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Microsampling allows the collection of blood samples using a method which is inexpensive, simple and minimally-invasive, without the need for specially-trained medical staff. Analysis of whole blood provides a more holistic understanding of per- and polyfluoroalkyl substances (PFAS) body burden. Capillary action microsamplers (Trajan hemaPEN®) allow the controlled collection of whole blood as dried blood spots (DBS) (four 2.74 µL ± 5 %). The quantification of 75 PFAS from DBS was evaluated by comparing five common extraction techniques. Spiked blood (5 ng/mL PFAS) was extracted by protein precipitation (centrifuged; filtered), acid-base liquid-liquid extraction, trypsin protease digestion, and weak anion exchange (WAX) solid-phase extraction with analysis by high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Filtered protein precipitation was the most effective extraction method, recovering 72 of the 75 PFAS within 70 to 130 % with method reporting limit (MRL) for PFOS of 0.17 ng/L and ranging between 0.05 ng/mL and 0.34 ng/mL for all other PFAS. The optimised method was applied to human blood samples to examine Inter- (n = 7) and intra-day (n = 5) PFAS blood levels in one individual. Sixteen PFAS were detected with an overall Σ 16 PFAS mean = 6.3 (range = 5.7-7.0) ng/mL and perfluorooctane sulfonate (branched and linear isomers, ΣPFOS) = 3.3 (2.8-3.7) ng/mL being the dominant PFAS present. To the authors knowledge, this minimally invasive self-sampling protocol is the most extensive method for PFAS in blood reported and could be a useful tool for large scale human biomonitoring studies., Competing Interests: Declaration of Competing Interest Human blood was voluntarily self-sampled with informed consent by a member of the research cohort, in compliance with The University of Melbourne Research Ethics and Biorisk Management Policy (MPF1341) and the Australian Government National Statement on Ethical Conduct in Human Research (2007). Ethics approval was gained through the University of Melbourne STEMM 1 Human Research Ethics Committee (2023-25725-44910-3). The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Some types of poultry bedding made from recycled materials have been reported to contain environmental contaminants such as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs, dioxins), polychlorinated biphenyls (PCBs) brominated flame retardants (BFRs) polychlorinated naphthalenes (PCNs), polybrominated dioxins (PBDD/Fs), perfluoroalkyl substances (PFAS), etc. In one of the first studies of its kind, the uptake of these contaminants by chicken muscle tissue, liver, and eggs from three types of recycled, commercially available bedding material was simultaneously investigated using conventional husbandry to raise day old chickens to maturity. A weight of evidence analysis showed that PCBs, polybrominated diphenylethers (PBDEs), PCDD/Fs, PCNs and PFAS displayed the highest potential for uptake which varied depending on the type of bedding material used. During the first three to four months of laying, an increasing trend was observed in the concentrations of ΣTEQ (summed toxic equivalence of PCDD/Fs, PCBs, PBDD/Fs, PCNs and polybrominated biphenyls), NDL-PCBs and PBDEs in the eggs of chickens raised on shredded cardboard. Further analysis using bio-transfer factors (BTFs) when egg production reached a steady state, revealed that some PCB congeners (PCBs 28, 81, 138, 153 and 180) irrespective of molecular configuration or chlorine number, showed the highest tendency for uptake. Conversely, BTFs for PBDEs showed good correlation with bromine number, increasing to a maximum value for BDE-209. This relationship was reversed for PCDFs (and to some extent for PCDDs) with tetra- and penta- chlorinated congeners showing a greater tendency for selective uptake. The overall patterns were consistent, although some variability in BTF values was observed between tested materials which may relate to differences in bioavailability. The results indicate a potentially overlooked source of food chain contamination as other livestock products (cow's milk, lamb, beef, duck, etc.) could be similarly impacted., Competing Interests: Declaration of competing interest The authors assert that they have no conflict of interest (financial or non-financial) in the subject matter discussed in this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We investigated how the biodistribution of cannabidiol (CBD) within the central nervous system (CNS) is influenced by two different formulations, an oil-in-water (O/W) nanoemulsion and polymer-coated nanoparticles (PCNPs). We observed that both CBD formulations administered were preferentially retained in the spinal cord, with high concentrations reaching the brain within 10 min of administration. The CBD nanoemulsion reached C max in the brain at 210 ng/g within 120 min (T max ), whereas the CBD PCNPs had a C max of 94 ng/g at 30 min (T max ), indicating that rapid brain delivery can be achieved through the use of PCNPs. Moreover, the AUC 0 - 4 h of CBD in the brain was increased 3.7-fold through the delivery of the nanoemulsion as opposed to the PCNPs, indicating higher retention