Search

Background: The Italian Fund for Alzheimer's and other dementias approved in 2020 enabled the conducting of a survey in the Italian Centers for Cognitive Disorders and Dementias (CCDDs) to analyse the organization, the administrative features and the professionals' characteristics. Aims: To investigate the current use of neuropsychological (NP) tests in Italian CCDDs and the association between the use of a basic set of tests for neuropsychological assessment (NPA) and organizational/structural characteristics of CCDDs. Methods: A survey was conducted with an online questionnaire in all CCDDs between July 2022 and February 2023. To verify the use of a comprehensive NPA in the diagnosis of cognitive disorders and dementia, we identified a minimum core test (MCT). Results: The CCDDs using a Minimum Core Test (MCT) significantly increased from 45.7% in 2015 to the current 57.1%. Territorial CCDDs using MCT significantly increased from 24.9% in 2015 to 37% in 2022 (p = 0.004). As multivariable results, the presence of psychologist/neuropsychologist in the staff and the University-based/IRCCS CCDDs increased the probability of using MCT (OR = 9.2; 95% CI 5.6–15.0; p < 0.001 and OR = 5.4; 95% CI 1.9–15.9; p = 0.002, respectively), while CCDDs in Southern Italy-Islands showed a lower probability than those in the North (OR = 0.4; 95% CI 0.2–0.7; p = 0.001). Discussion: Almost half of CCDDs (43%) do not use MCT in their clinical practice. The presence of the psychologist/neuropsychologist on the staff has a key role in the adoption of MCT and regional differences have increased over the past years. NPA is crucial in the diagnostic process and in characterizing risk profiles in order to implement targeted interventions for risk reduction. Conclusions: Our results could help to identify good practices aimed at improving dementia diagnosis. An intervention by health policymakers is urgently needed with the aim of improving diagnostic appropriateness and overcoming regional differences. [ABSTRACT FROM AUTHOR]

Smell and taste are extensively studied in fish species as essential for finding food and selecting mates while avoiding toxic substances and predators. Depending on the evolutionary position and adaptation, a discrete variation in the morphology of these sense organs has been reported in numerous teleost species. Here, for the first time, we approach the phenotypic characterization of the olfactory epithelium and taste buds in the African turquoise killifish (Nothobranchius furzeri), a model organism known for its short lifespan and use in ageing research. Our observations indicate that the olfactory epithelium of N. furzeri is organized as a simple patch, lacking the complex folding into a rosette, with an average size of approximately 600 µm in length, 300 µm in width, and 70 µm in thickness. Three main cytotypes, including olfactory receptor neurons (CalbindinD28K), supporting cells (β-tubulin IV), and basal cells (Ki67), were identified across the epithelium. Further, we determined the taste buds' distribution and quantification between anterior (skin, lips, oral cavity) and posterior (gills, pharynx, oesophagus) systems. We identified the key cytotypes by using immunohistochemical markers, i.e. CalbindinD28K, doublecortin, and neuropeptide Y (NPY) for gustatory receptor cells, glial fibrillary acidic protein (GFAP) for supporting cells, and Ki67, a marker of cellular proliferation for basal cells. Altogether, these results indicate that N. furzeri is a microsmatic species with unique taste and olfactory features and possesses a well-developed posterior taste system compared to the anterior. This study provides fundamental insights into the chemosensory biology of N. furzeri, facilitating future investigations into nutrient-sensing mechanisms and their roles in development, survival, and ageing. [ABSTRACT FROM AUTHOR]

Objective: To describe the implementation of a multi-step antimicrobial stewardship program in a haemato-oncology and stem cell transplantation program unit. Methods: Pre-post quasi-experimental study with two interrupted time-series analyses, conducted between 01/01/2019 and 31/12/2022 in the Paediatric Haemato-Oncology Unit of the Padua Paediatric Hospital. The interventions were: (1) 02/2020: dissemination of febrile neutropenia clinical pathways, (2) April 2021: provision of the clinical pathways via a customized App (Firstline.org) and implementation of a twice-a-week prospective audit and feedback. The main outcome was antibiotic consumption measured by days of administered therapy (DOTs)/1000 patients’ days for all antibiotics and most used molecules. Results: The first intervention (clinical pathways) resulted in a decrease in the overall antibiotic use by the haemato-oncology unit, with an abrupt reduction of 3-gen cephalosporins in favor of piperacillin-tazobactam, as indicated by the clinical pathways. Meropenem and glycopeptide use did not vary. The second intervention (antimicrobial stewardship) further decreased total antibiotic consumption, and a significant decline in meropenem, amikacin, and glycopeptides was achieved. Conclusions: Multi-step stewardship based on guidelines dissemination, multidisciplinary team intervention and collaboration (“handshake” stewardship) was highly effective in optimizing guidelines adherence and reducing overprescriptions in a fragile patient cohort. [ABSTRACT FROM AUTHOR]

The current diagnostic criteria for the behavioural variant of frontotemporal dementia (bvFTD) foresee a relative sparing of long-term memory. Although bvFTD patients were thought to report secondary memory deficits associated with prefrontal dysfunctions, some studies indicated the presence of a "genuine memory deficit" related to mesial temporal lobe dysfunctions. Among various neuropsychological tests, the Free and Cue Selective Reminding Test (FCSRT) has been recommended to distinguish genuine from apparent amnesia. We conducted a systematic review and a random effect Bayesian meta-analysis to evaluate the nature and severity of memory deficit in bvFTD. Our objective was to determine whether the existing literature offers evidence of genuine or apparent amnesia in patients with bvFTD, as assessed via the FCSRT. On 06/19/2021, we conducted a search across four databases (PMC, Scopus, Web of Science, and PubMed). We included all studies that evaluated memory performance using the FCSRT in patients with bvFTD, as long as they also included either cognitively unimpaired participants or AD groups. We tested publication bias through the Funnel plot and Egger's test. To assess the quality of studies, we used the Newcastle-Ottawa quality assessment scale adapted for cross-sectional studies. We included 16 studies in the meta-analysis. The results showed that bvFTD patients perform better than AD patients (pooled effects between 0.95 and 1.14), as their memory performance stands between AD and control groups (pooled effects between − 2.19 and − 1.25). Moreover, patients with bvFTD present both genuine and secondary memory disorders. As a major limitation of this study, due to our adoption of a rigorous methodology and stringent inclusion criteria, we ended up with just 16 studies. Nonetheless, our robust findings can contribute to the ongoing discussion on international consensus criteria for bvFTD and the selection of appropriate neuropsychological tools to facilitate the differential diagnosis between AD and bvFTD. [ABSTRACT FROM AUTHOR]

