Search

Background: Alzheimer's disease (AD) heritability is estimated to be around 70–80%. Yet, much of it remains to be explained. Studying transmission patterns may help in understanding other factors contributing to the development of AD. Objective: In this study, we aimed to search for evidence of autosomal recessive or X- and Y-linked inheritance of risk factors in a large cohort of Portuguese AD patients. Methods: We collected family history from patients with AD and cognitively healthy controls over 75 years of age. We compared the proportions of maternal and paternal history in male and female patients and controls (to search for evidence of X-linked and Y-linked inherited risk factors). We compared the risk of developing AD depending on parents' birthplace (same vs. different), as a proxy of remote consanguinity. We performed linear regressions to study the association of these variables with different endophenotypes. Results: We included 3090 participants, 2183 cognitively healthy controls and 907 patients with AD. Men whose mother had dementia have increased odds of developing AD comparing to women whose mother had dementia. In female patients with a CSF biomarker-supported diagnosis of AD, paternal history of dementia is associated with increased CSF phosphorylated Tau levels. People whose parents are from the same town have higher risk of dementia. In multivariate analysis, this proxy is associated with a lower age of onset and higher CSF phosphorylated tau. Conclusions: Our study gives evidence supporting an increased risk of developing AD associated with an X-linked inheritance pattern and remote consanguinity. [ABSTRACT FROM AUTHOR]

The offshore environment of southeastern Brazil is an important area for oil exploration. In this region, the formation of weak layers can occur due to variations in the rate of soil deposition. Although several studies have analyzed the seismic response of topographic features, centrifuge modeling including the presence of weak layers has been little explored. To address this gap, the present study employs centrifuge modeling to investigate the seismic response of three different ground profiles: one with a uniform clay deposit and two incorporating weak layers. Each profile begins with a flat ground configuration and subsequently, a canyon is excavated to assess the impact of topography on the seismic response of soft clay profiles. The centrifuge tests were conducted at an acceleration level of 40 g. The results showed that the weak layer intensifies the non-linearity of the soil and acts as a filter in the spectral response of the soil, limiting the propagation of higher frequency waves. While this leads to a reduction in amplification and spectral response energy, it also results in a noticeable extension of the earthquake's significant duration at the model's surface. [ABSTRACT FROM AUTHOR]

Introduction: Gestational diabetes (GD) is a risk factor for neonatal hypoglycaemia (NH), but other factors can increase this risk. Objectives: To create a score to predict NH in women with GD. Methods: Retrospective study of women with GD with a live singleton birth between 2012 and 2017 from the Portuguese GD registry. Pregnancies with and without NH were compared. A logistic regression was used to study NH predictors. Variables independently associated with NH were used to score derivation. The model's internal validation was performed by a bootstrapping. The association between the score and NH was assessed by logistic regression. Results: We studied 10216 pregnancies, 410 (4.0%) with NH. The model's AUC was 0.628 (95%CI: 0.599–0.657). Optimism-corrected c-index: 0.626. Points were assigned to variables associated with NH in proportion to the model's lowest regression coefficient: insulin-treatment 1, preeclampsia 3, preterm delivery 2, male sex 1, and small-for-gestational-age 2, or large-for-gestational-age 3. NH prevalence by score category 0-1, 2, 3, 4, and ≥5 was 2.3%, 3.0%, 4.5%, 6.0%, 7.4%, and 11.5%, respectively. Per point, the OR for NH was 1.35 (95% CI: 1.27–1.42). A score of 2, 3, 4, 5 or ≥6 (versus ≤1) had a OR for NH of 1.67 (1.29–2.15), 2.24 (1.65–3.04), 2.83 (2.02–3.98), 3.08 (1.83–5.16), and 6.84 (4.34–10.77), respectively. Conclusion: Per each score point, women with GD had 35% higher risk of NH. Those with ≥6 points had 6.8-fold higher risk of NH compared to a score ≤1. Our score may be useful for identifying women at a higher risk of NH. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the intramucosal retention system in patients' masticatory efficiency and quality of life in this case series. Material and Methods: A total of 3 individuals with maxillectomy were included for rehabilitation with a complete obturator prostheses with an intramucosal retention system (OPI). The complete obturator prostheses was made for 60 days, and electromyography assessments and bite force were applied before, after 30, 60, and 90 days of surgery and prostheses installation. The University of Washington Quality of Life Questionnaire (UW-QoL) and the Obturator Functional Scale (OFS) were also administered at baseline and in the same follow-up periods. The electromyography was evaluated on both sides of the masseter, temporalis, and buccinator muscles while chewing hard and soft food. The maximum bite force was recorded in the central incisors and both sides of the first molar region. Results: Bite force values increased in the first molar region, and muscular electrical activity remained constant. Items related to the taste and swallowing of the UW-QOL impacted. Most OFS questionnaire data responses indicated that patients improved in swallowing liquid foods and appearance. Conclusions: The rehabilitative capacity improves masticatory efficiency and QoL in adults maxilectomized and rehabilitated with OPI analysis in the study. Further clinical studies should be encouraged to determine the effectiveness of this retentive system. [ABSTRACT FROM AUTHOR]

This study investigates the influence of particle size on the chemical, technological, rheological, thermal, and structural properties of whole pinhão flour, employing pre-gelatinized seeds, in response to the growing demand for diverse and healthier food choices. The fractionation conducted using RO-TAP® at different particle sizes (210 μm - P1, 149 μm - P2, 105 μm - P3, and < 105 μm - P4) led to significant changes in chemical composition, mineral content, viscosity, and thermal characteristics. The P3 fraction emerged as particularly promising, with elevated levels of total carbohydrates (60.27 g/100 g), total starch (46.14 g/100 g), and viscosity (1,545.50 cP), making it ideal for baking. Remarkably, P1 and P4 fractions exhibited elevated levels of fiber (46.96 and 38.57 g/100 g), phenolic compounds (13.35 and 13.51 mg EAG/g), and in vitro antioxidant activity. Lipid content increased inversely with particle size, accompanied by a decrease in resistant starch. All the pinhão fractions exhibited substantial mineral content, ranging from 2 to 2.24 g/100 g. Infrared spectroscopy analyses highlighted compositional similarities in samples, which uniformly exhibited type C crystallinity and high crystallinity indices (38.89%, 44.28%, 47.11%, and 46.46%, respectively). Fibers negatively affected viscosity, thermal properties, and starch gelatinization. Notably, the fraction with the smallest particle size demonstrated improved suitability for developing gluten-free bread products. This study highlights the importance of processing and fractionating pinhão flour to enhance resource utilization efficiency. Furthermore, the findings provide tangible insights to enhance pinhão production and processing chains, fortifying the food industry and addressing consumer preferences for healthier and more diverse products. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate how the coupling of Material and Energy Flow Analysis (MEFA) with Life Cycle Assessment (LCA) under an urban metabolism (UM) perspective (referred to as the UM-LCA approach) can support the design, evaluation, and monitoring of urban-level circular strategies. For this purpose, we apply the UM-LCA approach to the urban area of Umeå (Sweden) by expanding the goal and scope of a recent MEFA study conducted by the authors of the article. Methods: The modeling combines MEFA with LCA and is performed both retrospectively and prospectively. The MEFA was performed in the prior study following a bottom-up approach to map and quantify material and energy flows in the urban system at the sectoral level. The quantified flows are used in the present study to construct the life cycle inventory (LCI) model of the urban system. The LCI model is first used as a basis of the retrospective LCA (rLCA), which is conducted to assess the environmental performance of the urban system with its sectors. The LCI model is then modified according to future scenarios and is used as a basis of the prospective LCA (pLCA), which is performed to assess the environmental implications of implementing circular strategies in the future. Results and discussion: The rLCA shows that the construction and household sectors are major drivers of environmental impacts in the urban system, with households being the largest contributors to 11 out of 12 analyzed impact categories. It also reveals the most impacting flows within these sectors, including food in households and steel in the construction sector. These findings indicate that the construction and household sectors and their most impacting flows should be prioritized in a circular strategy. Furthermore, the pLCA highlights that a future circular strategy promoting reductions in the material used in these two sectors could lead to higher reductions in all impact categories, ranging from 4.3 to 8.6%, than a strategy focused only on recycling, which could lead to reductions ranging from 0.2 to 1.2%. Conclusions: This study concludes that the UM-LCA approach has great potential to comprehensively analyze, both retrospectively and prospectively, the environmental performance of an urban system providing valuable insights that could support policy makers in designing, assessing, and monitoring urban-level circular strategies. However, further research should address identified limitations of the UM-LCA approach (e.g., limited available data, inability to consider social and economic aspects) to facilitate its applicability and enhance its comprehensiveness. [ABSTRACT FROM AUTHOR]

