Fatty Acid Conjugated Chalcones as Tubulin Polymerization Inhibitors: Design, Synthesis, QSAR, and Apoptotic and Antiproliferative Activity.

Cancer is often associated with an aberrant increase in tubulin and microtubule activity required for cell migration, invasion, and metastasis. A new series of fatty acid conjugated chalcones have been designed as tubulin polymerization inhibitors and anticancer candidates. These conjugates were designed to harness the beneficial physicochemical properties, ease of synthesis, and tubulin inhibitory activity of two classes of natural components. New lipidated chalcones were synthesized from 4-aminoacetophenone via N-acylation followed by condensation with different aromatic aldehydes. All new compounds showed strong inhibition of tubulin polymerization and antiproliferative activity against breast and lung cancer cell lines (MCF-7 and A549) at low or sub-micromolar concentrations. A significant apoptotic effect was shown using a flow cytometry assay that corresponded to cytotoxicity against cancer cell lines, as indicated by a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay. Decanoic acid conjugates were more potent than longer lipid analogues, with the most active being more potent than the reference tubulin inhibitor, combretastatin-A4 and the anticancer drug, doxorubicin. None of the newly synthesized compounds caused any detectable cytotoxicity against the normal cell line (Wi-38) or hemolysis of red blood cells below 100 µM. It is unlikely that the new conjugates described would affect normal cells or interrupt with cell membranes due to their lipidic nature. A quantitative structure-activity relationship analysis was performed to determine the influence of 315 descriptors of the physicochemical properties of the new conjugates on their tubulin inhibitory activity. The obtained model revealed a strong correlation between the tubulin inhibitory activity of the investigated compounds and their dipole moment and degree of reactivity.

Clinical supervision in medical education: A citation analysis.

PURPOSE: Medical education relies on clinical supervision for critical functions, including trainee assessment and ensuring patient safety. Yet, there is substantial variance in supervision, which has led to calls for a shared definition of the concept and guidelines to inform practice. AMEE Guide No. 27 provided these desired elements and is highly cited, suggesting that translation and utilization of the Guide's knowledge is suboptimal. This study investigates utilization by systematically characterizing citations to the Guide and by describing translation of its recommendations in relation to supervision. MATERIALS AND METHODS: Citations were identified using Web of Science, Scopus, and Google Scholar. The authors coded all citations and conducted a subanalysis of studies specific to supervision. RESULTS: 583 studies were identified; 268 met inclusion criteria for general analysis of which 167 studies were further analyzed. Most studies reiterated the Guide's characterization of effective supervision, but few demonstrate how these recommendations inform innovations in supervisory practice. CONCLUSION: Translation of the Guide's recommendations regarding clinical supervision appears limited. Future research should consider the extent of knowledge translation occurring in clinical supervision literature as well as AMEE Guides. Increased attention to knowledge translation in medical education may benefit the distribution of similar knowledge products.

Effects of Lidocaine-Derived Organic Compounds on Eosinophil Activation and Survival.

Lidocaine, a local anesthetic, is known to possess anti-inflammatory properties. However, its clinical use is limited by inconveniences, such as its local synesthetic effects. This study evaluated lidocaine analogs designed and synthesized to overcome the disadvantages of lidocaine, having anti-inflammatory properties. Interleukin 5 (IL-5)-induced eosinophil activation and survival were evaluated using 36 lidocaine analogs with modified lidocaine structure on the aromatic or the acyl moiety or both. Eosinophil survival was evaluated using a CellTiter 96® aqueous cell proliferation assay kit. Superoxide production was determined using the superoxide dismutase-inhibitable reduction of cytochrome C method. Eosinophil cationic protein (ECP), IL-8, and transcription factor expression were determined using enzyme-linked immunosorbent assay. The platelet-activating factor (PAF)-induced migration assay was performed using a Transwell insert system. Compounds EI137 and EI341 inhibited IL-5-induced eosinophil survival and superoxide and ECP production in a concentration-dependent manner. These compounds also significantly reduced IL-8 production. Although compounds EI137 and EI341 significantly reduced phosphorylated ERK 1/2 expression, they did not influence other total and phosphorylated transcription factors. Moreover, 1000 µM of compound EI341 only inhibited PAF-induced migration of eosinophils. Lidocaine analogs EI137 and EI341 inhibited IL-5-mediated activation and survival of eosinophils. These compounds could be new therapeutic agents to treat eosinophilic inflammatory diseases.

