Development and application of a multiple reaction monitoring method for the simultaneous quantification of sodium channels Nav 1.1, Nav 1.2, and Nav 1.6 in solubilized membrane proteins from stable HEK293 cell lines, rodents, and human brain tissues.

RATIONALE: Nav 1.1, 1.2, and 1.6 are transmembrane proteins acting as voltage-gated sodium channels implicated in various forms of epilepsy. There is a need for knowing their actual concentration in target tissues during drug development. METHODS: Unique peptides for Nav 1.1, Nav 1.2, and Nav 1.6 were selected as quantotropic peptides for each protein and used for their quantification in membranes from stably transfected HEK293 cells and rodent and human brain samples using ultra-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry. RESULTS: Nav 1.1, 1.2, and 1.6 protein expressions in three stably individually transfected HEK293 cell lines were found to be 2.1 ± 0.2, 6.4 ± 1.2, and 4.0 ± 0.6 fmol/µg membrane protein, respectively. In brains, Nav 1.2 showed the highest expression, with approximately three times higher (P < 0.003) in rodents than in humans at 3.05 ± 0.57, with 3.35 ± 0.56 in mouse and rat brains and 1.09 ± 0.27 fmol/µg in human brain. Both Nav 1.1 and 1.6 expressions were much lower in the brains, with approximately 40% less expression in human Nav 1.1 than rodent Nav 1.1 at 0.49 ± 0.1 (mouse), 0.43 ± 0.3 (rat), and 0.28 ± 0.04 (humans); whereas Nav 1.6 had approximately 60% less expression in humans than rodents at 0.27 ± 0.09 (mouse), 0.26 ± 0.06 (rat), and 0.11 ± 0.02 (humans) fmol/µg membrane proteins. CONCLUSIONS: Multiple reaction monitoring was used to quantify sodium channels Nav 1.1, 1.2, and 1.6 expressed in stably transfected HEK293 cells and brain tissues from mice, rats, and humans. We found significant differences in the expression of these channels in mouse, rat, and human brains. Nav expression ranking among the three species was Nav 1.2 ≫ Nav 1.1 > Nav 1.6, with the human brain expressing much lower concentrations overall compared to rodent brain.

Point-of-Care Ultrasound of a Nasal Septal Abscess.

ABSTRACT: Although nasal septal abscesses (NSA) are rare, complications can be significant and devastating. Thus, timely diagnosis of NSA is critical. In this case report, we describe the use of point-of-care ultrasound in diagnosing NSA in a healthy boy presenting with viral upper respiratory infection symptoms and fever. Point-of-care ultrasound findings resulted in expediting this patient's treatment and transfer to a quaternary care center for definitive treatment.

Novel RXFP3 negative allosteric modulator RLX-33 reduces alcohol self-administration in rats.

There is much interest in identifying novel pharmacotherapeutic targets that improve clinical outcomes for the treatment of alcohol use disorder (AUD). One promising target for therapeutic intervention is the relaxin family peptide 3 (RXFP3) receptor, a cognate receptor for neuropeptide relaxin-3, which has previously been implicated in regulating alcohol drinking behavior. Recently, we developed the first small-molecule RXFP3-selective negative allosteric modulator (NAM) RLX-33. Therefore, the goal of the present work was to characterize the impact of this novel NAM on affective-related behaviors and alcohol self-administration in rats. First, the effects of RLX-33 were tested on alcohol and sucrose self-administration in Wistar and alcohol-preferring P rats to determine the dose-response profile and specificity for alcohol. Then, we assessed the effects of systemic RLX-33 injection in Wistar rats in a battery of behavioral assays (open-field test, elevated zero maze, acoustic startle response test, and prepulse inhibition) and tested for alcohol clearance. We found that the lowest effective dose (5 mg/kg) reduced alcohol self-administration in both male and female Wistar rats, while in alcohol-preferring P rats, this effect was restricted to males, and there were no effects on sucrose self-administration or general locomotor activity. The characterization of affective and metabolic effects in Wistar rats generally found few locomotor, affective, or alcohol clearance changes, particularly at the 5 mg/kg dose. Overall, these findings are promising and suggest that RXFP3 NAM has potential as a pharmacological target for treating AUD.

