Detection and evaluation of parameters influencing the identification of heterozygous-enriched regions in Holstein cattle based on SNP chip or whole-genome sequence data.

BACKGROUND: A heterozygous-enriched region (HER) is a genomic region with high variability generated by factors such as balancing selection, introgression, and admixture processes. In this study, we evaluated the genomic background of HERs and the impact of different parameters (i.e., minimum number of SNPs in a HER, maximum distance between two consecutive SNPs, minimum length of a HER, maximum number of homozygous allowed in a HER) and scenarios [i.e., different SNP panel densities and whole-genome sequence (WGS)] on the detection of HERs. We also compared HERs characterized in Holstein cattle with those identified in Angus, Jersey, and Norwegian Red cattle using WGS data. RESULTS: The parameters used for the identification of HERs significantly impact their detection. The maximum distance between two consecutive SNPs did not impact HERs detection as the same average of HERs (269.31 ± 787.00) was observed across scenarios. However, the minimum number of markers, maximum homozygous markers allowed inside a HER, and the minimum length size impacted HERs detection. For the minimum length size, the 10 Kb scenario showed the highest average number of HERs (1,364.69 ± 1,483.64). The number of HERs decreased as the minimum number of markers increased (621.31 ± 1,271.83 to 6.08 ± 21.94), and an opposite pattern was observed for the maximum homozygous markers allowed inside a HER (54.47 ± 195.51 to 494.89 ± 1,169.35). Forty-five HER islands located in 23 chromosomes with high Tajima's D values and differential among the observed and estimated heterozygosity were detected in all evaluated scenarios, indicating their ability to potentially detect regions under balancing selection. In total, 3,440 markers and 28 genes previously related to fertility (e.g., TP63, ZSCAN23, NEK5, ARHGAP44), immunity (e.g., TP63, IGC, ARHGAP44), residual feed intake (e.g., MAYO9A), stress sensitivity (e.g., SERPINA6), and milk fat percentage (e.g., NOL4) were identified. When comparing HER islands among breeds, there were substantial overlaps between Holstein with Angus (95.3%), Jersey (94.3%), and Norwegian Red cattle (97.1%), indicating conserved HER across taurine breeds. CONCLUSIONS: The detection of HERs varied according to the parameters used, but some HERs were consistently identified across all scenarios. Heterozygous genotypes observed across generations and breeds appear to be conserved in HERs. The results presented could serve as a guide for defining HERs detection parameters and further investigating their biological roles in future studies.

Dimensions of Arachnoid Bulk Ratio: A Superior Optic Nerve Sheath Index for Intracranial Pressure.

Background Discrepancies in the literature regarding optimal optic nerve sheath diameter (ONSD) cutoffs for intracranial pressure (ICP) necessitate alternative neuroimaging parameters to improve clinical management. Purpose To evaluate the diagnostic accuracy of the dimensions of the perineural subarachnoid space to the optic nerve sheath ratio, measured using US, in predicting increased ICP. Materials and Methods In a prospective cohort study from April 2022 to December 2023, patients with suspected increased ICP underwent optic nerve US to determine the dimensions of arachnoid bulk (DAB) ratio and ONSD before invasive ICP measurement. Correlation between the parameters and ICP, as well as diagnostic accuracy, was assessed using area under the receiver operating characteristic curve (AUC) analysis. Results A total of 30 participants were included (mean age, 39 years ± 14 [SD]; 24 female). The DAB ratio and ONSD were significantly larger in participants with increased ICP (38% [0.16 of 0.42] and 14% [0.82 of 6.04 mm], respectively; P < .001). The DAB ratio showed a stronger correlation with ICP than ONSD (rs = 0.87 [P < .001] vs rs = 0.61 [P < .001]). The DAB ratio and ONSD optimal cutoffs for increased ICP were 0.5 and 6.5 mm, respectively, and the ratio had higher sensitivity (100% vs 92%) and specificity (94% vs 83%) compared with ONSD. Moreover, the DAB ratio better predicted increased ICP than ONSD, with a higher AUC (0.98 [95% CI: 0.95, 1.00] vs 0.86 [95% CI: 0.71, 0.95], P = .047). Conclusion An imaging ratio was proposed to predict ICP based on the relative anatomy of the cerebrospinal fluid space, demonstrating more accurate diagnosis of increased ICP and a strong correlation with ICP values, suggesting its potential utility as a neuroimaging marker in clinical settings. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Shepherd in this issue.

