Canine Retina Has a Primate Fovea-Like Bouquet of Cone Photoreceptors Which Is Affected by Inherited Macular Degenerations

Retinal areas of specialization confer vertebrates with the ability to scrutinize corresponding regions of their visual field with greater resolution. A highly specialized area found in haplorhine primates (including humans) is the fovea centralis which is defined by a high density of cone photoreceptors connected individually to interneurons, and retinal ganglion cells (RGCs) that are offset to form a pit lacking retinal capillaries and inner retinal neurons at its center. In dogs, a local increase in RGC density is found in a topographically comparable retinal area defined as the area centralis. While the canine retina is devoid of a foveal pit, no detailed examination of the photoreceptors within the area centralis has been reported. Using both in vivo and ex vivo imaging, we identified a retinal region with a primate fovea-like cone photoreceptor density but without the excavation of the inner retina. Similar anatomical structure observed in rare human subjects has been named fovea-plana. In addition, dogs with mutations in two different genes, that cause macular degeneration in humans, developed earliest disease at the newly-identified canine fovea-like area. Our results challenge the dogma that within the phylogenetic tree of mammals, haplorhine primates with a fovea are the sole lineage in which the retina has a central bouquet of cones. Furthermore, a predilection for naturally-occurring retinal degenerations to alter this cone-enriched area fills the void for a clinically-relevant animal model of human macular degenerations

Pyridoxine for Prevention of Hand-Foot Syndrome Caused by Chemotherapy: A Systematic Review

<div><p>Background</p><p>Hand-foot syndrome (HFS) is a relatively frequent dermatologic toxic reaction to certain anti-cancer chemotherapies. The syndrome can evolve into a distressing condition that limits function and affects quality of life. Pyridoxine (vitamin B6) has been used empirically for the prevention of HFS caused by anti-cancer therapy. However, evidence of its efficacy remains controversial.</p><p>Methodology//Principal Findings</p><p>Systematic literature searches were conducted on the Cochrane Library, PUBMED, EMBASE, LILACS, CBM, CNKI, VIP, WANFANG and the U.S. ClinicalTrials.gov website. We included all related randomized controlled trials (RCTs) irrespective of language. Reviewers from different professions independently assessed all potential studies and extracted data. Subgroup analysis was planned according to dose of pyridoxine. 5 RCTs involving 607 patients were contributed to the meta-analysis. No significant differences were found between patients receiving pyridoxine and placebo for prevention of incidence of HFS and grade 2 or worse HFS (relative risk (RR) 0.96, 95%confidence interval (CI) 0.86–1.06; RR0.95, 95%CI 0.73–1.24, respectively). Similarly, no significant improvement in quality of life was detected among patients. However, significant difference was found for prevention of grade 2 or worse HFS with pyridoxine 400 mg daily compared to 200 mg (RR0.55, 95%CI 0.33–0.92).</p><p>Conclusions/Significance</p><p>There is inadequate evidence to make any recommendation about using pyridoxine for prevention of HFS caused by chemotherapy. However, pyridoxine 400 mg may have some efficacy. Further studies of large sample sizes are needed to evaluate the efficacy and safety of pyridoxine, especially at high dose, in comparison with placebo.</p></div

Data_Sheet_1_Associations between benign paroxysmal positional vertigo and seven mental disorders: a two-sample Mendelian randomization study.docx

BackgroundThe association between benign paroxysmal positional vertigo (BPPV) and various mental disorders is still controversial. This study used the Mendelian randomization (MR) method to clarify the correlation between BPPV and seven mental disorders (bipolar disorder, depression, anxiety disorder, schizophrenia, suicidality, neuroticism, and mood swings) to aid in the exploration of BPPV complications and prevention and early treatment of mental disorders.MethodsThe datasets for BPPV and seven mental disorders were obtained from genome-wide association studies (GWASs). Two-sample MR was used to analyze the correlation between exposure (BPPV) and various outcomes (bipolar disorder, depression, anxiety disorder, schizophrenia, suicidality, neuroticism, and mood swings). A reverse MR study was also performed. The inverse variance weighting (IVW) method, the MR–Egger method, the simple mode method, the weighted mode method, and the weighted median method were selected.ResultsThe MR analysis and the reverse MR analysis results did not reveal significant associations between BPPV and bipolar disorder, depression, anxiety disorder, schizophrenia, suicidal tendencies, neuroticism, and mood swings. Interestingly, neuroticism (IVW: OR = 1.142, 95% CI: 1.059–1.231, P = 0.001; P-MR-PRESSO adjustment = 0.0002) and mood swings (IVW: OR = 3.119, 95% CI: 1.652–5.884, P = 0.0004) may have a significant association with BPPV. After MR-PRESSO adjustment, there was no horizontal pleiotropy or heterogeneity, and a significant association between neuroticism, mood swings, and BPPV has still been suggested.ConclusionWe conducted MR analysis on genetic data from European populations and discovered a causal relationship between BPPV and the seven mental disorders. Our research findings suggest that BPPV may not have a significant causal relationship with bipolar disorder, depression, anxiety disorder, schizophrenia, or suicidal tendencies. However, neuroticism and mood swings may be risk factors for BPPV.</p

