Preconception sleep duration, non-daytime work schedules, and incidence of spontaneous abortion: a prospective cohort study.

STUDY QUESTION: To what extent do self-reported sleep duration and non-daytime work schedules in either partner affect the rate of spontaneous abortion (SAB)? SUMMARY ANSWER: Incidence of SAB had little association with female sleep duration and a modest positive association with male short sleep duration, female work at night, and discrepant work schedules among partners. WHAT IS KNOWN ALREADY: Several studies have reported an association between short sleep duration in either partner and reproductive health outcomes, including fecundability. Moreover, certain types of female occupational exposures during pregnancy have been associated with an increased risk of SAB. No studies have evaluated SAB risk in relation to male sleep and work schedules, or joint exposures within a couple. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 9357 female participants and 2602 of their male partners residing in North America (June 2013 to April 2023). PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants enrolled when they were attempting pregnancy and completed self-administered baseline questionnaires about their average sleep duration and work schedules. Among those who conceived, we ascertained SAB and gestational age at loss via follow-up questionnaires. We used multivariable Cox proportional hazards models with gestational weeks as the time scale to estimate hazard ratios (HRs) and 95% CIs relating SAB with sleep duration and non-daytime work schedules for female and male participants, and the couple. We used inverse probability weighting to account for potential selection bias due to the possibility of differential participation of male partners with respect to the exposures. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to female participants with recommended sleep (7-8.9 h), those reporting short sleep duration (<6 h) did not have a higher rate of SAB (HR 0.88, 95% CI 0.69, 1.13). Short self-reported sleep duration among male participants was modestly associated with a higher rate of SAB (adjusted and weighted HR 1.30, 95% CI 0.96, 1.75). Female night work at night (adjusted HR 1.19, 95% CI 1.02, 1.38) and male non-daytime work (adjusted and weighted HR 1.26, 95% CI 1.00, 1.59) were associated with modestly higher rates of SAB, whereas female rotating shift work was not (adjusted HR 0.91, 0.78, 1.05) compared with daytime workers. Couples in which work schedules were discrepant had an elevated rate of SAB if the male partner worked a non-daytime shift (adjusted and weighted HR 1.46, 95% CI 1.13, 1.88) compared with couples in which both members worked during the day. The corresponding HR if only the female partner worked a non-daytime shift was 1.21 (95% CI 0.92, 1.58). LIMITATIONS, REASONS FOR CAUTION: Data on sleep duration and work schedules were based on self-report, which is vulnerable to misclassification, particularly since participants were asked to report their average sleep duration during the past month. Work exposures were heterogeneous, as many different types of employment may require night and shift work and may have different associations with SAB. WIDER IMPLICATIONS OF THE FINDINGS: Our findings are consistent with previous research indicating that some types of female employment schedules may be associated with SAB incidence. This is the first study to indicate a relationship between SAB and male employment schedules, indicating that discrepant work schedules within a couple might be relevant. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development grants R01HD105863 (PIs: L.A.W. and M.L.E.), R01HD086742 (PIs: L.A.W. and E.E.H.), and R21HD072326 (PI: L.A.W.). PRESTO has received in-kind donations from Swiss Precision Diagnostics and Kindara.com for primary data collection. L.A.W. is a consultant for AbbVie, Inc. and the Gates Foundation. M.L.E. is an advisor for and holds stock in Ro, Hannah, Dadi, Underdog, Vseat, & Doveras. The other authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Self-reported periodontitis and fecundability in a population of pregnancy planners.

