Ancestry of the major long-range regulatory site of the α-globin genes in the Portuguese population with the common 3.7 kb α-thalassemia deletion.

BACKGROUND: The α-Major Regulatory Element (α-MRE), also known as HS-40, is located upstream of the α-globin gene cluster and has a crucial role in the long-range regulation of the α-globin gene expression. This enhancer is polymorphic and several haplotypes were identified in different populations, with haplotype D almost exclusively found in African populations. The purpose of this research was to identify the HS-40 haplotype associated with the 3.7 kb α-thalassemia deletion (-α3.7del) in the Portuguese population, and determine its ancestry and influence on patients' hematological phenotype. METHODS AND RESULTS: We selected 111 Portuguese individuals previously analyzed by Gap-PCR to detect the presence of the -α3.7del: 50 without the -α3.7del, 34 heterozygous and 27 homozygous for the -α3.7del. The HS-40 region was amplified by PCR followed by Sanger sequencing. Four HS-40 haplotypes were found (A to D). The distribution of HS-40 haplotypes and genotypes are significantly different between individuals with and without the -α3.7del, being haplotype D and genotype AD the most prevalent in patients with this deletion in homozygosity. Furthermore, multiple correspondence analysis revealed that individuals without the -α3.7del are grouped with other European populations, while samples with the -α3.7del are separated from these and found more closely related to the African population. CONCLUSION: This study revealed for the first time an association of the HS-40 haplotype D with the -α3.7del in the Portuguese population, and its likely African ancestry. These results may have clinical importance as in vitro analysis of haplotype D showed a decrease in its enhancer activity on α-globin gene.

Use of coronary artery calcium score and coronary CT angiography to guide cardiovascular prevention and treatment.

Currently, cardiovascular risk stratification to guide preventive therapy relies on clinical scores based on cardiovascular risk factors. However, the discriminative power of these scores is relatively modest. The use of coronary artery calcium score (CACS) and coronary CT angiography (CCTA) has surfaced as methods for enhancing the estimation of risk and potentially providing insights for personalized treatment in individual patients. CACS improves overall cardiovascular risk prediction and may be used to improve the yield of statin therapy in primary prevention, and possibly identify patients with a favorable risk/benefit relationship for antiplatelet therapies. CCTA holds promise to guide anti-atherosclerotic therapies and to monitor individual response to these treatments by assessing individual plaque features, quantifying total plaque volume and composition, and assessing peri-coronary adipose tissue. In this review, we aim to summarize current evidence regarding the use of CACS and CCTA for guiding lipid-lowering and antiplatelet therapy and discuss the possibility of using plaque burden and plaque phenotyping to monitor response to anti-atherosclerotic therapies.

Use of Local Melatonin with Xenogeneic Bone Graft to Treat Critical-Size Bone Defects in Rats with Osteoporosis: A Randomized Study.

The aim of this study was to evaluate the effect of local administration of melatonin (MLT) on molecular biomarkers and calvaria bone critical defects in female rats with or without osteoporosis, associated or not with a xenogeneic biomaterial. Forty-eight female rats were randomly divided into two groups: (O) ovariectomized and (S) placebo groups. After 45 days of osteoporosis induction, two critical-size defects (5 mm diameter) were created on the calvaria. The groups were subdivided according to the following treatment: (C) Clot, MLT, MLT associated with Bio-Oss® (MLTBO), and Bio-Oss® (BO). After 45 days, the defect samples were collected and processed for microtomography, histomorphometry, and biomolecular analysis (Col-I, BMP-2, and OPN). All animals had one femur harvested to confirm the osteoporosis. Microtomography analysis demonstrated a bone mineral density reduction in the O group. Regarding bone healing, the S group presented greater filling of the defects than the O group; however, in the O group, the defects treated with MLT showed higher mineral filling than the other treatments. There was no difference between the treatments performed in the S group (p = 0.05). Otherwise, O-MLT had neoformed bone higher than in the other groups (p = 0.05). The groups that did not receive biomaterial demonstrated lower levels of Col-I secretion; S-MLT and S-MLTBO presented higher levels of OPN, while O-C presented statistically lower results (p < 0.05); O-BO showed greater BMP-2 secretion (p < 0.05). In the presence of ovariectomy-induced osteoporosis, MLT treatment increased the newly formed bone area, regulated the inflammatory response, and increased OPN expression.

High Pressure Promotes Binding of the Allosteric Inhibitor Zn2+-Cyclen in Crystals of Activated H-Ras.

