Inactivation of face-selective neurons alters eye movements when free viewing faces.

During free viewing, faces attract gaze and induce specific fixation patterns corresponding to the facial features. This suggests that neurons encoding the facial features are in the causal chain that steers the eyes. However, there is no physiological evidence to support a mechanistic link between face-encoding neurons in high-level visual areas and the oculomotor system. In this study, we targeted the middle face patches of the inferior temporal (IT) cortex in two macaque monkeys using an functional magnetic resonance imaging (fMRI) localizer. We then utilized muscimol microinjection to unilaterally suppress IT neural activity inside and outside the face patches and recorded eye movements while the animals free viewing natural scenes. Inactivation of the face-selective neurons altered the pattern of eye movements on faces: The monkeys found faces in the scene but neglected the eye contralateral to the inactivation hemisphere. These findings reveal the causal contribution of the high-level visual cortex in eye movements.

Beyond faces: the contribution of the amygdala to visual processing in the macaque brain.

The amygdala is present in a diverse range of vertebrate species, such as lizards, rodents, and primates; however, its structure and connectivity differs across species. The increased connections to visual sensory areas in primate species suggests that understanding the visual selectivity of the amygdala in detail is critical to revealing the principles underlying its function in primate cognition. Therefore, we designed a high-resolution, contrast-agent enhanced, event-related fMRI experiment, and scanned 3 adult rhesus macaques, while they viewed 96 naturalistic stimuli. Half of these stimuli were social (defined by the presence of a conspecific), the other half were nonsocial. We also nested manipulations of emotional valence (positive, neutral, and negative) and visual category (faces, nonfaces, animate, and inanimate) within the stimulus set. The results reveal widespread effects of emotional valence, with the amygdala responding more on average to inanimate objects and animals than faces, bodies, or social agents in this experimental context. These findings suggest that the amygdala makes a contribution to primate vision that goes beyond an auxiliary role in face or social perception. Furthermore, the results highlight the importance of stimulus selection and experimental design when probing the function of the amygdala and other visually responsive brain regions.

Single-cell insights into development of the bovine placenta†.

A central determinant of pregnancy success is proper development of the conceptus (embryo/fetus and associated extraembryonic membranes including the placenta). Although the gross morphology and histology of the bovine placenta have been well studied, the cellular and molecular mechanisms regulating placenta development and trophoblast differentiation and function remain essentially undefined. Here, single-cell transcriptome (scRNA-seq) analysis was performed on the day 17 bovine conceptus and chorion of day 24, 30, and 50 conceptuses (n = 3-4 samples per day) using the 10X Genomics platform. Bioinformatic analyses identified cell types and their ontogeny including trophoblast, mesenchyme, and immune cells. Loss of interferon tau-expressing trophoblast uninucleate cells occurred between days 17 and 30, whereas binucleate cells, identified based on expression of placental lactogen (CSH2) and specific pregnancy-associated glycoprotein genes (PAGs), first appeared on day 24. Several different types of uninucleate cells were present in day 24, 30, and 50 samples, but only one (day 24) or two types of binucleate cells (days 30 and 50). Cell trajectory analyses provided a conceptual framework for uninucleate cell development and binucleate cell differentiation, and bioinformatic analyses identified candidate transcription factors governing differentiation and function of the trophoblasts. The digital atlas of cell types in the developing bovine conceptus reported here serves as a resource to discover key genes and biological pathways regulating its development during the critical periods of implantation and placentation.

The Diet Quality of Australian Stroke Survivors in a Community Setting.

INTRODUCTION: Diet quality is a marker of how closely eating patterns reflect dietary guidelines. The highest tertile for diet quality scores is associated with 40% lower odds of first stroke compared with the lowest tertile. Little is known about the diet of stroke survivors. We aimed to assess dietary intake and quality of Australian stroke survivors. METHODS: Stroke survivors enrolled in the ENAbLE pilot trial (2019/ETH11533, ACTRN12620000189921) and Food Choices after Stroke study (2020ETH/02264) completed the Australian Eating Survey Food Frequency Questionnaire (AES), a 120-item, semiquantitative questionnaire of habitual food intake over the previous 3-6 months. Diet quality was determined by calculating the Australian Recommended Food Score (ARFS): a higher score indicates higher diet quality. RESULTS: Eighty-nine adult, stroke survivors (female: n = 45, 51%) of mean age 59.5 years (±9.9) had a mean ARFS of 30.5 (±9.9) (low diet quality). Mean energy intake was similar to the Australian population: 34.1% from noncore (energy-dense/nutrient-poor) and 65.9% from core (healthy) foods. However, participants in the lowest tertile for diet quality (n = 31) had significantly lower intake of core (60.0%) and higher intake from noncore foods (40.0%). Most participants did not meet daily requirements for fiber, potassium, or omega 3 fatty acids (2%, 15%, and 18%), nutrients important to reduce stroke risk. CONCLUSION: The diet quality of stroke survivors was poor, with inadequate intake of nutrients important for reducing recurrent stroke risk. Further research is needed to develop effective interventions to improve diet quality.

