Comparing clinical trial population representativeness to real-world users of 17 biologics approved for immune-mediated inflammatory diseases: An external validity analysis of 66,639 biologic users from the Italian VALORE project.

To date, no population-based studies have specifically explored the external validity of pivotal randomized clinical trials (RCTs) of biologics simultaneously for a broad spectrum of immuno-mediated inflammatory diseases (IMIDs). The aims of this study were, firstly, to compare the patients' characteristics and median treatment duration of biologics approved for IMIDs between RCTs' and real-world setting (RW); secondly, to assess the extent of biologic users treated for IMIDs in the real-world setting that would not have been eligible for inclusion into pivotal RCT for each indication of use. Using the Italian VALORE distributed database (66,639 incident biologic users), adult patients with IMIDs treated with biologics in the Italian real-world setting were substantially older (mean age ± SD: 50 ± 15 years) compared to those enrolled in pivotal RCTs (45 ± 15 years). In the real-world setting, certolizumab pegol was more commonly used by adult women with psoriasis/ankylosing spondylitis (F/M ratio: 1.8-1.9) compared to RCTs (F/M ratio: 0.5-0.6). The median treatment duration (weeks) of incident biologic users in RW was significantly higher than the duration of pivotal RCTs in almost all indications for use and most biologics (4-100 vs. 6-167). Furthermore, almost half (46.4%) of biologic users from RW settings would have been ineligible for inclusion in the respective indication-specific pivotal RCTs. The main reasons were: advanced age, recent history of cancer and presence of other concomitant IMIDs. These findings suggest that post-marketing surveillance of biologics should be prioritized for those patients.

A Phyto-mycotherapeutic Supplement, Namely Ganostile, as Effective Adjuvant in Brain Cancer Management: An In Vitro Study Using U251 Human Glioblastoma Cell Line.

The current standard oncotherapy for glioblastoma is limited by several adverse side effects, leading to a short-term patient survival rate paralleled by a worsening quality of life (QoL). Recently, Complementary and Integrative Medicine's (CIM) innovative approaches have shown positive impacts in terms of better response to treatment, side effect reduction, and QoL improvement. In particular, promising potential in cancer therapy has been found in compounds coming from phyto- and mycotherapy. The objective of this study was to demonstrate the beneficial effects of a new phyto-mycotherapy supplement, named Ganostile, in the human glioblastoma cell line U251, in combination with chemotherapeutic agents, i.e., Cisplatin and a new platinum-based prodrug. Choosing a supplement dosage that mimicked oral supplementation in humans (about 1 g/day), through in vitro assays, microscopy, and cytometric analysis, it has emerged that the cells, after 48hr continuous exposure to Ganostile in combination with the chemical compounds, showed a higher mortality and a lower proliferation rate than the samples subjected to the different treatments administered individually. In conclusion, our data support the use of Ganostile in integrative oncology protocols as a promising adjuvant able to amplify conventional and new drug effects and also reducing resistance mechanisms often observed in brain tumors.

Study on the activation of cell death mechanisms: in search of new therapeutic targets in glioblastoma multiforme.

Malignant primary brain tumors remain among the most difficult cancers to treat, in particular, Glioblastoma Multiforme (GBM) is the deadliest brain tumor. The standard therapies currently used are not efficient enough in improving patients' survival and quality of life. Cisplatin (CDDP), a platinum-based drug, has shown efficacy against different solid neoplasms, but it is also associated to different forms of off-target toxicity. To overcome the limitation in the use of CDDP in the treatment of GBM patients, fourth generation platinum compounds are been synthesized, one of them is the Pt(IV)Ac-POA, a prodrug with a medium-chain fatty acid as axial ligand, which acts as a histone 3 deacetylase inhibitor. Moreover, recently, the antioxidant effects of medicinal mushrooms have been shown to induce a lowering of the toxicity of chemotherapy drugs, inducing greater therapeutic efficiency, thus the combined therapy of chemotherapy and micotherapy could be helpful in the treatment of GBM reducing the adverse effects of the former thanks to phytotherapy's antioxidant, anti-inflammatory, immunomodulatory and antitumoral activities. Here, through immunoblotting, ultrastructural and immunofluorescence analysis, we evaluated the contribution in the activation of different cell death pathway of Micotherapy U-Care, a medicinal blend supplement, used together with platinum-based compounds on human glioblastoma U251 cells.

