Vitiligo prevalence and quality of life among adults in Europe, Japan and the USA.

BACKGROUND: Vitiligo, an autoimmune disorder characterised by skin depigmentation, is associated with reduced quality of life (QoL). Vitiligo may be under-reported, in part because of misconceptions that it is a cosmetic disease. OBJECTIVES: This survey sought to characterise vitiligo prevalence and explore the relationship between sociodemographic and clinical characteristics with QoL in a population-based, multinational study. METHODS: Participants aged ≥18 years were recruited via an online panel in Europe, Japan and the USA to answer questions regarding skin disorders they may have experienced. Those reporting vitiligo (diagnosed or undiagnosed) or vitiligo signs (experiencing loss of skin colour but unaware of vitiligo and not diagnosed) were included in the analyses of vitiligo prevalence. Participants who self-reported physician-diagnosed vitiligo were given a broader survey to characterise disease progression, management and QoL (as measured with the Vitiligo-specific QoL [VitiQoL] instrument). RESULTS: The total estimated vitiligo prevalence among 35 694 survey participants (Europe, n = 18 785; USA, n = 8517; Japan, n = 8392) was 1.3% (diagnosed, 0.6%; undiagnosed, 0.4%; vitiligo signs, 0.3%). Among 219 patients formally diagnosed with vitiligo (Europe, n = 150; USA, n = 48; Japan, n = 21), total VitiQoL scores were associated with age (P = 0.00017), disease extent (P < 0.0001), disease progression (P < 0.0001), disease management (P < 0.0001) and time since diagnosis (P = 0.0015). Behaviour scores varied based on skin phototype (P = 0.024) and ethnicity (P = 0.048). Higher total VitiQoL scores were reported in patients with head lesions (P = 0.027) and those with head and hand and/or wrist lesions (P = 0.018). Substantial high concern (rated 8-10 on an 11-point Likert scale) for lesions was found across all body areas and varied with geographical region. CONCLUSIONS: The vitiligo prevalence rate may be higher than previously reported, with a substantial proportion attributed to people who have not received a formal diagnosis. Among formally diagnosed patients with vitiligo, QoL was most severely impacted by more progressive and higher extent of disease.

Modifiable factors related to life-space mobility in community-dwelling older adults: results from the Canadian Longitudinal Study on Aging.

BACKGROUND: The most common methods for measuring mobility in older adulthood include performance-based tests, such as the Timed-Up-and-Go and gait speed. While these measures have strong predictive validity for adverse outcomes, they are limited to assessing what older adults do in standardized settings, rather than what they do in their daily life. Life-space mobility, which is the ability to move within environments that expand from one's home to the greater community, has been proposed as a more comprehensive measure of mobility. The aim of this study was to determine the association between modifiable factors and life-space mobility in older adults enrolled in the Canadian Longitudinal Study on Aging (CLSA). METHODS: Life-space mobility was measured using the Life Space Index (LSI). Explanatory factors included physical, psychosocial and cognitive determinants, as well as pain, fatigue, driving status, nutrition, body mass index, smoking status, and vision. To estimate the association between the LSI and explanatory variables, univariate and multivariable ordinary least squares regression analyses were performed. RESULTS: All adults 65 years and older (n = 12,646) were included in the analysis. Fifty percent were women and the mean age was 73.0 (SD5.7). The mean LSI score was 80.5, indicating that, on average, the sample was able to move outside of their neighborhood independently. All explanatory variables were significantly associated with the LSI except for balance and memory. The top 3 variables that explained the most variation in the LSI were driving, social support and walking speed. CONCLUSION: To our knowledge, this was the first study to examine the association between life-space mobility and a comprehensive set of modifiable factors that were selected based on a theoretical framework and existing research evidence. This study had two important messages. First, driving, social support and walking speed emerged as the most significant correlates of life-space mobility in older adults. Second, life-space mobility is multifactorial and interventions that are pragmatic in their design and testing are needed that consider the complexity involved. A multi-disciplinary approach to examining life-space mobility in older adults is needed to optimize opportunities for healthy aging and develop strategies that support mobility in older adulthood.

International Initiative for Outcomes (INFO) for vitiligo: workshops with patients with vitiligo on repigmentation.