Potent, Gut-Restricted Inhibitors of Divalent Metal Transporter 1: Preclinical Efficacy against Iron Overload and Safety Evaluation.

Divalent metal transporter 1 (DMT1) cotransports ferrous iron and protons and is the primary mechanism for uptake of nonheme iron by enterocytes. Inhibitors are potentially useful as therapeutic agents to treat iron overload disorders such as hereditary hemochromatosis or ß-thalassemia intermedia, provided that inhibition can be restricted to the duodenum. We used a calcein quench assay to identify human DMT1 inhibitors. Dimeric compounds were made to generate more potent compounds with low systemic exposure. Direct block of DMT1 was confirmed by voltage clamp measurements. The lead compound, XEN602, strongly inhibits dietary nonheme iron uptake in both rats and pigs yet has negligible systemic exposure. Efficacy is maintained for >2 weeks in a rat subchronic dosing assay. Doses that lowered iron content in the spleen and liver by >50% had no effect on the tissue content of other divalent cations except for cobalt. XEN602 represents a powerful pharmacological tool for understanding the physiologic function of DMT1 in the gut. SIGNIFICANCE STATEMENT: This report introduces methodology to develop potent, gut-restricted inhibitors of divalent metal transporter 1 (DMT1) and identifies XEN602 as a suitable compound for in vivo studies. We also report novel animal models to quantify the inhibition of dietary uptake of iron in both rodents and pigs. This research shows that inhibition of DMT1 is a promising means to treat iron overload disorders.

Prevalence and characteristics of advocacy curricula in Australian public health degrees.

BACKGROUND: Public health advocacy is a fundamental part of health promotion practice. Advocacy efforts can lead to healthier public policies and positive impacts on society. Public health educators are responsible for equipping graduates with cross-cutting advocacy competencies to address current and future public health challenges. PROBLEM: Knowledge of the extent to which students are taught public health advocacy is limited. To determine whether advocacy teaching within public health degrees matches industry needs, knowledge of pedagogical approaches to advocacy curricula is required. This study sought to understand the extent to which advocacy is taught and assessed within Australian public health degrees. METHODOLOGY: Australian public health Bachelor's and Master's degrees were identified using the CRICOS database. Open-source online unit guides were reviewed to determine where and how advocacy was included within core and elective units (in title, unit description or learning outcomes). Degree directors and convenors of identified units were surveyed to further garner information about advocacy in the curriculum. RESULTS: Of 65 identified degrees, 17 of 26 (65%) undergraduate degrees and 24 of 39 (62%) postgraduate degrees included advocacy within the core curriculum, while 6 of 26 (23%) undergraduate and 8 of 39 (21%) postgraduate offered no advocacy curriculum. IMPLICATIONS: Australian and international public health competency frameworks indicate advocacy curriculum should be included in all degrees. This research suggests advocacy competencies are not ubiquitous within Australian public health curricula. The findings support the need to advance public health advocacy teaching efforts further.

Knowledge, attitudes, and practice of cervical cancer prevention among health workers in rural health centres of Northern Uganda.

BACKGROUND: Cervical cancer is a leading cancer and cause of premature death among women in Uganda aged 15 to 44 years. To address the increasing burden of cervical cancer in Uganda, the Ministry of Health has adopted several strategies which include public education and advocacy. This study aims to assess knowledge, attitudes, and practice of cervical cancer prevention among health workers employed in rural health centres (HCs) III and IV in the Acholi sub-region of Northern Uganda. METHODS: We conducted a cross-sectional survey of nurses, midwives, and clinical officers between February and April 2019 using self-administered questionnaire. We sampled fifty-four HCs III and eight HCs IV. In Uganda, HCs are structured from HC I to HC IV and the health care package provided increases with increasing level of the HC. We used Epidata version 3.1 to create database and analysis was performed using Stata 16. Descriptive and logistic regression analyses were performed. Factors with p-values ≤ 0.05 were considered as predictors of outcome. RESULTS: There were 286 participants who completed the questionnaire: Majority (188, 66%) were females. Nurses were 153 (54%). 141 (75%) female participants self-reported to have been screened for cervical cancer. 171 (60%) participants had adequate knowledge of cervical cancer. 187 (66%) participants had positive attitudes. Participants who indicated not to have ever received training on cervical cancer screening were less likely to have adequate knowledge (AOR = 0.39, 95% CI 0.21-0.71). Participants who indicated not to have ever been trained on cervical cancer screening were less likely to have positive attitudes (AOR = 0.52, 95% CI 0.28-0.97). CONCLUSION: Health workers from rural HCs in Uganda play crucial role in cervical cancer prevention as they can reach a wider community. Their significance in the prevention of cervical cancer points to the need for Uganda and other sub-Sahara Africa (SSA) countries to establish training to improve their knowledge, attitudes, and practical skills on cervical cancer screening. Furthermore, Uganda government should develop and disseminate guidelines for cervical cancer prevention to rural health workers to promote standardised cervical cancer prevention activities.

