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BMC Women's Health Jun 2024Cervical cancer is the second most common malignancy in Ethiopia and first in some African countries. It is six times more likely to occur in positive cases of the human...
BACKGROUND
Cervical cancer is the second most common malignancy in Ethiopia and first in some African countries. It is six times more likely to occur in positive cases of the human immunodeficiency virus than in the general population. If diagnosed and treated early enough, cervical cancer is both treatable and preventable. However, among Ethiopian women who test positive for HIV, the uptake of cervical cancer screening is low. Its determinant factors were not well studied in the study area. Hence, this study was aimed at filling this information gap.
OBJECTIVE
To assess uptake of cervical cancer screening services and associated factors among HIV-positive women attending an adult antiretroviral treatment clinic at public hospitals in Addis Ababa, Ethiopia, June 1-30, 2022.
METHODS
A cross-sectional investigation was carried out in a hospital. 407 participants in all were chosen using the systematic sampling technique. A pretested interviewer-administered questionnaire was used to collect the data from respondents. The data were entered into Epi data version 4.6 and exported to SPSS version 25 for analysis. Bivariable and multivariable logistic regression analysis was employed. Adjusted odds ratio with its 95% confidence interval and p value < 0.05 were used to estimate the strength and significance of the association.
RESULT
Among a total of 407 respondents, 238 (58.5%), 95% CI (53.5-63.3), HIV-positive women were screened at least once in the last five years. In multivariable analysis, age > 45 years old (AOR = 0.18, 95% CI: 0.053-0.644), number of children (3 children) (AOR = 0.19, 95% CI:0.036-0.979), perception of being susceptible to cervical cancer (AOR = 6.39, 95% CI: 1.79-22.74), knowledge of cervical cancer and its screening (AOR = 19.34, 95% CI: 7.87-47.75), and positive attitude towards cervical cancer screening (AOR = 8.06, 95% CI:3.62-17.91) were significantly associated factors with the uptake of cervical cancer screening.
CONCLUSION AND RECOMMENDATION
in this study, Age > 45 years, having less than three children, feeling susceptible, knowing about cervical cancer and screening, and having a positive attitude toward cervical cancer screening were significant factor of uptake of cervical cancer screening service. There is a need to strengthen the policy and health education on safe sexual practices and healthy lifestyles through information dissemination and communication to scale up screening service utilization.
Topics: Humans; Female; Uterine Cervical Neoplasms; Ethiopia; Adult; Cross-Sectional Studies; Early Detection of Cancer; Hospitals, Public; HIV Infections; Middle Aged; Patient Acceptance of Health Care; Health Knowledge, Attitudes, Practice; Young Adult; Surveys and Questionnaires; Mass Screening
PubMed: 38943118
DOI: 10.1186/s12905-024-03169-x -
Biophysical Chemistry Jun 2024Human islet amyloid polypeptide (hIAPP) forms amyloid deposits that contribute to β-cell death in pancreatic islets and are considered a hallmark of Type II diabetes...
Human islet amyloid polypeptide (hIAPP) forms amyloid deposits that contribute to β-cell death in pancreatic islets and are considered a hallmark of Type II diabetes Mellitus (T2DM). Evidence suggests that the early oligomers of hIAPP formed during the aggregation process are the primary pathological agent in islet amyloid induced β-cell death. The self-assembly mechanism of hIAPP, however, remains elusive, largely due to limitations in conventional biophysical techniques for probing the distribution or capturing detailed structures of the early, structurally dynamic oligomers. The advent of Ion-mobility Mass Spectrometry (IM-MS) has enabled the characterisation of hIAPP early oligomers in the gas phase, paving the way towards a deeper understanding of the oligomerisation mechanism and the correlation of structural information with the cytotoxicity of the oligomers. The sensitivity and the rapid structural characterisation provided by IM-MS also show promise in screening hIAPP inhibitors, categorising their modes of inhibition through "spectral fingerprints". This review delves into the application of IM-MS to the dissection of the complex steps of hIAPP oligomerisation, examining the inhibitory influence of metal ions, and exploring the characterisation of hetero-oligomerisation with different hIAPP variants. We highlight the potential of IM-MS as a tool for the high-throughput screening of hIAPP inhibitors, and for providing insights into their modes of action. Finally, we discuss advances afforded by recent advancements in tandem IM-MS and the combination of gas phase spectroscopy with IM-MS, which promise to deliver a more sensitive and higher-resolution structural portrait of hIAPP oligomers. Such information may help facilitate a new era of targeted therapeutic strategies for islet amyloidosis in T2DM.
