Hydrogel foam dressings with angiogenic and immunomodulatory factors from mesenchymal stem cells.

Stem cell therapy and skin substitutes address the stalled healing of chronic wounds in order to promote wound closure; however, the high cost and regulatory hurdles of these treatments limit patient access. A low-cost method to induce bioactive healing has the potential to substantially improve patient care and prevent wound-induced limb loss. A previous study reported that bioactive factors derived from apoptotic-like mesenchymal stem cells (MSCs) demonstrated anti-inflammatory and proangiogenic effects and improved ischemic muscle regeneration. In this work, these MSC-derived bioactive factors were loaded into a hydrogel foam to harness immunomodulatory and angiogenic properties from MSC components to facilitate chronic wound healing without the high cost and translational challenges of cell therapies. After incorporation of bioactive factors, the hydrogel foam retained high absorbency, moisture retention, and target water vapor transmission rate. High loading efficiency was confirmed and release studies indicated that over 90% of loaded factors were released within 24 h. Ethylene oxide sterilization and 4-week storage did not affect the bioactive factor release profile or physical properties of the hydrogel foam dressing. Bioactivity retention of the released factors was also confirmed for as-sterilized, 4°C-stored, and -20°C-stored bioactive hydrogel foams as determined by relevant gene expression levels in treated pro-inflammatory (M1) macrophages. These results support the use of the bioactive dressings as an off-the-shelf product. Overall, this work reports a new method to achieve a first-line wound dressing with the potential to reduce persistent inflammation and promote angiogenesis in chronic wounds.

Laterality and performance: Are golfers learning to play backwards?

When using a bimanual tool to strike an object, most people place their preferred hand closer to the striking end. In sports, a player is deemed to adopt a "right- or left-handed" stance depending on the hand that is lower on the club or bat. Research has suggested there is an advantage in going against this convention by placing the preferred hand at the top in a "reversed-stance". This study aimed to establish if the reversed-stance advantage exists in golf, whether it is underpinned by the preferred hand or dominant eye, and why players adopt such a stance. We tested hand preference, eye dominance, and full swing stance in 150 golfers (30 for each handicap category) and conducted follow-up interviews with 12 reversed-stance players. Professional or category 1 golfers were 21.5 times more likely to adopt a reversed-stance. The advantage could not be explained by ambidexterity or the dominant eye but could be explained by the position of the preferred hand. Reversed-stance players cited a variety of reasons for adopting it and were more likely to display a left-hand preference. Findings offer initial evidence of a reversed-stance advantage in golf and can inform work identifying its origins and mechanisms.

Fatal nefopam overdose.

Nefopam hydrochloride (Acupan) is a potent non-opioid analgesic widely used for the relief of moderate to severe postoperative pain. The drug is generally well tolerated, but it has a broad spectrum of side effects including tachycardia, sweating, nausea, seizures and hallucinations. When taken in overdose, nefopam has been reported to cause cardiac conduction abnormalities, cerebral oedema, fever and renal failure. The case is presented of a previously healthy 19-year-old man who presented to the emergency department in cardiac arrest following intentional nefopam overdose. It is only the fourth reported case of fatal nefopam overdose in the literature.

WNT5A expression increases during melanoma progression and correlates with outcome.

PURPOSE: Wnt ligands play a major role in development and are important in cancer. Expression microarray analysis correlates one member of this family, WNT5A, to a subclass of melanomas with increased motility and invasion. There are no large studies of clinical samples primarily addressing the importance of WNT5A in melanoma progression or outcome. Therefore, this study aimed to assess the protein expression of WNT5A during melanoma progression and its effect on outcome. EXPERIMENTAL DESIGN: Expression of WNT5A was determined in a series of 59 primary melanomas with matched metastases. To provide a benchmark of progression against which to assess WNT5A, expression of p16(ink4a) was analyzed, as this has been previously well documented in melanoma. The effect of WNT5A protein expression on outcome was assessed in 102 melanomas. RESULTS: Cytoplasmic WNT5A showed a trend of increasing expression with melanoma progression (P = 0.013), whereas there was diminishing p16(ink4a) expression (P = 0.006). Nevi showed relatively strong WNT5A expression. Strong cytoplasmic WNT5A was an independent risk factor for reduced metastasis-free and overall survival in multivariate analysis (P = 0.001 and 0.003, respectively). CONCLUSION: Cytoplasmic WNT5A increases with melanoma progression and strong expression is associated with poor outcome.

It could have happened to Van Gogh: a case of fatal purple foxglove poisoning and review of the literature.

Although death owing to the toxic effects of the therapeutic Digitalis lanata extract, digoxin has been reported, there are no reported cases of fatal Digitalis purpurea (digitoxin) plant intoxication in humans in the literature. We describe a case of ingestion of Digitalis purpurea in a 64-year-old man, which was fatal despite administration of Digibind. A review of the literature and aspects of management of plant digitalis poisoning are discussed.

Kimura disease of the eyelid: a clinicopathologic study with electron microscopic observations.

A 70-year-old white man presented with a solitary eyelid nodule of 6 months' duration. Because lymphoma could not be excluded on the initial biopsy, the mass was completely excised. Histologic examination confirmed the diagnosis of Kimura disease, an uncommon chronic inflammatory condition. Peripheral eosinophilia was present. The patient did not have any other lesions of Kimura disease on follow-up examination. The clinical, radiologic, histologic, and electron microscopic findings of Kimura disease are discussed. To our knowledge, solitary involvement of the eyelid has not been reported previously. Kimura disease should be included in the differential diagnosis of an eyelid mass lesion.

