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Background: In 2020, Malawi had 6.9 million malaria cases and 2551 deaths, mainly in children under five years of age. The 2017-2022 Malawi malaria control strategic plan promoted the consistent use of insecticide-treated nets through free distribution and mass campaigns. Despite widespread availability of the control strategy plan, Chikwawa District continues to suffer from high malaria burden especially among under five children, due to inconsistent insecticide-treated (ITN) net usage. For this reason, this study aimed at exploring caregivers' perceptions on insecticide-treated net utilisation and also find out about its effectiveness among those who consistently use them., Methods: This study used a sequential exploratory mixed methods design. The data used for quantitative analysis was drawn from the population of under-five children's caregivers within the catchment area of Chikwawa district hospital. The sample size was 96 participants, as determined by Cochran's formula. The data collection lasted from December 2023 to April 2024 and included four in-depth interviews and three focus group discussions to address the objectives qualitatively., Results: The study revealed that 91.67% of households used ITNs, with 87.50% using them daily. The significant factors influencing ITN utilisation included the number of nets, user satisfaction, perceived impact, user habits, acquisition method, and usage frequency (all p values < 0.001). Under-five malaria cases were also significant (p = 0.025). The odds of the perceived net impact influencing utilisation were 4.956 times greater. Non-usage was due to heat, quality concerns, limited access, breathing difficulties, health conditions such as asthma, and misconceptions about net treatment., Conclusion: The study revealed a strong belief in insecticide-treated net efficacy. However, some challenges such as access, durability, and misinformation of insecticide-treated nets were discovered. These challenges affected utilisation of insecticide-treated nets in agreement with some literature reviewed. The insights found in this study will help policymakers in addressing health interventions for the reduction of malaria cases in Malawi., Competing Interests: Declarations Ethics approval and consent to participate Permission to conduct this study was obtained from the Parul institute of public health technical review committee, reference number PIPH/FOM/PU/2023–2024/319, and from the Malawi national health sciences research committee (NHSRC), protocol number 24/02/4339, approval number 4339. Clearance was obtained from the Chikwawa district health directorate before the commencement of the study activities. Permission was also sought from local leaders verbally before they entered their villages. Before data collection, informed consent was obtained from each study participant to ensure voluntary participation. All necessary information about the study, including its purpose, risks, and benefits, was explained to the participants. Furthermore, the study participants were told that they had the right to withdraw from the study at any point during the study period. Those participants who agreed to be interviewed were requested to sign or thumbprint the informed consent form. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

In 2021, avian influenza A (H5N1) clade 2.3.4.4b virus spread to North America and then to Central and South America in October 2022, extending from Colombia to Chile in three months. During 2023, several countries, mostly in the Americas, reported outbreaks in poultry, wild birds and mammals, as well as the emergence of two cases in humans (one in Ecuador in January and one in Chile in March). As of September 20th, 2023, 17 countries in the Americas Region have recorded cases of A (H5N1) in birds and mammals. On February 14th, 2023, Argentina confirmed the first case of avian influenza in wild birds, which was later detected in backyard and commercial poultry, and in the South-American sea lion (Otaria flavescens) in Tierra del Fuego, in the south of the country. So far, 21 suspected cases have been recorded in humans; however, all of them tested negative for Influenza A virus. Hemagglutinin sequence data of animal viruses analyzed in this report showed that Argentinian viruses clustered together with those isolated in other countries of the region. Epidemiological data suggested the possibility of multiple simultaneous entries of the avian virus, highlighting the role of migratory avian populations in the introduction and dissemination of the disease in Argentina. Continued comprehensive surveillance of these viruses in animals and people worldwide, along with ongoing preparedness efforts, are critical to determine the public health risk., (Copyright © 2024 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.)

A 14-month-old girl with very early-onset inflammatory bowel disease (VEO-IBD) was admitted with a flare of her bowel disease and subsequently developed high fevers, joint pain, and skin lesions during her hospitalization. Workup demonstrated bowel-associated dermatosis-arthritis syndrome in the setting of VEO-IBD, a neutrophilic dermatosis rarely reported in children that can be challenging to diagnose and treat, with limited literature for patients under 2 years of age., (© 2024 Wiley Periodicals LLC.)

Objectives: To describe the proportion of patients with liver fibrosis in at-risk populations in primary care (PC). To know the agreement between FIB-4 and transitional elastography (TE), interobserver agreement between PC and hospital care (HC) in TE, and associated risk Factors (RF)., Methods: Observational, descriptive, cross-sectional study in ≥16 years of age with RF for chronic liver disease. Sex and age, RF (alteration of liver tests [LT], metabolic syndrome, diabetes, obesity, alcohol consumption, hepatic steatosis), and FIB-4, controlled attenuation parameter and TE in PC and in HC, were collected. According to a consensus algorithm, vibration-controlled TE was performed in PC in patients with FIB-4≥1,3, and those with measurement ≥8kPa were referred to HC., Results: 326 patients were studied. 71% were not referred to HC, due to liver stiffness <8kPa. 83 of the 95 derivations did TE in HC. 45 (54%) had TE ≥8, and 25 (30%) ≥12. The proportion of patients with stiffness ≥8kPa was 13,8% (45/326) and ≥12kPa, 7,6% (25/326). The predictive values of the FIB-4 were low. The interobserver correlation coefficient between TE in PC and HC was 0,433. Variables associated with TE ≥8 in PC: LT alteration, diabetes and steatosis. With TE ≥12: LT alteration, diabetes and obesity., Predictor Variables: LT alteration and obesity., Conclusions: The study supports the sequential performance of serum indices and TE as a screening for fibrosis in the at-risk population in PC, which allows a reduction in the percentage of patients referred to AH, and a better stratification of risk patients., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

