Apoptosis may underlie the pathology of zinc-deficient skin

The trace element zinc is essential for the survival and function of all cells. Zinc deficiency, whether nutritional or genetic, is fatal if left untreated. The effects of zinc deficiency are particularly obvious in the skin, seen as an erythematous rash, scaly plaques, and ulcers. Electron microscopy reveals degenerative changes within keratinocytes. Despite the well-documented association between zinc deficiency and skin pathology, it is not clear which cellular processes are most sensitive to zinc deficiency and could account for the typical pathological features. We used the cultured HaCaT keratinocyte line to obtain insight into the cellular effects of zinc deficiency, as these cells show many characteristics of normal skin keratinocytes. Zinc deficiency was induced by growing cells in the presence of the zinc chelator, TPEN, or by growth in zinc-deficient medium. Growth of cells in zinc-deficient medium resulted in a 44% reduction of intracellular zinc levels and a 75% reduction in the activity of the zinc-dependent enzyme, 5'-nucleotidase, relative to the control cells. Over a period of 7 days of exposure to zinc-deficient conditions, no changes in cell viability and growth, or in the cytoskeletal and cell adhesion systems, were found in HaCaT cells. At 7 days, however, induction of apoptosis was indicated by the presence of DNA fragmentation and expression of active caspase-3 in cells. These results demonstrate that apoptosis is the earliest detectable cellular change induced by zinc deficiency in HaCaT keratinocytes. Our observations account for many of the features of zinc deficiency, including the presence of degenerate nuclei, chromatin aggregates and abnormal organization of keratin, that may represent the later stages of apoptosis. In summary, a major causal role for apoptosis in the pathology of zinc deficiency in the skin is proposed. This role is consistent with the previously unexplained diverse range of degenerative cellular changes seen at the ultrastructural level in zinc-deficient keratinocytes.

Habit retraining for the management of urinary incontinence in adults (review)

Background
Habit retraining is toileting assistance given by a caregiver to adults with urinary incontinence. It involves the identification of an incontinent person's natural voiding pattern and the development of an individualised toileting schedule which pre-empts involuntary bladder emptying.

Objectives
To assess the effects of habit retraining for the management of urinary incontinence in adults.

Search strategy
We searched the Cochrane Incontinence Group specialised register (9 May 2002), MEDLINE (January 1966 to February 2004), EMBASE (January 1980 to Week 18-2002), CINAHL (January 1982 to February 2001), PsychINFO (January 1972 to August 2002), Biological Abstracts (January 1980 to December 2000), Current Contents (January 1993 to December 2001) and the reference lists of relevant articles. We also contacted experts in the field, searched relevant websites and hand searched journals and conference
proceedings.

Selection criteria
All randomised or quasi-randomised controlled trials comparing habit retraining delivered either alone or in conjunction with another intervention for urinary incontinence in adults.

Data collection and analysis
Data extraction and quality assessment were undertaken by at least two people working independendy of each other. Any differences were resolved by discussion. The relative risks for dichotomous data were calculated with 95% confidence intervals. Where data were insufficient for a quantitative analysis, a narrative overview was undertaken.

Main results
Three trials with a total of 337 participants met the inclusion criteria, describing habit retraining combined with other approaches compared with usual care. Participants were primarily care-dependent elderly women with concurrent cognitive and/or physical impairment, residing in either a residential aged-care facility or in their own home. Outcomes included incidence and/or severity of urinary incontinence, the prevalences of urinary tract infection, skin rash and skin breakdown, cost and caregiver preparedness, role strain and burden. Caregivers found it difficult to maintain voiding records and to implement the toileting program. A 61% compliance rate was reported in one trial .

