Medial prefrontal cortex and hippocampal activity differentially contribute to ordinal and temporal context retrieval during sequence memory

Remembering sequences of events defines episodic memory, but retrieval can be driven by both ordinality and temporal contexts. Whether these modes of retrieval operate at the same time or not remains unclear. Theoretically, medial prefrontal cortex (mPFC) confers ordinality, while the hippocampus (HC) associates events in gradually changing temporal contexts. Here, we looked for evidence of each with BOLD fMRI in a sequence task that taxes both retrieval modes. To test ordinal modes, items were transferred between sequences but retained their position (e.g., AB3). Ordinal modes activated mPFC, but not HC. To test temporal contexts, we examined items that skipped ahead across lag distances (e.g., ABD). HC, but not mPFC, tracked temporal contexts. There was a mPFC and HC by retrieval mode interaction. These current results suggest that the mPFC and HC are concurrently engaged in different retrieval modes in support of remembering when an event occurred

Selective Role of the Catalytic PI3K Subunit p110β in Impaired Higher Order Cognition in Fragile X Syndrome

SummaryDistinct isoforms of the PI3K catalytic subunit have specialized functions in the brain, but their role in cognition is unknown. Here, we show that the catalytic subunit p110β plays an important role in prefrontal cortex (PFC)-dependent cognitive defects in mouse models of Fragile X syndrome (FXS), an inherited intellectual disability. FXS is caused by loss of function of the fragile X mental retardation protein (FMRP), which binds and translationally represses mRNAs. PFC-selective knockdown of p110β, an FMRP target that is translationally upregulated in FXS, reverses deficits in higher cognition in Fmr1 knockout mice. Genetic full-body reduction of p110β in Fmr1 knockout mice normalizes excessive PI3K activity, restores stimulus-induced protein synthesis, and corrects increased dendritic spine density and behavior. Notably, adult-onset PFC-selective Fmr1 knockdown mice show impaired cognition, which is rescued by simultaneous p110β knockdown. Our results suggest that FMRP-mediated control of p110β is crucial for neuronal protein synthesis and cognition

Couples' voluntary counselling and testing and nevirapine use in antenatal clinics in two African capitals: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>With the accessibility of prevention of mother to child transmission (PMTCT) services in sub-Saharan Africa, more women are being tested for HIV in antenatal care settings. Involving partners in the counselling and testing process could help prevent horizontal and vertical transmission of HIV. This study was conducted to assess the feasibility of couples' voluntary counseling and testing (CVCT) in antenatal care and to measure compliance with PMTCT.</p> <p>Methods</p> <p>A prospective cohort study was conducted over eight months at two public antenatal clinics in Kigali, Rwanda, and Lusaka, Zambia. A convenience sample of 3625 pregnant women was enrolled. Of these, 1054 women were lost to follow up. The intervention consisted of same-day individual voluntary counselling and testing (VCT) and weekend CVCT; HIV-positive participants received nevirapine tablets. In Kigali, nevirapine syrup was provided in the labour and delivery ward; in Lusaka, nevirapine syrup was supplied in pre-measured single-dose syringes. The main outcome measures were nurse midwife-recorded deliveries and reported nevirapine use.</p> <p>Results</p> <p>In eight months, 1940 women enrolled in Kigali (984 VCT, 956 CVCT) and 1685 women enrolled in Lusaka (1022 VCT, 663 CVCT). HIV prevalence was 14% in Kigali, and 27% in Lusaka. Loss to follow up was more common in Kigali than Lusaka (33% vs. 24%, p = 0.000). In Lusaka, HIV-positive and HIV-negative women had significantly different loss-to-follow-up rates (30% vs. 22%, p = 0.002). CVCT was associated with reduced loss to follow up: in Kigali, 31% of couples versus 36% of women testing alone (p = 0.011); and in Lusaka, 22% of couples versus 25% of women testing alone (p = 0.137). Among HIV-positive women with follow up, CVCT had no impact on nevirapine use (86-89% in Kigali; 78-79% in Lusaka).</p> <p>Conclusions</p> <p>Weekend CVCT, though new, was feasible in both capital cities. The beneficial impact of CVCT on loss to follow up was significant, while nevirapine compliance was similar in women tested alone or with their partners. Pre-measured nevirapine syrup syringes provided flexibility to HIV-positive mothers in Lusaka, but may have contributed to study loss to follow up. These two prevention interventions remain a challenge, with CVCT still operating without supportive government policy in Zambia.</p

