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(1) Background: The clinical implications of COVID-19 outbreaks following SARS-CoV-2 vaccination in immunocompromised recipients are a worldwide concern. Cancer patients on active treatment remain at an increased risk of developing breakthrough infections because of waning immunity and the emergence of SARS-CoV-2 variants. There is a paucity of data on the effects of COVID-19 outbreaks on long-term survival outcomes in this population. (2) Methods: We enrolled 230 cancer patients who were on active treatment for advanced disease and had received booster dosing of an mRNA-BNT162b2 vaccine as part of the Vax-On-Third trial between September 2021 and October 2021. Four weeks after the third immunization, IgG antibodies against the spike receptor domain of SARS-CoV-2 were tested in all patients. We prospectively evaluated the incidence of breakthrough infections and disease outcomes. The coprimary endpoints were the effects of antibody titers on the development of breakthrough infections and the impact of COVID-19 outbreaks on cancer treatment failure. (3) Results: At a median follow-up of 16.3 months (95% CI 14.5–17.0), 85 (37%) patients developed SARS-CoV-2 infection. Hospitalization was required in 11 patients (12.9%) and only 2 (2.3%) deaths related to COVID-19 outbreaks were observed. Median antibody titers were significantly lower in breakthrough cases than in non-cases (291 BAU/mL (95% CI 210–505) vs. 2798 BAU/mL (95% CI 2323–3613), p < 0.001). A serological titer cut-off below 803 BAU/mL was predictive of breakthrough infection. In multivariate testing, antibody titers and cytotoxic chemotherapy were independently associated with an increased risk of outbreaks. Time-to-treatment failure after booster dosing was significantly shorter in patients who contracted SARS-CoV-2 infection (3.1 months (95% CI 2.3–3.6) vs. 16.2 months (95% CI 14.3–17.0), p < 0.001) and had an antibody level below the cut-off (3.6 months (95% CI 3.0–4.5) vs. 14.6 months (95% CI 11.9–16.3), p < 0.001). A multivariate Cox regression model confirmed that both covariates independently had a worsening effect on time-to-treatment failure. (4) Conclusions: These data support the role of vaccine boosters in preventing the incidence and severity of COVID-19 outbreaks. Enhanced humoral immunity after the third vaccination significantly correlates with protection against breakthrough infections. Strategies aimed at restraining SARS-CoV-2 transmission in advanced cancer patients undergoing active treatment should be prioritized to mitigate the impact on disease outcomes.

Resumo Este trabalho analisa, sob a ótica das propriedades desejáveis das curvas de juros, a adequação à realidade brasileira das Estruturas a Termo das Taxas de Juros fixadas pela Susep para fins de avaliação dos passivos atuariais e de determinação do requerimento de capital adicional baseado no risco de mercado. Com o intuito de analisar a aderência das curvas aos dados observados, foram calculados os erros de estimação, suas estatísticas descritivas e a média dos erros quadráticos médios. Para analisar a volatilidade das taxas estimadas, definiram-se prazos de interesse e apurou-se, para cada prazo, o desvio-padrão ao longo do período de análise. Os resultados encontrados indicam que as curvas fixadas apresentam, em geral, aderência satisfatória aos pontos observados no mercado. Não obstante, há evidências de que as taxas de longo prazo estimadas pelas curvas construídas pela Susep possuem volatilidade mais elevada do que a verificada para as taxas de longo prazo observadas, o que se configura uma questão relevante de ordem prática. Por fim, as curvas prefixada e cupom de IPCA da Susep foram comparadas às da Anbima e estas últimas se mostraram mais eficazes, justificando a decisão da Susep de parar de gerar algumas de suas curvas.

Background Childhood cancer survivors are vulnerable to long-term treatment-related health conditions, which can lead to poor quality of life. Little data exist on the overall health of long-term Australian and New Zealand childhood cancer survivors or on survivors’ motivations for attending survivorship clinics. Methods This study administers a cross-sectional questionnaire to long-term survivors ≥5 years from their primary diagnosis. We compared participant-reported number of late effects by a cancer diagnosis, and identified clinical (eg, treatment) and demographic (eg, age) factors that were associated with late effects burden and engagement in cancer survivorship care. Results A total of 634 participants completed questionnaires (48% male, mean age = 21.7 years). Most participants (79%) reported at least one cancer-related late effect, most commonly fatigue (40%) and memory/learning difficulties (34%). Brain tumor survivors reported a higher total number of late effects than survivors with other diagnoses (mean = 5.7 vs. 3.2, P Conclusion Survivors report a range of health problems decades after treatment completion. Understanding the burden of late effects, and motivators for seeking survivorship care to manage these health problems, is important for ensuring that tailored interventions or services are available to meet the needs of this growing population and to design effective models of survivorship care.

Introduction:Coronavirus disease 2019 (COVID-19) has dramatically changed the epidemiology of several diseases. Much evidence on this has been published in the pandemic phase. In addition, many studies have shown that phenomena such as stress, substance abuse, and burnout increased in the general population during the lockdown. Unfortunately, few studies analyze the post-pandemic phase.Study Objective:The study aimed to evaluate the trend of broad social problems, such as a diagnosis by the emergency department (ED), in the post-pandemic phase in the Lombardy (Italy) region.Methods:The study is a retrospective observational cohort study. All admissions to emergency rooms in the Lombardy region registered in the Emergency Urgency OnLine (EUOL) portal made from January through June 2019 were analyzed, having as main causes: psychiatric disorders, self-harm, substance abuse, social disadvantage, and violence. All accesses in emergency rooms in the Lombardy region registered in the EUOL portal made from January 1, 2019 through June 30, 2019 were analyzed and compared with the same period in 2022.Results:The study recorded an increase in the likelihood of events of self-harm (OR = 2.1; 95% CI, 1.8-2.6; P Conclusion:The increase in diagnoses of these social problems in the ED is only the culmination of a phenomenon that hides an underlying rise in social illness. In the post-COVID-19 phase, there is a need to invest in community care and social illness prevention policies.

