Effects of temperature and nutrient supply on resource allocation, photosynthetic strategy, and metabolic rates of Synechococcus sp.

Temperature and nutrient supply are key factors that control phytoplankton ecophysiology, but their role is commonly investigated in isolation. Their combined effect on resource allocation, photosynthetic strategy, and metabolism remains poorly understood. To characterize the photosynthetic strategy and resource allocation under different conditions, we analyzed the responses of a marine cyanobacterium ( Synechococcus PCC 7002) to multiple combinations of temperature and nutrient supply. We measured the abundance of proteins involved in the dark (RuBis CO , rbc L) and light (Photosystem II , psbA) photosynthetic reactions, the content of chlorophyll a , carbon and nitrogen, and the rates of photosynthesis, respiration, and growth. We found that rbc L and psbA abundance increased with nutrient supply, whereas a temperature‐induced increase in psbA occurred only in nutrient‐replete treatments. Low temperature and abundant nutrients caused increased RuBis CO abundance, a pattern we observed also in natural phytoplankton assemblages across a wide latitudinal range. Photosynthesis and respiration increased with temperature only under nutrient‐sufficient conditions. These results suggest that nutrient supply exerts a stronger effect than temperature upon both photosynthetic protein abundance and metabolic rates in Synechococcus sp. and that the temperature effect on photosynthetic physiology and metabolism is nutrient dependent. The preferential resource allocation into the light instead of the dark reactions of photosynthesis as temperature rises is likely related to the different temperature dependence of dark‐reaction enzymatic rates versus photochemistry. These findings contribute to our understanding of the strategies for photosynthetic energy allocation in phytoplankton inhabiting contrasting environments.Agencia Estatal de Investigación | Ref. PGC2018‐094553‐B‐I00National Science Foundation (USA) | Ref. ANT‐0944254National Environmental Research Council (UK) | Ref. NE/F019254/1National Environmental Research Council (UK) | Ref. NE/G009155/1Xunta de Galici

Presence of inorganictrace elements with an important nutritional value in ruminant’s milk

La caracterización composicional y la cuantificación de micronutrientes de los productos lácteos de los distintos tipos de rumiantes son fundamentales para brindarle a los consumidores calidad nutricional y garantía de inocuidad. Entre los elementos de mayor importancia encontramos cobre (Cu), manganeso (Mn), hierro (Fe) y zinc (Zn). Existe un rango óptimo de estos nutrientes, y su concentración depende de su metabolismo y su interacción con otros elementos. El objetivo de este trabajo es caracterizar y comparar los niveles de estos micronutrientes en leches pertenecientes a bovinos, caprinos y ovinos; analizando la relación entre las concentraciones de dichos elementos con los niveles de grasas y proteínas totales. Los resultados obtenidos señalaron que las características de las leches difieren entre especies y presentan gran variabilidad intraespecífica. En la leche de oveja solo se encontró una correlación significativa entre Cu y Zn; y en la de vaca, entre Cu y Mn, y entre Zn y Mn. En ninguna de las leches se encontró correlación alguna con el Fe. A partir de los resultados obtenidos se hace evidente la necesidad de profundizar el estudio de la caracterización y de los factores que influyen en su composición y sus características físico-químicas.Knowing the milk composition of several ruminant species is fundamental to produce healthy and safety food. The most important trace elements with nutritional value are copper (Cu), manganese (Mn), iron (Fe) and zinc (Zn). There is an optimal concentration range for this micronutrients, and their levels in milk depend on the metabolism and to the interaction with other elements. The aim of this study is characterizing and comparing the micronutrients levels in several ruminant milks, and assessing the relationship between the micronutrient levels with the fat and protein contents. The results showed that the milk characteristics are different among species and present intraspecific variability. It was found a significative correlation between Cu and Zn in ovine milk, between Cu and Mn, and between Zn and Mn in cattle milk. No milk showed a correlation with iron levels. After these results, it is showed the importance to know about the milk composition and the different facts that determine its composition and physicochemistry characteristics.Fil: Arellano, Flavia Elisa. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Centro de Estudios Transdisciplinarios del Agua; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Produccion Animal; ArgentinaFil: Alvarez Gonçalvez, Cristina Viviana. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Centro de Estudios Transdisciplinarios del Agua; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Produccion Animal; ArgentinaFil: Pérez Carrera, Alejo Leopoldo. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Centro de Estudios Transdisciplinarios del Agua; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Produccion Animal; ArgentinaFil: Calzetta Resio, Andrea Nilda. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Centro de Estudios Transdisciplinarios del Agua; ArgentinaFil: Fernandez Cirelli, Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones En Produccion Animal; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Centro de Estudios Transdisciplinarios del Agua; Argentin