The twin group TWn on n strands is the group generated by t 1 , ... , t n − 1 with defining relations t i 2 = 1 , titj = tjti if |i − j| > 1. We find a new instance of semisimple Schur–Weyl duality for tensor powers of a natural n-dimensional reflection representation of TWn, depending on a parameter q. At q = 1, the representation coincides with the natural permutation representation of the symmetric group, so the new Schur–Weyl duality may be regarded as a q-analogue of the one motivating the definition of the partition algebra. [ABSTRACT FROM AUTHOR]

Introduction: A new national survey has been carried out by the Italian Centers for Cognitive Disorders and Dementias (CCDDs). The aim of this new national survey is to provide a comprehensive description of the characteristics, organizational aspects of the CCDDs, and experiences during the COVID-19 pandemic. Methods: A list of all national CCDDs was requested from the delegates of each Italian region. The online questionnaire is divided in two main sections: a profile section, containing information on location and accessibility, and a data collection form covering organization, services, treatments, activities, and any service interruptions caused by the COVID-19 outbreak. Results: In total, 511 out of 534 (96%) facilities completed the profile section, while 450 out of 534 (84%) CCDDs also completed the data collection form. Almost half of the CCDDs (55.1%) operated for 3 or fewer days a week. About one-third of the facilities had at least two professional figures among neurologists, geriatricians and psychiatrists. In 2020, only a third of facilities were open all the time, but in 2021, two-thirds of the facilities were open. Conclusion: This paper provides an update on the current status of CCDDs in Italy, which still shows considerable heterogeneity. The survey revealed a modest improvement in the functioning of CCDDs, although substantial efforts are still required to ensure the diagnosis and care of patients with dementia. [ABSTRACT FROM AUTHOR]

Children have been mostly excluded from COVID-19 clinical trials, and, as a result, most medicines approved for COVID-19 have no pediatric indication. In addition, access to COVID-19 therapeutics remains limited. Collecting physicians' experiences with off-label use of therapeutics is important to inform global prioritization processes and better target pediatric research and development. A standardized questionnaire was designed to explore the use of therapeutics used to treat COVID-19 and multisystem inflammatory syndrome in children (MIS-C) in pediatric patients globally. Seventy-three physicians from 29 countries participated. For COVID-19, steroids were used by 75.6% of respondents; remdesivir and monoclonal antibodies were prescribed by 48.6% and 27.1% of respondents, respectively. For MIS-C, steroids were prescribed by 79.1% of respondents and intravenous immunoglobulins by 69.6%. The use of these products depended on their pediatric approval and the limited availability of antivirals and most monoclonal antibodies in Africa, South America, Southeast Asia, and Eastern Europe. Off-label prescription resulted widespread due to the paucity of clinical trials in young children at the time of the survey; though, based on our survey results, it was generally safe and led to clinical benefits. Conclusion: This survey provides a snapshot of current practice for treating pediatric COVID-19 worldwide, informing global prioritization efforts to better target pediatric research and development for COVID-19 therapeutics. Off-label use of such medicines is widespread for the paucity of clinical trials under 12 years and 40 kg, though appears to be safe and generally results in clinical benefits, even in young children. However, access to care, including medicine availability, differs widely globally. Clinical development of COVID-19 antivirals and monoclonal antibodies requires acceleration to ensure pediatric indication and allow worldwide availability of therapeutics that will enable more equitable access to COVID-19 treatment. What is Known: • Children have been mostly excluded from COVID-19 clinical trials, and, as a result, most medicines approved for COVID-19 have no pediatric indication. • Access to care differs widely globally, so because of the diversity of national healthcare systems; the unequal availability of medicines for COVID-19 treatment represents an obstacle to the pediatric population's universal right to health care. What is New: • Off-label COVID-19 drug prescription is widespread due to the lack of clinical trials in children younger than 12 years and weighing less than 40 kg, but relatively safe and generally leading to clinical benefit. • The application of the GAP-f framework to COVID-19 medicines is crucial, ensuring widespread access to all safe and effective drugs, enabling the rapid development of age-appropriate formulations, and developing specific access plans (including stability, storage, packaging, and labeling) for distribution in low- and middle-income countries (LMICs). Antivirals and monoclonal antibodies may benefit from the acceleration to reach widespread and equal diffusion. [ABSTRACT FROM AUTHOR]

