Search

Background: Definitions of childhood and adolescent hypertension (HTN) do not precisely elucidate the relationship between HTN and cardiovascular outcomes. Carotid intima-media thickness (CIMT), as a substitute for cardiovascular outcomes, enables the early identification of cardiovascular events throughout early adulthood., Purpose: This study aimed to compare the ability of childhood HTN definitions to predict a high CIMT in early adulthood., Methods: This prospective cohort study included 921 individuals aged 10-17 years from the Tehran Lipid and Glucose Study. The CIMT was measured after 18 years of follow-up. Participants were categorized into normal blood pressure (BP), high-normal BP, HTN stage 1, and HTN stage 2 groups based on the childhood HTN definitions of the 4th report, European Society of Hypertension (ESH), and American Academy of Pediatrics Clinical Practice Guidelines (AAP-CPG). Akaike information criterion (AIC) and relative efficiencies (RE) were calculated to compare the ability of each to predict a high CIMT (≥95th percentile) during early adulthood., Results: The highest and lowest prevalence of stage 1 HTN was observed with the AAP-CPG (17.7%) and ESH (8.8%), respectively. Similarly, the highest and lowest prevalence of stage 2 HTN was noted with the AAP-CPG (1.5%) and ESH (0.8%), respectively. According to the RE values, the highest to lowest predictive abilities belonged to the 4th report, ESH, and AAP-CPG, respectively. In all models, the 4th report's pediatric HTN definition had the lowest AIC value and offered the best predictive ability., Conclusion: Among the various definitions of pediatric HTN, the 4th report offered the best ability to predict a high CIMT during early adulthood, followed by the ESH and AAP-CPG. Because the reference population of the 4th report includes overweight, obese, and normal- weight individuals, our findings suggest that excessive adiposity is among the main predictors of early adulthood atherosclerosis risk.

Background: Limb ischemia is a severe vascular condition that can lead to critical complications, endangering both limbs and lives. The goal of this research was to explore the role of neutrophil to lymphocyte ratio (NLR) in limb ischemia., Methods: From inception to June 8, 2022, PubMed/MEDLINE, Institute for Scientific Information Web of Science, and Scopus were searched for articles comparing NLR in limb ischemia to healthy individuals., Results: Finally, a total of 23 studies were included in the review. There was a direct link between NLR and critical limb ischemia (CLI) development in peripheral arterial disease patients. Elevated NLR levels predict a higher risk of CLI among peripheral arterial disease patients. Also, it was concluded that NLR is a dependable predictor of survival in patients with limb ischemia, and higher NLR readings are linked to decreased survival rates. Moreover, the risk of amputation is related to the level of NLR in CLI patients. However, based on the data, NLR is not a reliable indicator of sarcopenia in CLI patients. More research is needed to determine the relationship between NLR and response to treatment in CLI patients. Also, we recommend investigating the effect of each treatment on NLR level in these patients., Conclusions: Our results provide evidence that NLR level is associated with risk of amputation and mortality in patients with limb ischemia. It is a promising biomarker that can be easily incorporated into clinical practice to assist in the prediction and prevention of CLI., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Diabetes mellitus (DM), a worldwide disease affecting more than 400 million people, is associated with high blood pressure (BP). In addition to macrovascular complications, high BP in DM patients is potentially linked to microvascular complications. More than 70% of DM patients have retinopathy. To our knowledge, no systematic review and meta-analysis has been conducted on the relationship between visit-to-visit variability in blood pressure and diabetic retinopathy risk., Methods: This systematic review and meta-analysis study was performed on the related articles. The search strategy, screening, and data selection were all checklist-based. A comprehensive search was done in three databases, including PubMed, Google Scholar, and Scopus. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) were followed. English clinical studies published up to January 2023 contained diabetic patients as the population, retinopathy as the outcome, and visit-to-visit blood pressure as the intervention. Using the QUIPS technique, two authors independently quantify the risk of bias in included publications. The meta-analysis was conducted using R version 4.4.1. We calculated relative risk (RR) as the effect size, applying the random effect model. Standard deviation (SD) and coefficient of variation (CV), were used as measures of BP variability., Results: A total number of 8 studies with 743,315 participants were covered in this systematic review. After meta-analysis, we concluded that the group with higher SD of BP variability had 2 percent higher risk than the control group (RR = 1.02, 95% CI = 1.01-1.03, I-squared = 41%); however, results of our analysis for CV of BP variability showed no significant contrast with control group thus no increased risk was reported (RR = 1.04, 95% CI = 0.94-1.15, I-squared = 32%, P -value = 0.23)., Conclusion: In conclusion, an increased SD of BP variability significantly increased the relative risk for the development of retinopathy., Competing Interests: None., (AJCD Copyright © 2024.)

Background and Objectives: Computed tomography pulmonary angiography (CTPA) is a standard imaging technique employed for the detection of pulmonary embolism (PE). This systematic review and meta-analysis aims to examine the prevalence of PE among the trauma patients undergoing CTPA., Methods: A comprehensive search across PubMed, Scopus, Google Scholar, and Web of Science yielded 13 studies encompassing 5,570 individuals conducted following Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guideline. Studies that used CTPA for the detection of PE among the trauma patients were selected. This resulted in an evaluation of prevalence, trauma types, clinical manifestations, radiological findings, and mortality rates of PE among traumatic patients undergoing CTPA., Results: The overall prevalence of PE among trauma patients undergoing CTPA was 18% (95% CI = 13-24%). After pooling the existing data, femur fractures were determined to be the most prevalent trauma type (12%). The most prevalent clinical manifestations of PE among trauma patients included shortness of breath, chest pain, and altered vital signs. Radiological findings encompassed various pulmonary abnormalities, such as opacity, ground-glass opacities, and pleural effusions. Mortality rates of PE among the trauma patients ranged from 0% to 29.4% across the included studies., Conclusion: This study provides comprehensive insights into the prevalence, clinical manifestations, radiological findings and mortality of PE among trauma patients undergoing CTPA. According to our findings, lower threshold for CTPA is recommended in patients with lower extremity or spine fractures., (© 2024. The Author(s).)

