The effect of cartilage dehydration and rehydration on quantitative ultrashort echo time biomarkers.

Background: The effect of dehydration of ex vivo cartilage samples and rehydration with native synovial fluid or normal saline on quantitative ultrashort echo time (UTE) biomarkers are unknown. We aimed to investigate the effect of cartilage dehydration-rehydration on UTE biomarkers and to compare the rehydration capabilities of native synovial fluid and normal saline. Methods: A total of 37 cartilage samples were harvested from patients (n=5) who underwent total knee replacement. Fresh cartilage samples were exposed to air to dehydrate for 2 hours after baseline magnetic resonance (MR) scanning, then randomly divided into two groups: one soaking in native synovial fluid (n=17) and the other in normal saline (n=20) to rehydrate for 4 hours. UTE-based biomarkers [T1, adiabatic T1r (AdiabT1r), macromolecular fraction (MMF), magnetization transfer ratio (MTR), and T2*] and sample weights were evaluated for fresh, dehydrated, and rehydrated cartilage samples. Differences and agreements between groups were assessed using the values of fresh cartilage samples as reference standard. Results: Dehydrating in air for 2 hours resulted in significant weight loss (P=0.000). T1, AdiabT1r, and T2* decreased significantly while MMF and MTR increased significantly (all P<0.02). Non-significant differences were observed in cartilage weights after rehydrating in both synovial fluid and normal saline, with P values being 0.204 and 0.769, respectively. There were no significant differences in T1, AdiabT1r, MMF, and MTR after rehydrating in synovial fluid (P>0.0167, with Bonferroni correction) while T2* (P=0.001) still had significant differences compared with fresh samples. However, no significant differences were detected for any of the evaluated UTE biomarkers after rehydrating in normal saline (all P>0.05). No differences were detected in the agreement of UTE biomarker measurements between fresh samples and samples rehydrated with synovial fluid and normal saline. Conclusions: Cartilage dehydration resulted in significant changes in UTE biomarkers. Rehydrating with synovial fluid or normal saline had non-significant effect on all the evaluated UTE biomarkers except T2* values, which still had significant differences compared with fresh samples after rehydrating with synovial fluid. No significant difference was observed in the rehydration capabilities of native synovial fluid and normal saline.

The Power of Advocacy: Advancing Vision for Everyone to Meet the Sustainable Development Goals.

Advocacy is instrumental to achieving significant policy change for vision. Global advocacy efforts over the past decades enabled recognition of vision as a major public health, human rights, and development issue. The United Nations General Assembly adopted its first-ever Resolution on vision: "Vision for Everyone-Accelerating Action to Achieve the Sustainable Development Goals (SDGs)" on 23 July 2021. The Resolution sets the target and commits the international community to improve vision for the 1.1 billion people living with preventable vision impairment by 2030. To fulfill their commitments, governments and international institutions must act now. Advocacy remains instrumental to mobilize funding and empower governments and stakeholders to include eye health in their implementation agenda. In this paper, we discuss the pivotal role advocacy plays in advancing vision for everyone now and in the post-COVID-19 era. We explore the link between improved eye health and the advancement of SDGs and define the framework and key pillars of advocacy to scaling-up success by 2030.

Novel fluorescent staining protocol for thick sections of human osteochondral tissues to facilitate correlation with MRI and CT.

OBJECTIVE: To describe a novel fluorescent histochemical protocol to visualize osteoclasts, vasculature, and nerves in thick sections of human osteochondral tissues and to demonstrate its feasibility for use in radiologic-pathologic research correlation studies. MATERIALS AND METHODS: Consecutive patients scheduled for total knee arthroplasty surgeries underwent pre-operative MRI. CT imaging was performed after tissue collection, and abnormal osteochondral regions were sectioned to 1-2 mm in thickness and decalcified. Fluorescent labeling of osteoclasts was performed by staining for tartrate-resistant alkaline phosphatase activity with a fluorescent substrate. Vascular structure was visualized with fluorescently labeled lectin Ulex europaeus Agglutinin I (UEA-I). Immunostaining was performed for proteins including smooth muscle actin expressed in smooth muscle cells surrounding arterioles and fibrotic myofibroblasts, as well as for neuropeptide Y expressed in sympathetic nerves. Sections were then recut at 5 µm and stained with hematoxylin and eosin (H&E). RESULTS: Edema-like and cyst-like regions identified with MRI and CT were easily located in fluorescent images and appeared to have increased osteoclast activity. Fibrotic regions were identified with thickened arterioles and increased myofibroblasts. Sympathetic nerve fibers traveled alongside arborizing blood vessels. Stained sections became transparent in a water-based refractive index-matched medium, permitting deep 3D visualization of the elaborate neurovascular network in bone. Sequential staining procedures were successfully performed with the same sections, demonstrating the potential to compare multiple cellular markers from the same locations. Routine H&E staining could be performed after the fluorescent staining protocol. CONCLUSION: We have developed a multimodal framework to facilitate comparisons between histology and clinical MRI and CT.

