Ancient viral DNA in the human genome linked to neurodegenerative diseases.

BACKGROUND: Human endogenous retroviruses (HERVs) are sequences in the human genome that originated from infections with ancient retroviruses during our evolution. Previous studies have linked HERVs to neurodegenerative diseases, but defining their role in aetiology has been challenging. Here, we used a retrotranscriptome-wide association study (rTWAS) approach to assess the relationships between genetic risk for neurodegenerative diseases and HERV expression in the brain, calculated with genomic precision. METHODS: We analysed genetic association statistics pertaining to Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, and Parkinson's disease, using HERV expression models calculated from 792 cortical samples. Robust risk factors were considered those that survived multiple testing correction in the primary analysis, which were also significant in conditional and joint analyses, and that had a posterior inclusion probability above 0.5 in fine-mapping analyses. RESULTS: The primary analysis identified 12 HERV expression signatures associated with neurodegenerative disease susceptibility. We found one HERV expression signature robustly associated with amyotrophic lateral sclerosis on chromosome 12q14 (MER61_12q14.2) and one robustly associated with multiple sclerosis on chromosome 1p36 (ERVLE_1p36.32a). A co-expression analysis suggested that these HERVs are involved in homophilic cell adhesion via plasma membrane adhesion molecules. CONCLUSIONS: We found HERV expression profiles robustly associated with amyotrophic lateral sclerosis and multiple sclerosis susceptibility, highlighting novel risk mechanisms underlying neurodegenerative disease, and offering potential new targets for therapeutic intervention.

Reference Values for Handgrip Strength, Five Times Sit-to-stand, and Gait Speed in Patients on Hemodialysis.

BACKGROUND AND HYPOTHESIS: Low levels of muscle strength and function predict adverse clinical outcomes in patients on hemodialysis; however, reference values remain lacking. We described reference values for handgrip strength, five times sit-to-stand (STS-5), and 4-m gait speed in a large-scale sample in patients on hemodialysis. METHODS: Baseline data from the SARCopenia trajectories and associations with adverse clinical outcomes in patients on HemoDialysis (SARC-HD) study were analyzed. Muscle strength was evaluated using handgrip strength and the STS-5, whereas physical performance was evaluated using usual 4-m gait speed before a midweek dialysis session. Sex- and age-specific smoothed reference curves for each test at the 3rd, 15th, 50th, 85th, and 97th percentiles were constructed using generalized additive models for location shape and scale. Comparisons between sex and age were also performed. RESULTS: Data from 1004 patients (39% female; 19 to 96 years; 49% ≥ 60 years) were analyzed. Declines in muscle strength and physical performance were observed with advancing age in both sexes. However, among males, muscle strength and performance were similar between 18 and 49 years of age. Males exhibited substantially greater performance in handgrip strength (10.3 kg, 95% confidence interval (CI) 9.1 to 11.4) and 4-m gait speed (-0.10 seconds, 95% CI: -0.14 to -0.05) compared to females. Older patients, independent of sex, exhibited poorer performance on most tests. Lower handgrip strength in the arm with arteriovenous fistula was observed in both sexes (males -2.3 kg, 95% CI: -2.8 to -1.7; and females -2.1 kg, 95% CI: -2.6 to -1.6). CONCLUSION: Reference values obtained in this study may be used in clinical and research settings to identify patients on hemodialysis with low physical function according to sex and age. Future studies should test these reference values as potential predictors of adverse clinical outcomes.

Thrombogenic Risk Assessment of Transcatheter Prosthetic Heart Valves Using a Fluid-Structure Interaction Approach.

