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Key summary points: Aim: Our objective was to study the predictive value of the Short Physical Performance Battery (SPPB) in the cohort of the SCOPE project on falls, injurious falls, and possible difference of prediction between indoors and outdoors falls. Findings: No association of SPPB and falls was found in models adjusted for age, sex, marital status, number of medications, quality of life, handgrip strength, and muscle mass. While SPPB fails to differentiate between injurious and non-injurious falls (p = 0.48), a lower SPPB score was associated with falls at home (p < 0.01) after 24 months. Message: SBPP was not able to significantly predict the risk of falling as well as experiencing an injurious fall. Introduction: Falls and fall-related injuries in older persons are a major public health problem. Our objective was to study the predictive value of the Short Physical Performance Battery (SPPB) in the cohort of the SCOPE project on falls, injurious falls, and possible difference of prediction between indoors and outdoors falls. Methods: For this sub-study of the SCOPE project participants reporting no falls at baseline, and survey data on falls at the 12-month and 24-month follow-up were included. Participant´s characteristics were assessed during the baseline interview and medical examinations. Falls as well as injurious falls and fall circumstances were obtained self-reported. SPPB and its association with fallers vs. no fallers at 12 and at 24 months were studied with logistic regression models. Results: The 1198 participants had a median age of 79 years (77–82), and a median SPPB of 10 (8–11), with a 52.5% of female. A total of 227 and 277 falls (12- and 24- month visits, respectively) were reported. In the crude model, the SPPB sum scores (p < 0.001) as well as most single item scores were significant different between fallers and non-fallers over time. However, the association was attenuated in models adjusted for age, sex, marital status, number of medications, quality of life, handgrip strength, and muscle mass [e.g., 12 months; OR 0.94 (0.87–1.02)]. While SPPB fails to differentiate between injurious and non-injurious falls (p = 0.48), a lower SPPB score was associated with falls at home (p < 0.01) after 24 months. Conclusion: SBPP was not able to significantly predict the risk of falling as well as experiencing an injurious fall. Trial registration: This study was registered prospectively on 25th February 2016 at clinicaltrials.gov (NCT02691546). [ABSTRACT FROM AUTHOR]

Purpose: To investigate the incidence of nephrolithiasis in a cohort of children with congenital adrenal hyperplasia (CAH), and to study if there is an association with the metabolic control of the disease. Methods: This study was designed as a multicenter 1 year-prospective study involving 52 subjects (35 males) with confirmed molecular diagnosis of CAH due to 21-hydroxylase deficiency (21-OHD). Each patient was evaluated at three different time-points: T0, T1 (+6 months of follow-up), T2 (+12 months of follow up). At each follow up visit, auxological data were collected, and adrenocorticotrophic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), Δ4-androstenedione, dehydroepiandrosterone sulfate (DHEAS) serum levels, and urinary excretion of creatinine, calcium, oxalate and citrate were assayed. Moreover, a renal ultrasound was performed. Results: The incidence of nephrolithiasis, assessed by ultrasound was 17.3% at T0, 13.5% at T1 and 11.5% at T2. At T0, one subject showed nephrocalcinosis. In the study population, a statistically significant difference was found for 17-OHP [T0: 11.1 (3.0–25.1) ng/mL; T1: 7.1 (1.8–19.9) ng/mL; T2: 5.9 (2.0–20.0) ng/mL, p < 0.005], and Δ4-androstenedione [T0: 0.9 (0.3–2.5) ng/mL; T1: 0.3 (0.3–1.1) ng/mL; T2: 0.5 (0.3–1.5) ng/mL, p < 0.005] which both decreased over the follow up time. No statistically significant difference among metabolic markers was found in the group of the subjects with nephrolithiasis, even if 17-OHP, DHEAS and Δ4-androstenedione levels showed a tendency towards a reduction from T0 to T2. Principal component analysis (PCA) was performed to study possible hidden patterns of associations/correlations between variables, and to assess the trend of them during the time. PCA revealed a decrease in the amount of the variables 17-OHP, Δ4-androstenedione, and ACTH that occurred during follow-up, which was also observed in subjects showing nephrolithiasis. Conclusions: our data demonstrated that children affected with 21-OHD can be at risk of developing nephrolithiasis. Additional studies are needed to clarify the pathogenesis and other possible risk factors for this condition, and to establish if regular screening of kidney ultrasound in these patients can be indicated. [ABSTRACT FROM AUTHOR]

MultiMorbidity (MM), defined as the co-occurrence of two or more chronic conditions, is associated with poorer health outcomes, such as recurrent hospital readmission and mortality. As a group of conditions, cardiovascular disease (CVD) exemplifies several challenges of MM, and the identification of prognostic minimally invasive biomarkers to stratify mortality risk in patients affected by cardiovascular MM is a huge challenge. Circulating miRNAs associated to inflammaging and endothelial dysfunction, such as miR-17, miR-21-5p, and miR-126-3p, are expected to have prognostic relevance. We analyzed a composite profile of circulating biomarkers, including miR-17, miR-21-5p, and miR-126-3p, and routine laboratory biomarkers in a sample of 246 hospitalized geriatric patients selected for cardiovascular MM from the Report-AGE INRCA database and BioGER INRCA biobank, to evaluate the association with all-cause mortality during 31 days and 12 and 24 months follow-up. Circulating levels of miR-17, miR-126-3p, and some blood parameters, including neutrophil to lymphocyte ratio (NLR) and eGFR, were significantly associated with mortality in these patients. Overall, our results suggest that in a cohort of geriatric hospitalized patients affected by cardiovascular MM, lower circulating miR-17 and miR-126-3p levels could contribute to identify patients at higher risk of short- and medium-term mortality. [ABSTRACT FROM AUTHOR]

Senescent cells may have a prominent role in driving inflammation and frailty. The impact of cellular senescence on frailty varies depending on the assessment tool used, as it is influenced by the criteria or items predominantly affected by senescent cells and the varying weights assigned to these items across different health domains. To address this challenge, we undertook a thorough review of all available studies involving gain- or loss-of-function experiments as well as interventions targeting senescent cells, focusing our attention on those studies that examined outcomes based on the individual frailty phenotype criteria or specific items used to calculate two humans (35 and 70 items) and one mouse (31 items) frailty indexes. Based on the calculation of a simple "evidence score," we found that the burden of senescent cells related to musculoskeletal and cerebral health has the strongest causal link to frailty. We deem that insight into these mechanisms may not only contribute to clarifying the role of cellular senescence in frailty but could additionally provide multiple therapeutic opportunities to help the future development of a desirable personalized therapy in these extremely heterogeneous patients. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (DM) in older people is a heterogeneous condition that exhibits differential characteristics in comparison with younger adults. DM increases the risk of disability, is associated with dementia and loss of function, and cognition may often be interrelated and more pronounced in older patients with DM than in those without. Aims: Our aim was to evaluate the incidence of functional and/or cognitive impairment in older adults with and without DM, and its associated factors in DM participants. Methods: A 2-year prospective analysis was conducted in a European multicenter prospective cohort (SCOPE study). Older community-dwelling adults (aged ≥ 75 years) underwent a comprehensive geriatric assessment. New functional and/or cognitive decline was explored. Results: Of 1611 participants, 335 (22.0%) had DM at baseline. The percentage of participants scoring at least one ADL impairment and/or cognitive impairment (MMSE < 24) was similar in both groups (9.6%). Factors associated with any new disability in participants with DM in the multivariate analysis were female sex (OR 3.28, 95% CI 1.42–7.56), history of stroke (OR 4.58, 95% CI 1.64–12.7), and greater IADL dependency (OR 1.08 95% CI 1.02–1.15). Discussion: Association between DM and cognitive or functional decline in outpatients of 75 years and older was not found, but factors such as female gender, history of stroke, and IADL dependency could be related. Conclusion: Decline in functional and cognitive status of community-dwelling older adults with DM was similar to participants without DM in a short period of 2 years of follow-up, though several clinical factors may increase its risk in this population. [ABSTRACT FROM AUTHOR]