Purpose: Laparoscopic ventral rectopexy (LVR) plus sacral colpopexy (LSC) is a high-complexity surgical procedure. The aim of the present study was to evaluate a new approach to rectal-mesh fixation during LVR with continuous locked suture.Methods: This is a prospective randomized double-blinded clinical trial enrolling 80 patients with severe POP and obstructed defecation syndrome (ODS) from November 2016 to January 2021. Patients underwent a "two-meshes" LSC plus LVR and were randomized, regarding rectal mesh fixation, in Group A (extracorporeal interrupted 0 delayed absorbable sutures) and Group B ("U-shaped" running locked 0 delayed absorbable suture). Our primary endpoints were the operative times (OT); the secondary endpoints were the incidence of anatomical failures, vaginal mesh erosions and surgical complications.Results: A total of 75 patients completed the study. Baseline characteristics were similar between the groups. Overall OT (156 vs 138 min; p < 0.05; treatment reduction of 11.5%) and LVR mesh fixation time (29 vs 16 min; p < 0.05; treatment reduction of 44%), resulted in significantly lower in Group B. No differences were found in terms of anatomic failure, vaginal mesh erosion or intra- or post-operative complications. PGI-I, FSDS and Wexner questionnaires resulted significantly improved after surgery, without statistical differences between the studied surgical procedures.Conclusion: Laparoscopic continuous locked 0 absorbable suture for LVR mesh fixation guaranteed a faster and effective alternative to multiple interrupted sutures. The significant OT reduction linked to this technique should be considered even more helpful when performing a highly complex surgery such as LVR.Clinical Trial Registration: NCT05254860 (13/02/2017). [ABSTRACT FROM AUTHOR]

Cannabidiol (CBD) is a substance derived from Cannabis sativa, widely studied in medicine for controlling neural diseases in humans. Besides the positive effects on humans, it also presents anxiolytic proprieties and decreases aggressiveness and stress in mammals. Therefore, CBD has the potential to increase welfare in reared animals, as it seems to reduce negative states commonly experienced in artificial environments. Here, we tested the effect of different CBD doses (0, 1, 10 and 20 mg/kg) on aggressiveness, stress and reproductive development of the Nile tilapia (Oreochromis niloticus) a fish reared worldwide for farming and research purposes. CBD mixed with fish food was offered to isolated fish for 5 weeks. The 10 mg/kg dose decreased fish's aggressiveness over time, whereas 20 mg/kg attenuated non-social stress. Both doses decreased the baseline cortisol level of fish and increased the gonadosomatic index. However, CBD 1 and 10 mg/kg doses decreased the spermatozoa number. No CBD dose affected feeding ingestion and growth variables, showing that it is not harmful to meat production amount. Despite the effect on spermatozoa, CBD supplementation exhibits high potential to benefit animals' lives in artificial environments. Therefore, we showed for the first time that CBD could be used as a tool to increase non-mammal welfare, presenting a great potential to be explored in other husbandry and captivity species. [ABSTRACT FROM AUTHOR]

Norovirus is a leading cause of epidemic acute gastroenteritis. More than 30 genotypes circulate in humans, some are common, and others are only sporadically detected. Here, we investigated whether serology can be used to determine which genotypes infect children. We established a multiplex protein microarray with structural and non-structural norovirus antigens that allowed simultaneous antibody testing against 30 human GI and GII genotypes. Antibody responses of sera obtained from 287 children aged < 1 month to 5.5 years were profiled. Most specific IgG and IgA responses were directed against the GII.2, GII.3, GII.4, and GII.6 capsid genotypes. While we detected antibody responses against rare genotypes, we found no evidence for wide circulation. We also detected genotype-specific antibodies against the non-structural proteins p48 and p22 in sera of older children. In this study, we show the age-dependent antibody responses to a broad range of norovirus capsid and polymerase genotypes, which will aid in the development of vaccines. [ABSTRACT FROM AUTHOR]

SARS-CoV-2, like other coronaviruses, builds a membrane-bound replication organelle to enable RNA replication1. The SARS-CoV-2 replication organelle is composed of double-membrane vesicles (DMVs) that are tethered to the endoplasmic reticulum (ER) by thin membrane connectors2, but the viral proteins and the host factors involved remain unknown. Here we identify the viral non-structural proteins (NSPs) that generate the SARS-CoV-2 replication organelle. NSP3 and NSP4 generate the DMVs, whereas NSP6, through oligomerization and an amphipathic helix, zippers ER membranes and establishes the connectors. The NSP6(ΔSGF) mutant, which arose independently in the Alpha, Beta, Gamma, Eta, Iota and Lambda variants of SARS-CoV-2, behaves as a gain-of-function mutant with a higher ER-zippering activity. We identified three main roles for NSP6: first, to act as a filter in communication between the replication organelle and the ER, by allowing lipid flow but restricting the access of ER luminal proteins to the DMVs; second, to position and organize DMV clusters; and third, to mediate contact with lipid droplets (LDs) through the LD-tethering complex DFCP1–RAB18. NSP6 thus acts as an organizer of DMV clusters and can provide a selective means of refurbishing them with LD-derived lipids. Notably, both properly formed NSP6 connectors and LDs are required for the replication of SARS-CoV-2. Our findings provide insight into the biological activity of NSP6 of SARS-CoV-2 and of other coronaviruses, and have the potential to fuel the search for broad antiviral agents.The non-structural protein NSP6 in SARS-CoV-2 has a key role in viral replication by zippering the endoplasmic reticulum membrane to establish connectors between the double-membrane vesicles of the viral replication organelle and the endoplasmic reticulum. [ABSTRACT FROM AUTHOR]

Grounded in the interdisciplinary crosstalk among physics and biological sciences, precision medicine-based diagnosis and treatment strategies have recently gained great attention for the actual applicability of new engineered approaches in many medical fields, particularly in oncology. Within this framework, the use of ultrasounds employed to attack cancer cells in tumors to induce possible mechanical damage at different scales has received growing attention from scholars and scientists worldwide. With these considerations in mind, on the basis of ad hoc elastodynamic solutions and numerical simulations, we propose a pilot study for in silico modeling of the propagation of ultrasound waves inside tissues, with the aim of selecting proper frequencies and powers to be irradiated locally through a new teragnostic platform based on Lab-on-Fiber technology, baptized as a hospital in the needle and already the object of a patent. It is felt that the outcomes and the related biophysical insights gained from the analyses could pave the way for envisaging new integrated diagnostic and therapeutic approaches that might play a central role in future applications of precise medicine, starting from the growing synergy among physics, engineering and biology. [ABSTRACT FROM AUTHOR]

