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Dystrophic calcinosis cutis can be associated with severe pain, decreased mobility, increased risk of infection and significantly decreased quality of life. We report a case of recalcitrant calcinosis cutis on the background of eosinophilic fasciitis, which achieved rapid reduction in calcium deposits following a novel injecting protocol of intralesional sodium thiosulfate.

In Canada, people from culturally and linguistically diverse (CALD) backgrounds are at a greater risk of developing a chronic illness, and are more likely to experience adverse health effects and challenges in accessing high-quality care compared with Canadian-born individuals. This, in part, has been attributed to having inadequate access to information and resources needed to manage their illness(es). A qualitative descriptive design and inductive content analysis were used to explore the information needs of 24 CALD patients with chronic illnesses. Participants identified medical, lifestyle, and psychosocial information needs. How much information was needed depended on such antecedents as illness trajectory, severity, and perception. Most information needs remained unmet. A number of communication strategies were identified to bridge language barriers that go beyond translation and are based on effective health education strategies. Findings can help health care professionals better identify CALD patients’ information needs and provide strategies that go beyond translation.

Lesbian, gay, bisexual, and transgender (LGBT) people experience a multitude of barriers to healthcare access, particularly in highly stigmatising contexts, such as Jamaica. Access to a regular healthcare source can contribute to uptake of health knowledge and services. Yet social-ecological factors associated with access to a regular healthcare provider among LGBT persons in Jamaica are underexplored. We conducted a cross-sectional survey with LGBT persons in Jamaica to examine socio-demographic and social-ecological factors associated with having a regular healthcare provider. Nearly half (43.6%) of 911 participants reported having a regular healthcare provider. In multivariate analyses, socio-demographic factors (higher age; identifying as a cisgender sexual minority man or woman compared to a transgender woman) were associated with higher odds of having a regular healthcare provider. Socio-demographic (living in Ocho Rios or Montego Bay compared to Kingston), stigma/discrimination (a bad past healthcare experience), and structural factors (insufficient money for housing; reporting medication costs as a barrier; no health insurance) were associated with decreased odds of having a regular healthcare provider. Findings support a multi-level approach to understanding and addressing barriers to having a regular healthcare provider among LGBT people in Jamaica.

Solid organ transplant recipients (SOTR) are at high risk of keratinocyte carcinoma (KC). Long-term evidence for acitretin as chemoprophylaxis in this population is lacking.To determine the benefit of long-term acitretin for KC chemoprevention in SOTR.A retrospective cohort study of SOTR treated with acitretin at an Australian transplant dermatology clinic was performed. General estimating equations were used to evaluate change in rates of histologically confirmed KC in the 6-12 months prior to acitretin and following a minimum 6 months of treatment. A control group of patients within the same service was included, comprising SOTR who were not treated with acitretin.Twenty-two patients received acitretin treatment for at least 6 months, eighteen for at least 5 years and four for at least 9 years. The median KC rate pretreatment was 3.31 per year (IQR 1.93, 5.40). There was a significant reduction in the rate of KC in the first year of acitretin treatment (IRR 0.41, 95% CI 0.22, 0.76, P = 0.005), and this effect was observed for 5 years (IRR at 5 years 0.34, 95% CI 0.17, 0.67, P = 0.002). The control group had no statistically significant change in KC rate over time in the study.Acitretin appears to be well-tolerated and effective in reducing KC in SOTR for at least 5 years. Study limitations include its retrospective nature, small sample size and lack of blinding.

Intracranial germ cell tumors (iGCTs) are classified into two pathological subtypes (germinomas [GEs] and nongerminomatous germ cell tumors [NGGCTs]), with distinct treatment strategy and prognosis. Accurate preoperative determination of iGCT subtypes is essential to guide clinical decision-making and prognosis assessment.To investigate the diagnostic value of diffusion-weighted imaging (DWI), susceptibility weighted imaging (SWI), and dynamic susceptibility-contrast perfusion-weighted imaging (DSC-PWI) combined with conventional magnetic resonance imaging (cMRI) in finding subtypes of iGCTs.Retrospective.A total of 40 patients (45% male and 55% female) with iGCTs.A 3 T;lt;T1WI, T2WI, T1WI + C, DWI, SWI, DSC-PWIgt;.The parameters of DWI and DSC-PWI were calculated based on extracted parameters of multiparametric MRIs. The characteristics of SWI and cMRI were also compared in GEs and NGGCTs.The diagnostic efficacy of the minimum apparent diffusion coefficient (ADCmin), time-to-peak (TTP), relative mean transit time (rMTT), relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV) maps, and cMRI features in iGCT classification was evaluated by receiver operating characteristic curve (ROC) analyses. We calculated the sensitivity, specificity, AUC, and Youden index of the hybrid MR evaluation methods. A prospective cohort (five GEs and five NGGCTs) was designed as a simulation set to test the model. The significance threshold was set at P lt; 0.01.The ADCmin (1039.100 ± 453.830 vs. 1400.050 ± 394.650), rCBF values (20.650 ± 6.260 vs. 51.170 ± 6.570), and TTP values (24.450 ± 3.160 vs. 28.950 ± 5.120) were significantly lower in GEs than in NGGCTs. The combination of ADCmin, DSC-PWI, and cMRI showed the heights AUC (AUC = 0.962). The iGCT multiparametric framework showed the AUC was 0.958 in the simulation set.The iCGT multiparametric framework might be an effective diagnostic approach of iGCT subtype. The application of cMRI (T1WI, T2WI, and Gd-T1WI) with advanced imaging modalities (DWI, SWI, and PWI) had the best performance for classifying iGCT subtypes.3 TECHNICAL EFFICACY: Stage 2.