Healthcare-acquired infections (HCAI) represent a major health problem worldwide. Stroke and dementia are considered risk factors for HCAI. Preliminary data suggest that use of antipsychotic drugs also increase the risk for HCAI. Here, we performed a retrospective study aimed at investigating the major risk and protective factors for HCAI in a cohort of elderly subjects hospitalized at an Italian tertiary Neurology Clinics. We included all patients with age ≥ 65 years hospitalized at Neurology Clinics of National Institute on Ageing, Ancona, Italy from 1st January 2018 to 31st December 2021. For each patient, the following data were collected: age, sex, use of medical devices, comorbidities, use of antipsychotic medications, development of HCAI. We included 1543 patients (41.4% males; median age 85 years [80–89]). According to multivariable analysis, age, stroke, duration of urinary catheter placement (for all p < 0.001) and midline placement (p = 0.035) resulted to be risk factors for HCAI, Diabetes resulted to be a protective factor for pneumonia (p = 0.041), while dementia and nasogastric tube were risks factor for this condition (p = 0.022 and p < 0.001, respectively). Urinary catheter was a risk factor for urinary tract infections (p < 0.001). Duration of placement of vascular catheters and use of antipsychotic drugs resulted to significantly increase the risk for bloodstream infections. Stroke, age and use of medical devices were confirmed to be risk factors for HCAI. Antipsychotic drugs resulted to increase risk for bloodstream infections. Further prospective studies will be needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Frailty is an age-related condition characterized by a multisystem functional decline, increased vulnerability to stressors, and adverse health outcomes. Quantifying the degree of frailty in humans and animals is a health measure useful for translational geroscience research. Two frailty measurements, namely the frailty phenotype (FP) and the clinical frailty index (CFI), have been validated in mice and are frequently applied in preclinical research. However, these two tools are based on different concepts and do not necessarily identify the same mice as frail. In particular, the FP is based on a dichotomous classification that suffers from high sample size requirements and misclassification problems. Based on the monthly longitudinal non-invasive assessment of frailty in a large cohort of mice, here we develop an alternative scoring method, which we called physical function score (PFS), proposed as a continuous variable that resumes into a unique function, the five criteria included in the FP. This score would not only reduce misclassification of frailty but it also makes the two tools, PFS and CFI, integrable to provide an overall measurement of health, named vitality score (VS) in aging mice. VS displays a higher association with mortality than PFS or CFI and correlates with biomarkers related to the accumulation of senescent cells and the epigenetic clock. This longitudinal non-invasive assessment strategy and the VS may help to overcome the different sensitivity in frailty identification, reduce the sample size in longitudinal experiments, and establish the effectiveness of therapeutic/preventive interventions for frailty or other age-related diseases in geriatric animals. [ABSTRACT FROM AUTHOR]

We study the short- and long-run effects of having a child on labour market outcomes of mothers compared to non-mothers. Using matched employer-employee data for Italy over 1985–2018, through an event study methodology around childbirth, we show that the long-run child penalty in annual earnings is 52 log points and the penalty largely depends on the reduction in weeks worked by mothers. We then investigate sorting of women with and without children across different types of firms, providing evidence that mothers work in firms with lower productivity, sales, capital and wages after childbirth. Differences in rent-sharing between mothers and non-mothers explain 11.3% of the long-run child penalty in weekly wages, mostly due to between-firm components. Finally, we explore the individual-level, firm-level, and cultural factors that influence the size of child penalties. We find that the child penalty is higher for young, low-wage mothers and those taking longer leaves. It is larger in small firms with less generous pay and worse peers, and in more gender-conservative regions. [ABSTRACT FROM AUTHOR]

Older patients are at high risk of infections, which often present atypically and are associated with high morbidity and mortality. Antimicrobial treatment in older individuals with infectious diseases represents a clinical challenge, causing an increasing burden on worldwide healthcare systems; immunosenescence and the coexistence of multiple comorbidities determine complex polypharmacy regimens with an increase in drug–drug interactions and spread of multidrug-resistance infections. Aging-induced pharmacokinetic and pharmacodynamic changes can additionally increase the risk of inappropriate drug dosing, with underexposure that is associated with antimicrobial resistance and overexposure that may lead to adverse effects and poor adherence because of low tolerability. These issues need to be considered when starting antimicrobial prescriptions. National and international efforts have been made towards the implementation of antimicrobial stewardship (AMS) interventions to help clinicians improve the appropriateness and safety of antimicrobial prescriptions in both acute and long-term care settings. AMS programs were shown to decrease consumption of antimicrobials and to improve safety in hospitalized patients and older nursing home residents. With the abundance of antimicrobial prescriptions and the recent emergence of multidrug resistant pathogens, an in-depth review of antimicrobial prescriptions in geriatric clinical practice is needed. This review will discuss the special considerations for older individuals needing antimicrobials, including risk factors that shape risk profiles in geriatric populations as well as an evidence-based description of antimicrobial-induced adverse events in this patient population. It will highlight agents of concern for this age group and discuss interventions to mitigate the effects of inappropriate antimicrobial prescribing. [ABSTRACT FROM AUTHOR]