Identification of aryl sulfonamides as novel and potent inhibitors of NaV1.5.

We describe the synthesis and biological evaluation of a series of novel aryl sulfonamides that exhibit potent inhibition of NaV1.5. Unlike local anesthetics that are currently used for treatment of Long QT Syndrome 3 (LQT-3), the most potent compound (-)-6 in this series shows high selectivity over hERG and other cardiac ion channels and has a low brain to plasma ratio to minimize CNS side effects. Compound (-)-6 is also effective inshortening prolonged action potential durations (APDs) in a pharmacological model of LQT-3 syndrome in pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Unlike most aryl sulfonamide NaV inhibitors that bind to the channel voltage sensors, these NaV1.5 inhibitors bind to the local anesthetic binding site in the central pore of the channel.

Cardioprotective Effect of Anesthetics: Translating Science to Practice.

Cardiovascular diseases are the number one cause of mortality in the world, particularly among the aging population. Major adverse cardiac events are also a major contributor to perioperative complications, affecting 2.6% of noncardiac surgeries and up to 18% of cardiac surgeries. Cardioprotective effects of volatile anesthetics and certain intravenous anesthetics have been well-documented in preclinical studies; however, their clinical application has yielded conflicting results in terms of their efficacy. Therefore, better understanding of the underlying mechanisms and developing effective ways to translate these insights into clinical practice remain significant challenges and unmet needs in the area. Several recent reviews have focused on mechanistic dissection of anesthetic-mediated cardioprotection. The present review focuses on recent clinical trials investigating the cardioprotective effects of anesthetics in the past five years. In addition to highlighting the main outcomes of these trials, the authors provide their perspectives about the current gap in the field and potential directions for future investigations.

Balancing the Blood Component Transfusion Ratio for High- and Ultra High-Dose Cell Salvage Cases.

OBJECTIVE: To assess the ratio of non-red blood cell to red blood cell components required to avoid coagulopathy when transfusing large amounts of salvaged blood using laboratory test-guided therapy. DESIGN: Retrospective cohort study. SETTING: Single-center, academic hospital. PARTICIPANTS: Thoracoabdominal and abdominal open aortic surgery patients. MEASUREMENT AND MAIN RESULTS: Thirty-eight patients in whom at least 1,000 mL of salvaged red blood cells were transfused were identified and divided into the following 2 cohorts: 1,000-to-2,000 mL of salvaged red blood cells (high dose) (n = 20) and >2,000 mL of salvaged red blood cells (ultra-high dose) (n = 18). Compared with the high-dose cohort, the ultra high-dose cohort received ∼4 times more salvaged red blood cells (1,240 ± 279 mL v 5,550 ± 3,801 mL). With transfusion therapy guided by intraoperative coagulation tests and thromboelastography, the adjusted ratio of non-red blood cell to red blood cell components (plasma + platelets + cryoprecipitate:allogeneic + salvaged red blood cells) was 0.59 ± 0.66 in the high-dose and 0.93 ± 0.27 in the ultra high-dose cohorts. Multiple coagulation parameters were normal and similar between cohorts at the end of surgery, as determined by the mean, median, and 95% confidence intervals. CONCLUSIONS: When transfusing large volumes of salvaged blood, it is important to balance the ratio between non-red blood cell and red blood cell components. Through a laboratory test-guided approach, coagulopathy was not detected when transfusing blood in ratios of approximately 1:2 for patients receiving 1,000-to-2,000 mL of salvaged blood and 1:1 for patients receiving >2,000 mL of salvaged blood.