STUDY QUESTION: Is a history of periodontitis among women associated with reduced fecundability? SUMMARY ANSWER: A history of periodontitis, as assessed by three different self-reported measures, may be associated with reduced fecundability. WHAT IS KNOWN ALREADY: Periodontitis is a chronic inflammatory condition affecting the hard and soft tissues surrounding the teeth. Few studies have evaluated the association between periodontitis and time to pregnancy, and findings are mixed. It is hypothesized that periodontitis may adversely affect time to pregnancy. STUDY DESIGN, SIZE, DURATION: We conducted a prospective cohort study of 2764 female pregnancy planners residing in North America (March 2015-June 2020). PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible participants had been attempting pregnancy for six or fewer menstrual cycles at enrollment and were not using fertility treatment. Women answered questions about their oral health. Pregnancy was ascertained via bi-monthly follow-up questionnaires. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs) for three different measures indicative of a history of periodontitis: ever diagnosed with periodontitis (N = 265), ever received treatment for periodontitis (N = 299), and ever had an adult tooth become loose on its own (N = 83). We adjusted for potential confounders and precision variables. Women at risk of misclassification of periodontitis diagnosis due to pregnancy-related gingivitis were reclassified in a sensitivity analysis. MAIN RESULTS AND THE ROLE OF CHANCE: All three indices of periodontitis may be associated with reduced fecundability. FRs were 0.89 (95% CI 0.75-1.06) comparing women with and without a previous periodontitis diagnosis, 0.79 (95% CI 0.67-0.94) comparing women with and without previous periodontitis treatment, and 0.71 (95% CI 0.44-1.16) comparing women with and without a tooth that became loose. After reclassification of pregnancy-related gingivitis in the sensitivity analysis, the FR for periodontitis diagnosis was 0.83 (95% CI 0.68-1.00). Weaker FRs were observed among parous women as compared with nulliparous women for periodontitis diagnosis and tooth becoming loose, but not for periodontitis treatment. LIMITATIONS, REASONS FOR CAUTION: Though we used validated self-report measures of periodontitis, clinical confirmation is the gold standard. These questions may be functioning as markers of different levels of periodontitis severity, but we were unable to measure disease severity in this population. Finally, we cannot eliminate the possibility of unmeasured confounding. WIDER IMPLICATIONS OF THE FINDINGS: This is the first preconception prospective cohort study to evaluate the association between self-reported periodontitis and fecundability. Our results indicate that periodontitis may be associated with lower fecundability. STUDY FUNDING/COMPETING INTEREST(S): This work was partially funded by R01HD086742/Eunice Kennedy Shriver National Institute of Child Health and Human Development and R21HD072326/Eunice Kennedy Shriver National Institute of Child Health and Human Development. PRESTO has received in-kind donations from Swiss Precision Diagnostics, Sandstone Diagnostics, FertilityFriend.com, and Kindara.com for primary data collection. L.A.W. is a fibroid consultant for AbbVie, Inc. J.C.B., S.W., J.Y., K.J.R., E.E.H., and B.H. have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.

Diversity and potential distribution of culicids of medical importance of the Yucatan Peninsula, Mexico.

OBJECTIVE: To determine the species distribution, abundance, and diversity of culicids in the Yucatan Peninsula (YP); their potential distribution, using ecological niche modeling (ENM), and the risk of contact with urban and rural populations. MATERIALS AND METHODS: A cross-sectional study was carried out through the YP. The diversity of species was determined with the Shannon index. The potential distribution of the culicids was determined through the ENM, as well as the risk of urban and rural populations through contact with vectors. RESULTS: A total of 10 699 specimens, 15 genera and 52 species were registered. Campeche and the Biosphere Reserve of Calakmul exhibited the highest diversity. CONCLUSIONS: The ENM predict a high suitability in all the YP of Ae. aegypti, An. albimanus, An. pseudopuntipennis, Cx. coronator, and Cx. quinquefasciatus. The vector species that exhibited the highest risk of contact in the YP were Cx. quinquefasciatus, Ae. aegypti and Ae. albopictus.

OBJETIVO: Determinar la distribución, abundancia y diversidad de los culícidos de la Península de Yucatán (PY), su distribución potencial utilizando modelos de nicho ecológico (MNE) y el riesgo de contacto con poblaciones urbanas y rurales. MATERIAL Y MÉTODOS: Se realizó un estudio transversal. La diversidad fue determinada por el índice de Shannon. La distribución potencial de los culícidos se determinó a través de MNE, así como el riesgo de las poblaciones urbanas y rurales al contacto con los vectores. RESULTADOS: En total, se registraron 10 699 especímenes, 15 géneros y 52 especies. Campeche y la Reserva de la Biosfera de Calakmul presentaron la mayor diversidad. CONCLUSIONES: El MNE predice una alta idoneidad en toda la PY para Ae. aegypti, An. albimanus, An. pseudopuntipennis, Cx. coronador y Cx. quinquefasciatus. Las especies de vectores que presentaron el mayor riesgo de contacto en la PY fueron Cx. quinquefasciatus, Ae. aegypti y Ae. albopictus.

