The interplay between sodium/glucose cotransporter type 2 and mitochondrial ionic environment.

Mitochondrial volume is maintained through the permeability of the inner mitochondrial membrane by a specific aquaporin and the osmotic balance between the mitochondrial matrix and cellular cytoplasm. Various electrolytes, such as calcium and hydrogen ions, potassium, and sodium, as well as other osmotic substances, affect the swelling of mitochondria. Intracellular glucose levels may also affect mitochondrial swelling, although the relationship between mitochondrial ion homeostasis and intracellular glucose is poorly understood. This article reviews what is currently known about how the Sodium-Glucose transporter (SGLT) may impact mitochondrial sodium (Na+) homeostasis. SGLTs regulate intracellular glucose and sodium levels and, therefore, interfere with mitochondrial ion homeostasis because mitochondrial Na+ is closely linked to cytoplasmic calcium and sodium dynamics. Recently, a large amount of data has been available on the effects of SGLT2 inhibitors on mitochondria in different cell types, including renal proximal tubule cells, endothelial cells, mesangial cells, podocytes, neuronal cells, and cardiac cells. The current evidence suggests that SGLT inhibitors (SGLTi) may affect mitochondrial dynamics regarding intracellular Sodium and hydrogen ions. Although the regulation of mitochondrial ion channels by SGLTs is still in its infancy, the evidence accumulated thus far of the effect of SGLTi on mitochondrial functions certainly will foster further research in this direction.

Anopheles sacharovi in Italy: first record of the historical malaria vector after over 50 years.

BACKGROUND: Anopheles sacharovi, a member of the Anopheles maculipennis complex, was a historical malaria vector in Italy, no longer found since the last report at the end of 1960s. In September 2022, within the Surveillance Project for the residual anophelism, a single specimen of An. maculipennis sensu lato collected in Lecce municipality (Apulia region) was molecularly identified as An. sacharovi. This record led to implement a targeted entomological survey in September 2023. METHODS: Investigation was conducted in the areas around the first discovery, focusing on animal farms, riding stables and potential breeding sites. Adult and immature mosquitoes were collected, using active search or traps, in several natural and rural sites. Mosquitoes belonging to An. maculipennis complex were identified morphologically and molecularly by a home-made routine quantitative polymerase chain reaction (qPCR) assay, developed specifically for the rapid identification of An. labranchiae, and, when necessary, by amplification and sequencing of the ITS-2 molecular marker. RESULTS: Out of the 11 sites investigated, 6 were positive for Anopheles presence. All 20 An. maculipennis s.l. (7 adults, 10 larvae and 3 pupae) collected in the areas were identified as An. sacharovi by ITS-2 sequencing. CONCLUSIONS: The discovery of An. sacharovi, considered to have disappeared from Italy for over 50 years, has a strong health relevance and impact, highlighting an increase in the receptivity of the southern areas. As imported malaria cases in European countries are reported every year, the risk of Plasmodium introduction by gametocyte carriers among travellers from endemic countries should be taken into greater consideration. Our findings allow rethinking and building new models for the prediction and expansion of introduced malaria. Furthermore, to prevent the risk of reintroduction of the disease, the need to strengthen the surveillance of residual anophelism throughout the South should be considered.

Ecological and social factors influence interspecific pathogens occurrence among bees.

The interspecific transmission of pathogens can occur frequently in the environment. Among wild bees, the main spillover cases are caused by pathogens associated with Apis mellifera, whose colonies can act as reservoirs. Due to the limited availability of data in Italy, it is challenging to accurately assess the impact and implications of this phenomenon on the wild bee populations. In this study, a total of 3372 bees were sampled from 11 Italian regions within the BeeNet project, evaluating the prevalence and the abundance of the major honey bee pathogens (DWV, BQCV, ABPV, CBPV, KBV, Nosema ceranae, Ascosphaera apis, Crithidia mellificae, Lotmaria passim, Crithidia bombi). The 68.4% of samples were positive for at least one pathogen. DWV, BQCV, N. ceranae and CBPV showed the highest prevalence and abundance values, confirming them as the most prevalent pathogens spread in the environment. For these pathogens, Andrena, Bombus, Eucera and Seladonia showed the highest mean prevalence and abundance values. Generally, time trends showed a prevalence and abundance decrease from April to July. In order to predict the risk of infection among wild bees, statistical models were developed. A low influence of apiary density on pathogen occurrence was observed, while meteorological conditions and agricultural management showed a greater impact on pathogen persistence in the environment. Social and biological traits of wild bees also contributed to defining a higher risk of infection for bivoltine, communal, mining and oligolectic bees. Out of all the samples tested, 40.5% were co-infected with two or more pathogens. In some cases, individuals were simultaneously infected with up to five different pathogens. It is essential to increase knowledge about the transmission of pathogens among wild bees to understand dynamics, impact and effects on pollinator populations. Implementing concrete plans for the conservation of wild bee species is important to ensure the health of wild and human-managed bees within a One-Health perspective.