Voghera Sweet Pepper: A Potential Ally against Oxidative Stress and Aging.

In the present study, the potential functional properties of the extracts from the edible part of Capsicum annuum L. var. Peperone di Voghera (VP) were studied. The phytochemical analysis revealed a high amount of ascorbic acid, paralleled by a low carotenoid content. Normal human diploid fibroblasts (NHDF) were chosen as the in vitro model models to investigate the effects of the VP extract on oxidative stress and aging pathways. The extract of Carmagnola pepper (CP), another important Italian variety, was used as the reference vegetable. The cytotoxicity evaluation was performed firstly, using a 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay, while the VP potential antioxidant and antiaging activity was investigated by immunofluorescence staining focusing on specifically selected proteins. The MTT data revealed the highest cell viability at a concentration of up to 1 mg/mL. The immunocytochemical analyses highlighted an increased expression of transcription factors and enzymes involved in redox homeostasis (Nrf2, SOD2, catalase), improved mitochondrial functionality, and the up-regulation of the longevity gene SIRT1. The present results supported the functional role of the VP pepper ecotype, suggesting a feasible use of its derived products as valuable food supplements.

Role of Na+/Ca2+ Exchanger (NCX) in Glioblastoma Cell Migration (In Vitro).

Glioblastoma (GBM) is the most malignant form of primary brain tumor. It is characterized by the presence of highly invasive cancer cells infiltrating the brain by hijacking neuronal mechanisms and interacting with non-neuronal cell types, such as astrocytes and endothelial cells. To enter the interstitial space of the brain parenchyma, GBM cells significantly shrink their volume and extend the invadopodia and lamellipodia by modulating their membrane conductance repertoire. However, the changes in the compartment-specific ionic dynamics involved in this process are still not fully understood. Here, using noninvasive perforated patch-clamp and live imaging approaches on various GBM cell lines during a wound-healing assay, we demonstrate that the sodium-calcium exchanger (NCX) is highly expressed in the lamellipodia compartment, is functionally active during GBM cell migration, and correlates with the overexpression of large conductance K+ channel (BK) potassium channels. Furthermore, a NCX blockade impairs lamellipodia formation and maintenance, as well as GBM cell migration. In conclusion, the functional expression of the NCX in the lamellipodia of GBM cells at the migrating front is a conditio sine qua non for the invasion strategy of these malignant cells and thus represents a potential target for brain tumor treatment.

Diaphragm Fatigue in SMNΔ7 Mice and Its Molecular Determinants: An Underestimated Issue.

Spinal muscular atrophy (SMA) is a genetic disorder characterized by the loss of spinal motor neurons leading to muscle weakness and respiratory failure. Mitochondrial dysfunctions are found in the skeletal muscle of patients with SMA. For obvious ethical reasons, the diaphragm muscle is poorly studied, notwithstanding the very important role that respiratory involvement plays in SMA mortality. The main goal of this study was to investigate diaphragm functionality and the underlying molecular adaptations in SMNΔ7 mice, a mouse model that exhibits symptoms similar to that of patients with intermediate type II SMA. Functional, biochemical, and molecular analyses on isolated diaphragm were performed. The obtained results suggest the presence of an intrinsic energetic imbalance associated with mitochondrial dysfunction and a significant accumulation of reactive oxygen species (ROS). In turn, ROS accumulation can affect muscle fatigue, cause diaphragm wasting, and, in the long run, respiratory failure in SMNΔ7 mice. Exposure to the antioxidant molecule ergothioneine leads to the functional recovery of the diaphragm, confirming the presence of mitochondrial impairment and redox imbalance. These findings suggest the possibility of carrying out a dietary supplementation in SMNΔ7 mice to preserve their diaphragm function and increase their lifespan.

The independent and moderating role of choice of non-financial reporting format on forecast accuracy and ESG disclosure.

