Search

Cellular senescence is a plausible mediator of age-associated declines in physical performance. To test this premise, we examined cross-sectional associations between circulating components of the senescence-associated secretory phenotype (SASP) and measures of physical function and muscle strength in 1377 older adults. We showed significant associations between multiple SASP proteins and the short physical performance battery (SPPB), its subcomponents (gait speed, balance, chair rise time), and 400-m walk time. Activin A, ICAM1, MMP7, VEGFA, and eotaxin showed strong associations based on gradient boost machine learning (GBM), and, when combined with other proteins, effectively identified participants at the greatest risk for mobility disability (SPPB score $$\le$$ ≤ 7). Senescence biomarkers were also associated with lower grip strength, and GBM identified PARC, ADAMTS13, and RANTES as top candidates in females, and MMP2, SOST, and MCP1 in males. These findings highlight an association between senescence biomarkers and physical performance in older adults. ClinicalTrials.gov Identifier: NCT01072500.

Purpose The precise effects of non-steroidal anti-inflammatory drugs on the neuroendocrine hydro-electrolytic regulation are not precisely understood. The aim of this pilot study was to evaluate, in healthy subjects, the neuroendocrine response of the antidiuretic system to intravenous diclofenac infusion. Methods For this single-blinded, cross-over study, we recruited 12 healthy subjects (50% women). Test sessions were divided into three observation times (pre-test; test; 48 h post-test), which were repeated equally on two different occasions, with the administration of diclofenac (75 mg in saline solution 0.9% 100 cc) on 1 day, or placebo (saline solution 0.9% 100 cc) on another day. The night before the test the subjects were asked to collect a salivary cortisol and cortisone sample, which was repeated on the night of the procedure session. Serial urine and blood samples were collected on the test day (for osmolality, electrolytes, ACTH, cortisol, copeptin, MR-proADM, MR-proANP; the last three represent more stable and analytically reliable molecules than their respective active peptides). Moreover, the subjects were evaluated with the bioimpedance vector analysis (BIVA) before and after the test. Forty-eight hours after the end of the procedure urine sodium, urine potassium, urine osmolality, serum sodium and copeptin were revaluated together with BIVA. Results No significant changes in circulating hormone levels were observed; anyway, 48 h after diclofenac, BIVA showed a significant water retention (p p p = 0.054 cortisol; p = 0.021 cortisone). Conclusion Diclofenac resulted in an increased ECF at 48 h, but this phenomenon seems to be associated with a greater renal sensibility to the action of vasopressin rather than with an increase in its secretion. Moreover, a partial inhibitory effect on cortisol secretion can be hypothesized.

Background Cellular senescence is a cell fate in response to diverse forms of age-related damage and stress that has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The associations between circulating levels of candidate senescence biomarkers and disease outcomes have not been specifically studied in IPF. In this study we assessed the circulating levels of candidate senescence biomarkers in individuals affected by IPF and controls and evaluated their ability to predict disease outcomes. Methods We measured the plasma concentrations of 32 proteins associated with senescence in Lung Tissue Research Consortium participants and studied their relationship with the diagnosis of IPF, parameters of pulmonary and physical function, health-related quality of life, mortality, and lung tissue expression of P16, a prototypical marker of cellular senescence. A machine learning approach was used to evaluate the ability of combinatorial biomarker signatures to predict disease outcomes. Results The circulating levels of several senescence biomarkers were significantly elevated in persons affected by IPF compared to controls. A subset of biomarkers accurately classified participants as having or not having the disease and was significantly correlated with measures of pulmonary function, health-related quality of life and, to an extent, physical function. An exploratory analysis revealed senescence biomarkers were also associated with mortality in IPF participants. Finally, the plasma concentrations of several biomarkers were associated with their expression levels in lung tissue as well as the expression of P16. Conclusions Our results suggest that circulating levels of candidate senescence biomarkers are informative of disease status, pulmonary and physical function, and health-related quality of life. Additional studies are needed to validate the combinatorial biomarkers signatures that emerged using a machine learning approach.

