Congenital Cytomegalovirus Infection With Isolated "Minor" Lesions at Fetal Magnetic Resonance Imaging: Long-Term Neurological Outcome.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Validation of the prevalence to incidence conversion method for healthcare associated infections in long-term care facilities.

INTRODUCTION: Residents of long-term care facilities (LTCFs) are a population at high risk of developing severe healthcare associated infections (HAIs). In the assessment of HAIs in acute-care hospitals, selection bias can occur due to cases being over-represented: patients developing HAIs usually have longer lengths of stays compared to controls, and therefore have an increased probability of being sampled in PPS, leading to an overestimation of HAI prevalence. Our hypothesis was that in LTCFs, the opposite may occur: residents developing HAIs either may have a greater chance of being transferred to acute-care facilities or of dying, and therefore could be under-represented in PPS, leading to an underestimation of HAI prevalence. Our aim was to test this hypothesis by comparing HAI rates obtained through longitudinal and cross-sectional studies. METHODS: Results from two studies conducted simultaneously in four LTCFs in Italy were compared: a longitudinal study promoted by the European Centre for Disease Prevention and Control (ECDC, HALT4 longitudinal study, H4LS), and a PPS. Prevalence was estimated from the PPS and converted into incidence per year using an adapted version of the Rhame and Sudderth formula proposed by the ECDC. Differences between incidence rates calculated from the PPS results and obtained from H4LS were investigated using the Byar method for rate ratio (RR). RESULTS: On the day of the PPS, HAI prevalence was 1.47% (95% confidence interval, CI 0.38-3.97), whereas the H4LS incidence rate was 3.53 per 1000 patient-days (PDs, 95% CI 2.99-4.08). Conversion of prevalence rates obtained through the PPS into incidence using the ECDC formula resulted in a rate of 0.86 per 1000 PDs (95% CI 0-2.68). Comparing the two rates, a RR of 0.24 (95% CI 0.03-2.03, p 0.1649) was found. CONCLUSIONS: This study did not find significant differences between HAI incidence estimates obtained from a longitudinal study and through conversion from PPS data. Results of this study support the validity of the ECDC method.

Implementation of a centralized, web-based surveillance for healthcare associated infections among residents of long-term care facilities in Italy.

Objective: The Italian National Action Plan to contrast AMR identified among its objectives the development and implementation of a national Healthcare-Associated Infection (HAI) surveillance system based on European Centre for Disease Prevention and Control (ECDC) indications, through point prevalence surveys (PPS) of HAIs and antibiotic use in acute-care hospitals and long-term care facilities (LTCFs). We aimed to assess feasibility and appropriateness of proposed tools for a national surveillance system of HAIs and antibiotic use in LTCFs. Study design: Point prevalence survey. Methods: A pilot PPS was conducted between May-June 2022, among 15 LTCFs of 7 Italian regions. Data were collected in a single day in each LTCF, at the LTCF, ward, and resident levels, using a web-based data collection tool developed ad hoc. Data collector teams of each facility were invited to complete a questionnaire investigating opinions on the proposed tools. Results: Among 1025 included residents, the prevalence of residents with at least one HAI was 2.5% (95% CI 1.7%-3.7%) considering all HAIs and 2.2% (95% CI 1.3%-3%) without considering SARS-CoV-2 infections. The prevalence of antimicrobial use was 3% (95% CI 0.2%-4.3%). Overall, most respondents were satisfied with the web-based software, training and protocol, even though some difficulties were reported. Conclusions: A national surveillance network was established, which will facilitate future surveillance efforts. Further studies are necessary to evaluate the impact of the pandemic on HAI transmission and antibiotic use in LTCFs.

The expert vascular access nurse: a pilot study of competencies.

Background and aim In health care, competencies evolving with clinical and professional practice increasingly need to be defined. Identifying professional competencies in a general sense is no longer enough; it is necessary to define what competencies the professional must possess to ensure the appropriateness and effectiveness of their work. This pilot study aims to outline an initial competency framework specifically for vascular access nurses Methods: A cross-sectional observational study was conducted through structured interviews with professionals of a competency framework (108) to assess content validity and ensure relevance, comprehensibility, and completeness Results: The research involved 14 expert professionals who reported no significant language barriers or comprehensibility difficulties. The expert review showed that the content was valid for all proposed items (CVR .571 to 1.0). Conclusions: The framework identified could be a good starting point for a more in-depth assessment of expert nursing skills in venous access (www.actabiomedica.it).