There were no statistically significant differences in the incidence and in the volume of incontinence between groups. Within group analyses did however show improvements on these measures. Reductions were also reported for the intervention group in one study for skin rash, skin breakdown and in caregivers' perceptions of their level of stress. Descriptive data on the. intervention suggests that habit retraining is a labour-intense activity. Electronic loggers, used as an adjunct to caregiver-delivered wet/dry checks, were reported as providing more accurate data than that from caregiver conducted wet/dry checks. To date, no analysis of the time and resources associated with these comparisons is available.

Reviewers' conclusions
Data on habit retraining are few and of insufficient quality to provide a firm basis for practice.

Clinical effectiveness of barrier preparations in the prevention and treatment of nappy dermatitis in infants and preschool children of nappy age

Nappy dermatitis is a broad term used to describe an acute inflammatory reaction of the skin in the nappy area because of irritation from urine, faeces, moisture or friction. The prevalence is estimated to be between 7% and 35% in infants. Regular application of a barrier preparation at every nappy change may be a valuable component of nappy dermatitis prevention and/or treatment.

Alcohol expectancies and drinking refusal self-efficacy mediate the association of impulsivity with alcohol misuse

Background: Recent work suggests that 2 biologically based traits convey risk for alcohol misuse: reward sensitivity ⁄ drive and (rash) impulsiveness. However, the cognitive mechanisms through which these traits convey risk are unclear. This study tested a model predicting that the risk conveyed by reward sensitivity is mediated by a learning bias for the reinforcing outcomes of alcohol consumption (i.e., positive alcohol expectancy). The model also proposed that the risk conveyed by rash impulsiveness (RI) is mediated by drinkers’ perceived ability to resist alcohol (i.e., drinking refusal self-efficacy).
Methods: Study 1 tested the model in a sample of young adults (n = 342). Study 2 tested the model in a sample of treatment-seeking substance abusers (n = 121). All participants completed a battery of personality, cognitive, and alcohol use questionnaires and models were tested using structural equation modeling.
Results: In both studies, the hypothesized model was found to provide a good fit to the data, and a better fit than alternative models. In both young adults and treatment-seeking individuals, positive alcohol expectancy fully mediated the association between reward sensitivity and hazardous alcohol use. For treatment seekers, drinking refusal self-efficacy fully mediated the association between RI and hazardous drinking. However, there was partial mediation in the young adult sample. Furthermore, neither trait was directly associated with the other cognitive mediator.
Conclusions: The hypothesized model was confirmed on a large sample of young adults and replicated on a sample of treatment-seeking substance abusers. Taken together, these findings shed further light on the mechanisms through which an impulsive temperament may convey risk for alcohol misuse.

Risk-taking in young people: the role of impulsivity

This study investigated rash impulsivity, reward sensitivity and a range of adolescent risk-taking behaviours using both self-report and behavioural measures of each of these variables. It found that (a) rash impulsivity and reward sensitivity were related dimensions of the impulsivity construct, (b) self-report and behavioural measures were not correlated even when theoretically assessing the same dimension of impulsivity, and (c) of all the risk-taking behaviours examined, rash impulsivity and reward sensitivity were significantly correlated with riding without a seatbelt.

Isolation of a novel Orientia species (O. chuto sp. nov.) from a patient infected in Dubai

In July 2006, an Australian tourist returning from Dubai, in the United Arab Emirates (UAE), developed acute scrub typhus. Her signs and symptoms included fever, myalgia, headache, rash, and eschar. Orientia tsutsugamushi serology demonstrated a 4-fold rise in antibody titers in paired serum collections (1:512 to 1:8,192), with the sera reacting strongest against the Gilliam strain antigen. An Orientia species was isolated by the in vitro culture of the patient's acute blood taken prior to antibiotic treatment. The gene sequencing of the 16S rRNA gene (rrs), partial 56-kDa gene, and the full open reading frame 47-kDa gene was performed, and comparisons of this new Orientia sp. isolate to previously characterized strains demonstrated significant sequence diversity. The closest homology to the rrs sequence of the new Orientia sp. isolate was with three strains of O. tsutsugamushi (Ikeda, Kato, and Karp), with a nucleotide sequence similarity of 98.5%. The closest homology to the 47-kDa gene sequence was with O. tsutsugamushi strain Gilliam, with a nucleotide similarity of 82.3%, while the closest homology to the 56-kDa gene sequence was with O. tsutsugamushi strain TA686, with a nucleotide similarity of 53.1%. The molecular divergence and geographically unique origin lead us to believe that this organism should be considered a novel species. Therefore, we have proposed the name “Orientia chuto,” and the prototype strain of this species is strain Dubai, named after the location in which the patient was infected.

