Zonal differences in meniscus MR relaxation times in response to in vivo static loading in knee osteoarthritis

This study assessed the effects of static loading on MRI relaxation times of menisci in individuals with and without radiographic knee OA. High‐resolution fast spin‐echo (FSE) and T_1ρ/T₂ relaxation time MR sequences were obtained with and without loading at 50% body weight in 124 subjects. T_1ρ/T₂ relaxation times were calculated in menisci, and meniscus lesions were assessed through clinical grading. Student's t‐test compared OA and control unloaded relaxation times as well as within‐group changes with loading, Generalized Linear Models evaluated zonal variation, and ANCOVA compared loading response between groups. Unloaded T_1ρ and T₂ in the middle and inner zones of the lateral anterior horn and outer zone of the medial posterior horn were significantly higher in OA and suggest that meniscal OA change occurs unevenly. Zonal T_1ρ and T₂ showed differing patterns between anterior and posterior horns, suggesting differences in macromolecular organization. Significant increases with loading were seen largely in the T₂ of controls and less frequently in subjects with OA. In the medial posterior horn, T_1ρ and T₂ decreased with loading in OA but changed negligibly in controls; these significantly different loading responses between groups may indicate load transmission failure in OA menisci. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:249–261, 2016.     

Regulation of the immune system by SOCS family adaptor proteins

Signal transduction via cytokine receptors is regulated by several mechanisms that control initiation, magnitude and duration of the signaling pathways. Cytokine-induced SOCS family adaptors function as feedback inhibitors of cytokine receptor signaling by inhibiting the JAK-STAT signal transduction pathway. Specific gene-targeted mice have unveiled critical, non-overlapping functions for SOCS1 and SOCS3 in lymphocyte development and homeostasis, and in the regulation of macrophage and dendritic cell functions. In this review, we will discuss the structure of SOCS proteins, mechanisms by which they control the JAK-STAT pathway and their role in immune regulation.     

Leukocyte(s) degranulation: therapeutic targets in [NTP]O and [NDP]O mediated leukocyte(s) degranulation

Extracellular nucleotide-induced stimulation and activation of peripheral blood leukocyte(s) and subsequent degranulation plays a critical role in immediate type hypersensitivity reaction and other inflammatory diseases. The extracellular nucleotides [NTP]O stimulate a P2Y receptor(s) on human PMN with the pharmacological profile similar to that of the P2Y2 receptor. Whereas, [NTP]O and [NDP]O, bind to P2Y2 and P2Y1 receptors on mononuclear leukocytes. Based on a recent proposal on the molecular mechanism of [NTP]O- and [NDP]O-induced leukocyte(s) degranulation, a scheme indicating the therapeutic targets with potential avenues for attenuating leukocyte(s) degranulation is suggested.     

Application and validation of a computerized cough acquisition system for objective monitoring of acute cough: a meta-analysis

STUDY OBJECTIVE: The purpose of the meta-analysis was to understand the antitussive effect of treatment with dextromethorphan hydrobromide, 30 mg, vs placebo over a 3-h treatment period in patients with cough due to uncomplicated upper respiratory tract infection (URTI), and to show that the computerized system for acquisition and analysis of cough sound was consistent and reproducible across the individual studies. STUDY DESIGN: The six studies used for the meta-analysis were randomized, double-blind, parallel-group, single-dose, placebo-controlled studies with a 3-h postdose cough evaluation period. SETTING: One study was conducted in Durban, South Africa, and five studies were conducted in Bombay, India. Four studies took place in clinics, and two studies were in-home studies. PATIENTS: Seven hundred ten adult patients with cough due to uncomplicated URTI who were otherwise healthy and who satisfied the inclusion/exclusion criteria for the meta-analysis. Measurements and results: For each patient, a standard baseline was calculated pretreatment, then a 3-h continuous cough recording was made after treatment was initiated. Five efficacy variables were measured in 30-min intervals: cough bouts, cough components, cough effort, cough intensity, and cough latency. The meta-analysis showed consistent results across most of the studies for each of the efficacy variables. It demonstrated significantly greater overall reductions in cough bouts, cough components, and cough effort, and an increase in cough latency for patients treated with dextromethorphan hydrobromide, 30 mg, vs those treated with placebo. CONCLUSION: The results of a meta-analysis of the six clinical studies show that the antitussive effect of a single dose of dextromethorphan hydrobromide, 30 mg, has been established. The consistent nature of the results shows that the computerized cough acquisition and analysis system is a valid and reproducible methodology for evaluating cough associated with URTI.     