Objective: To overview the literature to answer the following question: “What is the performance of different therapies on wound healing and postoperative discomfort after palatal ASTG removal?” Methods: SRs that evaluated the wound healing (WH), postoperative pain, bleeding, and analgesic consumption of patients submitted to de-epithelialized/free gingival grafts (FGG) or subepithelial connective tissue grafts (SCTG) removed from the palate were included. The searches were conducted on six white and two gray databases up to December 2023. Methodological quality was evaluated through AMSTAR 2. The synthesis of results was described as a narrative analysis. Results: Ten SRs (involving 25 randomized clinical trials) related to low-level laser therapy (LLLT) (3), platelet-rich fibrin (PRF) (4), cyanoacrylate tissue adhesives (CTA) (2), and ozone therapy (OT) (1) were included in this overview. All techniques demonstrated improvements in WH. LLT, PRF, and CTA reduced pain and analgesic consumption. PRF and CTA reduced bleeding. Regarding methodological quality, the SRs were classified as critically low (2), low (5), moderate (2), or high quality (1). Conclusions: In SRs related to LLLT, PRF, CTA, and OT, the use of different therapies after palatal ASTG removal improved WH and postoperative discomfort. Due to the studies’ low methodological quality and high heterogeneity, data should be interpreted with caution. Clinical relevance: The present overview compiles the evidence of SRs related to different therapies for WH and patients’ postoperative experience and reveals that different treatments can significantly improve the clinical outcomes of patients who require ASTG removal for periodontal or peri-implant surgeries. Registration: PROSPERO registration number: CRD42022301257. [ABSTRACT FROM AUTHOR]

NAD is an essential co-factor for cellular energy metabolism and multiple other processes. Systemic NAD+ deficiency has been implicated in skeletal deformities during development in both humans and mice. NAD levels are maintained by multiple synthetic pathways but which ones are important in bone forming cells is unknown. Here, we generate mice with deletion of Nicotinamide Phosphoribosyltransferase (Nampt), a critical enzyme in the NAD salvage pathway, in all mesenchymal lineage cells of the limbs. At birth, NamptΔPrx1 exhibit dramatic limb shortening due to death of growth plate chondrocytes. Administration of the NAD precursor nicotinamide riboside during pregnancy prevents the majority of in utero defects. Depletion of NAD post-birth also promotes chondrocyte death, preventing further endochondral ossification and joint development. In contrast, osteoblast formation still occurs in knockout mice, in line with distinctly different microenvironments and reliance on redox reactions between chondrocytes and osteoblasts. These findings define a critical role for cell-autonomous NAD homeostasis during endochondral bone formation. Deficiency in NAD+ has been implicated in skeletal deformities during development in both humans and mice. Here, the authors use mice that lack the critical enzyme of the NAD+ salvage pathway Nampt in mesenchymal lineage cells to show that the NAD salvage pathway is indispensable for endochondral but not intramembranous bone development. [ABSTRACT FROM AUTHOR]

The height, diameter, and leaf area of trees influence the anatomical structures because rapid growth requires maintenance of the water conduction in sapwood, despite environmental variations that may limit water supply. Our objective was to evaluate the influence of water availability conditions on the soil in humid and dry sites, on the percentage of sapwood along the trunk, and on the hydraulic properties of the wood of eucalyptus clones. The experimental plantings were carried out in Brazil in humid and dry sites. Six-year-old E. urophylla and E. grandis × E. camaldulensis clones were evaluated under 100% water (W) at each site considering local precipitation and 33% rainfall exclusion (WE) conditions. The wood was evaluated for heartwood and sapwood percentage, apparent sapwood density, diameter, wall thickness and vessel area, potential hydraulic conductivity, and Huber value. Rainfall exclusion at the dry site promoted an increase of 9% of sapwood when compared to the humid site, with an impact on diameter, area, wall thickness and vessel composition index, and lower Huber value for E. grandis × E. camaldulensis wood. The rainfall exclusion increased the sapwood percentage and reduced the growth of E. urophylla. E. grandis × E. camaldulensis had a higher sapwood apparent density at the dry site, while E. urophylla had a higher density at the humid site. The genetic diversity of the clones was expressed in the tree growth and in the sapwood content and was modified by humid and dry sites, which demonstrates different rusticity levels of the clones. [ABSTRACT FROM AUTHOR]

Purpose of Review: Circular RNAs (circRNAs) are RNA transcripts derived from fragments of pre-messenger RNAs through a back-splicing process. An advantage that rises from their circular covalently closed conformation is their high stability, when compared with their linear counterparts. The current review focuses on the emerging roles of circRNAs in osteoporosis, including in osteogenic differentiation and osteoclastogenesis. Their potential as osteoporosis biomarkers will also be discussed. Recent Findings: Although firstly described as non-coding, some of these single-stranded RNAs were recently reported to possess protein-coding capacity. On the other hand, the circRNAs exhibit cell and tissue-specific patterns at the transcriptome level in eukaryotes and are regulated throughout the development or disease progression. Even though thousands of these circular transcripts are listed and annotated, only a limited number of studies describe their biological role in bone processes. Recent evidence indicates inhibitory activator roles in both osteoblasts and osteoclasts differentiation and function. Latest screenings in the blood, plasma, or serum of osteoporosis patients support the potential for circRNA signature to be used as biomarkers in osteoporosis, but further validation is required. Summary: While intense research into circRNAs has been detailing their biological roles, there remains a need for standardization and further research to fulfil the future potential of this emerging and highly promising class of regulatory molecules. [ABSTRACT FROM AUTHOR]