Midterm Survival Results of Preserflo® in a Real-world Setting: A Retrospective 2-year Analysis.

PRCIS: Preserflo® surgery is a safe procedure, effective in reducing intraocular pressure into the "low teens", surgical survival is greatest in cases of high baseline intraocular pressure (above 21 mmHg) and when performed as a standalone procedure. PURPOSE: To evaluate midterm surgical survival and safety profile of Preserflo® filtering surgery. METHODS: Retrospective, cohort study. Consecutive patients who underwent standardized Preserflo® implantation with mitomycin C from December 2019 to April 2021 were included. Clinical data was retrieved from patient charts. Primary outcome was surgical survival at twenty-four months in accordance with World Glaucoma Association guidelines. Survival was evaluated using Kaplan-Meier statistics. Analysis was performed at eye-level and as intention-to-treat. RESULTS: Ninety-five eyes were included in this study (18 cases combined with cataract surgery). Over half of cases (n=51) were primary open angle glaucoma, with over a fifth having a prior filtering glaucoma procedure. Intraocular pressure at twenty-four months was significantly decreased from baseline (22.4±6.28 mmHg vs 12.0±3.43 mmHg), as well as the need for IOP-lowering medication (2.88 (±0.92) vs 0.79 (±1.3), P<0.001 all comparisons. Standalone Preserflo® achieved a qualified survival (irrespective of medication) of 71% (CI 95% 62%-83%) and 44% (CI 95% 27%-75%) in the combined procedure subgroup (P<0.05 when considering absolute survival). Eyes with baseline intraocular pressure ≥21 mmHg showed a greater qualified survival when compared to eyes with baseline ≤18 mmHg (80% (CI 95% 65%-100%) vs (50% (CI 95% 32%-76%; P<0.05). Intra and early operative complications were few, self-limited, and did not require surgical management. The reoperation rate was low (18%). CONCLUSION: Preserflo ® filtering surgery is effective in reducing intraocular pressure into the "low teens" and presents an adequate surgical survival and safety profile. Surgical survival appears greatest when performed as standalone and when pre-operative intraocular pressure is high (≥21 mmHg).

Molecular frequency of bovine leukemia virus in Creole cattle of Eastern Colombia.

Enzootic Bovine Leukosis (EBL), caused by the bovine leukosis virus (BLV), is a global infectious disease affecting livestock. This study focuses on studying the frequency and genetic traits of BLV in three Creole breeds including Chino Santandereano (Chino), Casanareño (CAS), and Sanmartinero (SM) in Eastern Colombia. We implemented a cross-sectional survey between 2019 and 2020 across four departments (Arauca, Casanare, Santander and Meta) in Eastern Colombia to assess the molecular characteristics of BLV infection in these breeds. A total of 253 cattle were analyzed, of which 42.6 %, 28.8 %, and 28.4 % belonged to the Chino, CAS, and SM breeds, respectively. BLV provirus was detected using nested polymerase chain reaction (n-PCR) targeting the conserved region of the env viral gene. Subsequently, the obtained amplicons were sequenced and subjected to phylogenetic analyses. The overall BLV infection frequency was 26.48 % (95 % CI: 21.01 - 31.98 %), with Chino exhibiting the highest frequency (35.1 %) following by SAM and CAS, respectively (P < 0.05). Other epidemiological variables associated with the infection included age, department, and season (P < 0.05). BLV-positive animals exhibited elevated levels of total serum proteins (P < 0.05), while molecular characterization revealed the exclusive circulation of BLV genotype 1 within these breeds. This study provides an updated assessment of BLV infection in Creole breeds from the eastern of Colombia, underscoring their lower infection frequency compared to introduced breeds and their reduced susceptibility to developing clinical signs. The epidemiological and molecular characteristics observed should be considered in developing control programs aimed at improving genetic resistance to BLV in Colombian cattle.

