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Background. Workplace violence (WPV) is a major healthcare problem with important consequences in healthcare areas and may impact negatively not only healthcare workers but also the quality and safety of patient care. Objectives: This an observational online web-based survey using Google® Modules, specifically aiming to investigate the phenomenon of WPV in Italian healthcare services. Methods. Data collection for this study lasted one month, with the questionnaire available from 1 May 2021 to 31 May 2021. Continuous variables were considered as either mean ± standard deviation (SD) or median and interquartile range (IQR) based on their distribution. Comparison between groups was assessed by unpaired t-test or Mann–Whitney U test according to variable distribution. Categorical variables were analyzed using the chi-squared test. Results. The study population consisted of 203 healthcare workers, represented by nurses (61.6%), medical doctors (16.8%), patient care assistants (4.9%), and others (16.7%). Female gender was associated with a 2.6 times higher risk for the presence of aggression (p = 0.034), and nurse as a job with about 4 times increased risk for the presence of aggression (p = 0.006). The risk for aggression increased by 5% for each year of work experience. Conclusions. WPV is still matter of concern in Italian healthcare services. A strong organizational effort is demanded from healthcare institutions in order prevent internal and external violence in healthcare settings.

Background. Insomnia is one of the major health problems related with a decrease in quality of life (QOL) and also in poor functioning in night-shift nurses, that also may negatively affect patients’ care. The aim of this study is to evaluate the prevalence of insomnia in night shift nurses. This observational online web-based survey using Google®® modules specifically aimed to investigate the prevalence and risk factors for insomnia among Italian nurses. Methods. Data collection for this study lasted one month, with the questionnaire available from 1 March 2021 to 1 April 2021. Continuous variables were considered as either mean ± standard deviation (SD) or median and interquartile range (IQR) based on their distribution. Comparison among insomnia categories was assessed by one-way ANOVA or Kruskal–Wallis test according to variable distribution. Categorical variables were analyzed using chi-square test. Results. A total of 2355 responses were included in the final analysis, with 917 from the Northern zone, 815 from the Western zone, and 623 from the Southern zone of Italy. The prevalence of insomnia in the overall population was 65.4% (1524 out 2355 nurses suffered from insomnia). Conclusions. Nursing is a high-pressure profession, with heavy duties and high professional risks. We found an important prevalence of insomnia in night shift nurses, and we hope it may help to solicit further studies aimed to identify the risk factors for this working disorder among nurses.

Breast cancer represents one of the main reasons of death among women. As an alternative to the gold standard techniques for breast cancer diagnosis, microwave imaging has been proposed from research community and many microwave systems have been designed mainly to work at low microwave frequencies. Based both on the results of recent dielectric characterization campaigns on human breast ex-vivo tissues up to 50 GHz and on the promising feasibility studies of mm-wave imaging systems, in this article, we propose and test inverse scattering techniques as effective tool to process mm-wave data to image breast cancer. Differently from radar techniques so far adopted in conjunction with mm-wave imaging system, inverse scattering techniques turn out to be more versatile and robust with respect to the reduction of the amount of data and eventually also able to characterize the anomaly in terms of electromagnetic properties. In particular, in the above, two image reconstruction techniques, the Linear Sampling Method and the Born Approximation, are proposed and compared against both simulated and experimental data.

Background Trans-sphenoidal endoscopic surgery has drawn huge benefits from advances in surgical visualization. The Ultra-HD "4K" endoscope has improved 4-fold image resolution compared with HD, but its actual advantages are unclear. Aim of the present study was to assess its usefulness in the early outcome of trans-sphenoidal surgery. Methods We analyzed a series of 199 trans-sphenoidal pituitary adenoma procedures performed by an experienced team using alternatively HD (n=102) or 4K (n=97) endoscopes. We evaluated extent of resection both subjectively, based on intraoperative surgeon's impression, and objectively based on post-operative MR scan. Results Baseline patients' characteristics were balanced. Objective near-total and total resection rates were comparable between 4K and HD groups (91.5% vs 86.3% and 64.9% vs 56.9%, respectively). 4K endoscope slightly improved resection rate in recurrent adenoma. At multivariate analysis, the only independent prognosticator of total resection was cavernous sinus invasion. Importantly, 4K endoscope enhanced the reliability of intraoperative judgement on extent of resection, significantly reducing unexpected residuals (12.8% vs 33.3% for HD). Operative features and clinical outcomes were similar. Conclusions The HD endoscope remains the standard-of-care for pituitary surgery. The 4K enhanced, "immersive" visualization significantly improved the reliability of surgeon's judgment on resection and might be useful in surgically difficult cases.

Background Chronic Venous Disease (CVD) has a high prevalence in the western world. Varicose veins (VVs) are the main signs of this disease that is characterized by important pathological vessel wall changes. The aim of this study is to correlate the main histopathological abnormalities with related clinical issues of CVD. Methods A cohort of patients with VVs scheduled for open surgical treatment namely stab avulsion of VVs was recruited. Subsequently, venous tissue from stab avulsion was collected in order to evaluate the following biomarkers: Vascular-Endothelial Growth Factor (VEGF), Protein Gene Product 9.5 (PGP 9.5), Fibronectin (FN), and Matrix Metalloproteinase-9 (MMP-9). The Clinical-Etiology-Anatomy-Pathophysiology (CEAP) criteria were used to classify CVD. Results Fourteen tissue fragments were processed for histological and immunohistochemical studies. Of these, 43% were from CEAP C2 patients, 36% from CEAP C3 patients, and 21% from CEAP C4 patients. CEAP Class C2 had few to moderate structures positive to VEGF; occasional structures positive to Fibronectin, numerous structures positive to MMP9, few to moderate structures positive to PGP 9.5. CEAP Class C3 had moderate structures positive to VEGF; few to moderate structures positive to Fibronectin; many structures positive to MMP9; few to moderate structures positive to PGP 9.5. CEAP Class C4 had numerous structures positive to VEGF; numerous structures positive to Fibronectin; abundant structures positive to MMP-9; few structures positive to PGP 9.5. Conclusions In this study, positive VEGF, FN, and MMP-9 structures were found with increasing trends in relation to the disease staging. VEGF and FN are associated with a progressive increase from C2 to C4. The MMP-9 marker has an important positivity even at early stage of the disease, being higher in CEAP C4 patients. PGP 9.5 decreases in CEAP C4 patients and this is concordant to decreased vein wall innervation.

