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Abstract The healthy lifestyle index (HLI), defined as the unweighted sum of individual lifestyle components, was used to investigate the combined role of lifestyle factors on health-related outcomes. We introduced weighted outcome-specific versions of the HLI, where individual lifestyle components were weighted according to their associations with disease outcomes. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined the association between the standard and the outcome-specific HLIs and the risk of T2D, CVD, cancer, and all-cause premature mortality. Estimates of the hazard ratios (HRs), the Harrell’s C-index and the population attributable fractions (PAFs) were compared. For T2D, the HR for 1-SD increase of the standard and T2D-specific HLI were 0.66 (95% CI: 0.64, 0.67) and 0.43 (0.42, 0.44), respectively, and the C-index were 0.63 (0.62, 0.64) and 0.72 (0.72, 0.73). Similar, yet less pronounced differences in HR and C-index were observed for standard and outcome-specific estimates for cancer, CVD and all-cause mortality. PAF estimates for mortality before age 80 were 57% (55%, 58%) and 33% (32%, 34%) for standard and mortality-specific HLI, respectively. The use of outcome-specific HLI could improve the assessment of the role of lifestyle factors on disease outcomes, thus enhancing the definition of public health recommendations.

Abstract Background Healthy lifestyles are inversely associated with the risk of noncommunicable diseases, which are leading causes of death. However, few studies have used longitudinal data to assess the impact of changing lifestyle behaviours on all-cause and cancer mortality. Methods Within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, lifestyle profiles of 308,497 cancer-free adults (71% female) aged 35–70 years at recruitment across nine countries were assessed with baseline and follow-up questionnaires administered on average of 7 years apart. A healthy lifestyle index (HLI), assessed at two time points, combined information on smoking status, alcohol intake, body mass index, and physical activity, and ranged from 0 to 16 units. A change score was calculated as the difference between HLI at baseline and follow-up. Associations between HLI change and all-cause and cancer mortality were modelled with Cox regression, and the impact of changing HLI on accelerating mortality rate was estimated by rate advancement periods (RAP, in years). Results After the follow-up questionnaire, participants were followed for an average of 9.9 years, with 21,696 deaths (8407 cancer deaths) documented. Compared to participants whose HLIs remained stable (within one unit), improving HLI by more than one unit was inversely associated with all-cause and cancer mortality (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.81, 0.88; and HR: 0.87; 95% CI: 0.82, 0.92; respectively), while worsening HLI by more than one unit was associated with an increase in mortality (all-cause mortality HR: 1.26; 95% CI: 1.20, 1.33; cancer mortality HR: 1.19; 95% CI: 1.09, 1.29). Participants who worsened HLI by more than one advanced their risk of death by 1.62 (1.44, 1.96) years, while participants who improved HLI by the same amount delayed their risk of death by 1.19 (0.65, 2.32) years, compared to those with stable HLI. Conclusions Making healthier lifestyle changes during adulthood was inversely associated with all-cause and cancer mortality and delayed risk of death. Conversely, making unhealthier lifestyle changes was positively associated with mortality and an accelerated risk of death.