Genetic Fitness and Bottleneck of Threadfin (Sea Catfish), Arius arius (Hamilton, 1822) in South Indian Coastline

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - To resolve the taxonomy and assess the population structure of threadfin (sea catfish), Arius arius in south...     

Association of MR relaxation and cartilage deformation in knee osteoarthritis

We assessed the relationship between cartilage MR relaxation times and biomechanical response of tibiofemoral articular cartilage to physiological loading in healthy subjects and patients with osteoarthritis (OA). Female subjects above 40 years of age with (N₁ = 20) and without (N₂ = 10) OA were imaged on a 3T MR scanner using a custom made loading device. MR images were acquired with the knee flexed at 20° with and without a compressive load of 50% of the subject's bodyweight. The subjects were categorized based on the clinical MRI scoring of medial and lateral cartilage surfaces. Data were stratified twice into two equal groups (low and high) at the median value of T_1ρ and T₂ relaxation time. The change in contact area and cartilage deformation was measured within these groups. Paired Student's t‐test (α = 0.05) was used to analyze the effect of loading on contact area and deformation. The average area of the contact region in the medial compartment was significantly higher in OA subjects compared with normal subjects in both unloaded (314 ± 112 mm² vs. 227 ± 106 mm², p = 0.023) and loaded (425 ± 128 mm² vs. 316 ± 107 mm², p = 0.01) conditions. The overall relative change of cartilage thickness in the medial compartment was significantly higher than the lateral compartment (?5.3 ± 9.9% vs. ?1.9 ± 9.2%, p = 0.042). When cartilage was divided into deep and superficial layers, superficial layers showed higher changes in relaxation time (T_1ρ and T₂) than the changes in relaxation time of whole cartilage (Normal: 12.5% vs. 6.9%; OA: 10.9% vs. 4.6%). The average T_1ρ and T₂ times, change in area of contact region, and change in cartilage thickness in subjects with OA were higher when compared to normal subjects. This study provides support for a relationship between the mechanical response of cartilage to physiological loading (cartilage‐on‐cartilage contact area and cartilage deformation) and MR relaxation times (T_1ρ and T₂) in both OA patients and normal subjects. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:919–926, 2012     

A prospective,randomized clinical study to compare the efficacy of recipient site preparation using dermabrasion,cryoblister, and dermaroller in autologous noncultured epidermal cell suspension in stable vitiligo

Noncultured epidermal cell suspension (NCES) is a well‐established surgical treatment modality for stable vitiligo. The outcome of this procedure significantly depends on the method of recipient site preparation, a critical step to achieve cosmetically acceptable repigmentation. To compare the efficacy of recipient site preparation using three methods namely, dermabrasion, cryoblister, and dermaroller followed by NCES in stable vitiligo. In this single‐center, prospective, intra‐patient, randomized clinical trial; 36 participants having at least three vitiligo patches in same anatomic region with minimum lesional stability of 1 year were randomized 1:1:1 for recipient site preparation using manual dermabrasion, cryoblister, and dermaroller followed by NCES. Patients were followed up at 4, 8, and 12 weeks and assessment of extent and pattern of repigmentation, color match and patient satisfaction were done. Among 36 patients, 22 (61.1%) were females; mean (SD) age was 28.33 (9.4) years. Dermabrasion and cryoblister techniques showed equal efficacy with respect to extent of repigmentation (>75% repigmentation; 55.6% vs 47.2%; P = .63) and patient satisfaction score (20.2 ± 9.6 vs 19.9 ± 7.9, P = .194). However, dermabrasion was superior to cryoblister in terms of rapidity (65% vs 32.5% at 4 weeks, P = .04) and color match (47.2% vs 19.4%, P = .004). Dermaroller had poor repigmentation outcomes compared to both dermabrasion and cryoblister. Cryoblister as a method of recipient site preparation is equally effective as manual dermabrasion in NCES for attaining good to excellent repigmentation, but with risk of hyperpigmentation. However, dermaroller is inferior to both dermabrasion and cryoblister.