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We critically examine a broad class of explicitly polarizable soft solvent models aimed at applications in dissipative particle dynamics. We obtain the dielectric permittivity using the fluctuating box dipole method in linear response theory and verify the models in relation to several test cases, including demonstrating ion desorption from an oil–water interface due to image charge effects. We additionally compute the Kirkwood factor and find that it uniformly lies in the range g K ≃ 0.7 –0.8, indicating that dipole–dipole correlations are not negligible in these models. This is supported by the measurements of dipole–dipole correlation functions. As a consequence, Onsager theory over-predicts the dielectric permittivity by 20%–30%. The mean square molecular dipole moment can be accurately estimated with a first-order Wertheim perturbation theory. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate clasp-retained removable partial dentures (C-RPDs) with a metal framework for survival, maintenance requirements, and biologic implications. Method and materials: C-RPDs were retrospectively analyzed based on patient records. Treatment failure was defined as fracture of a framework component (metal base or connector) or loss of an abutment tooth. Other outcome variables included factors that might conceivably impact C-RPD survival (maxilla vs mandible, Kennedy classes, opposing dentitions, treatment by students vs certified dental practitioners), mobility and caries of abutment teeth (in relation to clasp designs), and maintenance requirements (relining, clasp or resin fractures). Differences were evaluated by appropriate statistical tests at the P≤.05 level. Results: A total of 612 patients (339 men, 273 women) 60.0±11.5years old at delivery were included, covering 842 C-RPDs and a mean observation period of 42.1±33.2months. Kaplan-Meier C-RPD survival was 76.2% after 5years and 49.5% after 10years. Biologic complications (ie, loss of abutment teeth) accounted for the vast majority (95.6%) of C-RPD failures, and Kaplan-Meier C-RPD survival was significantly better in the mandible (P=.015). Some clasp designs contributed significantly to caries and removal of abutment teeth (both P<.05). No other significant differences were noted. Conclusion: Tooth loss both emerges as the main cause of C-RPD failure and might be amenable to careful selection of clasp designs. Overall, better C-RPD survival should be expected in the mandible. A noncon-tributory role of Kennedy classes and opposing dentitions is tentatively suggested based on numerically heterogenous subgroups. [ABSTRACT FROM AUTHOR]

This paper systematises the theoretical perspectives that inform the consumer-object relationship (C-OR) debate and its evolutionary trajectories to organise how a theory of the object has been developed in marketing and consumer research. We build on a diachronic critical reading of the key turning points in the debate to conduct a systematic review, combining a bibliometric and semantic-lexicographic analysis. Our analysis organises the contribution that each theoretical perspective offered to the development of a theory of the object, highlighting the interplays, contrasts, mesh-ups, and distinctions in terms of theoretical underpinnings, vocabularies, and ideological viewpoints. In so doing, it raises awareness about the significance of embracing diverse theoretical perspectives to guide further inquiry on the expanding role of smart and technological objects in C-OR. [ABSTRACT FROM AUTHOR]

Purpose: Marginal bone resorption (MBR) around dental implants may sometimes be a self-limiting condition due to balancing immunologic reactions against utilized materials rather than a progressive bacterial infection. Contrary to previous assumptions from ligature-induced experimental peri-implantitis studies, a recent 8-week experiment by the present authors showed that marginal ligatures trigger an inflammatory immune response, resulting in bone resorption around implants in the absence of plaque. The present study aimed to investigate whether this inflammatory/immunologic reaction attenuates or progresses toward implant failure after a longer healing time (12 weeks). Materials and Methods: Sterile silk ligatures were placed around the top of titanium (Ti) implants and compressed against the femoral cortical bone plate of six rabbits. A nonligated implant was used as a control. After 12 weeks of submerged healing, ground sections of implants and surrounding tissues were investigated with light microscopy. The marginal soft tissues were also analyzed using selected quantitative polymerase chain reaction (qPCR) markers. Results: Histologically, the ligatures were outlined by immune cells, including multinucleated giant cells (MNGCs), with adjacent fibrous encapsulation and resorbed peripheral bone that contrasted from the osseointegrated nonligated control implants. The difference in expression of qPCR markers was not significant, but > two-fold upregulation of markers CDIIb, IL1β, ARG1, NCF1, and CD4 and > twofold downregulation of CD8 indicated a mild, focal inflammatory/immune response against the ligatures compared to controls, with upregulation of M1 and M2 macrophages, neutrophils, and helper T-cells as well as downregulation of killer T cells. Further, the bone formation markers OC and ALPL were > two-fold downregulated (consistent with the lack of osseointegration of the ligatures) compared to control implants. Conclusions: Marginal silk ligatures trigger an inflammatory/immune response and aseptic bone resorption around implants. Compared to the previous 8-week study, the inflammatory reaction against the silk appears to attenuate with time, with only a mild persisting inflammation that may block osseointegration; instead, a fibrous tissue encapsulation-type reaction is maintained. This may explain why traditional ligature experiments have required regular exchange of ligatures for the bone resorption to progress. [ABSTRACT FROM AUTHOR]

Although evolutionary economics has extensively analyzed the evolution of industries in relation to innovation and technology lifecycles, the interplay between industry lifecycles and evolutionary patterns of knowledge networks has not been fully explored yet. This work aims to bridge this gap by analyzing the co-evolutionary patterns of knowledge and trade flows in the mining industry, using social network tools in combination with the Schumpeterian tradition of analysis. The study focuses on three Latin American countries: Brazil, Chile, and Peru, where the mining sector plays a significant role in the economy, particularly in the context of energy and digital transitions. Our findings suggest that the innovation network and the global value chain-trade network display divergent co-evolutionary patterns; while the former tends to be stable and concentrated, the latter shows increasing fragmentation and turbulence. The analysis also shows remarkable evolutionary evidence at the country level. [ABSTRACT FROM AUTHOR]

The structural, conformational, and spectroscopic properties in the gas phase of 20 bicyclic monoterpenes and monoterpenoids have been analyzed by a new accurate, reduced-cost computational strategy. In detail, the revDSD-PBEP86 double-hybrid functional in conjunction with the D3BJ empirical dispersion corrections and a suitable triple-zeta basis set provides accurate geometrical parameters, whence equilibrium rotational constants, which are further improved by proper account of core–valence correlation. Average deviations within 0.1% between computed and experimental rotational constants are reached when taking into account the vibrational corrections obtained by the B3LYP functional in conjunction with a double-zeta basis set in the framework of second-order vibrational perturbation theory. In addition to their intrinsic interest, the studied terpenes further extend the panel of systems for which the proposed strategy has provided accurate results at density functional theory cost. Therefore, a very accurate yet robust and user-friendly tool is now available for systematic investigations of the role of stereo-electronic effects on the properties of large systems of current technological and/or biological interest by experimentally oriented researchers. [ABSTRACT FROM AUTHOR]