Impact of coronary microvascular dysfunction in heart failure with preserved ejection fraction: a meta-analysis.

AIMS: Several mechanisms have been identified in the aetiopathogenesis of heart failure with preserved ejection fraction (HFpEF). Among these, coronary microvascular dysfunction (CMD) may play a key pathophysiological role. We performed a systematic review and meta-analysis to investigate the prevalence, echocardiographic correlates, and prognostic implications of CMD in patients with HFpEF. METHODS AND RESULTS: A systematic search for articles up to 1 May 2023 was performed. The primary aim was to assess the prevalence of CMD. Secondary aims were to compare key echocardiographic parameters (E/e' ratio, left atrial volume index [LAVi], and left ventricular mass index [LVMi]), clinical outcomes [death and hospitalization for heart failure (HF)], and prevalence of atrial fibrillation (AF) between patients with and without CMD. Meta-regressions according to baseline patient characteristics and study features were performed to explore potential heterogeneity sources. We identified 14 observational studies, enrolling 1138 patients with HFpEF. The overall prevalence of CMD was 58%. Compared with patients without CMD, patients with HFpEF and CMD had larger LAVi [mean difference (MD) 3.85 confidence interval (CI) 1.19-6.5, P < 0.01)], higher E/e' ratio (MD 2.76 CI 1.54-3.97; P < 0.01), higher prevalence of AF (odds ratio 1.61 CI 1.04-2.48, P = 0.03) and higher risk of death or hospitalization for HF [hazard ratio 3.19, CI 1.04-9.57, P = 0.04]. CONCLUSIONS: CMD is present in little more than half of the patients with HFpEF and is associated with echocardiographic evidence of more severe diastolic dysfunction and a higher prevalence of AF, doubling the risk of death or HF hospitalization.

A Narrative Review Exploring the Similarities between Cilento and the Already Defined "Blue Zones" in Terms of Environment, Nutrition, and Lifestyle: Can Cilento Be Considered an Undefined "Blue Zone"?

Longevity is rightly considered one of the greatest achievements of modern society, not only as a function of lifespan, but, more importantly, as a function of healthspan. There are Longevity Blue Zones (LBZs), regions around the world, such as in Okinawa, Japan; the Nicoya Peninsula, Costa Rica; Loma Linda, California; Icaria, Greece; and Ogliastra, Sardinia, that are characterized by a significant percentage of residents who live exceptionally long lives, often avoiding age-related disability to a significantly higher degree than in the Western way of life. Longevity is not a universal phenomenon, so if there are places in the world with characteristics similar to the LBZs, it is important to identify them in order to better understand what other factors, in addition to the known ones, might contribute to a long and healthy life. This narrative review aims to identify common factors between Cilento and the five LBZs, taking into account environmental, nutritional, and lifestyle factors. Articles from 2004 to the present, limited to studies published in English, German, and Italian, were searched in PubMed/Medline, Scopus, and Google Scholar. The co-authors agreed on 18 final reference texts. In order to evaluate the similarities between Cilento and the LBZs, a descriptive comparative approach was used. Cilento and the LBZs share several common factors, including a hilly altitude ranging from 355 to 600 m; a mild climate throughout the year, with temperatures between 17.4 and 23.5 degrees Celsius; traditional professions, such as agriculture and animal husbandry; and a predominantly Mediterranean or plant-based diet, with typical recipes based on legumes, tubers, vegetables, and extra virgin olive oil. Additionally, maintenance of strong intergenerational family relationships, religious devotion, and social relationships within the community are also prevalent. Given the similarities to Cilento, one might wonder if this is an LBZ waiting to be discovered. The lessons learned from this discovery could be applied to the general population to protect them from non-communicable chronic diseases and help slow the aging process.