In this work, we experimentally investigate the potency of high pressure to drive a protein toward an excited state where an inhibitor targeted for this state can bind. Ras proteins are small GTPases cycling between active GTP-bound and inactive GDP-bound states. Various states of GTP-bound Ras in active conformation coexist in solution, amongst them, state 2 which binds to effectors, and state 1, weakly populated at ambient conditions, which has a low affinity for effectors. Zn2+-cyclen is an allosteric inhibitor of Ras protein, designed to bind specifically to the state 1. In H-Ras(wt).Mg2+.GppNHp crystals soaked with Zn2+-cyclen, no binding could be observed, as expected in the state 2 conformation which is the dominant state at ambient pressure. Interestingly, Zn2+-cyclen binding is observed at 500 MPa pressure, close to the nucleotide, in Ras protein that is driven by pressure to a state 1 conformer. The unknown binding mode of Zn2+-cyclen to H-Ras can thus be fully characterized in atomic details. As a more general conjunction from our study, high pressure x-ray crystallography turns out to be a powerful method to induce transitions allowing drug binding in proteins that are in low-populated conformations at ambient conditions, enabling the design of specific inhibitors.

Effectiveness of Laser Acupuncture for Reducing Pain and Increasing Mouth Opening Range in Individuals with Temporomandibular Disorder: A Systematic Review and Network Meta-Analysis.

PURPOSE OF REVIEW: Laser acupuncture (LA) demonstrates promising results in the treatment of musculoskeletal disorders. However, its effects on temporomandibular disorder (TMD) are not yet fully understood. Thus, the aim of this systematic review and network meta-analysis was to assess the effectiveness of LA on pain intensity and maximum mouth opening range (MMO) related to TMD. A search was carried out in 11 electronic databases and references of included studies to locate randomized clinical trials (RCTs) that evaluated LA as a primary treatment for TMD. The risk of bias was assessed using the RoB 2 tool. Network meta-analysis was conducted on the MetaInsight platform, considering the pain intensity and counseling (C) as the outcome of reference. The GRADE system was used to assess the certainty of the evidence. RECENT FINDINGS: Five studies evaluated pain intensity, four with a high risk of bias and one with a low risk. Two studies evaluated pain intensity on palpation (one with high and one with low risk of bias), and one study with high risk of bias evaluated MMO. Laser parameters were: 690-810 nm, 40-150 mW, and 7.5-112.5 J/cm2. Occlusal splint (OS) [- 2.47; CI 95% - 3.64, - 1.30] and Physiotherapy (PT) [-2.64; CI 95% - 3.94, - 1.34] reduced pain intensity compared to C. The ranking of treatments in order of effectiveness was PT > OS > LA > C > CR (craniopuncture). The certainty of the evidence was very low or low. The data do not support the indication of LA for the treatment of TMDs and new placebo-controlled RCTs must be conducted to demonstrate its effectiveness more precisely.

Economic Injury Levels and Economic Thresholds for Leucoptera coffeella as a Function of Insecticide Application Technology in Organic and Conventional Coffee (Coffea arabica), Farms.

Leucoptera coffeella (Lepidoptera: Lyonetiidae) is one of the main pests in coffee crops. The economic injury level (EIL) is the lowest density of the pest at which economic damages match the costs of control measures. The economic threshold (ET) is the density of the pest at which control measures must be taken so that this population does not reach the EIL. These are the main indices used for pest control decision-making. Control of L. coffeella is carried out by manual, tractor, airplane or drone applications. This work aimed to determine EILs and ETs for L. coffeella as a function of insecticide application technology in conventional and organic Coffea arabica crops. Data were collected over five years in commercial C. arabica crops on seven 100 ha central pivots. The cost of control in organic crops was 16.98% higher than conventional. The decreasing order of control cost was manual > drone > airplane > tractor application. Coffee plants were tolerant to low densities (up to 15% mined leaves) of the pest that caused losses of up to 6.56%. At high pest densities (54.20% mined leaves), losses were high (85.62%). In organic and conventional crops and with the use of different insecticide application technologies, EIL and ET were similar. The EIL and ET were 14% and 11% of mined leaves, respectively. Therefore, these indices can be incorporated in integrated pest management programs in C. arabica crops. The indices determined as a function of insecticide application technology in organic and conventional coffee are important as they serve producers with different technological levels. Additionally, EILs and ETs can contribute to more sustainable production, as control methods will only be employed when the pest density reaches these indices.