BACKGROUND AND OBJECTIVE: Prosthetic heart valve interventions such as TAVR have surged over the past decade, but the associated complication of long-term, life-threatening thrombotic events continues to undermine patient outcomes. Thus, improving thrombogenic risk analysis of TAVR devices is crucial. In vitro studies for thrombogenicity are typically difficult to perform. However, revised ISO testing standards include computational testing for thrombogenic risk assessment of cardiovascular implants. We present a fluid-structure interaction (FSI) approach for assessing thrombogenic risk of transcatheter aortic valves. METHODS: An FSI framework was implemented via the incompressible computational fluid dynamics multi-physics solver of the ANSYS LS-DYNA software. The numerical modeling approach for flow analysis was validated by comparing the derived flow rate of the 29 mm CoreValve device from benchtop testing and orifice areas of commercial TAVR valves in the literature to in silico results. Thrombogenic risk was analyzed by computing stress accumulation (SA) on virtual platelets seeded in the flow fields via ANSYS EnSight. The integrated FSI-thrombogenicity methodology was subsequently employed to examine hemodynamics and thrombogenic risk of TAVR devices with two approaches: 1) engineering optimization and 2) clinical assessment. RESULTS: Simulated effective orifice areas for commercial valves were in reported ranges. In silico cardiac output and flow rate during the positive pressure differential period matched experimental results by approximately 93 %. The approach was used to analyze the effect of various TAVR leaflet designs on hemodynamics, where platelets experienced instantaneous stresses reaching around 10 Pa. Post-TAVR deployment hemodynamics in patient-specific bicuspid aortic valve anatomies revealed varying degrees of thrombogenic risk with the highest median SA around 70 dyn·s/cm2 - nearly double the activation threshold - despite those being clinically classified as "mild" paravalvular leaks. CONCLUSIONS: Our methodology can be used to improve the thromboresistance of prosthetic valves from the initial design stage to the clinic. It allows for unparalleled optimization of devices, uncovering key TAVR leaflet design parameters that can be used to mitigate thrombogenic risk, in addition to patient-specific modeling to evaluate device performance. This work demonstrates the utility of advanced in silico analysis of TAVR devices that can be utilized for thrombogenic risk assessment of other blood recirculating devices.

Brain-Derived Neurotrophic Factor (BDNF) as a Predictor of Treatment Response in Schizophrenia and Bipolar Disorder: A Systematic Review.

Brain-derived neurotrophic factor (BDNF) is a potential biomarker of response to treatment in psychiatric disorders. As it plays a role in the pathophysiological development of schizophrenia and bipolar disorder, it is of interest to study its role in predicting therapeutic responses in both conditions. We carried out a systematic review of the literature, looking for differences in baseline BDNF levels and the Val66Met BDNF polymorphism in these disorders between responders and non-responders, and found information showing that the Val/Val genotype and higher baseline BDNF levels may be present in patients that respond successfully to pharmacological and non-pharmacological treatments. However, there is still limited evidence to support the role of the Val66Met polymorphism and baseline BDNF levels as predictors of treatment response.

Lymph Node Sampling in Pediatric Renal Tumors: Survey of Current Practices and Impact of Education.

OBJECTIVE: To characterize how often and to what extent surgeons are willing to perform retroperitoneal node sampling (RPLNS) for a unilateral renal tumor, and whether they would be encouraged to change goal number of LNs after "targeted education" (TE) METHODS: A survey with selected demographic and LN sampling practice questions was distributed to practicing members of the Society of Pediatric Urology (SPU). After answering a 7-question questionnaire, participants were provided with an abstract on the adequacy of LN yield for staging. This served as the TE and then participants were asked to answer a final question on LN sampling goals. RESULTS: A total of 76 (19.2%) of participants, out of 395 invitations, returned complete surveys. Cross tabulation between sampling goals before and after TE showed that among surgeons sampling 1-4 nodes, 13/24 (54.16%) would be willing to change their practice and sample ≥10 nodes. A higher proportion of participants who were already systematically surveilling 5-9 LNs would be willing to change their current practice: 30/39 (77%) would now aim for ≥10 LNs. On multivariate analysis, only willingness to sample ≥5 LNs in current practice was predictive of changing to sample ≥10 LNs after TE. CONCLUSION: Retroperitoneal LNs are currently still under sampled by pediatric urologists operating on children and adolescents with unilateral renal tumors. TE appears to encourage change in LN sampling practices.