A simple method for mapping winter recreational fishing ecosystem services supply in lakes. A contribution to mapping freshwater ecosystem services.

Although urban areas negatively impact the environment, they supply a wide range of ecosystem services (ES), mainly cultural ones. Recreation near urban green areas is widespread, including fishing. In northern latitudes, during the winter, lakes are frozen, and several urban dwellers practice ice fishing. Although this activity is well known, no attempts were made to assess and map winter recreational fishery ES supply in lakes. In this work, we developed a methodology to map this ES, taking an urban lake in Vilnius (Lithuania) as an example. A standardized protocol was developed using an unmanned aerial vehicle (proximal sensing), further georeferencing and correcting the gathered images, vectorizing the fishing ice holes, and mapping them using two different methods: Kernel and Point Density. The method developed in this work can be applied in northern areas to identify recreational fishing ES during the winter.•A novel method was developed to map winter recreational fishery ES supply in lakes;•High-resolution images were taken from an unmanned aerial vehicle to identify fishing ice holes in an urban lake.•The method maps a cultural ES, which is trendy in northern latitudes.

A systematic review with meta-analysis of heritability estimates for temperament-related traits in beef and dairy cattle populations.

Temperament (docility) is a key breeding goal in the cattle industry due to its direct relationship with animal welfare, cattle handler's safety and animal productivity. Over the past six decades, numerous studies have reported heritability estimates for temperament-related traits in cattle populations ranging from low to high values. Therefore, the primary objective of this study was to perform a comprehensive systematic review with meta-analysis to obtain weighted estimates of heritability for temperament-related traits in worldwide cattle populations. After data editing and quality control, 106 studies were included in the systematic review, of which 29.2% and 70.8% reported estimates of heritability for temperament-related traits in dairy and beef cattle populations, respectively. Meta-analyses were performed for 95 heritability estimates using a random model approach. The weighted heritability estimates were as follow: (a) flight score at weaning = 0.23 (95% CI: 0.15-0.32); (b) flight speed at weaning = 0.30 (95% CI: 0.26-0.33); (c) joint analysis of flight speed and flight score at weaning = 0.27 (95% CI: 0.22-0.31); (d) flight speed at yearling = 0.26 (95% CI: 0.21-0.30); (e) joint analysis of flight speed at weaning and yearling = 0.27 (95% CI: 0.24-0.30); (f) movement score = 0.12 (95% CI: 0.08-0.15); (g) crush score at weaning = 0.21 (95% CI: 0.17-0.25); (h) pen score at weaning = 0.27 (95% CI: 0.19-0.34); (i) pen score at yearling = 0.20 (95% CI: 0.17-0.23); (j) joint analysis of pen score at weaning and yearling = 0.22 (95% CI: 0.18-0.26); (k) cow's aggressiveness at calving = 0.10 (95% CI: 0.01-0.19); (l) general temperament = 0.13 (95% CI: 0.06-0.19); (m) milking temperament = 0.16 (95% CI: 0.11-0.21); and (n) joint analysis of general and milking temperament = 0.14 (95% CI: 0.11-0.18). The heterogeneity index ranged from 0% to 77%, and the Q-test was significant (p < 0.05) for four single-trait meta-analyses. In conclusion, temperament is moderately heritable in beef cattle populations, and flight speed at weaning had the highest weighted heritability estimate. Moreover, between-study heterogeneity was low or moderate in beef cattle traits, suggesting reasonable standardization across studies. On the other hand, low-weighted heritability and high between-study heterogeneity were estimated for temperament-related traits in dairy cattle, suggesting that more studies are needed to better understand the genetic inheritance of temperament in dairy cattle populations.

Treatment Outcomes Comparing the Paul and Baerveldt Glaucoma Implants After One Year of Follow-Up.

