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The WNT1 gene is crucial for bone development and homeostasis. Homozygous mutations in WNT1 cause severe bone fragility known as osteogenesis imperfecta type XV. Moreover, heterozygous WNT1 mutations have been found in adults with early-onset osteoporosis. We identified a 35 year-old Caucasian woman who experienced multiple vertebral fractures two months after her second pregnancy. There was no history of risk factors for secondary osteoporosis or family history of osteoporosis. Dual-energy X-ray absorptiometry confirmed a marked reduction of bone mineral density (BMD) at the lumbar spine (0.734 g/cm2, Z-score -2.8), femoral neck (0.48 g/cm2, Z-score -3.5), and total hip (0.589 g/cm2, Z-score -3.0). Blood tests excluded secondary causes of bone fragility. Genetic analysis revealed a heterozygous missense mutation (p.Leu370Val) in the WNT1 gene. Varsome classified it as a variant of uncertain significance. However, the fact that the Leucine residue at position 370 is highly conserved among vertebrate species and the variant has a very low allelic frequency in the general population would exclude the possibility of a polymorphism. The patient was treated for two years with teriparatide therapy associated with calcium and vitamin D supplements. During the follow-up period she did not report further clinical fractures. After 24 months of teriparatide, BMD increased at lumbar spine (+14.6%), femoral neck (+8.3%) and total hip (+4.9%) compared to baseline. We confirm that the heterozygous WNT1 mutation could cause a variable bone fragility and low turnover osteoporosis. We suggest that teriparatide is one of the most appropriate available therapies for this case.

Clozapine is one of the most widely used second-generation antipsychotic drugs (SGAs) for the treatment of schizophrenia. Despite advantages over first-generation drugs, clozapine still shows significant side effects and interindividual variations in efficacy. In order to ensure frequent therapeutic drug monitoring (TDM) and improve the compliance of psychiatric patients undergoing clozapine treatment, two novel dried microsampling approaches based on whole blood and plasma volumetric absorptive microsampling (b-VAMS and p-VAMS) and microfluidic generated-dried blood spot technology (mfDBS) were developed and coupled to HPLC with electrochemical detection (ED). The proposed miniaturized strategies by means of VAMS and microfluidic channel-based devices provide several advantages in terms of collection, storage, and handling compared to classical blood and plasma processing. Satisfactory validation results were obtained for all microsampling platforms, with mean extraction yields >85.1%, precision as relative standard deviation (RSD) < 5.1%, and stability < 4.5% analyte loss after 30 days for p-VAMS; mean extraction yields > 83.4%, precision RSD < 5.4%, and stability < 4.6% analyte loss after 30 days for b-VAMS, and mean extraction yields > 74.0%, precision RSD < 5.6%, and stability < 4.9% analyte loss after 30 days for mfDBS. The original microsampling methodologies have been successfully applied to the blood and plasma collected from five psychiatric patients for the monitoring of the levels of clozapine and its main metabolites, providing robust and reliable quali-quantitative results. Comparisons between results of the two dried microsampling technologies with those obtained by classic fluid plasma analysis were in good agreement and have demonstrated that the proposed miniaturized approaches could be suitable for TDM purposes.

Introduction: The COVID-19 pandemic has compelled a majority of hospital systems to reduce surgical and procedural volumes in an attempt to preserve resources. Elective surgery and procedures resumption has proven to be a calculated risk between COVID-19 exposure and resource depletion and patient morbidity and mortality from surgical deferral. Methods: Within a few days of halting elective surgery and procedures, our 7-hospital (2427 in-patient beds, 26,647 inpatient surgeries) healthcare system developed a multidisciplinary Pivot Plan with the primary outcome of a phased resumption of elective surgery and procedures. The plan entailed the integration of our electronic medical record, order entry automatization, perioperative staff utilization, partnering with primary care providers, and a stepwise COVID-19 testing algorithm based on a predetermined hierarchy of case acuity and timeliness of patient care. Results: The Pivot Plan was instituted on May 10, 2020. Since then, 22,624 patients have been tested for COVID-19 in anticipation of an elective surgery and procedures; 140 (0.62%) tested positive for COVID-19 and had their procedure deferred. As our testing capability has increased, we have been able to increase our added elective surgery and procedures capacity from 13 cases per day to 531 cases per day. In turn, we have seen the case volume increase by 52%. Conclusion: Our academic healthcare system located in one of the initial COVID-19 hotspots in the United States has successfully resumed elective surgery and procedures in part due to a receptive and supportive culture based upon nimbleness, agility, and rapid integration of multiple resources from a cohort of diverse disciplines applied to the perioperative services workflow.

