Health-related quality of life and assessment in patients with lower limb lymphoedema: a systematic review.

OBJECTIVE: To determine the impact of lower limb lymphoedema (LLL) on health-related quality of life (HRQoL), and to identify the methodologies used to assess HRQoL and their adherence to the World Health Organization (WHO)-recommended HRQoL dimensions. METHOD: A systematic review was used following the PRISMA guidance. Studies were eligible if they assessed HRQoL in adult patients with LLL. The search was conducted between September 2019 and February 2020 using CINAHL, PubMed, Scopus, EMBASE and the Cochrane Library database. Data were placed onto a pre-developed data extraction table and analysed using a narrative synthesis. Evidence-based Librarianship (EBL) was used for quality appraisal. RESULTS: A total of 18 studies were identified, among which 10 were cross-sectional and eight were longitudinal studies. Twelve HRQoL questionnaires were identified and the Lymphoedema Quality of Life tool (LYMQoL) was the most commonly used. All of the studies except one had an EBL validity score of ≥75%. Although LLL causes a considerable impairment in HRQoL, the findings varied across the studies. All the studies considered at least four of the six WHO recommended dimensions, with none considering the spirituality dimension. Furthermore, physical functioning and wellbeing were discovered to be the worst affected HRQoL dimensions. CONCLUSION: LLL adversely affects physical function, wellbeing and thus the HRQoL. The LYMQoL is the most commonly used questionnaire; despite this, all elements of the WHO recommendations were not captured in the included studies. However, accurate information on HRQoL indicating the impact of the disease on survivors' lives and complete wellbeing is needed to inform evidence-based decision-making. Furthermore, having a universally accepted, disease-specific methodology will facilitate comparison and contrasting of HRQoL in patients with LLL. DECLARATION OF INTEREST: The authors have no conflicts of interest.

ddRAD sequencing: an emerging technology added to the biosecurity toolbox for tracing the origin of brown marmorated stink bug, Halyomorpha halys (Hemiptera: Pentatomidae).

BACKGROUND: Brown marmorated stink bug (BMSB), Halyomorpha halys (Hemiptera: Pentatomidae) is native to East Asia but has invaded many countries in the world. BMSB is a polyphagous insect pest and causes significant economic losses to agriculture worldwide. Knowledge on the genetic diversity among BMSB populations is scarce but is essential to understand the patterns of colonization and invasion history of local populations. Efforts have been made to assess the genetic diversity of BMSB using partial mitochondrial DNA sequences but genetic divergence on mitochondria is not high enough to precisely accurately identify and distinguish various BMSB populations. Therefore, in this study, we applied a ddRAD (double digest restriction-site associated DNA) sequencing approach to ascertain the genetic diversity of BMSB populations collected from 12 countries (2 native and 10 invaded) across four continents with the ultimate aim to trace the origin of BMSBs intercepted during border inspections and post-border surveillance. RESULT: A total of 1775 high confidence single nucleotide polymorphisms (SNPs) were identified from ddRAD sequencing data collected from 389 adult BMSB individuals. Principal component analysis (PCA) of the identified SNPs indicated the existence of two main distinct genetic clusters representing individuals sampled from regions where BMSB is native to, China and Japan, respectively, and one broad cluster comprised individuals sampled from countries which have been invaded by BMSB. The population genetic structure analysis further discriminated the genetic diversity among the BMSB populations at a higher resolution and distinguished them into five potential genetic clusters. CONCLUSION: The study revealed hidden genetic diversity among the studied BMSB populations across the continents. The BMSB populations from Japan were genetically distant from the other studied populations. Similarly, the BMSB populations from China were also genetically differentiated from the Japanese and other populations. Further genetic structure analysis revealed the presence of at least three genetic clusters of BMSB in the invaded countries, possibly originating via multiple invasions. Furthermore, this study has produced novel set of SNP markers to enhance the knowledge of genetic diversity among BMSB populations and demonstrates the potential to trace the origin of BMSB individuals for future invasion events.

Health-related quality of life and associated factors in people with HIV: an Irish cohort study.