During implant surgery procedures, surgical precision is an essential prerequisite for the functional and aesthetic success of the prosthetic crown to be placed on the dental implant. A modern implant surgical approach should be standardized as much as possible to guarantee extreme precision in the insertion of the implant into the upper and lower bone jaws. Among the most common surgical errors during implant surgery there is the over-preparation of the surgical alveolus with possible damage to the contiguous anatomical structures. To avoid this problem, in the recent years, there has been an increasing attention to the development of new control techniques. In this paper, we describe an innovative ultrasound approach, which exploits the integration of an electro-acoustic transducer with the surgical drill used for realizing the alveolus in the bone that will host the implant. Specifically, he proposed approach is based on the "time-of-flight" detection technique for measuring the thickness of the residual bone subjected to the drilling. In order to demonstrate the feasibility of the proposed approach, here we report on a detailed numerical analysis aimed at studying the propagation of ultrasonic waves through the drill-bit and through the involved tissues. The obtained results confirm the validity of our approach, and enable for a future first prototype implementation of a hi-tech surgical drill-bit, which in general is suitable not only for dental implant surgery but also for other uses in oral surgery, maxillofacial surgery and for bone surgery. [ABSTRACT FROM AUTHOR]

Artin's braid group B n is generated by σ 1 , ... , σ n - 1 subject to the relations σ i σ i + 1 σ i = σ i + 1 σ i σ i + 1 , σ i σ j = σ j σ i if | i - j | > 1. For complex parameters q 1 , q 2 such that q 1 q 2 ≠ 0 , the group B n acts on the vector space E = ∑ i C e i with basis e 1 , ... , e n by σ i · e i = (q 1 + q 2) e i + q 1 e i + 1 , σ i · e i + 1 = - q 2 e i , σ i · e j = q 1 e j if j ≠ i , i + 1. This representation is (a slight generalization of) the Burau representation. If q = - q 2 / q 1 is not a root of unity, we show that the algebra of all endomorphisms of E ⊗ r commuting with the B n -action is generated by the place-permutation action of the symmetric group S r and the operator p 1 , given by p 1 (e j 1 ⊗ e j 2 ⊗ ⋯ ⊗ e j r) = q j 1 - 1 ∑ i = 1 n e i ⊗ e j 2 ⊗ ⋯ ⊗ e j r. Equivalently, as a (C B n , P r ′ ([ n ] q)) -bimodule, E ⊗ r satisfies Schur–Weyl duality, where P r ′ ([ n ] q) is a certain subalgebra of the partition algebra P r ([ n ] q) on 2r nodes with parameter [ n ] q = 1 + q + ⋯ + q n - 1 , isomorphic to the semigroup algebra of the "rook monoid" studied by W. D. Munn, L. Solomon, and others. [ABSTRACT FROM AUTHOR]

Water turbidity deteriorates visibility and thereby may change the physiology and behavior of aquatic animals that rely on vision. In the guppy fish (Poecilia reticulata), a key element in the mating behavior and reproductive success of males is female mate choice, which is predominantly based on visual signals. Females choose attractive males based on body coloration, and males court females by displaying their coloration. Here, we demonstrate that guppy males exhibit morphological and behavioral adjustments in response to changes in the visual environment. Males reared in turbid water had more conspicuous coloration than males reared in clear water, with higher intensity of carotenoid-based and ultraviolet colors, but not a larger area of red spots on the body. However, they performed less courtship displays in turbid water than males reared in clear water performed in clear water. Thus, increased coloration in turbid-water males was not accompanied by increased effort to display it. Although our findings demonstrated developmental plasticity in mating-related traits, turbidity-induced alteration in coloration did not match behavior change as could be predicted by favoring male attractiveness. [ABSTRACT FROM AUTHOR]

Bisphosphonates are the first-choice treatment of osteoporosis and Paget's disease of bone. Among the bisphosphonates, the non-amino-bisphosphonates, such as clodronic acid, are intracellular converted into toxic analogues of ATP and induce cellular apoptosis whereas the amino-bisphosphonates, such as zoledronic acid, inhibit the farnesyl-diphosphate-synthase, an enzyme of the mevalonate pathway. This pathway regulates cholesterol and glucose homeostasis and is a target for statins. In this retrospective cohort study, we evaluated the effects of an intravenous infusion of zoledronic acid (5 mg) or clodronic acid (1500 mg) on blood lipid (i.e. total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and triglycerides) and glucose levels in patients with osteoporosis and Paget's disease of bone. All patients were evaluated before, 1 and 6 months after bisphosphonate treatment. Pagetic and osteoporotic patients treated with zoledronic acid showed a significant reduction in glucose and atherogenic lipids during follow-up whereas these phenomena were not observed after clodronic treatment. The effect on circulating lipid levels was similar in naïve and re-treated Pagetic patients. Zoledronic acid treatment was associated with a reduction in blood glucose and atherogenic lipids in patients with metabolic bone disorders. The extent of change was similar to that obtained with the regular assumption of a low-intensity statin. Further studies are warranted to better evaluate the clinical implications of these observations. [ABSTRACT FROM AUTHOR]

Between February and May 2020, during the first wave of the COVID-19 pandemic, paediatric emergency departments in 12 European countries were prospectively surveyed on their implementation of SARS-CoV-2 disease (COVID-19) testing and infection control strategies. All participating departments (23) implemented standardised case definitions, testing guidelines, early triage and infection control strategies early in the outbreak. Patient testing criteria initially focused on suspect cases and later began to include screening, mainly for hospital admissions. Long turnaround times for test results likely put additional strain on healthcare resources. Conclusion: Shortening turnaround times for SARS-CoV-2 tests should be a priority. Specific paediatric testing criteria are needed. What is Known: • WHO and public health authorities issued case definitions, testing and infection control recommendations for COVID-19 in January. • SARS-CoV-2 testing was made available across Europe in February. What is New: • Paediatric emergency departments implemented COVID-19-specific procedures rapidly, including case definitions, testing guidelines and early triage. • A third of surveyed departments waited more than 24 h for SARS-CoV-2 test to be reported, resulting in additional strain on resources. [ABSTRACT FROM AUTHOR]

