Steroid hormones, energetic state, and immunocompetence vary across reproductive contexts in a parthenogenetic lizard.

Reproduction is energetically expensive and investing in this life history trait is likely accompanied by significant changes in physiological activity. Investment strategy necessary for achieving reproductive success in reptiles can vary with reproductive form and pattern, potentiating different consequences for competing fitness-related traits such as those key to survival. The goal of this study was to assess if and how energetic state (i.e., energy metabolites) and self-maintenance (i.e., immunocompetence) are hormonally modulated across reproductive contexts in an oviparous, parthenogenetic lizard, the Colorado Checkered Whiptail Aspidoscelis neotesselata. Here blood plasma samples were collected from lizards within the US Army Fort Carson Military Installation near Colorado Springs, CO, USA, during seasons of reproductive activity (i.e., June) and inactivity (i.e., August). Measures of reproductive (i.e., estradiol) and energy-mobilizing (i.e., corticosterone) hormones, energy metabolites (i.e., glucose, triglycerides, and free glycerol), and innate immunity (i.e., bactericidal ability) were compared by season and reproductive stage. Levels of energy metabolites and bactericidal ability were compared to levels of E2 and CORT. Bactericidal ability was also compared to levels of energy metabolites. Corticosterone and glucose levels were lower during the reproductive season while triglyceride levels and bactericidal ability were higher, but both estradiol and free glycerol levels did not differ between seasons. Throughout vitellogenesis, corticosterone and glucose levels as well as bactericidal ability did not differ, but estradiol levels were higher during early and mid-stage and both triglyceride and free glycerol levels were lower during gravidity. Corticosterone levels were negatively associated with circulating triglycerides and bactericidal ability, but were not related to glucose nor free glycerol levels. Estradiol levels were positively associated with free glycerol levels and bactericidal ability, but were not related to glucose nor triglyceride levels. Finally, bactericidal ability was negatively associated with glucose, but positively associated with triglycerides. Differences in energetic state and immunocompetence are thus reflected by shifts in hormone secretion across reproductive investment. These findings provide partial support for the hypothesis that energetic state is differentially regulated by steroid hormones to afford reproduction, potentially at the cost of future survival.

Parenchymal pattern in women with dense breasts. Variation with age and impact on screening outcomes: observations from a UK screening programme.

OBJECTIVES: To assess patterns of parenchymal tissue on mammography in women with dense breasts and to determine how this varies with age and affects recall to assessment and cancer diagnosis. METHOD: Breast density data was obtained in women attending routine mammographic screening from April 2013 to March 2015 using automated breast density assessment software. Women with the densest breasts were selected for visual interpretation of parenchymal pattern (PP). One hundred non-assessed women, aged 50, 55, 60, 65 and 69-71 years (total = 500), provided controls. Cases included women recalled for assessment (mastectomy or implants excluded) (total = 280). Mammograms reviewed by ten readers and PP classified as: (1) very smooth; (2) mainly smooth; (3) mixed; (4) mainly nodular; (5) very nodular. The ratio of women in each category at each age and screening outcomes were compared by Pearson's chi-squared test. RESULTS: Reader agreement for scoring PP was good (intraclass correlation = 0.6302). Proportions of women in each PP category were similar at all ages for controls (p = 0.147) and cases (p = 0.657). The ratio of PP categories did not vary significantly with age in those who underwent biopsy (p = 0.484). Thirty-four cancers were diagnosed. There was a significant correlation between a diagnosis of cancer and nodular PP compared to not nodular PP (p = 0.043). CONCLUSIONS: The ratio of smooth to nodular pattern in women with the densest breasts did not vary with age. The PP of the breast tissue did not affect likelihood of recall to assessment or biopsy. There was a significant relationship between a nodular parenchymal pattern and diagnosis of cancer. KEY POINTS: • This paper shows that there is good agreement between mammogram readers when classifying mammographic PP on a five-point scale from very smooth to very nodular. • In non-assessed women with the densest breasts, there is no significant change in the proportions of smooth to nodular patterns with increasing age. • The likelihood of recall for further assessment or biopsy at assessment is not related to PP in women with highest breast density. • When recalled for further assessment, significantly more women are diagnosed with cancer in the group with nodular PP on mammography when compared with smooth and mixed patterns.

