-
GeroScience Jun 2024A growing body of research suggested that there was a link between poor periodontal health and systemic diseases, particularly with the early development of cognitive... (Review)
Review
A growing body of research suggested that there was a link between poor periodontal health and systemic diseases, particularly with the early development of cognitive disorders, dementia, and depression. This is especially true in cases of changes in diet, malnutrition, loss of muscular endurance, and abnormal systemic inflammatory response. Our study aimed to determine the extent of these associations to better target the multi-level healthy aging challenge investigating the impact of periodontal disease on cognitive disorders (cognitive impairment and cognitive decline), dementia, and depression. We conducted a comprehensive literature search up to November 2023 using six different electronic databases. Two independent researchers assessed the eligibility of 7363 records against the inclusion criteria and found only 46 records that met the requirements. The study is registered on PROSPERO (CRD42023485688). We generated random effects pooled estimates and 95% confidence intervals (CI) to evaluate whether periodontal disease increased the risk of the investigated outcomes. The quality assessment revealed moderate quality of evidence and risk of bias. Periodontal disease was found to be associated with both cognitive disorders (relative risk (RR) 1.25, 95% CI 1.11-1.40, in the analysis of cross-sectional studies); cognitive impairment (RR 3.01, 95% CI 1.52-5.95 for longitudinal studies, cognitive decline); and dementia (RR 1.22, 95% CI 1.10-1.36). However, no significant increased risk of depression among subjects with periodontal disease was found (RR 1.07, 95% CI 0.95-1.21). Despite the association with two of the three explored outcomes, the available evidence on periodontal diseases and dementia, cognitive disorders, and depression is controversial due to several limitations. Therefore, further investigations involving validated and standardized tools are required.
PubMed: 38943006
DOI: 10.1007/s11357-024-01243-8 -
Scientific Reports Jun 2024Plekhm2 is a protein regulating endosomal trafficking and lysosomal distribution. We recently linked a recessive inherited mutation in PLEKHM2 to a familial form of...
Plekhm2 is a protein regulating endosomal trafficking and lysosomal distribution. We recently linked a recessive inherited mutation in PLEKHM2 to a familial form of dilated cardiomyopathy and left ventricular non-compaction. These patients' primary fibroblasts exhibited abnormal lysosomal distribution and autophagy impairment. We therefore hypothesized that loss of PLEKHM2 impairs cardiac function via autophagy derangement. Here, we characterized the roles of Plekhm2 in the heart using global Plekhm2 knockout (PLK2-KO) mice and cultured cardiac cells. Compared to littermate controls (WT), young PLK2-KO mice exhibited no difference in heart function or autophagy markers but demonstrated higher basal AKT phosphorylation. Older PLK2-KO mice had body and heart growth retardation and increased LC3II protein levels. PLK2-KO mice were more vulnerable to fasting and, interestingly, impaired autophagy was noted in vitro, in Plekhm2-deficient cardiofibroblasts but not in cardiomyocytes. PLK2-KO hearts appeared to be less sensitive to pathological hypertrophy induced by angiotensin-II compared to WT. Our findings suggest a role of Plekhm2 in murine cardiac autophagy. Plekhm2 deficiency impaired autophagy in cardiofibroblasts, but the autophagy in cardiomyocytes is not critically dependent on Plekhm2. The absence of Plekhm2 in mice appears to promote compensatory mechanism(s) enabling the heart to manage angiotensin-II-induced stress without detrimental consequences.
Topics: Animals; Autophagy; Mice, Knockout; Fibroblasts; Mice; Myocytes, Cardiac; Protein Serine-Threonine Kinases; Myocardium; Cells, Cultured; Phosphorylation
PubMed: 38942823
DOI: 10.1038/s41598-024-65670-5 -
Scientific Reports Jun 2024In tuberculosis (TB), chest radiography (CXR) patterns are highly variable, mimicking pneumonia and many other diseases. This study aims to evaluate the efficacy of...