BACKGROUND: Considering the chronic and debilitating nature of HIV infection, health-related quality of life (HRQoL) is an important patient-reported clinical outcome to better understand the effects of this infection and its treatment on patients' lives. The purpose of this study was to assess the HRQoL and its association with sociodemographic, behavioural, clinical, nutrition-related factors and social support in an Irish HIV cohort. METHODS: A cross-sectional, prospective study using the Medical Outcomes Study HIV Health survey assessed the 10 dimensions of HRQoL and summarised as Physical Health Summary (PHS) and Mental Health Summary (MHS) scores. Participants were categorised as having good or poor PHS and MHS using the standardised mean score of 50. The variables independently associated with PHS and MHS were identified using multivariable logistic regression models. RESULTS: Overall, 521 participants completed the HRQoL questionnaire. The median (IQR) PHS and MHS scores were 56 (47-60) and 51 (41-58) respectively. All the covariate groups had lower MHS than PHS. Participants with symptoms of HIV reported the lowest median (IQR) PHS score 44.7 (32.-54.5) and MHS score 36.1 (28.6-48.4). Of the 10 dimensions of HRQoL, the lowest scores were for the energy level and general health. Symptoms of HIV, co-morbidities, social support, employment and ethnicity had independent association with both PHS and MHS. Gender, education, alcohol intake and HIV-complications were associated with PHS. Age, illicit drugs, BMI and malnutrition were associated with MHS. However, CD4 count and viral load were not independently associated with PHS and MHS in multivariable regression models. CONCLUSION: Overall, HIV-infected people in this cohort had an average level of HRQoL. However, it is impaired in people with symptoms and co-morbidities, and not independently associated with CD4 and viral load. Alleviating HIV symptoms and preventing co-morbidities are important in managing HIV. Providing psychosocial supports for behaviour modification and return to work or exploring new opportunities will help to improve HRQoL. Healthcare providers and policy makers need to plan and implement programs to routinely assess the HRQoL in a systematic method to facilitate a holistic management of HIV.

Direct healthcare costs in the first 2 years of life: A comparison of screened and clinically diagnosed children with cystic fibrosis - The Irish comparative outcomes study of CF (ICOS).

BACKGROUND: In July 2011, Cystic Fibrosis (CF) was added to the Newborn Bloodspot Screening Programme in Ireland. The Irish Comparative Outcomes Study (ICOS) is a historical cohort study established to compare outcomes between clinically-detected and screen-detected children with CF. Here we present the results of economic analysis comparing direct healthcare costs in the first 2 years of life of children born between mid-2008 and mid-2016, in the pre-CF transmembrane conductance regulator modulator era. METHODS: Healthcare resource use information was obtained from Cystic Fibrosis Registry of Ireland (CFRI), medical records and parental questionnaire. Hospital admissions, emergency department visits, outpatient appointments, antibiotics and maintenance medications were included. Costs were estimated using the Health Service Executive Casemix, Irish Medicines Formulary and hospital pharmacy data, adjusted for inflation using Consumer Price Index data from the Central Statistics Office. A Negative Binomial regression was used, with time in the study as an offset. RESULTS: Overall participation was 93 %. After exclusion of those with meconium ileus, data from 139 patients, with follow-up to 2 years of age, were available. 72 (51.8 %) were from the clinically diagnosed cohort. In the final model (n=105), clinically diagnosed children had 2.62-fold higher costs per annum (p<0.0001), when adjusted for confounders, including homozygous ΔF508 or G511D mutation, socio-demographic factors and time between diagnosis and first CFRI interaction. CONCLUSIONS: There are few studies evaluating economic aspects of newborn screening for CF using routine care data. These results imply that the benefits of newborn screening extend to direct healthcare costs borne by the State.

Acute on chronic exposure to endotoxin in preterm fetal sheep.

