Joint response from Latin American, European Obstetric Violence Observatories and others organizations all over Europe to the Joint Position Statement on Substandard and Disrespectful Care in Labour - Because Words Matter.

The issue of obstetric violence is internationally acknowledged as a serious violation of human rights. First identified by the Committee of Experts of the Inter-American Belém do Pará Convention in 2012, it is recognized as a form of gender-based violence that infringes upon women's rights during childbirth. Nations such as Argentina, Mexico, Venezuela, and certain regions in Spain have implemented laws against it, highlighting its severity and the need for protective legislation. Major international organizations, including WHO and the Council of Europe, advocate for the elimination of disrespectful and abusive treatment in maternity care. In 2019, the UN Special Rapporteur on violence against women called on states to protect women's human rights in reproductive services by enforcing laws, prosecuting perpetrators, and providing compensation to victims. However, despite advances, there remains institutional and systemic resistance to recognizing obstetric violence, which undermines trust in healthcare and impacts women's quality of life. Addressing this violence is imperative, requiring education and training in women's human rights for all healthcare professionals. As part of the coalition of experts from various organizations (InterOVO), we respond to the publication by EAPM, EBCOG, and EMA: "Joint Position Statement: Substandard and Disrespectful Care in Labor - Because Words Matter." We are committed to preventing and mitigating obstetric violence and improving care for women and newborns.

Tipifarnib Reduces Extracellular Vesicles and Protects From Heart Failure.

BACKGROUND: Heart failure (HF) is one of the leading causes of mortality worldwide. Extracellular vesicles, including small extracellular vesicles or exosomes, and their molecular cargo are known to modulate cell-to-cell communication during multiple cardiac diseases. However, the role of systemic extracellular vesicle biogenesis inhibition in HF models is not well documented and remains unclear. METHODS: We investigated the role of circulating exosomes during cardiac dysfunction and remodeling in a mouse transverse aortic constriction (TAC) model of HF. Importantly, we investigate the efficacy of tipifarnib, a recently identified exosome biogenesis inhibitor that targets the critical proteins (Rab27a [Ras associated binding protein 27a], nSMase2 [neutral sphingomyelinase 2], and Alix [ALG-2-interacting protein X]) involved in exosome biogenesis for this mouse model of HF. In this study, 10-week-old male mice underwent TAC surgery were randomly assigned to groups with and without tipifarnib treatment (10 mg/kg 3 times/wk) and monitored for 8 weeks, and a comprehensive assessment was conducted through performed echocardiographic, histological, and biochemical studies. RESULTS: TAC significantly elevated circulating plasma exosomes and markedly increased cardiac left ventricular dysfunction, cardiac hypertrophy, and fibrosis. Furthermore, injection of plasma exosomes from TAC mice induced left ventricular dysfunction and cardiomyocyte hypertrophy in uninjured mice without TAC. On the contrary, treatment of tipifarnib in TAC mice reduced circulating exosomes to baseline and remarkably improved left ventricular functions, hypertrophy, and fibrosis. Tipifarnib treatment also drastically altered the miRNA profile of circulating post-TAC exosomes, including miR 331-5p, which was highly downregulated both in TAC circulating exosomes and in TAC cardiac tissue. Mechanistically, miR 331-5p is crucial for inhibiting the fibroblast-to-myofibroblast transition by targeting HOXC8, a critical regulator of fibrosis. Tipifarnib treatment in TAC mice upregulated the expression of miR 331-5p that acts as a potent repressor for one of the fibrotic mechanisms mediated by HOXC8. CONCLUSIONS: Our study underscores the pathological role of exosomes in HF and fibrosis in response to pressure overload. Tipifarnib-mediated inhibition of exosome biogenesis and cargo sorting may serve as a viable strategy to prevent progressive cardiac remodeling in HF.

Unlocking sustainable livestock production potential in the Colombian Amazon through paddock division and gender inclusivity.