of CBD at this site. Both formulations exhibited immediate anti-nociceptive effects in comparison to the respective blank formulations., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Context: The COVID-19 pandemic has highlighted variability in intensity of care. We aimed to characterize intensity of care among hospitalized patients with COVID-19., Objectives: Examine the prevalence and predictors of admission code status, palliative care consultation, comfort-measures-only orders, and cardiopulmonary resuscitation (CPR) among patients hospitalized with COVID-19., Methods: This cross-sectional study examined data from an international registry of hospitalized patients with COVID-19. A proportional odds model evaluated predictors of more aggressive code status (i.e., Full Code) vs. less (i.e., Do Not Resuscitate, DNR). Among decedents, logistic regression was used to identify predictors of palliative care consultation, comfort measures only, and CPR at time of death., Results: We included 29,923 patients across 179 sites. Among those with admission code status documented, Full Code was selected by 90% (n = 15,273). Adjusting for site, Full Code was more likely for patients who were of Black or Asian race (ORs 1.82, 95% CIs 1.5-2.19; 1.78, 1.15-3.09 respectively, relative to White race), Hispanic ethnicity (OR 1.89, CI 1.35-2.32), and male sex (OR 1.16, CI 1.0-1.33). Of the 4951 decedents, 29% received palliative care consultation, 59% transitioned to comfort measures only, and 29% received CPR, with non-White racial and ethnic groups less likely to receive comfort measures only and more likely to receive CPR., Conclusion: In this international cohort of patients with COVID-19, Full Code was the initial code status in the majority, and more likely among patients who were Black or Asian race, Hispanic ethnicity or male. These results provide direction for future studies to improve these disparities in care., (Copyright © 2022 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this scoping review was to outline the extent of available literature including the prevalence of video quality appraisal tools, characterize how online videos were used, and identify the gaps in the literature with implications for future research., Design: The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for scoping reviews (PRISMA-ScR). Six databases were searched: (1) MEDLINE (Ovid), (2) EMBASE, (3) Cochrane, (4) ERIC, (5) CINAHL PLUS, and (6) Google Scholar for Medical Subject Headings terms online videos, postgraduate health education, and health professional/s., Results: A total of 6948 articles were identified, of which 78 were included in the review. The articles included were primarily either experimental or observational studies, with most being from North America. Twelve concepts were identified: (1) procedural skills teaching; (2) video assessment; (3) validation of an assessment tool; (4) video feedback; (5) coaching; (6) broadcasting; (7) learner characteristics; (8) video characteristics; (9) video quality; (10) a quality assessment tool; (11) platforms and video library; and (12) health information governance., Conclusions: While there is a diverse and growing body of literature on this area, information is lacking about the quality appraisal of online videos., (Copyright © 2022 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To examine dispensed opioid prescription patterns for limb fractures across racial/ethnic groups in a pediatric population., Methods: We used South Carolina's Medicaid claims data 2000 to 2018 for pediatric limb fracture cases (under age 19) discharged from the emergency department. The key independent variable was the child's race/ethnicity. The outcomes were: 1) whether the patient had a dispensed opioid prescription; and 2) whether dispensed opioid supply was longer than 5 days among cases with any dispensed opioid prescriptions. Logistic regression models were used to test the association between race/ethnicity and the outcomes. Covariates included age-at-service, gender, service year, and having multiple fracture injuries., Results: Compared with non-Hispanic White cases (NHW), the odds of receiving dispensed opioid prescriptions were lower for cases of non-Hispanic Black (NHB) (OR = 0.73; 95% confidence interval [CI]: 0.71, 0.75), Asian (OR = 0.69; CI: 0.53, 0.90), Other/Unknown (OR = 0.86; CI: 0.80, 0.92), and Hispanic (OR = 0.84; CI: 0.79, 0.90) race/ethnicity. The odds of receiving >5 days of dispensed opioid prescription supply did not differ significantly among race/ethnic categories., Conclusions: Our study confirms previous findings that as compared to NHW, the NHB children were less likely to receive dispensed opioid prescriptions. Also, it reveals that the different minority race/ethnic groups are not homogenous in their likelihoods of receiving dispensed opioid prescriptions after a limb fracture compared to NHW, findings underreported in previous studies. Children in the Other/Unknown race/ethnicity category have prescribing patterns different from those of other minority race/ethnic groups and should be analyzed separately., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: Conducting a systematic country-level