High-Density Mineralized Protrusions and Central Osteophytes: Associated Osteochondral Junction Abnormalities in Osteoarthritis.

The aim of this study was to determine the association between high-density mineralized protrusions (HDMPs) and central osteophytes (COs), and describe the varying appearance of these lesions using advanced clinical imaging and a novel histological protocol. Seventeen consecutive patients with clinically advanced knee osteoarthritis undergoing knee arthroplasty were included. Surgical tissues containing the osteochondral region were investigated using computed tomography (CT); a subset was evaluated using confocal microscopy with fluorescence. Tissues from seven subjects (41.2%) contained HDMPs, and tissues from seven subjects (41.2%) contained COs. A significant association between HDMPs and COs was present (p = 0.003), with 6 subjects (35.2%) demonstrating both lesions. In total, 30 HDMPs were found, most commonly at the posterior medial femoral condyle (13/30, 43%), and 19 COs were found, most commonly at the trochlea (5/19, 26.3%). The HDMPs had high vascularity at their bases in cartilaginous areas (14/20, 70%), while the surrounding areas had elevated levels of long vascular channels penetrating beyond the zone of calcified cartilage (p = 0.012) compared to HDMP-free areas. Both COs and HDMPs had noticeable bone-resorbing osteoclasts amassing at the osteochondral junction and in vascular channels entering cartilage. In conclusion, HDMPs and COs are associated lesions in patients with advanced knee osteoarthritis, sharing similar histologic features, including increased vascularization and metabolic bone activity at the osteochondral junction. Future studies are needed to determine the relationship of these lesions with osteoarthritis progression and symptomatology.

Juvenile dermatomyositis resembling late-stage Degos disease with gastrointestinal perforations successfully treated with combination of cyclophosphamide and rituximab: case-based review.

Dermatomyositis (DM) is a multi-system disease that results in chronic inflammation principally of the skin and striated muscle. Small blood vessel injury in the GI tract has been described in dermatomyositis, manifesting as bleeding, ulceration, pneumatosis intestinalis, and ultimately perforation. Recent histopathological studies have shown deposits in the capillaries of the skin, gastrointestinal tract, and brain of patients with dermatomyositis similar to that found in patients with Degos disease, suggesting these disease processes are closely related or represent varying degrees of severity on the same pathologic spectrum. We report a case of juvenile dermatomyositis (JDM) resembling late-stage Degos disease with gastrointestinal perforations successfully treated with combination rituximab and cyclophosphamide therapy. We systematically reviewed the literature detailing the medical and surgical treatments for gastrointestinal perforation in dermatomyositis, Degos-like dermatomyositis, and Degos disease. In addition to our case, as of October 2019, we identified 36 cases describing gastrointestinal perforation in patients with underlying dermatomyositis, 5 cases of Degos-like dermatomyositis and 17 cases of idiopathic Degos disease. Corticosteroid therapy was used widely for dermatomyositis and Degos-like dermatomyositis, while antiplatelet and anticoagulant medications were chiefly used for patients with idiopathic Degos disease. However, there were no cases that detailed the successful treatment of dermatomyositis or Degos disease with gastrointestinal perforation with rituximab alone or combined with cyclophosphamide. We report that rituximab, in combination with cyclophosphamide, can be used as a novel adjunctive therapy to successfully treat dermatomyositis with Degos-like gastrointestinal perforation.

Ultrashort echo time magnetic resonance imaging (UTE-MRI) of cortical bone correlates well with histomorphometric assessment of bone microstructure.

Ultrashort echo time magnetic resonance imaging (UTE-MRI) techniques have been increasingly used to assess cortical bone microstructure. High resolution micro computed tomography (µCT) is routinely employed for validating the MRI-based assessments. However, water protons in cortical bone may reside in micropores smaller than the detectable size ranges by µCT. The goal of this study was to evaluate the upper limit of UTE-MRI and compare its efficacy to µCT at determining bone porosity ex vivo. This study investigated the correlations between UTE-MRI based quantifications and histomorphometric measures of bone porosity that cover all pores larger than 1 µm. Anterior tibial midshaft specimens from eleven donors (51 ±â€¯16 years old, 6 males, 5 females) were scanned on a clinical 3 T-MRI using UTE magnetization transfer (UTE-MT, three power levels and five frequency offsets) and UTE-T2* sequences. Two-pool MT modeling and bi-component exponential T2* fitting were performed on the MRI datasets. Specimens were then scanned by µCT at 9 µm voxel size. Histomorphometry was performed on hematoxylin and eosin (H&E) stained slides imaged at submicron resolution. Macromolecular fraction from MT modeling, bi-component T2* fractions, and short component T2* showed strong correlations (R > 0.7, p < 0.01) with histomorphometric total and large-pores (>40 µm) porosities as well as with µCT-based porosity. UTE-MRI could also assess small pores variations with moderate correlations (R > 0.5, p < 0.01). The UTE-MRI techniques can detect variations of bone porosity comprised of pores below the range detectable by µCT. Such fine pore variations can contribute differently to the development of bone diseases or to the bone remodeling process, however, this needs to be investigated. In scanned specimens, major porosity changes were from large pores, therefore the µCT employment was likely adequate to validate UTE-MRI biomarkers.