PubMed: 38941872
DOI: 10.1016/j.bpc.2024.107285 -
PloS One 2024Many newborn screening programs worldwide have introduced screening for diseases using DNA extracted from dried blood spots (DBS). In Germany, DNA-based assays are...
BACKGROUND
Many newborn screening programs worldwide have introduced screening for diseases using DNA extracted from dried blood spots (DBS). In Germany, DNA-based assays are currently used to screen for severe combined immunodeficiency (SCID), spinal muscular atrophy (SMA), and sickle cell disease (SCD).
METHODS
This study analysed the impact of pre-analytic DNA carry-over in sample preparation on the outcome of DNA-based newborn screening for SCID and SMA and compared the efficacy of rapid extraction versus automated protocols. Additionally, the distribution of T cell receptor excision circles (TREC) on DBS cards, commonly used for routine newborn screening, was determined.
RESULTS
Contaminations from the punching procedure were detected in the SCID and SMA assays in all experimental setups tested. However, a careful evaluation of a cut-off allowed for a clear separation of true positive polymerase chain reaction (PCR) amplifications. Our rapid in-house extraction protocol produced similar amounts compared to automated commercial systems. Therefore, it can be used for reliable DNA-based screening. Additionally, the amount of extracted DNA significantly differs depending on the location of punching within a DBS.
CONCLUSIONS
Newborn screening for SMA and SCID can be performed reliably. It is crucial to ensure that affected newborns are not overlooked. Therefore a carefully consideration of potential contaminating factors and the definition of appropriate cut-offs to minimise the risk of false results are of special concern. It is also important to note that the location of punching plays a pivotal role, and therefore an exact quantification of TREC numbers per μl may not be reliable and should therefore be avoided.
Topics: Humans; Neonatal Screening; Infant, Newborn; Muscular Atrophy, Spinal; Severe Combined Immunodeficiency; DNA; Dried Blood Spot Testing; High-Throughput Screening Assays; Polymerase Chain Reaction
PubMed: 38941330
DOI: 10.1371/journal.pone.0306329 -
The Journal of Clinical Endocrinology... Jun 2024Investigating the co-occurrence of obstructive sleep apnea (OSA) and primary aldosteronism (PA) is crucial for understanding their interrelation.
CONTEXT
Investigating the co-occurrence of obstructive sleep apnea (OSA) and primary aldosteronism (PA) is crucial for understanding their interrelation.
OBJECTIVE
This work aimed to evaluate the prevalence of OSA in individuals diagnosed with PA and to assess the prevalence of PA within the OSA population, with a specific focus on hypertensive individuals.
METHODS
An exhaustive search was performed across PubMed, Embase, CINAHL, Scopus, and Web of Science up to September 2023, without restrictions on language or publication date. Studies were selected based on their focus on the prevalence of OSA in PA patients and vice versa, specifically in hypertensive individuals. Data were extracted using standard guidelines, focusing on patient characteristics, prevalence rates, and other relevant clinical parameters.
RESULTS
Proportional meta-analysis using a random-effects model revealed a 59.8% prevalence of OSA in hypertensive PA patients, with 45.4% exhibiting moderate-to-severe OSA. Meta-regression showed no significant effect of age, sex, body mass index, antihypertensive medication, systolic blood pressure, diastolic blood pressure, or serum potassium on OSA prevalence. However, a significant positive association was found with the glomerular filtration rate (GFR) (P < .001). Subgroup analysis also revealed that a hyperfiltration rate (GFR ≥ 100 mL/min per 1.73 m2) may be associated with a higher prevalence of OSA (71%, P value for interaction < .01). Among hypertensive OSA patients, 11.2% had PA.
CONCLUSION
A substantial prevalence of OSA in individuals with PA was identified, demonstrating a complex interplay between these conditions in hypertensive patients. Notably, the prevalence of OSA was significantly associated with kidney hyperfiltration.