Low-emissions livestock production can be achieved through scaling production systems integrating trees, forages, and livestock within the same area. Such systems are known as silvopastoral production systems (SPS). However, despite SPS reported benefits, adoption rates globally remain low. This paper, therefore, aims to inform land use policy oriented towards increasing SPS adoption. This study intends to capture this by assessing SPS adoption benefits, identifying determinants of SPS adoption, and thus to contribute to policy for scaling low-emissions livestock production. Data was collected on socioeconomic status, livestock farming technical and economic indicators, and farm and paddock practices through farm-level surveys in four municipalities in the Amazon Piedmont of Colombia. Unlike previous studies that assume homogeneous farm management, when in fact, it is heterogeneous, this study assessed SPS adoption determinants using the paddock (n = 2819) as the unit of analysis. This methodological approach is consistent with paddock-level land use decisions taken by farmers based on socioeconomic and biophysical factors such as soil financial resources, type, and topography. The methodological approach allows us to provide new insights into the determinant of adopting SPS and an understanding of intra-farm level land use decisions. The results show that the adoption of SPS at both paddocks and farm levels in Caquetá is low. The main factors associated with higher SPS adoption levels at the paddock level are framed in gender, resources, and knowledge. We observe that women are more motivated to conserve the environment. Cattle paddocks managed by women, smaller in size, and those with more SPS-related projects show a tendency for medium or high SPS adoption. Furthermore, the positive relationship between access to credit and SPS adoption emphasizes the importance of financial resources tailored to SPS projects. Enhancing gender roles, improving access to finance in land use, and providing training programs on SPS systems can contribute to low-emission livestock production in Colombia. This research paper highlights the significance of implementing diverse management strategies and reaching out to farmers not involved in SPS projects. It emphasizes investments in low-emission livestock production, especially for female heads of households. This approach recognizes the broader benefits of SPS, beyond production and financial gains, promoting the division of paddocks and the adoption of SPS.

Effect of Bacillus Calmette-Guerin Exposure on Prostate Cancer Detection Using Magnetic Resonance Imaging: A Cohort Study.

BACKGROUND: Granulomatous prostatitis is a medical condition that may mimic prostate cancer. PURPOSE: Granulomatous prostatitis resulting from BCG-exposure can confound the diagnosis of prostate cancer based on prostate imaging and data system (PI-RADS) classification observed on multiparametric prostate magnetic resonance imaging (mpMRI). STUDY TYPE, POPULATION, ASSESSMENT AND STATISTICAL TESTS: A cohort study was conducted, enrolling consecutive males at risk for prostate cancer who underwent an mpMRI-targeted prostate biopsy between February 2016 and August 2023. The focus of the study was on prior BCG-exposure as adjuvant treatment for non-muscle-invasive urothelial carcinoma within the 3 years prior the magnetic resonance imaging (MRI). Exclusion criteria were a prior androgen deprivation therapy, prostate surgery or radiation, and BCG-exposure occurring more than 3 years and less than 3 months before the MRI. Chi-square, logistic-regression, statistical association, and homogeneity tests were used. RESULTS: Total 712 patients, 899 biopsied lesions (218 PI-RADS 3, 521 PI-RADS 4 and 160 PI-RADS 5) and 20 patients with 30 lesions within the BCG-exposed cohort. Chi-square and logistic-regression tests showed an association between PI-RADS with malignancy and significant tumor (ST), considering PI-RADS3 as the reference (OR: 4.9 [95% CI, 3.4-7.1] for PI-RADS4 and OR: 21.7 [95% CI, 12.4-37.8] for PI-RADS5 for malignancy, and OR: 5.3 [95% CI, 3.2-8.7] for PI-RADS4 and OR: 16.5 [95% CI, 9.4-28.9] for PI-RADS5 regarding ST). A statistically significant negative association was demonstrated between malignancy and ST with respect to BCG-exposure (OR: 0.15 [95% CI, 0.06-0.39] and OR: 0.39 [95% CI, 0.15-1.0], respectively). Statistically significant risk-difference for malignancy in patients nonexposed to BCG regarding those exposed was 45% (61.6% vs. 16.7%) for PI-RADS4, and 68.5% (90.7% vs. 22.2%) and 42.7% (64.9% vs. 22.2%) concerning malignancy and ST for PI-RADS5, respectively. DATA CONCLUSIONS: Granulomatous prostate reaction caused by BCG-exposure acts as confounding factor for prostate MRI interpretation. The risk of malignancy and significant tumor on targeted biopsy to PI-RADS 3, 4 and 5 is notably lower in exposed patients.

Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors-a nationwide, prospective Swedish study.

Background: Childhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors. Methods: gWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients. Findings: The prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35). Interpretation: Overall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients. Funding: The study was supported by the Swedish Childhood Cancer Fund and the Ministry of Health and Social Affairs.