Cardiac magnetic resonance patterns of left ventricular remodeling in patients with severe aortic stenosis referred to surgical aortic valve replacement.

Left ventricular (LV) hypertrophy is a common finding in patients with severe aortic stenosis (AS). Cardiac magnetic resonance (CMR) is the gold-standard technique to evaluate LV remodeling. Our aim was to assess the prevalence and describe the patterns of LV adaptation in AS patients before and after surgical aortic valve replacement (AVR). Prospective study of 130 consecutive patients (71y [IQR 68-77y], 48% men) with severe AS, referred for surgical AVR. Patterns of LV remodeling were assessed by CMR. Besides normal LV ventricular structure, four other patterns were considered: concentric remodeling, concentric hypertrophy, eccentric hypertrophy, and adverse remodeling. At baseline CMR study: mean LV indexed mass: 81.8 ± 26.7 g/m2; mean end-diastolic LV indexed volume: 85.7 ± 23.1 mL/m2 and median geometric remodeling ratio: 0.96 g/mL [IQR 0.82-1.08 g/mL]. LV hypertrophy occurred in 49% of subjects (concentric 44%; eccentric 5%). Both normal LV structure and concentric remodeling had a prevalence of 25% among the cohort; one patient had an adverse remodeling pattern. Asymmetric LV wall thickening was present in 55% of the patients, with predominant septal involvement. AVR was performed in 119 patients. At 3-6 months after AVR, LV remodeling changed to: normal ventricular geometry in 60%, concentric remodeling in 27%, concentric hypertrophy in 10%, eccentric hypertrophy in 3% and adverse remodeling (one patient). Indexes of AS severity, LV systolic and diastolic function and NT-proBNP were significantly different among the distinct patterns of remodeling. Several distinct patterns of LV remodelling beyond concentric hypertrophy occur in patients with classical severe AS. Asymmetric hypertrophy is a common finding and LV response after AVR is diverse.

Dietary metabarcoding reveals the simplification of bird-pest interaction networks across a gradient of agricultural cover.

Agriculture is vital for supporting human populations, but its intensification often leads to landscape homogenization and a decline in non-provisioning ecosystem services. Ecological intensification and multifunctional landscapes are suggested as nature-based alternatives to intensive agriculture, using ecological processes like natural pest regulation to maximize food production. Birds are recognized for their role in increasing crop yields by consuming invertebrate pests in several agroecosystems. However, the understanding of how bird species, their traits and agricultural land cover influence the structure of bird-pest interactions remains limited. We sampled bird-pest interactions monthly for 1 year, at four sites within a multifunctional landscape, following a gradient of increasing agricultural land cover. We analysed 2583 droppings of 55 bird species with DNA metabarcoding and detected 225 pest species in 1139 samples of 42 bird species. As expected, bird-pest interactions were highly variable across bird species. Dietary pest richness was lower in the fully agricultural site, while predation frequency remained consistent across the agricultural land cover gradient. Network analysis revealed a reduction in the complexity of bird-pest interactions as agricultural coverage increased. Bird species abundance affected the bird's contribution to the network structure more than any of the bird traits analysed (weight, phenology, invertebrate frequency in diet and foraging strata), with more common birds being more important to network structure. Overall, our results show that increasing agricultural land cover increases the homogenization of bird-pest interactions. This shows the importance of maintaining natural patches within agricultural landscapes for biodiversity conservation and enhanced biocontrol.

A agricultura é essencial para suportar a população humana, mas a sua intensificação geralmente leva à homogeneização da paisagem e à redução dos serviços do ecossistema que não sejam de provisão. A intensificação ecológica e paisagens multifuncionais são sugeridas como alternativas naturais à agricultura intensiva, utilizando processos ecológicos como a regulação natural de pragas para maximizar a produção de alimentos. As aves são conhecidas pelo seu papel no aumento da produtividade das culturas por consumirem pragas em diversos agroecossistemas. Contudo, o conhecimento de como as espécies de aves, as suas características e a cobertura agrícola influenciam as interações entre aves e pragas são limitados. Nós amostrámos estas interações mensalmente durante um ano, em quatro locais, numa paisagem multifuncional, ao longo um gradiente de aumento da cobertura agrícola. Analisamos 2583 dejetos de 55 espécies de aves com DNA metabarcoding e detetamos 225 espécies praga em 1139 amostras de 42 espécies de aves. Como esperado, as interações entre aves e pragas foram muito distintas entre as várias espécies de aves. A riqueza de pragas na dieta foi menor no local completamente dominado por área agrícola, enquanto a frequência de predação de pragas foi constante ao longo do gradiente de cobertura agrícola. A análise de redes demonstrou uma redução na complexidade das interações entre aves e pragas à medida que a cobertura agrícola aumenta. A abundância das espécies de aves influenciou mais a contribuição das aves para a estrutura da rede do que qualquer uma das características analisadas (peso, fenologia, frequência de invertebrados na dieta e estrato de alimentação), sendo as aves mais comuns as mais importantes na estrutura da rede. De forma geral, os nossos resultados indicam que o aumento da cobertura agrícola aumenta a homogeneização das interações entre aves e pragas. Isto demonstra a importância de preservar áreas naturais em paisagem agrícolas para a conservação de biodiversidade e melhor controlo biológico.