Around ten million people are infected with HTLV-1 worldwide, and 1–4% develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), characterized by an important degeneration of the spinal cord, which can lead to death. Distinct HLA alleles have been associated with either HAM/TSP susceptibility or protection. However, these HLA alleles set may change according to the population studied. Brazil is the second country in the number of HTLV-1-infected people and there are few reports addressing the HLA influence on HTLV-1 infection as well as on disease outcome. The objective of this study was to evaluate the influence of HLA alleles as a risk factor for HAM/TSP and the proviral load (PVL) levels, clinical progression, and death outcomes in an admixed Brazilian population. The HLA-A, -B, -C, and -DRB1 were genotyped in 375 unrelated HTLV-1-infected individuals divided into asymptomatic carriers (AC) (n = 165) and HAM/TSP (n = 210) in a longitudinal cohort from 8 to 22 years of follow-up. Because locus B deviated from Hardy–Weinberg Equilibrium for the study groups, the results represented for HLA-B alleles were inconclusive. The alleles HLA-A*68 and -C*07 were related to HAM/TSP risk in multivariate analysis. The alleles HLA-A*33, and -A*36 were associated with protection against disease progression in HAM/TSP patients, while -C*12, -C*14, and -DRB1*08 were associated with increased risk of death. In the AC group, the presence of, -C*06 and -DRB1*15 alleles influenced an increased PVL, in an adjusted linear regression model, while -A*30, -A*34, -C*06, -C*17 and -DRB1*09 alleles were associated with increased PVL in HAM/TSP group compared to HAM/TSP individuals not carrying these alleles. All these alleles were also related to increased PVL associated with clinical progression outcome. Increased PVL associated with the death outcome was linked to the presence of HLA-A*30. PVL has been associated with HLA, and several alleles were related in AC and HAM/TSP patients with or without interacting with clinical progression outcomes. Understanding the prognostic value of HLA in HAM/TSP pathogenesis can provide important biomarkers tools to improve clinical management and contribute to the discovery of new therapeutic interventions. [ABSTRACT FROM AUTHOR]

The threats to agrobiodiversity ultimately affect our future food security. Countries bonded to national or international biodiversity conservation legislation should conserve and sustainably use their agrobiodiversity. Landraces are a key element of agrobiodiversity which is largely endangered due to lack of their systematic conservation, and partially due to obstacles in developing inventories which may be assigned to the difficulties in applying a standard landrace' definition and to complications associated with nomenclature (synonyms/homonyms). Effective national conservation of landraces can be best achieved with a comprehensive inventory. In this paper, we developed a comprehensive inventory of food and other Portuguese agricultural landraces by surveying literature, local media, and farms. Farms were selected based on knowledge of experts and using an ecogeographic diversity approach based on Geographic Information Systems. We compiled 14,813 records of 7492 different landraces. Grape vine (Vitis vinifera L.), common beans (Phaseolus vulgaris L.), and maize (Zea mays L. subsp. mays) have the highest number of landraces in Portugal according with the gathered data. Bragança and Faro are the districts with more records of landraces. The landrace inventory for Portugal that we developed is a first iteration of such kind and should be updated systematically. [ABSTRACT FROM AUTHOR]

Development is generally viewed as one-way traffic of cell state transition from primitive to developmentally advanced states. However, molecular mechanisms that ensure the unidirectional transition of cell fates remain largely unknown. Through exact transcription start site mapping, we report an evolutionarily conserved BTB domain-containing zinc finger protein, ZBTB12, as a molecular barrier for dedifferentiation of human pluripotent stem cells (hPSCs). Single-cell RNA sequencing reveals that ZBTB12 is essential for three germ layer differentiation by blocking hPSC dedifferentiation. Mechanistically, ZBTB12 fine-tunes the expression of human endogenous retrovirus H (HERVH), a primate-specific retrotransposon, and targets specific transcripts that utilize HERVH as a regulatory element. In particular, the downregulation of HERVH-overlapping long non-coding RNAs (lncRNAs) by ZBTB12 is necessary for a successful exit from a pluripotent state and lineage derivation. Overall, we identify ZBTB12 as a molecular barrier that safeguards the unidirectional transition of metastable stem cell fates toward developmentally advanced states. The metastability of stem cells requires a mechanism for actively blocking dedifferentiation to achieve successful differentiation. Here the authors show that ZBTB12 serves as a molecular barrier to dedifferentiation by repressing a primate-specific retrotransposon, HERVH. [ABSTRACT FROM AUTHOR]

Purpose: Short stature predicts higher risk of developing type 2 diabetes. We studied the association between height and glucose intolerance in women with gestational diabetes mellitus (GDM) and whether this association differed according to body mass index (BMI). Methods: Retrospective study of the Portuguese GDM registry. Exclusion criteria: missing data on postpartum oral glucose tolerance test (OGTT) or BMI. Endpoint: postpartum glucose intolerance (diabetes mellitus or prediabetes on the 6–8 weeks postpartum OGTT). Women were divided by mean height and compared. A multivariate logistic regression was used, and the analysis was stratified by BMI (cut-off: 30 kg/m2) and interaction was tested. Results: We included 7402 women; mean height was 161.9 ± 6.2 cm. Taller women had lower BMI and lower rates of glucose intolerance (6.8 vs. 8.8%, p = 0.002). Women with BMI < 30 kg/m2 were taller than those with obesity. Height associated with glucose intolerance. The multivariate adjusted OR of glucose intolerance was 0.98 (95% CI 0.96–0.99), p = 0.001, per 1 cm increase in height. This association was only observed in women with BMI < 30 kg/m2: OR 0.97 (95% CI 0.95–0.99), < 0.001. There was no such association in women with BMI ≥ 30 kg/m2: OR 0.99 (95% CI 0.97–1.02), p = 0.65. P for interaction between BMI and height was 0.09. Conclusions: In non-obese pre-gestational women, height is inversely associated with postpartum glucose intolerance. Per 1 cm increase in height, women present a 3% decrease in the risk of developing diabetes mellitus or prediabetes. [ABSTRACT FROM AUTHOR]

Dementia with Lewy bodies is a neurodegenerative disease, sharing features with Parkinson's and Alzheimer's diseases. We report a case of a patient dementia with Lewy bodies carrying combined PSEN1 and ATP7B mutations. A man developed dementia with Lewy bodies starting at the age of 60 years. CSF biomarkers were of Alzheimer's disease and DaTSCAN was abnormal. Whole-exome sequencing revealed a heterozygous p.Ile408Thr PSEN1 variant and a homozygous p.Arg616Trp ATP7B variant. This case reinstates the need of considering ATP7B mutations when evaluating a patient with parkinsonism and supports p.Ile408Thr as a pathogenic PSEN1 variant. [ABSTRACT FROM AUTHOR]