PRCIS: In reducing intraocular pressure (IOP), Paul (PGI) and Baerveldt (BGI) glaucoma implants are safe and effective in patients with glaucoma. OBJECTIVE: To compare efficacy and safety profiles of the PGI and BGI in the treatment of medically uncontrolled glaucoma at 1 year of follow-up. METHODS: Retrospective analysis of patients implanted with a PGI or BGI with a minimum of 12 months follow-up. The primary outcome was surgical success defined as IOP ≥6 and ≤18 mm Hg and at least 20% IOP reduction from baseline. Secondary outcomes included IOP measurements, number of medications, and complications. RESULTS: Twenty-three patients implanted with PGI and 27 with BGI were included. At last visit (12 mo), mean IOP had decreased from 23.7 ± 6.9 to 0.1 ± 2.9 mm Hg in the PGI group versus 26 ± 7.3 to 10.4 ± 4.9 mm Hg with the BGI ( P < 0.001 for both comparisons). Overall qualified success rates were similar between groups (PGI 91% vs BGI 89%, P = 0.784). IOP was significantly lower in the PGI at week 1 and month 1 of follow-up versus the BGI (13.6 ± 6.1 vs 20.1 ± 7.4; 14.6±3.8 vs 21.2 ± 5.8 mm Hg; P < 0.002 for both) with a lower number of medications (1.57 ± 1.47 vs 2.52 ± 1.16 at mo 1, P = 0.015). Most complications were minor and similar in both groups. CONCLUSION: Both PGI and BGI are safe and effective in reducing IOP in patients with glaucoma, with similar success rates.

Additional Guidance on the Use of the PRESERFLO™ MicroShunt in the Treatment of Glaucoma: Insights from a Second Delphi Consensus Panel.

INTRODUCTION: The PRESERFLO™ MicroShunt (PMS) has been proven to significantly lower intraocular pressure (IOP) in patients with glaucoma and has been available for use since 2019. With increasing published evidence and growing experience of glaucoma surgeons, the aim of this modified Delphi panel was to build on the findings of a previous Delphi panel conducted in 2021 and provide further guidance on the role of the PMS to treat patients with glaucoma in Europe. METHODS: Thirteen European glaucoma surgeons experienced in the PMS procedure participated in a 3-round modified Delphi panel. A targeted literature review and expert steering committee guided Round 1 questionnaire development. Consensus was pre-defined at a threshold of ≥ 70% of panellists selecting 'strongly agree'/'agree' or 'strongly disagree'/'disagree' for 6-point Likert scale questions or ≥ 70% selecting the same option for multiple or single-choice questions. Questions not reaching consensus were restated/revised for the next round, following guidance from free-text responses/scoping questions. RESULTS: In total, 28% (n = 9/32), 52% (n = 16/31) and 91% (n = 10/11) of statements reached consensus in Rounds 1, 2 and 3, respectively. There was agreement that the PMS may be used in patients with pigmentary, post-trauma or post-vitrectomy glaucoma and for patients with uveitic glaucoma without active inflammation. The PMS may be more suitable for patients with contact lenses than other subconjunctival filtering surgeries, without eliminating bleb-associated risks. Consensus was reached that combining PMS implantation and phacoemulsification may be as safe as standalone PMS surgery, but further efficacy data are required. Following a late rise in IOP ≥ 4 months post-surgery, topical aqueous suppressant drops or bleb revision may be suitable management options. CONCLUSIONS: This Delphi panel builds on the considerations explored in the 2021 Delphi panel and provides further detailed guidance for glaucoma surgeons on the use of the PMS, reflecting the availability of novel evidence and surgical experience. Videos are available for this article.

Genome-wide association and functional annotation analysis for the calving interval in Nellore cattle.