In tuberculosis (TB), chest radiography (CXR) patterns are highly variable, mimicking pneumonia and many other diseases. This study aims to evaluate the efficacy of Google teachable machine, a deep neural network-based image classification tool, to develop algorithm for predicting TB probability of CXRs. The training dataset included 348 TB CXRs and 3806 normal CXRs for training TB detection. We also collected 1150 abnormal CXRs and 627 normal CXRs for training abnormality detection. For external validation, we collected 250 CXRs from our hospital. We also compared the accuracy of the algorithm to five pulmonologists and radiological reports. In external validation, the AI algorithm showed areas under the curve (AUC) of 0.951 and 0.975 in validation dataset 1 and 2. The accuracy of the pulmonologists on validation dataset 2 showed AUC range of 0.936-0.995. When abnormal CXRs other than TB were added, AUC decreased in both human readers (0.843-0.888) and AI algorithm (0.828). When combine human readers with AI algorithm, the AUC further increased to 0.862-0.885. The TB CXR AI algorithm developed by using Google teachable machine in this study is effective, with the accuracy close to experienced clinical physicians, and may be helpful for detecting tuberculosis by CXR.
Topics: Humans; Deep Learning; Tuberculosis, Pulmonary; Radiography, Thoracic; Algorithms; Female; Male; Middle Aged; Adult; Area Under Curve
PubMed: 38942819
DOI: 10.1038/s41598-024-65703-z -
Scientific Reports Jun 2024HIV/AIDS is one of the most devastating infectious diseases affecting humankind all over the world and its impact goes beyond public health problems. This study was...
Determinants of hemoglobin level and time to default from Highly Active Antiretroviral Therapy (HAART) for adult clients living with HIV under treatment; a retrospective cohort study design.
HIV/AIDS is one of the most devastating infectious diseases affecting humankind all over the world and its impact goes beyond public health problems. This study was conducted to investigate the joint predictors of hemoglobin level and time to default from treatment for adult clients living with HIV/AIDS under HAART at the University of Gondar Comprehensive and Specialized Hospital, North-west Ethiopia. The study was conducted using a retrospective cohort design from the medical records of 403 randomly selected adult clients living with HIV whose follow-ups were from September 2015 to March 2022. Hemoglobin level was projected using Sahli's acid-hematin method. Hence, the hemoglobin tube was filled with N/10 hydrochloric acid up to 2 g % marking and the graduated tube was placed in Sahli's hemoglobin meter. The blood samples were collected using the finger-pick method, considering 22 G disposable needles. The health staff did this. From a total of 403 adult patients living with HIV/AIDS included in the current study, about 44.2% defaulted from therapy. The overall mean and median estimated survival time of adult clients under study were 44.3 and 42 months respectively. The patient's lymphocyte count (AHR = 0.7498, 95% CI: (0.7411: 0.7587), p-value < 0.01), The weight of adult patients living with HIV/AIDS (AHR = 0.9741, 95% CI: (0.9736: 0.9747), p-value = 0.012), sex of adult clients (AHR = 0.6019, 95% CI: (0.5979, 0.6059), p-value < 0.01), WHO stages III compared to Stage I (AHR = 1.4073, 95% CI: (1.3262, 1.5078), p-value < 0.01), poor adherence level (AHR = 0.2796, 95% CI: (0.2082, 0.3705) and p-value < 0.01), bedridden patients (AHR = 1.5346, 95% CI: (1.4199, 1.6495), p-value = 0.008), and opportunistic infections (AHR = 0.2237, 95% CI: (0.0248, 0.4740), p-value = 0.004) had significant effect on both hemoglobin level and time to default from treatment. Similarly, other co-morbidity conditions, disclosure status of the HIV disease, and tobacco and alcohol addiction had a significant effect on the variables of interest. The estimate of the association parameter in the slope value of Hgb level and time default was negative, indicating that the Hgb level increased as the hazard of defaulting from treatment decreased. A patient with abnormal BMI like underweight, overweight, or obese was negatively associated with the risk of anemia (lower hemoglobin level). As a recommendation, more attention should be given to those patients with abnormal BMI, patients with other co-morbidity conditions, patients with opportunistic infections, and low lymphocytes, and bedridden and ambulatory patients. Health-related education should be given to adult clients living with HIV/AIDS to be good adherents for medical treatment.
