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Objective: For 3 decades, studies have reported that the usual sequence of drug initiation is licit drugs, then cannabis, and then other illicit drugs. This article describes the prevalence of violations of this sequence, the predictors of violations, and the relationship between violations and the onset of alcohol or drug dependence.Method: The New Zealand Mental Health Survey is a nationally representative sample with 12,992 face-to-face interviews carried out in 2003-2004. The response rate was 73.3%. The World Health Organization Composite International Diagnostic Interview (CIDI 3.0) was used in the survey. Reports of the age at first use were obtained for alcohol and drugs but not for smoking.Results: Violations of the usual sequence of drug initiation were uncommon in the population (2.6%). Use of other illicit drugs before cannabis was the main violation, found in 2.3% of alcohol users, 3.0% of cannabis users, 8.6% of cocaine users, and 16.7% of those who had used other illicit drugs. Use of other illicit drugs before cannabis was more predominant in younger cohorts and those with more early-onset internalizing disorders. Violations had little association with the development of dependence in users when other important predictors such as age at onset of use and the number of illicit drugs used were taken into account. Internalizing disorders and early-onset bipolar disorder also predicted dependence.Conclusions: In New Zealand, violations of the gateway sequence are not common and they are not markers of progression to dependence. [ABSTRACT FROM AUTHOR]

The relationship between mental disorders and chronic physical conditions is well established, but the possibility of ethnic group differences in mental-physical associations has seldom been investigated. This study investigated ethnic differences in associations between four physical conditions (chronic pain, cardiovascular disease, diabetes, and respiratory disease) and 12-month mood and anxiety disorders. A nationally representative face-to-face household survey was carried out in New Zealand from 2003 to 2004 with 12,992 participants aged 16 and older, achieving a response rate of 73.3%. The current study is of the subsample of 7,435 participants who were assessed for chronic physical conditions (via a standard checklist), and compares Maori, Pacific and Other New Zealanders. DSM-IV mental disorders were measured with the Composite International Diagnostic Interview (CIDI 3.0). The ethnic groups differed significantly in prevalences of both physical and mental disorders, but almost no ethnic differences in mental-physical associations were found. Independent of ethnicity, associations were observed between chronic pain and mood and anxiety disorders, cardiovascular disease and anxiety disorders, respiratory disease and mood and anxiety disorders. Despite differences in mental and physical health status between ethnic groups in New Zealand, mental-physical disorder associations occur with considerable consistency across the groups. These results suggest that whatever factors are conducive to the development of a mental disorder from a physical disorder (or vice versa), they are either unaffected by the cultural differences manifest in these ethnic groups, or, any cultural factors operating serve to both increase and decrease comorbidity such that they cancel each other out. [ABSTRACT FROM AUTHOR]

Background: A better understanding of the factors associated with the size and/or progression of osteolytic lesions has been hampered by a lack of sensitivity of radiographic measurement techniques.Methods: We retrospectively analyzed quantitative computed tomography scans that had been made with use of a high-resolution multi-slice scanner with a metal artifact-suppression protocol. The scans had been made to determine the volume of osteolytic lesions around thirty-five cementless Harris-Galante acetabular components that had been in situ for at least ten years. Repeat scans of thirty hips allowed for the measurement of progression in the size of osteolytic lesions over a one-year period. Associations between the volume of osteolytic lesions, progression in the size of the lesions, polyethylene wear since the time of implantation, change in component position, and patient-related variables (age, gender, body mass index, activity level, walking limitations, joint pain, and function) were determined.Results: In sixteen of the thirty hips that had repeat computed tomography scans, the lesions progressed in size during the study period. The median size of the lesions in these sixteen hips was 10.3 cm(3) at the time of the initial scan, compared with 13.3 cm(3) at a median of fifteen months later (p = 0.001). Osteolytic lesions measuring >10 cm(3) in volume on the initial scan were 2.5 times (95% confidence interval 1.3 to 4.8 times) more likely to progress in size over one year than smaller lesions were. Patients with greater polyethylene wear rates, higher activity levels, no walking limitations, and larger prosthetic femoral head dimensions (26 or 28 mm) had significantly larger osteolytic lesions (p < 0.0001, p = 0.009, p = 0.006, and p = 0.028, respectively). Progression in the size of the osteolytic lesions over one year was significantly associated with larger initial osteolytic lesions (p = 0.002), greater polyethylene wear rates (p = 0.009), and larger (26 or 28-mm) prosthetic femoral head dimensions (p = 0.019).Conclusions: There is considerable variation in the rates of progression of the size of osteolytic lesions around stable acetabular components. Lesion size and the progression of lesion size are generally related to polyethylene wear rates, higher patient activity levels, and larger-diameter femoral heads. Osteolytic lesions measuring >10 cm(3) in volume are associated with a high rate of progression. [ABSTRACT FROM AUTHOR]

BACKGROUND: Evidence is needed for the best long-term diet for weight loss, and improvement in cardiac risk and disease in obese adults. METHODS: We systematically reviewed randomized controlled trials (RCTs) in any language. We searched 13 databases and handsearched journals. Trials lasted 1 year or more. One investigator extracted the data and a second checked data extraction. Trial quality was assessed. RESULTS: Low fat diets (LFDs) produced significant weight losses up to 36 months (-3.55 kg; 95% CI, -4.54 to -2.55 kg). Blood pressure, lipids and fasting plasma glucose improved with these diets after 12 months. Four studies found that LFDs may prevent type 2 diabetes and reduce antihypertensive medication for up to 3 years. A very low calorie diet (VLCD, < 4.2 MJ day(-1)) was associated with the most weight loss after 12 months (-13.40 kg; 95% CI, -18.43 to -8.37 kg) in one small study with beneficial effects on asthma. There was no evidence that low carbohydrate protein sparing modified fasts (PSMFs) were associated with greater long-term weight loss than low calorie diets (LCDs, 4.2-6.7 MJ day(-1)) or VLCDs. PSMFs were, however, associated with greater lowering of fasting plasma glucose and HbA1c than LCDs. CONCLUSIONS: Little evidence supports the use of diets other than LFDs for weight reduction. With the increasing prevalence of morbid obesity, long-term follow-up in RCTs is needed to evaluate the effect of LCDs, VLCDs and PSMFs more fully. [ABSTRACT FROM AUTHOR]

