RGS14 limits seizure-induced mitochondrial oxidative stress and pathology in hippocampus.

RGS14 is a complex multifunctional scaffolding protein that is highly enriched within pyramidal cells (PCs) of hippocampal area CA2. In these neurons, RGS14 suppresses glutamate-induced calcium influx and related G protein and ERK signaling in dendritic spines to restrain postsynaptic signaling and plasticity. Previous findings show that, unlike PCs of hippocampal areas CA1 and CA3, CA2 PCs are resistant to a number of neurological insults, including degeneration caused by temporal lobe epilepsy (TLE). While RGS14 is protective against peripheral injury, similar roles for RGS14 during pathological injury in hippocampus remain unexplored. Recent studies showed that area CA2 modulates hippocampal excitability, generates epileptiform activity and promotes hippocampal pathology in animal models and patients with TLE. Because RGS14 suppresses CA2 excitability and signaling, we hypothesized that RGS14 would moderate seizure behavior and early hippocampal pathology following seizure activity, possibly affording protection to CA2 PCs. Using kainic acid (KA) to induce status epilepticus (KA-SE) in mice, we show that the loss of RGS14 (RGS14 KO) accelerated onset of limbic motor seizures and mortality compared to wild type (WT) mice, and that KA-SE upregulated RGS14 protein expression in CA2 and CA1 PCs of WT. Our proteomics data show that the loss of RGS14 impacted the expression of a number of proteins at baseline and after KA-SE, many of which associated unexpectedly with mitochondrial function and oxidative stress. RGS14 was shown to localize to the mitochondria in CA2 PCs of mice and reduce mitochondrial respiration in vitro. As a readout of oxidative stress, we found that RGS14 KO dramatically increased 3- nitrotyrosine levels in CA2 PCs, which was greatly exacerbated following KA-SE and correlated with a lack of superoxide dismutase 2 (SOD2) induction. Assessing for hallmarks of seizure pathology in RGS14 KO, we unexpectedly found no differences in neuronal injury in CA2 PCs. However, we observed a striking and surprising lack of microgliosis in CA1 and CA2 of RGS14 KO compared to WT. Together, our data demonstrate a newly appreciated role for RGS14 in limiting intense seizure activity and pathology in hippocampus. Our findings are consistent with a model where RGS14 limits seizure onset and mortality and, after seizure, is upregulated to support mitochondrial function, prevent oxidative stress in CA2 PCs, and promote microglial activation in hippocampus.

New insights into the effects of ethylene on ABA catabolism, sweetening and dormancy in stored potato tubers.

Continuous ethylene supplementation suppresses postharvest sprouting, but it can increase reducing sugars, limiting its use as an alternative to chlorpropham for processing potatoes. To elucidate the mechanisms involved, tubers were treated after curing with or without the ethylene binding inhibitor 1-methylcyclopropene (1-MCP at 1 µL L-1 for 24 h), and then stored in air or air supplemented with continuous ethylene (10 µL L-1). Across three consecutive seasons, changes in tuber physiology were assessed alongside transcriptomic and metabolomic analysis. Exogenous ethylene alone consistently induced a respiratory rise and the accumulation of undesirable reducing sugars. The transient respiratory peak was preceded by the strong upregulation of two genes encoding 1-aminocyclopropane-1-carboxylate oxidase (ACO), typical of wound and stress induced ethylene production. Profiles of parenchymatic tissue highlighted that ethylene triggered abscisic acid (ABA) catabolism, evidenced by a steep fall in ABA levels and a transient rise in the catabolite phaseic acid, accompanied by upregulation of transcripts encoding an ABA 8'-hydroxylase. Moreover, analysis of non-structural carbohydrate-related genes revealed that ethylene strongly downregulated the expression of the Kunitz-type invertase inhibitor, already known to be involved in cold-induced sweetening. All these ethylene-induced effects were negated by 1-MCP with one notable exception: 1-MCP enhanced the sprout suppressing effect of ethylene whilst preventing ethylene-induced sweetening. This study supports the conclusions that: i) tubers adapt to ethylene by regulating conserved pathways (e.g. ABA catabolism); ii) ethylene-induced sweetening acts independently from sprout suppression, and is similar to cold-induced sugar accumulation.

Associations between affect, craving, and smoking in Korean smokers: An ecological momentary assessment study.

Cigarette smoking remains the largest cause of preventable death in the United States and worldwide. In South Korea and other Asian countries, a large proportion of males smoke, increasing the need to examine cigarette smoking in these populations. Research suggests that the association between positive affect and negative affect, and between affect and craving, may differ across cultures, and that it is useful to examine these associations using Ecological Momentary Assessment (EMA). South Korean smokers (N = 20, Mean Age = 21.15, 25% female) completed baseline questionnaires and downloaded an EMA app which prompted 4 random assessments (RAs) each day for 1-week. At each assessment, participants responded to items assessing momentary negative affect (NA) and positive affect (PA), craving, and number of cigarettes smoked since the previous EMA assessment. Linear mixed models (LMMs) were used to analyze EMA data (544 assessments), separating out between- and within- subject associations. There was a significant positive association between positive affect and negative affect at the between-subjects level. Both positive affect and negative affect were significantly positively associated with craving at between-subjects and within-subject levels. Craving was associated with subsequent smoking behavior at the within-subjects level. Overall, results suggest that associations between positive affect and negative affect may be different in South Korean smokers than in Western smokers, and that there are robust associations between both negative and positive affect and craving.

