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Ascaris lumbricoides is the most common type of helminth infection in humans. It affects more than one billion of the world's population. Children living in developing nations are prone to ascariasis, presenting with obstructive biliary illnesses. Migration of Ascaris worms through the major duodenal papilla to the hepatobiliary system leads to symptoms of biliary colic and complications along the biliary tree. In April 2022, we performed a systematic review of case reports to identify and examine cases of gallbladder ascariasis worldwide. A methodical search using PubMed, Semantic Scholar, ScienceDirect, and Directory of Open Access Journals yielded 2773 studies. After duplicate removal, title, abstract, and content screening, retrieval, and quality assessment, 13 studies met the criteria for this systematic review of case reports. The cases and results from these 13 studies revealed gallbladder ascariasis in different age groups worldwide. This systematic review discusses ascariasis, explicitly highlighting its presence in the gallbladder, symptomatic presentation, laboratory/imaging findings, complications, and approach to management., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Inyang et al.)

Background: Use of a standardized verbal autopsy (VA) questionnaire, such as the World Health Organization (WHO) instrument, can improve the consistency and reliability of the data it collects. Systematically revising a questionnaire, however, requires evidence about the performance of its questions. The purpose of this investigation was to use a mixed methods approach to evaluate the performance of questions related to 14 previously reported issues in the 2016 version of the WHO questionnaire, where there were concerns of potential confusion, redundancy, or inability of the respondent to answer the question. The results from this mixed methods analysis are discussed across common themes that may have contributed to the underperformance of questions and have been compiled to inform decisions around the revision of the current VA instrument., Methods: Quantitative analysis of 19,150 VAs for neonates, children, and adults from five project teams implementing VAs predominately in Sub-Saharan Africa included frequency distributions and cross-tabulations to evaluate response patterns among related questions. The association of respondent characteristics and response patterns was evaluated using prevalence ratios. Qualitative analysis included results from cognitive interviewing, an approach that provides a detailed understanding of the meanings and processes that respondents use to answer interview questions. Cognitive interviews were conducted among 149 participants in Morocco and Zambia. Findings from the qualitative and quantitative analyses were triangulated to identify common themes., Results: Four broad themes contributing to the underperformance or redundancy within the instrument were identified: question sequence, overlap within the question series, questions outside the frame of reference of the respondent, and questions needing clarification. The series of questions associated with one of the 14 identified issues (the series of questions on injuries) related to question sequence; seven (tobacco use, sores, breast swelling, abdominal problem, vomiting, vaccination, and baby size) demonstrated similar response patterns among questions within each series capturing overlapping information. Respondent characteristics, including relationship to the deceased and whether or not the respondent lived with the deceased, were associated with differing frequencies of non-substantive responses in three question series (female health related issues, tobacco use, and baby size). An inconsistent understanding of related constructs was observed between questions related to sores/ulcers, birth weight/baby size, and diagnosis of dementia/presence of mental confusion. An incorrect association of the intended construct with that which was interpreted by the respondent was observed in the medical diagnosis question series., Conclusions: In this mixed methods analysis, we identified series of questions which could be shortened through elimination of redundancy, series of questions requiring clarification due to unclear constructs, and the impact of respondent characteristics on the quality of responses. These changes can lead to a better understanding of the question constructs by the respondents, increase the acceptance of the tool, and improve the overall accuracy of the VA instrument., Competing Interests: The authors have declared that no competing interests exist.

Various factors may have a role in the development of attention deficit hyperactivity disorder (ADHD). Although the specific pathophysiology of this disease is still not entirely understood, it is believed to be caused by a mix of genetic, maternal, dietary, and environmental factors. The effect of these factors can determine the severity of ADHD; for example, some of them are dose-dependent, but there is a typical pattern that all are known to be associated with either early childhood exposure or maternal exposure during pregnancy. Some factors share a similar mechanism of affecting pathways and increasing the risk of ADHD. ADHD is not a disorder that can be detected before symptoms appear in a child, making it more challenging to anticipate even if a child has been exposed to a known trigger. Environmental pollutants were investigated, and it was shown that there was a link between ADHD in childhood and exposure to pollutants throughout childhood or during pregnancy. It is well known that maternal health is a significant factor in the unborn child's development in many health aspects. The central nervous system (CNS) is a primary system that can suffer irreversible damage from health conditions, stress, depression, or specific nutritional deficiency when the pregnant mother is subjected to these conditions. Even though numerous studies have been conducted to investigate the probable causes of ADHD, with some of them having robust findings, no conclusive explanation can be provided to identify a definitive cause or a risk factor., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Yusuf Ali et al.)