workforce needs-assessment is a way to develop coherent strategic and justifiable workforce planning., Objective(s): This article describes a country-level needs-assessment process using a systematic approach (via the FIP Development Goals (FIP DGs) workforce element) as an analytical framework. The needs-assessment aimed to prioritise gaps toward transforming the pharmacy workforce as a prelude to practice and pharmaceutical services reform in Indonesia., Methods: The needs assessment consisted of three stages: needs identification, needs analysis, and needs prioritisation. The needs (workforce development gaps) were defined as the discrepancies between the perceived workforce challenges and the existing national workforce development projects. Interviews or group discussions were conducted to gather the workforce challenges of individual pharmacists. A structured workshop was conducted to identify workforce challenges and existing organisations' projects, with main stakeholders contributing to pharmacists' development in Indonesia. Perceived challenges findings and identified national workforce projects were mapped to the FIP DGs workforce element. The needs prioritisation was conducted by comparing the proportional mapping to the FIP DGs workforce element., Results: There were forty-three individual pharmacists and 7 principal stakeholder categories that provided information related to perceived workforce challenges; thirty national projects were identified from stakeholders. While this study identified perceived challenges with workforce "competency development" and "pharmacy workforce intelligence," there were no active ongoing national projects mapped to those goals. The framework mapping analysis showed there are workforce development gaps centred on "competency development" initiatives, "advanced and specialist development" initiatives, and strategic pharmacy workforce intelligence data gathering. Additionally, there were policy gaps with initiatives for strengthening "working with others" and a lack of clarity on infrastructure for early-career training strategies and workforce impact., Conclusions: This study prioritises the gaps in developing pharmacists in Indonesia. This process could be used in conducting needs assessment of pharmacy workforce development in other Low and Middle-Income Countries (LMICs)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Systematic education and training strategies play a critical role in preparing a competent pharmacy workforce to meet the evolving healthcare needs of nations. Reports have shown that investing in healthcare workers' education and training not only has a positive impact on employment rates and economic growth but also results in measurable improvement in health and population outcomes. The goal of this study was to evaluate the use of globally validated workforce goals as a guide to the planning and advancement of the Kuwait pharmacy workforce's education and training., Methods: A mixed-approach qualitative study involving representatives of key stakeholders was conducted. Focus group interviews were carried out with pharmacists with patient and non-patient facing roles (N = 33). In addition, semi-structured interviews with the three main pharmacy Continuing Professional Development (CPD) providers in the country were conducted. Data were analysed using a framework analysis method. Interviews were transcribed verbatim and data were analysed and coded using MAXQDA-12. The International Pharmaceutical Federation Workforce Development Goals (FIP WDGs) were used as the framework for data analysis., Results: Participants' responses highlighted three main priorities: the importance of initial and post-graduation needs-based education (WDG 2), the need for competency development and competency frameworks (WDG 5), and the crucial role of active policy and regulations that would enforce the profession development (WDG 9). Investing in competency development was seen the top priority for the pharmacy workforce in Kuwait., Conclusion: This study provided insights into areas in need of systematic development for pharmacy workforce in Kuwait including foundation training for early career pharmacists, competency development and competency frameworks, and policies and regulations that would enforce the profession development. In addition, the use of the FIP WDGs framework was found to offer a framing device to better understand and identify priorities and needs for pharmacy workforce development., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: With current accelerated changes in the role of the pharmacists across different sectors, evidence-based developmental tools are needed to re-define the scope of practice for early career pharmacists (foundation level) and to support pharmacists' career development. This study aimed to develop a foundation competency framework for pharmacists in Kuwait using the International Pharmaceutical Federation (FIP) Global Competency Framework (GbCF) in an adopt and adapt approach., Methods: A 4-phase adopt and adapt approach was followed to develop the Kuwait Foundation Competency Framework (KFCF). Phase one involved translating the FIP GbCF, into Arabic using parallel