Sex as a Critical Variable in Basic and Pre-Clinical Studies of Fibrodysplasia Ossificans Progressiva.

Heterotopic ossification (HO) is most dramatically manifested in the rare and severely debilitating disease, fibrodysplasia ossificans progressiva (FOP), in which heterotopic bone progressively accumulates in skeletal muscles and associated soft tissues. The great majority of FOP cases are caused by a single amino acid substitution in the type 1 bone morphogenetic protein (BMP) receptor ACVR1, a mutation that imparts responsiveness to activin A. Although it is well-established that biological sex is a critical variable in a range of physiological and disease processes, the impact of sex on HO in animal models of FOP has not been explored.

Differential CD4+ T-Cell Cytokine and Cytotoxic Responses Between Reactivation and Latent Phases of Herpes Zoster Infection.

Background: CD4+ T cells are a critical component of effective immune responses to varicella zoster virus (VZV), but their functional properties during the reactivation acute vs latent phase of infection remain poorly defined.

Methods: Here we assessed the functional and transcriptomic properties of peripheral blood CD4+ T cells in persons with acute herpes zoster (HZ) compared to those with a prior history of HZ infection using multicolor flow cytometry and RNA sequencing.

Results: We found significant differences between the polyfunctionality of VZV-specific total memory, effector memory, and central memory CD4+ T cells in acute vs prior HZ.

Slow Binocular Reading in Amblyopic Children Is a Fellow Eye Deficit.

Significance: Amblyopic children read 25% slower than their peers during binocular silent reading.

Purpose: We compared binocular reading to fellow eye reading to determine whether slow reading in amblyopic children is due to binocular inhibition; that is, the amblyopic eye is interfering during binocular reading.

Methods: In a cross-sectional study, 38 children with amblyopia and 36 age-similar control children who completed grades 1 to 6 were enrolled.

An anti-ACVR1 antibody exacerbates heterotopic ossification by fibro-adipogenic progenitors in fibrodysplasia ossificans progressiva mice.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease characterized by progressive and catastrophic heterotopic ossification (HO) of skeletal muscle and associated soft tissues. FOP is caused by dominantly acting mutations in the gene encoding the bone morphogenetic protein (BMP) type I receptor, ACVR1 (ALK2), the most prevalent of which results in an arginine to histidine substitution at position 206 (ACVR1[R206H]). The fundamental pathological consequence of FOP-causing ACVR1 receptor mutations is to enable activin A to initiate canonical BMP signaling in fibro-adipogenic progenitors (FAPs), which drives HO.

Randomized clinical trial of streaming dichoptic movies versus patching for treatment of amblyopia in children aged 3 to 7 years.

Contrast-rebalanced dichoptic movies have been shown to be an effective binocular treatment for amblyopia in the laboratory. Yet, at-home therapy is a more practical approach. In a randomized clinical trial, we compared dichoptic movies, streamed at-home on a handheld 3D-enabled game console, versus patching as amblyopia treatment.

Plasma-Soluble Biomarkers for Fibrodysplasia Ossificans Progressiva (FOP) Reflect Acute and Chronic Inflammatory States.

Fibrodysplasia ossificans progressiva (FOP) is a progressive, debilitating genetic disease in which skeletal muscle and connective tissue is episodically replaced by heterotopic bone. Discovery of surrogate biomarkers of disease (genotype)-related and flare-up-associated activity of FOP in a readily accessible matrix, such as plasma, would facilitate an understanding of the complex pathophysiology of FOP, aid patient care, and provide a valuable tool for the development and monitoring of potential therapeutics. In a case-control study, using a carefully collected and curated set of plasma samples from 40 FOP patients with the classic ACVR1 mutation and 40 age- and sex-matched controls, we report the identification of disease-related and flare-up-associated biomarkers of FOP using a multiplex analysis of 113 plasma-soluble analytes.

Reach Kinematics During Binocular Viewing in 7- to 12-Year-Old Children With Strabismus.

Purpose: Eye-hand coordination is essential for normal development and learning. Discordant binocular experience from childhood strabismus results in sensory and ocular motor impairments that can affect eye-hand coordination. We assessed reach kinematics during visually guided reaching in children treated for strabismus compared with controls.

