The antibacterial activity of a photoactivatable diarylacetylene against Gram-positive bacteria.

The emergence of antibiotic resistance is a growing threat to human health, and therefore, alternatives to existing compounds are urgently needed. In this context, a novel fluorescent photoactivatable diarylacetylene has been identified and characterised for its antibacterial activity, which preferentially eliminates Gram-positive over Gram-negative bacteria. Experiments confirmed that the Gram-negative lipopolysaccharide-rich outer surface is responsible for tolerance, as strains with reduced outer membrane integrity showed increased susceptibility. Additionally, bacteria deficient in oxidative damage repair pathways also displayed enhanced sensitivity, confirming that reactive oxygen species production is the mechanism of antibacterial activity. This new diarylacetylene shows promise as an antibacterial agent against Gram-positive bacteria that can be activated in situ, potentially for the treatment of skin infections.

Modified CRISPR/Cas9 mediated generation of two MKK7 knockout human embryonic stem cell lines.

Two cell lines were generated by CRISPR/Cas9 mediated knockout of MKK7 (MAP2K7) by removal of exon 1 or exons 4 through 7. These knockouts were confirmed at the transcript and protein levels. These hESCs are pluripotent and maintain tri-lineage differentiation capacity. These cell lines are a useful resource for studying MKK7 function in humans.

Engineering Prostate Cancer from Induced Pluripotent Stem Cells-New Opportunities to Develop Preclinical Tools in Prostate and Prostate Cancer Studies.

One of the key issues hampering the development of effective treatments for prostate cancer is the lack of suitable, tractable, and patient-specific in vitro models that accurately recapitulate this disease. In this review, we address the challenges of using primary cultures and patient-derived xenografts to study prostate cancer. We describe emerging approaches using primary prostate epithelial cells and prostate organoids and their genetic manipulation for disease modelling. Furthermore, the use of human prostate-derived induced pluripotent stem cells (iPSCs) is highlighted as a promising complimentary approach. Finally, we discuss the manipulation of iPSCs to generate 'avatars' for drug disease testing. Specifically, we describe how a conceptual advance through the creation of living biobanks of "genetically engineered cancers" that contain patient-specific driver mutations hold promise for personalised medicine.

Changes in local free-living parasite populations in response to cleaner manipulation over 12 years.

Predation on parasites is an important ecological process, but few experimental studies have examined the long-term impacts on the prey. Cleaner fish prey upon large numbers and selectively feed on the larger individuals of the ectoparasitic stage of gnathiid isopods. Removal of cleaner fish Labroides dimidiatus for 1.5-12.5 years negatively affects coral reef fishes, but the mechanism is unclear. A reduction in local parasite populations or the size of individual parasites would benefit all susceptible fishes. We tested whether cleaner presence reduces local gnathiid populations using 18 patch-reefs distributed between two sites (both at Lizard Island, Great Barrier Reef) which were maintained cleaner-free or undisturbed for 12 years. Using emergence traps (1 m2), free-living gnathiid stages were sampled before and after cleaner fish were removed during the day and night, up to 11 times over the course of the experiment. There were effects of the removal in the predicted direction, driven largely by the response at one site over the other involving 200% more gnathiids, but manifested only in the daytime sampling after 4 months. There was also a main effect (36%) for the shared sample dates at both sites after 12 years. Gnathiid size occasionally differed with cleaner presence, but in no consistent way over time. Contrary to our predictions, changes in free-living gnathiid population numbers and their size structure rarely reflected the changes in fish populations and individuals observed on cleaner-free reefs. Therefore, evidence that this predator alone regulates gnathiids remains limited, suggesting other contributing processes are involved.

The utilization of small amounts of residual endodontic material for dental identification.

Dental information is one of the three scientific methods of identifying a deceased person. However, when an investigator is faced with dental ante-mortem information that indicates the deceased has had all his teeth extracted, it may be assumed that the dental information will not be useful, especially if no retained roots are visible in the post-mortem triage. The following case report highlights that careful examination including radiography, may reveal specific detailed information which was useful for identification to be established. Two small radiopaque objects were located in the apical area where the upper left canine root apex would have been. The radiopacities size, location, positioning to both each other and to the left maxillary sinus corresponded to ante-mortem radiographs. This case reveals an unusual use of extruded root canal material being of evidential value even though the tooth was extracted.

A review of daycase GA services for Special Care patients at University Hospital, Bristol.

This paper describes and discusses a review of adult special care dentistry day cases in a UK hospital over a two year period and makes recommendations for other such reviews and for practice. Dental public health competencies illustrated: oral health needs assessment and evaluation of dental health services.

Prolonged fasting of children before anaesthesia is common in private practice.

