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Molecular Genetics & Genomic Medicine Mar 2024Okur-Chung neurodevelopmental syndrome (OCNDS) is a rare autosomal dominant disorder caused by pathogenic variants in CSNK2A1. It is characterized by intellectual... (Review)
Review
BACKGROUND
Okur-Chung neurodevelopmental syndrome (OCNDS) is a rare autosomal dominant disorder caused by pathogenic variants in CSNK2A1. It is characterized by intellectual disability, developmental delay, and multisystemic abnormalities.
METHODS
We performed the whole-exome sequencing for a patient in a Chinese family. The co-segregation study using the Sanger sequencing method was performed among family members. Reverse transcription and quantitative real-time polymerase chain reaction were carried out using total RNA from blood samples of the proband and wild-type control subjects. A review of patients with OCNDS harboring CSNK2A1 pathogenic variants was conducted through a comprehensive search of the PubMed database.
RESULTS
We identified a novel CSNK2A1 frameshift variant p.Tyr323Leufs*16 in a Chinese family. The proband, a 31-year-old female, presented with abnormal eating habits, recurrent seizures, language impairment, and intellectual disability. Her mother exhibited postnatal hernias, splenomegaly, and a predisposition to infections, but showed no significant developmental impairments or intellectual disability. Genetic studies revealed the presence of this variant in CSNK2A1 in both the proband and her mother. Transcription analysis revealed this variant may lead to nonsense-mediated mRNA decay, suggesting haploinsufficiency as a potential disease mechanism. We reviewed 47 previously reported OCNDS cases and discovered that individuals carrying CSNK2A1 null variants may exhibit a diminished frequency of symptoms linked to language deficits, dysmorphic facial features, or intellectual disability, consequently presenting an overall milder phenotype when compared to those with missense variants.
CONCLUSION
We report a novel frameshift variant, p.Tyr323Leufs*16, in an OCNDS family with a generally mild phenotype. This study may broaden the spectrum of clinical presentations associated with OCNDS and contribute novel insights into the genotype-phenotype correlation of this condition.
Topics: Adult; Female; Humans; Asian People; Databases, Factual; Genotype; Intellectual Disability; Phenotype
PubMed: 38444259
DOI: 10.1002/mgg3.2398 -
Parasites & Vectors Mar 2024The study of parasites provides insight into intricate ecological relationships in ecosystem dynamics, food web structures, and evolution on multiple scales. Hepatozoon... (Review)
Review
BACKGROUND
The study of parasites provides insight into intricate ecological relationships in ecosystem dynamics, food web structures, and evolution on multiple scales. Hepatozoon Eucoccidiorida: Hepatozoidae) is a genus of protozoan hemoparasites with heteroxenous life cycles that switch infections between vertebrates and blood-feeding invertebrates. The most comprehensive review of the genus was published 26 years ago, and currently there are no harmonized data on the epizootiology, diagnostics, genotyping methods, evolutionary relationships, and genetic diversity of Hepatozoon in the Americas.
METHODS
Here, we provide a comprehensive review based on the PRISMA method regarding Hepatozoon in wild mammals within the American continent, in order to generate a framework for future research.
RESULTS
11 out of the 35 countries of the Americas (31.4%) had data on Hepatozoon, with Carnivora and Rodentia orders having the most characterizations. Bats, ungulates, and shrews were the least affected groups. While Hepatozoon americanum, H. americanum-like, H. canis, H. didelphydis, H. felis, H. milleri, H. griseisciuri, and H. procyonis correspond to the identified species, a plethora of genospecies is pending for a formal description combining morphology and genetics. Most of the vectors of Hepatozoon in the Americas are unknown, but some flea, mite, and tick species have been confirmed. The detection of Hepatozoon has relied mostly on conventional polymerase chain reaction (PCR), and the implementation of specific real time PCR for the genus needs to be employed to improve its diagnosis in wild animals in the future. From a genetic perspective, the V4 region of the 18S rRNA gene has been widely sequenced for the identification of Hepatozoon in wild animals. However, mitochondrial and apicoplast markers should also be targeted to truly determine different species in the genus. A phylogenetic analysis of herein retrieved 18S ribosomal DNA (rDNA) sequences showed two main clades of Hepatozoon: Clade I associated with small mammals, birds, and herpetozoa, and Clade II associated with Carnivora. The topology of the tree is also reflected in the haplotype network.