Forest plot showing the meta-analysis of pyridoxine versus placebo in the incidence of Hand-foot syndrome.

<p>This forest plot is created by the software of RevMan 5.1.0. Horizontal lines indicate 95% CIs. Solid boxes indicate the response rate in each study. Test of heterogeneity (I² = 0%) indicates the absence of substantial heterogeneity. The bottom of diamond indicates the pooled response rate (RR0.96, <i>P</i> = 0.99).</p

Table_1_Associations between benign paroxysmal positional vertigo and seven mental disorders: a two-sample Mendelian randomization study.xls

BackgroundThe association between benign paroxysmal positional vertigo (BPPV) and various mental disorders is still controversial. This study used the Mendelian randomization (MR) method to clarify the correlation between BPPV and seven mental disorders (bipolar disorder, depression, anxiety disorder, schizophrenia, suicidality, neuroticism, and mood swings) to aid in the exploration of BPPV complications and prevention and early treatment of mental disorders.MethodsThe datasets for BPPV and seven mental disorders were obtained from genome-wide association studies (GWASs). Two-sample MR was used to analyze the correlation between exposure (BPPV) and various outcomes (bipolar disorder, depression, anxiety disorder, schizophrenia, suicidality, neuroticism, and mood swings). A reverse MR study was also performed. The inverse variance weighting (IVW) method, the MR–Egger method, the simple mode method, the weighted mode method, and the weighted median method were selected.ResultsThe MR analysis and the reverse MR analysis results did not reveal significant associations between BPPV and bipolar disorder, depression, anxiety disorder, schizophrenia, suicidal tendencies, neuroticism, and mood swings. Interestingly, neuroticism (IVW: OR = 1.142, 95% CI: 1.059–1.231, P = 0.001; P-MR-PRESSO adjustment = 0.0002) and mood swings (IVW: OR = 3.119, 95% CI: 1.652–5.884, P = 0.0004) may have a significant association with BPPV. After MR-PRESSO adjustment, there was no horizontal pleiotropy or heterogeneity, and a significant association between neuroticism, mood swings, and BPPV has still been suggested.ConclusionWe conducted MR analysis on genetic data from European populations and discovered a causal relationship between BPPV and the seven mental disorders. Our research findings suggest that BPPV may not have a significant causal relationship with bipolar disorder, depression, anxiety disorder, schizophrenia, or suicidal tendencies. However, neuroticism and mood swings may be risk factors for BPPV.</p

Forest plot showing the meta-analysis of pyridoxine 400 mg versus 200 mg in the incidence of grade 2 or worse Hand-foot syndrome.

<p>This forest plot is created by the software of RevMan 5.1.0. The diamond indicates the response rate (RR0.55, <i>P</i> = 0.02).</p

Results of Sensitivity Analyses(fixed-effect model).

<p>Abbreviation: NS, not significant.</p

Additional file 1 of Evaluation of marketing authorization and labels of medicines in 2021 WHO Model List of Essential Medicines for Children in China, the Russian Federation and Brazil

Additional file 1: Table S1. Evaluation of Pediatric Medication in China, Russia and Brazil for Medicines Contained in the WHO Model List of Essential Medicines for Children 2021

Additional file 1: of The effect of CBT and its modifications for relapse prevention in major depressive disorder: a systematic review and meta-analysis

Results from the systematic search strategy. (DOC 36 kb

Characteristics of the included studies.

<p>Abbreviation: T, treatment group; C, control group; –, no treatment; po. per os.</p><p>Outcomes reported:(1)Incidence of all grades HFS; (2)Incidence of grade 2 or worse HFS; (3)Time to development of grade 2 or worse HFS; (4)Factors affecting development of HFS;(5)Tumor response;(6)Quality of life;(7)Chemotherapy drug dose modification;(8)Progression-free survival;(9)Incidence of Adverse Events excluding HFS.</p