Search Results (22)

Starting Active Materials for Synthesis (SAMS) represents a critical stage in drug manufacturing, directly influencing the microbiological quality and safety of the final product. The introduction of SAMS marks the point where Good Manufacturing Practices (GMP) begin to apply, which are essential for ensuring sterility and preventing microbial contamination during the synthesis process. However, defining the exact point in the process that qualifies as the SAMS is subject to uncertainties, as earlier stages are not always governed by stringent GMP standards. The regulatory differences between various countries further contribute to this issue. This study explores the implications of SAMS selection and use in relation to sterility and infection control, analyzing the guidelines of major Regulatory Authorities and comparing their approaches to GMP. Regulations from several international regulatory agencies were examined, with a particular focus on microbiological control measures and infection protection in the SAMS manufacturing process. The analysis focused on the microbiological control requirements and safety measures applicable to the stages preceding the introduction of SAMS into the production of the final Active Pharmaceutical Ingredients (APIs). Documents published between 2015 and 2025 were included based on predefined criteria regarding relevance, accessibility, and regulatory authority. The analysis revealed significant discrepancies between regulations regarding the definition and management of SAMS. In particular, the regulations in Mexico and India have notable gaps, failing to provide clear guidelines on SAMS sterility and protection against infectious contamination. Conversely, China has introduced risk-based approaches and early-stage microbiological controls, especially for sterile products, aligning with international standards. The European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), the Pharmaceutical Inspection Co-operation Scheme (PIC/S), and the World Health Organization (WHO) have well-established systems for microbiological quality control of SAMS, including rigorous measures for the validation of suppliers and risk management to ensure that SAMS does not compromise the microbiological safety of the final product. The regulations in Brazil and Canada introduce additional measures to protect the microbiological quality of SAMS, with specifications for contamination control and certification of critical stages. The lack of a harmonized language for the definition of SAMS, coupled with a fragmented regulatory framework, presents a challenge for infection protection in pharmaceutical manufacturing. Key issues include the absence of specific regulations for stages prior to the introduction of SAMS and the lack of standards for inspections related to these stages. A desirable solution would be the mandatory extension of GMPs to the stages before SAMS introduction, with centralized control to ensure sterility and protection against infection throughout the entire manufacturing process. Full article

Background: Cancer survivors who do not engage in regular physical activity often experience persistent psychological distress and fatigue, which can significantly impact their quality of life. While handgrip strength (HGS) is recognized as an indicator of overall health and physical resilience, the combined role of HGS and physical inactivity in predicting psychological distress and fatigue in this population remains unclear. This study aimed to examine the relationships between self-reported physical inactivity, HGS, and psychological distress, specifically depressive symptoms, anxiety, and cancer-related fatigue (CRF), in physically inactive cancer survivors. Methods: This cross-sectional study included 42 physically inactive cancer survivors (mean age = 63.2 years, SD = 8.96) recruited from the Cancer Institute (IRCCS) in Bari, Italy. Physical inactivity was quantified based on self-reported weekly physical activity minutes, with all participants engaging in less than 150 min per week. The participants underwent HGS assessment and completed validated psychological measures, including the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI-Y1 and STAI-Y2), and the Fatigue Severity Scale (FSS). Results: Bivariate correlations were examined via Spearman’s rank correlation coefficients, and multiple linear regression analyses were performed to identify independent predictors of psychological distress and fatigue, adjusting for covariates such as age, sex, cancer type, and time since treatment completion. Both lower HGS and greater physical inactivity were significantly correlated with greater depressive symptoms (HGS: ρ = −0.524, p < 0.001; physical inactivity: ρ = −0.662, p < 0.001), greater fatigue severity (HGS: ρ = −0.599, p < 0.001; physical inactivity: ρ = −0.662, p < 0.001), and increased trait anxiety (HGS: ρ = −0.532, p < 0.001; physical inactivity: ρ = −0.701, p < 0.001). No significant associations were found between physical inactivity or HGS and state anxiety (p > 0.05). Multiple regression analyses confirmed that both HGS and physical inactivity independently predicted depressive symptoms (HGS: β = −0.435, p = 0.009; physical inactivity: β = −0.518, p = 0.002), trait anxiety (HGS: β = −0.313, p = 0.038; physical inactivity: β = −0.549, p < 0.001), and fatigue (HGS: β = −0.324, p = 0.033; physical inactivity: β = −0.565, p < 0.001), even after adjusting for covariates. Low physical activity and reduced muscle strength independently predict psychological distress and fatigue in cancer survivors. Conclusions: These findings highlight the potential exacerbating role of physical inactivity in both physical and psychological vulnerability, underscoring the need for interventions promoting regular exercise. Integrating strength assessments and structured physical activity programs may be key strategies in survivorship care to improve mental well-being and overall quality of life. Full article