BACKGROUND: Evidence is needed for the effectiveness of interventions given with reducing diets for obese adults: drug therapy, exercise, or behaviour therapy. METHODS: We systematically reviewed randomized controlled trials in any language. We searched 13 databases and handsearched journals. Trials lasted 1 year or more. One investigator extracted data and a second checked data extraction. Trial quality was assessed. RESULTS: Adding orlistat to diet was associated with weight change for up to 24 months (-3.26 kg, 95% CI, -4.15 to -2.37 kg), and statistically significant beneficial changes were found for total and LDL cholesterol, blood pressure and glycaemic control. Adding sibutramine to diet was associated with a 12 month weight change of -4.18 kg (95% CI, -5.14 to -3.21 kg), and statistically significant beneficial effects on high density lipoprotein cholesterol (HDL) and triglycerides (TGs), but an increase in diastolic blood pressure. Adding exercise to diet, or to diet and behaviour therapy, was associated with improved weight loss for up to 36 months and improvements in HDL, TGs and blood pressure. Adding behaviour therapy to diet, or to diet and sibutramine together, was associated with improved weight loss for up to 18 months. Adding drugs, exercise or behaviour therapy to dietary advice was each associated with similar weight change. CONCLUSIONS: Adding orlistat, sibutramine, exercise, or behaviour modification to dietary advice can improve long-term weight loss. [ABSTRACT FROM AUTHOR]

Background: Surgeons traditionally undertake a prospective evaluation of patients undergoing total hip arthroplasty in order to determine outcomes. The validity of doctor-derived data is questionable because of the potential for interobserver error, reporting bias, and differences between the perceptions of doctors and patients. Also, the use of doctor-derived data necessitates the use of costly outpatient services. Consequently, there are likely to be benefits associated with the use of patient-derived clinical evaluation data. However, few studies have focused on whether data obtained from the patient and doctor differ.Methods: The agreement between patient and doctor responses on a sixteen-item total hip arthroplasty clinical evaluation questionnaire completed at more than 2900 clinical assessments was determined. Data from repeated assessments performed preoperatively and postoperatively enabled stratified analyses that were used to examine reasons for disagreement and factors influencing agreement. Agreement was measured with use of the kappa coefficient.Results: For twelve of the sixteen items, the patient responses had acceptable agreement with the doctor responses. Some important differences between patient-derived and doctor-derived data were found. If the patient had other joint or health problems, had a revision total hip arthroplasty, or reported mild or moderate pain, there was a greater chance of reduced agreement on the pain items. Younger patients demonstrated better agreement with doctors than older patients did.Conclusions: Patients' perceptions of symptoms and outcomes after total hip arthroplasty are relatively similar to those of their doctor. There is minimum risk of misinterpreting outcomes data by replacing doctor-completed questionnaires with patient-completed questionnaires in uncomplicated total hip arthroplasty cases. For patients with comorbid joint problems or other health problems, and for those reporting substantial pain, direct physician involvement in the evaluation of pain is recommended. The selective use of patient-completed questionnaires has the potential to substantially reduce the costs of outcomes evaluation programs by minimizing doctor input. Pending revision of some of the items, the use of this patient-completed questionnaire is advocated. [ABSTRACT FROM AUTHOR]

OBJECTIVE: to provide a profile of disorders and disabilities in the older population. DESIGN: the MRC CFAS drew population samples of people aged 64 years and over from Family Health Service Authority lists at five sites and asked participants about sociodemographic variables, physical and cognitive health and activities of daily living, We calculated the prevalence of co-morbidity from the number of different types of complaint or disability (physical, functional and cognitive), and calculated healthy life expectancies in each of these co-morbid states. SETTING: three urban (Newcastle, Nottingham and Oxford) and two rural sites (Cambridgeshire and Gwynedd). RESULTS: the prevalence of morbidity is low at the youngest ages, as is co-morbidity. Women have consistently greater morbidity than men. Morbidity increases sharply with age, with a more dramatic rise in women. Life expectancy without any morbidity is short at all ages over 64, with the number of years expected with two or more areas affected virtually constant up to 90 years. As a proportion of remaining life expectancy, the period of time spent with two or more areas affected rises by the age of 90 to 30% in men and 60% in women. CONCLUSIONS: preventive programmes for the older population should take into account the large differences between the young old, the middle old and the old old. Our study provides a baseline against which to compare future changes in health in older populations, as well as benchmark expectancies for the UK population. [ABSTRACT FROM AUTHOR]

Background: Chinese females are distinguished internationally as having relatively high lung cancer incidence rates despite a low prevalence of cigarette smoking. In Singapore, this population comprises several dialect groups which have origins in different regions in China, each with its own traditional cultural practices.Methods: An analysis of 4029 incident cases of the disease notified to the Singapore Cancer Registry for 1968-1992 was undertaken to provide some insight into important aetiologic factors among these women.Results: The age-standardized incidence rate of lung cancer rose from 17.3 per 100,000 woman-years in 1968-1972 to 23.0 in 1978-1982 before falling off in more recent years. Age-period-cohort analysis indicated significant period and birth cohort effects, with the risk being highest for women born around 1908. Between the major dialect groups, Cantonese women had a significantly high rate compared with Hokkiens (relative risk [RR] = 2.6, 95% CI: 2.4-2.8). Histologically, there appears to be an increase in the proportion of adenocarcinomas diagnosed over this period (25.8% in 1968-1972 to 51.3% in 1988-1992).Conclusion: Our results suggest that traditional practices which have decreased over the years, and are more prominent among Southern Chinese, may play a part in the aetiology of lung cancer locally. [ABSTRACT FROM AUTHOR]