Fasting guidelines for children are well established. Despite these guidelines, previous studies have shown children are often fasted for prolonged periods before anaesthesia, potentially causing discomfort and distress. Moreover, recent publications indicate shorter fasting times for oral clear fluids in children may be safe. We audited fasting times of children having elective surgery at a local large private hospital that provides care for both adults and children. We gave feedback and education to our caregivers, then repeated the audit. Data were collected from 307 children (age 6.0 ± 4.1 years) in an initial eight-week audit, and from 153 children (age 6.7 ± 4.5 years) in a follow-up four-week audit. We found fasting durations were excessive in many children. Sixty-two percent of children in each audit fasted longer than four hours for clear fluids. Children on morning lists fasted longer than children on afternoon lists. Fasting from solids was also excessively long. In the initial audit, 30% fasted more than 12 hours for solids, including 18 who last ate more than 16 hours before surgery. Data from the follow-up audit were similar. We conclude that fasting of children at our hospital is excessive, despite our efforts to shorten the duration. We suspect that our hospital is not the only one with a high incidence of prolonged fasting for children and suggest possible solutions.

Initial venous lactate levels in patients with isolated penetrating extremity trauma: a retrospective cohort study.

INTRODUCTION: Elevated initial lactate levels have been shown to be associated with severe injury in trauma patients, but some patients who do not appear to be in shock also presented with elevated lactate levels. We hypothesized that in hemodynamically stable patients with isolated penetrating extremity trauma, initial lactate level does not predict clinically significant bleeding. METHODS: A 5-year institutional database review was performed. Hemodynamically stable patients (HR < 101, SBP > 90) with isolated penetrating extremity trauma with an initial lactate sent were included. The exposure of interest was captured as a dichotomous variable by initial lactate level normal (N ≤ 2.2 mEq/L), elevated (E > 2.2 mEq/L). The primary outcome measurement was clinically significant bleeding, defined by need for intervention (operation, angioembolization, or transfusion) or laboratory evidence of bleeding (presenting Hg < 7 g/dL, or Hg decrease by >2 g/dL/24 h). Chi-squared and Mann-Whitney tests were used to compare variables. RESULTS: A total of 132 patients were identified. There were no differences in demographics or mechanism of injury between the N (n = 43, 7%) and E (n = 89, 14%) groups. Median lactate levels were 1.6 (IQR 1.2-1.9) mEq/dL vs. 3.8 (IQR 2.8-5.2) in the N and E groups, p < 0.001. Lactate was elevated in 89 (67%) patients but was not associated with clinically significant bleeding (37% elevated vs. 39 % not elevated p = 0.82). CONCLUSIONS: In hemodynamically stable patients with isolated penetrating trauma to the extremity, elevated initial venous lactate levels (>2.2 mEq/L) are not associated with bleeding or need for interventions. Clinical judgment remains the gold standard for evaluation and management of these patients.

Targeting mitochondrial oxidants may facilitate recovery of renal function during infant sepsis.

Sepsis-induced acute kidney injury (SAKI) is a frequent complication of infant sepsis that approximately doubles the mortality rate. The poor prognosis of these patients is a result of care that is mainly supportive, nontargeted, and usually begun only after symptoms of the systemic inflammatory response syndrome are observed. Preclinical studies from relevant rodent models of SAKI suggest that mitochondria-targeted antioxidants may be a new mode of therapy that could promote recovery.

Psoas:lumbar vertebra index: central sarcopenia independently predicts morbidity in elderly trauma patients.

INTRODUCTION: Central sarcopenia as a surrogate for frailty has recently been studied as a predictor of outcome in elderly medical patients, but less is known about how this metric relates to outcomes after trauma. We hypothesized that psoas:lumbar vertebral index (PLVI), a measure of central sarcopenia, is associated with increased morbidity and mortality in elderly trauma patients. METHODS: A query of our institutional trauma registry from 2005 to 2010 was performed. Data was collected prospectively for the Pennsylvania Trauma Outcomes Study (PTOS). INCLUSION CRITERIA: age >55 years, ISS >15, and ICU LOS >48 h. Using admission CT scans, psoas:vertebral index was computed as the ratio between the mean cross-sectional areas of the psoas muscles and the L4 vertebral body at the level of the L4 pedicles. The 50th percentile of the psoas:L4 vertebral index value was determined, and patients were grouped into high (>0.84) and low (≤0.83) categories based on their relation to the cohort median. Primary endpoints were mortality and morbidity (as a combined endpoint for PTOS-defined complications). Univariate logistic regression was used to test the association between patient factors and mortality. Factors found to be associated with mortality at p < 0.1 were entered into a multivariable model. RESULTS: A total of 180 patients met the study criteria. Median age was 74 years (IQR 63-82), median ISS was 24 (IQR 18-29). Patients were 58 % male and 66 % Caucasian. Mean PLVI was 0.86 (SD 0.25) and was higher in male patients than female patients (0.91 ± 0.26 vs. 0.77 ± 0.21, p < 0.001). PLVI was not associated with mortality in univariate or multivariable modeling. After controlling for comorbidities, ISS, and admission SBP, low PLVI was found to be strongly associated with morbidity (OR 4.91, 95 % CI 2.28-10.60). CONCLUSIONS: Psoas:lumbar vertebral index is independently and negatively associated with posttraumatic morbidity but not mortality in elderly, severely injured trauma patients. PLVI can be calculated quickly and easily and may help identify patients at increased risk of complications.