The effectiveness of ibandronate in reducing the risk of nonvertebral fractures in women with osteoporosis: systematic review and meta-analysis of observational studies.

BACKGROUND: Ibandronate is effective in reducing the risk of vertebral fractures, but experimental evidence offers conflicting results regarding nonvertebral fractures. Real-world evidence has been published evaluating the anti-nonvertebral fracture effect of ibandronate. AIM: This meta-analysis of observational studies assessed the effectiveness of ibandronate in reducing the risk of nonvertebral fractures in women with osteoporosis. METHOD: Pubmed/Embase databases were searched for observational studies. Risks of nonvertebral fractures and hip fractures were the outcomes. Meta-analyses were performed pooling rate ratios (RRs), using random-effects models. Data were reanalysed in sensitivity analyses considering Knapp-Hartung method and Bayesian random-effects. RESULTS: Six cohort studies were included. Overall, once-monthly 150 mg oral ibandronate reduced the risk of nonvertebral fractures (RR 0.84; 95% CI 0.76-0.94). Similar results were obtained when the comparison was restricted to once-monthly 150 mg risedronate, but no differences were found when the comparator was other oral bisphosphonates (weekly alendronate/risedronate). Ibandronate didn't significantly change the risk of hip fractures (RR 1.25; 95% CI 0.89-1.76). The risk of hip fracture was comparable between once monthly, 150 mg oral ibandronate and other oral bisphosphonates. Intravenous ibandronate was not effective in reducing hip fractures comparing to intravenous zoledronate. The low number of studies diminished the robustness of sensitivity analyses. CONCLUSION: Results suggest that once-monthly 150 mg oral ibandronate may be as effective as other oral bisphosphonates in reducing the risk of nonvertebral fractures. However, uncertainty associated to the small number of included studies, which are characterized by heterogeneous demographics and methodologies, precluded definitive conclusions.

Rickettsial Infection in the COVID-19 Era: The Correlation between the Detection of Rickettsia aeschlimannii in Ticks and Storytelling Photography of a Presumable Human Rickettsiosis Case.

Rickettsia aeschlimannii infection is an emerging human tick-borne disease with only a few recorded cases. We reported a presumable autochthonous case of rickettsiosis in an Italian cattle breeder associated with a Hyalomma marginatum bite. Rickettsia aeschlimannii DNA was detected in both the tick specimen from the patient and the grazing cattle close to his farm.

Functional and Clinical Importance of SGLT2-inhibitors in Frailty: From the Kidney to the Heart.

SGLT2 (sodium-glucose cotransporter 2) enables glucose and sodium reabsorption in the kidney. SGLT2-inhibitors (also known as gliflozins, which include canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin) act by increasing glycosuria, thereby reducing glycemia. These drugs are critical to reach and keep glycemic control, a crucial feature, especially in patients with comorbidities, like frail individuals. Several studies evaluated the effects of SGLT2-inhibitors in different settings beyond diabetes, revealing that they are actually pleiotropic drugs. We recently evidenced the favorable effects of SGLT2-inhibition on physical and cognitive impairment in frail older adults with diabetes and hypertension. In the present overview, we summarize the latest clinical and preclinical studies exploring the main effects of SGLT2-inhibitors on kidney and heart, emphasizing their potential beneficial actions in frailty.

GENERATOR HEART FAILURE DataMart: An integrated framework for heart failure research.

