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Given previous results showing that auditory imagery is associated with subvocal muscle movements related to pitch control, the present study addressed whether subvocalization of pitch is differentially involved during imagery that precedes the execution of an imagined action as compared to non-preparatory imagery. We examined subvocal activity using surface electromyography (sEMG) during auditory imagery that preceded sung reproduction of a pitch sequence (preparatory) or recognition of a pitch sequence (non-preparatory). On different trials, participants either imagined the sequence as presented, or imagined a mental transformation of that sequence. Behavioral results replicated previous findings of poorer reproduction and recognition of transformed sequences compared to sequences in their original form. Physiological results indicated that subvocal activity was significantly above baseline for all conditions, greater than activity observed for the bicep control site, and greater for longer sequences, but did not reliably scale with transformation type. Furthermore, greater subvocal activity during preparatory imagery was associated with greater subvocal activity during non-preparatory imagery for muscles involved in pitch control and articulation. Muscle activity involved in pitch control was similarly recruited for both preparatory and non-preparatory auditory imagery. In contrast, muscle activity involved in vocal articulation was most strongly recruited during motor preparation. Our findings suggest that pitch imagery recruits subvocal muscle activity regardless of whether the imagined action is intended to be effected.

Alternative splicing transitions occur during organ development, and, in numerous diseases, splicing programs revert to fetal isoform expression. We previously found that extensive splicing changes occur during postnatal mouse heart development in genes encoding proteins involved in vesicle-mediated trafficking. However, the regulatory mechanisms of this splicing-trafficking network are unknown. Here, we found that membrane trafficking genes are alternatively spliced in a tissue-specific manner, with striated muscles exhibiting the highest levels of alternative exon inclusion. Treatment of differentiated muscle cells with chromatin-modifying drugs altered exon inclusion in muscle cells. Examination of several RNA-binding proteins revealed that the poly-pyrimidine tract binding protein 1 (PTBP1) and quaking regulate splicing of trafficking genes during myogenesis, and that removal of PTBP1 motifs prevented PTBP1 from binding its RNA target. These findings enhance our understanding of developmental splicing regulation of membrane trafficking proteins which might have implications for muscle disease pathogenesis.

Background We recently sought to integrate our orthopaedic and plastic hand surgeons with the goal of improving education, patient care, and providing seamless, continuous coverage for our trauma center. Our hypothesis was that integration could serve both the orthopaedic and plastic surgery training programs well and provide more consistent care for the trauma patients. Materials and Methods Program director approval was granted for blinded analysis of case logs from plastic and orthopaedic surgery programs from 2012 through 2019. Data on mean and total number of hand cases were analyzed and compared for both specialties. Institutional Review Board approval was granted for a retrospective review of patient outcomes. Results For both orthopaedic and plastics resident trainees, the mean number of hand cases increased during this study period suggesting that the integration had a favorable impact on both programs. The mean number of hand cases for orthopaedic residents rose from 163 to 246. The mean number of hand cases for plastic surgery residents rose from 218 to 295. Patient outcomes as reflected in length of stay and time to consultation also improved. Conclusion To improve hand surgical training and patient care, an integrated orthoplastics approach to hand surgery was implemented at our institution. Plastic surgery trainees are completing more hand surgery cases in an integrated model (p