Feasibility and impact of online HIV/STI screening addressed to men who have sex with men and transgender women users of pre-exposure prophylaxis (PrEP) in Spain (TESTATE PrEP): a study protocol for a non-blinded randomised controlled trial

HIV & AIDS; Clinical trial; Sexually transmitted diseaseVIH y SIDA; Ensayo clínico; Enfermedad de transmisión sexualVIH i sida; Assaig clínic; Malaltia de transmissió sexualIntroduction The objectives of the study are: to design and implement a pilot intervention to offer self-sampling kits to detect HIV, Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Treponema pallidum (TP) among gay, bisexual and other men who have sex with men and transgender women users of pre-exposure prophylaxis (PrEP) as part of PrEP follow-up. To evaluate if the pilot intervention causes a reduction of the retention to PrEP follow-up among the target population. To analyse the capacity of the intervention to reduce the healthcare burden on the PrEP service. To evaluate the acceptability of the intervention among PrEP users and PrEP service healthcare workers and; to validate dried blood samples for treponemal and non-treponemal antibody detection using the Dual Path Platform syphilis screening and confirmatory assay compared with blood drawn by venous puncture. Methods and analysis We will perform a non-blinded randomised controlled non-inferiority trial among PrEP users on follow-up. Participants on the control arm will follow the usual follow-up protocol with quarterly face-to-face visits where they will be tested for HIV and sexually transmitted infections (STIs). Participants in the experimental arm will alternate face-to-face meetings with online screening of HIV and STIs. The website https://testate.org/ will include a module for online follow-up visits of participants. Participants of the experimental arm will order self-sampling kits for HIV, CT, NG and TP through the website, will send the samples to the laboratory and check their results online. We will compare the retention to follow up and the healthcare burden in both arms. The acceptability of the intervention among participants and healthcare workers will be assessed. Ethics and dissemination The project has been approved by the CEIC-HUGTIP (Reference: PI-22-051). Subjects will be included after giving their informed consent. Final conclusions and recommendations will be shared with stakeholders. Two publications in peer-reviewed journals are expected. Trial registration number NCT05752643.This work was supported by the Instituto de Salud Carlos III (PI21/01589) and the Ministry of Health of the Government of Catalonia (Spain) (no grant number)

Family connections in the treatment of relatives of people with eating disorders and personality disorders: study protocol of a randomized control trial

Background: Eating disorders (EDs) are serious disorders that significantly affect not only the lives of patients, but also those of their family members who often experience high levels of burden, suffering and helplessness. If, in addition to ED, the patient has a personality disorder (PD), the psychological distress experienced by family members can be devastating. However, few treatments have been developed for family members of people with ED and PD. Family Connections (FC) is a programme that has been shown to be effective for family members of people with borderline personality disorder. The overall aims of this work are: (a) to adapt FC for application to family members of patients with BPD-PD (FC: ED-PD); (b) to analyse, in a randomised controlled clinical trial, the efficacy of this programme in a Spanish population, compared to a control condition consisting of treatment as usual optimised treatment (TAU-O); (c) to analyse the feasibility of the intervention protocol; (d) to analyse whether the changes that may occur in relatives are related to improvements in the family climate and/or improvements observed in patients; and (e) to analyse the perceptions and opinions of relatives and patients about the two intervention protocols. Methods: The study uses a two-arm randomised controlled clinical trial with two experimental conditions: adaptation of FC programme (FC: ED-PD) or Treatment as usual optimised (TAU-O). Participants will be family members of patients who meet DSM-5 criteria for ED and PD or dysfunctional personality traits. Participants will be assessed before and after treatment and at one-year follow-up. The intention-to-treat principle will be used when analysing the data. Discussion: The results obtained are expected to confirm the effectiveness of the programme and its good acceptance by family members.We want to thank the National Education Alliance for Borderline Personality Disorder Spain (NEABPD-Spain), the Valencian Association of Personality Disorders (ASVA TP), and ITA Salut Mental, for their collaboration in this study.Funding for the study was provided by grants: Regional Ministry of Innovation, Universities, Science and Digital Society: Subsidies for Consolidable Research Groups,–AICO/2021 (Generalitat Valenciana) has been awarded to VG as the main investigator of the project. This funding source had no role in the design of this study and will not have any role during its execution, analyses, interpretation of the data, or decision to submit results