Background: To evaluate the influence of previous physical activity (PA) during childhood, adolescence, and current PA practice on the production of antibodies and inflammatory response between the first and second doses of the COVID-19 vaccine. Methods: Fifty-nine men and 56 women were evaluated before the first vaccine, and 12 weeks later, blood samples were taken to quantify production of anti-severe acute respiratory syndrome coronavirus-2 immunoglobulin G antibodies and cytokines. Previous PA during childhood and adolescence was self-referred, and current PA was assessed using the International Physical Activity Questionnaire. Results: A positive and significant association was observed only between PA practice during adolescence and an increase in antibody production in adulthood (β = 2012.077, 95% confidence interval, 257.7953–3766.358, P =.025). Individuals who practiced PA during adolescence showed higher production of antibodies between the first and second vaccine dose compared to nonpractitioners (P =.025) and those that accumulated ≥150 minutes per week of current moderate–vigorous PA (MVPA), and presented higher antibody production in relation to who did <150 minutes per week of MVPA (P =.046). Individuals that were practitioners during childhood produced higher G-CSF (P =.047), and those that accumulated ≥150 minutes per week of current MVPA demonstrated lower IP-10 levels (P =.033). However, PA practitioners during adolescence presented higher G-CSF (P =.025), IL-17 (P =.038), IL-1RA (P =.005), IL-1β (P =.020), and IL-2 (P =.026) levels. Conclusion: Our results suggest that adults that accumulated at least 150 minutes of MVPA per week or practiced PA during adolescence developed an improved immune and inflammatory response against COVID-19 vaccination. [ABSTRACT FROM AUTHOR]

This paper investigates the effects of digitalization and organizational practices on innovation in Europe, between 2010 and 2016. We analyze the cross-country and industry differences in firms' investments and capabilities to adopt and use new technologies and their effects on innovation outputs. Along with traditional drivers of innovation, such as research and development (R&D) expenditure, two composite indicators are constructed. One encompasses direct measures of the adoption and use in enterprises of a set of digital technologies. The other measures the learning capacity of organizations, which captures the use of management tools and organizational practices concerned with the improvement of individual and organizational learning. Product, process, organizational, and marketing innovations are identified as well as their combinations within companies. Empirical evidence is provided by a unique dataset based on the integration at the sector within the country level of European Union (EU)-wide employers' and employees' surveys: the Community Innovation Survey (CIS), the Community Information and Communication Technologies (ICT) usage and e-commerce in enterprises survey (Eurostat), and the European Working Conditions Survey (Eurofound). The descriptive evidence shows that Digital technology adoption and use is rapidly growing across Europe, while the Learning capacity of organizations remains stagnant. By contrast, our results from the econometric analysis show that these investments can favor all forms of innovations and that, further, they may show some complementarity. Overall, a mix of product/process innovations and organizational/marketing innovations rests on joint investments in R&D, digital technology adoption and use, and learning capacity of the organization. [ABSTRACT FROM AUTHOR]

The sourcing of raw materials with low environmental impact, e.g., "upcycled" ingredients from short supply chains, has currently become necessary, and agri-food waste represents a very attractive hub to produce innovative cosmetic extracts. In this paper, an integrated approach considering all the different steps, starting from material selection, extraction, chemical characterization, biological activity evaluation, and environmental impact calculation, was adopted to obtain innovative, sustainable, and effective cosmetic raw materials from food waste. As case report, a supercritical CO2 extract obtained from wild-strawberry-processing waste after jam production (WSWSCO2 extract) was developed. The fatty acids profile of the waste material and WSWSCO2 extract was investigated via a GC–MS method, and mainly polyunsaturated fatty acids (PUFAs) such as linoleic and linolenic acids were detected. Furthermore, the ability of the WSWSCO2 extract to inhibit 5α-reductase type 1 expression in skin fibroblasts was assessed, confirming significant efficacy at the dose of 5 mg/mL. Finally, in view of the eco-sustainability approach, the environmental impact related to WSWSCO2 extract was calculated using a life cycle assessment (LCA) analytical approach, considering different parameters and indicators (e.g., carbon footprint) and verifying the eco-friendly approach in extract development and production. Although further research is needed, for example, to check the full composition of the extract and its effect on skin cells, these results suggest that the WSWSCO2 extract may represent an innovative and sustainable ingredient for cosmetic applications especially in topical preparation for the treatment of some androgenic-related discomfort, such as acne and androgenic alopecia, reflecting the potentiality of the holistic and pioneering approach related to ingredient development presented in this study for the cosmetic sector. [ABSTRACT FROM AUTHOR]

Fetal undernutrition establishes the foundations for hypertension development, with oxidative stress being a key hallmark. A growing interest in nutraceuticals for treating hypertension and environmental waste concerns prompted the present study aiming to evaluate whether supplementation with a polyphenol enriched extract from cocoa shell (CSE), a by‐product from the chocolate industry with antioxidant properties, reduces hypertension of developmental origin, thus improving mesenteric resistance artery (MRA) vasodilatation. Adult male and female offspring from rats exposed to 50% food restriction from mid‐gestation (maternal undernutrition, MUN) and controls were used. Supplementation was given through a gelatine (vehicle, VEH) or containing CSE (250 mg kg−1 day−1) 5 days week−1 for 3 weeks. Systolic blood pressure (SBP) was assessed by tail‐cuff plethysmography. MRA function was studied by wire myography, and superoxide anion and nitric oxide were investigated by fluorescent indicators and confocal microscopy. Compared to control‐VEH, MUN‐VEH males showed significantly higher SBP, reduced MRA as well as relaxation to ACh, sodium nitroprusside and the AMPK agonist 5‐aminoimidazole‐4‐carboxamide riboside, but not to isoproterenol. In MUN males, endothelial endothelium‐derived hyperpolarizing factor and nitric oxide were unaltered, but MRA released a vasoconstrictor prostanoid and produced higher levels of superoxide anion. CSE normalized blood pressure and improved all above‐mentioned MRA alterations in MUN males without an effect on control counterparts, except the reduction of superoxide anion. MUN‐VEH females were normotensive and only showed a tendency towards larger superoxide anion production, which was abolished by CSE. CSE supplementation reduces SBP improving endothelium‐dependent and independent MRA vasodilatation, related to local superoxide anion reduction, being a potential nutraceutical ingredient to counteract hypertension, in addition to contributing to the circular economy. Key points: Fetal undernutrition induces hypertension in males associated with deficient resistance artery vasodilatation, being normalized by cocoa shell extract (CSE).Release of a cyclooxygenase‐derived contractile factor is the main endothelial alteration, which is abolished by CSE.AMPK and soluble guanylyl cyclase‐mediated relaxation are also reduced in smooth muscle cells from maternal undernutrition resistance arteries, being improved by CSE.Vascular oxidative damage caused by excess superoxide anion generation can account for impaired vasodilatation, which is improved by CSE.The capacity of CSE to improve relaxation is probably related to its antioxidant bioactive factors, and thus cocoa shell is a potential food by‐product to treat hypertension. [ABSTRACT FROM AUTHOR]

Background/Objective: Lysosomal storage diseases (LSDs) are a group of rare, inborn, metabolic errors characterized by deficiencies in normal lysosomal function and by the intralysosomal accumulation of undegraded substrates, resulting in the damage of multiple organ systems. The spectrum of clinical manifestations is extremely heterogeneous. LSD diagnosis and management still present many issues. Methods: A group of Italian experts and patients' representatives met to discuss some critical aspects, and among the most impactful are early diagnosis, the transition of the patient from pediatric to adult age, territorial management, and the multidisciplinary approach. Results: Possible solutions to diagnostic delays may be a widespread newborn screening and screening programs on selected populations. The lack of a structured transition process could be helped by the drafting of shared diagnostic and therapeutic care pathways beyond the availability of databases accessible to the different levels that manage a patient. Territorial management could benefit from telemedicine, but a homogeneous diffusion of home therapy, not yet everywhere possible, is essential. A fundamental role is played by the patient associations, which should be increasingly involved in the political choices. It is also crucial to create structured multidisciplinary teams of experts for disease management and comorbidities. A transversal need appears to be greater training on LSDs. In Italy, the "Statement of Udine" was developed to guide further steps towards improvements in inherited metabolic medicine in adults, referencing the experience from the United Kingdom. Conclusions: Much can be done for the early diagnosis and management of LSDs with an effective treatment, but many aspects need improvement for the overall management of the patient. An investment in dedicated resources, formal recognition, and training is needed to address these unmet needs. [ABSTRACT FROM AUTHOR]