Provision of cervical cancer prevention services in Northern Uganda: a survey of health workers from rural health centres.

BACKGROUND: Cervical cancer is the leading cancer among Ugandan women, contributing to 40 % of all cancer cases recorded in the cancer registry. Having identified the substantial impact of cervical cancer among Ugandan women, the Ministry of Health in 2010 launched a Strategic Plan for Cervical Cancer prevention and control. This study was conducted to determine if health workers working in rural health centres (HCs) III and IV in Northern Uganda provide cervical cancer screening services as recommended in the Strategic Plan. METHODS: A cross-sectional survey using a structured questionnaire was conducted among nurses, midwives and clinical officers working in rural HC III and IV in Northern Uganda. Data were entered in Epidata 3.1 and analysed using Stata 16 statistical software. Univariate, bivariate, and multivariate analyses were performed. Any factor with p-value ≤ 0.05 was considered a significant predictor of outcome. RESULTS: We surveyed 286 health workers. Fifty-one (18 %) health workers were screening women for cervical cancer. Fifty-eight (21 %) health workers have guideline for cervical cancer screening in their HCs, 93 (33 %) participants were trained to screen women for cervical cancer. Two hundred sixty-two (92 %) participants provided HPV vaccination. Two hundred forty-six (87 %) participants were conducting health education about cervical cancer in their HCs. Factors associated with screening women for cervical cancer include: being a staff member from HCs III (AOR = 0.30, 95 % CI 0.13-0.68, p = 0.00), being staff of HCs that have organization to support cervical cancer screening services (AOR = 4.38, 95 % CI 1.99-9.63, p-=0.00), being a health worker who had been trained to screen for cervical cancer (AOR = 2.21, 95 % CI 1.00-4.90, p = 0.05) and staff from HCs that has guideline for cervical cancer screening (AOR = 2.89, 95 % CI 1.22-6.86, p = 0.02). CONCLUSIONS: This study shows an overall structural problem related to the delivery of cervical cancer screening services in HC III and IV in Northern Uganda which the Strategic Plan has not addressed. These structural problems need urgent attention if the Uganda government and other sub-Saharan African (SSA) countries are to achieve the World Health Organization (WHO) 90-70-90 targets by 2030 to be on track for cervical cancer elimination.

Perceptions of key informants on the provision of cervical cancer prevention and control programme in Uganda: implication for cervical cancer policy.

BACKGROUND: Uganda has one of the highest burdens of cervical cancer globally. In 2010 the Ugandan Ministry of Health launched the Strategic Plan for Cervical Cancer Prevention and Control with the hope of developing cervical cancer policy in Uganda. This study explored the beliefs of senior key informants in Uganda about cervical cancer prevention, the control programme, and the relevance of cervical cancer policy. METHODS: We conducted 15 key informant interviews with participants from six organisations across Northern and Central Uganda. Participants were drawn from district local government health departments, St. Mary's Hospital Lacor, Uganda Nurses and Midwifery Council, non-governmental organisations (NGOs) and Ministry of Health in Kampala, Uganda. The interview recordings were transcribed and analysed using thematic analysis. RESULTS: Seven themes emerged relating to the cervical cancer prevention and control programmes in Uganda: (1) policy frameworks for cervical cancer, (2) operationalising cervical cancer prevention and control, (3) financial allocation and alignment, (4) human resources and capability, (5) essential supplies and vaccines, (6) administrative data and resource distribution, and (7) cervical cancer services. CONCLUSIONS: The key informants perceive that the lack of a cervical cancer policy in Uganda is hindering cervical cancer prevention and control programmes. Therefore, the Ministry of Health and stakeholders need to work together in coming up with an effective policy framework that will accelerate efforts towards cervical cancer prevention and control in Uganda.

Artefactual inflation of type 2 diabetes prevalence in WHO STEP surveys.