Molecular evidence for a new endemic species of Acartia (Copepoda, Calanoida) from the Southeast Pacific coast.

The loss of biodiversity in marine populations is one of the consequences of the increased events of extreme environmental conditions in the oceans, which can condition the persistence of populations to future scenarios of climate change. Therefore, it is extremely necessary to explore and monitor the genetic diversity of natural populations. In the Southeast Pacific Ocean (SEPO), specifically on the coast of Chile, the presence of the copepod Acartia tonsa has been indicated solely using morphological evidence, due to the absence of genetic information. In the present work, the genetic diversity, population structure and phylogenetic position within the genus Acartia, of populations identified morphologically as A. tonsa, was evaluated by amplification of the mitochondrial cytochrome c oxidase subunit I and nuclear marker 18 s. Our results showed that the populations identified as A. tonsa correspond to a new monophyletic group endemic to SEPO (GMYC = 1.00; PTP = 0.95). The populations showed moderate to high genetic diversity with an incipient structuring between populations and biogeographic zones. Our results suggest that despite the homogenizing effect of the Humboldt Current, isolation by distance and contrasting environmental conditions at different geographic scales have an important influence on the genetic diversity of zooplankton in the SEPO region.

Epigenetic mechanisms regulate sex differences in cardiac reparative functions of bone marrow progenitor cells.

Historically, a lower incidence of cardiovascular diseases (CVD) and related deaths in women as compared with men of the same age has been attributed to female sex hormones, particularly estrogen and its receptors. Autologous bone marrow stem cell (BMSC) clinical trials for cardiac cell therapy overwhelmingly included male patients. However, meta-analysis data from these trials suggest a better functional outcome in postmenopausal women as compared with aged-matched men. Mechanisms governing sex-specific cardiac reparative activity in BMSCs, with and without the influence of sex hormones, remain unexplored. To discover these mechanisms, Male (M), female (F), and ovariectomized female (OVX) mice-derived EPCs were subjected to a series of molecular and epigenetic analyses followed by in vivo functional assessments of cardiac repair. F-EPCs and OVX EPCs show a lower inflammatory profile and promote enhanced cardiac reparative activity after intra-cardiac injections in a male mouse model of myocardial infarction (MI). Epigenetic sequencing revealed a marked difference in the occupancy of the gene repressive H3K9me3 mark, particularly at transcription start sites of key angiogenic and proinflammatory genes in M-EPCs compared with F-EPCs and OVX-EPCs. Our study unveiled that functional sex differences in EPCs are, in part, mediated by differential epigenetic regulation of the proinflammatory and anti-angiogenic gene CCL3, orchestrated by the control of H3K9me3 by histone methyltransferase, G9a/Ehmt2. Our research highlights the importance of considering the sex of donor cells for progenitor-based tissue repair.

Seguimiento a 5 años de pacientes octogenarios post cirugía cardíaca

Introducción: El aumento significativo de la esperanza de vida en el grupo de octogenarios en Chile ha generado preocupación sobre la eficacia y la necesidad de cirugías cardíacas mayores en esta población incluso cuando el 85 % de ellos llega a dicha edad en condiciones de salud favorables. Objetivos: Este estudio se propuso evaluar la mortalidad hospitalaria y a mediano plazo, así como identificar complicaciones postoperatorias en pacientes octogenarios sometidos a cirugía cardíaca en Chile. Métodos: Se llevó a cabo un estudio observacional retrospectivo en el Hospital Las Higueras de Talcahuano entre enero de 2014 y diciembre de 2022, con una muestra de 79 pacientes. Resultados: Se encontró que el 86% de los procedimientos utilizaron circulación extracorpórea, y el 84% fueron electivos, principalmente cirugías coronarias (54%). La mortalidad intrahospitalaria fue 9%, con el uso preoperatorio de Balón Contrapulsación Intraaórtico identificado como un factor de mal pronóstico. Complicaciones postoperatorias como la Fibrilación Auricular afectaron al 17%, mientras que solo Neumonía y Falla Renal influyeron significativamente en la mortalidad. La supervivencia a 1, 3 y 5 años fue 81%, 76% y 73%, respectivamente. Conclusión: La cirugía cardíaca en octogenarios en Chile presenta resultados comparables a nivel mundial, destacando la importancia del análisis individual por un equipo multidisciplinario al considerar cirugías mayores en pacientes frágiles. El uso de técnicas mínimamente invasivas podría mejorar la calidad de vida, aunque se requieren estudios adicionales con más pacientes para confirmar esta hipótesis.

