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Background and aims: The pathophysiology of SARS-CoV-2-associated diarrhea is unknown. Using an experimental model validated for rotavirus-induced diarrhea, we investigated the effects of SARS-CoV-2 on transepithelial ion fluxes and epithelial integrity of human intestinal cells. The effect of the antidiarrheal agent diosmectite on secretion was also evaluated following its inclusion in COVID-19 management protocols. Methods: We evaluated electrical parameters (intensity of short-circuit current [Isc] and transepithelial electrical resistance [TEER]) in polarized Caco-2 cells and in colonic specimens mounted in Ussing chambers after exposure to heat-inactivated (hi) SARS-CoV-2 and spike protein. Spectrofluorometry was used to measure reactive oxygen species (ROS), a marker of oxidative stress. Experiments were repeated after pretreatment with diosmectite, an antidiarrheal drug used in COVID-19 patients. Results: hiSARS-CoV-2 induced an increase in Isc when added to the mucosal (but not serosal) side of Caco-2 cells. The effect was inhibited in the absence of chloride and calcium and by the mucosal addition of the Ca2+-activated Cl– channel inhibitor A01, suggesting calcium-dependent chloride secretion. Spike protein had a lower, but similar, effect on Isc. The findings were consistent when repeated in human colonic mucosa specimens. Neither hiSARS-CoV-2 nor spike protein affected TEER, indicating epithelial integrity; both increased ROS production. Pretreatment with diosmectite inhibited the secretory effect and significantly reduced ROS of both hiSARS-CoV-2 and spike protein. Conclusions: SARS-CoV-2 induces calcium-dependent chloride secretion and oxidative stress without damaging intestinal epithelial structure. The effects are largely induced by the spike protein and are significantly reduced by diosmectite. SARS-CoV-2 should be added to the list of human enteric pathogens.

Introducción: Las reintervenciones en las arterias coronarias siempre representan un gran desafío para todo el equipo quirúrgico. Muy a menudo, el único injerto permeable es la arteria mamaria interna izquierda conectada a la arteria descendente anterior, y es el que mantiene vivo al paciente. En estas condiciones, la re-esternotomía puede originar un episodio catastrófico. Por esta razón, muchos abordajes alternativos han sido propuestos para minimizar este riesgo y mejorar los resultados operatorios. No solo se debe considerar el abordaje, sino también un conjunto de medidas preventivas que representan una estrategia especial que ameritan estos pacientes, generalmente de edad avanzada con patologías asociadas, que comprometen tanto el acto quirúrgico como el curso postoperatorio. Material y métodos: Presentamos nuestra experiencia desde 2003 hasta 2015 de 95 pacientes sometidos a reintervención coronaria evitando la re-esternotomía en todos ellos mediante abordaje por toracotomía izquierda, toracotomía derecha o subxifoideo, con uso de balón intraaórtico profiláctico, máquina de autotransfusión, cirugía sin circulación extracorpórea, no manipulación de la aorta y mínima manipulación del corazón. Resultados: La mortalidad operatoria fue de solo el 1,05%, permitiendo la recuperación rápida y el egreso precoz de la mayoría de los pacientes.

Childhood tuberculosis (TB) indicates a recent infection, particularly in children aged

Objective: To assess the impact of Clostridium difficile infection (CDI) on hospital resources and costs in Spain and Italy. Methods: CDI data were collected from institutions in Spain and Italy. Each patient was matched with two randomly selected uninfected controls in the same institution. Patient outcomes were assessed for the first and second episodes of CDI and for patients aged ≤65 and >65 years. The impact of CDI on hospital length of stay (LOS) was used to calculate CDI-attributable costs. A multivariate analysis using duration of stay as the continuous outcome variable assessed the independent effect of CDI on hospital costs and LOS. Results: LOS attributable to CDI ranged from 7.6–19.0 days in adults and was 5.0 days in children; the increases were greater in adults in Italy than in Spain. Attributable costs per adult patient ranged from €4396 in Madrid to €14 023 in Rome, with the majority of the cost being due to hospitalization. For children, the total attributable cost was €3545/patient. Conclusions: These data show that the burden of CDI is considerable in Spain and Italy. Treatments that can reduce LOS, disease severity, and recurrence rates, as well as effective infection control measures to prevent transmission, have the potential to reduce the burden of CDI.

A case of visceral disseminated infection by Mycobacterium sherrisii in an African HIV-infected adolescent with multiple abdominal abscesses is reported. Despite multiple drug resistance to first-line antibiotics in vitro, long-term treatment with clarithromycin, moxifloxacin, and clindamycin, together with appropriate antiretroviral treatment, resulted in clinical and radiological cure after 19 months of therapy and follow-up.

SUMMARY: Introduction: Scarless latissimus dorsi (LD) flap is a breast reconstruction technique, which allow to cover the lower pole of implant with a large portion of the LD muscle without skin paddle; it represents a surgical solution that transpose vascularized tissue avoiding the failure of breast reconstruction, following necrosis of mastectomy skin flaps. Material and Method: A retrospective review of patients undergoing immediate or delayed breast reconstruction using scarless LD flap reconstructions was performed. Clinical data obtained from follow-up visits were recorded. To evaluate breast shape contentment and patient satisfaction, the patients were requested to answer the Breast-Q, version 2.0 reduction module postoperative scales questionnaire at the 12-month follow-up. Results: We performed 19 scarless LD flap reconstructions between September 2019 and June 2022. The surgical time in average (considering minutes ± SD) was 130 (±15) minutes. The aesthetic assessment was good/excellent in 83% of patients. This was statistically significant (P=0.0). Conclusions: The scarless LD flap reconstruction is a valid and reliable solution, which has the advantage to reduce the risk of exposed prosthesis if native skin necrosis occurs.