Autoimmune epilepsy, retrospective case series of clinical features, management, and outcomes.

OBJECTIVES: To evaluate the clinical and electrographic features of patients with autoimmune epilepsy and assess the influence of early diagnosis and treatment on reducing seizure frequency. METHODS: A retrospective observational case series was conducted utilizing medical records from King Abdullah Medical Hospital between 2017 and 2022. Cases of newly diagnosed seizures were chosen based on laboratory-proven autoimmunity. RESULTS: Five female inpatients were identified, primarily presenting with seizures suggestive of an autoimmune origin. Autoimmune antibodies were detected in all patients as follows: GAD (3), NMDA-R (2). One patient exhibited unilateral temporal lobe onset while three displayed bilateral onset. One patient had an associated malignancy. Rituximab was administered as an immunomodulatory therapy to four patients, resulting in successful seizure reduction post-immunotherapy initiation. CONCLUSION: Autoimmune epilepsy is recognized as a distinct condition. The clinical presentation can be complex and antibody testing may warrant repetition if initial results are negative or if specific antibodies are not detected. Early initiation of immunosuppression, coupled with prompt treatment escalation when required, is vital for achieving optimal patient outcomes.

Dust, Sand, and Winds Within an Active Martian Storm in Jezero Crater.

Rovers and landers on Mars have experienced local, regional, and planetary-scale dust storms. However, in situ documentation of active lifting within storms has remained elusive. Over 5-11 January 2022 (LS 153°-156°), a dust storm passed over the Perseverance rover site. Peak visible optical depth was ∼2, and visibility across the crater was briefly reduced. Pressure amplitudes and temperatures responded to the storm. Winds up to 20 m s-1 rotated around the site before the wind sensor was damaged. The rover imaged 21 dust-lifting events-gusts and dust devils-in one 25-min period, and at least three events mobilized sediment near the rover. Rover tracks and drill cuttings were extensively modified, and debris was moved onto the rover deck. Migration of small ripples was seen, but there was no large-scale change in undisturbed areas. This work presents an overview of observations and initial results from the study of the storm.

Knowledge, attitudes, and experiences in suicide assessment and management: a qualitative study among primary health care workers in southwestern Uganda.

BACKGROUND: Suicide is one of the leading causes of death globally, with over 75% of all suicides occurring in low-and middle-income Countries. Although 25% of people have contact with their health care workers before suicide attempts, most never receive proper suicide assessment and management. We explored primary care health workers' knowledge, attitudes, and experiences in evaluating and managing suicidality in structured primary healthcare services in Uganda. METHODS: This was a cross-sectional qualitative study among health workers in southwestern Uganda from purposively selected health facilities. A semi-structured interview guide was used, and data were analyzed using thematic analysis. RESULTS: The in-depth interviews were conducted with 18 individuals (i.e., five medical doctors, two clinical officers, two midwives, and nine nurses) from 12 health facilities in the five selected districts. Four themes emerged from the discussions: a) Knowledge and attitudes of primary healthcare workers in the assessment and management of suicidality, b) Experiences in the assessment and management of suicidality, c) challenges faced by primary healthcare workers while assessing and managing suicidality, and d) Recommendations for improving assessment and management of suicidality in PHC. Most participants were knowledgeable about suicide and the associated risk factors but reported challenges in assessing and managing individuals with suicide risk. The participants freely shared individual experiences and attitudes in the assessment and management of suicide. They also proposed possible ways to improve the evaluation and management of suicidality in PHC, such as setting up a system of managing suicidality, regularizing community sensitization, and training health workers. CONCLUSION: Suicidality is commonly encountered by primary health care workers in Uganda who struggle with its assessment and management. Improving the knowledge and attitudes of primary health care workers would be a big step towards ensuring equitable services.