Background and Objective: Dietary interventions are the first-line treatment for overweight individuals (OW) and individuals with obesity (OB) with high-normal blood pressure (BP) or grade I hypertension, especially when at low-to-moderate cardiovascular risk (CVR). However, current guidelines do not specify the most effective dietary approach for optimising cardiovascular and metabolic outcomes in this population. This study aimed to compare the effects of a low-calorie, high-protein ketogenic diet (KD) vs. a low-calorie, low-sodium, and high-potassium Mediterranean diet (MD) on BP profiles assessed via ambulatory BP monitoring (ABPM), as well as on anthropometric measures, metabolic biomarkers, and body composition evaluated by bioelectrical impedance analysis (BIA). Methods: This prospective observational bicentric pilot study included 26 non-diabetic adult outpatients with central OW status or OB status (body mass index, BMI > 27 kg/m²) and high-normal BP (≥130/85 mmHg) or grade I hypertension (140–160/90–100 mmHg), based on office BP measurements. All participants had low-to-moderate CVR according to the second version of the systemic coronary risk estimation (SCORE2) and were selected and categorized as either KD (n = 15) or MD (n = 11). Comprehensive blood analysis, BIA, and ABPM were conducted at baseline and after three months. Results: At baseline, no significant differences were observed between the groups. Following three months of dietary intervention, both groups exhibited substantial reductions in body weight (KD: 98.6 ± 13.0 to 87.3 ± 13.4 kg; MD: 93.8 ± 17.7 to 86.1 ± 19.3 kg, p < 0.001) and waist circumference. Mean 24 h systolic BP (SBP) and diastolic BP (DBP) significantly declined in both groups (24 h mean SBP decreased from 125.0 ± 11.3 to 116.1 ± 8.5 mmHg (p = 0.003) and 24 h mean DBP decreased from 79.0 ± 8.4 to 73.7 ± 6.4 mmHg (p < 0.001)). Fat-free mass (FFM) increased, whereas fat mass (FM), blood lipid levels, and insulin concentrations decreased significantly. The ΔFM/ΔFFM correlates with ABP improvements. However, no significant between-group differences were detected at follow-up. Conclusions: The KD and the MD mediated weight loss and body composition changes, effectively improving bio-anthropometric and cardiovascular parameters in individuals with OW status or OB status and high BP. Although more extensive studies are warranted to elucidate potential long-term differences, our findings suggest the manner in which these two different popular dietary approaches may equally confer metabolic and cardiovascular benefits, emphasising the importance of weight and FM loss. Full article

Cardiovascular diseases (CVDs) remain the leading cause of death globally. In recent years, interest in multicomponent interventions has grown as a response to the multifactorial complexity of CVDs. However, the literature still shows little systematic investigation into the effectiveness of multicomponent training (MCT) in the field of CVDs, accompanied by terminological confusion. This study aims to summarize and critically appraise the recent literature through a narrative review. A narrative review was conducted, synthesizing evidence from studies published between 2010 and January 2025. The databases searched included PubMed, Scopus, and Google Scholar using predefined search terms related to CVDs and MCT, and medical subject headings (MeSHs) and Boolean syntax. Two team authors independently extracted relevant information from the included studies. MCT significantly improved hemodynamic parameters in CVD patients, with reductions in systolic, diastolic, mean blood pressure, and heart rate. Physical fitness measures showed consistent enhancements whereas anthropometric improvements often corresponded with blood pressure reductions. Psychological outcomes varied across studies, with intervention duration emerging as a key factor in effectiveness. MCT interventions could lead to improvements in clinical outcomes, risk factor reduction, and patient adherence. Although findings on psychological parameters remain inconsistent, the overall evidence supports their integration into both clinical and community settings. Full article

