Evidence for tactile 3D shape discrimination by octopus.

Octopuses integrate visual, chemical and tactile sensory information while foraging and feeding in complex marine habitats. The respective roles of these modes are of interest ecologically, neurobiologically, and for development of engineered soft robotic arms. While vision guides their foraging path, benthic octopuses primarily search "blindly" with their arms to find visually hidden prey amidst rocks, crevices and coral heads. Each octopus arm is lined with hundreds of suckers that possess a combination of chemo- and mechanoreceptors to distinguish prey. Contact chemoreception has been demonstrated in lab tests, but mechanotactile sensing is less well characterized. We designed a non-invasive live animal behavioral assay that isolated mechanosensory capabilities of Octopus bimaculoides arms and suckers to discriminate among five resin 3D-printed prey and non-prey shapes (all with identical chemical signatures). Each shape was introduced inside a rock dome and was only accessible to the octopus' arms. Octopuses' responses were variable. Young octopuses discriminated the crab prey shape from the control, whereas older octopuses did not. These experiments suggest that mechanotactile sensing of 3D shapes may aid in prey discrimination; however, (i) chemo-tactile information may be prioritized over mechanotactile information in prey discrimination, and (ii) mechanosensory capability may decline with age.

Physiological regulation of bone length and skeletal proportion in mammals.

NEW FINDINGS: What is the topic of this review? Mechanisms regulating bone length and skeletal proportions What advances does it highlight? The study of differential bone length between leg and finger bones, metatarsals of the Egyptian jerboa and genomic analysis of giraffes. ABSTRACT: Among mammalian species, skeletal structures vary greatly in size and shape, leading to a dramatic variety of body sizes and proportions. How different bones grow to different lengths, whether among different species, different individuals of the same species, or even in different anatomical parts of our the body, has always been a fascinating subject of research in biology and physiology. In the current review, we focus on some of the recent advances in the field and discuss how these provided important new insights into the mechanisms regulating bone length and skeletal proportions.

Genetic evaluation in children with short stature.

PURPOSE OF REVIEW: Short stature is a common clinical manifestation in children. Yet, a cause is often unidentifiable in the majority of children with short stature by a routine screening approach. The purpose of this review is to describe the optimal genetic approach for evaluating short stature, challenges of genetic testing, and recent advances in genetic testing for short stature. RECENT FINDINGS: Genetic testing, such as karyotype, chromosomal microarray, targeted gene sequencing, or exome sequencing, has served to identify the underlying genetic causes of short stature. When determining which short stature patient would benefit from genetic evaluation, it is important to consider whether the patient would have a single identifiable genetic cause. Specific diagnoses permit clinicians to predict responses to growth hormone treatment, to understand the phenotypic spectrum, and to understand any associated co-morbidities. SUMMARY: The continued progress in the field of genetics and enhanced capabilities provided by genetic testing methods expands the ability of physicians to evaluate children with short stature for underlying genetic defects. Continued effort is needed to elaborate new genetic causes of linear growth disorders, therefore, we expand the list of known genes for short stature, which will subsequently increase the rate of genetic diagnosis for children with short stature.

FREQUENT SUBCLINICAL MACULAR CHANGES IN COMBINED BRAF/MEK INHIBITION WITH HIGH-DOSE HYDROXYCHLOROQUINE AS TREATMENT FOR ADVANCED METASTATIC BRAF MUTANT MELANOMA: Preliminary Results From a Phase I/II Clinical Treatment Trial.