Novel Amiloride Derivatives That Inhibit Bacterial Motility across Multiple Strains and Stator Types.

The bacterial flagellar motor (BFM) is a protein complex that confers motility to cells and contributes to survival and virulence. The BFM consists of stators that are ion-selective membrane protein complexes and a rotor that directly connects to a large filament, acting as a propeller. The stator complexes couple ion transit across the membrane to torque that drives rotation of the motor. The most common ion gradients that drive BFM rotation are protons (H+) and sodium ions (Na+). The sodium-powered stators, like those in the PomA/PomB stator complex of Vibrio spp., can be inhibited by sodium channel inhibitors, in particular, by phenamil, a potent and widely used inhibitor. However, relatively few new sodium motility inhibitors have been described since the discovery of phenamil. In this study, we characterized two possible motility inhibitors, HM2-16F and BB2-50F, from a small library of previously reported amiloride derivatives. We used three approaches: effect on rotation of tethered cells, effect on free-swimming bacteria, and effect on rotation of marker beads. We showed that both HM2-16F and BB2-50F stopped rotation of tethered cells driven by Na+ motors comparable to phenamil at matching concentrations and could also stop rotation of tethered cells driven by H+ motors. Bead measurements in the presence and absence of stators confirmed that the compounds did not inhibit rotation via direct association with the stator, in contrast to the established mode of action of phenamil. Overall, HM2-16F and BB2-50F stopped swimming in both Na+ and H+ stator types and in pathogenic and nonpathogenic strains. IMPORTANCE Here, we characterized two novel amiloride derivatives in the search for antimicrobial compounds that target bacterial motility. These compounds were shown to inhibit flagellar motility at 10 µM across multiple strains: from nonpathogenic Escherichia coli with flagellar rotation driven by proton or chimeric sodium-powered stators, to proton-powered pathogenic E. coli (enterohemorrhagic E. coli or uropathogenic E. coli [EHEC or UPEC, respectively]), and finally, sodium-powered Vibrio alginolyticus. Broad antimotility compounds such as these are important tools in our efforts to control virulence of pathogens in health and agricultural settings.

Pushing the super-resolution limit: recent improvements in microscopy below the diffraction limit.

Super-resolution microscopy has revolutionised the way we observe biological systems. These methods are now a staple of fluorescence microscopy. Researchers have used super-resolution methods in myriad systems to extract nanoscale spatial information on multiple interacting parts. These methods are continually being extended and reimagined to further push their resolving power and achieve truly single protein resolution. Here, we explore the most recent advances at the frontier of the 'super-resolution' limit and what opportunities remain for further improvements in the near future.

Nuclear heterogeneity is prevalent in high-quality fractionated human sperm cells typically used for assisted conception.

