Photo-induced structural dynamics of o-nitrophenol by ultrafast electron diffraction.

The photo-induced dynamics of o-nitrophenol, particularly its photolysis, has garnered significant scientific interest as a potential source of nitrous acid in the atmosphere. Although the photolysis products and preceding photo-induced electronic structure dynamics have been investigated extensively, the nuclear dynamics accompanying the non-radiative relaxation of o-nitrophenol on the ultrafast timescale, which include an intramolecular proton transfer step, have not been experimentally resolved. Herein, we present a direct observation of the ultrafast nuclear motions mediating photo-relaxation using ultrafast electron diffraction. This work spatiotemporally resolves the loss of planarity which enables access to a conical intersection between the first excited state and the ground state after the proton transfer step, on the femtosecond timescale and with sub-Angstrom resolution. Our observations, supported by ab initio multiple spawning simulations, provide new insights into the proton transfer mediated relaxation mechanism in o-nitrophenol.

Preliminary study of a new online and equipment-free vision screening alternative for remote and isolated community.

INTRODUCTION: Vision screening has been initiated to detect potential vision problems, paving referral pathways towards a full eye examination. Time-cost-labour practicality challenges of equipment-based vision screening have lingered for decades. Going for the highest sensitivity and specificity or opting for a pragmatic and affordable vision screening program remains a dilemma in public eye health. We aimed to report the development of a new online and equipment-free vision screening called Eye: Questionnairebased Vision Screening (EyeQVS). We also analysed the visual profile of Orang Bateq resided in a remote locality, using findings from EyeQVS, single test vision screening and full eye examination. MATERIALS AND METHODS: Multi-perspective development strategies were employed in designing EyeQVS. The questionnaire items were constructed using the working backward technique, compiling common vision disorders from the literature and face validation using expert panels. Face validation and usability assessment were performed on EyeQVS. The vision screening was carried out using EyeQVS and single test visual acuity screening method. The full eye examination included visual acuity, refraction, binocular vision and ocular health assessment. The visual profile of indigenous people (Orang Bateq) at Kampung Bengoi and Kampung Atok, Jerantut, Pahang was analysed using EyeQVS, single test visual acuity screening method and full eye examination. RESULTS: The performance of EyeQVS was affirmative in both face validation and usability. About 95% of Orang Bateq failed full eye examination, while 55% failed EyeQVS screening. None of them failed single test vision screening. Binocular disorders and dry eye problems were commonly found in Orang Bateq. EyeQVS unearthed more various vision problems compared to the single test vision screening (visual acuity alone) as a screening tool in a remote location. CONCLUSION: EyeQVS can screen for binocular disorders and dry eyes problem commonly found among indigenous people, which might be missed using a single-test visual acuity screening approach. EyeQVS is a practical alternative for vision screening in places where financial or location hinders eye healthcare access.

Clonal Hematopoiesis of Indeterminate Potential and Kidney Function Decline in the General Population.

RATIONALE & OBJECTIVE: Clonal hematopoiesis of indeterminate potential (CHIP), defined by the age-related ontogenesis of expanded leukemogenic variants indicative of a genetically distinct clonal leukocyte population, is associated with risk of hematologic malignancy and cardiovascular disease. In experimental models, recapitulation of CHIP promotes kidney interstitial fibrosis with direct tissue infiltration of donor macrophages. We tested the hypothesis that CHIP is associated with kidney function decline in the general population. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 12,004 individuals from 3 community-based cohorts in the TOPMed Consortium. EXPOSURE: CHIP status from whole-genome sequences obtained from DNA extracted from peripheral blood. OUTCOME: Risk of 30% decline in estimated glomerular filtration rate (eGFR) and percent eGFR decline per year during the follow-up period. ANALYTICAL APPROACH: Cox proportional hazards models for 30% eGFR decline end point and generalized estimating equations for annualized relative change in eGFR with meta-analysis. Study-specific estimates were combined using fixed-effect meta-analysis. RESULTS: The median baseline eGFR was 84mL/min/1.73m2. The prevalence of CHIP was 6.6%, 9.0%, and 12.2% in persons aged 50-60, 60-70, and>70 years, respectively. Over a median follow-up period of 8 years, for the 30% eGFR outcome 205 events occurred among 1,002 CHIP carriers (2.1 events per 100 person-years) and 2,041 events in persons without CHIP (1.7 events per 100 person-years). In meta-analysis, CHIP was associated with greater risk of a 30% eGFR decline (17% [95% CI, 1%-36%] higher; P=0.04). Differences were not observed between those with baseline eGFR above or below 60mL/min/1.73m2, of age above or below 60 years, or with or without diabetes. LIMITATIONS: Small number of participants with moderate-to-advanced kidney disease and restricted set of CHIP driver variants. CONCLUSIONS: We report an association between CHIP and eGFR decline in 3 general population cohorts without known kidney disease. Further studies are needed to investigate this novel condition and its potential impact among individuals with overt kidney disease.