Objective: to determine lifestyle changes, such as physical activity, nutrition, and sleep in an Argentinean university population, caused by confinement during the COVID-19 pandemic. Methods: Cross-sectional study via web survey. 1021 the Argentinean university population (women, n = 645 and men, n = 376) aged between 18–70 years old was participate. Survey was utilized to measure participant physical activity behavior, nutrition, and sleep April to May 2020. Results: the main findings revealed that 4.3% of the sample showed obesity; the highest proportion of the sample stayed more than 6 hours in a sedentary status; 21.74% reported bad sleep quality; a reduction in good feeding pattern; and an increase in subjects who do not perform physical activity. According to socio-demographic and anthropometric factors, being a student (OR 2.19, CI95% 1.18 - 4, p= .012), overweight (OR 1.71, CI95% 1.19 – 2.44, p= .003), obesity (OR 4.45, CI95% 2.27 – 8.7, p< .001), and have been confined more than 45 days was associated with bad feeding. Likewise, low physical activity levels were associated with obesity (OR 3.2 CI95% 1.66 – 6.18, p= .001), being female (OR 1.61, CI95% 1.14 –2.28, p= .006) and get married (OR 1.72, CI95% 1.14 – 2.61, p= .009). Moreover, being a student was associated with poor sleep quality (OR 43.6, CI95%5.4 – 350, p< .001). Conclusion: This study suggests that confinement decreased healthy living habits such as good nutrition and physical activity and affected the quality of sleep in young subjects. Resumen. Objetivo: determinar los cambios en el estilo de vida, como la actividad física, la nutrición y el sueño en una población universitaria argentina, causados por el confinamiento durante la pandemia de COVID-19. Métodos: Estudio transversal mediante encuesta por Internet. Participaron 1021 personas de la población universitaria argentina (mujeres, n = 645 y hombres, n = 376) de entre 18 y 70 años de edad. La encuesta fue utilizada para medir el comportamiento de la actividad física, la nutrición y el sueño de los participantes de abril a mayo de 2020.Resultados: los principales hallazgos mostraron que el 4,3% de la muestra presentaba obesidad; la mayor proporción de la muestra permaneció más de 6 horas en estado sedentario; el 21,74% informó sobre la mala calidad del sueño; una reducción de los hábitos correctos de alimentación; y un aumento de los participantes que no realizan actividad física. De acuerdo con factores socio-demográficos y antropométricos, ser estudiante (OR 2.19, CI95% 1.18 - 4, p= .012), el sobrepeso (OR 1.71, CI95% 1.19 - 2.44, p= .003), la obesidad (OR 4.45, CI95% 2.27 - 8.7, p< .001), y haber estado confinado más de 45 días se asoció con una mala alimentación. Asimismo, los bajos niveles de actividad física se asociaron con la obesidad (OR 3,2; IC95% 1,66 - 6,18, p= .001), ser mujer (OR 1,61; IC95% 1,14 -2,28, p= .006) y estar casado (OR 1,72; IC95% 1,14 - 2,61, p= .009). Además, ser estudiante se asoció con una mala calidad de sueño (OR 43,6, CI95% 5,4 - 350, p< .001). Conclusión: Este estudio sugiere que el confinamiento disminuyó los hábitos de vida saludables como la buena nutrición, la actividad física, y afectó la calidad del sueño en sujetos jóvenes.

The physiological functions of many vital tissues and organs continue to mature after birth, but the genetic mechanisms governing this postnatal maturation remain an unsolved mystery. Human pancreatic β-cells produce and secrete insulin in response to physiological cues like glucose, and these hallmark functions improve in the years after birth. This coincides with expression of the transcription factors SIX2 and SIX3, whose functions in native human β-cells remain unknown. Here, we show that shRNA-mediatedSIX2orSIX3suppression in human pancreatic adult islets impairs insulin secretion. However, transcriptome studies revealed thatSIX2andSIX3regulate distinct targets. Loss ofSIX2markedly impaired expression of genes governing β-cell insulin processing and output, glucose sensing, and electrophysiology, whileSIX3loss led to inappropriate expression of genes normally expressed in fetal β-cells, adult a-cells and other non-β-cells. Chromatin accessibility studies identified genes directly regulated by SIX2. Moreover, β-cells from diabetic humans with impaired insulin secretion also had reducedSIX2transcript levels. Revealing howSIX2andSIX3govern functional maturation and maintain developmental fate in native human β-cells should advance β-cell replacement and other therapeutic strategies for diabetes.

Intervista al prof. Francesco Emma Nefrologia e Dialisi, Ospedale Pediatrico “Bambino Gesù” IRCCS, Roma

Background: Giant intracranial meningiomas (GIMs) are extremely rare and are usually considered arduous to resect totally with poorer prognosis. The real mechanisms by which a meningioma can grow to be defined as "giant" are unknown, as well as the real biological , radiological profile and the different outcomes.Methods: We performed a retrospective review of a consecutive series of surgically-treated patients suffering from intracranial Meningioma. All the patients were assigned on the ground of the preoperative imaging to the Giant and Medium/Large Meningiomas. We investigated whether the presence large diameter on radiological diagnosis is indicative for different mortality rate, grading, characteristic and clinical/neurological outcome.Results: The study shows that surgically treated giant meningiomas have a higher risk of developing complications in the postoperative phase (Chi square= 11.121, dF=1, p=0.001). The direct proportional relationship between peritumoral brain edema (PBE) volume and tumor volume was present only in the medium/large group and was not present in the giant meningioma group. When comparing the degree of performance there is a statistically significant difference between localization and KPS immediately postoperatively (p=0.04) particularly for sphenopetroclival meningiomas (p=0.071), and partially with GIM of the olfactory groove with arterial encasement. The most frequently encountered complications include the occurrence of ischemia (p=0.049), infection (p=0.03), and the occurrence of postoperative seizures.Conclusions: We identified that the major surgical risk factor for GIMs is location, where the petro-clival region and, to a lesser extent the anterior basicranium offer a greater risk of neurovascular involvement and arterial encasement. On other hand, the risk correlated with PBE is poorer in GIM although there is a well-noted correlation between the Edema volume and outcome in meningiomas.