Methyl-CpG binding protein 2 (MeCP2) is a ubiquitous transcriptional regulator. The study of this protein has been mainly focused on the central nervous system because alterations of its expression are associated with neurological disorders such as Rett syndrome. However, young patients with Rett syndrome also suffer from osteoporosis, suggesting a role of MeCP2 in the differentiation of human bone marrow mesenchymal stromal cells (hBMSCs), the precursors of osteoblasts and adipocytes. Here, we report an in vitro downregulation of MeCP2 in hBMSCs undergoing adipogenic differentiation (AD) and in adipocytes of human and rat bone marrow tissue samples. This modulation does not depend on MeCP2 DNA methylation nor on mRNA levels but on differentially expressed miRNAs during AD. MiRNA profiling revealed that miR-422a and miR-483-5p are upregulated in hBMSC-derived adipocytes compared to their precursors. MiR-483-5p, but not miR-422a, is also up-regulated in hBMSC-derived osteoblasts, suggesting a specific role of the latter in the adipogenic process. Experimental modulation of intracellular levels of miR-422a and miR-483-5p affected MeCP2 expression through direct interaction with its 3′ UTR elements, and the adipogenic process. Accordingly, the knockdown of MeCP2 in hBMSCs through MeCP2-targeting shRNA lentiviral vectors increased the levels of adipogenesis-related genes. Finally, since adipocytes released a higher amount of miR-422a in culture medium compared to hBMSCs we analyzed the levels of circulating miR-422a in patients with osteoporosis—a condition characterized by increased marrow adiposity—demonstrating that its levels are negatively correlated with T- and Z-scores. Overall, our findings suggest that miR-422a has a role in hBMSC adipogenesis by downregulating MeCP2 and its circulating levels are associated with bone mass loss in primary osteoporosis. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder characterized by motor and non-motor disturbances as a result of a complex and not fully understood pathogenesis, probably including neuroinflammation, oxidative stress, and formation of alpha-synuclein (α-syn) aggregates. As age is the main risk factor for several neurodegenerative disorders including PD, progressive aging of the immune system leading to inflammaging and immunosenescence may contribute to neuroinflammation leading to PD onset and progression; abnormal α-syn aggregation in the context of immune dysfunction may favor activation of nucleotide-binding oligomerization domain-like receptor (NOD) family pyrin domain containing 3 (NLRP3) inflammasome within microglial cells through interaction with toll-like receptors (TLRs). This process would further lead to activation of Caspase (Cas)-1, and increased production of pro-inflammatory cytokines (PC), with subsequent impairment of mitochondria and damage to dopaminergic neurons. All these phenomena are mediated by the translocation of nuclear factor kappa-B (NF-κB) and enhanced by reactive oxygen species (ROS). To date, drugs to treat PD are mainly aimed at relieving clinical symptoms and there are no disease-modifying options to reverse or stop disease progression. This review outlines the role of the TLR/NLRP3/Cas-1 pathway in PD-related immune dysfunction, also focusing on specific therapeutic options that might be used since the early stages of the disease to counteract neuroinflammation and immune dysfunction. [ABSTRACT FROM AUTHOR]

On the other hand, Hermansson et al. reported that plasma NfL did not correlate with serum creatinine among patients infected with HIV with a mean age of 40 years, suggesting that the relationship between blood NfL and renal function becomes more evident among older adults [[5]]. Here, we assessed admission levels of serum NfL (sNfL) in geriatric patients with COVID-19 with the aim to evaluate the ability of circulating NfL to improve COVID-19 mortality prediction alone and/or in association with other demographic, biochemical, and molecular circulating biomarkers. The minimum number of days for which patients in the recovered group remained hospitalized was one day, while the maximum hospital stay was 53 days for survived patients and 56 days for deceased patients. In conclusion, serum NfL could be associated with severe outcomes in geriatric patients affected by COVID-19, even if caution should be used when interpreting these findings in patients with impaired renal function. [Extracted from the article]

We investigate the short-term effects of COVID-19 on labor market flows and how they are mediated by labor market policy. Using Italian administrative data on a sample of active contracts between 2009 and the second quarter of 2020, we show that, before the pandemic, a higher share of female compared to male, young compared to old and low educated compared to high educated workers is employed in non-essential activities. When we look at the change in hirings and separations, from the 9th week of 2020 - the time when first cases and deaths due to COVID-19 were recorded -, we find a pronounced drop in hirings and endings of fixed-term contracts. Layoffs and quits increase after the 9th week, and then decline significantly, reflecting the effects of government intervention. The lifting of the lockdown triggers a slow recovery of labor market flows. Young workers, those on temporary contracts, low-educated workers, those employed in the South and those with no opportunities of working from home experience a greater decline in separation probability, indicating that government policy partly protected them from the labor market impact of the recession. The decline in the separation probability for women is lower than that for men. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess respiratory function at the time of clinical recovery, 6 weeks, 6 months, and 12 months after discharge in patients surviving to COVID-19 pneumonia. Methods: Our case series consisted of 13 hospitalized patients with COVID-19 pneumonia. Results: Baseline pulmonary function tests were 55.7 ± 15.6 for FEV1%, 68.6 ± 16.0 for FVC%, and 1.2 ± 0.1 for FEV1/FVC%. Although pulmonary function showed a small improvement after 6 weeks, patients experienced a more significant improvement after 6 and 12 months in FEV1% (95.4 ± 13.7 and 107.2 ± 16.5, respectively; p < 0.001), FVC% (91.3 ± 14.5, and 105.9 ± 15.6, respectively; p < 0.001), and FEV1/FVC% values (1.04 ± 0.04, and 1.01 ± 0.05, respectively; p < 0.001). Conclusion: COVID-19 pneumonia may result in significant alterations in lung function, with a mainly restrictive pattern, partly persisting at 6 weeks after recovery from acute phase, but significantly improving during a 12-month follow-up period. [ABSTRACT FROM AUTHOR]

The aim of the present study was to describe foveal eversion patterns in diabetic macular edema (DME) and to assess their relationship with the course of the disease and the outcome. The study was designed as prospective, observational, with two years of follow-up. DME patients were divided in two groups, one treated by combined anti-VEGF injections and dexamethasone (DEX) implants, and the other treated by fluocinolone acetonide (FAc) implant with additional anti-VEGF retreatments if needed. Main outcome measures were foveal eversion prevalence, foveal eversion patterns, best-corrected visual acuity (BCVA), central macular thickness (CMT), structural OCT metrics, number of intravitreal injections. One hundred and forty-six eyes (146 patients; 80 males; mean age 67 ± 8 years) affected by already treated DME, with 84 eyes treated with anti-VEGF/DEX treatments (mean of 10 ± 3 injections) and 62 treated with FAc implant. Looking at the treatments administered before the inclusion into the study, 84 eyes (58%) were treated with anti-VEGF injections, whereas 62 eyes (42%) underwent a combination of anti-VEGF and corticosteroids implants. DME eyes showed statistically significant improvements of LogMAR BCVA and CMT over the 2-year follow-up. Foveal eversion was found in 83 eyes (57%), categorized as follows: Pattern 1a (16;19%); Pattern 1b (22;27%) and Pattern 2 (45;54%). BCVA improvement was detected in all the subgroups, excepting for Pattern 2, which showed also significantly worse structural OCT parameters. Pattern 1b and Pattern 2 were characterized by significantly higher prevalence of persistent DME (64% and 89% of cases, respectively). Foveal eversion patterns were correlated with progressively worse DME outcome. Foveal eversion may be associated to the loss of foveal homeostasis, with consequent poor response to intravitreal treatments and worse DME outcome. [ABSTRACT FROM AUTHOR]