STUDY QUESTION: What is the nuclear heterogeneity of high-density purified human spermatozoa typically used for IVF purposes. SUMMARY ANSWER: The data show that while density gradient separation has improved the overall sperm population, there is still a large degree of nuclear heterogeneity within these cells. WHAT IS KNOWN ALREADY: Chromomycin A3 (CMA3) is an important DNA binding fluorochrome for the assessment of male-factor fertility. It is typically used to predict IVF outcomes on entire sperm ejaculates with very high receiver operating characteristic. Here we used CMA3 to characterise typical populations of human spermatozoa that would be used for IVF purposes after density gradient separation. STUDY DESIGN, SIZE, DURATION: We compared the intensity of CMA3 binding within high-dense sperm populations obtained from men. Binding heterogeneity was confirmed through fluorescence microscopy and FACS analysis independently. We also looked at CMA3 staining directly with head morphology in this sperm population. Finally, we looked at electron micrographs of nuclear heterogeneity (vacuoles, chromatin compaction) of spermatozoa following density gradient sorting of CMA3-stained cells. PARTICIPANTS/MATERIALS, SETTING, METHODS: We used sperm donors who had fathered one or more children. Semen was collected after 2 days abstinence and purified over Percoll gradients. Only the high-quality spermatozoa, the same used for assisted conception, were then used. Cells were stained with CMA3 and sorted using FACS. Following this, electron micrographs were used to assess nuclear heterogeneity of CMA3-dependent sorted spermatozoa. MAIN RESULTS AND THE ROLE OF CHANCE: CMA3 staining occurs within morphologically normal as well as abnormal spermatozoa. High-intensity CMA3-stained sperm possessed large vacuoles that were not seen in the low-CMA3 population. In addition, the high-CMA3 stained cells possess higher amounts of nuclear granulation. LIMITATIONS, REASONS FOR CAUTION: The present study only describes the issues within the chromatin of these cells and does not suggest an alternate selection technique. WIDER IMPLICATIONS OF THE FINDINGS: CMA3 is one of the better reported prognostic assays in predicting pregnancy outcomes, especially in cases where the male is at fault. However, it is clear that even in fractionated populations of human spermatozoa, there are sperm cells that are morphologically normal yet possess high levels of CMA3 staining and chromatin granulation. The implication of this is that the embryologist, whom selects on the basis of sperm morphology, may choose a cell with poor chromatin, which may lead to poor embryo outcomes. STUDY FUNDING/COMPETING INTEREST(S): The project was funded by the National Health and Medical Research council, APP1118943. The authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19.

We present a supercomputer-driven pipeline for in silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. Ensemble docking makes use of MD results by docking compound databases into representative protein binding-site conformations, thus taking into account the dynamic properties of the binding sites. We also describe preliminary results obtained for 24 systems involving eight proteins of the proteome of SARS-CoV-2. The MD involves temperature replica exchange enhanced sampling, making use of massively parallel supercomputing to quickly sample the configurational space of protein drug targets. Using the Summit supercomputer at the Oak Ridge National Laboratory, more than 1 ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to 10 configurations of each of the 24 SARS-CoV-2 systems using AutoDock Vina. Comparison to experiment demonstrates remarkably high hit rates for the top scoring tranches of compounds identified by our ensemble approach. We also demonstrate that, using Autodock-GPU on Summit, it is possible to perform exhaustive docking of one billion compounds in under 24 h. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and artificial intelligence (AI) methods to cluster MD trajectories and rescore docking poses.

Update on the campylobacter epidemic from chicken meat in New Zealand: The urgent need for an upgraded regulatory response.

New Zealand has a long-running campylobacter infection (campylobacteriosis) epidemic with contaminated fresh chicken meat as the major source. This is both the highest impact zoonosis and the largest food safety problem in the country. Adding to this burden is the recent rapid emergence of antibiotic resistance in these campylobacter infections acquired from locally-produced chicken. Campylobacteriosis rates halved in 2008, as compared with the previous 5 years, following the introduction of regulatory limits on allowable contamination levels in fresh chicken meat, with large health and economic benefits resulting. In the following decade, disease rates do not appear to have declined further. The cumulative impact would equate to an estimated 539 000 cases, 5480 hospitalisations, 284 deaths and economic costs of approximately US$380 million during the last 10 years (2009-2018). Additional regulatory interventions, that build on previously successful regulations in this country, are urgently needed to control the source of this epidemic.

Signal transducer and activator of transcription (STAT) 1 and STAT3 are expressed in the human ovary and have Janus kinase 1-independent functions in the COV434 human granulosa cell line.

