Flipping the Switch: Reverse-Demand Voltage-Sensitive Fluorophores.

Fluorescence microscopy with fluorescent reporters that respond to environmental cues is a powerful method for interrogating biochemistry and biophysics in living systems. Photoinduced electron transfer (PeT) is commonly used as a trigger to modulate fluorescence in response to changes in the biological environment. PeT-based indicators rely on PeT either into the excited state (acceptor PeT) or out of the excited state (donor PeT). Our group has been developing voltage-sensitive fluorophores (VF dyes) that respond to changes in biological membrane potential (Vm). We hypothesize that the mechanism of voltage sensitivity arises from acceptor PeT (a-PeT) from an electron-rich aniline-containing molecular wire into the excited-state fluorophore, resulting in decreased fluorescence at negative Vm. In this work, we reversed the direction of electron flow to access donor-excited PeT (d-PeT) VF dyes by introducing electron-withdrawing rather than electron-rich molecular wires. VF dyes containing electron-withdrawing groups show voltage-sensitive fluorescence, but with the opposite polarity: hyperpolarizing Vm now gives fluorescence increases. We used a combination of computation and experiment to design and synthesize five d-PeT VF targets, two of which are voltage-sensitive.

Hydrocolloid dressing in pediatric burns may decrease operative intervention rates.

INTRODUCTION: Partial-thickness scalds are the most common pediatric burn injury, and primary management consists of wound dressings to optimize the environment for reepithelialization. Operative intervention is reserved for burns that fail to heal using conservative methods. Worldwide, paraffin-based gauze (Jelonet) is the most common burn dressing; but literature suggests that it adheres to wounds and requires more frequent dressing change that may traumatize newly epithelialized surfaces. Hydrocolloid dressings (DuoDERM) provide an occlusive moist environment to optimize healing and are associated with less frequent dressing changes. AIM: The aim of the study was to retrospectively analyze pediatric burns in a single tertiary referral center over a 10-year period comparing the impact of Jelonet and DuoDERM dressings relative to operative intervention rates. METHODS: All pediatric burns admitted between 1997 and 2007 were identified using the Hospital Inpatient Enquiry system. Demographics were collected from hospital records and theater logbooks. Acute, partial-thickness burns in patients younger than 15 years were analyzed according to dressing type applied (Jelonet or DuoDERM). RESULTS: Two hundred forty-eight pediatric burns were analyzed between 1997 and 2007. One hundred thirty-nine patients were treated with Jelonet dressings, and 109 were treated with DuoDERM. Debridement and grafting were required in 60 (43%) of the Jelonet patients compared with 10 (9%) of the DuoDERM patients (P < .05). The DuoDERM-managed patients maintained a significantly lower graft rate on subanalysis of scalds excluding early grafting within 5 days (P < .001). CONCLUSION: Observational evidence suggests that DuoDERM leads to less operative intervention and should be preferentially used in pediatric burns.

Illness representations in patients with hand injury.

PURPOSE: Differences in illness perception about hand injury may partly explain the variation in health behaviours such as adherence to post-operative therapy, coping strategy, emotional response and eventual clinical outcome. This study examined the illness perception of patients with hand injuries in the acute trauma setting. METHODS: The disability and severity of injury were assessed using the Disability of the Arm, Shoulder and Hand (DASH) questionnaire and the Hand Injury Severity Score (HISS). The revised Illness Perception Questionnaire (IPQ-R) was used to explore patients' illness beliefs and perception on hand injury. RESULTS: Fifty seven patients were recruited over the 2 month period. The IPQ-R showed good internal reliability (Cronbach's alpha, 0.68-0.86). There was no correlation between the DASH or HISS scores and the various components of the IPQ-R scores, suggesting that illness perceptions were not influenced by the recent trauma experience. Patients with dominant hand injuries and females reported significantly higher subjective disability. Younger patients believed their injury would last for a limited duration but reported a significantly higher number of related symptoms. Overall, the cohort was optimistic about their treatment and duration of recovery (high treatment control score and low time line score). Beliefs of negative consequences, chronic/cyclical duration and low illness coherence were linked with negative emotional response. High illness identity was associated with perception of pessimistic outcome (high consequences score) and negative emotional response. CONCLUSIONS: The lack of correlations suggests that illness perceptions of patients do not necessarily relate to the recent trauma experience or the severity of their hand injury. Patients in this cohort were optimistic about treatment and their recovery. There was some evidence to suggest that patients with severe injury were over-optimistic about recovery. These findings suggest that there could be a role for psychological intervention in hand injury.

