Combined Supplementation of Two Selenium Forms (Organic and Inorganic) and Iodine in Dairy Cows' Diet to Obtain Enriched Milk, Cheese, and Yogurt.

This study evaluated the effects of dietary supplementation in dairy cows with two Se forms (organic and inorganic) and I at the maximum levels permitted in the European Union, with the aim to obtain naturally enriched milk and derived products. A total of 20 Holstein Friesian cows in lactation were fed 2 diets for 64 days: a control diet with a supply of 0.57 mg of inorganic Se and 0.57 mg of I per kg of ration in dry matter (DM), and an experimental diet (SeI) with a supply of 0.34 mg of inorganic Se, 0.23 mg of organic Se, and 5.68 mg of I per kg of ration in DM. The SeI diet did not modify the performance or, in general, the metabolic profile of cows. Se and I levels in milk were affected by diet type and time of measurement (p < 0.01). Thus, a marked increase of both microminerals was evident between the beginning and the end of the test, when the SeI diet was administered. For Se, this increase ranged from 1.95 to 3.29 µg/100 g of milk; and for I, from 19.69 to 110.06 µg/100 g of milk. The SeI diet increased (p < 0.01) the Se and I content in the cheese, reaching levels of 16.4 µg/100 g for Se and 269.7 µg/100 g for I. An increase in I was observed in yogurt from the SeI diet (p < 0.001). The supplementation of two forms of Se and I in the cows' ration, at the levels evaluated, produced milk and dairy products enriched in these microelements without altering their quality parameters. However, a responsible intake of these products is necessary to avoid risks of deficiencies or excesses that could negatively affect the health of consumers.

T-reg transcriptomic signatures identify response to check-point inhibitors.

Regulatory T cells (Tregs) is a subtype of CD4+ T cells that produce an inhibitory action against effector cells. In the present work we interrogated genomic datasets to explore the transcriptomic profile of breast tumors with high expression of Tregs. Only 0.5% of the total transcriptome correlated with the presence of Tregs and only four transcripts, BIRC6, MAP3K2, USP4 and SMG1, were commonly shared among the different breast cancer subtypes. The combination of these genes predicted favorable outcome, and better prognosis in patients treated with checkpoint inhibitors. Twelve up-regulated genes coded for proteins expressed at the cell membrane that included functions related to neutrophil activation and regulation of macrophages. A positive association between MSR1 and CD80 with macrophages in basal-like tumors and between OLR1, ABCA1, ITGAV, CLEC5A and CD80 and macrophages in HER2 positive tumors was observed. Expression of some of the identified genes correlated with favorable outcome and response to checkpoint inhibitors: MSR1, CD80, OLR1, ABCA1, TMEM245, and ATP13A3 predicted outcome to anti PD(L)1 therapies, and MSR1, CD80, OLR1, ANO6, ABCA1, TMEM245, and ATP13A3 to anti CTLA4 therapies, including a subgroup of melanoma treated patients. In this article we provide evidence of genes strongly associated with the presence of Tregs that modulates the response to check point inhibitors.

NRN1 epistasis with BDNF and CACNA1C: mediation effects on symptom severity through neuroanatomical changes in schizophrenia.