Agreement between the EWGSOP2 and SDOC consensuses for sarcopenia in patients receiving hemodialysis: Findings of a cross sectional analysis from the SARC-HD study.

BACKGROUND: Differences in definitions and operational diagnoses for sarcopenia create difficulties in understanding the epidemiology of the disease. We examined the prevalences of sarcopenia using the revised European Working Group on Sarcopenia in Older People (EWGSOP2) and the Sarcopenia Definitions and Outcomes Consortium (SDOC) consensuses and analyzed their level of agreement in patients receiving hemodialysis. METHODS: Data from the SARCopenia trajectories and associations with clinical outcomes in patients receiving hemodialysis (SARC-HD) multicenter study in Brazil were analyzed. Muscle strength was assessed using handgrip strength, muscle mass by calf circumference, and physical performance by the 4-m gait speed test. Sarcopenia was diagnosed according to both the EWGSOP2 (low muscle strength plus low muscle mass) and the SDOC (low muscle strength plus low physical performance). The Cohen kappa statistic was used to determine the level of agreement between the consensuses. RESULTS: 838 patients (57.8 ± 15.0 years; 61% men) from 19 dialysis units were included. We found similar prevalences of sarcopenia between the consensuses (EWGSOP2, n = 128, 15.3%; SDOC, n = 105, 12.5%) but with weak agreement (50 of 233 patients, 21.5%; κ = 0.34, 95% CI 0.25-0.43). Agreement was also weak within age categories (≥60 years, κ = 0.34; <60 years, κ = 0.15; both P < 0.001). Of the 51 patients diagnosed by the EWGSOP2 criterion as having severe sarcopenia, all but 1 (98.0%) met the SDOC criterion for sarcopenia (κ = 0.61, 95% CI 0.52-0.70). Low muscle strength was more frequently diagnosed using the SDOC than with the EWGSOP2 (52.3% vs 25.9%). CONCLUSION: We found a weak agreement between the EWGSOP2 and SDOC consensuses for the diagnosis of sarcopenia in patients receiving hemodialysis. Although still weak, agreement was marginally better for older patients. These findings highlight the importance of a global and standardized conceptual diagnosis of sarcopenia.

The deeper the rounder: body shape variation in lice parasitizing diving hosts.

Seal lice, unique among insects, show remarkable adaptability to the extreme conditions of the deep sea. Evolving with their seal and sea lion hosts, they have managed to tolerate hypoxia, high salinity, low temperature, and elevated hydrostatic pressure. Given the diving capabilities of their mammalian hosts, which can reach depths of hundreds to thousands of meters, our study examines the morphological variation among closely related seal lice species infesting hosts with different maximum diving depths. In particular, our research reveals a significant morphological difference between lice associated with regular and deep-diving hosts, where lice from deep-diving hosts tend to be rounder. This could be an adaptation to withstand the high hydrostatic pressures found in the deep ocean. The rounded shape optimizes the louse's ability to withstand external pressure by redistributing it over a larger ventral/dorsal plane. This in turn minimizes the internal energy required to support body deformations, thereby increasing the louse's resilience in the deep sea environment.

Microbiota diversity of three Brazilian native fishes during ice and frozen storage.

