01%) had borderline fatty liver disease. Bilirubin, albumin, and partial thromboplastin time (PTT), along with other markers such as HCO3, C-reactive protein (CRP), triglyceride, and length of admission, were significantly associated with ICU admission and mortality. Prothrombin time (PT), platelet count, and low-density lipoprotein (LDL) levels were also correlated with mortality. Fasting blood sugar (FBS) and pH were important indices in ICU admitted patients. CONCLUSION Liver function tests accurately predict a worse prognosis in patients with COVID-19. However, liver enzymes were only slightly increased in those who died or needed ICU admission and were not related to the fatty liver changes.

Problem-based learning as an effective method for teaching theoretical surgery courses to medical students.

BACKGROUND: This study was designed to assess the clinical judgment of medical students in surgery clinical decision-making by a standard examination after lecture-based learning (LBL) or problem-based learning (PBL). MATERIALS AND METHODS: A prospective randomized trial study on 175 medical students whom were randomly allocated to three groups was performed during November 2017 and January 2018. LBL group (n = 103), PBL group led by an attending (n = 39), and PBL group (n = 33) led by an intern. Chi-squared test and independent student t-test were used to compare between the two groups. All the analyses were performed by the two-sided method using the Statistical Package for the Social Sciences software (SPSS version 22; SPSS, Inc., Chicago, IL, USA), and a P < 0.05 set as statistically significant. RESULTS: The students in the PBL group scored significantly higher on the posttraining multiple-choice examination, compared to the LBL group (P = 0.048). However, there was no significant difference between the PBL group led by an attending and the PBL group led by an intern (P = 0.892). CONCLUSION: We concluded that PBL remarkably increased the students' scores in the problem-solving examination, as compared to the conventional method. We found no significant differences in PBL facilitated by an attending or an intern.

Predictive value of initial CT scan for various adverse outcomes in patients with COVID-19 pneumonia.

BACKGROUND: Chest computed tomography (CT) scan is frequently used in the diagnosis of COVID-19 pneumonia. OBJECTIVES: This study investigates the predictive value of CT severity score (CSS) for length-of-stay (LOS) in hospital, initial disease severity, ICU admission, intubation, and mortality. METHODS: In this retrospective study, initial CT scans of consecutively admitted patients with COVID-19 pneumonia were reviewed in a tertiary hospital. The association of CSS with the severity of disease upon admission and the final adverse outcomes was assessed using Pearson's correlation test and logistic regression, respectively. RESULTS: Total of 121 patients (60±16 years), including 54 women and 67 men, with positive RT-PCR tests were enrolled. We found a significant but weak correlation between CSS and qSOFA, as a measure of disease severity (r: 0.261, p = 0.003). No significant association was demonstrated between CSS and LOS. Patients with CSS>8 had at least three-fold higher risk of ICU admission, intubation, and mortality. CONCLUSIONS: CSS in baseline CT scan of patients with COVID-19 pneumonia can predict adverse outcomes and is weakly correlated with initial disease severity.

Clinical characteristics, outcomes, and risk factors for mortality in hospitalized patients with COVID-19 and cancer history: a propensity score-matched study.

BACKGROUND: COVID-19 has caused great concern for patients with underlying medical conditions. We aimed to determine the prognosis of patients with current or previous cancer with either a PCR-confirmed COVID-19 infection or a probable diagnosis according to chest CT scan. METHODS: We conducted a case control study in a referral hospital on confirmed COVID-19 adult patients with and without a history of cancer from February25th to April21st, 2020. Patients were matched according to age, gender, and underlying diseases including ischemic heart disease (IHD), diabetes mellitus (DM), and hypertension (HTN). Demographic features, clinical data, comorbidities, symptoms, vital signs, laboratory findings, and chest computed tomography (CT) images have been extracted from patients' medical records. Multivariable logistic regression was used to estimate odd ratios and 95% confidence intervals of each factor of interest with outcomes. RESULTS: Fifty-three confirmed COVID-19 patients with history of cancer were recruited and compared with 106 non-cancerous COVID-19 patients as controls. Male to female ratio was 1.33 and 45% were older than 65. Dyspnea and fever were the most common presenting symptoms in our population with 57.86 and 52.83% respectively. Moreover, dyspnea was significantly associated with an increased rate of mortality in the cancer subgroup (p = 0.013). Twenty-six patients (49%) survived among the cancer group while 89 patients (84%) survived in control (p = 0.000). in cancer group, patients with hematologic cancer had 63% mortality while patients with solid tumors had 37%. multivariate analysis model for survival prediction showed that history of cancer, impaired consciousness level, tachypnea, tachycardia, leukocytosis and thrombocytopenia were associated with an increased risk of death. CONCLUSION: In our study, cancer increased the mortality rate and hospital stay of COVID-19 patients and this effect remains significant after adjustment of confounders. Compared to solid tumors, hematologic malignancies have been associated with worse consequences and higher mortality rate. Clinical and para-clinical indicators were not appropriate to predict death in these patients.