BACKGROUND: There is no cure or firm clinical recommendations for the treatment of vitiligo. One of the main issues is the heterogeneity of outcome measures used in randomized controlled trials for vitiligo. OBJECTIVES: To define successful repigmentation from the patients' point of view and to propose how and when repigmentation should be evaluated in clinical trials in vitiligo. METHODS: We conducted three workshops with patients with vitiligo and their parents or caregivers. Workshop 1 was held at World Vitiligo Day (Detroit, MI), workshop 2 at the University of Texas Southwestern Medical Center and workshop 3 at the Vitiligo and Pigmentation Institute of Southern California, University of California. RESULTS: Seventy-three participants were recruited. Consensus on the following questions was achieved unanimously: (i) the definition of 'successful repigmentation' was 80-100% of repigmentation of a target lesion and (ii) both an objective and a subjective scale to measure repigmentation should be used. CONCLUSIONS: This was the largest patients' outcomes workshop. We followed the guidance from the CSG-COUSIN and the Vitiligo Global Issues Consensus Group. Our recommendations to use percentage of repigmentation quartiles (0-25%, 26-50%, 51-79%, 80-100%) and the Vitiligo Noticeability Scale are based on the best available current evidence. A limitation of the research is that the workshops were conducted only in the U.S.A., due to pre-existing organisational support and the availability of funding.

COL1A1 C-propeptide cleavage site mutation causes high bone mass, bone fragility and jaw lesions: a new cause of gnathodiaphyseal dysplasia?

Gnathodiaphyseal dysplasia (GDD) is a rare autosomal dominant condition characterized by bone fragility, irregular bone mineral density (BMD) and fibro-osseous lesions in the skull and jaw. Mutations in Anoctamin-5 (ANO5) have been identified in some cases. We aimed to identify the causative mutation in a family with features of GDD but no mutation in ANO5, using whole exome capture and massive parallel sequencing (WES). WES of two affected individuals (a mother and son) and the mother's unaffected parents identified a mutation in the C-propeptide cleavage site of COL1A1. Similar mutations have been reported in individuals with osteogenesis imperfecta (OI) and paradoxically increased BMD. C-propeptide cleavage site mutations in COL1A1 may not only cause 'high bone mass OI', but also the clinical features of GDD, specifically irregular sclerotic BMD and fibro-osseous lesions in the skull and jaw. GDD patients negative for ANO5 mutations should be assessed for mutations in type I collagen C-propeptide cleavage sites.

Whole exome sequencing is an efficient, sensitive and specific method for determining the genetic cause of short-rib thoracic dystrophies.

Short-rib thoracic dystrophies (SRTDs) are congenital disorders due to defects in primary cilium function. SRTDs are recessively inherited with mutations identified in 14 genes to date (comprising 398 exons). Conventional mutation detection (usually by iterative Sanger sequencing) is inefficient and expensive, and often not undertaken. Whole exome massive parallel sequencing has been used to identify new genes for SRTD (WDR34, WDR60 and IFT172); however, the clinical utility of whole exome sequencing (WES) has not been established. WES was performed in 11 individuals with SRTDs. Compound heterozygous or homozygous mutations were identified in six confirmed SRTD genes in 10 individuals (IFT172, DYNC2H1, TTC21B, WDR60, WDR34 and NEK1), giving overall sensitivity of 90.9%. WES data from 993 unaffected individuals sequenced using similar technology showed two individuals with rare (minor allele frequency <0.005) compound heterozygous variants of unknown significance in SRTD genes (specificity >99%). Costs for consumables, laboratory processing and bioinformatic analysis were

Utilization of motor imagery in upper limb rehabilitation: a systematic scoping review.

OBJECTIVE: To determine how motor imagery is being delivered in upper limb rehabilitation to guide practice and research. DATA SOURCE: MEDLINE, PubMed, CINAHL, EMBASE, PsychINFO databases were searched from 1987 to November 2014 STUDY SELECTION: English, adults, any clinical population or diagnosis, intervention for upper limb with an outcome measure used. All types of studies were included. Two authors independently selected studies for review using consensus. DATA EXTRACTION: Seven motor imagery elements were extracted using a model implemented in sport research: PETTLEP model (Physical, Environment, Task, Timing, Learning, Emotion, and Perspective). RESULTS: The search yielded 1107 articles with 1059 excluded leaving 48 articles for full review. A total of 38 articles involved individuals with stroke, five articles involved individuals with complex regional pain syndrome, and five articles for other conditions. Motor imagery elements most commonly described were physical, environment, task, and perspective. Elements less commonly described were timing, learning, and emotional aspects. There were significant differences between study populations (e.g. stroke and complex regional pain syndrome) and within populations on how motor imagery was delivered. CONCLUSION: Many of the imagery elements reviewed are not being considered or reported on in the selected studies. How motor imagery is being delivered within and between populations is inconsistent, which may lead to difficulties in determining key elements of effectiveness.