Background: Until recently relatively little data have been available on the prevalence of dementia in the oldest age groups, and yet it is these age groups which are expanding fastest. It is therefore important to understand whether the prevalence of dementia rises inexorably with age ('age-dependent'), or, as some suggest, levels off or even declines in the very oldest age groups ('age-related'). Combined analysis of the many prevalence studies now available has led to modelled curves which do suggest a slowing of rise in prevalence at these great ages, and has been interpreted as meaning that dementia is age-related. This interpretation does not take into account the differential survival of individuals with cognitive impairment compared with normals of the same age.Method: Flexible prevalence-incidence-duration models were generated using a deterministic approach applied to published combined analyses of prevalence rates, population death rates and mortality odds ratios.Results: The variation in observed prevalence patterns with age is explained to a great extent by the mortality observed in the cognitively impaired. Simple examination of age patterns in prevalence does not answer the fundamental question surrounding the age-dependence of cognitive impairment.Conclusion: Inferring biological meaning from these observed curves is not valid without examining the mathematical phenomena of the relationship of incidence, mortality and prevalence. This approach allows an examination of the impact of varying mortality and incidence on the prevalence of dementia and cognitive impairment and will be useful in determining the potential impact of preventive strategies on the population. [ABSTRACT FROM AUTHOR]

Abstract Background Weaning of beef calves is a necessary husbandry practice and involves separating the calf from its mother, resulting in numerous stressful events including dietary change, social reorganisation and the cessation of the maternal-offspring bond and is often accompanied by housing. While much recent research has focused on the physiological response of the bovine immune system to stress in recent years, little is known about the molecular mechanisms modulating the immune response. Therefore, the objective of this study was to provide new insights into the molecular mechanisms underlying the physiological response to weaning at housing in beef calves using Illumina RNA-seq. Results The leukocyte transcriptome was significantly altered for at least 7 days following either housing or weaning at housing. Analysis of differentially expressed genes revealed that four main pathways, cytokine signalling, transmembrane transport, haemostasis and G-protein-coupled receptor (GPRC) signalling were differentially regulated between control and weaned calves and underwent significant transcriptomic alterations in response to weaning stress on day 1, 2 and 7. Of particular note, chemokines, cytokines and integrins were consistently found to be up-regulated on each day following weaning. Evidence for alternative splicing of genes was also detected, indicating a number of genes involved in the innate and adaptive immune response may be alternatively transcribed, including those responsible for toll receptor cascades and T cell receptor signalling. Conclusions This study represents the first application of RNA-Seq technology for genomic studies in bovine leukocytes in response to weaning stress. Weaning stress induces the activation of a number of cytokine, chemokine and integrin transcripts and may alter the immune system whereby the ability of a number of cells of the innate and adaptive immune system to locate and destroy pathogens is transcriptionally enhanced. Stress alters the homeostasis of the transcriptomic environment of leukocytes for at least 7 days following weaning, indicating long term effects of stress exposure in the bovine. The identification of gene signature networks that are stress activated provides a mechanistic framework to characterise the multifaceted nature of weaning stress adaptation in beef calves. Thus, capturing subtle transcriptomic changes provides insight into the molecular mechanisms that underlie the physiological response to weaning stress.

Abstract Background The effect of pre-weaning concentrate supplementation on peripheral distribution of leukocytes, functional activity of neutrophils, acute phase protein response, metabolic and behavioural response, and performance of abruptly weaned and housed beef calves was investigated. Calves were grazed with their dams until the end of the grazing season when they were weaned and housed (day (d) 0) in a concrete slatted floor shed, and offered grass silage ad libitum plus supplementary concentrates. Twenty-six days prior to weaning and housing, 20 singled suckled, pure-bred Simmental male (non-castrated), (n = 10, m) and female (n = 10, f) calves were assigned to one of two treatments (i) concentrate supplement (CS: n = 10 (5 m and 5 f), mean age (s.d.) 201 (12.8) d, mean weight (s.d.) 258 (20.2) kg) or (ii) no concentrate supplement (controls) (NCS: n = 10, (5 m and 5 f), mean age (s.d.) 201 (13.4) d, mean weight (s.d.) 257 (19.6) kg) pre-weaning. Results There was a treatment × sampling time interaction (P < 0.05) for percentage CD4+ and WC1+ (γδ T cells) lymphocytes and concentration of plasma globulin. On d 2, percentage CD4+ lymphocytes decreased (P < 0.001) in both treatments. Subsequently on d 7, percentage of CD4+ lymphocytes increased (P < 0.01) in CS compared with d 0, whereas percentage of CD4+ lymphocytes in NCS did not differ (P > 0.05) from d 0. On d 2, WC1+ lymphocytes decreased (P < 0.05) in both treatments but the decrease was greater (P <0.05) in NCS than CS. Subsequently, percentages did not differ (P > 0.05) from pre-weaning baseline. On d 2, the increase in concentration of globulin was greater (P < 0.05) in CS compared with NCS, and subsequently there was no difference between treatments. Pre-weaning ADG was 1.07 (s.e.m.) (0.26) kg and 0.99 (s.e.m.) (0.26) kg for CS and NCS, respectively. Post-weaning, CS calves spent more time lying compared with NCS calves. Conclusions Calves supplemented with concentrate prior to weaning had a lesser reduction in WC1+ lymphocytes, increased percentage CD4+ lymphocytes and concentration of total protein, and spent more time lying post-weaning, compared with non-supplemented calves.

Abstract Background The molecular mechanisms by which stress induces the development of pathologies remains unclear, although it is recognised that one of the major factors affecting health as a consequence of stress is the involvement of the neuroendocrine system. In cattle, a number of necessary husbandry practices have been shown to activate the stress response, yet very little is known about the impact these have at the molecular level. The objectives of the study were to characterise, in male and female beef calves, the immune response to weaning stress in bovine leukocytes at the physiological and molecular levels and to assess the difference between calves weaned in the presence of the dam and those weaned and penned away from the dam. Results Following exposure to weaning stress, total neutrophil number and neutrophil:lymphocyte (N:L) ratio increased (P < 0.01) in calves. Additionally, expression of pro-inflammatory cytokine genes, including IL-1β, IL-8, IFN-γ and TNFα, were up-regulated (P < 0.01). Furthermore, there was increased (P < 0.001) expression of the glucocorticoid receptor, GRα, the pro-apoptotic gene, Fas and the Gram-negative pattern recognition receptor, TLR4. Calves penned away from the dam post-weaning had increased (P < 0.01) neutrophil number and N:L ratio compared with calves penned next to the dam, and female calves had higher (P < 0.05) expression levels of IL-2, IL-8, IFN-γ and TNFα than male calves. Conclusions Weaning elicits an immediate and somewhat short-lived acute stress response in the calf. The effects serve to enhance, rather than suppress, the immune response by means of a heightened inflammatory response and cellular mobilization. The earlier and more profound increase in neutrophil number and N:L ratio together with reduced lymphocyte number in calves penned away compared with calves penned near their dams post-weaning suggests that the former may be more sensitive to weaning stress. The data also show a clear effect of gender in differential gene expression in response to stress with IFN-γ having increased expression in female calves compared with male calves over the course of the study. Additionally, this study has helped to characterise the inflammatory response to stress in calves and identify a number of novel candidate biomarkers suitable for investigation in future studies of stress.