translation. Phase two utilises 2 consensus panels validation involving pharmacists from public and private sectors. Phase three involved a national survey to all registered pharmacists in Kuwait. The final phase involved focus groups with pharmacists and a consensus panel validation with key policy and decision makers in the pharmacy practice and education sectors in Kuwait. Qualitative data were thematically analysed, while quantitative data were analysed using IBM SPSS Statistics for Windows., Results: The translation phase yielded a bilingual framework that could be utilised by pharmacists in Kuwait. The initial validation phase identified 70 behavioural statements (out of the GbCF's 100) as 'highly relevant' or 'relevant' to pharmacy practice in Kuwait. Findings from the national survey identified a list of behaviours that could be adapted in Kuwait context as well as competencies that were perceived as least relevant to Kuwait practice. The final validation phase generated a list of 98 behavioural statements to be included in the KFCF along with recommendations and an action plan to facilitate the adaptation of the framework., Conclusion: This study presents the first bilingual (Arabic/English) pharmacy foundation competency framework that builds on the FIP GbCF. The KFCF could be utilised as a developmental tool to support pharmacists' performance at foundation level., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Changes to the pharmacy profession have meant that a pharmacy degree can no longer serve as an endpoint to professional training within pharmacy. Continuing learning and training are imperative in order to provide high-quality healthcare services. Investing in healthcare workers' education and training not only has a positive impact on employment rates and economic growth but also results in remarkable improvement in health and population outcomes., Objectives: To identify factors affecting pharmacists' participation in Continuing Education (CE) or Continuing Professional Development (CPD) activities., Methods: Relevant literature was identified through a systematic search of the following databases: EMBASE, (CINAHL Plus, SCOPUS, PsysINFO, PubMed, Australian Education Index (AEI) and British Education Index (BEI)., Results: Two hundred eighty-seven studies were screened, and thirty-two studies were included in this review. Reviewing the retrieved studies identified four factors that may influence pharmacists' participation in professional development activities. Factors identified comprised: attitudes, access to needs-based education, support, and policy., Conclusion: Understanding the connection between needs-based education, systems of support, and professional policies may help leaders and policy makers to make more informed decisions with regards to pharmacy workforce development by creating better strategies for pharmacists' education, training, and career development., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To explore health care providers' communication practices during contraceptive counseling for women with substance use disorders (SUDs)., Study Design: In 2019, we conducted semi-structured phone interviews with a purposive sample of medical doctors and advanced practice nurses (n = 24). A two-member team analyzed these interviews for themes using deductive and inductive techniques and ATLAS.ti to manage the data., Results: Providers discussed that developing strong interpersonal relationships and trust is critically important to provide effective contraceptive counseling to women with SUDs. Providers reported exchanging information with patients by asking open-ended questions, tailoring discussions to patients' responses, and being direct but not judgmental. To facilitate contraceptive decision-making, providers described eliciting patients' preferences for contraceptive methods while simultaneously using their own clinical judgment and professional experience to identify which methods would be most effective and appropriate for their patients. Most often these were long-acting reversible contraceptive methods, and providers emphasized the benefits of these methods for women with SUDs., Conclusion: Providers used a variety of communication strategies, some of which were grounded in the principles of patient-centered care and others that were directive, to discuss contraception with women with SUDs., Implications: Because of past and ongoing stigma and discrimination by health care professionals and the general public, women with SUDs may be distrustful of contraceptive providers. Patient-centered contraceptive counseling may be an effective approach to increase trust and improve relationships and communication between women with SUDs and their providers. Additional research with women with SUDs is needed to understand women's experiences with and preferences for patient-provider communication during contraceptive counseling., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Literature data on the occurrence and prevalence of polybrominated dibenzo-p-dioxins (PBDDs) and polybrominated dibenzofurans (PBDFs) in foods including seafood are scarce. In this study, a number of cod-derived products including medicinal grade cod