Rapid Analytical Method for Quantification of Gamma-Hydroxybutyrate (GHB) in Hair by UPLC-MS/MS.

Gamma-hydroxybutyrate (GHB), an endogenous compound related to the neurotransmitter gamma-aminobutyric acid (GABA), is used as a therapeutic and recreational drug and as a "weapon" in drug-facilitated crimes. The very short window of detection of GHB in conventional matrices (blood and urine) makes necessary the use of alternative matrices like hair. Hair has a long window of detection and the possibility to perform segmental analysis, which makes it very useful for proving GHB intake. In the present work, a method for quantification of GHB in hair was developed and validated. Hair (10 mg) was washed twice with dichloromethane and then incubated at room temperature with Milli-Q water in an ultrasound bath for 30 min. Analysis was performed by UPLC-MS/MS using a CORTECS UPLC HILIC (1.6 µm), 2.1 × 100-mm column, and a gradient with acetonitrile and ammonium acetate (10 mM) at pH 6.0, with a total run-time of 10 min. For detection, a triple quadrupole mass spectrometer in ESI negative mode was used. The method was validated, following the criteria established in the "AAFS Standard Practices for Method Validation in Forensic Toxicology" guideline, obtaining satisfactory results for linearity (0.5-50 ng/mg), accuracy (95.0%-103.2%), imprecision (< 10.2%), limit of detection (0.1 ng/mg) and quantification (0.5 ng/mg), exogenous selectivity (no interferences), matrix effect (less than -44.2%), extraction efficiency (> 86.4%), process efficiency (> 46.1%), and autosampler stability (< 4.3%). The method was used for the analysis of 26 authentic hair samples, 25 from non-drug users, obtaining values between < LOQ and 6.25 ng/mg of endogenous GHB and 1 from a former GHB chronic user to prove abstinence.

Prevalence and anti-microbial resistance of Staphylococcus spp. isolated from the environment and veterinary personnel in a Spanish veterinary teaching hospital.

Methicillin-resistant Staphylococcus (MRS) bacteria, including methicillin-resistant S. aureus and methicillin-resistant S. pseudintermedius (MRSP), pose a significant threat in veterinary medicine, given their potential for zoonotic transmission and their implications for companion animals and humans' health. This study aimed to assess the prevalence of MRS and anti-microbial resistance patterns at a university clinical hospital in Madrid, Spain. Samples were collected from both the environment and hospital staff at Veterinary Clinical Hospital of Alfonso X el Sabio University. Anti-microbial susceptibility assays, molecular detection of mecA gene and genetic relationships among the identified bacterial strains were performed. The study revealed an MRS prevalence of 1.50% in environmental samples, with MRSP accounting for 0.75% of the cases. Genetically related MRSP strains were found in different hospital areas. Among hospital staff, there was a MRS prevalence of 14.03%, including S. pseudintermedius and S. epidermidis strains. Antibiogram tests revealed multi-drug resistance among MRSP strains. Additionally, methicillin-resistant coagulase-negative staphylococci were isolated, suggesting potential cross-species transmission. This study underscores the presence of MRS in a veterinary clinical hospital, highlighting the significance of infection control through the implementation of protective measures, stringent hygiene practices among personnel and in the environment and responsible use of antibiotics. Further research is necessary to assess MRS incidence in animal patients and explore geographical variations, enhancing our understanding of MRS in veterinary medicine and addressing its challenges.

HIV-1-DNA/RNA and immunometabolism in monocytes: contribution to the chronic immune activation and inflammation in people with HIV-1.