In Italy, two clinical practice guidelines for the diagnosis and treatment of bronchiolitis were published in October 2014 and December 2015. We evaluated prescriptions for bronchiolitis in children aged 0–24 months before (December 2012–December 2014), in between (December 2014–December 2015) and after (December 2015–December 2018) the guidelines publications. Data were retrieved from the Pedianet database; the measured outcomes were prescriptions rates of antibiotics, corticosteroids, β2-agonists, and other respiratory drugs. In 1011 out of 1581 episodes, patients received at least one treatment, with a total of 2003 prescriptions. The rate of treated bronchiolitis decreased from 66% to 57% (p < 0.001) after the publication of the second guideline; the highest reduction was in younger patients (from 57% to 44%, p = 0.013). Overall antibiotic prescriptions rate did not change, with 31.6% of the patients still receiving them. Our results confirm unnecessary non-evidence-based treatments in the primary care setting, with few changes after the guidelines publications. [ABSTRACT FROM AUTHOR]

The need for information about new and existing drugs used in children was recognized in the European Union (EU) with the implementation of the Paediatric Regulation in 2007. In 2017, the 10-year review of the Paediatric Regulation identified barriers to the conduct of clinical trials, including delays in setting up and completing paediatric trials. Across Europe, the difficulties with clinical research are compounded by variation within countries and between countries. Ethics and regulatory review have national specificities. This paper describes the Collaborative Network for European Clinical Trials for Children (conect4children, c4c), which addresses selected difficulties in the design and conduct of paediatric clinical trials. c4c is a time-limited public–private consortium funded by the Innovative Medicines Initiative (IMI2). The elements of c4c are as follows: expert advice providing input on study design and/or paediatric development programmes (including patient involvement activities); a network of sites following harmonised procedures coordinated by National Hubs and a single point of contact for Europe; a facility for education and training for sites and trial teams; and support for managing data used by the network and a common paediatric data dictionary. c4c does not sponsor trials. c4c is taking a phased approach with careful piloting through industry and non-industry studies intended to demonstrate the viability of the network (proof-of-viability studies). c4c uses a co-design approach involving industry and academics within a clearly defined scope. A sustainable, successor organization open to all potential service users will be open for business before the end of IMI2 funding in 2024. [ABSTRACT FROM AUTHOR]

Homcology is a project that represents both an opportunity for patients who may benefit from chemotherapy so far, but present physical and social problems that prevent day-hospital access, and a model of "no-profit" contribution to the Public Health System. Our medical oncology department conducted the project from May 2014 to January 2019. We included frail patients (G-8 < 14), with advanced disease, treated with oral, subcutaneous, or parenteral biological agents, with limitations to day-hospital access, comorbidities, and at least 6-month life expectancy. A multidisciplinary team included three oncologists, four nurses, an anesthetist, a psychologist, and a physiotherapist. Satisfaction was evaluated with FAMCARE scale. A total of 188 patients (median age of 73 years, 38-87) were enrolled. Ninety percent of patients presented with metastatic disease and a median G-8 score of 8.8 (3-13.5). All of them received anticancer treatment and concomitant supportive care; 24 patients received two or more lines of treatment. The median duration of taking care was 175 days (7-1200). A median number of 254 (195-325) nursing and 164 (139-190) medical visits were performed a year, with an average of 1.9 and 1.2 visits a month per patient respectively. The median number of in-line patients was 20 (17-25). Hospitalization occurred in 18% of cases. One-third of them died at home. The others were referred to hospice. Our experience shows that the integration of home cancer treatment and supportive care is effective. Hospitalization rate is lower than data reported in the literature. Results need to be confirmed in prospective pharmacoeconomics studies. [ABSTRACT FROM AUTHOR]

Introduction: Several studies have assessed the histological co-existence of endometrial carcinoma (EC) and adenomyosis. However, the significance of this association is still unclear. Objective: To assess the prevalence of adenomyosis in women with EC for a better understanding of the association between the two diseases. Materials and methods: A systematic review and meta-analysis was performed by searching electronics databases from their inception to March 2020, for all studies that allowed extraction of data about prevalence of adenomyosis in EC patients. Adenomyosis prevalence was calculated for each included study and as pooled estimate, with 95% confidence interval (CI). Results: Eight retrospective cohort studies assessing 5573 EC patients were included in our analysis. Of total, 1322 were patients with adenomyosis, and 4251 were patients without adenomyosis. Pooled prevalence of adenomyosis in EC patients was 22.6% (95% CI 12.7–37.1%). Conclusion: Adenomyosis prevalence in EC patients was not different from that reported for other gynecological conditions. The supposed association between the two diseases appears unsupported. [ABSTRACT FROM AUTHOR]

Introduction: Leptin is associated with cardiovascular risk. Some studies analyzed the potential association between leptin and arterial stiffness, an independent cardiovascular risk factor. However, the studies that investigated this association provided inconsistent and heterogeneous results. Aim: We performed a systematic review and a meta-analysis of the available studies on the relationship between leptin and arterial stiffness to achieve definitive conclusions. Methods: A systematic search of the on-line databases available (up to December 2019) was conducted including the observational studies that reported the evaluation of the relationship between non-invasively assessed arterial stiffness (expressed by carotid–femoral pulse wave velocity) and leptin. For each study, the effect size was standardized and pooled using a random effect model. Sensitivity analysis, heterogeneity, publication bias, meta-regression and sub-group analyses were also assessed. Results: Ten studies met the pre-defined inclusion criteria and provided 11 cohorts with 7,580 total participants. Leptin levels were positively and significantly associated with risk of increased arterial stiffness (odds ratio 1.04; p < 0.01), with no significant heterogeneity among studies. Likewise, pooled analysis of correlation showed a significant and positive association between leptin and pulse wave velocity (z = 0.27, p < 0.01), with significant heterogeneity among studies. Conclusion: The results of this meta-analysis indicate that leptin is positively associated with arterial stiffness. This association significantly adds to the recognized value of leptin in cardiovascular disease. [ABSTRACT FROM AUTHOR]