Background: Whether solid organ transplant (SOT) can be safely performed in recipients with ongoing SARS-CoV-2 infection is still a debated question. Methods: A systematic review of the literature on recipients with ongoing SARS-CoV-2 infection at the time of surgery and the associated outcomes. Results: From 29 studies, we identified 54 recipients; their median age was 47.5 years, and over half (23/54, 54.85%) were affected by fewer than two comorbidities. Kidney was the most common transplanted organ (24/54, 44.4%). SOT was performed without knowing the ongoing infection in 11.1% (6/54) of patients. On average, 16.1 (SD 23.2) days elapsed between SARS-CoV-2 infection and SOT, with a mean Ct value at diagnosis and transplantation of 29 and 31.9, respectively. Most patients (25/39,64.1%) had received previous COVID-19 vaccinations. Twenty-four patients (45.3%) received an anti-SARS-CoV-2 therapy. Ten patients (18.5%) required oxygen support, while seven (13.7%) were admitted to the intensive care unit. There were two reported cases (3.7%) of all-cause death, while there were no cases of COVID-19-related death. Conclusions: Deliberate SOT of recipients with ongoing SARS-CoV-2 is performed worldwide in candidates of nonlung transplant who are fit, immunized against the virus, and displaying a nonsevere disease course. No COVID-19-related deaths were recorded.

Summary: CombiVacS study has demonstrated a strong immune response of the heterologous ChAdOx1-S/BNT162b2 vaccine combination. The primary outcomes of the study were to assess the humoral immune response against SARS-CoV-2, 28 days after a third dose of a mRNA vaccine, in subjects that received a previous prime-boost scheme with ChAdOx1-S/BNT162b2. Secondary outcomes extended the study to 3 and 6 months. The third vaccine dose of mRNA-1273 in naive participants previously vaccinated with ChAdOx1-S/BNT162b2 regimen reached higher neutralizing antibodies titers against the variants of concern Delta and BA.1 lineage of Omicron compared with those receiving a third dose of BNT162b2 at day 28. These differences between BNT162b2 and mRNA-1273 arms were observed against the ancestral variant G614 at day 90. Suboptimal neutralizing response was observed against BQ.1.1, XBB.1.5/XBB.1.9, and JN.1 in a relevant proportion of individuals 180 days after the third dose, even after asymptomatic Omicron breakthrough infections. EudraCT (2021-001978-37); ClinicalTrials.gov (NCT04860739).

Background: Despite the well-known efficacy of anti-COVID-19 vaccines in preventing morbidity and mortality, several vaccinated individuals are diagnosed with SARS-CoV-2 breakthrough infection, which might require hospitalisation. This multicentre, observational, and retrospective study aimed to investigate the clinical characteristics and outcomes of vaccinated vs. non-vaccinated patients, both hospitalised with SARS-CoV-2 infection in 3 major hospitals in Northern Italy. Methods: Data collection was retrospective, and paper and electronic medical records of adult patients with a diagnosed SARS-CoV-2 infection were pseudo-anonymised and analysed. Vaccinated and non-vaccinated individuals were manually paired, using a predetermined matching criterion (similar age, gender, and date of hospitalisation). Demographic, clinical, treatment, and outcome data were compared between groups differing by vaccination status using Pearson’s Chi-square and Mann-Whitney tests. Moreover, multiple logistic regression analyses were performed to assess the impact of vaccination status on ICU admission or intra-hospital mortality. Results: Data from 360 patients were collected. Vaccinated patients presented with a higher prevalence of relevant comorbidities, like kidney replacement therapy or haematological malignancy, despite a milder clinical presentation at the first evaluation. Non-vaccinated patients required intensive care more often than their vaccinated counterparts (8.8% vs. 1.7%, p = 0.002). Contrariwise, no difference in intra-hospital mortality was observed between the two groups (19% vs. 20%, p = 0.853). These results were confirmed by multivariable logistic regressions, which showed that vaccination was significantly associated with decreased risk of ICU admission (aOR=0.172, 95%CI: 0.039–0.542, p = 0.007), but not of intra-hospital mortality (aOR=0.996, 95%CI: 0.582–1.703, p = 0.987). Conclusions: This study provides real-world data on vaccinated patients hospitalised with COVID-19 in Northern Italy. Our results suggest that COVID-19 vaccination has a protective role in individuals with higher risk profiles, especially regarding the need for ICU admission. These findings contribute to our understanding of SARS-CoV-2 infection outcomes among vaccinated individuals and emphasise the importance of vaccination in preventing severe disease, particularly in those countries with lower first-booster uptake rates.