Developing assessment of emergency nurse practitioner competence--a pilot study.

AIM: This paper reports a study evaluating baseline competence levels among Emergency Nurse Practitioners using an Objective Structured Clinical Examination. The study also aimed to document change in competence over time and following an educational intervention. BACKGROUND: Emergency Nurse Practitioners form an increasingly established part of the minor injury service workforce in the United Kingdom (UK). At present, there is no national requirement for them to undergo formal preparation, gain a formal qualification, have continuing professional development or revalidate. Given that it is certain that the use of these professionals to deliver unplanned emergency care will increase in the UK, skill maintenance and extension of skills need to be considered in order to ensure the continued delivery of a quality service. Objective Structured Clinical Examinations aim to test a wide range of knowledge and skills in an objective fashion and can be developed to serve a number of educational requirements. METHODS: A competence assessment was planned using an Objective Structured Clinical Examination. It was developed following questionnaire consultation with Emergency Nurse Practitioners and also in conjunction with Emergency Department specialists and experts in medical education. The Objective Structured Clinical Examination was piloted with Emergency Department junior doctors. Baseline Objective Structured Clinical Examination assessment was conducted in 2001. An educational intervention followed and then a further Objective Structured Clinical Examination assessment took place in 2002. RESULTS: A total of 17 of 20 Emergency Nurse Practitioners consented to involvement in the study. Comparison of their performance showed a statistically significant overall improvement in performance between the two assessment periods (P < 0.05). Participant feedback on the experience of undertaking an Objective Structured Clinical Examination assessment was very positive. CONCLUSIONS: The assessment process worked well, and provides a framework for competence assessment that can be compared over time, between practitioners and between departments.

Paraneoplastic limbic encephalitis--case report and review of literature.

We report a 77-year old man who presented with a sub-acute dementia associated with aggressive behaviour, ataxia, rapid progression and death. No cause for his illness could be detected in his lifetime, but at post mortem he was found to have paraneoplastic limbic encephalitis and a bronchogenic tumour. A diagnosis of paraneoplastic limbic encephalitis should be considered in the differential diagnosis of unexplained dementias and appropriate investigations performed to diagnose the condition.

High BRAF mutation frequency does not characterize all melanocytic tumor types.

Cutaneous melanoma (CM) is the most lethal form of skin cancer. Along with some benign melanocytic tumors, the majority shows BRAF or NRAS mutation, but it is not known whether these are essential to all forms of melanocytic neoplasia. We screened 79 melanocytic tumors of different types for BRAF and NRAS mutations and looked at MAPK pathway activity using immunohistochemistry in a subset. Significant differences in BRAF exon 15 mutation frequency were found: 14/16 (87.5%) in common acquired naevi (CANs), 9/12 (75%) in CMs, 0/26 in Spitz naevi and 3/25 (12%) in blue naevi (p < 0.01). We looked at whether Spitz and blue naevi showed a compensatory increase in BRAF exon 11 and/or NRAS exons 1 and 2 mutations to account for the low BRAF exon 15 mutation frequency. NRAS mutations were found in only 1/16 (6.3%) Spitz naevi and 0/15 blue naevi. In addition, NRAS mutations were found in 2/11 (18.2%) CANs and 3/12 (25%) CMs. None of the tumors showed BRAF exon 11 mutations. Despite their low combined BRAF and NRAS mutation frequency, Spitz naevi showed strong MAPK pathway activation as measured by cytoplasmic expression of dually phosphorylated ERK1/2, while blue naevi had weak pathway activation. We conclude that BRAF and NRAS mutations are not necessary for melanocytic tumor development and that some types of tumor must arise by alternative mechanisms.

Three-in-one femoral nerve block as analgesia for fractured neck of femur in the emergency department: a randomized, controlled trial.

STUDY OBJECTIVE: We determine whether 3-in-1 femoral nerve block is effective as analgesia for fractured neck of femur when administered by emergency physicians. METHODS: This was a prospective, randomized controlled trial with blinded assessors conducted in a district general hospital emergency department in the United Kingdom. Over a 6-month period, all patients with fractured neck of femur were considered for study. Patients were randomly assigned to receive 3-in-1 nerve block with bupivacaine plus intravenous morphine or intravenous morphine. An accreditation package for all ED medical staff was devised to ensure competence in the technique of 3-in-1 nerve block. Pain scores were recorded on arrival and at intervals up to 24 hours after admission. Morphine consumption in the first 24 hours was recorded. RESULTS: Ninety-four patients sustained fractured neck of femur during the study period; 50 were studied. Of 44 not studied, 42 were confused, 1 did not consent, and 1 was overlooked. Patients receiving 3-in-1 nerve blocks recorded a faster time to reach the lowest pain score: 2.88 hours for patients with nerve block and 5.81 hours for control patients (mean difference -2.93 h; 95% confidence interval [CI] -5.48 to -0.38 h). Nerve block recipients required significantly less morphine per hour than control patients (mean of 0.49 mg/h versus 1.17 mg/h; mean difference -0.68 mg/h; 95% CI -1.23 to -0.12 mg/h). CONCLUSION: Three-in-one femoral nerve block is an effective method of providing analgesia to patients with fractured neck of femur in the ED. All grades of medical staff were able to apply and consolidate this skill.