Osteoporosis and nephrolithiasis are common multifactorial disorders with high incidence and prevalence in the adult population worldwide. Both are associated with high morbidity and mortality if not correctly diagnosed and accurately treated. Nephrolithiasis is considered a risk factor for reduced bone mineral density. Aim of this retrospective longitudinal study was to evaluate if osteoporosis is a predictive factor for the nephrolithiasis occurrence. Free-living subjects referring to "COMEGEN" general practitioners cooperative operating in Naples, Southern Italy. Twelve thousand seven hundred ninety-four Caucasian subjects (12,165 female) who performed bone mineral density by dual-energy X-ray absorptiometry and have a negative personal history for nephrolithiasis. Subjects aged less than 40 years or with signs or symptoms suggestive of secondary osteoporosis were excluded from the study. In a mean lapse of time of 19.5 months, 516 subjects had an incident episode of nephrolithiasis. Subjects with osteoporosis had an increased risk of nephrolithiasis than subjects without osteoporosis (Hazard Ratio = 1.33, 95% Confidence Interval 1.01–1.74, p = 0.04). Free-living adult subjects over the age of 40 with idiopathic osteoporosis have an increased risk of incident nephrolithiasis, suggesting the advisability of appropriate investigation and treatment of the metabolic alterations predisposing to nephrolithiasis in patients with osteoporosis. The study protocol was approved by the ASL Napoli 1 Ethical Committee, protocol number 0018508/2018 [ABSTRACT FROM AUTHOR]

Background: Acute osteomyelitis still represents a significant clinical challenge, with an increasing incidence in paediatric population. A careful assessment and a rapid diagnosis with proper timing and choice of empirical antimicrobial therapy are necessary to avoid sequelae. The initial treatment should consist of empirical antibiotic therapy, to cover the major responsible pathogens in each age group. Data sources: We made a literature search with PubMed and Cochrane database from 2000 to 2019 in English, French, and Spanish languages using the key words "osteomyelitis, children, clinical, diagnosis, and treatment". Results: The child's clinical features, age, and the microbiological profile of the geographic area should be evaluated for diagnosis and in the choice of antibiotic treatment. Latest data suggest the administration of intravenous antibiotics for a short period, with subsequent oral therapy, according to the improvement of clinical status and inflammatory markers. For children older than 3 months, the shift to oral medications is already possible after a short course of intravenous therapy, until recovery. The timing for the shift from cefazolin to cephalexin or cefuroxime, intravenous clindamycin to oral clindamycin, and intravenous ceftriaxone + oxacillin to oral equivalents will be decided according to the improvement of clinical status and inflammatory markers. We also present the approach to osteomyelitis due to difficult pathogens, such as Methicillin-resistant Staphylococcus aureus (MRSA) and Panton-Valentine leukocidin (PVL)-positive S. aureus infections. Conclusion: In this review, we present the current approach to the clinical diagnosis and management of osteomyelitis in childhood, with an update on recent recommendations, as a useful instrument to understand the rationale of antibiotic therapy. [ABSTRACT FROM AUTHOR]

Analysis of irradiated material shortly after irradiation can be non-trivial due to highly radioactive activation and fission isotopes increasing dead time in gamma-ray detection systems, often requiring a "cooling-period" between receipt of a sample and the subsequent analysis. A direct separation–detection method has been developed combining ion chromatography and inductively coupled mass spectrometry for rapid, low-level analysis of fission products; it cannot, however, detect certain short-lived species below the detection limit of the system. Here we report the implementation of an inline gamma-ray detector, which was added post-separation, pre-analysis, to test the quality and utility of elementally-isolated gamma-ray spectroscopy. [ABSTRACT FROM AUTHOR]

Background: Patients and health care professionals receive information about pharmaceutical companies through various sources, including but not limited to print media, social media, and electronic media. The objective of this research was to benchmark the sentiment of electronic newspaper media coverage between 2014 and 2016 and investigate the potential relationship to the public perception of the select pharmaceutical companies. Methods: Reputation Institute's RepTrak System report was used for selection of 5 highly rated pharmaceutical companies (A-E). Electronic newspapers were selected based on US circulation within the selected time period. Lexalytics sentiment analysis software was used for analysis of relevant articles appearing in the selected newspapers. Results: A total of 797 articles were analyzed; 63% were assessed as neutral, 24% as negative, and 14% as positive. The overall median sentiment scores (scale ranging from −2 through + \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$+$$\end{document} 2) for companies A through E across all newspapers were determined to be + \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$+$$\end{document} 0.026, + \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$+$$\end{document} 0.03, + \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$+$$\end{document} 0.028, + \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$+$$\end{document} 0.034, and + \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$+$$\end{document} 0.033, respectively. The most frequent topics were merger/acquisition/ re-structuring, finances/stocks/profits, and other, which included topics such as transparency of pharmaceutical industry data, lack of drug efficacy, and innovation. Conclusion: Overall, pharmaceutical companies were represented similarly across newspapers and most articles were assessed as neutral. However, on analysis of all nonneutral articles, all categories were assessed as negative with the exception of finances/stocks/profits. [ABSTRACT FROM AUTHOR]