Purpose: To investigate the long-term safety (primary endpoint) and effectiveness (secondary endpoint) of the somatropin biosimilar Omnitrope®. Methods: PATRO Children is an ongoing, multicenter, observational, post-marketing surveillance study. Children who received Omnitrope® for any indication were included. Adverse events (AEs) were evaluated in all study participants. Auxological data, including height standard deviation scores (HSDS) and height velocity standard deviation scores (HVSDS), were used to assess effectiveness. In this snapshot analysis, data from the Italian subpopulation up to August 2017 were reported. Results: A total of 291 patients (mean age 10.0 years, 56.0% male) were enrolled at 19 sites in Italy. The mean duration of Omnitrope® treatment was 33.1 ± 21.7 months. There were 48 AEs with a suspected relationship to the study drug (as reported by the investigator) that occurred in 35 (12.0%) patients, most commonly headache, pyrexia, arthralgia, insulin-like growth factor above normal range, abdominal pain, pain in extremity and acute gastroenteritis. There were no confirmed cases of type 1 or type 2 diabetes; however, two patients (0.7%) had impaired glucose tolerance that was considered Omnitrope® related. The mean HSDS increased from − 2.41 ± 0.73 at baseline (n = 238) to − 0.91 ± 0.68 at 6.5 years (n = 10). The mean HVSDS increased from − 1.77 ± 1.38 at baseline (n = 136) to 0.96 ± 1.13 at 6.5 years (n = 10). Conclusions: In this sub-analysis of PATRO Children, Omnitrope® appeared to have acceptable safety and effectiveness in the treatment of in Italian children, which was consistent with the earlier findings from controlled clinical trials.

Over the last decade, the enormous potential of metal additive manufacturing (AM) processes has led these technologies to establish their position in many industries. Much effort is being made toward their widespread application; however, much remains to be done to achieve full industrialization of these processes. Therefore, many companies, research centers and universities are investing in comprehensive research and development activities in order to further promote the industrialization of metal AM. This review traces the progress of metal AM technologies through an investigation of patents. In the present study, beam-based metal AM patents were searched through the Orbit Intelligence database. First, the number of patents per year was studied, indicating that, as expected, there is strong growth in AM patenting activities. The patents were afterward examined in order to highlight the key players in the field, and it was found that the main players investing in this market are: multidisciplinary companies, AM machine producers, end users working, especially in the aerospace sector, universities and research centers. The patents were then analyzed to understand the technology domains covered by each key player and their trend of investments. Finally, the patents in the field of Materials and Metallurgy were studied individually to identify the main topics faced by the most used alloy classes: Al-, Ni- and Ti-based alloys and steels. The extensive study of these patents clearly indicated that the main gaps to fill in metal AM are strongly material dependent and that it is possible to find correlations between the alloy classes, their main industrial applications and their specific AM processability issues. The current study provides insights into global trends that can help industrial markets to identify the right investment direction and research to identify topics for future investigation.

The COVID-19 epidemic and its lockdown dramatically impacted the general well-being of the population and affected sociosexual experiences, thus modifying sexual behavior, desire, and well-being. Clustering analysis has not yet been applied to research and data investigating sociosexuality. The cluster analysis method could be a valid support for clinicians in investigating the condition of a population with respect to problems related to sociosexuality. The aim of the present study was to analyze the different perceptions of the sociosexual experiences in southern population during the COVID-19 pandemic.We enrolled 734 (450 female) participants with a carried out anonymous web-based survey from the 16th of April 2020 to the 3rd June of 2020. The revised Sociosexual Orientation Inventory (SOI-R) is a self-report test assessing three theoretically meaningful facets of sociosexual orientation (behavior, attitude, and desire).We found eleven clusters, and the findings showed, for the first time, an intra- and inter-diagnostic heterogeneity in the sexual profile of participants. Theoretically, we identified subtype clusters whose sexual attitude was to avoid sexual promiscuity with significant gender differences. Women show a greater propensity for attitude and desire facet than men.Our new method of unsupervised learning could represent a reliable tool to support socio-cultural analysis studies on issues influenced by cultural mechanisms in a quick and explanatory way, as in the case of sexual orientation and attitude differences between men and women.Understanding these gaps is fundamental for policy makers, managers of social networks, those who deal with engaged couples and families, and sexuality starting from the very youngest adolescents. We claim to devise a strategy to measure how much a sexist culture implicitly and explicitly limits the freedom of sexual expression and how this can affect psycho-sexual well-being in a society.The online version contains supplementary material available at 10.1007/s13178-022-00771-2.

