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Cognitive and motor/physical functions may evolve at different speeds along the entire lifespan, and with different impact on aging processes, although running parallel along the same temporal continuum. The investigation of the shared association between cognitive and motor/physical functions has represented a challenging subject of debate in the last decades. However, the direction of this cognitive-motor link still needs to be furtherly clarified. A first approach suggests that pre-clinical cognitive decline, such as the MCI, may have a negative impact also on strength, walking speed and balance. Conversely, the presence of earlier motor dysfunction has been discussed as a potential predictor of further cognitive impairment, such in the Motoric Cognitive Risk syndrome, which is characterized by primary reduced gait speed in absence of cognitive deficits. Moreover, reduced handgrip strength has been discussed as a risk factor for the onset of further cognitive impairment. Recent studies have started to investigate the association between cognitive and motor/physical functions in a bidirectional way, suggesting instead both the predictive role of strength on the onset of further cognitive decline, as well as the predictive role of cognitive status on progressively higher risk to develop strength reduction. In conclusion, cognitive and motor/physical decline could often identify a common way, rather than parallel pathways. This integrated perspective should be addressed in the context of geriatric assessments, and it may also promote an increasingly multi-dimensional approach to frailty, together with a significant concern in the end of life stages such as disability and mortality.

The high worldwide prevalence of osteoporosis means it is considered a serious public health concern, possibly leading to physical disability and an increased mortality rate. Although osteoporosis is known as a silent disease affecting aging populations, its primary symptom remains pain. Acute pain is reported by patients with osteoporosis-related fractures, but chronic pain, mainly back pain, is also a characteristic of severe osteoporosis. Pain is associated not only with fractures but also with bodily changes in patients with osteoporosis that may include sensory, affective, and cognitive aspects. Chronic pain leads to progressive loss of independence and the need for long-term care, especially in the elderly. Pain prevention is linked to the appropriate treatment of osteoporosis, and pain management in patients with osteoporosis requires a multidimensional approach to preserve and improve quality of life. Our aim was to review and discuss the main causes of pain in patients with osteoporosis and suggest possible strategies for its management and prevention.

Adverse drug reactions (ADRs) are an important public health problem, representing a major cause of morbidity and mortality. However, several countries have no recent studies available. Since 2014, a prospective active pharmacovigilance project, aimed to improve ADRs monitoring in hospital wards (FORWARD) was performed in Sicily. This study, as part of FORWARD project, was aimed to describe ADRs occurred during the hospital stay in Internal Medicine wards. ADRs related to hospital admission, characteristics and preventability of ADRs were also evaluated. Demographic, clinical, and pharmacological data on patients admitted to six wards of Internal Medicine, from 2014 to 2015, were collected by trained, qualified monitors, who screened all medical records. The rate of ADRs occurred during hospital stay and those leading to hospitalization were analyzed. A descriptive analysis of the reactions, suspected drugs, and associated factors was performed according to the setting analyzed. During the study period, 4,802 admissions were recorded; in 3.2% of them ADRs occurred during hospital stay while in 6.2%, admission was due to ADRs. The duration of hospital stay was longer in patients who experienced ADRs during hospitalization, compared to patients without ADRs [median days 12 (Q1-Q3: 8-17) vs. 9 (6-13)]; < 0.001). Females [OR1.39 (95% CI 1.03-1.93)] and patients taking ≥ 4 drugs [OR1.46 (95% CI 1.06-2.03)] were more likely to experience ADRs during hospital stay, as well as to be admitted because of ADRs [female: OR1.75 (95% CI 1.37-2.24); ≥ 4 drugs: OR2.14 (95% CI 1.67-2.74)]. The most frequent ADRs occurred during hospital stay were (26.8%), (13.4%), (13.4%), and (11.5%) disorders and the drug classes mainly involved were anti-bacterials (38.2%) and antithrombotic agents (21.7%). ADRs were serious in 44.6% and probably preventable in 69.4%. (27.7%), (26.5%), (18.1%), and (16.1%) disorders were the main ADRs cause of hospitalization, primarily due to antithrombotic agents (39.0%) RAS-inhibitors (13.9%), NSAIDs (11.9%), and diuretics (9.0%). Only 12.9% of them was not preventable. Adverse drug reactions occurred during hospitalization or contributing to admission to Internal Medicine wards were considerable and most of them were preventable. Females and patients taking many medications were more likely to present ADRs both during hospital stay or as cause of admission.

