High fat diet increases cognitive decline and neuroinflammation in a model of orexin loss.

Midlife obesity is a risk factor for cognitive decline and is associated with the earlier onset of Alzheimer's disease (AD). Diets high in saturated fat potentiate the onset of obesity, microglial activation, and neuroinflammation. Signaling deficiencies in the hypothalamic peptide orexin and/or orexin fiber loss are linked to neurodegeneration, cognitive impairment, and neuroinflammation. Prior studies show that orexin is neuroprotective, suppresses neuroinflammation, and that treatment with orexin improves cognitive processes in orexin/ataxin-3 (O/A3) mice, a transgenic mouse model of orexin neurodegeneration. Our overall hypothesis is that loss of orexin contributes to high fat diet (HFD)-induced hippocampal neuroinflammation and cognitive decline. To examine this, we tested male O/A3 mice (7-8 mo. of age) in a two-way active avoidance (TWAA) hippocampus-dependent memory task. We tested whether (1) orexin loss impaired cognitive function; (2) HFD worsened cognitive impairment; and (3) HFD increased microglial activation and neuroinflammation. O/A3 mice showed significant impairments in TWAA task learning vs. wild type (WT) mice (increased escapes p < 0.05, reduced avoidances p < 0.0001). Mice were then placed on HFD (45% total fat, 31.4% saturated fat) or remained on normal chow (NC; 4% total fat and 1% saturated fat), and TWAA was retested at 2 and 4 weeks. Learning impairment was evident at both 2 and 4 weeks in O/A3 mice fed HFD for following diet exposure vs. WT mice on normal chow or HFD (increased escapes, reduced avoidances p < 0.05). Additionally, O/A3 mice had increased gene expression of the microglial activation marker Iba-1 (measured via qRT-PCR, p < 0.001). Further characterization of the microglial immune response genes in hippocampal tissue revealed a significant increase in CX3 chemokine receptor 1 (CX3CR1), tumor necrosis factor-alpha (TNF-α) and the mitochondria-associated enzyme immune responsive gene-1 (Irg1). Collectively, our results indicate that orexin loss impairs memory, and that HFD accelerates hippocampus-dependent learning deficits and the onset of neuroinflammation.

Impact of timing of delivery on maternal and neonatal outcomes for women after three previous caesarean deliveries; a secondary analysis of the caesarean section registry.

BACKGROUND: As more women are presenting with three previous caesarean deliveries (CD), providers may suggest early term delivery as a means to avoid the risk of spontaneous labour and associated maternal morbidity. OBJECTIVE: To determine whether early term delivery is associated with lower maternal and neonatal morbidity for women with three previous CD. STUDY DESIGN: Secondary analysis of a prospective registry of CD at 19 US academic centres from 1999 to 2002. POPULATION: Women with three previous CD undergoing scheduled or emergent delivery with live, singleton gestations 37-41+ weeks of gestation were included. Women with non-low transverse incisions, antepartum stillbirth, previous myomectomy, fetal anomalies, more or fewer than three previous CD or attempting trial of labour after caesarean section were excluded. METHODS: Gestational age was categorised by week. We fitted logistic regression models to adjust for clinically relevant or statistically significant confounders. MAIN OUTCOME MEASURES: The primary and secondary outcomes were composites, respectively, of maternal and neonatal morbidity. RESULTS: In all, 821 women met the inclusion criteria; maternal morbidity composite occurred in 9.86% and neonatal morbidity occurred in 10.5%. After adjusting for confounding variables, maternal and neonatal morbidity occurred least frequently at 39 weeks. CONCLUSIONS: In women with three previous CDs, adverse maternal outcomes do not increase with increasing gestational age beyond 37 weeks but early term elective repeat CDs are associated with higher neonatal morbidity. Elective delivery of women with three previous CD at 39 weeks of gestation is safe in the absence of maternal or fetal indications for early term delivery. TWEETABLE ABSTRACT: Delivery of women with three previous caesarean deliveries at 39 weeks, in the absence of maternal or fetal indications for early term delivery, is associated with decreased maternal morbidity.