Implementation Strategies for Preventing Healthcare-Associated Infections across the Surgical Pathway: An Italian Multisociety Document.

Healthcare-associated infections (HAIs) result in significant patient morbidity and can prolong the duration of the hospital stay, causing high supplementary costs in addition to those already sustained due to the patient's underlying disease. Moreover, bacteria are becoming increasingly resistant to antibiotics, making HAI prevention even more important nowadays. The public health consequences of antimicrobial resistance should be constrained by prevention and control actions, which must be a priority for all health systems of the world at all levels of care. As many HAIs are preventable, they may be considered an important indicator of the quality of patient care and represent an important patient safety issue in healthcare. To share implementation strategies for preventing HAIs in the surgical setting and in all healthcare facilities, an Italian multi-society document was published online in November 2022. This article represents an evidence-based summary of the document.

Prevalence, Outcome, and Prevention of Congenital Cytomegalovirus Infection in Neonates Born to Women With Preconception Immunity (CHILd Study).

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov (NCT03973359).

Disease Burden Affects Aging Brain Function.

BACKGROUND: Most older adults live with multiple chronic disease conditions, yet the effect of multiple diseases on brain function remains unclear. METHODS: We examine the relationship between disease multimorbidity and brain activity using regional cerebral blood flow (rCBF) 15O-water PET scans from 97 cognitively normal participants (mean baseline age 76.5) in the Baltimore Longitudinal Study of Aging (BLSA). Multimorbidity index scores, generated from the presence of 13 health conditions, were correlated with PET data at baseline and in longitudinal change (n = 74) over 5.05 (2.74 SD) years. RESULTS: At baseline, voxel-based analysis showed that higher multimorbidity scores were associated with lower relative activity in orbitofrontal, superior frontal, temporal pole and parahippocampal regions, and greater activity in lateral temporal, occipital, and cerebellar regions. Examination of the individual health conditions comprising the index score showed hypertension and chronic kidney disease individually contributed to the overall multimorbidity pattern of altered activity. Longitudinally, both increases and decreases in activity were seen in relation to increasing multimorbidity over time. These associations were identified in orbitofrontal, lateral temporal, brainstem, and cerebellar areas. CONCLUSION: Together, these results show that greater multimorbidity is associated with widespread areas of altered brain activity, supporting a link between health and changes in aging brain function.

Severe Fetal Symptomatic Infection from Human Cytomegalovirus following Nonprimary Maternal Infection: Report of Two Cases.

INTRODUCTION: Human cytomegalovirus (HCMV) is the most common congenital infection, especially severe after a maternal primary infection; sequelae in neonates born to mothers experiencing a nonprimary infection have been already reported. Hereby, two cases of severe fetal HCMV disease in seroimmune gravidas referred to our Unit are described. CASES PRESENTATION: Case 1: A fetus at 21 weeks' gestation with signs of anemia and brain abnormalities at ultrasound, described at magnetic resonance (MR) imaging as ependymal irregularity and bilateral asymmetric parenchymal thinning; amniotic fluid sample was positive for HCMV although the woman had a previous immunity; after termination of pregnancy, autopsy demonstrated a thicken layer of disorganized neurons on the right cortical plate, while on the left, there was a morphological pattern coherent with polymicrogyria. Case 2: A fetus at 20 weeks' gestation with anemia, moderate atrioventricular insufficiency, hepatosplenomegaly but no major cerebral lesions. Fetal blood was positive for HCMV, although unexpected for prepregnancy maternal immunity, and intrauterine transfusion was needed. A cesarean section at 34 weeks' gestation was performed due to worsening condition of the fetus, who had a birthweight of 2,210 g and needed platelet transfusions, but MR examination and clinical evaluation were normal. CONCLUSION: The impact of nonprimary maternal infection on pregnancy outcome is unknown and fetal brain damage in HCMV seroimmune transmitter-mothers can occur as a consequence of maternal reinfection or reactivation for a hypotetic different role of HCMV-primed CD4+ or CD8+ T-cells in fetal brain, with progressive brain lesions coexistent in the first case and with severe unexpected anemia in the second case. A previous maternal HCMV immunity should not exempt to test anemic fetuses for such infection, nor to consider a potential transplacental transmission.