The escalating challenges of Helicobacter pylori-induced gastric complications, driven by rising antibiotic resistance and persistent cancer risks, underscore the demand for innovative therapeutic strategies. This study addresses this urgency through the development of tailored semi-interpenetrating polymer networks (semi-IPN) serving as gastroretentive matrices for amoxicillin (AMOX). They are biodegradable, absorb significant volume of simulated gastric fluid (swelling index > 360 %) and exhibit superporous microstructures, remarkable mucoadhesion, and buoyancy. The investigation includes assessment at pH 1.2 for comparative analysis with prior studies and, notably, at pH 5.0, reflecting the acidic environment in H. pylori-infected stomachs. The semi-IPN demonstrated gel-like structures, maintaining integrity throughout the 24-hour controlled release study, and disintegrating upon completing their intended function. Evaluated in gastroretentive drug delivery system performance, AMOX release at pH 1.2 and pH 5.0 over 24 h (10 %-100 %) employed experimental design methodology, elucidating dominant release mechanisms. Their mucoadhesive, buoyant, three-dimensional scaffold stability, and gastric biodegradability make them ideal for accommodating substantial AMOX quantities. Furthermore, exploring the inclusion of the potassium-competitive acid blocker (P-CAB) vonoprazan (VONO) in AMOX-loaded formulations shows promise for precise and effective drug delivery. This innovative approach has the potential to combat H. pylori infections, thereby preventing the gastric cancer induced by this pathogen., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The duplication-triplication/inverted-duplication (DUP-TRP/INV-DUP) structure is a complex genomic rearrangement (CGR). Although it has been identified as an important pathogenic DNA mutation signature in genomic disorders and cancer genomes, its architecture remains unresolved. Here, we studied the genomic architecture of DUP-TRP/INV-DUP by investigating the DNA of 24 patients identified by array comparative genomic hybridization (aCGH) on whom we found evidence for the existence of 4 out of 4 predicted structural variant (SV) haplotypes. Using a combination of short-read genome sequencing (GS), long-read GS, optical genome mapping, and single-cell DNA template strand sequencing (strand-seq), the haplotype structure was resolved in 18 samples. The point of template switching in 4 samples was shown to be a segment of ∼2.2-5.5 kb of 100% nucleotide similarity within inverted repeat pairs. These data provide experimental evidence that inverted low-copy repeats act as recombinant substrates. This type of CGR can result in multiple conformers generating diverse SV haplotypes in susceptible dosage-sensitive loci., Competing Interests: Declaration of interests Baylor College of Medicine and Miraca Holdings have formed a joint venture with shared ownership and governance of BG, which performs clinical microarray analysis, clinical ES, and clinical biochemical studies. J.R.L. serves on the scientific advisory board of the BG. J.R.L. has stock ownership in 23andMe, is a paid consultant for Genomics International, and is a co-inventor on multiple US and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, genomic disorders, and bacterial genomic fingerprinting. E.H. and S.J. are employees of ONT and shareholders and/or share option holders of ONT. D.P. provides consulting services for Ionis Pharmaceuticals. F.J.S. receives research support from Genetech, Illumina, Pacbio, and ONT., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The primary objective is to describe the real-life effectiveness and safety of nivolumab treatment in patients with relapsed or refractory classical Hodgkin's lymphoma. The secondary objective is to describe the therapeutic management after nivolumab monotherapy., Method: Observational, retrospective, multidisciplinary study including all patients with relapsed or refractory classical Hodgkin's lymphoma treated with nivolumab monotherapy from November 2015 to March 2023. Patient and treatment-related variables were collected. Effectiveness was measured as overall response rate, progression-free survival and overall survival. Safety was measured as percentage of patients with adverse effects and severity., Results: Thirteen patients were included, median age 37.5 years (RIQ: 25.3-54.7), 84.6% male. The median number of previous lines of therapy was 3 (RIQ: 2.0-4.5), including autologous hematopoietic stem cell transplantation (84.6%) and brentuximab vedotin (100%). All received nivolumab 3 mg/kg/14 days, with a median of 11 cycles (RIQ: 6.5-20.5) per patient. Median time on treatment was 4.9 months (RIQ: 3.0-9.6) and median follow-up time was 9.2 months (RIQ: 5.6-32.3). Complete response was achieved by 3 patients (23.1%), partial response by 3 (23.1%), stable disease by 3 (23.1%) and progression by 4 (30.8%). The objective response rate was 46.2%. Median progression-free survival was 23.9 months (95%CI: 0-49.1), median overall survival was not reached. At the study cutoff date, five patients had died (38.5%), four were in complete remission without active treatment (30.8%) and four were continuing treatment (30.8%). Adverse events occurred in 76.9% of patients, 44% of severity ≥3, the most frequent being hypothyroidism and hepatotoxicity. One patient discontinued treatment due to pneumonitis, two suffered treatment delays (thrombocytopenia and hypertransaminemia) and one changed the regimen to monthly (pulmonary toxicity)., Conclusions: Nivolumab in the treatment of relapsed or refractory classical Hodgkin's lymphoma has confirmed in the study sample favorable effectiveness data, expressed as objective response rate of 46.2% and clinical benefit of 69.2%. Safety was acceptable, manageable, and consistent with that described in the literature., (Publicado por Elsevier España, S.L.U.)

