MYB24 orchestrates terpene and flavonol metabolism as light responses to anthocyanin depletion in variegated grape berries.

Variegation is a rare type of mosaicism not fully studied in plants, especially fruits. We examined red and white sections of grape (Vitis vinifera cv. 'Béquignol') variegated berries and found that accumulation of products from branches of the phenylpropanoid and isoprenoid pathways showed an opposite tendency. Light-responsive flavonol and monoterpene levels increased in anthocyanin-depleted areas in correlation with increasing MYB24 expression. Cistrome analysis suggested that MYB24 binds to the promoters of 22 terpene synthase (TPS) genes, as well as 32 photosynthesis/light-related genes, including carotenoid pathway members, the flavonol regulator HY5 HOMOLOGUE (HYH), and other radiation response genes. Indeed, TPS35, TPS09, the carotenoid isomerase gene CRTISO2, and HYH were activated in the presence of MYB24 and MYC2. We suggest that MYB24 modulates ultraviolet and high-intensity visible light stress responses that include terpene and flavonol synthesis and potentially affects carotenoids. The MYB24 regulatory network is developmentally triggered after the onset of berry ripening, while the absence of anthocyanin sunscreens accelerates its activation, likely in a dose-dependent manner due to increased radiation exposure. Anthocyanins and flavonols in variegated berry skins act as effective sunscreens but for different wavelength ranges. The expression patterns of stress marker genes in red and white sections of 'Béquignol' berries strongly suggest that MYB24 promotes light stress amelioration but only partly succeeds during late ripening.

Publisher Correction: Two dynamically distinct circuits drive inhibition in the sensory thalamus.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Two dynamically distinct circuits drive inhibition in the sensory thalamus.

Most sensory information destined for the neocortex is relayed through the thalamus, where considerable transformation occurs1,2. One means of transformation involves interactions between excitatory thalamocortical neurons that carry data to the cortex and inhibitory neurons of the thalamic reticular nucleus (TRN) that regulate the flow of those data3-6. Although the importance of the TRN has long been recognised7-9, understanding of its cell types, their organization and their functional properties has lagged behind that of the thalamocortical systems they control. Here we address this by investigating the somatosensory and visual circuits of the TRN in mice. In the somatosensory TRN we observed two groups of genetically defined neurons that are topographically segregated and physiologically distinct, and that connect reciprocally with independent thalamocortical nuclei through dynamically divergent synapses. Calbindin-expressing cells-located in the central core-connect with the ventral posterior nucleus, the primary somatosensory thalamocortical relay. By contrast, somatostatin-expressing cells-which reside along the surrounding edges of the TRN-synapse with the posterior medial thalamic nucleus, a higher-order structure that carries both top-down and bottom-up information10-12. The two TRN cell groups process their inputs in pathway-specific ways. Synapses from the ventral posterior nucleus to central TRN cells transmit rapid excitatory currents that depress deeply during repetitive activity, driving phasic spike output. Synapses from the posterior medial thalamic nucleus to edge TRN cells evoke slower, less depressing excitatory currents that drive more persistent spiking. Differences in the intrinsic physiology of TRN cell types, including state-dependent bursting, contribute to these output dynamics. The processing specializations of these two somatosensory TRN subcircuits therefore appear to be tuned to the signals they carry-a primary central subcircuit tuned to discrete sensory events, and a higher-order edge subcircuit tuned to temporally distributed signals integrated from multiple sources. The structure and function of visual TRN subcircuits closely resemble those of the somatosensory TRN. These results provide insights into how subnetworks of TRN neurons may differentially process distinct classes of thalamic information.

Epigenetic differences between wild and cultivated grapevines highlight the contribution of DNA methylation during crop domestication.