Introduction: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke that mainly affects young adults. Early, accurate diagnosis can reduce the rate and severity of complications. Objective: The aim of this study was to analyse the clinical characteristics, management, and treatment of CVT in different centres in Spain. Methods: We conducted a multicentre, retrospective, descriptive study of patients hospitalised due to CVT between 2008 and 2017 at 10 Spanish centres. Results: We included 256 patients, with a mean age (SD) of 49.8 (18.7) years; 51% of patients were women. The most frequent symptoms were headache (73%), focal deficits (50%), epileptic seizures (33%), and encephalopathy (21%). The most frequent localisations were the superior sagittal sinus (12.5%), the transverse sinus (10.9%), and 2 or more sinuses or veins (66.4%). Thrombophilia was the most frequent known aetiology (24%), and was most commonly associated with the prothrombin G20210A mutation (19%). Forty-six percent of patients were treated with antithrombotics for 3 to 6 months, 21% for one year, and 22.6% required indefinite anticoagulation. Endovascular therapy was performed in 5% of cases, and 33% required neurosurgery. Regarding outcomes, 75% of patients were independent at 3 months (modified Rankin Scale [mRS] score ≤ 2), with papilloedema (P = .03), focal deficits (P = .001), and encephalopathy (P 3). The in-hospital mortality rate was 4.3%, with a 3-month mortality rate of 6.3%. Conclusion: The diverse risk factors and variable presentation of CVT represent a challenge in the diagnosis and treatment of this condition. To improve prognosis and reduce mortality, it is essential to establish management protocols for this entity. Resumen: Introducción: La trombosis venosa cerebral (TVC) es una causa poco común de ictus que afecta principalmente a adultos jóvenes. Un diagnóstico precoz y preciso puede reducir la tasa y gravedad de las complicaciones. Objetivo: Analizar las características clínicas, manejo y tratamiento de la TVC en diferentes centros de nuestro país. Métodos: Estudio descriptivo retrospectivo multicéntrico de pacientes hospitalizados por TVC entre 2008 y 2017 en 10 centros sanitarios en nuestro país. Resultados: Se incluyeron 256 pacientes, edad media 49,8 ± 18,7 años y el 51% fueron mujeres. Los síntomas más frecuentes fueron: cefalea (73%), déficits focales (50%), crisis epilépticas (33%) y encefalopatía (21%). Las localizaciones más frecuentes fueron: seno longitudinal superior (12,5%), transverso (10,9%) y afectación de dos o más senos o venas (66,4%). La etiología conocida más frecuente fue la trombofilia (24%), siendo la mutación de la protrombina G20210A la más común (19%). El 46% fue tratado con antitrombóticos durante 3-6 meses, el 21% durante 1 año y un 22,6% de los pacientes requirieron anticoagulación indefinida. En un 5% de los sujetos fue preciso terapia endovascular y un 33% requirió neurocirugía. En relación al pronóstico, el 75% fueron independientes a los 3 meses con una puntuación en la escala de Rankin modificada (mRS) ≤ 2 y la presencia de papiledema (p = 0,03), déficit focal (p = 0,001) y encefalopatía (p 3). La tasa de mortalidad intrahospitalaria fue del 4,3% y el 6,3% de los pacientes fallecieron a los 3 meses. Conclusión: La diversidad de factores de riesgo y la presentación variable suponen un desafío en el diagnóstico y tratamiento de la TVC. Para mejorar el pronóstico y reducir la mortalidad es fundamental la instauración de protocolos en el manejo de esta patología.

Resumen: Introducción: La trombosis venosa cerebral (TVC) es una causa poco común de ictus que afecta principalmente a adultos jóvenes. Un diagnóstico precoz y preciso puede reducir la tasa y gravedad de las complicaciones. Objetivo: Analizar las características clínicas, manejo y tratamiento de la TVC en diferentes centros de nuestro país. Métodos: Estudio descriptivo retrospectivo multicéntrico de pacientes hospitalizados por TVC entre 2008 y 2017 en 11 centros sanitarios en nuestro país. Resultados: Se incluyeron 256 pacientes, edad media 49,8 ± 18,7 años y el 51% fueron mujeres. Los síntomas más frecuentes fueron: cefalea (73%), déficits focales (50%), crisis epilépticas (33%) y encefalopatía (21%). Las localizaciones más frecuentes fueron: seno longitudinal superior (12,5%), transverso (10,9%) y afectación de dos o más senos o venas (66,4%). La etiología conocida más frecuente fue la trombofilia (24%), siendo la mutación de la protrombina G20210A la más común (19%). El 46% fue tratado con antitrombóticos durante 3-6 meses, el 21% durante un año y un 22,6% de los pacientes requirieron anticoagulación indefinida. En un 5% de los sujetos fue preciso terapia endovascular y un 33% requirió neurocirugía. En relación al pronóstico, el 75% fueron independientes a los 3 meses con una puntuación en la escala de Rankin modificada (mRS) ≤ 2 y la presencia de papiledema (p = 0,03), déficit focal (p = 0,001) y encefalopatía (p 3). La tasa de mortalidad intrahospitalaria fue del 4,3% y el 6,3% de los pacientes fallecieron a los 3 meses. Conclusión: La diversidad de factores de riesgo y la presentación variable suponen un desafío en el diagnóstico y tratamiento de la TVC. Para mejorar el pronóstico y reducir la mortalidad es fundamental la instauración de protocolos en el manejo de esta patología. Abstract: Introduction: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke that mainly affects young adults. Early, accurate diagnosis can reduce the rate and severity of complications. Objective: The aim of this study was to analyse the clinical characteristics, management, and treatment of CVT in different centres in Spain. Methods: We conducted a multicentre, retrospective, descriptive study of patients hospitalised due to CVT between 2008 and 2017 at 11 Spanish centres. Results: We included 256 patients, with a mean age (SD) of 49.8 (18.7) years; 51% of patients were women. The most frequent symptoms were headache (73%), focal deficits (50%), epileptic seizures (33%), and encephalopathy (21%). The most frequent localisations were the superior sagittal sinus (12.5%), the transverse sinus (10.9%), and 2 or more sinuses or veins (66.4%). Thrombophilia was the most frequent known aetiology (24%), and was most commonly associated with the prothrombin G20210A mutation (19%). Forty-six percent of patients were treated with antithrombotics for 3-6 months, 21% for one year, and 22.6% required indefinite anticoagulation. Endovascular therapy was performed in 5% of cases, and 33% required neurosurgery. Regarding outcomes, 75% of patients were independent at 3 months (modified Rankin Scale [mRS] score ≤ 2), with papilloedema (P = .03), focal deficits (P = .001), and encephalopathy (P 3). The in-hospital mortality rate was 4.3%, with a 3-month mortality rate of 6.3%. Conclusion: The diverse risk factors and variable presentation of CVT represent a challenge in the diagnosis and treatment of this condition. To improve prognosis and reduce mortality, it is essential to establish management protocols for this entity.