A Injúria Renal Aguda (IRA) é uma doença cujas principais causas são as doenças primárias, mas também pode ser resultado de terapias medicamentosas e procedimentos médicos. O aumento da expectativa de vida e consequente envelhecimento populacional, juntamente com maior incidência de condições comórbidas, principalmente Diabetes Mellitus (DM) e Hipertensão Arterial Sistêmica (HAS), pode levar ao desenvolvimento de Doença Renal Crônica (DRC) e, por conseguinte, ao desenvolvimento de Insuficiência Renal Aguda (IRA). Quanto à epidemiologia, a incidência de IRA é difícil de avaliar devido à falta de consenso em torno de sua definição. É importante que se estabeleça uma definição padrão para que possamos ter uma melhor compreensão da magnitude do problema. A incidência de infecções hospitalares depende de fatores como idade, sexo, comorbidades e local de internação dentro do hospital. Em países desenvolvidos, a incidência varia de 3 a 18,3%, enquanto em países menos desenvolvidos é de 21%. A IRA tem diversos subtipos que são importantes para identificar o prognóstico, as opções terapêuticas, as causas e outras condições associadas. Quanto às manifestações clínicas, incluem distúrbios neurológicos, cardiovasculares, respiratórios, hepáticos, digestivos, cutâneos e de mucosas e renais. O diagnóstico da IRA é feito com base na concentração sérica de creatinina ou na diminuição do débito urinário, para que o tratamento e prognóstico sejam melhores. Já a abordagem terapêutica, depende de vários fatores, incluindo idade, comorbidades crônicas, DRC subjacente, estágio e duração do episódio e gravidade da recuperação renal. Quanto mais grave, maior o risco de desfechos ruins. Para prevenir as IRA, é necessário realizar o manejo de fatores de risco modificáveis, como a retirada de medicamentos nefrotóxicos, o controle adequado de comorbidades pré-existentes, o controle precoce do foco infeccioso em casos de sepse, entre outros.

Background: Major depressive disorders represent a significant burden to society, and it is recommended that antidepressant therapy should last at least 6 months. In Italy, antidepressant use in clinical practice was reported to increase by 1.7% in 2020 compared to 2019, but only 40% of new prescriptions are characterized by a treatment duration longer than 3 months. Objective: The study aims to describe adherence and persistence to therapy in a subset of antidepressants (citalopram, duloxetine, escitalopram, paroxetine, sertraline, venlafaxine) vs. vortioxetine in Italy during a 2-year period from 2017 to 2019. Methods: A retrospective analysis of the longitudinal patient database reporting data from general practitioners on drug prescriptions in Italy was carried out in a cohort of 8,235 adult patients who were prescribed antidepressants. Results: Overall, 32.4% of the patients adhered to treatment for ≥6 months over a 1-year period. Vortioxetine had a lower risk of low adherence compared to duloxetine, paroxetine, and venlafaxine and a higher risk compared to citalopram, escitalopram, and sertraline. 68.7% of patients discontinued treatment during follow-up. The greatest percentage of patients continuing therapy was seen with duloxetine, while citalopram was associated with the highest proportion of patients discontinuing therapy. No significant differences in discontinuation were observed when comparing vortioxetine to the other antidepressants. Conclusion: Adherence results were considerably less than the 6-month recommendation in this real- world analysis of antidepressant therapies. Also, persistence to therapy was low, with most patients discontinuing treatment. Thus, there is a need for interventions to help patients adhere to their planned therapy.

Inositol is a natural sugar-like compound, commonly present in many plants and foods. It is involved in several biochemical pathways, most of them controlling vital cellular mechanisms, such as cell development, signaling and nuclear processes, metabolic and endocrine modulation, cell growth, signal transduction, etc. In this narrative review, we focused on the role of inositol in human brain physiology and pathology, with the aim of providing an update on both potential applications and current limits in its use in psychiatric disorders. Overall, imaging and biomolecular studies have shown the role of inositol levels in the pathogenesis of mood disorders. However, when administered as monotherapy or in addition to conventional drugs, inositol did not seem to influence clinical outcomes in both mood and psychotic disorders. Conversely, more encouraging results have emerged for the treatment of panic disorders. We concluded that, despite its multifaceted neurobiological activities and some positive findings, to date, data on the efficacy of inositol in the treatment of psychiatric disorders are still controversial, partly due to the heterogeneity of supporting studies. Therefore, systematic use of inositol in routine clinical practice cannot be recommended yet, although further basic and translational research should be encouraged.

The etiopathogenesis of schizophrenia to date appears unclear. Multiple types of research have focused attention on the possible etiological role of the amygdala. The amygdala is involved in emotion processing, cognitive function, and social cognition; these aspects appear severely impaired in schizophrenia. In this brief review, we will look at studies that have correlated morpho-functional aspects of the amygdala with the psychopathological domains of schizophrenia.

Il saggio ricostruisce alcuni aspetti ancora poco indagati della storia di Giuseppe De Felice Giuffrida, ovvero le sue curiosità culturali e la sua produzione letteraria. In particolare, viene preso in considerazione un lavoro sulle guerre servili in Sicilia, pubblicato a Catania per i tipi dell'editore Giannotta nel 1911, durante una pausa dal suo impegno in prima linea come sindaco. Il saggio aveva per l'autore una motivazione squisitamente politica, ma egli vi si dedicò con grande passione, tanto da spingersi al di là della compilazione dilettantesca, addentrandosi nel terreno della ricerca, dell'analisi delle fonti e del confronto storiografico..

AML is a biologically and clinically heterogeneous disease that is associated with poor overall long-term survival. The expanding knowledge of genomic landscape in AML as well as advancements in molecular and chemical biology over the pathway in AML. After 40 years of stagnancy, the recent approval of numerous novel oral anti-leukemic agents for the treatment of AML has changed both the armamentarium of medications and treatment paradigms. These agents have unique clinical considerations in terms of administration, adverse effects, and monitoring parameters which may differ from clinician's historical expectations. Understanding the data, indication and clinical considerations for such novel oral anti-leukemic agents is paramount for clinicians caring patients with AML.