There has been a steady rise in the use of dormant propagules to study biotic responses to environmental change over time. This is particularly important for organisms that strongly mediate ecosystem processes, as changes in their traits over time can provide a unique snapshot into the structure and function of ecosystems from decades to millennia in the past. Understanding sources of bias and variation is a challenge in the field of resurrection ecology, including those that arise because often‐used measurements like seed germination success are imperfect indicators of propagule viability. Using a Bayesian statistical framework, we evaluated sources of variability and tested for zero‐inflation and overdispersion in data from 13 germination trials of soil‐stored seeds of Schoenoplectus americanus, an ecosystem engineer in coastal salt marshes in the Chesapeake Bay. We hypothesized that these two model structures align with an ecological understanding of dormancy and revival: zero‐inflation could arise due to failed germinations resulting from inviability or failed attempts to break dormancy, and overdispersion could arise by failing to measure important seed traits. A model that accounted for overdispersion, but not zero‐inflation, was the best fit to our data. Tetrazolium viability tests corroborated this result: most seeds that failed to germinate did so because they were inviable, not because experimental methods failed to break their dormancy. Seed viability declined exponentially with seed age and was mediated by seed provenance and experimental conditions. Our results provide a framework for accounting for and explaining variability when estimating propagule viability from soil‐stored natural archives which is a key aspect of using dormant propagules in eco‐evolutionary studies.

To investigate if changes to hospital operational models during the COVID-19 pandemic negatively impacted overall time to surgery (TtS) as well as morbidity and mortality rates of hip fractures (HFx).416 patients treated for OTA 31 fractures at a single institution between January 2019 and November 2020 were reviewed. TtS as well as morbidity and mortality rates were obtained from pre-pandemic and pandemic groups.263 patients were treated pre-pandemic and 153 were treated during the pandemic. There were no significant differences in median TtS, readmission rates (p = 0.134), reoperation rates (p = 0.052), 30-day (p = 0.095) and 90-day (p = 0.22) mortality rates.Reallocation of hospital resources in response to the COVID-19 pandemic did not negatively impact surgical timing or complications. TtS for HFx remains a challenge and often requires multidisciplinary care, which is complicated by a pandemic. However, this study demonstrates HFx standard of care can be maintained despite COVID-19 obstacles to treatment efficiency and efficacy.

Vesicle-mediated transport is necessary for maintaining cellular homeostasis and proper signaling. The synaptosome-associated protein 23 (SNAP23) is a member of the SNARE protein family and mediates the vesicle docking and membrane fusion steps of secretion during exocytosis. Skeletal muscle has been established as a secretory organ; however, the role of SNAP23 in the context of skeletal muscle development is still unknown. Here, we show that depletion of SNAP23 in C2C12 mouse myoblasts reduces their ability to differentiate into myotubes as a result of premature cell cycle exit and early activation of the myogenic transcriptional program. This effect is rescued when cells are seeded at a high density or when cultured in conditioned medium from wild type cells. Proteomic analysis of collected medium indicates that SNAP23 depletion leads to a misregulation of exocytosis, including decreased secretion of the insulin-like growth factor 1 (IGF1), a critical protein for muscle growth, development, and function. We further demonstrate that treatment of SNAP23-depleted cells with exogenous IGF1 rescues their myogenic capacity. We propose that SNAP23 mediates the secretion of specific proteins, such as IGF1, that are important for achieving proper differentiation of skeletal muscle cells during myogenesis. This work highlights the underappreciated role of skeletal muscle as a secretory organ and contributes to the understanding of factors necessary for myogenesis.

For superficial colonic lesions, the NICE and Kudo classifications are used in the in vivo prediction of histology and as guide to therapy. The NICE system derives information from unmagnified NBI endoscopic images. The Kudo one necessitates a magnification, but, as this tool is not commonly available, it is applied also to characterize unmagnified pictures to compare their diagnostic performances. We conducted a prospective comparison of the NICE versus the Kudo classification for the differential diagnosis of colonic polyps taking histology as the gold standard. The inter-observer agreement for both classifications among 11 colonoscopists was also evaluated. Short unmagnified NBI videoclips of 64 colonic polyps were sent twice to the participants. In the first round, they classified the lesions according to the NICE classification; 4 months later, the same videos were assessed with the Kudo system. The diagnosis provided by the participants was grouped in non-neoplastic, non-invasive neoplasia, invasive neoplasia. Overall, the diagnostic accuracy was 82% (95%CI: 79–85) with the NICE system and 81% (95%CI: 78–84) with the Kudo one (ρ = 0.78). The accuracy of the NICE classification for non-neoplastic lesions was greater compared with the Kudo’s (ρ = 0.03). Sensitivity sub-analyses revealed a higher ability of the NICE in distinguishing between neoplastic vs. non-neoplastic lesions (ρ = 0.01). The overall inter-rater agreement did not differ when the classifications were compared. The NICE and the Kudo classifications might be considered comparable. Our data could allow the use of the NBI Kudo classification even in those centers where magnification is not available.