OBJECTIVES: In view of erroneous type 2 diabetes prevalence reported in 3 small Pacific Island countries, a study was conducted to investigate whether this error occurred in other countries which have conducted WHO STEPS surveys associated with glucose thresholds for point-of-care (POC) measuring devices calibrated to plasma. METHODS: Published STEPS surveys conducted over 2001-2017 were obtained. For each survey, information was obtained on diabetes prevalence, POC glucose measuring device, blood sample tested and the fasting glucose threshold used for prevalence calculations. POC device user manuals were obtained to determine calibration. The current WHO glucose threshold for type 2 diabetes was used: ≥7.0 mmol/l for plasma glucose; ≥6.1 mmol/l for whole blood glucose. RESULTS: POC devices were used in 75 of the STEPS surveys identified to measure blood glucose. An incorrect glucose threshold was employed in 17 surveys (23%) to define diabetes. The correct threshold was applied in 20 surveys (27%). Estimates from meta-analysis and meta-regression show that diabetes prevalence in surveys using the incorrect glucose thresholds have prevalences 50% higher than surveys which use the correct glucose threshold. A definite conclusion could not be made for 38 surveys (51%) because of the absence or unclear information on the glucose metre and/or the threshold employed. CONCLUSION: WHO STEPS surveys with likely incorrect published diabetes prevalences have been conducted across the globe, resulting in a 50% artefactual inflation. Inaccurate reporting of diabetes prevalence from widely cited STEPS surveys would have significant impacts on disease burden monitoring, policy development and resource allocation.

OBJECTIFS: Compte tenu de la prévalence erronée du diabète de type 2 rapportée dans 3 petits pays insulaires du Pacifique, une étude a été menée pour déterminer si cette erreur s'était produite dans d'autres pays ayant mené des surveillances STEPS de l'OMS, associées à des seuils de glucose pour des appareils de mesure aux points de soins, calibrés sur du plasma. MÉTHODES: Les surveillances STEPS publiées, menées entre 2001 et 2017 ont été obtenues. Pour chaque surveillance, les informations ont été obtenues sur la prévalence du diabète, l'appareil de mesure du glucose aux points des soins, les échantillons de sang testés et le seuil de glycémie à jeun utilisé pour les calculs de prévalence. Les manuels d'utilisation des appareils ont été obtenus pour déterminer l'étalonnage. Le seuil de glucose actuel de l'OMS pour le diabète de type 2 a été utilisé: ≥ 7,0 mmol/L pour le glucose plasmatique; ≥ 6,1 mmol/L pour le glucose du sang total. RÉSULTATS: Les dispositifs de mesure aux points des soins ont été utilisés dans 75 des surveillances STEPS identifiées pour mesurer la glycémie. Un seuil de glucose incorrect a été utilisé dans 17 surveillances (23%) pour définir le diabète. Le seuil correct a été appliqué dans 20 surveillances (27%). Les estimations issues de méta-analyses et de méta-régressions montrent que la prévalence du diabète dans les surveillances utilisant des seuils de glucose incorrects est supérieure de 50% à celle des surveillances utilisant le seuil de glucose correct. Une conclusion définitive n'a pu être tirée pour 38 surveillances (51%) à cause de l'absence ou du manque de clarté des informations sur le glucomètre et/ou le seuil utilisé. CONCLUSION: Les enquêtes STEPS de l'OMS avec des prévalences de diabète publiées probablement incorrectes ont été menées dans le monde entier, entraînant une inflation artéfactuelle de 50%. Des reports inexacts de la prévalence du diabète provenant de surveillances STEPS largement citées auraient des impacts significatifs sur la surveillance de la charge de morbidité, l'élaboration de politiques et l'allocation des ressources.

The Use of Ultrasound-Measured Optic Nerve Sheath Diameter to Predict Ventriculoperitoneal Shunt Failure in Children.

