Human cytomegalovirus (HCMV) is the leading infectious cause of congenital disabilities. We designed a prospective study to investigate the rate, outcome, and risk factors of congenital CMV (cCMV) ...infection in neonates born to immune women, and the potential need and effectiveness of hygiene recommendations in this population.
The study was composed of 2 sequential parts: an epidemiology (part 1) and a prevention (part 2) study. Performance of part 2 depended upon a cCMV rate >0.4%. Women enrolled in part 1 did not receive hygiene recommendations. Newborns were screened by HCMV DNA testing in saliva and cCMV was confirmed by urine testing.
Saliva swabs were positive for HCMV DNA in 45/9661 newborns and cCMV was confirmed in 18 cases. The rate of cCMV was .19% (95% confidence interval CI: .11-.29%), and 3 out of 18 infants with cCMV had symptoms of CMV at birth. Age, nationality, occupation, and contact with children were similar between mothers of infected and noninfected newborns. Twin pregnancy (odds ratio OR: 7.2; 95% CI: 1.7-32.2; P = .037) and maternal medical conditions (OR: 3.9; 95% CI: 1.5-10.1; P = .003) appeared associated with cCMV. Given the rate of cCMV was lower than expected, the prevention part of the study was cancelled.
Newborns from women with preconception immunity have a low rate of cCMV, which appears to be mostly due to reactivation of the latent virus. Therefore, serological screening in childbearing age would be pivotal to identify HCMV-seropositive women, whose newborns have a low risk of cCMV.
www.clinicaltrials.gov (NCT03973359).
The current phase of development of health services is characterised by multiple changes that affect the organisational models of primary production lines (hospital, clinics, etc.) and the method of ...use by users. The clinical governance is a "strategy by which healthcare organisations are responsible for continuous improvement in the quality of services and achievement-maintaining high professional standards, stimulating the creation of an environment that fosters professional excellence". In this perspective of clinical governance, the role of the case manager with its clinical and managerial and financial skills becomes a key figure to ensure quality as a set of aspects of efficiency, effectiveness, safety, appropriateness, participation and equity. Case management fits perfectly in the context of assistance, to promote an increased quality of care, resulting in improved life, through coordination, integrating different professional contributions and ensuring continuity of care through all stages of treatment. In conclusion, preliminary results indicate that the increase of this organisation could be more functionally to reduce some team's gap.
The prognostic relevance of fetal/early postnatal magnetic resonance (MR) imaging (MRI) isolated “minor” lesions in congenital cytomegalovirus (CMV) infection is still unclear, because of the ...heterogeneity of previously reported case series. The aim of this study was to report the imaging and long-term clinical follow-up data on a relatively large cohort of infected fetuses.
Among 140 CMV-infected fetuses from a single-center 12-year-long fetal MRI database, cases that showed isolated “minor” lesions at MRI, mainly represented by polar temporal lesions, were selected. MRI features were described, and clinical follow-up information was collected through consultation of medical records and telephone interview to establish the auditory and neurological outcome of each patient.
Thirty-six cases were included in the study. The frequency of “minor” lesions increased progressively with ongoing gestational age in cases who underwent serial MR examination; 31% of cases were symptomatic at birth for unilateral altered auditory brainstem response. At long-term clinical follow-up, performed in 35 patients at a mean age of 64.5 months (range: 25 to 138), 43% of patients were asymptomatic and 57% presented with mild/moderate disability including hearing loss (34%), unilateral in all cases but one (therefore classified as severe), and/or minor cognitive and behavioral disorders (49%).
Descriptive analysis of the type and modality of occurrence of “minor” lesions suggests performing serial fetal/postnatal MR examinations not to miss later-onset lesions. Follow-up data from the present cohort, combined with maternal/fetal factors and serologic-laboratory parameters may contribute to improve prenatal and neonatal period counselling skills.