ABSTRACT: Background: An increasing number of patients are using online information regarding medical issues; however, the Internet is not subject to content ratings or filters. Unreliable information found on the web can heavily influence patients to the extent that it can lead to wrong decisions in the choice of treatment. In our daily experience we meet more informed patients and given the increasing use of polyurethane-coated implants in breast reconstruction in Europe, we wondered about the level of information available online. Our study aims to assess the quality of information available online on breast reconstruction with polyurethane-coated implants. Materials and Methods: Assuming that the most used search engines are Google and Yahoo, we used a search strategy to identify online information regarding prepectoral breast reconstruction with polyurethane-coated implants. The selected websites were divided into 5 groups (practitioners, hospitals, healthcare portals, professional societies, and encyclopedias), and the quality of information was assessed by using an expanded version of the Ensuring Quality Information for Patients (EQIP) tool, which is a checklist applicable to all existing types of information. Results: Fifty-six websites were selected and were categorized into 5 groups: 17 practitioners, 9 hospitals, 13 healthcare portals, 7 professional societies, 10 encyclopedias. The average score was 17 points (range: 12 – 25). We found 13 reliable websites with a score higher than 20 using the expanded version of the EQIP tool, whereas 43 were deemed unreliable, as they scored lower. Conclusion: Proper communication between surgeon and patient is crucial in the therapeutic choice, as the available online information presently is scarce and can lead to wrong decisions if not properly verified.

Background: Adverse childhood experiences (ACE) encompass traumatic events occurring before age 18, with lasting impacts on health. While ACE disclosure is important for understanding these effects, some individuals decline to respond to ACE-related survey items due to sensitivity, privacy concerns, or psychological distress. This study explores the relationship between non-response to ACE items and health outcomes, shedding light on the implications for those who choose not to disclose. Methods: We performed a secondary analysis of the 2021 Behavioral Risk Factor Surveillance System (BRFSS)—a national telephone survey querying health behaviors and conditions. Sociodemographic factors, ACE exposure, and non-response to ACE items were analyzed. Results: Individuals who decline to respond to ACE items exhibit similar patterns of health behaviors and conditions as those reporting ACE exposure. Non-response is linked to both healthier behaviors (lifetime HIV testing) and riskier behaviors (higher odds of smoking and e-cigarette use). Moreover, non-responders have higher odds of being underweight or obese, experiencing concentration difficulties, reporting poor self-rated health, and reporting multiple health diagnoses including depression, diabetes, high blood pressure, heart attack, and stroke. Conclusions: The study underscores the need to address health disparities associated with ACE, regardless of disclosure status. Healthcare interventions should target respondents and non-respondents of ACE screeners, tailoring strategies to promote healthier coping mechanisms and mitigate maladaptive behaviors. These results emphasize the importance of trauma-informed care, early intervention, and targeted public health initiatives for individuals affected by ACE, irrespective of their disclosure choices.

Smoking has been considering a crucial factor in promoting skin and systemic aging that is associated with the development of a low-level, systemic, chronic inflammation known as ''inflammaging'' in which monocytes play a pivotal role. Our aim was to investigate the effects of AM3 plus antioxidants vs placebo in the activation status, function of monocytes and cutaneous aging parameters in healthy smoker middle-aged women. A total of 32 women were 1:1 randomly assigned to AM3 plus antioxidants or placebo for three months. Peripheral mononuclear blood cells and cutaneous biopsy were obtained and flow cytometry and immunohistological studies, respectively, were performed before and after the treatment. AM3 plus antioxidants treatment compared with placebo significantly reduced the monocyte production of the proinflammatory interleukin 1 (IL-1), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) cytokines as well as increased the regulatory IL-10 in middle-aged smoker women. Furthermore, AM3 and antioxidants did not modify ROS production by monocytes and granulocytes but increased their phagocytic activity. The active combination also stimulated a significative increase in reticular dermis depth as well as an increase in the expression of CD117 and CD31. Thus, AM3 and antioxidants treatment reduces the systemic proinflammatory monocyte disturbance of heathy smoker middle-aged women and encourage skin repair mechanisms.

Objectives: To develop and validate a simple approach for building cost-effective imaging phantoms for Cone Beam Computed Tomography (CBCT) using a modified Polyjet additive manufacturing technology where a single material can mimic a range of human soft-tissue radiation attenuation. Materials and Methods: Single material test phantoms using a cubic lattice were designed in 3-Matic 15.0 software . Keeping the individual cubic lattice volume constant, eight different percentage ratio (R) of air: material from 0% to 70% with a 10% increment were assigned to each sample. The phantoms were printed in three materials, namely Vero PureWhite, VeroClear and TangoPlus using Polyjet technology. The CT value analysis, non-contact profile measurement and microCT-based volumetric analysis was performed for all the samples. Results: The printed test phantoms produced a grey value spectrum equivalent to the radiation attenuation of human soft tissues in the range of −757 to +286 HU on CT. The results from dimensional comparison analysis of the printed phantoms with the digital test phantoms using non-contact profile measurement showed a mean accuracy of 99.07 % and that of micro-CT volumetric analysis showed mean volumetric accuracy of 84.80–94.91%. The material and printing costs of developing 24 test phantoms was 83.00 Euro. Conclusions: The study shows that additive manufacturing-guided macrostructure manipulation modifies successfully the radiographic visibility of a material in CBCT imaging with 1 mm3 resolution, helping customization of imaging phantoms.