The preferences of young adults with Type 1 diabetes at clinics using a discrete choice experiment approach: the D1 Now Study.

AIM: Attending routine outpatient clinic appointments is a central self-management behaviour of individuals living with Type 1 diabetes. A large number of young adults with Type 1 diabetes disengage from diabetes services, which may contribute to poor psychosocial and diabetes outcomes. The aim of this study is to elicit preferences from young adults with Type 1 diabetes regarding clinic-related services to inform service delivery. METHODS: A discrete choice experiment was developed to understand the preferences of young adults with Type 1 diabetes for clinic-related services. RESULTS: Young adults recruited from young adult Type 1 diabetes clinics in 2016 completed the experiment (n = 105). Young adults with Type 1 diabetes showed a preference for shorter waiting times, seeing a nurse and a consultant, relative to a nurse alone, and a flexible booking system compared with fixed appointment times. Results suggest no preference for a nurse and a doctor, relative to a nurse alone, or other optional services (e.g. seeing dietitians or psychologists), type of HbA1c test and digital blood glucose diaries over paper-based diaries. CONCLUSION: This study highlights aspects of routine clinic appointments that are valued by young adults living with Type 1 diabetes, namely shorter waiting times at clinic, the option to see both a nurse and consultant at each visit and a flexible clinic appointment booking system. These findings suggest young adults with Type 1 diabetes value convenience and should help services to restructure their clinics to be more responsive to the needs of young adults.

Evidence for multiple paternity in the school shark Galeorhinus galeus found in New Zealand waters.

This study assessed the levels of relatedness of Galeorhinus galeus of progeny arrays using six microsatellite DNA markers. A parentage analysis from five families (mother and litter) from the North Island of New Zealand suggested the occurrence of genetic polyandry in G. galeus with two of the five litters showing multiple sires involved in the progeny arrays. This finding may be consistent with the reproductive characteristics of G. galeus, in which females can potentially store sperm for long periods of time after the mating season.

Light-harvesting processes in the dynamic photosynthetic antenna.

We present our perspective on the theoretical basis of light-harvesting within the photosynthetic membrane. Far from being a static structure, the photosynthetic membrane is a highly dynamic system, with protein mobility playing an important role in the damage/repair cycle of photosystem II (PSII), in balancing the input of energy between PSI and PSII, and in the photoprotection of PSII in response to a sudden excess of illumination. The concept of a photosynthetic antenna is illustrated and the state transition phenomenon is discussed as an example of purposeful antenna mobility. We discuss fluorescence recovery after photo-bleaching as a technique for visualising membrane mobility, before introducing light-induced grana membrane reorganisation as an integral part of the rapid photoprotective switch in plants. We then discuss current theoretical approaches to modelling the energy transfer dynamics of the PSII antenna: the atomistic models of intra-complex transfer and the coarse-grained approach to the inter-complex dynamics. Finally we discuss the future prospect of extending these methods, beyond the static picture of the membrane, to the dynamic PSII photosynthetic antenna.

Intra- and inter-rater reliability of jumping mechanography muscle function assessments.

Muscle function can be assessed through jumping mechanography, where portable ground reaction force plates collect dynamic information as a subject jumps. The aim of this study was to assess both intra- and inter- rater reliability of jumping mechanography. Ten healthy adults underwent 3 sets of testing (collected by 3 different raters) at two separate sessions, one week apart. They performed a number of tests in each session: multiple one-legged hopping (M1LH; on right and left legs) and single two-legged jumps (S2LJ; with or without arm swing). The S2LJ assessed variables of power per body mass, jump height, velocity and efficiency; whereas, M1LH assessed maximum force per body mass and stiffness. Inter-rater coefficients of variation (CV) were less than 0.6% and 2.6% for the S2LJ and M1LH, respectively, for the primary outcome variables of power/body mass and force/body mass. Analyzing intra-rater results also produced CVs less than 5.3% for all variables. The present study reports that the Leonardo ground reaction force plate system yields reproducible results between sessions, without significant contribution of variability from the test operator. Jumping mechanography is an easy, safe and reliable method for the assessment of lower limb musculoskeletal function.