Aims: To access the impact of increasing use of metformin on cesarean section and large for gestational age rates, when compared to insulin. Methods: A retrospective observational study was developed using data from the Portuguese National Registry, between 2011 and 2019, of 5038 Portuguese women with single pregnancies and gestational diabetes treated with metformin and/or insulin. Three groups were defined according to the therapeutic regimen adopted: g1–insulin in monotherapy (n = 3027[60.1%]); g2–metformin in monotherapy (n = 1366[27.1%]); g3–metformin and insulin (n = 645[12.8%]). Multivariate analysis was adjusted for statistically significant covariates. Results: The cesarean section rate in g1 was similar to g2 (g1:36.9% vs. g2:37%, p = 0.982), although g3 was associated with cesarean delivery (g3:43.6% vs. g1:36.9%, p = 0.005; g3:43.6% vs. g1:37.0%, p = 0.002), with no differences reported in the multivariate analysis adjusted for year of delivery and pregestational body mass index. A delivery of a large for gestational age newborn was less frequently observed in g2 than in g1 (g2:4.1% vs. g1:5.4%, p = 0.044) and in g3 (g2:4.1% vs. g3:9.1%, p < 0.001), and in g1, when compared to g3 (g1:5.4% vs. g3:9.1%, p < 0.001). In the multivariate analysis, g2 showed lower odds of delivering a large for gestational age newborn, compared to g1 (β = −0.511, OR = 0.596, CI95% = 0.428–0.832, p < 0.001). Conclusions: The use of metformin was not associated with higher cesarean section rates, compared to insulin. Instead, it was suggested a protective role of metformin on large gestational age rates. The concomitant use of dual therapy suggests more complex pregnancies, requiring closer surveillance that mitigate serious perinatal and obstetrical outcomes. [ABSTRACT FROM AUTHOR]

We describe in vivo follow-up PET imaging and postmortem findings from an autosomal dominant Alzheimer's disease (ADAD) PSEN1 E280A carrier who was also homozygous for the APOE3 Christchurch (APOE3ch) variant and was protected against Alzheimer's symptoms for almost three decades beyond the expected age of onset. We identified a distinct anatomical pattern of tau pathology with atypical accumulation in vivo and unusual postmortem regional distribution characterized by sparing in the frontal cortex and severe pathology in the occipital cortex. The frontal cortex and the hippocampus, less affected than the occipital cortex by tau pathology, contained Related Orphan Receptor B (RORB) positive neurons, homeostatic astrocytes and higher APOE expression. The occipital cortex, the only cortical region showing cerebral amyloid angiopathy (CAA), exhibited a distinctive chronic inflammatory microglial profile and lower APOE expression. Thus, the Christchurch variant may impact the distribution of tau pathology, modulate age at onset, severity, progression, and clinical presentation of ADAD, suggesting possible therapeutic strategies. [ABSTRACT FROM AUTHOR]

The protective effect of estrogens against cortical bone loss is mediated via direct actions on mesenchymal cells, but functional evidence for the mediators of these effects has only recently begun to emerge. We report that the matrix metalloproteinase 13 (MMP13) is the highest up-regulated gene in mesenchymal cells from mice lacking the estrogen receptor alpha (ERα). In sham-operated female mice with conditional Mmp13 deletion in Prrx1 expressing cells (Mmp13ΔPrrx1), the femur and tibia length was lower as compared to control littermates (Mmp13f./f). Additionally, in the sham-operated female Mmp13ΔPrrx1 mice cortical thickness and trabecular bone volume in the femur and tibia were higher and osteoclast number at the endocortical surfaces was lower, whereas bone formation rate was unaffected. Notably, the decrease of cortical thickness caused by ovariectomy (OVX) in the femur and tibia of Mmp13f./f mice was attenuated in the Mmp13ΔPrrx1 mice; but the decrease of trabecular bone caused by OVX was not affected. These results reveal that mesenchymal cell–derived MMP13 may regulate osteoclast number and/or activity, bone resorption, and bone mass. And increased production of mesenchymal cell-derived factors may be important mediators of the adverse effect of estrogen deficiency on cortical, but not trabecular, bone. [ABSTRACT FROM AUTHOR]

The formation of membraneless organelles can be a proteotoxic stress control mechanism that locally condenses a set of components capable of mediating protein degradation decisions. The breadth of mechanisms by which cells respond to stressors and form specific functional types of membraneless organelles, is incompletely understood. We found that Bcl2-associated athanogene 2 (BAG2) marks a distinct phase-separated membraneless organelle, triggered by several forms of stress, particularly hyper-osmotic stress. Distinct from well-known condensates such as stress granules and processing bodies, BAG2-containing granules lack RNA, lack ubiquitin and promote client degradation in a ubiquitin-independent manner via the 20S proteasome. These organelles protect the viability of cells from stress and can traffic to the client protein, in the case of Tau protein, on the microtubule. Components of these ubiquitin-independent degradation organelles include the chaperone HSP-70 and the 20S proteasome activated by members of the PA28 (PMSE) family. BAG2 condensates did not co-localize with LAMP-1 or p62/SQSTM1. When the proteasome is inhibited, BAG2 condensates and the autophagy markers traffic to an aggresome-like structure. While cellular stress shuts down translation, how protein degradation occurs with stress is incompletely understood. The authors describe a stress-induced phase separated organelle that mediates ubiquitin-independent degradation in the proteasome. [ABSTRACT FROM AUTHOR]

Hyperglycaemia first detected during pregnancy is either gestational diabetes mellitus (GDM) or previous undiagnosed diabetes. We aimed to study if there were a first trimester fasting glycaemia (FTG) and a glycated haemoglobin (HbA1c) cut-off values associated with type 2 diabetes mellitus (T2DM) or abnormal glucose homeostasis (AGH) at the post-partum oral glucose tolerance test (OGTT) reclassification. We retrospectively studied a group of pregnant women from the Portuguese National Registry of GDM. Receiver-operating characteristic (ROC) curves were used to determine the best FTG and HbA1c cut-offs to predict T2DM and AGH. We studied 4068 women. The area under the ROC curves (AUC) for the association with T2DM was 0.85 (0.80–0.90) for FTG and 0.85 (0.80–0.91) for HbA1c. The best FTG cut-off for association with T2DM was 99 mg/dL: sensitivity 77.4%, specificity 74.3%, positive predictive value (PPV) 4.8%, and negative predictive value (NPV) 99.5%. The best HbA1c cut-off for association with T2DM was 5.4%: sensitivity 79.0%, specificity 80.1%, PPV 5.7%, and NPV 99.6%. The AUC for the association of FTG and HbA1c with AGH were 0.73 (0.70–0.76) and 0.71 (0.67–0.74), respectively. The best FTG cut-off for predicting AGH was 99 mg/dL: sensitivity 59.4%, specificity 76.2%, PPV 17.0%, and NPV 95.8%. The best HbA1c cut-off was 5.4%: sensitivity 48.7%, specificity 81.5%, PPV 17.8%, and NPV 95.1%. We suggest an FTG of 99 mg/dL and an HbA1c of 5.4% as the best cut-offs below which T2DM is unlikely to be present. Almost all patients with FTG < 99 mg/dL and HbA1c < 5.4% did not reclassify as T2DM. These early pregnancy cut-offs might alert the physician for the possibility of a previous undiagnosed diabetes and alert them to the importance of testing for it after delivery. [ABSTRACT FROM AUTHOR]