Acute, high-dose exposure to endotoxin lipopolysaccharide (LPS) in preterm fetal sheep can trigger periventricular white matter lesions (PVL), in association with severe hypotension/hypoxemia and significant mortality. Intriguingly, however, chronic or repeated exposure to LPS can induce tachyphylaxis. We therefore tested the hypothesis that progressive, acute on chronic fetal infection would be associated with white matter injury with little fetal mortality. Chronically instrumented preterm (0.7 gestational age) fetal sheep were exposed to a continuous low-dose LPS infusion (100 ng over 24 h, followed by 250 ng/24 h for 96 h) or saline. Boluses of 1 µg LPS or saline were given at 48, 72, and 96 h; sheep were killed at day 10. Six of 11 fetal sheep exposed to saline infusion + LPS boluses died 4-7 h after the first bolus. In contrast, there was no fetal mortality after saline infusions alone (n = 9), low-dose LPS infusion + saline boluses (n = 5), or low-dose LPS + LPS boluses (n = 9). Low-dose LPS infusion + LPS boluses was associated with greater microglial induction than low-dose LPS + saline boluses but a similar area of periventricular white matter inflammation. One fetus developed severe focal white matter necrosis after LPS infusion + boluses. The acute cardiovascular compromise associated with high-dose, acute exposure to LPS is markedly attenuated by previous low-dose infusions, with limited apparent exacerbation of periventricular white matter injury compared with low-dose infusion alone.

What is the impact of daily oral supplementation of vitamin D3 (cholecalciferol) plus calcium on the incidence of hip fracture in older people? A systematic review and meta-analysis.

INTRODUCTION: Hip fractures have a huge impact in reducing the quality of life and increasing mortality. This review aims to assess the impact of daily oral supplementation of vitamin D3 plus calcium on the incidence of hip fracture in people over 65 years. METHODS: PRISMA guidelines were followed and RCTs that evaluated the effectiveness of daily oral supplementation of vitamin D3 plus calcium in preventing hip fracture in adults over 65 years were included in the study. The databases such as Cochrane Library, Embase, Medline, PubMed, CINAHL, Web of Science and Scopus were searched from October 2019- January 2020.The Cochrane risk of bias tool was used to check the quality of the included studies. A meta-analysis with fixed effect model using Review Manager (Revman 5.3) was used to analyse the data. RESULTS: The meta-analysis of seven RCTs on vitamin D3 plus calcium supplementation and hip fracture (n = 12,620) identified odds ratio (OR) of 0.75; 95% Confidence interval (CI): 0.64, 0.87; p = .0003. Daily oral supplementation of 800 IU of Vitamin D3 plus 1200 mg of calcium was found more effective (n = 5676 participants; OR = 0.69; 95% CI: 0.58, 0.82; p < .0001) than daily oral supplementation of 800 IU of Vitamin D3 plus 1000 mg of calcium (n = 6555,OR = 1.08; 95% CI: 0.74, 1.56; p = .70) in reducing hip fracture. A meta-analysis of the seven RCTs to identify the incidence of non-vertebral fracture gave the OR of 0.80; 95% CI: 0.72, 0.89; p < .0001. A meta-analysis of three RCTs on femoral neck bone mineral density (BMD) (n = 483) gave a mean difference of 1.21; 95% CI: -0.79, 3.20; p = .24. CONCLUSION: Daily oral supplementation 800 IU of vitamin D3 plus 1200 mg of calcium reduces hip fracture and non-vertebral fracture in older people. Administering vitamin D3 and calcium supplements had no effect in increasing the femoral neck BMD. IMPLICATIONS FOR PRACTICE: Even though it is evident from the review that optimal daily intake of vitamin D3 plus calcium supplementation help in the prevention of fracture, it is only one essential element in fracture prevention. Also, people who are on dietary supplements should be compliant with same for better result. Efforts to prevent bone loss and osteoporosis should begin from an early age. It includes maintaining a healthy lifestyle, optimal intake of calcium and vitamin D3, proper nutrition, adequate exposure to sunlight, exercise etc. Proper education on healthy lifestyle, avoiding risk factors like smoking, caffeine, alcohol and awareness of bone health should continue throughout life with emphasis during menopause when increased bone loss is expected.