Genome-wide association study reveals novel genetic loci: a new polygenic risk score for mitral valve prolapse.

AIMS: Mitral valve prolapse (MVP) is a common valvular heart disease with a prevalence of >2% in the general adult population. Despite this high incidence, there is a limited understanding of the molecular mechanism of this disease, and no medical therapy is available for this disease. We aimed to elucidate the genetic basis of MVP in order to better understand this complex disorder. METHODS AND RESULTS: We performed a meta-analysis of six genome-wide association studies that included 4884 cases and 434 649 controls. We identified 14 loci associated with MVP in our primary analysis and 2 additional loci associated with a subset of the samples that additionally underwent mitral valve surgery. Integration of epigenetic, transcriptional, and proteomic data identified candidate MVP genes including LMCD1, SPTBN1, LTBP2, TGFB2, NMB, and ALPK3. We created a polygenic risk score (PRS) for MVP and showed an improved MVP risk prediction beyond age, sex, and clinical risk factors. CONCLUSION: We identified 14 genetic loci that are associated with MVP. Multiple analyses identified candidate genes including two transforming growth factor-ß signalling molecules and spectrin ß. We present the first PRS for MVP that could eventually aid risk stratification of patients for MVP screening in a clinical setting. These findings advance our understanding of this common valvular heart disease and may reveal novel therapeutic targets for intervention.

Cage Environment Regulates Gut Microbiota Independent of Toll-Like Receptors.

The gut microbiome orchestrates epithelial homeostasis and both local and remote immunological responses. Critical to these regulatory interactions are innate immune receptors termed Toll-like receptors (TLRs). Studies to date have implicated innate immunity and Toll-like receptors in shaping key features of the gut microbiome. However, a variety of biological and environmental variables are also implicated in determining gut microbiota composition. In this report, we hypothesized that cohousing and environment dominated the regulation of the gut microbiota in animal models independent of innate immunity. To determine the importance of these variables, innate immunity, or environment in shaping gut microbiota, we used a randomized cohousing strategy and transgenic TLR-deficient mice. We have found that mice cohoused together by genotype exhibited limited changes over time in the composition of the gut microbiota. However, for mice randomized to cage, we report extensive changes in the gut microbiota, independent of TLR function, whereby the fecal microbiota of TLR-deficient mice converges with that of wild-type mice. TLR5-deficient mice in these experiments exhibit greater susceptibility to comparative changes in the microbiota than other TLR-deficient mice and wild-type mice. Our work has broad implications for the study of innate immunity and host-microbiota interactions. Given the profound impact that gut dysbiosis may have on immunity, this report highlights the potential impact of cohousing on the gut microbiota and indices of inflammation as outcomes in biological models of infectious or inflammatory disease.

Rapid multi-generational acclimation of coralline algal reproductive structures to ocean acidification.