Background: the aim of this study was to perform an Italian telematics survey analysis on the changes in couples’ sex lives during the coronavirus disease 2019 (COVID-19) lockdown. Methods: a multicenter cross sectional study was conducted on people sexually active and in stable relationships for at least 6 months. To evaluate male and female sexual dysfunctions, we used the international index of erectile function (IIEF-15) and the female sexual function index (FSFI), respectively, marital quality and stability were evaluated by the marital adjustment test (items 10–15), to evaluate the severity of anxiety symptoms, we used the Hamilton Anxiety Rating Scale. The effects of the quarantine on couples’ relationships was assessed with questions created in-house. Results: we included 2149 participants. The sex lives improved for 49% of participants, particularly those in cohabitation, for 29% it deteriorated, while for 22% of participants it did not change. Women who responded that their sex lives deteriorated had no sexual dysfunction, but they had anxiety, tension, fear, and insomnia. Contrarily, men who reported deteriorating sex lives had erectile dysfunctions and orgasmic disorders. In both genders, being unemployed or smart working, or having sons were risk factors for worsening the couples’ sex lives. Conclusion: this study should encourage evaluation of the long-term effects of COVID-19 on the sex lives of couples.

Chronic kidney disease (CKD) is a clinical condition characterized by high morbidity and mortality. Globally, CKD is also increasing in prevalence and incidence. The two principal kidney measures namely estimated glomerular filtration rate (eGFR) and albuminuria have been found to be predictors of renal and cardiovascular (CV) endpoints including peripheral artery disease (PAD). The prevalence of PAD was increased in CKD patients and, particularly, in patients with more severe CKD stages. Despite the fact that revascularization strategies are suitable in CKD patients in similar fashion to non-CKD patients, few CKD patients underwent these procedures. In fact, if it is true that revascularization improves prognosis in PAD patients irrespective of baseline eGFR, it was also demonstrated that CKD patients, who underwent revascularization, were at higher risk for amputations, mortality, re-intervention and perioperative complications. With the present review article, we have examined the association between CKD, PAD and peripheral revascularization highlighting data about epidemiology, pathophysiologic mechanisms, and results from previous observational and intervention studies. We have also examined the future perspectives and challenges of research around the association between CKD and PAD.

The high frequency of the radiofrequency (RF) fields used in high field magnetic resonance imaging (MRI) causes electromagnetic field variations which increase the specific absorption rate (SAR) local level and also imaging artifacts degrading the quality of MRI images. For this reason, different approaches have been proposed in literature, which aim at simultaneously improving the B 1 + homogeneity and reduce the SAR level in the body. However, most of them do not involve the determination of the complex excitation currents pertaining to the RF coil of MRI systems. In this contribution, starting from a recently introduced field intensity shaping technique, we propose a novel procedure for B 1 + shimming which is also able to control the purity of polarization of the total RF field as well as to limit the SAR level within the biological tissues. This procedure is based on convex optimization and is assessed in the following in case of brain imaging.

El proceso investigativo tuvo el objetivo de determinar la percepción que tienen los pacientes diagnosticados con ansiedad y depresión acerca de la efectividad de los tratamientos breves y focalizados recibidos en el departamento de psicología del Sanatorio San Gabriel, de la sede de la Ciudad Autónoma de Buenos Aires (Argentina), durante 2017 y 2018. El diseño empleado fue no experimental, descriptivo y con enfoque cuantitativo. La población estuvo constituida las historias clínicas de 19 pacientes de ese contexto de estudio. El 52,63% de los participantes consideró que existió una reinstauración de los síntomas originales, lo que prevaleció en el estudio, además de los que valoraron su rehabilitación como bien o muy bien y aquellos que consideraban requerir renovar las sesiones de terapia.

In applied behavior analysis, the use of function-based treatments to reduce problem behavior is well-supported. However, in some cases, function-based treatments alone may not be as effective as nonfunction-based treatments or function-based treatments with additional, nonfunction-based components. In this case study, we compared the delivery of preferred edible items (a nonfunction-based treatment), a break from a task (a function-based treatment), and an enhanced break, which consisted of a break plus access to a preferred tangible item (combination of a nonfunction-based and function-based treatment), to treat escape-maintained aggression exhibited by a young child with attention deficit hyperactivity disorder. Across all three treatments, reinforcement (i.e., edible, break, or enhanced break) was delivered contingent upon compliance with instructions and problem behavior resulted in escape. The nonfunction-based treatment and the combination treatment reduced aggression to zero levels; the function-based treatment did not. Finally, we allowed the participant to choose which of the three treatments he preferred to experience; he selected the combination treatment most often.

Pancreatic islets are vital endocrine regulators of systemic metabolism, and recent investigations have increasingly focused on understanding human islet biology. Studies of isolated human islets have advanced understanding of the development, function, and regulation of cells comprising islets, especially pancreatic α- and β-cells. However, the multicellularity of the intact islet has stymied specific experimental approaches—particularly in genetics and cell signaling interrogation. This barrier has been circumvented by the observation that islet cells can survive dispersion and reaggregate to form ‘pseudoislets’, organoids that retain crucial physiological functions, including regulated insulin and glucagon secretion. Recently, exciting advances in the use of pseudoislets for genetics, genomics, islet cell transplantation, and studies of intra-islet signaling and islet cell interactions have been reported by investigators worldwide. Here we review molecular and cellular mechanisms thought to promote islet cell reaggregation, summarize methods that optimize pseudoislet development, and detail recent insights about human islet biology from genetic and transplantation-based pseudoislet experiments. Owing to robust, international programs for procuring primary human pancreata, pseudoislets should serve as both a durable paradigm for primary organoid studies and as an engine of discovery for islet biology, diabetes, and metabolism research.

Emerging evidence points toward an intricate relationship between the pandemic of coronavirus disease 2019 (COVID-19) and diabetes. While preexisting diabetes is associated with severe COVID-19, it is unclear whether COVID-19 severity is a cause or consequence of diabetes. To mechanistically link COVID-19 to diabetes, we tested whether insulin-producing pancreatic β cells can be infected by SARS-CoV-2 and cause β cell depletion. We found that the SARS-CoV-2 receptor, ACE2, and related entry factors (TMPRSS2, NRP1, and TRFC) are expressed in β cells, with selectively high expression of NRP1. We discovered that SARS-CoV-2 infects human pancreatic β cells in patients who succumbed to COVID-19 and selectively infects human islet β cells in vitro. We demonstrated that SARS-CoV-2 infection attenuates pancreatic insulin levels and secretion and induces β cell apoptosis, each rescued by NRP1 inhibition. Phosphoproteomic pathway analysis of infected islets indicates apoptotic β cell signaling, similar to that observed in type 1 diabetes (T1D). In summary, our study shows SARS-CoV-2 can directly induce β cell killing., Graphical abstract, Diabetic patients are at risk for severe COVID-19, but the virus may further damage insulin-secreting β cells. Wu et al. found that patient β cells are virally infected and the highly expressed neuropilin-1 receptor is critical for viral entry, causing cell death and reduced insulin secretion, exacerbating diabetes in patients.