Sexual selection is considered the primary driver of morph turnover in many color polymorphic taxa, yet the potential for other factors (like climate) to contribute to polymorphism maintenance and evolution remains unclear. Appreciation for a role of environmental conditions in the maintenance and evolution of color polymorphisms has grown in recent years, generating evidence suggesting that color morphs linked to sexual selection may also diverge in climate sensitivity. Focusing on the three color components contributing to the male tree lizard (Urosaurus ornatus) color morphs, I reveal a marked concordance between patterns of turnover over space and time, with a general affinity of orange- and yellow-colored males to hotter, more variable conditions, and blue colored males to wetter, cooler conditions. An assessment of long-term turnover in the blue color component in response to recent climate change over the past 60 years reinforces these findings. Overall, behavioral asymmetries attributed to sexual selection likely expose competing morphs to divergent environmental conditions in heterogeneous habitats, creating opportunity for natural selection to shape climate sensitivities that also drive turnover in morph color composition. Ultimately, these processes may favor stark asymmetries in morph persistence over the coming decades. [ABSTRACT FROM AUTHOR]

The relaxation time limit from the quantum Navier–Stokes–Poisson system to the quantum drift–diffusion equation is performed in the framework of finite energy weak solutions. No assumptions on the limiting solution are made. The proof exploits the suitably scaled a priori bounds inferred by the energy and BD entropy estimates. Moreover, it is shown how from those estimates the Fisher entropy and free energy estimates associated to the diffusive evolution are recovered in the limit. As a byproduct, our main result also provides an alternative proof for the existence of finite energy weak solutions to the quantum drift–diffusion equation. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a common condition in older people and represents a global health issue since it increases the risk of associated comorbidities and all-cause mortality. Furthermore, older people with reduced renal function might be at higher risk for developing functional limitation and disability. Moreover, the current creatinine-based measures of renal function are influenced by several factors in older population. The aims of the CKD-3D project are to perform an observational study to expand the knowledge about CKD-disability relationship and to investigate the use of novel biomarkers of kidney function. Methods: An observational, multicenter, prospective cohort study will be conducted in 75 + old patients consecutively admitted to acute care wards of geriatric medicine at participating hospitals. The study planned to enroll 440 patients undergoing clinical and laboratory evaluations at baseline and after 12 months. Face-to-face follow-up at 6 months and telephone follow-up at 3 and 9 months will be carried out. Comprehensive Geriatric Assessment (CGA) and the measurement of Cystatin C, Beta-Trace Protein and Beta2-Microglobulin levels will be included. Discussion: This study will provide useful information to prevent CKD-related disability by collecting real-life data over 1-year period. The combined approach of CGA and the investigation of innovative existing biomarkers will make it possible to develop new recommendations and guidelines for a patient-centered approach. It is believed that such a study may lead to an improvement of knowledge on CKD in elderly patients and may also have implications in daily clinical practice and in decision-making process. [ABSTRACT FROM AUTHOR]

The R2TP chaperone cooperates with HSP90 to integrate newly synthesized proteins into multi-subunit complexes, yet its role in tissue homeostasis is unknown. Here, we generated conditional, inducible knock-out mice for Rpap3 to inactivate this core component of R2TP in the intestinal epithelium. In adult mice, Rpap3 invalidation caused destruction of the small intestinal epithelium and death within 10 days. Levels of R2TP substrates decreased, with strong effects on mTOR, ATM and ATR. Proliferative stem cells and progenitors deficient for Rpap3 failed to import RNA polymerase II into the nucleus and they induced p53, cell cycle arrest and apoptosis. Post-mitotic, differentiated cells did not display these alterations, suggesting that R2TP clients are preferentially built in actively proliferating cells. In addition, high RPAP3 levels in colorectal tumors from patients correlate with bad prognosis. Here, we show that, in the intestine, the R2TP chaperone plays essential roles in normal and tumoral proliferation. RPAP3 is a subunit of the R2TP complex, a co-chaperone of HSP90, with substrate proteins involved in transcription, ribosome biogenesis, DNA repair and cell growth. Here the authors report that deletion of Rpap3 abrogates cell proliferation and homeostasis in mouse intestine, partly through destabilization of PI3K-like kinases, while elevated RPAP3 levels in colorectal tumors are associated with poor prognosis. [ABSTRACT FROM AUTHOR]

Executive abilities are frequently impaired in patients with chronic obstructive pulmonary disease (COPD). We aimed at investigating the association between trail making test (TMT) and survival. Our series consisted of 68 stable COPD outpatients followed-up every 6 months for 52.6 ± 27.6 months. Enrolled patients underwent a baseline comprehensive neuropsychological assessment, including mini-mental state exam, attentional matrices, digit span, Rey auditory verbal learning, Rey–Osterrieth complex figure, copy drawing, tokens test, verbal fluency, category fluency, frontal assessment battery, Raven's progressive matrices, TMT-A, -B and -B-A. The association between neuropsychological deficits and overall mortality was investigated by Cox regression. During follow-up period, 41 patients (60.3%) died. After adjusting for potential confounders, TMT-B was significantly associated with mortality (HR = 2.42, 95% CI = 1.10–5.31), along with age (HR = 1.06, 95% CI = 1.0–1.13), overall comorbidity (HR = 1.29, 95% CI = 1.02–1.62) and use of noninvasive ventilation (HR = 2.16, 95% CI = 1.05–4.45). Defective TMT-B may be associated with long-term mortality in patients with stable COPD. [ABSTRACT FROM AUTHOR]

Objectives: Frailty is a major health issue as it encompasses functional decline, physical dependence, and increased mortality risk. Recent studies explored Information and Communication Technology (ICT) interventions as alternatives to manage frailty in older persons. The aim of the present systematic review was to synthesize current evidence on ICT application within the complex models of frailty care in older people. Methods: Data sources included PubMed, PsycINFO, EMBASE and Web of Science, considering eligible those reviews on ICT application in samples of older persons formally assessed as frail. Records were screened by two independent researchers, who extracted data and appraised methodological quality of reviews and studies. Results: Among the 764 retrieved papers, two systematic reviews were included. Most of the studies analyzed defined frailty considering only few components of the phenotype and used ICT to stratify different levels of frailty or to support traditional screening strategies. Assessment of frailty was the context in which ICT has been mostly tested as compared to intervention. Cost effectiveness evaluations of the ICT technologies were not reported. Conclusions: The research investigating the use of ICT in the context of frailty is still at the very beginning. Few studies strictly focused on the assessment of frailty, while intervention on frailty using ICT was rarely reported. The lack of a proper characterization of the frail condition along with the methodological limitations prevented the investigation of ICT within complex care models. Future studies are needed to effectively integrate ICT in the care of frailty in orders. [ABSTRACT FROM AUTHOR]