Background: Background: The significant increase in life expectancy among octogenarians in Chile has raised concerns about the efficacy and need of major cardiac surger in this population, even as 85% of them reach this age in favorable health conditions. Objectives: This study aimed to evaluate in-hospital and medium-term mortality and identify postoperative complications in octogenarian patients undergoing cardiac surgery in Chile. Methods: An observational retrospective study was conducted at Hospital Las Higueras de Talcahuano between January 2014 and December 2022, involving a sample of 79 patients. Results: 86% of procedures utilized extracorporeal circulation, and 84% were elective, predominantly coronary artery surgeries (54%). In-hospital mortality was 9%. Preoperative Intra-Aortic Balloon Pump use identified as a poor prognostic factor. Postoperative complications such as Atrial Fibrillation affected 17%, while only Pneumonia and Renal Failure significantly influenced mortality. Survival at 1, 3, and 5 years was 81%, 76%, and 73%, respectively. Conclusion: Cardiac surgery in octogenarians in Chile yields comparable outcomes to those worldwide, emphasizing the importance of individual assessment by a multidisciplinary team when considering major surgeries in frail patients. The use of minimally invasive techniques may enhance quality of life, although further studies with larger patient cohorts are needed to confirm this hypothesis.

Microcystin-LR sensitizes the Oncorhynchus mykiss intestinal epithelium and interacts with paralytic shellfish toxins to alter oxidative balance.

In the context of harmful algal blooms, fish can be exposed to the combined effects of more than one toxin. We studied the effects of consecutive exposure to Microcystin-LR (MCLR) in vivo and paralytic shellfish toxins (PST) ex vivo/in vitro (MCLR+PST) in the rainbow trout Oncorhynchus mykiss's middle intestine. We fed juvenile fish with MCLR incorporated in the feed every 12 h and euthanized them 48 h after the first feeding. Immediately, we removed the middle intestine to make ex vivo and in vitro preparations and exposed them to PST for one hour. We analyzed glutathione (GSH) and glutathione disulfide (GSSG) contents, glutathione S-transferase (GST), glutathione reductase (GR), catalase (CAT), and protein phosphatase 1 (PP1) activities in ex vivo intestinal strips; apical and basolateral ATP-biding cassette subfamily C (Abcc)-mediated transport in ex vivo everted and non- everted sacs; and reactive oxygen species (ROS) production in isolated enterocytes in vitro. MCLR+PST treatment decreased the GSH content, GSH/GSSG ratio, GST activity, and increased ROS production. GR activity remained unchanged, while CAT activity only increased in response to PST. MCLR inhibited PP1 activity and activated Abcc-mediated transport only at the basolateral side of the intestine. Our results show a combined effect of MCLR+PST on the oxidative balance in the O. mykiss middle intestine, which is not affected by the two toxins groups when applied individually. Basolateral Abcc transporters activation by MCLR treatment could lead to an increase in the absorption of toxicants (including MCLR) into the organism. Therefore, MCLR makes the O. mykiss middle intestine more sensitive to possibly co-occurring cyanotoxins like PST.

The Effects of Nature Exposure Therapies on Stress, Depression, and Anxiety Levels: A Systematic Review.

BACKGROUND: Mental well-being plays a pivotal role within the broader spectrum of health and illness, encompassing factors such as stress, depression, and anxiety. Nature-based therapeutic interventions have emerged as a promising approach to addressing these mental health challenges. This study seeks to assess the impact of these interventions on stress, depression, and anxiety levels. METHODS: We conducted an extensive search for randomized clinical trials that examined stress, anxiety, and depression levels. The selected studies underwent a rigorous risk-of-bias assessment following the guidelines outlined in the Cochrane Handbook for Systematic Reviews. RESULTS: Our review encompassed findings from eight publications. Among them, two studies measuring cortisol levels revealed significant differences between the pre-test and post-test measurements within the intervention groups. In two studies that employed the Stress Response Inventory, a significant decrease in stress levels was observed within the intervention groups in contrast to the control groups. However, no significant differences were noted in studies that utilized the Restorative Outcome Scale. In the assessment of anxiety and depression levels, three studies employed the Positive and Negative Affect Schedule, while four studies utilized The Profile of Mood States scale; none of these studies demonstrated significant differences. CONCLUSIONS: The current body of evidence offers limited support for advocating nature-based therapeutic interventions as a primary approach to reducing stress, depression, and anxiety.