BACKGROUND: Among people living with HIV-1 (PHIV), immunological non-responders (INR) experience incomplete immune recovery despite suppressive antiretroviral treatment (ART), facing more severe non-AIDS events than immunological responders (IR) due to higher chronic immune activation and inflammation (cIA/I). We analyzed the HIV-1 reservoir and immunometabolism in monocytes as a source of cIA/I. METHODS: Cross-sectional study in which 110 participants were enrolled: 25 treatment-naïve; 35 INR; 40 IR; and 10 healthy controls. Cell-associated HIV-1-DNA (HIV-DNA) and -RNA (HIV-RNA) were measured in FACS-isolated monocytes using digital droplet PCR. Intact, 5' deleted, and 3' deleted proviruses were quantified by the intact proviral DNA assay. Systemic inflammation, monocyte immunophenotype, and immunometabolism were characterized by immunoassays, flow cytometry, and real-time cellular bioenergetics measurements, respectively. FINDINGS: Monocytes from INR harbor higher HIV-RNA and HIV-DNA levels than IR. HIV-RNA was found in 14/21 treatment-naïve [2512 copies/106 TBP (331-4666)], 17/33 INR [240 (148-589)], and 15/28 IR [144 (15-309)], correlating directly with sCD163, IP-10, GLUT1high cells and glucose uptake, and inversely with the CD4+/CD8+ ratio. HIV-DNA was identified in all participants with detectable HIV-RNA, with intact provirus in 9/12 treatment-naïve [13 copies/106 monocytes (7-44)], 8/14 INR [46 (18-67)], and 9/13 IR [9 (7-24)]. INR presented glucose metabolism alterations and mitochondrial impairment; decreased coupling efficiency and BHI, and increased mitochondrial dysfunction inversely correlating with the CD4+/CD8+ ratio. INTERPRETATION: HIV-RNA, more than HIV-DNA, in monocytes and their altered metabolism are factors associated with the higher cIA/I that characterize INR. FUNDING: This work was supported by the European Regional Development Fund, ISCIII, grant PI20/01646. Other funding sources: Instituto de Salud Carlos III through the Subprogram Miguel Servet (CP19/00159) to AGV, PFIS contracts (FI19/00304) to EMM, (FI21/00165) to ASA, and (FI19/00083) to CGC, and a mobility grant (MV21/00103) to EMM, from the Ministerio de Ciencia e Innovación, Spain. AJM was granted by a CSL Centenary Award.

The persistence of low CD4/CD8 ratio in chronic HIV-infection, despite ART suppression and normal CD4 levels, is associated with pre-therapy values of inflammation and thymic function.

BACKGROUND: Persistence of a low CD4/CD8 ratio is associated with an increased morbimortality in people living with HIV (PLWH) under effective antiretroviral therapy. We aimed to explore the immunological significance of a persistently low CD4/CD8 ratio, even despite normal CD4 levels, and assess whether these features vary from those associated to a low nadir-CD4, another well-established predictor of disease progression. METHODS: CD4-recovered PLWH were classified by CD4/CD8 ratio after three-years of ART (viral suppression, CD4≥500; R < 0.8, n = 24 and R > 1.2, n = 28). sj/ß-TRECs ratio and inflammatory-related markers were quantified. PBMCs were immunophenotyped by CyTOF and functionally characterized by ELISPOT. Subjects were also reclassified depending on nadir-CD4 (N ≤ 350/N > 350). RESULTS: R < 0.8 showed a differential inflammatory profile compared to R > 1.2 (increased ß2-microglobulin, D-dimers and IP-10 before ART). R < 0.8 presented lower baseline thymic function, being inversely correlated with post-ART inflammation. R < 0.8 at follow-up showed most alterations in CD8 subsets (increasing frequency and exhibiting a senescent phenotype [e.g., CD57+, CD95+]) and enhanced T-cell IFNγ/IL-2 secretion. However, comparing N ≤ 350 to N > 350, the main features were altered functional markers in CD4 T-cells, despite no differences in maturational subsets, together with a restricted T-cell cytokine secretion pattern. CONCLUSION: Persistence of low CD4/CD8 ratio in successfully-treated PLWH, with normal CD4 counts, is associated with baseline inflammation and low thymic function, and it features post-therapy alterations specific to CD8 T-cells. Differently, subjects recovered from low nadir-CD4 in this setting feature post-therapy alterations on CD4 T-cells. Hence, different mechanisms of disease progression could underlie these biomarkers, potentially requiring different clinical approaches.

Integrating the water-energy-food nexus and LCA + DEA methodology for sustainable fisheries management: A case study of Cantabrian fishing fleets.

The fishing sector constitutes an important source of economic revenue in northern Spain. In this context, various research studies have focused on the application of the five-step Life Cycle Assessment (LCA) and Data Envelopment Analysis (DEA) methodology to quantify environmental impacts of fishing systems. However, some of them have used environmental indicators that focus on individual environmental issues, hindering the goal of achieving integrated resource management. Therefore, in this study, the Water-Energy-Food (WEF) Nexus is employed as an integrative perspective that considers the synergies and trade-offs between carbon footprint, energy requirements, and water demand. The main objective of this study is to evaluate the operational efficiency and environmental impacts of Cantabrian fishing fleets. To this end, the combined use of LCA and DEA, along with the WEF Nexus, was applied to the Cantabrian purse seine fleet. DEA matrices were generated using the LCA-derived WEF nexus values as inputs to calculate efficiency scores for each vessel. Subsequently, based on the efficiency projections provided by the DEA model, a new impact assessment was performed to understand the eco-efficiency and potential environmental benefits of operating at higher levels of efficiency within this fleet. The average efficiency of the fleet was above 60 %. Inefficient units demonstrated a greater potential to reduce their environmental impacts (up to 65 %) by operating according to efficiency projections. Furthermore, the results revealed a strong dependence of environmental impacts on one of the operational inputs, i.e., fuel consumption. These findings highlight the significance of embracing holistic approaches that combine technical, economic, and social factors to achieve a sustainable balance in fisheries systems. In this regard, the five-step LCA + DEA method applied in conjunction with the WEF Nexus emerged as a suitable tool for measuring operational and environmental objectives.