Mode of birth in women with low-lying placenta: protocol for a prospective multicentre 1:3 matched case-control study in Italy (the MODEL-PLACENTA study).

INTRODUCTION: The term placenta praevia defines a placenta that lies over the internal os, whereas the term low-lying placenta identifies a placenta that is partially implanted in the lower uterine segment with the inferior placental edge located at 1-20 mm from the internal cervical os (internal-os-distance). The most appropriate mode of birth in women with low-lying placenta is still controversial, with the majority of them undergoing caesarean section. The current project aims to evaluate the rate of vaginal birth and caesarean section in labour due to bleeding by offering a trial of labour to all women with an internal-os-distance >5 mm as assessed by transvaginal sonography in the late third trimester. METHODS AND ANALYSIS: The MODEL-PLACENTA is a prospective, multicentre, 1:3 matched case-control study involving 17 Maternity Units across Lombardy and Emilia-Romagna regions, Italy. The study includes women with a placenta located in the lower uterine segment at the second trimester scan. Women with a normally located placenta will be enrolled as controls. A sample size of 30 women with an internal-os-distance >5 mm at the late third trimester scan is needed at each participating Unit. Since the incidence of low-lying placenta decreases from 2% in the second trimester to 0.4% at the end of pregnancy, 150 women should be recruited at each centre at the second trimester scan. A vaginal birth rate ≥60% in women with an internal-os-distance >5 mm will be considered appropriate to start routinely admitting to labour these women. ETHICS AND DISSEMINATION: Ethical approval for the study was given by the Brianza Ethics Committee (No 3157, 2019). Written informed consent will be obtained from study participants. Results will be disseminated by publication in peer-reviewed journals and presentation in international conferences. TRIAL REGISTRATION NUMBER: NCT04827433 (pre-results stage).

Measuring biological aging in humans: A quest.

The global population of individuals over the age of 65 is growing at an unprecedented rate and is expected to reach 1.6 billion by 2050. Most older individuals are affected by multiple chronic diseases, leading to complex drug treatments and increased risk of physical and cognitive disability. Improving or preserving the health and quality of life of these individuals is challenging due to a lack of well-established clinical guidelines. Physicians are often forced to engage in cycles of "trial and error" that are centered on palliative treatment of symptoms rather than the root cause, often resulting in dubious outcomes. Recently, geroscience challenged this view, proposing that the underlying biological mechanisms of aging are central to the global increase in susceptibility to disease and disability that occurs with aging. In fact, strong correlations have recently been revealed between health dimensions and phenotypes that are typical of aging, especially with autophagy, mitochondrial function, cellular senescence, and DNA methylation. Current research focuses on measuring the pace of aging to identify individuals who are "aging faster" to test and develop interventions that could prevent or delay the progression of multimorbidity and disability with aging. Understanding how the underlying biological mechanisms of aging connect to and impact longitudinal changes in health trajectories offers a unique opportunity to identify resilience mechanisms, their dynamic changes, and their impact on stress responses. Harnessing how to evoke and control resilience mechanisms in individuals with successful aging could lead to writing a new chapter in human medicine.

Targeted Metabolomics Shows Low Plasma Lysophosphatidylcholine 18:2 Predicts Greater Decline of Gait Speed in Older Adults: The Baltimore Longitudinal Study of Aging.

Background: Gait speed is an important measure of lower extremity physical performance in older adults and is predictive of disability and mortality. The biological pathways involved in the decline of lower extremity physical performance are not well understood. We used a targeted metabolomics approach to identify plasma metabolites predictive of change in gait speed over time. Methods: Gait speed was measured at baseline and over median follow-up of 50.5 months in 504 adults, aged ≥50 years, who had two or more study visits in the Baltimore Longitudinal Study of Aging (BLSA). Plasma metabolites were measured using targeted mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates). Results: Of 148 plasma metabolites (amino acids, biogenic amines, hexoses, glycerophospholipids) measured, eight were significantly associated with gait speed at baseline, independent of age and sex: hexoses (r = -0.148, p < .001), [sphingomyelin (SM) 16:1 (r = -0.091, p = .0009), SM 18:0 (r = -0.085, p = .002), SM 18:1 (r = -0.128, p < .0001], phosphatidylcholine aa 32:3 (r = -0.088, p = .001), lysophosphatidylcholine (LPC) 17:0 (r = 0.083, p = .003), LPC 18:1 (r = 0.089, p = .001), and LPC 18:2 (r = 0.104, p < .0001). Adjusting for baseline age, sex, and chronic diseases, baseline plasma LPC 18:2 was an independent predictor of the rate of change of gait speed over subsequent follow-up (p = .003). No other plasma metabolites were significantly associated longitudinal changes of gait speed over time. Conclusions: Low plasma LPC 18:2, which has previously been shown to predict impaired glucose tolerance, insulin resistance, type 2 diabetes, coronary artery disease, and memory impairment, is an independent predictor of decline in gait speed in older adults.