The functional impact and cellular context of mosaic structural variants (mSVs) in normal tissues is understudied. Utilizing Strand-seq, we sequenced 1,133 single-cell genomes from 19 human donors of increasing age, and discovered the heterogeneous mSV landscapes of hematopoietic stem and progenitor cells. While mSVs are continuously acquired throughout life, expanded subclones in our cohort are confined to individuals >60. Cells already harboring mSVs are more likely to acquire additional somatic structural variants, including megabase-scale segmental aneuploidies. Capitalizing on comprehensive single-cell micrococcal nuclease digestion with sequencing reference data, we conducted high-resolution cell-typing for eight hematopoietic stem and progenitor cells. Clonally expanded mSVs disrupt normal cellular function by dysregulating diverse cellular pathways, and enriching for myeloid progenitors. Our findings underscore the contribution of mSVs to the cellular and molecular phenotypes associated with the aging hematopoietic system, and establish a foundation for deciphering the molecular links between mSVs, aging and disease susceptibility in normal tissues., (© 2024. The Author(s).)

Roux-en-Y gastric bypass (RYGB) is a treatment for severe obesity. However, many patients have insufficient total weight loss (TWL) after RYGB. Although multiple factors have been involved, their influence is incompletely known. The aim of this exploratory study was to evaluate the feasibility and reliability of the use of machine learning (ML) techniques to estimate the success in weight loss after RYGP, based on clinical, anthropometric and biochemical data, in order to identify morbidly obese patients with poor weight responses. We retrospectively analyzed 118 patients, who underwent RYGB at the Hospital Clínico Universitario of Valencia (Spain) between 2013 and 2017. We applied a ML approach using local linear embedding (LLE) as a tool for the evaluation and classification of the main parameters in conjunction with evolutionary algorithms for the optimization and adjustment of the parameter model. The variables associated with one-year postoperative %TWL were obstructive sleep apnea, osteoarthritis, insulin treatment, preoperative weight, insulin resistance index, apolipoprotein A, uric acid, complement component 3, and vitamin B12. The model correctly classified 71.4% of subjects with TWL < 30% although 36.4% with TWL ≥ 30% were incorrectly classified as "unsuccessful procedures". The ML-model processed moderate discriminatory precision in the validation set. Thus, in severe obesity, ML-models can be useful to assist in the selection of patients before bariatric surgery.

To deliver spiritual care, professionals must be skilled in physical, mental, social, and spiritual care. Spiritual care competence includes knowledge, behaviors, attitudes, and skills that enable successful or efficient care. This review aims to identify the scope of competence and the specific skills, knowledge, and attitudes used in providing spiritual care to people needing palliative care, and the main challenges and facilitators. A scoping review was developed using the Joanna Briggs Institute methodology. Six databases (Web of Science; MEDLINE/Pubmed; Scopus; CINAHL; MedicLatina and SciELO) were searched in September 2023, with an update in January 2024. The resulting 30 articles were analyzed using a content analysis approach. Information was categorized into three domains: cognitive, affective, and functional (based on three personal resources: intrapersonal, interpersonal, and transpersonal). Palliative care professionals face a lack of training and insufficient preparation to deliver spiritual care. Spiritual care competence depends on professional spiritual development and experience, spiritual intelligence (cognitive), spiritual humility (affective), and having a critical and reflexive mind (functional). In the future, palliative care should seek to improve competent spiritual care. This review could help clarify the real configuration of competent spiritual care and lead to improvements in a professional's empowerment when delivering effective spiritual care to patients and families.