Over the last two decades, the non-financial disclosure requirement has become a major concern for companies, consumers, governments, and policymakers. While compelling evidence has accumulated over time on the positive effect that moving away from disclosing non-financial information within mandatory financial statements, conflicting findings have emerged on the relative merits that choice of non-financial reporting format, in particular between sustainability and integrated reporting, can have on analysts' forecast accuracy. In addition, recent evidence from a non-voluntary setting has suggested that such choice could influence the effect of ESG disclosure and consequently reduce information asymmetry. Aiming to shed some light on these propositions within a voluntary setting, we conducted an empirical study focusing on a representative sample of listed European companies. We retrieved and analysed the last ten years (2012-2021) of publicly available financial information about the top 600 companies listed in the Eurostoxx. Our findings indicate that both a sustainability and an integrated report are significantly associated with improved forecast accuracy, relative to an annual report. We also find that ESG disclosure is significantly moderated by such choice. The environmental pillar score was found to strongly and positively affect forecast error, independently from other controls including the social and governance pillars. For companies opting to disclose non-financial information within an annual report, alternative forms of communication will therefore become critical to ensure that financial analysts, and ultimately investors, are informed about the company's sustainability-related activities and plans. Future research should be directed at examining the magnitude and direction of these effects among small and medium-size listed companies and in other decision-making settings to test the generalisability of these findings.

Postmarketing active surveillance of myocarditis and pericarditis following vaccination with COVID-19 mRNA vaccines in persons aged 12 to 39 years in Italy: A multi-database, self-controlled case series study.

BACKGROUND: Myocarditis and pericarditis following the Coronavirus Disease 2019 (COVID-19) mRNA vaccines administration have been reported, but their frequency is still uncertain in the younger population. This study investigated the association between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA vaccines, BNT162b2, and mRNA-1273 and myocarditis/pericarditis in the population of vaccinated persons aged 12 to 39 years in Italy. METHODS AND FINDINGS: We conducted a self-controlled case series study (SCCS) using national data on COVID-19 vaccination linked to emergency care/hospital discharge databases. The outcome was the first diagnosis of myocarditis/pericarditis between 27 December 2020 and 30 September 2021. Exposure risk period (0 to 21 days from the vaccination day, subdivided in 3 equal intervals) for first and second dose was compared with baseline period. The SCCS model, adapted to event-dependent exposures, was fitted using unbiased estimating equations to estimate relative incidences (RIs) and excess of cases (EC) per 100,000 vaccinated by dose, age, sex, and vaccine product. Calendar period was included as time-varying confounder in the model. During the study period 2,861,809 persons aged 12 to 39 years received mRNA vaccines (2,405,759 BNT162b2; 456,050 mRNA-1273); 441 participants developed myocarditis/pericarditis (346 BNT162b2; 95 mRNA-1273). Within the 21-day risk interval, 114 myocarditis/pericarditis events occurred, the RI was 1.99 (1.30 to 3.05) after second dose of BNT162b2 and 2.22 (1.00 to 4.91) and 2.63 (1.21 to 5.71) after first and second dose of mRNA-1273. During the [0 to 7) days risk period, an increased risk of myocarditis/pericarditis was observed after first dose of mRNA-1273, with RI of 6.55 (2.73 to 15.72), and after second dose of BNT162b2 and mRNA-1273, with RIs of 3.39 (2.02 to 5.68) and 7.59 (3.26 to 17.65). The number of EC for second dose of mRNA-1273 was 5.5 per 100,000 vaccinated (3.0 to 7.9). The highest risk was observed in males, at [0 to 7) days after first and second dose of mRNA-1273 with RI of 12.28 (4.09 to 36.83) and RI of 11.91 (3.88 to 36.53); the number of EC after the second dose of mRNA-1273 was 8.8 (4.9 to 12.9). Among those aged 12 to 17 years, the RI was of 5.74 (1.52 to 21.72) after second dose of BNT162b2; for this age group, the number of events was insufficient for estimating RIs after mRNA-1273. Among those aged 18 to 29 years, the RIs were 7.58 (2.62 to 21.94) after first dose of mRNA-1273 and 4.02 (1.81 to 8.91) and 9.58 (3.32 to 27.58) after second dose of BNT162b2 and mRNA-1273; the numbers of EC were 3.4 (1.1 to 6.0) and 8.6 (4.4 to 12.6) after first and second dose of mRNA-1273. The main study limitations were that the outcome was not validated through review of clinical records, and there was an absence of information on the length of hospitalization and, thus, the severity of the outcome. CONCLUSIONS: This population-based study of about 3 millions of residents in Italy suggested that mRNA vaccines were associated with myocarditis/pericarditis in the population younger than 40 years. According to our results, increased risk of myocarditis/pericarditis was associated with the second dose of BNT162b2 and both doses of mRNA-1273. The highest risks were observed in males of 12 to 39 years and in males and females 18 to 29 years vaccinated with mRNA-1273. The public health implication of these findings should be considered in the light of the proven mRNA vaccine effectiveness in preventing serious COVID-19 disease and death.