Zusammenfassung Hintergrund Zu Beginn der Coronapandemie wurden auch in der Schweiz Personen im Alter ab 65 Jahren der besonders gefährdeten Bevölkerungsgruppe zugeordnet. Aufgrund vermehrter Vorerkrankungen wurde vermutet, sie seien einem erhöhten Risiko für schwere Krankheitsverläufe ausgesetzt. Dadurch rückten ältere Personen in den Fokus der Aufmerksamkeit, wodurch deren gebrechliche und hilflose Seite betont wurde. Dies lässt Fragen offen, bezüglich der Selbsteinschätzung der älteren Menschen, was ihr konkretes subjektives Befinden und Erleben während der Pandemie betrifft. Ziel der Arbeit Die Studie ergründet die subjektive Sichtweise von Personen ab 65 Jahren und hat zum Ziel, ihre Alltagsbewältigung während der Pandemie zu untersuchen, insbesondere in Bezug auf die Auswirkungen auf ihre Lebenssituation, ihre Selbsteinschätzung als vulnerable Gruppe und ihre Ängste rund um COVID-19. Material und Methoden Es handelt sich um eine Längsschnittstudie im Mixed-Methods-Design, bei welcher von Ende April bis Mitte Juni 2020 2‑wöchentlich ein leitfadengestütztes Telefoninterview mit geschlossenen und offenen Fragen durchgeführt wurde. Es wurden 40 Personen (m = 18, w = 22) im Alter zwischen 65 und 90 Jahren zu verschiedenen Aspekten der Alltagsbewältigung während der Coronapandemie und ihren Folgen befragt. Die quantitativen Daten wurden deskriptiv ausgewertet. Die qualitativen Daten wurden mittels strukturierter Inhaltsanalyse mit induktiver Kategorienbildung evaluiert. Ergebnisse Die Studie zeigte, dass sich das Alltagsleben der Befragten trotz des Lockdowns zu Hause kaum veränderte. Auch wurde mehrheitlich über eine gute Stimmungslage berichtet. Als große Belastung wurden die sozialen Einschränkungen erlebt. Die Einordnung als Risikogruppe wurde als undifferenziert und willkürlich empfunden. Angst oder Sorgen hinsichtlich einer Ansteckung mit dem Coronavirus waren wenig vorhanden. Diskussion Die Befragten schienen die Krise deutlich besser bewältigt zu haben, als der öffentliche Diskurs nahelegte. Aktivitäten und Routinen können als Strategien im Alltag schützend gewirkt haben. Eine homogene Einteilung der älteren Personen als Risikogruppe vernachlässigt deren Ressourcen und fördert sowohl negative Stereotype als auch Altersdiskriminierung.

Transgender (trans) people (including non-binary persons) experience high rates of violence and discrimination regarding their gender identity and expression, necessitating a deeper understanding of trans peoples’ perceptions of safety within their communities and their perspectives on well-being. The purpose of this study was to gather insight into the perceptions of safety and community inclusion among trans people, through the lens of Meyer’s Minority Stress Model. Thirty-three trans individuals residing in a mid-sized urban and rural region, 100 kms west of Toronto, Canada, were interviewed for a larger study focused on experiences of discrimination. For this paper, we conducted a thematic analysis using NVivo (version 12), that included 18 participants from the larger study, including trans men, trans women, and non-binary individuals. Both experiences of prejudice and anticipations of prejudice resulted in participants feeling unsafe. This negatively affected their well-being, consistent with Meyer’s Minority Stress Model. Additionally, we found that environments absent of prejudice or considered supportive, such as places participants received social gender affirmation and LGBT-connectedness, fostered feelings of safety and positive well-being. Our study indicates a need to address not only the external events of prejudice towards trans people, but also the stress associated with the anticipation of prejudice.