IntroductionPain assessment in horses presents a significant challenge due to their nonverbal nature and their tendency to conceal signs of discomfort in the presence of potential threats, including humans. Therefore, this study aimed to identify pain-associated behaviors amenable to automated AI-based detection in video recordings. Additionally, it sought to determine correlations between pain intensity and behavioral and postural parameters by analyzing factors such as time budgets, weight shifting, and unstable resting. The ultimate goal is to facilitate the development of AI-based quantitative tools for pain assessment in horses.Materials and methodsA cohort of 20 horses (mean age 15 ± 8) admitted to a university equine hospital underwent 24-h video recording. Behaviors were manually scored and retrospectively analyzed using Loopy® software. Three pain groups were established based on the Pain Score Vetmeduni Vienna : pain-free (P0), mild to moderate pain (P1), and severe pain (P2).ResultsWeight shifting emerged as a reliable indicator for discriminating between painful and pain-free horses, with significant differences observed between pain groups (p

Abstract Background The quality of the statistics on causes of death (CoD) does not present consolidated indicators in literature further than the coding group of ill-defined conditions of the International Classification of Diseases. Our objective was to assess the territorial quality of CoD by reliability of the official mortality statistics in Spain over the years 1980–2019. Methods A descriptive epidemiological design of four decades (1980-, 1990-, 2000-, and 2010–2019) by region (18) and sex was implemented. The CoD cases, age-adjusted rates and ratios (to all-cause) were assigned by reliability to unspecific and ill-defined quality categories. The regional mortality rates were contrasted to the Spanish median by decade and sex by the Comparative Mortality Ratio (CMR) in a Bayesian perspective. Statistical significance was considered when the CMR did not contain the value 1 in the 95% credible intervals. Results Unspecific, ill-defined, and all-cause rates by region and sex decreased over 1980–2019, although they scored higher in men than in women. The ratio of ill-defined CoD decreased in both sexes over these decades, but was still prominent in 4 regions. CMR of ill-defined CoD in both sexes exceeded the Spanish median in 3 regions in all decades. In the last decade, women’s CMR significantly exceeded in 5 regions for ill-defined and in 6 regions for unspecific CoD, while men’s CMR exceeded in 4 and 2 of the 18 regions, respectively on quality categories. Conclusions The quality of mortality statistics of causes of death has increased over the 40 years in Spain in both sexes. Quality gaps still remain mostly in Southern regions. Authorities involved might consider to take action and upgrading regional and national death statistics, and developing a systematic medical post-grade training on death certification.