Melatonin and Its Role in the Epithelial-to-Mesenchymal Transition (EMT) in Cancer.

The epithelial-to-mesenchymal transition (EMT) is a cell-biological program that occurs during the progression of several physiological processes and that can also take place during pathological situations such as carcinogenesis. The EMT program consists of the sequential activation of a number of intracellular signaling pathways aimed at driving epithelial cells toward the acquisition of a series of intermediate phenotypic states arrayed along the epithelial-mesenchymal axis. These phenotypic features include changes in the motility, conformation, polarity and functionality of cancer cells, ultimately leading cells to stemness, increased invasiveness, chemo- and radioresistance and the formation of cancer metastasis. Amongst the different existing types of the EMT, type 3 is directly involved in carcinogenesis. A type 3 EMT occurs in neoplastic cells that have previously acquired genetic and epigenetic alterations, specifically affecting genes involved in promoting clonal outgrowth and invasion. Markers such as E-cadherin; N-cadherin; vimentin; and transcription factors (TFs) like Twist, Snail and ZEB are considered key molecules in the transition. The EMT process is also regulated by microRNA expression. Many miRNAs have been reported to repress EMT-TFs. Thus, Snail 1 is repressed by miR-29, miR-30a and miR-34a; miR-200b downregulates Slug; and ZEB1 and ZEB2 are repressed by miR-200 and miR-205, respectively. Occasionally, some microRNA target genes act downstream of the EMT master TFs; thus, Twist1 upregulates the levels of miR-10b. Melatonin is an endogenously produced hormone released mainly by the pineal gland. It is widely accepted that melatonin exerts oncostatic actions in a large variety of tumors, inhibiting the initiation, progression and invasion phases of tumorigenesis. The molecular mechanisms underlying these inhibitory actions are complex and involve a great number of processes. In this review, we will focus our attention on the ability of melatonin to regulate some key EMT-related markers, transcription factors and micro-RNAs, summarizing the multiple ways by which this hormone can regulate the EMT. Since melatonin has no known toxic side effects and is also known to help overcome drug resistance, it is a good candidate to be considered as an adjuvant drug to conventional cancer therapies.

Financial burden following adult liver transplantation is common and associated with adverse recipient outcomes.

The financial impact of liver transplantation has been underexplored. We aimed to identify associations between high financial burden (≥10% annual income spent on out-of-pocket medical costs) and work productivity, financial distress (coping behaviors in response to the financial burden), and financial toxicity (health-related quality of life, HRQOL) among adult recipients of liver transplant. Between June 2021 and May 2022, we surveyed 207 adult recipients of liver transplant across 5 US transplant centers. Financial burden and distress were measured by 25 items adapted from national surveys of cancer survivors. Participants also completed the Work Productivity and Activity Impairment and EQ-5D-5L HRQOL questionnaires. In total, 23% of recipients reported high financial burden which was significantly associated with higher daily activity impairment (32.9% vs. 23.3%, p =0.048). In adjusted analyses, the high financial burden was significantly and independently associated with delayed or foregone medical care (adjusted odds ratio, 3.95; 95% CI, 1.85-8.42) and being unable to afford basic necessities (adjusted odds ratio, 5.12; 95% CI: 1.61-16.37). Recipients experiencing high financial burden had significantly lower self-reported HRQOL as measured by the EQ-5D-5L compared to recipients with low financial burden (67.8 vs. 76.1, p =0.008) and an age-matched and sex-matched US general population (67.8 vs. 79.1, p <0.001). In this multicenter cohort study, nearly 1 in 4 adult recipients of liver transplant experienced a high financial burden, which was significantly associated with delayed or foregone medical care and lower self-reported HRQOL. These findings underscore the need to evaluate and address the financial burden in this population before and after transplantation.

A Novel Heterozygous De Novo MORC2 Missense Variant Causes an Early Onset and Severe Neurodevelopmental Disorder.