Methods: This study assessed data from two cohorts of patients with alpha‐synucleinopathies (University of Brescia and University of Rome Tor‐Vergata cohorts). Consecutive participants with video‐polysomnography‐confirmed iRBD, Parkinson's disease (PD), dementia with Lewy bodies (DLB) and controls underwent neurological, clinical and 123I‐FP‐CIT SPECT imaging assessments. Individuals with iRBD were longitudinally monitored to collect clinical phenoconversion to PD or DLB. The main outcome was to identify whole brain 123 I‐FP‐CIT SPECT measures reflecting monoaminergic deficits in each clinical group as compared to controls. Results: The cohort (n = 184) included 45 patients with iRBD, 47 PD, 42 DLB and 50 age‐matched controls. Individuals with iRBD were categorized as RBD‐DAT− (n = 32) and RBD‐DAT+ (n = 13), according to nigrostriatal assessment used in clinical practice. Compared to controls, RBD‐DAT− showed an early involvement of the left insula, which increased in RBD‐DAT+, and was present in patients with Parkinson's disease and dementia with Lewy bodies. Longitudinal cox regression analyses revealed a higher risk of phenoconversion in individuals with iRBD and insular monoaminergic deficits [HR = 3.387; CI 95%: 1.18–10.27]. Interpretation: In this study, altered insular monoaminergic binding in iRBD was associated with phenoconversion to DLB or PD. These findings may provide a helpful stratification approach for future pharmacological or non‐pharmacological interventions. [ABSTRACT FROM AUTHOR]

Impaired numerosity perception in developmental dyscalculia (low "number acuity") has been interpreted as evidence of reduced representational precision in the neurocognitive system supporting non‐symbolic number sense. However, recent studies suggest that poor numerosity judgments might stem from stronger interference from non‐numerical visual information, in line with alternative accounts that highlight impairments in executive functions and visuospatial abilities in the etiology of dyscalculia. To resolve this debate, we used a psychophysical method designed to disentangle the contribution of numerical and non‐numerical features to explicit numerosity judgments in a dot comparison task and we assessed the relative saliency of numerosity in a spontaneous categorization task. Children with dyscalculia were compared to control children with average mathematical skills matched for age, IQ, and visuospatial memory. In the comparison task, the lower accuracy of dyscalculics compared to controls was linked to weaker encoding of numerosity, but not to the strength of non‐numerical biases. Similarly, in the spontaneous categorization task, children with dyscalculia showed a weaker number‐based categorization compared to the control group, with no evidence of a stronger influence of non‐numerical information on category choice. Simulations with a neurocomputational model of numerosity perception showed that the reduction of representational resources affected the progressive refinement of number acuity, with little effect on non‐numerical bias in numerosity judgments. Together, these results suggest that impaired numerosity perception in dyscalculia cannot be explained by increased interference from non‐numerical visual cues, thereby supporting the hypothesis of a core number sense deficit. Research Highlights: A strongly debated issue is whether impaired numerosity perception in dyscalculia stems from a deficit in number sense or from poor executive and visuospatial functions.Dyscalculic children show reduced precision in visual numerosity judgments and weaker number‐based spontaneous categorization, but no increasing reliance on continuous visual properties.Simulations with deep neural networks demonstrate that reduced neural/computational resources affect the developmental trajectory of number acuity and account for impaired numerosity judgments.Our findings show that weaker number acuity in developmental dyscalculia is not necessarily related to increased interference from non‐numerical visual cues. [ABSTRACT FROM AUTHOR]

Corporate sustainability is a multifaceted concept with different definitions and measures proposed by the literature and the standards. This study aims to develop and validate a scale of corporate sustainability implementation that can face the complexity and multidimensionality of the concept. Specifically, the scale was designed around four dimensions (governance, prosperity, planet, and people), a three‐level structure, and a formative approach. The scale validation process entailed the engagement of experts, a survey of 303 Italian firms, and a case study application. The findings highlight the nature of the third‐order construct of sustainability implementation and the relevance of adding the governance dimensions to the most spread triple bottom line approach. As a theoretical contribution, this study argues that the missed recognition of these features could originate differences in previous sustainability measures. Further studies would apply the scale to measure firm sustainability in different contexts and in relationship with relevant drivers and outcomes. [ABSTRACT FROM AUTHOR]

Anthracyclines' cardiotoxicity involves an accelerated generation of reactive oxygen species. This oxidative damage has been found to accelerate the expression of hexose-6P-dehydrogenase (H6PD), that channels glucose-6-phosphate (G6P) through the pentose phosphate pathway (PPP) confined within the endoplasmic/sarcoplasmic reticulum (SR). To verify the role of SR-PPP in the defense mechanisms activated by doxorubicin (DXR) in cardiomyocytes, we tested the effect of this drug in H6PD knockout mice (H6PD−/−). Twenty-eight wildtype (WT) and 32 H6PD−/− mice were divided into four groups to be treated with intraperitoneal administration of saline (untreated) or DXR (8 mg/Kg once a week for 3 weeks). One week thereafter, survivors underwent imaging of 18F-deoxyglucose (FDG) uptake and were sacrificed to evaluate the levels of H6PD, glucose-6P-dehydrogenase (G6PD), G6P transporter (G6PT), and malondialdehyde. The mRNA levels of SR Ca2+-ATPase 2 (Serca2) and ryanodine receptors 2 (RyR2) were evaluated and complemented with Hematoxylin/Eosin staining and transmission electron microscopy. During the treatment period, 1/14 DXR-WT and 12/18 DXR-H6PD−/− died. At microPET, DXR-H6PD−/− survivors displayed an increase in left ventricular size (p < 0.001) coupled with a decreased urinary output, suggesting a severe hemodynamic impairment. At ex vivo analysis, H6PD−/− condition was associated with an oxidative damage independent of treatment type. DXR increased H6PD expression only in WT mice, while G6PT abundance increased in both groups, mismatching a generalized decrease of G6PD levels. Switching-off SR-PPP impaired reticular accumulation of Ca2+ decelerating Serca2 expression and upregulating RyR2 mRNA level. It thus altered mitochondrial ultrastructure eventually resulting in a cardiomyocyte loss. The recognized vulnerability of SR to the anthracycline oxidative damage is counterbalanced by an acceleration of G6P flux through a PPP confined within the reticular lumen. The interplay of SR-PPP with the intracellular Ca2+ exchanges regulators in cardiomyocytes configure the reticular PPP as a potential new target for strategies aimed to decrease anthracycline toxicity. [ABSTRACT FROM AUTHOR]