The domestication process in grapevines has facilitated the fixation of desired traits. Nowadays, vegetative propagation through cuttings enables easier preservation of these genotypes compared to sexual reproduction. Nonetheless, even with vegetative propagation, various phenotypes are often present within the same vineyard due to the accumulation of somatic mutations. These mutations are not the sole factors influencing phenotype. Alongside somatic variations, epigenetic variation has been proposed as a pivotal player in regulating phenotypic variability acquired during domestication. The emergence of these epialleles might have significantly influenced grapevine domestication over time. This study aims to investigate the impact of domestication on methylation patterns in cultivated grapevines. Reduced-representation bisulfite sequencing was conducted on 18 cultivated and wild accessions. Results revealed that cultivated grapevines exhibited higher methylation levels than their wild counterparts. Differential Methylation Analysis between wild and cultivated grapevines identified a total of 9955 differentially methylated cytosines, of which 78% were hypermethylated in cultivated grapevines. Functional analysis shows that core methylated genes (consistently methylated in both wild and cultivated accessions) are associated with stress response and terpenoid/isoprenoid metabolic processes. Meanwhile, genes with differential methylation are linked to protein targeting to the peroxisome, ethylene regulation, histone modifications, and defense response. Collectively, our results highlight the significant roles that epialleles may have played throughout the domestication history of grapevines.

Fosfatriclaben: Effective dose determination and comparative efficacy assessment with closantel, triclabendazole+ivermectin, triclabendazole+albendazole in artificially infected cattle.

Two controlled efficacy studies were conducted to determine the effective dose of fosfatriclaben (FTCB) and compare its fasciolicidal efficacy with that of three commercial products against eggs and adult stages of Fasciola hepatica in artificially infected cattle. In study 1, 20 trematode-free Holstein Friesian steers were infected on day 0 with 500 F. hepatica metacercariae. Ten weeks after infection and the steers were confirmed to be positive for trematode eggs through a modified sedimentation method. On day 75, they were divided into five groups of four animals each for treatment. Group 1 (G1) served as the untreated control; G2, G3, and G4 received FTCB at 4, 6, and 8 mg/kg/intramuscularly (IM), respectively. G5 received a combined treatment of triclabendazole (TCBZ) (12 mg/kg IM + ivermectin (0.2 mg/kg IM). Individual faecal analyses were performed on days -8, 0, 70, 75, and 105 to evaluate the reduction in trematode eggs. Four weeks after treatment, the steers were humanely slaughtered to harvest the livers and remove the parasites present in the bile ducts. Efficacy was evaluated by the reduction in fecal egg counts or in number of adult parasites, compared to the untreated control. The effective FTCB dose was 6 mg/kg. Once the effective dose was determined, study 2 was conducted on another 20 steers infected with 500 F. hepatica metacercariae, to compare the effectiveness of FTCB with three commercials fasciolicides. All procedures were performed as described in study 1, and treatments were as follows: Group 1 (G1), closantel (5 mg/kg subcutaneously (SC)); G2, TCBZ (12 mg/kg IM) + ivermectin (0.2 mg/kg IM); G3, FTCB (6 mg/kg IM); G4, triclabendazole (12 mg/kg) + albendazole (5 mg/kg/PO (orally); and G5 served as an untreated control. The results indicated that all tested compounds were highly effective in the reduction of faecal egg excretion (99.7-100%) and adult parasites (98.9-100%), except closantel, which exhibited low efficacy (74.4%) when tested against adult trematodes. We concluded that the effective dose of FTCB for cattle was 6 mg/kg IM, which is half the recommended clinical dose of the commercial combination of TCBZ and ivermectin. The fasciolicidal efficacy of FTCB was like the other three flukicides in reducing adult F. hepatica and Fasciola eggs; however, closantel was not sufficiently efficient against adult flukes.

Synthesis, and evaluation of photophysical properties of a potential DPP-derived photosensitizer for photodynamic therapy with D-A-D architecture.

The study of a macromolecule derived from DPP and triphenylamine, (DPP-BisTPA) by computational chemistry, its synthesis by direct arylation, optical characterization (UV-Vis and fluorescence) and electrochemistry (cyclic voltammetry), as well as its evaluation as a generator of reactive oxygen species indirectly, through the degradation of uric acid. The results obtained by DFT using B3LYP/6-31G (d, p) and TD-DFT using CAM-B3LYP/6-31G (d, p) reveal values of energy levels of the first singlet and triplet excited state that indicate a possible intersystem crossover and the possible generation of reactive oxygen species by a type I mechanism. The compound presents an absorption region within the phototherapeutic window. The electrochemical bandgap is 1.64 eV which suggests a behavior as a semiconductor. DPP-BisTPa were processed as hemispherical nanoparticles with a size around 100 nm, and NPOs were evaluated as a photosensitizer with a ROS generation yield of 4% using a photodynamic therapy flashlight as the light source.