Calving interval (CI) measures the number of days between two consecutive calves of the same cow, and previous studies based on phenotype and pedigree data reported low heritability for this trait. However, the genetic architecture of CI in the Nellore breed was not evaluated based on genomic data. Thus, this study aimed to estimate the heritability based on genomic data and carry out a genome-wide association study (GWAS) for CI in the Nellore breed, using 12,599 pedigree records, 5078 CI records, and 3818 animals genotyped with 50k SNPchip panel. Both quality control and GWAS were performed in BLUPF90 family packages, which use the single-step genomic best linear unbiased predictor (ssGBLUP) method. The average CI was 427.6 days, with a standard deviation of 106.9 and a total range of 270-730 days. The heritability estimate was 0.04 ± 0.04. The p-values of GWAS analysis resulted in a genomic inflation factor (lambda) of 1.08. The only significant SNP (rs136725686) at the genome-wide level (p-value = 1.53E-06) was located on BTA13. Other 19 SNPs were significant at the chromosome-wide level, distributed on BTA1, 2, 3, 6, 10, 13, 14, 17, 18, 22, and 26. Functional annotation analysis found thirty-six protein-coding genes, including genes related to cell cycle (RAD21, BCAR3), oocyte function (LHX8, CLPX, UTP23), immune system (TXK, TEC, NFATC2), endocrine function (LRRFIP2, GPR158), estrous cycle (SLC38A7), and female fertility (CCK, LYZL4, TRAK1, FOXP1, STAC). Therefore, CI is a complex trait with small heritability in Nellore cattle, and various biological processes may be involved with the genetic architecture of CI in Nellore cattle.

Pre and Post-high-intensity Interval Training Delays Colon Tumor Onset in a Syngeneic Mouse Model.

BACKGROUND/AIM: High-intensity interval training (HIIT) can trigger transient anti-tumor cytotoxicity through the mobilization of natural killer cells (NK cells) and myokines. Yet, the effects of HIIT on tumor development and microenvironment are unclear. MATERIALS AND METHODS: Male C57/BL6 mice were administered either MC38 of syngeneic colon cancer cells or vehicle in a single subcutaneous injection. Before injection, the training group completed four weeks of the HIIT program (progressive swimming training, 3/week, 10-12 min, 4-6% of body weight for overload). Following injection, trained mice continued to exercise for two additional weeks. RESULTS: Pre and post-HIIT training was effective in preventing tumor onset (p=0.0065), maintaining body weight gain, and counteracting splenomegaly by 40% compared to the tumor group. However, HIIT had no impact on suppressing tumor growth, modifying final tumor volume, or significantly changing tumor proliferation (Ki-67), connective tissue content, or DNA double-strand damage detected by phospho-histone gamma-H2AX (γ-H2AX). CONCLUSION: Pre and post-HIIT program is feasible for mice carrying a subcutaneous syngeneic tumor and effective in delaying tumor burden; however, HIIT did not alter colon tumor endpoints.

ALCAM is a biomarker of tumor aggressiveness and worse prognosis in glottic laryngeal squamous cell carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is the second most frequent head and neck tumor. Prognosis of patients with LSCC has not improved in recent decades, showing a need for the identification of prognostic biomarkers and new therapeutic targets. Recently, we showed that ALCAM overexpression was associated with glottic LSCC prognosis. OBJECTIVES AND METHODS: Aiming to validate the prognostic value of ALCAM, we evaluate the ALCAM protein levels by immunohistochemistry in 263 glottic LSCC surgically treated with neck dissection. RESULTS: ALCAM was expressed in 48.7% and overexpressed in 36.5% of glottic LSCC samples. ALCAM overexpression was associated with lymph node metastasis (p = 0.030), lymphovascular involvement (p = 0.0002), high-grade tumors (p = 0.025), and tumor relapse (p = 0.043). Multivariate survival analyses showed an overfitting between ALCAM overexpression and lymph node metastasis as a prognostic variable. CONCLUSIONS: High ALCAM expression was associated with an aggressive glottic LSCC profile.

Hydroxytyrosol recovery from olive pomace: a simple process using olive mill industrial equipment and membrane technology.

In this work, pilot-scale nanofiltration was used to obtain aqueous solutions rich in hydroxytyrosol and tyrosol from olive oil by-products. A large-scale simple process involving olive mill standard machinery (blender and decanter) was used for the olive pomace pre-treatment with water. The aqueous extract was then directly fed to a nanofiltration unit and concentrated by reverse osmosis. Final concentration factors ranged between 7 and 9 for hydroxytyrosol and between 4 and 7 for tyrosol. The final aqueous solution, obtained as retentate stream of reverse osmosis, was highly concentrated in hydroxytyrosol and tyrosol and their concentrations remained stable over at least 14 months.

Genome-wide association and functional genomic analyses for various hoof health traits in North American Holstein cattle.