Fibromyalgia and Nutrition: An Updated Review.

Due to the lack of specific and standardized treatments for the management of fibromyalgia (FM), available evidence suggests a multidisciplinary approach, and nutrition represents an important therapeutic strategy. This work aims to update the relationship between FM and nutrition, through a review of more recent scientific evidence based on a systematic research on PubMed. Of 66 records initially identified, 26 studies were selected and included in the present work. Although there is not sufficient evidence for the efficacy of specific nutritional protocols, the examined papers indicate a potential role of selected nutrients, micronutrients and food components in managing FM symptoms. However, several concerns persist as nutritional status and/or nutritional integration can improve FM symptoms, without expecting to lead to a remission of the disease. The use of targeted nutritional supplements may be of some relevance for the management of FM, but the up to date evidence remains weak. It is advisable, thus, to perform further studies of higher quality.KEY TEACHING POINTSFibromyalgia (FM) is characterized by chronic and diffuse musculoskeletal pain, often associated with a large set of symptoms.The therapeutic approach of FM include pharmacological and non-pharmacological interventions. Among them, an important role is played by nutrition.Of 66 record screened, 12 studies were included in the present review and five of them were randomized controlled trials. Nevertheless, the overall quality of those trials was scarce.Literature concerning FM and nutritions is growing. However, little evidence suggests that nutrition and/or nutritional intervention play a significant role on FM severity.The results of this review underline the need to carry out clinical studies of higher quality and rigor, possibly RCTs, focused on the role of nutrition in the symptoms and/or severity of FM.

Neuroprotective Metabolites of Hericium erinaceus Promote Neuro-Healthy Aging.

Frailty is a geriatric syndrome associated with both locomotor and cognitive decline, typically linked to chronic systemic inflammation, i.e., inflammaging. In the current study, we investigated the effect of a two-month oral supplementation with standardized extracts of H. erinaceus, containing a known amount of Erinacine A, Hericenone C, Hericenone D, and L-ergothioneine, on locomotor frailty and cerebellum of aged mice. Locomotor performances were monitored comparing healthy aging and frail mice. Cerebellar volume and cytoarchitecture, together with inflammatory and oxidative stress pathways, were assessed focusing on senescent frail animals. H. erinaceus partially recovered the aged-related decline of locomotor performances. Histopathological analyses paralleled by immunocytochemical evaluation of specific molecules strengthened the neuroprotective role of H. erinaceus able to ameliorate cerebellar alterations, i.e., milder volume reduction, slighter molecular layer thickness decrease and minor percentage of shrunken Purkinje neurons, also diminishing inflammation and oxidative stress in frail mice while increasing a key longevity regulator and a neuroprotective molecule. Thus, our present findings demonstrated the efficacy of a non-pharmacological approach, based on the dietary supplementation using H. erinaceus extract, which represent a promising adjuvant therapy to be associated with conventional geriatric treatments.

Squaring the Circle: A New Study of Inward and Outward-Rectifying Potassium Currents in U251 GBM Cells.

In the present study, the functional role of the inwardly rectifying K+ channel, Kir4.1, and large-conductance Ca2+-activated K+ (BK) channel during cell migration in U251 cell line was investigated. We focused on polarised cells which are positive for the active-Cdc42 migration marker. The perforated patch technique was used to avoid intracellular dialysis and to maintain physiological changes in intracellular calcium. Wound healing was employed to assay migration after 24 h. Polarised cells recorded displayed different hallmarks of undifferentiated glial cells: depolarised resting membrane potential and high membrane resistance. Cells recorded outside wounded area did not display either constitutive inward or outward rectification. After migration, U251 cells were characterised by a constitutively smaller Kir4.1 and larger BK currents with a linearly related amplitude. Menthol modulation increased both currents in a linearly dependent manner, indicating a common mechanism triggered by activation of transient receptor potential melastatin 8 (TRPM8), a Ca2+-permeable non-selective cation channel. We hypothesised that both migration and menthol modulation would share an increase of intracellular calcium triggering the increase in Kir4.1 and BK channels. Immunocytochemistry demonstrated the cytoplasmic expression of both Kir4.1 and BK channels and a mislocation in the nucleus under basal conditions. Before and after migration, polarised cells increased the expression of Kir4.1 and BK channels both in the cytoplasm and nucleus. TEM ultrastructural analysis displayed a different nuclear distribution of Kir4.1 and BK channels. In the present study, the physiological role of Kir4.1 and BK currents at membrane potential, their involvement in migration, and the functional role of nuclear channels were discussed.