The future of coral reef ecosystems is under threat because vital reef-accreting species such as coralline algae are highly susceptible to ocean acidification. Although ocean acidification is known to reduce coralline algal growth rates, its direct effects on the development of coralline algal reproductive structures (conceptacles) is largely unknown. Furthermore, the long-term, multi-generational response of coralline algae to ocean acidification is extremely understudied. Here, we investigate how mean pH, pH variability and the pH regime experienced in their natural habitat affect coralline algal conceptacle abundance and size across six generations of exposure. We show that second-generation coralline algae exposed to ocean acidification treatments had conceptacle abundances 60% lower than those kept in present-day conditions, suggesting that conceptacle development is initially highly sensitive to ocean acidification. However, this negative effect of ocean acidification on conceptacle abundance disappears after three generations of exposure. Moreover, we show that this transgenerational acclimation of conceptacle development is not facilitated by a trade-off with reduced investment in growth, as higher conceptacle abundances are associated with crusts with faster growth rates. These results indicate that the potential reproductive output of coralline algae may be sustained under future ocean acidification.

A narrative review of the definition of 'flare' in hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory condition that can have periodic worsening or flares. Measurement of flare is important because it can inform treatment efficacy; however, it is unclear how HS flare should be defined. OBJECTIVES: This study reviewed the literature for definitions of HS flare. METHODS: The PubMed MEDLINE online database was searched on 10 January 2018 and the search was repeated on 8 December 2018 for new publications. Titles and abstracts were screened for inclusion. Subsequently, full articles were screened for inclusion. Papers were included if the publication was a systematic review, clinical trial, cohort study, case report or series, or cross-sectional study. Studies were excluded if they were journalistic reviews, did not discuss clinical findings of HS or did not use the words 'flare', 'exacerbation', 'relapse' or 'recurrence'. RESULTS: Two hundred and seventy-four papers were identified and 154 fulfilled the study criteria. Of these, 27 (17.5%) included the term 'flare' and 16 (10.4%) included the term 'exacerbation'. Two of the 27 papers (7%) defined the term flare and both included patient report of changes in symptoms or signs. One of 16 papers (6%) defined exacerbation, which was taken as one new HS lesion. The terms 'recurrence' and 'relapse' were more apt to be defined: 13% (13 of 100) and 14% (six of 44), respectively. CONCLUSIONS: The lack of a specific and measurable definition of HS flare is a barrier to assessment of this important outcome. Once a specific and measurable definition is established, validated and reliable measures of HS flare can be incorporated into future studies. What's already known about this topic? Hidradenitis suppurativa (HS) is a chronic, relapsing inflammatory skin condition. The ability to assess flares is important to people who have HS; however, it is unclear how this is defined. HS flare is one of the core outcomes in the core outcome set for HS clinical trials; however, it is unclear how this should be assessed. What does this study add? This literature review reveals the paucity of measurable definitions associated with the use of the term 'flare' in the HS literature. It also highlights the variation and lack of a validated and reliable measure of HS flare.

Activation of the cannabinoid receptor 2 increases renal perfusion.

Acute kidney injury (AKI) is an increasing clinical problem that is associated with chronic kidney disease progression. Cannabinoid receptor 2 (CB2) activation has been shown to mitigate some of the deleterious tubular effects due to AKI, but its role on the renal vasculature has not been fully described. In this study, we investigated the effects of our novel CB2 receptor agonist, SMM-295, on renal vasculature by assessing cortical perfusion with laser Doppler flowmetry and changes in luminal diameter with isolated afferent arterioles. In this study, intravenously infused SMM-295 (6 mg/kg) significantly increased cortical renal perfusion (13.8 ± 0.6%; P < 0.0001; n = 7) compared with vehicle (0.1 ± 1.5%; n = 10) normalized to baseline values in anesthetized C57BL/6J mice. This effect was not dependent upon activation of the CB1 receptor (met-anandamide; 6 mg/kg iv) and was predominantly abolished in Cnr2 knockout mice with SMM-295 (6 mg/kg iv). Ablation of the renal afferent nerves with capsaicin blocked the SMM-295-dependent increase in renal cortical perfusion, and the increased renal blood flow was not dependent upon products synthesized by cyclooxygenase or nitric oxide synthase. The increased renal perfusion by CB2 receptor activation is also attributed to a direct vascular effect, since SMM-295 (5 µM) engendered a significant 37 ± 7% increase ( P < 0.0001; n = 4) in luminal diameters of norepinephrine-preconstricted afferent arterioles. These data provide new insight into the potential benefit of SMM-295 by activating vascular and nonvascular CB2 receptors to promote renal vasodilation, and provide a new therapeutic target to treat renal injuries that impact renal blood flow dynamics.