Comparison of novaluron, pyriproxyfen, spinosad and temephos as larvicides against Aedes aegypti in Chiapas, Mexico.

OBJECTIVE: To compare the efficacy of three modern larvicides with the organophosphate temephos for control of Aedes aegypti in water tanks in Chiapas. MATERIALS AND METHODS: Trials were performed to compare the efficacy of pyriproxyfen, novaluron, two formulations of spinosad (granules and tablets) and temephos in oviposition traps and domestic water tanks. RESULTS: Pyriproxyfen and temephos provided 2-3 weeks of complete control of larvae in oviposition traps, whereas spinosad granules and novaluron provided 7-12 weeks of control. Treatment of water tanks resulted in a significant reduction in oviposition by Ae. aegypti in houses (p<0.001). Higher numbers of larvae were present in temephos and pyriproxyfen-treated water tanks compared to novaluron and spinosad tablet treatments during most of the study. CONCLUSIONS: Spinosad formulations and novaluron were effective larvicides in this region. The poor performance of temephos may be indicative of reduced susceptibility in Ae. aegypti populations in Chiapas.

OBJETIVO: Comparar la eficacia de tres larvicidas modernos para el control de Aedes aegypti en tanques de agua doméstica en Chiapas. MATERIAL Y MÉTODOS: Se comparó la eficacia de piriproxifeno, novalurón, dos formulaciones de spinosad (gránulos y tabletas) y temefos en ovitrampas y tanques domésticos de agua. RESULTADOS: El piriproxifeno y el temefos proporcionaron de 2 a 3 semanas de control de larvas en ovitrampas, mientras que los gránulos de spinosad y novaluron proporcionaron de 7 a12 semanas. Los tanques de agua tratados produjeron una reducción significativa en la oviposición por Ae. aegypti en las casas (p<0.001). Se encontró gran cantidad de larvas en los tanques tratados con temefos y piriproxifeno en comparación con los tratados con novaluron y tabletas de spinosad durante la mayor parte del estudio. CONCLUSIONES: Las formulaciones de spinosad en tabletas y novaluron fueron larvicidas efectivos en esta región. El bajo desempeño de temefos puede indicar una susceptibilidad reducida en poblaciones de Ae. aegypti en Chiapas.

Thermoneutral conditions correct the obese phenotype in female, but not male, Kiss1r knockout mice.

Kisspeptin, a neuropeptide that activates gonadotropin-releasing hormone (GnRH) neurons, has also been implicated as a regulator of energy balance. Kisspeptin receptor (Kiss1r) knockout (KO) mice display an obese phenotype in adulthood compared to wild-type (WT) controls due to reduced energy expenditure. Additionally, experimental evidence shows that the temperature of typical rodent housing conditions (22 °C) increases the metabolism of mice above basal levels. Female Kiss1r KO mice show reduced core temperature and impaired temperature adaptation to an acute cold challenge, suggesting their temperature homeostasis processes are altered. The present study examined the phenotype of gonadectomised Kiss1r KO mice at both sub-thermoneutral and thermoneutral temperature (22 °C and 30 °C). Our results confirmed the obese phenotype in Kiss1r KO mice at 22 °C, and revealed a sexually dimorphic effect of thermal neutrality on the phenotype. In female KO mice, the obesity observed at 22 °C was attenuated at 30 °C. Plasma leptin levels were higher in KO than WT female mice at 22 °C (P < 0.001) but not at 30 °C. Importantly, the expression of Ucp1 mRNA in brown adipose tissue was lower in KO mice compared to WT mice at 22 °C (P < 0.05), but not different from WT at 30 °C. In male KO mice, a metabolic phenotype was observed at 22 °C and 30 °C. These results provide further evidence for kisspeptin-mediated regulation of adiposity via altered energy expenditure. Moreover, thermoneutral housing alleviated the obese phenotype in female Kiss1r KO mice, compared to WT, indicating the impairment in these mice may relate to an inability to adapt to the chronic cold stress that is experienced at 22 °C.