Topics: Humans; Male; Adult; Female; Retrospective Studies; HIV Infections; Antiretroviral Therapy, Highly Active; Hemoglobins; Middle Aged; Ethiopia; Young Adult; Anti-HIV Agents; Undertreatment
PubMed: 38942753
DOI: 10.1038/s41598-024-62952-w -
Nature Communications Jun 2024Individuals with Down syndrome, the genetic condition caused by trisomy 21, exhibit strong inter-individual variability in terms of developmental phenotypes and...
Individuals with Down syndrome, the genetic condition caused by trisomy 21, exhibit strong inter-individual variability in terms of developmental phenotypes and diagnosis of co-occurring conditions. The mechanisms underlying this variable developmental and clinical presentation await elucidation. We report an investigation of human chromosome 21 gene overexpression in hundreds of research participants with Down syndrome, which led to the identification of two major subsets of co-expressed genes. Using clustering analyses, we identified three main molecular subtypes of trisomy 21, based on differential overexpression patterns of chromosome 21 genes. We subsequently performed multiomics comparative analyses among subtypes using whole blood transcriptomes, plasma proteomes and metabolomes, and immune cell profiles. These efforts revealed strong heterogeneity in dysregulation of key pathophysiological processes across the three subtypes, underscored by differential multiomics signatures related to inflammation, immunity, cell growth and proliferation, and metabolism. We also observed distinct patterns of immune cell changes across subtypes. These findings provide insights into the molecular heterogeneity of trisomy 21 and lay the foundation for the development of personalized medicine approaches for the clinical management of Down syndrome.
Topics: Down Syndrome; Humans; Chromosomes, Human, Pair 21; Female; Transcriptome; Male; Child; Child, Preschool; Adult; Gene Expression Profiling; Proteome; Adolescent
PubMed: 38942750
DOI: 10.1038/s41467-024-49781-1 -
American Journal of Medical Genetics.... Jun 2024Pseudo-TORCH Syndrome (PTS) encompasses a heterogeneous group of genetic disorders that may clinically and radiologically resemble congenital TORCH infections. These...
Pseudo-TORCH Syndrome (PTS) encompasses a heterogeneous group of genetic disorders that may clinically and radiologically resemble congenital TORCH infections. These mimickers present with overlapping features manifested as intracranial and systemic abnormalities. Collagen type IV alpha 1 chain (COL4A1)-related diseases, characterized by autosomal dominant inheritance, exhibit a diverse phenotypic spectrum involving cerebrovascular, renal, ophthalmological, cardiac, and muscular abnormalities. Cerebrovascular manifestations range from small-vessel brain disease to large vessel abnormalities, resulting in intracerebral hemorrhage, periventricular leukoencephalopathy, and ventriculomegaly. Additional features include cortical malformations, eye defects, arrhythmias, renal disease, muscular abnormalities, and hematological manifestations. Age of onset varies widely, and phenotypic variability exists even among individuals with the same variant. In this study, we present two cases of COL4A1-related disorder mimicking congenital TORCH infections, highlighting the importance of recognizing genetic mimics in clinical practice.
PubMed: 38942733
DOI: 10.1002/ajmg.a.63804 -
Journal of Cystic Fibrosis : Official... Jun 2024To study the prevalence of cystic fibrosis related liver disease (CFLD) as defined by ultrasound (US) and describe difference in clinical and radiological features in...
AIMS
To study the prevalence of cystic fibrosis related liver disease (CFLD) as defined by ultrasound (US) and describe difference in clinical and radiological features in those with CFLD and those without CFLD (nCFLD); with and without portal hypertension (PHT and nPHT).