Occult contralateral inguinal hernias: what is their true incidence and should they be repaired?

BACKGROUND: The true incidence of occult contralateral inguinal hernia is unknown; however, when found, there exists controversy as to whether or not they should be repaired. The aim of our study is to identify the incidence of contralateral incidental inguinal hernias in our surgical population, compare our results to previous studies timelining occult hernia identification to repair need, and generate debate as to whether incidental contralateral hernias should be repaired at the index operation. METHODS: We reviewed the charts of 297 consecutive patients undergoing robotic inguinal hernia repair between October 2014 and April 2018 at a single facility. By comparing preoperative physical examination to intraoperative findings, we determined the number of occult contralateral inguinal hernias in our patient population. RESULTS: Of 297 patients, 158 (53.2%) presented with a right inguinal hernia, 90 (30.3%) presented with a left inguinal hernia, and 49 (16.5%) presented with bilateral inguinal hernias. Forty-seven of the 297 patients (15.8%) were found to have an incidental contralateral inguinal hernia. Excluding patients with known bilateral inguinal hernias, 20% of patients with a left inguinal hernia were found to have an occult right inguinal hernia and 18.4% of patients with a right inguinal hernia were found to have an occult left inguinal hernia. CONCLUSIONS: The true incidence of occult contralateral inguinal hernia may be higher than originally thought. When inguinal hernia repair is performed through a transabdominal approach, these occult hernias may be easily addressed during the same operation without additional skin incisions. This may ultimately prevent the morbidity of developing a metachronous hernia that requires repair.

Fibroblast growth factor-21 (FGF21) administration to early-lactating dairy cows. I. Effects on signaling and indices of insulin action.

Modern dairy cows rely on hormonally driven mechanisms to coordinate the metabolic adaptations needed to meet the energy and nutrient deficits of early lactation. In the case of glucose, dairy cows cope with its scarcity during early lactation via reduced plasma concentrations of insulin and the insulin sensitizing hormone adiponectin and increased insulin resistance. Reduced insulin action promotes diversion of available glucose to the mammary gland but increases susceptibility to diseases if excessive. In earlier work, we reported that the insulin sensitizing hormone fibroblast growth factor-21 (FGF21) is increased in periparturient dairy cows and identified liver and adipose tissue as possible targets. These observations raised the possibility that FGF21 acts directly on these tissues to limit the insulin resistance of early lactation. To test this hypothesis, dairy cows were randomly assigned on d 12.6 ± 2.2 (± standard error) of lactation to receive either excipient (n = 6) or recombinant human FGF21 (n = 7), first as an FGF21 bolus of 3 mg/kg of body weight, followed 2 d later by a constant i.v. infusion of FGF21 at the rate of 6.3 mg/kg of metabolic body weight for 9 consecutive days. Biopsies of liver and adipose tissue were collected during the bolus phase of the experiment and used to analyze FGF21 signaling by Western blotting and expression of its receptor components by quantitative PCR. Bolus FGF21 administration caused a 4-fold increase in p44/42 MAPK (ERK1/2) activation in adipose tissue but had no effect on AKT and signal transducer and activator of transcription-3 (STAT3) signaling. The liver expressed negligible levels of the preferred FGF21 receptor FGFR1c and failed to mount any FGF21 signaling response. The FGF21 administered as a bolus had no effect on plasma glucose or insulin and did not stimulate an acute release of adiponectin from adipose tissue. Similarly, FGF21 infusion had no effect on plasma levels of glucose or insulin measured over the 9-d infusion or on glucose disposal during an i.v. glucose tolerance test performed on d 8 of infusion. Finally, the chronic FGF21 infusion had no effect on indices of adiponectin production, including plasma adiponectin and adipose tissue mRNA abundance of adiponectin and the endoplasmic reticulum chaperones ERO1A and DSBA-L involved in the assembly of adiponectin into multimeric complexes. These data show that human FGF21 does not act as an insulin sensitizer during the energy and glucose deficit of early lactation but do not rule out such a role in other physiological states.