Various soft markers can be detected in the ultrasonography of foetuses, which can be related to chromosomal abnormalities and increases the risk of abnormalities, or they can be considered as normal variations that can disappear due to the pregnancy progress. There are different tools to detect chromosomal abnormalities like conventional karyotyping, chromosomal microarray analysis (CMA), single nucleotide polymorphism (SNP) array, non-invasive prenatal test (NIPT), and non-invasive prenatal screening (NIPS). Therefore, in the present study, we aim to assess the accuracy of ultrasonic soft markers in the diagnosis of chromosomal abnormalities such as chromosomal structural abnormalities, aneuploidy, and triploidy, especially Trisomy 21 and Trisomy 18. A systemic literature search was performed using PubMed, Scopus, Google Scholar, and Web of Science. We gathered all articles published before August 2023. We selected English studies such as retrospective and cross-sectional ones that assessed the relationship between ultrasonic soft markers and foetal chromosomal abnormalities. A total of 10 articles with 18,580 cases were included in our systematic review article that assessed the foetal abnormalities and aneuploidies by using conventional karyotyping, SNP array, CMA, and NIPT (or NIPS). Trisomy 21, Trisomy 18, and chromosomal structural abnormalities were the most common abnormalities related to ultrasonic soft markers by karyotyping; however, Trisomy 13, 47, XXY, 45, X, and mosaic chromosomal abnormalities were other abnormalities detected. Results by CMA showed Trisomy 21 and Trisomy 18 as the most common abnormalities in the foetuses also with ultrasonic soft markers, and other abnormalities were pathogenic copy-number variations, Turner (XO), polyploidy, 22q11.2deletion, and Trisomy13, respectively. It was discovered that there is a greater possibility of having pathogenic copy number variations (CNVs) in the groups with multiple ultrasonic soft markers, while foetuses with ultrasonic soft markers have a decreased prevalence of CMA abnormality compared to those who had significant abnormalities or abnormal nuchal translucency. Trisomy 21 was the only abnormality found by NIPT in the groups with 1 and 2 soft markers, while groups with multiple soft markers were all normal. By using SNP array, it was identified that the rate of chromosomal abnormalities such as aneuploidy and triploidy, LOH, and CNVs was lower in the group with a single ultrasonic soft marker compared to the group with structural abnormalities in multiple systems. Trisomy 21, Trisomy 18, and chromosomal structural abnormalities were the most common chromosomal abnormalities that ultrasound soft markers could diagnose. Therefore, it is recommended to employ soft markers besides CMA, SNP array, and NIPS (or NIPT) for greater accuracy in detecting foetus abnormalities., Competing Interests: None., (Copyright © 2024 Termedia.)

Introduction: Concerns regarding the adverse consequences of radiation have increased due to the expanded application of computed tomography (CT) in medical practice. Certain studies have indicated that the radiation dosage depends on the anatomical region, the imaging technique employed and patient-specific variables. The aim of this study is to present fitting models for the estimation of age-specific dose estimates (ASDE), in the same direction of size-specific dose estimates, and effective doses based on patient age, gender and the type of CT examination used in paediatric head, chest and abdomen-pelvis imaging., Methods: A total of 583 paediatric patients were included in the study. Radiometric data were gathered from DICOM files. The patients were categorised into five distinct groups (under 15 years of age), and the effective dose, organ dose and ASDE were computed for the CT examinations involving the head, chest and abdomen-pelvis. Finally, the best fitting models were presented for estimation of ASDE and effective doses based on patient age, gender and the type of examination., Results: The ASDE in head, chest, and abdomen-pelvis CT examinations increases with increasing age. As age increases, the effective dose in head and abdomen-pelvis CT scans decreased. However, for chest scans, the effective dose initially showed a decreasing trend until the first year of life; after that, it increases in correlation with age., Conclusions: Based on the presented fitting model for the ASDE, these CT scan quantities depend on factors such as patient age and the type of CT examination. For the effective dose, the gender was also included in the fitting model. By utilising the information about the scan type, region and age, it becomes feasible to estimate the ASDE and effective dose using the models provided in this study., (© 2024 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.)

Ultrasonography, a radiation-free and cost-effective modality, stands out as a promising tool for evaluating nasal bone fractures. Despite limited literature on its pediatric application, there is an increasing recognition of its potential to enhance diagnostic precision. To evaluate the diagnostic efficacy of ultrasound in detecting pediatric nasal bone fractures. Employing established guidelines, a systematic review and meta-analysis were conducted through a comprehensive literature search in PubMed, Scopus, Web of Science, and Embase databases until December 5, 2023. Inclusion criteria encompassed studies reporting diagnostic accuracy measures of ultrasound in pediatric patients with nasal bone fractures. Data extraction and analysis were undertaken for the selected studies. Involving four studies with 277 patients, ultrasound demonstrated a pooled sensitivity of 66.1% (95% CI: 35.1-87.5%) and specificity of 86.8% (95% CI: 80.1-91.4%) in diagnosing pediatric nasal fractures. The area under the receiver operating characteristic curve (AUC) was 0.88 (95% CI: 0.72-0.93). After excluding an outlier study, sensitivity and specificity increased to 78.0% (95% CI: 65.6-86.9%) and 87.8 (95% CI: 78.1-93.6%), respectively, with an AUC of 0.79 (95% CI: 0.75-0.94). Pooled positive and negative likelihood ratios were 5.11 (95% CI: 2.12-9.15) and 0.40 (95% CI: 0.14-0.77) before exclusion and 6.75 (95% CI: 3.47-12.30) and 0.26 (95% CI: 0.15-0.40) after exclusion of an outlier study, respectively. This study highlighted ultrasonography's utility in diagnosing pediatric nasal bone fractures with high accuracy and specificity. However, caution is advised in relying solely on ultrasound due to suboptimal overall diagnostic performance, evident in likelihood ratios., (© 2024. The Author(s).)