Abstract Background Weaning involves the permanent separation of the calf from the dam and has been shown to be stressful for both. The objectives of this study were to characterise the effect of i) abrupt weaning and ii) subsequent housing on the extended physiological and immunological responses of beef cows. At weaning (day (d) 0, mean age of calf (s.d.) 212 (24.5) d), cows were abruptly separated from their calves and returned to the grazing area. After 35 d at pasture, cows were housed in a slatted floor shed and offered grass silage ad libitum plus a mineral-vitamin supplement daily. Rectal body temperature was recorded and blood samples were obtained on i) d 0 (weaning), 2, 7, 14, 21, 28, 35 and subsequently on ii) d 0 (housing), 2, 7, 14 and 21 for physiological, haematological and immunological measurements. Results Post-weaning, concentration of cortisol and dehydroepiandrosterone were unchanged (P > 0.05). Rectal body temperature, neutrophil number and neutrophil: lymphocyte ratio increased (P < 0.01) on d 2 compared with pre-weaning baseline. Lymphocyte and neutrophil number decreased (P < 0.05) on d 2 to 7 and d 7 to 21, respectively, compared with pre-weaning baseline. Interferon-γ production decreased (P < 0.05) on d 2 compared with pre-weaning baseline. An increase (P < 0.05) in acute phase proteins, fibrinogen and haptoglobin was evident on d 2 to 35 compared with pre-weaning baseline. Concentration of glucose increased on d 2 to 28, whereas non-esterified fatty acid decreased on d 2 to 35 compared with pre-weaning baseline. Post-housing, concentrations of cortisol, rectal body temperature, total leukocyte number, and glucose were unchanged (P > 0.05). On d 2 post-housing, neutrophil number and neutrophil: lymphocyte ratio increased (P < 0.05), whereas lymphocyte number and concentrations of dehydroepiandrosterone, fibrinogen and non-esterified fatty acid decreased (P < 0.05) compared with pre-housing baseline. Concentration of haptoglobin increased (P < 0.05) on d 14 to 21 post-housing. Conclusions A transitory increase in neutrophil number and decrease in lymphocyte number, increased neutrophil:lymphocyte ratio coupled with decreased interferon-γ production, and increased concentration of acute phase proteins indicate a stress response in cows post-weaning, whereas post-housing, changes were less marked.

Objectives: Developing the capacity of the health system, and the practitioners within it, to provide quality gender responsive care to men and boys remains critical to advancing men's health, and reducing health inequities amongst men. The aim for this study was to undertake a formative evaluation of Australian university health curricula for men's health content and scope the opportunities for future enhancement., Methods: A two-stage evaluation first involved a review of online course information for a sample of medicine ( n  = 10), nursing ( n  = 10), pharmacy ( n  = 10), clinical psychology ( n  = 10), social work ( n  = 12) and public health ( n  = 15) university curricula for men's health and gender content and opportunities for curricula enhancement. Secondly, university staff completed a survey on the coverage of men's health in their course(s), and receptivity, barriers and facilitators to curricula enhancement., Results: The curricula review found no dedicated men's health courses, and men's health was referenced in the information for 10 of 1246 courses (0.8%) in 8 of 67 curricula. Gender was rarely referenced in course information, particularly for the disciplines of medicine, nursing, pharmacy, and clinical psychology. There was an average of 16 enhancement opportunities per curricula with 40% relating to communicating and engaging with men within healthcare. Seventy staff from 25 universities and all target disciplines validated the curricula review findings of limited dedicated men's health content. Eighty-three percent were receptive to curricula enhancement, facilitated by content integration into existing courses., Conclusion: This review provides clear evidence that there are gaps, opportunities, and educator receptiveness for improving and implementing content regarding men's health education and gender responsive care in Australian university health curricula., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2024.)

Background: While there have been calls over the last 15 years for the inclusion of training in sex and gender-based medicine in medical school curricula and to sustain such improvements through a more gender responsive health system, little progress has been made. A related objective of the Australian National Men's Health Strategy (2020-30) is to improve practitioner core learning competencies in men's health as a critical step to reducing the burden of disease in men and disparities between men in health care access and outcomes. The aim of this study was therefore to obtain Australian medical student perspectives on the extent to which men's health and sex and gender-based medicine education is delivered in their curricula, their preparedness for engaging with men in clinical practice, and the men's health content they would have found useful during their training., Methods: Eighty-three students (48% male) from 17 accredited medical schools, and in at least their fourth year of training, completed an online survey. The survey was co-designed by a multidisciplinary team of men's health researchers and clinicians, alongside a student representative. A mix of quantitative and qualitative survey items inquired about students' preparedness for men's health clinical practice, and coverage of men's health and sex- and gender-based medicine in their curricula., Results: Most students reported minimal to no men's health coverage in their medical school education (65%). While few were offered optional men's health units (10.5%), the majority would have liked more formal training on the topic (78%). Accompanying qualitative findings substantiated a lack of preparedness among medical students to engage male patients, likely stemming from minimal coverage of men's health in their medical education., Conclusions: Australian medical students may feel underprepared for contemporary men's health clinical practice, as well as, albeit to a lesser extent, women's health clinical practice. There is a clear need and desire amongst medical students to enhance curricula with sex and gender-based medicine training., (© 2024. The Author(s).)