Background/Objectives: Human papillomavirus (HPV) is a leading cause of cervical cancer. Despite the proven effectiveness of vaccination programs, global coverage remains uneven, with significant disparities across regions due to various socioeconomic, cultural, and political factors. This study explores the primary barriers to HPV vaccination worldwide and proposes recommendations to improve access to screening and vaccination programs. Methods: A systematic literature review was conducted, analyzing studies published in the past ten years from databases such as PubMed, Scopus, and Embase, following the PRISMA methodology. Study selection involved multiple researchers, with discrepancies resolved through consultation. The quality of the included studies was assessed using CASP checklists. The protocol was registered on Open Science Framework (OSF). Results: Out of 2119 records, eight studies were included. The findings indicate that the main barriers to HPV vaccination include insufficient public awareness, cultural and religious resistance, financial constraints, and limited access in rural and underserved areas. Additionally, political factors, such as low prioritization of HPV vaccination and the absence of supportive policies, were identified as significant obstacles. Multidisciplinary and cross-cultural collaboration, along with the integration of HPV vaccination into existing health programs, was suggested as a strategic approach to improve vaccine uptake. Conclusions: Barriers to HPV vaccination, including limited awareness, inadequate healthcare infrastructure, and socioeconomic factors, vary across regions but must be addressed to improve global coverage. Targeted interventions such as health education, inclusive policies, and culturally sensitive campaigns can significantly boost vaccine uptake. Strengthening local health systems and fostering international collaboration are key strategies to overcoming these barriers and ensuring equitable access to HPV vaccination. Full article

Introduction: Pressure ulcers (PUs) represent a significant challenge in chronic care, particularly among the elderly with reduced mobility. They result in substantial socio-healthcare costs and negatively impact patients’ psychological well-being. Malnutrition is a key risk factor, hindering healing and increasing the risk of complications. As such, appropriate nutritional interventions are crucial for managing PUs. However, these interventions are often underestimated in clinical practice, underscoring the need for a more comprehensive approach to elder care and healthy aging. Objectives: The primary objective of this study was to identify the best scientific evidence on nutritional interventions implemented by nurses in community settings to prevent complications related to PUs. Additionally, qualitative and quantitative outcomes reported in the included studies were analyzed. Method: This systematic review was conducted following PRISMA international guidelines. Searches were performed in PubMed, Scopus, Embase, and CINAHL databases. A predefined search strategy using Boolean operators was employed, and two researchers independently selected papers, with a third researcher resolving any discrepancies. Additional sources and manual reviews were conducted to minimize selection bias. Results: Out of 1003 records, 6 studies were included. Findings indicate that nurses play a fundamental role in managing PUs in community settings through specific nutritional intervention assistance processes. These healthcare professionals are pivotal in the prevention, care, and rehabilitation of vulnerable individuals with PUs. Conclusions: Nurses are strategic in the management of PUs within community care for frail populations. With nutritional support that plays a key role in both preventing and accelerating the healing of PUs. Policymakers are encouraged to invest in nursing roles to enhance assistance in community contexts, supporting healthy aging and lifestyle medicine approaches. Full article