METHODS
Children with CF (CwCF) from our clinic who had regular screening liver US from 3 years of age were included. Liver parenchyma findings were classified into normal, homogeneous, heterogeneous and nodular. For our study, we defined PHT as US evidence of splenomegaly and/or ascites, abnormal portal flow, varices, ligamentum teres recanalization if present. Demographic, clinical, nutritional and lung function between the two groups-CFLD/nCFLD; and subgroups- PHT and nPHT were compared. Gamma glutamyl transferase (GGT)/ platelet ratio (GPR) as a marker of fibrosis was measured.
RESULTS
From 227 CwCF,40 (17 %) were excluded (below the age of 3 years or alternative cause of liver disease). Of the remaining 187, 107 (57 %) had a normal US, 80 (43 %) had CFLD; 25 (13.4 %) had PHT. There was no significant difference in demographics, BMI-z score, lung function, presence of gastrostomy or pancreatic insufficiency in CFLD vs nCFLD and PHT vs nPHT. CF related diabetes mellitus (CFRD) was significantly associated with CFLD vs nCFLD (P = 0.0086). GGT was higher and platelet count was lower in PHT vs nPHT (P = 0.0256 and P = 0.0001). Nodularity was strongly associated with an elevated GPR (P = 0.016). There was a strong association between nodularity on US and PHT (P = 0.0006).
CONCLUSION
Nodularity is a clear marker for advanced liver disease with higher scores for a non-invasive marker for fibrosis. There was no difference in nutrition and FEV1 between advanced liver disease and absent/ milder liver disease.
PubMed: 38942721
DOI: 10.1016/j.jcf.2024.06.008 -
Brain & Development Jun 2024This study aimed to investigate the clinical characteristics of pediatric-onset dystonia in Japan, addressing the diagnostic challenges arising from symptom variations...
OBJECTIVE
This study aimed to investigate the clinical characteristics of pediatric-onset dystonia in Japan, addressing the diagnostic challenges arising from symptom variations and etiological diversity.
METHODS
From 2020 to 2022, questionnaires were distributed to 1218 board certified child neurologists (BCCNs) by Japanese Society of Child Neurology. In the primary survey, participants were asked to report the number of patients with pediatric-onset dystonia under their care. Subsequently, the follow-up secondary survey sought additional information on the clinical characteristics of these patients.
RESULTS
The primary survey obtained 550 responses (response rate: 45 %) from BCCNs for their 736 patients with dystonia. The predominant etiologies included inherited cases (with DYT10
being the most prevalent, followed by DYT5 and ATP1A3-related neurologic disorders), acquired cases (with perinatal abnormalities being the most common), and idiopathic cases. The secondary survey provided clinical insights into 308 cases from 82 BCCNs. Infancy-onset dystonia presented as persistent and generalized with diverse symptoms, primarily linked to ATP1A3-related neurologic disorders and other genetic disorders resembling acquired dystonia. Conversely, childhood/adolescent-onset dystonia showed paroxysmal, fluctuating courses, predominantly affecting limbs. The most common etiologies were DYT5 and DYT10 , leading to therapeutic diagnoses. CONCLUSION
Pediatric-onset dystonia in Japan was treated by 28 % of BCCNs. The majority of cases were inherited, with high prevalence rates of DYT5
and DYT10 . Infancy-onset dystonia exhibits diverse etiologies and symptoms, emphasizing the utility of various examinations, including genetic testing. These findings significantly contribute to our understanding of pediatric-onset dystonia in Japan, although this study has the limitation of questionnaire survey. PubMed: 38942709
DOI: 10.1016/j.braindev.2024.06.002 -
Journal of the American Society of... Jun 2024The finding of atypical glandular cells (AGC) on Papanicolaou test is becoming more important as the incidence of squamous intraepithelial lesions decreases in recent...