Novel Medicinal Mushroom Blend as a Promising Supplement in Integrative Oncology: A Multi-Tiered Study using 4T1 Triple-Negative Mouse Breast Cancer Model.

Although medicinal mushroom extracts have been proposed as promising anti-cancer agents, their precise impacts on metastatic breast cancer are still to be clarified. For this purpose, the present study exploited the effect of a novel medicinal mushroom blend, namely Micotherapy U-care, in a 4T1 triple-negative mouse breast cancer model. Mice were orally administered with Micotherapy U-care, consisting of a mixture of Agaricus blazei, Ophiocordyceps sinensis, Ganoderma lucidum, Grifola frondosa, and Lentinula edodes. The syngeneic tumor-bearing mice were generated by injecting 4T1 cells in both supplemented and non-supplemented mice. After sacrifice 25 days later, specific endpoints and pathological outcomes of the murine pulmonary tissue were evaluated. (i) Histopathological and ultrastructural analysis and (ii) immunohistochemical assessment of TGF-ß1, IL-6 and NOS2, COX2, SOD1 as markers of inflammation and oxidative stress were performed. The QoL was comparatively evaluated. Micotherapy U-care supplementation, starting before 4T1 injection and lasting until the end of the experiment, dramatically reduced the pulmonary metastases density, also triggering a decrease of fibrotic response, and reducing IL-6, NOS, and COX2 expression. SOD1 and TGF-ß1 results were also discussed. These findings support the valuable potential of Micotherapy U-care as adjuvant therapy in the critical management of triple-negative breast cancer.

From a Medicinal Mushroom Blend a Direct Anticancer Effect on Triple-Negative Breast Cancer: A Preclinical Study on Lung Metastases.

Bioactive metabolites isolated from medicinal mushrooms (MM) used as supportive treatment in conventional oncology have recently gained interest. Acting as anticancer agents, they interfere with tumor cells and microenvironment (TME), disturbing cancer development/progression. Nonetheless, their action mechanisms still need to be elucidated. Recently, using a 4T1 triple-negative mouse BC model, we demonstrated that supplementation with Micotherapy U-Care, a MM blend, produced a striking reduction of lung metastases density/number, paralleled by decreased inflammation and oxidative stress both in TME and metastases, together with QoL amelioration. We hypothesized that these effects could be due to either a direct anticancer effect and/or to a secondary/indirect impact of Micotherapy U-Care on systemic inflammation/immunomodulation. To address this question, we presently focused on apoptosis/proliferation, investigating specific molecules, i.e., PARP1, p53, BAX, Bcl2, and PCNA, whose critical role in BC is well recognized. We revealed that Micotherapy U-Care is effective to influence balance between cell death and proliferation, which appeared strictly interconnected and inversely related (p53/Bax vs. Bcl2/PARP1/PCNA expression trends). MM blend displayed a direct effect, with different efficacy extent on cancer cells and TME, forcing tumor cells to apoptosis. Yet again, this study supports the potential of MM extracts, as adjuvant supplement in the TNBC management.

Array of Metabolites in Italian Hericium erinaceus Mycelium, Primordium, and Sporophore.

Hericium erinaceus is a medicinal mushroom that contains many molecules promising a plethora of therapeutic properties. In this study, the strain H.e.2 (MicUNIPV, University of Pavia, Italy) was isolated from a sporophore collected in Tuscany (Italy). Mycelium, primordium, and wild type and cultivated sporophores were analyzed by HPLC-UV-ESI/MS. Erinacine A in the mycelium and hericenones C and D in the sporophores were quantified by comparison with their standard molecules. For the first time, H. erinaceus primordium was also investigated for the presence of these molecules. Comparing with the literature data, hericenes, molecules structurally similar to hericenones, were present in all our samples. The highest contents of hericenones C and D were detected in cultivated sporophores, compared to the wild type. The comparison of these data with those of another Italian H. erinaceus strain (H.e.1 MicUNIPV) was discussed. The results led us to select H. erinaceus strains more suitable for mycelium production or sporophore cultivation to obtain extracts with a higher content of bioactive compounds. This work provides a further step towards standardizing the procedures in the development of dietary supplements made from mushrooms.