PURPOSE: To assess the potential ocular toxicity of a combined BRAF inhibition (BRAFi) + MEK inhibition (MEKi) + hydroxychloroquine (HCQ) regime used to treat metastatic BRAF mutant melanoma. METHODS: Patients with stage IV metastatic melanoma and BRAF V600E mutations (n = 11, 31-68 years of age) were included. Treatment was with oral dabrafenib, 150 mg bid, trametinib, 2 mg/day, and HCQ, 400 mg to 600 mg bid. An ophthalmic examination, spectral domain optical coherence tomography, near-infrared and short-wavelength fundus autofluorescence, and static perimetry were performed at baseline, 1 month, and q/6 months after treatment. RESULTS: There were no clinically significant ocular events; there was no ocular inflammation. The only medication-related change was a separation of the photoreceptor outer segment tip from the apical retinal pigment epithelium that could be traced from the fovea to the perifoveal retina noted in 9/11 (82%) of the patients. There were no changes in retinal pigment epithelium melanization or lipofuscin content by near-infrared fundus autofluorescence and short-wavelength fundus autofluorescence, respectively. There were no inner retinal or outer nuclear layer changes. Visual acuities and sensitivities were unchanged. CONCLUSION: BRAFi (trametinib) + MEKi (dabrafenib) + HCQ causes very frequent, subclinical separation of the photoreceptor outer segment from the apical retinal pigment epithelium without inner retinal changes or signs of inflammation. The changes suggest interference with the maintenance of the outer retinal barrier and/or phagocytic/pump functions of the retinal pigment epithelium by effective MEK inhibition.

Intraorbital Arteriovenous Fistula From the Superficial Temporal Artery.

Intraorbital arteriovenous fistula is a rare vascular disease characterized by an acquired arteriovenous communication without direct cavernous sinus involvement. Intraorbital arteriovenous fistula may develop slowly and present similarly to other insidious orbitopathies, such as carotid-cavernous fistula. The authors present a case of a superficial temporal artery to superior ophthalmic vein fistula arising in the absence of trauma or prior surgery. This is the first report of a spontaneous intraorbital arteriovenous fistula arising between these vessels and further describes the rare occurrence of intraorbital arteriovenous fistula.

Providing prescheduled appointments as a strategy for improving follow-up compliance after community-based glaucoma screening: results from an urban underserved population.

To determine if receiving a prescheduled appointment is associated with an increased likelihood of complying with follow-up eye care among individuals identified as at risk for glaucoma during community-based glaucoma screening in an urban underserved population. This study sampled 362 individuals aged ≥30 years without known glaucoma from low-income, predominantly black/Hispanic neighborhoods in New Haven, Connecticut presenting to one of twelve community-based glaucoma screening events from May 2010 to October 2012. A quasi-experimental design systematically assigned 63 individuals identified as at risk for glaucoma into either intervention or control group with a 1:2 ratio. Individuals in the control group (n = 41) received counseling on glaucoma and a recommendation for obtaining a follow-up appointment at the eye department of a local community health center, which offers affordable health services with income-adjusted fee discounts to uninsured, low-income patients. Those in the intervention group (n = 22) received the same counseling and a prescheduled appointment at the community health center. The overall rate of follow-up compliance within 3 months of screening was 30 % (41 % in the intervention group; 24 % in the control group). Multivariate logistic regression analysis adjusting for sex, age, ethnicity, health insurance status, car access, living situation, and smoking status found that follow-up compliance was significantly associated with intervention (adjusted odds ratio 4.8; 95 % confidence interval 1.1-20.9). Providing prescheduled appointments can improve follow-up compliance after community-based glaucoma screening. This finding may be potentially applicable to community-based health screening for other preventable diseases.

Plasminogen activator inhibitor-1 4G/5G polymorphism and retinopathy risk in type 2 diabetes: a meta-analysis.