Background: Syphilis is a sexually transmitted disease caused by the spirochete Treponema pallidum, whose incidence has increased significantly in recent years. Some patients may develop sudden hearing loss (SHL) against the background of otosyphilis., Objectives: The objective of our study was to determine whether routine lues serology is useful in patients presenting with sudden hearing loss., Methods: For this purpose, all cases of SHL treated in our hospital during a period of 6 years were propectively collected. The frequency of positivity for syphilis in these patients, the treatment received, and their evolution were determined., Results: Of the total number of patients evaluated during that period, 71 underwent serological screening for syphilis, of whom 2 (2.8 %) presented positive screening antibodies. In one of them, the RPR was normal and had been treated with lues a few years before. After treatment there was no improvement. The other patient, diagnosed with otosyphilis with unconfirmed suspected neurological disease, showed normalization of hearing after specific treatment., Conclusions: Since it is a potentially curable disease, despite the low overall frequency of syphilis in patients with SHL it is advisable to perform serological screening for syphilis in high risk patients (e.g., incarceration, multiple recent sexual partners, men who have sex with men) or atypical clinical presentation (e.g., concurrent neuropathies)., Competing Interests: Declaration of competing interest The authors report there are no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study introduces an efficient strategy for synthesizing polyhydroxyurethane-based multicomponent hydrogels with enhanced rheological properties. In a single-step process, 3D materials composed of Polymer 1 (PHU) and Polymer 2 (PVA or gelatin) were produced. Polymer 1, a crosslinked polyhydroxyurethane (PHU), grew within a colloidal solution of Polymer 2, forming an interconnected network. The synthesis of Polymer 1 utilized a Non-Isocyanate Polyurethane (NIPU) methodology based on the aminolysis of bis(cyclic carbonate) (bisCC) monomers derived from 1-thioglycerol and 1,2-dithioglycerol (monomers A and E, respectively). This method, applied for the first time in Semi-Interpenetrating Network (SIPN) formation, demonstrated exceptional orthogonality since the functional groups in Polymer 2 do not interfere with Polymer 1 formation. Optimizing PHU formation involved a 20-trial methodology, identifying influential variables such as polymer concentration, temperature, solvent (an aprotic and a protic solvent), and the organo-catalyst used [a thiourea derivative (TU) and 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU)]. The highest molecular weights were achieved under near-bulk polymerization conditions using TU-protic and DBU-aprotic as catalyst-solvent combinations. Monomer E-based PHU exhibited higher Mw¯ than monomer A-based PHU (34.1 kDa and 16.4 kDa, respectively). Applying the enhanced methodology to prepare 10 multicomponent hydrogels using PVA or gelatin as the polymer scaffold revealed superior rheological properties in PVA-based hydrogels, exhibiting solid-like gel behavior. Incorporating monomer E enhanced mechanical properties and elasticity (with loss tangent values of 0.09 and 0.14). SEM images unveiled distinct microstructures, including a sponge-like pattern in certain PVA-based hydrogels when monomer A was chosen, indicating the formation of highly superporous interpenetrated materials. In summary, this innovative approach presents a versatile methodology for obtaining advanced hydrogel-based systems with potential applications in various biomedical fields.

Background: The COVID-19 pandemic had a major psychological impact on health care workers (HCWs). This study was embedded in a larger quantitative study on the mental health care of out-of-hospital HCWs in Spain. To better understand this, a qualitative study was conducted to explore the experiences, coping strategies, and influencing factors of out-of-hospital HCWs who scored high (> 25 points) on the Depression Anxiety Stress Scale (DASS-21) in a previous quantitative mental health study., Methods: A qualitative study was conducted using six in-depth interviews with individuals who scored high on the depression scale and agreed to be contacted by email between May and June 2021, using the phenomenological approach. The data were analysed using Brawn and Clare's method., Results: The main results findings related to four themes. The emotional impact of assuming a professional role with high self-demands and responsibilities; Factors influencing the development of negative emotions such as the cruelty of the pandemic, the helplessness in relation to health management and policy, the changing role of the professional and the relationship with society; Personal protection through coping strategies to manage negative emotions such as support from colleagues and family; Good practices for the future looking for different management strategies that can influence individuals and their personal, professional, and social relationships., Conclusion: The strong impact of the circumstances experienced points to the need to develop psychological support programmes that can protect people's mental health from depression during a crisis and improve the relationship between workers and their managers., (© 2024. The Author(s).)

Background and Objectives : Left atrial (LA) remodelling and dilatation predicts atrial fibrillation (AF) recurrences after catheter ablation. However, whether right atrial (RA) remodelling and dilatation predicts AF recurrences after ablation has not been fully evaluated. Materials and Methods : This is an observational study of 85 consecutive patients (aged 57 ± 9 years; 70 [82%] men) who underwent cardiac magnetic resonance before first catheter ablation for AF (40 [47.1%] persistent AF). Four-chamber cine-sequence was selected to measure LA and RA area, and ventricular end-systolic image phase to obtain atrial 3D volumes. The effect of different variables on event-free survival was investigated using the Cox proportional hazards model. Results : In patients with persistent AF, combined LA and RA area indexed to body surface area (AILA + RA) predicted AF recurrences (HR = 1.08, 95% CI 1.00-1.17, p = 0.048). An AILA + RA cut-off value of 26.7 cm 2 /m 2 had 72% sensitivity and 73% specificity for predicting recurrences in patients with persistent AF. In this group, 65% of patients with AILA + RA > 26.7 cm 2 /m 2 experienced AF recurrence within 2 years of follow-up (median follow-up 11 months), compared to 25% of patients with AILA + RA ≤ 26.7 cm 2 /m 2 (HR 4.28, 95% CI 1.50-12.22; p = 0.007). Indices of LA and RA dilatation did not predict AF recurrences in patients with paroxysmal AF. Atrial 3D volumes did not predict AF recurrences after ablation. Conclusions : In this pilot study, the simple measurement of AILA + RA may predict recurrences after ablation of persistent AF, and may outperform measurements of atrial volumes. In paroxysmal AF, atrial dilatation did not predict recurrences. Further studies on the role of RA and LA remodelling are needed.