Resumen: Introducción: considerar la educación superior como un derecho humano implica prestar atención a la igualdad de oportunidades en el acceso, la permanencia y el egreso. Desde esta perspectiva se reconoce a la equidad como rasgo de la calidad educativa.Se considera que hay equidad cuando el acceso, la permanencia o el egreso no dependen de las características socioeconómicas y demográficas de los hogares, de las capacidades físicas de las personas y la etnia. El estudio se propuso como objetivo analizar la relación entre las variables demográficas y socioeducativas con los resultados del proceso de ingreso, egreso y la demora en completar los estudios. Esta información se considera importante para orientar políticas educativas institucionales. Métodos: estudio cuantitativo, descriptivo, censal sobre 18 cohortes de aspirantes y 10 cohortes de estudiantes de Medicina, Enfermería y tecnicaturas en una universidad latinoamericana, estatal y gratuita. Resultados: la jurisdicción de la escuela secundaria y el nivel de estudios de la madre y el padre son 2 características que diferencian el perfil de los ingresantes a la carrera de Medicina, de los aspirantes en general y de los ingresantes a las otras carreras de salud. Estas características se acentúan en el perfil de egreso y demora en completar la carrera. Conclusión: las prácticas institucionales no mitigarían las desigualdades socioeducativas de origen, en especial en la carrera de Medicina. La caracterización de los aspirantes, ingresantes y egresados según las variables demográficas y socioeducativas es una manera de visibilizar la equidad educativa, información valiosa para revisar políticas educativas de ingreso, permanencia y egreso. Abstract: Introduction: To consider higher education as a Human Right implies paying attention to equal opportunities in access, permanence and graduation. From this perspective, equity is recognized as a feature of educational quality.It is considered that there is equity when access, permanence or graduation do not depend on socioeconomic and demographic characteristics of the households, physical abilities or ethnicity of students. The study objective was to analyze the relationship between demographic and socio-educational variables with the results of the admission process, the discharge condition and the delay to complete the studies. This information is considered to be important as a guide for institutional educational policies. Methods: Quantitative, descriptive, census study on 18 cohorts of applicants and 10 cohorts of Medicine, Nursing and Technical students at a Latin American, state and free university. Results: The jurisdiction of the secondary school and the educational level of the mother and father are two characteristics that differentiate the profile of the entrants to the Medicine career, from the applicants in general and from the entrants to the other health careers. These characteristics are accentuated in the graduation profile and the delay in completing the degree. Conclusion: Institutional practices would not mitigate the socio-educational inequalities of origin, especially in the Medicine career. The characterization of applicants, entrants, and graduates according to demographic and socio-educational variables is a way to make educational equity visible, valuable information to review educational policies for admission, permanence and graduation.

Background: Children and adolescents are highly vulnerable to the impact of sustained stressors during developmentally sensitive times. We investigated how demographic characteristics intersect with socioeconomic dimensions to shape the social patterning of quality of life and mental health in children and adolescents, two years into the COVID-19 pandemic. Methods: We used data from the prospective SEROCoV-KIDS cohort study of children and adolescents living in Geneva (Switzerland, 2022). We conducted an intersectional Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy by nesting participants within 48 social strata defined by intersecting sex, age, immigrant background, parental education and financial hardship in Bayesian multilevel logistic models for poor health-related quality of life (HRQoL, measured with PedsQL) and mental health difficulties (measured with the Strengths and Difficulties Questionnaire). Results: Among participants aged 2–17 years, 240/2096 (11.5%, 95%CI 10.1–12.9) had poor HRQoL and 105/2135 (4.9%, 95%CI 4.0–5.9) had mental health difficulties. The predicted proportion of poor HRQoL ranged from 3.4% for 6–11 years old Swiss girls with highly educated parents and no financial hardship to 34.6% for 12–17 years old non-Swiss girls with highly educated parents and financial hardship. Intersectional strata involving adolescents and financial hardship showed substantially worse HRQoL than their counterparts. Between-stratum variations in the predicted frequency of mental health difficulties were limited (range 4.4%–6.5%). Conclusions: We found considerable differences in adverse outcomes across social strata. Our results suggest that, post-pandemic, interventions to address social inequities in HRQoL should focus on specific intersectional strata involving adolescents and families experiencing financial hardship, while those aiming to improve mental health should target all children and adolescents.

Passive immunization with mAbs has been employed in COVID-19. We performed a systematic review of the literature assessing the endogenous humoral immune response against SARS-CoV-2 in patients treated with mAbs. Administration of mAbs in seronegative patients led to a reduction in both antibody titres and neutralizing activity against the virus.