OBJECTIVE: The goal of this study was to assess the accuracy of ultrasound-measured optic nerve sheath diameter (ONSD) as a screen for ventriculoperitoneal shunt failure. METHODS: We prospectively enrolled a convenience sample of children presenting to the ED with suspected shunt failure. The ONSD was measured by ultrasound and compared with computed tomography/magnetic resonance imaging (CT/MRI) and neurosurgical impression. We defined shunt failure on ultrasound as an ONSD greater than 4.0 mm in infants 12 months and younger or greater than 4.5 mm in children older than 12 months. A single emergency radiologist at our institution read all CTs and MRIs for categorical determination of shunt failure. We defined shunt failure based on neurosurgical impression as a decision to admit and perform shunt revision. We report test characteristics and 95% confidence intervals of ONSD as a predictor for shunt failure. RESULTS: We enrolled 32 subjects. The sensitivities of ONSD compared with CT/MRI and neurosurgical impression, 60.0% and 75.0%, respectively, were low. However, the negative predictive values of ONSD compared with CT/MRI and neurosurgical impression were 90.0% and 95.0%, respectively. CONCLUSIONS: Optic nerve sonography may be a useful tool to identify children presenting with suspected ventriculoperitoneal shunt failure who do not require further imaging. This would reduce the use of CT scan and exposure to ionizing radiation in children with suspected shunt malfunction who do not require neurosurgical intervention. Consideration of additional risk factors and a larger sample size may yield stronger results.

Continued increases in blood pressure over two decades in Samoa (1991-2013); around one-third of the increase explained by rising obesity levels.

BACKGROUND: To analyse trends over the period 1991-2013 in systolic blood pressure (SBP), diastolic blood pressure (DBP) and the prevalence of hypertension in adults aged 25-64 years in Samoa; and to assess the contribution of rising obesity levels to period trends. METHODS: Unit record data from seven population-based surveys (n = 10,881) conducted between 1991 and 2013 were included for analysis. Surveys were adjusted to the nearest previous census to improve national representativeness. Hypertension was defined as SBP ≥140 mmHg and/or DBP ≥90 mmHg and/or on medication for hypertension. Obesity was measured by body mass index (BMI). Poisson, linear and meta-regression were used to assess period trends. RESULTS: Over 1991-2013 mean SBP and DBP (mmHg), and the prevalence of hypertension (%) increased in both sexes. Increases in hypertension were: from 18.3 to 33.9% (p < 0.001) in men (mean BP from 122/74 to 132/78); and from 14.3 to 26.4% (p < 0.001) in women (mean BP from 118/73 to 126/78). The estimate of the age-adjusted mean SBP and DBP over 1991-2013, and the relative risk for hypertension in 2013 compared to 1991, were attenuated after adjusting for BMI: by 22% (men) and 32% (women) for mean SBP; 37% (men) and 32% (women) for mean DBP; and 19% in both sexes for hypertension. CONCLUSIONS: Significant increases have occurred in SBP/DBP and hypertension prevalence in both sexes in Samoa during 1991-2013, which would contribute significantly to premature mortality from cardiovascular disease. Obesity accounts for around one-third of the rising trend in blood pressure in the Samoan population. Strengthening of population control of hypertension through reduction in obesity and salt intake, and case detection and treatment through primary care, is required to reduce premature mortality from cardiovascular disease in Samoa.

Affinity-Driven Covalent Modulator of the Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) Cascade.

Traditional medicines provide a fertile ground to explore potent lead compounds, yet their transformation into modern drugs is fraught with challenges in deciphering the target that is mechanistically valid for its biological activity. Herein we reveal that (Z)-(+)-isochaihulactone (1) exhibited significant inhibition against multiple-drug-resistant (MDR) cancer cell lines and mice xenografts. NMR spectroscopy showed that 1 resisted an off-target thiolate, thus indicating that 1 was a target covalent inhibitor (TCI). By identifying the pharmacophore of 1 (α,ß-unsaturated moiety), a probe derived from 1 was designed and synthesized for TCI-oriented activity-based proteome profiling. By MS/MS and computer-guided molecular biology approaches, an affinity-driven Michael addition of the noncatalytic C247 residue of GAPDH was found to control the "ON/OFF" switch of apoptosis through non-canonically nuclear GAPDH translocation, which bypasses the common apoptosis-resistant route of MDR cancers.

Measuring inequalities in the distribution of the Fiji Health Workforce.