The human POLH gene is not mutated, and is expressed in a cohort of patients with basal or squamous cell carcinoma of the skin.

Skin cancer, the most common cancer in the general population, is strongly associated with exposure to the ultraviolet component of sunlight. To investigate the relationship between DNA damage processing and skin tumour development, we determined the POLH status of a cohort of skin cancer patients. The human POLH gene encodes DNA polymerase eta (poleta), which normally carries out accurate translesion synthesis past the major UV-induced photoproduct, the dithymine cyclobutane dimer. In the absence of active poleta in xeroderma pigmentosum variant (XPV) patients, mutations accumulate at sites of UV-induced DNA damage, providing the initiating step in skin carcinogenesis. Forty patients diagnosed with skin cancer were genotyped for polymorphisms in the POLH protein-coding sequence, using glycosylase-mediated polymorphism detection (GMPD) and direct DNA sequencing of POLH PCR products derived from white blood cell genomic DNA. All individuals carried the wild-type POLH sequence. No POLH mutations were identified in genomic DNA from skin tumours derived from 15 of these patients. As determined by RT-PCR, POLH mRNA was expressed in all normal and skin tumour tissue examined. Poleta protein was also detectable by Western blotting, in two matched normal and skin tumour extracts. An alternatively spliced form of POLH mRNA, lacking exon 2, was more readily detected in skin tissue than in white blood cells from the same patient. Real-time PCR was used to quantify POLH expression in matched normal and skin tumour-derived mRNA from a series of patients diagnosed with either basal or squamous cell carcinoma. Compared to matched normal skin tissue from the same patient, 1 of 7 SCC, and 4 of 10 BCC tumours examined showed at least a 2-fold reduction in POLH expression, while 1 of 7 SCC, and 3 of 10 BCC tumours showed at least a 2-fold increase in POLH expression. Differences in gene expression, rather than sequence changes may be the main mechanism by which POLH status varies between normal and skin tumours in the population under investigation. Knowledge of the POLH status in skin tumours could contribute to an understanding of the role of this gene in the development of the most common cancer in the general population.

Hair-thread tourniquet syndrome in an infant with bony erosion: a case report, literature review, and meta-analysis.

Hair-thread tourniquet syndrome is a rare condition where appendages are strangulated by an encircling strand of hair, a thread, or a fiber. The condition usually occurs in very young patients in the first few months of life. We present a unique case of a 3-month-old baby girl with hair-thread tourniquet syndrome in whom a hair cheese-wired through the skin and soft tissue of the toe and caused bony erosion of the underlying phalanx. An extensive literature review and meta-analysis of the topic are also presented.

Moray eel attack in the tropics: a case report and review of the literature.

As more people use the oceans for recreational purposes, encounters with potentially dangerous sea creatures are becoming more common. We report the case of a scuba diver bitten by a moray eel off the coast of Cuba. The diver received an extensive crush avulsion injury with near loss of his right upper arm. A review of the existing literature identifies the significant characteristics of such attacks. Given the potential seriousness and complications of these attacks, a greater awareness among both treating physicians and emergency personnel may improve overall management of injuries. In addition, greater respect for moray eels among divers and other ocean users may decrease the likelihood of serious eel encounters.