Selective phosphodiesterase 4 (PDE4) inhibitors have been extensively studied for the treatment of various respiratory diseases due to their broad anti-inflammatory and/or bronchodilator effects. Roflumilast, an oral selective PDE4 inhibitor, is currently used as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) with chronic bronchitis. Despite its proven efficacy in other respiratory disorders, including asthma, no other PDE4 inhibitor is approved for respiratory pathologies. This systematic review summarizes the therapeutic action of PDE4 inhibitors, their limitations, recent therapeutic success, and future targets for their use in respiratory diseases other than COPD. An electronic literature search was conducted on four databases, namely, PubMed, PubMed Central, Google Scholar, and ScienceDirect, to collect data on related studies done in humans and published in the English language in the last five years. After extensive analysis and quality appraisal, 11 studies were eligible and thus included in this review, consisting of two randomized controlled trials (RCT), one systematic review and meta-analysis, and eight literature reviews. Roflumilast is not approved for the treatment of asthma due to associated adverse effects and comparable efficacy to inhaled corticosteroids, which are considered the mainstay of asthma maintenance therapy. Hence, the importance of balancing the efficacy with minimizing the side effects is highlighted. Tanimilast (CHF6001), an inhalational selective PDE4 inhibitor, and ensifentrine, a combined PDE3/4 inhibitor, demonstrate the recent therapeutic success in asthma and warrant further large-scale clinical studies. Future researchers will focus on the specific endotype than the phenotype in asthma as a meaningful therapeutic approach due to the high heterogeneity noted in asthma. Current evidence suggests the possibility of PDE4 inhibitors as a novel therapeutic option for chronic cough, allergic rhinitis, and cystic fibrosis. Further evidence from new studies is eagerly anticipated to better understand the efficacy and safety of PDE4 inhibitors in these respiratory diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Goonathilake et al.)

The effect of thyroid hormones on bone mineral density in postmenopausal women has been reported but is not completely established. To better understand this relationship, this systematic review of the reported association, differences, and effects of thyroxine and/or thyrotropin levels on bone mineral density was conducted. An electronic literature search was conducted on MEDLINE, PMC, Google Scholar, Cochrane Library, and Science Direct from inception to April 2022; 20 studies were identified which include five quasi-experimental studies, three community cohort studies, and 12 hospital-based cross-sectional studies. Following an extensive evaluation, it was difficult to conclusively determine the association or effect of thyroxine or thyrotropin levels on bone mineral density in postmenopausal women. It is therefore suggested to conduct additional non-randomized or randomized control studies on this topic for the benefit of postmenopausal women. Particular attention should be given to the adjustment of age, body mass index, smoking status, alcohol consumption, and dietary calcium in future research on this topic for rigorous analysis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Poudel et al.)