Periostin's role in uterine leiomyoma development: a mini-review on the potential periostin poses as a pharmacological intervention for uterine leiomyoma.

Uterine leiomyomas, also known as fibroids or myomas, occur in an estimated 70-80% of reproductive aged women. Many experience debilitating symptoms including pelvic pain, abnormal uterine bleeding (AUB), dyspareunia, dysmenorrhea, and infertility. Current treatment options are limited in preserving fertility, with many opting for sterilizing hysterectomy as a form of treatment. Currently, surgical interventions include hysterectomy, myomectomy, and uterine artery embolization in addition to endometrial ablation to control AUB. Non-surgical hormonal interventions, including GnRH agonists, are connotated with negative side effects and are unacceptable for women desiring fertility. Periostin, a regulatory extra cellular matrix (ECM) protein, has been found to be expressed in various gynecological diseases including leiomyomas. We previously determined that periostin over-expression in immortalized myometrial cells led to the development of a leiomyoma-like cellular phenotype. Periostin is induced by TGF-ß, signals through the PI3K/AKT pathway, induces collagen production, and mediates wound repair and fibrosis, all of which are implicated in leiomyoma pathology. Periostin has been linked to other gynecological diseases including ovarian cancer and endometriosis and is being investigated as pharmacological target for treating ovarian cancer, post-surgical scarring, and numerous other fibrotic conditions. In this review, we provide discussion linking pathological inflammation and wound repair, with a TGF-ß-periostin-collagen signaling in the pathogenesis of leiomyomas, and ultimately the potential of periostin as a druggable target to treat leiomyomas.

Clutter substantially reduces selectivity for peripheral faces in the macaque brain.

According to a prominent view in neuroscience, visual stimuli are coded by discrete cortical networks that respond preferentially to specific categories, such as faces or objects. However, it remains unclear how these category-selective networks respond when viewing conditions are cluttered, i.e., when there is more than one stimulus in the visual field. Here, we asked three questions: (1) Does clutter reduce the response and selectivity for faces as a function of retinal location? (2) Is the preferential response to faces uniform across the visual field? And (3) Does the ventral visual pathway encode information about the location of cluttered faces? We used fMRI to measure the response of the face-selective network in awake, fixating macaques (2 female, 5 male). Across a series of four experiments, we manipulated the presence and absence of clutter, as well as the location of the faces relative to the fovea. We found that clutter reduces the response to peripheral faces. When presented in isolation, without clutter, the selectivity for faces is fairly uniform across the visual field, but, when clutter is present, there is a marked decrease in the selectivity for peripheral faces. We also found no evidence of a contralateral visual field bias when faces were presented in clutter. Nonetheless, multivariate analyses revealed that the location of cluttered faces could be decoded from the multivoxel response of the face-selective network. Collectively, these findings demonstrate that clutter blunts the selectivity of the face-selective network to peripheral faces, although information about their retinal location is retained.SIGNIFICANCE STATEMENTNumerous studies that have measured brain activity in macaques have found visual regions that respond preferentially to faces. Although these regions are thought to be essential for social behavior, their responses have typically been measured while faces were presented in isolation, a situation atypical of the real world. How do these regions respond when faces are presented with other stimuli? We report that, when clutter is present, the preferential response to foveated faces is spared but preferential response to peripheral faces is reduced. Our results indicate that the presence of clutter changes the response of the face-selective network.

Endometrial hyperplasia with loss of APC in a novel population of Lyz2-expressing mouse endometrial epithelial cells.