liver oils sourced from Northern Atlantic waters (Iceland, Norway) and the Baltic Sea (Poland) during 1972-2001 and canned cod liver sourced from the Baltic Sea in 2017, showed detectable levels of PBDFs: such as 2,3,8-TrBDF at 0.57 to 5.249 pg g -1 fat and 1,2,3,4,6,7,8-HpBDF at <0.018 to 0.302 pg g -1 fat. PBDDs were not detected in the cod liver oils. Canned cod liver products showed low levels of 2,3,7,8-TeBDD in the range <0.017 to 0.022 pg g -1 whole weight and 1,2,3,7,8-PeBDD at <0.03 to 0.039 pg g -1 whole weight. These concentrations were computed to yield upper bound toxic equivalences (TEQs) of 0.14 to 0.17 pg g -1 for the oils and 0.12 to 0.25 pg g -1 for the canned products (0.08 pg g -1 ww for both products). The resulting supplementary and dietary intakes are low (0.02 to 0.11 pg kg -1 bm day -1 for the oils and 0.07 to 0.17 pg kg -1 bm week -1 for the canned livers) in comparison to the recently expressed tolerable weekly intake of 2 pg kg -1 bm week -1 . However, the intakes are underestimates, as due to a lack of analytical standards not all PBDD/F TEQ contributing congeners could be included. The PBDD/F TEQ contributes to the cumulative toxicity arising from other contaminants such as chlorinated dioxins and polychlorinated biphenyls., Competing Interests: Declaration of competing interest The authors assert no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In recent years, the Stockholm Convention has listed an additional set of persistent organic pollutants (POPs) for elimination or restricted use/release. Data on the occurrence of these contaminants in food is scarce. Validated analytical methodology was developed to investigate the occurrence of hexachlorobutadiene (HCBD), pentachlorobenzene (PCBz), hexachlorobenzene (HCB) pentachlorophenol (PCP) and polychlorinated naphthalenes (PCNs) in 120 retail foods and 19 total diet study samples. The foods covered the range of commonly consumed dietary items including dairy products, eggs (hen and other species), poultry, meat, fish, vegetables, etc. HCBD showed a low frequency of detection, whereas PCBz, HCB and PCNs occurred in most samples (ranges: <0.01 to 0.19 μg/kg; <0.01 to 3.16 μg/kg and 0.1 to 166 ng ΣPCNs/kg respectively). PCP (<0.01 to 1.9 μg/kg) was detected more frequently in meat products, offal and eggs. Fish, shellfish, eggs from all species, animal fats, meat, offal and meat products showed higher contamination levels, which is normal when investigating lipophilic POPs. These levels of occurrence are similar to more recently reported literature levels but perhaps lower, relative to historic data. This is not unexpected, given the restrictions/limitations on these chemicals within the UK and Western Europe. The estimated human exposure to population groups through dietary intake is correspondingly low and based on current toxicological knowledge, the levels in the examined samples do not suggest a cause for health concern. The data also provide a current baseline for HCBD, PCBz and PCP, and update existing data for PCN and HCB occurrence in foods., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

New Zealand was one of the first countries to establish a universal, tax-funded national health service. Unique features include innovative Māori services, the no-fault accident compensation scheme, and the Pharmaceutical Management Agency, which negotiates with pharmaceutical companies to get the best value for medicines purchased by public money. The so-called universal orientation of the health system, along with a strong commitment to social service provision, have contributed to New Zealand's favourable health statistics. However, despite a long-standing commitment to reducing health inequities, problems with access to care persist and the system is not delivering the promise of equitable health outcomes for all population groups. Primary health services and hospital-based services have developed largely independently, and major restructuring during the 1990s did not produce the expected efficiency gains. A focus on individual-level secondary services and performance targets has been prioritised over tackling issues such as suicide, obesity, and poverty-related diseases through community-based health promotion, preventive activities, and primary care. Future changes need to focus on strengthening the culture and capacity of the system to improve equity of outcomes, including expanding Māori health service provision, integrating existing services and structures with new ones, aligning resources with need to achieve pro-equity outcomes, and strengthening population-based approaches to tackling contemporary drivers of health status., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The potential for contaminant uptake from recycled materials used in livestock farming, to animal tissues and organs, was investigated in three practical modular studies involving broiler chickens, laying chickens and pigs. Six types of commercially available recycled materials were used either as bedding material for chickens or as fertilizer for cropland that later housed outdoor reared pigs. The contaminants studied included regulated contaminants e.g. polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs, dioxins) and