This study aimed to assess the bacterial microbiota involved in the spoilage of pacu (Piaractus mesopotamics), patinga (female Piaractus mesopotamics x male Piaractus brachypomus), and tambacu (female Colossoma macropomum × male Piaractus mesopotamics) during ice and frozen storage. Changes in the microbiota of three fish species (N = 22) during storage were studied through 16S rRNA amplicon-based sequencing and correlated with volatile organic compounds (VOCs) and metabolites assessed by nuclear magnetic resonance (NMR). Storage conditions (time and temperature) affected the microbiota diversity in all fish samples. Fish microbiota comprised mainly of Pseudomonas sp., Brochothrix sp., Acinetobacter sp., Bacillus sp., Lactiplantibacillus sp., Kocuria sp., and Enterococcus sp. The relative abundance of Kocuria, P. fragi, L. plantarum, Enterococcus, and Acinetobacter was positively correlated with the metabolic pathways of ether lipid metabolism while B. thermosphacta and P. fragi were correlated with metabolic pathways involved in amino acid metabolism. P. fragi was the most prevalent spoilage bacteria in both storage conditions (ice and frozen), followed by B. thermosphacta. Moreover, the relative abundance of identified Bacillus strains in fish samples stored in ice was positively correlated with the production of VOCs (1-hexanol, nonanal, octenol, and 2-ethyl-1-hexanol) associated with off-flavors. 1H NMR analysis confirmed that amino acids, acetic acid, and ATP degradation products increase over (ice) storage, and therefore considered chemical spoilage index of fish fillets.

Adjunctive use of hypnosis for clinical pain: a systematic review and meta-analysis.

Systematic reviews suggest that stand-alone hypnotic suggestions may improve pain outcomes compared with no treatment, waitlist, or usual care. However, in clinical practice, hypnosis is often provided adjunctively with other interventions, which might have different effects than those reported in previous reviews. This systematic review aimed to summarize the analgesic effects of adjunctive hypnosis in adults with clinical pain. Seven databases (MEDLINE, Embase, PsycINFO, Emcare, SCOPUS, CENTRAL, Cochrane) were searched up to January 2024. Randomised controlled trials comparing the analgesic effects of adjunctive hypnosis (hypnosis + primary intervention) with those of the primary intervention alone were included. Meta-analyses (random-effects model) calculated mean differences (MD, [95% confidence intervals]) for pain intensity (0-100). Seventy studies were pooled in meta-analyses (n = 6078). Hypnosis adjunctive to usual care had a small additional analgesic effect (chronic pain: -8.2 [-11.8, -1.9]; medical procedures/surgical pain: -6.9 [-10.4, -3.3]; burn wound care: -8.8 [-13.8, -3.9]). Hypnosis adjunctive to education had a medium additional analgesic effect for chronic pain (-11.5 [-19.7, 3.3]) but not postsurgery pain (-2.0 [-7.8, 3.7]). When paired with psychological interventions, hypnosis slightly increased analgesia in chronic pain only at the three-month follow-up (-2 [-3.7, -0.3]). Hypnosis adjunctive to medicines had a medium additional analgesic effect for chronic pain (-13.2, [-22.5, -3.8]). The overall evidence certainty is very low; therefore, there is still uncertainty about the analgesic effects of adjunctive hypnosis. However, hypnosis adjunct to education may reduce pain intensity for chronic pain. Clarification of proposed therapeutic targets of adjunctive hypnosis to evaluate underlying mechanisms is warranted.

Bicycle Set-Up Dimensions and Cycling Kinematics: A Consensus Statement Using Delphi Methodology.

Bicycle set-up dimensions and cycling kinematic data are important components of bicycle fitting and cyclist testing protocols. However, there are no guidelines on how bicycles should be measured and how kinematic data should be collected to increase the reliability of outcomes. This article proposes a consensus regarding bicycle set-up dimensions and recommendations for collecting cycling-related kinematic data. Four core members recruited panellists, prepared the document to review in each round for panellists, analysed the scores and comments of the expert panellists, reported the decisions and communicated with panellists. Fourteen experts with experience in research involving cycling kinematics and/or bicycle fitting agreed to participate as panellists. An initial list of 17 statements was proposed, rated using a five-point Likert scale and commented on by panellists in three rounds of anonymous surveys following a Delphi procedure. The consensus was agreed upon when more than 80% of the panellists scored the statement with values of 4 and 5 (moderately and strongly agree) with an interquartile range of less than or equal to 1. A consensus was achieved for eight statements addressing bicycle set-up dimensions (e.g. saddle height, saddle setback, etc.) and nine statements for cycling kinematic assessment (e.g. kinematic method, two-dimensional methodology, etc.). This consensus statement provides a list of recommendations about how bicycle set-up dimensions should be measured and the best practices for collecting cycling kinematic data. These recommendations should improve the transparency, reproducibility, standardisation and interpretation of bicycle measurements and cycling kinematic data for researchers, bicycle fitters and cycling related practitioners.