Dynamic properties of different liquid states in systems with competing interactions studied with lysozyme solutions.

Recent studies of colloidal systems with a short-range attraction and long-range repulsion (SALR) have been demonstrated to have a generalized phase diagram with multiple liquid states defined by their structures. In this paper, we identify the different liquid states of previous experimentally studied lysozyme samples within this proposed generalized state diagram and explore the dynamic properties of each liquid state. We show that most lysozyme samples studied here and previously at low and intermediate concentrations are dispersed fluids while a few high concentration samples are randomly percolated liquids. In the dispersed fluid region, the short-time diffusion coefficient measured by neutron spin echo agrees well with the long time diffusion coefficient estimated with the solution viscosity. This dynamic feature is maintained even for some samples in the random percolated region. However, the short-time and long-time diffusion coefficients of random percolated fluids deviate at larger concentration and attraction strength. At high enough concentrations, the mean square displacement can be as slow as those of many glassy colloidal systems at time scales near the characteristic diffusion time even though these lysozyme samples remain in liquid states at the long-time limit. We thus identify the region in the generalized phase diagram where these equilibrium states with extremely slow local dynamics exist relative to bulk percolation and kinetic arrest (gel and glassy) transitions.

Catalytic Ring-Opening of Cyclic Alcohols Enabled by PCET Activation of Strong O-H Bonds.

We report a new photocatalytic protocol for the redox-neutral isomerization of cyclic alcohols to linear ketones via C-C bond scission. Mechanistic studies demonstrate that key alkoxy radical intermediates in this reaction are generated via the direct homolytic activation of alcohol O-H bonds in an unusual intramolecular PCET process, wherein the electron travels to a proximal radical cation in concert with proton transfer to a weak Brønsted base. Effective bond strength considerations are shown to accurately forecast the feasibility of alkoxy radical generation with a given oxidant/base pair.

Catalytic Olefin Hydroamidation Enabled by Proton-Coupled Electron Transfer.

Here we report a ternary catalyst system for the intramolecular hydroamidation of unactivated olefins using simple N-aryl amide derivatives. Amide activation in these reactions occurs via concerted proton-coupled electron transfer (PCET) mediated by an excited state iridium complex and weak phosphate base to furnish a reactive amidyl radical that readily adds to pendant alkenes. A series of H-atom, electron, and proton transfer events with a thiophenol cocatalyst furnish the product and regenerate the active forms of the photocatalyst and base. Mechanistic studies indicate that the amide substrate can be selectively homolyzed via PCET in the presence of the thiophenol, despite a large difference in bond dissociation free energies between these functional groups.

Measuring maternal responsiveness in a community-based sample of slow-to-talk toddlers: a cross-sectional study.

BACKGROUND: Maternal responsiveness is important in early language development, but its measurement by direct observation has to date been unrealistic in community settings because of training and time constraints. We report on the development and cross-sectional comparison of a global rating of maternal responsiveness against a detailed measure of responsiveness at age 24 months. METHODS: The community-based sample comprised 246 toddlers and their mothers, identified as being slow-to-talk at age 18 months within the Let's Learn Language population-based randomized controlled trial. At age 24 months, mother-child dyads were videotaped during 15 minutes of free-play and children undertook a standardized language assessment. Videos were blindly rated on both the new global measure, comprising a single rating of responsiveness on a five-point Likert scale, and a detailed rating of responsiveness known to predict language outcomes, comprising a sum of specific maternal responsive behaviours. RESULTS: The global rating scale required relatively little training and ratings could be conducted in real time. The global and detailed ratings of maternal responsiveness showed moderate correlation (r = 0.44; P < 0.001). Small positive correlations were found between the global rating and expressive (r = 0.23; P < 0.001), receptive (r = 0.28, P < 0.001) and total language (r = 0.28; P < 0.001) at age 24 months. CONCLUSION: The global rating scale was efficient and moderately effective as a measure of maternal responsiveness. It is possible that, combined with other risk measures including concurrent language skills, it could strengthen prediction of which children will and will not go on to experience lasting language difficulties.

Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment.

BACKGROUND: Systemic bacterial infections often result in enduring cognitive impairment and are a risk factor for dementia. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that intermittent fasting (IF) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of IF on the cognitive sequelae of systemic and brain inflammation is unknown. METHODS: Rats on IF for 30 days received 1 mg/kg of lipopolysaccharide (LPS) or saline intravenously. Half of the rats were subjected to behavioral tests and the other half were euthanized two hours after LPS administration and the hippocampus was dissected and frozen for analyses. RESULTS: Here, we report that IF ameliorates cognitive deficits in a rat model of sepsis by a mechanism involving NF-κB activation, suppression of the expression of pro-inflammatory cytokines, and enhancement of neurotrophic support. Treatment of rats with LPS resulted in deficits in cognitive performance in the Barnes maze and inhibitory avoidance tests, without changing locomotor activity, that were ameliorated in rats that had been maintained on the IF diet. IF also resulted in reduced levels of mRNAs encoding the LPS receptor TLR4 and inducible nitric oxide synthase (iNOS) in the hippocampus. Moreover, IF prevented LPS-induced elevation of IL-1α, IL-1ß and TNF-α levels, and prevented the LPS-induced reduction of BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced elevations of serum IL-1ß, IFN-γ, RANTES, TNF-α and IL-6 levels. CONCLUSIONS: Taken together, our results suggest that IF induces adaptive responses in the brain and periphery that can suppress inflammation and preserve cognitive function in an animal model of systemic bacterial infection.

A randomised trial of weekend and evening breast screening appointments.

BACKGROUND: There is a need to research interventions that improve access to and convenience of breast cancer screening services. METHODS: We conducted a randomised trial comparing invitations to out-of-hours appointments with standard office hour appointments. Women who were to be invited for routine breast screening were randomised (3 : 1 : 1 : 1) to one of these screening invitations: standard office hour appointment, office hour appointment with the option to change to an out-of-hours appointment, weekday evening appointment, or weekend appointment. RESULTS: A total of 9410 women were invited to an office hour, 3519 to an office hour with the option to change, 3271 to a weekday evening, and 3162 to a weekend appointment. The offer of an initial out-of-hours appointment was associated with a non-significant decrease in attendance rates (73.7% vs 74.1%). The highest attendance was observed in the group offered an initial office hour appointment with the option to change to out-of-hours (76.1% vs 73.3% for standard office hour, P=0.001), with 7% of invitees exercising the option to change. CONCLUSION: The optimum strategy for improving attendance at breast screening is to offer a traditional office hour appointment and including in the letter of invitation an option to change to an evening or weekend appointment if wished.

Minimally constrained model of self-organized helical states in reversed-field pinches.

We show that the self-organized single-helical-axis (SHAx) and double-axis (DAx) states in reversed field pinches can be reproduced in a minimally constrained equilibrium model using only five parameters. This is a significant reduction on previous representations of the SHAx which have required an infinite number of constraints. The DAx state, which has a nontrivial topology, has not previously been reproduced using an equilibrium model that preserves this topological structure. We show that both states are a consequence of transport barrier formation in the plasma core, in agreement with experimental results. We take the limit of zero pressure in this work, although the model is also valid for finite pressure.

The relationships among knowledge, self-efficacy, preparedness, decisional conflict, and decisions to participate in a cancer clinical trial.