PubMed: 38941133
DOI: 10.1210/clinem/dgae415 -
JAMA Network Open Jun 2024Studies on the familial effects of body mass index (BMI) status have yielded a wide range of data on its heritability.
IMPORTANCE
Studies on the familial effects of body mass index (BMI) status have yielded a wide range of data on its heritability.
OBJECTIVE
To assess the heritability of obesity by measuring the association between the BMIs of fathers, mothers, and their offspring at the same age.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used data from population-wide mandatory medical screening before compulsory military service in Israel. The study included participants examined between January 1, 1986, and December 31, 2018, whose both parents had their BMI measurement taken at their own prerecruitment evaluation in the past. Data analysis was performed from May to December 2023.
MAIN OUTCOMES AND MEASURES
Spearman correlation coefficients were calculated for offsprings' BMI and their mothers', fathers', and midparental BMI percentile (the mean of the mothers' and fathers' BMI cohort- and sex-specific BMI percentile) to estimate heritability. Logistic regression models were applied to estimate the odds ratios (ORs) and 95% CIs of obesity compared with healthy BMI, according to parental BMI status.
RESULTS
A total of 447 883 offspring (235 105 male [52.5%]; mean [SD] age, 17.09 [0.34] years) with both parents enrolled and measured for BMI at 17 years of age were enrolled in the study, yielding a total study population of 1 343 649 individuals. Overall, the correlation between midparental BMI percentile at 17 years of age and the offspring's BMI at 17 years of age was moderate (ρ = 0.386). Among female offspring, maternal-offspring BMI correlation (ρ = 0.329) was somewhat higher than the paternal-offspring BMI correlation (ρ = 0.266). Among trios in which both parents had a healthy BMI, the prevalence of overweight or obesity in offspring was 15.4%; this proportion increased to 76.6% when both parents had obesity and decreased to 3.3% when both parents had severe underweight. Compared with healthy weight, maternal (OR, 4.96; 95% CI, 4.63-5.32), paternal (OR, 4.48; 95% CI, 4.26-4.72), and parental (OR, 6.44; 95% CI, 6.22-6.67) obesity (midparent BMI in the ≥95th percentile) at 17 years of age were associated with increased odds of obesity among offspring.
CONCLUSIONS AND RELEVANCE
In this cohort study of military enrollees whose parents also underwent prerecruitment evaluations, the observed correlation between midparental and offspring BMI, coupled with a calculated narrow-sense heritability of 39%, suggested a substantive contribution of genetic factors to BMI variation at 17 years of age.
Topics: Humans; Body Mass Index; Male; Female; Israel; Adolescent; Obesity; Cohort Studies; Adult; Fathers
PubMed: 38941093
DOI: 10.1001/jamanetworkopen.2024.19029 -
Journal of Comparative Physiology. A,... Jun 2024Evidence has been accumulating that elements of the vertebrate pituitary adenylate cyclase-activating polypeptide (PACAP) system are missing in non-chordate genomes,...
Evidence has been accumulating that elements of the vertebrate pituitary adenylate cyclase-activating polypeptide (PACAP) system are missing in non-chordate genomes, which is at odds with the partial sequence-, immunohistochemical-, and physiological data in the literature. Multilevel experiments were performed on the great pond snail (Lymnaea stagnalis) to explore the role of PACAP in invertebrates. Screening of neuronal transcriptome and genome data did not reveal homologs to the elements of vertebrate PACAP system. Despite this, immunohistochemical investigations with an anti-human PAC receptor antibody yielded a positive signal in the neuronal elements in the heart. Although Western blotting of proteins extracted from the nervous system found a relevant band for PACAP-38, immunoprecipitation and mass spectrometric analyses revealed no corresponding peptide fragments. Similarly to the effects reported in vertebrates, PACAP-38 significantly increased cAMP synthesis in the heart and had a positive ionotropic effect on heart preparations. Moreover, it significantly modulated the effects of serotonin and acetylcholine. Homologs to members of Cluster B receptors, which have shared common evolutionary origin with the vertebrate PACAP receptors, PTHRs, and GCGRs, were identified and shown not to be expressed in the heart, which does not support a potential role in the mediation of PACAP-induced effects. Our findings support the notion that the PACAP system emerged after the protostome-deuterostome divergence. Using antibodies against vertebrate proteins is again highlighted to have little/no value in invertebrate studies. The physiological effects of vertebrate PACAP peptides in protostomes, no matter how similar they are to those in vertebrates, should be considered non-specific.