Background Food Protein-Induced Enterocolitis Syndrome (FPIES) is a non IgE-mediated food allergy that generally affects children in the first year of life. Usually symptoms break out when formula milk or solid foods are introduced for the first time but they might also appear in exclusively breastfed infants, since the trigger elements, especially cow’s milk proteins, can be conveyed by maternal milk as well. FPIES in exclusively breastfed babies is a very rare clinical condition and only few cases have been reported in the medical literature. Case presentation We describe two cases of FPIES in exclusively breastfed babies. The first one is a two-month-old infant with a brief history of vomit and diarrhea that presented to the Emergency Department in septic-like conditions. The main laboratory finding was a significant increase in methemoglobin (13%). Clinically, we noted that, when breastfeeding was suspended, diarrhea drastically improved, and vice versa when maternal milk was reintroduced. An amino acid-based formula allowed a complete normalization of the symptoms. The second one is a three-month-old infant admitted for a 3 days history of persistent vomit and diarrhea. Blood tests showed a raised level of methemoglobin (7%). An esophagogastroduodenoscopy was performed and biopsies showed an eosinophilic infiltration of the duodenal mucosa. A maternal exclusion diet and an amino acid-based formula allowed a rapid regularization of the bowel function. Conclusions We searched all the cases of FPIES in exclusively breastfed babies reported in the medical literature, identifying eight patients, with an average age of 3 months (range 15 days – 6 months). The majority of the cases were initially diagnosed as gastroenteritis or sepsis, five cases were characterized by an acute on chronic scenario and cow’s milk was the most frequently involved food. Methemoglobin was never tested. An oral food challenge test was performed in two patients. FPIES in exclusively breastfed infants is a rare condition that, in the presence of compatible history and symptoms, should be considered also in exclusively breastfed babies. The evaluation of methemoglobin can simplify the diagnostic process.

Background: It has been 15 years since sirolimus, an mTOR inhibitor, received Food and Drug Administration approval to prevent acute rejection in kidney transplantation, and 8 years since its analog everolimus acquired the same status. Since then, these drugs have become more and more utilized and their immunosuppressive and antiproliferative properties have been tested in a great variety of clinical conditions, often achieving excellent results. Despite such positive evidence, the on-label indications for these rapalogs are still very restrictive, especially in children. Aims: The aims of this study were to describe our center’s experience with sirolimus and everolimus in managing rare pediatric conditions for which mTOR inhibitors have been reported as a therapeutic option, although without conclusive approval from regulatory agencies, and to evaluate safety and tolerability of the treatment at the prescribed doses. Methods: All the subjects who received off-label sirolimus or everolimus at the Pediatric Department of the IRCCS Burlo Garofolo in the last 13 years were included. For each disease found in our case series, we reviewed the current scientific literature. Results: Off-label treatment with rapalogs was prescribed in 16 children (11 males, 5 females, median age of 9.5 years, range 1–16 years). Seven had immunologic disorders: four autoimmune lymphoproliferative syndrome (ALPS), one multicentric Castleman disease (mCD), one activated PI3K delta kinase syndrome (APDS), and one immunodysregulation with polyendocrinopathy enteropathy X-linked (IPEX). Eight had proliferative disorders or vascular anomalies: one cystic lymphangioma, two Bannayan–Riley–Ruvalcaba syndrome (BRRS), one blue rubber bleb nevus syndrome (BRBNS), two tuberous sclerosis complex (TSC), and one low-flow mixed arterial and venous malformation. One case had congenital hyperinsulinism (CHI). The average dosage administered was 1 mg/m2 for sirolimus and 7 mg/m2 for everolimus. We experienced a good measurable clinical improvement in 14 patients. Nobody experienced serious adverse events (SAEs). The therapy was interrupted in two cases, for lack of efficacy and poor tolerance in one case and for occurrence of bacterial pneumonia in the other one. A review of the literature identified 101 published reports that met our inclusion criteria. Conclusions: Although use of mTOR inhibitors has been considered to be complicated, our experience shows that, using low dosages, it is possible to obtain relevant clinical improvements, with a good profile of safety and tolerability.

Introduction: Pre-surgical mapping is clinically essential in the surgical management of brain tumors to preserve functions. A common technique to localize eloquent areas is functional magnetic resonance imaging (fMRI). In tumors involving the peri-rolandic regions, the finger tapping task (FTT) is typically administered to delineate the functional activation of hand-knob area. However, its selectivity may be limited. Thus, here, a novel cue-induced fMRI task was tested, the visual-triggered finger movement task (VFMT), aimed at eliciting a more accurate functional cortical mapping of the hand region as compared with FTT.Method: Twenty patients with glioma in the peri-rolandic regions underwent pre-operative mapping performing both FTT and VFMT. The fMRI data were analyzed for surgical procedures. When the craniotomy allowed to expose the motor cortex, the correspondence with intraoperative direct electrical stimulation (DES) was evaluated through sensitivity and specificity (mean sites = 11) calculated as percentage of true-positive and true-negative rates, respectively.Results: Both at group level and at single-subject level, differences among the tasks emerged in the functional representation of the hand-knob. Compared with FTT, VFMT showed a well-localized activation within the hand motor area and a less widespread activation in associative regions. Intraoperative DES confirmed the greater specificity (97%) and sensitivity (100%) of the VFMT in determining motor eloquent areas.Conclusion: The study provides a novel, external-triggered fMRI task for pre-surgical motor mapping. Compared with the traditional FTT, the new VFMT may have potential implications in clinical fMRI and surgical management due to its focal identification of the hand-knob region and good correspondence to intraoperative DES.

Multiple G protein-coupled receptors (GPCRs) are expressed in pancreatic islet cells, but the majority have unknown functions. We observed specific GPCRs localized to primary cilia, a prominent signaling organelle, in pancreatic α and β cells. Loss of cilia disrupts β-cell endocrine function, but the molecular drivers are unknown. Using functional expression, we identified multiple GPCRs localized to cilia in mouse and human islet α and β cells, including FFAR4, PTGER4, ADRB2, KISS1R, and P2RY14. Free fatty acid receptor 4 (FFAR4) and prostaglandin E receptor 4 (PTGER4) agonists stimulate ciliary cAMP signaling and promote glucagon and insulin secretion by α- and β-cell lines and by mouse and human islets. Transport of GPCRs to primary cilia requires TULP3, whose knockdown in primary human and mouse islets relocalized ciliary FFAR4 and PTGER4 and impaired regulated glucagon or insulin secretion, without affecting ciliary structure. Our findings provide index evidence that regulated hormone secretion by islet α and β cells is controlled by ciliary GPCRs providing new targets for diabetes.