Malaria remains a widespread public health problem in tropical and subtropical regions around the world, and there is still no vaccine available for full protection. In recent years, it has been observed that spores of Bacillus subtillis can act as a vaccine carrier and adjuvant, promoting an elevated humoral response after co-administration with antigens either coupled or integrated to their surface. In our study, B. subtillis spores from the KO7 strain were used to couple the recombinant CSP protein of P. falciparum (rPfCSP), and the nasal humoral-induced immune response in Balb/C mice was evaluated. Our results demonstrate that the spores coupled to rPfCSP increase the immunogenicity of the antigen, which induces high levels of serum IgG, and with balanced Th1/Th2 immune response, being detected antibodies in serum samples for 250 days. Therefore, the use of B. subtilis spores appears to be promising for use as an adjuvant in a vaccine formulation. [ABSTRACT FROM AUTHOR]

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common inherited cerebral small vessel disease. It is caused by mutations in the NOTCH3 gene, which encodes a membranebound receptor protein with three main distinct functional domains. Thus far, several different NOTCH3 mutations, most of them cysteine altering variants, have been described and although they tend to cluster in certain exons, their distribution varies in different geographically populations. Therefore, in this study, we describe the mutation analysis of NOTCH3 gene in 24 Portuguese families with small vessel disease suspected to have CADASIL from the central region of Portugal. The genetic analysis revealed 15 different heterozygous variants, eight pathogenic cysteine altering variants, six cysteine sparing variants and one nonsense variant, located mainly in the exons 4, 8 and 11. Thus, in our population, the genetic testing should initially be focused on these exons. In addition, the genetic findings broaden the mutational and clinical spectrum of CADASIL related phenotype and provide additional evidences for genetic counseling and clinical management. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: The objective was to estimate the prevalence and assess the impact of lower urinary tract symptoms (LUTS) on the quality of life of incarcerated women. Methods: Cross-sectional study conducted with 307 incarcerated women from the state of Ceará, Brazil, from June to September 2018. To identify the prevalence of symptoms, an instrument was developed according to the recommendations of the International Continence Society. To assess the frequency, intensity, and impact of the identified symptoms on quality of life, the International Consultation on Incontinence Questionnaire—Short Form and King's Health Questionnaire were applied. Results: The profile of the inmates was mostly young women (mean = 32.9 ± 11.8 years), Black, who had been in prison for a mean of 17.3 ± 12.0 months. Approximately half (n = 152, 49.5%) presented with storage complaints, with emphasis on urinary incontinence (n = 61, 19.9%), nocturia (n = 55, 17.9%), and urinary urgency (n = 45, 14.7%). Among the voiding symptoms (n = 71, 23.1%), dysuria (n = 39, 12.7%), and recurrent UTI (n = 44, 14.3%) were the most frequent. The complaint of incomplete bladder emptying (19.5%) was mentioned by 60 of the inmates. Sociodemographic data and environmental conditions were mainly associated with storage symptoms (p = 0.019). Women from prisons 2 and 3 presented with a greater impact on the quality of life. Conclusions: The high prevalence of LUTS in female inmates, together with unhealthy toileting behaviors within the prison units, indicate that incarceration might play a role in the occurrence of these symptoms, while also affecting quality of life. The acknowledgement and investigation of these symptoms is important for improving health care in prisons. [ABSTRACT FROM AUTHOR]

Local crystallization of ferromagnetic layers is crucial in the successful realization of miniaturized tunneling magnetoresistance (TMR) devices. In the case of Co–Fe–B TMR devices, used most successfully so far in applications and devices, Co–Fe–B layers are initially deposited in an amorphous state and annealed post-deposition to induce crystallization in Co–Fe, thereby increasing the device performance. In this work, first direct proof of locally triggered crystallization of 10 nm thick Co–Fe–B films by laser irradiation is provided by means of X-ray diffraction (XRD) using synchrotron radiation. A comparison with furnace annealing is performed for benchmarking purposes, covering different annealing parameters, including temperature and duration in the case of furnace annealing, as well as laser intensity and scanning speed for the laser annealing. Films of Co–Fe–B with different stoichiometry sandwiched between a Ru and a Ta or MgO layer were systematically assessed by XRD and SQUID magnetometry in order to elucidate the crystallization mechanisms. The transformation of Co–Fe–B films from amorphous to crystalline is revealed by the presence of pronounced CoFe(110) and/or CoFe(200) reflexes in the XRD θ-2θ scans, depending on the capping layer. For a certain window of parameters, comparable crystallization yields are obtained with furnace and laser annealing. Samples with an MgO capping layer required a slightly lower laser intensity to achieve equivalent Co–Fe crystallization yields, highlighting the potential of laser annealing to locally enhance the TMR ratio. [ABSTRACT FROM AUTHOR]

Although native to Australia, Eucalyptus species are found throughout Europe. At present, they are located mainly in the Iberian Peninsula and Eucalyptus globulus is the most commonly planted species. Climate forecasts anticipate an expansion of Eucalyptus to other regions of Europe. The fast growth of E. globulus, together with its resprouting ability and wood properties, has promoted the use of this species in the Iberian Peninsula. The total volume of E. globulus harvested there was close to 14 million m3 in 2019. Eucalyptus species represent the main source of raw material for the pulp and paper industries and provide an important source of income to non-industrial owners. Being exotic fast-growing trees, their expansion has also been associated with negative environmental impacts. The species therefore poses a series of challenges, while also generating opportunities. The objectives of this review paper are: (1) to summarize the importance of Eucalyptus plantations in Europe; (2) to analyse the opportunities and challenges of this genus in present and future plantations in Europe; (3) to assess to what extent forest management, at both stand and landscape levels, can reduce negative impacts; (4) to make policy and management recommendations that may support the use of this genus in other European regions. These aims are accomplished based on a thorough literature review, particularly focused on research developed in the Iberian Peninsula. [ABSTRACT FROM AUTHOR]

Aim: Metformin use in gestational diabetes (GDM) is a common practice. Although its use in combination with insulin might be advantageous, it was never formally tested. We studied whether combined treatment was associated with better obstetric or neonatal outcomes compared to insulin alone. Methods: This is a retrospective study, using the Portuguese National Registry of GDM (2012–2017), of women treated with insulin ± metformin. Primary endpoints were obstetric and neonatal complications. Secondary endpoints were gestational weight gain (GWG) and insulin dose. A propensity score-matched analysis was performed to balance the distribution of age, BMI, insulin treatment duration, HbA1c, first trimester diagnosis of GDM and previous GDM or macrosomia. Women treated with metformin plus insulin and insulin only were then compared. Results: A total of 4034 women were treated with insulin or insulin plus metformin (10.2%). After propensity score matching, we studied two groups of 386 patients. Obstetric and neonatal complications were similar. Women treated with metformin plus insulin had 201 (52.1%) obstetric complications versus 184 (47.7%) in insulin-only group, p = 0.22; and 112 (29.0%) neonatal complications versus 96 (24.9%), p = 0.19. Patients treated with metformin plus insulin had similar GWG, excessive weight gain and insulin dose compared to the insulin-only group. Conclusions: Women with GDM treated with insulin plus metformin had similar obstetric and neonatal complications, weight gained and insulin dose compared to those only treated with insulin. [ABSTRACT FROM AUTHOR]