The incidence of type 2 diabetes mellitus (T2DM) and its potential complications, such as cancers, are increasing worldwide at an astounding rate. There are many factors such as obesity, diabetes, alcohol consumption, and the adoption of sedentary lifestyles that are driving pancreatic cancer (PC) to become one of the leading causes of cancer mortality in the United States. PC is notorious for its generic symptoms and late-stage presentation with rapid metastasis. The connection between T2DM and the risk of PC development is multifaceted and complex. Some of the proposed theories reveal that chronic inflammation, insulin resistance, hyperinsulinemia, hyperglycemia, and abnormalities in the insulin and insulin-like growth factor axis (IGF) contribute to the disease association between these two conditions. This literature review aims to highlight relevant studies and explore the molecular mechanisms involved in the etiology of diabetes and its impact on PC development, as well as the role of anti-diabetic agents on PC. Despite extensive studies, the exact interaction between T2DM and PC remains obscure and will need further investigation. According to current knowledge, there is a substantial link between diabetes, obesity, and dietary patterns in the development and progression of PC. Consequently, focusing our efforts on preventive measures by reducing modifiable risk factors remains the most effective strategy to reduce the risk of PC at this time. Antidiabetic drugs can have various effects on the occurrence and prognosis of PC with metformin offering a clear benefit of inhibiting PC and insulin increasing the risk of PC. The development of future novel therapies will require a deeper knowledge of the triggering mechanisms and interplay between these two disease states., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, George et al.)

Melanocytic lesions have a wide morphological spectrum, ranging from benign nevi to malignant melanoma. In contrast to a diagnosis of a benign nevus, a diagnosis of melanoma could mean intensive treatment, lifetime monitoring, and a worse prognosis. Therefore, melanocytic tumors are notoriously challenging and associated with a high risk of litigation in surgical pathology. After describing the basic features of nevi and melanoma, this article describes the detailed clinical and histological features of those lesions that share many similar features with melanoma. The entities included are Spitz nevi and atypical Spitz tumors (AST), Reed nevus, dysplastic nevus, cellular blue nevus (CBN), deep penetrating nevus, combined nevus, recurrent nevus, irritated nevus, congenital pattern nevus, acral nevus, and nevi of special sites. Knowledge of these imitators can help pathologists distinguish between benign and malignant cases and avoid misdiagnosis., Competing Interests: This article has copyrighted material in the form of histopathological images, used with permission from © 2019 Innovative Pathology Press and Archives of Pathology & Laboratory Medicine, © 2010 College of American Pathologists., (Copyright © 2022, Waqar et al.)

The aim of this review is to analyze previously conducted randomized controlled trials and investigate the relationship between various exercise regimes and their effect on bone mineral density in postmenopausal women. To determine whether exercise can be used as a non-pharmacological modality for osteoporosis prevention, a thorough search was performed on various databases (PubMed, ScienceDirect, and Google Scholar). Only bone mineral density studies and trials with intervention versus control groups were included, and 13 randomized controlled trials were deemed relevant. The majority of trials concluded that exercise positively impacted bone mineral density in postmenopausal women. High-impact exercises seem to have the most significant effect on bone mineral density due to compression, shear stress, and high loading on the bone, causing bone remodeling. Considering all the limitations, exercise seems to be an effective tool for preventing postmenopausal osteoporosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Koshy et al.)

Exploration of novel biomarkers has been gaining popularity in preeclampsia, which is currently being diagnosed based on clinical criteria alone. Soluble syndecan-1, released from one of the proteoglycans associated with the syncytiotrophoblastic layer of the placenta, is affected in patients with abnormal placentation. This article is the first systematic literature review that evaluates the relationship between the antepartum serum levels of the syndecan-1 and preeclampsia. Eight studies were selected after screening and quality appraisal, and data were analyzed. The serum concentration of syndecan-1 was found to correlate positively with the gestational age in all pregnancies and negatively with the systolic blood pressure in patients with preeclampsia. Extremely low levels of soluble syndecan-1 may be helpful as a predictor for the development of preeclampsia during gestation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, George et al.)

Myocardial infarction (MI) is a global cause of morbidity and mortality. MI is the outcome of a chronic process termed atherosclerosis, a buildup of fatty and other substances called plaques inside the coronary vessels, causing hardening and thickening of the arterial wall. Erythropoietin (EPO) is a pleiotropic cytokine released mainly by the kidneys in adults. Besides its well-known erythropoietic functions, EPO possesses anti-apoptotic, mitogenic, and angiogenic effects. This review aims to analyze the strength of any therapeutic or protective value of EPO on the heart and safety concerns regarding its administration in MI individuals. This systematic review was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Four databases (PubMed, PubMed Central, Google Scholar, and Sciences Direct) were employed to search for articles published in the last 10 years. Focused studies were relevant articles in the English language, trials, reviews, meta-analyses, and studies with a control group. Following the quality assessment process, nine studies were eligible and hence were included in the review consisting of six randomized controlled trials and three systematic reviews and meta-analyses. Contrary to preclinical studies, EPO administration did not significantly have notable effects on mortality, major adverse cardiovascular events, or infarction size reduction. Significant left ventricle ejection fraction amelioration was not appreciated either. However, EPO seems to reduce the incidence of post-MI arrhythmias., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Jean-Baptiste et al.)