Stress-Dependent Enhancement And Impairment Of Retention By Naloxone: Evidence For An Endogenous Opioid-Based Modulatory System Protective Of Memory

The opiate-receptor antagonist naloxone was administered to rats after passive-avoidance training either alone or in combination with forced-swim stress. A retention test revealed that while naloxone enhanced retention when administered alone, it impaired retention when administered in combination with forced-swim stress. The findings provide evidence for a “protective” endogenous opioid-based system that, when not blocked pharmacologically, limits enhancement or impairment of retention under conditions of mild and intense stress, respectively

Unmet clinical needs for COVID-19 tests in UK health and social care settings

There is an urgent requirement to identify which clinical settings are in most need of COVID-19 tests and the priority role(s) for tests in these settings to accelerate the development of tests fit for purpose in health and social care across the UK. This study sought to identify and prioritize unmet clinical needs for COVID-19 tests across different settings within the UK health and social care sector via an online survey of health and social care professionals and policymakers. Four hundred and forty-seven responses were received between 22nd May and 15th June 2020. Hospitals and care homes were recognized as the settings with the greatest unmet clinical need for COVID-19 diagnostics, despite reporting more access to laboratory molecular testing than other settings. Hospital staff identified a need for diagnostic tests for symptomatic workers and patients. In contrast, care home staff expressed an urgency for screening at the front door to protect high-risk residents and limit transmission. The length of time to test result was considered a widespread problem with current testing across all settings. Rapid tests for staff were regarded as an area of need across general practice and dental settings alongside tests to limit antibiotics use

Is the pharmacy profession innovative enough?: meeting the needs of Australian residents with chronic conditions and their carers using the nominal group technique

Background Community pharmacies are ideally located as a source of support for people with chronic conditions. Yet, we have limited insight into what innovative pharmacy services would support this consumer group to manage their condition/s. The aim of this study was to identify what innovations people with chronic conditions and their carers want from their ideal community pharmacy, and compare with what pharmacists and pharmacy support staff think consumers want. Methods We elicited ideas using the nominal group technique. Participants included people with chronic conditions, unpaid carers, pharmacists and pharmacy support staff, in four regions of Australia. Themes were identified via thematic analysis using the constant comparison method. Results Fifteen consumer/carer, four pharmacist and two pharmacy support staff groups were conducted. Two overarching themes were identified: extended scope of practice for the pharmacist and new or improved pharmacy services. The most innovative role for Australian pharmacists was medication continuance, within a limited time-frame. Consumers and carers wanted improved access to pharmacists, but this did not necessarily align with a faster or automated dispensing service. Other ideas included streamlined access to prescriptions via medication reminders, electronic prescriptions and a chronic illness card. Conclusions This study provides further support for extending the pharmacist’s role in medication continuance, particularly as it represents the consumer’s voice. How this is done, or the methods used, needs to optimise patient safety. A range of innovative strategies were proposed and Australian community pharmacies should advocate for and implement innovative approaches to improve access and ensure continuity of care

The SAMI Galaxy Survey: Global stellar populations on the size-mass plane

We present an analysis of the global stellar populations of galaxies in the SAMI Galaxy Survey. Our sample consists of 1319 galaxies spanning four orders of magnitude in stellar mass and includes all morphologies and environments. We derive luminosity-weighted, single stellar population equivalent stellar ages, metallicities and alpha enhancements from spectra integrated within one effective radius apertures. Variations in galaxy size explain the majority of the scatter in the age--mass and metallicity--mass relations. Stellar populations vary systematically in the plane of galaxy size and stellar mass, such that galaxies with high stellar surface mass density are older, more metal-rich and alpha-enhanced than less dense galaxies. Galaxies with high surface mass densities have a very narrow range of metallicities, however, at fixed mass, the spread in metallicity increases substantially with increasing galaxy size (decreasing density). We identify residual correlations with morphology and environment. At fixed mass and size, galaxies with late-type morphologies, small bulges and low Sersic n are younger than early-type, high n, high bulge-to-total galaxies. Age and metallicity both show small residual correlations with environment; at fixed mass and size, galaxies in denser environments or more massive halos are older and somewhat more metal rich than those in less dense environments. We connect these trends to evolutionary tracks within the size--mass plane.Comment: 25 pages, 18 figures, MNRAS in press Corrected typo in author lis