Eating Disorders (EDs) are potentially serious disabling, pervasive, and life-threatening mental disorders that can greatly impair physical health and significantly alter an individual's psychosocial functioning. They are some of the most prevalent disorders during adolescence and often take a chronic and disabling course, although they can occur across the whole lifespan. Prevalence appears to be higher in Western populations and in the female sex. They play a key role in the origin and maintenance of symptomatology, predominantly: distorted beliefs, distorted perceptions, dysfunctional attitudes toward weight, body shape, and nutrition, which take hold beginning in childhood or adolescence, but also genetic bases, socio-cultural and environmental factors. Given the complexity of the etiology of such psychopathologies and maintenance factors, treatment must contemplate a multidimensional and multidisciplinary approach. To date, the deep understanding of the pathophysiology and psychobiology of EDs remains to be further investigated.

Objectives: There is limited evidence about the factors influencing antidepressant (AD) prescription for the treatment of major depressive disorder (MDD) in Real World clinical practice in Italy. In this retrospective, population-based study, we set out to describe a patient cohort initiated on AD treatment for MDD and investigate the possible predictors of different ADs prescription in the primary care setting. Methods: Patients with a diagnosis of MDD who received an initial prescription of one of 11 selected ADs between 1-Apr-2017 and 31-Mar-2019 (index date) were identified from primary care electronic medical records in the Longitudinal Patient Database. Patients prescribed ≥1 AD in the 12 months before index date were excluded. Results were stratified by AD molecule. Multivariable logistic regression models estimated the association between patients’ demographic, clinical factors, and choice of AD molecule. Results: The study cohort comprised 8,823 patients (67.1% female; mean age 61.6 years). Previous AD treatments (prescribed in the 10 years before index date) had been received by 46.6% of patients (non-naïve patients). The most commonly reported psychiatric and medical comorbidities reported in the 12 months before index date were anxiety (8.4%) and hypertension (41.9%), respectively. Patients’ age was a significant predictor of AD molecule prescribed at index date in eight of the 11 molecules investigated while patients’ gender influenced clinician prescribing of bupropion, citalopram, fluoxetine, fluvoxamine, sertraline, and vortioxetine. Conclusions: Results from this Real World study provide useful information for clinicians on the clinical factors influencing AD prescription in patients treated for MDD in primary care.

This study aims to compare the accelerometer-measured daily patterns of PA and sedentary behaviour among participants with and without prevalent/incident depressive symptoms. We used data from 5,582 individuals in The Maastricht Study (59.9 ± 8.6 years, 50.3% women). Daily patterns of sedentary time, light-intensity physical activity (LiPA), moderate-to-vigorous physical activity (MVPA), and sit-to-stand transitions were objectively measured at baseline with the activPAL3 activity monitor. Depressive symptoms were assessed using the 9-item Patient Health Questionnaire, both at baseline and annually (median follow-up: 5.1 years). General linear models were used to compare patterns of physical activity and sedentary behaviour between those with and without prevalent/incident depressive symptoms. Participants with prevalent depressive symptoms had significantly more sedentary time (18.6 min/day) and lower LiPA (26.8 min/day) and MVPA (4.8 min/day) than participants without depressive symptoms. Considering the daily patterns, participants with prevalent depressive symptoms had significantly more sedentary time early in the afternoon (12:00-18:00), early evening (18:00-21:00), and during the night (00:00-03:00), less time in LiPA in all periods between 09:00-21.00 and less MVPA in the morning (09:00:12:00), early afternoon (12:00-15:00), and evening (18:00-21:00), then those without. Similar differences in activity and sedentary behaviour patterns between those and without incident depressive symptoms were observed albeit the differences were smaller Overall, we did not find specific time slots particularly associated with both prevalent and incident depressive symptoms. These findings may indicate that less sedentary time and more intense PA can be important targets for the prevention of depression irrespective of the timing of the day.

O presente artigo tem por objetivo expor as dificuldades enfrentadas pelos gestores públicos ao longo dos anos, pelo que poderá ser chamado de ativismo judicial desproporcional. O princípio da reserva financeira do possível é o mecanismo garantidor para que as políticas públicas universais não sejam preteridas em relação as individuais, como vem ocorrendo por meio das decisões jurisdicionais, onde este vem sendo injustamente mitigado e, muitas vezes, até mesmo desconsiderado. Para atenuar tal problemática, poderá o gestor público invocar as determinações trazidas pela Lei 13.655/2018, que estabelece novas diretrizes para interpretar e aplicar o direito público.

Inflammatory bowel diseases (IBDs) are chronic diseases that demand continuous interaction between patients and healthcare providers. Quality of care (QoC) is a factor that contributes to a patient's adherence to treatment and its success.To evaluate QoC in patients from a single IBD reference center.This cross-sectional study included 133 patients from a single Brazilian IBD public health center. QoC was evaluated through the QoC Through the Eyes of Patients with IBD (QUOTE-IBD) questionnaire (based on patient perspectives), which measures eight dimensions of care. We compared QoC among patients with Crohn's disease and ulcerative colitis and analyzed the clinical and psychological factors associated with QoC satisfaction. Clinical evaluations assessed disease characteristics, quality of life, anxiety, and depression levels.Sixty-nine patients with Crohn's disease and 64 with ulcerative colitis were interviewed. The mean age was 37.26 years ± 13.05 years, and 63.91% of the patients were women. The mean duration of the disease was 8.44 years ± 7.59 years, where most patients were in remission (70.31% of patients with ulcerative colitis and 62.32% with Crohn's disease). The total QoC score of the sample was 8.61 years ± 1.31 points, indicating that the QoC provided by the center was unsatisfactory. According to univariate logistic regression, patients with Crohn's disease had higher satisfaction rates than those with ulcerative colitis [odds ratio (OR): 2.746; 95% confidence interval (CI): 1.360-5.541;Patients from the IBD public center reported good doctor-patient relationships, but had problems related to the healthcare structure. Evaluation of healthcare centers is of paramount to improve QoC for the patients involved.