Influence of free and microencapsulated recombinant rabbit nerve growth factor with chitosan on rabbit sperm quality parameters.

ß-nerve growth factor (ßNGF) plays a crucial role in reproductive physiology and sperm quality. Enzymatic activity of seminal plasma and vaginal fluids reduces available ßNGF and it has been demonstrated that chitosan microspheres could protect rrßNGF from degradation. This study examined the effects of microencapsulated rrbNGF with chitosan on rabbit sperm viability, motility and capacitation status. Results showed that 0.5 and 1 µg/mL of microencapsulated rrßNGF, as well as free rrßNGF or empty microspheres, did not adversely affect sperm viability or total motility after 2 h of incubation. However, the highest progressivity kinetic parameters were observed with 1 µg/mL free rrßNGF, while the highest curvilinear velocity (VCL) occurred with 0.5 µg/mL microencapsulated rrßNGF. Empty chitosan microspheres did not induce acrosome reaction (AR), but both concentrations of free and rrßNGFch favoured AR during in vitro incubation. The study suggests that using chitosan spheres did not show any adverse effects on sperm traits, unlike free rßNGF and rrßNGFch promoted capacitation and AR. Further research is needed to explore the potential of rrßNGFch in modifying in vitro capacitation and inducing ovulation during artificial insemination.

Impact of the COVID-19-pandemic and perception of self-efficacy on the mental health of out-of-hospital emergency healthcare professionals by modality of care.

OBJECTIVE: To analyse the influence of the COVID-19 pandemic and the perception of self-efficacy on the health professionals of the Spanish out-of-hospital emergency services. DESIGN: Observational, cross-sectional and descriptive with a survey methodology of 1710 participants from Spain (1 February-30 April, 2021). METHODS: The mental health of healthcare workers was assesed in terms of stress, anxiety and depression, as well as their self-efficacy. Linear and logistic regression models were fitted to predict these variables. A moderation analysis was conducted to determine the effect of self-efficacy on mental health. RESULTS: The means of the sample for stress, anxiety, depression and self-efficacy were 20.60, 15.74, 13.07 and 70.87, respectively. In the regression models, being a woman was the most significant factor for severe mental health impairment. Female gender was also a relevant factor for self-efficacy. Self-efficacy had a direct effect on the mental health for working in patient care. CONCLUSIONS: Healthcare workers showed moderate stress, severe anxiety, mild depression and good self-efficacy. Direct patient care was associated with more stress and severe anxiety. Age, female gender, job changes and job adjustment were associated with levels of stress, anxiety and depression. Self-efficacy is a determining factor of mental health in the direct care modality. IMPLICATIONS: The mental health of healthcare workers has been of great importance in the aftermath of the pandemic, but out-of-hospital emergency workers have been neglected in research. The levels of stress, anxiety and depression during the pandemic justify the creation of prevention and early diagnosis programmes, as they are essential in a health disaster. Surprisingly, their high level of perceived self-efficacy directly impact on the mental health of patient helthcare workers, so improving it will reduce the psychological risk. REPORTING METHOD: We have followed the STROBE guidelines. It has been partially funded by the Asistencia Sanitanitaria Interprovincial de Seguros - ASISA Foundation (Spain). PATIENT OR PUBLIC CONTRIBUTION: 'No patient or public involvement'.

Synergistic Effect between the APOE ε4 Allele with Genetic Variants of GSK3B and MAPT: Differential Profile between Refractory Epilepsy and Alzheimer Disease.

Temporal Lobe Epilepsy (TLE) is a chronic neurological disorder characterized by recurrent focal seizures originating in the temporal lobe. Despite the variety of antiseizure drugs currently available to treat TLE, about 30% of cases continue to have seizures. The etiology of TLE is complex and multifactorial. Increasing evidence indicates that Alzheimer's disease (AD) and drug-resistant TLE present common pathological features that may induce hyperexcitability, especially aberrant hyperphosphorylation of tau protein. Genetic polymorphic variants located in genes of the microtubule-associated protein tau (MAPT) and glycogen synthase kinase-3ß (GSK3B) have been associated with the risk of developing AD. The APOE ε4 allele is a major genetic risk factor for AD. Likewise, a gene-dose-dependent effect of ε4 seems to influence TLE. The present study aimed to investigate whether the APOE ɛ4 allele and genetic variants located in the MAPT and GSK3B genes are associated with the risk of developing AD and drug-resistant TLE in a cohort of the Mexican population. A significant association with the APOE ε4 allele was observed in patients with AD and TLE. Additional genetic interactions were identified between this allele and variants of the MAPT and GSK3B genes.