Utility of temporal artery biopsy samples for genome-wide analysis of giant cell arteritis.

Giant Cell Arteritis (GCA) is the most common vasculitis affecting the elderly. Archived formalin-fixed paraffin-embedded (FFPE) temporal artery biopsy (TAB) specimens potentially represent a valuable resource for large-scale genetic analysis of this disease. FFPE TAB samples were obtained from 12 patients with GCA. Extracted TAB DNA was assessed by real time PCR before restoration using the Illumina HD FFPE Restore Kit. Paired FFPE-blood samples were genotyped on the Illumina OmniExpress FFPE microarray. The FFPE samples that passed stringent quality control measures had a mean genotyping success of >97%. When compared with their matching peripheral blood DNA, the mean discordant heterozygote and homozygote single nucleotide polymorphisms calls were 0.0028 and 0.0003, respectively, which is within the accepted tolerance of reproducibility. This work demonstrates that it is possible to successfully obtain high-quality microarray-based genotypes FFPE TAB samples and that this data is similar to that obtained from peripheral blood.

Review of enteric outbreaks in prisons: effective infection control interventions.

OBJECTIVES: To identify documented outbreaks, worldwide, of enteric illness in correctional facilities over the last 10 years to understand the epidemiology of the outbreaks and explicitly identify effective infection control measures. STUDY DESIGN: Review of literature and outbreak investigation reports. METHODS: Computer-aided searches of literature databases and systematic searches of government websites were completed to identify relevant outbreak reports. Reference lists were hand-searched to validate the electronic search methodology. Reports identified through personal communications with public health officials were also included. RESULTS: Of the 72 outbreaks meeting the inclusion criteria, 76% and 21% were associated with bacterial agents and viral agents, respectively. The majority of outbreaks were associated with Salmonella (n=20), Clostridium perfringens (n=14), norovirus (n=14), pathogenic Escherichia coli (n=10) and Campylobacter spp. (n=5). Transmission was primarily foodborne (67%). During an outbreak, the most common control measures included limiting movements of ill inmates and staff, and their exclusion from kitchen duty. The most common retrospectively reported preventative recommendations included monitoring food temperatures and effective infection control procedures. CONCLUSIONS: It is essential to monitor food temperatures to prevent enteric outbreaks in prisons. Training in safe food handling should be offered to inmates who work in the kitchen. Enteric outbreaks are best controlled by effective infection control practices, while active surveillance and early diagnosis may prevent further spread of illness.

Mummy of the "Elder Lady" in the tomb of Amenhotep II: Egyptian museum catalog number 61070.

An unidentified female mummy found in a cache of great kings and queens in 1898 in the Valley of the Kings was examined from the viewpoint of Egyptology, x-ray cephalometry, biostatistics, and biochemistry. The result was the identification of Queen Tiye, of the Eighteenth Dynasty, wife of Amenhotep III and mother of Akhenaton.

Treatment of degloving injuries with autogenous full thickness mesh scrotal free grafts.

In this report, we evaluated the effectiveness of scrotal tissue as an autogenous free skin graft to treat cutaneous degloving injuries of the distal limb in dogs. Surgery was performed on two male intact dogs with distal extremity degloving wounds. Dog #1 had a tarsal degloving wound with exposure of the distal tibial and tarsal bones. Dog #2 had a degloving injury over the metacarpals. Wounds were treated with daily wet-to-dry bandages in order to develop a healthy bed of granulation tissue at the graft recipient site. Scrotal ablation castration was performed once the recipient site had been prepared. Subcutaneous and adipose tissue were excised from the scrotal graft and mesh slits were created. The graft was applied to the recipient site with monofilament absorbable simple interrupted sutures. Bandaging was performed postoperatively, and bandage changes occurred four, seven, nine and 11 days postoperatively. Follow-up was performed at 30 days. In dog #1, the tarsal degloving injury graft had first intention healing with 100% graft take on day 11. In dog #2, the metacarpal degloving injury graft had 90% graft take on day nine, with second intention healing adjacent to the fifth digit pad. The scrotum is often discarded at the time of scrotal ablation castration. Distal extremity wounds can be successfully treated with free skin grafts. In male dogs, the scrotum is a viable option as a full thickness mesh free graft for distal extremity reconstructive surgery.