The expression of Neuritin-1 (NRN1), a neurotrophic factor crucial for neurodevelopment and synaptic plasticity, is enhanced by the Brain Derived Neurotrophic Factor (BDNF). Although the receptor of NRN1 remains unclear, it is suggested that NRN1's activation of the insulin receptor (IR) pathway promotes the transcription of the calcium voltage-gated channel subunit alpha1 C (CACNA1C). These three genes have been independently associated with schizophrenia (SZ) risk, symptomatology, and brain differences. However, research on how they synergistically modulate these phenotypes is scarce. We aimed to study whether the genetic epistasis between these genes affects the risk and clinical presentation of the disorder via its effect on brain structure. First, we tested the epistatic effect of NRN1 and BDNF or CACNA1C on (i) the risk for SZ, (ii) clinical symptoms severity and functionality (onset, PANSS, CGI and GAF), and (iii) brain cortical structure (thickness, surface area and volume measures estimated using FreeSurfer) in a sample of 86 SZ patients and 89 healthy subjects. Second, we explored whether those brain clusters influenced by epistatic effects mediate the clinical profiles. Although we did not find a direct epistatic impact on the risk, our data unveiled significant effects on the disorder's clinical presentation. Specifically, the NRN1-rs10484320 x BDNF-rs6265 interplay influenced PANSS general psychopathology, and the NRN1-rs4960155 x CACNA1C-rs1006737 interaction affected GAF scores. Moreover, several interactions between NRN1 SNPs and BDNF-rs6265 significantly influenced the surface area and cortical volume of the frontal, parietal, and temporal brain regions within patients. The NRN1-rs10484320 x BDNF-rs6265 epistasis in the left lateral orbitofrontal cortex fully mediated the effect on PANSS general psychopathology. Our study not only adds clinical significance to the well-described molecular relationship between NRN1 and BDNF but also underscores the utility of deconstructing SZ into biologically validated brain-imaging markers to explore their mediation role in the path from genetics to complex clinical manifestation.

SARS-CoV-2 infection among psoriasis patients in Germany: Data from the German registries PsoBest and CoronaBest.

BACKGROUND: Limited data exist on the characteristics of SARS-CoV-2 infections in German patients with psoriasis or psoriasis arthritis (PsA). This study analyses COVID-19 prevalence and severity of symptoms in these patients. PATIENTS AND METHODS: Participants of the German registries PsoBest and CoronaBest were surveyed in February 2022. Descriptive analyses were conducted. RESULTS: 4,818 patients were included in the analysis, mean age of 56.4 years. Positive SARS-CoV-2 tests were reported by 737 (15.3%) patients. The most frequently reported acute symptoms were fatigue (67.3%), cough (58.8%), and headache (58.3%). Longer-lasting symptoms after COVID-19 were reported by 231 of 737 patients after the acute phase. For most patients (92.9%), systemic treatment for their psoriasis or PsA was not modified during the pandemic. Patients positively tested for SARS-CoV-2 were younger on average and had more often changes in the therapy of psoriasis than negatively tested patients (8.5% vs. 5.4%). CONCLUSIONS: In this cohort of patients with psoriasis or PsA undergoing systemic treatment, SARS-CoV-2 infections were common but less frequent than in the general German population. No risk signals for more severe COVID-19 or increased infection rates were observed in the patients. In addition, systemic treatments remained largely unchanged, so that no risks can be attributed to these therapies.

Oleogels for the ocular delivery of epalrestat: formulation, in vitro, in ovo, ex vivo and in vivo evaluation.

The ocular administration of lipophilic and labile drugs such as epalrestat, an aldose reductase inhibitor with potential for diabetic retinopathy treatment, demands the development of topical delivery systems capable of providing sufficient ocular bioavailability. The aim of this work was to develop non-aqueous oleogels based on soybean oil and gelators from natural and sustainable sources (ethyl cellulose, beeswax and cocoa butter) and to assess their reproducibility, safety and efficiency in epalrestat release and permeation both ex vivo and in vivo. Binary combinations of gelators at 10% w/w resulted in solid oleogels (oleorods), while single gelator oleogels at 5% w/w remained liquid at room temperature, with most of the oleogels displaying shear thinning behavior. The oleorods released up to 4 µg epalrestat per mg of oleorod in a sustained or burst pattern depending on the gelator (approx. 10% dose in 24 h). The HET-CAM assay indicated that oleogel formulations did not induce ocular irritation and were safe for topical ocular administration. Corneal and scleral ex vivo assays evidenced the permeation of epalrestat from the oleorods up to 4 and 2.5 µg/cm2 after six hours, respectively. Finally, the capacity of the developed oleogels to sustain release and provide significant amounts of epalrestat to the ocular tissues was demonstrated in vivo against aqueous-based niosomes and micelles formulations loaded with the same drug concentration. Overall, the gathered information provides valuable insights into the development of oleogels for ocular drug delivery, emphasizing their safety and controlled release capabilities, which have implications for the treatment of diabetic neuropathy and other ocular conditions.