Background: The aging population drives a growing demand for care, particularly in Europe. It is estimated that approximately 1.5–2 million individuals have a chronic wound. Among these, pressure ulcers (PUs) are one of the most prevalent complications in vulnerable individuals. Malnutrition is a primary risk factor, yet it can be mitigated through proper nutrition and adequate community support. The community nurse plays a crucial role in managing chronic conditions and nutrition through constant and professional monitoring. Aim: This article presents a comprehensive systematic review (SR) protocol to examine the role of community nursing of nutritional intervention of frail population with wound care. Methods: A SR will be conducted according to international standards and reported following the PRISMA Guidelines for SRs. The search will be conducted in PubMed/Medline, Scopus, Embase, and CINAHL, supplemented by grey literature sources. The methodological quality and risk of bias will be assessed using the Critical Appraisal Skills Programme (CASP) framework. The protocol has been registered in the Open Science Framework (OSF). Conclusions: It is anticipated that the findings of this SR will provide new evidence on the relationships between nutritional nursing interventions and wound care management primarily in the community setting. Full article

Background and Objectives: In Italy, as in the rest of the world, government restrictions aimed at containing the spread of COVID-19 primarily imposed limitations on social relationships and personal behavior. This situation significantly affected the management of chronic illnesses, including type 2 diabetes (T2D). The objective was to evaluate the perceptions of patients with T2D regarding the quality of care received during the COVID-19 pandemic and the impact on dietary and physical activity behaviors. Materials and Methods: We conducted a retrospective cross-sectional survey. Data were collected from June to July 2023 using the convenience sampling of patients with T2D, and the Patient Assessment of Chronic Illness Care (PACIC) and Medi-Lite questionnaires were administered. Results: During the research period, out of the 130 subjects who met all enrollment criteria, 103 patients were included in this study (79.23%). The results of the administered questionnaires were heterogeneous. The average scores from the PACIC Questionnaire for each question displayed significant variability, indicating a range of experiences in the quality of care. In the Medi-Lite survey, fruit, cereals, and olive oil showed the highest adherence levels, with mean scores ranging from 2.58 (SD ± 1.18) for fruit to 1.89 (SD ± 0.34) for olive oil and 1.97 (SD ± 0.17) for cereals. Patients who reported increased food intake during the lockdown attributed it to having more time to prepare meals. Physical activity levels remained unchanged for 48 patients, decreased for 45 patients, and only 9 patients managed to exercise more during the COVID-19 restrictions. Conclusions: Healthcare systems must prioritize comprehensive care plans for T2D that address not only physical health, but also emotional and social well-being. Post-pandemic, promoting healthier lifestyles and empowering patients to manage their condition is crucial. A multidisciplinary and multidimensional approach could support the care of vulnerable individuals, such as patients with T2D, especially during crises like pandemics or other dramatic events. Full article

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a novel class of incretin mimetics for treating type 2 diabetes (T2D). This study evaluated the impact of semaglutide, the first oral GLP-1RA, on glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and body composition and anthropometric parameters. Additionally, the effects on cardiovascular risk factors and quality of life (QoL) in T2D patients were assessed. Methods: A prospective observational study with a six-month follow-up was conducted. Clinical parameters, including HbA1c, FPG, anthropometric measurements, blood pressure, cardiovascular risk factors, Diabetes Treatment Satisfaction Questionnaire (DTSQ) responses, and Short Form (36) Health Survey (SF-36) responses, were collected at baseline (T0) and at six months (T1). Results: Sixty-one subjects were enrolled, with there being an average T2D duration of 4.67 ± 3.93 years. Significant decreases were observed in HbA1c (µ = −1.24; SD = 1.33; p < 0.05), FPG (µ = −31.01 mg/dL; SD = 41.71; p < 0.05), body composition and anthropometric parameters (p < 0.05), and cardiovascular risk factors (p < 0.05), with an increase in DTSQ scores (p < 0.05). Conclusions: The administration of 14 mg/day oral semaglutide improved several clinical parameters after six months of treatment. These findings suggest semaglutide is effective in improving glycemic control, weight management, and some cardiovascular risk factors in T2D patients. Full article