The research proposes to investigate the psychological reasons that may explain women's addiction to smoking during pregnancy and the perception of combustible cigarettes, electronic cigarettes and heated tobacco cigarettes. The sample included 30 participants who smoke or people who previously smoked who chose to quit or continue smoking during pregnancy. The data was gathered via a semi-structured interview and developed from three research questions: feelings, opinions and perceptions of pregnant women toward e-cigarettes, heated tobacco cigarettes, and combustible cigarettes. The study used thematic qualitative analysis for the methodological formulation of the results. The Standards for Reporting Qualitative Research Standards (QRRS) checklist was used. In this qualitative research, three psychological reasons for the onset of smoking were found and analyzed: feelings of stress, nervousness, and loneliness. According to the results: 40.91% of the women who smoked combustible cigarettes decided to keep on smoking and 59.09% decided to quit, 16.67% of participants who use heated tobacco cigarette decided to continue during pregnancy and the remaining 83.33% decide to stop; lastly, there is a condition of fairness for adults who use e-cigarette, 50% decided to continue smoking during pregnancy and the other 50% decided to stop smoking. The data indicate that those who continue to smoke during pregnancy are participants who smoke combustible cigarettes, stating that they reduce the amount of smoke inhaled. Meanwhile, participants who use heated tobacco cigarettes or e-cigarettes are certain that they pose less risk than combustible cigarettes; nevertheless, most of them decide to quit smoking during pregnancy. Another important aspect that has been noted is that of formal abandonment treatments, as quite unexpectedly, there has been a unanimous recognition of strong distrust toward the possible risks to the unborn child. There is a lot of distrust and little knowledge of official smoking cessation therapies, and because of this, participants stated that they can quit smoking whenever they want and only with their own willpower. Five categories and related themes emerged from the thematic analysis, such as reasons for starting with themes such as stress, irritation, loneliness, adolescence and integration; reasons for attachment to topics such as habit and carelessness about one's health; perceptions of traditional cigarettes compared to e-cigarettes and heated cigarettes with related topics such as sensory experiences and side effects; feelings and use of official smoking cessation therapies with issues as willpower and knowledge; information on the effects of smoke during pregnancy and breastfeeding, including risk information. [ABSTRACT FROM AUTHOR]

The long sedimentary sequence of Notarchirico has yielded evidence of one of the earliest Acheulean manifestations in Europe and of recurrent hominin occupation, spanning from the end of the interglacial MIS 17 to the glacial MIS 16 (~695–610 ka). Here, we report the new discovery of a lion, Panthera spelaea, from the site, based on a metatarsal from layer A. This part of the sequence dates to ~660–612 ka (MIS 16, 40Ar/39Ar age). Therefore, Notarchirico's lion represents the earliest confirmed occurrence of the species in southwestern Europe, although older findings are known from adjacent areas. Lions and several other large mammal species dispersed into Europe during the Early–Middle Pleistocene Transition, which also witnessed the spread of the Acheulean. Ecological and behavioural adaptability was probably key, for hominins and other species, to cope with the intense and recurrent environmental fluctuations that occurred during this period. [ABSTRACT FROM AUTHOR]