Tooth grooves, occlusal striations, dental calculus, and evidence for fiber processing in an Italian eneolithic/bronze age cemetery.

OBJECTIVES: We conducted a systematic macroscopic and microscopic examination of occlusal and para-occlusal wear in a large dental sample (n = 3,014) from 217 individuals dated to the Early Bronze age site of Gricignano d'Aversa, Italy. We used macroscopic and microscopic techniques to document nondietary occlusal and para-occlusal wear and to analyze calculus inclusions in some of the teeth. In combining an analysis of the wear with the calculus inclusions we linked the specific wear to the likely fiber that was involved in producing it. MATERIALS AND METHODS: Teeth and their high resolution epoxy casts were analyzed through SEM and reflected light microscopes. Nineteen individuals (fifteen with activity induced dental modifications and four as a control sample) were examined for the presence of calculus inclusions. RESULTS: Activity induced dental modifications (AIDMs), notches, grooves and micro-striations, were found in the 62.2% of the adult females, in 21.2% of the adults of unknown sex and in a single male. We found the full spectrum of dental manipulations from very minor nonocclusal wear in some young individuals to severe attrition at the other extreme. The width of the striations and grooves, mostly on the upper incisors, suggests a craft activity involving fibers and thread production and manipulation. From the dental calculus of two females with grooves and striations, we extracted three fragments of fibers, identified as hemp (Cannabis, sp.). Previously from Gricignano woven hemp fibers were found on both surfaces of a metal blade associated with a male burial. DISCUSSION: This study found the co-occurrence of tooth AIDMs and the actual fibers preserved in the dental calculus. As more work is done analyzing dental calculus in a variety of humans, it is apparent that this biological material holds rich resources documenting non-dietary habits.

Illicit drug policy in Spain: the opinion of health and legal professionals. / Política de drogas ilegales en España: la opinión de los profesionales del ámbito sanitario y del legal.

The high frequency of criminal behaviour and related legal problems associated with substance addiction generates a field of interaction between legal and healthcare systems. This study was developed as a multicentre project to investigate the opinions of professionals from legal and healthcare systems about policies on illegal drugs and their implementation in practice. A multiple choice questionnaire designed ad hoc was administered to a sample of 230 professionals from legal and healthcare fields working in the cities of Barcelona, Granada and Bilbao. The questionnaire included sociodemographic and work-related data, and assessed interviewees' information about the response to drug-related crime and opinion on drug policy issues. This article presents the results from Spain. The main results showed that both groups of professionals value alternative measures to imprisonment (AMI) as useful tools to prevent offenses related to drug use and claim a broader application of AMI. They also evaluated positively the regulations on cannabis use in effect. Though the attitude of healthcare professionals towards the application of AMI is more permissive, both groups favour restricting these sanctions in cases of recidivism. Both groups show mild satisfaction with the current addiction healthcare system and express dissatisfaction with actual drug policies in Spain.

La elevada frecuencia de conductas delictivas y problemas legales relacionados con las adicciones a sustancias genera un terreno de interacción entre los ámbitos legal y sanitario. En este contexto se ha llevado a cabo un estudio multicéntrico de las opiniones de los profesionales tanto del ámbito legal como del sanitario sobre la legislación relacionada con las drogas y su implementación en la práctica de acuerdo al marco legal vigente. Se administró a 230 profesionales tanto del ámbito legal como del sanitario de Barcelona, Granada y Bilbao un cuestionario de respuesta múltiple diseñado ad hoc, con datos sociodemográficos y laborales y preguntas para valorar la opinión de los encuestados sobre la respuesta a la delincuencia relacionada con drogas y su postura en relación con la política en materia de drogas. Los principales resultados mostraron que ambos grupos de profesionales valoran las medidas penales alternativas (MPA) como herramientas útiles para prevenir los delitos relacionados al consumo, apostando por la ampliación de su aplicación. También coinciden en valorar positivamente la actual regulación del consumo de cannabis. Los profesionales del ámbito sanitario muestran una actitud más permisiva de cara a la aplicación de MPA, pero ambos grupos reconocen oportuno endurecer la sanción en caso de reincidencia delictiva. Los dos grupos muestran una satisfacción relativa con el sistema de atención a las adicciones en los aspectos estudiados y expresan insatisfacción con las políticas actuales sobre drogas.