BACKGROUND: Cancer clinical trials (CCTs) are important tools in the development of improved cancer therapies; yet, participation is low. Key psychosocial barriers exist that appear to impact a patient's decision to participate. Little is known about the relationship among knowledge, self-efficacy, preparation, decisional conflict, and patient decisions to take part in CCTs. OBJECTIVE: The purpose of this study was to determine if preparation for consideration of a CCT as a treatment option mediates the relationship between knowledge, self-efficacy, and decisional conflict. We also explored whether lower levels of decisional conflict are associated with greater likelihood of CCT enrollment. METHOD: In a pre-post test intervention study, cancer patients (N = 105) were recruited before their initial consultation with a medical oncologist. A brief educational intervention was provided for all patients. Patient self-report survey responses assessed knowledge, self-efficacy, preparation for clinical trial participation, decisional conflict, and clinical trial participation. RESULTS: Preparation was found to mediate the relationship between self-efficacy and decisional conflict (p = 0.003 for a test of the indirect mediational pathway for the decisional conflict total score). Preparation had a more limited role in mediating the effect of knowledge on decisional conflict. Further, preliminary evidence indicated that reduced decisional conflict was associated with increased clinical trial enrollment (p = 0.049). CONCLUSIONS: When patients feel greater CCT self-efficacy and have more knowledge, they feel more prepared to make a CCT decision. Reduced decisional conflict, in turn, is associated with the decision to enroll in a clinical trial. Our results suggest that preparation for decision-making should be a target of future interventions to improve participation in CCTs.

Mapping bark bacteria: initial insights of stemflow-induced changes in bark surface phyla.

IMPORTANCE: Compared with the phyllosphere, bacteria inhabiting bark surfaces are inadequately understood. Based on a preliminary pilot study, our work suggests that microbial populations vary across tree bark surfaces and may differ in relation to surrounding land use. Initial results suggest that stemflow, the water that flows along the bark surface, actively moves bacterial communities across a tree. These preliminary findings underscore the need for further study of niche microbial populations to determine whether there are connections between the biodiversity of microbiomes inhabiting corticular surfaces, land use, and hydrology.

Isotonitazene, a novel psychoactive substance opioid, detected in two cases following a local surge in opioid overdoses.

BACKGROUND: Isotonitazene is a novel opioid that was first reported in Europe in 2019. There have been no reports of the detection of isotonitazene in patients presenting to the emergency department with acute drug toxicity. AIM: There was an increase in presentations to our emergency department with acute opioid toxicity in August 2021. We aim to describe this outbreak and provide detail on two cases in which isotonitazene was quantified in serum samples. METHODS: Serum samples were available for comprehensive toxicological analysis for two presentations. Written consent was obtained and the samples were analysed through a Thermo XRS ultrahigh-performance liquid chromatography system, interfaced to a Thermo Q Exactive high-resolution accurate mass spectrometer, operating in heated positive ion electrospray mode. Acquired data were processed using Toxfinder software (Thermo) against a regularly updated in-house database. RESULTS: There was an increase in acute opioid presentations to our emergency department from a median of 10 per month to 36 in August 2021. Twenty were treated with naloxone, and 23 were admitted to the hospital for observation and treatment. Serum sample analysis from two patients with acute opioid toxicity responsive to naloxone detected the presence of isotonitazene (0.18 and 0.81 ng/ml). CONCLUSION: We report a cluster of acute opioid toxicity presentations to our Emergency Department with detection of isotonitazene in two cases. Analytical screening is important in determining the presence of novel psychoactive substances (NPS) and to help inform the public health of the implications of NPS use, particularly during clusters of acute recreational drug toxicity presentations.

Clinical features associated with ADB-BUTINACA exposure in patients attending emergency departments in England.

OBJECTIVE: Synthetic cannabinoid receptor agonists (SCRA) are commonly encountered new psychoactive substances. Here we report the recent detection of ADB-BUTINACA in samples from patients attending United Kingdom emergency departments with toxicity after suspected drug misuse and describe the associated clinical features. METHODS: Consenting adults (≥16 y) presenting to participating hospitals with toxicity after suspected drug misuse have been included in the Identification Of Novel psychoActive substances (IONA) study since March 2015. Demographic and clinical features are recorded and blood and/or urine samples analysed using high-resolution accurate mass liquid chromatography-mass spectrometry. RESULTS: By December 2021, analytical data were available for 1279 IONA participants and ADB-BUTINACA was detected in at least one sample from 10 (9 males, age range 16-51 median 45 years), all presenting since February 2021. Smoking 'spice' was reported by four patients, two had ingested edible "cannabis" gums and four reported heroin use (2 intravenous, 1 smoked, 1 route not known). Co-use of pregabalin (oral) and crack cocaine (smoked) were also reported. In 3 cases ADB-BUTINACA was the only substance detected, while in seven other substances of misuse were also detected including other SCRA, opioids, benzodiazepines cocaine and pregabalin. Clinical features reported in these 2 groups respectively included reduced level of consciousness (3/3, 6/7), agitation (0/3, 4/7), tachycardia (0/3, 3/7), seizures (1/3, 1/7), hallucinations (1/3, 1/7), hypotension (1/3, 1/7). Metabolic acidosis (1/3, 0/7) and respiratory acidosis (1/3, 0/7), All 10 patients recovered with supportive care, including intubation and ventilation for one case. The median length of hospital stay was 19 h (range 2.6-131 h). CONCLUSIONS: ADB-BUTINACA has recently emerged as a drug of misuse in England. Clinical features of toxicity are consistent with those of other SCRA and include reduced level of consciousness, respiratory and/or metabolic acidosis, seizures, confusion and hallucinations.