BACKGROUND: Despite the centrality of health personnel to the health of the population, the planning, production and management of human resources for health remains underdeveloped in many low- and middle-income countries (LMICs). In addition to the general shortage of health workers, there are significant inequalities in the distribution of health workers within LMICs. This is especially true for countries like Fiji, which face major challenges in distributing its health workforce across many inhabited islands. METHODS: In this study, we describe and measure health worker distributional inequalities in Fiji, using data from the 2007 Population Census, and Ministry of Health records of crude death rates and health workforce personnel. We adopt methods from the economics literature including the Lorenz Curve/Gini Coefficient and Theil Index to measure the extent and drivers of inequality in the distribution of health workers at the sub-national level in Fiji for three categories of health workers: doctors, nurses, and all health workers (doctors, nurses, dentists and health support staff). Population size and crude death rates are used as proxies for health care needs. RESULTS: There are greater inequalities in the densities of health workers at the provincial level, compared to the divisional level in Fiji - six of the 15 provinces fall short of the recommended threshold of 2.3 health workers per 1,000 people. The estimated decile ratios, Gini co-efficient and Thiel index point to inequalities at the provincial level in Fiji, mainly with respect to the distribution of doctors; however these inequalities are relatively small. CONCLUSION: While populations with lower mortality tend to have a slightly greater share of health workers, the overall distribution of health workers on the basis of need is more equitable in Fiji than for many other LMICs. The overall shortage of health workers could be addressed by creating new cadres of health workers; employing increasing numbers of foreign doctors, including specialists; and increasing funding for health worker training, as already demonstrated by the Fiji government. Close monitoring of the equitable distribution of additional health workers in the future is critical.

Declines and Plateaux in Smoking Prevalence Over Three Decades in Fiji.

OBJECTIVES: To examine trends from 1980 to 2011 in daily tobacco smoking by sex, ethnicity, age, and urban/rural in Fiji Melanesian (i-Taukei) and Indian adults aged 25-64 years. METHODS: Unit record data from five population-based surveys (n = 14 528) allowed classification of participants as: (1) never-smoker, ex-smoker, or non-daily smoker; or (2) daily smoker, reporting smoking <20 or ≥20 tobacco products (cigarettes/cigars/pipes) a day. Trends were examined using spline analyses. RESULTS: Over 1980-2011 the prevalence of reported daily tobacco smoking decreased significantly in both sexes and ethnicities, with the greatest decline during 1980-2000. Declines were from 81.7% to 27.0% in i-Taukei men; 55.3% to 26.3% in Indian men; 48.1% to 9.5% in i-Taukei women; and 13.8% to 1.3% in Indian women (p < .0001). Declines were consistent across all age groups in men, while there were greater declines among older age groups in women; and greater declines from higher prevalences in rural compared to urban areas in both sexes and ethnicities. Smoking ≥20 tobacco products per day declined significantly in i-Taukei men from 8.0% to 1.9% (p < .0001); there were also declines in Indian men (4.6% to 2.0%) and i-Taukei women (2.6% to 0.6%), but these were not statistically significant; and Indian women remained <0.2% throughout the period. CONCLUSIONS: Significant declines in daily tobacco smoking have occurred in Fiji in both sexes and ethnicities during the past 30 years, which is consistent with declines in tobacco apparent consumption and household expenditure. However, prevalence remains high in men at around 27% in 2011, with plateau at this level in i-Taukei. IMPLICATIONS: This is the first study to show nationally representative population trends in tobacco smoking in a developing country over such a long period (>30 years) based on empirical unit record data (n = 14 528). Cardiovascular disease is a leading cause of mortality throughout the Pacific Island region. This is the first study to show evidence of substantial declines over several decades in a cardiovascular disease risk factor in a Pacific Island country, and provides important evidence for further research into the interventions and events which may have facilitated this decline.

Tobacco smoking trends in Samoa over four decades: can continued globalization rectify that which it has wrought?