Evaluating Glass Ionomer Cement Longevity in the Primary and Permanent Teeth-An Umbrella Review.

The aim of this umbrella review was to evaluate the longevity of glass ionomer cement (GIC) as a restorative material for primary and permanent teeth. Research in the literature was conducted in three databases (MedLine/PubMed, Web of Science, and Scopus). The inclusion criteria were: (1) to be a systematic review of clinical trials that (2) evaluated the clinical longevity of GICs as a restorative material in primary and/or permanent teeth; the exclusion criteria were: (1) not being a systematic review of clinical trials; (2) not evaluating longevity/clinical performance of GICs as a restorative material; and (3) studies of dental restorative materials in teeth with enamel alterations, root caries, and non-carious cervical lesions. Twenty-four eligible articles were identified, and 13 were included. The follow-up periods ranged from 6 months to 6 years. Different types of GICs were evaluated in the included studies: resin-modified glass ionomer cement (RMGIC), compomers, and low- and high-viscosity glass ionomer cement. Some studies compared amalgam and composite resins to GICs regarding longevity/clinical performance. Analyzing the AMSTAR-2 results, none of the articles had positive criteria in all the evaluated requisites, and none of the articles had an a priori design. The criteria considered for the analysis of the risk of bias of the included studies were evaluated through the ROBIS tool, and the results of this analysis showed that seven studies had a low risk of bias; three studies had positive results in all criteria except for one criterion of unclear risk; and two studies showed a high risk of bias. GRADE tool was used to determine the quality of evidence; for the degree of recommendations, all studies were classified as Class II, meaning there was still conflicting evidence on the clinical performance/longevity of GICs and their recommendations compared to other materials. The level of evidence was classified as Level B, meaning that the data were obtained from less robust meta-analyses and single randomized clinical trials. To the best of our knowledge, this is the first umbrella review approaching GIC in permanent teeth. GICs are a good choice in both dentitions, but primary dentition presents more evidence, especially regarding the atraumatic restorative treatment (ART) technique. Within the limitation of this study, it is still questionable if GIC is a good restorative material in the medium/long term for permanent and primary dentition. Many of the included studies presented a high risk of bias and low quality. The techniques, type of GIC, type of cavity, and operator experience highly influence clinical performance. Thus, clinical decision-making should be based on the dental practitioner's ability, each case analysis, and the patient's wishes. More evidence is needed to determine which is the best material for definitive restorations in permanent and primary dentition.

3D Printed Gallium Battery with Outstanding Energy Storage: Toward Fully Printed Battery-on-the-Board Soft Electronics.

The last decade observed rapid progress in soft electronics. Yet, the ultimate desired goal for many research fields is to fabricate fully integrated soft-matter electronics with sensors, interconnects, and batteries, at the ease of pushing a print button. In this work, an important step is taken toward this by demonstrating an ultra-stretchable thin-film Silver-Gallium (Ag-Ga) battery with an unprecedented combination of areal capacity and mechanical strain tolerance. The Biphasic Gallium-Carbon anode electrode demonstrates a record-breaking areal capacity of 78.7 mAh cm-2, and an exceptional stretchability of 170%, showing clear progress over state-of-the-art. The exceptional theoretical capacity of gallium, along with its natural liquid phase self-healing, and its dendrite-free operation permits excellent electromechanical cycling. All composites of the battery including liquid-metal-based current collectors, and electrodes are sinter-free and digitally printable at room temperature, enabling the use of a wide range of substrates, including heat-sensitive polymer films. Consequently, it is demonstrated for the first time multi-layer, and multi-material digital printing of complex battery-on-the-board stretchable devices that integrate printed sensor, multiple cells of printed battery, highly conductive interconnects, and silicone chips, and demonstrate a tailor-made patch for body-worn electrophysiological monitoring.