Resistance of corals and coralline algae to ocean acidification: physiological control of calcification under natural pH variability.

Ocean acidification is a threat to the continued accretion of coral reefs, though some undergo daily fluctuations in pH exceeding declines predicted by 2100. We test whether exposure to greater pH variability enhances resistance to ocean acidification for the coral Goniopora sp. and coralline alga Hydrolithon reinboldii from two sites: one with low pH variability (less than 0.15 units daily; Shell Island) and a site with high pH variability (up to 1.4 pH units daily; Tallon Island). We grew populations of both species for more than 100 days under a combination of differing pH variability (high/low) and means (ambient pH 8.05/ocean acidification pH 7.65). Calcification rates of Goniopora sp. were unaffected by the examined variables. Calcification rates of H. reinboldii were significantly faster in Tallon than in Shell Island individuals, and Tallon Island individuals calcified faster in the high variability pH 8.05 treatment compared with all others. Geochemical proxies for carbonate chemistry within the calcifying fluid (cf) of both species indicated that only mean seawater pH influenced pHcf pH treatments had no effect on proxies for Ωcf These limited responses to extreme pH treatments demonstrate that some calcifying taxa may be capable of maintaining constant rates of calcification under ocean acidification by actively modifying Ωcf.

Development and evaluation of an online educational resource about cancer survivorship for cancer nurses: a mixed-methods sequential study.

Cancer survivorship is recognised globally as a key issue. In spite of the key role played by nurses in survivorship care, there is an identified gap in nurse's knowledge in this area. This study reports on the development and evaluation of an educational resource for nurses working with people affected by cancer. The resource was designed using adult learning principles and includes a variety of learning materials and point of care resources. A mixed-methods sequential exploratory design was used to undertake an evaluation of the programme. This included the use of online surveys and semi-structured interviews with pilot participants. A total of 21 participants completed an online survey and 11 participants completed a telephone interview. Overall, the participants found the Cancer Survivorship resource to be engaging, practical and intuitive. A major theme emerging from the survey and interview data was that the resource was applicable to practice and useful in developing survivorship care plans. Respondents requested additional information be included on the role of various health professionals working in survivorship as well as guidelines on when to make referrals. This study provides evidence that the Cancer Survivorship tool may be a promising vehicle for delivering evidence-based education on survivorship care.

Northward expansion of paddy rice in northeastern Asia during 2000-2014.

Paddy rice in monsoon Asia plays an important role in global food security and climate change. Here we documented annual dynamics of paddy rice areas in the northern frontier of Asia, including Northeastern (NE) China, North Korea, South Korea, and Japan, from 2000-2014 through analysis of satellite images. The paddy rice area has increased by 120% (2.5 to 5.5 million ha) in NE China, in comparison to a decrease in South Korea and Japan, and the paddy rice centroid shifted northward from 41.16 °N to 43.70 °N (~310 km) in this period. Market, technology, policy, and climate together drove the rice expansion in NE China. The increased use of greenhouse nurseries, improved rice cultivars, agricultural subsidy policy, and a rising rice price generally promoted northward paddy rice expansion. The potential effects of large rice expansion on climate change and ecological services should be paid more attention in the future.

Good Publication Practice for Communicating Company-Sponsored Medical Research: GPP3.

This updated Good Publication Practice (GPP) guideline, known as GPP3, builds on earlier versions and provides recommendations for individuals and organizations that contribute to the publication of research results sponsored or supported by pharmaceutical, medical device, diagnostics, and biotechnology companies. The recommendations are designed to help individuals and organizations maintain ethical and transparent publication practices and comply with legal and regulatory requirements. These recommendations cover publications in peer-reviewed journals and presentations (oral or poster) at scientific congresses. The International Society for Medical Publication Professionals invited more than 3000 professionals worldwide to apply for a position on the steering committee, or as a reviewer, for this guideline. The GPP2 authors reviewed all applications (n = 241) and assembled an 18-member steering committee that represented 7 countries and a diversity of publication professions and institutions. From the 174 selected reviewers, 94 sent comments on the second draft, which steering committee members incorporated after discussion and consensus. The resulting guideline includes new sections (Principles of Good Publication Practice for Company-Sponsored Medical Research, Data Sharing, Studies That Should Be Published, and Plagiarism), expands guidance on the International Committee of Medical Journal Editors' authorship criteria and common authorship issues, improves clarity on appropriate author payment and reimbursement, and expands information on the role of medical writers. By following good publication practices (including GPP3), individuals and organizations will show integrity; accountability; and responsibility for accurate, complete, and transparent reporting in their publications and presentations.