For people with chronic conditions, people recovering from an illness or surgery, frail older people with complex needs, and people with disabilities, quality home health care and community services are vital to help them to live independently and well in their homes.1-3 Integrated care at home may help reduce their use of expensive inpatient care, help early discharge from hospitals and the delivery of rehabilitation programs.3 From the viewpoint of healthcare professionals, the effective and continuous monitoring of patients’ health status and communication with patients are the basis of providing appropriate diagnosis, treatment, and care.4,5 However, home health care faces the challenges of patient education, patient self-management, patient-clinician communication and remote clinical monitoring.6 Furthermore, it also requires health and social care workers from multiple backgrounds and different organizations and units (e.g. hospitals, subacute units, nursing homes, primary care services, community services) to work effectively together, but this has not been well achieved.7 To improve the situation, significant attention and research effort has recently been focused on the development of emerging technologies for home health care to support person-centred integrated care, and more specifically, the development of technologies and virtual platforms to support the monitoring of patient conditions, remote delivery of home health care, improvement of patients’ compliance to care programs as well as patient-clinician and clinician-clinician communications.8–13 The primary objective of this special issue is to foster focused attention in this emerging area and to serve as a forum for researchers and healthcare professionals to exchange and discuss the latest advances in technologies and issues in practices. This special issue targets on new models, novel technologies and systems that support patient monitoring and remote delivery of home health services, addressing design, user experience, implementation and impact. Our call for submissions had received positive responses from the community. After a rigorous peer-reviewed process, five papers were accepted based on their quality and relevance to the theme of this special issue. In the following sections, we introduce each of the special issue papers and conclude the editorial with future opportunities.

The rapid spread of coronavirus disease (COVID-19) in many countries has caused inconvenience in conducting daily life activities, and even deaths. Dexamethasone is a corticosteroid applied in clinical medicine since 1957, especially in immune therapy fields. Herein, we present the characteristics of Dexamethasone, from molecular mechanisms such as genomic and nongenomic pathways by cellular signal regulations, to clinical applications in various phases of the disease. During COVID-19 pandemic, Dexamethasone given to patients who required oxygen or ventilation therapy showed improved life efficacy.

Objectives The safety and efficacy of medications can vary significantly between patients as a result of genetic variability. As genomic screening technologies become more widely available, pharmacists are ideally suited to use such tools to optimize medication therapy management. The objective of this study was to evaluate the feasibility of implementing personalized medication services into community pharmacy practice and to assess the number of drug therapy problems identified as a result of pharmacogenomic screening. Setting The study was conducted in 2 busy urban community pharmacies, operating under the brand Shoppers Drug Mart, in Toronto, Ontario. Practice innovation Pharmacists offered pharmacogenomic screening as part of their professional services program. Eligible patients received a buccal swab followed by DNA analysis with the use of Pillcheck. Pillcheck is a genotyping assay that translates genomic data and generates a personalized evidence-based report that provides insight into patients' inherited drug metabolic profile. After receiving the report, pharmacists invited patients back to the clinic for interpretation of the results. Clinically significant drug therapy problems were identified and recommendations for medication optimization forwarded to the primary care physician. Results One hundred patients were enrolled in the study. Average age was 56.7 years, and patients were taking a mean of 4.9 chronic medications. Pharmacists cited the most common reasons for testing as ineffective therapy (43.0%), to address an adverse reaction (32.6%), and to guide initiation of therapy (10.4%). An average of 1.3 drug therapy problems directly related to pharmacogenomic testing were identified per patient. Pharmacist recommendations included change in therapy (60.3%), dose adjustment (13.2%), discontinuation of a drug (4.4%), and increased monitoring (22.1%). Conclusion These results highlight the readiness of community pharmacists to adopt pharmacogenomic screening into practice and their ability to leverage this novel technology to positively affect medication therapy management. Community pharmacists are ideally suited to both offer personalized medication services and interpret genomic results.

Community health workers in primary care programs increasingly use Mobile Health Data Collection Systems (MDCSs) to report their activities and conduct health surveys, replacing paper-based approaches. The mHealth systems are inherently privacy invasive, thus informing individuals and obtaining their consent is important to protect their rights to privacy. In this paper, we introduce an e-Consent tool tailored for MDCSs. It is developed based on the requirement analysis of consent management for data privacy and built upon the solutions of Participant-Centered Consent toolkit and Consent Receipt specification. The e-Consent solution has been evaluated in a usability study. The study results show that the design is useful for informing individuals on the nature of data processing, allowing them to make informed decisions.

Dengue virus, the causative agent for the dengue fever, infects approximately 50-100 million people worldwide per year. The high incidence of dengue fever, along with its potential to develop into a severe, life-threatening form, resulted in great interest in the discovery of an antiviral against it. In this study, we constructed a DENV2-EGFP infectious clone, established a fluorescence-based, high-throughput screening platform, and conducted a screen for anti-DENV compounds on a flavonoid-derivative library, Amongst the hits identified, ST081006 was found to be a strong inhibitor of the DENV replication. Time-course studies suggest that the presence of ST081006 is necessary to inhibit successive rounds of virus replication. Further investigations demonstrated that ST081006 affects the synthesis of both viral protein and viral RNA, and one anti-DENV mechanism is the direct inhibition of viral protein synthesis. The replication of all dengue serotypes, along with that of the enterovirus EV-A71, was shown to be affected by ST081006. Attempts to generate ST081006-resistant DENV were unsuccessful, and thus hints at host factors as potential drug target. Together, these results suggest that ST081006 affect DENV replication, likely by acting on a target involved in the viral protein and/or RNA synthesis pathway.

Although memory T cells within barrier tissues can persist as permanent residents, at least some exchange with blood. The extent to which this occurs is unclear. Here we show that memory CD4+ T cells in mouse skin are in equilibrium with the circulation at steady state. These cells are dispersed throughout the inter-follicular regions of the dermis and form clusters with antigen presenting cells around hair follicles. After infection or administration of a contact sensitizing agent, there is a sustained increase in skin CD4+ T-cell content, which is confined to the clusters, with a concomitant CCL5-dependent increase in CD4+ T-cell recruitment. Skin CCL5 is derived from CD11b+ cells and CD8+ T cells, with the elimination of the latter decreasing CD4+ T-cell numbers. These results reveal a complex pattern of tissue-retention and equilibration for CD4+ memory T cells in skin, which is altered by infection and inflammation history., Memory T cells are vital responders to skin inflammation, but cell localization and dynamics of exchange with the bloodstream are not clear. Here the authors use parabiosis and intravital microscopy to show that CD4+ memory T cells equilibrate with the circulation and cluster around hair follicles in response to CCL5-dependent responses to viral infection or contact sensitization.

Home telemonitoring has been used as a solution to support the care of individuals living with chronic disease. While effectiveness of telemonitoring have been widely studied, more research is needed to understand the perceptions among patients and clinicians in incorporating telemonitoring into their daily routine and practices. This paper presents an investigation of patients’ and clinicians’ experiences in a care augmenting telemonitoring service, their perceived impact delivered through the service, and clinicians’ perceptions on how the service was introduced in their organizations. This work was embedded in a large multi-site trial of home telemonitoring using a mixed method approach for evaluation. Interviews with clinicians involved in the study were conducted at multiple time points during the trial. Questionnaires were administered to clinicians and patients at the end of the trial. Results showed that both patients and clinicians recognized the benefits of patient empowerment through telemonitoring, and patient-clinician interactions. Results identified the needs of a dedicated telemonitoring clinical care coordinator role, guidelines that translate telemonitoring services into clinical pathways and engagement of different healthcare providers, especially general practitioners, to support the integration of telemonitoring into chronic disease management programs and long-term organizational strategic plans.