Gender-responsive healthcare is critical to advancing men's health given that masculinities intersect with other social determinants to impact help-seeking, engagement with primary healthcare, and patient outcomes. A scoping review was undertaken with the aim to synthesize gender-responsive approaches used by healthcare providers (HCPs) to engage men with primary healthcare. MEDLINE, PubMed, CINAHL, and PsycINFO databases were searched for articles published between 2000 and February 2024. Titles and abstracts for 15,659 citations were reviewed, and 97 articles met the inclusion criteria. Data were extracted and analyzed thematically. Thirty-three approaches were synthesized from across counseling/psychology, general practice, social work, nursing, psychiatry, pharmacy, and unspecified primary healthcare settings. These were organized into three interrelated themes: (a) tailoring communication to reach men; (b) purposefully structuring treatment to meet men's health needs, and (c) centering the therapeutic alliance to retain men in care. Strength-based and asset-building approaches focused on reading and responding to a diversity of masculinities was reinforced across the three findings. While these approaches are recommended for the judicious integration into health practitioner education and practice, this review highlighted that the evidence remains underdeveloped, particularly for men who experience health inequities. Critical priorities for further research include intersectional considerations and operationalizing gender-responsive healthcare approaches for men and its outcomes, particularly at first point-of-contact encounters., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Metabolic engineering strategies have been successfully implemented to improve the production of isobutanol, a next-generation biofuel, in Saccharomyces cerevisiae . Here, we explore how two of these strategies, pathway re-localization and redox cofactor-balancing, affect the performance and physiology of isobutanol producing strains. We equipped yeast with isobutanol cassettes which had either a mitochondrial or cytosolic localized isobutanol pathway and used either a redox-imbalanced (NADPH-dependent) or redox-balanced (NADH-dependent) ketol-acid reductoisomerase enzyme. We then conducted transcriptomic, proteomic and metabolomic analyses to elucidate molecular differences between the engineered strains. Pathway localization had a large effect on isobutanol production with the strain expressing the mitochondrial-localized enzymes producing 3.8-fold more isobutanol than strains expressing the cytosolic enzymes. Cofactor-balancing did not improve isobutanol titers and instead the strain with the redox-imbalanced pathway produced 1.5-fold more isobutanol than the balanced version, albeit at low overall pathway flux. Functional genomic analyses suggested that the poor performances of the cytosolic pathway strains were in part due to a shortage in cytosolic Fe-S clusters, which are required cofactors for the dihydroxyacid dehydratase enzyme. We then demonstrated that this cofactor limitation may be partially recovered by disrupting iron homeostasis with a fra2 mutation, thereby increasing cellular iron levels. The resulting isobutanol titer of the fra2 null strain harboring a cytosolic-localized isobutanol pathway outperformed the strain with the mitochondrial-localized pathway by 1.3-fold, demonstrating that both localizations can support flux to isobutanol., Competing Interests: JJC is a consultant for Thermo Fisher Scientific., (© 2022 The Authors.)

Objectives: A randomised controlled trial was undertaken to compare the efficacy of topical Calendula officinalis (Calendula) versus standard of care (Sorbolene: 10% glycerine in cetomacragol cream) in reducing the prevalence of radiation-induced dermatitis in women undergoing breast cancer radiotherapy., Methods: A total of 271 women were screened and 82 were randomised. The primary outcome was prevalence of acute radiation-induced dermatitis (RTOG grade 2+) assessed at multiple skin sites. A chi-squared test was conducted for the primary outcome with a worst-case scenario imputation., Results: The recruitment target (n = 178) was not achieved. A total of n = 81 participants were analysed (n = 40 Calendula; n = 41 Sorbolene). There was no detectable difference in prevalence of radiation-induced dermatitis grade 2+ between the Calendula (53%) and Sorbolene (62%) groups (primary analysis OR = 0.87, 95% CI: [0.36, 2.09], P = 0.92; covariate adjusted complete case analysis OR 0.40, 95% CI: [0.13, 1.20], P = 0.10)., Conclusion: This randomised controlled trial showed no difference between Calendula and standard of care (Sorbolene) for the prevention of radiation-induced dermatitis. However, the study was underpowered (limited recruitment) for the primary comparison., (© 2020 The Australasian College of Dermatologists.)

Invited for this month's cover is the research team from the D.O.E. Great Lake Bioenergy Research Center (GLBRC) at the University of Wisconsin-Madison. The cover image shows how a diverse team with expertise in many different fields works together in an integrated fashion to address complex problems. Only when the whole system, from field to the liquid fuels and co-products, is assessed, can we identify the key parameters needed to design an economically viable biorefinery-based economy. Cover art by Chelsea Mamott. The Full Paper itself is available at 10.1002/cssc.201903345., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Operons are a hallmark of bacterial genomes, where they allow concerted expression of functionally related genes as single polycistronic transcripts. They are rare in eukaryotes, where each gene usually drives expression of its own independent messenger RNAs. Here, we report the horizontal operon transfer of a siderophore biosynthesis pathway from relatives of Escherichia coli into a group of budding yeast taxa. We further show that the co-linearly arranged secondary metabolism genes are expressed, exhibit eukaryotic transcriptional features, and enable the sequestration and uptake of iron. After transfer, several genetic changes occurred during subsequent evolution, including the gain of new transcription start sites that were sometimes within protein-coding sequences, acquisition of polyadenylation sites, structural rearrangements, and integration of eukaryotic genes into the cluster. We conclude that the genes were likely acquired as a unit, modified for eukaryotic gene expression, and maintained by selection to adapt to the highly competitive, iron-limited environment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Redesigning primary health services may enhance timely and effective uptake by men. The primary aim of this study was to assess the likelihood of Australian men attending a dedicated men's health service (DMHS). The further aims were to better understand the reasons for their preferences and determine how health behaviours influence likelihood., Methods: A survey on health service use and preferences, health help-seeking behaviours, and the likelihood of attending a DMHS was administered by telephone to 1506 randomly selected men (median age 56 years, range 19-95). Likelihood of attending a DMHS was rated using a single item Likert scale where 0 was not at all likely and 10 highly likely. Respondents were classified by age (< or > = 65 years) and health status. Principal component analyses were used to define health behaviours, specifically help-seeking and delay/avoidance regarding visiting a doctor. Multivariable linear and logistic regression analyses were used to examine predictors of likelihood of attending a DMHS., Results: The mean likelihood of attending a DMHS was 5.8 (SD 3.3, median 6, moderate likelihood) and 21%, 26% and 23% of men rated likelihood as moderate, high and very high respectively. Being happy with their existing doctor was the most common reason (52%) for being less likely to attend a DMHS. In unadjusted analyses, younger men reported being more likely to attend a DMHS (p < 0.001) with older-sick men reporting being least likely (p < 0.001). Younger men were more likely than older men to score higher on delay/avoidance and were more likely to self-monitor. In the full model, men with current health concerns (p ≤ 0.01), who scored higher on delay/avoidance (p ≤ 0.0006), who were more likely to be information-seekers (p < 0.0001) and/or were motivated to change their health (p ≤ 0.0001) reported a higher likelihood of attending a DMHS irrespective of age and health status., Conclusions: Seventy percent of men reported a moderate or higher likelihood of attending a DMHS. As young healthy men are more likely than older men to display health behaviours that are associated with a higher likelihood of attending a DHMS, such as delay/avoidance, marketing a DMHS to such men may be of value.