Microrchidia CW-type zinc finger protein 2 (MORC2) is an ATPase-containing nuclear protein which regulates transcription through chromatin remodelling and epigenetic silencing. MORC2 may have a role in the development of neurones, and dominant variants in this gene have recently been linked with disorders including Charcot-Marie-Tooth type 2Z disease, spinal muscular atrophy and, more recently, a neurodevelopmental syndrome consisting of developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy (DIGFAN), presenting with hypotonia, microcephaly, brain atrophy, intellectual disability, hearing loss, faltering growth, and craniofacial dysmorphism. Notably, variants in MORC2 have shown clinical features overlapping with those of Cockayne and Leigh syndromes. Here, we report a case of MORC2-related DIGFAN syndrome in a female infant caused by a novel heterozygous de novo variant. The condition was early onset and severe, further expanding the range of genotypes associated with this disorder. Clinical features included unilateral hearing loss, developmental delay and regression within the first year of life, microcephaly, severe feeding difficulties, and faltering growth, resulting in death at 13 months of age.

Health care-related transportation insecurity is associated with adverse health outcomes among adults with chronic liver disease.

BACKGROUND: Health care-related transportation insecurity (delayed or forgone medical care due to transportation barriers) is being increasingly recognized as a social risk factor affecting health outcomes. We estimated the national burden and adverse outcomes of health care-related transportation insecurity among US adults with chronic liver disease (CLD). METHODS: Using the U.S. National Health Interview Survey from 2014 to 2018, we identified adults with self-reported CLD. We used complex weighted survey analysis to obtain national estimates of health care-related transportation insecurity. We examined the associations between health care-related transportation insecurity and health care-related financial insecurity, food insecurity, self-reported health status, work productivity, health care use, and mortality. RESULTS: Of the 3643 (representing 5.2 million) US adults with CLD, 267 [representing 307,628 (6%; 95% CI: 5%-7%)] reported health care-related transportation insecurity. Adults with CLD experiencing health care-related transportation insecurity had 3.5 times higher odds of cost-related medication nonadherence [aOR, 3.5; (2.4-5.0)], 3.5 times higher odds of food insecurity [aOR, 3.5; (2.4-5.3)], 2.5 times higher odds of worsening self-reported health status over the past year [aOR, 2.5; (1.7-3.7)], 3.1 times higher odds of being unable to work due to poor health over the past year [aOR, 3.1; (2.0-4.9)], and 1.7 times higher odds of being in a higher-risk category group for number of hospitalizations annually [aOR, 1.7; (1.2-2.5)]. Health care-related transportation insecurity was independently associated with mortality after controlling for age, income, insurance status, comorbidity burden, financial insecurity, and food insecurity [aHR, 1.7; (1.4-2.0)]. CONCLUSIONS: Health care-related transportation insecurity is a critical social risk factor that is associated with health care-related financial insecurity, food insecurity, poorer self-reported health status and work productivity, and increased health care use and mortality among US adults with CLD. Efforts to screen for and reduce health care-related transportation insecurity are warranted.

Prefrontal Regulation of Safety Learning during Ethologically Relevant Thermal Threat.

Learning and adaptation during sources of threat and safety are critical mechanisms for survival. The prelimbic (PL) and infralimbic (IL) subregions of the medial prefrontal cortex (mPFC) have been broadly implicated in the processing of threat and safety. However, how these regions regulate threat and safety during naturalistic conditions involving thermal challenge still remains elusive. To examine this issue, we developed a novel paradigm in which adult mice learned that a particular zone that was identified with visuospatial cues was associated with either a noxious cold temperature ("threat zone") or a pleasant warm temperature ("safety zone"). This led to the rapid development of avoidance behavior when the zone was paired with cold threat or approach behavior when the zone was paired with warm safety. During a long-term test without further thermal reinforcement, mice continued to exhibit robust avoidance or approach to the zone of interest, indicating that enduring spatial-based memories were formed to represent the thermal threat and thermal safety zones. Optogenetic experiments revealed that neural activity in PL and IL was not essential for establishing the memory for the threat zone. However, PL and IL activity bidirectionally regulated memory formation for the safety zone. While IL activity promoted safety memory during normal conditions, PL activity suppressed safety memory especially after a stress pretreatment. Therefore, a working model is proposed in which balanced activity between PL and IL is favorable for safety memory formation, whereas unbalanced activity between these brain regions is detrimental for safety memory after stress.

Validation of prognostic and predictive value of total tumoral load after primary systemic therapy in breast cancer using OSNA assay.