Resistance training improves cardiac function in older women: a randomized controlled trial.

This investigation aimed to determine the effects of 24 weeks of resistance training (RT) on cardiac function in older women. Seventy-three physically independent older women were selected for this investigation. Participants were randomized into a training group (TG, n = 38) and a control group (CG, n = 35). The RT program was conducted over 24 weeks and consisted of three sessions a week. Participants performed eight exercises for the whole body in three sets of 8-12 repetitions. Tissue Doppler echocardiography was performed, according to current guidelines, before and after 24 weeks of the intervention. One-repetition maximum (1-RM) tests were used to assess muscular strength. A group vs. time interaction (P < 0.05) was shown for left ventricular end-diastolic volume (TG = - 8.3% vs. CG = - 0.6%), left ventricular end-systolic volume (TG = - 10.6% vs. CG = + 1.1%), and left atrial volume index (TG = - 9.1% vs. CG = + 3.9%). A main time effect (P < 0.05) was found for left ventricular mass index (TG = + 4.9% vs. CG = - 0.6%), septal thickness (TG = + 3.3% vs. CG = - 1.7%), left ventricular ejection fraction (TG = + 3.7% vs. CG = - 0.5%), E'/E septal (TG = - 4.8% vs. CG = + 0.5%), deceleration time (TG = - 4.1% vs. CG = + 3.9%), E septal (TG = + 4.6% vs. CG = - 0.6%), and E lateral (TG = + 5.2% vs. CG = - 1.1%). These results suggest that 24 weeks of RT improves cardiac morphological and functional variables in older women.

Curcumin Attenuates Doxorubicin-Induced Cardiac Oxidative Stress and Increases Survival in Mice.

Doxorubicin (DOX) is a potent chemotherapeutic agent used to treat multiple types of cancer, but its clinical application is limited by cardiotoxicity, mainly due to oxidative stress. Curcumin (CUR) is a natural polyphenolic compound with strong antioxidant properties, but its potential protective effects against DOX-induced cardiotoxicity need further investigation. This study aimed to evaluate CUR's efficacy in mitigating DOX-induced oxidative stress in the hearts of BALB/c mice. Mice received a DOX dose of 9 mg/kg or 16 mg/kg; half of the mice received daily doses of 100 mg/kg CUR for 15 days. Survival analysis, histopathological examination, and oxidative stress markers were assessed to determine the cardioprotective effects of CUR. Results showed that CUR significantly reduced oxidative damage and improved survival rates, particularly at the lower DOX dose (9 mg/kg). Mice treated with DOX-9 mg/kg plus CUR showed improved health conditions and reduced levels of reactive oxygen species (ROS), lipid peroxidation, sulfhydryl production, and protein carbonylation. Histopathological analysis confirmed reduced cardiac tissue damage. In conclusion, CUR combined with a lower dose of DOX effectively reduces oxidative stress and cardiac injury, enhancing survival in BALB/c mice. These findings suggest that CUR is a promising adjunct therapy to mitigate DOX-induced cardiotoxicity, potentially improving the DOX therapeutic index in cancer treatment.

Discordance Between the Initial Diagnosis of Sarcomas and Subsequent Histopathological Revision and Molecular Analyses in a Sarcoma Reference Center in Brazil.