Long-term effects on immunological, inflammatory markers, and HIV-1 reservoir after switching to a two-drug versus maintaining a three-drug regimen based on integrase inhibitors.

Objective: To compare the long-term effects on immune parameters, inflammation, and HIV-1 reservoir after switching to a two-drug (2DR) versus maintaining an integrase inhibitor (InSTI)-based three-drug regimen (3DR). Methods: Cross-sectional study in which HIV-1 treatment-naïve people started and maintained an InSTI-based 3DR or, at different times, switched to 2DR (dolutegravir or darunavir/cobicistat + lamivudine). CD4+ and CD8+ T-cell activation and exhaustion, plasma concentrations of hs-CRP, D-dimer, P-selectin, IL-1ß, IL-6, TNF-α, IFN-γ, IP-10, sTNFR-I/II, MIP-1α/ß, I-FABP, LBP, sCD14, sCD163, MCP-1, and cellular-associated HIV-1-DNA and -RNA were quantified by flow cytometry, different immunoassays, and droplet digital PCR, respectively. The U de Mann-Whitney test evaluated differences between 3DR and 2DR. Immune recovery was evaluated using a general linear model for repeated measures adjusted for different co-variables. Results: Fifty participants per group were included. The median time on 3DR was 82 months for the 3DR group and 30 months for the 2DR group, after which it switched to 2DR for a median of 57 months. We did not find differences between both groups in any of the parameters analyzed. Specifically, some values in 3DR and 2DR were hs-CRP, 0.92 mg/L (0.45-2.23) vs. 1.23 (0.61-2.38); D-dimer, 190.0 µg/L (150.0-370.0) vs. 190.0 (150.0-397.5); IL-6, 2.8 pg/mL (1.3-5.3) vs. 3.2 (2.1-4.7); sCD14, 4.5 ng/mL (3.3-6.2) vs. 5.0 (3.6-6.1), respectively, all p ≥ 0.399. Conclusion: In the long term, switching to 2DR does not negatively affect immunologic parameters, inflammatory markers, or HIV-1 reservoir. Clinical trial registration: identifier NCT04076423.

Vedolizumab and ART in recent HIV-1 infection unveil the role of α4ß7 in reservoir size.

BACKGROUNDWe evaluated the safety and viral rebound, after analytical treatment interruption (ATI), of vedolizumab and ART in recent HIV-1 infection. We used this model to analyze the effect of α4ß7 on the HIV-1 reservoir size.METHODSParticipants started ART with monthly vedolizumab infusions, and ATI was performed at week 24. Biopsies were obtained from ileum and cecum at baseline and week 24. Vedolizumab levels, HIV-1 reservoir, flow cytometry, and cell-sorting and antibody competition experiments were assayed.RESULTSVedolizumab was safe and well tolerated. No participant achieved undetectable viremia off ART 24 weeks after ATI. Only a modest effect on the time to achieve more than 1,000 HIV-1 RNA copies/mL and the proportion of participants off ART was observed, being higher in the vedolizumab group compared with historical controls. Just before ATI, α4ß7 expression was associated with HIV-1 DNA and RNA in peripheral blood and with PD1 and TIGIT levels. Importantly, a complete blocking of α4ß7 was observed on peripheral CD4+ T cells but not in gut (ileum and cecum), where α4ß7 blockade and vedolizumab levels were inversely associated with HIV-1 DNA.CONCLUSIONOur findings support α4ß7 as an important determinant in HIV-1 reservoir size, suggesting the complete α4ß7 blockade in tissue as a promising tool for HIV-cure combination strategies.TRIAL REGISTRATIONClinicalTrials.gov NCT03577782.FUNDINGThis work was supported by the Instituto de Salud Carlos III (Fondo Europeo de Desarrollo Regional, "a way to make Europe," research contracts FI17/00186 and FI19/00083 and research projects PI18/01532, PI19/01127, PI22/01796), Conserjería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía (research projects P20/00906), the Red Temática de Investigación Cooperativa en SIDA (RD16/0025/0020), and the Spanish National Research Council.