Unlocking the potential of probiotic administration in caries management: a systematic review.

BACKGROUND: The use of prebiotics and/or probiotic bacteria with the potential to modulate the oral ecosystem may play an important role in the prevention and management of dental caries. To assess the evidence of the potential of pre/probiotics both in the prevention and treatment of dental caries, we focused on the PICO question "In individuals with caries, after probiotic administration, is there an improvement in outcomes directly related to caries risk and development?". METHODS: An extensive systematic search was conducted in electronic databases PubMed, Web of Science, Scopus and Cochrane, to identify articles with relevant data. This systematic review included trials performed in Humans; published in English; including the observation of patients with caries, with clear indication of the probiotic used and measuring the outcomes directly involved with the cariogenic process, including the quantification of bacteria with cariogenic potential. To evaluate the methodological quality of the studies, the critical assessment tool from the Joanna Briggs Institute was used. RESULTS: Eight hundred and fifty articles, potentially relevant, were identified. Following PRISMA guidelines 14 articles were included in this systematic review. Outcomes such as reduction of cariogenic microorganism counts, salivary pH, buffer capacity, and caries activity were assessed. The probiotic most often referred with beneficial results in dental caries outcomes is Lacticaseibacillus rhamnosus. Regarding the most used administration vehicle, in studies with positive effects on the caries management, probiotic supplemented milk could be considered the best administration vehicle. CONCLUSIONS: Evidence suggests a beneficial effect of probiotic supplemented milk (Lacticaseibacillus rhamnosus) as an adjuvant for caries prevention and management. However, comparable evidence is scarce and better designed and comparable studies are needed.

Histopathological Myocardial Changes in Patients with Severe Aortic Stenosis Referred for Surgical Valve Replacement: A CMR Correlation Study.

Myocardial fibrosis (MF) takes part in left ventricular (LV) remodeling in patients with aortic stenosis (AS), driving the transition from hypertrophy to heart failure. The structural changes that occur in this transition are not fully enlightened. AIM: to describe histopathology changes at endomyocardial biopsy (EMB) in patients with severe AS referred to surgical aortic valve replacement (AVR); to correlate them with LV tissue characterization from pre-operative cardiac magnetic resonance (CMR). METHODS: one-hundred-fifty-eight patients (73[68-77]years, 50%women) referred for surgical AVR because of severe symptomatic AS, with pre-operative CMR (n = 143) with late gadolinium enhancement (LGE), T1, T2 mapping and extracellular volume fraction (ECV) quantification. Intra-operative septal EMB was obtained in 129 patients. MF was assessed through Masson´s Trichrome histochemistry. Immunohistochemistry was performed for both inflammatory cells and extracellular matrix (ECM) characterization (Type I Collagen, Fibronectin, Tenascin C). RESULTS: non-ischemic LGE was present in 106 patients (67.1%) (median fraction:5.0% [2.0-9.7]). Native T1 was above normal: 1053 ms[1024-1071] and T2 within normal range (39.3 ms[37.3-42.0]). Median MF was 11.9%[6.54-19.97], with predominant type I collagen perivascular distribution (95.3%). Subendocardial cardiomyocyte ischemic-like changes were identified in 45% of EMB. There was no inflammation, despite ECM remodeling expression. MF quantification at EMB was correlated with LGE mass (p = 0.008) but not with global ECV (p = 0.125). CONCLUSION: patients with severe symptomatic AS referred for surgical AVR have unspecific histological myocardial changes, including signs of cardiomyocyte ischemic insult. ECM remodeling is ongoing, with MF heterogeneity. These features may be recognized by comprehensive CMR protocols. However, no single CMR parameter captures the burden of MF and histological myocardial changes in this setting.

White spot lesions: diagnosis and treatment - a systematic review.