PURPOSE: To investigate the discordance in sarcoma diagnoses between nonspecialized institutions following revision by dedicated sarcoma pathologists at a reference center in Brazil and the relevance of molecular pathology in this context. METHODS: We conducted a retrospective analysis of sarcoma samples initially analyzed at outside laboratories and subsequently reviewed by two specialized pathologists between January 2014 and December 2020. After obtaining demographic and tumor characteristics, pathology results were matched and classified as complete discordance (CD; benign v malignant, sarcoma v other malignancies), partial concordance (similar diagnosis of connective tumor, but different grade/histological subtype/differentiation), and complete concordance (CC). The concordance for histology or grade, and the role of molecular assessments supporting the diagnosis were also independently determined. Statistical analyses were conducted through the kappa coefficient of agreement and adherence by χ2 test, χ2 test by Person, and Fisher exact test. RESULTS: In total, 197 cases were included, with samples obtained predominately from male patients (57.9%) and localized/primary tumors (86.8%). Following revision, the most frequent final diagnoses were undifferentiated pleomorphic sarcoma (17.8%), well-differentiated/dedifferentiated liposarcoma (8.6%), and leiomyosarcoma (7.6%). CD was found in 13.2%, partial discordance in 45.2%, and CC in 41.6% of reviews (P < .001). We found a concordance for histology or grade of 53.5% (P < .001) and 51.8% (P < .001), respectively. Molecular assessments, comprising next-generation sequencing panels (79.5%) and fluorescent in situ hybridization (20.5%), were performed in 44 (22.3%) cases, with findings classified as of diagnostic relevance in 31.8%. CONCLUSION: In nearly 60% of the cases, the initial sarcoma diagnosis was modified when revised by a reference center and dedicated pathologists, assisted by molecular pathology techniques. These results justify the assembly of referral networks in countries with limited health care resources.

Influence of Different Apical Foramen Morphologies on the Accuracy of Four Electronic Foramen Locators.

OBJECTIVE: The aim of this study was to evaluate the accuracy of the Root ZX II (RZX), Raypex 6 (RAY), EPex Pro (EPEX), and CanalPro (CNP) electronic foramen locators (EFLs) in different foraminal morphologies (fully formed foramen, immature foramen with parallel walls, and immature foramen with divergent walls); this article also evaluated the influence of different penetration levels (0.0 mm and -1.0 mm). MATERIALS AND METHODS: Thirty single-rooted human premolars were accessed and had their cervical/middle thirds prepared with SX ProTaper files. The apical foramens (AF) were standardized to 250 µm and the initial root canal length (RCL1) was measured under 16x magnification with aid of a digital caliper. Using the alginate model, electronic measurements (EM) were taken 1.0 mm up to AF (EM1/-1) and at AF (EM1/0), always using adjusted hand K-files. The root apexes were then cross-sectioned 3.0 mm from the foramen; then, new RCL (RCL2) and electronic measurements were performed (EM2/-1 and EM2/0.0). Finally, retropreparations were performed with instruments SX ProTaper files introduced 4.0 mm in the apicocervical direction. Then new RCL (RCL3) and electronic measurements (EM3/-1 and EM3/0) were performed. STATISTICAL ANALYSIS: Values were tabulated and tested for normality using the Shapiro-Wilk test, which yielded nonparametric distributions of the data. Data were subjected to the Kruskal-Wallis and Dunn tests to estimate possible differences between devices as a function of foramen morphology and/or apical limit. The significance level was set at 5.0%. RESULTS: In general, the EFLs were accurate in determining the RCL. Statistically significant differences were observed between EPEX and RAY at 0.0, when measuring the divergent AF canals (p < 0.05). Regarding the different foramen morphologies in each EFL, RZX and EPEX showed no interference (p > 0.05), whereas RAY and CNP had lower accuracy levels at 0.0 with divergent AF (p < 0.05). CONCLUSION: The four devices evaluated are accurate to determine the RCL in the conditions tested. The apical limit of penetration did not have significant influence on their accuracy. Conversely, the presence of divergence in the AF walls negatively influenced de RAY and CNP precisions at the foraminal level.

Molecular breeding of flower load related traits in dioecious autotetraploid Actinidia arguta.