Nonadditive neuroprotection with early glutamate receptor blockade and delayed hypothermia after asphyxia in preterm fetal sheep.

BACKGROUND AND PURPOSE: Hypothermia induced after perinatal hypoxia-ischemia is partially protective. This study examined whether early treatment with the noncompetitive N-methyl-d-aspartate receptor antagonist, dizocilpine, can augment neuroprotection with delayed hypothermia after severe asphyxia in preterm fetal sheep at 0.7 weeks gestation (equivalent to 28-32 weeks in humans). METHODS: Fifty minutes after umbilical cord occlusion for 25 minutes, fetuses were randomized to either dizocilpine (2 mg/kg estimated fetal weight intravenously, then 0.07 mg/kg/h for 4 hours) and then after 5.5 hours to whole-body cooling to 3°C below baseline, or sham cooling, until 72 hours, and euthanized 7 days after umbilical cord occlusion. RESULTS: Delayed hypothermia was associated with improved neuronal survival (P<0.02) and reduced microglia (P=0.004) and caspase-3-positive cells (P<0.01) compared with umbilical cord occlusion. Dizocilpine was associated with reduced microglia (P<0.05) but no effect on caspase-3 induction and improved survival only in CA1/2 (P<0.05) with no apparent additive effect with delayed hypothermia. CONCLUSIONS: Early N-methyl-d-aspartate blockade and a clinical regime of delayed whole-body hypothermia provide nonadditive neuroprotection in the preterm brain.

Caloric Vestibular Stimulation Induced Enhancement of Behavior and Neurotrophic Factors in Chronic Mild Stress Induced Rats.

Background: Caloric Vestibular Stimulation (CVS) is a non-invasive technique for stimulating the vestibular system. The vestibular system maintains equilibrium and acts as a moderator of mood, emotional control, and stress levels. Stress is a disruption of psychological, behavioral, and physiological homeostasis that affects people of all ages in today's world. Thus, modest therapeutic procedures like vestibular stimulation can be practiced to effectively reduce stress. Hence, the purpose of the study was to determine the effect of vestibular stimulation on improving behavioral alterations and neurotrophic factors in rats exposed to Chronic Mild Stress (CMS). Methodology: The study employed 24 healthy male Sprague Dawley rats divided into four groups (n = 6). CMS was induced for 28 days with a variety of stimuli. Bilateral CVS with hot water (temperature ≈40°C) was started on Day 14 of CMS and continued for 15 days. On days 1, 15, and 28, locomotor activity (LA), wire grip strength (WGS), fall off time (FT), and immobilization time (IT) were measured, and the data were analyzed statistically. Additionally, neurotrophic factors such as Brain Derived Neurotrophic Factor (BDNF) and Glial cell line-Derived Neurotrophic Factor (GDNF) were observed in rats' hippocampus. Results: On days 15 and 28, the CMS-induced group showed a significant reduction in LA, WGS, FT and IT in comparison to the control group. On day 28, the CVS-induced group demonstrated a significant increase in WGS, FT and IT when compared to the CMS group. Immunohistochemical analysis revealed that animals subjected to CMS had decreased BDNF and GDNF expression compared to the control group, indicating neuronal dysfunction in the hippocampus in response to stress. However, therapy with CVS increased BDNF and GDNF expression, thereby regenerating damaged hippocampus nerve terminals. Conclusion: The findings of the current study revealed that CVS is a safe and simple neuroprotective treatment against stress and a promising non-invasive technique for overcoming the motor symptoms associated with it. The findings may pave the way for future research and therapeutic applications of CVS for stress management.

Maternal dexamethasone and EEG hyperactivity in preterm fetal sheep.

