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.