CONCLUSIONS
Finally, our review emphasizes Hepatozoon as a potential disease agent in threatened wild mammals and the role of wild canids as spreaders of Hepatozoon infections in the Americas.
Topics: Animals; Cats; Ecosystem; Phylogeny; Chiroptera; Eucoccidiida; Shrews; Animals, Wild; Canidae
PubMed: 38444020
DOI: 10.1186/s13071-024-06154-3 -
JMIR Public Health and Surveillance Feb 2024COVID-19 screening is an effective nonpharmaceutical intervention for identifying infected individuals and interrupting viral transmission. However, questions have been... (Review)
Review
BACKGROUND
COVID-19 screening is an effective nonpharmaceutical intervention for identifying infected individuals and interrupting viral transmission. However, questions have been raised regarding its effectiveness in controlling the spread of novel variants and its high socioeconomic costs. Therefore, the optimization of COVID-19 screening strategies has attracted great attention.
OBJECTIVE
This review aims to summarize the evidence and provide a reference basis for the optimization of screening strategies for the prevention and control of COVID-19.
METHODS
We applied a methodological framework for scoping reviews and the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) checklist. We conducted a scoping review of the present publications on the optimization of COVID-19 screening strategies. We searched the PubMed, Web of Science, and Elsevier ScienceDirect databases for publications up to December 31, 2022. English publications related to screening and testing strategies for COVID-19 were included. A data-charting form, jointly developed by 2 reviewers, was used for data extraction according to the optimization directions of the screening strategies.
RESULTS
A total of 2770 unique publications were retrieved from the database search, and 95 abstracts were retained for full-text review. There were 62 studies included in the final review. We summarized the results in 4 major aspects: the screening population (people at various risk conditions such as different regions and occupations; 12/62, 19%), the timing of screening (when the target population is tested before travel or during an outbreak; 12/62, 19%), the frequency of screening (appropriate frequencies for outbreak prevention, outbreak response, or community transmission control; 6/62, 10%), and the screening and detection procedure (the choice of individual or pooled detection and optimization of the pooling approach; 35/62, 56%).
CONCLUSIONS
This review reveals gaps in the optimization of COVID-19 screening strategies and suggests that a number of factors such as prevalence, screening accuracy, effective allocation of resources, and feasibility of strategies should be carefully considered in the development of future screening strategies.
Topics: Humans; COVID-19; Databases, Factual; Disease Outbreaks; Travel
PubMed: 38412011
DOI: 10.2196/44349 -
Diagnostics (Basel, Switzerland) Feb 2024Giardiasis, caused by the protozoan , affects around 400 million people worldwide, emphasizing the critical need for accurate diagnosis to enhance human health,... (Review)
Review
Giardiasis, caused by the protozoan , affects around 400 million people worldwide, emphasizing the critical need for accurate diagnosis to enhance human health, especially in children. Prolonged giardiasis in childhood can lead to intellectual deficits and other complications. A variety of diagnostic tools, including microscopic, immunological, and molecular methods, are available for detecting infection. Choosing the most suitable method can be challenging due to the abundance of options. This systematic review assesses the reliability and applicability of these diagnostic modalities. Utilizing the Dimensions and Wordart platforms for data analysis, we focus on relevant literature addressing diagnostic methods for human giardiasis. Microscopic techniques, particularly Ritchie's method, emerge as the primary choice, followed by enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). PCR's limited use is attributed to its high cost and infrastructure challenges in developing nations. In conclusion, our analysis supports microscopic methods as the gold standard for giardiasis diagnosis. However, in cases where symptoms persist despite a negative diagnosis, employing more sensitive diagnostic approaches is advisable.
PubMed: 38396402
DOI: 10.3390/diagnostics14040364 -
The Journal of Infection Mar 2024Streptococcus pyogenes (S. pyogenes) is a Gram-positive bacteria which causes a spectrum of diseases ranging from asymptomatic infection to life-threatening sepsis.... (Review)
Review
UNLABELLED
Streptococcus pyogenes (S. pyogenes) is a Gram-positive bacteria which causes a spectrum of diseases ranging from asymptomatic infection to life-threatening sepsis. Studies report up to 2000 times greater risk of invasive S. pyogenes disease in close contacts of index cases within 30-days of symptom onset. Despite this, there is variability in the management of asymptomatic carriage of S. pyogenes and those at risk of secondary cases of invasive S. pyogenes infection.