Background and Objective: Neoadjuvant chemotherapy is a standard treatment approach for locally advanced breast cancer. Conventional imaging modalities, such as magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound, have been used for axillary lymph node evaluation which is crucial for treatment planning and prognostication. This systematic review aims to comprehensively examine the current research on applying machine learning algorithms for predicting positive axillary lymph nodes following neoadjuvant chemotherapy utilizing imaging modalities, including MRI, CT, and ultrasound., Methods: A systematic search was conducted across databases, including PubMed, Scopus, and Web of Science, to identify relevant studies published up to December 2023. Articles employing machine learning algorithms to predict positive axillary lymph nodes using MRI, CT, or ultrasound data after neoadjuvant chemotherapy were included. The review follows the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, encompassing data extraction and quality assessment., Results: Seven studies were included, comprising 1502 patients. Four studies used MRI, two used CT, and one applied ultrasound. Two studies developed deep-learning models, while five used classic machine-learning models mainly based on multiple regression. Across the studies, the models showed high predictive accuracy, with the best-performing models combining radiomics and clinical data., Conclusion: This systematic review demonstrated the potential of utilizing advanced data analysis techniques, such as deep learning radiomics, in improving the prediction of positive axillary lymph nodes in breast cancer patients following neoadjuvant chemotherapy., Competing Interests: Authors declare no conflict of interests., (© 2024 The Authors.)

Background and Objective: Multiple sclerosis (MS) is a chronic progressive autoimmune disorder of the central nervous system (CNS) that can cause inflammation, demyelination, and axon degeneration. Insulin-like growth factor-1 (IGF-1) is a single-chain polypeptide mainly synthesized in the liver and brain. IGF-1 causes neuronal and non-neuronal cell proliferation, survival, and differentiation. Therefore, it can be used in treating neuro-demyelinating diseases such as MS. The current systematic review and meta-analysis aims to compare the levels of IGF-1 in MS patients and healthy controls and also investigates IGF binding proteins (IGF-BP) and growth hormone (GH) levels between MS patients and healthy controls., Methods: In this study, we systematically searched electronic databases of PubMed, Scopus, Web of Science (WOS), and Google Scholar, up to December 2022. Studies that measured IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and healthy controls in either blood or cerebral spinal fluid (CSF) were identified. We calculated Standardized mean differences (SMD) to compare levels of IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and controls., Results: Finally, we included 11 eligible studies from 1998 to 2018. The sample size of included studies varied from 20 to 200 resulting in a total sample size of 1067 individuals, 531 MS patients, and 536 healthy controls. The mean age of the patient and control groups were 38.96 and 39.38, respectively. The average EDSS among patients was 4.56. We found that blood levels of IGF-1 (SMD = 0.20, 95% CI = -0.20 to 0.59, I2 = 82.4%, K = 8, n = 692), CSF level of IGF-1 (SMD = 0.25, 95% CI = -0.06 to 0.56, I2 = 0.0%, K = 3 n = 164) and blood levels of GH were not significantly higher in MS patients than controls (SMD = 0.08, 95% CI = -0.33 to 0.49, I2 = 77.0% K = 3, n = 421). Moreover, the blood levels of IGFBP-1 (SMD = 0.70, 95% CI = 0.01 to 1.40, I2 = 77%, K = 4, n = 255) were significantly higher in MS cases than in controls. However, the blood levels of IGFBP-2 (SMD = 0.43, 95% CI = -0.34 to 1.21, I2 = 64.2%, K = 3, n = 78) and blood levels of IGFBP-3 (SMD = 1.04, 95% CI = -0.09 to 2.17, I2 = 95.6%, K = 6, n = 443) were not significantly higher in patients than controls., Conclusion: Our meta-analysis revealed no significant difference in serum levels of IGF-1, GH, IGFBP-2, and IGFBP-3 between the MS group and healthy controls, except for IGFBP1. However, our systematic review showed that the studies were controversial for IGFBP-3 serum levels. Some studies found an increase in serum level of IGFBP-3 in MS patients compared to the healthy group, while others showed a decrease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yaghoobpoor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Bronchopulmonary Dysplasia (BPD) has a multifactorial etiology. Vitamin E and vitamin D play an important role in lung development and can potentially be beneficial in the prevention of BPD., Objective: The study aimed to compare the risk of BPD occurrence in preterm neonates supplemented with vitamin D or E versus those who did not get supplementation., Methods: The literature search was conducted for this systematic review by searching the PubMed, Scopus, and Web of Science databases up to December 2022. Randomized controlled trials involved administering vitamin D or E to preterm neonates and examining the occurrence of BPD. We excluded non-English articles, and articles with non-relevant and insufficient data. We used the Critical Appraisal Skills Programme (CASP) checklist to assess the quality of the included studies. We used Egger's test to evaluate the risk of bias among the included studies. Heterogeneity was also assessed through Q-test and I2. We applied the random effect model for analysis. A P-value less than 0.05 was considered as significant. All the statistical analysis in the current study was performed using STATA 14. The Relative Risk (RR) was calculated as the effect size with 95% Confidence Interval (CI)., Results: Three eligible studies seeking the role of vitamin D in the prevention of BPD were analysed. Meta-analysis revealed that receiving vitamin D supplementation can significantly reduce the risk of BPD in preterm infants (RR = 0.357, 95% CI: 0.189-0.675, I2 = 0.0%; p = 0.002). Similarly, for assessing the role of Vitamin E in the prevention of BPD, three eligible studies were analysed. Vitamin E supplementation was not found to play a significant role in the reduction of BPD (RR = 0.659, 95%CI = 0.243-1.786, I2 = 38.7%; p = 0.412)., Conclusion: Vitamin D supplementation could be beneficial in preventing BPD in preterm infants. However, evidence is not enough regarding vitamin E's role in reducing the incidence of BPD in preterm infants., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Trauma is a significant cause of mortality and morbidity. It is crucial to diagnose trauma patients quickly to provide effective treatment interventions in such conditions. Whole-body computed tomography (WBCT)/pan-scan is an imaging technique that enables a faster and more efficient diagnosis for polytrauma patients. The purpose of this systematic review and meta-analysis is to evaluate the efficacy of WBCT in diagnosing injuries in polytrauma patients. We will also assess its impact on the mortality rate and length of hospital stay among trauma centers between patients who underwent WBCT and those who did not (non-WBCT). Twenty-seven studies meeting our inclusion criteria were selected among PubMed, Scopus, Web of Science, and Google Scholar. The criteria were centered on the significance of WBCT/pan-scan application in trauma patients. Stata version 15 was used to perform statistical analysis on the data. The authors have also used I 2 statistics to evaluate heterogeneity. Egger and Begg's tests were performed to rule out any publication bias. Total of twenty-seven studies including 68,838 trauma patients with a mean age of 45.0 ± 24.7 years were selected. Motor vehicle collisions were the most common cause of blunt injuries (80.0%). Head, neck, and face injuries were diagnosed in 44% (95% CI, 0.28-0.60; I 2  = 99.8%), 6% (95% CI, 0.02-0.09; I 2  = 97.2%), and 9% (95% CI, 0.05-0.13; I 2  = 97.1%), respectively. Chest injuries were diagnosed by WBCT in 39% (95% CI, 0.28-0.51; I 2  = 99.8%), abdominal injuries in 23% (95% CI, 0.03-0.43; I 2  = 99.9%) of cases, spinal injuries 19% (95% CI, 0.11-0.27; I 2  = 99.4%), extremity injuries 33% (95% CI, 0.23-0.43; I 2  = 99.2%), and pelvic injuries 11% (95% CI, 0.04-0.18; I 2  = 97.4%). A mortality odd ratio of 0.94 (95% CI, 0.83-1.06; I 2  = 40.1%) was calculated while comparing WBCT and non-WBCT groups. This systematic review and meta-analysis provide insight into the possible safety, efficacy, and efficiency of WBCT/pan-scan as a diagnostic tool for trauma patients with serious injuries, regardless of their hemodynamic status. In patients with serious injuries from trauma, whether or not there are indicators of hemodynamic instability, our recommended approach is to, wherever possible, perform a WBCT without stopping the hemostatic resuscitation. By using this technology, the optimal surgical strategy for these patients can be decided upon without causing any delays in their final care or greatly raising their radiation dose., (© 2024. The Author(s).)