Current medical imaging phantoms are usually limited by simplified geometry and radiographic skeletal homogeneity, which confines their usage for image quality assessment. In order to fabricate realistic imaging phantoms, replication of the entire tissue morphology and the associated CT numbers, defined as Hounsfield Unit (HU) is required. 3D printing is a promising technology for the production of medical imaging phantoms with accurate anatomical replication. So far, the majority of the imaging phantoms using 3D printing technologies tried to mimic the average HU of soft tissue human organs. One important aspect of the anthropomorphic imaging phantoms is also the replication of realistic radiodensities for bone tissues. In this study, we used filament printing technology to develop a CT-derived 3D printed thorax phantom with realistic bone-equivalent radiodensity using only one single commercially available filament. The generated thorax phantom geometry closely resembles a patient and includes direct manufacturing of bone structures while creating life-like heterogeneity within bone tissues. A HU analysis as well as a physical dimensional comparison were performed in order to evaluate the density and geometry agreement between the proposed phantom and the corresponding CT data. With the achieved density range (-482 to 968 HU) we could successfully mimic the realistic radiodensity of the bone marrow as well as the cortical bone for the ribs, vertebral body and dorsal vertebral column in the thorax skeleton. In addition, considering the large radiodensity range achieved a full thorax imaging phantom mimicking also soft tissues can become feasible. The physical dimensional comparison using both Extrema Analysis and Collision Detection methods confirmed a mean surface overlap of 90% and a mean volumetric overlap of 84,56% between the patient and phantom model. Furthermore, the reproducibility analyses revealed a good geometry and radiodensity duplicability in 24 printed cylinder replicas. Thus, according to our results, the proposed additively manufactured anthropomorphic thorax phantom has the potential to be efficiently used for validation of imaging- and radiation-based procedures in precision medicine.

Background and objectives: Pneumocystis jirovecii pneumonia (PCP) still has substantial morbidity and mortality. For non-HIV patients, the course of infection is severe, and management guidelines are relatively recent. We collected all PCP cases (European Organization for Research and Treatment of Cancer criteria) diagnosed in HIV-negative adult inpatients in 2019-2020 at our center in northern Italy. Results: Of 20 cases, nine had microbiologic evidence of probable (real-time polymerase chain reaction, RT-PCR) and 11 proven (immunofluorescence) PCP on respiratory specimens. Half were female; the median age was 71.5 years; 14 of 20 patients had hematologic malignancies, five had autoimmune/hyperinflammatory disorders, and one had a solid tumor. RT-PCR cycle threshold (Ct) was 24-37 for bronchoalveolar lavage (BAL) and 32-39 for sputum; Ct was 24-33 on BAL proven cases. Of 20 cases, four received additional diagnoses on BAL. At PCP diagnosis, all patients were not on anti-pneumocystis prophylaxis. We retrospectively assessed prophylaxis indications: 9/20 patients had a main indication, 5/9 because of prednisone treatment ≥ 20 mg (or equivalents) for ≥4 weeks. All patients underwent antimicrobial treatment according to guidelines; 18/20 with concomitant corticosteroids. A total of 4/20 patients died within 28 days from diagnosis. Conclusion: Despite appropriate treatment, PCP is still associated to high mortality (20%) among non-HIV patients. Strict adherence to prophylaxis guidelines, awareness of gray areas, and prompt diagnosis can help manage this frequently overlooked infection.

Background: Immunological treatments (immune checkpoint inhibitors [ICIs], chimeric antigen receptor T [CAR-T] cells, bispecific T-cell engagers [BiTEs]) have deeply changed the treatment of several cancers. However, the impact of these treatments on the risk of developing infections has not been completely ascertained yet. Methods: We reviewed all the registration studies of currently approved ICIs, CAR-T cells, and BiTEs to collect all the reported infections. For each drug, we have generated a report with the infections occurring in at least 10% of the patients enrolled. Results: The most frequently reported infections involving patients treated with ICIs involved the respiratory tract, including nasopharyngitis, upper respiratory tract infections, and pneumonia and the urinary tract. Those treated with CAR-T cells frequently reported the incidence of unspecified infections and infestations, bacterial infections, and viral infections. In patients treated with BiTEs, nasopharyngitis, pneumonia, and device-related infections were the most frequently reported conditions. Conclusions: A wide range of infections are reported in registration studies and clinical trials of ICIs, CAR-T cells, and BiTEs.

Summary: The impact of body mass index (BMI) on surgical outcomes has previously been studied in relation to several oncological procedures. Regarding gastric cancer surgery, published results have been contradicting in terms of degree of technical difficulty, risk of postoperative complications and survival. In an attempt to clarify these issues, we performed a meta-analysis to evaluate the impact of obesity (defined as BMI ≥ 30 kg/m2) on outcomes after gastrectomy for gastric cancer. The meta-analysis was performed according to the PRISMA guidelines. Eligible studies were identified through search of PubMed, EMBASE, Web of Science and Cochrane Library databases. Quality assessment was performed using the Newcastle-Ottawa scale. The meta-analysis was conducted using random-effects modeling. A total of 11 studies with 13 538 patients were eligible for analysis. Obesity was associated with a significantly longer operation time (WMD = 19.38 min, 95% CI 12.72–26.04; p