As the demand in cancer care continues to increase, health systems require a workforce of highly educated specialists and generalists to provide continuity of care across settings. Led by de Souza Institute in Canada, an interdisciplinary working group was formed to develop a competency framework with relevance across regulated health professionals involved in cancer care. The working group was presented with results from a scoping review of national and international guidelines, standards, and competencies in oncology, as well as data from needs assessments on continuing education opportunities and oncology topics most relevant to clinicians. Fifty-one professionals from, e.g., family medicine, pharmacy, social work, psychology, occupational therapy, and nursing participated in seven focus groups. An additional 32 nurses participated in a nursing-specific needs assessment survey. Using modified Delphi technique, working group members conducted three iterative rounds to review data and built consensus on competency items in relation to three levels of expertise, from early learner/novice practitioner, advancing practitioner, to expert practitioner. A final consensus was reached for the selection of competencies that reflect optimal cancer care mapped into three levels of expertise, as well as knowledge, skills, and attitudes expected of each level. Examples for the competency for early learner/novice practitioner include the following: Have awareness of common ethical issues in cancer care (knowledge); demonstrate ability to discuss, educate, and counsel patients and their support persons(s) regarding preferences (skills); and appreciate the impact of culture, the sensitivity, and diversity of attitudes in relation to cancer (attitude). Expert practitioner examples include: recognition of need for, and ability to advocate for challenges involving equity and access in order to improve health outcomes (skill) and awareness of workplace complexities, such as provider roles, team functioning, and organizational environments affecting patient-practitioner relationships (attitude). The de Souza Interprofessional practice cancer competency framework provides a set of shared competencies and a novice to expert pathway for clinicians across disciplines and supports a more standardized learning and comprehensive approach in organizing professional development towards a coordinated, high quality, and person-centered care.

Wearable and mobile devices are now commonly used in our daily activities, giving users instant access to various information. One the one hand, wearable and mobile technologies are developing at a fast rate and have been increasingly ubiquitous. On the other hand, the potential of their application in health is yet to be fully explored. This paper attempts to sketch an overview of wearable and mobile applications in the healthcare domain. We first review how various wearable and mobile applications are being used to monitor and manage health conditions. Then how connections between physiological factors and psychological factors can help with disease prevention is presented. Finally, challenges and future directions for further developments of these emerging technologies in health are discussed.

We present our work in designing mobile interaction and guidance technologies for the application of remote consultation between healthcare professionals. We describe design case studies which address the needs and scenarios in this application: a hybrid and rich media tool which supports mobile one-on-one consultations; a remote guidance tool which allows an expert to remotely guide a nurse or junior clinician to perform clinical procedures; an integrated collaboration platform which supports remote consultations in a group meeting environment by enabling shared interaction with patient records and mobile interaction with large displays. These tools have been evaluated in usability studies in which the usefulness and potential value have been demonstrated. By presenting these case studies, we highlight the trend of incorporating emerging collaboration technologies and the need of integrated and multi-model interaction systems in a broader telehealth context.

This study described a pH-gradient dissolution method combined with flux measurements as an in vitro tool for assessing the risk of bioavailability reduction due to drug-drug interactions (DDI) caused by acid reducing agents (ARAs). The device incorporates absorption chambers into USP II dissolution vessels, with fiber optic UV-probes monitoring concentration in situ. Dosage forms of Genentech BCS class II drugs, GDC-0810, GDC-0941, and compound A, were tested by starting the dissolution in either pH 1.6 or pH 4.0 media then converting to FaSSIF after 30 min. GDC-0810 showed no significant difference in flux between the two conversion experiments. A supersaturation phase was observed for GDC-0941 in the pH 1.6 experiments after media conversion to FaSSIF; however, it did not appear to occur in the pH 4.0 experiment due to low drug solubility at pH 4.0, resulting in a 95% decrease in flux compared to pH 1.6 experiment. The extent of flux reduction and the total accumulated API mass in the absorption chamber agreed well with the 89% reduction in mean Cmax and the 82% reduction in mean AUC from dog PK study between animals treated with pentagastrin and famotidine. Testing of the compound A optimized formulation tablets showed a 25% reduction in flux and in vitro absorbed amount by changing pH 1.6 to 4.0, correlating well with the AUC decrease in clinical studies. Good correlation between in vitro data and in vivo PK data demonstrated the applicability of the method for formulators to develop drug products mitigating DDI from ARAs.

Purpose: Endometrioid endometrial carcinoma (EEC) is the major histologic type of endometrial cancer, the most prevalent gynecologic malignancy in the United States. EEC recurrence or metastasis is associated with a poor prognosis. Early-stage EEC is generally curable, but a subset has high risk of recurrence or metastasis. Prognosis estimation for early-stage EEC mainly relies on clinicopathologic characteristics, but is unreliable. We aimed to identify patients with high-risk early-stage EEC who are most likely to benefit from more extensive surgery and adjuvant therapy by building a prognostic model that integrates clinical variables and protein markers. Experimental Design: We used two large, independent early-stage EEC datasets as training (n = 183) and validation cohorts (n = 333), and generated the levels of 186 proteins and phosphoproteins using reverse-phase protein arrays. By applying an initial filtering and the elastic net to the training samples, we developed a prognostic model for overall survival containing two clinical variables and 18 protein markers and optimized the risk group classification. Results: The Kaplan–Meier survival analyses in the validation cohort confirmed an improved discriminating power of our prognostic model for patients with early-stage EEC over key clinical variables (log-rank test, P = 0.565 for disease stage, 0.567 for tumor grade, and 1.3 × 10−4 for the integrative model). Compared with clinical variables (stage, grade, and patient age), only the risk groups defined by the integrative model were consistently significant in both univariate and multivariate analyses across both cohorts. Conclusions: Our prognostic model is potentially of high clinical value for stratifying patients with early-stage EEC and improving their treatment strategies. Clin Cancer Res; 22(2); 513–23. ©2015 AACR.