Selection favors females that make use of reliable information on the genetic quality of males, which affects mating decisions. Although studies have shown that females prefer dominant males, it may not be adaptive for females to choose very aggressive males, as aggression can be misdirected towards females. The Nile tilapia Oreochromis niloticus is an appropriate model species for testing this dilemma because it shows dominance hierarchy, in which dominant males defend territories, build nests, court females and have priority of access to mating. In addition, in this species, odor recognition affects sexual and social status. We tested whether females can select, by means of chemical cues, dominant males with aggressive profiles. Females were allowed to choose between the odors of two dominant males differing in their aggression level. Our findings show that females discriminate dominant males that have a high aggressivity profile in favor of males that are less aggressive. [ABSTRACT FROM AUTHOR]

An automated online separation-direct analysis method, RAPID (rapid analysis of post-irradiation debris), has been developed for the measurement of the concentration and isotopic composition of over 40 elements down to the low-picogram level. Here we discuss the application of RAPID to irradiated highly-enriched uranium, demonstrating that it has the sensitivity required to achieve precise, low-level analyses of non-natural isotopes, even in the presence of a bulk uranium matrix. Isotopic ratios have been successfully measured at the low-picogram level, and the accuracy of these ratios was confirmed using an isotopic depletion and decay modeling software to within 1-2%. [ABSTRACT FROM AUTHOR]

Measurement methods for the analysis of trace impurities in uranium materials, essential in nuclear fuel production and nuclear forensics, are continuously improving. Analytical methods were developed with the goal of lowering uncertainties of next generation certified uranium oxide reference materials for trace impurity concentrations. Through addition of a traceable standard directly into the sample, gravimetric standard addition and isotope dilution followed by analysis on an inductively coupled plasma mass spectrometer can achieve lower uncertainties. Results for 28 impurities in CRM 124-1 and 124-6 from NBL Program Office were used for validation of accuracy and comparisons of uncertainties. [ABSTRACT FROM AUTHOR]

Rapid measurement of transplutonium isotopic mass distributions during 252Cf production campaigns at Oak Ridge National Laboratory is a critical need. Mass measurements for the isotopes of plutonium, americium, curium, and californium are routinely requested to support the α-hydroxy-isobutyrate runs for the purification and recovery of the heavy curium target material and final 249Bk, 252Cf, and 254Es enriched isotope products. This paper presents the integration of an online high-pressure ion chromatography inductively coupled plasma mass spectrometry technique together with the protocol and chemistry that allows for rapid baseline separation and direct quantification of the transplutonium elemental concentrations and isotopic compositions. [ABSTRACT FROM AUTHOR]

Classical conditioning in animals is a learning procedure involving a biologically relevant stimulus paired with a previously neutral stimulus. In fish, light and sound are frequently used as previously neutral stimuli for conditioning tests. However, in laboratory experiments with replicates, such stimuli may influence the responses of fish in nearby aquariums. Herein, we developed a simple applicable methodology for classical conditioning in fish that prevents this type of influence. We isolated fish in individual aquariums and introduced a water jet that caused localized water movement, followed by the introduction of a food pellet. These procedures were repeated for each fish for 20 days. After 14 days, all fish were conditioned. Moreover, in subsequent probe trials (memory retention tests) conducted within 32 days after conditioning procedures, fish responded accordingly. These findings corroborate the applicability and usefulness of the method tested herein especially under lab conditions. Therefore, we suggest that a simple water jet is a useful and reliable tool for fish conditioning in future studies. [ABSTRACT FROM AUTHOR]

Introduction: Antibiotics are the most commonly prescribed drug class in children. Real-world data mining on the paediatric population showed potential associations between antibiotic use and acute liver injury.Objective: We assessed risk estimates of liver injury associated with antibiotic use in children and adolescent outpatients.Methods: A large, multi-database, population-based, case-control study was performed in people <18 years of age from two European countries (Italy and The Netherlands) during the period 2000-2008. All potential cases of liver injury were automatically extracted from three databases and then manually validated based on Council for International Organizations of Medical Sciences (CIOMS) criteria and by exclusion of all competing causes for liver injury. Up to 100 control participants were sampled for each case and were matched on index date of the event, age, sex and database. Based on prescription data, antibiotic exposure was categorized as current, recent or past use by calculating the time period between the end of prescription and the index date. Multivariate conditional logistic regression analyses were applied to calculate odds ratios (ORs) as a measure of the association (with 95% confidence interval [CI]).Results: We identified 938 cases of liver injury and matched to 93,665 controls. Current use of overall antibiotics is associated with a threefold increased risk of liver injury compared with past use (adjusted OR [ORadj] 3.22, 95% CI 2.57-4.03). With regard to individual antibiotics, the risk is significantly increased for current use of each antibiotic (p < 0.005), except for azithromycin. Risk estimates vary from the lowest ORadj of 1.86 (95% CI 1.08-3.21) for amoxicillin to the highest ORadj of 24.16 (95% CI 11.78-49.54) for cotrimoxazole (i.e. sulphamethoxazole/trimethoprim) and 26.70 (95% CI 12.09-58.96) for ceftriaxone. Sensitivity analyses confirm the associations for ceftriaxone, cotrimoxazole, and clarithromycin.Conclusion: Antibiotic-induced liver injury in children is heterogeneous across the use of individual antibiotics. When prescribing ceftriaxone, cotrimoxazole and clarithromycin in children, paediatricians should definitely be aware of their potential risk of liver injury, even if for short periods. [ABSTRACT FROM AUTHOR]