This meta-analysis assessed the use of the neutrophil-to-lymphocyte ratio (NLR) as a means of early detection of contrast-induced nephropathy (CIN) following diagnostic or therapeutic procedures. We used Web of Science, PubMed, and Scopus to conduct a systematic search. There was no limitation regarding language or date of publication. We reported standardized mean difference (SMD) with a 95% confidence interval (CI). Due to high heterogeneity, a random-effects model was used, and the Newcastle-Ottawa scale was used for quality assessment. Thirty-one articles were included in the analysis. Patients in the CIN group had elevated levels of NLR compared with those in the non-CIN group (SMD = 0.78, 95% CI = 0.52-1.04, P < .001). Similar results were observed in either prospective (SMD = 1.03, 95% CI = 0.13-1.93, P = .02) or retrospective studies (SMD = 0.70, 95% CI = 0.45-0.96, P < .001). The pooled sensitivity of NLR was 74.02% (95% CI = 66.54%-81.02%), and the pooled specificity was 60.58% (95% CI = 53.94%-66.84%). NLR shows potential as a cost-effective biomarker for predicting CIN associated with contrast-involved treatments. This could help implement timely interventions to mitigate CIN and improve outcomes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: We conducted a systematic review and meta-analysis to compare the neutrophil lymphocyte ratio (NLR) levels between women with post-menopausal osteopenia or osteoporosis to those with normal bone mineral density (BMD)., Methods: We used Web of Science, PubMed, and Scopus to conduct a systematic search for relevant publications published before June 19, 2022, only in English language. We reported standardized mean difference (SMD) with a 95% confidence interval (CI). Because a significant level of heterogeneity was found, we used the random-effects model to calculate pooled effects. We used the Newcastle-Ottawa scale for quality assessment., Results: Overall, eight articles were included in the analysis. Post-menopausal women with osteoporosis had elevated levels of NLR compared to those without osteoporosis (SMD = 1.03, 95% CI = 0.18 to 1.88, p = 0.017, I 2  = 98%). In addition, there was no difference between post-menopausal women with osteopenia and those without osteopenia in neutrophil lymphocyte ratio (NLR) levels (SMD = 0.58, 95% CI=-0.08 to 1.25, p = 0.085, I 2  = 96.8%). However, there was no difference between post-menopausal women with osteoporosis and those with osteopenia in NLR levels (SMD = 0.75, 95% CI=-0.01 to 1.51, p = 0.05, I 2  = 97.5%, random-effect model)., Conclusion: The results of this study point to NLR as a potential biomarker that may be easily introduced into clinical settings to help predict and prevent post-menopausal osteoporosis., (© 2024. The Author(s).)