Lipid metabolism impacts immune cell differentiation, activation, and functions, modulating inflammatory mediators, energy homeostasis, and cell membrane composition. Despite preclinical evidence, data in humans lack concerning tumors and immunotherapy (IO). We aimed at investigating the correlations between circulating lipids and the outcome of non-small cell lung cancer (NSCLC) patients treated with IO.We identified all patients with advanced NSCLC treated with IO at our Institution with available baseline plasma samples. Fatty acids (FAs) were analyzed through gas chromatography. Survival curves were estimated by the Kaplan-Meier method. Cox multivariate models were constructed through a stepwise procedure, with entry and exit P value set at .2.We identified 112 patients, mostly with performance status 1 (65.2%) and PD-L1≥1% (75.3%). Median progression-free survival (PFS) and overall survival (OS) were 2.8 and 11.0 months, respectively. Multivariable model for survival identified a positive association of circulating free (FFA) C16:0 (P .005) and esterified (EFA) C16:1 (P .030) with PFS, and a positive association of EFA C16:1 (P .001) and EFA C18:0 (P .020) with OS. EFA C16:0 was negatively associated with PFS (P .008).FFA C16:0 and FAs derived from its unsaturation (EFA C16:1) and elongation (EFA C18:0) are associated with a better outcome in NSCLC patients treated with IO. It is conceivable that the ratio among those FAs may modify membrane fluidity and receptor activity, influencing IO efficacy. These data pave the way for the investigation of lipid-modulating strategies in association with IO in NSCLC.

This manuscript presents the study of the microstructural evolution, plastic anisotropy, and mechanical behavior of a duplex stainless steel (DSS) processed by the equal channel angular pressing (ECAP) technique. The ECAP process produced shear bands affecting both phases, austenite and ferrite, which in turns act as preferential sites for the appearance of the new ultrafine grains. Microstructural observations indicated grain sizes smaller than 300 nm in both phases. However, marked differences in the grain boundary misorientations were observed. Most ferrite grain boundaries showed low misorientations (average misorientation of 30°). In contrast, the austenite grain boundaries were mainly dominated by high-angle grain boundaries (average misorientation of 39°). The ECAP processing allowed to reach a yield strength over 1.1 GPa after one ECAP pass. Dislocations formed walls in the ferrite, while they were distributed evenly in the austenite grains creating plastic gradients between the two phases. Through the visco-plastic self-consistent model, it was found that austenite and ferrite strain hardening at different rates, generating plastic instabilities at different strain magnitudes. In this way, it was shown that austenite is the phase that provides more hardening while ferrite provides ductility. Regarding the anisotropy of the steel, crystal plasticity simulations showed that during the first passes of ECAP, the Lankford coefficients increase notably due to the heterogeneous microstructure of sheared grains with a higher density of defects forming subgrains in ferrite than austenite. Moreover, the austenite was more responsible for the larger planar anisotropy ($$\Delta r$$ Δ r = 2.18) values than ferrite ($$\Delta r$$ Δ r = 1.67) after two ECAP passes.

Background Primary antiphospholipid syndrome (PAPS) is characterized by the presence of antiphospholipid antibodies (aPL), repetitive fetal loss, and arterial/venous thrombosis and no association with other autoimmune rheumatic disease. Ocular involvement can also occur including retinal vascular thrombosis and neuro-ophthalmological manifestations, such as optic neuropathy and amaurosis fugax. Early detection of ocular changes is crucial to minimize functional loss. Purpose To perform a multimodal evaluation, including the use of Optical Coherence Angiotomography (OCTA), in patients with PAPS without ocular complaints and compare with healthy individuals. Methods We performed a complete structural and functional ophthalmological evaluation using OCTA and microperimetry exam in patients with PAPS, followed at a tertiary Rheumatology outpatient clinic. Results We included 104 eyes of 52 subjects [PAPS without ocular complaints (N = 26) and healthy individuals (N = 26)]. Among PAPS patients, 21 were female (80.8%) and 21 (80.8%) were Caucasians. PAPS manifestations were venous (65.4%), arterial thrombosis (34.6%), and obstetrical (34.6%) and all of them had lupus anticoagulant. Ophthalmologic findings were more frequent in PAPS compared to healthy individuals (19.2% vs. 0%, p = 0.05). The most common retinal change was paracentral acute middle maculopathy (PAMM) (3 patients, 5 eyes), followed by drusen (1 patient, 2 eyes) and pachychoroid pigment epitheliopathy (PPE) (1 patient, 1 eye). Hypertension and hyperlipidemia were present in 100% of the PAPS patients with PAMM, while only six patients (26.1%) with PAPS without PAMM presented these two risk factors together ( p = 0.03). Conclusions We provide novel evidence that approximately 20% of our asymptomatic PAPS patients without ocular symptoms have ophthalmologic findings that require early identification and careful surveillance focusing on minimizing systemic and vascular risk factors.

Total hip arthroplasty (THA) surgeries are increasing; to assess quality of life after THA, an instrument that considers patient's perspective on surgical outcomes is necessary. The objective of this study is to assess the psychometric properties of the Italian version of the Forgotten Joint Score (FJS-I) in patients with THA. The FJS-I was administered to 111 patients with THA, as well as the Western Ontario and McMaster Universities (WOMAC), Numerical Pain Rating Scale (NPRS), and the EuroQol 5D-5L (EQ-5D-5L). Structural validity [confirmatory factor analysis (CFA)], internal consistency (Cronbach's alpha), test-retest reliability [intraclass correlation coefficient (ICC 2,1 )], measurement error [standard error of the measurement (SEM)], and construct validity (hypothesis testing with correlation of the WOMAC, NPRS, and EQ-5D-5L) were assessed. In addition, the minimal detectable change (MDC) was computed. The result of CFA confirmed the one-factor structure. Internal consistency was supported (α = 0.944). A high test-retest reliability (ICC = 0.958; 95% confidence interval, 0.914-0.980) was found with an SEM and an MDC of 5.3 and 16.6 points, respectively. The a-priori hypotheses were fully met, determining the construct validity to be satisfactory. Psychometric properties of the FJS-I were confirmed, and it can be used for single-person assessment. Further research is suggested to refine its structural validity.