BACKGROUND: Mounting evidence has suggested that plasminogen activator inhibitor-1 (PAI-1) is a candidate for increased risk of diabetic retinopathy. Studies have reported that insertion/deletion polymorphism in the PAI-1 gene may influence the risk of this disease. To comprehensively address this issue, we performed a meta-analysis to evaluate the association of PAI-1 4G/5G polymorphism with diabetic retinopathy in type 2 diabetes. METHODS: Data were retrieved in a systematic manner and analyzed using Review Manager and STATA Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. RESULTS: Nine studies with 1, 217 cases and 1, 459 controls were included. Allelic and genotypic comparisons between cases and controls were evaluated. Overall analysis suggests a marginal association of the 4G/5G polymorphism with diabetic retinopathy (for 4G versus 5G: OR 1.13, 95%CI 1.01 to 1.26; for 4G/4G versus 5G/5G: OR 1.30, 95%CI 1.04 to 1.64; for 4G/4G versus 5G/5G + 4G/5G: OR 1.26, 95%CI 1.05 to 1.52). In subgroup analysis by ethnicity, we found an association among the Caucasian population (for 4G versus 5G: OR 1.14, 95% CI 1.00 to 1.30; for 4G/4G versus 5G/5G: OR 1.33, 95%CI 1.02 to 1.74; for 4G/4G versus 5G/5G + 4G/5G: OR 1.41, 95%CI 1.13 to 1.77). When stratified by the average duration of diabetes, patients with diabetes histories longer than 10 years have an elevated susceptibility to diabetic retinopathy than those with shorter histories (for 4G/4G versus 5G/5G: OR 1.47, 95%CI 1.08 to 2.00). We also detected a higher risk in hospital-based studies (for 4G/4G versus 5G/5G+4G/5G: OR 1.27, 95%CI 1.02 to 1.57). CONCLUSIONS: The present meta-analysis suggested that 4G/5G polymorphism in the PAI-1 gene potentially increased the risk of diabetic retinopathy in type 2 diabetes and showed a discrepancy in different ethnicities. A higher susceptibility in patients with longer duration of diabetes (more than 10 years) indicated a gene-environment interaction in determining the risk of diabetic retinopathy.

Loss-of-function variant in SPIN4 causes an X-linked overgrowth syndrome.

Overgrowth syndromes can be caused by pathogenic genetic variants in epigenetic writers, such as DNA and histone methyltransferases. However, no overgrowth disorder has previously been ascribed to variants in a gene that acts primarily as an epigenetic reader. Here, we studied a male individual with generalized overgrowth of prenatal onset. Exome sequencing identified a hemizygous frameshift variant in Spindlin 4 (SPIN4), with X-linked inheritance. We found evidence that SPIN4 binds specific histone modifications, promotes canonical WNT signaling, and inhibits cell proliferation in vitro and that the identified frameshift variant had lost all of these functions. Ablation of Spin4 in mice recapitulated the human phenotype with generalized overgrowth, including increased longitudinal bone growth. Growth plate analysis revealed increased cell proliferation in the proliferative zone and an increased number of progenitor chondrocytes in the resting zone. We also found evidence of decreased canonical Wnt signaling in growth plate chondrocytes, providing a potential explanation for the increased number of resting zone chondrocytes. Taken together, our findings provide strong evidence that SPIN4 is an epigenetic reader that negatively regulates mammalian body growth and that loss of SPIN4 causes an overgrowth syndrome in humans, expanding our knowledge of the epigenetic regulation of human growth.

Effect of stimulants on final adult height.

BACKGROUND: The use of stimulant medications for treatment of ADHD has raised concern as to whether they adversely impact linear growth. Previous studies have indicated that stimulant medications may suppress growth for a short period after treatment initiation; however, more information is needed to evaluate the long-term effects on final adult stature. This mini review aims to evaluate the effect of stimulant medications on final adult height in children with ADHD. CONTENTS: We performed a literature review across PubMed/MEDLINE database. Only articles that included data on final adult height or near final adult height (age≥16 or 17 years) were included. SUMMARY: Early studies investigating the long-term impacts of stimulant medications observed growth suppression during the active treatment period, but when comparing final adult height, there was no difference between the control and ADHD groups. A recent larger comprehensive study (Multimodal Treatment of ADHD study) has suggested that the long-term use of significant doses of stimulants during childhood may compromise final adult height to a clinically significant degree when comparing adult height across three long-term patterns of stimulant treatment (Consistent, Intermittent, Negligible). The consistent use subgroup was significantly shorter than other subgroups. OUTLOOK: For children with ADHD, a significant long-term dose of stimulant treatment should be used with caution to avoid diminishing adult height potential. Pediatric endocrinologists should consider chronic use of stimulants as a factor contributing to reduced adult height.

A novel approach to quantifying ciliary physiology: microfluidic mixing driven by a ciliated biological surface.

From the lungs to the central nervous system, cilia-driven fluid flow plays a fundamental role in many facets of life. Yet, there are few quantitative methods for analysing the function of ciliated surfaces. Here, we report a novel microfluidic approach for quantifying the performance of a ciliated surface using mixing performance as an integrated readout.