OBJECTIVE
Our systematic review assessed the efficacy of different antibiotic regimens used for eradication of S. pyogenes from the pharynx in asymptomatic individuals.
METHODS
We searched Pubmed, EMBASE (1974-), OVID Medline (1948-) and the Cochrane CENTRAL registry. We included randomised controlled trials (RCTs) with asymptomatic participants with >50% with pharyngeal cultures positive with S. pyogenes at baseline. Only studies with microbiological methods including culture (+/- polymerase chain reaction, PCR) were included. We included studies published in English. Each included study was assessed by two independent reviewers for data extraction and risk of bias.
RESULTS
Of 1166 unique records identified, three RCTs were included in the review. Two of the three included RCTs found oral clindamycin for 10-days was the most efficacious regimen, compared to intramuscular benzathine penicillin G followed by 4 days of oral rifampicin, or monotherapy using benzathine penicillin, phenoxymethylpenicillin or erythromycin. Two RCTs were assessed as being at high risk of bias, with the third study demonstrating low/some risk of bias.
CONCLUSIONS
Current available evidence for the optimal antibiotic in eradicating pharyngeal S. pyogenes carriage is limited. Future RCTs should include penicillin, first-generation cephalosporins, rifampicin, macrolides (such as azithromycin) and clindamycin.
Topics: Child; Adult; Humans; Anti-Bacterial Agents; Streptococcus pyogenes; Clindamycin; Penicillin G Benzathine; Pharynx; Rifampin; Streptococcal Infections
PubMed: 38360357
DOI: 10.1016/j.jinf.2024.01.003 -
Indian Journal of Pathology &... 2024Ovarian tuberculosis is a rare entity with non-specific clinical manifestations, difficult diagnosis, and specific medical management. Ovarian involvement in...
Ovarian tuberculosis is a rare entity with non-specific clinical manifestations, difficult diagnosis, and specific medical management. Ovarian involvement in tuberculosis (TB) may occur in two forms, namely, perioophoritis and oophoritis. The constitutional symptoms of tuberculosis such as anorexia, weight loss, night sweats, and evening rise in temperature have been reported in up to 45% of patients. Misdiagnosis and delayed diagnosis are common. A direct histopathological demonstration is the best diagnostic modality. Fine needle aspiration cytology (FNAC) is the study of choice and polymerase chain reaction (PCR) assay increases its sensitivity. The standard short-course antituberculous for 6 months is recommended for isolated ovarian tuberculosis and for widespread disease, 12 months of therapy is recommended. Surgery is reserved for failure of medical therapy and abscess formation. There are many studies on genito-urinary tuberculosis but a detailed study defining diagnostic studies and management guidelines is still lacking. This article aims to present and share a review of the English-language literature on ovarian tuberculosis to gain a better understanding of etiopathogenesis and diagnostic methods and to provide guidelines for its management.
Topics: Female; Humans; Tuberculosis; Biopsy, Fine-Needle; Cytodiagnosis; Polymerase Chain Reaction
PubMed: 38358181
DOI: 10.4103/ijpm.ijpm_6_23 -
BMC Infectious Diseases Feb 2024Leptospirosis is an underdiagnosed infectious disease with non-specific clinical presentation that requires laboratory confirmation for diagnosis. The serologic... (Meta-Analysis)
Meta-Analysis
Diagnosis of human leptospirosis: systematic review and meta-analysis of the diagnostic accuracy of the Leptospira microscopic agglutination test, PCR targeting Lfb1, and IgM ELISA to Leptospira fainei serovar Hurstbridge.
BACKGROUND
Leptospirosis is an underdiagnosed infectious disease with non-specific clinical presentation that requires laboratory confirmation for diagnosis. The serologic reference standard remains the microscopic agglutination test (MAT) on paired serum samples. However, reported estimates of MAT's sensitivity vary. We evaluated the accuracy of four index tests, MAT on paired samples as well as alternative standards for leptospirosis diagnosis: MAT on single acute-phase samples, polymerase chain reaction (PCR) with the target gene Lfb1, and ELISA IgM with Leptospira fainei serovar Hurstbridge as an antigen.
METHODS
We performed a systematic review of studies reporting results of leptospirosis diagnostic tests. We searched eight electronic databases and selected studies that tested human blood samples and compared index tests with blood culture and/or PCR and/or MAT (comparator tests). For MAT selection criteria we defined a threshold for single acute-phase samples according to a national classification of leptospirosis endemicity. We used a Bayesian random-effect meta-analysis to estimate the sensitivity and specificity of MAT in single acute-phase and paired samples separately, and assessed risk of bias using the Quality Assessment of Studies of Diagnostic Accuracy Approach- 2 (QUADAS-2) tool.