Longitudinal determinants of consistent condom use by partner type among young injection drug users: the role of personal and partner characteristics.

We investigated the longitudinal influence of individual-, relationship- and social-level factors on condom use by partner type among young injections drug users (IDUs) enrolled in the Collaborative Injection Drug Users Study-III/Drug Users Intervention Trial (CIDUS-III/DUIT) from 2002 to 2004. Based on longitudinal analysis using generalized estimating equations (GEE), consistent condom use with main partners was more commonly reported among males and those with greater self-efficacy for condom use; main partner's desire for pregnancy and needle sharing were negatively associated with consistent condom use. Among those with casual partners, having fewer sex partners was associated with consistent condom use. Positive attitudes toward condom use and partner norms supporting condom use were associated with greater consistent condom use with both partner types. These findings suggest that intervention strategies targeting individual- and partner-level factors may provide avenues for intervening upon sexual risks among young IDUs.

Defocus image contrast in hexagonally-ordered mesoporous material.

A transmission electron microscope was used to characterize a powder form of hexagonally-ordered mesoporous silica material. The structural symmetry built into this amorphous material allowed one to obtain three characteristic images, i.e. a hexagonal honey-comb structure and wide/narrow parallel lines. These images were found to originate primarily from phase contrast, which changed sensitively with defocusing. To further understand the contrast behaviour of these images, an analytical form of the defocus contrast theory was developed and applied to the simulation of the characteristic wide/narrow parallel line images. The simulation was found to be in good qualitative agreement with experiments, where changes in focus conditions and specimen thickness were predicted to alter the contrast in the resulting parallel-line type images.

The bioactivity and ion release of titanium-containing glass polyalkenoate cements for medical applications.

The ion release profiles and bioactivity of a series of Ti containing glass polyalkenoate cements. Characterization revealed each material to be amorphous with a T(g) in the region of 650-660°C. The network connectivity decreased (1.83-1.35) with the addition of TiO(2) which was also evident with analysis by X-ray photoelectron spectroscopy. Ion release from cements were determined using atomic absorption spectroscopy for zinc (Zn(2+)), calcium (Ca(2+)), strontium (Sr(2+)), Silica (Si(4+)) and titanium (Ti(4+)). Ions such as Zn(2+) (0.1-2.0 mg/l), Ca(2+) (2.0-8.3 mg/l,) Sr(2+) (0.1-3.9 mg/l), and Si(4+) (14-90 mg/l) were tested over 1-30 days. No Ti(4+) release was detected. Simulated body fluid revealed a CaP surface layer on each cement while cell culture testing of cement liquid extracts with TW-Z (5 mol% TiO(2)) produced the highest cell viability (161%) after 30 days. Direct contact testing of discs resulted in a decrease in cell viability of the each cement tested.

Wrinkling and strain softening in single-wall carbon nanotube membranes.

The nonlinear elasticity of thin supported membranes assembled from length purified single-wall carbon nanotubes is analyzed through the wrinkling instability that develops under uniaxial compression. In contrast with thin polymer films, pristine nanotube membranes exhibit strong softening under finite strain associated with bond slip and network fracture. We model the response as a shift in percolation threshold generated by strain-induced nanotube alignment in accordance with theoretical predictions.

Influence of anabolic steroid treatment associated to physical exercise in the ultrasonic vocalization of rats.