BACKGROUND: White spot lesions represent the first stage of caries and their prevalence has been increasing in recent years, particularly in patients undergoing orthodontic treatment. DIferential diagnosis and lesion activity are essential to decide on the clinical approaches to treatment. The aim of this study is to understand if the new diagnostic tools such as fluorescence, microradiography and computed microtomography have the potential to change the conventional treatment of white spots". METHODS: A systematic search of available studies in the literature was carried out, using PRISMA guidelines, in Pubmed and Scopus electronic databases and manually to identify relevant articles to answer the PICO question: "Do the new diagnostic tools have the potential to change the conventional treatment of white spots?". This systematic review included randomized controlled trials (RCT), cross-sectional and longitudinal studies complying with the following inclusion criteria: (i) studies in humans, (ii) studies about white spot lesions, (iii) studies published between 2012 and 2023, (iv) studies having both diagnosis and treatment and (v) studies with full text available. In this review we excluded other systematic reviews of clinical trials and in vitro studies. The RoB tool was used to assess the risk of bias. RESULTS: The systematic literature search identified 143 potentially relevant references, which after applying the exclusion criteria, resulted in 20 articles. Regarding diagnostic methods, most articles found were based on conventional methods of visual examination (n:10) or fluorescence (n:7). The least referenced diagnostic techniques were based on the use of clinical photographs (n:2), cross-sectional microradiography (n:1) and computed microtomography (n:1). The use of DIAGNOdent was reported by 3 in vitro studies. With regard to therapies, most studies reported the use of infiltrating resin (n:7) and fluoride-based products (n:5). Other studies have reported the use of self-assembling peptide P11-4 (n:1), home care (n:1), casein phosphopeptide-amorphous calcium phosphate (n:2) and hydrochloric acid (n:1). Combination therapies were also considered. CONCLUSION: Diagnostic tool does not have the potential to change the form of treatment, whether it is a conventional method or a more differentiated one.

The impact of anastomotic leakage after curative colon cancer resection on long-term survival: A retrospective cohort study / El impacto de la fuga anastomótica después de la resección curativa del cáncer de colon en la supervivencia a largo plazo: un estudio de cohorte retrospectivo

Introduction: Anastomotic leakage (AL) is one of the most feared postoperative complications in colon cancer surgery due to an association with increased morbidity and mortality, although its impact on long-term survival is not consensual. The aim of this study was to investigate the influence of AL on long-term survival of patients undergoing curative colon cancer resection. Methods: A single-centre retrospective cohort study was designed. Clinical records of all consecutive patients undergoing surgery at our institution between 01/01/2010 and 12/31/2019 were reviewed. Survival analysis was performed by Kaplan–Meier method to estimate overall and conditional survival and Cox regression to search for risk factors impacting survival. Results: A total of 2351 patients submitted to colorectal surgery were screened for eligibility, of which 686 with colon cancer were included. AL occurred in 57 patients (8,3%) and was associated with higher postoperative morbidity and mortality, length of stay and early readmissions (P < 0,05). Overall survival was inferior in the leakage group (Hazard Ratio 2,08 [1,02–4,24]). Conditional overall survival at 30, 90 days and 6 months was also inferior in the leakage group (P < 0,05), but not at 1 year. Risk factors independently associated with reduced overall survival included AL occurrence, higher ASA classification and delayed/missed adjuvant chemotherapy. AL did not impact local and distant recurrence (P > 0,05). Conclusion: AL has a negative impact on survival. Its effect is more pronounced on short-term mortality. AL does not appear to be associated with disease progression.(AU)

Objetivo: La fuga anastomótica (FA) es una complicación postoperatoria temida en la cirugía del cáncer de colon por asociación con mayor morbimortalidad, aunque su impacto en la supervivencia a largo plazo no es consensuado. Nuestro objetivo fue investigar el efecto de la FA en la supervivencia a largo plazo de pacientes sometidos a resección curativa del cáncer de colon. Métodos: Se realizó un estudio de cohorte retrospectivo unicéntrico de pacientes consecutivos intervenidos quirúrgicamente entre 01/01/2010 y el 31/12/2019. El análisis de supervivencia se realizó por el método de Kaplan-Meier para evaluar la supervivencia global (SG) y condicional y una regresión de Cox para evaluar los factores de riesgo con efecto en la supervivencia. Resultados: De 2351 pacientes sometidos a cirugía colorrectal, se incluyeron 686 con cáncer de colon. FA afectó 57 pacientes (8,3%) y se asoció con mayor morbimortalidad postoperatoria, duración de estancia hospitalaria y reingresos (P < 0,05). La SG fue inferior en el grupo de fuga (Hazard Ratio 2,08 [1,02–4,24]). La SG condicional a los 30, 90 días y 6 meses fue inferior en el grupo de fugas (P < 0,05), pero no a 1 año. Los factores de riesgo que se asociaron con SG reducida incluyeron la FA, clasificación ASA más alta y quimioterapia adyuvante retrasada/perdida. FA no afectó la recurrencia local y distante (P > 0.05). Conclusiones: FA tiene un impacto negativo en la supervivencia, con efecto más pronunciado sobre la mortalidad a corto plazo, pero no es asociado con la progresión de la enfermedad oncológica.(AU)

The impact of anastomotic leakage after curative colon cancer resection on long-term survival: A retrospective cohort study.