RESULTS
For the MAT accuracy evaluation, 15 studies were included, 11 with single acute-phase serum, and 12 with paired sera. Two included studies used PCR targeting the Lfb1 gene, and one included study used IgM ELISA with Leptospira fainei serovar Hurstbridge as antigen. For MAT in single acute-phase samples, the pooled sensitivity and specificity were 14% (95% credible interval [CrI] 3-38%) and 86% (95% CrI 59-96%), respectively, and the predicted sensitivity and specificity were 14% (95% CrI 0-90%) and 86% (95% CrI 9-100%). Among paired MAT samples, the pooled sensitivity and specificity were 68% (95% CrI 32-92%) and 75% (95% CrI 45-93%) respectively, and the predicted sensitivity and specificity were 69% (95% CrI 2-100%) and 75% (2-100%).
CONCLUSIONS
Based on our analysis, the accuracy of MAT in paired samples was not high, but it remains the reference standard until a more accurate diagnostic test is developed. Future studies that include larger numbers of participants with paired samples will improve the certainty of accuracy estimates.
Topics: Humans; Serogroup; Bayes Theorem; Antibodies, Bacterial; Leptospira; Leptospirosis; Agglutination Tests; Sensitivity and Specificity; Enzyme-Linked Immunosorbent Assay; Immunoglobulin M; Polymerase Chain Reaction
PubMed: 38326762
DOI: 10.1186/s12879-023-08935-0 -
Journal of Clinical Epidemiology Apr 2024To systematically evaluate the performance of COVID-19 prognostic models and scores for mortality risk in older populations across three health-care settings: hospitals,...
OBJECTIVES
To systematically evaluate the performance of COVID-19 prognostic models and scores for mortality risk in older populations across three health-care settings: hospitals, primary care, and nursing homes.
STUDY DESIGN AND SETTING
This retrospective external validation study included 14,092 older individuals of ≥70 years of age with a clinical or polymerase chain reaction-confirmed COVID-19 diagnosis from March 2020 to December 2020. The six validation cohorts include three hospital-based (CliniCo, COVID-OLD, COVID-PREDICT), two primary care-based (Julius General Practitioners Network/Academisch network huisartsgeneeskunde/Network of Academic general Practitioners, PHARMO), and one nursing home cohort (YSIS) in the Netherlands. Based on a living systematic review of COVID-19 prediction models using Prediction model Risk Of Bias ASsessment Tool for quality and risk of bias assessment and considering predictor availability in validation cohorts, we selected six prognostic models predicting mortality risk in adults with COVID-19 infection (GAL-COVID-19 mortality, 4C Mortality Score, National Early Warning Score 2-extended model, Xie model, Wang clinical model, and CURB65 score). All six prognostic models were validated in the hospital cohorts and the GAL-COVID-19 mortality model was validated in all three healthcare settings. The primary outcome was in-hospital mortality for hospitals and 28-day mortality for primary care and nursing home settings. Model performance was evaluated in each validation cohort separately in terms of discrimination, calibration, and decision curves. An intercept update was performed in models indicating miscalibration followed by predictive performance re-evaluation.
MAIN OUTCOME MEASURE
In-hospital mortality for hospitals and 28-day mortality for primary care and nursing home setting.
RESULTS
All six prognostic models performed poorly and showed miscalibration in the older population cohorts. In the hospital settings, model performance ranged from calibration-in-the-large -1.45 to 7.46, calibration slopes 0.24-0.81, and C-statistic 0.55-0.71 with 4C Mortality Score performing as the most discriminative and well-calibrated model. Performance across health-care settings was similar for the GAL-COVID-19 model, with a calibration-in-the-large in the range of -2.35 to -0.15 indicating overestimation, calibration slopes of 0.24-0.81 indicating signs of overfitting, and C-statistic of 0.55-0.71.
CONCLUSION
Our results show that most prognostic models for predicting mortality risk performed poorly in the older population with COVID-19, in each health-care setting: hospital, primary care, and nursing home settings. Insights into factors influencing predictive model performance in the older population are needed for pandemic preparedness and reliable prognostication of health-related outcomes in this demographic.