Background: Cardiac troponin release is related to the cardiomyocyte loss occurring in heart failure (HF). The prognostic role of high-sensitivity cardiac troponin T (hs-cTnT) in several settings of HF is under investigation. The aim of the study is to assess the prognostic role of intrahospital hs-cTnT in patients admitted due to HF. Methods: In this observational, single center, prospective study, patients hospitalized due to HF have been enrolled. Admission, in-hospital peak, and discharge hs-cTnT have been assessed. Patients were followed up for 6 months. Cardiovascular (CV) death, HF hospitalization (HFH), and worsening HF (WHF) (i.e., urgent ambulatory visit/loop diuretics escalation) events have been assessed at 6-month follow up. Results: 253 consecutive patients have been enrolled in the study. The hs-cTnT median values at admission and discharge were 0.031 ng/mL (IQR 0.02–0.078) and 0.031 ng/mL (IQR 0.02–0.077), respectively. The risk of CV death/HFH was higher in patients with admission hs-cTnT values above the median (p = 0.02) and in patients who had an increase in hs-cTnT during hospitalization (p = 0.03). Multivariate Cox regression analysis confirmed that hs-cTnT above the median (OR: 2.06; 95% CI: 1.02–4.1; p = 0.04) and increase in hs-cTnT during hospitalization (OR:1.95; 95%CI: 1.006–3.769; p = 0.04) were predictors of CV death/HFH. In a subgroup analysis of patients with chronic HF, hs-cTnT above the median was associated with increased risk of CV death/HFH (p = 0.03), while in the subgroup of patients with HFmrEF/HFpEF, hs-cTnT above the median was associated with outpatient WHF events (p = 0.03). Conclusions: Inpatient hs-cTnT levels predict CV death/HFH in patients with HF. In particular, in the subgroup of chronic HF patients, hs-cTnT is predictive of CV death/HFH; while in patients with HFmrEF/HFpEF, hs-cTnT predicts WHF events. [ABSTRACT FROM AUTHOR]

Background/Objectives: To date, data regarding the characteristics and management of obstructive, stable coronary artery disease (CAD) encountered in patients undergoing transcatheter aortic valve implantation (TAVI) are sparse. The aim of the study was to analyze granular details, treatment, and outcomes of patients undergoing TAVI with obstructive, stable CAD from real-world practice. Methods: REVASC-TAVI (Management of myocardial REVASCularization in patients undergoing Transcatheter Aortic Valve Implantation with coronary artery disease) is an investigator-initiated, multicenter registry, which collected data from patients undergoing TAVI with obstructive stable CAD found during the pre-TAVI work-up. Results: A total of 2025 patients from 30 centers worldwide with complete follow-up were included in the registry. Most patients had single-vessel CAD (56.1%). An involvement of proximal coronary tracts was detected in 62.5% of cases, with 12.0% of patients having CAD in left main (LM). Most patients received percutaneous coronary intervention (PCI) (n = 1617, 79.9%), especially those with proximal CAD (90.4%). At 2 years, the rates of all-cause death [Kaplan–Meier (KM) estimates 20.1% vs. 18.8%, plog-rank = 0.86] and of the composite of all-cause death, stroke, myocardial infarction, and rehospitalization for heart failure (KM estimates 29.7% vs. 27.5%, plog-rank = 0.82) did not differ between patients undergoing PCI and those who were not. Conclusions: Patients undergoing TAVI with obstructive CAD more commonly had a single-vessel disease and an involvement of proximal coronary tracts. They were commonly treated with PCI, with similar outcomes compared to those treated conservatively. [ABSTRACT FROM AUTHOR]

A series of supported N‐heterocyclic carbene silver complexes (NHC‐Ag(I)) were prepared and characterized as catalysts for the borono‐Minisci reaction. After characterization, the synthesized catalysts were evaluated in batch mode to determine the reaction performance and kinetics. Interestingly, cyclic voltammetric analysis showed that the structure of both the complex and the ligand significantly influences the Ag(I)/Ag(II) redox potential and, in turn, the catalytic efficiency. Among the tested catalysts, the Si‐supported NHC‐Ag(I) 6 afforded the desired products in good to excellent yields in only 15 min, providing a complementary tactic to standard homogeneous approaches. [ABSTRACT FROM AUTHOR]