Ovarian granulosa cells are fundamental for oocyte maintenance and maturation. Recent studies have demonstrated the importance of members of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway in the granulosa cell population of mouse and horse ovaries, with perturbation of JAK1 signalling in the mouse shown to impair oocyte maintenance and accelerate primordial follicle activation. The presence and role of the JAK/STAT pathway in human granulosa cells has yet to be elucidated. In this study, expression of JAK1, STAT1 and STAT3 was detected in oocytes and granulosa cells of human ovarian sections from fetal (40 weeks gestation) and premenopausal ovaries (34-41 years of age; n=3). To determine the effects of JAK1 signalling in granulosa cells, the human granulosa-like cell line COV434 was used, with JAK1 inhibition using ruxolitinib. Chemical inhibition of JAK1 in COV434 cells with 100nM ruxolitinib for 72h resulted in significant increases in STAT3 mRNA (P=0.034) and p-Y701-STAT1 protein (P=0.0117), demonstrating a role for JAK1 in modulating STAT in granulosa cells. This study implicates a conserved role for JAK/STAT signalling in human ovary development, warranting further investigation of this pathway in human granulosa cell function.

Validated spectrophotometric determination of maduramicin ammonium using three charge transfer complexation reactions.

Direct spectrophotometric determination of Maduramicin ammonium (MAD) represents an analytical challenge since it is a weak UV-absorbing and lacking a strong chromophore. This work represents the first spectrophotometric determination of MAD as no direct spectrophotometric or colorimetric determination methods for MAD are available in the literature. The present study illustrates the development of three simple, rapid and inexpensive colorimetric methods for the routine quality control analysis of MAD based on the formation of colored charge transfer complexes with three electron acceptors namely p-chloranilic acid (p-CA), 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) and picric acid (PA). The color products of MAD with p-CA, DDQ and PA were measured at 519, 588 and 405nm respectively. The proposed methods were validated in terms of linearity, ranges, precision, accuracy, robustness and limits of detection and quantification. MAD was effectively determined over concentration ranges of 100-1000, 25-250 and 30-150µg/mL using p-CA, DDQ and PA, respectively with good linearity as shown by the values of correlation coefficients not less than 0.9991. The developed methods were successfully implemented in the assay of MAD powder pharmaceutical formulation for veterinary use.

Adjunctive Dexamethasone in HIV-Associated Cryptococcal Meningitis.

BACKGROUND: Cryptococcal meningitis associated with human immunodeficiency virus (HIV) infection causes more than 600,000 deaths each year worldwide. Treatment has changed little in 20 years, and there are no imminent new anticryptococcal agents. The use of adjuvant glucocorticoids reduces mortality among patients with other forms of meningitis in some populations, but their use is untested in patients with cryptococcal meningitis. METHODS: In this double-blind, randomized, placebo-controlled trial, we recruited adult patients with HIV-associated cryptococcal meningitis in Vietnam, Thailand, Indonesia, Laos, Uganda, and Malawi. All the patients received either dexamethasone or placebo for 6 weeks, along with combination antifungal therapy with amphotericin B and fluconazole. RESULTS: The trial was stopped for safety reasons after the enrollment of 451 patients. Mortality was 47% in the dexamethasone group and 41% in the placebo group by 10 weeks (hazard ratio in the dexamethasone group, 1.11; 95% confidence interval [CI], 0.84 to 1.47; P=0.45) and 57% and 49%, respectively, by 6 months (hazard ratio, 1.18; 95% CI, 0.91 to 1.53; P=0.20). The percentage of patients with disability at 10 weeks was higher in the dexamethasone group than in the placebo group, with 13% versus 25% having a prespecified good outcome (odds ratio, 0.42; 95% CI, 0.25 to 0.69; P<0.001). Clinical adverse events were more common in the dexamethasone group than in the placebo group (667 vs. 494 events, P=0.01), with more patients in the dexamethasone group having grade 3 or 4 infection (48 vs. 25 patients, P=0.003), renal events (22 vs. 7, P=0.004), and cardiac events (8 vs. 0, P=0.004). Fungal clearance in cerebrospinal fluid was slower in the dexamethasone group. Results were consistent across Asian and African sites. CONCLUSIONS: Dexamethasone did not reduce mortality among patients with HIV-associated cryptococcal meningitis and was associated with more adverse events and disability than was placebo. (Funded by the United Kingdom Department for International Development and others through the Joint Global Health Trials program; Current Controlled Trials number, ISRCTN59144167.).