Atlantoaxial rotatory fixation (AARF) in adults is a rare and clinically challenging condition characterized by a spectrum of etiological factors, predominantly attributed to traumatic and inflammatory pathologies within the craniovertebral region. Trauma is the most frequently identified cause within the adult population, with the first case report published in 1907. This study aims to conduct a systematic review that addresses the clinical presentations and management strategies relating to traumatic atlantoaxial rotatory fixation in adults. A comprehensive search of the PubMed database was executed, adhering to the PRISMA guidelines. The inclusion criteria encompassed case reports and series documenting AARF cases in individuals aged 18 and above, spanning database inception to July 2022. Studies not published in the English language were excluded. A total of 61 articles reporting cases of AARF in the adult population were included in the study. The mean age of affected individuals was 36.1 years (± 15.6), with a distribution of 46% females and 54% males. Predominant mechanisms of injury included motor vehicle accidents and falls, constituting 38% and 22% of cases, respectively. Among the classification systems employed, Fielding and Hawkins type I accounted for the majority at 63%, followed by type II at 10%, and type III at 4%. Conservative management was used for treatment in 65% of acute (65%) cases and 29% of chronic cases. Traumatic AARF is a rare phenomenon in the adult population, is more common in younger adults, and does not often present with neurologic deficits. Patients diagnosed acutely are more likely to be successfully treated with conservative management, while patients diagnosed chronically are less likely to be reduced with conservatively and often require surgical treatment. Surgery should be considered for patients with irreducible dislocations, ligamentous injuries, unstable associated fractures, and persistent pain resistant to conservative management., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: Vitamin D is a prominent modulator of immunity and respiratory function. It plays a vital role in respiratory diseases such as cystic fibrosis (CF). S. However, there is a dearth of information on patients with CF. The purpose of the meta-analysis is to highlight the importance of following the existing guidelines regarding maintenance of Vitamin D serum levels in patients with CF., Methods: The systematic search was conducted without utilizing any time or language limitations in original database from the beginning until March 2022. The meta-analysis was performed using a random-effects model. Heterogeneity was determined by I 2 statistics and Cochrane Q test., Results: Pooled analysis using the random-effects model of the 8 case-control studies with 13 effect sizes revealed that the serum 25-OH-vitamin D in participants with cystic fibrosis was significantly lower than controls in pediatrics and adolescences (WMD: - 3.41 ng/ml, 95% CI - 5.02, - 1.80, p =  < 0.001) and adults (WMD: - 2.60 ng/ml, 95% CI - 4.32, - 0.89, p = 0.003). Based on data from 12 studies (21 effect sizes) with a total of 1622 participants, the prevalence of vitamin D levels of 20-30 ng/ml in CF patients was 36% among pediatrics/adolescents and 63% among adults. In addition, 27% of pediatric/adolescent CF patients and 35% of adult CF patients had vitamin D levels of below 20 ng/ml., Conclusions: As a result, according to the existing guidelines, our results proved the need to pay attention to the level of vitamin D in these patients., (© 2024. The Author(s).)

Epilepsy significantly reduces the patient's quality of life, and we still need to develop new therapeutic approaches to control it. Transplantation of cells such as Sertoli cells (SCs), having a potent ability to release a variety of growth and immunoprotective substances, have made them a potential candidate to deal with neurological diseases like epilepsy. Hence, this study aims to evaluate whether SCs transplant effectively protects the hippocampus astrocytes and neurons to oppose seizure damage. For this purpose, the effects of bilateral intrahippocampal transplantation of SCs were investigated on the rats with the pentylenetetrazol (PTZ) induced seizure. After one-month, post-graft analysis was performed regarding behavior, immunohistopathology, and the distribution of the hippocampal cells. Our findings showed SCs transplantation reduced astrogliosis, astrocytes process length, the number of branches, and intersections distal to the soma of the hippocampus in the seizure group. In rats with grafted SCs, there was a drop in the hippocampal caspase-3 expression. Moreover, the SCs showed another protective impact, as shown by an improvement in pyramidal neurons' number and spatial distribution. The findings suggested that SCs transplantation can potently modify astrocytes' reactivation and inflammatory responses., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The present study aims to review the existing scientific literature on the role of neutrophil to lymphocyte ratio (NLR) in diabetic peripheral neuropathy (DPN) to perform a meta-analysis on the available data., Methods: The electronic repositories Web of Science, PubMed, and Scopus were systematically explored starting from their establishment up until June 9, 2022., Results: Fifteen articles were included in the meta-analysis after multiple screening according to the PRISMA guidelines. The combined findings indicated that individuals with DPN had higher levels of NLR in comparison to those without DPN (SMD = 0.61; CI 95% = 0.40-0.81, p < 0.001). In the subgroup assessment based on ethnicity, it was observed that diabetic patients with DPN exhibited increased NLR levels in contrast to those without DPN in studies conducted in India (SMD = 1.30; CI 95% = 0.37-2.24, p = 0.006) and East Asia (SMD = 0.53; CI 95% = 0.34-0.73, p < 0.001) but not in studies conducted in Turkey (SMD = 0.30; CI 95% = - 0.06-0.67, p = 0.104) and Egypt (SMD = 0.34; CI 95% = -0.14-0.82, p = 0.165). The pooled sensitivity of NLR was 0.67 (95% CI = 0.49-0.81), and the pooled specificity was 0.70 (95% CI, 0.56-0.81). The pooled positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR) of NLR were 2.30 (95% CI = 1.71-3.09), 0.45 (95%CI = 0.30-0.67), and 5.06 (95% CI = 3.16-8.12), respectively., Conclusion: NLR serves as a distinct marker of inflammation, and its rise in cases of DPN suggests an immune system imbalance playing a role in the development of the disease., (© 2023. The Author(s).)