The interplay between cervical cancer (CC) and immune cells, mainly intratumoral lymphocytes, has a pivotal role in carcinogenesis. In this context, we evaluated the distribution of CD45RA+ and CD45RO+ cells as well as CCR6+ and CCL20+ cells in intraepithelial (IE) and marginal stroma (MS) areas from cervical intraepithelial neoplasia (CIN) I–III, and CC as 'immunoscore' for HPV-induced CC outcome. We observed increased CD45RA+ and CD45RO+ cells distribution in IE and MS areas in the CC group compared to CIN groups and healthy volunteers. Interestingly, there is a remarkable reduction of CCL20+ expressing cells distribution according to lesion severity. The CC group had a significant decrease in CCL20+ and CCR6+-expressing cells distribution in both IE and MS areas compared to all groups. Using the 'immunoscore' model, we observed an increased number of women presenting high CD45RA+/CD45RO+ and low CCL20+/CCR6+ 'immunoscore' in the CC group. Our results suggested a pattern in cervical inflammatory process with increasing CD45RA+/CD45RO+, and decreasing CCL20+/CCR6+ expression in accordance with CIN severity. Taken together, these markers could be evaluated as 'immunoscore' predictors to CC response. A more comprehensive analysis of longitudinal studies should be conducted to associate CD45RA+/CD45RO+ and CCL20+/CCR6+ 'immunoscore' to CC progression and validate its value as a prognosis method. [ABSTRACT FROM AUTHOR]

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common inherited cerebral small vessel disease and is caused by mutations in the NOTCH3 gene. Interestingly, CADASIL patients present a large phenotypic variability even harboring the same pathogenic variant. We describe two CADASIL siblings with a particularly aggressive clinical phenotype characterized by early-onset stroke, gait disturbances and/or dementia, severe emotional dysregulation, and dysexecutive syndrome together with a severe white matter burden on MRI. The genetic analysis revealed the co-occurrence of NOTCH3 (p.Gly420Cys) and SQSTM1 (p.Ser275Phefs*17) pathogenic variants which might worsen the aggressiveness of disease progression in both siblings. Interestingly, to the best of our knowledge, mutations in SQSTM1 gene have never been described in CADASIL patients before. Curiously, both Notch3 and p62 encoded proteins have a key role in the autophagy-lysosomal pathway which is impaired in CADASIL patients. Thus, the contribution of SQSTM1 gene to the clinical heterogeneity of CADASIL patients, in particular for those who develop cognitive impairment or dementia at an early age, is certainly overlooked. Therefore, we advocate expanding the genetic analysis to other genes associated with the phenotype spectrum of CADASIL patients using NGS-customized gene panel. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Regulation of hnRNPA1 by microRNAs controls the miR-18a-K-RAS axis in chemotherapy-resistant ovarian cancer." The correction addresses errors in Figure 3b and Figure 4c of the original publication. The errors involved duplicated images in the wrong positions, but did not affect the interpretation of the results. The corrected versions of the figures have been provided. The article discusses the effects of miR-25-3p and miR-15a-5p on the proliferation, colony formation, migration, and invasion of ovarian cancer cells, as well as the antitumor effects of anti-miR-25-3p and anti-miR-15a-5p in ovarian cancer mouse models. The authors of the article are Cristian Rodriguez-Aguayo, Paloma del C Monroig, Roxana S. Redis, Emine Bayraktar, Maria I. Almeida, Cristina Ivan, Enrique Fuentes-Mattei, Mohammed H. Rashed, Arturo Chavez-Reyes, Bulent Ozpolat, Rahul Mitra, Anil K. Sood, George A. Calin, and Gabriel Lopez-Berestein. [Extracted from the article]

Biochar from sewage sludge is a low-cost sorbent that may be used for several environmental functions. This study evaluates the induced effects of pyrolysis temperature on the physicochemical characteristics of sewage sludge (SS) biochar produced at 350 (SSB350), 450 (SSB450) and 600 (SSB600), based on the metal enrichment index, metal mobility index (MMI), and potential ecological risk index (PERI) of Cd, Cu, Pb, and Zn. Increased pyrolysis temperature reduced the biochar concentration of elements that are lost as volatile compounds (C, N, H, O, and S), while the concentration of stable aromatic carbon, ash, alkalinity, some macro (Ca, Mg, P2O5, and K2O) and micronutrients (Cu and Zn), and toxic elements such as Pb and Cd increased. Increasing the pyrolysis temperature is also important in the transformation of metals from toxic and available forms into more stable potentially available and non-available forms. Based on the individual potential ecological risk index, Cd in the SS and SSB450 were in the moderate and considerable contamination ranges, respectively. For all pyrolysis temperature biochar Cd was the highest metal contributor to the PERI. Despite this, the potential ecological risk index of the SS and SSBs was graded as low. [ABSTRACT FROM AUTHOR]

Although seismic activity in Brazil is low to moderate, some earthquakes with damage potential occurred in the past. Engineering structures located along the coast and those installed in deep waters need to comply with safety requirements. In addition, there is a need to address the public interest regarding the effects of seismically-induced landslides. Therefore, a probabilistic seismic hazard assessment was carried out for the offshore south/southeast regions of Brazil, in order to estimate potential levels of ground motion. A historical and recent instrumental seismicity catalog for this region has been compiled. A stochastic attenuation relation with different seismic source models and recurrence parameters was used in a hazard analysis with the CRISIS 2012 software. To capture the epistemic and aleatoric uncertainties in the hazard calculations, a logic tree approach was adopted, considering different seismic zone models, seismic activity parameters, and scaling factors in the Ground Motion Prediction Equation. It was verified that the Peak Ground Accelerations are mostly less than 2.0% g in the continental portion of the region (for 10% exceedance probability in 50 years). At a particular point of interest located offshore in the continental slope of the study area, the seismic hazard is also low, with the maximum acceleration for the probability of exceedance of 10% and 2% in 50 years reaching mean values of 3.2% and 19.1% g, respectively, for very hard rock conditions. [ABSTRACT FROM AUTHOR]

Loss of estrogens at menopause is a major cause of osteoporosis and increased fracture risk. Estrogens protect against bone loss by decreasing osteoclast number through direct actions on cells of the myeloid lineage. Here, we investigated the molecular mechanism of this effect. We report that 17β-estradiol (E2) decreased osteoclast number by promoting the apoptosis of early osteoclast progenitors, but not mature osteoclasts. This effect was abrogated in cells lacking Bak/Bax—two pro-apoptotic members of the Bcl-2 family of proteins required for mitochondrial apoptotic death. FasL has been previously implicated in the pro-apoptotic actions of E2. However, we show herein that FasL-deficient mice lose bone mass following ovariectomy indistinguishably from FasL-intact controls, indicating that FasL is not a major contributor to the anti-osteoclastogenic actions of estrogens. Instead, using microarray analysis we have elucidated that ERα-mediated estrogen signaling in osteoclast progenitors decreases "oxidative phosphorylation" and the expression of mitochondria complex I genes. Additionally, E2 decreased the activity of complex I and oxygen consumption rate. Similar to E2, the complex I inhibitor Rotenone decreased osteoclastogenesis by promoting osteoclast progenitor apoptosis via Bak/Bax. These findings demonstrate that estrogens decrease osteoclast number by attenuating respiration, and thereby, promoting mitochondrial apoptotic death of early osteoclast progenitors. [ABSTRACT FROM AUTHOR]