Cardiovascular events in patients with coronary artery disease with and without myocardial ischemia: Long-term follow-up.

BACKGROUND: After the results of the ISCHEMIA Trial, the role of myocardial ischemia in the prognosis of coronary artery disease (CAD) was under debate. We sought to comparatively evaluate the long-term prognosis of patients with multivessel CAD with or without documented myocardial ischemia. METHODS: This is a single-center, retrospective, observational cohort study that included patients with CAD obtained from the research protocols database of "The Medicine, Angioplasty or Surgery Study," the MASS Study Group. Patients were stratified according to the presence or absence of myocardial ischemia. Cardiovascular events (overall mortality and myocardial infarction) were tracked from the registry entry up to a median follow-up of 8.7 years. Myocardial ischemia was assessed at baseline by a functional test with or without imaging. RESULTS: From 1995 to 2018, 2015 patients with multivessel CAD were included. Of these, 1001 presented with conclusive tests at registry entry, 790 (79%) presenting with ischemia and 211 (21%) without ischemia. The median follow-up was 8.7 years (IQR 4.04 to 10.07). The primary outcome occurred in 228 (28.9%) patients with ischemia and in 64 (30.3%) patients without ischemia (plog-rank=0.60). No significant interaction was observed with the presence of myocardial ischemia and treatment strategies in the occurrence of the combined primary outcome (pinteration=0.14). CONCLUSIONS: In this sample, myocardial ischemia was not associated with a worse prognosis compared with no ischemia in patients with multivessel CAD. These results refer to debates about the role of myocardial ischemia in the occurrence of cardiovascular events.

International Society for Cell & Gene Therapy Stem Cell Engineering Committee: Cellular therapies for the treatment of graft-versus-host-disease after hematopoietic stem cell transplant.

BACKGROUND AIMS: Allogeneic hematopoietic stem cell transplant is a curative approach for many malignant and non-malignant hematologic conditions. Despite advances in its prevention and treatment, the morbidity and mortality related to graft-versus-host disease (GVHD) remains. The mechanisms by which currently used pharmacologic agents impair the activation and proliferation of potentially alloreactive T cells reveal pathways essential for the detrimental activities of these cell populations. Importantly, these same pathways can be important in mediating the graft-versus-leukemia effect in recipients transplanted for malignant disease. This knowledge informs potential roles for cellular therapies such as mesenchymal stromal cells and regulatory T cells in preventing or treating GVHD. This article reviews the current state of adoptive cellular therapies focused on GVHD treatment. METHODS: We conducted a search for scientific literature in PubMed® and ongoing clinical trials in clinicaltrial.gov with the keywords "Graft-versus-Host Disease (GVHD)," "Cellular Therapies," "Regulatory T cells (Tregs)," "Mesenchymal Stromal (Stem) Cells (MSCs)," "Natural Killer (NK) Cells," "Myeloid-derived suppressor cells (MDSCs)," and "Regulatory B-Cells (B-regs)." All the published and available clinical studies were included. RESULTS: Although most of the existing clinical data focus on cellular therapies for GVHD prevention, there are observational and interventional clinical studies that explore the potential for cellular therapies to be safe modalities for GVHD treatment while maintaining the graft-versus-leukemia effect in the context of malignant diseases. However, there are multiple challenges that limit the broader use of these approaches in the clinical scenario. CONCLUSIONS: There are many ongoing clinical trials to date with the promise to expand our actual knowledge on the role of cellular therapies for GVHD treatment in an attempt to improve GVHD-related outcomes in the near future.

Post-traumatic stress disorder as a predictor for incident hypertension: a 3-year retrospective cohort study.