Emergent symmetry in a low-dimensional superconductor on the edge of Mottness.

Upon cooling, condensed-matter systems typically transition into states of lower symmetry. The converse-i.e., the emergence of higher symmetry at lower temperatures-is extremely rare. In this work, we show how an unusually isotropic magnetoresistance in the highly anisotropic, one-dimensional conductor Li0.9Mo6O17 and its temperature dependence can be interpreted as a renormalization group (RG) flow toward a so-called separatrix. This approach is equivalent to an emergent symmetry in the system. The existence of two distinct ground states, Mott insulator and superconductor, can then be traced back to two opposing RG trajectories. By establishing a direct link between quantum field theory and an experimentally measurable quantity, we uncover a path through which emergent symmetry might be identified in other candidate materials.

Time-resolved hadronic particle acceleration in the recurrent nova RS Ophiuchi.

Recurrent novae are repeating thermonuclear explosions in the outer layers of white dwarfs, due to the accretion of fresh material from a binary companion. The shock generated when ejected material slams into the companion star's wind can accelerate particles. We report very-high-energy (VHE; [Formula: see text]) gamma rays from the recurrent nova RS Ophiuchi, up to 1 month after its 2021 outburst, observed using the High Energy Stereoscopic System (H.E.S.S.). The temporal profile of VHE emission is similar to that of lower-energy giga-electron volt emission, indicating a common origin, with a 2-day delay in peak flux. These observations constrain models of time-dependent particle energization, favoring a hadronic emission scenario over the leptonic alternative. Shocks in dense winds provide favorable environments for efficient acceleration of cosmic rays to very high energies.

Production, characterisation and applications of monoclonal antibodies to two novel porcine bocaviruses from swine in Northern Ireland.

The production, preliminary characterisation and applications of monoclonal antibodies (mAbs) against two novel swine bocaviruses isolated in cell culture from swine in Northern Ireland are described. Of the 17 stable final clones produced, four were characterised. All were of the IgG2a isotype and showed no cross-reactivity with either bocavirus strain. Partial neutralisation was observed with PBoV4 mAbs and homologous virus. The two mAbs selected for use in antigen-detecting ELISAs were successful in highlighting those fractions containing infectious virus within sucrose gradients. This is the first report of the production of specific reagents that will prove useful in the study of the biology of these viruses and swine bocavirus-associated diseases.

Revealing x-ray and gamma ray temporal and spectral similarities in the GRB 190829A afterglow.

Gamma-ray bursts (GRBs), which are bright flashes of gamma rays from extragalactic sources followed by fading afterglow emission, are associated with stellar core collapse events. We report the detection of very-high-energy (VHE) gamma rays from the afterglow of GRB 190829A, between 4 and 56 hours after the trigger, using the High Energy Stereoscopic System (H.E.S.S.). The low luminosity and redshift of GRB 190829A reduce both internal and external absorption, allowing determination of its intrinsic energy spectrum. Between energies of 0.18 and 3.3 tera-electron volts, this spectrum is described by a power law with photon index of 2.07 ± 0.09, similar to the x-ray spectrum. The x-ray and VHE gamma-ray light curves also show similar decay profiles. These similar characteristics in the x-ray and gamma-ray bands challenge GRB afterglow emission scenarios.

Long-term potentiation in the hippocampal slice: evidence for stimulated secretion of newly synthesized proteins.

Long-term potentiation of the hippocampal slice preparation results in an increase in the incorporation of labeled valine into the proteins destined for secretion into the extracellular medium. Double-labeling methods established that the increased secretion of the labeled proteins was limited to the potentiated region of a slice; incorporation of labeled valine was increased in the hippocampus if potentiation was through the Schaffer collaterals and in the dentate if potentiation was through the perforant path. Controls for nonspecific stimulation showed no changes. There appears to be a link between long-term potentiation and the metabolic processes that lead to protein synthesis in the hippocampal slice system.

A scanning Kelvin probe study of charge trapping in zone-cast pentacene thin film transistors.