polychlorinated biphenyls (PCBs), but related contaminants such as polybrominated diphenylethers (PBDEs), hexabrominated cyclododecane (HBCDD), polychlorinated naphthalenes (PCNs), polybrominated dioxins (PBDD/Fs) and perfluoroalkyl substances (PFAS) were also investigated. Contaminant occurrence in the recycled materials was verified prior to the studies and the relationship to tissue and egg concentrations in market ready animals was investigated using a weights of evidence approach. Contaminant uptake to animal tissues and eggs was observed in all the studies but the extent varied depending on the species and the recycled material. PCBs, PBDEs, PCDD/Fs, PCNs and PFAS showed the highest potential to transfer, with laying chickens showing the most pronounced effects. PBDD/Fs showed low concentrations in the recycled materials, making it difficult to evaluate potential transfer. Higher resulting occurrence levels in laying chickens relative to broilers suggests that period of contact with the materials may influence the extent of uptake in chickens. Bio-transfer factors (BTFs) estimated for PCDD/F and PCBs showed a greater magnitude for chicken muscle tissue relative to pigs with the highest values observed for PCBs in laying chickens. There were no significant differences between BTFs for the different chicken tissues which contrasted with the high BTF values for pigs liver relative to muscle. The study raises further questions which require investigation such as the effects of repeated or yearly application of recycled materials as fertilizers, and the batch homogeneity/consistency of available recycled materials., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Aims: Individual susceptibility to develop obesity may impact the development of cardio-metabolic risk factors that lead to obesity-related comorbid conditions. Obesity-prone Osborne-Mendel (OM) rats expressed higher levels of visceral adipose inflammation than obesity-resistant, S5B/Pl (S5B) rats. However, the consumption of a high fat diet (HFD) differentially affected OM and S5B rats and induced an increase in visceral adipose inflammation in S5B rats. The current study examined the effects of HFD consumption on cardio-metabolic risk factors in OM and S5B rats., Materials & Methods: Glucose regulation and circulating levels of lipids, adiponectin and C-reactive protein were assessed following 8 weeks of HFD or low fat diet (LFD) consumption. Left ventricle hypertrophy and mRNA expression of cardiovascular disease biomarkers were also quantified in OM and S5B rats., Key Findings: Circulating levels of triglycerides were higher, while HDL cholesterol, adiponectin and glycemic control were lower in OM rats, compared to S5B rats. In the left ventricle, BNP and CTGF mRNA expression were higher in OM rats and IL-6, IL-1β, VEGF, and iNOS mRNA expression were higher in S5B rats., Significance: These findings support the hypothesis that cardio-metabolic risk factors are increased in obesity-prone individuals, which may increase the risk for the development of obesity-related comorbidities. In the current models, obesity-resistant S5B rats also exhibited cardiovascular risk factors supporting the importance of monitoring cardiovascular health in individuals characterized as obesity-resistant., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Lower extremity amputation (LEA) is more common in people from lower socio-economic groups. This study examined this further by investigating the influence of socio-economic status on mobility, participation, and quality of life (QoL) after LEA., Methods: Prospective data were gathered for all LEAs performed in one year in one Scottish Health Board, commencing March 2014. A postcode derived Scottish Index of Multiple Deprivation (SIMD) was applied by quintile (SIMD 1 = most deprived). Routine data were collected on the cohort of 171 patients; 101 participants consented and received postal questionnaires on QoL (EQ-5D-5L), participation (Reintegration to Normal Living Index [RNLI]), and mobility (Prosthetic Limb User Survey of Mobility), six (n = 67) and 12 months (n = 50) after LEA., Results: The mean ± SD age of the cohort was 66.2 ± 11.4 years; 75% were male and 53% had diabetes. In total, 67% lived in SIMD 1 and 2 and 11.1% in SIMD 5. Sixty per cent had a transtibial amputation. Mortality was 6% at 30 days 17% at six, and 29% at 12 months. Those in SIMD 1 were significantly younger (62.9 years) than those in SIMD 5 (76.3 years). Significantly more participants with a transfemoral amputation (TFA) lived in SIMD 1 (44%) compared with SIMD 5 (11%) (p = .004). Participation was low (RNLI scores: 6 months = 55.7; 12 months = 56.6) and PLUS M scores suggested mobility was poor overall at six (39.1) and 12 months (38.9). Mean QoL was 0.37 at 6 months and 0.33 at 12 months., Conclusion: Although this study observed more LEAs in those from low socio-economic areas, it is impossible to conclude whether QoL after LEA is truly influenced by socio-economic status. There was an association between the disproportionately high rate of LEAs in SIMD groups 1 and 2 and the high prevalence of smoking, 61% vs. only 21% of those in the least deprived areas (SIMD 3, 4, and 5) being current smokers., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