An archaeological watching brief undertaken during the excavation of 1400m of loop trenching required for the installation of a ground source heat pump. The watching brief revealed no evidence of any large scale bloomery within the excavated areas. It is likely that metal working evidence may be located closer to the river Esk and to the woods to the south; both areas were located just outside the monitored area. It was notable that there was no residual metal working waste found across the site. The stratigraphic matrix of the site was incredibly clean, no residual pottery or other domestic waste was observed within the silty sandy alluvial soils. To the south of the site was evidence of a paleochannel and a gravel deposit, both were situated in the exact locations determined during the 2007 geophysical survey. The earliest archaeological evidence on site was contained within a small, bloomery/burned post hole that revealed a backfill rich in burned oak charcoal and iron smelting tap slag. The tap slag was dated to between 1322-1500. Another cobble filled pit was found within a similar archaeological level to the burned pit/post hole but contained no dating evidence. The tap slag is dated to the period contemporary with Danby Castle and it is likely there was a connection between both sites due to the absence of any other large institution. A drainage system that had undergone two phases of improvement was observed traversing the site from east to west, as indicated on the 1853 Ordnance Survey Map. A 17th-18th century stone capped drain was later improved with additional 19th century parallel clay field pipes. Further to this, at ground level, directly above the drainage system, a clay lined ditch had been dug to further accommodate the flow of water down from the moors towards the river Esk. This drainage system is likely associated with Danby Lodge.

In the MEG II detector, the measurement of the momentum of the charged particle is performed by a high transparency single volume, full stereo cylindrical Drift Chamber (CDCH). It is composed by 9 concentric layers, each consisting of 192 drift cells. The single drift cell is approximately squared, with a 20 μm gold plate tungsten sense wire surrounded by 40 μm/50 μm silver plated aluminum field wires in a ratio of 5:1. During the construction of the first CDCH, we observed the breaking of about hundred cathode wires: 97 of these were 40 μm aluminum wires, while 10 were 50 μm wires. Since the number of broken cathodes is less than 1% of the total, one can expect the influence on the track reconstruction efficiency to be not so dramatic. We verified by means of simulations that the loss of one cathode does not change the cell electric field appreciably. Here we present the results of the analysis of the effects of mechanical stress and chemical corrosion observed on these broken wires. Finally, we show the studies carried out on new wires to overcome the weaknesses found and the process that will be used for the construction of the new drift chamber (CDCH2). It will be built with the same modular technique, as for the previous one, the use of the wiring robot will be optimized to improve some weaker step in the procedure, new wires will be adopted with a 25% thicker diameter, which has very little effects on the resolution and efficiency of the detector. Furthermore these wires are made with a manufacturing process different from that used previously.

The aim of this study was to evaluate the diagnostic performance of contrast-enhanced spectral mammography (CESM) in predicting breast lesion malignancy due to microcalcifications compared to lesions that present with other radiological findings. Three hundred and twenty-one patients with 377 breast lesions that underwent CESM and histological assessment were included. All the lesions were scored using a 4-point qualitative scale according to the degree of contrast enhancement at the CESM examination. The histological results were considered the gold standard. In the first analysis, enhancement degree scores of 2 and 3 were considered predictive of malignity. The sensitivity (SE) and positive predictive value (PPV) were significative lower for patients with lesions with microcalcifications without other radiological findings (SE = 53.3% vs. 82.2%, p-value < 0.001 and PPV = 84.2% vs. 95.2%, p-value = 0.049, respectively). On the contrary, the specificity (SP) and negative predictive value (NPV) were significative higher among lesions with microcalcifications without other radiological findings (SP = 95.8% vs. 84.2%, p-value = 0.026 and NPV = 82.9% vs. 55.2%, p-value < 0.001, respectively). In a second analysis, degree scores of 1, 2, and 3 were considered predictive of malignity. The SE (80.0% vs. 96.8%, p-value < 0.001) and PPV (70.6% vs. 88.3%, p-value: 0.005) were significantly lower among lesions with microcalcifications without other radiological findings, while the SP (85.9% vs. 50.9%, p-value < 0.001) was higher. The enhancement of microcalcifications has low sensitivity in predicting malignancy. However, in certain controversial cases, the absence of CESM enhancement due to its high negative predictive value can help to reduce the number of biopsies for benign lesions

Background: Affective temperaments represent the stable, biologically determined substrates of mood disorders. The relationship between affective temperaments and bipolar disorder (BD) or major depressive disorder (MDD) has been described. However, the strength of such relationship should be tested while considering other factors influencing the diagnosis of BD/MDD. Literature also lacks a comprehensive description of the interplay between affective temperament and characteristics of mood disorders. The aim of the present study is to address these issues. Methods: This is a multicentric observational study including 7 Italian university sites. Five-hundred-fifty-five euthymic subjects with BD/MDD were enrolled and further divided in those with hyperthymic (Hyper, N=143), cyclothymic (Cyclo, N=133), irritable (Irr, N=49), dysthymic (Dysth, N=155), and anxious (Anx N=76) temperaments. Linear, binary, ordinal and logistic regressions were performed to assess the association between affective temperaments and i) diagnosis of BD/MDD; ii) characteristics of illness severity and course. Results: Hyper, Cyclo and Irr were more likely to be associated with BD, together with earlier age of onset and presence of a first-degree relative with BD. Anx and Dysth were more associated with MDD. Differences in association between affective temperaments and characteristics of BD/MDD were observed for hospital admissions, phase-related psychotic symptoms, length and type of depression, comorbidity and pharmacological intake. Limitations: Small sample size, cross-sectional design, recall biases. Conclusion: Specific affective temperaments were associated to certain characteristics of illness severity and course of BD or MDD. Evaluation of affective temperaments might help a deeper understanding of mood disorders.