Characterization and modulation of voltage-gated potassium channels in human lymphocytes in schizophrenia.

BACKGROUND: It is known that the immune system is dysregulated in schizophrenia, having a state similar to chronic neuroinflammation. The origin of this process is unknown, but it is known that T and B lymphocytes, which are components of the adaptive immune system, play an important role in the pathogenic mechanisms of schizophrenia. METHODS: We analysed the membrane of PBMCs from patients diagnosed with schizophrenia through proteomic analysis (n = 5 schizophrenia and n = 5 control). We found the presence of the Kv1.3 voltage-gated potassium channel and its auxiliary subunit ß1 (KCNAB1) and ß2 (KCNAB2). From a sample of 90 participants, we carried out a study on lymphocytes with whole-cell patch-clamp experiments (n = 7 schizophrenia and n = 5 control), western blot (n = 40 schizophrenia and n = 40 control) and confocal microscopy to evaluate the presence and function of different channels. Kv in both cells. RESULTS: We demonstrated the overexpression of Kv1.1, Kv1.2, Kv1.3, Kv1.6, Kv4.2, Kv4.3 and Kv7.2 channels in PBMCs from patients with schizophrenia. This study represents a groundbreaking exploration, as it involves an electrophysiological analysis performed on T and B lymphocytes from patients diagnosed of schizophrenia compared to healthy participants. We observed that B lymphocytes exhibited an increase in output current along with greater peak current amplitude and voltage conductance curves among patients with schizophrenia compared with healthy controls. CONCLUSIONS: This study showed the importance of the B lymphocyte in schizophrenia. We know that the immune system is altered in schizophrenia, but the physiological mechanisms of this system are not very well known. We suggest that the B lymphocyte may be relevant in the pathophysiology of schizophrenia and that it should be investigated in more depth, opening a new field of knowledge and possibilities for new treatments combining antipsychotics and immunomodulators. The limitation is that all participants received antipsychotic medication, which may have influenced the differences observed between patients and controls. This implies that more studies need to be done where the groups can be separated according to the antipsychotic drug.

Fronto-thalamic networks and the left ventral thalamic nuclei play a key role in aphasia after thalamic stroke.

Thalamic aphasia results from focal thalamic lesions that cause dysfunction of remote but functionally connected cortical areas due to language network perturbation. However, specific local and network-level neural substrates of thalamic aphasia remain incompletely understood. Using lesion symptom mapping, we demonstrate that lesions in the left ventrolateral and ventral anterior thalamic nucleus are most strongly associated with aphasia in general and with impaired semantic and phonemic fluency and complex comprehension in particular. Lesion network mapping (using a normative connectome based on fMRI data from 1000 healthy individuals) reveals a Thalamic aphasia network encompassing widespread left-hemispheric cerebral connections, with Broca's area showing the strongest associations, followed by the superior and middle frontal gyri, precentral and paracingulate gyri, and globus pallidus. Our results imply the critical involvement of the left ventrolateral and left ventral anterior thalamic nuclei in engaging left frontal cortical areas, especially Broca's area, during language processing.

Usefulness of a predictive model to hospitalize patients with low-risk community-acquired pneumonia.

INTRODUCTION: A high proportion of patients with low-risk community-acquired pneumonia (CAP) (classes I-III of the Pneumonia Severity Index) are hospitalized. The purpose of this study was to determine whether validated severity scales are used in clinical practice to make admission decisions, identify the variables that influence this decision, and evaluate the potential predictive value of these variables. MATERIALS AND METHODS: A prospective, observational study of patients ≥ 18 years of age with a diagnosis of low-risk CAP hospitalized or referred from the Emergency Department to outpatient consultations. A multivariate logistic regression predictive model was built to predict the decision to hospitalize a patient. RESULTS: The study population was composed of 1,208 patients (806 inpatients and 402 outpatients). The severity of CAP was estimated in 250 patients (20.7%). The factors that determined hospitalization were "abnormal findings in complementary studies" (643/806: 79.8%; due to respiratory failure in 443 patients) and "signs of clinical deterioration" [64/806 (7.9%): hypotension (16/64, 25%); hemoptoic expectoration (12/64, 18.8%); tachypnea (10/64, 15.6%)]. In total, ambulatory management was not contraindicated in 24.7% of hospitalized patients (199). The predictive model built to decide about hospitalization had a good power of discrimination (AUC 0.876; 95%CI: 0.855-0.897). CONCLUSIONS: Scales are rarely used to estimate the severity of CAP at the emergency department. The decision to hospitalize or not a patient largely depends on the clinical experience of the physician. Our predictive model showed a good power to discriminate the patients who required hospitalization. Further studies are warranted to validate these results.