Glycogen storage disease (GSD) is the most prevalent inherited disorder of glycogen metabolism for which no causal treatment is available. In recent years, thanks to the improved clinical management, the life expectancy of these patients extended, disclosing previously unidentified adverse conditions in other organs. In this study, we evaluated the clinical bone complications and the cellular responses in 20 patients (aged 14.1 ± 3.4 years) affected by GSD type I. Fragility fractures were reported in 35% of the patients, which were older than unfractured patients. They involved appendicular skeletal segments, while no vertebral deformity was detected. 60% of the patients had a bone mineral density (BMD) "below the expected range for age", and lumbar spine (LS) BMD Z-scores positively correlated with muscle strength. Circulating mineral and bone markers showed reduction in the older subjects, with no increase in the pubertal age. Significant correlations could not be detected between circulating markers and LS BMD Z-scores, except for sclerostin levels, which also correlated with muscle strength. The osteoclasts differentiated from patients' peripheral blood mononuclear cells did not show cell-autonomous alterations. However, circulating osteoclast precursors from healthy individuals cultured in the presence of patients' sera exhibited increased osteoclastogenesis compared to control sera suggesting that GSD type I serum factors could affect osteoclast function in a non-autonomous manner. In contrast, circulating osteoprogenitors were unremarkable. [ABSTRACT FROM AUTHOR]

The Dominican Republic, like other economically developing countries, has begun to shift national focus away from food security to concentrate on improving food safety and nutrition. The government of the Dominican Republic has promoted and implemented measures aimed at eradicating poverty and malnutrition and reducing the diseases that are a direct consequence of nutritional deficiencies. However, between 2013 and 2018, the Dominican Republic reported approximately 23,000 cases of foodborne illness annually. Additionally, the number of annual cases of acute diarrhea has increased to approximately 80,000 cases per year with a mortality rate (per 100,000 inhabitants) between 5.98 and 6.94. While the etiological agents responsible for these cases are often not identified, foodborne pathogens including Shigella, E. coli, Klebsiella pneumoniae, Salmonella, and Campylobacter have been isolated from food exported from the Dominican Republic as well as locally consumed foods. This review describes the status of food safety in the Dominican Republic. The review focuses on what is known regarding the etiological agents involved in foodborne disease outbreaks in the country, the impact of foodborne disease, measures the Dominican Republic government has taken to ensure the safety of both exported foods and foods consumed locally, barriers to improving food safety, as well as current and emerging food safety challenges. [ABSTRACT FROM AUTHOR]

Primary ovarian insufficiency (POI) is a disorder of insufficient ovarian follicle function before the age of 40 years with an estimated prevalence of 3.7% worldwide. Its relevance is emerging due to the increasing number of women desiring conception late or beyond the third decade of their lives. POI clinical presentation is extremely heterogeneous with a possible exordium as primary amenorrhea due to ovarian dysgenesis or with a secondary amenorrhea due to different congenital or acquired abnormalities. POI significantly impacts non only on the fertility prospect of the affected women but also on their general, psychological, sexual quality of life, and, furthermore, on their long-term bone, cardiovascular, and cognitive health. In several cases the underlying cause of POI remains unknown and, thus, these forms are still classified as idiopathic. However, we now know the age of menopause is an inheritable trait and POI has a strong genetic background. This is confirmed by the existence of several candidate genes, experimental and natural models. The most common genetic contributors to POI are the X chromosome-linked defects. Moreover, the variable expressivity of POI defect suggests it can be considered as a multifactorial or oligogenic defect. Here, we present an updated review on clinical findings and on the principal X-linked and autosomal genes involved in syndromic and non-syndromic forms of POI. We also provide current information on the management of the premature hypoestrogenic state as well as on fertility preservation in subjects at risk of POI. [ABSTRACT FROM AUTHOR]

Introduction: Vaginal delivery can cause genital tract trauma and lacerations of different severity. This study aims to establish if routinary use of Ritgen's maneuver decreases the prevalence and severity of perineal lacerations compared to the traditional manual perineal protection (MPP). Methods: This prospective case-control study was conducted in the labor ward of Fondazione Policlinico A. Gemelli, Rome, Italy. One hundred sixteen women who met inclusion criteria were included. The study group (n=58) consisted of women who were assisted using the Ritgen maneuver, whereas the women who gave birth immediately afterward were selected as the control group (n=58). All information was retrieved through electronic medical records. Results: In all, 22% women of the study group reported no perineal lacerations compared with 5% of the control group (p=0.007). Regarding the degree of lacerations, the study group exhibited more first-degree lacerations and fewer second-degree lacerations, while the control group exhibited the opposite trend. Among women who received epidural analgesia, 24% of the study group did not experience perineal lacerations, compared to 4.5% of the control (OR=0.15; 95% CI: 0.03–0.72; p=0.008). Similarly, 23.4% of cases in the study group with oxytocin-enhanced labor, experienced no perineal trauma while none in the control group had no perineal trauma in cases of oxytocin augmentation (p=0.005). Conclusions: Our results suggest that using Ritgen's maneuver in childbirth care may reduce the incidence and severity of perineal lacerations, even in the presence of known risk factors for perineal lacerations such as oxytocin augmentation and epidural analgesia. [ABSTRACT FROM AUTHOR]

The characteristic expansion of T CD38high/HLA‐DR+CD8+ lymphocytes observed in hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) proved able to distinguish HLH/MAS from sepsis and systemic juvenile idiopathic arthritis. However, the performance of this marker in differentiating HLH/MAS from other pediatric febrile conditions with similar clinical onset and yet entirely different treatments remains unexplored. CD38high/HLA‐DR+CD8+ frequencies measured in the peripheral fresh blood of pediatric patients attended for suspicion of HLH/MAS were retrospectively recorded and clinical characteristics were retrieved. CD38high/HLA‐DR+CD8+ frequencies in HLH/MAS patients (15 patients; median: 22.0%, IQR: 11.0–49.0%) were compared with those who presented febrile conditions other‐than‐HLH (28 patients; median: 13.0%, IQR: 3.9–28.7%; p = 0.24). HLH and non‐HLH patients were subsequently regrouped based on the presence of an identified infection (22 patients; median: 27.0%, IQR: 15.2‐72.1%) and compared with those without infections (21 patients; median: 7.6%, IQR: 3.7–24.3%; p = 0.0035). CD38high/HLA‐DR+CD8+ percentages were significantly higher only in the infection group compared with the noninfection one, with a patent pathogen‐specific expansion in Epstein–Barr virus primoinfection and visceral leishmaniasis regardless of the presence of HLH. CD38high/HLA‐DR+CD8+ frequencies do not appear as an HLH‐specific marker as they naturally expand in other clinical situations that are common in childhood and may mimic HLH initial presentation. [ABSTRACT FROM AUTHOR]

Restaurants have been becoming increasingly aware of their responsibilities and impact; however, literature on corporate social responsibility has mainly applied quantitative methods to analyze the environmental dimension of sustainability. By drawing on the stakeholder theory approach (normative vs. instrumental) and through a qualitative narrative method based on the analysis of 41 open interviews, this study aims to evaluate which stakeholders are engaged in restaurant‐related CSR practices and the nature of the relationship that ties them together. The results show that although a normative approach is more common, both approaches coexist in many cases. The emergence of multisided collaboration and a double approach enables achieving sustainability issues outside a strictly instrumental logic. This study contributes to the scant literature on CSR in restaurants by analyzing a wider set of stakeholders engaged in sustainability practices and indicating which practices are common and why and how stakeholders are involved. [ABSTRACT FROM AUTHOR]

Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene. Despite advancements in research, no cure exists due to an incomplete understanding of the molecular effects of MeCP2 deficiency. Previous studies have identified impaired tropomyosin receptor kinase (Trk) neurotrophin (NTP) signaling and mitochondrial redox imbalances as key drivers of the pathology. Moreover, altered glycosphingolipid metabolism has been reported in RTT. GM1 ganglioside is a known regulator of the nervous system, and growing evidence indicates its importance in maintaining neuronal homeostasis via its oligosaccharide chain, coded as GM1-OS. GM1-OS directly interacts with the Trk receptors on the cell surface, triggering neurotrophic and neuroprotective pathways in neurons. In this study, we demonstrate that GM1-OS ameliorates RTT deficits in the Mecp2-null model. GM1-OS restored synaptogenesis and reduced mitochondrial oxidative stress of Mecp2-knock-out (ko) cortical neurons. When administered in vivo, GM1-OS mitigated RTT-like symptoms. Our findings indicate that GM1-OS effects were mediated by Trk receptor activation on the neuron's plasma membrane. Overall, our results highlight GM1-OS as a promising candidate for RTT treatment. [ABSTRACT FROM AUTHOR]

In the construction area, as well as in the restoration of old and historical buildings, different metallic materials are frequently in contact with gypsum plaster. Due to the high porosity of gypsum plaster, and particularly in high relative humidity environments, the risk of corrosion exists. In the present work, carbon, galvanized and stainless steel, as well as copper, were embedded in gypsum plaster (with varying water/gypsum ratios) and exposed to different environmental conditions, and the corrosion rate was assessed by electrochemical techniques. Stainless steel showed very low corrosion rates, carbon and galvanized steel showed considerable corrosion rates, and copper showed moderate corrosion rates. The higher the humidity, the higher the corrosion rate, independently of the water/gypsum ratio. A comparison with results obtained for the same materials embedded in mortar was performed. Except for stainless steel, the corrosion rates obtained in gypsum are higher than those obtained in mortar, being this difference up to two orders of magnitude. The differences in the pH of both matrices explained the lower corrosion rates measured in mortar. [ABSTRACT FROM AUTHOR]

In nature, germination of orchid seeds and early plant development rely on a symbiotic association with orchid mycorrhizal (ORM) fungi. These fungi provide the host with the necessary nutrients and facilitate the transition from embryos to protocorms. Despite recent advances in omics technologies, our understanding of this symbiosis remains limited, particularly during the initial stages of the interaction. To address this gap, we employed transcriptomics and metabolomics to investigate the early responses occurring in the mycorrhizal fungus Tulasnella sp. isolate SV6 when co-cultivated with orchid seeds of Serapias vomeracea. The integration of data from gene expression and metabolite profiling revealed the activation of some fungal signalling pathways before the establishment of the symbiosis. Prior to seed contact, an indole-related metabolite was produced by the fungus, and significant changes in the fungal lipid profile occurred throughout the symbiotic process. Additionally, the expression of plant cell wall-degrading enzymes (PCWDEs) was observed during the pre-symbiotic stage, as the fungus approached the seeds, along with changes in amino acid metabolism. Thus, the dual-omics approach employed in this study yielded novel insights into the symbiotic relationship between orchids and ORM fungi and suggest that the ORM fungus responds to the presence of the orchid seeds prior to contact. [ABSTRACT FROM AUTHOR]

The "Left Perceptual Bias" (LPB) is the effect for which the left side of a picture such as a face is used to a greater extent than its right side as shown in a wide variety of experimental tasks. This effect has been observed for faces, body parts and objects. The present work investigated the presence of a LPB in recognizing hand gestures in two experiments. The role of the side of stimuli presentation (left /right), stimuli orientation (palm/back), participants' handedness and gender were analyzed. Participants were presented with images of meaningless gestures performed by an actor with the right or left hand, from a palm or a back view. Immediately afterward, participants were shown a drawing and had to discriminate whether it represented the same gesture or not. In the first experiment, the task was administered to a sample of right-handed participants, half males. Results showed shorter response times for stimuli presented on the left side and for those shown from the palm. No gender differences were observed. The second experiment included a sample of left-handed participants and the LPB was replicated. Taken together, our results suggest an interpretation of the bias in terms of asymmetries in perceptual processing rather than the involvement of motor representations. [ABSTRACT FROM AUTHOR]

Background: In Italy, knee osteoarthritis (KOA) accounts for over 5 million prevalent cases and requires long-term multidisciplinary management. The most frequent KOA symptom is pain. The aim of the survey is to provide a national overview of the current management of moderate-to-severe pain associated with KOA from both clinicians' and patients' perspectives. Methods: An exploratory qualitative survey was conducted in Italy between July and October 2023. The survey participants were members of four national scientific societies and two patient associations who were invited to participate via email and given an online questionnaire. Questions included a mix of single and multiple responses and scalar items. Results: In total, 1473 clinicians and 150 patients with KOA completed the questionnaire. Patients rated knee pain as both the most burdensome symptom and the most frequent reason for treatment dissatisfaction and seeking consultation. One in two patients declared that they were unsatisfied/little satisfied with the current prescribed analgesic treatments. The clinicians surveyed preferentially prescribed intra-articular hyaluronic acid, oral non-steroidal anti-inflammatory drugs/paracetamol, non-pharmacological intervention, and intra-articular corticosteroids. The clinicians' selection of analgesic therapy often failed to adequately meet patients' expectations for pain relief. Conclusions: Our findings highlight the current unmet needs of patients with KOA in Italy and call for new approaches to effectively optimize the management of KOA-associated pain. [ABSTRACT FROM AUTHOR]

During storage, infestation by insect pests occurs, causing quantitative and qualitative losses in grains, which requires the control of these insects with phosphine gas. Rice husk has a high phosphine adsorption capacity, influencing the gas concentration during fumigation and potentially leading to inefficient fumigation. Additionally, the high sorption of rice husk results in a higher residue of phosphine in the grain. Therefore, the objective of this study was to evaluate the phosphine sorption and phosphine residue in rice husk, paddy rice, and brown rice, as well as the industrial quality (head rice yield, rehydration capacity, cooking time, colorimetric profile) of brown and white rice during storage. To achieve this, fumigation of paddy rice, brown rice, and rice husks with 3.0 g·m−3 of phosphine was carried out for 240 h (recommended duration in the industry). A high sorption rate was observed in the rice husk (94.77%), paddy rice (97.61%), and, lastly, brown rice (35.17%). Due to the high sorption rate, only brown rice maintained a concentration above the recommended level for effective pest control (400 ppm for 120 h). Higher phosphine residues than permitted were observed in the rice husk (0.25 ppm). Lower rice head yields were observed in non-fumigated rice samples when analyzing the brown rice samples (66.21% for paddy rice and 65.01% for brown rice). A greater rehydration capacity was observed in fumigated samples at the beginning of storage when analyzing the brown rice samples (1.21 for paddy rice, 1.23 for brown rice), reducing the cooking time (24.00 for paddy rice, 23.80 for brown rice). More studies should be carried out to evaluate the effectiveness of fumigation on paddy rice, considering the high sorption rate of the paddy. [ABSTRACT FROM AUTHOR]

Primary ovarian insufficiency (POI) is a disorder of insufficient ovarian follicle function before the age of 40 years with an estimated prevalence of 3.7% worldwide. Its relevance is emerging due to the increasing number of women desiring conception late or beyond the third decade of their lives. POI clinical presentation is extremely heterogeneous with a possible exordium as primary amenorrhea due to ovarian dysgenesis or with a secondary amenorrhea due to different congenital or acquired abnormalities. POI significantly impacts non only on the fertility prospect of the affected women but also on their general, psychological, sexual quality of life, and, furthermore, on their long-term bone, cardiovascular, and cognitive health. In several cases the underlying cause of POI remains unknown and, thus, these forms are still classified as idiopathic. However, we now know the age of menopause is an inheritable trait and POI has a strong genetic background. This is confirmed by the existence of several candidate genes, experimental and natural models. The most common genetic contributors to POI are the X chromosome-linked defects. Moreover, the variable expressivity of POI defect suggests it can be considered as a multifactorial or oligogenic defect. Here, we present an updated review on clinical findings and on the principal X-linked and autosomal genes involved in syndromic and non-syndromic forms of POI. We also provide current information on the management of the premature hypoestrogenic state as well as on fertility preservation in subjects at risk of POI. [ABSTRACT FROM AUTHOR]