Relationship of Circulating Growth and Differentiation Factors 8 and 11 and Their Antagonists as Measured Using Liquid Chromatography-Tandem Mass Spectrometry With Age and Skeletal Muscle Strength in Healthy Adults.

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.

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty.

Most older individuals develop inflammageing, a condition characterized by elevated levels of blood inflammatory markers that carries high susceptibility to chronic morbidity, disability, frailty, and premature death. Potential mechanisms of inflammageing include genetic susceptibility, central obesity, increased gut permeability, changes to microbiota composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections. Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials suggest that this association is causal. Inflammageing is also a risk factor for chronic kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but whether modulating inflammation beneficially affects the clinical course of non-CVD health problems is controversial. This uncertainty is an important issue to address because older patients with CVD are often affected by multimorbidity and frailty - which affect clinical manifestations, prognosis, and response to treatment - and are associated with inflammation by mechanisms similar to those in CVD. The hypothesis that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and interfering with homeostatic signalling is supported by mechanistic studies but requires confirmation in humans. Whether early modulation of inflammageing prevents or delays the onset of cardiovascular frailty should be tested in clinical trials.

Altered Plasma Amino Acids and Lipids Associated With Abnormal Glucose Metabolism and Insulin Resistance in Older Adults.

Context and Objectives: Glucose metabolism becomes progressively impaired with older age. Fasting glucose and insulin resistance are risk factors for premature death and other adverse outcomes. We aimed to identifying plasma metabolites associated with altered glucose metabolism and insulin resistance in older community-dwelling adults. Participants and Methods: A targeted metabolomics approach was used to identify plasma metabolites associated with impaired fasting plasma glucose, 2-hour plasma glucose on oral glucose tolerance testing, and homeostatic model assessment insulin resistance (HOMA-IR) in 472 participants who participated in the Baltimore Longitudinal Study of Aging, with a mean (SD) age of 70.7 (9.9) years. Results: We measured 143 plasma metabolites. In ordinal logistic regression analyses, using a false discovery rate of 5% and adjusting for potential confounders, we found that alanine, glutamic acid, and proline were significantly associated with increased odds of abnormal fasting plasma glucose. Phosphatidylcholine (diacyl C34:4, alkyl-acyl C32:1, C32:2, C34:2, C34:3, and C36:3) was associated with decreased odds of abnormal fasting plasma glucose. Glutamic and acid phosphatidylcholine alkyl-acyl C34:2 were associated with increased and decreased odds of 2-hour plasma glucose, respectively. Glutamic acid was associated with increased odds of higher tertiles of HOMA-IR. Glycine; phosphatidylcholine (diacyl C32:0, alkyl-acyl C32:1, C32:2, C34:1, C34:2, C34:3, C36:2, C36:3, C40:5, C40:6, C42:3, C42:4, and C42:5); sphingomyelin C16:0, C24:1, and C26:1; and lysophosphatidylcholine C18:1 were associated with decreased odds of abnormal HOMA-IR. Conclusions: Targeted metabolomics identified four plasma amino acids and 16 plasma lipid species, primarily containing polyunsaturated fatty acids, that were associated with abnormal glucose metabolism and insulin resistance in older adults.

Predictors of cognitive impairment assessed by Mini Mental State Examination in community-dwelling older adults: relevance of the step test.