The Berlin questionnaire (BQ), with its ten questions, stands out as one of the simplest and most widely implemented non-invasive screening tools for detecting individuals at a high risk of Obstructive Sleep Apnea (OSA), a still underdiagnosed syndrome characterized by the partial or complete obstruction of the upper airways during sleep. The main aim of this study was to enhance the diagnostic accuracy of the BQ through Machine Learning (ML) techniques. A ML classifier (hereafter, ML-10) was trained using the ten questions of the standard BQ. Another ML model (ML-2) was trained using a simplified variant of the BQ, BQ-2, which comprises only two questions out of the total ten. A 10-fold cross validation scheme was employed. Ground truth was provided by the Apnea–Hypopnea Index (AHI) measured by Home Sleep Apnea Testing. The model performance was determined by comparing ML-10 and ML-2 with the standard BQ in the Receiver Operating Characteristic (ROC) space and using metrics such as the Area Under the Curve (AUC), sensitivity, specificity, and accuracy. Both ML-10 and ML-2 demonstrated superior performance in predicting the risk of OSA compared to the standard BQ and were also capable of classifying OSA with two different AHI thresholds (AHI ≥ 15, AHI ≥ 30) that are typically used in clinical practice. This study underscores the importance of integrating ML techniques for early OSA detection, suggesting a direction for future research to improve diagnostic processes and patient outcomes in sleep medicine with minimal effort. Full article

(1) Background: Venous thromboembolism (VTE) is a frequent complication in ambulatory lung cancer patients during chemotherapy and is associated with increased mortality. (2) Methods: We analyzed 568 newly diagnosed metastatic lung cancer patients prospectively enrolled in the HYPERCAN study. Blood samples collected before chemotherapy were tested for thrombin generation (TG) and a panel of hemostatic biomarkers. The Khorana risk score (KRS), new-Vienna CATS, PROTECHT, and CONKO risk assessment models (RAMs) were applied. (3) Results: Within 6 months, the cumulative incidences of VTE and mortality were 12% and 29%, respectively. Patients with VTE showed significantly increased levels of D-dimer, FVIII, prothrombin fragment 1 + 2, and TG. D-dimer and ECOG performance status were identified as independent risk factors for VTE and mortality by multivariable analysis and utilized to generate a risk score that provided a cumulative incidence of VTE of 6% vs. 25%, death of 19% vs. 55%, and in the low- vs. high-risk group, respectively (p < 0.001). While all published RAMs significantly stratified patients for risk of death, only the CATS and CONKO were able to stratify patients for VTE. (4) Conclusions: A new prediction model was generated to stratify lung cancer patients for VTE and mortality risk, where other published RAMs failed. Full article

The maintenance of a proper NAD⁺ pool is essential for cell survival, and tumor cells are particularly sensitive to changes in coenzyme levels. In this view, the inhibition of NAD⁺ biosynthesis is considered a promising therapeutic approach. Current research is mostly focused on targeting the enzymes nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPRT), which regulate NAD⁺ biosynthesis from nicotinamide and nicotinic acid, respectively. In several types of cancer cells, both enzymes are relevant for NAD⁺ biosynthesis, with NAPRT being responsible for cell resistance to NAMPT inhibition. While potent NAMPT inhibitors have been developed, only a few weak NAPRT inhibitors have been identified so far, essentially due to the lack of an easy and fast screening assay. Here we present a continuous coupled fluorometric assay whereby the product of the NAPRT-catalyzed reaction is enzymatically converted to NADH, and NADH formation is measured fluorometrically. The assay can be adapted to screen compounds that interfere with NADH excitation and emission wavelengths by coupling NADH formation to the cycling reduction of resazurin to resorufin, which is monitored at longer wavelengths. The assay system was validated by confirming the inhibitory effect of some NA-related compounds on purified human recombinant NAPRT. In particular, 2-hydroxynicotinic acid, 2-amminonicotinic acid, 2-fluoronicotinic acid, pyrazine-2-carboxylic acid, and salicylic acid were confirmed as NAPRT inhibitors, with Ki ranging from 149 to 348 µM. Both 2-hydroxynicotinic acid and pyrazine-2-carboxylic acid were found to sensitize OVCAR-5 cells to the NAMPT inhibitor FK866 by decreasing viability and intracellular NAD⁺ levels. Full article