INTRODUCTION: Anastomotic leakage (AL) is one of the most feared postoperative complications in colon cancer surgery due to an association with increased morbidity and mortality, although its impact on long-term survival is not consensual. The aim of this study was to investigate the influence of AL on long-term survival of patients undergoing curative colon cancer resection. METHODS: A single-centre retrospective cohort study was designed. Clinical records of all consecutive patients undergoing surgery at our institution between 01/01/2010 and 12/31/2019 were reviewed. Survival analysis was performed by Kaplan-Meier method to estimate overall and conditional survival and Cox regression to search for risk factors impacting survival. RESULTS: A total of 2351 patients submitted to colorectal surgery were screened for eligibility, of which 686 with colon cancer were included. AL occurred in 57 patients (8,3%) and was associated with higher postoperative morbidity and mortality, length of stay and early readmissions (P < 0,05). Overall survival was inferior in the leakage group (Hazard Ratio 2,08 [1,02-4,24]). Conditional overall survival at 30, 90 days and 6 months was also inferior in the leakage group (P < 0,05), but not at 1 year. Risk factors independently associated with reduced overall survival included AL occurrence, higher ASA classification and delayed/missed adjuvant chemotherapy. AL did not impact local and distant recurrence (P > 0,05). CONCLUSION: AL has a negative impact on survival. Its effect is more pronounced on short-term mortality. AL does not appear to be associated with disease progression.

Subendocardial "ischemic-like" state in patients with severe aortic stenosis: Insights from myocardial histopathology and ultrastructure.

BACKGROUND: Myocardial adaptation to severe aortic stenosis (AS) is a complex process that involves myocardial fibrosis (MF) beyond cardiomyocyte hypertrophy. Perfusion impairment is believed to be involved in myocardial remodeling in chronic pressure overload. AIM: To describe morphological and ultrastructural myocardial changes at endomyocardial tissue sampling, possibly reflecting subendocardial ischemia, in a group of patients with severe AS referred to surgical aortic valve replacement (AVR), with no previous history of ischemic cardiomyopathy. METHODS: One-hundred-fifty-eight patients (73 [68-77] years, 50% women) referred for surgical AVR because of severe symptomatic AS with preoperative clinical and imaging study and no previous history of ischemic cardiomyopathy. Intra-operative septal endomyocardial sampling was obtained in 129 patients. Tissue sections were stained with Masson´s Trichrome for MF quantification and periodic acid-Schiff (PAS) staining was performed to assess the presence of intracellular glycogen. Ultrastructure was analyzed through Transmission electron microscopy (TEM). RESULTS: MF totalized a median fraction of 11.90% (6.54-19.97%) of EMB, with highly prevalent perivascular involvement (95.3%). None of the samples had histological evidence of myocardial infarction. In 58 patients (45%) we found subendocardial groups of cardiomyocytes with cytoplasmatic enlargement, vacuolization and myofiber derangement, surrounded by extensive interstitial fibrosis. These cardiomyocytes were PAS positive, PAS-diastase resistant and Alcian Blue/PAS indicative of the presence of neutral intracellular glyco-saccharides. At TEM there were signs of cardiomyocyte degeneration with sarcomere disorganization and reduction, organelle rarefaction but no signs of intracellular specific accumulation. CONCLUSION: Almost half of the patients with severe AS referred for surgical AVR have histological and ultrastructural signs of subendocardial cardiomyocyte ischemic insult. It might be inferred that local perfusion imbalance contributes to myocardial remodeling and fibrosis in chronic pressure overload.

Oral Health Strategies: Surveying the Present to Plan the Future of Community-Based Learning.