Maternal treatment with synthetic corticosteroids such as dexamethasone (DEX)significantly reduces neonatal morbidity and mortality, but its effects on the fetal brain remain unclear. In this study we evaluated the effects of DEX on EEG activity in preterm fetal sheep. Ewes at 103 days gestation received two intramuscular injections of DEX (12 mg, n = 8) or saline vehicle (n = 7) 24 h apart. Fetal EEG activity was recorded from 6 h before until 120 h after the first injection (DEX-1). DEX-1 was associated with a marked transient rise in total EEG power, maximal at 12 h (P < 0.001), with a relative increase in delta and reduced theta, alpha and beta activity, resolving by 24 h. Continuous EEG records showed a shift to larger but less frequent transient waveforms (P < 0.001). Unexpectedly, evolving epileptiform activity, consistent with electrographic and clinical seizures, developed from 178 ± 44 min after DEX-1.Similar but smaller changes were seen after the second injection. Following the injections, total power returned to control values, but the proportion of alpha activity progressively increased vs. controls (P < 0.001), with reduced interburst interval duration and number (P < 0.001). No histological neural injury or microglial activation was seen. In summary, exposure to maternal dexamethasone was associated with dramatic, evolving low-frequency hyperactivity on fetal cortical EEG recordings, followed by sustained changes consistent with maturation of fetal sleep architecture. We postulate that these effects may contribute to improved neonatal outcomes.

Pitfalls in the quest of neuroprotectants for the perinatal brain.

Sick preterm and term newborns are highly vulnerable to neural injury, and thus there has been a major search for new, safe and efficacious neuroprotective interventions in recent decades. Preclinical studies are essential to select candidate drugs for clinical trials in humans. This article focuses on 'negative' preclinical studies, i.e. studies where significant differences cannot be detected. Such findings are critical to inform both clinical and preclinical investigators, but historically they have been difficult to publish. A significant amount of time and resources is lost when negative results or nonpromising therapeutics are replicated in separate laboratories because these negative results were not shared with the research community in an open and accessible format. In this article, we discuss approaches to strengthen conclusions from negative preclinical studies and, conversely, to reduce false-negative preclinical evaluations of potential therapeutic compounds. Without being exhaustive, we address three major issues in conducting and interpreting preclinical experiments, including: (a) the choice of animal models, (b) the experimental design, and (c) issues concerning statistical analyses of the experiments. This general introduction is followed by synopses of negative data obtained from studies of three potential therapeutics for perinatal brain injury: (1) the somatostatin analog octreotide, (2) an AMPA/kainate receptor antagonist, topiramate, and (3) a pyruvate derivative, ethyl pyruvate.

Differential activity and expression of human 5ß-reductase (AKR1D1) splice variants.

Steroid hormones, including glucocorticoids and androgens, exert a wide variety of effects in the body across almost all tissues. The steroid A-ring 5ß-reductase (AKR1D1) is expressed in human liver and testes, and three splice variants have been identified (AKR1D1-001, AKR1D1-002, AKR1D1-006). Amongst these, AKR1D1-002 is the best described; it modulates steroid hormone availability and catalyses an important step in bile acid biosynthesis. However, specific activity and expression of AKR1D1-001 and AKR1D1-006 are unknown. Expression of AKR1D1 variants were measured in human liver biopsies and hepatoma cell lines by qPCR. Their three-dimensional (3D) structures were predicted using in silico approaches. AKR1D1 variants were overexpressed in HEK293 cells, and successful overexpression confirmed by qPCR and Western blotting. Cells were treated with either cortisol, dexamethasone, prednisolone, testosterone or androstenedione, and steroid hormone clearance was measured by mass spectrometry. Glucocorticoid and androgen receptor activation were determined by luciferase reporter assays. AKR1D1-002 and AKR1D1-001 are expressed in human liver, and only AKR1D1-006 is expressed in human testes. Following overexpression, AKR1D1-001 and AKR1D1-006 protein levels were lower than AKR1D1-002, but significantly increased following treatment with the proteasomal inhibitor, MG-132. AKR1D1-002 efficiently metabolised glucocorticoids and androgens and decreased receptor activation. AKR1D1-001 and AKR1D1-006 poorly metabolised dexamethasone, but neither protein metabolised cortisol, prednisolone, testosterone or androstenedione. We have demonstrated the differential expression and role of AKR1D1 variants in steroid hormone clearance and receptor activation in vitro. AKR1D1-002 is the predominant functional protein in steroidogenic and metabolic tissues. In addition, AKR1D1-001 and AKR1D1-006 may have a limited, steroid-specific role in the regulation of dexamethasone action.