Osteoarthritis (OA) is a debilitating inflammation related disease characterized by joint pain and effusion, loss of mobility, and deformity that may result in functional joint failure and significant impact on quality of life. Once thought of as a simple "wear and tear" disease, it is now widely recognized that OA has a considerable metabolic component and is related to chronic inflammation. Defects associated with primary cilia have been shown to be cause OA-like changes in Bardet-Biedl mice. We examined the role of dysfunctional primary cilia in OA in mice through the regulation of the previously identified degradative and pro-inflammatory molecular pathways common to OA. We observed an increase in the presence of pro-inflammatory markers TGFβ-1 and HTRA1 as well as cartilage destructive protease MMP-13 but a decrease in DDR-2. We observed a morphological difference in cartilage thickness in Bbs1 M390R/M390R mice compared to wild type (WT). We did not observe any difference in OARSI or Mankin scores between WT and Bbs1 M390R/M390R mice. Primary cilia appear to be involved in the upregulation of biomarkers, including pro-inflammatory markers common to OA.

Recent studies showed that the circulating stress hormones, epinephrine and corticosterone/cortisol, are involved in mediating ozone-induced pulmonary effects through the activation of the sympathetic-adrenal-medullary (SAM) and hypothalamus-pituitary-adrenal (HPA) axes. Hence, we examined the role of adrenergic and glucocorticoid receptor inhibition in ozone-induced pulmonary injury and inflammation. Male 12-week old Wistar-Kyoto rats were pretreated daily for 7days with propranolol (PROP; a non-selective β adrenergic receptor [AR] antagonist, 10mg/kg, i.p.), mifepristone (MIFE; a glucocorticoid receptor [GR] antagonist, 30mg/kg, s.c.), both drugs (PROP+MIFE), or respective vehicles, and then exposed to air or ozone (0.8ppm), 4h/d for 1 or 2 consecutive days while continuing drug treatment. Ozone exposure alone led to increased peak expiratory flow rates and enhanced pause (Penh); with greater increases by day 2. Receptors blockade minimally affected ventilation in either air- or ozone-exposed rats. Ozone exposure alone was also associated with marked increases in pulmonary vascular leakage, macrophage activation, neutrophilic inflammation and lymphopenia. Notably, PROP, MIFE and PROP+MIFE pretreatments significantly reduced ozone-induced pulmonary vascular leakage; whereas PROP or PROP+MIFE reduced neutrophilic inflammation. PROP also reduced ozone-induced increases in bronchoalveolar lavage fluid (BALF) IL-6 and TNF-α proteins and/or lung Il6 and Tnfα mRNA. MIFE and PROP+MIFE pretreatments reduced ozone-induced increases in BALF N-acetyl glucosaminidase activity, and lymphopenia. We conclude that stress hormones released after ozone exposure modulate pulmonary injury and inflammatory effects through AR and GR in a receptor-specific manner. Individuals with pulmonary diseases receiving AR and GR-related therapy might experience changed sensitivity to air pollution., (Published by Elsevier Inc.)

Previous studies have demonstrated that exposure to the pulmonary irritant ozone causes myriad systemic metabolic and pulmonary effects attributed to sympathetic and hypothalamus-pituitary-adrenal (HPA) axis activation, which are exacerbated in metabolically impaired models. We examined respiratory and systemic effects following exposure to a sensory irritant acrolein to elucidate the systemic and pulmonary consequences in healthy and diabetic rat models. Male Wistar and Goto Kakizaki (GK) rats, a nonobese type II diabetic Wistar-derived model, were exposed by inhalation to 0, 2, or 4 ppm acrolein, 4 h/d for 1 or 2 days. Exposure at 4 ppm significantly increased pulmonary and nasal inflammation in both strains with vascular protein leakage occurring only in the nose. Acrolein exposure (4 ppm) also caused metabolic impairment by inducing hyperglycemia and glucose intolerance (GK > Wistar). Serum total cholesterol (GKs only), low-density lipoprotein (LDL) cholesterol (both strains), and free fatty acids (GK > Wistar) levels increased; however, no acrolein-induced changes were noted in branched-chain amino acid or insulin levels. These responses corresponded with a significant increase in corticosterone and modest but insignificant increases in adrenaline in both strains, suggesting activation of the HPA axis. Collectively, these data demonstrate that acrolein exposure has a profound effect on nasal and pulmonary inflammation, as well as glucose and lipid metabolism, with the systemic effects exacerbated in the metabolically impaired GKs. These results are similar to ozone-induced responses with the exception of lung protein leakage and ability to alter branched-chain amino acid and insulin levels, suggesting some differences in neuroendocrine regulation of these two air pollutants., (Published by Oxford University Press on behalf of the Society of Toxicology 2017. This work is written by US Government employees and is in the public domain in the US.)