Scalable synthesis of a biocompatible, transparent and superparamagnetic photoresist for microdevice fabrication.

The functionalization of photoresists with colloids has enabled the development of novel active and passive components for microfabricated devices. Incorporation of colloidal particles often results in undesirable reductions in photolithographic fidelity and device transparency. We present a novel photoresist composite incorporating poly(methyl methacrylate-co-methacrylic acid) (PMMA/MMA), the epoxy resin 1002F and colloidal maghemite nanoparticles to produce a stable, transparent and biocompatible photoresist. The composite photoresist was prepared in a scalable fashion in batches up to 1 kg with the particles remaining dispersed during room-temperature storage for at least 6 months. Following photolithography to form films, the nanoparticle size remained well below that of visible-light wavelengths as demonstrated by electron microscopy. Structures fabricated from the photoresist by conventional photolithography displayed aspect ratios greater than ten. When grown on the photoresist, the metabolic rate of HeLa cells was unchanged relative to cells grown on glass. Primary murine mesenchymal stem cells also displayed a normal morphology on the resist surface. The ability to manipulate microstructures formed from the composite was demonstrated by magnetically collecting clonal colonies of HeLa cells from a micropallet array. The transparency, biocompatibility, scalable synthesis and superparamagnetic properties of the novel composite address key limitations of existing magnetic composites.

Gonosomal mosaicism for an NF1 deletion in a sperm donor: evidence of the need for coordinated, long-term communication of health information among relevant parties.

BACKGROUND: Screening of gamete donors can reduce but cannot eliminate the risks for medical problems in donor-conceived offspring. We present a case of gonosomal mosaicism discovered in an anonymous sperm donor after receiving two reports of neurofibromatosis type 1 (NF1) in donor-conceived offspring, to illustrate that long-term, systematic investigation of health issues in donors and offspring can be invaluable to the welfare of these individuals. METHODS: A repeat physical evaluation and ophthalmology examination were performed on the donor. DNA samples were examined by RTPCR fragment analysis, multiplex ligation-dependent probe amplification (MLPA) and targeted array-comparative genomic hybridization (aCGH). RESULTS: Gonosomal mosaicism for a deletion mutation in the NF1 gene was identified in 20% of sperm and a smaller percentage of lymphocytes. CONCLUSIONS: Long-term communication of medical information among donors, recipients and donor-conceived offspring is beneficial for the health management of all parties. Development of a secure, coordinated data system is critical to achieving this goal. Recommendations are provided for management and communication of critical information based on this experience.

Clinical outcomes following invasive versus noninvasive preoperative stabilization of closed diaphyseal femur fractures.

BACKGROUND: The use of invasive traction (INV-T) to stabilize femur fractures prior to fixation (open reduction and internal fixation, ORIF) remains controversial. Some centers have utilized noninvasive traction (NINV-T) or splinting preoperatively. It is possible that INV-T decreases hemorrhage. However, the use of INV-T in pediatric patients and for femoral neck fractures in adults is associated with worsened outcomes. We hypothesized that there is no difference in the need for transfusion between those who receive INV-T and NINV-T. METHODS: A retrospective study was performed at two level I and one level II trauma center from January 2006 to December 2009. Patients ≥18 years with a closed diaphyseal femur fracture who underwent ORIF within 48 h of arrival were included. Patients were grouped by method of preoperative fracture stabilization. Primary endpoint was need for transfusion. A power analysis found that 94 patients were needed to detect a 25 % difference with 80 % power. RESULTS: Fifty-six (22 %) received INV-T and 199 (78 %) received NINV-T stabilization. No significant differences were found between groups in terms of age, injury severity score, or ORIF method. There was no significant difference between the two groups in the hemoglobin value on arrival, preoperative hemoglobin value, or the difference between admission and preoperative hemoglobin values. We did not find a significant difference in the need for red blood cell transfusion between the two groups. There was no difference in length of stay or discharge destination. CONCLUSION: INV-T is not associated with improved outcomes in adult patients with closed mid-shaft femoral fractures who are operated upon within 48 h of arrival.