Key summary points: Aim: Aim To provide an updated overview of studies on under-prescription in older subjects, describing its prevalence, causes, consequences as well as potential interventions to reduce it. Findings: Findings Under-prescription is common in older patients and associated with negative clinical outcomes, such as higher risk of cardiovascular events, worsening disability, hospitalization and death. Promising interventions to correct it include the implementation of explicit under-prescription criteria, the use of comprehensive geriatric assessment by geriatricians, and the involvement of a clinical pharmacist. Message: Message Further studies should be performed to provide a better understanding of under-prescription and to confirm the efficacy of corrective interventions. Purpose: Under-prescription is defined as the omission of a medication that is indicated for the treatment of a condition or a disease, without any valid reason for not prescribing it. The aim of this review is to provide an updated overview of under-prescription, summarizing the available evidence concerning its prevalence, causes, consequences and potential interventions to reduce it. Methods: A PubMed search was performed, using the following keywords: under-prescription; under-treatment; prescribing omission; older adults; polypharmacy; cardiovascular drugs; osteoporosis; anticoagulant. The list of articles was evaluated by two authors who selected the most relevant of them. The reference lists of retrieved articles were screened for additional pertinent studies. Results: Although several pharmacological therapies are safe and effective in older patients, under-prescription remains widespread in the older population, with a prevalence ranging from 22 to 70%. Several drugs are underused, including cardiovascular, oral anticoagulant and anti-osteoporotic drugs. Many factors are associated with under-prescription, e.g. multi-morbidity, polypharmacy, dementia, frailty, risk of adverse drug events, absence of specific clinical trials in older patients and economic factors. Under-prescription is associated with negative consequences, such as higher risk of cardiovascular events, worsening disability, hospitalization and death. The implementation of explicit criteria for under-prescription, the use of the comprehensive geriatric assessment by geriatricians, and the involvement of a clinical pharmacist seem to be promising options to reduce under-prescription. Conclusion: Under-prescription remains widespread in the older population. Further studies should be performed, to provide a better comprehension of this phenomenon and to confirm the efficacy of corrective interventions. [ABSTRACT FROM AUTHOR]

The goal of this paper is to accurately describe the metastable dynamics of the solutions to the hyperbolic relaxation of the Cahn–Hilliard equation in a bounded interval of the real line, subject to homogeneous Neumann boundary conditions. We prove the existence of an approximately invariant manifold M 0 for such boundary value problem, that is we construct a narrow channel containing M 0 and satisfying the following property: a solution starting from the channel evolves very slowly and leaves the channel only after an exponentially long time. Moreover, in the channel the solution has a transition layer structure and we derive a system of ODEs, which accurately describes the slow dynamics of the layers. A comparison with the layer dynamics of the classic Cahn–Hilliard equation is also performed. [ABSTRACT FROM AUTHOR]

Background: Older adults are a complex population, at risk of adverse events during and after hospital stay. Aim: To investigate the association of walking speed (WS) and grip strength (GS) with adverse outcomes, during and after hospitalization, among older individuals admitted to acute care wards. Methods: Multicentre observational study including 1123 adults aged ≥ 65 years admitted to acute wards in Italy. WS and GS were measured at admission and discharge. Outcomes were length-of-stay, in-hospital mortality, 1-year mortality and rehospitalisation. Length-of-stay was defined as a number of days from admission to discharge/death. Results: Mean age was 81 ± 7 years, 56% were women. Compared to patients with WS ≥ 0.8 m/sec, those unable to perform or with WS < 0.8 m/sec had a higher likelihood of longer length-of-stay (OR 2.57; 95% CI 1.63–4.03 and 2.42; 95% CI 1.55–3.79) and 1-year mortality and rehospitalization (OR 1.47, 95% CI 1.07–2.01; OR 1.57, 95% CI 1.04–2.37); those unable to perform WS had a higher likelihood of in-hospital mortality (OR 9.59; 95% CI 1.23–14.57) and 1-year mortality (OR 2.60; 95% CI 1.37–4.93). Compared to good GS performers, those unable to perform had a higher likelihood of in-hospital mortality (OR 17.43; 95% CI 3.87–28.46), 1-year mortality (OR 3.14; 95% CI 1.37–4.93) and combination of 1-year mortality and rehospitalisation (OR 1.46; 95% CI 1.01–2.12); poor GS performers had a higher likelihood of 1-year mortality (OR 1.39; 95% CI 1.03–2.35); participants unable to perform GS had a lower likelihood of rehospitalisation (OR 0.59; 95% CI 0.39–0.89). Conclusion: Walking speed (WS) and grip strength (GS) are easy-to-assess predictors of length-of-stay, in-hospital and post-discharge death and should be incorporated in the standard assessment of hospitalized patients. [ABSTRACT FROM AUTHOR]

Purpose: The aim of our study was to assess respiratory function at the time of clinical recovery and 6 weeks after discharge in patients surviving to COVID-19 pneumonia. Methods: Our case series consisted of 13 patients with COVID-19 pneumonia. Results: At the time of clinical recovery, FEV1 (2.07 ± 0.72 L) and FVC (2.25 ± 0.86 L) were lower compared to lower limit of normality (LLN) values (2.56 ± 0.53 L, p = 0.004, and 3.31 ± 0.65 L, p < 0.001, respectively), while FEV1/FVC (0.94 ± 0.07) was higher compared to upper limit of normality (ULN) values (0.89 ± 0.01, p = 0.029). After 6 weeks pulmonary function improved but FVC was still lower than ULN (2.87 ± 0.81, p = 0.014). Conclusion: These findings suggest that COVID-19 pneumonia may result in clinically relevant alterations in pulmonary function tests, with a mainly restrictive pattern. [ABSTRACT FROM AUTHOR]

Besides its metabolic and endocrine effects, growth hormone (GH)-releasing hormone (GHRH) is involved in the modulation of inflammation. Recently synthetized GHRH antagonist MIA-690 and MR-409, GHRH agonist, developed by us have shown potent pharmacological effects in various experimental paradigms. However, whether their administration modify resistance to chronic inflammatory stimuli in colon is still unknown. Ex vivo results demonstrated that MIA-690 and MR-409 inhibited production of pro-inflammatory and oxidative markers induced by lipopolysaccharide on isolated mouse colon specimens. In vivo, both MIA-690 and MR-409 have also been able to decrease the responsiveness to nociceptive stimulus, in hot plate test. Additionally, both peptides also induced a decreased sensitivity to acute and persistent inflammatory stimuli in male mice, in formalin test and dextran sodium sulfate (DSS)-induced colitis model, respectively. MIA-690 and MR-409 attenuate DSS-induced colitis with particular regard to clinical manifestations, histopathological damage and release of pro-inflammatory and oxidative markers in colon specimens. Respect to MR-409, MIA-690 showed higher efficacy in inhibiting prostaglandin (PG)E2, 8-iso-PGF2α and serotonin (5-HT) levels, as well as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and nitric oxide synthase gene expression in colon specimens of DSS-induced colitis. Furthermore, MIA-690 decreased serum insulin-like growth factor (IGF)-1 levels in mice DSS-treated, respect to MR-409. Thus, our findings highlight the protective effects of MIA-690 and MR-409 on inflammation stimuli. The higher antinflammatory and antioxidant activities observed with MIA-690 could be related to decreased serum IGF-1 levels. [ABSTRACT FROM AUTHOR]