Endometrial cancer incidence is increasing, due in part to a strong association with obesity. Mutations in the phosphatidylinositol 3‐kinase (PI3K) pathway, the central relay pathway of insulin signals, occur in the majority of endometrioid adenocarcinomas, the most common form of endometrial cancer. We sought to determine the impact of PI3K pathway alterations on progression free survival in a cohort of endometrioid endometrial cancers. Prognostic utility of PIK3CA, PIK3R1, and PTEN mutations, as well as PTEN protein loss by immunohistochemistry, was explored in the context of patient body mass index. Reverse‐phase protein arrays were utilized to assess protein expression based on PTEN status. Among 187 endometrioid endometrial cancers, there were no statistically significant associations between PFS and PIK3CA, PIK3R1, PTEN mutation or loss. When stratified by body mass index, PTEN loss was associated with improved progression free survival (P

The purpose of this work is to investigate the effect of microenvironmental pH modulation on the in vitro dissolution rate and oral absorption of GDC-0810, an oral anti-cancer drug, in human. The pH-solubility profile of GDC-0810 free acid and pHmax of its N-Methyl-D-glucamine (NMG) salt were determined. Precipitation studies were conducted for GDC-0810 NMG salt at different pH values. GDC-0810 200-mg dose NMG salt tablet formulations containing different levels of sodium bicarbonate as the pH modifier were tested for dissolution under the dual pH-dilution scheme. Three tablet formulations were evaluated in human as a part of a relative bioavailability study. A 200-mg dose of GDC-0810 was administered QD with low fat food. Intrinsic solubility of GDC-0810 free acid was found to be extremely low. The pHmax of the NMG salt suggested a strong tendency for form conversion to the free acid under GI conditions. In vitro dissolution profiles showed that the dissolution rate and extent of GDC-0810 increased with increasing the level of sodium bicarbonate in the formulation. The human PK data showed a similar trend for the geometric mean of Cmax and AUC0-t for formulations containing 5%, 10%, and 15% sodium bicarbonate, but the difference is not statistically significant. Incorporation of a basic pH modifier, sodium bicarbonate, in GDC-0810 NMG salt tablet formulations enhanced in vitro dissolution rate of GDC-0810 via microenvironmental pH modulation. The human PK data showed no statistically significant difference in drug exposure from tablets containing 5%, 10%, and 15% sodium bicarbonate.

Many statisticians and policy researchers are interested in using data generated through the normal delivery of health care services, rather than carefully designed and implemented population-representative surveys, to estimate disease prevalence. These larger databases allow for the estimation of smaller geographies, for example, states, at potentially lower expense. However, these health care records frequently do not cover all of the population of interest and may not collect some covariates that are important for accurate estimation. In a recent paper, the authors have described how to adjust for the incomplete coverage of administrative claims data and electronic health records at the state or local level. This article illustrates how to adjust and combine multiple data sets, namely, national surveys, state-level surveys, claims data, and electronic health record data, to improve estimates of diabetes and prediabetes prevalence, along with the estimates of the method's accuracy. We demonstrate and validate the method using data from three jurisdictions (Alabama, California, and New York City). This method can be applied more generally to other areas and other data sources.

PTEN mutations are the most common genetic alterations in endometrial cancer. Loss of PTEN and subsequent AKT activation stimulate estrogen receptor α–dependent pathways that play an important role in endometrial tumorigenesis. The major pathologic phenomenon of endometrial cancer is the loss of ovarian steroid hormone control over uterine epithelial cell proliferation and apoptosis. However, the precise mechanism of PTEN/AKT signaling in endometrial cancer remains poorly understood. The progesterone signaling mediator MIG-6 suppresses estrogen signaling and it has been implicated previously as a tumor suppressor in endometrial cancer. In this study, we show that MIG-6 also acts as a tumor suppressor in endometrial cancers associated with PTEN deficiency. Transgenic mice, where Mig-6 was overexpressed in progesterone receptor–expressing cells, exhibited a relative reduction in uterine tumorigenesis caused by Pten deficiency. ERK1/2 was phosphorylated in uterine tumors and administration of an ERK1/2 inhibitor suppressed cancer progression in PRcre/+Ptenf/f mice. In clinical specimens of endometrial cancer, MIG-6 expression correlated inversely with ERK1/2 phosphorylation during progression. Taken together, our findings suggest that Mig-6 regulates ERK1/2 phosphorylation and that it is crucial for progression of PTEN-mutant endometrial cancers, providing a mechanistic rationale for the evaluation of ERK1/2 inhibitors as a therapeutic treatment in human endometrial cancer. Cancer Res; 74(24); 7371–82. ©2014 AACR.

Object The development of minimally invasive surgical techniques is driven by the quest for better patient outcomes. There is some evidence for the use of minimally invasive surgery for degenerative lumbar spine stenosis (LSS), but there are currently no studies comparing outcomes with matched controls. The object of this study was to compare outcomes following minimally invasive unilateral laminectomy for bilateral decompression (ULBD) to a standard “open” laminectomy for LSS. Methods The authors conducted a prospective, 1:1 randomized trial comparing ULBD to open laminectomy for degenerative LSS. The study enrolled 79 patients between 2007 and 2009, and adequate data for analysis were available in 54 patients (27 in each arm of the study). Patient demographic characteristics and clinical characteristics were recorded and clinical outcomes were obtained using pre- and postoperative Oswestry Disability Index (ODI) scores, visual analog scale (VAS) scores for leg pain, patient satisfaction index scores, and postoperative 12-Item Short Form Health Survey (SF-12) scores. Results Significant improvements were observed in ODI and VAS scores for both open and ULBD interventions (p < 0.001 for both groups using either score). In addition, the ULBD-treated patients had a significantly better mean improvement in the VAS scores (p = 0.013) but not the ODI scores (p = 0.055) compared with patients in the open-surgery group. ULBD-treated patients had a significantly shorter length of postoperative hospital stay (55.1 vs 100.8 hours, p = 0.0041) and time to mobilization (15.6 vs 33.3 hours, p < 0.001) and were more likely to not use opioids for postoperative pain (51.9% vs 15.4%, p = 0.046). Conclusions Based on short-term follow-up, microscopic ULBD is as effective as open decompression in improving function (ODI score), with the additional benefits of a significantly greater decrease in pain (VAS score), postoperative recovery time, time to mobilization, and opioid use.

