Delayed and deficient dermal maturation in mice lacking the CXCR3 ELR-negative CXC chemokine receptor

Replacement of wounded skin requires the initially florid cellular response to abate and even regress as the dermal layer returns to a relatively paucicellular state. The signals that direct this "stop and return" process have yet to be deciphered. CXCR3 chemokine receptor and its ligand CXCL11/IP-9/I-TAC are expressed by basal keratinocytes and CXCL10/IP-10 by keratinocytes and endothelial cells during wound healing in mice and humans. In vitro, these ligands limit motility in dermal fibroblasts and endothelial cells. To examine whether this signaling pathway contributes to wound healing in vivo, full-thickness excisional wounds were created on CXCR3 wild-type (+/+) or knockout (-/-) mice. Even at 90 days, long after wound closure, wounds in the CXCR3(-/-) mice remained hypercellular and presented immature matrix components. The CXCR3(-/-) mice also presented poor remodeling and reorganization of collagen, which resulted in a weakened healed dermis. This in vivo model substantiates our in vitro findings that CXCR3 signaling is necessary for inhibition of fibroblast and endothelial cell migration and subsequent redifferentiation of the fibroblasts to a contractile state. These studies establish a pathophysiologic role for CXCR3 and its ligand during wound repair.     

The enhanced recovery after surgery (ERAS) protocol to promote recovery following esophageal cancer resection

Surgery Today - Esophageal cancer surgery, comprising esophagectomy with radical lymphadenectomy, is a complex procedure associated with considerable morbidity and mortality. The enhanced recovery...     

Substituted phenyl containing 1,3,4-oxadiazole-2-yl-but-2-enamides: synthesis and preliminary evaluation as promising anticonvulsants

A series of 3-(4-substitutedphenyl)-N-(5-(4-substitutedphenyl-1,3,4-oxadiazol-2-yl)but-2-enamide were synthesized using pharmacophoric elements for in vivo anticonvulsant activity yielding two potent candidates (4d and 4j) in the Phase I and Phase II screening employing maximal electroshock seizure and subcutaneous pentylenetetrazole test having minimal neurotoxicity. Their Phase II screen depicted an increment of nearly 2–10 times for MES and 7–67 folds for scPTZ in the therapeutic index and protective index—the two mainstays in the drug discovery.     

Improvement of Sleep Disturbance and Insomnia Following Parathyroidectomy for Primary Hyperparathyroidism

Background

The aim of the present study was to investigate the incidence of sleep disturbance and insomnia in patients with primary hyperparathyroidism (PHPT), and to evaluate the effect of parathyroidectomy.

Methods

A questionnaire was prospectively administered to adult patients with PHPT who underwent curative parathyroidectomy over an 11-month period. The questionnaire, administered preoperatively and 6 months postoperatively, included the Insomnia Severity Index (ISI) and eight additional questions regarding sleep pattern. Total ISI scores range from 0 to 28, with >7 signifying sleep difficulties and scores >14 indicating clinical insomnia.

Results

Of 197 eligible patients undergoing parathyroidectomy for PHPT, 115 (58.3 %) completed the preoperative and postoperative questionnaires. The mean age was 60.0 ± 1.2 years and 80.0 % were women. Preoperatively, 72 patients (62.6 %) had sleep difficulties, and 29 patients (25.2 %) met the criteria for clinical insomnia. Clinicopathologic variables were not predictive of clinical insomnia. There was a significant reduction in mean ISI score after parathyroidectomy (10.3 ± 0.6 vs 6.2 ± 0.5, p < 0.0001). Postoperatively, 79 patients (68.7 %) had an improved ISI score. Of the 29 patients with preoperative clinical insomnia, 21 (72.4 %) had resolution after parathyroidectomy. Preoperative insomnia patients had an increase in total hours slept after parathyroidectomy (5.4 ± 0.3 vs 6.1 ± 0.3 h, p = 0.02), whereas both insomnia patients and non-insomnia patients had a decrease in the number of awakenings (3.7 ± 0.4 vs 1.9 ± 0.2 times, p = 0.0001).

Conclusions

Sleep disturbances and insomnia are common in patients with PHPT, and the majority of patients will improve after curative parathyroidectomy.     

The utility of patient specific induced pluripotent stem cells for the modelling of Autistic Spectrum Disorders

Until now, models of psychiatric diseases have typically been animal models. Whether they were to be used to further understand the pathophysiology of the disorder, or as drug discovery tools, animal models have been the choice of preference in mimicking psychiatric disorders in an experimental setting. While there have been cellular models, they have generally been lacking in validity. This situation is changing with the advent of patient-specific induced pluripotent stem cells (iPSCs). In this article, we give a methodological evaluation of the current state of the iPS technology with reference to our own work in generating patient-specific iPSCs for the study of autistic spectrum disorder (ASD). In addition, we will give a broader perspective on the validity of this technology and to what extent it can be expected to complement animal models of ASD in the coming years.     

Feasibility,benefits and challenges of using telemonitoring for the aging with Developmental Disabilities (DD): An exploratory study

Telemonitoring is being increasingly used to provide services to patients with developmental disabilities in residential community settings. The objective of this study is to assess the feasibility, benefits and challenges of using telemonitoring for aging patients with developmental disabilities. We also assess the benefits and challenges of telemonitoring for the caregivers of these patients. Focus groups and questionnaire-based surveys were used to collect data from patients and caregivers. The study found that telemonitoring was feasible and beneficial for the aging with developmental disabilities, albeit for those who are moderate to high functioning. It was not beneficial or feasible for those with very low functional capabilities. The study found that telemonitoring was beneficial towards providing more independence, more self-confidence in carrying out daily activities, and more knowledge regarding their disease. The study also found that telemonitoring was useful for caregivers to better understand their patients and their needs, better coordinate the services delivered, and to enhance the satisfaction of caregiving. The discussions include limitations of using quantitative methods in this type of setting.