Circulating polypeptides and proteins have been implicated in reversing or accelerating aging phenotypes, including growth/differentiation factor 8 (GDF8), GDF11, eotaxin, and oxytocin. These ...proteoforms, which are defined as the protein products arising from a single gene due to alternative splicing and PTMs, have been challenging to study. Both GDF8 and GDF11 have known antagonists such as follistatin (FST), and WAP, Kazal, immunoglobulin, Kunitz, and NTR domain‐containing proteins 1 and 2 (WFIKKN1, WFIKKN2). We developed a novel multiplexed SRM assay using LC‐MS/MS to measure five proteins related to GDF8 and GDF11 signaling, and in addition, eotaxin, and oxytocin. Eighteen peptides consisting of 54 transitions were monitored and validated in pooled human plasma. In 24 adults, the mean (SD) concentrations (ng/mL) were as follows: GDF8 propeptide, 11.0 (2.4); GDF8 mature protein, 25.7 (8.0); GDF11 propeptide, 21.3 (10.9); GDF11 mature protein, 16.5 (12.4); FST, 29.8 (7.1); FST cleavage form FST303, 96.4 (69.2); WFIKKN1, 38.3 (8.3); WFIKKN2, 32.2 (10.5); oxytocin, 1.9 (0.9); and eotaxin, 2.3 (0.5). This novel multiplexed SRM assay should facilitate the study of the relationships of these proteoforms with major aging phenotypes.
Abstract
Background
Growth and differentiation factors 8 (GDF8) and 11 (GDF11) have attracted attention as targets for rejuvenating interventions. The biological activity of these proteins may be ...affected by circulating antagonists such as their respective prodomains, follistatin (FST315), WFIKKN1, and WFIKKN2. Reports of the relationship of GDF8 and GDF11 and their antagonists with aging and aging phenotypes such as skeletal muscle strength have been conflicting possibly because of difficulties in measuring these proteins and polypeptides.
Methods
Plasma GDF8 and GDF11 and their antagonists were measured using a multiplexed selected reaction monitoring assay and liquid chromatography–tandem mass spectrometry in 160 healthy adults aged 22–93 years. Quadriceps strength was measured by knee extensor torque using isokinetic dynamometry.
Results
Spearman correlations with age were the following: GDF11 prodomain (r = .30, p = .001), GDF11 mature protein (r = .23, p = .004), FST315 (r = .32, p < .0001), WFIKKN1 (r = −.21, p = 0.008), and WFIKKN2 (r = .18, p = .02). Independent of age, FST315 and WFIKKN1 were negatively associated with knee strength (p = .02, p = .03, respectively) in a multivariable model that included both GDF8 and GDF11 mature proteins.
Conclusions
When measured by an antibody-free selected reaction monitoring assay, GDF8, GDF11, and their antagonists are found in the circulation in the ng/mL range. In healthy adults, plasma GDF11 and antagonists FST315, WFIKKN1, and WFIKKN2 differed by age. Antagonists of GDF8 and GDF11, but not GDF8 and GDF11, were independently associated with skeletal muscle strength. Further work is needed to characterize the relationship of these protein and polypeptides with sarcopenia-related phenotypes such as physical function and walking disability.
Summary
Cardiorespiratory fitness (VO2 peak) declines with age and is an independent risk factor for morbidity and mortality in older adults. Identifying biomarkers of low fitness may provide insight ...for why some individuals experience an accelerated decline of aerobic capacity and may serve as clinically valuable prognostic indicators of cardiovascular health. We investigated the relationship between circulating ceramides and VO2 peak in 443 men and women (mean age of 69) enrolled in the Baltimore Longitudinal Study of Aging (BLSA). Individual species of ceramide were quantified by HPLC–tandem mass spectrometry. VO2 peak was measured by a graded treadmill test. We applied multiple regression models to test the associations between ceramide species and VO2 peak, while adjusting for age, sex, blood pressure, serum LDL, HDL, triglycerides, and other covariates. We found that higher levels of circulating C18:0, C20:0, C24:1 ceramides and C20:0 dihydroceramides were strongly associated with lower aerobic capacity (P < 0.001, P < 0.001, P = 0.018, and P < 0.001, respectively). The associations held true for both sexes (with men having a stronger association than women, P value for sex interaction <0.05) and were unchanged after adjusting for confounders and multiple comparison correction. Interestingly, no significant association was found for C16:0, C22:0, C24:0, C26:0, and C22:1 ceramide species, C24:0 dihydroceramide, or total ceramides. Our analysis reveals that specific long‐chain ceramides strongly associate with low cardiovascular fitness in older adults and may be implicated in the pathogenesis of low fitness with aging. Longitudinal studies are needed to further validate these associations and investigate the relationship between ceramides and health outcomes.