Socioeconomically disadvantaged children experience a high burden of obesity but few interventions address obesity prevention in this population subgroup. The Healthy Kids & Families study tested the effect of a parent-focused community health worker (CHW)-delivered lifestyle intervention to prevent childhood obesity. Participants were child-parent/guardian (Kindergarten to 6th grade at baseline) dyads (n = 247) recruited through schools located in socioeconomically disadvantaged neighborhoods in Worcester, MA, USA. Using a quasi-experimental design, the study tested the impact of Healthy Kids & Families, a theory-based, low-intensity, parent-focused, CHW-delivered intervention to improve children’s weight, healthy eating and physical activity. The attention-control comparison condition was a positive parenting intervention. The primary outcome was change in child body mass index (BMI) z-score at 24 months. Secondary outcomes included number of positive child and parent changes in selected diet and physical activity behaviors targeted by the intervention and change in parent BMI. Outcomes were assessed following the intent-to-treat principle and using multivariable generalized linear mixed models. Compared to the attention-control comparison condition, the Healthy Kids & Families intervention led to a greater reduction in children’s BMI z-score (β = −0.17, 95 %CI: −1.92 to −0.36; p = 0.057) and a greater number of positive behavior changes among children (β = 0.57, 95 %CI: 0.08–1.06; p = 0.02) at 24 months. There was no significant change in parent outcomes. The Healthy Kids & Families intervention shows promise for obesity prevention among children in socioeconomically disadvantaged communities.

Background: Uveitis is a vision-threatening inflammation and is considered an ophthalmic emergency. It generally arises as a result of autoimmune conditions, infections, or ocular trauma, but it may also occur as an isolated disorder. Over the past decades, several cases of vaccine-associated uveitis have been described, with the hepatitis B virus vaccine being the leading cause. Clinical case: A case of anterior uveitis in a 23-year-old male, with onset 14 days after the second dose of BNT162b2 COVID-19 vaccine, is reported here. Initial symptoms were pain, photophobia, and red eye. Ocular examination showed pericheratic and conjunctival hyperaemia, posterior synechiae, and anterior chamber cells ± keratic precipitates in the lower quadrants. The posterior segment did not show any alteration, and optical coherence tomography ruled out the presence of cystoid macular oedema. After a 10-day treatment course of topical steroids and cycloplegic eye drops, the ocular inflammatory signs disappeared and visual acuity was completely restored. Even if causality remains presumed, a warning should be given to physicians about the possibility of eye inflammation following SARS-CoV-2 vaccination.

Background: Capsular contracture (CC) is the most common complication following Immediate Breast Reconstruction (IBR) with breast implants. Different implant surfaces were developed aiming to reduce the incidence of CC. We evaluated the incidence and degree of CC after Direct-to-Implant (DTI) IBR with insertion of textured (TE) or polyurethane (PU) covered implants. Methods: A retrospective review of consecutive patients treated at our Institution with mastectomy and one-stage IBR and implant reconstruction between 2013 and 2018, with or without post mastectomy radiation therapy (PMRT), was conducted. Immediate breast reconstruction was performed by implanting 186 PU covered implants and 172 TE implants. Results: Three-hundred-twelve women underwent 358 DTI IBR with PU or TE implants, were analyzed with a median follow-up time of 2.3 years (range 1.0–3.0). The overall rate of CC Baker grade III and IV was 11.8% (95%CI: 8.4–16.3), while, after PU and TE implant placement it was 8.1% (95% CI: 4.1–15.7) and 15.8% (95% CI: 4.1–15.7) [p = 0.009]), respectively. Irradiated breasts developed CC more frequently rather than non-irradiated breasts (HR = 12.5, p

Great expectations are placed in vaccines against COVID-19 to control the pandemic. We reviewed the antibody titres in a cohort of healthcare workers (HCWs) vaccinated with BNT162b2 to assess the influence of a previous infection on them. We stratified the results according to the individual history of nasopharyngeal swab (NPS) and symptoms. Among 3475 HCWs the highest titres were recorded among those infected more than 6 months before vaccination, independently of symptoms, followed by those infected less than 6 months before vaccination, especially in those with symptoms, and by uninfected HCWs. Vaccination with BNT162b2 can boost immunity acquired through infection, particularly in those infected more than 6 months before vaccination.

Introduction: Focal segmental glomerulosclerosis (FSGS), a histologic lesion in the kidney caused by varied pathophysiological processes, leads to end-stage kidney disease in a large proportion of patients. Sparsentan is a first-in-class orally active compound combining endothelin type A (ETA) receptor blockade with angiotensin II type 1 (AT1) receptor antagonism in a single molecule. A Randomized, Multicenter, Double-Blind, Parallel, Active-Control Study of the Effects of Sparsentan, a Dual Endothelin Receptor and Angiotensin Receptor Blocker, on Renal Outcomes in Patients With Primary FSGS (DUPLEX) study evaluates the long-term antiproteinuric efficacy, nephroprotective potential, and safety profile of sparsentan compared with an AT1 receptor blocker alone in patients with FSGS. Methods: DUPLEX is a multicenter, international, phase 3, randomized, double-blind, active-controlled study of sparsentan in patients with FSGS. Approximately 300 patients aged 8 to 75 years, inclusive (United States), and 18 to 75 years, inclusive (outside United States) will be randomized 1:1 to daily treatment with sparsentan or irbesartan. After renin-angiotensin-aldosterone system inhibitor washout, treatment will be administered for 108 weeks, with the final assessment at week 112, four weeks after withdrawal of study drug. Results: The primary endpoint will be the slope of estimated glomerular filtration rate from week 6 to week 108. A novel surrogate efficacy endpoint, the proportion of patients achieving urinary protein-to-creatinine (UP/C) ratio of ≤1.5 g/g and >40% reduction from baseline in UP/C (FSGS partial remission endpoint: FPRE), will be evaluated at a planned interim analysis at week 36. Safety and tolerability of sparsentan will also be assessed. Conclusion: The phase 3 DUPLEX study will characterize the long-term antiproteinuric efficacy and nephroprotective potential of dual ETA and AT1 receptor blockade with sparsentan in patients with FSGS. Keywords: angiotensin II type 1 receptor blockade, endothelin type A receptor blockade, focal segmental glomerulosclerosis, irbesartan, proteinuria, sparsentan