Background: Heart failure (HF) is a multifaceted clinical syndrome characterized by different etiologies, risk factors, comorbidities, and a heterogeneous clinical course. The current model, based on data from clinical trials, is limited by the biases related to a highly-selected sample in a protected environment, constraining the applicability of evidence in the real-world scenario. If properly leveraged, the enormous amount of data from real-world may have a groundbreaking impact on clinical care pathways. We present, here, the development of an HF DataMart framework for the management of clinical and research processes. Methods: Within our institution, Fondazione Policlinico Universitario A. Gemelli in Rome (Italy), a digital platform dedicated to HF patients has been envisioned (GENERATOR HF DataMart), based on two building blocks: 1. All retrospective information has been integrated into a multimodal, longitudinal data repository, providing in one single place the description of individual patients with drill-down functionalities in multiple dimensions. This functionality might allow investigators to dynamically filter subsets of patient populations characterized by demographic characteristics, biomarkers, comorbidities, and clinical events (e.g., re-hospitalization), enabling agile analyses of the outcomes by subsets of patients. 2. With respect to expected long-term health status and response to treatments, the use of the disease trajectory toolset and predictive models for the evolution of HF has been implemented. The methodological scaffolding has been constructed in respect of a set of the preferred standards recommended by the CODE-EHR framework. Results: Several examples of GENERATOR HF DataMart utilization are presented as follows: to select a specific retrospective cohort of HF patients within a particular period, along with their clinical and laboratory data, to explore multiple associations between clinical and laboratory data, as well as to identify a potential cohort for enrollment in future studies; to create a multi-parametric predictive models of early re-hospitalization after discharge; to cluster patients according to their ejection fraction (EF) variation, investigating its potential impact on hospital admissions. Conclusion: The GENERATOR HF DataMart has been developed to exploit a large amount of data from patients with HF from our institution and generate evidence from real-world data. The two components of the HF platform might provide the infrastructural basis for a combined patient support program dedicated to continuous monitoring and remote care, assisting patients, caregivers, and healthcare professionals.

Ibandronate in the Prevention of Vertebral and Nonvertebral Osteoporotic Fractures: A Systematic Review of Experimental and Observational Studies.

BACKGROUND/OBJECTIVE: This study aims to evaluate ibandronate clinical effectiveness in the prevention of osteoporosis-related vertebral fractures (VFs) and nonvertebral fractures (NVFs) in the treatment of postmenopausal osteoporosis. METHODS: This systematic review was conducted in accordance with the Centre for Reviews and Dissemination's guidance and reporting in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement 2020. A literature search was performed in PubMed and EMBASE since their inception until February 7, 2022. Randomized controlled trials (RCTs), meta-analysis, experimental, and observational studies evaluating adult patients treated with ibandronate and assessed to osteoporotic fractures prevention were included. The risk of bias was assessed according to study design. Data were analyzed using descriptive statistics. RESULTS: Eight references from 4 RCTs, 7 meta-analyses, and 6 observational studies were included. In RCTs, oral ibandronate was superior to placebo in the prevention of VF. However, the doses were lower than those approved. The meta-analyses confirmed these results and showed that adequate doses of oral ibandronate reduce the risk of NVF compared with insufficient doses. In observational studies, oral ibandronate (in approved doses) reduced the risk of VF compared with no treatment or risedronate or alendronate and the risk of NVF versus risedronate or alendronate; the risk of hip fractures was similar between ibandronate and other oral bisphosphonates. CONCLUSIONS: There is strong evidence that ibandronate reduces the risk of VF in postmenopausal osteoporosis. The available evidence further suggests that ibandronate may reduce the risk of NVF versus insufficient doses of ibandronate, as well as risedronate or alendronate.

Linguatula serrata (Fröhlich, 1789) in Gray Wolf (Canis lupus) from Italy: A Neglected Zoonotic Parasite.

Linguatula serrata, Frohlich, 1789, is a cosmopolitan zoonotic worm-like parasite of carnivores and other vertebrates including herbivores and omnivores. The adult form of the parasite typically inhabits the upper respiratory system, nares, and frontal sinuses of dogs, wolves, and cats. Infective eggs may be spread by sneezing, nasal secretions, and stool. The immature stages of the parasite are localized in the visceral organs of intermediated hosts, usually ruminants or rodents, and they are orally transmitted to predators during the ingestion of infested viscera. This paper reports the morphological identification and the molecular characterization of L. serrata specimen collected from a gray wolf in the Apulia region (southern Italy) and it also provides epidemiological information on this rarely reported zoonosis.