We analysed the major, minor and trace elements chemistry of forty-two Cr-spinels from four Siberian kimberlites. They showed a wide range in Mg# (Mg/(Mg + Fe²⁺); 0.42–0.78) and Cr# (Cr/(Cr + Al); 0.32–0.92) and a common trend of increasing Cr# with decreasing Mg#. The major element classification schemes suggested that there were spinels deriving from a peridotitic source (Xen) and spinels crystallised from kimberlitic melts (Chr). Laser-Ablation Inductively Coupled Plasma Mass Spectrometry on both groups showed that the trace elements with the highest abundance were Mn (985–3390 ppm), Ni (531–3162 ppm), V (694–2510 ppm) and Zn (475–2230 ppm). Testing the effectiveness of trace elements in determining the source for Cr-spinels, we found out that Cr-spinels crystallised directly from a kimberlitic melt usually showed higher Mn, Ni, Sc and V concentrations with respect to those of peridotitic origin. In addition, using the available partitioning models, we found that the correlations between major elements and Ni, Co, Sc and Ga in the Xen group could be explained by subsolidus equilibration between spinel, olivine and clinopyroxene at 800–1000 °C, thus supporting a peridotitic source for this group. Finally, we calculated the composition of the possible melts in equilibrium with the Cr-spinels of the Chr group, using a selected set of partition coefficients. Calculated abundances of Cu, Ga and Zr were comparable to those of the kimberlite, while V was never close to the kimberlite composition. This simulation highlighted the need for new data on the trace elements partition coefficients between kimberlitic melts and Cr-spinel. Full article

Background: the tight and reciprocal interaction between cancer and hemostasis has stimulated investigations on the possible role of hemostatic biomarkers in predicting specific cancer outcomes, such as disease progression (DP) and overall survival (OS). In a prospective cohort of newly diagnosed metastatic gastrointestinal (GI) cancer patients from the HYPERCAN study, we aimed to assess whether the hemostatic biomarker levels measured before starting any anticancer therapy may specifically predict for 6-months DP (6m-DP) and for 1-year OS (1y OS). Methods: plasma samples were collected and tested for thrombin generation (TG) as global hemostatic assay, and for D-dimer, fibrinogen, and prothrombin fragment 1 + 2 as hypercoagulation biomarkers. DP and mortality were monitored during follow-up. Results: A prospective cohort of 462 colorectal and 164 gastric cancer patients was available for analysis. After 6 months, DP occurred in 148 patients, providing a cumulative incidence of 24.8% (21.4–28.4). D-dimer and TG endogenous thrombin potential (ETP) were identified as independent risk factors for 6m-DP by multivariate Fine–Gray proportional hazard regression model corrected for age, cancer site, and >1 metastatic site. After 1 year, we observed an OS of 75.7% (71.9–79.0). Multivariate Cox regression analysis corrected for age, site of cancer, and performance status identified D-dimer and ETP as independent risk factors for 1y OS. Patients with one or both hemostatic parameters above the dichotomizing threshold were at higher risk for both 6m-DP and 1-year mortality. Conclusion.: in newly diagnosed metastatic GI cancer patients, pretreatment ETP and D-dimer appear promising candidate biomarkers for predicting 6m-DP and 1y OS. In this setting, for the first time, the role of TG as a prognostic biomarker emerges in a large prospective cohort. Full article

In the present work we summarize the first achievements of the RockStar Group of the Department of Physics and Geology (at the University of Perugia, Italy), which is made of a strict collaboration between Physicists and Geologists on astrophysical and planetological studies. The RockStar Group acts on two research lines: (i) astrophysical modeling and (ii) mineralogical and geochemical studies of meteorites. In the first part of the article we review the recent results concerning the development of theoretical modeling of nucleosynthesis and mixing process in asymptotic giant branch. In the second part we report (1) the catalog of the Meteorite collection of University of Perugia and (2) major and trace elements mapping, performed through EPMA and LA-ICP-MS, of the Mineo pallasite, a unique sample hosted by the collection. The new data constrain the Mineo meteorite among the Main Group Pallasites and support the hypothesis of the “early giant impact” formation. Full article