Normative Values, Testability, and Validity for a New Preferential Looking Stereoacuity Test.

: Age norms and testability for 3-5 year old children have been reported for the PASS III stereotest using a pointing response. We aimed to expand the normative data to children as young as 6 months, assess testability, and evaluate validity use of the PASS III as a preferential-looking test for younger children and children with special needs. : 68 control children, 362 children with eye conditions, and 167 children with special needs were tested with the PASS III.

A randomized clinical trial of contrast increment protocols for binocular amblyopia treatment.

Background: Most clinical trials of contrast-rebalanced binocular amblyopia treatment used a contrast increment protocol of 10% daily with successful play. Paired with a definition of success requiring only 15-30 min/day of gameplay, this increment protocol could allow children to reach 100% fellow eye contrast in 3-9 hours; however, this may not provide adequate therapeutic time with reduced fellow eye contrast. The purpose of this study was to compare the original protocol against three alternative contrast increment protocols designed to increase the number of treatment hours.

Endoscopic removal of eroded laparoscopic adjustable gastric bands: a preferred approach.

Background: Complications related to laparoscopic adjustable gastric banding (LAGB) have led to an increased number of removals. An uncommon but potentially devastating complication is gastric band erosion into the gastric lumen, which can be managed by open surgical, laparoscopic, and endoscopic approaches.

Objective: A wide array of management techniques has been reported for removal of LAGB that have eroded into the stomach.

Activin-dependent signaling in fibro/adipogenic progenitors causes fibrodysplasia ossificans progressiva.

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal-dominant disorder characterized by progressive and profoundly disabling heterotopic ossification (HO). Here we show that fibro/adipogenic progenitors (FAPs) are a major cell-of-origin of HO in an accurate genetic mouse model of FOP (Acvr1 ). Targeted expression of the disease-causing type I bone morphogenetic protein (BMP) receptor, ACVR1(R206H), to FAPs recapitulates the full spectrum of HO observed in FOP patients.

Positional ocular flutter and thickened optic nerves as sentinel signs of Krabbe disease.

A 5-month-old boy developed a large-amplitude, horizontal pendular flutterlike oscillation of the eyes, when placed in the supine position. Magnetic resonance imaging (MRI) 1 month earlier had shown isolated thickening of the optic nerves and chiasm without other central nervous system signal abnormalities. Repeat MRI at 5½ months of age showed a constellation of central nervous system signal abnormalities suggestive of Krabbe disease.

A TPO receptor agonist, ALXN4100TPO, mitigates radiation-induced lethality and stimulates hematopoiesis in CD2F1 mice.

Thrombopoietin (TPO) receptor agonists lacking sequence homology to TPO were designed by grafting a known peptide sequence into the hinge and/or kappa constant regions of a human anti-anthrax antibody. Some of these proteins were equipotent to TPO in stimulating cMpl-r activity in vitro and in increasing platelet levels in vivo. ALXN4100TPO (4100TPO), the best agonist in this series with a K(d) of 30 nM for cMpl-r, exhibited potent activity as a radiation countermeasure in CD2F1 mice exposed to lethal total-body radiation from a cobalt-60 γ-ray source.

A comparison of rates of lymph node metastases between patients undergoing sentinel and axillary lymphadenectomy.

Background: Recommendations regarding credentialing for sentinel lymphadenectomy in the staging of breast cancer emphasize the need for a trial period during which novice surgeons remove both the sentinel lymph node and the axillary packet, to demonstrate acceptably low rates of both operative failure and inaccuracy.

Methods: We initiated sentinel lymph node mapping in our institution without planned axillary dissection. To establish our ability to accurately stage patients using sentinel lymphadenectomy, we compared 225 patients who underwent that procedure and 343 patients previously staged with axillary lymph node dissection.

Long-term rates of PCO following small incision foldable acrylic intraocular lens implantation in children.

Purpose: To evaluate the long-term incidence of postoperative posterior capsular opacification (PCO) in children undergoing small incision foldable acrylic lens implantation with at least 2 years of follow up.

Methods: In 18 children, 26 eyes underwent small incision cataract extraction with posterior chamber foldable acrylic lens implantation. The posterior capsule was left intact in all patients at the time of surgery.