La psicología existencial se ha centrado casi exclusivamente en el análisis de la relación terapéutica entre sus protagonistas: terapeuta y paciente. Son pocas las investigaciones sobre temas que atañen a la vida del ser humano. Sin embargo, en toda terapia se presentan múltiples alternativas en la vida de los pacientes y en la propia del terapeuta que son plausibles de un estudio fenomenológico existencial. Me referiré en este trabajo a un escenario posible de este tipo de análisis, en este caso, a todo lo que le acontece al paciente oncológico, a su familia, al equipo tratante y a la sociedad en su conjunto, en cómo afrontan al cáncer. Abordar temas relacionados con la muerte siempre será difícil pero un terapeuta existencial es indudable que no puede soslayarlo. Es tarea de todo terapeuta estar abierto a las distintas alternativas que se presentan en la vida de sus consultantes, teniendo siempre presente la visión de mundo de cada uno de ellos en particular, en las circunstancias que sean

A pesquisa buscou compreender o fenômeno da violência nas vivências LGBTs. Realizou-se o estudo na cidade de Cuité, Paraíba, por meio de entrevistas semiestruturadas com 10 sujeitos participantes de um movimento social LGBT local. As entrevistas foram analisadas à luz da Análise de Conteúdo, da qual emergiram três categorias: 1. a violência em múltiplos espaços e fases da vida; 2. ecos da violência ao longo da vida; e 3. mecanismos de apoio e enfrentamento. Compreendeu-se o itinerário da violência sofrida: iniciando-se em casa, com a família, até as instituições – como escolas, delegacias e serviços de saúde –, refletindo em consequências físicas e psicológicas no decorrer de suas vidas e repercutindo, à medida que também são produzidas, na ininteligibilidade dos seus corpos pelos profissionais de saúde.

The coronavirus disease 2019 (COVID-19) pandemic changed the time-dependent cardiac arrest network. This study aims to understand whether the rescue standards of cardiopulmonary resuscitation (CPR) and out-of-hospital cardiac arrest (OHCA) were handled differently during pandemic compared to the previous year.Data for the years 2019 and 2020 were provided by the records of the Lombardy office of the Regional Agency for Emergency and Urgency. We analysed where the cardiac arrest occurred, when CPR started and whether the bystanders used public access to defibrillation (PAD).During 2020, there was a reduction in CPRs performed by bystanders (odds ratio [OR] = 0.936 [95% confidence interval (CICOVID-19 had a profound impact on the time-dependant OHCA network. During the first pandemic wave, CPR and PAD used by bystanders decreased. The different contexts in which OHCAs occurred may partially explain these differences.

Joseph Elliot Alchin,1,2 Christina Signorelli,1,2 Jordana Kathleen McLoone,1,2 Claire Elizabeth Wakefield,1,2 Joanna Elizabeth Fardell,1,2 Karen Johnston,1 Richard J Cohn1,2 1Kids Cancer Centre, Sydney Children’s Hospital, Randwick, NSW, Australia; 2School of Women’s and Children’s Health,UNSW Medicine, University of New South Wales, Sydney, NSW, AustraliaCorrespondence: Christina Signorelli, Kids Cancer Centre, Level 1 South, Sydney Children’s Hospital, High St, Randwick, NSW, 2031, Australia, Tel +61 431 547 350, Fax +61-2-9382-1789, Email c.signorelli@unsw.edu.auPurpose: Ongoing survivorship care allows childhood cancer survivors the opportunity to address treatment-related health problems and improve their quality of life. However, many survivors do not adhere to their healthcare professionals’ recommendations and the factors supporting their adherence remain unclear.Patients and Methods: Long-term childhood cancer survivors completed the “Re-engage” program, which assessed survivors’ heath needs and provided individualised recommendations for health interventions and surveillance developed by an expert multi-disciplinary team (MDT). We measured survivors’ recall of, and adherence to, their individualised healthcare recommendations at one and six months post-intervention. We conducted a series of univariate negative binomial regressions to investigate factors associated with the total number of recommendations that were correctly recalled and adhered to.Results: We analysed the data of 25 childhood cancer survivors who participated in Re-engage (mean age = 31.9 years). On average, survivors were provided with 6.6 recommendations (range = 1– 11). Survivors accurately recalled receiving 3.0 recommendations at one month post-intervention and 1.9 at six months. Survivors had adhered to an average of 1.3 recommendations by six-month follow-up. In total, 56% of participants reported that they did not adhere to any recommendations. By six-month follow-up, greater adherence to MDT recommendations was associated with having a history of a second cancer (B = 1.391; 95% confidence interval [CI], 0.686 to 2.097; p

Hydrogen cyanamide (HC) has been widely used in horticulture to trigger bud burst following dormancy. Its use has been banned in some countries due to human health concerns, however the search for effective safe alternatives is delayed by lack of knowledge of the mechanism of HC action. Earlier studies demonstrate that HC stimulates the production of reactive oxygen species (ROS) and alters the rate of cell division. However, the relationships between HC effects on ROS, redox (reduction/oxidation) homeostasis and cell division are unknown. This study used Arabidopsis thaliana ((L.) Heynh.) seedlings expressing the redox reporter roGFP2 to measure the oxidation states of the nuclei and cytosol in response to HC treatment. The Cytrap dual cell cycle phase marker system and flow cytometry were used to study associated changes in cell proliferation. HC (1.5 mM) reversibly inhibited root growth during a 24 h treatment. Higher concentrations were not reversible. HC did not synchronise the cell cycle, in contrast to hydroxyurea. Rather, HC caused a gradual accumulation of cells in the G2/M phase and decline of G1/S phase cells, 16 to 24 h post-treatment. This was accompanied by increased oxidation of both the nuclei and cytosol. Taken together, these findings show that HC impairs proliferation of embryonic root meristem cells in a reversible manner through restriction of G2/M transition accompanied by increased cellular oxidation.