The incidence rate of breast cancer among women worldwide shows an increasing trend. Early detection plays a key role in increasing women's chances of survival. Several breast-imaging methods are currently used. However, due to the limitations of each of them, the proposal of new methods for breast imaging is still a hot topic in the scientific community. Among the proposed solutions, microwave imaging systems are attracting great interest, thanks to the significant dielectric contrast between healthy and tumor tissues of the breast. Several prototypes with central frequencies from few to tens of GHz have been proposed, both based on radar and tomographic reconstructions. In this paper, a quantitative solution combining both approaches for millimeter wave imaging of the breast is proposed. In particular, the radar approach is used to quickly detect the possible presence of a suspicious region, while the derivation of the nature of the lesion is pursued via a tomographic approach. Here the main idea is presented, along with a possible road map for further developments.

Objectives: Restrictive measures adopted during the COVID-19 pandemic, in order to limit contagion, have had a severe impact on mental health. The burden of lockdown has been particularly heavy on patients with chronic neurologic diseases such as People with Epilepsy (PwE). Our survey aims to describe the struggles and needs of Drug-Resistant (DR) PwE with implanted Vagal Nerve Stimulator (VNS) during the first wave of the COVID-19 lockdown in order to find strategies that help patients cope with present or future periods of restriction.Methods: We collected answers from 30 respondents who underwent an online survey including socio-demographic and clinical information and COVID-19-related information. Depression, anxiety symptoms, and sleep quality were investigated in patients through BDI II, GAD-7, and the PSQI scale.Results: In all, 46% of our sample reported an increase in the number of seizures; the entire sample complained of epilepsy-related issues (medication availability, VSN adjustments, anxiety, sleep disturbance); one out of three participants reported major epilepsy issues felt urgent; 30% had to postpone scheduled examination. Significantly higher scores for depression and anxiety scales were found in patients who perceived seizure frequency worsening and reported major epilepsy-related issues.Conclusion: Preliminary findings showed that the first lockdown influenced the clinical and psychological status of PwE and was related to seizures worsening. The lack of medical assistance and control on VNS therapy left patients to cope with the situation without a chance to contact a specialist. We discuss how a wider implementation of telemedicine programs could facilitate remote assistance of PwE with a VNS implant.

SummaryMultiple G protein coupled receptors (GPCRs) are expressed in pancreatic islet cells but the majority have unknown functions. We observe specific GPCRs localized to primary cilia, a prominent signaling organelle, in pancreatic α- and β-cells. Loss of cilia disrupts β-cell endocrine function, but the molecular drivers are unknown. Using functional expression, we identified multiple GPCRs localized to cilia in mouse and human islet α- and β-cells, including FFAR4, PTGER4, DRD5, ADRB2, KISS1R, and P2RY14. Free fatty acid receptor 4 (FFAR4) and prostaglandin E receptor 4 (PTGER4) agonists stimulate ciliary cAMP signaling and promote glucagon and insulin secretion by α- and β-cell lines, and by mouse and human islets. Transport of GPCRs to primary cilia requires TULP3, whose knockdown in primary human and mouse islets depleted ciliary FFAR4 and PTGER4, and impaired regulated glucagon or insulin secretion, without affecting ciliary structure. Our findings provide index evidence that regulated hormone secretion by islet α- and β-cells is regulated by ciliary GPCRs providing new targets for diabetes.

The baculovirus Autographa californica multiple nucleopolyhedrovirus is an insect virus with a circular double-stranded DNA genome, which, among other multiple biotechnological applications, is used as an expression vector for gene delivery in mammalian cells. Nevertheless, the nonspecific immune response triggered by viral vectors often suppresses transgene expression. To understand the mechanisms involved in that response, in the present study, we studied the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway by using two approaches: the genetic edition through CRISPR/Cas9 technology of genes encoding STING or cGAS in NIH/3T3 murine fibroblasts and the infection of HEK293 and HEK293 T human epithelial cells, deficient in cGAS and in cGAS and STING expression, respectively. Overall, our results suggest the existence of two different pathways involved in the establishment of the antiviral response, both dependent on STING expression. Particularly, the cGAS-STING pathway resulted in the more relevant production of beta interferon (IFN-β) and IFN-λ1 in response to baculovirus infection. In human epithelial cells, IFN-λ1 production was also induced in a cGAS-independent and DNA-protein kinase (DNA-PK)-dependent manner. Finally, we demonstrated that these cellular responses toward baculovirus infection affect the efficiency of transduction of baculovirus vectors. IMPORTANCE Baculoviruses are nonpathogenic viruses that infect mammals, which, among other applications, are used as vehicles for gene delivery. Here, we demonstrated that the cytosolic DNA sensor cGAS recognizes baculoviral DNA and that the cGAS-STING axis is primarily responsible for the attenuation of transduction in human and mouse cell lines through type I and type III IFNs. Furthermore, we identified DNA-dependent protein kinase (DNA-PK) as a cGAS-independent and alternative DNA cytosolic sensor that contributes less to the antiviral state in baculovirus infection in human epithelial cells than cGAS. Knowledge of the pathways involved in the response of mammalian cells to baculovirus infection will improve the use of this vector as a tool for gene therapy. Fil: Amalfi, Sabrina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Molina, Guido Nicolás. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Bevacqua, Romina Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; Argentina Fil: López, María Gabriela. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Taboga, Oscar Alberto. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; Argentina Fil: Alfonso, Victoria. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Agronómicas. Instituto de Agrobiotecnología y Biología Molecular. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Agrobiotecnología y Biología Molecular; Argentina

Breast cancer imaging represents a relevant and promising application area of microwave imaging technology. As breast tissues exhibit different electromagnetic properties at microwave frequencies depending on their typology and physio-pathological status, retrieving the complex-valued permittivity allows differentiating normal and diseased tissues. Recently, efforts have been made to obtain highquality prior information in order to improve both the accuracy and resolution of microwave imaging reconstructions. In this work, the use of prior information based on a combination of linear/orthogonal sampling method results is proposed in order to generate spatial priors to be used within the Contrast Source Inversion scheme. Results are compared to contrast source inversion images generated using prior information obtain from a non-iterative eigenfunction-based inversion method.