Flowering plants exhibit a wide range of sexual reproduction systems, with the majority being hermaphroditic. However, some plants, such as Actinidia arguta (kiwiberry), have evolved into dioecious species with distinct female and male vines. In this study, we investigated the flower load and growth habits of female kiwiberry genotypes to identify the genetic basis of high yield with low maintenance requirements. Owing to the different selection approaches between female and male genotypes, we further extended our study to male kiwiberry genotypes. By combining both investigations, we present a novel breeding tool for dioecious crops. A population of A. arguta seedlings was phenotyped for flower load traits, in particular the proportion of non-floral shoots, proportion of floral shoots, and average number of flowers per floral shoot. Quantitative trait locus (QTL) mapping was used to analyse the genetic basis of these traits. We identified putative QTLs on chromosome 3 associated with flower-load traits. A pleiotropic effect of the male-specific region of the Y chromosome (MSY) on chromosome 3 affecting flower load-related traits between female and male vines was observed in an A. arguta breeding population. Furthermore, we utilized Genomic Best Linear Unbiased Prediction (GBLUP) to predict breeding values for the quantitative traits by leveraging genomic data. This approach allowed us to identify and select superior genotypes. Our findings contribute to the understanding of flowering and fruiting dynamics in Actinidia species, providing insights for kiwiberry breeding programs aiming to improve yield through the utilization of genomic methods and trait mapping. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01476-7.

Improving access to cancer clinical research in Brazil: recent advances and new opportunities. Expert opinions from the 4th CURA meeting, São Paulo, 2023.

Clinical research is the cornerstone of improvements in cancer care. However, it has been conducted predominantly in high-income countries with few clinical trials available in Brazil and other low-and-middle-income countries (LMIC). Of note, less than one-third of registered clinical trials addressing some of the most commonly diagnosed cancers (breast, lung and cervical) recruited patients from LMIC in the last years. The Institute Project CURA promoted the fourth CURA meeting, discussing barriers to cancer clinical research and proposing potential solutions. A meeting was held in São Paulo, Brazil, in June 2023 with representatives from different sectors: Brazilian Health Regulatory Agency (Anvisa), National Commission of Ethics in Research (CONEP), non-governmental organisations, such as the Latin American Cooperative Oncology Group, the Brazilian Society of Clinical Oncology (SBOC), Contract Research Organisations, pharmaceutical companies and investigators. A total of 16 experts pointed out achievements as shortening the time of regulatory processes involving Anvisa and CONEP, development of staff training programs, maintenance of the National Program of Oncological Attention (PRONON), and the foundation of qualified centres in North and Northeast Brazilian regions. Participants also highlighted the need to be more competitive in the field, which requires optimising ongoing policies and implementing new strategies as decentralisation of clinical research centres, public awareness campaigns, community-centered approaches, collaborations and partnerships, expansion of physicians-directed policies, exploring the role of the steering committee. Active and consistent reporting of the initiatives might help to propagate ongoing advances, increasing Brazilian participation in clinical cancer research. Engagement of all players is crucial to maintain continuous progress with further improvements in critical points including regulatory timelines and increments in qualified human resources which aligned with new educational initiatives focused on physicians and the general population will expand access to cancer clinical trials in Brazil.

Integrating human endogenous retroviruses into transcriptome-wide association studies highlights novel risk factors for major psychiatric conditions.

Human endogenous retroviruses (HERVs) are repetitive elements previously implicated in major psychiatric conditions, but their role in aetiology remains unclear. Here, we perform specialised transcriptome-wide association studies that consider HERV expression quantified to precise genomic locations, using RNA sequencing and genetic data from 792 post-mortem brain samples. In Europeans, we identify 1238 HERVs with expression regulated in cis, of which 26 represent expression signals associated with psychiatric disorders, with ten being conditionally independent from neighbouring expression signals. Of these, five are additionally significant in fine-mapping analyses and thus are considered high confidence risk HERVs. These include two HERV expression signatures specific to schizophrenia risk, one shared between schizophrenia and bipolar disorder, and one specific to major depressive disorder. No robust signatures are identified for autism spectrum conditions or attention deficit hyperactivity disorder in Europeans, or for any psychiatric trait in other ancestries, although this is likely a result of relatively limited statistical power. Ultimately, our study highlights extensive HERV expression and regulation in the adult cortex, including in association with psychiatric disorder risk, therefore providing a rationale for exploring neurological HERV expression in complex neuropsychiatric traits.