Loss of heterozygosity and promoter hypermethylation of APC is frequently observed in human endometrial cancer, which is the most common gynecological cancer in the USA, but its carcinogenic driver status in the endometrial epithelium has not been confirmed. We have identified a novel population of progenitor endometrial epithelial cells (EECs) in mice that express lysozyme M (LysM) and give rise to approximately 15% of all EECs in adult mice. LysM is a glycoside hydrolase that is encoded by Lyz2 and functions to protect cells from bacteria as part of the innate immune system. Its expression has been shown in a subset of hematopoietic stem cells and in specialized lung and small intestinal epithelial cells. Conditional deletion of Apc in LysM + EECs results in significantly more epithelial cells compared to wild-type mice. At 5 months of age, the ApccKO mice have enlarged uterine horns with pathology that is consistent with endometrial hyperplasia with cystic endometrial glands, non-villous luminal papillae and nuclear atypia. Nuclear accumulation of ß-catenin and ERα, both of which are known to induce endometrial hyperplasia, was observed in the EECs of the ApccKO mice. These results confirm that loss of APC in EECs can result in a phenotype similar to endometrial hyperplasia.

A re-appraisal of mesenchymal-epithelial transition (MET) in endometrial epithelial remodeling.

Mesenchymal-epithelial transition (MET) is a mechanism of endometrial epithelial regeneration. It is also implicated in adenocarcinoma and endometriosis. Little is known about this process in normal uterine physiology. Previously, using pregnancy and menses-like mouse models, MET occurred only as an epithelial damage/repair mechanism. Here, we hypothesized that MET also occurs in other physiological endometrial remodeling events, outside of damage/repair, such as during the estrous cycle and adenogenesis (gland development). To investigate this, Amhr2-Cre-YFP/GFP mesenchyme-specific reporter mice were used to track the fate of mesenchymal-derived (MD) cells. Using EpCAM (epithelial marker), EpCAM+YFP+ MD-epithelial cells were identified in all stages of the estrous cycle except diestrus, in both postpartum and virgin mice. EpCAM+YFP+ MD-epithelial cells comprised up to 80% of the epithelia during estrogen-dominant proestrus and significantly declined to indistinguishable from control uteri in diestrus, suggesting MET is hormonally regulated. MD-epithelial cells were also identified during postnatal epithelial remodeling. MET occurred immediately after birth at postnatal day (P) 0.5 with EpCAM+GFP+ cells ranging from negligible (0.21%) to 82% of the epithelia. EpCAM+GFP+ MD-epithelial cells declined during initiation of adenogenesis (P8, avg. 1.75%) and then increased during gland morphogenesis (P14, avg. 10%). MD-epithelial cells expressed markers in common with non-MD-epithelial cells (e.g., EpCAM, FOXA2, ESR1, PGR). However, MD-epithelial cells were differentially regulated postnatally and in adults, suggesting a functional distinction in the two populations. We conclude that MET occurs not only as an epithelial damage/repair mechanism but also during other epithelial remodeling events, which to our knowledge has not been demonstrated in other tissues.

Effects of Using Websites on Physical Activity and Diet Quality for Adults Living With Chronic Health Conditions: Systematic Review and Meta-Analysis.

BACKGROUND: Adults with chronic health conditions need support to manage modifiable risk factors such as physical inactivity and poor diet. Disease-specific websites with health information on physical activity and diet quality may be effective in supporting adults in managing their chronic illnesses. OBJECTIVE: The primary aim of this review was to determine whether using websites with health information can lead to improvements in physical activity levels or diet quality in adults with chronic health conditions. METHODS: Randomized controlled trials evaluating the effectiveness of website use on levels of physical activity or diet quality in adults with chronic health conditions were included. MEDLINE, Embase, CINAHL, and the Physiotherapy Evidence Database were searched from the earliest available record until February 2023. Data for outcomes measuring physical activity levels; diet quality; and, where reported, self-efficacy and quality of life were independently extracted by 2 reviewers. The risk of bias was assessed using the Physiotherapy Evidence Database scale, and the overall certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Where values were presented as the same unit of measure, postintervention scores were pooled for meta-analysis to yield an overall mean difference (MD). A standardized MD (SMD) was calculated for the pooled data in which different units for the same outcome were used. Individual trial data were described in cases where the data of trials could not be pooled. RESULTS: A total of 29 trials (N=6418 participants) across 8 different disease groups with intervention periods ranging from 4 weeks to 12 months were included in the analysis. There was moderate-certainty evidence that using websites with health information increased levels of moderate to vigorous physical activity (MD=39 min/wk, 95% CI 18.60-58.47), quality of life (SMD=0.36, 95% CI 0.12-0.59), and self-efficacy (SMD=0.26, 95% CI 0.05-0.48) and high-certainty evidence for reduction in processed meat consumption (MD=1.1 portions/wk, 95% CI 0.70-1.58) when compared with usual care. No differences were detected in other measures of diet quality. There was no increased benefit for website users who were offered additional support. CONCLUSIONS: The use of websites for risk factor management has the potential to improve physical activity levels, quality of life, and self-efficacy as well as reduce processed meat consumption for adults living with chronic health conditions when compared with usual care. However, it remains unclear whether using websites leads to meaningful and long-lasting behavior change. TRIAL REGISTRATION: PROSPERO CRD42021283168; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=283168.