Genetic diversity analysis of brown marmorated stink bug, Halyomorpha halys based on mitochondrial COI and COII haplotypes.

BACKGROUND: In the past decade, the brown marmorated stink bug (BMSB), Halyomorpha halys (Hemiptera: Pentatomidae) has caused extensive damage to global agriculture. As a high-risk pest for many countries, including New Zealand, it is important to explore its genetic diversity to enhance our knowledge and devise management strategies for BMSB populations. In this study, two mitochondrial genes, Cytochrome c oxidase I (COI) and Cytochrome c oxidase II (COII) were used to explore the genetic diversity among 463 BMSB individuals collected from 12 countries. RESULT: In total, 51 COI and 29 COII haplotypes of BMSB were found, which formed 59 combined haplotypes (5 reported and 54 novel). Of these, H1h1 was the predominant haplotype. The haplotype diversity (Hd) and nucleotide diversity (π) were high while the neutrality (Fu's Fs) values were negative for the BMSB populations in the native countries, China, and Japan. For the BMSB populations from the invaded countries, the Fu's Fs values were negative for populations from Chile, Georgia, Hungary, Italy, Romania, Turkey, and USA, indicating that those populations are under demographic expansion. In comparison, the Fu's Fs values were positive for the populations from Austria, Serbia, and Slovenia, revealing a potential population bottleneck. Analysis of molecular variance (AMOVA) suggested that significant genetic difference exists among the BMSB populations from China, Japan, and the invasive countries. CONCLUSION: This study revealed that the haplotype diversity of the BMSB populations was high in those two studied countries where BMSB is native to (China and Japan) but low in those countries which have been invaded by the species. The analysis indicated that multiple invasions of BMSB occurred in Europe and the USA. The study also revealed three ancestral lines and most of the novel haplotypes were evolved from them. Moreover, we observed two genetic clusters in the invasive populations that are formed during different invasion events. Our study provided a comprehensive overview on the global haplotypes distribution thus expanding the existing knowledge on BMSB genetic diversity that potentially could play an important role in formulating feasible pest management strategies.

A biosecurity response to Aedes albopictus (Diptera: Culicidae) in Auckland, New Zealand.

A biosecurity response was triggered by the detection of Aedes albopictus (Skuse) (Diptera: Culicidae) at the Port of Auckland, New Zealand. Ae. albopictus does not occur in New Zealand and is the most significant mosquito threat to this country. The possibility that a founding population had established, resulted in a large-scale biosecurity surveillance and control program. The response was initiated in early March 2007 and completed by mid-May 2007. No further exotic mosquitoes were detected. The response surveillance program consisted of larval habitat surveys and high density ovi- and light trapping. It was coordinated with a habitat modification and S-methoprene treatment control program. The response policies were guided by analysis of surveillance and quality assurance data, population modeling, and trace-back activities. Mosquito habitat and activity close to port were both more abundant than expected, particularly in storm water drain sumps. Sumps are difficult to treat, and during the response some modification was required to the surveillance program and the control regime. We were assured of the absence or eradication of any Ae. albopictus population, as a result of nil detection from surveillance, backed up by four overlapping rounds of insecticide treatment of habitat. This work highlights the importance of port surveillance and may serve as a guide for responses for future urban mosquito incursions.

Ontogenetic stages of Oulenziella bakeri (Hughes) (Acari: Winterschmidtiidae).

The ontogenetic stages of mite family Winterschmidtiidae are rarely studied. Here we provide detailed descriptions and illustrations of all developmental stages of Oulenziella bakeri (Hughes). A comparison of the idiosomal and leg chaetotaxy of all stages are presented. New data on hosts and distribution of O. bakeri are provided.

Life stages and phylogenetic position of the wool carder bee mite Sennertionyx manicati (Acari: Acaridae).