We have used scanning Kelvin probe microscopy (SKPM) as a local probe to study charge trapping in zone-cast pentacene field effect transistors on both SiO(2) and benzocyclobutene (BCB) substrates. Annealing at 130 degrees C was found to reduce the threshold voltage, susceptibility to negative gate bias stress and trapping of positive charges within single pentacene grains. We conclude that oxygen is able to penetrate and disassociatively incorporate into crystalline pentacene, chemically creating electrically active defect states. Screening of a positive gate bias caused by electron injection from Au into pentacene was directly observed with SKPM. The rate of screening was found to change significantly after annealing of the film and depended on the choice of gate dielectric.

The Gerbode defect: the significance of a left ventricular to right atrial shunt.

BACKGROUND: The so-called Gerbode ventriculo-atrial defect is a rare defect that permits shunting from the left ventricle to the right atrium. It takes 2 forms, either a deficiency of the atrioventricular membranous septum, or shunting initially through a ventricular septal defect, with atrial shunting occurring through a deficiency in the septal leaflet of the tricuspid valve. In this review, we describe the natural history and outcomes of surgical repair for the variant with shunting through a deficiency at the site of the atrioventricular membranous septum. METHODS: From 1990 to 2008, we identified 6 patients from our departmental database who had undergone surgical closure of a congenital defect of the atrioventricular component of the membranous septum. Median age at repair was 1.6 years, with a range, from 0.4 to 19 years. All patients were symptomatic, with 3 having congestive cardiac failure, 2 failing to thrive, and 2 having intolerance to exercise. All had a dilated right atrium demonstrated by echocardiogram, with a mean preoperative gradient measured by echocardiogram to be 109 millimetres of mercury, with a range from 65 to 150 millimetres of mercury. RESULTS: There was no operative or late mortality. The mean size of the defect was 6.2 +/- 2.0 millimetres, with a range from 4 to 8 millimetres. All were closed by insertion of a patch. The mean period of cardiopulmonary bypass was 90.5 +/- 11.3 minutes, the mean time of aortic cross-clamping 54.8 +/- 6.9 minutes, and the mean length of stay in hospital 4.3 +/- 1.0 days. No patient had a residual defect, and only trivial regurgitation of the tricuspid valve was evident by postoperative echocardiography. There were no complications or reoperations. CONCLUSION: The membranous ventriculo-atrial defect can be recognized echocardiographically on the basis of dilation of the right atrium in the setting of an unusually high Doppler echocardiogram gradient compared to the ventricular septal defect with shunting only at ventricular level. Since all patients in our series were symptomatic, we recommend surgical closure of all these defects.

Genetic relatedness reveals total population size of white sharks in eastern Australia and New Zealand.

Conservation concerns exist for many sharks but robust estimates of abundance are often lacking. Improving population status is a performance measure for species under conservation or recovery plans, yet the lack of data permitting estimation of population size means the efficacy of management actions can be difficult to assess, and achieving the goal of removing species from conservation listing challenging. For potentially dangerous species, like the white shark, balancing conservation and public safety demands is politically and socially complex, often leading to vigorous debate about their population status. This increases the need for robust information to inform policy decisions. We developed a novel method for estimating the total abundance of white sharks in eastern Australia and New Zealand using the genetic-relatedness of juveniles and applying a close-kin mark-recapture framework and demographic model. Estimated numbers of adults are small (ca. 280-650), as is total population size (ca. 2,500-6,750). However, estimates of survival probability are high for adults (over 90%), and fairly high for juveniles (around 73%). This represents the first direct estimate of total white shark abundance and survival calculated from data across both the spatial and temporal life-history of the animal and provides a pathway to estimate population trend.

Strength in Numbers: an international consensus conference to develop a novel approach to care delivery for young adults with type 1 diabetes, the D1 Now Study.