The objective of this study is to analyze the outcome of the safety and efficiency of the surgical interventions (ventriculoperitoneal shunt [VPS] and endoscopic third ventriculostomy [ETV]) in patients with hydrocephalus due to tuberculous (TB) meningitis. A systematic literature search has been conducted using PubMed, Google Scholar, PMC, and ScienceDirect databases from 2001 to 2022 April. A total of 16 studies have been included, irrespective of their design. These studies include patients diagnosed with hydrocephalus secondary to TB meningitis (TBM) treated with VPS or ETV. A systematic review was conducted to determine the efficiency of surgical procedures based on the outcomes and complications associated with these procedures. A total of 2207 patients (aged one month to 68 years) have been included in this study, out of which 1723 underwent VPS and 484 underwent ETV. The overall success rate in the VPS group varied from 21.1% to 77.5%. The overall success rate in the ETV group ranged from 41.1% to 77%. The overall complications rate in the VPS group varied from 10% to 43.8%, and the complications rate in the ETV group varied from 3.8% to 22.5%. After ruling out the significant differences in the average percentages of outcomes and complications followed by VPS and ETV, ETV is suggested in patients with chronic phases of illness because the chances of ETV failure are high during the initial stage. The uncertainty of the ETV gradually decreases over time. To attain favourable long-term outcomes with ETV in patients with TBM hydrocephalus (TBMH), ETV should be performed after chemotherapy, anti-tubercular treatment, and steroids. In addition, ETV is considered beneficial over VP shunt as associated long-term complications are significantly less compared to VP shunt. In contrast, VP shunt is suggested as a modified Vellore grading which shows a more favourable outcome in patients with acute illness than ETV., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Chalasani et al.)

Colon cancer (CC) is the fourth deadliest cancer in the world. New insights into prognostication might be helpful to define the optimal adjuvant treatments for patients in routine clinical practice. Here, a microarray dataset with 30 primary tumors and 30 normal samples was analyzed using GEO2R to find differentially expressed genes (DEGs). Then, DAVID, KEGG, ChEA and X2K were used to analyze DEGs-related Gene Ontology, pathways, transcription factors (TFs) and kinases, respectively. Protein-protein interaction (PPI) networks were constructed using the STRING database and Cytoscape. The modules and hub genes of DEGs was determined through MCODE and CytoHubba plugins, and the expression of hub genes was verified using GEPIA. To find microRNAs and metabolites associated with DEGs, miRTarBase and HMDB were used, respectively. It was found that 233 and 373 genes were upregulated and downregulated in CC, respectively. GO analysis showed that the upregulated DEGs were mainly involved in mitotic nuclear division and cell division. Top 10 hub genes were identified, including AURKB, CDK1, DLGAP5, AURKA, CCNB2, CCNB1, BUB1B, CCNA2, KIF20A and BUB1. Whereas, FOMX1, E2F7, E2F1, E2F4 and AR were identified as top 5 TFs in CC. Moreover, CDK1, CDC2, MAPK14, ATM and CK2ALPHA was identified as top 5 kinases in CC. miRNAs analysis showed that Hsa-miR-215-5p hsa-miR-193b-3p, hsa-miR-192-5p and hsa-miR-16-5p could target the largest number of CC genes. Taken together, CC-related genes, especially the hub genes, TFs, and metabolites might be used as novel biomarkers for CC, as well as for diagnosis and guiding therapeutic strategies for CC., (© 2021. The International CCN Society.)