Purpose: Magnetic resonance imaging (MRI) can reduce the need for unnecessary invasive diagnostic tests by nearly half. In this meta-analysis, we investigated the diagnostic accuracy of intravoxel incoherent motion modeling (IVIM) and dynamic contrast-enhanced (DCE) MRI in differentiating benign from malignant breast lesions., Method: We systematically searched PubMed, EMBASE, and Scopus. We included English articles reporting diagnostic accuracy for both sequences in differentiating benign from malignant breast lesions. Articles were assessed by quality assessment of diagnostic accuracy studies-2 (QUADAS-2) questionnaire. We used a bivariate effects model for standardized mean difference (SMD) analysis and diagnostic test accuracy analysis., Results: Ten studies with 537 patients and 707 (435 malignant and 272 benign) lesions were included. The D, f, Ktrans, and Kep mean values significantly differ between benign and malignant lesions. The pooled sensitivity (95 % confidence interval) and specificity were 86.2 % (77.9 %-91.7 %) and 70.3 % (56.5 %-81.1 %) for IVIM, and 93.8 % (85.3 %-97.5 %) and 68.1 % (52.7 %-80.4 %) for DCE, respectively. Combined IVIM and DCE depicted the highest area under the curve of 0.94, with a sensitivity and specificity of 91.8 % (82.8 %-96.3 %) and 87.6 % (73.8 %-94.7 %), respectively., Conclusions: Combined IVIM and DCE had the highest diagnostic accuracy, and multiparametric MRI may help reduce unnecessary benign breast biopsy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Objectives: Carotid-cavernous fistulas (CCFs) represent a group of rare, abnormal arteriovenous communications between the carotid arterial system and the cavernous sinuses (CS). CCFs often produce ophthalmologic symptoms related to increased CS pressures and retrograde venous drainage of the eye. Although endovascular occlusion remains the preferred treatment for symptomatic or high-risk CCFs, most of the data for these lesions is limited to small, single-center series. As such, we performed a systematic review and meta-analysis evaluating endovascular occlusions of CCFs to determine any differences in clinical outcomes based on presentation, fistula type, and treatment paradigm., Method: A retrospective review of all studies discussing the endovascular treatment of CCFs published through March 2023 was conducted using PubMed, Scopus, Web of Science, and Embase databases. A total of 36 studies were included in the meta-analysis. Data from the selected articles were extracted and analyzed using Stata software version 14., Results: 1494 patients were included. 55.08% were female and the mean age of the cohort was 48.10 years. A total number of 1516 fistulas underwent endovascular treatment, 48.05% of which were direct and 51.95% of which were indirect. 87.17% of CCFs were secondary to a known trauma while 10.18% were spontaneous. The most common presenting symptoms were 89% exophthalmos (95% CI: 78.0-100.0; I 2  = 75.7%), 84% chemosis (95% CI: 79.0-88.0; I 2  = 91.6%), 79% proptosis (95% CI: 72.0-86.0; I 2  = 91.8%), 75.0% bruits (95% CI: 67.0-82.0; I 2  = 90.7%), 56% diplopia (95% CI: 42.0-71.0; I 2  = 92.3%), 49% cranial nerve palsy (95% CI: 32.0-66.0; I 2  = 95.1%), 39% visual decline (95% CI: 32.0-45.0; I 2  = 71.4%), 32% tinnitus (95% CI: 6.0-58.0; I 2  = 96.7%), 29% elevated intraocular pain (95% CI: 22.0-36.0; I 2  = 0.0%), 31% orbital or pre-orbital pain (95% CI: 14.0-48.0; I 2  = 89.9%) and 24% headache (95% CI: 13.0-34.0; I 2  = 74.98%). Coils, balloons, and stents were the three most used embolization methods respectively. Immediate complete occlusion of the fistula was seen in 68% of cases and complete remission was seen in 82%. Recurrence of CCF occurred in only 35% of the patients. Cranial nerve paralysis after treatment was observed in 7% of the cases., Conclusions: Exophthalmos, Chemosis, proptosis, bruits, cranial nerve palsy, diplopia, orbital and periorbital pain, tinnitus, elevated intraocular pressure, visual decline and headache are the most common clinical manifestations of CCFs. The majority of endovascular treatments involved coiling, balloons and onyx and a high percentage of CCF patients experienced complete remission with the improvement of their clinical symptoms., Competing Interests: None., (© 2023 Published by Elsevier Inc.)

MicroRNAs (miRNAs) are small non-coding RNAs regulating the expression of several target genes. miRNAs play a significant role in cancer biology, as they can downregulate their corresponding target genes by impeding the translation of mRNA (at the mRNA level) as well as degrading mRNAs by binding to the 3'-untranslated (UTR) regions (at the protein level). miRNAs may be employed as cancer biomarkers. Therefore, miRNAs are widely investigated for early detection of cancers which can lead to improved survival rates and quality of life. This is particularly important in the case of gastrointestinal cancers, where early detection of the disease could substantially impact patients' survival. MicroRNA-21 (miR-21 or miRNA-21) is one of the most frequently researched miRNAs, where it is involved in the pathophysiology of cancer and the downregulation of several tumor suppressor genes. In gastrointestinal cancers, miR-21 regulates phosphatase and tensin homolog (PTEN), programmed cell death 4 (PDCD4), mothers against decapentaplegic homolog 7 (SMAD7), phosphatidylinositol 3-kinase /protein kinase B (PI3K/AKT), matrix metalloproteinases (MMPs), β-catenin, tropomyosin 1, maspin, and ras homolog gene family member B (RHOB). In this review, we investigate the functions of miR-21 in pathogenesis and its applications as a diagnostic and prognostic cancer biomarker in four different gastrointestinal cancers, including colorectal cancer (CRC), pancreatic cancer (PC), gastric cancer (GC), and esophageal cancer (EC)., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The gut microbiota undergoes significant alterations in response to viral infections, particularly the novel SARS-CoV-2. As impaired gut microbiota can trigger numerous neurological disorders, we suggest that the long-term neurological symptoms of COVID-19 may be related to intestinal microbiota disorders in these patients. Thus, we have gathered available information on how the virus can affect the microbiota of gastrointestinal systems, both in the acute and the recovery phase of the disease, and described several mechanisms through which this gut dysbiosis can lead to long-term neurological disorders, such as Guillain-Barre syndrome, chronic fatigue, psychiatric disorders such as depression and anxiety, and even neurodegenerative diseases such as Alzheimer's and Parkinson's disease. These mechanisms may be mediated by inflammatory cytokines, as well as certain chemicals such as gastrointestinal hormones (e.g., CCK), neurotransmitters (e.g., 5-HT), etc. (e.g., short-chain fatty acids), and the autonomic nervous system. In addition to the direct influences of the virus, repurposed medications used for COVID-19 patients can also play a role in gut dysbiosis. In conclusion, although there are many dark spots in our current knowledge of the mechanism of COVID-19-related gut-brain axis disturbance, based on available evidence, we can hypothesize that these two phenomena are more than just a coincidence and highly recommend large-scale epidemiologic studies in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vakili, Fathi, Yaghoobpoor, Sayehmiri, Nazerian, Nazerian, Mohamadkhani, Khodabakhsh, Réus, Hajibeygi and Rezaei-Tavirani.)