In the present study, we investigated the cardioprotective effects of coenzyme Q10 (Q10) against doxorubicin (DOXO) induced cardiomyopathy. Twenty adult rats were distributed in four experimental groups: group 1 received NaCl 0.9% at 1 ml/day for 14 days; group 2 received Q10 at 1 mg/kg/day for 14 days; group 3 received initial 7 days of treatment with NaCl 0.9% followed by a single dose of doxorubicin (12.5 mg/kg IP) and another 7 days of NaCl; and group 4 received initial 7 days of Q10 1 mg/kg/day, followed by a single dose of doxorubicin (12.5 mg/kg IP) and another 7 days of Q10. At the end of 14 days, systolic, diastolic and mean blood pressure, electrocardiogram (ECG), complete blood count, and serum biochemical profile were evaluated. We also analyzed heart histological and ultrastructure analysis, and estimated heart's oxidative stress and lipid peroxidation. DOXO administration altered ECG, with increase heart rate, P-wave duration, PR interval duration, and T-wave amplitude. All the parameters were significantly reduced following Q10 treatment. DOXO also caused increase in CK, CK-MB, LDH, and urea levels, which were not mitigated by Q10 treatment. However, Q10 reduced oxidative stress by interfering with superoxide dismutase, significantly decreasing lipid peroxidation in heart tissue. DOXO administration also leads to several histological and ultrastructure alterations including cardiomyocyte degeneration and intense intracelullar autophagosomes, all minimized by Q10 treatment. Q10 treatment prevented the ECG changes, minimized oxidative stress, lipid peroxidation, and DOXO-induced heart tissue alterations. Our findings suggest that pre- and post-treatment with Q10 exerts potential cardioprotective effect against the DOX-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

Small molecules that selectively kill senescent cells (SCs), termed senolytics, have the potential to prevent and treat various age-related diseases and extend healthspan. The use of Bcl-xl inhibitors as senolytics is largely limited by their on-target and dose-limiting platelet toxicity. Here, we report the use of proteolysis-targeting chimera (PROTAC) technology to reduce the platelet toxicity of navitoclax (also known as ABT263), a Bcl-2 and Bcl-xl dual inhibitor, by converting it into PZ15227 (PZ), a Bcl-xl PROTAC, which targets Bcl-xl to the cereblon (CRBN) E3 ligase for degradation. Compared to ABT263, PZ is less toxic to platelets, but equally or slightly more potent against SCs because CRBN is poorly expressed in platelets. PZ effectively clears SCs and rejuvenates tissue stem and progenitor cells in naturally aged mice without causing severe thrombocytopenia. With further improvement, Bcl-xl PROTACs have the potential to become safer and more potent senolytic agents than Bcl-xl inhibitors. Senolytics have the potential to extend healthspan by selectively killing senescent cells (SCs), but senolytics that target Bcl-xl may cause platelet toxicity. Here, the authors generated a Bcl-xl proteolysis-targeting chimera (PROTAC) senolytic, which effectively clears SCs and rejuvenates tissue stem and progenitor cells in naturally aged mice without causing severe thrombocytopenia. [ABSTRACT FROM AUTHOR]

Literature on earthquake impact on hospital admissions is lacking, particularly in low-resource settings. Our aim was to study the pattern of admissions before and after the 2015 earthquake in a tertiary hospital in Nepal. We used routine hospital data from 9,596 admissions, and defined four periods: pre-earthquake (pre-EQ), acute (EQ1), post-acute (EQ2), and post-earthquake (post-EQ). We compared length of hospital stay (LOS) across the study periods using negative binomial regressions. We used logistic regressions to study changes in probability of admission for diagnostic categories, and Generalized Additive Models to model the difference in number of admissions compared to pre-EQ baseline. LOS was longer in EQ1 than during pre-EQ, in particular for injury-related admissions. In EQ1, the odds of injury admissions increased, while they decreased for the majority of other diagnoses, with the odds of pregnancy-related admissions remaining low until post-EQ. The number of admissions dropped in EQ1 and EQ2, and returned to pre-EQ trends in post-EQ, accumulating 381 admissions lost (CI: 206–556). Our findings suggest that hospital disaster plans must not only foresee injury management after earthquakes, but also ensure accessibility, in particular for pregnant women, and promote a quick return to normality to prevent additional negative health outcomes. [ABSTRACT FROM AUTHOR]

In Portugal people aged 65 and above will be the populational group with the highest growth rate of the next decades. Healthy ageing constitutes a challenge as not only the number of years lived are essential, but also the quality of life becomes a priority. The aim of this study was to understand the relationship between health self-perception (HSP), food consumption and nutritional status among Portuguese older adults. Four hundred fifty-nine older adults (aged ≥ 65) were interviewed, almost half had a positive HSP. The most significant predictor of HSP was nutritional status, p = 0.005, but independence in shopping had the largest impact on how they compared to others, p < 0.001. Interventions need to focus on factors like nutritional status, independency on Activities of Daily Living, Satisfaction with Food-Related Life and utilize them to modify the negative HSP and attitudes towards ageing and health and maximize the positive aspects of old age. [ABSTRACT FROM AUTHOR]

Purpose: Computed tomography (CT) is commonly used to guide drainage of deep-seated abdominal fluid collections. However, in some cases, these collections seem to be inaccessible due to surrounding organs or their being in difficult locations. The aim of this study is to describe a modified Trocar technique to drain collections in difficult locations, especially those in the subphrenic space, without passing through intervening organs.Materials and Methods: This retrospective case series study describes seven inpatients who underwent CT-guided drainage using a modified Trocar technique for abscesses that are difficult to access percutaneously. All patients provided written informed consent prior to the procedure. After placement of a 12-14F catheter inside the peritoneum, the Trocar stylet was removed so that the tip of the catheter became blunt and flexible to avoid injury to organs and structures in the catheter route, and the catheter was slowly advanced towards the collection using CT guidance and tactile sensation. After reaching the target, the stylet was reintroduced to enter the abscess wall.Results: All procedures were performed using an anterior abdominal wall access with adequate catheter positioning and resulted in clinical status improvement in the days after the drainage. No complications related to the procedure were identified in any of the patients.Conclusions: The modified Trocar technique for percutaneous CT-guided drainage of abdominal abscesses may be feasible for lesions that are difficult to access with conventional methods. [ABSTRACT FROM AUTHOR]