Exploring the viral landscape of saffron through metatranscriptomic analysis.

Saffron (Crocus sativus L.), a historically significant crop valued for its nutraceutical properties, has been poorly explored from a phytosanitary perspective. This study conducted a thorough examination of viruses affecting saffron samples from Spanish cultivars, using high-throughput sequencing alongside a systematic survey of transcriptomic datasets from Crocus sativus at the Sequence Read Archive. Our analysis unveiled a broad diversity and abundance, identifying 17 viruses across the 52 analyzed libraries, some of which were highly prevalent. This includes known saffron-infecting viruses and previously unreported ones. In addition, we discovered 7 novel viruses from the Alphaflexiviridae, Betaflexiviridae, Potyviridae, Solemoviridae, and Geminiviridae families, with some present in libraries from various locations. These findings indicate that the saffron-associated virome is more complex than previously reported, emphasizing the potential of phytosanitary analysis to enhance saffron productivity.

Bacterial community of ticks (Acari: Ixodidae) and mammals from Arauca, Colombian Orinoquia.

Ticks are obligate hematophagous ectoparasites of vertebrates and are relevant worldwide due to the number of bacterial and other pathogens they can transmit. To date, the knowledge about the microorganisms that ticks harbor and transmit to their hosts is incipient. In this study, 24 samples of mammals belonging to four taxonomic orders and ticks of the genera Amblyomma and Rhipicephalus from the Orinoco region of Colombia were analyzed to described and compare the bacterial microbiome. Genetic extraction was performed, and the V3-V4 region of the 16S rRNA gene was amplified by PCR. Libraries were created, and those samples with adequate quality indices were sequenced using Illumina MiSeq technology. Bacterial taxonomic assignment analyses were conducted through Amplicon Sequence Variants (ASVs) and Operational Taxonomic Units (OTUs). The results correspond to 16 samples that passed the quality filters, with 3218 OTUs (415 families). Although a considerable number of unknown bacteria was found, Enterobacteriaceae, Beijerinckiaceae, Moraxellaceae, and Burkholderiaceae are the most prevalent families, and the presence of the genera Coxiella, Escherichia-Shigella, Enterobacter, which can harbor pathogenic species was confirmed. In individuals of Amblyomma mixtum found actively feeding on Hydrochoerus hydrochaeris, bacteria of the genera Escherichia-Shigella and Enterobacter were documented. Similarly, Rhipicephalus microplus found actively feeding on Odocoileus virginianus cariacou shared Escherichia-Shigella. Ralstonia was shared among the blood samples of H. hydrochaeris, while Anaplasma and Eubacterium were shared in blood and liver samples of O. v. cariacou. Shared bacteria between A. mixtum and R. microplus included Bacillus, Coxiella, and Escherichia-Shigella. The results highlight the need of additional studies in other natural regions of Colombia and other American countries where tick-borne diseases have been detected. Likewise, the recorded data are the first at the level of bacterial communities in ticks of the family Ixodidae and provide valuable knowledge for the understanding host-tick and pathogen interactions.

Editorial for the Special Issue Titled "Design of Polymeric Hydrogels Biomaterials".

Hydrogels have attracted great interest in the biomedical applications field in recent years [...].

Epigenomic and transcriptomic persistence of heat stress memory in strawberry (Fragaria vesca).