Background : Current treatments for mental disorders, like pharmacotherapy or psychological approaches, do not lead to full remission in all individuals. Physical activity (PA) is effective at improving psycho-physical health in major depressive and anxiety disorders. However, the efficacy of PA as an adjunctive treatment for borderline personality disorder (BPD) has not been studied. To date, there are no approved pharmacological treatments for this severe condition and limited accessibility to effective psychotherapeutic interventions. This study tests the efficacy of a structured PA programme as an additional treatment for BPD outpatients. Methods: The PABORD is a randomised controlled trial for female outpatients (18–40 years) with a BPD diagnosis. The intervention group (n = 32) will participate in a 12-week structured PA programme supervised by a sport medicine physician and preceded by three psychoeducation sessions on healthy eating habits. The control group (n = 32) will receive a 12-week psychoeducation programme on PA, diet, and health risks of a sedentary lifestyle for a total of 8 sessions. The study aims to determine if the PA intervention is superior to the control in reducing BPD symptoms. Secondary aims include improving PA levels and physical and psychological health. Assessments will be conducted at baseline, post-intervention, and 3 months post-intervention. Discussion: The structured PA programme is expected to outperform the control group in terms of health and PA outcomes at the end of the intervention. Repeated assessments will also help to identify psychosocial factors that influence PA maintenance. Findings will support the potential widespread implementation of PA programmes for BPD treatment. Trial registration: ClinicalTrials.gov NCT06461104. Registered on 6 June 2024 {2a}. [ABSTRACT FROM AUTHOR]

Aim: A workshop on concordance and oral hygiene was held in February 2024. To address the topic, a systematic review aimed at investigating the effectiveness of motivational interventions in improving oral hygiene and focusing on periodontal clinical indices outcomes was designed. Materials and Methods: A comprehensive literature search was conducted across PubMed and Scopus electronic databases to identify relevant articles published up to 2024. Inclusion criteria encompassed studies comparing motivational interventions targeting oral hygiene behaviours, with a focus on periodontal clinical indices. Twelve articles meeting the eligibility criteria were selected for analysis. Quality assessment and data extraction were performed systematically. Results: The synthesis of findings from the selected studies revealed a consistent positive effect of motivational interventions on periodontal clinical indices. These interventions encompassed various strategies, including educational sessions, personalized feedback and motivational interviewing. Improvement in indices such as plaque index (PI), gingival index (GI) and periodontal probing depth was observed following motivational interventions, despite the variety of motivational protocols employed. Conclusion: Motivational interventions are effective in enhancing oral hygiene practices and improving periodontal clinical indices. Tailored motivational approaches can serve as valuable tools in promoting oral health behaviours among individuals, potentially reducing the risk of periodontal diseases. Further research is warranted to explore the long‐term sustainability and scalability of motivational interventions in diverse populations and settings. [ABSTRACT FROM AUTHOR]

Primary ovarian insufficiency (POI) is a disorder of insufficient ovarian follicle function before the age of 40 years with an estimated prevalence of 3.7% worldwide. Its relevance is emerging due to the increasing number of women desiring conception late or beyond the third decade of their lives. POI clinical presentation is extremely heterogeneous with a possible exordium as primary amenorrhea due to ovarian dysgenesis or with a secondary amenorrhea due to different congenital or acquired abnormalities. POI significantly impacts non only on the fertility prospect of the affected women but also on their general, psychological, sexual quality of life, and, furthermore, on their long-term bone, cardiovascular, and cognitive health. In several cases the underlying cause of POI remains unknown and, thus, these forms are still classified as idiopathic. However, we now know the age of menopause is an inheritable trait and POI has a strong genetic background. This is confirmed by the existence of several candidate genes, experimental and natural models. The most common genetic contributors to POI are the X chromosome-linked defects. Moreover, the variable expressivity of POI defect suggests it can be considered as a multifactorial or oligogenic defect. Here, we present an updated review on clinical findings and on the principal X-linked and autosomal genes involved in syndromic and non-syndromic forms of POI. We also provide current information on the management of the premature hypoestrogenic state as well as on fertility preservation in subjects at risk of POI. [ABSTRACT FROM AUTHOR]

The present work investigates whether financial abilities can be associated with numerical abilities and with general cognitive abilities. We compared performance on numerical and financial tests, and on tests routinely used to measure general cognitive performance, in healthy controls and in a group of people with heterogeneous pathological conditions including mild cognitive impairment, amyotrophic lateral sclerosis, traumatic brain injury, and schizophrenia. Patients showed lower performances in both numerical and financial abilities compared to controls. Numerical and financial skills were positively correlated in both groups, but they correlated poorly with measures of general cognitive functioning. Crucially, only basic financial tasks -such as counting currencies- but not advanced ones -like financial judgments- were associated with numerical or general cognitive functioning in logistic regression analyses. Conversely, advanced financial abilities, but not basic ones, were associated with abstract reasoning. At a qualitative analysis, we found that deficits in numerical and financial abilities might double dissociate. Similarly, we observed double dissociations between difficulties in financial abilities and cognitive deficits. In conclusion, financial abilities may be independent of numerical skills, and financial deficits are not always related to the presence of cognitive difficulties. These findings are important for both clinical and legal practice. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess whether quantitative susceptibility imaging (QSM)-based measures of iron accumulation in the cerebellum predict cognitive and behavioral features in non-demented amyotrophic lateral sclerosis (ALS) patients. Methods: A total of ALS patients underwent 3-T MRI and a clinical assessment using the ALS Functional Rating Scale-Revised (ALSFRS-R) and the Edinburgh Cognitive and Behavioural ALS Screen (ECAS). Regression models were applied to each subscale of the cognitive section of the ECAS and the ECASCarer Interview to examine the effect of QSM-based measures in white and gray matter (WM; GM) of the cerebellum, separately for right, left, and bilateral cerebellar regions of interest (ROIs). These effects were compared to those of cerebellar volumetrics in WM/GM, right and left hemispheres while controlling for demographics, disease status, and total intracranial volume. Results: Higher QSM measures of the cerebellar GM on the left, right, and bilateral sides significantly predicted (ps = 0.003) a greater number of errors on the executive functioning (EF) subscale of the ECAS (ECAS-EF). Moreover, higher GM-related, QSM measures of the cerebellum were associated with an increased probability of a below-cut-off performance on the ECAS-EF (ps = 0.024). No significant effects were observed for QSM measures of the cerebellar WM or for volumetric measures on the ECAS-EF. Other ECAS measures showed no significant effects. Bilateral QSM measures of the cerebellar GM also selectively predicted performance on backward digit span and social cognition tasks. Discussion: Iron accumulation within the cerebellar GM, particularly in the cerebellar cortices, may be associated with executive functioning deficits in nondemented ALS patients. Therefore, QSM-based measures could be useful for identifying the neural correlates of extra-motor cognitive deficits in ALS patients. [ABSTRACT FROM AUTHOR]