Follicle-stimulating hormone (FSH), acting on its receptor (FSHR), plays a pivotal role in the stimulation of follicular development and maturation. Multiple injections of protein formulations are used during clinical protocols for ovulation induction and for in vitro fertilization that are followed by a selection of assisted reproductive technologies. In order to increase patient convenience and compliance several research groups have searched for orally bioavailable FSH mimetics for innovative fertility medicines. We report here the discovery of a series of substituted benzamides as positive allosteric modulators (PAM) targeting FSHR. Optimization of this series has led to enhanced activity in primary rat granulosa cells, as well as remarkable selectivity against the closely related luteinizing hormone receptor (LHR) and thyroid stimulating hormone receptor (TSHR). Two modulators, 9j and 9k, showed promising in vitro and pharmacokinetic profiles.

Signals from the tumor suppressors PTEN and LKB1 converge on mTOR to negatively regulate its function in cancer cells. Notably, both of these suppressors are attenuated in a significant fraction of human endometrial tumors. In this study, we generated a genetic mouse model of endometrial cancer driven by concomitant loss of these suppressors to gain pathophysiological insight into this disease. Dual loss of Pten and Lkb1 in the endometrial epithelium led to rapid development of advanced endometrioid endometrial tumors with 100% penetrance and short host survival. The tumors displayed dysregulated phosphatidylinositol 3-kinase (PI3K)/Akt and Lkb1/Ampk signaling with hyperactivation of mTOR signaling. Treatment with a dual PI3K/mTOR inhibitor, BEZ235, extended the time before tumor onset and prolonged overall survival. The PI3K inhibitor GDC-0941 used as a single agent reduced the growth rate of primary tumor implants in Pten/Lkb1-deficient mice, and the mTOR inhibitor RAD001 was unexpectedly as effective as BEZ235 in triggering tumor regression. In parallel, we also found that ectopic expression of LKB1 in PTEN/LKB1-deficient human endometrial cancer cells increased their sensitivity to PI3K inhibition. Together, our results demonstrated that Pten/Lkb1-deficient endometrial tumors rely strongly on deregulated mTOR signaling, and they provided evidence that LKB1 status may modulate the response of PTEN-deficient tumors to PI3K or mTOR inhibitors. Cancer Res; 74(1); 15–23. ©2013 AACR.

Background Mycophenolate mofetil (MMF) has enjoyed increasing popularity as an emerging immunosuppressant treatment for various autoimmune dermatologic conditions, including pyoderma gangrenosum (PG). Objective The aim of this study was to examine the efficacy and safety of MMF as used in PG. Methods A retrospective chart review was conducted for all patients with PG treated with MMF at our institution (Victoria, Australia) for the past 11 years (2001-2012). Results We identified 26 patients, 14 female and 12 male. Nine patients (34.6%) had associated systemic conditions. All patients received prednisolone. MMF was used as a first-line steroid-sparing agent in 11 patients (42.3%), second-line in 14 (53.8%), and third-line in 1 (3.85%). The average duration of treatment was 12.1 months. Fourteen patients experienced side effects (53.8%), although most were mild (26.9%). One patient died after a sigmoid colon perforation (3.85%). Overall 22 patients demonstrated clinical improvement during MMF treatment (84.6%). Thirteen patients achieved complete ulcer healing (50%), 10 while taking MMF and 3 after ceasing it. Limitations This is a retrospective study based on a single-center cohort. Conclusion Our experience suggests that MMF is highly efficacious in PG together with prednisolone, or as part of combination therapy with other immunosuppressants.

Cancer is one of the leading causes of death in the world. Along with increased new cases, cancer care has become increasingly complex due to advances in diagnostics and treatments, greater survival, and new models of palliative care. Nurses are a critical resource for cancer patients and their families. Their roles and responsibilities are expanding across the cancer care continuum, calling for specialized training and support. Formal education prepares nurses for entry level of practice, however, it does not provide the specialized competencies required for quality care of cancer patients. There is urgent need to align the educational system to the demands of the health care system, ease transition from formal academic systems to care settings, and to instill a philosophy of lifelong learning. We describe a model of education developed by de Souza Institute in Canada, based on the Novice to Expert specialty training framework, and its success in offering structured oncology continuing education training to nurses, from undergraduate levels to continued career development in the clinical setting. This model may have global relevance, given the challenge in managing the demand for high quality care in all disease areas and in keeping pace with the emerging advances in technologies.

Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103—, and were retained within the spleen and tonsils in the absence of recent T cell stimulation. These two types of memory cells were distinct not only in their phenotype and transcriptional profile, but also in their anatomical localization within tonsils and spleen. The EBV-specific, but not CMV-specific, CD8+ memory T cells preferentially accumulated in the tonsils and acquired a phenotype that ensured their retention at the epithelial sites where EBV replicates. In vitro studies revealed that the cytokine IL-15 can potentiate the retention of circulating effector memory CD8+ T cells by down-regulating the expression of sphingosine-1-phosphate receptor, required for T cell exit from tissues, and its transcriptional activator, Kruppel-like factor 2 (KLF2). Within the tonsils the expression of IL-15 was detected in regions where CD8+ T cells localized, further supporting a role for this cytokine in T cell retention. Together this study provides evidence for the compartmentalization of distinct types of resident memory T cells that could contribute to the long-term protection against persisting viral infections., Author Summary Some viruses have the capacity to establish chronic infections in humans. How different T cell populations effectively control these infections has not been clear. Continuous circulation of memory T cells was thought to be crucial for effective immune surveillance against such infections. Recent studies in mice however, have shown that non-circulating tissue resident memory populations can also contribute to protective immunity. In this study we have examined the distribution, localization and characteristics of Epstein-Barr virus and Cytomegalovirus-specific T cells in different human tissues. This showed that virus-specific T cells were differentially distributed in different tissues and there was preferential accumulation of EBV-specific resident memory T cells at sites where EBV reactivates. In vitro studies showed that IL-15 and TGF-β could cooperate to extinguish tissue exit signals in T cells and therefore potentiate their retention within tissues. IL-15 expression was also detected in areas where T cells aggregated within the tissue. Together our study provides insight into how distinct memory T cells are compartmentalized in tissues to maintain long-term protection against persisting viral infections.