BACKGROUND: In plants, epigenetic stress memory has so far been found to be largely transient. Here, we wanted to assess the heritability of heat stress-induced epigenetic and transcriptomic changes following woodland strawberry (Fragaria vesca) reproduction. Strawberry is an ideal model to study epigenetic inheritance because it presents two modes of reproduction: sexual (self-pollinated plants) and asexual (clonally propagated plants named daughter plants). Taking advantage of this model, we investigated whether heat stress-induced DNA methylation changes can be transmitted via asexual reproduction. RESULTS: Our genome-wide study provides evidence for stress memory acquisition and maintenance in F. vesca. We found that specific DNA methylation marks or epimutations are stably transmitted over at least three asexual generations. Some of the epimutations were associated with transcriptional changes after heat stress. CONCLUSION: Our findings show that the strawberry methylome and transcriptome respond with a high level of flexibility to heat stress. Notably, independent plants acquired the same epimutations and those were inherited by their asexual progenies. Overall, the asexual progenies can retain some information in the genome of past stresses encountered by their progenitors. This molecular memory, also documented at the transcriptional level, might be involved in functional plasticity and stress adaptation. Finally, these findings may contribute to novel breeding approaches for climate-ready plants.

Perception and Impact of COVID-19 Pandemic in Psoriasis Patients: Data from the German PsoBest and the CoronaBest Registries.

Background: Limited data are available characterizing the impact of the SARS-CoV-2 pandemic on psoriasis care for patients in Germany. Objective: To analyze patient perception and impact of the pandemic on well-being and psoriasis management of German patients with moderate-to-severe psoriasis or psoriasis arthritis under systemic therapies. Methods: The CoronaBest registry captures events of SARS-CoV-2 infections and analyzes the impact of the pandemic on patients with psoriasis or psoriasis arthritis. In June 2020, and independently in February 2022, patients with psoriasis or psoriasis arthritis received a standardized questionnaire for current treatment, protective measures, well-being, and individual risks for COVID-19, among others. Results: Included were 4,194 patients in 2020 (mean age of 47.7 years and 41.8% women) and 4,818 patients in 2022 (mean age of 56.4 and 42.9% women). Treatment discontinuations were observed in 2.7% and 1.7% of patients in 2020 and 2022, respectively. In the vast majority of the cases (>92%), no additional measures were taken concerning the management of psoriasis treatments in either 2020 or 2022. Those patients with changes reported most frequently: telephone calls instead of face-to-face visits (80.2%, in 2020 vs 40.5% in 2022) or more frequent controls (27.1%, 2020 vs 22.0%, 2022). A majority (66.7%, 2020, and 70.6%, 2022) did not perceive the virus as a considerable threat. The proportion of patients feeling well informed about COVID-19 by physicians increased from 42.6% in 2020 to 51.8% in 2022. About 81.1% of patients in 2020 and 67.5% in 2022 stated that their overall personal condition was not affected due to the pandemic. Physicians attributed no special risk of contracting SARS-CoV-2 in most of the patients. Conclusion: A high rate of systemic treatment persistence and awareness of risks and protective measures indicate that health care for psoriasis largely followed current national and international recommendations during the COVID-19 pandemic.

Dysregulation of Plasma Growth Factors and Chemokines in Cocaine Use Disorder: Implications for Dual Diagnosis with Schizophrenia and Antisocial Personality Disorder in an Exploratory Study.