Background: Low back pain (LBP) is one of the most frequent diseases for which patients seek advice in a community pharmacy. The study aimed to evaluate the feasibility of the administration by community pharmacists of questionnaires to assess the LBP intensity and disability degree in patients entering community pharmacies and the attitudes they have toward pain management by pharmacological and non-pharmacological strategies. Methods: An explorative, cross-sectional, observational, and quantitative study was performed. Twelve Italian community pharmacists were asked to submit a questionnaire on LBP to patients visiting their pharmacies. The questionnaire included a pain intensity scale, and two validated tools: the Roland and Morris Disability Questionnaire (RMDQ) and the Start Back Screening Tool (SBST) to determine the degree and risk of patient disability, respectively. Results: 872 patients filled out the questionnaires in 6 months. No statistical differences between genders (p &gt, 0.30) were recorded for pain intensity (Female: median score 6, IQR 4&ndash, 7, Male: median scores 5, IQR 4&ndash, p &gt, 0.30) and disability associated with LBP (RMDQ high-disability level: Females, 14.7%, Males, 15.0%, 0.90). Most of the patients (69%) reported a low degree of disability, but the risk of disability was medium and high in 36% and 18% of them, respectively (p &lt, 0.05). About 14% of patients declare to never seek for physician&rsquo, s advice despite their medium-high degree of disability. Conclusion: The study demonstrated the feasibility of validated tools for assessing the degree and risk of disability in LBP patients administrable in community pharmacies. Moreover, the community pharmacy resulted in an important care portal for patients suffering from moderate LBP and for intercepting patients who suffered from severe LBP but had never reported their problem to their physician.

CRISPR-mediated transcriptional activation, also known as CRISPR-on, has proven efficient for activation of individual or multiple endogenous gene expression in cultured cells from several species. However, the potential of CRISPR-on technology in preimplantation mammalian embryos remains to be explored. Here, we report for the first time the successful modulation of endogenous gene expression in bovine embryos by using the CRISPR-on system. As a proof of principle, we targeted the promoter region of either SMARCA4 or TFAP2C genes, transcription factors implicated in trophoblast lineage commitment during embryo development. We demonstrate that CRISPR-on provides temporal control of endogenous gene expression in bovine embryos, by simple cytoplasmic injection of CRISPR RNA components into one cell embryos. dCas9VP160 activator was efficiently delivered and accurately translated into protein, being detected in the nucleus of all microinjected blastomeres. Our approach resulted in the activation of SMARCA expression shortly after microinjection, with a consequent effect on downstream differentiation promoting factors, such as TFAP2C and CDX2. Although targeting of TFAP2C gene did not result in a significant increase in TFAP2C expression, there was a profound induction in CDX2 expression on day 2 of development. Finally, we demonstrate that CRISPR-on system is suitable for gene expression modulation during the preimplantation period, since no detrimental effect was observed on microinjected embryo development. This study constitutes a first step toward the application of the CRISPR-on system for the study of early embryo cell fate decisions in cattle and other mammalian embryos, as well as to design novel strategies that may lead to an improved trophectoderm development. Fil: Savy, Virginia. Universidad de Buenos Aires. Facultad de Agronomía. Pabellón de Zootecnica. Laboratorio de Biotecnología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; Argentina Fil: Alberio, Virgilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Pabellón de Zootecnica. Laboratorio de Biotecnología Animal; Argentina Fil: Canel, Natalia Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Pabellón de Zootecnica. Laboratorio de Biotecnología Animal; Argentina Fil: Ratner, Laura Daniela. Universidad de Buenos Aires. Facultad de Agronomía. Pabellón de Zootecnica. Laboratorio de Biotecnología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; Argentina Fil: Gismondi, Maria Ines. Instituto Nacional de Tecnologia Agropecuaria. Centro de Investigacion En Ciencias Veterinarias y Agronomicas. Instituto de Agrobiotecnologia y Biologia Molecular. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Pque. Centenario. Instituto de Agrobiotecnologia y Biologia Molecular; Argentina Fil: Ferraris, Sergio Raúl. Universidad Maimónides. Centro de Ciencias Veterinarias; Argentina Fil: Fernández y Martín, Rafael. Universidad de Buenos Aires. Facultad de Agronomía. Pabellón de Zootecnica. Laboratorio de Biotecnología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; Argentina Fil: Knott, Jason G.. Department Of Animal Science; Estados Unidos Fil: Bevacqua, Romina Jimena. Universidad de Buenos Aires. Facultad de Agronomía. Pabellón de Zootecnica. Laboratorio de Biotecnología Animal; Argentina. University of Stanford; Estados Unidos Fil: Salamone, Daniel Felipe. Universidad de Buenos Aires. Facultad de Agronomía. Pabellón de Zootecnica. Laboratorio de Biotecnología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; Argentina

Varicose veins (VVs) and varicose ulceration (VU) are usually considered non-life-threatening conditions, but in some cases they can lead to major complications such as fatal bleeding. The aim of this systematic review is to evidence the most updated information on bleeding from VV and VU. As evidence acquisition, we planned to include all the studies dealing with "Haemorrhage/Bleeding" and "VVs/VU". We excluded all the studies, which did not properly fit our research question, and with insufficient data. As evidence synthesis, of the 172 records found, after removing of duplicates, and after records excluded in title and abstract, 85 matched our inclusion criteria. After reading the full-text articles, we decided to exclude 68 articles because of the following reasons: (1) not responding properly to our research questions; (2) insufficient data; the final set included 17 articles. From literature searching, we identify the following main issues to be discussed in the review: epidemiology and predisposing factors, pathophysiology and forensic aspects, first aid. It has been estimated that deaths for bleeding due to peripheral venous problems account up to 0.01% of autopsy cases. From a pathological point of view, venous bleeding may arise from either acute or chronic perforation of an enlarged vein segment through the weakened skin. From a forensic point of view, in cases of fatal haemorrhage the death scene can even simulate non-natural events, due to crime or suicide. In most cases, incorrect first aid led to fatal complications. Further investigation on epidemiology and prevention measures are needed.