Objective: Research on the psychological impact of the COVID-19 pandemic has pointed out that lockdowns had small effects on the overall mental health, despite considerable heterogeneity among studies is present. Psychological resilience may be responsible for an amount of variance in individual reactions to the pandemic, despite the fact that its longitudinal associations with mental health symptoms remain unclear. This study sought to investigate changes in resilience and its relationships with depression, anxiety, and stress during the COVID-19 pandemic. Method: A total of 814 participated in this longitudinal study via an online survey during the first lockdown consequent to the COVID-19 pandemic (T1) and during the third wave (T2). The Resilience Scale and the Depression Anxiety Stress Scales – 21 were administered. Sociodemographic data and COVID-19 related information were also collected. Results: Psychological resilience decreased during the third wave of the pandemic, whereas depression and stress increased. Moreover, psychological resilience had a direct effect only on depression during the third wave, while its effect on anxiety and stress is mediated by the mental health during the first lockdown. Conclusions: The mental health symptoms worsened during the third wave, while protective factors such as resilience decreased. Individuals showing high resilience experienced lower depression, anxiety, and stress over time. Psychological intervention that enhances resilience should be embraced in the action of health care authorities to reduce the impact of pandemic. [ABSTRACT FROM AUTHOR]

Background: Ischemic heart disease (IHD) represents the main cause of heart failure (HF). A prognostic stratification of HF patients with ischemic etiology, particularly those with acute coronary syndrome (ACS), may be challenging due the variability in clinical and hemodynamic status. The aim of this study is to assess the prognostic power of the HLM score in a population of patients with ischemic HF and in a subgroup who developed HF following ACS. Methods: This is an observational, prospective, single-center study, enrolling consecutive patients with a diagnosis of ischemic HF. Patients were stratified according to the four different HLM stages of severity, and the occurrence of CV death, HFH, and worsening HF events were evaluated at 6-month follow-up. A sub-analysis was performed on patients who developed HF following ACS at admission. Results: The study included 146 patients. HLM stage predicts the occurrence of CV death (p = 0.01) and CV death/HFH (p = 0.003). Cox regression analysis confirmed HLM stage as an independent predictor of CV death (OR: 3.07; 95% IC: 1.54–6.12; p = 0.001) and CV death/HFH (OR: 2.45; 95% IC: 1.43–4.21; p = 0.001) in the total population of patients with HF due to IHD. HLM stage potentially predicts the occurrence of CV death (p < 0.001) and CV death/HFH (p < 0.001) in patients with HF following ACS at admission. Conclusions: Pathophysiological-based prognostic assessment through HLM score is a potentially promising tool for the prediction of the occurrence of CV death and CV death/HFH in ischemic HF patients and in subgroups of patients with HF following ACS at admission. [ABSTRACT FROM AUTHOR]

Our work presents an updated overview of the Italian Middle Pleistocene records of hippopotamuses, including the two species Hippopotamus antiquus and Hippopotamus amphibius. In addition to reviewing several well-known fossils in the literature, a large number of samples are described herein for the first time. Following the recent results published in the literature, where the skull from the Middle Pleistocene of Cava Montanari (ca. MIS 13) was confirmed to belong to H. amphibius, one of the aims of this work was to investigate the H. antiquus–H. amphibius transition. A morphological analysis applied to a large sample confirmed the validity of the arrangement of the enamel ridges of the external surfaces of the lower canines as a diagnostic character for specific identifications. Finally, biometric analyses allowed us to test the size variability during the Middle Pleistocene, which confirmed that H. antiquus was generally larger than H. amphibius. Nevertheless, the remains of H. antiquus dated to ca. 600 ka show a reduced size when compared to older fossils of the same taxon, probably as a response to severe glacial conditions that occurred during MIS 16. [ABSTRACT FROM AUTHOR]