Background and study aims The Paris classification of superficial colonic lesions has been widely adopted, but a simplified description that subgroups the shape into pedunculated, sessile/flat and depressed lesions has been proposed recently. The aim of this study was to evaluate the accuracy and inter-rater agreement among 13 Western endoscopists for the two classification systems. Methods Seventy video clips of superficial colonic lesions were classified according to the two classifications, and their size estimated. The interobserver agreement for each classification was assessed using both Cohen k and AC1 statistics. Accuracy was taken as the concordance between the standard morphology definition and that made by participants. Sensitivity analyses investigated agreement between trainees (T) and staff members (SM), simple or mixed lesions, distinct lesion phenotypes, and for laterally spreading tumors (LSTs). Results Overall, the interobserver agreement for the Paris classification was substantial (κ = 0.61; AC1 = 0.66), with 79.3 % accuracy. Between SM and T, the values were superimposable. For size estimation, the agreement was 0.48 by the κ-value, and 0.50 by AC1. For single or mixed lesions, κ-values were 0.60 and 0.43, respectively; corresponding AC1 values were 0.68 and 0.57. Evaluating the several different polyp subtypes separately, agreement differed significantly when analyzed by the k-statistics (0.08–0.12) or the AC1 statistics (0.59–0.71). Analyses of LSTs provided a κ-value of 0.50 and an AC1 score of 0.62, with 77.6 % accuracy. The simplified classification outperformed the Paris classification: κ = 0.68, AC1 = 0.82, accuracy = 91.6 %. Conclusions Agreement is often measured with Cohen’s κ, but we documented higher levels of agreement when analyzed with the AC1 statistic. The level of agreement was substantial for the Paris classification, and almost perfect for the simplified system.

As agricultural intensification affects global environmental change, a redesign of our food production systems towards practices that replace external inputs with inbuilt ecosystem services is needed. Specifically, human-induced changes to biogeochemical flows of nitrogen (N) cycling exceed the proposed planetary boundaries, highlighting a priority area for reducing nutrient inputs in agricultural production systems. A new understanding of nutrient interactions in the complete agroecosystem will allow us to better predict and mitigate the consequences of anthropogenic environmental changes compared with a reductionist approach. Here, we review for the first time system-level nutrient interactions, particularly N, in perennial horticulture using high-producing kiwifruit and apple crops grown in New Zealand as a basis to identify critical knowledge gaps and prioritize new research. The major points identified are (1) current nutrient guidelines are from the 1980s to the early 2000s and do not take into account substantial production changes since that time; (2) few studies construct complete nutrient budgets of all sources and losses; (3) nutrient loss estimates are generally low relative to those from other agricultural land uses; (4) there is a lack of studies which address nutrient interactions between above- and below-ground food webs in perennial horticultural crops; (5) there is contradictory literature where fertilizer has been found both to increase and to decrease plant chemical signaling and defense mechanisms. New tools are emerging to improve orchard nutrient management, including advances in fertilizer application techniques, new methods to monitor plant and soil nutrients, and utilizing genetic variability to breed cultivars with improved nutrient use efficiency. To reduce adverse nutrient effects on the environment, new research is needed, addressing the relationships between carbon and nutrients and nutrient demands in modern fruit cultivars and growing systems; the nutrient balance for perennial horticultural crops considering all inputs and outputs; and interactions of the above- and below-ground nutrient flows in orchard food webs.