In mites of the family Acaridae, usually two developmental stages, adult (males, females) and deutonymphal stage (=hypopus) are used for diagnostic descriptions. Because these taxonomically important stages live in different habitats (i.e. deutonymphs are phoretic on a hymenopteran host, while adults live inside the nest of the host), one of these can be missing or they cannot be confidently corelated with each other. Sennertionyx manicati (Acari: Acaridae) was only known from hypopus. Herein, we describe all post-embryonic stages of S. manicati based on material obtained from a nest of Anthidium manicatum in Auckland, New Zealand, and provide a key to all life stages of this species. We also conducted a phylogenetic analysis of the 18S gene and the D2/D3 region of 28S genes from field-collected specimens and GenBank data. The molecular analysis indicated the New Zealand specimen shared the identical 18S and 99.5% identity of the D2D3 region of 28S sequences with S. manicati from Italy, and clustered together in the phylogenetic trees.

Natal origin of the invasive biosecurity pest, brown marmorated stink bug (Halyomorpha halys: Penatomidae), determined by dual-element stable isotope-ratio mass spectrometry.

BACKGROUND: Post-border detection of a single brown marmorated stink bug (BMSB) in New Zealand warranted a biosecurity response, the nature of which would be influenced by its status as part of an established population or as a new arrival. Stable isotope analysis has the potential to determine natal origins, but is difficult to achieve for samples as small as a single insect. Here an analytical modification to measure small samples was successfully trialled as a means to supply evidence as to the local or exotic natal origin of the intercepted BMSB specimen. RESULTS: Sufficient analytical sensitivity was achieved using a modified isotope ratio mass spectrometry method, involving thermolysis and carbon monoxide cryofocusing, to enable the simultaneous analysis of δ2 H and δ18 O from wings of the post-border BMSB sample. The values were much lower than those of the New Zealand green vegetable bug, used as a local reference. However, they fell within the range of those for BMSB of Northern Hemisphere origin intercepted at the New Zealand border over the same time period, specifically overlapping with the USA and Italy, but not China. CONCLUSION: The isotope signature of the post-border detected BMSB suggested a significantly cooler climate than the North Island of New Zealand, indicating that it was a new arrival and did not represent an established population. © 2019 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Neonatal screening programme for CF: Results from the Irish Comparative Outcomes Study (ICOS).

The introduction of NBS in Ireland in July 2011, provided a unique opportunity to investigate clinical outcomes using a comparative historical cohort study. Clinical cohort: children clinically diagnosed with CF born 1 July 2008 to 30 June 2011, and NBS cohort: children diagnosed with CF through NBS born 1 July 2011 to 30 June 2016. Clinical data were collected from the CF Registry of Ireland, medical charts, and data on weight/height before diagnosis from public health nurses and family doctors. SPSS was used for analysis. A total of 232 patients were recruited (response 93%) (93 clinically diagnosed, 139 NBS-detected). Following exclusions of meconium ileus (MI) (40), diagnosis outside Ireland (4), and being designated as CFSPID (2), a total of 77 clinically diagnosed patients and 109 NBS detected children were included in analysis. Over half were homozygous for F508del mutation. Being clinically diagnosed was independently associated with hospitalization for infective exacerbation of CF < 36 months (OR, 2.80; 95%CI 1.24-6.29). Diagnosis to first acquisition of Pseudomonas aeruginosa was significantly longer in NBS than clinically detected; from birth there was no significant difference. Weight and length/height were significantly greater in NBS cohort at 6 and 12 months. We provide evidence of improved growth, reduced hospitalization for acute exacerbations, and delayed P. aeruginosa acquisition (from diagnosis) to age 3 for the NBS cohort. Screening practices likely account for the non-significant difference in P. aeruginosa acquisition from birth.

Glucocorticoids regulate AKR1D1 activity in human liver in vitro and in vivo.