Unlike humans, who communicate in frequency bands between 250 Hz and 6 kHz, rats can communicate in frequencies above 18 kHz. Their vocalization types depend on the context and are normally associated to subjective or emotional states. It was reported significant vocal changes due to administration of replacement testosterone in a trained tenor singer with hypogonadism. Speech-Language Pathology clinical practices are being sought by singers who sporadically use anabolic steroids associated with physical exercise. They report difficulties in reaching and keeping high notes, "breakage" in the passage of musical notes and post singing vocal fatigue. Those abnormalities could be raised by the association of anabolic steroids and physical exercise. Thus, in order to verify if this association could promote vocal changes, maximum, minimum and fundamental frequencies and call duration in rats treated with anabolic steroids and physically trained (10 weeks duration) were evaluated. The vocalizations were obtained by handling the animals. At the end of that period, rats treated and trained showed significant decrease in call duration, but not in other parameters. The decrease in call duration could be associated to functional alterations in the vocal folds of treated and trained animals due to a synergism between anabolic steroids and physical training.

Surgery in the COVID-19 Era: A Narrative Review.

The coronavirus disease 2019 (COVID-19) pandemic affected the delivery of surgical care and services. This review article aims to appraise the impact of COVID-19 on surgical care. The authors discuss the literature on surgery and COVID-19 under the following themes: emergency case triaging, elective surgery triaging, operating on a COVID-19-positive patient, surgical smoke, management of scarce resources, and restarting elective surgery. Most of the large surgical societies recommended and most surgical departments all over the world implemented the cancellation of elective surgeries, while emergency surgeries proceeded as usual. Elective surgeries were triaged taking into consideration the COVID-19 infection rate in the locality, availability of resources, and the need for intensive care unit beds and ventilators. A COVID-19-positive patient should not be denied surgery if indicated, and the recommended precautions and use of personal protective equipment should be adhered to. The generation of surgical smoke occurs in both laparoscopic and open surgeries, and it has not been shown to contain this novel virus. Smoke generation should be minimized and laid down guidelines followed. Laparoscopic surgery seems to have an advantage over open surgery in this regard. In resuming elective surgeries, the local infection rates, bed occupancy rate, and availability of resources should be taken into cognizance. We should learn from this pandemic so as to be prepared for future occurrences, which is a significant possibility.

La pandémie de maladie à virus Corona 2019 (COVID-19) a affecté la prestation de soins et de services chirurgicaux. Cet examen dans notre article vise à évaluer l'impact des Covid-19 sur la chirurgie des soins. Les auteurs discutent de la littérature sur la chirurgie et Covid-19 sous les thèmes suivants: cas urgence triaging, la chirurgie élective triant, opérant sur un patient positif Covid-19, la fumée chirurgicale, la gestion des ressources rares et le redémarrage de la chirurgie élective. La plupart des grandes sociétés chirurgicales recommandaient, et la plupart des services de chirurgie du monde entier ont mis en oeuvre l'annulation des chirurgies électives tandis que les chirurgies d'urgence se déroulaient comme d'habitude. Sur électifs Guéries ont été triés en prenant en considération la Covid -19 taux d'infection dans la localité, la disponibilité des ressources et la nécessité d'I intensive C sont Unit (USI) lits et des ventilateurs. Un Covid -19 patients positif ne doit pas se voir refuser la chirurgie si cela est indiqué, et les précautions recommandées et l'utilisation d'Équipement de protection PERSONNEL LES (EPP) doivent être respectées. La génération de fumée chirurgicale se produit à la fois en chirurgie la périscopique et en chirurgie ouverte et il n'a pas été démontré qu'elle contenait ce nouveau virus. La production de fumée doit être réduite au minimum et des directives établies doivent être suivies. La chirurgie laparoscopie semble avoir un avantage sur la chirurgie ouverte dans ce domaine. En résumant les chirurgies électives, t- il des taux d'infection locale, le taux d'occupation des lits et la disponibilité des ressources devraient être prises en connaissance. Nous devons tirer les leçons de cette pandémie pour nous préparer à de futures occurrences, ce qui est une possibilité importante.