Conformal cooling coils have been developed during the last decades through the use of additive manufacturing (AM) technologies. The main goal of this study was to analyze how the presence of an internal channel that could act as a conformal cooling coil could affect compressive strength and quasi-elastic gradient of AlSi10Mg lattice structures produced by laser powder bed fusion (LPBF). Three different configurations of samples were tested in compression at 25 °C and 200 °C. The reference structures were body centered cubic (BBC) in the core of the samples with vertical struts alongZ(BCCZ) lattices in the outer perimeter, labelled as NC samples. The main novelty consisted in inserting a straight elliptical channel and a 45° elliptical channel inside the BCCZ lattice structures, labelled as SC and 45C samples respectively. All the samples were then tested in as-built (AB) condition, and after two post process heat treatments, commonly used for AlSi10Mg LPBF industrial components, a stress relieving (SR) and a T6 treatment. NC lattice structures AB exhibited an overall fragile fracture and therefore the SC and 45C configuration samples were tested only after thermal treatments. The test at 25 °C showed that all types of samples were characterized by negligible variations in their quasi-elastic gradients and yield strength. On the contrary, the general trend of stress-strain curves was influenced by the presence of the channel and its position. The test at 200 °C showed that NC, SC and 45C samples after SR and T6 treatments exhibited a metal-foam like deformation.

Background: Weight loss is a milestone in the prevention of chronic diseases associated with high morbility and mortality in industrialized countries. Very-low calorie ketogenic diets (VLCKDs) are increasingly used in clinical practice for weight loss and management of obesity-related comorbidities. Despite evidence on the clinical benefits of VLCKDs is rapidly emerging, some concern still exists about their potential risks and their use in the long-term, due to paucity of clinical studies. Notably, there is an important lack of guidelines on this topic, and the use and implementation of VLCKDs occurs vastly in the absence of clear evidence-based indications. Purpose: We describe here the biochemistry, benefits and risks of VLCKDs, and provide recommendations on the correct use of this therapeutic approach for weight loss and management of metabolic diseases at different stages of life.

The number of HLA-haploidentical hematopoietic cell transplants continues to increase worldwide due to recent improvements in outcomes, allowing more patients with hematological malignancies and non-malignant disorders to benefit from this procedure and have a chance to cure their disease. Despite these encouraging results, questions remain as multiple donors are usually available for transplantation, and choosing the best HLA-haploidentical donor for transplantation remains a challenge. Several approaches to haploidentical transplantation havebeen developed over time and, based on the graft received, can be grouped as follows: T-cell depleted haploidentical transplants, either complete or partial, or withT-cell replete grafts, performed with post-transplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis, or G-CSF-primed bone marrow graft and enhanced GVHD prophylaxis. Carefully selecting the donor can help optimize transplant outcomes for recipients of haploidentical donor transplants. Variables usually considered in the donor selection include presence of donor-specific antibodies in the recipient, donor age, donor/recipient gender and ABO combinations, and immunogenic variables, such as natural killer cell alloreactivity or KIR haplotype. Here we provide a comprehensive review of available evidence for selecting haploidentical donors for transplantation, and summarize the recommendations from the European Society for Blood and Marrow Transplantation (EBMT) on donor selection for different transplant platforms.

Pituitary adenomas (PAs) rarely occur in childhood and adolescence. Management of PAs in this critical age can be particularly challenging considering the auxological sequelae and potential long-term cardiometabolic consequences. We aimed to describe the clinical characteristics of patients with PA aged