Abstract Background This study aims to assess the sustained immunological response to the SARS-CoV-2 vaccine in patients with autoimmune inflammatory rheumatic diseases (AIRD) undergoing different treatment regimens. Methods We conducted a prospective observational study involving 157 AIRD patients without prior COVID-19 infection. Treatment regimens included non-treatment or glucocorticoid-only (not-treated/GCs), non-biological drugs, biological therapy, and JAK inhibitors. All participants completed the two-dose vaccine schedule, and 110 of them received an additional booster dose. Serum samples were collected approximately 3–6 months after the second and third vaccine doses to measure antibodies against the Spike protein (antiS-AB) and neutralizing antibodies (nAB) targeting six SARS-CoV-2 variants. Results Following the third dose, all patients exhibited a significant increase in antiS-AB (FC = 15, p

Abstract Background Despite existing extensive literature, a comprehensive and clinically relevant classification system for osteoarthritis (OA) has yet to be established. In this study, we aimed to further characterize four knee OA (KOA) inflammatory phenotypes (KOIP) recently proposed by our group, by identifying the inflammatory factors associated with KOA severity and progression in a phenotype-specific manner. Methods We performed an analysis within each of the previously defined four KOIP groups, to assess the association between KOA severity and progression and a panel of 13 cytokines evaluated in the plasma and synovial fluid of our cohort’s patients. The cohort included 168 symptomatic female KOA patients with persistent joint effusion. Results Overall, our analyses showed that associations with KOA outcomes were of higher magnitude within the KOIP groups than for the overall patient series (all p-values < 1.30e−16) and that several of the cytokines showed a KOIP-specific behaviour regarding their associations with KOA outcomes. Conclusion Our study adds further evidence supporting KOA as a multifaceted syndrome composed of multiple phenotypes with differing pathophysiological pathways, providing an explanation for inconsistencies between previous studies focussed on the role of cytokines in OA and the lack of translational results to date. Our findings also highlight the potential clinical benefits of accurately phenotyping KOA patients, including improved patient stratification, tailored therapies, and the discovery of novel treatments.

Liquid pyrolysis is presented as a new production method of SnO2 nanocrystalline powders suitable for gas sensor devices. The method is based on a pyrolytic reaction of high tensioned stressed drops of an organic solution of SnCl4•5(H2O). The main advantages of the method are its capability to produce SnO2 nanopowders with high stability, its accurate control over the grain size and other structural characteristics, its high level of repeatability and its low industrialization implementation cost. The characterization of samples of SnO2 nanoparticles obtained by liquid pyrolysis in the range between 200ºC and 900ºC processing temperature is carried out by X-ray diffraction, transmission electron microscopy, Raman and X-ray photoelectron spectroscopy. Results are analyzed and discussed so as to validate the advantages of the liquid pyrolysis method.La pirólisis líquida se presenta como un nuevo método para producir SnO2 nanocristalino en polvo ideal para sensores de gas. El método se basa en una reacción pirolítica de gotas altamente tensionadas procedentes de una solución orgánica de SnCl4•5(H2O). Las principales ventajas del método son la capacidad para producir nanopartículas de SnO2 con una gran estabilidad, el preciso control sobre el tamaño de grano y sobre otras características estructurales, el alto nivel de repetibilidad y el bajo coste en su implementación industrial.La caracterización de las muestras de las nanopartículas de SnO2 obtenidas por pirólisis líquida en un rango de temperatura de procesado que va de 200ºC a 900ºC se ha realizado mediante difracción de rayos X, microscopía electrónica de transmisión, espectroscopía Raman y espectroscopía fotoelectrónica de rayos X. Los resultados se han analizado y discutido. Éstos validan las ventajas del método de la pirólisis líquida.