PLAIN ENGLISH SUMMARY: Many young adults with type 1 diabetes struggle with the day-to-day management of their condition. They often find it difficult to find the time to attend their clinic appointments and to meet with their diabetes healthcare team. Young adults living with type 1 diabetes are not routinely involved in research that may help improve health services other than being invited to take part in studies as research participants. A 3-day international conference was held in Galway in June 2016 called "Strength In Numbers: Teaming up to improve the health of young adults with type 1 diabetes". It aimed to bring together people from a broad variety of backgrounds with an interest in young adults with type 1 diabetes. Young people with type 1 diabetes came together with healthcare professionals, researchers, software developers and policy makers to come up with and agree on a new approach for engaging young adults with type 1 diabetes with their health services and to improve how they manage their diabetes.The people involved in the conference aimed to reach agreement (consensus) on a fixed set of outcome measures called a core outcome set (COS) that the group would recommend future studies involving young adults with type 1 diabetes to use, to suggest a new approach (intervention) for providing health services to young adults with type 1 diabetes, and to come up with health technology ideas that could help deliver the new intervention. Over the 3 days, this diverse international group of people that included young adults living with type 1 diabetes, agreed on a COS, 3 key parts of a new intervention and 1 possible health technology idea that could help with how the overall intervention could be delivered.Involving young adults living with type 1 diabetes in a 3-day conference along with other key groups is an effective method for coming up with a new approach to improve health services for young adults with type 1 diabetes and better support their self-management. ABSTRACT: Background A 3-day international consensus meeting was hosted by the D1 Now study team in Galway on June 22-24, 2016 called "Strength In Numbers: Teaming up to improve the health of young adults with type 1 diabetes". The aim of the meeting was to bring together young adults with type 1 diabetes, healthcare providers, policy makers and researchers to reach a consensus on strategies to improve engagement, self-management and ultimately outcomes for young adults living with type 1 diabetes. Methods This diverse stakeholder group participated in the meeting to reach consensus on (i) a core outcome set (COS) to be used in future intervention studies involving young adults with type 1 diabetes, (ii) new strategies for delivering health services to young adults and (iii) potential digital health solutions that could be incorporated into a future intervention. Results A COS of 8 outcomes and 3 key intervention components that aim to improve engagement between young adults with type 1 diabetes and service providers were identified. A digital health solution that could potentially compliment the intervention components was proposed. Conclusion The outputs from the 3-day consensus conference, that held patient and public involvement at its core, will help the research team further develop and test the D1 Now intervention for young adults with type 1 diabetes in a pilot and feasibility study and ultimately in a definitive trial. The conference represents a good example of knowledge exchange among different stakeholders for health research and service improvement.

[Evaluation of malaria rapid diagnostic test Optimal-IT® pLDH along the Plasmodium falciparum distribution limit in Mauritania]. / Evaluation du test de diagnostic rapide du paludisme OptiMal-IT® pLDH à la limite de la distribution de Plasmodium falciparum en Mauritanie.

Performance of the malaria Rapid Diagnostic Test (RDT) OptiMal-IT® was evaluated in Mauritania where malaria is low and dependent on a short transmission season. Slide microscopy was considered as the reference method of diagnosis. Febrile patients with suspected malaria were recruited from six health facilities, 3 urban and 3 rural, during two periods (December 2011 to February 2012, and August 2012 to March 2013). Overall, 780 patients were sampled, with RDT and thick blood film microscopy results being obtained for 759 of them. Out of 774 slides examined, of which 200 were positive, P. falciparum and P. vivax mono-infections were detected in 63.5% (127) and 29.5% (59), while P. falciparum/P. vivax coinfections were detected in 7% (14). Both species were observed in all study sites, although in significantly different proportions. The proportions of thick blood film and OptiMal-IT® RDT positive individuals was 26.3% and 30.3% respectively. Sensitivity and specificity of OptiMal-IT® RDT were 89% [95% CI, 84.7-93.3] and 91.1% [88.6-93.4]. Positives and negative predictive values were 78.1% [72.2-83.7] and 95.9% [94.1-97.5]. These diagnostic values are similar to those generally reported elsewhere, and support the use of RDTs as the main diagnostic tool for malaria in Mauritanian health facilities. In the future, choice of RDTs to be used must take account of thermostability in a hot, dry environment and their ability to detect P. falciparum and P. vivax.