Pediatric Contact Dermatitis Registry Inaugural Case Data.

BACKGROUND: Little is known about the epidemiology of allergic contact dermatitis (ACD) in US children. More widespread diagnostic confirmation through epicutaneous patch testing is needed. OBJECTIVE: The aim was to quantify patch test results from providers evaluating US children. METHODS: The study is a retrospective analysis of deidentified patch test results of children aged 18 years or younger, entered by participating providers in the Pediatric Contact Dermatitis Registry, during the first year of data collection (2015-2016). RESULTS: One thousand one hundred forty-two cases from 34 US states, entered by 84 providers, were analyzed. Sixty-five percent of cases had one or more positive patch test (PPT), with 48% of cases having 1 or more relevant positive patch test (RPPT). The most common PPT allergens were nickel (22%), fragrance mix I (11%), cobalt (9.1%), balsam of Peru (8.4%), neomycin (7.2%), propylene glycol (6.8%), cocamidopropyl betaine (6.4%), bacitracin (6.2%), formaldehyde (5.7%), and gold (5.7%). CONCLUSIONS: This US database provides multidisciplinary information on pediatric ACD, rates of PPT, and relevant RPPT reactions, validating the high rates of pediatric ACD previously reported in the literature. The registry database is the largest comprehensive collection of US-only pediatric patch test cases on which future research can be built. Continued collaboration between patients, health care providers, manufacturers, and policy makers is needed to decrease the most common allergens in pediatric consumer products.

Pre-Emptive Avoidance Strategy (P.E.A.S.) - addressing allergic contact dermatitis in pediatric populations.

Pediatric allergic contact dermatitis (ACD) has been increasingly recognized in the United States. Reported rates of positive patch tests in children referred for suspected ACD range between 27 and 95.6%. Many young children are becoming sensitized to contact allergens found in personal hygiene products. We reviewed five recent pediatric patch test studies to determine the top allergens associated with this source of ACD in children. The top ten allergens were neomycin, balsam of Peru, fragrance mix, lanolin, cocamidopropylbetaine, formaldehyde, corticosteroids, methylchlorisothiazolinone (MCI)/methylisothiazolinone (MI), propylene glycol, and benzalkonium chloride. We estimate that one third of children suffering from ACD could potentially benefit from a 'pre-emptive avoidance strategy' (P.E.A.S.) of the stated top 10 allergens.

Scanning Electron Microscopic Hair Shaft Analysis in Ectodermal Dysplasia Syndromes.

OBJECTIVES: The objective of the current study was to catalog hair shaft abnormalities in individuals with ectodermal dysplasia (ED) syndromes using scanning electron microscopy (SEM) and to compare the findings with those in unaffected controls. This is the second of a two-part study, the first of which used light microscopy as the modality and was previously published. METHODS: Scanning electron microscopy was performed in a blinded manner on hair shafts from 65 subjects with seven types of ED syndromes and 41 unaffected control subjects. Assessment was performed along the length of the shaft and in cross section. SETTING: Hair donations were collected at the 28th Annual National Family Conference held by the National Foundation for Ectodermal Dysplasia. Control subjects were recruited from a private dermatology practice and an academic children's hospital outpatient dermatology clinic. RESULTS: SEM identified various pathologic hair shaft abnormalities in each type of ED and in control patients. When hairs with all types of ED were grouped together and compared with those of control patients, the difference in the presence of small diameter and shallow and deep grooves was statistically significant (p < 0.05). When the EDs were separated according to subtype, statistically significant findings were also seen. CONCLUSION: SEM is a possible adjuvant tool in the diagnosis of ED syndromes. There are significant differences, with high specificity, between the hairs of individuals with ED and those of control subjects and between subtypes.

Gianotti-Crosti syndrome following childhood vaccinations.