Abstract There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p

Abstract The rapid spread of the severe acute respiratory syndrome coronavirus 2 led to a global overextension of healthcare. Both Chest X-rays (CXR) and blood test have been demonstrated to have predictive value on Coronavirus Disease 2019 (COVID-19) diagnosis on different prevalence scenarios. With the objective of improving and accelerating the diagnosis of COVID-19, a multi modal prediction algorithm (MultiCOVID) based on CXR and blood test was developed, to discriminate between COVID-19, Heart Failure and Non-COVID Pneumonia and healthy (Control) patients. This retrospective single-center study includes CXR and blood test obtained between January 2017 and May 2020. Multi modal prediction models were generated using opensource DL algorithms. Performance of the MultiCOVID algorithm was compared with interpretations from five experienced thoracic radiologists on 300 random test images using the McNemar–Bowker test. A total of 8578 samples from 6123 patients (mean age 66 ± 18 years of standard deviation, 3523 men) were evaluated across datasets. For the entire test set, the overall accuracy of MultiCOVID was 84%, with a mean AUC of 0.92 (0.89–0.94). For 300 random test images, overall accuracy of MultiCOVID was significantly higher (69.6%) compared with individual radiologists (range, 43.7–58.7%) and the consensus of all five radiologists (59.3%, P

Mega ports, defined in this study as those handling over 5 million TEUs annually, are major hubs within the dynamic framework of global trade, influencing both economic and environmental landscapes. This study identifies climate change as the foremost environmental concern for these ports, necessitating urgent and strategic responses. Through comprehensive research, this paper explores the main Climate Change Mitigation (CCM) strategies and evaluates their implementation across mega ports worldwide. Findings indicate widespread adoption of certain strategies, such as setting greenhouse gas (GHG) reduction targets and providing on-shore power supply (OPS), while also identifying challenges, particularly in implementing environmentally differentiated port fees. Additionally, this paper outlines key strategies for climate change adaptation (CCA) in ports. The results of this research offer insights into sustainable practices and collaborative efforts to confront climate change challenges effectively. These findings have the potential to significantly improve maritime policy and ship management strategies.

We investigate the impact of "routinization" on the labor outcomes of displaced workers. We use a rich Brazilian panel dataset and an occupation-task mapping to examine the effect of job displacement in different groups, classified according to their tasks. Our main result is that following a layoff, workers previously employed in routine-intensive occupations suffer a more significant decline in wages and more extended periods of unemployment. As expected, job displacement has a negative and lasting impact on wages. Still, workers in routine-intensive occupations are more impacted than those in non-routine occupations in terms of wages (an increase of one point in the routine-intensity index results in a further decline of 2% in workers' relative wages) and employment. Furthermore, our results indicate that workers in routine-intensive occupations are more likely to change occupations after the shock, and those who do not switch occupational fields suffer a more significant decline in wages. Lastly, even though the loss of employer-specific wage premiums explains 13% of displaced workers' drop in wages, it does not explain routine-intensive workers' more substantial losses. [ABSTRACT FROM AUTHOR]

The objectives were 1) to characterize a Göttingen Minipig model of metabolic syndrome regarding its colon microbiota and circulating microbial products, and 2) to assess whether ovariectomized female and castrated male minipigs show similar phenotypes. Twenty-four nine-week-old Göttingen Minipigs were allocated to four groups based on sex and diet: ovariectomized females and castrated males fed either chow or high-fat diet (HFD) for 12 weeks. At study end, body composition and plasma biomarkers were measured, and a mixed meal tolerance test (MMT) and an intravenous glucose tolerance test (IVGTT) were performed. The HFD groups had significantly higher weight gain, fat percentage, fasting plasma insulin and glucagon compared to the chow groups. Homeostatic model assessment of insulin resistance index (HOMA-IR) was increased and glucose effectiveness derived from the IVGTT and Matsuda´s insulin sensitivity index from the MMT were decreased in the HFD groups. The HFD groups displayed dyslipidemia, with significantly increased total-, LDL- and HDL-cholesterol, and decreased HDL/non-HDL cholesterol ratio. The colon microbiota of HFD minipigs clearly differed from the lean controls (GuniFrac distance matrix). The main bacteria families driving this separation were Clostridiaceae, Fibrobacteraceae, Flavobacteriaceae and Porphyromonadaceae. Moreover, the species richness was significantly decreased by HFD. In addition, HFD decreased the circulating level of short chain fatty acids and beneficial microbial metabolites hippuric acid, xanthine and trigonelline, while increasing the level of branched chain amino acids. Six and nine metabolically relevant genes were differentially expressed between chow-fed and HFD-fed animals in liver and omental adipose tissue, respectively. The HFD-fed pigs presented with metabolic syndrome, gut microbial dysbiosis and a marked decrease in healthy gut microbial products and thus displayed marked parallels to human obesity and insulin resistance. HFD-fed Göttingen Minipig therefore represents a relevant animal model for studying host-microbiota interactions. No significant differences between the castrated and ovariectomized minipigs were observed.