Mutation of PPP2R1A has been observed at high frequency in endometrial serous carcinomas but at low frequency in ovarian clear cell carcinoma. However, the biological role of mutation of PPP2R1A in ovarian and endometrial cancer progression remains unclear. In this study, we found that PPP2R1A expression is elevated in high-grade primary tumor patients with papillary serous tumors of the ovary. To determine whether increased levels or mutation of PPP2R1A might contribute to cancer progression, the effects of overexpression or mutation of PPP2R1A on cell proliferation, migration, and PP2A phosphatase activity were investigated using ovarian and endometrial cancer cell lines. Among the mutations, PPP2R1A-W257G enhanced cell migration in vitro through activating SRC-JNK-c-Jun pathway. Overexpression of wild type (WT) PPP2R1A increased its binding ability with B56 regulatory subunits, whereas PPP2R1A-mutations lost the ability to bind to most B56 subunits except B56δ. Total PP2A activity and PPP2R1A-associated PP2Ac activity were significantly increased in cells overexpressing PPP2R1A-WT. In addition, overexpression of PPP2R1A-WT increased cell proliferation in vitro and tumor growth in vivo.

Minimally invasive techniques in spinal surgery are increasing in popularity due to numerous potential advantages, including reduced length of stay, blood loss and requirements for post-operative analgesia as well as earlier return to work. This review discusses guidelines for safe implantation of percutaneous pedicle screws using an image intensifier technique. As indications for percutaneous pedicle screw techniques expand, the nuances of the minimally invasive surgery technique will also expand. It is paramount that experienced surgeons share their collective knowledge to assist surgeons at their early attempts of these complex, and potentially dangerous, procedures. Technical challenges of percutaneous pedicle screw fixation techniques are also discussed including: small pedicle cannulation, percutaneous rod insertion for multilevel constructs, incision selection for multilevel constructs, changing direction with percutaneous pedicle screw placement, L5/S1 screw head proximity and sclerotic pedicles with difficult Jamshidi placement. We discuss potential indications for minimally invasive fusion techniques for complex spinal surgery and support these with descriptions of illustrative patients.

Chordomas are rare, malignant, low grade, primary bone tumours arising from notochord remnants. They are rarely located in the lumbar spine and consequently, the literature is lacking about the condition. There are very few case reports on the technical aspects of resection of extensive lesions such as our case. Treatment can be potentially curative only if aggressive surgical resection is utilised. We describe a case of an extensive lumbar chordoma, and demonstrate the possibility of performing a staged anterior and posterior total tumour resection with planned transgression in conjunction with an expandable cage, vascularised rib, fibula and latissimus dorsi grafts for the treatment and reconstruction of extensive spinal disease with this condition.

This preliminary report was attempted to compare the chemical components of mineral deposits on the surfaces of an opacified intraocular lens (IOL) and a calcified senile cataractous lens (SCL) by vibrational spectral diagnosis. An opacified intraocular lens (IOL) was obtained from a 65-year-old male patient who had a significant decrease in visual acuity 2-years after an ocular IOL implantation. Another SCL with grayish white calcified plaque on the subcapsular cortex was isolated from a 79-year-old male patient with complicated cataract after cataract surgery. Optical light microscope was used to observe both samples and gross pictures were taken. Fourier transform infrared (FT-IR) and Raman microspectroscopic techniques were employed to analyze the calcified deposits. The curve-fitting algorithm using the Gaussian function was also used to quantitatively estimate the chemical components in each deposit. The preliminary results of spectral diagnosis indicate that the opacified IOL mainly consisted of the poorly crystalline, immature non-stoichiometric hydroxyapatite (HA) with higher content of type B carbonated apatites. However, the calcified plaque deposited on the SCL was comprised of a mature crystalline stoichiometric HA having higher contents of type A and type B carbonate apatites. More case studies should be examined in future.

The purpose of this study was to identify and evaluate service quality gaps among 3 roles (ie, hospital executives, frontline employees, and outpatients). A modified Chinese SERVQUAL scale was used to pinpoint dimension-specific quality gaps. A total of 1556 subjects (including 685 outpatients, 787 frontline employees, and 84 executives) were randomly selected from 12 middle-sized hospitals across Taiwan. Significant quality gaps among the 3 roles for 5 dimensions were found. Accordingly, strategies and tactics for improving service quality of hospitals are discussed.

Raman microspectroscopy was first used to determine the composition of a calcified plaque located at the pterygium-excision site of a 51-year-old female patient's left nasal sclera after surgery. It was unexpectedly found that the Raman spectrum of the calcified sample at 1149, 1108, 1049, 756, 517, 376 and 352/cm was similar to the Raman spectrum of monoclinic form of calcium pyrophosphate dihydrate (CPPD) crystal, but differed from the Raman spectrum of triclinic form of CPPD. An additional peak at 958/cm was also observed in the Raman spectrum of the calcified plaque, which was identical to the characteristic peak at 958/cm of hydroxyapatite (HA). This is the first study to report the spectral biodiagnosis of both monoclinic CPPD and HA co-deposited in the calcified plaque of a patient with sclera dystrophic calcification using Raman microspectroscopy.

BACKGROUND:Migrant women in sex work experience unique risks and protective factors related to their sexual health. Given the dearth of knowledge in high-income countries, we explored factors associated with inconsistent condom use by clients among migrant female sex workers over time in Vancouver, BC. METHODS:Questionnaire and HIV/sexually transmitted infection testing data from a longitudinal cohort, An Evaluation of Sex Workers Health Access, were collected from 2010 to 2013. Logistic regression using generalized estimating equations was used to model correlates of inconsistent condom use by clients among international migrant sex workers over a 3-year study period. RESULTS:Of 685 participants, analyses were restricted to 182 (27%) international migrants who primarily originated from China. In multivariate generalized estimating equations analyses, difficulty accessing condoms (adjusted odds ratio [AOR], 3.76; 95% confidence interval [CI], 1.13-12.47) independently correlated with increased odds of inconsistent condom use by clients. Servicing clients in indoor sex work establishments (e.g., massage parlors) (AOR, 0.34; 95% CI, 0.15-0.77), and high school attainment (AOR, 0.22; 95% CI, 0.09-0.50) had independent protective effects on the odds of inconsistent condom use by clients. CONCLUSIONS:Findings of this longitudinal study highlight the persistent challenges faced by migrant sex workers in terms of accessing and using condoms. Migrant sex workers who experienced difficulty in accessing condoms were more than 3 times as likely to report inconsistent condom use by clients. Laws, policies, and programs promoting access to safer, decriminalized indoor work environments remain urgently needed to promote health, safety, and human rights for migrant workers in the sex industry.