Green banana is a great potential source for starch. The functional properties of starch can be improved by applying various innovative and safe technologies with the physical modifications being most desired by maintaining granular integrity and not making use of chemical reagents. The objective of this study was to investigate the effects of physical modification by low heat-moisture treatment (HMT) using moisture contents of 15%, 20%, and 25% in Prata green banana starch (Musa AAB-Prata). The extraction yield of starch was 23.80 ± 3.3%. The native starch showed a high amylose content (42.13 ± 0.26%), which was reduced by HMT at 15 and 20% moisture. The HMT did not change the morphology and the degree of molecular ordering in Prata green banana starch granule observed by scanning electron microscopy and Fourier-transform infrared spectrometry, respectively. However, starch modification caused a significant reduction in the swelling power of the starches at the higher temperatures (70 °C to 90 °C), besides increasing the gelatinization peak temperature and reducing the gelatinization enthalpy determined by differential scanning calorimetry. On the pasting profile of Rapid Visco Analyzer, it was possible to verify that the HMT reduced peak viscosity, trough, breakdown, and final viscosity and increased the pasting temperature and time to peak viscosity, thereby indicating improvements in starch thermostability and broadening the starch application range in the food industry. [ABSTRACT FROM AUTHOR]

Background: Perioperative chemotherapy and surgery is the standard of care in advanced gastroesophageal cancer patients, but its impact among those treated with radical surgery still needs further assessment. We present the results of this multimodality treatment approach in a gastric cancer patients cohort treated with D2 lymphadenectomy. We aimed to identify prognostic factors associated with improved survival. Patients and Methods: This retrospective cohort study enrolled patients treated with perioperative chemotherapy and resection in a single cancer center in Brazil between 2006 and 2016. Subjects presenting tumors of the gastric stump, esophageal tumors, or treated with intraperitoneal chemotherapy were excluded. Intention-to-treat survival analysis was performed for all subjects who started neoadjuvant chemotherapy, and prognostic factors were determined among those who had R0 resection. Results: This study included 239 patients, of whom 198 had R0 resection. The mean age was 59.9 years, and most had clinical stage IIB or III disease (88%). Among the 239 patients who started neoadjuvant chemotherapy, 207 (86.6%) completed all neoadjuvant treatment cycles, and surgical resection was performed in 225 subjects (94.1%). Overall 60-day morbidity and mortality rates were 35.6% and 4.4%, respectively. For the entire cohort, median survival was 78 months and the 5-year survival rate was 55.3%. Factors associated with worse survival were ypT3–4 stage, ypN + stage, extended resection, and no adjuvant chemotherapy. Conclusions: Perioperative chemotherapy resulted in very good outcomes for patients treated with radical surgery, and downstaging after chemotherapy was shown to be a major determinant of prognosis. [ABSTRACT FROM AUTHOR]

Recently, we have described, in non-genetically modified rats, that peripheral transient receptor potential vanilloid-4 (TRPV4) channels are activated and trigger warmth-defence responses at ambient temperatures of 26–30 °C. Evidence points to the presence of TRPV4 in the medial preoptic area, a region described to be involved in the activation of thermoeffector pathways, including those involved in heat loss. Thus, we tested the hypothesis that TRPV4 in the medial preoptic area modulates thermoregulation under warm conditions. To this end, under two ambient temperatures (21 and 28 °C), body temperature was measured in rats following blockade of preoptic TRPV4 with two antagonists, HC-067047 and GSK 2193874. Oxygen consumption, heat loss index and preferred ambient temperature were also determined in order to assess thermoeffector activity. Antagonism of central TRPV4 caused an increase in body temperature in rats exposed to 28 °C, but not in those exposed to 21 °C. The body temperature increase at 28 °C was accompanied by an increase in oxygen consumption and an earlier reduction of the heat loss index. In behavioural experiments, control animals previously exposed to warm ambient temperatures (28–30 °C) for 2 h selected colder temperatures in a thermogradient compared to those injected with HC-067047. Our results support the idea that preoptic TRPV4 modulates thermoregulation in a warm environment by activating both autonomic and behavioural heat loss responses. Thus, according to the present study and to that published recently by our group, the activation of warmth-defence responses by TRPV4 seems to be dependent on the activity of both peripheral and central channels. [ABSTRACT FROM AUTHOR]

This prospective cohort study aimed to assess the association of admission hypothermia (AH) with death and/or major neonatal morbidities among very low birth weight (VLBW) preterm infants based on the relative performance of 20 centers of the Brazilian Network of Neonatal Research. This is a retrospective analysis of prospectively collected data using the database registry of the Brazilian Network on Neonatal Research. Center performance was defined by the relative mortality rate using conditional inference trees. A total of 4356 inborn singleton VLBW preterm infants born between January 2013 and December 2016 without malformations were included in this study. The centers were divided into two groups: G1 (with lower mortality rate) and G2 (with higher mortality rate). Crude and adjusted relative risks (RR) and 95% confidence intervals (95%CI) were estimated by simple and multiple log-binomial regression models. An AH rate of 53.7% (19.8-93.3%) was significantly associated with early neonatal death in G1 (adjusted RR 1.41, 95% CI 1.09-1.84) and G2 (adjusted RR 1.29, 95%CI 1.01-1.65) and with in-hospital death in G1 (adjusted RR 1.29, 95%CI 1.07-1.58). AH was significantly associated with a lower frequency of necrotizing enterocolitis (adjusted RR 0.58, 95%CI 38-0.88) in G2.Conclusion: AH significantly associated with early neonatal death regardless of the hospital performance. In G2, an unexpected protective association between AH and necrotizing enterocolitis was found, whereas the other morbidities assessed were not significantly associated with AH. What is Known: • Admission hypothermia is associated with early neonatal death. • The association of admission hypothermia with major neonatal morbidities has not been fully established. What is New: • Admission hypothermia was significantly associated with early neonatal and in-hospital death in centers with the lowest relative mortality rates. • Admission hypothermia was not associated with major neonatal morbidities and with in-hospital death but was found to be a protective factor against necrotizing colitis in centers with the highest relative mortality rates. [ABSTRACT FROM AUTHOR]

Purpose: Chronic hepatitis C (CHC) is associated with a decreased health-related quality of life (HRQOL). More recent studies have pointed toward a genetic basis of patient-reported quality of life outcomes. Taking into account that the influence of single-nucleotide polymorphisms (SNPs) on the HRQOL of CHC patients has not been studied, we investigated the combined IL10-1082G/A, - 819C/T, and - 592C/A SNPs, and IL6-174G/C SNP. We also evaluated the association between demographic, clinical, psychiatric, virological, and genetic variables with domains and summaries of HRQOL in CHC patients.Methods: 132 consecutive CHC patients and 98 controls underwent psychiatric evaluation by using the Mini International Neuropsychiatric Interview. HRQOL was assessed by a generic questionnaire, the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), and by the specific Liver Disease Quality of Life Questionnaire (LDQOL). IL6 and IL10 polymorphisms were evaluated by Taqman SNP genotyping assay. Multivariate analysis was used to evaluate the associations.Results: Major depressive disorder was associated with lower SF-36 and LDQOL scores in seven and ten domains, respectively. Diabetes and hypertension were also associated with reduced HRQOL. CHC patients carrying the combination of IL10 ATA haplotype/IL6-GG genotype had lower scores in the SF-36-physical functioning domain, and reduced scores in the LDQOL effects of liver disease on activities of daily living, quality of social interaction, and sexual function domains than the non-carriers of the combined haplotype/genotype.Conclusion: This is the first study to demonstrate that combined IL6 high-producer GG genotype and IL10 low-producer ATA haplotype is associated with poorer HRQOL in CHC patients. [ABSTRACT FROM AUTHOR]