BACKGROUND: The goal of the present study was to investigate the association between PTSD and the onset of hypertension in previously normotensive individuals in a population living in the stressful environment of the urban slums while controlling for risk factors for cardiovascular disease (CVD). METHODS: Participants were 320 normotensive individuals who lived in slums and were attending a family doctor program. Measurements included a questionnaire covering sociodemographic characteristics, clinical status and life habits, the Posttraumatic Stress Disorder Checklist - Civilian Version, and the Beck Depression Inventory. Incident hypertension was defined as the first occurrence at the follow-up review of the medical records of (1) systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher, (2) the participant started taking antihypertensive medication, or (3) a new diagnosis of hypertension made by a physician. Differences in sociodemographic, clinical, and lifestyle characteristics between hypertensive and non-hypertensive individuals were compared using the χ2 and t tests. Multivariate Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Six variables - age, educational level, body mass, smoking, diabetes, and PTSD diagnosis - showed a statistically significant (p ≤ 0.20) association with the hypertensive status. In the Cox regression, only PTSD diagnosis was significantly associated with incident hypertension (multivariate HR = 1.94; 95% CI 1.11-3.40). CONCLUSIONS: The present findings highlight the importance of considering a diagnostic hypothesis of PTSD in the prevention and treatment of cardiovascular diseases.

Effectiveness of a minimally processed food-based nutritional counselling intervention on weight gain in overweight pregnant women: a randomized controlled trial.

PURPOSE: This study aimed at evaluating the effectiveness of a nutritional counselling intervention based on encouraging the consumption of unprocessed and minimally processed foods, rather than ultra-processed products, and the practice of physical activities to prevent excessive gestational weight gain in overweight pregnant women. METHODS: This was a two-armed, parallel, randomized controlled trial conducted in primary health units of a Brazilian municipality from 2018 to 2021. Overweight, adult pregnant women (n = 350) were randomly assigned to control (CG) or intervention groups (IG). The intervention consisted of three individualized nutritional counselling sessions based on encouraging the consumption of unprocessed and minimally processed foods rather than ultra-processed products, following the NOVA food classification system, and the practice of physical activities. The primary outcome was the proportion of women whose weekly gestational weight gain (GWG) exceeded the Institute of Medicine guidelines. Adjusted logistic regression models were employed. RESULTS: Complete data on weight gain were available for 121 women of the IG and 139 of the CG. In modified intention-to-treat analysis, there was a lower chance of the IG women having excessive GWG [OR 0.56 (95% CI 0.32, 0.98), p = .04], when compared to the CG. No between-group differences were observed for the other maternal outcomes investigated. CONCLUSION: The present study was unprecedented in demonstrating that nutritional counselling based on the NOVA food classification system, together with encouraging the practice of physical activity, is effective in preventing excessive weight gain in overweight pregnant women. TRIAL REGISTRATION: Registered on July 30th 2018 at Brazilian Registry of Clinical Trials (RBR-2w9bhc).

Effects of Gestational Intermittent Hypoxia on Placental Morphology and Fetal Development in a Murine Model of Sleep Apnea.

Obstructive sleep apnea (OSA) during pregnancy is characterized by episodes of intermittent hypoxia (IH) during sleep, resulting in adverse health outcomes for mother and offspring. Despite a prevalence of 8-20% in pregnant women, this disorder is often underdiagnosed.We have developed a murine model of gestational OSA to study IH effects on pregnant mothers, placentas, fetuses, and offspring. One group of pregnant rats was exposed to IH during the last 2 weeks of gestation (GIH). One day before the delivery date, a cesarean section was performed. Other group of pregnant rats was allowed to give birth at term to study offspring's evolution.Preliminary results showed no significant weight differences in mothers and fetuses. However, the weight of GIH male offspring was significantly lower than the controls at 14 days (p < 0.01). The morphological study of the placentas showed an increase in fetal capillary branching, expansion of maternal blood spaces, and number of cells of the external trophectoderm in the tissues from GIH-exposed mothers. Additionally, the placentas from the experimental males were enlarged (p < 0.05). Further studies are needed to follow the long-term evolution of these changes to relate the histological findings of the placentas with functional development of the offspring in adulthood.

Energy metabolism of juvenile scallops Nodipecten subnodosus under acute increased temperature and low oxygen availability.