Background: The risk of revision following primary total hip arthroplasty (THA) is increased in young patients who undergo THA for pathologies other than primary osteoarthritis. We report the results of primary THA performed with cemented polished stems in patients aged 40 years and younger for pathologies other than primary osteoarthritis., Methods: We investigated 52 patients (65 hips) who underwent primary THA for secondary osteoarthritis with a cemented tapered polished stem between 1990 and 2007. Clinical and radiographic outcomes, available in 46 patients (57 hips), included the Harris Hip Scores, Societe Internationale de Chirurgie Orthopedique et de Traumatologie activity, patient satisfaction, stem survival and reoperations, and assessment of prosthesis-cement-bone radiolucencies, osteolysis, and femoral bone deficiencies., Results: Median patient age was 34 years (16-40) and follow-up was 14 years (mean 13, range 5-22). Stem survival to the endpoint revision for loosening was 100% and to the endpoint revision for any reason, excluding infection was 88% (95% confidence interval 78-98) at 16 years. No stem was revised for aseptic loosening. Nine stems were revised for other reasons. Radiographically, one stem was definitely loose at 16 years. The median patient Harris pain score improved from marked pain to no pain at latest follow-up. Patient activity level improved, albeit minimally, for 8 years after surgery. At latest follow-up, 98% of the patients remained satisfied with their surgery., Conclusion: Primary THA with a cemented polished stem shows excellent results in young patients with pathology other than primary osteoarthritis. In addition, the stem design facilitates cement within cement exchange and therefore preservation of proximal femoral bone stock at revision surgery., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The inability of native Saccharomyces cerevisiae to convert xylose from plant biomass into biofuels remains a major challenge for the production of renewable bioenergy. Despite extensive knowledge of the regulatory networks controlling carbon metabolism in yeast, little is known about how to reprogram S. cerevisiae to ferment xylose at rates comparable to glucose. Here we combined genome sequencing, proteomic profiling, and metabolomic analyses to identify and characterize the responsible mutations in a series of evolved strains capable of metabolizing xylose aerobically or anaerobically. We report that rapid xylose conversion by engineered and evolved S. cerevisiae strains depends upon epistatic interactions among genes encoding a xylose reductase (GRE3), a component of MAP Kinase (MAPK) signaling (HOG1), a regulator of Protein Kinase A (PKA) signaling (IRA2), and a scaffolding protein for mitochondrial iron-sulfur (Fe-S) cluster biogenesis (ISU1). Interestingly, the mutation in IRA2 only impacted anaerobic xylose consumption and required the loss of ISU1 function, indicating a previously unknown connection between PKA signaling, Fe-S cluster biogenesis, and anaerobiosis. Proteomic and metabolomic comparisons revealed that the xylose-metabolizing mutant strains exhibit altered metabolic pathways relative to the parental strain when grown in xylose. Further analyses revealed that interacting mutations in HOG1 and ISU1 unexpectedly elevated mitochondrial respiratory proteins and enabled rapid aerobic respiration of xylose and other non-fermentable carbon substrates. Our findings suggest a surprising connection between Fe-S cluster biogenesis and signaling that facilitates aerobic respiration and anaerobic fermentation of xylose, underscoring how much remains unknown about the eukaryotic signaling systems that regulate carbon metabolism., Competing Interests: The authors have declared that no competing interests exist.

Excellent reviews on central N-methyl-D-aspartate receptor (NMDAR) signaling and function in cardiovascular regulating neuronal pools have been reported. However, much less attention has been given to NMDAR function in peripheral tissues, particularly the heart and vasculature, although a very recent review discusses such function in the kidney. In this short review, we discuss the NMDAR expression and complexity of its function in cardiovascular tissues. In conscious (contrary to anesthetized) rats, activation of the peripheral NMDAR triggers cardiovascular oxidative stress through the PI3K-ERK1/2-NO signaling pathway, which ultimately leads to elevation in blood pressure. Evidence also implicates Ca release, in the peripheral NMDAR-mediated pressor response. Despite evidence of circulating potent ligands (eg, D-aspartate and L-aspartate, L-homocysteic acid, and quinolinic acid) and also their coagonist (eg, glycine or D-serine), the physiological role of peripheral cardiovascular NMDAR remains elusive. Nonetheless, the cardiovascular relevance of the peripheral NMDAR might become apparent when its signaling is altered by drugs, such as alcohol, which interact with the NMDAR or its downstream signaling mechanisms.

Objectives: Hemiarthroplasty induces degenerative changes in the hip joint, which are difficult to evaluate in vivo. Radiostereometric analysis (RSA) is a radiographic measurement technique that has recently been used to measure acetabular cartilage wear in vivo. The aim of the study was to measure acetabular cartilage wear, using this technique, in an ovine model during the first 14 weeks post-implantation., Methods: Measurements of three-dimensional femoral head migration, combined with visual assessments at necropsy and safranin O staining for cartilage integrity, were undertaken., Results: Mean femoral head migration during the first six weeks was 0.525 mm in the medial, 0.144 mm in the cranial, and 0.517 mm in the dorsal direction. The majority of this migration was confirmed to be cartilage wear in the medial and dorsal aspects of the acetabulum at necropsy and with subsequent histological evaluation depicting significant cartilage degeneration., Clinical Significance: Radiostereometric analysis is the current gold standard technique for in vivo assessment of implant migration following total hip replacement. This study has utilized RSA to quantify the amount of early cartilage wear in vivo, which was supported by ex vivo evaluations. Accurately measuring the amount of cartilage wear will allow future studies to compare component material and design characteristics prior to clinical use.

Naturally occurring asbestos (NOA) fibers are found in geologic deposits that may be disturbed by mining, earthworks, or natural processes, resulting in adverse health risks to exposed individuals. The toxicities of Libby amphibole and NOA samples including Sumas Mountain chrysotile (SM), El Dorado tremolite (ED), and Ontario ferroactinolite cleavage fragments (ON) were compared in male Fischer 344 (F344) rats 15 mo after exposure. Rat-respirable fractions of LA and SM displayed greater mean lengths and aspect ratios than ED and ON. After a single intratracheal (IT) instillation (0.5 or 1.5 mg/rat), persistent changes in ventilatory parameters and a significant increase in lung resistance at baseline and after methacholine aerosol dosing were found only in rats exposed to 1.5 mg SM. High-dose ED significantly elevated bronchoalveolar lavage lactate dehydrogenase (LDH) activity and protein levels, while high-dose SM increased γ-glutamyl transferase and LDH activities. A moderate degree of lung interstitial fibrosis after exposure to 1.5 mg SM persisted 15 mo after exposure, unchanged from previous findings at 3 mo. LA induced mild fibrosis, while ED and ON produced minimal and no apparent fibrosis, respectively. Bronchioloalveolar carcinoma was observed 15 mo after exposure to LA or ED. Data demonstrated that SM, given by bolus IT dosing on an equivalent mass basis, induced greater pulmonary function deficits, airway hyperresponsiveness, and interstitial fibrosis than other NOA, although unlike LA and ED, no apparent evidence for carcinogenicity was found. All NOA samples except ON cleavage fragments produced some degree of long-term toxicity.