Investigating a Novel Measure of Brain Networking Following Sports Concussion.

Clinicians managing sports-related concussions are left to their clinical judgment in making diagnoses and return-to-play decisions. This study was designed to evaluate the utility of a novel measure of functional brain networking for concussion management. 24 athletes with acutely diagnosed concussion and 21 control participants were evaluated in a research laboratory. At each of the 4 post-injury time points, participants completed the Axon assessment of neurocognitive function, a self-report symptom inventory, and the auditory oddball and go/no-go tasks while electroencephalogram (EEG) readings were recorded. Brain Network Activation (BNA) scores were calculated from EEG data related to the auditory oddball and go/no-go tasks. BNA scores were unable to differentiate between the concussed and control groups or by self-report symptom severity. These findings conflict with previous work implementing electrophysiological assessments in concussed athletes, suggesting that BNA requires additional investigation and refinement before clinical implementation.

γ134.5-deleted HSV-1-expressing human cytomegalovirus IRS1 gene kills human glioblastoma cells as efficiently as wild-type HSV-1 in normoxia or hypoxia.

Pathophysiological hypoxia, which fosters the glioma stem-like cell (GSC) phenotype, is present in high-grade gliomas and has been linked to tumor development, invasiveness and resistance to chemotherapy and radiation. Oncolytic virotherapy with engineered herpes simplex virus-1 (HSV-1) is a promising therapy for glioblastoma; however, the efficacy of γ(1)34.5-deleted HSVs, which have been used in clinical trials, was diminished in hypoxia. We investigated the ability of a chimeric human cytolomegalovirus (HCMV)/HSV-1 virus, which expresses the human CMV protein kinase R evasion gene IRS1 and is in preparation for clinical trials, to infect and kill adult and pediatric patient-derived glioblastoma xenografts in hypoxia and normoxia. Infectivity, cytotoxicity and viral recovery were significantly greater with the chimeric virus compared with the γ(1)34.5-deleted virus, regardless of oxygen tension. The chimeric virus infected and killed CD133+ GSCs similarly to wild-type HSV-1. Increased activation of mitogen-activated protein kinase p38 and its substrate heat-shock protein 27 (Hsp27) was seen after viral infection in normoxia compared with hypoxia. Hsp27 knockdown or p38 inhibition reduced virus recovery, indicating that the p38 pathway has a role in the reduced efficacy of the γ(1)34.5-deleted virus in hypoxia. Taken together, these findings demonstrate that chimeric HCMV/HSV-1 efficiently targets both CD133+ GSCs and glioma cells in hypoxia.

Parasites as valuable stock markers for fisheries in Australasia, East Asia and the Pacific Islands.

Over 30 studies in Australasia, East Asia and the Pacific Islands region have collected and analysed parasite data to determine the ranges of individual fish, many leading to conclusions about stock delineation. Parasites used as biological tags have included both those known to have long residence times in the fish and those thought to be relatively transient. In many cases the parasitological conclusions have been supported by other methods especially analysis of the chemical constituents of otoliths, and to a lesser extent, genetic data. In analysing parasite data, authors have applied multiple different statistical methodologies, including summary statistics, and univariate and multivariate approaches. Recently, a growing number of researchers have found non-parametric methods, such as analysis of similarities and cluster analysis, to be valuable. Future studies into the residence times, life cycles and geographical distributions of parasites together with more robust analytical methods will yield much important information to clarify stock structures in the area.

Paramedic rapid sequence intubation in patients with non-traumatic coma.