Introduction: The primary objective is to analyse the impact of the COVID-19 pandemic on the triggers of psychopathology and on the delusional content of patients with psychotic symptoms treated during the first three months of the pandemic in a tertiary hospital in Madrid., Methods: We conducted a cross-sectional, observational and retrospective study of all patients attending the psychiatric emergency room (ER) between 11th March and 11th June 2020. Sociodemographic and clinical variables were included. The chi-squared test or Fisher's exact test were performed to compare categorical variables. The level of statistical significance was set at P<.05., Results: In the first month of the pandemic, COVID-19 conditioned the delirious content of 38.5% of the admitted patients and acted as a direct trigger for 46.2% of consultations. In the second week it affected 100.0% of the patients in both cases. Subsequently, a progressive and significant decrease was observed, with COVID-19 being the triggering factor for 17.6% and 11.5% of consultations in the second and third months of the pandemic respectively. Similarly, it was the main determinant of the delusional content in 13.7% and 3.8% of cases respectively., Conclusions: The current pandemic affects delirium's pathoplasty. The delusional content of patients admitted with psychotic symptoms is quickly conditioned, which may be related to the radical change in their life, without transition or prior preparation. The patient's environmental context and events have a huge impact on the dynamics and characteristics of mental disorders., (Copyright © 2021 Asociación Colombiana de Psiquiatría. Published by Elsevier España, S.L.U. All rights reserved.)

Somatic structural variants (SVs) are widespread in cancer, but their impact on disease evolution is understudied due to a lack of methods to directly characterize their functional consequences. We present a computational method, scNOVA, which uses Strand-seq to perform haplotype-aware integration of SV discovery and molecular phenotyping in single cells by using nucleosome occupancy to infer gene expression as a readout. Application to leukemias and cell lines identifies local effects of copy-balanced rearrangements on gene deregulation, and consequences of SVs on aberrant signaling pathways in subclones. We discovered distinct SV subclones with dysregulated Wnt signaling in a chronic lymphocytic leukemia patient. We further uncovered the consequences of subclonal chromothripsis in T cell acute lymphoblastic leukemia, which revealed c-Myb activation, enrichment of a primitive cell state and informed successful targeting of the subclone in cell culture, using a Notch inhibitor. By directly linking SVs to their functional effects, scNOVA enables systematic single-cell multiomic studies of structural variation in heterogeneous cell populations., (© 2022. The Author(s).)

The design and preparation of new vectors to transport genetic material and increase the transfection efficiency continue being an important research line. Here, a novel biocompatible sugar-based polymer derived from D-mannitol has been synthesized to be used as a gene material nanocarrier in human (gene transfection) and microalga cells (transformation process). Its low toxicity allows its use in processes with both medical and industrial applications. A multidisciplinary study about the formation of polymer/p-DNA polyplexes has been carried out using techniques such as gel electrophoresis, zeta potential, dynamic light scattering, atomic force microscopy, and circular dichroism spectroscopy. The nucleic acids used were the eukaryotic expression plasmid pEGFP-C1 and the microalgal expression plasmid Phyco69, which showed different behaviors. The importance of DNA supercoiling in both transfection and transformation processes was demonstrated. Better results were obtained in microalga cells nuclear transformation than in human cells gene transfection. This was related to the plasmid's conformational changes, in particular to their superhelical structure. It is noteworthy that the same nanocarrier has been used with eukaryotic cells from both human and microalga., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

This paper uncovers an inverted U-shaped relationship between firm exit and total factor productivity (TFP) growth using Spanish data. At low levels of firm exit, Schumpeterian cleansing effects dominate and the effect of firm destruction on TFP is positive, but when exit rates are very high, this effect turns negative. In order to rationalize this finding, we build on Asturias et al. (Firm entry and exit and aggregate growth, Technical report, National Bureau of Economic Research, 2017) and develop a model of firm dynamics with exit spillovers calibrated to match the nonlinearity found in the data. This reduced-form spillover captures amplification effects from very high destruction rates that might force viable firms to exit, for example, due to disruptions in the production network and a generalized contraction in credit supply. Armed with the calibrated model, we perform counterfactual scenarios depending on the severity of the shock to firm's outcomes. We find that when the shock is mild and firm destruction rates at impact are similar to those observed during the Global Financial Crisis (GFC), TFP growth increases, and the recovery is faster. However, when the shock is severe and firm exit is well above that of the GFC, TFP growth decreases, since high-efficiency firms are forced out of the market, which makes the recovery much slower., Competing Interests: Conflict of interestBeatriz González declares she has no conflict of interest. Enrique Moral-Benito declares he has no conflict of interest. Isabel Soler declares she has no conflict of interest., (© The Author(s) 2023.)