Steroid 5ß-reductase (AKR1D1) is highly expressed in human liver where it inactivates endogenous glucocorticoids and catalyses an important step in bile acid synthesis. Endogenous and synthetic glucocorticoids are potent regulators of metabolic phenotype and play a crucial role in hepatic glucose metabolism. However, the potential of synthetic glucocorticoids to be metabolised by AKR1D1 as well as to regulate its expression and activity has not been investigated. The impact of glucocorticoids on AKR1D1 activity was assessed in human liver HepG2 and Huh7 cells; AKR1D1 expression was assessed by qPCR and Western blotting. Genetic manipulation of AKR1D1 expression was conducted in HepG2 and Huh7 cells and metabolic assessments were made using qPCR. Urinary steroid metabolite profiling in healthy volunteers was performed pre- and post-dexamethasone treatment, using gas chromatography-mass spectrometry. AKR1D1 metabolised endogenous cortisol, but cleared prednisolone and dexamethasone less efficiently. In vitro and in vivo, dexamethasone decreased AKR1D1 expression and activity, further limiting glucocorticoid clearance and augmenting action. Dexamethasone enhanced gluconeogenic and glycogen synthesis gene expression in liver cell models and these changes were mirrored by genetic knockdown of AKR1D1 expression. The effects of AKR1D1 knockdown were mediated through multiple nuclear hormone receptors, including the glucocorticoid, pregnane X and farnesoid X receptors. Glucocorticoids down-regulate AKR1D1 expression and activity and thereby reduce glucocorticoid clearance. In addition, AKR1D1 down-regulation alters the activation of multiple nuclear hormone receptors to drive changes in gluconeogenic and glycogen synthesis gene expression profiles, which may exacerbate the adverse impact of exogenous glucocorticoids.

Partial neuroprotection with low-dose infusion of the alpha2-adrenergic receptor agonist clonidine after severe hypoxia in preterm fetal sheep.

We have previously shown that brief alpha(2)-adrenergic receptor blockade increased neuronal injury after severe hypoxia in preterm fetal sheep. We now examine whether infusion of an alpha(2)-adrenergic receptor agonist, clonidine, is neuroprotective. Preterm fetal sheep (70% gestation) received either saline-vehicle or clonidine at either 10 microg/kg/h (low-dose) or 100 microg/kg/h (high-dose) from 15 min until 4 h after 25 min of umbilical cord occlusion. Both low- and high-dose clonidine infusions after sham-occlusion were associated with transient EEG suppression but no neuronal loss. Low-dose but not high-dose clonidine infusions after umbilical cord occlusion were associated with a significant overall increase in numbers of surviving neurons after three days' recovery. High-dose clonidine was associated with transient hyperglycemia and increased numbers of delayed electrographic seizures. These results provide further evidence that alpha(2)-adrenergic receptor activation shortly after perinatal hypoxia-ischemia can promote neural recovery, but highlight the complex dose-response of exogenous therapy.

Molecular detection of small hive beetle Aethina tumida Murray (Coleoptera: Nitidulidae): DNA barcoding and development of a real-time PCR assay.

Small hive beetle (SHB), Aethina tumida can feed on honey, pollen and brood in honey bee colonies. It was endemic to Africa, but since 1996 has been detected in a number of countries worldwide, including Australia, Brazil, Canada, Italy, Mexico, South Korea, Philippines and the USA where it has had economic effects on local apiculture. To improve SHB identification, we obtained the first reference sequences from the DNA barcoding 5' COI gene region for SHB and some species of the family Nitidulidae associated with beehives. Phylogenetic analysis of SHB COI sequences (3' COI) revealed two divergent lineages, with those from Australia and USA being genetically different from the recent detection in Italy. Many countries, including New Zealand, are currently free from SHB, and require a rapid detection method for biosecurity. Here we present the development and validation of a real-time PCR assay for detection of SHB. The assay showed high specificity and sensitivity for detecting SHB, with no cross-reaction observed with closely related species, such as A. concolor. The real-time PCR is sensitive, detecting the target sequences up to 100 copies/µL. This assay should prove a useful biosecurity tool for rapid detection of SHB worldwide.