INTRODUCTION: Dual diagnosis in individuals with cocaine use disorders (CUDs) presents a mental health challenge marked by an increased susceptibility to disabling morbidities and premature mortality. Despite extensive research on depression and anxiety, other prevalent comorbidities, such as psychotic and personality disorders, have received less attention. This study explores inflammation-related mediators as potential biomarkers for CUD and dual diagnosis with schizophrenia (SCZ) or antisocial personality disorder (APD). METHODS: This exploratory study included 95 participants, comprising 40 healthy subjects and 55 abstinent patients with CUD. Lifetime CUD was diagnosed either as single diagnosis (CUD group, N = 25) or as a dual diagnosis (DD group. N = 30) with SCZ (CUD+SCZ subgroup) or APD (CUD+APD subgroup). Participants were clinically assessed, and the plasma concentrations of growth factors (i.e., G-CSF, BDNF, and VEGF-A) and chemokines (i.e., CCL11/eotaxin-1, CCL2/MCP-1, and CXCL12/SDF-1) were determined and log(10)-transformed for analysis. RESULTS: Growth factors and chemokines were dysregulated by CUD and psychiatric diagnoses. Specifically, patients in the CUD group exhibited significantly lower concentrations of G-CSF and CCL11/eotaxin-1 than the control group. In contrast, the DD group showed significantly higher concentrations of all analytes than both the CUD and control groups. Additionally, no differences in these analytes were observed between the CUD+SCZ and CUD+APD subgroups within the DD group. Regarding cocaine-related variables, significant associations were identified in the CUD group: an inverse correlation between the age at first cocaine use and the concentrations of BDNF and CCL2/MCP-1; and a positive correlation between the duration of the cocaine abstinence and the concentrations of BDNF and CCL11/eotaxin-1. Lastly, a logistic regression model incorporating all these analytes demonstrated high discriminatory power in distinguishing patients with CUD alone from those with dual diagnosis. CONCLUSIONS: Individuals with dual diagnosis of CUD exhibit elevated concentrations of growth factors and chemokines, distinguishing them from those with CUD alone. It is unclear whether the differences in these inflammatory mediators are specific to the presence of SCZ and APD. The study highlights potential biomarkers and associations, providing valuable insights into the intricate interplay of CUD and psychiatric disorders to enhance clinical diagnosis and therapeutics.

Evaluation of a HIV screening strategy in the hospital setting to reduce undiagnosed infection.

INTRODUCTION: In Spain, half of new HIV diagnoses are late and a significant proportion of people living with HIV have not yet been diagnosed. Our aim was to evaluate the effectiveness of an automated opportunistic HIV screening strategy in the hospital setting. METHODS: Between April 2022 and September 2023, HIV testing was performed on all patients in whom a hospital admission analytical profile, a pre-surgical profile and several pre-designed serological profiles (fever of unknown origin, pneumonia, mononucleosis, hepatitis, infection of sexual transmission, rash, endocarditis and myopericarditis) was requested. A circuit was started to refer patients the specialists. RESULTS: 6407 HIV tests included in the profiles were performed and 18 (0.3%) new cases were diagnosed (26.4% of diagnoses in the health area). Five patients were diagnosed by hospital admission and pre-surgery profile and 13 by a serological profile requested for indicator entities (fever of unknown origin, sexually transmitted infection, mononucleosis) or possibly associated (pneumonia) with HIV occult infection. Recent infection was documented in 5 (27.8%) patients and late diagnosis in 9 (50.0%), of whom 5 (55.5%) had previously missed the opportunity to be diagnosed. CONCLUSIONS: This opportunistic screening was profitable since the positive rate of 0.3% is cost-effective and allowed a quarter of new diagnoses to be made, so it seems a good strategy that contributes to reducing hidden infection and late diagnosis.

Health Benefits of High Voltage Electrostatic Field Processing of Fruits and Vegetables.

High voltage electrostatic field processing (HVEF) is a food preservation procedure frequently used to produce healthy minimally processed fruits and vegetables (F&V) as it reduces the growth of microorganisms and activates or inhibits various enzymes, thus retarding their natural ripening while preserving and even enhancing native nutritional quality and sensory characteristics. HVEF is one of the various nonthermal processing technology (NTPT) regarded as abiotic stress that can activate the antioxidant system of F&V and can also inhibith spoilage enzymes as, polyphenol oxidase (PPO), lipoxygenase (LOX), pectin methylesterase (PME), polygalacturonase (PG), cellulase (Cel), ß-xylosidase, xyloglucan and endotransglycosylase/hydrolase, bringing positive effect on hardness, firmness, colour attributes, electric conductivity, antioxidant compounds, microstructure and decreasing electrolyte leakage (EL), malondialdehyde (MDA) contents and browning degree. This technique can also increase the contents of fructose, glucose, and sucrose and decrease the production of CO2 and H2O2. Additionally, it has been reported that HVEF could be used with other treatments, such as modified atmosphere packaging (MAP) and acidic electrolyzed water (AEW) treatment, to enhance its effects. Future works should deepen on elucidating the activation of the antioxidant systems by applying HVEF of critical enzymes related to the synthesis pathways of phenolic compounds (PC) and carotenoids (Car). Holistic approaches to the effects of HVEF on metabolism based on systems biology also need to be studied by considering the overall biochemical, physical, and process engineering related aspects of this technique.