Glyphosate-based herbicides are widely used in agricultural systems. Although the target organism are particularly plant organisms, there are numerous studies showing adverse effects in aquatic animals, such as inhibition of acetyl cholinesterase, effects on kidney, liver, and gill and stressors effects. This study analyzed the effects of commercial formulation of glyphosate on feeding behavior in Pacu ( Piaractus mesopotamicus). Fish were exposed to three glyphosate concentrations (0.2, 0.6, and 1.8 ppm) for 15 days. At concentrations of 0.2 and 0.6 ppm, food intake decreased on day 13 and then returned to normal on day 15. At the highest glyphosate-based herbicide concentration, 1.8 ppm, food consumption decreased dramatically and did not recover on day 15. This study showed that glyphosate-based herbicide at sub-lethal concentrations can affect feed intake in pacu and consequently inhibits its growth. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) is a neuromuscular disease associated with nutritional status derangement and altered body composition. New drugs are changing the natural history of the disease, so now more than ever is important to focus on the correct assessment of nutritional status in SMA. We implemented a standardization process for the anthropometric measurement as part of our ongoing longitudinal study of growth patterns in SMA patients. It features a procedural manual, included in this communication, observers training and reliability assessment, of which we publish the values obtained in our pilot study. The standardization process was able to produce inter-observer reliability values in agreement with the literature and a procedure manual is now available for multicentre studies of nutritional status and body composition in SMA and possibly other pediatric neuromuscular disorders. [ABSTRACT FROM AUTHOR]

The MARC X Conference hosted a workshop for the scientific community to communicate needs for high-purity U and its by-products in order to preserve critical items otherwise slated for downblending and disposal. Currently, only small portions of the U.S. holdings of separated U are being preserved. However, many additional kilograms of U (>97 % pure) still are destined to be disposed, and it is unlikely that this material will ever be replaced due to a lack of operating production capability. Summaries of information conveyed at the workshop and feedback obtained from the scientific community are presented herein. [ABSTRACT FROM AUTHOR]

Unlabelled: The introduction of combination antiretroviral therapy has been associated with a dramatic clinical improvement in children with human immunodeficiency virus infection. However, the uptake of antiretroviral therapy has been variable across Europe. The Paediatric European Network for the Treatment of AIDS Steering Committee has performed a systematic literature review of paediatric antiretroviral therapy trials. An analysis of the evidence base for the commencement and maintenance of antiretroviral therapy was produced. Suggestions for when to commence antiretroviral therapy, which drugs to start with and how to monitor and sequence drug regimens are given.Conclusion: The aim of these guidelines is to help in obtaining equity of access to a uniformly high standard of care for children with human immunodeficiency virus infection in all European countries. [ABSTRACT FROM AUTHOR]

Background and Objectives: Acute otitis media (AOM) not only affects childhood quality of life (QoL), but can also affect parental QoL. We adapted a previously published questionnaire on the effect of childhood recurrent ear, nose and throat infections on parental QoL for use with AOM and used it in an observational, multicentre, prospective study of children with AOM. Methods: The AOM-specific parental QoL questionnaire grouped 15 items into emotional, daily disturbance, total and overall parental QoL impact scores. The questionnaire was assessed using item-convergent and item-discriminant validity criteria and internal consistency reliability; and then used with parents of children aged <6 years diagnosed with AOM at 73 practices in Germany, Italy, Spain, Sweden and the UK. Bivariate analyses explored the differences in mean parental QoL impact scores by various characteristics. Results: The questionnaire demonstrated good to excellent internal consistency reliability for the various components (Cronbach's α 0.82-0.97). There were 1419 AOM episodes among 5882 healthy children over 1 year, of which 1063 episodes (74.9 %) among 852 children had a questionnaire. Parents reported interrupted sleep (68.4 %), worry (51.0 %), altered daily schedule (44.6 %) and less leisure time (41.5 %) with a score ≥3 (1 = least to 5 = most impact). Factors that adversely affected parental QoL included: increased parental perception of AOM severity, younger child age and multiple AOM episodes. Conclusions: The AOM-specific parental QoL questionnaire demonstrated good performance across five European countries. Parental QoL was affected by childhood AOM proportionally to severity, number of episodes and younger child age. [ABSTRACT FROM AUTHOR]

The deformations of an infinite dimensional algebra may be controlled not just by its own cohomology but by that of an associated diagram of algebras, since an infinite dimensional algebra may be absolutely rigid in the classical deformation theory for single algebras while depending essentially on some parameters. Two examples studied here, the function field of a sphere with four marked points and the first Weyl algebra, show, however, that the existence of these parameters may be made evident by the cohomology of a diagram (presheaf) of algebras constructed from the original. The Cohomology Comparison Theorem asserts, on the other hand, that the cohomology and deformation theory of a diagram of algebras is always the same as that of a single, but generally rather large, algebra constructed from the diagram. [ABSTRACT FROM AUTHOR]

Unlabelled: The European Paediatric Regulation mandated the European Commission to fund research on off-patent medicines with demonstrated therapeutic interest for children. Responding to this mandate, five FP7 project calls were launched and 20 projects were granted. This paper aims to detail the funded projects and their preliminary results. Publicly available sources have been consulted and a descriptive analysis has been performed. Twenty Research Consortia including 246 partners in 29 European and non-European countries were created (involving 129 universities or public-funded research organisations, 51 private companies with 40 SMEs, 7 patient associations). The funded projects investigate 24 medicines, covering 10 therapeutic areas in all paediatric age groups. In response to the Paediatric Regulation and to apply for a Paediatric Use Marketing Authorisation, 15 Paediatric Investigation Plans have been granted by the EMA-Paediatric Committee, including 71 studies of whom 29 paediatric clinical trials, leading to a total of 7,300 children to be recruited in more than 380 investigational centres.Conclusion: Notwithstanding the EU contribution for each study is lower than similar publicly funded projects, and also considering the complexity of paediatric research, these projects are performing high-quality research and are progressing towards the increase of new paediatric medicines on the market. Private-public partnerships have been effectively implemented, providing a good example for future collaborative actions. Since these projects cover a limited number of off-patent drugs and many unmet therapeutic needs in paediatrics remain, it is crucial foreseeing new similar initiatives in forthcoming European funding programmes. [ABSTRACT FROM AUTHOR]