Successful outcomes with oral fluoroquinolones combined with rifampicin in the treatment of Mycobacterium ulcerans : an observational cohort study

Background: The World Health Organization currently recommends combined streptomycin and rifampicin antibiotic treatment as first-line therapy for Mycobacterium ulcerans infections. Alternatives are needed when these are not tolerated or accepted by patients, contraindicated, or neither accessible nor affordable. Despite in vitro effectiveness, clinical evidence for fluoroquinolone antibiotic use against Mycobacterium ulcerans is lacking. We describe outcomes and tolerability of
fluoroquinolone-containing antibiotic regimens for Mycobacterium ulcerans in south-eastern Australia.

Methodology/Principal Findings: Analysis was performed of prospectively collected data including all primary Mycobacterium ulcerans infections treated at Barwon Health between 1998 and 2010. Medical treatment involved antibiotic use for more than 7 days; surgical treatment involved surgical excision of a lesion. Treatment success was defined as complete lesion healing without recurrence at 12 months follow-up. A complication was defined as an adverse event attributed to an antibiotic that required its cessation. A total of 133 patients with 137 lesions were studied. Median age was
62 years (range 3–94 years). 47 (34%) had surgical treatment alone, and 90 (66%) had combined surgical and medical treatment. Rifampicin and ciprofloxacin comprised 61% and rifampicin and clarithromycin 23% of first-line antibiotic
regimens. 13/47 (30%) treated with surgery alone failed treatment compared to 0/90 (0%) of those treated with combination medical and surgical treatment (p,0.0001). There was no difference in treatment success rate for antibiotic combinations containing a fluoroquinolone (61/61 cases; 100%) compared with those not containing a fluoroquinolone (29/29 cases; 100%). Complication rates were similar between ciprofloxacin and rifampicin (31%) and rifampicin and clarithromycin (33%) regimens (OR 0.89, 95% CI 0.27–2.99). Paradoxical reactions during treatment were observed in 8 (9%) of antibiotic treated cases.

Conclusions: Antibiotics combined with surgery may significantly increase treatment success for Mycobacterium ulcerans infections, and fluoroquinolone combined with rifampicin-containing antibiotic regimens can provide an effective and safe oral treatment option.

When social anxiety co-occurs with substance use: does an impulsive social anxiety subtype explain this unexpected relationship?

Although most conceptualizations of social anxiety emphasise that socially anxious individuals are overtly shy, and utilise avoidant behavioural strategies (e.g., risk-aversion, passivity, and submissiveness), there is tentative support for the existence of an approach-motivated subtype, characterised by risk taking and a greater propensity for substance misuse. It is likely that this subtype may help explain the reported co-occurrence of substance misuse and social anxiety. The current study sought to test via latent class analysis whether an approach-motivated social anxiety subtype could be identified within a community sample. A self-report questionnaire was completed by 351 participants (age: 18-74 years). Two distinct social anxiety subgroups were identified: one characterised by prototypical SAD symptomatology (i.e., behavioural inhibition and risk-avoidance), the second by elevated levels of rash impulsiveness, reward sensitivity, risk-taking and co-occurring substance use problems. The current findings provides support for the existence of a distinct approach-motivated social anxiety subtype and indicates that impulsivity may be critical to understanding the comorbid substance use symptomatology of these individuals.