An Integrated Approach to Skeletal Muscle Health in Aging

A decline in muscle mass and function represents one of the most problematic changes associated with aging, and has dramatic effects on autonomy and quality of life. Several factors contribute to the inexorable process of sarcopenia, such as mitochondrial and autophagy dysfunction, and the lack of regeneration capacity of satellite cells. The physiologic decline in muscle mass and in motoneuron functionality associated with aging is exacerbated by the sedentary lifestyle that accompanies elderly people. Regular physical activity is beneficial to most people, but the elderly need well-designed and carefully administered training programs that improve muscle mass and, consequently, both functional ability and quality of life. Aging also causes alteration in the gut microbiota composition associated with sarcopenia, and some advances in research have elucidated that interventions via the gut microbiota-muscle axis have the potential to ameliorate the sarcopenic phenotype. Several mechanisms are involved in vitamin D muscle atrophy protection, as demonstrated by the decreased muscular function related to vitamin D deficiency. Malnutrition, chronic inflammation, vitamin deficiencies, and an imbalance in the muscle-gut axis are just a few of the factors that can lead to sarcopenia. Supplementing the diet with antioxidants, polyunsaturated fatty acids, vitamins, probiotics, prebiotics, proteins, kefir, and short-chain fatty acids could be potential nutritional therapies against sarcopenia. Finally, a personalized integrated strategy to counteract sarcopenia and maintain the health of skeletal muscles is suggested in this review