BACKGROUND: The island country of Samoa (population 188,000 in 2011) forms part of Polynesia in the South Pacific. Over the past several decades Samoa has experienced exceptional modernization and globalization of many sectors of society, with noncommunicable diseases (NCD) now the leading cause of morbidity and mortality. The evolution of risk factor prevalence underpinning the increase in NCDs, however, has not been well described, including tobacco smoking which is related to cardiovascular disease, lung cancer, and chronic obstructive pulmonary disease. METHODS: The present study examines tobacco smoking in relation to different forms and effects of globalization in Samoa using 7 population-based surveys (n = 9223) over 1978-2013. RESULTS: The prevalence of daily tobacco smoking steadily decreased over 1978-2013 from 76% to 36% in men, and from 27% to 15% in women (p < 0.0001 both sexes). During 1991-2013, current tobacco smoking also steadily decreased from 64% to 40% in men (p < 0.0001), and from 21% to 17% in women (p < 0.05). Declines were similar in younger (25-44 years) and older (45-64 years) men and women. Colonial globalization facilitated the introduction and prolific spread of tobacco trade and consumption in the Pacific Islands from the sixteenth century, with many populations inexorably pulled into trade relations and links to the global economy. It has also been a different globalization which may have led to the decline in smoking prevalence in Samoa in recent decades, through global dissemination since the 1950s of information on the harmful effects of tobacco smoking derived from research studies in the USA and Europe. CONCLUSIONS: Over the past 35 years tobacco smoking has steadily declined among Samoan adults; the only NCD risk factor to demonstrate marked declines during this period. By 2013 tobacco smoking in women had decreased to levels similar to Australia and New Zealand (ANZ), however in men smoking prevalence remained more than three times higher than ANZ. The impact on smoking prevalence of the variety of tobacco control interventions that have been implemented so far in Samoa need to be evaluated in order to determine the most effective initiatives that should be prioritized and strengthened.

Multi-scale silica structures for improved HIV-1 Capsid (p24) antigen detection.

Silica (SiO2) micro- and nanostructures fabricated with pre-stressed thermoplastic shrink wrap film have been shown to yield far-field fluorescence signal enhancements over their planar or wrinkled counterparts. The SiO2 structures have previously been used for improved detection of fluorescently labelled proteins and DNA. In this work, we probe the mechanism responsible for the dramatic increases in fluorescence signal intensity. Optical characterization studies attribute the fluorescence signal enhancements to increased surface density and light scattering from the rough SiO2 structures. Using this information, we come up with a theoretical approximation for the enhancement factor based off the scattering effects alone. We show that increased deposition thickness of SiO2 yields improved fluorescence signal enhancements, with an optimal SiO2 thin layer achieved at 20 nm. Finally, we show that the SiO2 substrates serve as a suitable platform for disease diagnostics, and show improved limits of detection (LOD) for the human immunodeficiency virus type 1 (HIV-1) p24 antigen.

Diabetes incidence and projections from prevalence surveys in Fiji.

BACKGROUND: Type 2 diabetes mellitus (T2DM) incidence is traditionally derived from cohort studies that are not always feasible, representative, or available. The present study estimates T2DM incidence in Fijian adults from T2DM prevalence estimates assembled from surveys of 25-64 year old adults conducted over 30 years (n = 14,288). METHODS: T2DM prevalence by five-year age group from five population-based risk factor surveys conducted over 1980-2011 were variously adjusted for urban-rural residency, ethnicity, and sex to previous censuses (1976, 1986, 1996, 2009) to improve representativeness. Prevalence estimates were then used to calculate T2DM incidence based on birth cohorts from the age-period (Lexis) matrix following the Styblo technique, first used to estimate annual risk of tuberculosis infection (incidence) from sequential Mantoux population surveys. Poisson regression of year, age, sex, and ethnicity strata (n = 160) was used to develop projections of T2DM prevalence and incidence to 2020 based on various scenarios of population weight measured by body mass index (BMI) change. RESULTS: T2DM prevalence and annual incidence increased in Fiji over 1980-2011. Prevalence was higher in Indians and men than i-Taukei and women. Incidence was higher in Indians and women. From regression analyses, absolute reductions of 2.6 to 5.1% in T2DM prevalence (13-26% lower), and 0.5-0.9 per 1000 person-years in incidence (8-14% lower), could be expected in 2020 in adults if mean population weight could be reduced by 1-4 kg, compared to the current period trend in weight gain. CONCLUSIONS: This is the first application of the Styblo technique to calculate T2DM incidence from population-based prevalence surveys over time. Reductions in population BMI are predicted to reduce T2DM incidence and prevalence in Fiji among adults aged 25-64 years.