PURPOSE: This study aimed to validate the classification of breast cancer (BC) patients in progression risk groups based on total tumor load (TTL) value to predict lymph node (LN) affectation after neo-adjuvant systemic therapy (NAST) obtained in the NEOVATTL study. METHODS/PATIENTS: This was an observational, retrospective, international, multicenter study including patients with infiltrating BC who received NAST followed by sentinel lymph node biopsy (SLNB) analyzed with one-step nucleic acid amplification (OSNA) from nine Spanish and two Italian hospitals. Patients were classified into three groups according to the progression risk, measured as disease-free survival (DFS), based on TTL values (> 250, 250-25,000, and > 25,000 copies/µL). The previous (NEOVATTL study) Cox regression model for prognosis was validated using prognostic index (PI) and Log ratio test (LRT) analyses; the value of TTL for axillary non-SLN affectation was assessed using receiver operating characteristic (ROC) curves. RESULTS: We included 263 patients with a mean age of 51.4 (± SD 10.5) years. Patients with TTL > 25,000 copies/µL had a shorter DFS (HR 3.561 [95% CI 1.693-7.489], p = 0.0008 vs. TTL ≤ 25,000). PI and LRT analyses showed no differences between the two cohorts (p = 0.2553 and p = 0.226, respectively). ROC analysis showed concordance between TTL and non-SLN involvement (area under the curve 0.828), with 95.7% sensitivity and 92.9% specificity at a TTL cut-off of > 15,000 copies/µL. CONCLUSIONS: In BC patients who had received NAST and underwent SLNB analysis using OSNA, a TTL value of > 25,000 copies/µL was associated with a higher progression risk and > 15,000 copies/µL was predictive of non-SLN involvement.

Psychometric properties of the parenting belief scale in a multi-country sample of parents from high-income countries.

BACKGROUND: Parents' beliefs about how private/public their parenting role is and their acceptability of the use of corporal punishment as a disciplinary measure have been associated with how parents raise their children and their willingness to seek support. However, there are no reliable and valid instruments measuring these beliefs. OBJECTIVE: This study evaluated the psychometric properties of the Parenting Belief Scale, a self-reported brief measure targeting parents' perception of parenting as a private concern and their attitudes towards the use of corporal punishment. PARTICIPANTS AND SETTING: Participants were 6949 parents from several high-income countries (i.e., Australia, Belgium, Canada, Germany, Hong Kong, Australia, and the UK) who completed the International Parenting Survey, an online cross-sectional survey focused on parents' self-report of their parenting, children, and family. METHODS: This study evaluated the internal consistency, factor structure (i.e., exploratory and confirmatory factor analyses), and convergent and discriminant validity of the Parenting Belief Scale. RESULTS: Findings indicated that this scale was a relatively reliable measure to evaluate parents' perceived privacy in their role and acceptability of corporal punishment. A two-factor structure was confirmed by both exploratory and confirmatory factor analyses. Correlations with scales of parenting practices supported the convergent and discriminant validity of the Parenting Belief Scale. CONCLUSIONS: This study supported the use of the Parenting Belief Scale across high-income countries to evaluate parenting beliefs in influencing parenting practices and parents' help-seeking behaviours.

Implicancias teórico-clínicas de las prácticas psicoterapéuticas feministas o con perspectiva de género en Chile / Theoretical-clinical implications of feminist or gender-sensitive psychotherapeutic practices in Chile

Este artículo tiene como objetivo comprender, mediante el análisis de 16 entrevistas semies-tructuradas, las implicancias teórico-clínicas del posicionamiento con perspectiva de género o feminista en la práctica psicoterapéutica contemporánea en Chile, desde la perspectiva de consultantes y psicoterapeutas. Como resultados, se observa que el valor de esta psicoterapia radica en entregar una lectura sociocultural del malestar generizado. Sin embargo, quienes consultan reproducen estereotipos de género al elegir este enfoque a propósito del género fe-menino de la psicoterapeuta, pues consideran que habría un mayor entendimiento “por ser mu-jer”, lo cual les garantizaría un espacio seguro, libre de juicios y revictimización. Se destaca que las intervenciones de este enfoque tienen un componente político que favorece el trabajo de la desculpabilización de las consultantes. Esto resulta favorable en ciertos casos, pero po-dría obstaculizar el abordaje y reconocimiento de aquellas características singulares del sujeto que inciden en el sufrimiento y trascienden la certeza ideológica. (AU)

This article aims to understand, through 16 semi-structured interviews analysis, the theoreti-cal-clinical implications of the gender or feminist perspective in contemporary psychothera-peutic practice in Chile, from the perspective of consultants and psychotherapists. As a result, it is observed that the value of this psychotherapy lies in providing a sociocultural reading of gendered discomfort. However, those who consult reproduce gender stereotypes by choosing this approach due to the female gender of the psychotherapist, as they consider that there would be a better understanding “because of her being a woman”, which would guarantee them a safe space, free of judgments and revictimization. It should be noted that the inter-ventions of this approach have a political component that favors the work of disempowerment of the consultants. This is favorable in certain cases but could hinder the approach and recog-nition of those unique characteristics that affect particularsuffering in every case and trans-cend ideological certainty. (AU)

Environmental risk management: A participatory diagnosis from a rural school in Colombia.