High temperature increases energy demand in ectotherms, limiting their physiological capability to cope with hypoxic events. The present study aimed to assess the metabolic tolerance of juvenile Nodipecten subnodosus scallops to acute hyperthermia combined with moderate hypoxia. A previous study showed that juveniles exhibited a high upper temperature limit (32 °C), but the responses of juveniles to combined hyperthermia and low dissolved oxygen are unknown. Scallops were exposed to control conditions (treatment C: 22 °C, ∼7.1 mg O2 L-1 or PO2 156.9 mmHg), acute hyperthermia under normoxia (treatment T: 30 °C, ∼6.0 mg O2 L-1 or PO2 150.9 mmHg) or acute hyperthermia plus hypoxia (treatment TH: 30 °C, ∼2.5 mg O2 L-1 or PO2 62.5 mmHg) for 18 h. In T, juveniles exhibited an enhanced oxygen consumption, together with a decrease in adenylate energy charge (AEC) and arginine phosphate (ArgP), and with no changes in metabolic enzyme activity in the muscle. In TH, scallops maintained similar AEC and ArgP levels in muscle as those observed in T treatment. This response occurred along with the accumulation of inosine monophosphate and hypoxanthine. Besides, reduced citrate synthase and pyruvate kinase activities, enhanced hexokinase activity, and a higher octopine dehydrogenase/lactate dehydrogenase ratio in the mantle indicated the onset of anaerobiosis in TH. These responses indicate that juvenile scallops showed tissue-specific compensatory responses regarding their energy balance under moderate hypoxia at high temperatures. Our results give an insight into the tolerance limit of this species to combined hyperthermia and hypoxia in its northern limit of distribution.

Biochemical composition and adenylate energy charge shifts in longfin yellowtail (Seriola rivoliana) embryos during development under different temperatures.

The longfin yellowtail Seriola rivoliana is an emerging species for aquaculture diversification worldwide and production relies on fertilized eggs from captive broodstock. Temperature is the main factor that influences the developmental process and success during fish ontogeny. However, the effects of temperature on the utilization of the main biochemical reserves and bioenergetics are scarcely investigated in fish, whereas protein, lipid and carbohydrate metabolism have critical roles in maintaining cellular energy homeostasis. In this context, we aimed to evaluate metabolic fuels (protein, lipids, triacylglicerides, carbohydrates), adenylic nucleotides and derivates (ATP, ADP, AMP, IMP), and the adenylate energy charge (AEC) during embryogenesis and in hatched larvae in S. rivoliana at different temperatures. For this purpose, fertilized eggs were incubated at six constant (20, 22, 24, 26, 28 and 30 °C) and two oscillating (21⇄29 °C) temperatures. Biochemical analyses were made at blastula, optic vesicles, neurula, prehatch and hatch periods. Results indicated that the developmental period had a major influence on the biochemical composition at any temperature regime tested during the incubation. Protein content decreased only at hatching mainly due to the loss of the chorion, total lipids tended to increase at the neurula period and variations in carbohydrates depended on the particular spawn analyzed. Triacylglicerides were a critical egg fuel during hatching. The high AEC during embryogenesis and even in hatched larvae suggested an optimal energy balance regulation. The lack of critical biochemical changes from different temperature regimes during embryo development confirmed that this species exhibits a high adaptive capacity in response to constant and fluctuating temperatures. However, the timing of hatching was the most critical period of development, where biochemical components and energy utilization significantly changed. The oscillating temperatures tested may have physiological advantages without detrimental energetic effects that will require further research on larval quality after hatching.

Machine Learning Quantification of Intraepithelial Tumor-Infiltrating Lymphocytes as a Significant Prognostic Factor in High-Grade Serous Ovarian Carcinomas.

The prognostic and predictive role of tumor-infiltrating lymphocytes (TILs) has been demonstrated in various neoplasms. The few publications that have addressed this topic in high-grade serous ovarian carcinoma (HGSOC) have approached TIL quantification from a semiquantitative standpoint. Clinical correlation studies, therefore, need to be conducted based on more accurate TIL quantification. We created a machine learning system based on H&E-stained sections using 76 molecularly and clinically well-characterized advanced HGSOC. This system enabled immune cell classification. These immune parameters were subsequently correlated with overall survival (OS) and progression-free survival (PFI). An intense colonization of the tumor cords by TILs was associated with a better prognosis. Moreover, the multivariate analysis showed that the intraephitelial (ie) TILs concentration was an independent and favorable prognostic factor both for OS (p = 0.02) and PFI (p = 0.001). A synergistic effect between complete surgical cytoreduction and high levels of ieTILs was evidenced, both in terms of OS (p = 0.0005) and PFI (p = 0.0008). We consider that digital analysis with machine learning provided a more accurate TIL quantification in HGSOC. It has been demonstrated that ieTILs quantification in H&E-stained slides is an independent prognostic parameter. It is possible that intraepithelial TIL quantification could help identify candidate patients for immunotherapy.