The twelve 1-n-pentyl-2-, 3-, 4-, 5-, 6- and 7-(1- and 2-naphthoyl)-indoles each have the same substituents attached to the indole ring, identical elemental composition (C 24 H 23 NO) yielding identical nominal and accurate masses. These twelve isomers cover all possible positions of carbonyl bridge substitution for both indole (positons 2-7) and naphthalene rings (positions 1 and 2). Regioisomeric compounds can represent significant challenges for mass based analytical methods however, infrared spectroscopy is a powerful tool for the identification of positional isomers in organic compounds. The vapor phase infrared spectra of these twelve uniquely similar compounds were evaluated in GC-IR experiments. These spectra show the bridge position on the indole ring is a dominating influence over the carbonyl absorption frequency observed for these compounds. Substitution on the pyrrole moiety of the indole ring yields the lowest CO frequency values for position 2 and 3 giving a narrow range from 1656 to 1654cm -1 . Carbonyl absorption frequencies are higher when the naphthoyl group is attached to the benzene portion of the indole ring yielding absorption values from 1674 to 1671cm -1 . The aliphatic stretching bands in the 2900cm -1 region yield a consistent triplet pattern because the N-alkyl substituent tail group remains unchanged for all twelve regioisomers. The asymmetric CH 2 stretch is the most intense of these three bands. Changes in positional bonding for both the indole and naphthalene ring systems results in unique patterns within the 700 wavenumber out-of-plane region and these absorption bands are different for all 12 regioisomers., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The six 1-n-pentyl-2-, 3-, 4-, 5-, 6- and 7-(2-naphthoyl)-indoles each have the same substituents attached to the indole ring, identical elemental composition (C 24 H 23 NO) yielding identical nominal and accurate masses. The electron ionization mass spectra of the 2-naphthoyl substituted isomers share equivalent major fragment ions resulting from cleavage of the groups attached to the central indole nucleus with some differences in relative abundances. These six regioisomers were successfully resolved on an Rtx-5 and Rxi-17Sil MS stationary phases and the molecules having both substituent groups on the same side of the indole ring (1,2- and 1,7-substituents) show the least retention. The more linear molecules have higher relative retention properties. A comparison of the GC properties of the 1-naphthoyl- and 2-naphthoyl groups attached at identical positions of the indole ring showed higher GC retention for the 2-naphthoyl substituted isomer in all cases evaluated. The amide inverse isomers (1-naphthoyl-3-n-pentylindoles) were separated from the 1-n-pentyl-3-naphthoyl-indoles on an Rtx-200 stationary phase. The two inverse amide isomers having the 1- and 2-naphthoyl groups substituted at the 1-position of the indole ring elute before either of the N-alkyl-indole isomers having the 1- and 2-naphthoyl groups substituted at the 3-position of the indole ring. The amide inverse isomers yield EI mass spectra easily distinguishing these amides from the ketone isomers having the naphthoyl groups at the indole 3-position., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Gonorrhoea is a major global public health problem that is exacerbated by drug resistance. Effective vaccine development has been unsuccessful, but surveillance data suggest that outer membrane vesicle meningococcal group B vaccines affect the incidence of gonorrhoea. We assessed vaccine effectiveness of the outer membrane vesicle meningococcal B vaccine (MeNZB) against gonorrhoea in young adults aged 15-30 years in New Zealand., Methods: We did a retrospective case-control study of patients at sexual health clinics aged 15-30 years who were born between Jan 1, 1984, and Dec 31, 1998, eligible to receive MeNZB, and diagnosed with gonorrhoea or chlamydia, or both. Demographic data, sexual health clinic data, and National Immunisation Register data were linked via patients' unique personal identifier. For primary analysis, cases were confirmed by laboratory isolation or detection of Neisseria gonorrhoeae only from a clinical specimen, and controls were individuals with a positive chlamydia test only. We estimated odds ratios (ORs) comparing disease outcomes in vaccinated versus unvaccinated participants via multivariable logistic regression. Vaccine effectiveness was calculated as 100×(1-OR)., Findings: 11 of 24 clinics nationally provided records. There were 14 730 cases and controls for analyses: 1241 incidences of gonorrhoea, 12 487 incidences of chlamydia, and 1002 incidences of co-infection. Vaccinated individuals were significantly less likely to be cases than controls (511 [41%] vs 6424 [51%]; adjusted OR 0·69 [95% CI 0·61-0·79]; p<0·0001). Estimate vaccine effectiveness of MeNZB against gonorrhoea after adjustment for ethnicity, deprivation, geographical area, and sex was 31% (95% CI 21-39)., Interpretation: Exposure to MeNZB was associated with reduced rates of gonorrhoea diagnosis, the first time a vaccine has