Intimate partner violence among female drug users admitted to the general hospital: screening and prevalence. / Violencia de género en mujeres con consumo de sustancias ingresadas en el hospital general: cribado y prevalencia.

Intimate partner violence (IPV) is a public health problem worldwide. Several factors have been found to be associated with an increased prevalence of IPV, such as substance use. A cross-sectional study was conducted with the aim of determining the prevalence of IPV among women entering Hospital del Mar (Barcelona) for any medical/surgical reason, and who had a diagnosis of substance use disorder. Secondly, it was intended to psychometrically validate the Spanish version of the Hurt, Insulted, Threatened with Harm, Screamed (HITS) questionnaire. All patients were assessed by two IPV questionnaires, the Composite Abuse Scale (CAS) and HITS. Out of 52 patients interviewed, 46 answered both questionnaires. According to the CAS questionnaire, 23 patients (50%) experienced IPV at some point in their lives and 11 (23.9%) in the last year. Cannabis consumption was also associated with an increased severity of IPV (95% CI 3.5-28.9, p = .013).According to the HITS questionnaire, there was a prevalence of 39.1% (18 patients) in the last 12 months. HITS had a specificity of 100% and a sensitivity of 78% relative to the CAS questionnaire. A cut-off score x∈ [6.7], derived through ROC analysis, correctly discriminated 91% of the victims and 100% of the non-victims. The results obtained showed that the prevalence of IPV was very high among women who suffered from more than one substance use disorder. Therefore, it is highly recommended to systematically screen for IPV victimization by putting the HITS questionnaire into practice.

La violencia de género (VG) es un problema de salud pública a escala mundial. Existen determinados factores asociados a un aumento de la prevalencia, como el consumo de sustancias. Se realizó un estudio transversal con el objetivo de determinar la prevalencia de VG en las mujeres que ingresaron en el Hospital del Mar (Barcelona) por cualquier motivo médico/quirúrgico y con el diagnóstico de trastorno por consumo de sustancias. Secundariamente, se pretendió validar la versión en español del cuestionario Hurt, Insulted, Threatened with Harm, Screamed (HITS). Se evaluaron a todas las pacientes mediante dos cuestionarios de detección de VG, el Composite Abuse Scale (CAS) y el HITS. De las 52 pacientes entrevistadas durante el período de estudio, 46 respondieron ambos cuestionarios. Según el cuestionario CAS, 23 pacientes (50%) presentaron VG alguna vez en la vida y 11 (23,9%) en el último año. El consumo de cannabis se asoció a una mayor gravedad de la VG (IC95% 3,5-28,9, p = .013). La prevalencia de VG, según el HITS, fue de 39,1% (18 pacientes) en los últimos 12 meses. El HITS mostró en relación al CAS una especificidad del 100% y una sensibilidad del 78%. Un punto de corte x∈ [6,7], obtenido mediante el análisis ROC, fue el que mejor discriminó al 91% de las víctimas y al 100% de las no-víctimas. Los resultados obtenidos demostraron una elevada prevalencia de VG entre las mujeres consumidoras de más de una sustancia de abuso. Por ese motivo, se recomienda incorporar el cribado sistemático mediante el cuestionario HITS.

Distinct expression patterns of inwardly rectifying potassium currents in developing cerebellar granule cells of the hemispheres and the vermis.

G-protein-coupled inwardly rectifying potassium (GIRK) channels play a crucial role during the migration and maturation of cerebellar granule cells (GCs) in the vermis. In the cerebellar hemispheres, however, only minor effects on the development of GCs are observed in mice with GIRK channel impairment. This regional difference may reflect distinct ontogenetic expression patterns of GIRK channels. Therefore, inwardly rectifying responses in mice were characterized at different stages of development in the vermis and the hemispheres. In the vermis, GCs in the premigratory zone (PMZ) at P7-P15 exhibit GIRK current but not constitutive inwardly rectifying potassium (CIRK) current, and are relatively depolarized at rest. In contrast, premigratory GCs in the hemispheres express only CIRK channels, which accounts for their more hyperpolarized resting membrane potential. Furthermore, the pattern of voltage-dependent inward currents in the PMZ GCs of cerebellar hemispheres is consistent with a more mature stage of development than the corresponding GCs in the vermis, resulting in robust firing properties mediated by sodium channels. Later in development (P21-P22), CIRK current is then observed in the majority of vermis GCs. This developmental pattern, revealed by electrophysiological recordings, was confirmed by immunohistological experiments that showed greater reactivity for GIRK2 in the PMZ of the vermis than in the hemispheres during development (P7-P15). These findings suggest that regional differences in development are responsible for the differential expression of inwardly rectifying potassium channels in the vermis and in the hemispheres.