A sterilizable platform based on crosslinked xanthan gum for controlled-release of polymeric micelles: Ocular application for the delivery of neuroprotective compounds to the posterior eye segment.

TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate) polymeric micelles show interesting properties for ocular administration thanks to their solubilization capability, nanometric size and tissue penetration ability. However, micelles formulations are generally characterized by low viscosity, poor adhesion and very short retention time at the administration site. Therefore, the idea behind this work is the preparation and characterization of a crosslinked film based on xanthan gum that contains TPGS micelles and is capable of controlling their release. The system was loaded with melatonin and cyclosporin A, neuroprotective compounds to be delivered to the posterior eye segment. Citric acid and heating at different times and temperatures were exploited as crosslinking approach, giving the possibility to tune swelling, micelles release and drug release. The biocompatibility of the platform was confirmed by HET-CAM assay. Ex vivo studies on isolated porcine ocular tissues, conducted using Franz cells and two-photon microscopy, demonstrated the potential of the xanthan gum-based platform and enlightened micelles penetration mechanism. Finally, the sterilization step was approached, and a process to simultaneously crosslink and sterilize the platform was developed.

Warm winters are associated to more intense West Nile virus circulation in southern Spain.

West Nile virus (WNV) is the most widely distributed mosquito-borne flavivirus in the world. This flavivirus can infect humans causing in some cases a fatal neurological disease and birds are the main reservoir hosts. WNV is endemic in Spain, and human cases have been reported since 2004. Although different studies analyse how climatic conditions can affect the dynamics of WNV infection, very few use long-term datasets. Between 2003 and 2020 a total of 2,724 serum samples from 1,707 common coots (Fulica atra) were analysed for the presence of WNV-specific antibodies. Mean (SD) annual seroprevalence was 24.67% (0.28) but showed high year-to-year variations ranging from 5.06% (0.17) to 68.89% (0.29). Significant positive correlations (p < 0.01) were observed between seroprevalence and maximum winter temperature and mean spring temperature. The unprecedented WNV outbreak in humans in the south of Spain in 2020 was preceded by a prolonged period of escalating WNV local circulation. Given current global and local climatic trends, WNV circulation is expected to increase in the next decades. This underscores the necessity of implementing One Health approaches to reduce the risk of future WNV outbreaks in humans. Our results suggest that higher winter and spring temperatures may be used as an early warning signal of more intense WNV circulation among wildlife in Spain, and consequently highlight the need of more intense vector control and surveillance in human inhabited areas.

Comparison between different conditions for the incorporation of foreign proteins into Autographa californica multiple polyhedrovirus polyhedra for biotechnological purposes.

The occlusion bodies of Autographa californica multiple nucleopolyhedrovirus are proteinaceous formations with significant biotechnological potential owing to their capacity to integrate foreign proteins through fusion with polyhedrin, their primary component. However, the strategy for successful heterologous protein inclusion still requires further refinement. In this study, we conducted a comparative assessment of various conditions to achieve the embedding of recombinant proteins within polyhedra. Two baculoviruses were constructed: AcPHGFP (polh+), with GFP as a fusion to wild type (wt) polyhedrin and AcΔPHGFP (polh+), with GFP fused to a fragment corresponding to amino acids 19 to 110 of polyhedrin. These baculoviruses were evaluated by infecting Sf9 cells and stably transformed Sf9, Sf9POLH, and Sf9POLHE44G cells. The stably transformed cells contributed another copy of wt or a mutant polyhedrin, respectively. Polyhedra of each type were isolated and characterized by classical methods. The fusion PHGFP showed more-efficient incorporation into polyhedra than ΔPHGFP in the three cell lines assayed. However, ΔPHGFP polyhedron yields were higher than those of PHGFP in Sf9 and Sf9POLH cells. Based on an integral analysis of the studied parameters, it can be concluded that, except for the AcΔPHGFP/Sf9POLHE44G combination, deficiencies in one factor can be offset by improved performance by another. The combinations AcPHGFP/Sf9POLHE44G and AcΔPHGFP/Sf9POLH stand out due to their high level of incorporation and the large number of recombinant polyhedra produced, respectively. Consequently, the choice between these approaches becomes dependent on the intended application.