This study aimed to describe factors relating to the psychological distress of healthcare workers (HCWs) in Spanish out-of-hospital emergency medical services (EMS), according to the previous or non-use of psychotropic drugs or psychotherapy. A multicentre, cross-sectional descriptive study was designed. The study population were all physicians, nurses, and emergency medical technicians (EMTs) working in any Spanish out-of-hospital EMS between February and April 2021. The main outcomes were the levels of stress, anxiety, depression, and self-efficacy, assessed by DASS-21 and G-SES. Differences in levels of stress, anxiety, depression, and self-efficacy, according to sex, age, previous use of psychotropic drug or psychotherapy, work experience, professional category, type of work, and modification of working conditions were measured using the Student's t -test for independent samples, one-way ANOVA, Pearson's correlation, or 2-factor analysis of covariance. A total of 1636 HCWs were included, of whom one in three had severe mental disorders because of the pandemic. The interaction of the previous or non-use of psychotropic drugs or psychotherapy with the rest of the factors considered did not modify the levels of stress, anxiety, depression, and self-efficacy. However, HCWs with a history of psychotropic drug or psychotherapy use had a more intense negative emotional response and lower self-efficacy, regardless of their sex, professional category, type of work, or change in the working conditions. These HCWs are considered particularly vulnerable to the development or recurrence of new disorders or other comorbidities; therefore, the implementation of monitoring and follow-up strategies should be a priority.

Spiritual care requires understanding the spiritual experiences of patients and recognizing their resources and needs. Therefore, educators and practitioners should develop their knowledge and understanding in this regard. Spiritual care helps people overcome their anxieties, worries, and suffering; reduces stress; promotes healing; and encourages patients to find inner peace. To provide comprehensive and appropriate care while upholding human/ethical virtues, the spiritual dimension must be a priority. We aim to develop spiritual care competence guidelines for Palliative Care (PC) education and practice in Portugal and Spain. The study detailed in this protocol paper will include three phases. In phase I, the phenomenon will be characterized and divided into two tasks: (1) a concept analysis of "spiritual care competence"; and (2) a systematic review of interventions or strategies used to integrate spiritual care in PC education and practice. Phase II will entail a sequential explanatory approach (online survey and qualitative interviews) to deepen understanding of the perceptions and experiences of educators, practitioners, and patients/family carers regarding spiritual care in PC education and practice and generate ideas for the next steps. Phase III will comprise a multi-phased, consensus-based approach to identify priority areas of need as decided by a group of experts. Results will be used to produce guidelines for integrating spirituality and spiritual care competence within PC education and practice and synthesized in a white book for PC professionals. The value of this improved examination of spiritual care competence will ultimately depend on whether it can inform the development and implementation of tailored educational and PC services. The project will promote the 'spiritual care' imperative, helping practitioners and patients/family carers in their preparedness for End-of-Life care, as well as improving curricular practices in this domain.

An increase in resistance to key antibiotics has made the need for novel treatments for the gastric colonization of Helicobacter pylori ( H. pylori ) a matter of the utmost urgency. Recent studies tackling this topic have focused either on the discovery of new compounds to ameliorate therapeutic regimes (such as vonoprazan) or the synthesis of gastroretentive drug delivery systems (GRDDSs) to improve the pharmacokinetics of oral formulations. The use of semi-interpenetrating polymer networks (semi-IPNs) that can act as super-porous hydrogels for this purpose is proposed in the present work, specifically those displaying low ecological footprint, easy synthesis, self-floating properties, high encapsulation efficiency for drugs such as amoxicillin (AMOX), great mucoadhesiveness, and optimal mechanical strength when exposed to stomach-like fluids. To achieve such systems, biodegradable synthetic copolymers containing acid-labile monomers were prepared and interpenetrated with guar gum (GG) in a one-pot polymerization process based on thiol-ene click reactions. The resulting matrices were characterized by SEM, GPC, TGA, NMR, and rheology studies, and the acidic hydrolysis of the acid-sensitive polymers was also studied. Results confirm that some of the obtained matrices are expected to perform optimally as GRDDSs for the sustained release of active pharmaceutical ingredients at the gastrointestinal level, being a priori facilitated by its disaggregation. Therefore, the optimal performance of these systems is assessed by varying the molar ratio of the labile monomer in the matrices.

Objective: The diagnosis of type 1 diabetes mellitus (DM1) has a major impact on young people and their families. Psychosocial factors, patient motivation, participation and acceptance of the disease are essential to achieve good blood glucose control. Our aims were to analyse personality traits and how they are related to blood glucose control in patients with DM1., Methods: Sixty-two patients with DM1 over 18 years of age, with at least one-year disease duration and absence of advanced chronic complications were studied. Clinical, biological and personality parameters were measured. The Millon Index of Personality Styles was administered for personality assessment., Results: Significant correlations between different personality variables and glycated haemoglobin (HbA1c) values were found. Individuals with poor blood glucose control had significantly higher scores on the Feeling-guided (53.6±25.7 vs 36.2±26.8, p=0.021), Innovation-seeking (36.7±24.1 vs 21.9±21.4, p=0.025), Dissenting (41.1±24.4 vs 15.6±16.6, p=0.001), Submissive (41.5±25.1 vs 28.3±14.7, p=0.038) and Dissatisfied (37.5±27.5 vs 19.5±20.2, p=0.015) scales. This psychological profile is characterised by greater focus on emotions and personal values (feeling-guided), the tendency to reject conventional ideas (innovation-seeking), an aversion to complying with norms and a preference for autonomy (unconventional/dissenting), labile self-confidence (submissive/yielding) and expressed disagreement with others (dissatisfied/complaining). Factor analysis based on the main components of the variance yielded four factors. Factor characterised as related to rebelliousness or independent judgement and action was correlated with poor blood glucose control (r=0.402, p<0.05)., Conclusion: The rebellious or non-conformist personality type is closely associated with poor blood glucose control in patients with DM1., (Copyright © 2021 The Author(s). Published by Elsevier España, S.L.U. All rights reserved.)