Microvascular dysfunction has been associated with adverse outcomes in critically ill patients, and the current concept of hemodynamic incoherence has gained attention. Our objective was to perform a comprehensive analysis of microcirculatory perfusion parameters and to investigate the best variables that could discriminate patients with and without circulatory shock during early intensive care unit (ICU) admission. This prospective observational study comprised a sample of 40 adult patients with and without circulatory shock (n = 20, each) admitted to the ICU within 24 h. Peripheral clinical [capillary refill time (CRT), peripheral perfusion index (PPI), skin-temperature gradient (Tskin-diff)] and laboratory [arterial lactate and base excess (BE)] perfusion parameters, in addition to near-infrared spectroscopy (NIRS)-derived variables were simultaneously assessed. While lactate, BE, CRT, PPI and Tskin-diff did not differ significantly between the groups, shock patients had lower baseline tissue oxygen saturation (StO2) [81 (76-83) % vs. 86 (76-90) %, p = 0.044], lower StO2min [50 (47-57) % vs. 55 (53-65)  %, p = 0.038] and lower StO2max [87 (80-92) % vs. 93 (90-95) %, p = 0.017] than patients without shock. Additionally, dynamic NIRS variables [recovery time (r = 0.56, p = 0.010), descending slope (r = - 0.44, p = 0.05) and ascending slope (r = - 0.54, p = 0.014)] and not static variable [baseline StO2 (r = - 0.24, p = 0.28)] exhibited a significant correlation with the administered dose of norepinephrine. In our study with critically ill patients assessed within the first twenty-four hours of ICU admission, among the perfusion parameters, only NIRS-derived parameters could discriminate patients with and without shock. [ABSTRACT FROM AUTHOR]

Aims: To compare the long-term functional and anatomical outcomes of cataract surgery with combined versus 1-month deferred intravitreal dexamethasone implant (DEX) in eyes with pre-existing diabetic macular edema (DME). Methods: Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were retrospectively evaluated in both groups before treatments, then 1, 4, 12 and 24 months after DEX. Results: Forty eyes were analyzed, 20 in each group. BCVA disclosed comparable trends, increasing from similar starting values (p = 0.9913) to akin scores 1 month after DEX (p = 0.4229). After 4 months, it similarly reduced without significant variations within each group throughout the whole observation period. CRT was similar at the time of surgery (p = 0.6134) and was reduced by DEX injection in both samples, with a superior beneficial effect in the combined group after 1 month (p = 0.0010). At 4 months, CRT further elevated and remained overall stable in the long term without differences. By 12 months, 19 (95%) eyes received further injections: 1 (5%) fluocinolone, 3 (15%) received other DEX and fluocinolone, 13 (65%) ≥ 1 DEX only and 2 (10%) anti-VEGFs. During the second year, 6 additional eyes (from the 13 receiving DEX) switched to fluocinolone, reaching a total of 10 (50%). Similar results were observed in the deferred group. Conclusions: DEX implant performed at the time of surgery achieved the same long-term functional and anatomical outcomes compared to a 1-month injection deferral in treating eyes with pre-existing DME that should undergo cataract extraction. [ABSTRACT FROM AUTHOR]

Purpose: To compare nonmydriatic montage widefield images with dilated fundus ophthalmoscopy for determining diabetic retinopathy (DR) severity. Materials and methods: In this prospective, observational, cross-sectional study, patients with a previous diagnosis of diabetes and without history of diabetes-associated ocular disease were screened for DR. Montage widefield imaging was obtained with a system that combines confocal technology with white-light emitting diode (LED) illumination (DRSplus, Centervue, Padua, Italy). Dilated fundus examination was performed by a retina specialist. Results: Thirty-seven eyes (20 patients, 8 females) were finally included in the analysis. Mean age of the patients enrolled was 58.0 ± 11.6 years [range 31–80 years]. The level of DR identified on montage widefield images agreed exactly with indirect ophthalmoscopy in 97.3% (36) of eyes and was within 1 step in 100% (37) of eyes. Cohen's kappa coefficient (κ) was 0.96, this suggesting an almost perfect agreement between the two modalities in DR screening. Nonmydriatic montage widefield imaging acquisition time was significantly shorter than that of dilated clinical examination (p = 0.010). Conclusion: Nonmydriatic montage widefield images were compared favorably with dilated fundus examination in defining DR severity; however, they are acquired more rapidly. [ABSTRACT FROM AUTHOR]

Cystic echinococcosis (CE) is a disease of livestock and humans caused by the larval stage of the Echinococcus granulosus sensu lato (s.l.) species complex and occurs especially in areas where sheep breeding is widespread. This survey evaluates, after more than a decade since the last epidemiological survey, the current situation and trend of CE in sheep of the highly endemic island of Sardinia (Italy). From 2012 to 2018, out of a total of 1416 sheep, 65.3% were found positive for CE. Cyst fertility has increased slightly from 10.3% in 2006 (Scala et al. 2006) to 11.7% in the present survey (χ2 = 1.07; P = 0.30018) with a peak of 14.0% in the province of Sassari. Overall, 6815 hydatids were found and classified as sterile (26.2%), fertile (14.4%), caseous (5.3%), or calcified (54.1%) based on their morphology. All isolates were identified as E. granulosus sensu stricto (former G1/G3, strains). Results shown as the implementation of new European Council Regulations and in particular of 21/2004 that established a system for the individual identification and tracking of sheep could be a step forward towards a better control of animal movement, preventing illegal slaughtering on the island as well as in other countries experiencing similar problems. Even if at first sight the general situation of Sardinia regarding CE seems a little better compared with the past, our findings indicate that in some Provinces the epidemiological situation is not improved since 2006. [ABSTRACT FROM AUTHOR]

Background and Objective: The relationship between anticholinergic burden and mortality is unclear, and the impact of anticholinergic burden on prognosis may vary in the presence of other conditions common in old age. We aimed to investigate the role of hand grip strength as a potential effect modifier in the association between anticholinergic burden and 1-year mortality in older patients discharged from hospital. Methods: Our series consisted of 620 older patients consecutively admitted to seven geriatric and internal medicine acute care wards in the context of a prospective multicenter observational study. Overall anticholinergic burden was assessed by Anticholinergic Cognitive Burden (ACB) score. Hand grip strength was assessed by the use of a North Coast medical hand dynamometer and categorized by using sex-specific cut-offs (women < 15 kg, men < 20 kg). The study outcome was 1-year mortality. Statistical analysis was performed by Cox regression analysis. Results: After adjusting for potential confounders, the co-occurrence of an ACB score of 2 or more and low hand grip strength was significantly associated with mortality (hazard ratio [HR] = 2.30, 95% confidence interval [CI] 1.07–6.01). Stratified analysis confirmed that an ACB score of 2 or more was associated with mortality among patients with low (HR = 2.15, 95% CI 1.08–5.02), but not normal hand grip strength (HR = 0.88, 95% CI 0.13–3.52). The association was confirmed among patients with low hand grip strength after adjusting for the ACB score at the 3-month follow-up (HR = 2.20; 95% CI 1.09–4.87), as well as when considering the ACB score as a continuous variable (HR = 1.24, 95% CI 1.03–1.48). Conclusions: The ACB score at discharge may predict mortality among older patients discharged from an acute care hospital with low hand grip strength. Hospital physicians should be aware that prescribing anticholinergic medications in such a vulnerable population may have negative prognostic implications. [ABSTRACT FROM AUTHOR]