Cigarette smoking among successive birth cohorts of men and women in the United States during 1900-80.

Trends in cigarette smoking among successive cohorts of men and women were reconstructed from smoking histories of respondents to the 1978-80 Health Interview Surveys. Estimated smoking rates among the older cohorts were then adjusted for the differential mortality of cigarette smokers and nonsmokers. By 1920, over half of the young male population smoked cigarettes. Not until 1950 did more than a third of the young female population smoke cigarettes. The proportion of men who ever smoked cigarettes progressively declined with each successive cohort born after 1920. By contrast, the proportion of women who ever smoked declined only among cohorts born after 1940. Cessation of cigarette smoking from age 30 years onward was observed for all cohorts of men. Cessation rates accelerated for men who reached age 30 after 1960. By contrast, smoking cessation from age 30 was observed only for women who reached age 30 after 1950. Cessation rates accelerated only for women who reached age 30 after 1970. For each cohort, recent smoking cessation rates for men have exceeded those for women. Maximum exposure to cigarette smoking probably occurred among men who are now in their seventh and eighth decades. By contrast, peak exposure to smoking probably occurred among women who are now only in their fifth and sixth decades.

Relationship of leukocyte numbers, immunoregulatory cell function, and phytohemagglutinin responsiveness in cancer patients.

Leukocytes were quantitated in peripheral blood from 35 solid-tumor cancer patients and related to levels of phytohemagglutinin (PHA)-induced DNA synthesis. Levels of glass-adherent, indomethacin-sensitive, or 24-hour preculture-sensitive immunoregulatory activity were evaluated in PHA-stimulated peripheral blood mononuclear cells (PBMC). Cancer patients and patients with depressed PHA responses had significantly greater monocyte percentages in their PBMC than did healthy subjects; patients with normal PHA responses did not. Patients with disseminated disease had significantly greater monocyte percentages and depressed T-cell percentages than did controls; patients with at most minimum residual disease did not. When monocyte and lymphocyte percentages were correlated by linear regression analysis to PHA responsiveness, no significant correlation was found. A highly significant negative correlation was noted between PHA responsiveness and levels of immunoregulatory cell function. Abnormal immunoregulatory function, apart from alterations in peripheral blood leukocyte percentages and numbers contributes to impaired T-cell function in cancer patients.

Quantitation of lymphocytes and T-cell subsets in patients with disseminated cancer.

Human peripheral blood T-cells were divided into subsets on the basis of their ability to bind to the Fc receptor portion of IgG (TG cells) or IgM (TM cells). These subsets were studied in 25 patients with newly diagnosed disseminated malignant solid tumors. When compared to a group of healthy, age-matched controls, cancer patients as a group exhibited signifcantly increased percentages of TG cells and significantly decreased percentages and numbers of TM cells. Comparison of the values determined for individual patients to those determined for groups of 10 healthy individuals in the same decade of life revealed that most cancer patients had normal levels of lymphocytes and T-cells, but many had aberrant values for T-cell subsets.

TG cell involvement in the leukocyte adherence inhibition phenomenon.