Topics: Adult; Humans; Aged; Prognosis; COVID-19; Retrospective Studies; COVID-19 Testing; Nursing Homes; Hospitals; Hospital Mortality; Primary Health Care
PubMed: 38311188
DOI: 10.1016/j.jclinepi.2024.111270 -
Immunity, Inflammation and Disease Jan 2024Glucocorticoids are the most commonly used anti-inflammatory drugs for a variety of diseases, despite the fact that resistance to them is growing in a number of... (Review)
Review
BACKGROUND
Glucocorticoids are the most commonly used anti-inflammatory drugs for a variety of diseases, despite the fact that resistance to them is growing in a number of conditions. There is currently no biomarker that can be used to identify steroid resistance. According to a number of studies, an overexpression of the glucocorticoid receptor beta (GR-β) isoform is associated with steroid-resistant illness. Our goal is to find out whether or not steroid-resistant disorders are associated with an increased level of GR-β expression.
METHODS
We conducted searches in the databases of Web of Science and PubMed until January 17, 2023. This systematic review was done according to the preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Joanna Briggs Institute Appraisal scale was used to assess the quality of the included studies.
RESULTS
After the initial search, we identified 556 papers and finally included 20 studies. Twelve of these studies found an elevated level of GR-β in the steroid resistant group. All five studies on asthma, two out of three on nasal polyps, both studies on ulcerative colitis found an up regulation of GR-β in steroid resistant group as compared to steroid-sensitive groups. GR-β was also shown to be elevated in patients with allergic rhinitis, Crohn's disease and rheumatoid arthritis. In the majority of the investigations, higher levels of GR-β were identified in peripheral blood mononuclear cells through the use of reverse transcription polymerase chain reaction.
CONCLUSION
GR-β was associated with steroid-resistant diseases. It was overexpressed in steroid-resistant diseases and has the potential to be used as a biomarker for disorders involving steroid resistance.
Topics: Humans; Leukocytes, Mononuclear; Receptors, Glucocorticoid; Glucocorticoids; Up-Regulation
PubMed: 38270313
DOI: 10.1002/iid3.1137 -
BMC Cancer Jan 2024Esophageal cancer (EC) is a deadly disease with limited therapeutic options. Although circulating tumor DNA (ctDNA) could be a promising tool in this regard, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Esophageal cancer (EC) is a deadly disease with limited therapeutic options. Although circulating tumor DNA (ctDNA) could be a promising tool in this regard, the availiable evidence is limited. We performed a systematic review and meta-analysis to summarize the clinical applicability of the next-generation sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR) technology on the ctDNA detection of the EC and listed the current challenges.
METHODS
We systematically searched MEDLINE (via PubMed), Embase (via OVID), ISI Web of Science database and Cochrane Library from January, 2000 to April, 2023. Progression-free survival (PFS) and overall survival (OS) were set as primary outcome endpoints. Pathologic response was evaluated by tumor regression grade (TRG), according to the eighth edition of the American Joint Committee on Cancer (AJCC). Major pathologic regression (MPR) was defined as TRG 1 and 2. The MPR was set as secondary endpoint. Hazard rate (HR) and associated 95% CI were used as the effect indicators the association between ctDNA and prognosis of EC. MPR rates were also calculated. Fixed-effect model (Inverse Variance) or random-effect model (Mantel-Haenszel method) was performed depending on the statistically heterogeneity.
RESULTS
Twenty-two studies, containing 1144 patients with EC, were included in this meta-analysis. The results showed that OS (HR = 3.87; 95% CI, 2.86-5.23) and PFS (HR = 4.28; 95% CI, 3.34-5.48) were shorter in ctDNA-positive patients. In the neoadjuvant therapy, the sensitivity analysis showed the clarified HR of ctDNA-positive was 1.13(95% CI, 1.01-1.28). We also found that TP53, NOTCH1, CCND1 and CNKN2A are the most frequent mutation genes.
CONCLUSIONS
Positive ctDNA is associated with poor prognosis, which demonstrated clinical value of ctDNA. Longitudinal ctDNA monitoring showed potential prognostic value in the neoadjuvant therapy. In an era of precision medicine, ctDNA could be a promising tool to individualize treatment planning and to improve outcomes in EC.
PROSPERO REGISTRATION NUMBER
CRD42023412465.
Topics: Humans; Circulating Tumor DNA; Esophageal Neoplasms; Databases, Factual; Gene Library; Genes, cdc
PubMed: 38267901
DOI: 10.1186/s12885-024-11879-6