An Ex-Vivo Study Comparing the Accuracy of the E-Connect S+ and Morita Tri Auto ZX2+ Endodontic Handpieces in Root Canal Length Determination.

INTRODUCTION: This ex vivo study evaluated the accuracy of the Electronic Apex Locator (EAL) and Automatic Apical Stop (AAS) functions of the E-Connect S+ and Morita Tri Auto ZX2+ cordless apex locators in determining patency length. METHODS: Sixty-four human teeth with a single root were randomly allocated into E-connect or Morita groups (n = 32). The canals were accessed and preflared, after which a size 15 K-file was inserted into the canal to the major foramen and recorded as the actual length (AL). Matched measurements were taken using the AAS and EAL functions and visually confirmed with confocal microscopy. The variance between canal length (mm), the persons correlation (ρ) between function and AL, and the accuracy (%) of the canal length relative to the AL (Δmm) between devices and functions were assessed. RESULTS: Regardless of device or function, all measurements were within 1±Δmm and correlated strongly (ρ > 0.97) with the AL. When considering a more stringent clinically acceptable range of 0.5±Δmm from the AL, all devices and functions demonstrated similar accuracy levels (84%-94%). However, at lower tolerance ranges, the E-connect device with the EAL function exhibited the highest accuracy. On average, all devices and functions stopped short of the AL (mean Δmm>0). CONCLUSION: The E-Connect S+ and Morita Tri Auto ZX2+ apex locators provided reliable accuracy in determining the position of the major foramen. These findings demonstrate a high level of reproducibility in canal length measurements using both cordless endodontic handpieces, regardless of whether the EAL or AAS functions were employed.

Emotion regulation skills-focused interventions for chronic pain: A systematic review and meta-analysis.

OBJECTIVES: To investigate the effect of emotion regulation skills-focused (ERSF) interventions to reduce pain intensity and improve psychological outcomes for people with chronic pain and to narratively report on safety and intervention compliance. METHODS: Six databases and four registries were searched for randomized controlled trials (RCTs) up to 29 April 2022. Risk of bias was evaluated using the Cochrane RoB 2.0 tool, and certainty of evidence was assessed according to the Grading, Assessment, Development and Evaluation (GRADE). Meta-analyses for eight studies (902 participants) assessed pain intensity (primary outcome), emotion regulation, affect, symptoms of depression and anxiety, and pain interference (secondary outcomes), at two time points when available, post-intervention (closest to intervention end) and follow-up (the first measurement after the post-intervention assessment). RESULTS: Compared to TAU, pain intensity improved post-intervention (weighted mean difference [WMD] = -10.86; 95% confidence interval [CI] [-17.55, -2.56]) and at follow-up (WMD = -11.38; 95% CI [-13.55, -9.21]). Emotion regulation improved post-intervention (standard mean difference [SMD] = 0.57; 95% CI [0.14, 1.01]), and depressive symptoms improved at follow-up (SMD = -0.45; 95% CI [-0.66, -0.24]). Compared to active comparators, anxiety symptoms improved favouring the comparator post-intervention (SMD = 0.10; 95% CI [0.03, 0.18]), and compared to CBT, pain interference improved post-intervention (SMD = -0.37; 95% CI [-0.69, -0.04]). Certainty of evidence ranged from very low to moderate. SIGNIFICANCE: The findings provide evidence that ERSF interventions reduce pain intensity for people with chronic pain compared to usual treatment. These interventions are at least as beneficial to reduce pain intensity as the current gold standard psychological intervention, CBT. However, the limited number of studies and certainty of evidence mean further high-quality RCTs are warranted. Additionally, further research is needed to identify whether ERSF interventions may be more beneficial for specific chronic pain conditions.