Does scientific effort reflect global need? A review of infectious disease publications over 100 years.

In a rational world, scientific effort would reflect society's needs. We tested this hypothesis using the area of infectious diseases, where the research response to emerging threats has obvious potential to save lives through informing interventions such as vaccination and prevention policies. Pathogens continue to evolve, emerge and re-emerge and infectious diseases that were once common become less so or their global distribution changes. A question remains as to whether scientific endeavours can adapt. Here, we identified papers on infectious diseases published in the four highest ranking, health-related journals over the 118 years from 1900. Focussing on outbreak-related and burden of disease-related metrics over the two time periods, 1990 to 2017 and 1900 to 2017, our analyses suggest that there is little underrepresentation of important infectious diseases among top ranked journals. Encouragingly our results suggest the scientific process is largely self-correcting.

Use of inline near-infrared spectroscopy to predict the viscosity of shampoo using multivariate analysis.

OBJECTIVE: In the personal care industry, viscosity is a critical quality attribute that influences product quality and process economics. Like many industrial liquids, personal care liquids are complex non-Newtonian liquids made up of aqueous surfactant systems whose viscosity depends on the build-up of micellar networks. Measuring the viscosity of complex liquids offline is easily done using benchtop rheometers and viscometers. The challenge lies in measuring the viscosity of personal care liquids online during manufacturing. Being able to track the viscosity of such products through their manufacturing cycle will not only allow for better process control but also more enhanced quality control. Therefore, the aim of this work was to investigate how proxy measurements using inline near-infrared (NIR) spectroscopy in transmission mode can be used to predict the viscosity of shampoo. NIR spectroscopy has not, to the best our knowledge, been used to predict the viscosity of complex surfactant systems like shampoo and could significantly affect the way quality is monitored in a manufacturing environment. METHOD: This work focuses on viscosity changes because of differences in chloride content as salt is often used to adjust viscosity. The relationship between salt content and the viscosity of shampoo is well known following the salt curve. From an industrial perspective the region of interest for the formulation studied in this work only covers a small section of this curve. Therefore, two predictive models were developed: one covering the full range of the salt curve and another focusing on the industrially applicable region. RESULT: Models were produced using partial least squares (PLS) where both datasets showed some predictive ability with the concentrated region of interest showing enhanced performance [root mean square error of prediction (RMSEP) - 2.32 Pa s] compared with the larger range (RMSEP - 4.44 Pa s). CONCLUSION: This work provides a good starting point for developing robust predictive models for in situ viscosity measurements for shampoo manufacturing, where further work into different sources of variation and the extent of the modelling capability with regards to different formulations should be studied.