Calcinosis cutis is characterized by the deposition of calcium salts in the subcutaneous tissues. Both Fourier transform infrared (FTIR) and Raman microspectroscopic analysis have been applied to easily get the chemical compositions of the skin calcified deposit (SCD), which was surgically excised from a female patient. This SCD was cut into two parts for histopathological (HE stain) examination and vibrational microspectroscopic study. The result indicates that the whole SCD in the skin lesion was found to be a well-developed, mature and hard mass. Several FTIR absorption bands at 873, 961 and 1,031 cm(-1) [the stretching modes of carbonate and phosphate of hydroxyapatite (HA)], 1,547 and 1,658 cm(-1) (the amide I and II bands of collagen) were detected in the IR spectrum of SCD. The Raman spectral bands at 1,665 and 1,450 cm(-1) (collagen); 1,519 and 1,156 cm(-1) (beta-carotene); and 1,072 and 958 cm(-1) (HA) were also obtained. To our knowledge, this is the first report using FTIR and Raman microspectroscopies to quickly identify and quantify three predominant components, collagen, beta-carotene and type B carbonated HA, in the SCD of a patient.

The aim of this study was to quickly and quantitatively detect the chemical composition of the calcified deposit on the surface of a surgically excised cornea by using vibrational microspectroscopy.Both attenuated total reflection (ATR)/Fourier transform infrared (FTIR) and confocal Raman microspectroscopies were used to evaluate the chemical composition of the excised corneal calcified opaque deposit of a 50-year-old male patient. Hydroxyapatite (HA) was used as a reference.Microscopic observations indicated that a whitish-grayish opaque plaquelike deposit was observed. A peak at 1020 cm(-1) assigned to the stretching vibration of phosphate of the poorly crystalline, immature and nonstoichiometric HA was observed from the IR spectrum of the corneal calcified deposit, as compared with the peak at 1030 cm(-1) of the mature, crystalline and stoichiometric HA reference sample. Higher contents of two IR spectral peaks at 871 cm(-1) due to the type-B carbonated apatite and at 866 cm(-1) corresponded to a labile carbonate were also evidenced in the corneal calcified deposit. The predominate peak at 959 cm(-1) due to the stretching mode of phosphate was also found in the Raman spectrum of corneal calcified deposit.The corneal calcified deposit was evidenced to contain much poor crystalline and immature HA having higher content of the type-B carbonated apatite within the corneal collagen matrix. The process of corneal calcification still proceeds on the surface of this cornea.

In order to investigate the thermal stability of human serum albumin (HAS) in three different states (aqueous solution, cast film, and solid powder), Fourier transform infrared (FTIR) spectroscopy was applied to determine the protein secondary structural changes of these HSA samples under non-isothermal or isothermal condition. The structural similarity of HSA before and after thermal treatment was also studied to estimate the thermo-reversible property of the HSA in these different states. The results indicate that with the increase of temperature, the maximum peaks at 1652 and 1547 cm(-1) (alpha-helix) shifted to 1647 and 1542 cm(-1) (random coil), respectively. An additional peak at 1620 cm(-1) assigned to intermolecular beta-sheet structure clearly appeared with temperature. The alpha-helix content was found to be reduced in favor of the formation of intermolecular hydrogen-bonded antiparallel beta-sheet structure beyond 60 degrees C in the heating process. From the data of structural similarity, HSA sample whether in solid powder or cast film form exhibited a better thermo-reversible property than HSA in aqueous solution even heating to 200 degrees C.

This study was performed to determine airborne manganese levels during welding practice and to establish the relationship between long-term, low-level exposure to manganese and altered serum concentrations of manganese, iron, and proteins associated with iron metabolism in career welders. Ninety-seven welders (average age of 36 years) who have engaged in electric arc weld in a vehicle manufacturer were recruited as the exposed group. Welders worked 7-8h per day with employment duration of 1-33 years. Control subjects consisted of 91 employees (average age of 35 years) in the same factory but not in the welding profession. Ambient manganese levels in welders' breathing zone were the highest inside the vehicle (1.5 +/- 0.7 mg/m3), and the lowest in the center of the workshop (0.2 +/- 0.05 mg/m3). Since the filter size was 0.8 microm, it is possible that these values may be likely an underestimation of the true manganese levels. Serum levels of manganese and iron in welders were about three-fold (p < 0.01) and 1.2-fold (p < 0.01), respectively, higher than those of controls. Serum concentrations of ferritin and transferrin were increased among welders, while serum transferrin receptor levels were significantly decreased in comparison to controls. Linear regression analyses revealed a lack of association between serum levels of manganese and iron. However, serum concentrations of iron and ferritin were positively associated with years of welder experience (p < 0.05). Moreover, serum transferrin receptor levels were inversely associated with serum manganese concentrations (p < 0.05). These findings suggest that exposure to welding fume among welders disturbs serum homeostasis of manganese, iron, and the proteins associated with iron metabolism. Serum manganese may serve as a reasonable biomarker for assessment of recent exposure to airborne manganese.

The attenuated total reflection/Fourier transform infrared technique has been utilized to characterize secondary structural changes in human serum albumin (HSA) before and after protein binding via incubation of HSA in different concentrations of ethanol, captopril or ethanol/captopril mixture. The results indicate that ethanol induced a transition from beta-sheet to an alpha-helical structure and promoted conversion of intramolecular hydrogen-bonded beta-sheet to intermolecular hydrogen-bonded beta-sheet. In contrast, captopril or captopril/ethanol mixture induced conversion of intramolecular hydrogen-bonded beta-sheet to intermolecular hydrogen-bonded beta-sheet and resulted in exposure of the aromatic side-chain groups in the unfolding conformation of HSA. Thus, protein binding between HSA and captopril or captopril/ethanol seems to play an important role in protein secondary structure.

Welders in this study were selected from a vehicle manufacturer; control subjects were from a nearby food factory. Airborne manganese levels in the breathing zones of welders and controls were 1.45 +/- SD1.08 mg/m and 0.11 +/- 0.07 microg/m, respectively. Serum levels of manganese and iron in welders were 4.3-fold and 1.9-fold, respectively, higher than those of controls. Blood lead concentrations in welders increased 2.5-fold, whereas serum zinc levels decreased 1.2-fold, in comparison with controls. Linear regression revealed the lack of associations between blood levels of five metals and welder's age. Furthermore, welders had erythrocytic superoxide dismutase activity and serum malondialdehyde levels 24% less and 78% higher, respectively, than those of controls. These findings suggest that occupational exposure to welding fumes among welders disturbs the homeostasis of trace elements in systemic circulation and induces oxidative stress.