shown any protection against gonorrhoea. These results provide a proof of principle that can inform prospective vaccine development not only for gonorrhoea but also for meningococcal vaccines., Funding: GSK Vaccines., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Multiple and complementary analytical methods are often necessary for the identification of a specific compound from a series of closely related structural isomers. Gas chromatography-mass spectrometry (GC-MS), gas chromatography-product ion mass spectrometry (GC-MS/MS) and gas chromatography-infrared spectroscopy (GC-IR) were used to differentiate between the six dimethoxypyrrovalerone (DMPV) regioisomers. The six regioisomeric aminoketones were separated on a 50% phenyl stationary phase and the elution order is related to the positioning of substituents on the aromatic ring. These six DMPV regioisomers yield essentially identical mass spectral data in both chemical ionization (CI-MS) and electron ionization (EI-MS) spectra as well as identical product ion MS/MS spectra of the iminium cation base peak (m/z 126). These various mass spectral techniques provide data to identify all major structural features of these molecules except the dimethoxy substitution pattern of the aromatic ring. The region of the vapor phase infrared spectra between 1600cm -1 and 1000cm -1 provides a significant number of unique absorption bands characteristic of each individual DMPV regioisomer., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The NOX (nicotinamide adenine dinucleotide phosphate oxidase) family includes seven unique members that are involved in a multitude of physiological functions, including extensive interaction with UVR and the skin. NOX1 is uniquely present and activated by UVB radiation with biphasic expression of the enzyme immediately and then after a several-hour delay. Specific inhibition of both early and late NOX1 activation leads to evidence of decreased photocarcinogenesis in in vitro keratinocytes and in well-characterized mouse models in which antitumor efficacy has been shown; inhibiting only late NOX activation does not exhibit such effects. These results suggest a crucial function of early NOX activation in transducing a signal for cellular protection after UVB carcinogenesis provocation. We term this an intrinsic cellular ROS priming function for quenching DNA damage and promoting survival. Evolutionally, this type of priming function may be essential for addressing various types of stimuli from adverse environments., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin malignant tumors with an increasing incidence. Studies have shown that Yes-associated protein (YAP) participates in the development of a variety of tumors as an oncogene, but to our knowledge its role in cSCC has not been reported. In this study, we used immunohistochemistry to show that YAP expression was elevated in cSCC samples of different stages versus in normal skin and that it was well correlated with the progression of the disease. Down-regulation of YAP in cSCC cell lines A431 and SCL-1 inhibited cell proliferation by inducing growth arrest during the G1/S phase transition, promoted apoptosis, and reduced invasion and migration abilities in vitro. Conversely, overexpression of YAP promoted cell proliferation and protected cells against basal and chemotherapy-induced apoptosis. These oncogenic effects of YAP were associated with activation of the RAS protein and its downstream AKT and ERK. Using a mouse xenograft model, we further showed that YAP depletion inhibited cSCC tumor growth in vivo. Our results suggested that YAP is involved in the carcinogenesis and development of cSCC and that it may serve as a biomarker or therapeutic target of this disease., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Obese pregnant women are at risk of aortocaval compression and associated hypotension with neuraxial anaesthesia. We hypothesised that addition of reverse Trendelenburg tilt to the standard practice of pelvic tilt may attenuate aortocaval compression., Methods: After ethical approval and consent, six women with a singleton pregnancy and booking body mass index of 30-35kg/m(2) underwent magnetic resonance imaging scanning in six different positions: right lateral decubitus; left lateral decubitus; supine with pelvic tilt; and reverse Trendelenburg positions of 5°, 10° and 15°. Dimensions of the inferior vena cava and abdominal aorta at the L2-3 intervertebral disc level were obtained from axial images using medical imaging software OsiriX™., Results: Inferior vena cava dimensions were higher in left lateral decubitus position compared to supine with pelvic tilt (P=0.002). Inferior vena cava compression was noted in all participants (59±33%, 95% CI 32 to 86). Addition of 15° reverse Trendelenburg tilt to standard pelvic tilt produced a non-statistically significant increase in inferior vena cava area (10.54±9.91cm(2), 95% CI 2.61 to 18.47, P=0.06)., Conclusion: A non-statistically significant improvement of aortocaval compression was noted with the addition of 15° reverse Trendelenburg tilt to the supine with pelvic tilt position in obese pregnant women., (Copyright © 2015 Elsevier Ltd. All rights reserved.)