OBJECTIF: Dans le secteur des soins personnels, la viscosité est une caractéristique de qualité cruciale qui influe sur la qualité du produit et l'économie en matière de processus. Comme de nombreux liquides industriels, les liquides destinés aux soins personnels sont des liquides non newtoniens complexes composés de systèmes tensioactifs aqueux dont la viscosité dépend de l'accumulation de réseaux micellaires. Mesurer la viscosité de liquides complexes hors ligne est facilement effectué à l'aide de rhéomètres et de viscosimètres de paillasse. Le défi consiste à mesurer la viscosité des liquides destinés aux soins personnels en ligne pendant la fabrication. Pouvoir suivre la viscosité de tels produits tout au long de leur cycle de fabrication permettra non seulement de mieux contrôler le processus mais aussi d'obtenir un meilleur contrôle qualité. Par conséquent, l'objectif de ce travail était d'étudier comment des mesures par procuration en utilisant la spectroscopie proche infrarouge (NIR) en ligne en mode de transmission peuvent être utilisées pour prédire la viscosité du shampooing. La spectroscopie proche infrarouge n'a pas, au mieux de nos connaissances, été utilisée pour prédire la viscosité de systèmes tensioactifs comme le shampooing, et elle pourrait significativement affecter la façon dont la qualité est surveillée dans un environnement de fabrication. MÉTHODE: Ce travail se concentre sur les changements au niveau de la viscosité en raison de différences dans la teneur en chlorure puisque le sel est souvent utilisé pour ajuster la viscosité. La relation entre la teneur en sel et la viscosité du shampooing est bien connue suivant la courbe du sel. D'un point de vue industriel, le domaine d'intérêt pour la formulation étudiée dans ce travail couvre seulement une petite section de cette courbe. Par conséquent, deux modèles prédictifs ont été développés : l'un portant sur la gamme complète de la courbe du sel et l'autre se concentrant sur le domaine applicable à l'industrie. RÉSULTAT: Les modèles ont été fabriqués en utilisant la méthode des moindres carrés partiels (partial least squares, PLS) où les deux ensembles de données ont montré un certain degré de capacité prédictive, le domaine concentré d'intérêt ayant fait preuve d'une meilleure performance (Root Mean Square Error of Prediction, RMSEP - 2,32 Pa s) par rapport à la plage de plus grande envergure (RMSEP - 4,44 Pa s). CONCLUSION: Ce travail fournit un bon point de départ pour élaborer des modèles prédictifs robustes servant à mesurer la viscosité in situ durant la fabrication des shampooings, mais d'autres travaux portant sur différentes sources de variation et sur l'ampleur de la capacité de modélisation de diverses formules doivent être effectués.

Relationship of American Indian blood quantum with osteoporosis risk: a cross-sectional study of American Indian women in Oklahoma.

Information regarding the prevalence and risk of osteoporosis among American Indian (AI) women is limited. This study showed that with increasing AI blood quantum, the prevalence of osteoporosis at the hip based on BMD T-scores decreased and this appeared to be independent of other risk factors. INTRODUCTION: This study was designed to investigate the effects of AI blood quantum (BQ) on osteoporosis prevalence and risk in a cohort of AI women in Oklahoma. METHODS: Women (n = 301), aged 50 years and older, were recruited to participate in the Oklahoma American Indian Women's Osteoporosis Study. Baseline bone density, fracture history, bone biochemical markers, and potential risk factors were assessed. Participants were stratified by AI BQ into BQ1 ≤ 25%, BQ2 = 25-49%, BQ3 = 50-74%, and BQ4 = 75-100%. The effects of BQ on the prevalence and risk of osteoporosis were evaluated. RESULTS: Based on T-scores, one in approximately eight women in the study was osteoporotic at one or more sites. The prevalence of osteoporosis decreased (p < 0.05) with increasing BQ, especially at the hip, trochanteric, and intertrochanter regions. No differences in bone-specific alkaline phosphatase and C-telopeptide were observed across BQ that could account for the differences in bone density. 25-OH vitamin D decreased with increasing BQ, but mean for each BQ1-4 was > 40 ng/mL. Fracture history did not differ across BQ, and though 52% of the population consumed less than the RDA for calcium, no effect of BQ was observed. CONCLUSIONS: In this cohort of women who identified as AI, greater Indian BQ was associated with a decrease in the prevalence of osteoporosis.

Estimating the likely true changes in rheumatic fever incidence using two data sources.