Background: Since May 2022, a new outbreak of monkeypox has been reported in several countries, including Spain. The clinical and epidemiological characteristics of the cases in this outbreak may differ from those in earlier reports., Objectives: To document the clinical and epidemiological characteristics of cases of monkeypox in the current outbreak., Methods: We conducted a prospective cross-sectional study in multiple medical facilities in Spain to describe the cases of monkeypox in the 2022 outbreak., Results: In total, 185 patients were included. Most cases started with primarily localized homogeneous papules, not pustules, in the probable area of inoculation, which could be cutaneous or mucous, including single lesions. Generalized small pustules appeared later in some of them. Heterogeneous lesions occurred during this generalized phase. All patients had systemic symptoms. Less common lesions included mucosal ulcers (including pharyngeal ulcers and proctitis) and monkeypox whitlows. Four patients were hospitalized, none died. Smallpox vaccination and well-controlled HIV disease were not associated with markers of severity. Contact during sex is the most likely mechanism of transmission. In this outbreak, cases have been described in men who have sex with men and are strongly associated with high-risk sexual behaviours. Seventy-six per cent of the patients had other sexually transmitted diseases upon screening., Conclusions: The clinical findings in this outbreak differ from previous findings and highly suggest contact transmission and initiation at the entry site. The characterization of the epidemiology of this outbreak has implications for control. What is already known about this topic? Monkeypox eruption is described as consisting of pustules. The roles of HIV and previous smallpox vaccination in the prognosis are unknown. The transmission route was initially described as respiratory droplets and was later suggested to be via sexual contact. What does this study add? Initial lesions at the probable inoculation area were homogeneous and papular (pseudopustules). Generalized small pustules appeared later in some of them. Heterogeneous lesions occurred during this generalized phase. All patients had systemic symptoms. Less common signs included mucosal ulcers (including pharyngeal ulcers and proctitis) and monkeypox whitlows. Well-controlled HIV and previous smallpox vaccination were not associated with severity. No patient died. The data support the hypothesis of transmission via contact during sex. Although this might change, the outbreak is currently limited mostly to men who have sex with men, with high-risk factors for sexually transmitted diseases., (© 2022 British Association of Dermatologists.)

Leber hereditary optic neuropathy is a mitochondrial disease mainly due to pathologic mutations in mitochondrial genes related to the respiratory complex I of the oxidative phosphorylation system. Genetic, physiological, and environmental factors modulate the penetrance of these mutations. We report two patients suffering from this disease and harboring a m.15950G > A mutation in the mitochondrial DNA-encoded gene for the threonine transfer RNA. We also provide evidences supporting the pathogenicity of this mutation., (© 2022 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

The cultivation of edible mushroom is an emerging sector with a potential yet to be discovered. Unlike plants, it is a less developed agriculture where many studies are lacking to optimize the cultivation. In this work we have employed high-throughput techniques by next generation sequencing to screen the microbial structure of casing soil employed in mushroom cultivation (Agaricus bisporus) while sequencing V3-V4 of the 16S rRNA gene for bacteria and the ITS2 region of rRNA for. In addition, the microbiota dynamics and evolution (bacterial and fungal communities) in peat-based casing along the process of incubation of A. bisporus have been studied, while comparing the effect of fungicide treatment (chlorothalonil and metrafenone). Statistically significant changes in populations of bacteria and fungi were observed. Microbial composition differed significantly based on incubation day, changing radically from the original communities in the raw material to a specific microbial composition driven by the A. bisporus mycelium growth. Chlorothalonil treatment seems to delay casing colonization by A. bisporus. Proteobacteria and Bacteroidota appeared as the most dominant bacterial phyla. We observed a great change in the structure of the bacteria populations between day 0 and the following days. Fungi populations changed more gradually, with A. bisporus displacing the rest of the species as the cultivation cycle progresses. A better understanding of the microbial communities in the casing will hopefully allow us to increase the biological efficiency of the crop., (© 2022. The Author(s).)