Immunomodulatory, liver depot gene therapy for Pompe disease.

Pompe disease is caused by mutations in acid alpha glucosidase (GAA) that causes accumulation of lysosomal glycogen affecting the heart and skeletal muscles, and can be fatal. Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA) improves muscle function by reducing glycogen accumulation. Limitations of ERT include a short half-life and the formation of antibodies that result in reduced efficacy. By harnessing the immune tolerance induction properties of the liver, liver-targeted gene delivery (with an adeno-associated virus vector containing a liver specific promoter), suppresses immunity against the GAA introduced by gene therapy. This induces immune tolerance to rhGAA by activating regulatory T cells and simultaneously, corrects GAA deficiency. Potentially, liver-targeted gene therapy can be performed once with lasting effects, by administering a relatively low dose of an adeno-associated virus type 8 vector to replace and induce immune tolerance to GAA.

Efficacy of larvicides for the control of dengue, Zika, and chikungunya vectors in an urban cemetery in southern Mexico.

Many countries in Latin America have recently experienced outbreaks of Zika and chikungunya fever, in additional to the usual burden imposed by dengue, all of which are transmitted by Aedes aegypti in this region. To identify potential larvicides, we determined the toxicity of eight modern insecticides to A. aegypti larvae from a colony that originated from field-collected insects in southern Mexico. The most toxic compounds were pyriproxyfen (which prevented adult emergence) and λ-cyhalothrin, followed by spinetoram, imidacloprid, thiamethoxam, and acetamiprid, with chlorantraniliprole and spiromesifen the least toxic products. Field trails performed in an urban cemetery during a chikungunya epidemic revealed that insecticide-treated ovitraps were completely protected from the presence of Aedes larvae and pupae for 6 and 7 weeks in spinosad (Natular G30) and λ-cyhalothrin-treated traps in both seasons, respectively, compared to 5-6 weeks for temephos granule-treated ovitraps, but was variable for pyriproxyfen-treated ovitraps with and 1 and 5 weeks of absolute control in the dry and rainy seasons, respectively. Insecticide treatments influenced the mean numbers of Aedes larvae + pupae in each ovitrap, mean numbers of eggs laid, and percentage of egg hatch over time in both trials. The dominant species was A. aegypti in both seasons, although the invasive vector Aedes albopictus was more prevalent in the rainy season (26.7%) compared to the dry season (10.2%). We conclude that the granular formulation of spinosad (Natular G30) and a suspension concentrate formulation of λ-cyhalothrin proved highly effective against Aedes spp. in both the dry and rainy seasons in the cemetery habitat in this region.

Evidence of lensing of the cosmic microwave background by dark matter halos.

We present evidence of the gravitational lensing of the cosmic microwave background by 10(13) solar mass dark matter halos. Lensing convergence maps from the Atacama Cosmology Telescope Polarimeter (ACTPol) are stacked at the positions of around 12 000 optically selected CMASS galaxies from the SDSS-III/BOSS survey. The mean lensing signal is consistent with simulated dark matter halo profiles and is favored over a null signal at 3.2σ significance. This result demonstrates the potential of microwave background lensing to probe the dark matter distribution in galaxy group and galaxy cluster halos.

Joint analysis of BICEP2/keck array and Planck Data.

We report the results of a joint analysis of data from BICEP2/Keck Array and Planck. BICEP2 and Keck Array have observed the same approximately 400 deg^{2} patch of sky centered on RA 0 h, Dec. -57.5°. The combined maps reach a depth of 57 nK deg in Stokes Q and U in a band centered at 150 GHz. Planck has observed the full sky in polarization at seven frequencies from 30 to 353 GHz, but much less deeply in any given region (1.2 µK deg in Q and U at 143 GHz). We detect 150×353 cross-correlation in B modes at high significance. We fit the single- and cross-frequency power spectra at frequencies ≥150 GHz to a lensed-ΛCDM model that includes dust and a possible contribution from inflationary gravitational waves (as parametrized by the tensor-to-scalar ratio r), using a prior on the frequency spectral behavior of polarized dust emission from previous Planck analysis of other regions of the sky. We find strong evidence for dust and no statistically significant evidence for tensor modes. We probe various model variations and extensions, including adding a synchrotron component in combination with lower frequency data, and find that these make little difference to the r constraint. Finally, we present an alternative analysis which is similar to a map-based cleaning of the dust contribution, and show that this gives similar constraints. The final result is expressed as a likelihood curve for r, and yields an upper limit r_{0.05}<0.12 at 95% confidence. Marginalizing over dust and r, lensing B modes are detected at 7.0σ significance.