WarpDrive: Improving spatial normalization using manual refinements.

Spatial normalization-the process of mapping subject brain images to an average template brain-has evolved over the last 20+ years into a reliable method that facilitates the comparison of brain imaging results across patients, centers & modalities. While overall successful, sometimes, this automatic process yields suboptimal results, especially when dealing with brains with extensive neurodegeneration and atrophy patterns, or when high accuracy in specific regions is needed. Here we introduce WarpDrive, a novel tool for manual refinements of image alignment after automated registration. We show that the tool applied in a cohort of patients with Alzheimer's disease who underwent deep brain stimulation surgery helps create more accurate representations of the data as well as meaningful models to explain patient outcomes. The tool is built to handle any type of 3D imaging data, also allowing refinements in high-resolution imaging, including histology and multiple modalities to precisely aggregate multiple data sources together.

Insucesso de indução por misoprostol em gestantes: revisão integrativa / Fracaso de la inducción por misoprostol en mujeres embarazadas: revisión integradora / Unsuccessful misoprostol induction in pregnant women: an integrative review

Resumo Objetivo Analisar as evidências disponíveis na literatura acerca do insucesso da indução do trabalho de parto com misoprostol em gestações a termo. Métodos Revisão integrativa, realizada entre janeiro e novembro de 2022, cuja pergunta de pesquisa e descritores foram delineados por meio da estratégia PECO. As buscas foram realizadas nas bases de dados MEDLINE; Web of Science; CINAHL; EMBASE e Scopus por duas pesquisadoras de forma independente, assim como a avaliação. Para a fase de seleção e identificação dos estudos foi utilizado o Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A avaliação do risco de viés dos artigos incluídos foi realizada através do questionário Newcastle Ottawa Scale. Resultados Foram identificados 3.674 artigos, 84 foram lidos na íntegra, dos quais 11 compuseram a revisão (n=9.010 gestantes), com publicação entre os anos de 2005 a 2021, sendo a maioria nos Estados Unidos. Quanto ao nível de evidência, todos os artigos foram classificados como 2b, avaliada coforme o delineamento de cada investigação. O estudo apontou evidências quanto aos seguintes fatores: IMC elevado (maior igual a 30kg/m2), nuliparidade, bishop imaturo, comprimento cervical (maior igual a 30mm), estatura, etnia (não caucasianas do sul da Europa) e peso fetal (maior igual a 4kg). Conclusão Alcançou-se o objetivo do estudo tendo sido demonstrado seis fatores maternos e um fetal que podem levar ao insucesso da indução. Vale ressaltar a necessidade de evidências que incorporem a individualidade de cada característica e destaca-se a contribuição desse estudo para embasar a escolha da melhor conduta para cada gestação de forma individualizada.

Resumen Objetivo Analizar las evidencias disponibles en la literatura acerca del fracaso de la inducción del trabajo de parto con misoprostol en gestaciones a término. Métodos Revisión integradora, realizada entre enero y noviembre de 2022, cuya pregunta de investigación y descriptores fueron definidos mediante la estrategia PECO. Las búsquedas fueron realizadas en las bases de datos MEDLINE, Web of Science, CINAHL, EMBASE y Scopus por dos investigadoras de forma independiente, al igual que la evaluación. Para la fase de selección e identificación de los estudios se utilizó el Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). La evaluación del riesgo de sesgo de los artículos incluidos se realizó a través del cuestionario Newcastle Ottawa Scale. Resultados Se identificaron 3.674 artículos, 84 se leyeron en su totalidad, de los cuales 11 conformaron la revisión (n=9.010 mujeres embarazadas), publicados entre los años 2005 y 2021, la mayoría en Estados Unidos. Respecto al nivel de evidencia, todos los artículos fueron clasificados como 2b, evaluada de acuerdo con el diseño de cada investigación. El estudio indicó evidencias respecto a los siguientes factores: IMC elevado (mayor igual a 30 kg/m2), nuliparidad, bishop bajo, longitud cervical (mayor o igual a 30 mm), estatura, etnia (no caucasoide del sur de Europa) y peso fetal (mayor igual a 4 kg). Conclusión Se alcanzó el objetivo del estudio y se demostraron seis factores maternos y uno fetal que pueden llevar al fracaso de la inducción. Cabe resaltar la necesidad de evidencias que incorporen la individualidad de cada característica y se destaca la contribución de este estudio para fundamentar la elección de la mejor conducta en cada gestación de forma individualizada.