Recovery is a broadly debated concept in the field of psychiatry research and in schizophrenia. Our study aims to understand the correlation between personal recovery from schizophrenia and factors such as mentalization, disability, quality of life, and antipsychotic side effects; Methods: Participants with schizophrenia (according to DSM-5 criteria) were consecutively recruited from the Psychiatry Unit of the University of Catania, Italy. Participants were assessed with the Recovery Assessment Scale (RAS), the Multidimensional Mentalizing Questionnaire (MMQ), the brief version of the WHO Disability Assessment Schedule (WHO-DAS), the EuroQoL-5 dimensions-5 levels, the Insight Orientation Scale (IOS) and the Glasgow Antipsychotic Side Effect Scale (GASS); Results: 81 patients were included. Our findings showed a positive correlation between RAS total scores and MMQ scores, especially in “good mentalizing” subdomains. IOS scores also had a positive association with RAS and MMQ scores. In contrast, poor mentalizing abilities negatively correlated with WHO-DAS 2.0 scores. While antipsychotic side effects influenced functioning, they did not impact perceived recovery. Conclusions: The study’s results identified potential predictors of personal recovery from schizophrenia. These findings could contribute to creating tailored interventions to facilitate the recovery process.

Purpose: This study aimed to investigate the use of contrast-free magnetic resonance imaging (MRI) as an innovative screening method for detecting breast cancer in high-risk asymptomatic women. Specifically, the researchers evaluated the diagnostic performance of diffusion-weighted imaging (DWI) in this population. Methods: MR images from asymptomatic women, carriers of a germline mutation in either the BRCA1 or BRCA2 gene, collected in a single center from January 2019 to December 2021 were retrospectively evaluated. A radiologist with experience in breast imaging (R1) and a radiology resident (R2) independently evaluated DWI/ADC maps and, in case of doubts, T2-WI. The standard of reference was the pathological diagnosis through biopsy or surgery, or ≥1 year of clinical and radiological follow-up. Diagnostic performances were calculated for both readers with a 95% confidence interval (CI). The agreement was assessed using Cohen’s kappa (κ) statistics. Results: Out of 313 women, 145 women were included (49.5 ± 12 years), totaling 344 breast MRIs with DWI/ADC maps. The per-exam cancer prevalence was 11/344 (3.2%). The sensitivity was 8/11 (73%; 95% CI: 46–99%) for R1 and 7/11 (64%; 95% CI: 35–92%) for R2. The specificity was 301/333 (90%; 95% CI: 87–94%) for both readers. The diagnostic accuracy was 90% for both readers. R1 recalled 40/344 exams (11.6%) and R2 recalled 39/344 exams (11.3%). Inter-reader reproducibility between readers was in moderate agreement (κ = 0.43). Conclusions: In female carriers of a BRCA1/2 mutation, breast DWI supplemented with T2-WI allowed breast cancer detection with high sensitivity and specificity by a radiologist with extensive experience in breast imaging, which is comparable to other screening tests. The findings suggest that DWI and T2-WI have the potential to serve as a stand-alone method for unenhanced breast MRI screening in a selected population, opening up new perspectives for prospective trials.

Background: Patients with refractory mCRC rarely undergo third-line or subsequent treatment. This strategy could negatively impact their survival. In this setting, regorafenib (R) and trifluridine/tipiracil (T) are two key new treatment options with statistically significant improvements in overall survival (OS), progression-free survival (PFS), and disease control with different tolerance profiles. This study aimed to retrospectively evaluate the efficacy and safety profiles of these agents in real-world practice. Materials and Methods: In 2012–2022, 866 patients diagnosed with mCRC who received sequential R and T (T/R, n = 146; R/T, n = 116]) or T (n = 325]) or R (n = 279) only were retrospectively recruited from 13 Italian cancer institutes. Results: The median OS is significantly longer in the R/T group (15.9 months) than in the T/R group (13.9 months) (p = 0.0194). The R/T sequence had a statistically significant advantage in the mPFS, which was 8.8 months with T/R vs. 11.2 months with R/T (p = 0.0005). We did not find significant differences in outcomes between groups receiving T or R only. A total of 582 grade 3/4 toxicities were recorded. The frequency of grade 3/4 hand-foot skin reactions was higher in the R/T sequence compared to the reverse sequence (37.3% vs. 7.4%) (p = 0.01), while grade 3/4 neutropenia was slightly lower in the R/T group than in the T/R group (66.2% vs. 78.2%) (p = 0.13). Toxicities in the non-sequential groups were similar and in line with previous studies. Conclusions: The R/T sequence resulted in a significantly longer OS and PFS and improved disease control compared with the reverse sequence. R and T given not sequentially have similar impacts on survival. More data are needed to define the best sequence and to explore the efficacy of sequential (T/R or R/T) treatment combined with molecular-targeted drugs.

Regulated systems for transgene expression are useful tools in basic research and a promising platform in biomedicine due to their regulated transgene expression by an inducer. The emergence of optogenetics expression systems enabled the construction of light-switchable systems, enhancing the spatial and temporal resolution of a transgene. The LightOn system is an optogenetic tool that regulates the expression of a gene of interest using blue light as an inducer. This system is based on a photosensitive protein (GAVPO), which dimerizes and binds to the UASG sequence in response to blue light, triggering the expression of a downstream transgene. Previously, we adapted the LightOn system to a dual lentiviral vector system for neurons. Here, we continue the optimization and assemble all components of the LightOn system into a single lentiviral plasmid, the OPTO-BLUE system. For functional validation, we used enhanced green fluorescent protein (EGFP) as an expression reporter (OPTO-BLUE-EGFP) and evaluated the efficiency of EGFP expression by transfection and transduction in HEK293-T cells exposed to continuous blue-light illumination. Altogether, these results prove that the optimized OPTO-BLUE system allows the light-controlled expression of a reporter protein according to a specific time and light intensity. Likewise, this system should provide an important molecular tool to modulate gene expression of any protein by blue light.