Introduction: Oral health literacy relates to the capacity of individuals to acquire, understand and to act upon oral health information to make appropriate health decisions. This scientific review's main goal is to analyze the strategies that improve oral health literacy within the community, specifically oriented to a community-based learning model focused on the most vulnerable risk groups in society. Materials and Methods: The current review is based on the literature on oral health literacy within community-based learning strategies. The present review selected scientific studies by searching MEDLINE and related databases, such as Web of Science and PUBMED, and by consulting existing bibliographies. Results: Based on the application of the inclusion criteria to the abstracts, 45 publications were retrieved which explicitly dealt with the definitions of oral health literacy, community-based learning, and service learning. Several studies have demonstrated that health consumers with low health literacy fail to understand the available health information. Therefore, innovative oral health literacy strategies should be undertaken. Service learning is an example of an educational approach where the student learns specific soft skills in the classroom and collaborates directly with an agency or institution and engages in reflection activities to deepen their understanding of what is being taught. Conclusions: One of the main strategies used to incorporate the oral health professional in social responsibility and direct contact in the community is through experiencing community-based learning projects. The future graduate must be an educator capable of educating patients in order to themselves acquire high-level skills in oral health literacy.

Temporal Dynamics of Brain Activity Predicting Sense of Agency over Muscle Movements.

Our muscles are the primary means through which we affect the external world, and the sense of agency (SoA) over the action through those muscles is fundamental to our self-awareness. However, SoA research to date has focused almost exclusively on agency over action outcomes rather than over the musculature itself, as it was believed that SoA over the musculature could not be manipulated directly. Drawing on methods from human-computer interaction and adaptive experimentation, we use human-in-the-loop Bayesian optimization to tune the timing of electrical muscle stimulation so as to robustly elicit a SoA over electrically actuated muscle movements in male and female human subjects. We use time-resolved decoding of subjects' EEG to estimate the time course of neural activity which predicts reported agency on a trial-by-trial basis. Like paradigms which assess SoA over action consequences, we found that the late (post-conscious) neural activity predicts SoA. Unlike typical paradigms, however, we also find patterns of early (sensorimotor) activity with distinct temporal dynamics predicts agency over muscle movements, suggesting that the "neural correlates of agency" may depend on the level of abstraction (i.e., direct sensorimotor feedback versus downstream consequences) most relevant to a given agency judgment. Moreover, fractal analysis of the EEG suggests that SoA-contingent dynamics of neural activity may modulate the sensitivity of the motor system to external input.SIGNIFICANCE STATEMENT The sense of agency, the feeling of "I did that," when directing one's own musculature is a core feature of human experience. We show that we can robustly manipulate the sense of agency over electrically actuated muscle movements, and we investigate the time course of neural activity that predicts the sense of agency over these actuated movements. We find evidence of two distinct neural processes: a transient sequence of patterns that begins in the early sensorineural response to muscle stimulation and a later, sustained signature of agency. These results shed light on the neural mechanisms by which we experience our movements as volitional.

Deep Carious Lesions Management with Stepwise, Selective, or Non-Selective Removal in Permanent Dentition: A Systematic Review of Randomized Clinical Trials.

OBJECTIVE: The goal of this systematic study was to investigate the effectiveness of selective, stepwise, and non-selective removal techniques for caries removal in permanent teeth with deep carious lesions. The primary focus was the results found comparing techniques for caries removal to check whether there was pulp exposition; the secondary was the materials used for pulp protection and clinical findings reported within the included studies. METHODS: The search was performed in two databases (PubMed/MEDLINE and Web Of Science). The studies included in this systematic review were selected based on eligibility criteria. The inclusion criteria were: (1) randomized controlled trials (RCTs), (2) that compared the total removal of carious tissue with selective removal in permanent teeth with deep carious lesions, (3) with a follow-up period of at least 6 months, and (4) publications in English. Regarding the exclusion criteria, the following were not considered: (1) articles published in other languages, (2) articles that did not compare the different types of total/selective decay removal, and (3) articles published before January 2008. The risk of bias and the quality of the included studies were independently assessed by two reviewers using the RoB 2 tool. RESULTS: 5 out of 105 potentially eligible studies were included. Regarding the teeth included in the study, three articles performed management only on permanent molars, while other studies also performed management on incisors/canines/premolars/molars. Management protocols were divided into nonselective caries removal and partial caries removal (selective/stepwise). The theory of non-selective caries removal was considered an excessive, unnecessarily invasive option and a form of outdated management, and selective removal was preferred. CONCLUSION: The selective removal technique presented a higher success rate and fewer incidences of pulpal exposure than total removal, after up to 18 months of follow up. Moreover, only one session seemed to be a better management choice compared to two sessions because the cavity re-opening procedure is more prone to pulp exposure and highly depends on patient commitment. Otherwise, at 5 years of follow up, there was no difference between selective removal and total removal in management longevity. In addition, there were also no differences between the success of the materials used for definitive restorations in teeth subjected to any of the techniques evaluated.