Abstract Objective To analyze the evidence available in literature regarding unsuccessful labor induction with misoprostol in full-term pregnancies. Methods This is an integrative review, carried out between January and November 2022, whose research question and descriptors were outlined using the PECO strategy. The searches were carried out in the MEDLINE, Web of Science, CINAHL, EMBASE and Scopus databases by two researchers independently as well as assessment. For the study selection and identification phase, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used. The risk of bias assessment of included articles was carried out using the Newcastle-Ottawa Scale. Results A total of 3,674 articles were identified, and 84 were read in full, of which 11 comprised the review (n=9,010 pregnant women), published between 2005 and 2021, with the majority in the United States. Regarding the level of evidence, all articles were classified as 2b, assessed according to the design of each study. The study showed evidence regarding the following factors: High BMI (greater than 30 kg/m2), nulliparity, immature bishop, cervical length (greater than 30 mm), height, ethnicity (non-Caucasians from southern Europe) and fetal weight (greater equal to 4 kg). Conclusion The objective study was achieved, having demonstrated six maternal factors and one fetal factor that can lead to unsuccessful induction. It is worth highlighting the need for evidence that incorporates the individuality of each characteristic and the contribution of this study to support the choice of the best conduct for each pregnancy on an individual basis stands out.

Genome-wide association study for reproduction traits in Colombian Creole Blanco Orejinegro cattle.

The profitability of the beef cattle production system relies heavily on reproductive traits. Unfortunately, certain traits, such as age at first calving (AFC), calving interval (CI), and gestation length (GL), can pose challenges in traditional breeding programs because of their low heritability (0.01-0.12) and sex-limited characteristics. Another important aspect is the conservation of the genetic resources of animals adapted to the Colombian regions, which implies the preservation and rational use of the creole breeds in the country market. Therefore, this study aimed to identify genomic regions in the creole cattle breed Blanco Orejinegro (BON) that influence the reproductive traits in females. The dataset comprised 439 animals and 118,116 single-nucleotide polymorphisms' (SNPs) markers. The GS3 program was used to identify the SNP effects employing the BAYES Cπ methodology. The number of SNPs with effect for AFC was 25, 1527 for CI, and 23 for GL. Some of the genes found associated with reproductive and growth traits as well as immune response and environmental adaptation ECE1, EPH, EPHB2, SMARCAL1, IGFBP5, IGFBP2, FCGRT, EGFR, MUL1, PINK1, STPG1, CNGB1, TGFB1, OXTR, IL22RA1, MYOM3, OXTR, CNR2, HIVEP3, CTPS1, CXCL8, FCGRT, MREG, TMEM169, PECR, and MC1R. Our results evidenced a high contribution of the genetic architecture of the Colombian creole cattle breed Blanco Orejinegro that may impact should be included in implementing genetic improvement and conservation programs.

Racemose neurocysticercosis presenting with thalamic stroke: A case report and literature review.

Racemose neurocysticercosis is an uncommon type of neurocysticercosis that represents a particularly aggressive infection. It is characterized by the presence of multiple confluent cysts within the subarachnoid space and it carries unique diagnostic challenges. Clinical manifestations include headache, cerebrovascular events, and life-threatening hydrocephalus. A 56-year-old female presented with sudden onset headache and right-sided hemisensory loss. Brain MRI revealed multiple cystic lesions in the subarachnoid space consistent with racemose neurocysticercosis and left thalamus acute lacunar infarct. This case report emphasizes the clinical importance, unique characteristics, and imaging features of racemose neurocysticercosis and its complications.

Implementing a Disease-specific Multidisciplinary Team and Order Set for Hemophagocytic Lymphohistiocytosis in a Pediatric Hospital.

OBJECTIVE: To improve outcomes of hemophagocytic lymphohistiocytosis (HLH), prompt recognition and treatment are necessary. A HLH multidisciplinary team was implemented at our institution, and we established an electronic order set to foster uniformity in the diagnostic approach. The goal of this study is to capture the impact of this diagnostic tool. METHODS: This is a retrospective study analyzing the utilization of a HLH-specific order set since time of implementation in June 2019 through December 2022. The trends in the utilization of the order set by providers were analyzed to evaluate the awareness and effectiveness of this tool. RESULTS: The order set was utilized 50 times, most commonly by hematology/oncology (50%) and infectious disease (26%). Utilization by providers on newly presenting patients included 4 times in the year 2019, 12 times in 2020, 16 times in 2021, and 18 times in 2022. Utilization was associated with the diagnosis of HLH in 9 patients (18%). CONCLUSION: Implementation of an HLH-specific order set facilitated a systematic method to approach patients with suspected HLH. The utilization of the order set displayed an upward trend over time, indicating support of this tool among these providers. This tool can increase awareness and early identification of HLH.