Peripheral blood mononuclear cells (PBMC), T-cells, non-T-cells, TG cells, and TM cells were tested for leukocyte adherence inhibition (LAI) reactivity to purified protein derivative (PPD) in normal human volunteers to determine the reactive cell subfractions. T-cells were separated by sheep red blood cell rosetting and TM and TG cells by rosetting with anti-ox red blood cell (ORBC) IgM- and IgG-treated ORBC. Fresh PBMC, T-cells, and TG cells gave positive LAI reactivity to PPD in PPD-positive donors only. PBMC that had undergone 24-hour incubation or extensive washing, non-T-cells, and TM cells were unreactive. All cell subfractions were negative in PPD-negative donors. Indirect LAI assay was performed on the spent media from overnight incubation of unstimulated PBMC and also following a 1-hour incubation of the various cell subfractions obtained from a PPD-reactive donor with PPD. Positive reactions, indicating the release of an LAI factor (LAIF), were obtained with the spent media and with the T-cell and TG cell subfractions following PPD stimulation, whereas non-T-cell and TM cell subfractions yielded no reactivity. Incubation of sensitized T-cells with PPD in the presence of cycloheximide and preincubation of T-cells for 24 hours with cycloheximide before PPD exposure failed to inhibit LAI reactivity. These data suggest that T-cells, specifically TG cells, can release LAIF upon specific antigen stimulation with PPD, whereas non-T-cell and TM cell subpopulations fail to respond to the same stimulus. LAIF may also be released into the culture media with prolonged (overnight) incubation in artificial media or with extensive washing. Inhibition of protein synthesis during antigen exposure or up to 24 hours before antigen exposure does not appear to inhibit LAI reactivity.

Inhibition of U937 eicosanoid and DNA synthesis by 5,8,11,14-eicosatetraynoic acid, an inhibitor of arachidonic acid metabolism and its partial reversal by leukotriene C4.

When replicating U937 cells were incubated with up to 80 microM concentrations of the in vitro inhibitor of eicosanoid biosynthesis, 5,8,11,14-eicosatetraynoic acid (ETYA), DNA synthesis measured by labeling with [3H]thymidine was inhibited in a concentration-dependent manner. No reduction in cellular viability occurred, as judged by exclusion of trypan blue, unaltered release of 51Cr-labeled proteins, and the reversibility of inhibition after incubation for 72 h with ETYA. Neither indomethacin nor acetylsalicylic acid, inhibitors of cyclooxygenase, altered DNA synthesis in control or ETYA-inhibited cells, excluding participation of the products of this enzyme in the inhibition of DNA synthesis. Incubation of inhibited cells with extracts prepared from log-phase media partially reversed the inhibition of DNA synthesis. Addition of leukotriene B4 or D4 at 10(-7) to 10(-8) M did not reverse ETYA-induced inhibition of DNA synthesis, nor did the addition of a series of long chain fatty acids, including arachidonic acid. However, leukotriene C4 at 10(-7) M partially reversed the inhibition of DNA synthesis. Extracts of media from log-phase cells were shown by high-pressure liquid chromatography to contain leukotriene C4, and synthesis of this compound was inhibited by ETYA, as judged by measurement of UV absorbance and radioactivity. Additional inhibitors of eicosanoid metabolism including nordihydroguaiaretic acid and esculetin also suppressed DNA synthesis in U937, K562, and prostate PC3 cells, without altered cellular viability; the effect is not limited to lymphohematopoietic cells or to a single inhibitor of arachidonic acid metabolism. Suppression of U937 DNA and eicosanoid synthesis by ETYA and the partial reversal of DNA synthesis by leukotriene C4 suggest that in these cells eicosanoids may modulate DNA synthesis. Other possible consequences of incubating cells with ETYA including creation of arachidonic acid-deficient membranes, and even incorporation of the agent into membrane phospholipids, may also contribute to the reversible inhibition of DNA synthesis.

A randomized study of low and high doses of leukocyte alpha-interferon in metastatic renal cell carcinoma: the American Cancer Society collaborative trial.

A prospective randomized trial of low versus high doses of human leukocyte alpha-interferon (1 X 10(6) units/day for 28 days versus 10 X 10(6) units/day for 28 days) was carried out in 30 patients with metastatic renal cell carcinoma, to test the tolerance and relative antitumor effects of these interferon doses. Both doses were tolerated well, and responses to the human leukocyte alpha-interferon were observed overall in seven individuals, including complete, partial, and minimal tumor regressions. Six of the seven responses occurred in patients who received the high dosage, and three of these responses were major responses. While not statistically significant, this result suggested a dose-response relationship. One minimal response was observed in a patient treated at low dosage. Nine individuals who were stable after 1 month of therapy at low dosage were randomized to a further month of therapy at low or high dosage, during which one of four at high dosage had a partial response, and none of five at low dosage manifested response. Regression of pulmonary disease in one individual was delayed, occurring 3 months after therapy at the high dose and enduring for a period of 28 months. Major objective responses in other patients were of 4 and 15 months duration. Human leukocyte alpha-interferon is an active agent in renal cell carcinoma at the dosage of 10 million units daily. No relationship of toxicity to response was evident in this trial. Optimum dosage and duration of treatment have yet to be established.