Regulated deficit irrigation, which is a common practice to cope with water scarcity, can impact plant-aphid interactions, and possibly lead to a reduction in the use of pesticides. To test the possible effect of water restriction on the apple tree-rosy apple aphid (Malus domestica-Dysaphis plantaginea) system, we performed a factorial experiment with two levels of water supply and two genotypes on artificially infested trees. Plant growth and aphid abundance were characterised during the entire infestation period at two scales of analysis: the apical shoot scale and the tree scale, and additional measures were performed to evaluate plant water status. Aphid abundance increased with plant vegetative growth at both scales of analysis, which is consistent with the Plant Vigor Hypothesis (i.e. with the fact that most of the phloem feeders prefer fast growing plants). At the tree scale, aphid abundance was lower on trees that underwent water restriction, but at the shoot scale, aphid abundance responded differently to water restriction depending on the tree genotype. Water restriction modified the relationship between aphid abundance and growth, thus indicating that host suitability for aphids was affected by different plant variables susceptible to water stress, among which growth. The different response patterns at the two scales of analysis highlight the importance of scale choice in the study of plant-insect interactions.

A 16-year-old boy was admitted for a few days’ history of mild headache, moderate to severe posterior neck and dorsal back pain, nausea, vomiting many times during the day, and subjective positional vertigo. There was no night awakening for pain, neither night or on awakening vomit. He had been treated with ibuprofen without benefit. His history was unremarkable. On admission, physical and neurological examinations were unremarkable except for thoracolumbar pain during the flexion-extension of the trunk and refusal to stay in the orthostatic (the upright posture) position. Systemic blood pressure was 100/65 mm Hg. An ear, nose and throat (ENT) examination was negative. A brain and spine MRI showed cerebral dural sinus congestion, with a widespread meningeal enhancement after administration of contrast (figure 1A,B). Figure 1 (A) Sagittal postcontrast T1-weighted section. The arrow indicates the expansion of dural venous sinuses. (B) Coronal postcontrast T1-weighted image. The arrow shows the venous distension with pachymeningeal enhancement. Which is the most likely diagnosis? 1. MRI evidence associated with cerebral spinal fluid (CSF) hypotension. 2. Pseudotumour cerebri. …

The use of ecological tests to assess executive functions (EFs) in patients with anorexia nervosa (AN) has not examined extensively. The objective of this study was to analyze and compare the performance of patients with AN and healthy controls (HCs) on standard versus ecologically valid tests on EFs. Sixty-two females aged between 16 and 42 who were diagnosed with AN and 70 matched HCs completed 2 neuropsychological test batteries: standard tests (WCST, TMT, Stroop, ToL, fluency test) and the Behavioral Assessment of Dysexecutive Syndrome (BADS). On the standard tests, patients with AN produced more perseverative response and were slower than HCs in the TMT; in contrast, they scored as well as HCs on tasks that assessed categorization, interference in color naming, planning and semantic fluency. Conversely, there were differences in the ecological tests with patients with AN systematically slower in the resolution of complex tasks. Results demonstrated the power of ecological tests in capturing selective impairments in multifaceted and unstructured tests. Patients with AN experienced systematic deceleration in the resolution of ecological tasks. Also, the increased time needed to solve the tasks, was not reflected in overall improvement in performance. This evidence is further discussed with respect to central coherence.

A 14-year-old boy was admitted for a painful swelling of the middle third of his right clavicle lasting 3 days. He denied any trauma and/or fever. Physical examination showed a soft swelling, without calor or hyperemia of the skin. Pain was exacerbated by bone percussion and by right arm abduction movements. Bone X-ray was normal, but an ultrasound showed enlargement with hypoechoic soft tissue and enhancement of the vascular signal with Doppler technique (figure 1). The blood tests were normal, with no elevation of erythrocyte sedimentation rate (ESR) and C reactive protein (CRP). Figure 1 Ultrasound of the right sternoclavicular joint showing an enlargement of the articular capsule filled of hypoechoic inflammatory tissue collected between the two bone heads (red arrows). Which of the following do you think is the diagnosis in this patient? 1. Infective osteomyelitis 2. Chronic recurrent multifocal osteomyelitis (CRMO) 3. Tietze syndrome (TS) 4. Primary chest wall tumour Which is the next diagnostic step to confirm the clinical hypothesis? 1. Bone biopsy 2. CT scan 3. MRI 4. Bone …

In bovine, intracytoplasmic sperm injection (ICSI) remains inefficient partially due to low levels of sperm decondensation. The aim of this study was to determine whether the injection of normal size sperm pretreated with heparin (Hep) and L-glutathione (GSH), the use of sex-sorted sperm, the double round of sperm freezing/thawing (re frozen), or the combination of these approaches can improve sperm decondensation and embryo development after ICSI in cattle. Cleavage and blastocyst rates were evaluated on days 2 and 7 post ICSI. Quality of ICSI blastocysts was analyzed by the relative expression of four genes by qPCR and the DNA fragmentation index by TUNEL assay. For all assays, semen samples were co-incubated with pCX-EGFP 50 ng/μl before ICSI. GFP expression, which can be detected by fluorescence microscopy, was used as a tool to estimate the success of sperm decondensation after ICSI. The use of normal size sperm pretreated with 80 μM Hep-15 mM GSH for 20 h (Hep-GSH) increased cleavage, blastocyst and EGFP + blastocysts rates (60.8, 19.4 and 61.9%) compared to control ICSI (35, 4.9 and 20%) (p

Breast cancer is one of the leading causes of cancer death among women in industrialized countries. Several microwave imaging systems have been proposed for the diagnosis of breast cancer, based on both the tomographic and radar approach, being tested in some cases even on real patients. However, the low working frequency of all these systems, which allows to reach non superficial targets, has been in some cases the main cause of a non-optimal resolution. Based both on the results of recent dielectric characterization campaigns on ex-vivo tissues of the human breast up to 50 GHz and on the promising achievements of the feasibility studies of mm-wave imaging systems, in this article, the tomographic approach to manipulate the simulated results of a linear radar scenario at the frequency of 30 GHz is proposed. In particular, two image reconstruction techniques, the Linear Sampling Method and the Born Approximation, are proposed and compared.

Author(s): Bevacqua, Michael Lujan; Cruz, Manuel Lujan | Abstract: The title of a 2004 New York Times article sums up well the curious political existence of the island of Guam: “Looking for friendly base overseas, Pentagon finds it already has one.” Guam is known as the “tip of America’s spear” and has for more than a century played a crucial role in securing US strategic interests in the Asia-Pacific region. Guam is also one of seventeen remaining colonies in the world, as recognized by the United Nations, in need of decolonization. In media representations and critical discourse around US imperialism, Guam also occupies a curious space, where it is a US military colony that somehow does not represent colonialism or imperialism. This essay will use the concept of banality to interrogate how this simultaneous fullness of Guam as a site for American military power, and its emptiness as a site for American critique, enable the US to project force largely unchallenged over a significant part of the globe.