This document summarizes a study on the effects of CFTR modulators on patients with cystic fibrosis (CF) and leukocyte adhesion deficiency type IV (LAD-IV). The study found that CFTR modulators improved certain cellular functions in CF patients, suggesting that they may correct both CF and LAD-IV phenotypes. However, there were some patients who showed improvement in CF symptoms but not in LAD-IV characteristics, indicating the need for further research. The study also suggests that measuring certain cellular markers could be a useful method for monitoring patients in the long term. [Extracted from the article]

We conducted a comprehensive umbrella review including all published meta-analyses and systematic reviews on suicide-related outcomes among adults in custody. Eligible studies were searched for in major scientific databases following the PRISMA method up to February 2023. The quality of each study was assessed using the AMSTAR-2 protocol. Twenty studies were included, consisting of 11 meta-analyses and nine systematic reviews. Factors associated with suicide outcomes among individuals in custody were categorized into five domains: clinical status, historical, custodial, criminological, and prevention. However, all systematic studies reported considerable heterogeneity (I2 > 50%–85%). Most systematic literature reviews and/or meta-analyses showed moderate quality based on AMSTAR-2. This umbrella review highlights individual factors (in the clinical status and historical domain), contextual factors (in the custodial and criminological domains), and protective factors (in the prevention domain) to provide a clearer understanding of the prison-related domains involved in the development and maintenance of suicide-related outcomes. [ABSTRACT FROM AUTHOR]

Introduction: In recent years, significant progress has been made in treatment strategies for intermediate-stage hepatocellular carcinoma (HCC), which is a highly heterogeneous patient population requiring tailored therapies based on tumor characteristics. Methods: We conducted a comprehensive review of treatment approaches for intermediate-stage HCC, highlighting the evolution of treatment options over time. While chemoembolization remains the standard therapy for many patients, it has advanced to include combinations with systemic therapies, known as combination therapy, which is becoming the new standard of care for this group. Conclusion: Based on our clinical and research experience, combination therapy is increasingly recognized as the preferred first-line treatment for intermediate-stage HCC patients. This approach allows most patients to be candidates for subsequent curative-intent treatments, while a smaller number will require palliative care. [ABSTRACT FROM AUTHOR]

Human leishmaniasis is facing important epidemiological changes in Southern Europe, driven by increased urbanization, climate changes, emerging of new animal reservoirs, shifts in human behavior and a growing population of immunocompromised and elderly individuals. In this evolving epidemiological landscape, we analyzed the clinical and epidemiological characteristics of human leishmaniasis in the Tuscany region of Central Italy. Through a multicentric retrospective analysis, we collected clinical and demographic data about all cases of leishmaniasis recorded between 2018 and 2023. We observed 176 cases of human leishmaniasis, with 128 (72.7%) visceral leishmaniasis (VL) and 47 (26.7%) cutaneous leishmaniasis (CL). Among these, 92.2% of VL and 85.1% of CL cases were autochthonous. The cumulative incidence of autochthonous human leishmaniasis was 0.22 cases per 100,000 inhabitants in 2018, but reached 1.81/100,000 in 2023. We identified three main areas of transmission: around the city of Florence (North-East Tuscany), around Grosseto city (South-West Tuscany) and Elba Island. Our findings confirm that the epidemiology of leishmaniasis is undergoing significant changes in Central Italy. Awareness towards this emerging health threat and surveillance strategies need to be improved in order to reliably assess the disease's burden. Further research is needed in a "One-Health" perspective, to clarify the epidemiological dynamics at the environmental, reservoir, vector and human levels. The role of climate change and specific climatic factors affecting the epidemiological patterns of human leishmaniasis should be assessed. Further knowledge in these fields would promote targeted control and prevention strategies at regional and national levels. [ABSTRACT FROM AUTHOR]

L. donovani and L. infantum infections are associated with a broad clinical spectrum, ranging from asymptomatic cases to visceral leishmaniasis (VL) with high mortality rates. Clinical manifestations such as post-kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis-associated hemophagocytic lymphohistiocytosis-mimic (VL-associated HLH-mimic) further contribute to the diversity of clinical manifestations. These clinical variations are intricately influenced by the complex interplay between the host's immune response and the parasite's escape mechanisms. This narrative review aims to elucidate the underlying immunological mechanisms associated with each clinical manifestation, drawing from published literature within the last 5 years. Specific attention is directed toward viscerotropic Leishmania sinfection in patients with inborn errors of immunity and acquired immunodeficiencies. In VL, parasites exploit various immune evasion mechanisms, including immune checkpoints, leading to a predominantly anti-inflammatory environment that favors parasite survival. Conversely, nearly 70% of individuals are capable of mounting an effective pro-inflammatory immune response, forming granulomas that contain the parasites. Despite this, some patients may experience reactivation of the disease upon immunosuppression, challenging current understandings of parasite eradication. Individuals living with HIV and those with inborn errors of immunity present a more severe course of infection, often with higher relapse rates. Therefore, it is crucial to exclude both primary and acquired immune deficiencies in patients presenting disease relapse and VL-associated HLH-mimic. The distinction between VL and HLH can be challenging due to clinical similarities, suggesting that the nosological entity known as VL-associated HLH may represent a severe presentation of symptomatic VL and it should be considered more accurate referring to this condition as VL-associated HLH-mimic. Consequently, excluding VL in patients presenting with HLH is essential, as appropriate antimicrobial therapy can reverse immune dysregulation. A comprehensive understanding of the immune-host interaction underlying Leishmania infection is crucial for formulating effective treatment and preventive strategies to mitigate the disease burden. [ABSTRACT FROM AUTHOR]

Mycoplasma hominis can be a part of human urogenital tract microbiome, and it is a frequent cause of urogenital infections. In rare cases, it can also cause extragenital infections, especially in immunocompromised patients. In this case series, we report two cases and provide a literature review of extragenital infections caused by M. hominis in patients with hypogammaglobulinemia. Patient 1 was a 61-year-old woman with diffuse large B-cell lymphoma who, after rituximab-containing chemotherapy and CAR-T therapy, developed M. hominis spondylodiscitis. Patient 2 was a 50-year-old woman with congenital hypogammaglobulinemia who developed disseminated M. hominis infection involving pleura, muscles, and right ankle. Antibiotic therapy with levofloxacin and doxycycline for 10 weeks in patient 1 and with levofloxacin alone for 6 weeks in patient 2 led to infection resolution. The literature review identified 14 additional cases reporting M. hominis extragenital infection in patients with hypogammaglobulinemia. M. hominis should also be suspected as an etiological agent of extragenital infection in patients with B-cell immunodeficiency with a clinical picture of persistent, standard-culture negative infection, particularly with arthritis or abscess formation. Even if M. hominis can grow on standard bacterial medium, in suspected cases molecular methods should be promptly used for correct diagnostic work-up and successful therapy. [ABSTRACT FROM AUTHOR]

Hepatocellular adenomas (HAs) are tumors that can develop under different conditions, including in patients harboring a germline mutation in HNF1A. However, little is known about the pathogenesis of such disease. This work aims to better define what mechanisms lie under the development of this condition. Six HAs were sampled from the liver of a 17-year-old male affected by diabetes and multiple hepatic adenomatosis harboring the heterozygous pathogenic germline variant c.815G>A, p.(Arg272His) in HNF1A, which has a dominant negative effect. All HAs were molecularly characterized. Four of them were shown to harbor a second somatic HNF1A variant and one had a mutation in the ARID1A gene, while no additional somatic changes were found in the remaining HA and normal parenchyma. A transcriptomic profile of the same HA samples was also performed. HNF1A biallelic mutations were associated with the up-regulation of several pathways including the tricarboxylic acid cycle, the metabolism of fatty acids, and mTOR signaling while angiogenesis, endothelial and vascular proliferation, cell migration/adhesion, and immune response were down-regulated. Contrariwise, in the tumor harboring the ARID1A variant, angiogenesis was up-modulated while fatty acid metabolism was down-modulated. Histological analyses confirmed the molecular data. Independently of the second mutation, energetic processes and cholesterol metabolism were up-modulated, while the immune response was down-modulated. This work provides a complete molecular signature of HNF1A-associated HAs, analyzing the association between specific HNF1A variants and the development of HA while identifying potential new therapeutic targets for non-surgical treatment. [ABSTRACT FROM AUTHOR]