Unlike copy number variants (CNVs), inversions remain an underexplored genetic variation class. By integrating multiple genomic technologies, we discover 729 inversions in 41 human genomes. Approximately 85% of inversions <2 kbp form by twin-priming during L1 retrotransposition; 80% of the larger inversions are balanced and affect twice as many nucleotides as CNVs. Balanced inversions show an excess of common variants, and 72% are flanked by segmental duplications (SDs) or retrotransposons. Since flanking repeats promote non-allelic homologous recombination, we developed complementary approaches to identify recurrent inversion formation. We describe 40 recurrent inversions encompassing 0.6% of the genome, showing inversion rates up to 2.7 × 10 -4 per locus per generation. Recurrent inversions exhibit a sex-chromosomal bias and co-localize with genomic disorder critical regions. We propose that inversion recurrence results in an elevated number of heterozygous carriers and structural SD diversity, which increases mutability in the population and predisposes specific haplotypes to disease-causing CNVs., Competing Interests: Declaration of interests E.E.E. is a scientific advisory board (SAB) member of Variant Bio. C.L. is an SAB member of Nabsys. The following authors have previously disclosed a patent application (no. EP19169090) relevant to Strand-seq: A.D.S., J.O.K., T.M., and D.P.; the other authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to analyze the psychological affectation of health professionals (HPs) of Spanish Emergency Medical Services (EMSs) according to the cumulative incidence (CI) of COVID-19 cases in the regions in which they worked. A cross-sectional descriptive study was designed, including all HPs working in any EMS of the Spanish geography between 1 February 2021 and 30 April 2021. Their level of stress, anxiety and depression (DASS-21) and the perception of self-efficacy (G-SES) were the study's main results. A 2-factor analysis of covariance was used to determine if the CI regions of COVID-19 cases determined the psychological impact on each of the studied variables. A total of 1710 HPs were included. A third presented psychological impairment classified as severe. The interaction of CI regions with the studied variables did not influence their levels of stress, anxiety, depression or self-efficacy. Women, younger HPs or those with less EMS work experience, emergency medical technicians (EMT), workers who had to modify their working conditions or those who lived with minors or dependents suffered a greater impact from the COVID-19 pandemic in certain regions. These HPs have shown high levels of stress, anxiety, depression and medium levels of self-efficacy, with similar data in the different geographical areas. Psychological support is essential to mitigate their suffering and teach them to react to adverse events.

Introduction: Bacterial/fungal coinfection and superinfections contribute to the increased morbi-mortality of viral respiratory infections (RIs). The main objective of this study was to determine the incidence of these infections in hospitalized patients with COVID-19., Method: Retrospective observational study of all patients admitted for COVID-19 and bacterial/fungal infections at the Hospital Clínico Universitario of Valladolid, Spain (March 1-May 31, 2020). Demographic, clinical and microbiological data were compared based on Intensive Care Unit (ICU) admission and predictors of mortality by were identified using multivariate logistic regression analyses., Results: Of the 712 COVID-19 patients, 113 (16%) presented bacterial/fungal coinfections or superinfections. Their median age was 73 years (IQR 57-89) and 59% were men. The profiles of ICU patients (44%) included male, SARS-CoV-2 pneumonia, leukocytosis, elevated inteleukin-6, with interferon β-1b and tocilizumab and superinfection (p < 0.05). Coinfections were diagnosed in 5% (39/712) patients. Most common pathogens of respiratory coinfection (18) were Streptococcus pneumoniae (6) and Staphylococcus aureus (6). Superinfections were detected in 11% (80/712) patients. Urinary (53) and RI (39) constituted the majority of superinfections Acinetobacter baumannii multidrug-resistant was the main agent of IR and bacteremia. An outbreak of A. baumannii contributed to this result. Three patients were considered to have probable pulmonary aspergillosis. Mortality was higher in UCI patients (50% vs. 29%, p = 0.028). The predictive factors of mortality included being a male with various comorbidities, SARS-CoV-2 pneumonia, bacteremia and superinfections from A. baumannii., Conclusion: The outbreak of A. baumannii was a determining factor in the increases of the incidence of infection and the morbi-mortality of ICU patients., (Copyright © 2020 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Catheter ablation of accessory pathways (AP) with bidirectional conduction may be challenging due to issues related to anatomical course or location., Objective: We describe an alternative electro-anatomical mapping technique which aims at depicting the entire anatomic course of the AP from the atrial toward the ventricular insertion in order to guide catheter ablation., Methods: Twenty consecutive patients with confirmed bidirectional AP conduction and at least one previous ablation procedure or para-Hisian location were included. 3-D electro-anatomical mapping was used to depict the merged 10-ms isochrone area of maximum early activation of both the ventricular and atrial signals during sinus rhythm and ventricular pacing/orthodromic tachycardia, respectively. Catheter ablation was performed within the depicted earliest isochrone area., Results: Acute bidirectional AP conduction block was achieved in all patients 4.2 ± 1.7 s after the first radiofrequency energy pulse was delivered, without reconnection during a 30 ± 10 min post-ablation observation time. No procedural complications were seen. After a mean follow-up period of 9 ± 7 months (range 3 to 16), no recurrences were documented., Conclusion: This merged two-way mapping technique is a safe, efficient, and effective technique for ablation of APs with bidirectional conduction., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Patients undergoing cavotricuspid isthmus (CTI) ablation for typical flutter (AFL) have a high incidence of new onset atrial fibrillation (AF). We aimed to analyze the influence of PACE score to predict new onset AF in this subset of patients to stratify thromboembolic risk., Methods: Between 2017 and 2019, patients undergoing CTI ablation for AFL and without history of AF were prospectively included. All patients were monitored continuously by implantable loop recorder and followed by remote monitoring., Results: Overall 48 patients were included. New onset AF rate at 12 months was 56.3%. We observed two very strong independent predictors for new onset AF: a PACE score ≥ 30 (HR:6.9; 95% CI:1.71-27.91; p = 0.007) and an HV interval ≥ 55 (HR:11.86; 95% CI:2.57-54.8; p = 0.002)., Conclusions: The incidence of newly diagnosed AF is high in patients with AFL after CTI ablation, and can occur early. A high PACE score and/or long HV interval predict even higher risk, and may be useful in the decision for empiric long-term anticoagulation., (Copyright © 2021. Published by Elsevier Ltd.)