Implementation of health and wellbeing policies and programs for students: Views of Australian universities.

ISSUE ADDRESSED: Universities are a crucial setting to address and promote optimal mental health of young Australians. However, there is a lack of knowledge of universities' views of current implementation of health and wellbeing initiatives. Therefore, we examined the views of Australian universities on the implementation of health and wellbeing policies and programs within Australian universities. METHODS: An online survey of Australian universities asked respondents to rate their level of agreement with five statements pertaining to the implementation of health and wellbeing policies and programs for students within Australian universities using a 5-point Likert scale (strongly agree to strongly disagree). RESULTS: Eleven universities completed the survey (28.2% response rate). All respondents (n = 11) agreed that universities play a crucial role in supporting the health and wellbeing of their students and report access to sufficient expertise to do this. Approximately three-quarters (8/11) agreed that universities know what policies and programs to implement to support their students' health and wellbeing. There was less agreement that universities have sufficient resources (2/11 agree) or access to sufficient information about the health and wellbeing of their student population (3/11 agree) to support the implementation of health and wellbeing policies and programs. CONCLUSIONS: Australian universities demonstrated strong organisational commitment to supporting the health and wellbeing of their students but highlighted some key barriers to implementation. SO WHAT?: Findings from this preliminary research highlight potential barriers and facilitators to the implementation of health and wellbeing policies and programs in Australian universities, and potential foci for future research.

Fit for purpose. Co-production of complex behavioural interventions. A practical guide and exemplar of co-producing a telehealth-delivered exercise intervention for people with stroke.

BACKGROUND: Careful development of interventions using principles of co-production is now recognized as an important step for clinical trial development, but practical guidance on how to do this in practice is lacking. This paper aims (1) provide practical guidance for researchers to co-produce interventions ready for clinical trial by describing the 4-stage process we followed, the challenges experienced and practical tips for researchers wanting to co-produce an intervention for a clinical trial; (2) describe, as an exemplar, the development of our intervention package. METHOD: We used an Integrated Knowledge Translation (IKT) approach to co-produce a telehealth-delivered exercise program for people with stroke. The 4-stage process comprised of (1) a start-up planning phase with the co-production team. (2) Content development with knowledge user informants. (3) Design of an intervention protocol. (4) Protocol refinement. RESULTS AND REFLECTIONS: The four stages of intervention development involved an 11-member co-production team and 32 knowledge user informants. Challenges faced included balancing conflicting demands of different knowledge user informant groups, achieving shared power and collaborative decision making, and optimising knowledge user input. Components incorporated into the telehealth-delivered exercise program through working with knowledge user informants included: increased training for intervention therapists; increased options to tailor the intervention to participant's needs and preferences; and re-naming of the program. Key practical tips include ways to minimise the power differential between researchers and consumers, and ensure adequate preparation of the co-production team. CONCLUSION: Careful planning and a structured process can facilitate co-production of complex interventions ready for clinical trial.

On-campus food purchasing behaviours and satisfaction of Australian university students.