Polypropylene Nanocomposites Attained by In Situ Polymerization Using SBA-15 Particles as Support for Metallocene Catalysts: Effect of Molecular Weight and Tacticity on Crystalline Details, Phase Transitions and Rheological Behavior.

In this study, nanocomposites based on polypropylene are synthesized by the in situ polymerization of propene in the presence of mesoporous SBA-15 silica, which acts as a carrier of the catalytic system (zirconocene as catalyst and methylaluminoxane as cocatalyst). The protocol for the immobilization and attainment of hybrid SBA-15 particles involves a pre-stage of contact between the catalyst with cocatalyst before their final functionalization. Two zirconocene catalysts are tested in order to attain materials with different microstructural characteristics, molar masses and regioregularities of chains. Some polypropylene chains are able to be accommodated within the silica mesostructure of these composites. Thus, an endothermic event of small intensity appears during heating calorimetric experiments at approximately 105 °C. The existence of these polypropylene crystals, confined within the nanometric channels of silica, is corroborated by SAXS measurements obtained via the change in the intensity and position of the first-order diffraction of SBA-15. The incorporation of silica also has a very significant effect on the rheological response of the resultant materials, leading to important variations in various magnitudes, such as the shear storage modulus, viscosity and δ angle, when a comparison is established with the corresponding neat iPP matrices. Rheological percolation is reached, thus demonstrating the role of SBA-15 particles as filler, in addition to the supporting role that they exert during the polymerizations.

Predictive factors for anti-MDA5 antibody in patients with dermatomyositis: a retrospective multicenter study.

BACKGROUND AND OBJECTIVES: Melanoma differentiation-associated gene 5 antibody (anti-MDA5) in dermatomyositis (DM) is associated with rapidly progressive interstitial lung disease and poor prognosis. Early diagnosis is key to improving the prognosis of these patients. The aim was to confirm cutaneous characteristics in patients with anti-MDA5 dermatomyositis and to explore new diagnostic markers for the presence of anti-MDA5 (anti-MDA5+ ). PATIENTS AND METHODS: A multicenter cross-sectional retrospective cohort study of 124 patients diagnosed with DM, of which 37 were anti-MDA5+ . Demographic data, laboratory data, and clinical manifestations were collected. RESULTS: Anti-MDA5+ DM is characterized by a distinct mucocutaneous phenotype that includes oral lesions, alopecia, mechanic's hands, palmar and dorsal papules, palmar erythema, vasculopathy, and skin ulceration. We found vasculopathy and digit tip involvement very frequently in anti-MDA5+ patients (p <0.001), being a diagnostic marker of anti-MDA5+ (OR, 12.355; 95% CI 2.850-79.263; p  =  0.012 and OR, 7.447; 95% CI 2.103-46.718; p  =  0.004, respectively). The presence of ulcers deserves special mention, especially in anti-MDA5+ patients, because in our cohort, up to 97% of the anti-MDA5+ patients had ulcers. CONCLUSIONS: In patients with suspected DM with digit tip involvement or vasculopathy, the presence of anti-MDA5 antibodies must be ruled out, as it may be a clinical predictor.

High SARS-CoV-2 Viral Load and Low CCL5 Expression Levels in the Upper Respiratory Tract Are Associated With COVID-19 Severity.

Mucosal immune response in the upper respiratory tract is crucial for initial control of viral replication, clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and progression of coronavirus disease 2019 (COVID-19). We analyzed SARS-CoV-2 RNA load and expression of selected immune genes in the upper respiratory tract (nasopharynx) of 255 SARS-CoV-2-infected patients and evaluated their association with severe COVID-19. SARS-CoV-2 replication in nasopharyngeal mucosa induces expression of several innate immune genes. High SARS-CoV-2 viral load and low CCL5 expression levels were associated with intensive care unit admission or death, although CCL5 was the best predictor of COVID-19 severity.