Outpatient parenteral antimicrobial therapy with continuous infusion of meropenem: A retrospective analysis of three years of clinical experience / Tratamiento antimicrobiano domiciliario endovenoso con infusión continua de meropenem: un análisis restrospectivo de tres años de experiencia clínica

Introduction: Data regarding outpatient parenteral antimicrobial therapy (OPAT) with continuous infusion of meropenem (CIM) remain scarce and controversial. We aimed to analyze its outcomes. Methods: We conducted a retrospective analysis of a cohort of patients who received OPAT with CIM during a three-year period at a single center in northwest Spain. Demographics, clinical data and OPAT outcomes were recorded. Results: Since January 2017–December 2019, 34 patients received 35 OPAT episodes with CIM. The median age was 75 years, and 18 (51.4%) had a Charlson comorbidity index>2. Twelve (34.3%) had respiratory infection, 11 (31.4%) urinary tract infection, and 12 (34.3%) other infections. Twenty-one (60%) received a dose of 6g/day, and 27 (77.1%) received combined antibiotic therapy. The duration of OPAT with CIM was 10 median days. Pseudomonas aeruginosa was the most frequently (34.3%) isolated microorganism and 10 (28.6%) infections were polymicrobial. During OPAT and hospital at home unit admission, 4 (11.4%) patients had any adverse reaction that required CIM withdrawal, 2 (5.7%) were readmitted, and 3 (8.8%) died (2 infection-related deaths). After 30 days from discharge 6 (18.8%) of 32 not-censored patients had unplanned readmissions (2 infection-related), 6 (18.8%) developed recurrence (3 relapses, 3 reinfections) and 1 (3.1%) died (none-infection-related death). Twenty-three (71.9%) of these 32 patients did not experience unplanned readmission, recurrence or death. Conclusion: CIM can be an option to be administrated in OPAT programs in selected patients. Further studies are warranted to increase evidence regarding its use, and to externally validate our findings.(AU)

Introducción: Los datos sobre el tratamiento antimicrobiano domiciliario endovenoso (TADE) con infusión continua de meropenem (ICM) son escasos y controvertidos. Nuestro objetivo fue analizar sus resultados. Métodos: Realizamos un análisis retrospectivo de una cohorte de pacientes que recibieron TADE con ICM durante tres años en un centro del noroeste de España. Se registraron datos demográficos, clínicos y resultados. Resultados: Desde enero de 2017 a diciembre de 2019, 34 pacientes recibieron 35 episodios de TADE con ICM. La mediana de edad fue de 75 años y 18 (51,4%) tenían un índice de comorbilidad de Charlson>2. Doce (34,3%) tenían infección respiratoria, 11 (31,4%) urinaria y 12 (34,3%) otras infecciones. Veintiuno (60%) recibieron una dosis de 6g/día y 27 (77,1%) antibioterapia combinada. La duración mediana del TADE con ICM fue de 10 días. Pseudomonas aeruginosa fue el microorganismo aislado más frecuentemente (34,3%) y 10 (28,6%) infecciones fueron polimicrobianas. Durante el TADE, 4 (11,4%) pacientes presentaron alguna reacción adversa que requirió retirada de ICM, 2 (5,7%) reingresaron y 3 (8,8%) fallecieron (2 muertes relacionadas con infección). Tras 30 días desde el alta, 6 (18,8%) de 32 pacientes tuvieron reingresos no programados (2 relacionados con infección), 6 (18,8%) desarrollaron recurrencia (3 recidivas, 3 reinfecciones) y 1 (3,1%) falleció (sin relación con infección). Veintitrés (71,9%) de 32 pacientes no experimentaron reingreso no programado, recidiva o muerte. Conclusión: La ICM puede ser una opción para ser administrada en programas de TADE en pacientes seleccionados. Se necesitan más estudios para aumentar la evidencia sobre su uso y validar externamente nuestros hallazgos.(AU)

Carbon accounting of negative emissions technologies integrated in the life cycle of spirulina supplements.