Characterization of Quinone Outside Inhibitor Fungicide Resistance in Cercospora sojina and Development of Diagnostic Tools for its Identification.

Frogeye leaf spot of soybean, caused by the fungus Cercospora sojina, reduces soybean yields in most of the top-producing countries around the world. Control strategies for frogeye leaf spot can rely heavily on quinone outside inhibitor (QoI) fungicides. In 2010, QoI fungicide-resistant C. sojina isolates were identified in Tennessee for the first time. As the target of QoI fungicides, the cytochrome b gene present in fungal mitochondria has played a key role in the development of resistance to this fungicide class. The cytochrome b genes from three QoI-sensitive and three QoI-resistant C. sojina isolates were cloned and sequenced. The complete coding sequence of the cytochrome b gene was identified and found to encode 396 amino acids. The QoI-resistant C. sojina isolates contained the G143A mutation in the cytochrome b gene, a guanidine to cytosine transversion at the second position in codon 143 that causes an amino acid substitution of alanine for glycine. C. sojina-specific polymerase chain reaction primer sets and TaqMan probes were developed to efficiently discriminate QoI-resistant and -sensitive isolates. The molecular basis of QoI fungicide resistance in field isolates of C. sojina was identified as the G143A mutation, and specific molecular approaches were developed to discriminate and to track QoI-resistant and -sensitive isolates of C. sojina.

A Coordinated Effort to Manage Soybean Rust in North America: A Success Story in Soybean Disease Monitoring.

Existing crop monitoring programs determine the incidence and distribution of plant diseases and pathogens and assess the damage caused within a crop production region. These programs have traditionally used observed or predicted disease and pathogen data and environmental information to prescribe management practices that minimize crop loss. Monitoring programs are especially important for crops with broad geographic distribution or for diseases that can cause rapid and great economic losses. Successful monitoring programs have been developed for several plant diseases, including downy mildew of cucurbits, Fusarium head blight of wheat, potato late blight, and rusts of cereal crops. A recent example of a successful disease-monitoring program for an economically important crop is the soybean rust (SBR) monitoring effort within North America. SBR, caused by the fungus Phakopsora pachyrhizi, was first identified in the continental United States in November 2004. SBR causes moderate to severe yield losses globally. The fungus produces foliar lesions on soybean (Glycine max) and other legume hosts. P. pachyrhizi diverts nutrients from the host to its own growth and reproduction. The lesions also reduce photosynthetic area. Uredinia rupture the host epidermis and diminish stomatal regulation of transpiration to cause tissue desiccation and premature defoliation. Severe soybean yield losses can occur if plants defoliate during the mid-reproductive growth stages. The rapid response to the threat of SBR in North America resulted in an unprecedented amount of information dissemination and the development of a real-time, publicly available monitoring and prediction system known as the Soybean Rust-Pest Information Platform for Extension and Education (SBR-PIPE). The objectives of this article are (i) to highlight the successful response effort to SBR in North America, and (ii) to introduce researchers to the quantity and type of data generated by SBR-PIPE. Data from this system may now be used to answer questions about the biology, ecology, and epidemiology of an important pathogen and disease of soybean.

Modeling Social Network Influences on Oral Health Outcomes among Women Living in Public Housing.