Background Human pancreatic islets are a central focus of research in metabolic studies. Transcriptomics is frequently used to interrogate alterations in cultured human islet cells using single-cell RNA-sequencing (scRNA-seq). We introduce single-nucleus RNA-sequencing (snRNA-seq) as an alternative approach for investigating transplanted human islets. Methods The Nuclei EZ protocol was used to obtain nuclear preparations from fresh and frozen human islet cells. Such preparations were first used to generate snRNA-seq datasets and compared to scRNA-seq output obtained from cells from the same donor. Finally, we employed snRNA-seq to obtain the transcriptomic profile of archived human islets engrafted in immunodeficient animals. Results We observed virtually complete concordance in identifying cell types and gene proportions as well as a strong association of global and islet cell type gene signatures between scRNA-seq and snRNA-seq applied to fresh and frozen cultured or transplanted human islet samples. Conclusions We propose snRNA-seq as a reliable strategy to probe transcriptomic profiles of freshly harvested or frozen sources of transplanted human islet cells especially when scRNA-seq is not ideal.

Aims/hypothesisSodium–glucose cotransporter 2 (SGLT2) inhibitors, which prevent the renal reabsorption of glucose, decrease blood glucose levels in an insulin-independent manner. We previously reported creating a mouse model of systemic inhibition of target receptors for both insulin and IGF-1 by treating animals with OSI-906, a dual insulin/IGF-1 receptor inhibitor, for 7 days. The OSI-906-treated mice exhibited an increased beta cell mass, hepatic steatosis and adipose tissue atrophy, accompanied by hyperglycaemia and hyperinsulinaemia. In the present study, we investigated the effects of an SGLT2 inhibitor, luseogliflozin, on these changes in OSI-906-treated mice.MethodsWe treated C57BL/6J male mice either with vehicle, luseogliflozin, OSI-906 or OSI-906 plus luseogliflozin for 7 days, and phenotyping was performed to determine beta cell mass and proliferation. Subsequently, we tested whether serum-derived factors have an effect on beta cell proliferation in genetically engineered beta cells, mouse islets or human islets.ResultsSGLT2 inhibition with luseogliflozin significantly ameliorated hyperglycaemia, but not hyperinsulinaemia, in the OSI-906-treated mice. Liver steatosis and adipose tissue atrophy induced by OSI-906 were not altered by treatment with luseogliflozin. Beta cell mass and proliferation were further increased by SGLT2 inhibition with luseogliflozin in the OSI-906-treated mice. Luseogliflozin upregulated gene expression related to the forkhead box M1 (FoxM1)/polo-like kinase 1 (PLK1)/centromere protein A (CENP-A) pathway in the islets of OSI-906-treated mice. The increase in beta cell proliferation was recapitulated in a co-culture of Irs2 knockout and Insr/IR knockout (βIRKO) beta cells with serum from both luseogliflozin- and OSI-906-treated mice, but not after SGLT2 inhibition in beta cells. Circulating factors in both luseogliflozin- and OSI-906-treated mice promoted beta cell proliferation in both mouse islets and cadaveric human islets.Conclusions/interpretationThese results suggest that luseogliflozin can increase beta cell proliferation through the activation of the FoxM1/PLK1/CENP-A pathway via humoral factors that act in an insulin/IGF-1 receptor-independent manner.

With the introduction of more and more monoclonal antibodies selectively targeting various mediators of the immune system, together with Janus-Kinase (JAK)-inhibitors with variable affinities towards different JAK subtypes, the available therapeutic options for the treatment of inflammatory bowel diseases (IBD) have undergone an acceleration in the last five years. On the other hand, the prevalence of IBD patients over 65-years-old is steadily increasing, and, with this, there is a large population of patients that presents more comorbidities, polypharmacy, and, more frequently, frailty compared to younger patients, exposing them to potentially major risks for adverse events deriving from newer therapies, e.g., infections, cardiovascular risks, and malignancies. Unfortunately, pivotal trials for the commercialization of new therapies rarely include older IBD patients, and those with serious comorbidities are virtually excluded. In the present review, we focus on existing literature from pivotal trials and real-world studies, analyzing data on efficacy/effectiveness and safety of newer therapies in older IBD patients with special emphasis on comorbidities and frailty, two distinct but intercorrelated aspects of the older population since age by itself seems to be of minor importance.

Analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs), weak and strong opioids are commonly used among elderly persons. The aim of this study was to describe the demographic and clinical characteristics of elderly analgesic users and to measure the frequency of analgesic use, including the frequency of potentially inappropriate analgesic use. The Arianna database was used to carry out this study. This database contains prescription data with associated indication of use for 1,076,486 inhabitants registered with their general practitioners (GPs) in the Caserta Local Health Unit (Caserta district, Campania region in Italy). A cohort of persons aged ≥65 years old with >1 year of database history having at least one analgesic drug (NSAIDs, strong or weak opioids) between 2010 and 2014 were identified. The date of the first analgesic prescription in the study period was considered the index date (ID). From a source population of 1,076,486 persons, 116,486 elderly persons were identified. Of these, 94,820 elderly persons received at least one analgesic drug: 36.6% were incident NSAID users (N = 36,629), while 13.2% were incident weak opioid users (N = 12,485) and 8.1% were incident strong opioid users (N = 7,658). In terms of inappropriate analgesic use, 9.2% (N = 10,763) of all elderly users were prescribed ketorolac/indomethacin inappropriately, since these drugs should not be prescribed to elderly persons. Furthermore, at least half all elderly persons with chronic kidney disease or congestive heart failure were prescribed NSAIDs, while these drugs should be avoided. Analgesics are commonly used inappropriately among elderly persons, suggesting that prescribing practice in the catchment area may yet be improved.

Diabetes mellitus has been knowingly associated with increased risk of fractures, so much so that skeletal fragility is considered a complication of diabetes. Determinants of bone fragility in this chronic condition are several, and the diabetes treatment choice could influence bone metabolism. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have recently expanded the therapeutic armamentarium for type 2 diabetes mellitus (T2D); these antihyperglycemic drugs act by reducing renal glucose reabsorption in the proximal tubule and have a proven cardiorenal benefit. The role of SGLT2i towards phospho-calcium metabolism is still unclear, so we aimed to review the current evidence of the relationship between SGLT2i and calcium and phosphate homeostasis. The PubMed, Scopus, and Web of Knowledge databases were searched to identify original research articles, meta-analyses, and scientific reviews on effects on bone metabolism in T2D patients treated with SGLT2i. Emerging data indicate that SGLT2i may lead to a rise of bone turnover markers, promoting a lower skeletal bone density and an increased fracture risk on murine models, but in real-world studies, results are controversial. Therefore, more clinical trials are needed to further clarify this topic, and the effects of SGLT2i on calcium homeostasis remain to date poorly understood.

Background and Objectives: Peak Cough Flow (PCF) is an objective measure of cough effectiveness, traditionally used in patients with neuromuscular disorders. Sarcopenia may also impair respiratory muscles, but its relationship with cough efficacy in hospitalized patients with respiratory diseases is not well established. This study investigated the correlation between PCF and sarcopenia indicators and evaluated the influence of comorbidities, anthropometric variables, and body position on PCF. Methods: A cross-sectional observational study was performed. PCF was measured using a portable peak flow meter in seated and supine positions. Sarcopenia was assessed through handgrip strength and validated questionnaires. Comorbidity burden was quantified using the Charlson Comorbidity Index (CCI). Nutritional status and sleep apnea risk were evaluated with the Mini Nutritional Assessment–Short Form (MNA-SF) and STOP-BANG questionnaire. Correlation analyses and linear regression were performed. Results: 53 patients were enrolled (mean age 72.6 ± 15.2 years; 64% male). Men showed significantly higher PCF values than women in both seated (p < 0.001) and supine positions (p < 0.001). Sarcopenic patients exhibited reduced PCF compared to non-sarcopenic subjects (p = 0.037). Handgrip strength was strongly correlated with PCF in seated and supine positions (p < 0.0001). CCI was negatively correlated with PCF (seated r2 = 0.17, p = 0.0021; supine r2 = 0.16, p = 0.0027). No significant associations were observed with BMI, MNA-SF, or STOP-BANG. Postural change resulted in comparable PCF reduction in men and women (ΔPCF: 20 ± 37.9 vs. 17 ± 37.9 L/min). Conclusions: Sarcopenia and comorbidity burden are significantly associated with reduced cough efficacy. Handgrip strength is a strong predictor of PCF, supporting routine PCF assessment beyond neuromuscular populations.