Background: The relationship between the estimated glomerular filtration rate (eGFR) and cognitive impairment may change as a function of the equation used. We aimed at investigating the association between four different eGFR equations and cognitive impairment among older hospitalized patients. Methods: Our series consisted of 795 older patients consecutively admitted to 7 geriatric and internal medicine acute care wards. The eGFR was calculated by Chronic Kidney Disease Epidemiologic Collaboration (CKD-EPI), Cockcroft-Gault (CG), Berlin Initiative Study (BIS) and Full Age Spectrum (FAS) equations. Study outcomes were total Mini Mental State Examination (MMSE) < 24 and sub-scores related to orientation to time, orientation to space, registration, calculation, three words recall, language and constructional praxis. Statistical analysis was carried out by logistic or Poisson regressions when appropriate. The accuracy of eGFR equations in identifying cognitive outcomes was investigated by calculating the area (AUC) under the receiver operating characteristic (ROC) curve for each equation. Results: After adjusting for potential confounders, eGFR < 30 was significantly associated with MMSE < 24 only with CKD-EPI equation (OR 2.03, 95% CI 1.04–3.96). eGFR < 30 was significantly associated with constructional apraxia with all study equations (CKD-EPI: OR 3.62, 95% CI 1.73–7.56; BIS: OR 2.86, 95% CI 1.31–6.26; FAS: OR 2.83, 95% CI 1.44–5.56; CG: OR 2.08, 95% CI 1.09–3.99). The accuracy of eGFR < 30 in identifying patients with defective constructional praxis was poor with all (BIS: AUC 0.54, 95% CI 0.52–0.55; CKD-EPI: AUC 0.55, 95% CI 0.53–0.57; CG: AUC 0.58, 95% CI 0.55–0.61; FAS: AUC 0.56, 95% CI 0.54–0.58). Conclusions: Constructional apraxia may characterize the cognitive profile of older patients with severe CKD. The accuracy in identifying patients with constructional apraxia is only fair, and studies including other biomarkers of kidney function are needed. [ABSTRACT FROM AUTHOR]

Background: Resuscitation of septic patients regarding goals, monitoring aspects and therapy is highly variable. Our aim was to characterize cardiovascular and fluid management of sepsis in Argentina, a low and middle-income country (LMIC). Furthermore, we sought to test whether the utilization of dynamic tests of fluid responsiveness, as a guide for fluid therapy after initial resuscitation in patients with persistent or recurrent hypoperfusion, was associated with decreased mortality. Methods: Secondary analysis of a national, multicenter prospective cohort study (n = 787) fulfilling Sepsis-3 definitions. Epidemiological characteristics, hemodynamic management data, type of fluids and vasopressors administered, physiological variables denoting hypoperfusion, use of tests of fluid responsiveness, and outcomes, were registered. Independent predictors of mortality were identified with logistic regression analysis. Results: Initially, 584 of 787 patients (74%) had mean arterial pressure (MAP) < 65 mm Hg and/or signs of hypoperfusion and received 30 mL/kg of fluids, mostly normal saline (53%) and Ringer lactate (35%). Vasopressors and/or inotropes were administered in 514 (65%) patients, mainly norepinephrine (100%) and dobutamine (9%); in 22%, vasopressors were administered before ending the fluid load. After this, 413 patients (53%) presented persisting or recurrent hypotension and/or hypoperfusion, which prompted administration of additional fluid, based on: lactate levels (66%), urine output (62%), heart rate (54%), central venous O2 saturation (39%), central venous–arterial PCO2 difference (38%), MAP (31%), dynamic tests of fluid responsiveness (30%), capillary-refill time (28%), mottling (26%), central venous pressure (24%), cardiac index (13%) and/or pulmonary wedge pressure (3%). Independent predictors of mortality were SOFA and Charlson scores, lactate, requirement of mechanical ventilation, and utilization of dynamic tests of fluid responsiveness. Conclusions: In this prospective observational study assessing the characteristics of resuscitation of septic patients in Argentina, a LMIC, the prevalent use of initial fluid bolus with normal saline and Ringer lactate and the use of norepinephrine as the most frequent vasopressor, reflect current worldwide practices. After initial resuscitation with 30 mL/kg of fluids and vasopressors, 413 patients developed persistent or recurrent hypoperfusion, which required further volume expansion. In this setting, the assessment of fluid responsiveness with dynamic tests to guide fluid resuscitation was independently associated with decreased mortality. [ABSTRACT FROM AUTHOR]

Chronic heart failure (CHF) is one of the main disabilities in elderly patients requiring frequent hospitalizations with high health care costs. We studied the outcome of CHF outpatient management in reducing hospitalization after discharge from a division of Internal Medicine at a large 3rd referral regional Hospital. 147 CHF inpatients (M:F: 63:84; mean age 76 ± 9.6 years) admitted for acute exacerbation of CHF were followed up as outpatients at 1, 6, 12 and 24 months after discharge. At baseline, patients underwent: laboratory tests, ECG, echocardiogram and a dedicated-intensive health care educational program involving also their families. The rate of hospitalization in the same group of patients was compared with data from the previous 24 months, a period when patients had been seen elsewhere without disease management programs. Patients had high prevalence of comorbidities and the majority was in NYHA class III or IV. Hypertension and valvular heart disease were the most common causes for CHF. Systolic function was preserved (LVEF ≥ 50%) in 61.9% of cases. Functional NYHA class improved significantly after 6 months and remained stable at 24 months. There was a significant increase in the use of the renin-angiotensin system blockers, beta-blockers and diuretics compared to admission to the ward. At 24 months, hospital readmissions were decreased by 42% as compared to the previous 24 months. Risk factors for re-hospitalizations were anemia, NYHA class III or IV and previous hospitalizations. Establishing an intensive outpatient management program for CHF patients leads to long-term beneficial effects with improved clinical parameters and decreased hospitalization in the setting of Internal Medicine. [ABSTRACT FROM AUTHOR]