The rural population is potentially exposed to several environmental risks. Environmental risk management is a recurring challenge in rural educational communities that are far from large urban areas. Assessing and identifying the knowledge on prevention and response to environmental risks and natural disasters is fundamental for planning and designing educational programs for communities to face disasters. This article presented the practical application of a participatory methodology to obtain information about the knowledge and experience in the prevention and attention of environmental threats and natural disasters in the rural school Las Huacas, village of Quintana, municipality of Popayán, in the region of Cauca, Colombia. The diagnosis methodology consisted of three phases: preparatory, fieldwork and analytical. The participatory diagnosis allowed the construction of instruments and tools for social interaction, the conduction of dynamic workshops and the systematisation of the collected information. The results evidenced the lack of knowledge on environmental disasters and how parents and children must face them. The absence of communication facilities implied a high degree of vulnerability, which was compensated with the awareness, commitment and participation in the processes led by the educational community. The next challenge is the participatory construction of a scholar environmental risk-management plan supported on appropriated information and communication technologies. Contribution: This article presents the practical application of a participatory methodology to obtain information about the rural context and the knowledge and experience in the prevention and attention of environmental threats and natural disasters in a rural school in Cauca, Colombia.

Real-world effectiveness and persistence of secukinumab in the treatment of patients with psoriatic arthritis.

Introduction: Psoriatic arthritis (PsA) is a complex and heterogeneous inflammatory disease. Secukinumab, a biologic disease-modifying antirheumatic drug (bDMARD), has extensive clinical evidence of efficacy and safety in the treatment of PsA but data in clinical practice are still limited. This study aims to provide real-world evidence on secukinumab use, effectiveness, and persistence in PsA. Methods: A retrospective, multicenter study was conducted on patients diagnosed with PsA and treated with secukinumab up to June 2021 at 12 centers in the Valencian Community (Spain). Data on DAS28-CRP, DAPSA, Tender and Swollen Joint Counts (TJC, SJC), enthesitis, dactylitis, skin and nail involvement, pain, patient and physician global assessment (ptGA, phGA) using 100-mm visual analog scale (VAS), and persistence for up to 24 months were collected. Results: A total of 178 patients were included (49% men; mean [standard deviation, SD] age: 51.4 [10.5] years; 39% obese). Secukinumab was used as a first-, second-, or ≥ third-line bDMARD in 37, 21, and 42% of patients, respectively. The percentage of patients achieving at least low disease activity (DAS28-CRP ≤ 3.2) increased from 25% at baseline to 66% at month 6 (M6) and was maintained (75%) up to M24. Mean (SD) DAS28-CRP baseline values (3.9 [1.2]) decreased to 2.9 (1.1) (p < 0.001) at M6 and remained low through M24 (2.6 [1.1]) (p < 0.001). Secukinumab also improved peripheral arthritis increasing the percentage of patients with TJC = 0 (20% baseline; 57% M24) and SJC = 0 (37% baseline; 80% M24). Treatment reduced the percentage of patients with enthesitis (25% baseline; 6% M24), dactylitis (20% baseline; 4% M24), and skin (70% baseline; 17% M24), and nail (32% baseline; 2% M24) involvement. Additionally, we observed improvements in the mean pain VAS (-26.4 mm M24), ptGA (-26.2 mm M24), and phGA (-24.8 mm M24). Secukinumab showed an overall 24-month persistence rate of 67% (95% confidence interval [CI]: 60-74%). Patients receiving first-line secukinumab showed the highest 24-month persistence rate (83, 95% CI: 73-92; p = 0.024). Conclusion: Secukinumab showed long-term effectiveness across the six key PsA domains thus reducing disease activity and pain, which are major treatment goals. This was accompanied by high persistence rates, especially in bDMARD naive patients.