Association between anti-PL7 antibodies and increased fibrotic component in patients with antisynthetase syndrome and interstitial lung disease: a cross-sectional study.

OBJECTIVE: To evaluate whether anti-PL7 and anti-PL12 autoantibodies are associated with a greater extent of the fibrotic component of ILD in ASSD patients. METHODS: Patients with ILD-ASSD who were positive for one of the following autoantibodies: anti-Jo1, anti-PL7, anti-PL12, and anti-EJ were included. Clinical manifestations, CPK levels, pulmonary function tests, and HCRT assessments were prospectively collected according to the Goh index. The fibrotic, inflammatory, and overall extension of the Goh index and DLCO were assessed by multiple linear analyses and compared between ASSD antibody subgroups. RESULTS: Sixty-six patients were included; 17 were positive for anti-Jo1 (26%), 17 for anti-PL7 (26%), 20 for anti-PL12 (30%), and 9 (14%) for anti-EJ. Patients with anti-PL7 and anti-PL12 had a more extensive fibrotic component than anti-Jo1. Anti-PL7 patients had a 7.9% increase in the fibrotic extension (cß = 7.9; 95% CI 1.863, 13.918), and the strength of the association was not modified after controlling for sex, age, and time of disease evolution (aß = 7.9; 95% CI 0.677, 15.076) and also was associated with an increase in ILD severity after adjusting for the same variables, denoted by a lower DLCO (aß = - 4.47; 95% CI - 8.919 to - 0.015). CONCLUSIONS: Anti-PL7-positive ASSD patients had more extensive fibrosis and severe ILD than the anti-Jo1 subgroup. This information is clinically useful and has significant implications for managing these patients, suggesting the need for early consideration of concurrent immunosuppressive and antifibrotic therapy.

Modelling the spatial risk of malaria through probability distribution of Anopheles maculipennis s.l. and imported cases.

Malaria remains one of the most important infectious diseases globally due to its high incidence and mortality rates. The influx of infected cases from endemic to non-endemic malaria regions like Europe has resulted in a public health concern over sporadic local outbreaks. This is facilitated by the continued presence of competent Anopheles vectors in non-endemic countries.We modelled the potential distribution of the main malaria vector across Spain using the ensemble of eight modelling techniques based on environmental parameters and the Anopheles maculipennis s.l. presence/absence data collected from 2000 to 2020. We then combined this map with the number of imported malaria cases in each municipality to detect the geographic hot spots with a higher risk of local malaria transmission.The malaria vector occurred preferentially in irrigated lands characterized by warm climate conditions and moderate annual precipitation. Some areas surrounding irrigated lands in northern Spain (e.g. Zaragoza, Logroño), mainland areas (e.g. Madrid, Toledo) and in the South (e.g. Huelva), presented a significant likelihood of A. maculipennis s.l. occurrence, with a large overlap with the presence of imported cases of malaria.While the risk of malaria re-emergence in Spain is low, it is not evenly distributed throughout the country. The four recorded local cases of mosquito-borne transmission occurred in areas with a high overlap of imported cases and mosquito presence. Integrating mosquito distribution with human incidence cases provides an effective tool for the quantification of large-scale geographic variation in transmission risk and pinpointing priority areas for targeted surveillance and prevention.