Study question Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can enter and actively infect human follicular and granulosa cells? Summary answer Follicular Granulosa (GCs) and Cumulus cells (CCs) are susceptible to SARS-CoV-2 infection that is able to reproduce. What is known already To enter host cells, SARS-CoV-2 uses Spike S1 subunit to bind the receptor angiotensin-converting enzyme2 (ACE2), S2 subunit is cleaved by the host transmembrane serine protease 2 (TMPRSS2) or by cathepsin L (CSTL) to produce unlocked, fusion-catalyzing viral forms. CD147 (BSG) has been proposed as an additional host receptor for SARS-CoV-2. Female fertility is strictly dependent on oocyte quality and competence. ACE2 is highly expressed in the human ovaries and in the stromal endometrial cells, as well as in GCs and oocytes. The expression of ACE2 strongly suggests that it is potentially at a high risk of SARS-CoV-2 infection. Study design, size, duration In order to analyze the presence of host receptors ACE2 and co-receptors TMPRSS2-CSTL and BSG and consequently the susceptibility of GCs and CCs to SARS-CoV2 infection. GCs and CCs were collected from about 25 patients undergoing IVF/ICSI cycles at the UOSA of Assisted Reproductive techniques, from March 2020 to October 2021 at the Center of Couple Sterility, Siena University Hospital. Participants/materials, setting, methods GCs and CCs were collected from women undergoing IVF cycle. GCs were recovered from the follicular fluid according to the procedure previously published. After oocyte denuding, CCs were isolated and both GCs and CCs co-cultured with SARS-CoV-2 then the supernatant was used to infect VERO6 Cells. Host factors and SARS-CoV2 expression/localization were confirmed by RT-PCR, Western blot and Immunofluorescence. SARS-CoV2 infection and its effect on GCs and CCs were evaluated by Transmission and Immuno-electron microscopy. Main results and the role of chance qRT-PCR analysis and WB showed that ACE2, TMPRSS2, BSG and CTSL transcripts were expressed in both GCs and CCs cells, even if at different levels. ACE2 transcript was significantly increased in the CCs (0.43 vs 0.15; p Limitations, reasons for caution This is a human in vitro study, and we cannot predict all the implications in female fertility and related to the oocyte Wider implications of the findings We provide evidence in favor of SARS-CoV-2 infection in GCs and CCs, the ovarian somatic cells that support oocyte development and competence acquisition. The close relationship between oocytes and follicular cells raises the hypothesis that these cells may represent a vehicle for the oocyte SARS-CoV-2 infection Trial registration number Not applicable