Background Stiff-limb syndrome is part of stiff person spectrum, presenting with fluctuating gait disorders attributed to leg stiffness, spasms, and posturing. It could also manifest with anxiety and specific phobias such as pseudoagoraphobia. We aimed to describe the importance of specific gait phobia as a diagnostic clue to anti-glutamic acid decarboxylase stiff-limb syndrome. Cases We reported on 2 cases of stiff-limb syndrome sharing a similar diagnostic path and phenomenology. Both were featured by pseudoagoraphobia, which has documented to typically cover organic conditions, and a remarkable diagnostic delay attributed to misdiagnoses. Presence of pseudoagoraphobia should not point to the diagnosis of a functional disorder-although a negative instrumental workup is documented. Conclusions Both cases are emblematic of the high misdiagnosis rate affecting stiff person syndrome patients. A proper diagnostic process, including the identification of a pseudoagoraphobia, should help in reaching a diagnosis and providing an early and effective treatment.

Reliance on rodents for understanding pancreatic genetics, development and islet function could limit progress in developing interventions for human diseases like diabetes mellitus. Similarities of pancreas morphology and function suggest that porcine and human pancreas developmental biology may have useful homologies. However, little is known about pig pancreas development. To fill this knowledge gap, we investigated fetal and neonatal pig pancreas at multiple, crucial developmental stages using modern experimental approaches. Purification of islet β-, α- and δ-cells followed by transcriptome analysis (RNA-Seq) and immunohistology identified cell- and stage-specific regulation, and revealed that pig and human islet cells share characteristic features not observed in mice. Morphometric analysis also revealed endocrine cell allocation and architectural similarities between pig and human islets. Our analysis unveiled scores of signaling pathways linked to native islet β-cell functional maturation, including evidence of fetal α-cell GLP-1 production and signaling to β-cells. Thus, the findings and resources detailed here show how pig pancreatic islet studies complement other systems for understanding the developmental programs that generate functional islet cells, and that are relevant to human pancreatic diseases.Summary StatementThis study reveals transcriptional, signaling and cellular programs governing pig pancreatic islet development, including striking similarities to human islet ontogeny, providing a novel resource for advancing human islet replacement strategies.

Background: Hepatic myofibroblasts (MFs) can originate from hepatic stellate cells, portal fibroblasts, or bone marrow-derived mesenchymal stem cells and can migrate towards the site of injury by aligning with nascent and established fibrotic septa in response to several mediators. Oncostatin M (OSM) is known to orchestrate hypoxia-modulated hepatic processes involving the hypoxia-inducible factor 1 (HIF-1). Methods. In vivo and in vitro experiments were performed to analyze the expression of OSM and OSM-receptor (OSMR) in three murine models of non-alcoholic-fatty liver disease (NAFLD) and -steatohepatitis (NASH) and in human NASH patients as well as the action of OSM on phenotypic responses of human MFs. Results: Hepatic OSM and OSMR levels were overexpressed in three murine NASH models and in NASH patients. OSM stimulates migration in human MFs by involving early intracellular ROS generation and activation of Ras/Erk, JNK1/2, PI3K/Akt as well as STAT1/STAT3 pathways and HIF-1&alpha, OSM-dependent migration relies on a biphasic mechanism requiring early intracellular generation of reactive oxygen species (ROS) and late HIF1-dependent expression and release of VEGF. Conclusion: OSM is overexpressed in experimental and human progressive NAFLD and can act as a profibrogenic factor by directly stimulating migration of hepatic MFs.

The molecule Dimethyl sulfoxide is widely used as drug solvent. However, its antioxidant property was poorly explored. In this study, we evaluated the effect of DMSO supplementation during oocyte in vitro maturation (IVM) on embryo development and quality. Bovine oocytes were matured with different DMSO concentrations (0, 0.1, 0.25, 0.5, 0.75, 1 and 10% v:v) followed by in vitro fertilization. Subsequently, quality indicators such as gene expression of SOX2, OCT4, CDX2, SOD1, oocyte and embryo redox status and DNA damage were evaluated. Polar body extrusion and blastocyst rates increased with 0.5% v:v DMSO. Moreover, first polar body extrusion and blastocyst rates did not increase with 1%, and 10% of DMSO reduced polar body extrusion and did not produce blastocyst. Optimal concentration of DMSO for the use on the maturation was estimated at around 0.45% v:v. Supplementation with 0.5% v:v DMSO has not affected mRNA abundance of genes key in blastocyst, however 0.75% increased gene expression of OCT4 and SOX2. Oocytes matured with 0.5% v:v DMSO and blastocyst from DMSO group showed reduced lipid peroxidation respect control. Total Glutathione concentrations increased in blastocyst stage in DMSO group. DMSO increased the total cell number of blastocysts but not TUNEL positive cells. In conclusion, our results suggest that low DMSO concentrations used during bovine oocytes in vitro maturation increases the maturation, as well as the blastocyst rate and its quality, without demonstrating deleterious effect on embryo cells. Fil: Ynsaurralde Rivolta, Amada Eugenia. Instituto Nacional de Tecnologia Agropecuaria. Centro Regional Buenos Aires Norte. Estacion Experimental Agropecuaria Pergamino. Agencia de Extension Rural Mercedes.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; Argentina Fil: Suvá, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; Argentina Fil: Luchetti, Carolina Griselda. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Instituto de Investigacion y Tecnología en Reproducción Animal; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Histología y Embriologías; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Bevacqua, Romina Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; Argentina Fil: Munilla Leguizamon, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; Argentina Fil: Rodríguez Álvarez, Lleretny L.. Universidad de Concepción; Chile Fil: Velásquez, Alejandra E.. Universidad de Concepción; Chile Fil: Briski, Olinda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; Argentina Fil: Lombardo, Daniel Marcelo. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Instituto de Investigacion y Tecnología en Reproducción Animal; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Histología y Embriologías; Argentina Fil: Salamone, Daniel Felipe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; Argentina

Aphids are commonly considered major agricultural pests because of their ability to alter host plant physiology and impair foliar growth. However, their effect on fruit production in perennial trees did not receive wide attention and few existing works have mainly focused on plant-aphid dynamics in a single growing season (i.e., few months). We modified an existing process based model for the peach tree Prunus persica - aphid Myzus persicae pathosystem, explicitly considering interactions between the two species under the influence of cultural practices (i.e., winter pruning and nitrogen fertilization), in order to consider multi-year dynamics. The new multi-year model suggests that consequences of aphid infestation, in terms of fruit production, become evident only when considering multi-year dynamics. (Resume d'auteur)