Severe COVID-19 during pregnancy and the subsequent premature delivery

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Part prematurCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Parto prematuroCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Premature deliveryCoronavirus disease 2019 (COVID-19), which is caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic in January 2020. Although most of the cases in pregnant women are mild, there are reports of increasing severe infection in pregnancy. Only a few case of SARS-CoV-2 infection in preterm neonates delivered by mothers with COVID-19 have been reported till date. The possibility of in utero transmission of SARS-CoV-2 is highly controversial.1,2 While SARS-CoV-2 has been detected in several neonates by reverse transcriptionpolymerase chain reaction (RT-PCR) of nasopharyngeal swabs collected in the early hours or days of life,3,4 the reliability of these swabs is under scrutiny, as there is a chance of contamination by coronavirus-infected maternal body fluids

PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study.

Corrigendum to "PBMCs gene expression signature of advanced cirrhosis with high risk for clinically significant portal hypertension in HIV/HCV coinfected patients: A cross-control study" [Biomed. Pharmacother. 159 (2023) 114220]. Biomed Pharmacother. 2023 Apr 27;114803. doi: 10.1016/j.biopha.2023.114803. PMID: 37120412.Background: Patients with advanced cirrhosis are at high risk of developing clinically significant portal hypertension (CSPH). We analyzed the gene expression profile of peripheral blood mononuclear cells (PBMCs) from HIV/HCV coinfected patients to identify a gene expression signature of advanced cirrhosis with high risk for CSPH. Methods: We conducted a cross-sectional study on 68 patients. Liver stiffness measurement (LSM) was used to stratify patients into < 12.5 kPa (no cirrhosis, n = 19), 12.5 - 24.9 kPa (cirrhosis, n = 20), and ≥ 25 kPa (advanced cirrhosis with high risk for CSPH, n = 29). Besides, we further evaluated LSM < 25 kPa (n = 39) vs. ≥ 25 kPa (n = 29). Total RNA was extracted from PBMCs, and poly(A) RNA sequencing was performed. Two significant differentially expressed (SDE) transcripts were validated by quantitative PCR in a different cohort (n = 46). Results: We found 60 SDE transcripts between patients with LSM < 12.5 kPa and ≥ 25 kPa. Partial least squares discriminant analysis showed that those 60 SDE transcripts collectively discriminated LSM ≥ 25 kPa, with an area under the receiver operating characteristic curve (AUROC) of 0.84. Eight genes had an AUROC ≥ 0.75 for LSM ≥ 25 kPa: five were positively associated with LSM values (SCAMP1, ABHD17B, GPR146, GTF2A1, and TMEM64), while three were inversely associated (ZFHX2-AS1, MDK, and STAG3L2). We validated the two SDE transcripts with the highest discrimination capacity in a different cohort, finding significant differences between < 25 kPa and ≥ 25 kPa (MDK (p = 0.006) and STAG3L2 (p = 0.021)). Conclusions: A gene expression signature of 60 transcripts was associated with advanced cirrhosis with high risk for CSPH in HIV/HCV coinfected patients.This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant numbers CP17CIII/00007 and PI18CIII/00028 to MAJS, PI17/00657 and PI20/00474 to JB, PI17/00903 and PI20/00507 to JGG, PI18CIII/00020 to AFR, and PI17CIII/00003 and PI20CIII/00004 to SR) and Ministerio de Ciencia e Innovación (AEI, PID2021-126781OB-I00 to AFR). The study was also funded by the CIBER -Consorcio Centro de Investigación Biomédica en Red- (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – NextGenerationEU (CB21/13/00044).S

The Free and Cued Selective Reminding Test in Parkinson's Disease Mild Cognitive Impairment : Discriminative Accuracy and Neural Correlates