Study question Bisphenol A (BPA) is a constituent of polycarbonate and epoxy resin plastics and is also a by-product of combustion of plastics, resulting harmful for health. Summary answer To evaluate the presence of BPA in the blood and Follicular Fluids, in women, subjected to IVF cycles, living in areas with different environmental impact. What is known already BPA is used in the production of polycarbonate plastics and epoxy resins. 1,3,5-triphenylbenzene is a tracer for burning plastic and has been related to levels of bisphenol A in the air, so the actual release of bisphenol A to the atmosphere could result from burning the plastic. Bisphenol A belongs to the group of endocrine disruptors. Little is known about the effects of BPA on human female reproduction. BPA levels appear to be inversely related to the number of oocytes retrieved in IVF cycles, and it also appears to negatively affect the ovulatory peak of estradiol. Study design, size, duration In the frame of EcoFoodFertility project a cross sectional study conducted in Campania Region (Southern Italy), between January 2019 and December 2020, 74 women, no smokers, no chronic diseases, not exposed to occupational risk factors. living for at least 5 years in areas with low environmental impact (LEI, 31 women), Alto-Medio Sele in province of Salerno and high environmental impact (HEI, 43 women), so-called “Land of Fires” in province of Naples, were selected. Participants/materials, setting, methods Participants have a normal ovarian reserve, average age 32.05 + 3.49, with infertility duration between 26 and 39 months and at the first experience of an IVF cycle. ELISA was used for measuring bisphenol A in blood and Follicular Fluids (FFs), expressed in ng/ mL. 5 mL glass tubes, without additives, not siliconized and kept in a horizontal position were used. FFs were bloodless with a negative albumin test. Main results and the role of chance Differents levels of BPA were found in all processed samples. In the LEI (Low Environmental Impact) group, serum levels vary from a minimum of 3.1 ng/mL to a maximum of 7.7 ng/mL (4.1 ± 1.6) and the Follicular Fluids levels vary from a minimum of 7,1 ng/mL to a maximum of 55.3 ng/mL (13.8 ± 10.9). In the HEI (High Environmental Impact) group, serum levels vary from a minimum of 69.2 ng/mL to a maximum of 167.8 ng/mL (95.5 ± 24.3) and Follicular Fluids levels vary from a minimum of 4.2 ng/mL to a maximum of 34.3 ng/mL (19.9 ± 9.2). Statistical processing of the data shows a highly significant variation in serum levels (p A moderately significant change (p Furthermore, the data did not show any correspondence between serum and Follicular Fluids for any of the participants tested. Limitations, reasons for caution The ELISA method for the determination of BPA seems suitable to us, however, the subject requires further biomonitoring studies, with a larger sample and greater selection of participants, to better understand the effects of BPA and its metabolites in FF and in other districts of the female reproductive system. Wider implications of the findings The results indicate that the greater bioaccumulation in women of the HEI group appears consistent with the environmental condition of the area and with the comparative studies already carried out within the EcoFoodFertility project. This is further evidence that pollution in this area can interfere with female fertility and beyond. Trial registration number G003

Study question Human exposure to polychlorinated biphenyls (PCBs) exists despite its ceased production since 1977. PCBs congeners harm reproductive health, but data remain inconclusive. Summary answer Evaluate relationship between blood concentrations of specific (PCBs) congeners and abortion rates in women undergoing IVF cycles living in areas with high and low pollution. What is known already PCBs are a class of synthetic chemicals that were widely used in industry until the 1970s and are found in many consumer products as refrigerants in electrical equipment, as flame retardants in plastics production and electronics. Continuous exposure to PCBs is of concern because they fall into the group of endocrine disruptors (EDCs), PCB congeners can spread throughout the female reproductive tract. Indeed, they have been found in human follicle fluids, placenta, amniotic fluid in embryos and fetuses Despite multiple reproductive health effects in women was reported, the results are sometimes inconsistent between experimental and epidemiological studies. Study design, size, duration In the frame of EcoFoodFertility Project, a cross sectional study conducted in Campania Region (Italy) to assess environmental impact on fertility and human health, blood samples were collected during the IVF cycles of the 65 women (aged 27.8 + 3.6) no smokers, BMI 23.5 – 27.9, normal menstruation, in two areas with high and low pollution between 2017 and 2019. The PCBs congeners we investigated were: estrogenic congeners (31,44,52,101,153), anti-estrogenic congeners (77,105,110,114,126,156,169) and other (28,118,138,180). Participants/materials, setting, methods Group A (n = 30) living in low polluted area (LPA), alto Medio Sele in province of Salerno, and group B (n = 35) living in highly polluted area (HPA), known as the “Land of Fires” due to the many sources of pollution. The blood sample was taken on the day of the oocyte pick-up and PCBs were measured by Gas Chromatography Coupled to (tandem) Mass Spectrometry. Statistical analyses were performed by GraphPad Prism 9. Main results and the role of chance Blood concentrations of PCBs are expressed as wet weight (nanograms per gram of serum) and as standardised lipid concentrations (nanograms per gram lipid). The PCB 169 congener was found in the highest concentration, 229.62 ng/g and, on average, accounted for 46.2 % of ΣPCBs tested. The PCB 77 (p Limitations, reasons for caution Although we have set up a strict control and survey protocol, our study also has limitations due to the relatively small sample size of the groups and as with almost all epidemiological studies on environmental impact, there may be confounders or co-exposures that could interfere with the observed associations. Wider implications of the findings Although PCBs are no longer produced, the exposure remains widespread due to their long biological half-life, accumulation in the food chain and human health impacts are still reported. Our findings confirm these concerns, therefore, the study of these old chemicals is still relevant and important and should be expanded. Trial registration number not applicable