ISSUE ADDRESSED: Many university students have unhealthy dietary intake. The food environment on university campuses is a potentially important contributor to students' diet. This study aimed to describe on-campus food purchasing behaviours; satisfaction with the cost and availability of foods and beverages on-campus; and preferences for the on-campus food environment, in a sample of Australian university students. METHODS: An online cross-sectional survey of 409 students at the University of Newcastle, Australia was conducted in 2017-2018. The survey assessed on-campus purchasing behaviours (frequency of purchase and expenditure), satisfaction with the cost and availability of foods, preferences for the on-campus food environment, and socio-demographics (eg age, domestic/international student). Results are reported as basic descriptive statistics. RESULTS: The majority of students (94%) purchased food or beverages on-campus, with 59% purchasing at least once per week. Satisfaction with the availability of foods was low (35.8% satisfied with the types of main meals available, and 48.5% for snacks); however, 72.8% were satisfied with types of beverages available. The majority of students were not satisfied with the cost of food and beverages (<40%). The top-rated preferences for changes to the on-campus food environment were healthier options, higher quality food, and cheaper food. CONCLUSION: Overall, the findings demonstrate strong support from students for healthier and cheaper food to be made available on-campus. SO WHAT?: There are two main factors of concern with regard to university food environments; the healthiness of food and beverage options and their cost. These should be key considerations of any future strategies aiming to improve university food environments.

The role of stem cells in uterine involution.

Uterine remodeling during pregnancy and repair postpartum are fundamental to the successful propagation of eutherian species. The most drastic remodeling occurs in species with invasively implanting embryos, including humans and mice. During embryo implantation, embryonic trophoblasts breach the epithelium, penetrating into the stroma. Stromal cell decidualization, which is critical for the establishment and maintenance of early pregnancy, occurs throughout the implantation site. Trophoblasts further invade into and remodel uterine spiral arteries, which is necessary for placental formation. The uterus increases in size up to 24-fold, which is largely attributed to myometrial expansion. Uterine changes that occur during pregnancy must then be resolved postpartum. Following parturition, the uterus repairs the remodeled tissue in the process of uterine involution. During involution, the majority of the endometrium is regenerated to replace the tissue that is shed postpartum. The myometrium returns to the pre-gravid state which is thought to occur through apoptosis and autophagy of smooth muscle cells. Although we understand the general process of postpartum uterine involution, the detailed mechanisms, particularly the role of putative stem cells, are poorly understood. This review discusses the evidence for the existence of epithelial, stromal and myometrial stem cells and their role in uterine involution. Gaps in knowledge and areas for future research are also considered. Studies of both postpartum and menstrual uterine repair, which likely involve similar mechanisms, are described under the broad definition of uterine involution. Although the primary focus of this review is human, mouse models are discussed to provide additional information.

Secondary Prevention of Stroke: Study Protocol for a Telehealth-Delivered Physical Activity and Diet Pilot Randomized Trial (ENAbLE-Pilot).

BACKGROUND: Increasing physical activity (PA) and improving diet quality are opportunities to improve secondary stroke prevention, but access to appropriate services is limited. Interventions co-designed with stroke survivors and delivered by telehealth are a potential solution. AIM: The aim of this study is to test the feasibility, safety, and potential efficacy of a 6-month, telehealth-delivered PA and/or dietary (DIET) intervention. METHODS: Pilot randomized trial. 80 adults with previous stroke who are living at home with Internet access and able to exercise will be randomized in a 2 × 2 factorial (4-arm) pilot randomized, open-label, blinded outcome assessment trial to receive PA, DIET, PA + DIET, or control interventions via telehealth. The PA intervention aims to support participants to meet the minimum recommended levels of PA (150 min/week moderate exercise), and the DIET intervention aims to support participants to follow the AusMed (Mediterranean-style) diet. The control group receives usual care plus education about PA and healthy eating. The co-primary outcomes are feasibility (proportion and characteristics of eligible participants enrolled and proportion of scheduled intervention sessions attended) and safety (adverse events) at 6 months. The secondary outcomes include recurrent stroke risk factors (blood pressure, physical activity levels, and diet quality), fatigue, mood, and quality of life. Outcomes are measured at 3, 6, and 12 months. CONCLUSION: This trial will produce evidence for the feasibility, safety, and potential effect of telehealth-delivered PA and DIET interventions for people with stroke. Results will inform development of an appropriately powered trial to test effectiveness to reduce major risk factors for recurrent stroke. TRIAL REGISTRATION: ACTRN12620000189921.

Epidemiological health assessment in primary healthcare in the State of Qatar- 2019.