A series of astronomical observations obtained over the period 1986 to 2018 supports the idea that life is a cosmic rather than a purely terrestrial or planetary phenomenon. These include (1) the detection of biologically relevant molecules in interstellar clouds and in comets, (2) mid-infrared spectra of interstellar grains and the dust from comets, (3) a diverse set of data from comets including the Rosetta mission showing consistency with biology and (4) the frequency of Earth-like or habitable planets in the Galaxy. We argue that the conjunction of all the available data suggests the operation of cometary biology and interstellar panspermia rather than the much weaker hypothesis of comets being only the source of the chemical building blocks of life. We conclude with specific predictions on the properties expected of extra-terrestrial life if it is discovered on Enceladus, Europa or beyond. A radically different biochemistry elsewhere can be considered as a falsification of the theory of interstellar panspermia. [ABSTRACT FROM AUTHOR]

Aims: Diabetic retinopathy remains asymptomatic until its late stages but remains a leading cause of vision impairment and blindness. We studied quality of life and the ability to deal with the discomfort deriving from the presence of a chronic disease in patients with type 1 diabetes and different stages of retinopathy. Methods: Multicenter collaborative observational study involving nine centers screening for retinopathy in different areas of Italy. The National Eye Institute 25-item visual functioning questionnaire and the locus of control tool were administered to 449 people with type 1 diabetes between February 2016 and March 2018. Socio-demographic and clinical data were collected. Results: On multivariable analysis, severe retinopathy is associated with worse scores for general vision, ocular pain, near vision activities, distance vision activities, driving, color vision, peripheral vision and lower values of internal control, independently of visual acuity. Women had a perception of worse general health, distance vision activities and driving, and lower internal control and trust in others. Worse scores for visual-specific social functioning, visual-specific mental health, visual-specific role difficulties, visual-specific dependency and peripheral vision were associated with higher HbA1c levels. Fatalism increased with rising HbA1c levels. Conclusions: These results confirm that a gap exists between patients' knowledge and expectations on retinopathy and providers' expertise and assumptions. To bridge this gap, patient-centered education and engaging approaches may be more effective than simple information given during consultations. [ABSTRACT FROM AUTHOR]

Various imaging modalities are of significant utility in the screening, grading, treatment, and follow-up of the different stages of diabetic retinopathy (DR) and diabetic macular edema. Color stereographic photography, fluorescein angiography, and optical coherence tomography (OCT) have been the gold standard for DR imaging for years. Besides these tools, newer technologies are gaining validation and popularity, such as fundus autofluorescence and OCT angiography. Furthermore, widefield retinography and ultra-widefield retinography have been introduced for a more comprehensive evaluation of the medium-far and very-far retinal peripheries, which is crucial for the assessment of the diverse manifestations of the disease. The aim of this review is to illustrate the recent advancements of the imaging systems for diagnosing DR, with a focus on the newest and noninvasive diagnostic tools. [ABSTRACT FROM AUTHOR]

Peptide Inhibitor of Complement C1 (PIC1) is a family of 15 amino acid peptides that inhibit complement activation via the classical and lectin pathways and inhibit myeloperoxidase. PIC1 peptides were originally derived from a region of limited homology with defensin human neutrophil peptide 1 (HNP-1). Despite having undergone extensive rearrangements of amino acid sequence subsequently, PIC1 peptides retain the defensin-like characteristics of being cysteine rich and amphiphilic. To date, defensin-like antimicrobial activity for PIC1 has not been explored. Here we report the antimicrobial activity of PIC1 for multiple pathogenic bacteria tested in minimum inhibitory concentration (MIC)-type assays. PIC1variant PA-dPEG24 was found to have antimicrobial activity against Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, Neisseria meningitidis, Neisseria gonorrhoeae, Gardnerella vaginalis, and Prevotella bivia. Confocal microscopy demonstrated PIC1 localized to the surface of P. aeruginosa and S. aureus consistent with the defensins. Testing PIC1 variants with amino acid substitutions revealed differences in complement inhibition and antimicrobial effects suggesting these occur via independent mechanisms. PIC1 inhibited P. aeruginosa growth in normal human serum suggesting the antimicrobial effect was dominant versus the survival benefit resulting from complement inhibition. In summary, these experiments demonstrate that PIC1 peptides have broad antimicrobial activity against pathogenic bacteria similar to defensins. [ABSTRACT FROM AUTHOR]

Objectives: To examine whether the introduction of an acoustic gunshot detection system (AGDS) allied to CCTV cameras increased the frequency of confirmed incidents of shots fired by bringing to notice gunfire events in public places that were not reported by the public.Methods: In a partially block-randomized experimental design, 17 acoustic sensors were co-located with CCTV cameras in a balanced design that matched the sensor camera sites with equivalent control locations. Gunshot-related incidents within 900 ft of both intervention and control sites for 8 months pre- and post-intervention were examined with multilevel negative binomial regression models.Results: After implementation of the AGDS, gunshot incidents increased by 259%; however, there was no significant increase in the number of confirmed shootings.Conclusions: The AGDS did not significantly affect the number of confirmed shootings, but it did increase the workload of police attending incidents for which no evidence of a shooting was found. While awaiting technological improvements and considering the operational goals, police departments may wish to reconsider the current operational plan and objective of an AGDS. [ABSTRACT FROM AUTHOR]

Purtscher syndrome consists in unilateral or bilateral retinopathy secondary to head or thorax traumas, characterized ophthalmoscopically by patches of retinal whitening and hemorrhages confined to the posterior pole and the peripapillary area [[1]]. Severe diabetic retinopathy (DR) has never been associated with this presentation; we present a case of new-onset DR with classic PLR features. 1 Multimodal imaging of a 59-year-old woman affected by diabetes mellitus and Purtscher-like diabetic retinopathy (DR). [Extracted from the article]

In the 2015 Ageing Report, the European Commission (EC) and the Economic Policy Committee stated that coping with the challenge posed by an ageing population will require determined policy action in Europe, particularly in reforming pension, health care and long-term care systems. The concern for this situation motivated the EC, the Parliament and many of the Member States (MS) to co-fund, in the 2015 call of the Third European Health Programme of the European Union 2014-2020, the first Joint Action (JA) on the prevention of frailty. ADVANTAGE JA brings together 33 partners from 22 MSs for 3 years. It aims to build a common understanding on frailty to be used in the MSs by policy makers and other stakeholders involved in the management, both at individual and population level, of older people who are frail or at risk for developing frailty throughout the European Union (EU). It is a formidable challenge but also a great opportunity for concerted action resulting in fostering effective and successful policies in frailty prevention and management in the participating MS. The Consortium has 2 years of hard work ahead to contribute to the needed change for frailty related disability free Europe. The first practical step towards this aim was the preparation of a document: the State of the Art on Frailty Report to support an overview of evidence of what works and what does not work on frailty prevention and management. Subsequently, this will be reflected in the advice that the JA will give to policy makers at MS level. Overall, these messages intend to be an instrument of added value to advocate for policy driven decisions on frailty prevention and management in the JA participating MSs and subsequently towards a frailty related disability free older population in Europe. The aim of this paper is to describe ADVANTAGE JA general structure, approach and recommendations towards a European health and social policy which will support frailty prevention in the participating MS. [ABSTRACT FROM AUTHOR]