As ductile derivatives of amorphous alloys, metallic glass composites balance high strength with the ability to mitigate catastrophic shear localization, which has long plagued monolithic metallic glasses. In this study, we employ a bonded-interface indentation technique coupled with strain field mapping to identify the governing yield criterion in metallic glass composites as a function of their microstructural length scales. A crossover from the shear plane to maximum shear stress yield criterion is uncovered at a crystalline fraction of approximately 60%, thus signaling an effective transition from incipient to homogeneous flow as the dominant deformation mode of the composite microstructure.

Background In Hospitals,interventions aimed at identifying adverse events are based on voluntary reporting by health care professionals. We evaluate the incident reporting system in a Private Clinic which provides medical-surgical-rehabilitative health care services both to NHS and Private Patients. Methods A retrospective study was carried out by retrieving reports of adverse events that occurred from January 2011 to December 2015(processing of the years 2016-2020 is ongoing).Data were obtained from various information sources: institutional incident reporting; reports for administrative and insurance purposes; surveillance activities of the health management; organizational environmental reports; tabulations of transfer to the emergency department. Results A total of 306 adverse events were recorded during the study period. The most reported were transfers(51%), followed by falls(31%).Among those reporting adverse events, the main ones were Doctors(44.72%), followed by Nurses(9.15%) and Physical Therapists(1.41%).The institutional incident reporting system detected 42.5% of the adverse events, underestimating at least 57.5%; moreover, only 27.7% of the events were reported in more than one of the above sources.We are now processing the 2016-2020 data,which can be presented at the EPH Conference. Conclusions It is necessary to use several information sources to reconstruct a reliable epidemiology of adverse events in the hospital,in order to structure an effective system of audit and quality improvement. Key messages Only an integrated risk assessment can promote changes in clinical practice. Reducing gaps in reporting tools means increasing the safety, effectiveness and efficiency.

Children and young people are particularly sensitive to the environmental pollution which is closely related to degenerative diseases. Several studies show that a genotoxic damage during young age can increase the risk of chronic diseases in adulthood. The young people are more vulnerable than adults to the environmental pollutants because they spend more time outdoors, they have immaturity of some organs and of the mechanisms involved in the cellular repair. In the present study, the early biological effects of exposure to a particularly polluted area of Southern Italy were evaluated in 200 children (6-10 year-old) and 100 young people (18-25 year-old). This area, worldwide known as Sarno basin, is characterized by strong anthropization, many agro-food processing industries, massive use of fertilizers and pesticides in agricultural practices and a strong river pollution. The comet assay was chosen because it reflects cumulative exposure to a variety of environmental factors and it was performed on salivary leukocytes in the children selected for the survey, while in the young people the DNA damage was evaluated in human peripheral blood lymphocytes. As in previous studies were not find significant differences between salivary leukocytes and blood lymphocytes we preferred the sampling of saliva for the children to avoid bloody practices. Furthermore, before cell sampling the children's parents were interviewed using an ad hoc questionnaire designed to gather additional information about exposure sources. A questionnaire was administered also to the young people to have more information on their lifestyle and some characteristic of the area of exposure (vehicular traffic and so on). The results showed a clear damage from exposure in the children differently from young people. Key messages Comet assay was performed in vitro on lymphocytes of 200 children (6-10 year-old) and 100 young people (18-25 year-old) exposed to a particularly polluted area of Southern Italy. An evident DNA damage was observed in lymphocytes coming from children; no genetic material alterations were observed in young people.