Carbon dioxide removal (CDR) technologies are considered essential to accomplish the Paris Agreement targets. Given the important contribution of the food sector to climate change, this study aims to investigate the role of two carbon capture and utilization (CCU) technologies in decarbonizing the production of spirulina, an algae product commonly consumed for its nutritional characteristics. The proposed scenarios considered the replacement of synthetic food-grade CO2 in Arthrospira platensis cultivation (BAU scenario) with CO2 from beer fermentation (BRW) and CO2 from DACC (direct air carbon capture) (SDACC), representing two alternatives with great potential in the short and medium-long term, respectively. The methodology follows the Life Cycle Assessment guidelines, considering a cradle-to-gate scope and a functional unit equivalent to the annual production of spirulina in a Spanish artisanal plant. Results showed a better environmental performance of both CCU scenarios as compared to BAU, reaching a reduction of greenhouse gas (GHG) emissions of 52 % in BRW and of 46 % in SDACC. Although the brewery CCU offers a deeper carbon mitigation of spirulina production, the process cannot reach net zero GHG emissions due to residual burdens across the supply chain. In comparison, the DACC unit could potentially supply both the CO2 needed in spirulina production and work as a CDR to compensate residual emissions, which opens the door for further research on its technical and economic feasibility in the food sector.

Toll-like receptor agonists enhance HIV-specific T cell response mediated by plasmacytoid dendritic cells in diverse HIV-1 disease progression phenotypes.

BACKGROUND: Plasmacytoid dendritic cells (pDCs) sense viral and bacterial products through Toll-like receptor (TLR)-7 and -9 and translate this sensing into Interferon-α (IFN-α) production and T-cell activation. The understanding of the mechanisms involved in pDCs stimulation may contribute to HIV-cure immunotherapeutic strategies. The objective of the present study was to characterize the immunomodulatory effects of TLR agonist stimulations in several HIV-1 disease progression phenotypes and in non HIV-1 infected donors. METHODS: pDCs, CD4 and CD8 T-cells were isolated from 450 ml of whole blood from non HIV-1 infected donors, immune responders (IR), immune non responders (INR), viremic (VIR) and elite controller (EC) participants. pDCs were stimulated overnight with AT-2, CpG-A, CpG-C and GS-9620 or no stimuli. After that, pDCs were co-cultured with autologous CD4 or CD8 T-cells and with/without HIV-1 (Gag peptide pool) or SEB (Staphylococcal Enterotoxin B). Cytokine array, gene expression and deep immunophenotyping were assayed. FINDINGS: pDCs showed an increase of activation markers levels, interferon related genes, HIV-1 restriction factors and cytokines levels after TLR stimulation in the different HIV-disease progression phenotypes. This pDC activation was prominent with CpG-C and GS-9620 and induced an increase of HIV-specific T-cell response even in VIR and INR comparable with EC. This HIV-1 specific T-cell response was associated with the upregulation of HIV-1 restriction factors and IFN-α production by pDC. INTERPRETATION: These results shed light on the mechanisms associated with TLR-specific pDCs stimulation associated with the induction of a T-cell mediated antiviral response which is essential for HIV-1 eradication strategies. FUNDING: This work was supported by Gilead fellowship program, the Instituto de Salud Carlos III (Fondo Europeo de Desarrollo Regional, FEDER, "a way to make Europe") and the Red Temática de Investigación Cooperativa en SIDA and by the Spanish National Research Council (CSIC).

Factors associated with the humoral response after three doses of COVID-19 vaccination in kidney transplant recipients.

Introduction: Kidney transplant recipients showed a weak humoral response to the mRNA COVID-19 vaccine despite receiving three cumulative doses of the vaccine. New approaches are still needed to raise protective immunity conferred by the vaccine administration within this group of high-risk patients. Methods: To analyze the humoral response and identify any predictive factors within these patients, we designed a prospective monocentric longitudinal study of Kidney transplant recipients (KTR) who received three doses of mRNA-1273 COVID-19 vaccine. Specific antibody levels were measured by chemiluminescence. Parameters related to clinical status such as kidney function, immunosuppressive therapy, inflammatory status and thymic function were analyzed as potential predictors of the humoral response. Results: Seventy-four KTR and sixteen healthy controls were included. One month after the administration of the third dose of the COVID-19 vaccine, 64.8% of KTR showed a positive humoral response. As predictive factors of seroconversion and specific antibody titer, we found that immunosuppressive therapy, worse kidney function, higher inflammatory status and age were related to a lower response in KTR while immune cell counts, thymosin-a1 plasma concentration and thymic output were related to a higher humoral response. Furthermore, baseline thymosin-a1 concentration was independently associated with the seroconversion after three vaccine doses. Discussion: In addition to the immunosuppression therapy, condition of kidney function and age before vaccination, specific immune factors could also be relevant in light of optimization of the COVID-19 vaccination protocol in KTR. Therefore, thymosin-a1, an immunomodulatory hormone, deserves further research as a potential adjuvant for the next vaccine boosters.