Hoof diseases are a major welfare and economic issue in the global dairy cattle production industry, which can be minimized through improved management and breeding practices. Optimal genetic improvement of hoof health could benefit from a deep understanding of the genetic background and biological underpinning of indicators of hoof health. Therefore, the primary objectives of this study were to perform genome-wide association studies, using imputed high-density genetic markers data from North American Holstein cattle, for 8 hoof-related traits: digital dermatitis, sole ulcer, sole hemorrhage, white line lesion, heel horn erosion, interdigital dermatitis, interdigital hyperplasia, and toe ulcer, and a hoof health index. De-regressed estimated breeding values from 25,580 Holstein animals were used as pseudo-phenotypes for the association analyses. The genomic quality control, genotype phasing, and genotype imputation were performed using the PLINK (version 1.9), Eagle (version 2.4.1), and Minimac4 software, respectively. The functional genomic analyses were performed using the GALLO R package and the DAVID platform. We identified 22, 34, 14, 22, 28, 33, 24, 43, and 15 significant markers for digital dermatitis, heel horn erosion, interdigital dermatitis, interdigital hyperplasia, sole hemorrhage, sole ulcer, toe ulcer, white line lesion disease, and the hoof health index, respectively. The significant markers were located across all autosomes, except BTA10, BTA12, BTA20, BTA26, BTA27, and BTA28. Moreover, the genomic regions identified overlap with various previously reported quantitative trait loci for exterior, health, meat and carcass, milk, production, and reproduction traits. The enrichment analyses identified 44 significant gene ontology terms. These enriched genomic regions harbor various candidate genes previously associated with bone development, metabolism, and infectious and immunological diseases. These findings indicate that hoof health traits are highly polygenic and influenced by a wide range of biological processes.

European Glaucoma Society research priorities for glaucoma care.

BACKGROUND/AIMS: The goal of health research is to improve patients care and outcomes. Thus, it is essential that research addresses questions that are important to patients and clinicians. The aim of this study was to develop a list of priorities for glaucoma research involving stakeholders from different countries in Europe. METHODS: We used a three-phase method, including a two-round electronic Delphi survey and a workshop. The clinician and patient electronic surveys were conducted in parallel and independently. For phase I, the survey was distributed to patients from 27 European countries in 6 different languages, and to European Glaucoma Society members, ophthalmologists with expertise in glaucoma care, asking to name up to five research priorities. During phase II, participants were asked to rank the questions identified in phase I using a Likert scale. Phase III was a 1 day workshop with patients and clinicians. The purpose was to make decisions about the 10 most important research priorities using the top 20 priorities identified by patients and clinicians. RESULTS: In phase I, 308 patients and 150 clinicians were involved. In phase II, the highest-ranking priority for both patients and clinicians was 'treatments to restore vision'. In phase III, eight patients and four clinicians were involved. The top three priorities were 'treatments to stop sight loss', 'treatments to restore vision' and 'improved detection of worsening glaucoma'. CONCLUSION: We have developed a list of priorities for glaucoma research involving clinicians and patients from different European countries that will help guide research efforts and investment.

Artificial intelligence for glaucoma: state of the art and future perspectives.

PURPOSE OF REVIEW: To address the current role of artificial intelligence (AI) in the field of glaucoma. RECENT FINDINGS: Current deep learning (DL) models concerning glaucoma diagnosis have shown consistently improving diagnostic capabilities, primarily based on color fundus photography and optical coherence tomography, but also with multimodal strategies. Recent models have also suggested that AI may be helpful in detecting and estimating visual field progression from different input data. Moreover, with the emergence of newer DL architectures and synthetic data, challenges such as model generalizability and explainability have begun to be tackled. SUMMARY: While some challenges remain before AI is routinely employed in clinical practice, new research has expanded the range in which it can be used in the context of glaucoma management and underlined the relevance of this research avenue.

Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation on chronic hemodialysis: a meta-analysis of randomized controlled trials.