Background: Multiple sclerosis (MS) is a debilitating neurodegenerative disorder characterized by axonal damage, demyelination, and perivascular inflammatory lesions in the white matter of the central nervous system (CNS). Kynurenine pathway (KP), which is the major route of tryptophan (TRP) metabolism, generates a variety of neurotoxic as well as neuroprotective compounds, affecting MS pathology and the severity of impairments. Alterations in KP have been described not only in MS, but also in various psychiatric and neurodegenerative diseases. The purpose of this systematic review is to investigate the previously reported dysregulation of KP and differences in its metabolites and enzymes in patients with MS compared to healthy control subjects., Method: Electronic databases of PubMed, Scopus, Cochrane Database of Systematic Reviews, and Web of Science were searched to identify studies measuring concentrations of KP metabolites and enzymes in MS patients and control subjects. The following metabolites and enzymes implicated in the KP were investigated: TRP, kynurenine (KYN), kynurenic acid (KYNA), quinolinic acid (QUIN), picolinic acid (PIC), hydroxyindoleacetic acid (HIAA), indoleamine 2,3-dioxygenase (IDO), kynurenine aminotransferase (KAT), and their related ratios., Result: Ten studies were included in our systematic review. Our review demonstrates that IDO expression is reduced in the peripheral blood mononuclear cells (PBMCs) of MS patients compared to healthy controls. Also, increased levels of QUIN and QUIN/KYNA in the serum and cerebrospinal fluid (CSF) of MS patients is observed. Differences in levels of other metabolites and enzymes of KP are also reported in some of the reviewed studies, however there are discrepancies among the included reports., Conclusion: The results of this investigation suggest a possible connection between alterations in the levels of KP metabolite or enzymes and MS. QUIN levels in CSF were higher in MS patients than in healthy controls, suggesting that QUIN may be involved in the pathogenesis of MS. The data indicate that differences in the serum/blood or CSF levels of certain KP metabolites and enzymes could potentially be used to differentiate between MS patients and control subjects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fathi, Vakili, Yaghoobpoor, Tavasol, Jazi, Mohamadkhani, Klegeris, McElhinney, Mafi, Hajiesmaeili and Sayehmiri.)

Background: COVID-19 is a viral infectious disease leading to a spectrum of clinical complications, especially cardiovascular. Evidence shows that this infection can potentially accompany a worse outcome in pregnant women. Cardiovascular complications in mothers and their fetuses are reported by previous studies., Objective: In this systematic review, we aim to investigate the cardiovascular complications of COVID-19 during pregnancy in the mothers and fetus, according to the published literature., Method: We systematically searched the online databases of PubMed, Scopus, Web of Science, and Google Scholar, using relevant keywords up to April 2022. We included all observational studies reporting cardiovascular complications among COVID-19-affected pregnant women and their fetuses., Results: We included 74 studies containing 47582 pregnant COVID-19 cases. Pre-eclampsia, hypertensive disorders, cardiomyopathy, heart failure, myocardial infarction, thrombosis formation, alterations in maternal-fetal Doppler patterns, and maternal and fetal arrhythmia were reported as cardiovascular complications. The highest incidences of pre-eclampsia/eclampsia among COVID-19 pregnant cases, reported by studies, were 69% and 62%, and the lowest were 0.5% and 3%. The highest and lowest incidences of fetal bradycardia were 20% and 3%, and regarding fetal tachycardia, 5.4% and 1%, respectively., Conclusion: SARS-CoV-2 infection during pregnancy can potentially be associated with cardiovascular complications in the mother, particularly pre-eclampsia and heart failure. Moreover, SARS-CoV-2 infection during pregnancy can potentially cause cardiovascular complications in the fetus, particularly arrhythmia., Competing Interests: The authors declare no conflict of interest.

Migraine headaches are highly prevalent, affecting 15% of the population. However, despite many studies to determine this disease's mechanism and efficient management, its pathophysiology has not been fully elucidated. There are suggested hypotheses about the possible mediating role of mast cells, immunoglobulin E, histamine, and cytokines in this disease. A higher incidence of this disease in allergic and asthma patients, reported by several studies, indicates the possible role of brain mast cells located around the brain vessels in this disease. The mast cells are more specifically within the dura and can affect the trigeminal nerve and cervical or sphenopalatine ganglion, triggering the secretion of substances that cause migraine. Neuropeptides such as calcitonin gene-related peptide (CGRP), neurokinin-A, neurotensin (NT), pituitary adenylate-cyclase-activating peptide (PACAP), and substance P (SP) trigger mast cells, and in response, they secrete pro-inflammatory and vasodilatory molecules such as interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) as a selective result of corticotropin-releasing hormone (CRH) secretion. This stress hormone contributes to migraine or intensifies it. Blocking these pathways using immunologic agents such as CGRP antibody, anti-CGRP receptor antibody, and interleukin-1 beta (IL-1β)/interleukin 1 receptor type 1 (IL-1R1) axis-related agents may be promising as potential prophylactic migraine treatments. This review is going to summarize the immunological aspects of migraine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Salahi, Parsa, Nourmohammadi, Razmkhah, Salimi, Rahmani, Zivary, Askarzadeh, Tapak, Vaezi, Sadeghsalehi, Yaghoobpoor, Mottahedi, Garousi and Deravi.)

The complement system, as a vital part of innate immunity, has an important role in the clearance of pathogens; however, unregulated activation of this system probably has a key role in the pathogenesis of acute lung injury, which is induced by highly pathogenic viruses (i.e. influenza A viruses and severe acute respiratory syndrome [SARS] coronavirus). The novel coronavirus SARS-CoV-2, which is the causal agent for the ongoing global pandemic of the coronavirus disease 2019 (Covid-19), has recently been spread to almost all countries around the world. Although most people are immunocompetent to SARS-CoV-2, a small group develops hyper-inflammation that leads to complications like acute respiratory distress syndrome, disseminated intravascular coagulation, and multi-organ failure. Emerging evidence demonstrates that the complement system exerts a crucial role in this inflammatory reaction. Additionally, patients with the severe form of Covid-19 show over-activation of the complement in their skin, sera, and lungs. This study aims to summarise current knowledge concerning the interaction of SARS-CoV-2 with the complement system and to critically appraise complement inhibition as a potential new approach for Covid-19 treatment., (© 2021 John Wiley & Sons Ltd.)