Lexical-semantic deficits in processing food and non-food items.

The study of category specific deficits in brain-damaged patients has been instrumental in explaining how knowledge about different types of objects is organized in the brain. Much of this research focused on testing putative semantic sensory/functional subsystems that could explain the observed dissociations in performance between living things (e.g., animals and fruits/vegetables) and non-living things (e.g., tools). As neuropsychological patterns that did not fit the original living/non-living distinction were observed, an alternative organization of semantic memory in domains constrained by evolutionary pressure was hypothesized. However, the category of food, that contains both living-natural items, such as an apple, and nonliving-manufactured items as in the case of a hamburger, has never been systematically investigated. As such, food category could turn out to be very useful to test whether the brain organizes the knowledge about food in sensory/functional subsystems, in a specific domain, or whether both approaches might need to be integrated. In the present study we tested the ability of patients with Alzheimer dementia (AD) and with Primary Progressive Aphasias (PPA) as well as healthy controls to perform a confrontation naming task, a categorization task, and a comprehension of edible (natural and manufactured food) and non edible items (tools and non-edible natural things) task (Tasks 1-3). The same photographs of natural and manufactured food were presented together with a description of food's sensory or functional property that could be either congruent or incongruent with that particular food (Task 4). Patients were overall less accurate than healthy individuals, and PPA patients were generally more impaired than AD patients, especially on the naming task. Food tended to be processed better than non-food in two out of three tasks (categorization and comprehension tasks). Patient groups showed no difference in naming food and non-food items, while controls were more accurate with non-food than food (controlling for the linguistic variables and calorie content). AD patients named manufactured food more accurately than natural food (with PPA and controls showing no difference). Recognition of food and, to some extent, of manufactured food seems to be more resilient to brain damage, possibly by virtue of its survival relevance. Furthermore, on Task 4 patients showed an advantage for the sensory-natural pairs over sensory-manufactured combination. Overall, findings do not fit an existing model of semantic memory and suggest that properties intrinsic to the food items (such as the level of transformation and the calorie content) or even to the participants like the Body Mass Index (as shown in another study reviewed here) should be considered.

Fear is the mother of invention: anuran embryos exposed to predator cues alter life-history traits, post-hatching behaviour and neuronal activity patterns.

Neurophysiological modifications associated to phenotypic plasticity in response to predators are largely unexplored, and there is a gap of knowledge on how the information encoded in predator cues is processed by prey sensory systems. To explore these issues, we exposed Rana dalmatina embryos to dragonfly chemical cues (kairomones) up to hatching. At different times after hatching (up to 40 days), we recorded morphology and anti-predator behaviour of tadpoles from control and kairomone-treated embryo groups as well as their neural olfactory responses, by recording the activity of their mitral neurons before and after exposure to a kairomone solution. Treated embryos hatched later and hatchlings were smaller than control siblings. In addition, the tadpoles from the treated group showed a stronger anti-predator response than controls at 10 days (but not at 30 days) post-hatching, though the intensity of the contextual response to the kairomone stimulus did not differ between the two groups. Baseline neuronal activity at 30 days post-hatching, as assessed by the frequency of spontaneous excitatory postsynaptic events and by the firing rate of mitral cells, was higher among tadpoles from the treated versus the control embryo groups. At the same time, neuronal activity showed a stronger increase among tadpoles from the treated versus the control group after a local kairomone perfusion. Hence, a different contextual plasticity between treatments at the neuronal level was not mirrored by the anti-predator behavioural response. In conclusion, our experiments demonstrate ontogenetic plasticity in tadpole neuronal activity after embryonic exposure to predator cues, corroborating the evidence that early-life experience contributes to shaping the phenotype at later life stages.