BACKGROUND: In the public sector in Qatar, the Primary Health Care Corporation (PHCC) is the major provider of primary healthcare services to families. Therefore, the PHCC conducted the first epidemiological health assessment to understand the burden of diseases and their subsequent risk factors impacting its registered population, to design better services, implement it and allocate resources to respond to the population health needs. METHODS: A cross-sectional study design was adopted among all PHCC registered populations between September 1, 2018, and August 31, 2019. The study target population was all persons residing in Qatar aged 0+ years and registered at the 27 health centers affiliated with the PHCC; excluding patients with an expired residence permit on August 31, 2019, and craft male workers were provided their primary healthcare services at the Qatar Red Crescent health facilities. The data were extracted from patients' electronic medical records (EMR). RESULTS: The burden of type 2 diabetes, hypertension, and dyslipidemia were the highest among the population of the central region at 13.9%, 15.7%, and 11.1%, respectively. Tobacco consumption among males was higher than females and ranged from 25.4% to 27.8%, with the highest rate in the northern region. Obesity rates ranged between 34.7% and 37.0% among the total population registered with the lowest rate in the central region, while 39.9% of females in the northern region had a body mass index above 30 kg/m2. Exclusive breastfeeding at 6 months was significantly lower than that at 4 months across all regions. Children in the northern region had the highest rate of overweight/obesity based on Z-scores. The western region population had the highest number of communicable diseases notifications. CONCLUSION: Understanding the patterns of disease in the local population will enable the PHCC to plan a clear set of services that meet the population's health needs, which include tailored health education and promotion components.

Putative human myometrial and fibroid stem-like cells have mesenchymal stem cell and endometrial stromal cell properties.

STUDY QUESTION: Can endometrial stromal stem/progenitor cell markers, SUSD2 and CD146/CD140b, enrich for human myometrial and fibroid stem/progenitor cells? SUMMARY ANSWER: SUSD2 enriches for myometrial and fibroid cells that have mesenchymal stem cell (MSC) characteristics and can also be induced to decidualise. WHAT IS KNOWN ALREADY: Mesenchymal stem-like cells have been separately characterised in the endometrial stroma and myometrium and may contribute to diseases in their respective tissues. STUDY DESIGN, SIZE, DURATION: Normal myometrium, fibroids and endometrium were collected from hysterectomies with informed consent. Primary cells or tissues were used from at least three patient samples for each experiment. PARTICIPANTS/MATERIALS, SETTING, METHODS: Flow cytometry, immunohistochemistry and immunofluorescence were used to characterise tissues. In vitro colony formation in normoxic and hypoxic conditions, MSC lineage differentiation (osteogenic and adipogenic) and decidualisation were used to assess stem cell activity. Xenotransplantation into immunocompromised mice was used to determine in vivo stem-like activity. Endpoint measures included quantitative PCR, colony formation, trichrome, Oil Red O and alkaline phosphatase activity staining. MAIN RESULTS AND THE ROLE OF CHANCE: CD146+CD140b+ and/or SUSD2+ myometrial and fibroid cells were located in the perivascular region and formed more colonies in vitro compared to control cells and differentiated down adipogenic and osteogenic mesenchymal lineages in vitro. SUSD2+ myometrial cells had greater in vitro decidualisation potential, and SUSD2+ fibroid cells formed larger tumours in vivo compared to control cells. LARGE-SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Markers used in this study enrich for cells with stem/progenitor cell activity; however, they do not distinguish stem from progenitor cells. SUSD2+ myometrial cells express markers of decidualisation when treated in vitro, but in vivo assays are needed to fully demonstration their ability to decidualise. WIDER IMPLICATIONS OF THE FINDINGS: These results suggest a possible common MSC for the endometrial stroma and myometrium, which could be the tumour-initiating cell for uterine fibroids. STUDY FUNDING/COMPETING INTEREST(S): These studies were supported by NIH grants to JMT (R01OD012206) and to ALP (F32HD081856). The authors certify that we have no conflicts of interest to disclose.

Improving diet quality over nine-years is associated with less weight gain in mid-age Australian women: A cohort study.