INTRODUCTION
The finding of atypical glandular cells (AGC) on Papanicolaou test is becoming more important as the incidence of squamous intraepithelial lesions decreases in recent decades. Therefore, the interpretation and follow-up of patients with AGC are particularly important. The aim of our study was to assess the histologic findings and clinical correlations in patients with AGC identified on Papanicolaou test.
MATERIALS AND METHODS
A total of 714 patients with AGC identified on cervical Papanicolaou tests were studied for their clinicopathologic features, such as follow-up histology and patient age. We investigated the histologic follow-up results for each individual subcategories of AGC and their correlation with patients' age.
RESULTS
Most of the glandular cell abnormalities (80.0%) in the study group were classified as "atypical glandular cells, not otherwise specified (NOS)". About 28.9% of patients' follow-up histology showed malignant or precancerous lesions. The mean age of patients with malignant or precancerous lesions was significantly higher than that of patients with benign or non-precancerous lesions. The malignant histologies included 52 cases of endometrial cancers and 31 cases of cervical carcinomas. The second most common subcategory was "atypical glandular cells, favor neoplastic" (5.0%), while "atypical endocervical cells, favor neoplastic" constituted about 2.7% of cases in our study. The average age of patients with "atypical glandular cells, favor neoplastic" was significantly higher than that of patients with "atypical endocervical cells, favor neoplastic". The follow-up histology of about 82.1% of "atypical glandular cells, favor neoplastic" showed endometrial (73.9%) or cervical malignancies (26.1%). The follow-up histology of about 70.6% of "atypical endocervical cells, favor neoplastic" showed endometrial (50.0%) or cervical cancers (50.0%). Other glandular abnormalities included 25 of 714 cases of "atypical endometrial cells" (3.5%) and 6 of 714 cases of "atypical endocervical cells" (0.8%).
CONCLUSION
Based on our data, we have observed significantly more endometrial malignancies in both "atypical glandular cells, NOS" and "atypical glandular cells, favor neoplastic" subcategories and even some in "atypical endocervical cells, favor neoplastic" category. This predominance of endometrial malignancies is also associated with patients' age and tumor types.
PubMed: 38942649
DOI: 10.1016/j.jasc.2024.05.002 -
Progress in Molecular Biology and... 2024Cardiovascular diseases (CVDs) are characterized by abnormalities in the heart, blood vessels, and blood flow. CVDs comprise a diverse set of health issues. There are... (Review)
Review
Cardiovascular diseases (CVDs) are characterized by abnormalities in the heart, blood vessels, and blood flow. CVDs comprise a diverse set of health issues. There are several types of CVDs like stroke, endothelial dysfunction, thrombosis, atherosclerosis, plaque instability and heart failure. Identification of a new drug for heart disease takes longer duration and its safety efficacy test takes even longer duration of research and approval. This chapter explores drug repurposing, nano-therapy, and plant-based treatments for managing CVDs from existing drugs which saves time and safety issues with testing new drugs. Existing drugs like statins, ACE inhibitor, warfarin, beta blockers, aspirin and metformin have been found to be useful in treating cardiac disease. For better drug delivery, nano therapy is opening new avenues for cardiac research by targeting interleukin (IL), TNF and other proteins by proteome interactome analysis. Nanoparticles enable precise delivery to atherosclerotic plaques, inflammation areas, and damaged cardiac tissues. Advancements in nano therapeutic agents, such as drug-eluting stents and drug-loaded nanoparticles are transforming CVDs management. Plant-based treatments, containing phytochemicals from Botanical sources, have potential cardiovascular benefits. These phytochemicals can mitigate risk factors associated with CVDs. The integration of these strategies opens new avenues for personalized, effective, and minimally invasive cardiovascular care. Altogether, traditional drugs, phytochemicals along with nanoparticles can revolutionize the future cardiac health care by identifying their signaling pathway, mechanism and interactome analysis.
Topics: Humans; Drug Repositioning; Drug Discovery; Animals; Heart Diseases
PubMed: 38942536
DOI: 10.1016/bs.pmbts.2024.02.001