OBJECTIVE: Research into the influence and role of social networks on oral health outcomes has been limited. This study aims to demonstrate via explanatory modeling the influence of social networks on oral health outcomes among women in who live in public housing in Boston, Massachusetts. METHODS: Individual- and network-level data were obtained from a cross-sectional survey of adult female residents of 2 public housing developments in Boston, Massachusetts. Participants responded to close-ended questions about sociodemographic characteristics, oral and general health status, and health-related behaviors for themselves as well as their named social contacts. Based on this information, network-level variables were calculated for each participant, including the proportion of the social network with certain characteristics or attributes. To assess the salience of network measures in explaining the variability in self-reported oral health status, overall health status, use of dental services within the last year, and current dental treatment needs, logistic regression models with individual-level covariates were compared with corresponding models that additionally included network-level variables with McFadden R2 for comparison purposes. RESULTS: Model comparisons for each outcome of interest demonstrated that adding network-level covariates significantly improved model fit. Additionally, network-level covariates displayed strong independent associations with the outcomes of interest. The network proportion needing dental treatment was positively associated with participants' odds of reporting current dental treatment needs (odds ratio, 4.71; 95% CI, 1.47 to 15.05). An individual's odds of reporting no dental visit within the past year decreased with increasing exposure to social contacts with reported dental visits within the past year (odds ratio, 0.26; 95% CI, 0.07 to 0.89). CONCLUSION: The salience of specific network attributes depended on the outcome under study. Interventions aimed at reducing the poor oral health burden in this and similar population groups may benefit from integrating information on social networks, including tailoring intervention delivery and/or messaging to account for the potential influence of social networks. KNOWLEDGE TRANSFER STATEMENT: This work may be beneficial to those developing policy solutions and interventions aimed at reducing the burden of poor oral health outcomes in socioeconomically disadvantaged populations, such as women who reside in public housing developments. The potential for leveraging social networks to seed messaging about oral health, for example, may enhance efforts to reduce oral health disparities.

Measles virus causes immunogenic cell death in human melanoma.

Oncolytic viruses (OV) are promising treatments for cancer, with several currently undergoing testing in randomised clinical trials. Measles virus (MV) has not yet been tested in models of human melanoma. This study demonstrates the efficacy of MV against human melanoma. It is increasingly recognised that an essential component of therapy with OV is the recruitment of host antitumour immune responses, both innate and adaptive. MV-mediated melanoma cell death is an inflammatory process, causing the release of inflammatory cytokines including type-1 interferons and the potent danger signal HMGB1. Here, using human in vitro models, we demonstrate that MV enhances innate antitumour activity, and that MV-mediated melanoma cell death is capable of stimulating a melanoma-specific adaptive immune response.

Release of sterile Aedes aegypti mosquitoes: chilling effect on mass-reared males survival and escape ability and on irradiated males sexual competitiveness.

In the sterile insect technique, it is important to measure the impact of mass-rearing and handling of sterile males to allow a successful control of the target wild population. This study evaluates the effect of pre-release chilling on the survival, escape ability, and sexual competitiveness of male Aedes aegypti. To determine survival and escape ability, mosquitoes were chilled at 4 °C using four different treatments of either one exposure (25 min) or two consecutive exposures (25 + 25 min, 25 + 50 min, 25 + 100 min). For sexual competitiveness, two different treatments were evaluated, chilling for 25 min once and twice. Results showed that the longest exposure to chilling caused a significant reduction of survival time, from 67 to 54 days. Escape ability was reduced by the first chilling from 25 to 7% and with the second chilling, it was reduced from 30 to 24% in the control to 4.9, 2.0 and 0.5% for 25, 50 and 100 min, respectively. Sexual competitiveness index was reduced from 1.16 in the control, to 0.32 and - 0.11 for treatments involving one and two chilling periods, respectively. It is recommended to increase the chilling temperature and reduce the exposure time to reduce the harmful effects on sterile males.

Quantitative Assessment of Systematic Bias: A Guide for Researchers.

Observational research provides valuable opportunities to advance oral health science but is limited by vulnerabilities to systematic bias, including unmeasured confounding, errors in variable measurement, or bias in the creation of study populations and/or analytic samples. The potential influence of systematic biases on observed results is often only briefly mentioned among the discussion of limitations of a given study, despite existing methods that support detailed assessments of their potential effects. Quantitative bias analysis is a set of methodological techniques that, when applied to observational data, can provide important context to aid in the interpretation and integration of observational research findings into the broader body of oral health research. Specifically, these methods were developed to provide quantitative estimates of the potential magnitude and direction of the influence of systematic biases on observed results. We aim to encourage and facilitate the broad adoption of quantitative bias analyses into observational oral health research. To this end, we provide an overview of quantitative bias analysis techniques, including a step-by-step implementation guide. We also provide a detailed appendix that guides readers through an applied example using real data obtained from a prospective observational cohort study of preconception periodontitis in relation to time to pregnancy. Quantitative bias analysis methods are available to all investigators. When appropriately applied to observational studies, findings from such studies can have a greater impact in the broader research context.