BACKGROUND AND AIMS: Most studies measure baseline diet quality exclusively and hence the impact of longitudinal changes in dietary intake in relation to weight change is not considered. Therefore, this study aimed to examine whether change in diet quality over nine-years was associated with weight change over the same period in mid-age Australian women. METHODS AND RESULTS: Healthy mid-age (45-49 years) women from the Australian Longitudinal study on Women's Health (ALSWH) were eligible a valid total energy intake (TEI) was reported at baseline (n = 2381), determined using Goldberg cut-offs. Diet quality was measured by the Australian Recommended Food Score (ARFS) using data derived from a validated food frequency questionnaire. Multiple linear regressions were used to evaluate relationships between change in diet quality and weight in mid-age women (n = 1999). Women in the highest tertile of ARFS change improved diet quality [mean ± SD] [7 ± 4 points], while those in the lowest [-9 ±5 points] and middle [-1±2 points] tertiles had worse diet quality at follow-up. Overall, mean weight gain was 2.3 ± 7.2 kg over nine years. Those in the highest tertile of ARFS change gained significantly less weight, compared to the lowest tertile; ß = -1.2 kg [95% CI: -2.31, -0.11; p = 0.03] after adjustment for changes in confounders and baseline weight, baseline ARFS, and total energy intake. CONCLUSIONS: Improving diet quality could be an important strategy for promoting modest weight loss and potentially contribute to preventing weight gain in mid-age women, which is important for metabolic health.

Better diet quality scores are associated with a lower risk of hypertension and non-fatal CVD in middle-aged Australian women over 15 years of follow-up.

OBJECTIVE: To explore if better diet quality scores as a measure of adherence to the Australian Dietary Guidelines (ADG) and the Mediterranean diet (MedDiet) are associated with a lower incidence of hypertension and non-fatal CVD. DESIGN: Prospective analysis of the 1946-1951 cohort of the Australian Longitudinal Study on Women's Health (ALSWH). The Australian Recommended Foods Score (ARFS) was calculated as an indicator of adherence to the ADG; the Mediterranean Diet Score (MDS) measured adherence to the MedDiet. Outcomes included hypertension and non-fatal CVD. Generalised estimating equations estimated OR and 95 % CI across quartiles of diet quality scores. SETTING: Australia, 2001-2016. PARTICIPANTS: 1946-1951 cohort of the ALSWH (n 5324), without CVD, hypertension and diabetes at baseline (2001), with complete FFQ data. RESULTS: There were 1342 new cases of hypertension and 629 new cases of non-fatal CVD over 15 years of follow-up. Multivariate analysis indicated that women reporting better adherence to the ARFS (≥38/74) had 15 % (95 % CI 1, 28 %; P = 0·05) lower odds of hypertension and 46 % (95 % CI 6, 66 %; P = 0·1) lower odds of non-fatal CVD. Women reporting better adherence to the MDS (≥8/17) had 27 % (95 % CI 15, 47 %; P = 0·0006) lower odds of hypertension and 30 % (95 % CI 2, 50 %; P = 0·03) lower odds of non-fatal CVD. CONCLUSIONS: Better adherence to diet quality scores is associated with lower risk of hypertension and non-fatal CVD. These results support the need for updated evidenced based on the ADG as well as public health nutrition policies in Australia.

Specific deletion of LKB1/Stk11 in the Müllerian duct mesenchyme drives hyperplasia of the periurethral stroma and tumorigenesis in male mice.

Nearly all older men will experience lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH), the etiology of which is not well understood. We have generated Stk11CKO mice by conditional deletion of the liver kinase B1 (LKB1) tumor suppressor gene, Stk11 (serine threonine kinase 11), in the fetal Müllerian duct mesenchyme (MDM), the caudal remnant of which is thought to be assimilated by the urogenital sinus primordial mesenchyme in males during fetal development. We show that MDM cells contribute to the postnatal stromal cells at the dorsal aspect of the prostatic urethra by lineage tracing. The Stk11CKO mice develop prostatic hyperplasia with bladder outlet obstruction, most likely because of stromal expansion. The stromal areas from prostates of Stk11CKO mice, with or without significant expansion, were estrogen receptor positive, which is consistent with both MD mesenchyme-derived cells and the purported importance of estrogen receptors in BPH development and/or progression. In some cases, stromal hyperplasia was admixed with epithelial metaplasia, sometimes with keratin pearls, consistent with squamous cell carcinomas. Mice with conditional deletion of both Stk11 and Pten developed similar features as the Stk11CKO mice, but at a highly accelerated rate, often within the first few months after birth. Western blot analyses showed that the loss of LKB1 and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) induces activation of the phospho-5' adenosine monophosphate-activated protein kinase and phospho-AKT serine/threonine kinase 1 signaling pathways, as well as increased total and active ß-catenin. These results suggest that activation of these signaling pathways can induce hyperplasia of the MD stroma, which could play a significant role in the etiology of human BPH.