LO STATO DI SALUTE DELLE POPOLAZIONI RESIDENTI NELLE AREE GEOTERMICHE DELLA TOSCANA

Introduzione. Nelle aree geotermiche le evidenze sui rischi per la salute delle esposizioni ambientali sono ancora limitate, anche a causa del ridotto numero di aree e di studi effettuati.In due aree della Toscana, una in provincia di Pisa (area Nord, AN) e una a cavallo tra le province di Siena eGrosseto (area Sud, AS) dal 1980 sono attivi 31 impianti per la produzione di energia elettrica mediante sfruttamento di fluidi geotermici. Le maggiori criticit? ambientali in queste aree sono dovute alle emissioni di acido solfidrico emercurio nell\u27aria, arsenico e boro nelle acque. Sui possibili rischi per l\u27ambiente e la salute ? da tempo attivo un acceso dibattito tra le parti interessate (ENEL, amministratori e comitati locali). Nel 2009 la Regione Toscana ha commissionato all\u27ARSToscana uno studio sullo stato di salute delle popolazioni residenti nelle aree geotermiche. Obiettivi. Valutare la distribuzione spazio-temporale di cause di mortalit? e di ospedalizzazione, per le quali esistono evidenze epidemiologiche di associazione con le criticit? ambientali presenti nell\u27area in studio. Metodi. L\u27AN formata da 8 Comuni ha circa 16 900 residenti e l\u27AS formata da 8 Comuni ha circa 26 500 residenti. Sono state analizzate cause selezionate di morte nel periodo 1980-2006 e cause di primo ricovero nel periodo 1998-2006. Sono stati valutati gli eccessi di eventi sanitari delle due aree e dei singoli Comuni rispetto a due riferimenti, il primo formato dai Comuni della RegioneToscana e il secondo formato da 98 Comuni della Toscana meridionale. Gli eccessi sono stati valutati con metodi statistici classici (rapporti di mortalit?/ospedalizzazione standardizzati per classi di et? [SMR/SHR] e aggiustati per l\u27indice di deprivazione socioeconomica di Caranci et al., 2010 [SMRID, SHRID]) e bayesiani [Besag et al., 1991]). Risultati. Di seguito sono presentati i risultati delle analisi di mortalit? 2000-2006 e dei ricoverati 2004-2006, sia a livello di area, sia a livello comunale, rispetto al riferimento della Toscana meridionale. In entrambe le aree sono risultati eccessi di mortalit? per pneumoconiosi nei maschi (AN: SMR=250, SMRID=351; AS: SMR=295, SMRID=388). Nella AN sono risultati eccessi di ricoverati per le leucemie nelle donne (SHR=268, SHRID=262) e per le malattie dell\u27apparato digerente in entrambi i sessi (SHR=113, SHRID=112). Nella AS sono risultati eccessi nei maschi di mortalit? generale (SMR=113, SMRID=115), per tutti i tumori (SMR, SMRID=120), per le malattie respiratorie (SMR=128, SMRID=132), per il tumore al polmone (SMR=148, SMRID=171) e al fegato (SMR=116, SMRID=121). Nelle donne sono risultati eccessi per le malattie respiratorie acute (SMR=140, SMRID=142) e dell\u27apparato digerente (SMR=132, SMRID=130). Eccessi di ricoverati in entrambi i sessi sono risultati per il tumore allo stomaco (maschi: SHR=152, SHRID=136; femmine: SHR=191, SHRID=161), per l\u27insufficienza renale (maschi: SMR=147, SHRID=150; femmine: SHR=143, SHRID=152) e per le malattie respiratorie (maschi: SHR=113, SHRID=116; femmine: SHR=113, SHRID=122). Le analisi a livello comunale hanno evidenziato alcuni Comuni con maggiori criticit? sanitarie (AN: Pomarance; AS: Abbadia S.S., Piancastagnaio, Arcidosso e Castel del Piano). Le analisi bayesiane hanno confermato la maggior parte degli eccessi evidenziati. Conclusioni.Dai risultati emerge che i maggiori determinanti del profilo di salute dell\u27area geotermica sono riconducibili a esposizioni occupazionali e/o a stili di vita individuali. Per alcune cause rilevate (respiratorie, digerente, urinarie, tumore allo stomaco) non ? da escludere il ruolo di esposizioni ambientali. I segnali emersi su alcune patologie sensibili agli inquinanti presenti nell\u27area di studio hanno suggerito la messa in opera di azioni di rafforzamento del sistema sanitario locale (screening, diagnosi precoce, vaccinazioni), il miglioramento dei sistemi di codifica delle malattie, l\u27attivazione di indagini epidemiologiche ad hoc.Introduzione. Nelle aree geotermiche le evidenze sui rischi per la salute delle esposizioni ambientali sono ancora limitate, anche a causa del ridotto numero di aree e di studi effettuati.In due aree della Toscana, una in provincia di Pisa (area Nord, AN) e una a cavallo tra le province di Siena eGrosseto (area Sud, AS) dal 1980 sono attivi 31 impianti per la produzione di energia elettrica mediante sfruttamento di fluidi geotermici. Le maggiori criticit? ambientali in queste aree sono dovute alle emissioni di acido solfidrico emercurio nell\u27aria, arsenico e boro nelle acque. Sui possibili rischi per l\u27ambiente e la salute ? da tempo attivo un acceso dibattito tra le parti interessate (ENEL, amministratori e comitati locali). Nel 2009 la Regione Toscana ha commissionato all\u27ARSToscana uno studio sullo stato di salute delle popolazioni residenti nelle aree geotermiche. Obiettivi. Valutare la distribuzione spazio-temporale di cause di mortalit? e di ospedalizzazione, per le quali esistono evidenze epidemiologiche di associazione con le criticit? ambientali presenti nell\u27area in studio. Metodi. L\u27AN formata da 8 Comuni ha circa 16 900 residenti e l\u27AS formata da 8 Comuni ha circa 26 500 residenti. Sono state analizzate cause selezionate di morte nel periodo 1980-2006 e cause di primo ricovero nel periodo 1998-2006. Sono stati valutati gli eccessi di eventi sanitari delle due aree e dei singoli Comuni rispetto a due riferimenti, il primo formato dai Comuni della RegioneToscana e il secondo formato da 98 Comuni della Toscana meridionale. Gli eccessi sono stati valutati con metodi statistici classici (rapporti di mortalit?/ospedalizzazione standardizzati per classi di et? [SMR/SHR] e aggiustati per l\u27indice di deprivazione socioeconomica di Caranci et al., 2010 [SMRID, SHRID]) e bayesiani [Besag et al., 1991]). Risultati. Di seguito sono presentati i risultati delle analisi di mortalit? 2000-2006 e dei ricoverati 2004-2006, sia a livello di area, sia a livello comunale, rispetto al riferimento della Toscana meridionale. In entrambe le aree sono risultati eccessi di mortalit? per pneumoconiosi nei maschi (AN: SMR=250, SMRID=351; AS: SMR=295, SMRID=388). Nella AN sono risultati eccessi di ricoverati per le leucemie nelle donne (SHR=268, SHRID=262) e per le malattie dell\u27apparato digerente in entrambi i sessi (SHR=113, SHRID=112). Nella AS sono risultati eccessi nei maschi di mortalit? generale (SMR=113, SMRID=115), per tutti i tumori (SMR, SMRID=120), per le malattie respiratorie (SMR=128, SMRID=132), per il tumore al polmone (SMR=148, SMRID=171) e al fegato (SMR=116, SMRID=121). Nelle donne sono risultati eccessi per le malattie respiratorie acute (SMR=140, SMRID=142) e dell\u27apparato digerente (SMR=132, SMRID=130). Eccessi di ricoverati in entrambi i sessi sono risultati per il tumore allo stomaco (maschi: SHR=152, SHRID=136; femmine: SHR=191, SHRID=161), per l\u27insufficienza renale (maschi: SMR=147, SHRID=150; femmine: SHR=143, SHRID=152) e per le malattie respiratorie (maschi: SHR=113, SHRID=116; femmine: SHR=113, SHRID=122). Le analisi a livello comunale hanno evidenziato alcuni Comuni con maggiori criticit? sanitarie (AN: Pomarance; AS: Abbadia S.S., Piancastagnaio, Arcidosso e Castel del Piano). Le analisi bayesiane hanno confermato la maggior parte degli eccessi evidenziati. Conclusioni.Dai risultati emerge che i maggiori determinanti del profilo di salute dell\u27area geotermica sono riconducibili a esposizioni occupazionali e/o a stili di vita individuali. Per alcune cause rilevate (respiratorie, digerente, urinarie, tumore allo stomaco) non ? da escludere il ruolo di esposizioni ambientali. I segnali emersi su alcune patologie sensibili agli inquinanti presenti nell\u27area di studio hanno suggerito la messa in opera di azioni di rafforzamento del sistema sanitario locale (screening, diagnosi precoce, vaccinazioni), il miglioramento dei sistemi di codifica delle malattie, l\u27attivazione di indagini epidemiologiche ad hoc

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction &gt;0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years