Cancer immunotherapy, largely represented by immune checkpoint inhibitors (ICIs), has led to substantial changes in preclinical cancer research and clinical oncology practice over the past decade. However, the efficacy and toxicity profiles of ICIs remain highly variable among patients, with only a fraction achieving a significant benefit. New combination therapeutic strategies are being investigated, and the search for novel predictive biomarkers is ongoing, mainly focusing on tumor- and host-intrinsic components. Less attention has been directed to all the external, potentially modifiable factors that compose the exposome, including diet and lifestyle, infections, vaccinations, and concomitant medications, which could affect the immune system response and its activity against cancer cells. We hereby provide a review of the available clinical evidence elucidating the impact of host-extrinsic factors on ICI response and toxicity.

Out-hospital cardiac arrest (OHCA) is a multifactor disease. Many studies have correlated OHCA with a patient's lifestyle; unfortunately, less evidence highlights the correlation with meteorological factors. Methods: We analysed 23959 OHCA rescue performed by the emergency medical system (EMS) of Lombardy Region, the most Italian populated region, in 2018 and 2019, the pre-pandemic era. The aim was to evaluate the probability of Return of spontaneous circulation (ROSC) in different months. In March and April, we highlight an increase of ROSC (OR: 1.20 IC 95% 1.04 - 1.31; p, Journal of Preventive Medicine and Hygiene, Vol. 64 No. 1 (2023): Vol. 64 No. 1 (2023)

Background Pronectins™ are a new class of fibronectin-3-domain 14th-derived (14Fn3) antibody mimics that can be engineered as bispecific T cell engager (BTCE) to redirect immune effector cells against cancer. We describe here the in vitro and in vivo activity of a Pronectin™ AXL-targeted first-in-class bispecific T cell engager (pAXLxCD3ε) against Epithelial Ovarian Cancer (EOC). Methods pAXLxCD3ε T-cell mediated cytotoxicity was evaluated by flow cytometry and bioluminescence. pAXLxCD3ε mediated T-cell infiltration, activation and proliferation were assessed by immunofluorescence microscopy and by flow cytometry. Activity of pAXLxCD3ε was also investigated in combination with poly-ADP ribose polymerase inhibitors (PARPi). In vivo antitumor activity of pAXLxCD3ε was evaluated in immunocompromised (NSG) mice bearing intraperitoneal or subcutaneous EOC xenografts and immunologically reconstituted with human peripheral blood mononuclear cells (PBMC). Results pAXLxCD3ε induced dose-dependent cytotoxicity by activation of T lymphocytes against EOC cells, regardless of their histologic origin. The addition of PARPi to cell cultures enhanced pAXLxCD3ε cytotoxicity. Importantly, in vivo, pAXLxCD3ε was highly effective against EOC xenografts in two different NSG mouse models, by inhibiting the growth of tumor cells in ascites and subcutaneous xenografts. This effect translated into a significantly prolonged survival of treated animals. Conclusion pAXLxCD3ε is an active therapeutics against EOC cells providing a rational for its development as a novel agent in this still incurable disease. The preclinical validation of a first-in-class agent opens the way to the development of a new 14Fn3-based scaffold platform for the generation of innovative immune therapeutics against cancer.

Honeybees and hive products have long been recognized as excellent bio-indicators, as they provide valuable information on the state of the environments concerned. As yet, however, no tool is capable of contextually assessing the level of pollution of different environmental matrices in order to create maps of areas in which to place hives. In this paper, a possible method of creating a regional map to support the implementation of targeted monitoring plans on beekeeping is described. We obtained and identified related-activity pressure factors, which were subsequently combined by means of a multi-criteria approach through the analytic hierarchy process method (AHP). The different levels used were drawn up by first attributing qualitative values; these were converted into quantitative values through scoring elaborations and pair comparisons and then elaborated and standardized by means of different techniques in order to create an index with a spatial distribution of five risk classes throughout the region. To verify the correct execution of the procedure, a consistency ratio method was implemented on this index and validated the reliability of the application as the main source of information for sampling activities on beekeeping products. Creation of the specific environmental risk index enabled us to construct a map displaying the areas of greatest impact on beekeeping activities and a representation of the cumulative effects generated by the different pollutants in the air, water, soil and subsoil compartments. This index may, therefore, constitute an essential tool to support beekeepers in choosing sites for their apiaries.

Introduction: Gastrointestinal (GI) symptoms are common in individuals with Cystic Fibrosis (CF). International research has highlighted that GI care for this group of patients is lacking. Gastroenterology services to CF clinics across Australasia are yet to be examined. This study aimed to describe the current service delivery model and to identify areas for improvement that may lead to positive patient outcomes. Methods: CF clinicians (dietitians, clinical nurse consultants, respiratory consultants), gastroenterologists (GE), and patients or their carers from Australia and New Zealand (NZ) were surveyed online to gather their opinions on CF gastroenterology services provided in their region. Data were analysed using descriptive statistics (frequencies and percentages). Likert scale questions were analysed by grouping responses 1-5 and 6-10, presented alongside the median and interquartile range (IQR). Mann-Whitney U and chi-square tests were used to look at differences between stakeholder groups. Results: One hundred and fifty-seven health professionals and 172 patients or their carers completed the survey. Results showed that the current GI model of care is predominantly a publicly funded service delivered outside of CF clinic time. GE are largely not integrated into the CF team and report a lack of training opportunities. There is a higher level of dissatisfaction with the current service model in NZ than Australia. Discussion: No stakeholder group deemed the current CF gastroenterology service model as adequate, leaving opportunity for transformations in this field. Ideally the data from this study will invigorate the need for promotion and integration of GI services that would ultimately benefit the whole CF community.