Abstract Background Differentiation of gastrointestinal cancer (GIC) from chronic inflammatory enteropathies (CIE) in cats can be challenging and often requires extensive diagnostic testing. MicroRNAs (miRNAs) have promise as non‐invasive biomarkers in serum and feces for diagnosis of GIC. Hypothesis/Objectives Cats with GIC will have serum and fecal miRNA profiles that differ significantly from healthy cats and cats with CIE. Identify serum and fecal miRNAs with diagnostic potential for differentiation between cats with GIC and CIE as compared to healthy cats. Animals Ten healthy cats, 9 cats with CIE, and 10 cats with GIC; all client‐owned. Methods Cats were recruited for an international multicenter observational prospective case‐control study. Serum and feces were screened using small RNA sequencing for miRNAs that differed in abundance between cats with GIC and CIE, and healthy cats. Diagnostic biomarker potential of relevant miRNAs from small RNA sequencing and the literature was confirmed using reverse transcription quantitative real‐time PCR (RT‐qPCR). Results Serum miR‐223‐3p was found to distinguish between cats with GIC and CIE with an area under the curve (AUC) of 0.9 (95% confidence interval [CI], 0.760‐1.0), sensitivity of 90% (95% CI, 59.6‐99.5%), and specificity of 77.8% (95% CI, 45.3‐96.1%). Serum miR‐223‐3p likewise showed promise in differentiating a subgroup of cats with small cell lymphoma (SCL) from those with CIE. No fecal miRNAs could distinguish between cats with GIC and CIE. Conclusion and Clinical Importance Serum miR‐223‐3p potentially may serve as a noninvasive diagnostic biomarker of GIC in cats, in addition to providing a much needed tool for the differentiation of CIE and SCL.

La pandemia Covid-19 supuso un fuerte impulso al teletrabajo y la formación virtual. El alumnado y el personal empleado tuvieron que desarrollar nuevas competencias para adaptarse al formato on-line. Ante esta situación, si bien han proliferado los estudios sobre los efectos de la pandemia tanto en el ámbito laboral como en el educativo, es poca la literatura acerca de su impacto en las prácticas curriculares. El presente estudio aborda el análisis, desde la perspectiva empresarial, de las competencias requeridas para la realización de teleprácticas eficaces. Se elaboró una encuesta exploratoria para conocer la opinión de las empresas que habían acogido estudiantes en prácticas on-line acerca de su intención de mantener esta modalidad en el futuro y de las competencias que más valoraban en su desempeño. A partir de esta, se ha realizado un análisis descriptivo de los resultados obtenidos, seguido de una prueba de proporciones Chi-Cuadrado. A continuación, se ha desarrollado un análisis factorial exploratorio y ejecutado un análisis de componentes principales (PCA). El objetivo era detectar relaciones de interdependencia entre las distintas competencias y, así, sintetizar la información mediante la creación de factores que las agrupan. Asimismo, se ha realizado un análisis cualitativo del contenido de la pregunta abierta sobre otras competencias requeridas. Los resultados del estudio introducen la singularidad competencial de las teleprácticas y permiten vislumbrar la necesidad de seguir investigando para crear un modelo eficaz que mejore la empleabilidad de los futuros egresados.

Abstract Obesity-related glomerulopathy and diabetic nephropathy (DN) are serious complications to metabolic syndrome and diabetes. The purpose was to study effects of a fat, fructose and cholesterol-rich (FFC) diet with and without salt in order to induce hypertension on kidney function and morphology in Göttingen Minipigs with and without diabetes. Male Göttingen Minipigs were divided into 4 groups: SD (standard diet, n = 8), FFC (FFC diet, n = 16), FFC-DIA (FFC diet + diabetes, n = 14), FFC-DIA + S (FFC diet with extra salt + diabetes, n = 14). Blood and urine biomarkers, glomerular filtration rate (GFR), blood pressure (BP) and resistive index (RI) were evaluated after 6–7 months (T1) and 12–13 months (T2). Histology, electron microscopy and gene expression (excluding FFC-DIA + S) were evaluated at T2. All groups fed FFC-diet displayed obesity, increased GFR and RI, glomerulomegaly, mesangial expansion (ME) and glomerular basement membrane (GBM) thickening. Diabetes on top of FFC diet led to increased plasma glucose and urea and proteinuria and tended to exacerbate the glomerulomegaly, ME and GBM thickening. Four genes (CDKN1A, NPHS2, ACE, SLC2A1) were significantly deregulated in FFC and/or FFC-DIA compared to SD. No effects on BP were observed. Göttingen Minipigs fed FFC diet displayed some of the renal early changes seen in human obesity. Presence of diabetes on top of FFC diet exacerbated the findings and lead to changes resembling the early phases of human DN.