Altres ajuts: This work was partially supported by grants from La Marató TV3 (20142910, 2014/U/477); FIS (PI14/02058, PI15/00962); CIBERNED.Introduction: Memory alterations are common in Parkinson's disease (PD) patients but the mechanisms involved in these deficits remain poorly understood. The study aims to explore the profile of episodic memory deficits in non-demented early PD patients. Methods: We obtained neurological, cognitive and behavioral data from 114 PD patients and 41 healthy controls (HC). PD participants were grouped as normal cognition (PD-NC) and mild cognitive impairment (PD-MCI) according to the Level II criteria of the Movement Disorders Society Task Force (MDS-TF). We evaluate the performance amongst groups on an episodic memory task using the Free and Cued Selective Reminding Test (FCSRT). Additionally, gray matter volume (GMV) voxel based morphometry, and mean diffusivity (MD) analyses were conducted in a subset of patients to explore the structural brain correlates of FCSRT performance. Results: Performance on all subscores of the FCSRT was significantly worse in PD-MCI than in PD-NC and HC. Delayed total recall (DTR) subscore was the best at differentiating PD-NC from PD-MCI. Using crosstabulation, DTR allowed identification of PD-MCI patients with an accuracy of 80%. Delayed free and cued recall was associated with decreased GMV and increased MD in multiple fronto-temporal and parietal areas. Conclusion: Encoding and retrieval deficits are a main characteristic of PD-MCI and are associated with structural damage in temporal, parietal and prefrontal areas

Long-Term Exposure to Nitrate and Trihalomethanes in Drinking Water and Prostate Cancer: A Multicase–Control Study in Spain (MCC-Spain)

BACKGROUND: Nitrate and trihalomethanes (THMs) in drinking water are widespread and are potential human carcinogens.OBJECTIVE: We evaluated the association between drinking-water exposure to nitrate and THMs and prostate cancer.METHODS: During the period 2008-2013, 697 hospital-based incident prostate cancer cases (97 aggressive tumors) and 927 population-based controls were recruited in Spain, providing information on residential histories and type of water consumed. Average nitrate and THMs levels in drinking water were linked with lifetime water consumption to calculate waterborne ingestion. Odds ratios (OR) and 95% confidence intervals (CI) were esti-mated using mixed models with recruitment area as random effect. Effect modification by tumor grade (Gleason score), age, education, lifestyle, and dietary factors was explored.RESULTS: Mean ( +/- standard deviation) adult lifetime waterborne ingested nitrate (milligrams per day), brominated (Br)-THMs (micrograms per day), and chloroform (micrograms per day) were 11.5 ( +/- 9.0), 20.7 ( +/- 32.4), and 15.1 ( +/- 14.7) in controls. Waterborne ingested nitrate >13.8 vs. = 8. Associations were higher in the youngest and those with lower intakes of fiber, fruit/vegetables, and vitamin C. Waterborne ingested THMs were not associated with prostate cancer. Residential tap water levels of Br-THMs and chloroform showed, respectively, inverse and positive associations with prostate cancer.CONCLUSIONS: Findings suggest long-term waterborne ingested nitrate could be a risk factor of prostate cancer, particularly for aggressive tumors. High intakes of fiber, fruit/vegetables and vitamin C may lower this risk. Association with residential levels but not ingested chloroform/Br-THM may suggest inhalation and dermal routes could be relevant for prostate cancer. https://doi.org/10.1289/EHP1139

Multilayer OMIC data in medullary thyroid carcinoma identifies the STAT3 pathway as a potential therapeutic target in RETM918T tumors