BACKGROUND: Several predictors of cognitive impairment assessed by Mini Mental State Examination (MMSE) have previously been identified. However, which predictors are the most relevant and what is their effect on MMSE categories remains unclear. METHODS: Cross-sectional and longitudinal study using data from 1116 older adults (72.6 ±â€¯5.6 years, 579 female), 350 of whom were followed for 7 years. At baseline, the following variables were collected: personal data, marital status, occupation, anthropometric measures, risk factors, previous cardiovascular events, self-rated health and physical activity during the last week. Furthermore, routine laboratory tests, abdominal echography and a step test (with measurement of the time needed to ascend and descend two steps 20 times) were performed. The associations of these variables with cross-sectional cognitive deficit (MMSE < 24) and longitudinal cognitive decline (decrease of MMSE score over 7 years of follow-up) were investigated using logistic regression models. RESULTS: Cross-sectional cognitive deficit was independently associated with school education ≤ 5 years, prolonged step test duration, having been blue collar or housewife (P ≤ 0.0001 for all) and, with lower significance, with advanced age, previous stroke and poor recent physical activity (P < 0.05). Longitudinal cognitive decline was mainly associated with step test duration (P = 0.0001) and diastolic blood pressure (P = 0.0002). The MMSE categories mostly associated with step test duration were orientation, attention, calculation and language, while memory appeared to be poorly or not affected. CONCLUSIONS: In our cohort of older adults, step test duration was the most relevant predictor of cognitive impairment.

Skeletal muscle ex vivo mitochondrial respiration parallels decline in vivo oxidative capacity, cardiorespiratory fitness, and muscle strength: The Baltimore Longitudinal Study of Aging.

Mitochondrial function in human skeletal muscle declines with age. Most evidence for this decline comes from studies that assessed mitochondrial function indirectly, and the impact of such deterioration with respect to physical function has not been clearly delineated. We hypothesized that mitochondrial respiration in permeabilized human muscle fibers declines with age and correlates with phosphocreatine postexercise recovery rate (kPCr), muscle performance, and aerobic fitness. Mitochondrial respiration was assessed by high-resolution respirometry in saponin-permeabilized fibers from vastus lateralis muscle biopsies of 38 participants from the Baltimore Longitudinal Study of Aging (BLSA; 21 men, age 24-91 years) who also had available measures of peak oxygen consumption (VO2max ) from treadmill tests, gait speed in different tasks, 31 P magnetic resonance spectroscopy, isokinetic knee extension, and grip strength. Results indicated a significant reduction in mitochondrial respiration with age (p < .05) that was independent of other potential confounders. Mitochondrial respiratory capacity was also associated with VO2max , muscle strength, kPCr, and time to complete a 400-m walk (p < .05). A negative trend toward significance (p = .074) was observed between mitochondrial respiration and BMI. Finally, transcriptional profiling revealed a reduced mRNA expression of mitochondrial gene networks with aging (p < .05). Overall, our findings reinforce the notion that mitochondrial function declines with age and may contribute to age-associated loss of muscle performance and cardiorespiratory fitness.

Case management: an up-to-date review of literature and a proposal of a county utilization.

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.

A targeted proteomic assay for the measurement of plasma proteoforms related to human aging phenotypes.

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.

Early body composition, but not body mass, is associated with future accelerated decline in muscle quality.

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.

Insulin Resistance Is Associated With Reduced Mitochondrial Oxidative Capacity Measured by 31P-Magnetic Resonance Spectroscopy in Participants Without Diabetes From the Baltimore Longitudinal Study of Aging.

Whether individuals with insulin resistance (IR) but without criteria for diabetes exhibit reduced mitochondrial oxidative capacity is unclear; addressing this question could guide research for new therapeutics. We investigated 248 participants without diabetes from the Baltimore Longitudinal Study of Aging (BLSA) to determine whether impaired mitochondrial capacity is associated with prediabetes, IR, and duration and severity of hyperglycemia exposure. Mitochondrial capacity was assessed as the postexercise phosphocreatine recovery time constant (τPCr) by 31P-magnetic resonance spectroscopy, with higher τPCr values reflecting reduced capacity. Prediabetes was defined using the American Diabetes Association criteria from fasting and 2-h glucose measurements. IR and sensitivity were calculated using HOMA-IR and Matsuda indices. The duration and severity of hyperglycemia exposure were estimated as the number of years from prediabetes onset and the average oral glucose tolerance test (OGTT) 2-h glucose measurement over previous BLSA visits. Covariates included age, sex, body composition, physical activity, and other confounders. Higher likelihood of prediabetes, higher HOMA-IR, and lower Matsuda index were associated with longer τPCr. Among 205 participants with previous OGTT data, greater severity and longer duration of hyperglycemia were independently associated with longer τPC In conclusion, in individuals without diabetes a more impaired mitochondrial capacity is associated with greater IR and a higher likelihood of prediabetes.