PURPOSE: Patients with atrial fibrillation (AF) and end-stage renal disease on chronic hemodialysis are at risk for thromboembolic and bleeding events. We aimed to perform a meta-analysis to evaluate the safety and efficacy of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in this population. METHODS: We systematically searched PubMed, Excerpta Medica Database (EMBASE) and Cochrane Library for randomized controlled trials (RCTs) comparing DOACs with VKAs in patients with AF on chronic hemodialysis from inception to February 2023 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Outcomes were reported using risk ratios (RRs) with 95% confidence intervals (CIs). Statistical analyses were performed using R version 4.2.2. RESULTS: We selected three RCTs including 341 patients, of whom 176 (51.6%) were randomized to DOACs. Follow-up ranged from 174 days to 3.38 years. There was no significant difference between groups in terms of cardiovascular mortality (RR 1.34; 95% CI 0.69-2.60; p = 0.39), all-cause mortality (RR 0.96; 95% CI 0.72-1.27; p = 0.77), ischemic/uncertain type of stroke or transient ischemic attack (RR 0.50; 95% CI 0.19-1.35; p = 0.17), or major or life-threatening bleeding (RR 0.70; 95% CI 0.39-1.25; p = 0.22). CONCLUSION: In this meta-analysis of three RCTs, no significant difference was observed between DOACs and VKAs in cardiovascular mortality, all-cause mortality, ischemic/uncertain type of stroke or transient ischemic attack, or major or life-threatening bleeding in patients with AF on chronic hemodialysis.

Vitamin B3 Supplementation for Optic Neuropathies: A Comprehensive Review.

Optic neuropathies, such as glaucoma, are some of the leading causes of irreversible blindness worldwide. There has been a lot of research for potential therapies that could attenuate and even reduce the impact of the pathological pathways that lead to the loss of retinal ganglion cells (RGCs). In recent years, vitamin B3 (nicotinamide) has gained some interest as a viable option for these neurodegenerative diseases due to its fundamental role in enhancing the mitochondria metabolism of the RGCs. This review focuses on elucidating the impact of vitamin B3 on retinal cells, especially when in a dysfunctional state like what happens in optic neuropathies, especially glaucoma. This review also summarizes the existing and future research on the clinical effects of vitamin B3 in these optic neuropathies, and determines appropriate recommendations regarding its dosing, efficacy, and eventual side effects.

Mapping ecosystem services in protected areas. A systematic review.

Protected areas (PAs) supply ecosystem services (ES) essential for human wellbeing. Mapping is a critical exercise that allows an understanding of the spatial distribution of the different ES in PAs. This work aims to conduct a systematic literature review on mapping ES in PAs. In order to carry out this systematic review, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method was applied. The results showed an increase in the number of works between 2012 and 2023, and they were especially conducted in Europe and Asia and less in North America, South America, and Oceania. Most studies were developed in terrestrial areas, and the International Union for Conservation of Nature classified them into types II and IV. Most of the works followed the Millennium Ecosystem Assessment classification and were mainly focused on the supply dimension. Regulating and maintenance and cultural ES were the most mapped dimensions in PAs. The most frequent provisioning ES mapped in PAs were Animals reared for nutritional purposes and Cultivated terrestrial plants grown for nutritional purposes. In regulating and maintenance, Maintaining nursery populations and habitats and Regulation of the chemical composition of the atmosphere and oceans were the most analysed. For cultural ES, Characteristics of living systems that enable activities promoting health, recuperation, or enjoyment through active or immersive interactions and Characteristics of living systems that enable aesthetic experiences were the most mapped ES in PAs. Most works followed a quantitative approach, although the number of qualitative studies is high. Finally, most of the works needed to be validated, which may hamper the credibility of mapping ES in PAs. Overall, this systematic review contributed to a global picture of studies distribution, the areas where they are needed, and the most popular dimensions and sections as the methodologies were applied.

Low-fidelity simulation models in urology resident's microsurgery training.