PubMed: 38940930
DOI: 10.1007/s00359-024-01706-5 -
Alzheimer's & Dementia : the Journal of... Jun 2024This study investigated the potential of phosphorylated plasma Tau217 ratio (pTau217R) and plasma amyloid beta (Aβ) 42/Aβ40 in predicting brain amyloid levels measured...
BACKGROUND
This study investigated the potential of phosphorylated plasma Tau217 ratio (pTau217R) and plasma amyloid beta (Aβ) 42/Aβ40 in predicting brain amyloid levels measured by positron emission tomography (PET) Centiloid (CL) for Alzheimer's disease (AD) staging and screening.
METHODS
Quantification of plasma pTau217R and Aβ42/Aβ40 employed immunoprecipitation-mass spectrometry. CL prediction models were developed on a cohort of 904 cognitively unimpaired, preclinical and early AD subjects and validated on two independent cohorts.
RESULTS
Models integrating pTau217R outperformed Aβ42/Aβ40 alone, predicting amyloid levels up to 89.1 CL. High area under the receiver operating characteristic curve (AUROC) values (89.3% to 94.7%) were observed across a broad CL range (15 to 90). Utilizing pTau217R-based models for low amyloid levels reduced PET scans by 70.5% to 78.6%.
DISCUSSION
pTau217R effectively predicts brain amyloid levels, surpassing cerebrospinal fluid Aβ42/Aβ40's range. Combining it with plasma Aβ42/Aβ40 enhances sensitivity for low amyloid detection, reducing unnecessary PET scans and expanding clinical utility.
HIGHLIGHTS
Phosphorylated plasma Tau217 ratio (pTau217R) effectively predicts amyloid-PET Centiloid (CL) across a broad spectrum. Integrating pTau217R with Aβ42/Aβ40 extends the CL prediction upper limit to 89.1 CL. Combined model predicts amyloid status with high accuracy, especially in cognitively unimpaired individuals. This model identifies subjects above or below various CL thresholds with high accuracy. pTau217R-based models significantly reduce PET scans by up to 78.6% for screening out individuals with no/low amyloid.
PubMed: 38940656
DOI: 10.1002/alz.14073 -
Postgraduate Medicine Jul 2024While several biomarkers were previously associated with frailty and mortality, data are still contradicting. We aimed to evaluate the association between novel...
OBJECTIVES
While several biomarkers were previously associated with frailty and mortality, data are still contradicting. We aimed to evaluate the association between novel biomarkers and frailty among community-dwelling older adults to enhance understanding of the pathophysiology of frailty.
METHODS
Nine hundred and sixty-three older adults were screened during the third phase (1999-2008) of the Israel study on Glucose Intolerance, Obesity, and Hypertension (GOH). Frailty was defined as sedentary individuals, past 10 years hospitalizations, or at least one of the following: body mass index (BMI) <21 kg/m; albumin <3.2 g/dl; ≥2 major baseline diseases. Biomarkers were evaluated for their association with frailty, all-cause, and cardiovascular mortality.
RESULTS
Mean baseline age was 72 ± 7 years, 471 (49%) were women, and 195 (20%) were classified as frail. Median follow-up for cardiovascular and all-cause mortality was 11 and 13 years, with 179 (18.6%) and 466 (48.4%) deaths recorded, respectively. Multivariable logistic regression showed greater odds for frailty with lower quartile of alanine aminotransferase (ALT) (OR = 1.8, 95%CI: 1.2-2.8, = 0.01), and for each 5 µmol/L increment in homocysteine levels (OR = 1.3, 95%CI: 1.1-1.5, = 0.001). Multivariate Cox regression showed greater all-cause and cardiovascular mortality risk for individuals with low ALT (HR = 1.6, 95%CI: 1.3-2.0, < 0.001 and HR = 1.5, 95% CI: 1.0-2.2, = 0.03, respectively), and high homocysteine (HR = 1.1, 95%CI: 1.1-1.3, = 0.003 and HR = 1.2, 95%CI: 1.0-1.3, = 0.04, respectively). Homocysteine association with mortality was more pronounced in those with baseline ischemic heart disease (IHD) compared with subjects free of IHD (P for interaction = 0.01).