The outcome of 219 revision total hip arthroplasties (THAs) in 98 male and 121 female patients, using 137 long length and 82 standard length cemented collarless double-taper femoral stems in 211 patients, with a mean age of 72 years (30 to 90) and mean follow-up of six years (two to 18) have been described previously. We have extended the follow-up to a mean of 13 years (8 to 20) in this cohort of patients in which the pre-operative bone deficiency Paprosky grading was IIIA or worse in 79% and 73% of femurs with long and standard stems, respectively. For the long stem revision group, survival to re-revision for aseptic loosening at 14 years was 97% (95% confidence interval (CI) 91 to 100) and in patients aged > 70 years, survival was 100%. Two patients (two revisions) were lost to follow-up and 86 patients with 88 revisions had died. Worst-case analysis for survival to re-revision for aseptic loosening at 14 years was 95% (95% CI 89 to 100) and 99% (95% CI 96 to 100) for patients aged > 70 years. One additional long stem was classified as loose radiographically but not revised. For the standard stem revision group, survival to re-revision for aseptic loosening at 14 years was 91% (95% CI 83 to 99). No patients were lost to follow-up and 49 patients with 51 hips had died. No additional stems were classified as loose radiographically. Femoral revision using a cemented collarless double-taper stem, particularly with a long length stem, and in patients aged > 70 years, continues to yield excellent results up to 20 years post-operatively, including in hips with considerable femoral metaphyseal bone loss., (©2015 The British Editorial Society of Bone & Joint Surgery.)

There are no studies on the acute effect of ethanol on peripheral N-methyl-d-aspartate receptor (NMDAR)-mediated increases in reactive oxygen species (ROS) and blood pressure (BP). We tested the hypothesis that ethanol antagonism of peripheral NMDAR dampens systemic NMDA-evoked increases in vascular ROS and BP. We investigated the effect of ethanol (1 g/kg) on BP and heart rate (HR) responses elicited by systemic bolus (125-1000 μg/kg, intra-venous [i.v.]) or infused (180 μg/kg/min) NMDA in conscious male Sprague-Dawley rats. We also hypothesized that peripheral NMDAR blockade with DL-2-Amino-5-phosphonopentanoic acid (AP-5; 5 mg/kg, i.v.) uncovers an ethanol- (1 or 1.5 g/kg) evoked hypotensive response. Ethanol attenuated the peripheral NMDAR-mediated pressor and bradycardic responses caused by NMDA infusion, and ex vivo studies revealed parallel ethanol attenuation of peripheral NMDAR-mediated increases in vascular ROS. While ethanol (1 or 1.5 g/kg) alone had no effect on BP, the higher dose caused a hypotensive response in the presence of NMDAR blockade (AP-5). Blood ethanol concentrations were not statistically different in the groups that received ethanol alone or along with NMDA or AP-5. These findings are the first to demonstrate ethanol attenuation of peripheral NMDAR-mediated pressor response, and the uncovering of ethanol-evoked hypotension in the presence of peripheral NMDAR blockade., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Near-road exposure to air pollutants has been associated with decreased lung function and other adverse health effects in susceptible populations. This study was designed to investigate whether different types of near-road particulate matter (PM) contribute to exacerbation of allergic asthma. Samples of upwind and downwind coarse, fine, and ultrafine PM were collected using a wind direction-actuated ChemVol sampler at a single site 100 m from Interstate-96 in Detroit, MI during winter 2010/2011. Upwind PM was enriched in crustal and wood combustion sources while downwind PM was dominated by traffic sources. Control and ovalbumin (OVA)-sensitized BALB/cJ mice were exposed via oropharyngeal (OP) aspiration to 20 or 100 μg of each PM sample 2 h prior to OP challenge with OVA. In OVA-allergic mice, 100 μg of downwind coarse PM caused greater increases than downwind fine/ultrafine PM in bronchoalveolar lavage neutrophils, eosinophils, and lactate dehydrogenase. Upwind fine PM (100 μg) produced greater increases in neutrophils and eosinophils compared to other upwind size fractions. Cytokine (IL-5) levels in BAL fluid also increased markedly following 100 μg downwind coarse and downwind ultrafine PM exposures. These findings indicate coarse PM downwind and fine PM upwind of an interstate highway promote inflammation in allergic mice.

The molecular mechanisms for peripheral N-methyl-D-aspartate receptor (NMDAR)-mediated vascular oxidative stress and pressor response are not known. We conducted integrative (in vivo) and ex vivo biochemical studies to test the hypothesis that reactive oxygen species (ROS)-dependent calcium influx, triggered by the activation of vascular kinases, underlies the NMDAR-mediated pressor response. Pharmacological inhibition of phosphoinositide 3-kinase (PI3K)/Akt (wortmannin, 15 μg/kg), protein kinase C (chelerythrine: 5 mg/kg, intravenous), Ca²⁺ influx (nifedipine, 0.35 or 0.75 mg/kg), or NADPH oxidase (NOX: apocynin, 5 mg/kg) attenuated the peripheral NMDAR-mediated pressor response in conscious male Sprague-Dawley rats. NMDAR activation enhanced the phosphorylation of Akt, ERK1, JNK and p38 (Western blot), and NOX activity in vascular tissues collected during the pressor response caused by NMDA infusion (180 μg·kg⁻¹·min⁻¹, 30 minutes). Furthermore, ex vivo studies showed that wortmannin, chelerythrine, or apocynin abrogated the NMDAR-mediated vascular nitric oxide (NO) and ROS generation and NOX activation in the vasculature. These findings implicate vascular PI3K/Akt-protein kinase C signaling in the peripheral NMDAR-mediated increases in vascular NO and NOX activation (ROS), which ultimately lead to calcium influx and pressor response in conscious rats.