Sensitivity of tumoricidal function in macrophages from different anatomical sites of cancer patients to modulation of arachidonic acid metabolism.

The sensitivity of cancer patient macrophages from different anatomical sites to arachidonic acid metabolism was investigated in tumor cell cytotoxicity assays. Alveolar macrophages and peripheral blood monocytes from 13 non-small cell lung cancer patients, peritoneal macrophages and peripheral blood monocytes from 13 ovarian cancer patients, and comparable macrophages from control patients with nonmalignant lung or gynecological diseases were tested. Inhibitors of either the cyclooxygenase pathway or the lipoxygenase pathway together with specific metabolites of each pathway were used to evaluate how these different macrophage populations are regulated by eicosanoids. In addition, metabolic studies were performed to compare directly the arachidonic acid metabolism of macrophages obtained from these different anatomical locations. The results demonstrate that the peripheral blood monocytes from lung cancer and ovarian cancer patients and the peritoneal macrophages from ovarian cancer patients are sensitive to cyclooxygenase inhibition; this was not seen with comparable macrophages from the relevant control patients. Sensitivity to modulation by cyclooxygenase inhibition correlated with increased cyclooxygenase metabolism and with the capacity of prostaglandin to mediate suppression of tumoricidal function in these populations of cancer patient macrophages. In contrast, alveolar macrophages from cancer patients were not sensitive to either cyclooxygenase inhibition or to prostaglandin-mediated suppression. No such differential influences were revealed for the lipoxygenase pathway of arachidonic acid metabolism in any macrophage population tested. Thus, eicosanoids, particularly those of the cyclooxygenase pathway, can be a critical immunoregulatory feature of certain tumor microenvironments.

Labelling of lipids and phospholipids with [3H]arachidonic acid and the biosynthesis of eicosanoids in U937 cells differentiated by phorbol ester.

Phorbol esters induce morphologic and biochemical differentiation in U937 cells, a monocyte/macrophage-like line derived from a human histiocytic lymphoma. We are interested in the phorbol ester-stimulated release of arachidonic acid from cellular membranes and the subsequent synthesis of eicosanoids, as it may prove to correlate with the induced cellular differentiation. Undifferentiated log-phase U937 cells released little recently incorporated [3H]arachidonic acid, but phorbol 12-myristate 13-acetate increased its apparent rate of release to that of cells differentiated by exposure to phorbol myristate acetate for 3 days. Exposure of washed differentiated cells immediately prelabelled with [3H]arachidonic acid to additional phorbol myristate acetate did not augment the release of [3H]arachidonic acid. The basal release of nonradioactive fatty acids from differentiated cells was 5-10 times that of undifferentiated cells, and phorbol myristate acetate increased their release from both types of cell 2- to 3-fold. Differentiated cells immediately prelabelled with [3H]arachidonic acid exhibited greater incorporation into phosphatidylinositol and phosphatidylcholine, and contained more radioactive free arachidonic acid, compared with undifferentiated cells. Undifferentiated cells contained more radioactivity in phosphatidylserine, phosphatidylethanolamine and neutral lipids. Phorbol myristate acetate caused differentiated cells to release [3H]arachidonic acid from phosphatidylinositol, phosphatidylserine, phosphatidylcholine and phosphatidylethanolamine, but release from neutral lipids was reduced, and the content of [3H]arachidonic acid increased. In undifferentiated cells incubated with phorbol myristate acetate, radioactivity associated with phosphatidylserine, phosphatidylethanolamine and neutral lipid was reduced and [3H]arachidonic acid was unchanged. Synthesis of cyclooxygenase products exceeded that of lipoxygenase products in both differentiated and undifferentiated cells. Phorbol myristate acetate increased the synthesis of both types of product, cyclooxygenase-dependent more than lipoxygenase-dependent, especially in differentiated cells. The biological significance of these changes in lipid metabolism that accompany phorbol myristate acetate-induced differentiation are yet to be established.