CONCLUSIONS
Lower ALT and higher homocysteine were associated with frailty, all-cause and cardiovascular mortality. These available and low-cost biomarkers underscore the nutritional and metabolic aspects of frailty when screening high-risk older adults, especially those with IHD, and may be considered as preferable screening biomarkers to be tested among these individuals for frailty and mortality risk.
PubMed: 38940517
DOI: 10.1080/00325481.2024.2374703 -
Health Technology Assessment... Jun 2024Health economic assessments are used to determine whether the resources needed to generate net benefit from an antenatal or newborn screening programme, driven by...
BACKGROUND
Health economic assessments are used to determine whether the resources needed to generate net benefit from an antenatal or newborn screening programme, driven by multiple benefits and harms, are justifiable. It is not known what benefits and harms have been adopted by economic evaluations assessing these programmes and whether they omit benefits and harms considered important to relevant stakeholders.
OBJECTIVES
(1) To identify the benefits and harms adopted by health economic assessments in this area, and to assess how they have been measured and valued; (2) to identify attributes or relevance to stakeholders that ought to be considered in future economic assessments; and (3) to make recommendations about the benefits and harms that should be considered by these studies.
DESIGN
Mixed methods combining systematic review and qualitative work.
SYSTEMATIC REVIEW METHODS
We searched the published and grey literature from January 2000 to January 2021 using all major electronic databases. Economic evaluations of an antenatal or newborn screening programme in one or more Organisation for Economic Co-operation and Development countries were considered eligible. Reporting quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards checklist. We identified benefits and harms using an integrative descriptive analysis and constructed a thematic framework.
QUALITATIVE METHODS
We conducted a meta-ethnography of the existing literature on newborn screening experiences, a secondary analysis of existing individual interviews related to antenatal or newborn screening or living with screened-for conditions, and a thematic analysis of primary data collected with stakeholders about their experiences with screening.
RESULTS
The literature searches identified 52,244 articles and reports, and 336 unique studies were included. Thematic framework resulted in seven themes: (1) diagnosis of screened for condition, (2) life-years and health status adjustments, (3) treatment, (4) long-term costs, (5) overdiagnosis, (6) pregnancy loss and (7) spillover effects on family members. Diagnosis of screened-for condition (115, 47.5%), life-years and health status adjustments (90, 37.2%) and treatment (88, 36.4%) accounted for most of the benefits and harms evaluating antenatal screening. The same themes accounted for most of the benefits and harms included in studies assessing newborn screening. Long-term costs, overdiagnosis and spillover effects tended to be ignored. The wide-reaching family implications of screening were considered important to stakeholders. We observed good overlap between the thematic framework and the qualitative evidence.
LIMITATIONS
Dual data extraction within the systematic literature review was not feasible due to the large number of studies included. It was difficult to recruit healthcare professionals in the stakeholder's interviews.
CONCLUSIONS
There is no consistency in the selection of benefits and harms used in health economic assessments in this area, suggesting that additional methods guidance is needed. Our proposed thematic framework can be used to guide the development of future health economic assessments evaluating antenatal and newborn screening programmes.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42020165236.
FUNDING
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR127489) and is published in full in ; Vol. 28, No. 25. See the NIHR Funding and Awards website for further award information.
Topics: Humans; Infant, Newborn; Neonatal Screening; Cost-Benefit Analysis; Female; Pregnancy; Qualitative Research; Technology Assessment, Biomedical; Prenatal Diagnosis; Quality-Adjusted Life Years
PubMed: 38938110
DOI: 10.3310/PYTK6591 -
Journal of Analytical Toxicology Jun 2024
Comment on "Comprehensive Toxicological Screening of Common Drugs of Abuse, New Psychoactive Substances, and Cannabinoids in Blood Using Supported Liquid Extraction and Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (LC-QTOF-MS)".
PubMed: 38937875
DOI: 10.1093/jat/bkae057