Changes to insulin sensitivity in glucose clearance systems and redox following dietary supplementation with a novel cysteine-rich protein: A pilot randomized controlled trial in humans with type-2 diabetes.

We recently developed a novel keratin-derived protein (KDP) rich in cysteine, glycine, and arginine, with the potential to alter tissue redox status and insulin sensitivity. The KDP was tested in 35 human adults with type-2 diabetes mellitus (T2DM) in a 14-wk randomised controlled pilot trial comprising three 2×20 g supplemental protein/day arms: KDP-whey (KDPWHE), whey (WHEY), non-protein isocaloric control (CON), with standardised exercise. Outcomes were measured morning fasted and following insulin-stimulation (80 mU/m2/min hyperinsulinaemic-isoglycaemic clamp). With KDPWHE supplementation there was good and very-good evidence for moderate-sized increases in insulin-stimulated glucose clearance rate (GCR; 26%; 90% confidence limits, CL 2%, 49%) and skeletal-muscle microvascular blood flow (46%; 16%, 83%), respectively, and good evidence for increased insulin-stimulated sarcoplasmic GLUT4 translocation (18%; 0%, 39%) vs CON. In contrast, WHEY did not effect GCR (-2%; -25%, 21%) and attenuated HbA1c lowering (14%; 5%, 24%) vs CON. KDPWHE effects on basal glutathione in erythrocytes and skeletal muscle were unclear, but in muscle there was very-good evidence for large increases in oxidised peroxiredoxin isoform 2 (oxiPRX2) (19%; 2.2%, 35%) and good evidence for lower GPx1 concentrations (-40%; -4.3%, -63%) vs CON; insulin stimulation, however, attenuated the basal oxiPRX2 response (4%; -16%, 24%), and increased GPx1 (39%; -5%, 101%) and SOD1 (26%; -3%, 60%) protein expression. Effects of KDPWHE on oxiPRX3 and NRF2 content, phosphorylation of capillary eNOS and insulin-signalling proteins upstream of GLUT4 translocation AktSer437 and AS160Thr642 were inconclusive, but there was good evidence for increased IRSSer312 (41%; 3%, 95%), insulin-stimulated NFκB-DNA binding (46%; 3.4%, 105%), and basal PAK-1Thr423/2Thr402 phosphorylation (143%; 66%, 257%) vs WHEY. Our findings provide good evidence to suggest that dietary supplementation with a novel edible keratin protein in humans with T2DM may increase glucose clearance and modify skeletal-muscle tissue redox and insulin sensitivity within systems involving peroxiredoxins, antioxidant expression, and glucose uptake.

Acute milk yield response to frequent milking during early lactation is mediated by genes transiently regulated by milk removal.

Milking dairy cows four times daily (4×) instead of twice daily (2×) during early lactation stimulates an increase in milk yield that partly persists through late lactation; however, the mechanisms behind this response are unknown. We hypothesized that the acute mammary response to regular milkings would be transient and would involve different genes from those that may be specifically regulated in response to 4×. Nine multiparous cows were assigned at parturition to unilateral frequent milking (UFM; 2× of the left udder half, 4× of the right udder half). Mammary biopsies were obtained from both rear quarters at 5 days in milk (DIM), immediately after 4× glands had been milked (experiment 1, n = 4 cows), or 2.5 h after both udder halves had last been milked (experiment 2, n = 5 cows). Affymetrix GeneChip Bovine Genome Arrays were used to measure gene expression. We found 855 genes were differentially expressed in mammary tissue between 2× vs. 4× glands of cows in experiment 1 (false discovery rate ≤ 0.05), whereas none were differentially expressed in experiment 2 using the same criterion. We conclude that there is an acute transcriptional response to milk removal, but 4× milking did not elicit differential expression of unique genes. Therefore, there does not appear to be a sustained transcriptional response to 4× milking on day 5 of lactation. Using a differential expression plot of data from both experiments, as well as qRT-PCR, we identified at least two genes (chitinase 3-like-1 and low-density lipoprotein-related protein-2 that may be responsive to both milk removal and to 4× milking. Therefore, the milk yield response to 4× milking may be mediated by genes that are acutely regulated by removal of milk from the mammary gland.