To determine when and why a company's apology for a moral transgression might backfire, this study considers a rarely researched cue: exposure of company misconduct by non-governmental organisations (NGOs). In three experimental studies, we demonstrate that after companies' moral transgressions are exposed by NGOs, their apologies exacerbate consumers' negative responses because consumers view the companies as having increased moral and behavioural hypocrisy. Consumers' political orientations moderate the mediating effect of companies' moral hypocrisy as, following exposure by an NGO, conservatives perceive the company issuing an apology to be more deceptive, which is not the case for liberals. Thus, this study expands upon the developing research stream related to the efficacy of apologies as strategic responses to preventable crises. It specifies an underlying mechanism that explains when and why exposure by NGOs causes apologies to backfire and suggests practical guidelines for companies when developing appropriate apologies. [ABSTRACT FROM AUTHOR]

The present randomized study investigated the effect of acute supplementation of 800 mg/kg of ketone monoester ingestion (KE) or placebo (PL) and 210 mg/kg of NaHCO3 co-ingestion on cycling performance of WorldTour cyclists during a road cycling stage simulation. Twenty-eight cyclists participated in the study (27.46 ± 4.32 years; 1.80 ± 0.06 m; 69.74 ± 6.36 kg). Performance, physiological, biochemical, and metabolism outcomes, gut discomfort, and effort perceived were assessed during a road cycling simulation composed of an 8-min time-trial (TT) performance + 30-s TT + 4.5 hr of outdoor cycling + a second 8-min TT + a second 30-s TT. Greater absolute and relative mean power during the first 8-min TT (F = 5.067, p =.033, η p 2 =.163 , F = 5.339, p =.029, η p 2 =.170 , respectively) was observed after KE than after PL (KE: 389 ± 34, PL: 378 ± 44 W, p =.002, d = 0.294 and KE: 5.60 ± 0.42, PL: 5.41 ± 0.44 W/kg, p =.001, d = 0.442). Additionally, greater concentration of β-hydroxybutyrate blood concentration (F = 42.195, p <.001, η p 2 =.619) was observed after KE than after PL during the first steps of the stage (e.g., after warm-up KE: 1.223 ± 0.642, PL: 0.044 ± 0.058 mM, p <.001, d = 2.589), although the concentrations returned to near baseline after 4.5 hr of outdoor cycling. Moreover, higher values of anion gap were observed (F = 2.333, p =.026, η p 2 =.080) after KE than after PL ingestion, after the warm-up and after the first 8-min and 30-s TT. Additionally, lower concentrations of HCO 3 − were reported in the KE condition after warm-up and after the first 8-min and 30-s TT. During the initial phase of the stage simulation, acute supplementation with KE + NaHCO3 co-ingestion enhanced 8-min TT cycling performance (3.1%) in WorldTour cyclists with a concomitant hyperketonaemia. [ABSTRACT FROM AUTHOR]

The community restrictions during the coronavirus disease 2019 pandemic adversely impacted older adults' physical activity levels. This convergent mixed-method study assessed the adaptation of the Recreovía, a community-based physical activity program in Bogotá, and characterized physical activity levels among older adult participants. Our results showed how the Recreovía adapted during the pandemic to continue promoting physical activity, through indoor and outdoor strategies, including virtual physical activity sessions and safety protocols. During this time, 72%–79% of the older adults attending the adapted program were physically active. A greater proportion of park users (84.2%) and more people involved in vigorous physical activity were observed during Recreovía days. Older adults had positive experiences and perceptions of the Recreovía program related to their health and social well-being. Even though the older adults prefer being outdoors, the adapted program allowed participants to continue with their physical activity routines as much as possible during the pandemic. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) features KRAS mutations in approximately 90% of human cases and excessive stromal response, termed desmoplastic reaction. Oncogenic KRAS drives pancreatic carcinogenesis by acting on both epithelial cells and tumor microenvironment (TME). We have previously shown that Homeodomain-Interacting Protein Kinase 2 (HIPK2) cooperates with KRAS in sustaining ERK1/2 phosphorylation in human colorectal cancers. Here, we investigated whether HIPK2 contributes to oncogenic KRAS-driven tumorigenesis in vivo, in the onset of pancreatic cancer. Methods: We employed an extensively characterized model of KRASG12D-dependent preinvasive PDAC, the Pdx1-Cre;LSL-KRasG12D/+ (KC) mice. In these mice, HIPK2 was inhibited by genetic knockout in the pancreatic epithelial cells (KCH−/−) or by pharmacologic inactivation with the small molecule 5-IodoTubercidin (5-ITu). The development of preneoplastic acinar-to-ductal metaplasia (ADM), intraepithelial neoplasia (PanIN), and their associated desmoplastic reaction were analyzed. Results: In Hipk2-KO mice (KCH−/−), ERK phosphorylation was lowered, the appearance of ADM was slowed down, and both the number and pathologic grade of PanIN were reduced compared to Hipk2-WT KC mice. The pancreatic lesion phenotype in KCH−/− mice was characterized by abundant collagen fibers and reduced number of αSMA+ and pSTAT3+ desmoplastic cells. These features were reminiscent of the recently described human "deserted" sub-TME, poor in cells, rich in matrix, and associated with tumor differentiation. In contrast, the desmoplastic reaction of KC mice resembled the "reactive" sub-TME, rich in stromal cells and associated with tumor progression. These observations were confirmed by the pharmacologic inhibition of HIPK2 in KC mice. Conclusion: This study demonstrates that HIPK2 inhibition weakens oncogenic KRAS activity and pancreatic tumorigenesis providing a rationale for testing HIPK2 inhibitors to mitigate the incidence of PDAC development in high-risk individuals. [ABSTRACT FROM AUTHOR]

The coffee pulp, a significant by-product of coffee processing, is often discarded but has potential for recycling and high-value uses. This study aimed to investigate the chemical composition of two coffee pulp ingredients, a flour (CPF) and an aqueous extract (CPE), and conducted acute and sub-chronic toxicity assays to determine their safety. The proximate composition revealed the high fiber content of both ingredients; the CPF mainly contained insoluble fiber, while CPE consisted exclusively of soluble pectic polysaccharides. The CPF had higher concentrations of amino acids and a better balance of essential/non-essential amino acids, whereas the CPE exhibited higher concentrations of free amino acids, ensuring higher bioavailability. Both ingredients showed elevated mineral content, while heavy-metal concentrations remained within acceptable limits. This study established the bioactive potential of the CPF and the CPE, demonstrating the high content of caffeine and gallic, protocatechuic, and 4-caffeoylquinic acids. The toxicity studies revealed that the CPF and the CPE exhibited safety when orally administered to mice. Administered doses were non-toxic, as they did not induce lethality or adverse effects in the mice or produce significant histopathological or biochemical adverse changes. This study represents a first step in valorizing the CPF and the CPE as safe novel food ingredients with health benefits for functional and nutritional foods. [ABSTRACT FROM AUTHOR]