We used Fourier transform infrared (FTIR) microspectroscopy to investigate pressure-induced conformational changes in secondary structure of fibrinogen (FBG). Solid state FBG was compressed on a KBr pellet (1KBr method) or between two KBr pellets (2KBr method). The peak positions of the original and second-derivative ir spectra of compressed FBG samples prepared by the 1KBr method were similar to FBG sample without pressure. When FBG was prepared by the 2KBr method and pressure was increased up to 400 kg/cm2, peaks at 1625 (intermolecular β-sheet) and 1611 (β-sheet aggregates structure and/or the side-chain absorption of the tyrosine residues) cm−1 were enhanced. The peaks near 1661 (β-sheet) and 1652 (α-helix) cm−1 also exhibited a marked change with pressure. A linear correlation was found between the peak intensity ratio of 1611/1652 cm−1 (r = 0.9879) or 1625/1652 cm−1 (r = 0.9752) and applied pressure. The curve-fitted compositional changes in secondary structure of FBG also indicate that the composition of the α-helix structure (1657–1659 cm−1) was gradually reduced with the increase in compression pressure, but the composition of the β-sheet structure (1681, 1629, and 1609 cm−1) gradually increased. This indicates that pressure-induced conformational changes in FBG include not only transformations from α-helix to β-sheet structure, but also unfolding and denaturation of FBG and the formation of aggregates. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004

Background: The Stanford BCNU protocol (carmustine, etoposide and cyclophosphamide) is a high-dose conditioning regimen widely used prior to autologous stem cell transplantation. While acute renal failure requiring renal replacement therapy is a known but rare complication of autologous stem cell transplantation, acute nephrotoxicity following carmustine and etoposide has not yet been reported. Case: We present the first case of carmustine-induced acute kidney injury in the setting of autologous stem cell transplantation and perform a review of the literature. Renal failure was associated with a sharp rise in serum creatinine, oliguria and trace proteinuria. Urgent haemodialysis was required; however, renal failure resolved after 7 days. Con clusion: Although a rare complication, its severity mandates close monitoring of renal function as early recognition and treatment may limit long-term sequelae.

Background Telehealth services based on at-home monitoring of vital signs and the administration of clinical questionnaires are being increasingly used to manage chronic disease in the community, but few statistically robust studies are available in Australia to evaluate a wide range of health and socio-economic outcomes. The objectives of this study are to use robust statistical methods to research the impact of at home telemonitoring on health care outcomes, acceptability of telemonitoring to patients, carers and clinicians and to identify workplace cultural factors and capacity for organisational change management that will impact on large scale national deployment of telehealth services. Additionally, to develop advanced modelling and data analytics tools to risk stratify patients on a daily basis to automatically identify exacerbations of their chronic conditions. Methods/Design A clinical trial is proposed at five locations in five states and territories along the Eastern Seaboard of Australia. Each site will have 25 Test patients and 50 case matched control patients. All participants will be selected based on clinical criteria of at least two hospitalisations in the previous year or four or more admissions over the last five years for a range of one or more chronic conditions. Control patients are matched according to age, sex, major diagnosis and their Socio-Economic Indexes for Areas (SEIFA). The Trial Design is an Intervention control study based on the Before-After-Control-Impact (BACI) design. Discussion Our preliminary data indicates that most outcome variables before and after the intervention are not stationary, and accordingly we model this behaviour using linear mixed-effects (lme) models which can flexibly model within-group correlation often present in longitudinal data with repeated measures. We expect reduced incidence of unscheduled hospitalisation as well as improvement in the management of chronically ill patients, leading to better and more cost effective care. Advanced data analytics together with clinical decision support will allow telehealth to be deployed in very large numbers nationally without placing an excessive workload on the monitoring facility or the patient's own clinicians. Trial registration Registered with Australian New Zealand Clinical Trial Registry on 1st April 2013. Trial ID: ACTRN12613000635763

To explore the experiences of family physicians and pediatricians delivering immunizations, including perceived barriers and supports.Qualitative study using focus groups.Ten cities throughout British Columbia.A total of 46 family physicians or general practitioners, 10 pediatricians, and 2 residents.A semistructured dialogue guide was used by a trained facilitator to explore participants' experiences and views related to immunization delivery in British Columbia. Verbatim transcriptions were independently coded by 2 researchers. Key themes were analyzed and identified in an iterative manner using interpretive description.Physicians highly valued vaccine delivery. Factors facilitating physician-delivered immunizations included strong beliefs in the value of vaccines and having adequate information. Identified barriers included the large time commitment and insufficient communication about program changes, new vaccines, and the adult immunization program in general. Some physicians reported good relationships with local public health, while others reported the opposite experience, and this varied by geographic location.These findings suggest that physicians are supportive of delivering vaccines. However, there are opportunities to improve the sustainability of physician-delivered immunizations. While compensation schemes remain under the purview of the provincial governments, local public health authorities can address the information needs of physicians.

Evaluating telehealth programs is a challenging task, yet it is the most sensible first step when embarking on a telehealth study. How can we frame and report on telehealth studies? What are the health services elements to select based on the application needs? What are the appropriate terms to use to refer to such elements? Various frameworks have been proposed in the literature to answer these questions, and each framework is defined by a set of properties covering different aspects of telehealth systems. The most common properties include application, technology, and functionality. With the proliferation of telehealth, it is important not only to understand these properties, but also to define new properties to account for a wider range of context of use and evaluation outcomes. This article presents a comprehensive framework for delivery design, implementation, and evaluation of telehealth services. We first survey existing frameworks proposed in the literature and then present our proposed comprehensive multidimensional framework for telehealth. Six key dimensions of the proposed framework include health domains, health services, delivery technologies, communication infrastructure, environment setting, and socioeconomic analysis. We define a set of example properties for each dimension. We then demonstrate how we have used our framework to evaluate telehealth programs in rural and remote Australia. A few major international studies have been also mapped to demonstrate the feasibility of the framework. The key characteristics of the framework are as follows: (a) loosely coupled and hence easy to use, (b) provides a basis for describing a wide range of telehealth programs, and (c) extensible to future developments and needs.

Alopecia areata (AA) is a T-cell-mediated hair loss disorder but the exact cause is unknown. In this report we describe patterns of onset, regrowth and relapse in AA and propose potential underlying mechanisms. We believe that these aspects of AA require integration into modern theories of AA pathogenesis.