INTRODUCTION: Pre-hospital intubation by paramedics is widely used in comatose patients prior to transportation to hospital, but the optimal technique for intubation is uncertain. One approach is paramedic rapid sequence intubation (RSI), which may improve outcomes in adult patients with traumatic brain injury. However, many patients present to emergency medical services with coma of non-traumatic cause and the role of paramedic RSI in these patients remains uncertain. METHODS: The electronic Victorian Ambulance Clinical Information System was searched for the term 'suxamethonium' between 2008 and 2011. We reviewed the patient care records and included patients with suspected non-traumatic coma who were treated and transported by road-based paramedics. Demographics, intubation conditions, vital signs (before and after drug administration) and complications were recorded. Younger patients (<60 years) were compared with older patients. RESULTS: There were 1152 paramedic RSI attempts of which 551 were for non-traumatic coma. The success rate for intubation was 97.5%. There was a significant drop in blood pressure in younger patients (<60 years) with the mean systolic blood pressure decreasing by 16 mm Hg (95% CI 11 to 21). In older patients, the systolic blood pressure also decreased significantly by 20 mm Hg (95% CI 17 to 24). Four patients suffered brief cardiac arrest during pre-hospital care, all of whom were successfully resuscitated and transported to hospital. CONCLUSIONS: Paramedic RSI in patients with non-traumatic coma has a high procedural success rate. Further studies are required to determine whether this procedure improves outcomes.

Keratocystic Odontogenic Tumour of the Mandible: a case report of decompression with a customised removable tube and review of literature.

Keratocystic odontogenic tumour (KOT or KCOT) is defined by the WHO to be 'a benign uni- or multicystic, intraosseous tumour of odontogenic origin'. In 2005, the World Health Organization renamed the lesion; previously known as an odontogenic keratocyst (OKC) as the KCOT. WHO recommends the term KCOT as it reflects its neoplastic nature. In this case report, a 21-year-old female with a histologically proven large parakeratinised KCOT of the right mandible underwent treatment that involved a 14-month period of decompression, followed by enucleation (with Carnoys application) of the residual cyst. During the period of decompression, a custom made removable mandibular chrome-cobalt appliance was used to hold the decompression tube in the oral cavity.

Effect of coadministered fat on the tolerability, safety, and pharmacokinetic properties of dihydroartemisinin-piperaquine in Papua New Guinean children with uncomplicated malaria.

Coadministration of dihydroartemisinin-piperaquine (DHA-PQ) with fat may improve bioavailability and antimalarial efficacy, but it might also increase toxicity. There have been no studies of these potential effects in the pediatric age group. The tolerability, safety, efficacy, and pharmacokinetics of DHA-PQ administered with or without 8.5 g fat were investigated in 30 Papua New Guinean children aged 5 to 10 years diagnosed with uncomplicated falciparum malaria. Three daily 2.5:11.5-mg-base/kg doses were given with water (n = 14, group A) or milk (n = 16, group B), with regular clinical/laboratory assessment and blood sampling over 42 days. Plasma PQ was assayed by high-performance liquid chromatography with UV detection, and DHA was assayed using liquid chromatography-mass spectrometry. Compartmental pharmacokinetic models for PQ and DHA were developed using a population-based approach. DHA-PQ was generally well tolerated, and initial fever and parasite clearance were prompt. There were no differences in the areas under the concentration-time curve (AUC0-∞) for PQ (median, 41,906 versus 36,752 µg · h/liter in groups A and B, respectively; P = 0.24) or DHA (4,047 versus 4,190 µg · h/liter; P = 0.67). There were also no significant between-group differences in prolongation of the corrected electrocardiographic QT interval (QTc) initially during follow-up, but the QTc tended to be higher in group B children at 24 h (mean ± standard deviation [SD], 15 ± 10 versus 6 ± 15 ms(0.5) in group A, P = 0.067) and 168 h (10 ± 18 versus 1 ± 23 ms(0.5), P = 0.24) when plasma PQ concentrations were relatively low. A small amount of fat does not change the bioavailability of DHA-PQ in children, but a delayed persistent effect on ventricular repolarization cannot be excluded.