ObjectiveThis study aimed to investigate the relationships between perceived support at the time of assistance, insecure attachment (i.e., avoidance and anxious attachment), and prolonged grief symptoms in family caregivers of palliative care patients deceased for at least one year. We also investigated the moderating role of insecure attachment in the relationship between perceived support and the intensity of prolonged grief symptoms.MethodAn exploratory cross-sectional design was used. A sample of 157 participants completed the Prolonged Grief Scale (PG-13) and the Attachment Style Questionnaire (ASQ).ResultsCorrelational analyses indicated that prolonged grief symptoms were positively correlated with Avoidance attachment but not with Anxious attachment. Perceived support was negatively correlated with both the Avoidance and Anxious attachment factors. Lastly, the two insecure attachment dimensions were moderately and positively correlated with each other. Results of moderation analysis showed that high Avoidance attachment moderated the effect of perceived family and social support on the intensity of prolonged grief symptoms among family caregivers of palliative home-care-assisted patients. Results also showed that the Anxious attachment factor had a significant effect on prolonged grief symptoms, even though the interaction with perceived support was not significant.ConclusionsOverall, these results underline that a high level of avoidance attachment may moderate the relationship between perceived support and the intensity of grief symptoms, thereby increasing the risk of developing a mental disorder. Interventions to prevent prolonged grief disorder among family caregivers should take these findings into account.

Accumulation of uremic toxins may lead to the life-threatening condition “uremic syndrome” in patients with advanced chronic kidney disease (CKD) requiring renal replacement therapy. Clinical evaluation of proximal tubular secretion of organic cations (OC), of which some are uremic toxins, is desired, but difficult. The biomedical knowledge on OC secretion and cellular transport partly relies on studies using the fluorescent tracer 4-dimethylaminostyryl)-N-methylpyridinium (ASP+), which has been used in many studies of renal excretion mechanisms of organic ions and which could be a candidate as a PET tracer. This study is aimed at expanding the knowledge of the tracer characteristics of ASP+ by recording the distribution and intensity of ASP+ signals in vivo both by fluorescence and by positron emission tomography (PET) imaging and at investigating if the fluorescence signal of ASP+ is influenced by the presence of albumin. Two-photon in vivo microscopy of male Münich Wistar Frömter rats showed that a bolus injection of ASP+ conferred a fluorescence signal to the blood plasma lasting for about 30 minutes. In the renal proximal tubule, the bolus resulted in a complex pattern of fluorescence including a rapid and strong transient signal at the brush border, a very low signal in the luminal fluid, and a slow transient intracellular signal. PET imaging using 11C-labelled ASP+ showed accumulation in the liver, heart, and kidney. Fluorescence emission spectra recorded in vitro of ASP+ alone and in the presence of albumin using both 1-photon excitation and two-photon excitation showed that albumin strongly enhance the emission from ASP+ and induce a shift of the emission maximum from 600 to 570 nm. Conclusion. The renal pattern of fluorescence observed from ASP+ in vivo is likely affected by the local concentration of albumin, and quantification of ASP+ fluorescent signals in vivo cannot be directly translated to ASP+ concentrations.

Clathrin-mediated endocytosis (CME) is one of the best studied cellular uptake pathways and its contributions to nutrient uptake, receptor signaling, and maintenance of the lipid membrane homeostasis have been already elucidated. Today, we still have a lack of understanding how the different components of this pathway cooperate dynamically in vivo. Therefore, we generated a reporter mouse model for CME by fusing eGFP endogenously in frame to clathrin light chain a (Clta) to track endocytosis in living mice. The fusion protein is expressed in all tissues, but in a cell specific manner, and can be visualized using fluorescence microscopy. Recruitment to nanobeads recorded by TIRF microscopy validated the functionality of the Clta-eGFP reporter. With this reporter model we were able to track the dynamics of Alexa594-BSA uptake in kidneys of anesthetized mice using intravital 2-photon microscopy. This reporter mouse model is not only a suitable and powerful tool to track CME in vivo in genetic or disease mouse models it can also help to shed light into the differential roles of the two clathrin light chain isoforms in health and disease.