Background
Muscle quality (MQ) or strength‐to‐mass ratio declines with aging, but the rate of MQ change with aging is highly heterogeneous across individuals. The identification of risk factors for ...accelerated MQ decline may offer clues to identity the underpinning physiological mechanisms and indicate targets for prevention and treatment. Using data from the Baltimore Longitudinal Study of Aging, we tested whether measures of body mass and body composition are associated with differential rates of changes in MQ with aging.
Methods
Participants included 511 men and women, aged 50 years or older, followed for an average of 4 years (range: 1–8). MQ was operationalized as ratio between knee‐extension isokinetic strength and CT‐thigh muscle cross‐sectional area. Predictors included body mass and body composition measures: weight (kg), body mass index (BMI, kg/m2), dual‐energy x‐ray absorptiometry‐measured total body fat mass (TFM, kg) and lean mass (TLM, kg), and body fatness (TFM/weight). Covariates were baseline age, sex, race, and body height.
Results
Muscle quality showed a significant linear decline over the time of the follow up (average rate of decline 0.02 Nm/cm2 per year, P < .001). Independent of covariates, neither baseline body weight (P = .756) nor BMI (P = .777) was predictive of longitudinal rate of decline in MQ. Instead, higher TFM and lower TLM at baseline predicted steeper longitudinal decline in MQ (P = .036 and P < .001, respectively). In particular, participants with both high TFM and low TLM at baseline experienced the most dramatic decline compared with those with low TFM and high TLM (about 3% per year vs. 0.5% per year, respectively). Participants in the higher tertile of baseline body fatness presented a significantly faster decline of MQ than the rest of the population (P = .021). Similar results were observed when body mass, TFM, and TLM were modeled as time‐dependent predictors.
Conclusions
Body composition, but not weight nor BMI, is associated with future MQ decline, suggesting that preventive strategies aimed at maintaining good MQ with aging should specifically target body composition features.
Small changes of bilirubin and liver enzymes are often detected during the acute phase of stroke, but their origin and significance are still poorly understood.
On days 0, 3, 7, and 14 after ...admission, 180 patients with ischemic stroke underwent serial determinations of bilirubin, GOT, GPT, γGT, alkaline phosphatase, C-reactive protein (CRP) and complete blood count. On days 0 and 7 common bile duct diameter was measured by ultrasound, and on day 3 cerebral infarct volume (IV) was calculated from CT scan slices.
During the first week GOT, GPT, γGT (P < 0.001) and CRP (P = 0.03) increased with subsequent plateau, while significant decrements (P < 0.001) concerned unconjugated bilirubin, erythrocytes and haemoglobin. Alkaline phosphatase, direct bilirubin and common bile duct diameter remained stable. IV correlated with CRP, leukocytes, GOT, γGT (r > 0.3, P < 0.001 for all) and direct bilirubin (r = 0.23, P = 0.008). In multivariate analysis only CRP and GOT remained independently associated with IV (P < =0.001). The correlation of IV with GOT increased progressively from admission to day 14. GOT independently correlated with GPT which, in turn, correlated with γGT. γGT was also highly correlated with leukocytes. Unconjugated bilirubin correlated with haemoglobin, which was inversely correlated with CRP.
The changes of bilirubin and liver enzymes during ischemic stroke reflect two phenomena, which are both related to IV: 1) inflammation, with consequent increment of CRP, leukocytes and γGT, and decrease of haemoglobin and unconjugated bilirubin and 2) an unknown signal, independent from inflammation, leading to increasing GOT and GPT levels.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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