Acute rheumatic fever (ARF) continues to produce a significant burden of disease in New Zealand (NZ) Maori and Pacific peoples. Serious limitations in national surveillance data mean that accurate case totals cannot be generated. Given the changing epidemiology of ARF in NZ and the major national rheumatic fever prevention programme (2012-2017), we updated our previous likely true case number estimates using capture-recapture analyses. Aims were to estimate the likely true incidence of ARF in NZ and comment on the changing ability to detect cases. Data were obtained from national hospitalisation and notification databases. The Chapman Estimate partially adjusted for bias. An estimated 2342 likely true new cases arose from 1997 to 2015, giving a mean annual incidence of 2·9 per 100 000 (95% CI 2·5-3·5). Compared with the pre-intervention (2009-2011) baseline incidence (3·4 per 100 000, 95% CI 2·9-4·0), the likely true 2015 incidence declined 44%. Large gaps in data completeness are slowly closing. During the period 2012-2015, 723 cases were identified; 83·8% of notifications were matched to hospitalisation data, and 87·2% of hospitalisations matched to notifications. Despite this improvement, clinicians need to remain aware of the need to notify atypical patients. A possible unintended consequence of the national ARF prevention programme is increased misdiagnosis.

The feasibility of a pragmatic distance-based intervention to increase physical activity in lung cancer survivors.

The purpose of this study was to investigate the feasibility and preliminary efficacy of a pragmatic distance-based intervention designed to increase physical activity (PA) participation in lung cancer survivors. Fourteen lung cancer survivors were recruited via invitation from the State Cancer Registry to join a 12-week PA intervention of print materials paired with brief telephone follow-up. Outcome measures of feasibility, PA participation and quality of life (QoL) were assessed at baseline, post-intervention and follow-up via telephone interview. Eligibility, recruitment and attrition rates were 16%, 58% and 29% respectively. No adverse events were reported; however, pain scores worsened following the intervention (median change -3.6, IQR -8.0, 0.0). Average intervention adherence was 91% with low median ratings of participation burden (i.e., all items 1/7) and high trial evaluation (i.e., all items 7/7). Post-intervention, median change in self-reported moderate and vigorous PA was 84 min (IQR -22, 188), and several domains of QoL improved. However, for both of these outcomes, improvements were not maintained at follow-up. Our findings suggest that this pragmatic distance-based intervention was safe, had good adherence rates, and indicate potential for improving short-term PA and QoL in lung cancer survivors. Additional strategies are needed to improve other indicators of feasibility, particularly recruitment, retention and long-term maintenance of improvements. Australian New Zealand Clinical Trials Registration: ACTRN12612000085875.

Validated spectrophotometric and chromatographic methods for analysis of the recently approved hepatitis C antiviral combination ledipasvir and sofosbuvir.

This work describes five simple and reliable spectrophotometric and chromatographic methods for analysis of hepatitis C antiviral binary mixture of ledipasvir (LPV) and sofosbuvir (SBV). Method I is based on the use of Amax and derivative spectrophotometry with the zero-crossing technique where LPV was determined using its Amax and 1D amplitudes at 324 and 338nm respectively, while SBV was determined by measuring the 1D amplitudes at 276nm. Method II involves the application of the ratio spectra derivative spectrophotometry. For LPV, 12µg/mL SBV was used as divisor and the 1DD amplitudes at 239.8nm were plotted against LPV concentrations; while by using 10µg/mL LPV, the amplitudes at 279.2nm were found proportional to SBV concentrations. Method III depends on ratio-difference measurement where the peak to trough amplitudes between 229.2 and 268.4nm were measured and correlated to LPV concentration. Similarly, the amplitudes between 268.6 and 229.2nm in the SBV ratio spectra were recorded. For method IV, the two compounds were separated using HPTLC sheets of silica gel and a mobile phase composed of chloroform-methanol (94:6) followed by densitometric measurement of LPV and SBV spots at 331 and 267nm respectively. Method V depends on HPLC-DAD. Effective chromatographic separation was achieved using Thermohypersil C8 column (4.6×250mm, 5µm) with a mobile phase consisting of 0.01M sodium dihydrogen phosphate (pH 2.5) and methanol (20:80) at a flow rate 1.2mL/min and detection at 332 and 262nm for LPV and SBV respectively. Analytical performance of the developed methods was validated according to the ICH guidelines with respect to linearity, ranges, precision, accuracy, detection and quantification limits. The validated methods were successfully applied to the simultaneous analysis of LPV and SBV in mixtures of different proportions and their combined tablet dosage form.