The goal of this study was to conduct a systematic review of the literature on the relationship between peripheral blood platelet to lymphocyte ratio (PLR) and mortality in sepsis and to integrate the findings in a meta-analysis. An electronic search of three main databases was performed: PubMed, Embase, and Scopus on 19 December 2021. Finally, 16 studies comprising 2403 septic patients, including 1249 survivors and 1154 nonsurvivors, were included in this meta-analysis. We found that PLR levels were significantly higher in nonsurvivors than in survivors (random effect model: SMD = 0.72, 95% CI; 0.35-1.10, p < 0.001). However, significant heterogeneity was observed across the studies ( I 2 = 94.1%, p < 0.01). So, we used random effect model in our meta-analysis. In the subgroup analysis, according to mortality time, patients deceased during one month after sepsis had elevated levels of PLR compared to survivors (SMD = 1.03, 95% CI = 0.15-1.92, p = 0.22). However, in-hospital mortality was not associated with PLR level (SMD = 0.41, 95% CI = -0.18-0.99, p = 0.175). Our findings support PLR to be a promising biomarker that can be readily integrated into clinical settings to aid in the prediction and prevention of sepsis mortality., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2022 Gancheng Wang et al.)

Diabetes mellitus and Alzheimer's disease are considered the most prevalent diseases in older ages worldwide. The main pathology of Alzheimer's disease is highly related with accumulation of misfolded proteins that lead to neuronal dysfunction in the brain. On the other hand, diabetes mellitus is associated with alteration of insulin signaling, which could cause the reduction of glucose uptake, metabolic prohibition of energy consuming cells, as well as suppression of glucose to fat conversion in the liver. In spite of having seemingly different pathological features, both diseases share common underlying biological mechanisms. Besides, the epidemiological and environmental links between these two diseases should not be overlooked. In this study, we aim to review shared pathological mechanisms of Alzheimer's disease and diabetes mellitus, including impaired glucose metabolism, increased Amyloid-Beta (Aβ) production, impaired lipid metabolism, mitochondrial dysfunction, increased inflammation and elevated oxidative stress. Furthermore, we discuss epidemiological association between these two diseases and also review animal investigations, which have evaluated the potential links between the two diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: It is known that vitamin D can increase the body's immunity against some viral infections. Many people worldwide have vitamin D deficiency; therefore, this has become a public concern whether vitamin D is an important factor protecting against COVID-19 infection. In this paper, the data about the roles of vitamin D in immunity and recovery from viral infections, especially novel Coronavirus disease (COVID- 19), are reviewed., Methods: The electronic databases of Pubmed, Google Scholar, Research Gate, Excerpta Media Database (EMBASE), and Medical and Health Education (Medrix) were searched., Results: Vitamin D is considered an important factor in immune homeostasis. Various effects have been considered for this nutrient on the immune system, particularly because of vitamin D receptor (VDR) and Cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1) expression in most of the immune cells. Vitamin D can increase cellular immunity, reduce cytokine storm, and enhance antioxidants production. It also has modulatory effects on Angiotensin-converting enzyme 2 (ACE2) receptors and might have protective functions against acute lung injuries, including COVID-19 infection. However, there are some articles against this positive effect., Conclusion: Vitamin D supplementation is reported to be effective in the enhancement of the immune system and might be effective in the treatment and prevention of COVID-19 infection, especially in those with its deficiency. However, it should be considered that vitamin D deficiency shows the overall health status of the patients and cannot be considered specific for COVID-19 infection., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

After the emergence of the novel 2019 coronavirus disease in P. R. China, this highly contagious disease has been currently spread out to almost all countries, worldwide. Novel 2019 coronavirus disease, Middle East respiratory syndrome, and severe acute respiratory syndrome are reported to cause a higher risk for severe infections in patients with chronic comorbidities, such as hypertension and diabetes. These severe infections can contribute to higher rates of morbidity and mortality in these patients. In the present review, we discussed the role and underlying mechanisms of the two most common chronic diseases, type-2 diabetes mellitus and hypertension, in clinical manifestations and disease severity of novel 2019 coronavirus disease, Middle East respiratory syndrome and severe acute respiratory syndrome, with the hope to provide evidence for better decision-making in the treatment of this vulnerable population., Competing Interests: All authors declare no conflicts of interest., (© 2020 Deravi et al. Published by IMR press.)

Around the end of December 2019, a new beta-coronavirus from Wuhan City, Hubei Province, China began to spread rapidly. The new virus, called SARS-CoV-2, which could be transmitted through respiratory droplets, had a range of mild to severe symptoms, from simple cold in some cases to death in others. The disease caused by SARS-CoV-2 was named COVID-19 by WHO and has so far killed more people than SARS and MERS. Following the widespread global outbreak of COVID-19, with more than 132758 confirmed cases and 4955 deaths worldwide, the World Health Organization declared COVID-19 a pandemic disease in January 2020. Earlier studies on viral pneumonia epidemics has shown that pregnant women are at greater risk than others. During pregnancy, the pregnant woman is more prone to infectious diseases. Research on both SARS-CoV and MERS-CoV, which are pathologically similar to SARS-CoV-2, has shown that being infected with these viruses during pregnancy increases the risk of maternal death, stillbirth, intrauterine growth retardation and, preterm delivery. With the exponential increase in cases of COVID-19 throughout the world, there is a need to understand the effects of SARS-CoV-2 on the health of pregnant women, through extrapolation of earlier studies that have been conducted on pregnant women infected with SARS-CoV, and MERS-CoV. There is an urgent need to understand the chance of vertical transmission of SARS-CoV-2 from mother to fetus and the possibility of the virus crossing the placental barrier. Additionally, since some viral diseases and antiviral drugs may have a negative impact on the mother and fetus, in which case, pregnant women need special attention for the prevention, diagnosis, and treatment of COVID-19., Competing Interests: The authors confirm that they have no conflicts of interest., (© National Institute of Public Health – National Institute of Hygiene.)