A 19-month-old boy was evaluated for a skin eruption after recent vaccinations. Clinical and histopathologic findings supported a diagnosis of Gianotti-Crosti syndrome (GCS). This case report examines the link between GCS and vaccinations, particularly the diphtheria, tetanus, and pertussis vaccine and the varicella virus live vaccine.

Gianotti-Crosti syndrome after childhood vaccination.

A 19-month-old boy was evaluated for a skin eruption after recent vaccinations. Clinical and histopathologic findings supported a diagnosis of Gianotti-Crosti syndrome (GCS). This case report examines the link between GCS and vaccinations, particularly the diphtheria, tetanus, and pertussis vaccine and the varicella virus live vaccine.

Light microscopic hair shaft analysis in ectodermal dysplasia syndromes.

The objective of the study was to catalog hair shaft abnormalities in individuals with ectodermal dysplasia (ED) syndromes using light microscopy and to compare findings with those in unaffected controls. Light microscopy was performed in a nonblinded manner on hair shafts from 65 participants with seven types of ED (hypohidrotic ED, ED-ectrodactyly-cleft lip or palate, ankyloblepharon-ectodermal defects-cleft lip and palate, Clouston syndrome, Goltz syndrome, Schopf-Schulz Passarge syndrome, and oculodentodigital dysplasia) and 41 unaffected controls. Hair donations were collected at the 28th Annual National Family Conference held by the National Foundation for Ectodermal Dysplasia. Control participants were recruited from a private dermatology practice and an academic children's hospital outpatient dermatology clinic. Sixty-five affected participants and 41 unaffected controls were included in the analysis. We assessed the hair shafts of ED and control participants for abnormalities visible using LM. Light microscopy identified various pathologic hair shaft abnormalities in each type of ED, although none of the findings were statistically significantly different from those of the control group. Light microscopy is a poor adjuvant tool in the diagnosis of ED syndromes. Most findings are nonspecific and not sufficiently sensitive.

Potential barriers to adherence in pediatric dermatology.

This study sought to identify barriers to treatment in children with chronic inflammatory skin disease, particularly those with atopic dermatitis, psoriasis, and acne vulgaris. Caregivers of 101 patients seen in the Children's Specialty Group Division of Dermatology, Children's Hospital of The King's Daughters, Norfolk, Virginia, completed an 11-item Likert scale questionnaire. This survey addressed complexity and time requirements for treatment, medication cost, vehicle formulation, perceived safety, and caregiver understanding of chronicity of skin disorders. Parents and caregivers indicated that adequate instructions for using the medications were provided but that they felt less comfortable with treating their child's skin disease during a severe flare. The complexity of treatment programs, time required to apply medications, and vehicle type were not considered prohibitive factors. Caregivers were concerned about the cost and safety of prescribed medications and had a less understanding of the chronicity of inflammatory skin disorders.

"Hot tub" Folliculitis from a nonchlorinated children's pool.

Pseudomonas aeruginosa is common cause of folliculitis following contact with contaminated water. We report a case of pseudomonal folliculitis that occurred after swimming in a children's pool filled with water from a well.

Are tutor behaviors in problem-based learning stable?: a generalizability study of social congruence, expertise and cognitive congruence.

The purpose of this study was to investigate the stability of three distinct tutor behaviors (1) use of subject-matter expertise, (2) social congruence and (3) cognitive congruence, in a problem-based learning (PBL) environment. The data comprised the input from 16,047 different students to a survey of 762 tutors administered in three consecutive semesters. Over the three semesters each tutor taught two of the same course and one different course. A generalizability study was conducted to determine whether the tutor behaviors were generalizable across the three measurement occasions. The results indicate that three semesters are sufficient to make generalizations about all three tutor behaviors. In addition the results show that individual differences between tutors account for the greatest differences in levels of expertise, social congruence and cognitive congruence. The study concludes that tutor behaviors are fairly consistent in PBL and somewhat impervious to change. Implications of these findings for tutor training are discussed.

Scurvy in a 10-year-old boy.

Scurvy, or hypovitaminosis C, is an uncommon condition that exists today primarily within certain unique populations-particularly the elderly subjects, patients with neurodevelopmental disabilities or psychiatric illnesses, or others with unusual dietary habits. Vitamin C is an essential nutrient in the human body, and is important in synthesizing collagen factor whose faulty production is responsible for most of the clinical manifestations of scurvy. These clinical manifestations can include dystrophic or corkscrew hairs, gingival hyperplasia, and weakened blood vessel walls, causing bleeding in the skin, joints, and other organs. Although rare in the Unites States, the presence of scurvy should not be forgotten because of its presence among susceptible populations. Moreover, with its diagnosis, treatment and cure is one of the simplest in modern medicine. We report a case of scurvy in a 10-year-old autistic child.