Peripheral blood levels of brain-derived neurotrophic factor in patients with post-traumatic stress disorder (PTSD): A systematic review and meta-analysis.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays a crucial role in the survival, differentiation, growth, and plasticity of the central nervous system (CNS). Post-traumatic stress disorder (PTSD) is a complex syndrome that affects CNS function. Evidence indicates that changes in peripheral levels of BDNF may interfere with stress. However, the results are mixed. This study investigates whether blood levels of BDNF in patients with post-traumatic stress disorder (PTSD) are different. METHODS: We conducted a systematic search in the major electronic medical databases from inception through September 2019 and identified Observational studies that measured serum levels of BDNF in patients with PTSD compared to controls without PTSD. RESULTS: 20 studies were eligible to be included in the present meta-analysis. Subjects with PTSD (n = 909) showed lower BDNF levels compared to Non-PTSD controls (n = 1679) (SMD = 0.52; 95% confidence interval: 0.18 to 0.85). Subgroup meta-analyses confirmed higher levels of BDNF in patients with PTSD compared to non-PTSD controls in plasma, not serum, and in studies that used sandwich ELISA, not ELISA, for BDNF measurement. Meta-regressions showed no significant effect of age, gender, NOS, and sample size. CONCLUSIONS: PTSD patients had increased serum BDNF levels compared to healthy controls. Our finding of higher BDNF levels in patients with PTSD supports the notion that PTSD is a neuroplastic disorder.

Interleukin-6 and severe COVID-19: a systematic review and meta-analysis.

BACKGROUND: Evidence links COVID-19 severity to hyper-inflammation. Treatment with tocilizumab, a monoclonal antibody directed against the interleukin-6 (IL-6) receptor, was shown to lead to clinical improvement in patients with severe COVID-19. We, therefore, performed the present systematic review and meta-analysis to investigate whether the circulating levels of IL-6 is a reliable indicator of disease severity among patients affected with COVID-19. METHODS: A systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar on April 19, 2020. RESULTS: Eleven studies provided data of IL-6 levels in patients with severe to critical COVID-19 (severe) and patients with mild to moderate COVID-19 (non-severe). The included studies were of moderate to high quality. The mean patients' age was 60.9 years, ranging from 45.2 to 76.7 years in the severe group and 46.8 years, ranging from 37.9 to 61 years, in the nonsevere group. Fifty-two percent were male in the severe group, as compared to 46% in the non-severe group. An overall random effects meta-analysis showed significantly higher serum levels of IL-6 in the severe group than in the non-severe group with a mean difference of +23.1 pg/mL (95% CI: 12.42-33.79) and the overall effect of 4.24 (P-value < 0.001). Meta-regressions showed that neither age nor sex significantly influenced the mean difference of IL-6 between the groups. CONCLUSIONS: Meta-analysis and meta-regression reveal a reliable relationship between IL-6 and COVID-19 severity, independent of age and sex. Future research is, however, required to assess the effect of BMI on the pattern of IL-6 production in patients with COVID-19. Also, there might be confounding factors that influence the relationship between IL-6 and COVID-19 severity and remain as yet unknown.

Giant Thrombosis at Left Anterior Descending Artery Aneurysm in a 10-Year Old Boy with Granulomatosis with Polyangiitis.

Granulomatosis with polyangiitis (GPA), necrotizing vasculitis of small and medium-sized vessels, is traditionally believed to mainly affect respiratory tract with additional focal kidney involvements as its primary manifestations with a relatively rare annual incidence rate of 20-50 cases per million. Six percent of the affected cases have cardiac involvements; among which, aneurysms comprise the lowest penetrance. By this paper, we aim to cast light on clinical diagnostic and treatment methods of a rare case presentation, a 10-year-old male GPA patient, diagnosed with massive thrombosis at his coronary artery aneurysm. GPA should be considered as differential diagnosis of prolong fever and coronary aneurysms in adolescents.

Can music influence cardiac autonomic system? A systematic review and narrative synthesis to evaluate its impact on heart rate variability.

BACKGROUND: and purpose: The impact of music on the human body extends beyond an emotional response. Music can bring benefits to the cardiovascular system by influencing heart rate variability (HRV), which is a well-accepted method to analyze the oscillations of the intervals between successive heartbeats and investigate the cardiovascular autonomic nervous system (ANS). This study is a systematic review to examine the effect of musical interventions on HRV. METHODS: We conducted a systematic search in PubMed, Scopus, Web of Science, and Cochrane and identified additional studies with hand searching of reference lists of relevant references. RESULTS: 29 original articles (24 pre-post intervention studies and five randomized controlled trials) with a total of 1368 subjects were available and eligible to be included in the systematic review. Within the whole, only three studies reveal no significant impact of music on HRV, which might be due to using a small sample size and a concise duration of music administration. Interestingly, the rest of the studies have suggested a positive impact of music on HRV with a 0.05 level of significance. CONCLUSION: This systematic review confirms music as a stimulus acting to the cardiac ANS that increases parasympathetic activity and HRV. The effects are, however, associated with a high risk of bias. Therefore, further studies are necessary to compare the impact of individualized music therapy to passive listening and preferred soundtracks.