Purpose: Medullary thyroid carcinoma (MTC) is a rare disease with few genetic drivers, and the etiology specific to each known susceptibility mutation remains unknown. Exploiting multilayer genomic data, we focused our interest on the role of aberrant DNA methylation in MTC development.Experimental Design: We performed genome-wide DNA methylation profiling assessing more than 27,000 CpGs in the largest MTC series reported to date, comprising 48 molecularly characterized tumors. mRNA and miRNA expression data were available for 33 and 31 tumors, respectively. Two human MTC cell lines and 101 paraffin-embedded MTCs were used for validation.Results: The most distinctive methylome was observed for RETM918T-related tumors. Integration of methylation data with mRNA and miRNA expression data identified genes negatively regulated by promoter methylation. These in silico findings were confirmed in vitro for PLCB2, DKK4, MMP20, and miR-10a, -30a, and -200c. The mutation-specific aberrant methylation of PLCB2, DKK4, and MMP20 was validated in 25 independent MTCs by bisulfite pyrosequencing. The methylome and transcriptome data underscored JAK/Stat pathway involvement in RETM918T MTCs. Immunostaining [immunohistochemistry (IHC)] for the active form of signaling effector STAT3 was performed in a series of 101 MTCs. As expected, positive IHC was associated with RETM918T-bearing tumors (P < 0.02). Pharmacologic inhibition of STAT3 activity increased the sensitivity to vandetanib of the RETM918T-positive MTC cell line, MZ-CRC-1.Conclusions: Multilayer OMIC data analysis uncovered methylation hallmarks in genetically defined MTCs and revealed JAK/Stat signaling effector STAT3 as a potential therapeutic target for the treatment of RETM918T MTCs.This work was supported by the Fondo de Investigaciones Sanitarias (FIS) project PI14/00240 and the Comunidad de Madrid (Grant S2011/BMD-2328 TIRONET) to MR. LI-P is supported by the Centro de Investigacion Biomédica en Red de Enfermedades Raras (CIBERER). VM was supported by a predoctoral fellowship from the "la Caixa"/CNIO international PhD programme. CM-C is supported by a postdoctoral fellowship from the Fundación AECC

HCV Cure With Direct-Acting Antivirals Improves Liver and Immunological Markers in HIV/HCV-Coinfected Patients

Hepatitis C virus (HCV) cure after all-oral direct-acting antiviral (DAA) therapy greatly improves the liver and immune system. We aimed to assess the impact of this HCV clearance on immune system-related markers in plasma and the gene expression profile in human immunodeficiency virus (HIV)/HCV-coinfected patients with advanced cirrhosis. We performed a prospective study on 33 HIV/HCV-coinfected patients at baseline and 36 weeks after the sustained virological response. Gene expression was evaluated by RNA-seq analysis on peripheral blood mononuclear cells (PBMCs) and plasma biomarkers by multiplex immunoassays. We found a decrease in plasma biomarkers (PD1, PDL1, CXCL10, CXCL8, IL12p70, IL10, and TGFβ) and liver disease markers (stiffness measurement (LSM), hepatic venous pressure gradient (HVPG), and transaminases, among others). Furthermore, decreased plasma levels of CXCL8, CXCL10, IL10, and PD1 were associated with reduced LSM values. We also found two upregulated (HAS1 and IRG1) and 15 downregulated (CXCL11, CCL8, CCL7, CCL2, ADARB2, RRAD, MX1, SIGLEC1, IFI44L, IFI44, IFI27, IFI6, IFIT3, IFIT1B, and IFIT1) genes at the end of follow-up, all interferon-stimulated genes (ISGs) grouped into four pathways ("cytokine-cytokine receptor interaction", "viral protein interaction with cytokine and cytokine receptor", "chemokine signaling pathway", and "hepatitis C"). Additionally, the decrease in most of these ISGs was significantly related to reduced LSM and HVPG values. In conclusion, HIV/HCV-coinfected patients with advanced-HCV-related cirrhosis who eradicated HCV following DAA therapy exhibited an improvement in liver disease markers and a significant decrease in plasma biomarkers and gene expression related to antiviral/inflammatory response, particularly in levels of several chemokines and ISGs.This study was supported by grants from Instituto de Salud Carlos III (ISCII; grant numbers PI20/00474 and PI17/00657 to JB, PI20/00507 and PI17/00903 to JGG, PI18CIII/00020 to AF-R, PI18CIII/00028 to MA, and PI20CIII/00004 and PI17CIII/00003 to SR). AF-R and MA are Miguel Servet researchers supported and funded by ISCIII (grant numbers: CP14CIII/00010 to AFR and CP17CIII/00007 to MAJS). The study was also funded by the RD16/0025/0017, RD16/0025/0018 and RD16CIII/0002/0002 projects as part of the Plan Nacional R + D + I and co-funded by ISCIII- Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER). JB is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS), Ref. INT16/00100. DS-C is a ‘Sara Borrell’ researcher from ISCIII (grant number CD20CIII/00001) and has also been supported through Fundación SEIMC-GESIDA by a fellowship award from Fundación ONCE ‘Oportunidad al Talento, 2019/20 and 2020/21’ co-financed by Fondo Social Europeo.S