PURPOSE: To evaluate the gain of microsurgical skills and competencies by urology residents, using low-fidelity experimental models. METHODS: The study involved the use of training boards, together with a low-fidelity microsurgery simulator, developed using a 3D printer. The model consists in two silicone tubes, coated with a resin, measuring 10 cm in length and with internal and external diameters of 0.5 and 1.5 mm. The support for the ducts is composed by a small box, developed with polylactic acid. The evaluation of the gain of skills and competencies in microsurgery occurred throughout a training course consisting of five training sessions. The first sessions (S1-S4) took place at weekly intervals and the last session (S5) was performed three months after S4. During sessions, were analyzed: the speed of performing microsurgical sutures in the pre and post-training and the performance of each resident through the Objective Structure Assessment of Technical Skill (OSATS) and Student Satisfaction Self-Confidence tools in Learning (SSSCL). RESULTS: There was a decrease in the time needed to perform the anastomosis (p=0.0019), as well as a progressive increase in the score in the OSATS over during sessions S1 to S4. At S5, there was a slightly decrease in performance (p<0.0001), however, remaining within the expected plateau for the gain of skills and competences. The SSSCL satisfaction scale showed an overall approval rating of 96.9%, with a Cronback alpha coefficient of 83%. CONCLUSIONS: The low-fidelity simulation was able to guarantee urology residents a solid gain in skills and competencies in microsurgery.

European Glaucoma Society - A guide on surgical innovation for glaucoma.

PROLOGUE: Glaucoma surgery has been, for many decades now, dominated by the universal gold standard which is trabeculectomy augmented with antimetabolites. Tubes also came into the scene to complement what we use to call conventional or traditional glaucoma surgery. More recently we experienced a changing glaucoma surgery environment with the "advent" of what we have become used to calling Minimally Invasive Glaucoma Surgery (MIGS). What is the unmet need, what is the gap that these newcomers aim to fill? Hippocrates taught us "bring benefit, not harm" and new glaucoma techniques and devices aim to provide safer surgery compared to conventional surgery. For the patient, but also for the clinician, safety is important. Is more safety achieved with new glaucoma surgery and, if so, is it associated with better, equivalent, or worse efficacy? Is new glaucoma surgery intended to replace conventional surgery or to complement it as an 'add-on' to what clinicians already have in their hands to manage glaucoma? Which surgery should be chosen for which patient? What are the options? Are they equivalent? These are too many questions for the clinician! What are the answers to the questions? What is the evidence to support answers? Do we need more evidence and how can we produce high-quality evidence? This EGS Guide explores the changing and challenging glaucoma surgery environment aiming to provide answers to these questions. The EGS uses four words to highlight a continuum: Innovation, Education, Communication, and Implementation. Translating innovation to successful implementation is crucially important and requires high-quality evidence to ensure steps forward to a positive impact on health care when it comes to implementation. The vision of EGS is to provide the best possible well-being and minimal glaucomainduced visual disability in individuals with glaucoma within an affordable healthcare system. In this regard, assessing the changes in glaucoma surgery is a pivotal contribution to better care. As mentioned, this Guide aims to provide answers to the crucial questions above. However, every clinician is aware that answers may differ for every person: an individualised approach is needed. Therefore, there will be no uniform answer for all situations and all patients. Clinicians would need, through the clinical method and possibly some algorithm, to reach answers and decisions at the individual level. In this regard, evidence is needed to support clinicians to make decisions. Of key importance in this Guide is to provide an overview of existing evidence on glaucoma surgery and specifically on recent innovations and novel devices, but also to set standards in surgical design and reporting for future studies on glaucoma surgical innovation. Designing studies in surgery is particularly challenging because of many subtle variations inherent to surgery and hence multiple factors involved in the outcome, but even more because one needs to define carefully outcomes relevant to the research question but also to the future translation into clinical practice. In addition this Guide aims to provide clinical recommendations on novel procedures already in use when insufficient evidence exists. EGS has a long tradition to provide guidance to the ophthalmic community in Europe and worldwide through the EGS Guidelines (now in their 5th Edition). The EGS leadership recognized that the changing environment in glaucoma surgery currently represents a major challenge for the clinician, needing specific guidance. Therefore, the decision was made to issue this Guide on Glaucoma Surgery in order to help clinicians to make appropriate decisions for their patients and also to provide the framework and guidance for researchers to improve the quality of evidence in future studies. Ultimately this Guide will support better Glaucoma Care in accordance with EGS's Vision and Mission. Fotis Topouzis EGS President