In the design of service facilities, whenever the behaviour of customers is impacted by queueing or congestion, the resulting equilibrium cannot be ignored by a firm that strives to maximize revenue within a competitive environment. In the present work, we address the problem faced by a firm that makes decisions with respect to location, service levels and prices and that takes explicitly into account user behaviour. This situation is modelled as a nonlinear mathematical program with equilibrium constraints that involves both discrete and continuous variables, and for which we propose an efficient algorithm based on an approximation that can be solved for its global optimum.

Summary: Background: Vaccines against COVID-19 are a powerful tool to control the current SARS-CoV-2 pandemic. A thorough description of their immunogenicity among people living with HIV (PLWHIV) is necessary. We aimed to assess the immunogenicity of the mRNA-1273 vaccine among PLWHIV. Methods: In this prospective cohort, adult PLWHIV outpatients were enrolled during the Italian vaccination campaign. Enrolment was allowed irrespective of ongoing combination antiretroviral therapy (ART), plasma HIV viral load and CD4+ T cell count. A two-dose regimen of mRNA-1273, with administrations performed 28 days apart, was employed. The primary outcomes were anti-spike (anti-S) antibody titres and neutralising antibody activity, assessed 28 days after completing the vaccination schedule. A convenient sample of individuals not affected by HIV was also collected to serve as control (referred as healthy-donors, HDs). Findings: We enrolled 71 PLWHIV, mostly male (84·5%), with a mean age of 47 years, a median CD4+ T cell count of 747·0 cells per µL and a median HIV viral load 500 cells/μL), anti-S antibody titres (6/71, median 2173 U/mL [IQR 987-4109]; 7/71, 5763 IU/mL [IQR 4801->12500]; 58/71, 2449 U/mL [IQR 1524-5704]) were not lower to those observed among HDs (10, median 1425 U/mL [IQR 599-6131]). In addition, neutralising antibody activity, stratified according to the CD4+ T cell count (6/71, median 1314 [IQR 606-2477]; 7/71, 3329 IU/mL [IQR 1905-10508]; 58/71, 1227 U/mL [IQR 761-3032]), was like those displayed by HDs (10, median 2112 U/mL [IQR 719-8889]). Interpretation: In our cohort of PLWHIV with well-controlled ART, stable viral suppression and robust CD4+ T cell count, inoculation with mRNA-1273 vaccine given 4 weeks apart produced detectable humoral immune response, similar to individuals without HIV infection, supporting vaccination in PLWHIV. Funding: This study was partially supported by Italian Ministry of Health Ricerca Corrente 2021, by Intesa San Paolo COVID-19 emergency 2020 funds, and by Fondazione Cariplo Grant (INNATE-CoV).

Summary: SARM1 is an NAD(P) glycohydrolase and TLR adapter with an essential, prodegenerative role in programmed axon death (Wallerian degeneration). Like other NAD(P)ases, it catalyzes multiple reactions that need to be fully investigated. Here, we compare these multiple activities for recombinant human SARM1, human CD38, and Aplysia californica ADP ribosyl cyclase. SARM1 has the highest transglycosidation (base exchange) activity at neutral pH and with some bases this dominates NAD(P) hydrolysis and cyclization. All SARM1 activities, including base exchange at neutral pH, are activated by an increased NMN:NAD ratio, at physiological levels of both metabolites. SARM1 base exchange occurs also in DRG neurons and is thus a very likely physiological source of calcium-mobilizing agent NaADP. Finally, we identify regulation by free pyridines, NADP, and nicotinic acid riboside (NaR) on SARM1, all of therapeutic interest. Understanding which specific SARM1 function(s) is responsible for axon degeneration is essential for its targeting in disease.

Conflicting evidence suggest that perturbations of GABAergic neurotransmission play crucial roles in disrupting cortical neuronal network oscillations, memory, and cognitive deficits in Alzheimer's disease (AD). However, the role and impact of sex differences on GABAergic transmission in AD are not well understood. Using an APP knock-in mouse model of AD, APPNLGF mice, we studied the effects of acute diazepam administration on memory and anxiety-like behavior to unveil sex-dependent dysregulation of GABAergic neurotransmission. We also examined sex differences in GABAA receptor subunit mRNA and protein expression and the role of epigenetic regulation in hippocampus of APPNLGF mice. We found that diazepam elicited dose-dependent suppression of locomotion in wildtype and APPNLGF mice. However, a low dose, which had no significant effect in both male and female wildtype as well as female APPNLGF mice, significantly suppressed locomotion in male APPNLGF mice. Furthermore, this low dose of diazepam was more efficacious at eliciting anxiolytic-like effects in male than female APPNLGF mice. The same low dose of diazepam disrupted recognition memory exclusively in male APPNLGF mice. Biochemical analyses revealed that hippocampal α1 and α5 GABAA receptor subunits mRNA and protein expression were significantly higher in male than female APPNLGF mice and were regulated by histone H3 tri-methylation (H3K4me3) but not histone H3 acetylation. The higher sensitivity of APPNLGF males to diazepam-induced behavioral effects may potentially be due to epigenetic-dependent upregulation of hippocampal α1 and α5 GABAA receptor subunits expression compared to female APPNLGF mice. These findings suggest that dysregulation of GABAergic neurotransmission plays a significant role in memory and affective behavior, particularly in male APPNLGF mice.