Sodium metasilicate affects antimicrobial, sensory, physical, and chemical characteristics of fresh commercial chicken breast meat stored at 4° C for 9 days.

The objectives of this study were to investigate antimicrobial properties of sodium metasilicate (SMS) on fresh boneless and skinless commercial broiler chicken breast fillets, and to ascertain effects of the treatments on sensory, chemical, and physical characteristics of the meat. Fillets were divided into 5 groups, weighed, treated with 0, 1, 2, 3, or 4% SMS marinades, vacuum tumbled at 172.32 kPa for 20 min, reweighed, packaged in styrofoam trays, stored at 4°C for 9 d, and analyzed at 0, 1, 3, 5, 6, 7, and 9 d for marination yield (d 0 only), pH, total psychrotrophic counts, water-holding capacity, purge loss, cooking yield, and objective texture, color, and sensory characteristics. Marination yield and water-holding capacity were similar (P > 0.05) among all SMS treatments and increased by 3 to 4% compared with that in control fillets. Fillets treated with at least 3% SMS had higher (P < 0.05) pH and cooking yields and lower (P < 0.05) purge loss (on d 9) compared with control fillets. The 3 and 4% SMS treatments retarded growth of psychrotrophic organisms for 1 additional day compared with control, 1, and 2% SMS-treated fillets. Color and texture measurements and sensory characteristics of the fillets were not adversely affected by the SMS treatments. The data in this study revealed that at least 3% SMS was necessary to retard growth of spoilage bacteria compared with untreated samples and samples treated with the USDA maximum allowable level of 2% SMS in poultry marinades.

Quantifying nonhomogeneous colors in agricultural materials. Part II: comparison of machine vision and sensory panel evaluations.

The average colors of mangos and apples were measured using machine vision. A method to quantify the perception of nonhomogeneous colors by sensory panelists was developed. Three colors out of several reference colors and their perceived percentage of the total sample area were selected by untrained panelists. Differences between the average colors perceived by panelists and those from the machine vision were reported as DeltaE values (color difference error). Effects of nonhomogeneity of color, and using real samples or their images in the sensory panels on DeltaE were evaluated. In general, samples with more nonuniform colors had higher DeltaE values, suggesting that panelists had more difficulty in evaluating more nonhomogeneous colors. There was no significant difference in DeltaE values between the real fruits and their screen image, therefore images can be used to evaluate color instead of the real samples.

Vena cava filters: a synopsis of complications and related topics.

Deep venous thrombosis and pulmonary embolism constitute common preventable causes of morbidity and mortality. The incidence of venous thromboembolism (VTE) continues to increase. Standard anticoagulation therapy may reduce the risk of fatal PE by 75% and that of recurrent VTE by over 90%. For patients who are not candidates for anticoagulation, a vena cava filter (VCF) may be beneficial. Despite a good overall safety record, significant complications related to VCF are occasionally seen. This review discusses both procedural and non-procedural complications associated with VCF placement and use. We will also discuss VCF use in the settings of pregnancy, malignancy, and the clinical need for more than one filter.

Cutaneous papillomatosis and carcinomatosis in the Western barred bandicoot (Perameles bougainville).

A progressive wart-like syndrome in both captive and wild populations of the Western barred bandicoot (WBB) is hindering conservation efforts to prevent the extinction of this endangered marsupial. In this study, 42 WBBs exhibiting the papillomatosis and carcinomatosis syndrome were examined. The disease was characterized by multicentric proliferative lesions involving cutaneous and mucosal surfaces, which were seen clinically to increase in size with time. Grossly and histologically the smaller skin lesions resembled papillomas, whereas the larger lesions were most commonly observed to be squamous cell carcinomas. Large amphophilic intranuclear inclusion bodies were observed in hyperplastic conjunctival lesions of 8 WBBs under light microscopy. Conjunctival lesions from 2 WBBs examined using transmission electron microscopy contained a crystalline array of spherical electron-dense particles of 45-nm diameter, within the nucleus of conjunctival epithelial cells, consistent with a papillomavirus or polyomavirus. Conjunctival samples from 3 bandicoots that contained intranuclear inclusion bodies also demonstrated a positive immunohistochemical reaction after indirect immunohistochemistry for papillomavirus structural antigens. Ultrastructural and/or immunohistochemical evidence of an etiologic agent was not identified in the nonconjunctival lesions examined. Here we describe the gross, histopathologic, ultrastructural, and immunohistochemical findings of a papillomatosis and carcinomatosis syndrome recently identified in the WBB.