Spatiotemporal distribution of phycotoxins and their co-occurrence within nearshore waters

Harmful algal blooms (HABs), varying in intensity and causative species, have historically occurred throughout the Chesapeake Bay, U.S.; however, phycotoxin data are sparse. The spatiotemporal distribution of phycotoxins was investigated using solid-phase adsorption toxin tracking (SPATT) across 12 shallow, nearshore sites within the lower Chesapeake Bay and Virginia\u27s coastal bays over one year (2017-2018). Eight toxins, azaspiracid-1 (AZA1), azaspiracid-2 (AZA2), microcystin-LR (MC-LR), domoic acid (DA), okadaic acid (OA), dinophysistoxin-1 (DTX1), pectenotoxin-2 (PTX2), and goniodomin A (GDA) were detected in SPATT extracts. Temporally, phycotoxins were always present in the region, with at least one phycotoxin group (i.e., consisting of OA and DTX1) detected at every time point. Co-occurrence of phycotoxins was also common; two or more toxin groups were observed in 76% of the samples analyzed. Toxin maximums: 0.03 ng AZA2/g resin/day, 0.25 ng DA/g resin/day, 15 ng DTX1/g resin/day, 61 ng OA/g resin/day, 72 ng PTX2/g resin/day, and 102,050 ng GDA/g resin/day were seasonal, with peaks occurring in summer and fall. Spatially, the southern tributary and coastal bay regions harbored the highest amount of total phycotoxins on SPATT over the year, and the former contained the greatest diversity of phycotoxins. The novel detection of AZAs in the region, before a causative species has been identified, supports the use of SPATT as an explorative tool in respect to emerging threats. The lack of karlotoxin in SPATT extracts, but detection of Karlodinium veneficum by microscopy, however, emphasizes that this tool should be considered complementary to, but not a replacement for, more traditional HAB management and monitoring methods

Canine pseudopregnancy: an evaluation of prevalence and current treatment protocols in the UK

Background: There is a dearth of literature on pseudopregnancy in the bitch, with only a few treatment-based studies published since the 1990s. Pseudopregnancy may be under-recognised in bitches and may account for a proportion of behavioural cases seen in veterinary practices including aggression. Little is known about commonly used treatments for overtly pseudopregnant bitches and it is possible that current regimes may not be prescribed for a sufficient duration to control any clinical signs including, physical and behavioural changes. To investigate current trends in diagnosis and treatment of canine pseudopregnancy, a postal survey was sent to 2000 randomly selected veterinary surgeons in UK veterinary practices. The questionnaire queried how often vets recognise cases of pseudopregnancy in spayed and entire bitches, which physical or behavioural signs are commonly recognised for diagnosis, and which management or treatment protocols are used. Results: The response rate was 19.8% (397/2000). Ninety-six percent of veterinary surgeons reported seeing pseudopregnant bitches showing behavioural changes without any physical changes within the last 12 months. Of those behavioural changes, collecting and mothering objects was the most frequently reported behavioural sign (96%). Ninety-seven percent of vets had seen aggression in pseudopregnant bitches. Nevertheless, only 52% of vets routinely asked owners about behavioural changes during consultations. Forty-nine percent of respondents reported seeing pseudopregnancy in spayed bitches. The most commonly reported physical sign was enlarged mammary glands and/or milk production (89%). Treatment options varied (surgical, medical or none) and depended on duration and severity of physical and behavioural signs, owners’ preference, cost, concurrent disease, drug availability and previous history. Conclusions: This is the largest epidemiological study of canine pseudopregnancy in the UK. The prevalence and severity of clinical signs in dogs with pseudopregnancy are variable and possibly under-estimated. Dogs with overt pseudopregnancy experience diverse physical and behavioural changes and information on standard treatment protocols are lacking. Although, progress on our understanding of diagnosis and treatment of pseudopregnancy in spayed and entire bitches has been made, further studies are warranted