Bovine mastitis is a disease of dairy cattle prevalent throughout the world that causes alterations in the quality and composition of milk, compromising technological performance. Staphylococcus aureus is one of the most important pathogens that produce clinical, subclinical, and chronic mastitis. Biofilms are considered a virulence factor necessary for the survival of S. aureus in the mammary gland. Its zoonotic potential is important not only for the dairy industry sector but also for public health. This study aimed to evaluate the effect of different growing culture conditions on the biofilm formation of S. aureus isolated from mastitis and to test the MALDI-TOF-MS's ability to discriminate among different biofilm formation levels. Fluids commonly found in the dairy environment were incorporated to approach the pathogen's behavior in natural surroundings. PIA production was also evaluated. All strains were able to form high biofilms in TSB, TSBg, and milk. Milk changed the behavior of some strains which formed more biofilms in this medium than in TSBg. The free iron medium CTSBg and milk whey inhibited the biofilm formation of the most strains. MALDI-TOF-MS performance was an excellent tool to discriminate between high, moderate, and low biofilm producers strains of S. aureus in each media, confirming the results of crystal violet assay. PIA production was variable among the strains and showed a media-dependent behavior. Our data highlights the importance of considering the growing conditions that mimic the natural ones to the study of biofilm formation in vitro.

ACE2 plays a pivotal role in the balance between the pro-oxidative pro-inflammatory and the anti-oxidative anti-inflammatory arms of the renin-angiotensin system. Furthermore, ACE2 is the entry receptor for SARS-CoV-2. Clarification of ACE2-related mechanisms is crucial for the understanding of COVID-19 and other oxidative stress and inflammation-related processes. In rat and monkey brain, we discovered that the intracellular ACE2 and its products Ang 1–7 and alamandine are highly concentrated in the mitochondria and bind to a new mitochondrial Mas-related receptor MrgE (MrgE) to produce nitric oxide. We found MrgE expressed in neurons and glia of rodents and primates in the substantia nigra and different brain regions. In the mitochondria, ACE2 and MrgE expressions decreased and NOX4 increased with aging. This new ACE2/MrgE/NO axis may play a major role in mitochondrial regulation of oxidative stress in neurons, and possibly other cells. Therefore, dysregulation of the mitochondrial ACE2/MrgE/NO axis may play a major role in neurodegenerative processes of dopaminergic neurons, where mitochondrial dysfunction and oxidative stress play a crucial role. Since ACE2 binds SARS-CoV-2 spike protein, the mitochondrial ACE2/MrgE/NO axis may also play a role in SARS-CoV-2 cellular effects.

Background: The gut microbiota represents a potential treatment target in heart failure (HF) through microbial metabolites such as trimethylamine N-oxide (TMAO) and systemic inflammation. Treatment with the probiotic yeast Saccharomyces boulardii have been suggested to improve left ventricular ejection fraction (LVEF). Methods: In a multicentre, prospective randomized open label, blinded end-point trial, we randomized patients with LVEF

The Feasibility Pump (fp) is probably the best-known primal heuristic for mixed-integer programming. The original work by Fischetti et al. (Math Program 104(1):91–104, 2005), which introduced the heuristic for 0–1 mixed-integer linear programs, has been succeeded by more than twenty follow-up publications which improve the performance of the fp and extend it to other problem classes. Year 2015 was the tenth anniversary of the first fp publication. The present paper provides an overview of the diverse Feasibility Pump literature that has been presented over the last decade.

Background: Although the diffusion of novel synthetic opioids has become a worldwide phenomenon, their prevalence of use in Italy seems to be limited. Existing national data is mainly derived by anamnestic surveyslacking of toxicological validation and not always disclosing the use of these compounds, which might remain under-diagnosed. Methods: an assessment of the metabolites of the main synthetic opioids on hair samples was carried out among patients admitted at the Addiction Treatment Unit of Trento. The analytical approach included: (a) screening by means of immunoenzymatic method for fentanyl, fentanyl analogs and oxicodone; (b) confirmation of the samples resulted positive for fentanyl and oxicodone by means of HPLC-MS/; (c) search and dosage detection of Tramadol by means of HPLC-MS/MS. Results: 3 out of 309 analysed samples were found positive: one was positive to Fentanyl and two to 4-ANPP. In the same cohort, 6 samples were also found positive for Oxycodone . Tramadol was searched in 189 samples and 12 of them resulted positive. Discussion and conclusion: Those found positive were mainly young adults engaging in dangerous patterns of use and lacking awareness of risks. The phenomenon requires further consideration by health professionals. Training and more evidence-based information on synthetic opioids as well as other Novel Psychoactive Substances (NPS) are urgently needed.