Cartografias do corpo em tempos pandêmicos / Cartographies of the Body in Pandemic Times

Como Fox e Alldred (2020) consideram, o dualismo Cultura / Natureza forneceu aos filósofos, cientistas e cientistas sociais pós-iluministas uma maneira elegante de estabelecer limites para as respectivas preocupações das ciências sociais e naturais (ver também Barad, 2007; Braidotti, 2013; Fullagar et al., 2019). Este dualismo tem permitido a criação de distinções entre corpos e modos de estar no mundo "modernos" (leia-se "civilizados") e "tradicionais" (leia-se "primitivos"). No entanto, quando questões pertencentes à incorporação do social são exploradas criticamente, a influência sobre o bem-estar do entorno construído, as transições climáticas e a pandemia de Covid-19 em curso começam a problematizar tais formas, como é argumentado nas últimas três décadas por autores com perspectivas feministas, pós-humanas, novo-materialistas e político-ecológicas, entre outras. Dando continuidade a um diálogo permanente iniciado em 2018 entre acadêmicos e ativistas da América Latina e Europa, organizamos o seminário online "Religando o nexo natureza-cultura-corpo: práticas e epistemologias". O evento virtual desenvolvido em duas partes explorou como os territórios inter-relacionados de saúde, atividade física e educação podem ser repensados a partir de perspectivas que desestabilizam as fronteiras ontológicas estabelecidas entre natureza, cultura e corpo, e suas possíveis articulações. Este artigo é a transcrição da segunda sessão, denominada "Cartografias do corpo em tempos de pandemia", e apresenta os diálogos entre Alice del Gabbo, Carla Panico, Gianluca De Fazio, Alexandre Fernandez Vaz e Eduardo Galak, pesquisadores da Itália, Portugal, Brasil e Argentina.

More-than-human Perspectives on Physical Activity, Health and Education

Como Fox e Alldred (2020) consideram, o dualismo Cultura / Natureza forneceu aos filósofos, cientistas e cientistas sociais pós-iluministas uma maneira elegante de estabelecer limites para as respectivas preocupações das ciências sociais e naturais (ver também Barad, 2007; Braidotti, 2013; Fullagar et al., 2019). Este dualismo tem permitido a criação de distinções entre corpos e modos de estar-no-mundo "modernos" (leia-se "civilizados") e "tradicionais" (leia-se "primitivos") (Denowski e Viveiros de Castro, 2014). No entanto, ao explorar criticamente as questões de incorporação (embodiment), a influência do ambiente construído sobre o bem-estar, as transições climáticas e/ou a pandemia de Covid-19 em curso, tais distinções começam a se tornar problemáticas, como argumentado eloquentemente nas últimas três décadas por debates e proposições feministas, pós humanistas, novo-materialistas e ecológico politicos, entre outros. Dando continuidade a um diálogo contínuo iniciado em 2018 entre acadêmicos e ativistas da América Latina e da Europa (ver Donato, Tonelli, Galak, 2019), este seminário explorou como os domínios inter-relacionados de saúde, atividade física e educação podem ser a partir de perspectivas que de des-estabilizar fronteiras ontológicas estabelecidas entre natureza, cultura, corpo e sua relação. Isto foi feito através de um diálogo entre Alessandro Bortolotti, Simone Fullagar, BrunoMora, Niamh Ni Shuilleabhain, (Austrália, Itália, Reino Unido e Uruguai, respectivamente). O evento online ocorreu como o primeiro de uma série de seminários online de duas partes sobre Remontando o nexo natureza-cultura-corpo: práticas e epistemologias.

Molecular Characterization of Anopheles algeriensis Theobald, 1903 (Diptera: Culicidae) Populations from Europe.

Anopheles algeriensis Theobald, 1903, considered a competent vector of Plasmodium parasites, is a mosquito species widely distributed in the Mediterranean area but rare in Northern and Central Europe. The disappearance of its suitable breeding sites in Italy is having a detrimental effect on the occurrence of this species once common along the Southern coasts and on the islands. Recently, molecular investigations have renewed interest in this species, highlighting a genetic heterogeneity among European populations. In this study, An. algeriensis populations from Italy, Germany, Romania, and Sweden were analyzed by molecular typing of the intergenic transcribed spacer 2 (ITS2). The mitochondrial cytochrome c oxidase subunit I (COI) was also analyzed from specimens collected in Southern Italy. With the aim of investigating the population structure of this species, the obtained data were compared to all publicly available ITS2 and COI sequences of An. algeriensis, adding specimens from Spain and Portugal. The analyses of both markers indicate a split between Iberian populations (Spain for ITS2 and Spain/Portugal for COI) and those from the rest of Europe, revealing two cryptic species. The analysis of the COI barcode revealed a third clade representing a cryptic species present in Danube Delta (Romania). The high levels of genetic divergence among the clades of An. algeriensis indicate that this taxon represents a species complex, potentially harboring several distinct cryptic species.