Evidence of galaxy cluster motions with the kinematic Sunyaev-Zel'dovich effect.

Using high-resolution microwave sky maps made by the Atacama Cosmology Telescope, we for the first time present strong evidence for motions of galaxy clusters and groups via microwave background temperature distortions due to the kinematic Sunyaev-Zel'dovich effect. Galaxy clusters are identified by their constituent luminous galaxies observed by the Baryon Oscillation Spectroscopic Survey, part of the Sloan Digital Sky Survey III. We measure the mean pairwise momentum of clusters, with a probability of the signal being due to random errors of 0.002, and the signal is consistent with the growth of cosmic structure in the standard model of cosmology.

Quantification of cytosol and membrane proteins in rumen epithelium of sheep with low or high CH4 emission phenotype.

BACKGROUND: Ruminant livestock are a major contributor to Australian agricultural sector carbon emissions. Variation in methane (CH4) produced from enteric microbial fermentation of feed in the reticulo-rumen of sheep differs with different digestive functions. METHOD: We isolated rumen epithelium enzymatically to extract membrane and cytosol proteins from sheep with high (H) and low (L) CH4 emission. Protein abundance was quantified using SWATH-mass spectrometry. RESULTS: The research found differences related to the metabolism of glucose, lactate and processes of cell defence against microbes in sheep from each phenotype. Enzymes in the methylglyoxal pathway, a side path of glycolysis, resulting in D-lactate production, differed in abundance. In the H CH4 rumen epithelium the enzyme hydroxyacylglutathione hydrolase (HAGH) was 2.56 fold higher in abundance, whereas in the L CH4 epithelium lactate dehydrogenase D (LDHD) was 1.93 fold higher. Malic enzyme 1 which converts D-lactate to pyruvate via the tricarboxylic cycle was 1.57 fold higher in the L CH4 phenotype. Other proteins that are known to regulate cell defence against microbes had differential abundance in the epithelium of each phenotype. CONCLUSION: Differences in the abundance of enzymes involved in the metabolism of glucose were associated with H and L CH4 phenotype sheep. Potentially this represents an opportunity to use protein markers in the rumen epithelium to select low CH4 emitting sheep.

Comparison of Ground Release and Drone-Mediated Aerial Release of Aedes aegypti Sterile Males in Southern Mexico: Efficacy and Challenges.

Sterile males of Aedes aegypti were released once a week for 8 weeks to evaluate the dispersal efficiency of ground and aerial drone release methods in a rural village of 26 Ha in southern Mexico. Indoor and outdoor BG-Sentinel traps were placed in 13−16 houses distributed throughout the village. The BG traps were activated 48 h after the release of the sterile males and functioned for a 24 h period following each release. Over the 8-week period of simultaneous ground and aerial releases, an average of 85,117 ± 6457 sterile males/week were released at ground level and 86,724 ± 6474 sterile males/week were released using an aerial drone. The ground release method resulted in higher numbers of captured males (mean = 5.1 ± 1.4, range 1.1−15.7 sterile males/trap) compared with the aerial release method (mean = 2.6 ± 0.8, range 0.5−7.3 sterile males/trap) (p < 0.05). Similarly, the prevalence of traps that captured at least one sterile male was significantly higher for ground release compared to the aerial release method (p < 0.01). The lower numbers of sterile males captured in the aerial release method could be due to mortality or physical injury caused by the chilling process for immobilization, or the compaction of these insects during transport and release. However, aerial releases by a two-person team distributed insects over the entire village in just 20 min, compared to ~90 min of work for a five-person team during the ground release method. Ground release also resulted in higher aggregations of males and some villagers reported feeling discomfort from the presence of large numbers of mosquitoes in and around their houses. We conclude that modifications to the handling and transport of sterile males and the design of containers used to store males are required to avoid injury and to improve the efficiency of aerial releases for area-wide SIT-based population suppression programs targeted at mosquito vectors of human disease.