Melanocytes can de-differentiate into neural crest cell (NCC)- like states during metastatic melanoma progression. Here the authors compare DNA methylation profiles of NCCs and melanocytes, as well as primary and metastatic patient tissues and identify that DNA methylation changes of NR2F2 isoform 2 influence cell state transitions and melanoma metastatic spread.

Summary: Spin crossover (SCO) complexes, through their reversible spin transition under external stimuli, can work as switchable memory materials. Here, we present a protocol for the synthesis and characterization of a specific polyanionic iron SCO complex and its diluted systems. We describe steps for its synthesis and the determination of crystallographic structure of the SCO complex in diluted systems. We then detail a range of spectroscopic and magnetic techniques employed to monitor the spin state of the SCO complex in both diluted solid- and liquid-state systems.For complete details on the use and execution of this protocol, please refer to Galán-Mascaros et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Introduction Malaria in pregnancy is a major driver of maternal and infant mortality in sub-Saharan Africa. The WHO recommends the administration of intermittent preventive treatment with sulfadoxine pyrimethamine (IPTp-SP) at antenatal care (ANC) visits. Despite being a highly cost-effective strategy, IPTp-SP coverage and uptake remains low. A pilot project was conducted to assess the cost-effectiveness (CE) of community-based delivery of IPTp (C-IPTp) in addition to ANC delivery to increase IPTp uptake in the Democratic Republic of Congo (DRC), Madagascar (MDG), Mozambique (MOZ) and Nigeria (NGA).Methods Costs and CE estimates of C-IPTp were calculated according to two scenarios: (1) costs in ‘programmatic mode’ (ie, costs if C-IPTp was to be implemented by national health systems) and (2) costs from the pilot project. The effectiveness of C-IPTp was obtained through estimates of the averted disability-adjusted life-years (DALYs) associated with maternal clinical malaria and anaemia, low birth weight and neonatal mortality.Results Net incremental costs of C-IPTp ranged between US$6138–US$47 177 (DRC), US$5552–US$31 552 (MDG), US$10 202–US$53 221 (MOZ) and US$667–US$28 645 (NGA) per 1000 pregnant women, under scenarios (1) and (2), respectively. Incremental cost-effectiveness ratios (ICERs) ranged between US$15–US$119 in DRC, US$9–US$53 in MDG, US$104–US$543 in MOZ and US$2–US$66 in NGA per DALY averted, under scenarios (1) and (2), respectively. ICERs fall below the WHO recommended CE threshold based on the gross domestic product per capita.Conclusion Findings suggest that C-IPTp is a highly cost-effective intervention. Results can inform policy decisions on adopting and optimising effective interventions for preventing malaria in pregnancy.

The Wild Probes (WPs) are a set of hybrid tools for designers and researchers to facilitate multi-stakeholder co-design engagements within the forest. They support situated forestry future-making by helping the participants of a co-design process pay attention to, reflect on, ideate around, and document their forestry experiences in ways that can inspire contextually grounded forest-related ideation. Here we present the design and early use of the first iteration of the WPs. The WPs extend existing tools available to designers by adapting their underlying mechanisms to the idiosyncratic character of the forest. We designed them building on recent research on the methodological underpinnings of (co-)designing for and from the forest. The WPs run on affordable, widely accessible electronics and can easily be built with basic DIY skills and equipment. We thus invite others to replicate, enhance, and repurpose them. Overall, here we contribute a first step towards creating a collection of tools to support co-design that is situated in the forest. We hope other designers will find our proposals useful and contribute to growing the collection by creating new WPs of their own.