Naive Forecast for COVID-19 in Utah Based on the South Korea and Italy Models-the Fluctuation between Two Extremes.

Differences in jurisdictional public health actions have played a significant role in the relative success of local communities in combating and containing the COVID-19 pandemic. We forecast the possible COVID-19 outbreak in one US state (Utah) by applying empirical data from South Korea and Italy, two countries that implemented disparate public health actions. Forecasts were created by aligning the start of the pandemic in Utah with that in South Korea and Italy, getting a short-run forecast based on actual daily rates of spread, and long-run forecast by employing a log-logistic model with four parameters. Applying the South Korea model, the epidemic peak in Utah is 169 cases/day, with epidemic resolution by the end of May. Applying the Italy model, new cases are forecast to exceed 200/day by mid-April, with the potential for 250 new cases a day at the epidemic peak, with the epidemic continuing through the end of August. We identify a 3-month variation in the likely length of the pandemic, a 1.5-fold difference in the number of daily infections at outbreak peak, and a 3-fold difference in the expected cumulative cases when applying the experience of two developed countries in handling this virus to the Utah context.

Effect of hypnotic suggestion on cognition and craving in smokers.

Cigarette smoking remains an important public health concern, and novel smoking cessation interventions are needed. Craving for cigarettes is a well-established target for intervention. Recent research has identified cognitive processes associated with craving, such as attentional bias to smoking cues, as targets for intervention. One intervention that may be effective in reducing attentional bias is hypnotic suggestion. Using a counterbalanced within-subjects design in a sample of active smokers (N = 33), this laboratory study examined if hypnotic suggestion can modify attention, assessed by the classic and smoking Stroop tasks, and craving. Hypnotic susceptibility was assessed using the Stanford Scale of Hypnotic Susceptibility. There was no evidence that hypnotic susceptibility moderated the effect of hypnotic suggestion on the classic or smoking Stroop effects. However, hypnotic susceptibility did moderate the effect of hypnotic suggestion on craving, such that hypnotic suggestion reduced craving in individuals with high levels of susceptibility. Further research into the mechanisms by which hypnotic suggestion reduces craving is warranted.

Ecological momentary assessment studies of comorbid PTSD and alcohol use: A narrative review.

INTRODUCTION: PTSD and harmful alcohol use, including alcohol use disorder (AUD), frequently co-occur. Recent research has used ecological momentary assessment (EMA) to examine the associations between PTSD symptoms and alcohol-related variables, such as craving for alcohol, alcohol use, and the presence of alcohol-related problems. The overall purpose of this narrative review is to summarize this emerging literature. METHODS: Inclusion criteria for studies were: 1) Use of ecological momentary assessment as the method for gathering data on alcohol use and/or craving in populations with both problematic alcohol use and PTSD, and the inclusion of an assessment of both PTSD symptoms and at least one alcohol use variable during EMA; and 2) At screening, participants were required to meet study criteria for a) elevated PTSD symptoms or trauma exposure, and b) alcohol use. RESULTS: The pertinent extant literature is reviewed in terms of four underlying themes: Methodological considerations of EMA research in a population with PTSD symptoms and harmful alcohol use; Associations between PTSD symptoms and alcohol use variable/s; Moderators of PTSD-alcohol use associations; Mediators of PTSD-alcohol use associations. CONCLUSIONS: Collectively, studies provide support for the self-medication hypothesis. Several variables were found to moderate association between PTSD symptoms and alcohol-related variables. EMA data may ultimately be useful in identifying when individuals are at risk for harm due to increased symptoms or alcohol misuse and may inform treatment approaches administered remotely.

Genomics and epigenetics of sexual commitment in Plasmodium.

Malaria is the disease caused by the apicomplexan parasites belonging to the genus Plasmodium. Expanding our arsenal to include transmission-blocking agents in our fight against malaria is becoming increasingly important. Such an implementation requires detailed understanding of the biology of the Plasmodium life cycle stages that are transmissible. Plasmodium gametocytes are the only parasite stage that can be transmitted to the mosquito vector and are the product of sexual development in a small percentage of parasites that continually proliferate in host blood. The critical decision made by asexual erythrocytic stages to cease further proliferation and differentiate into gametocytes, as well as the first steps they take into maturity, have long remained unknown. Recent studies have contributed to a breakthrough in our understanding of this branch point in development. In this review, we will discuss the findings that have allowed us to make this major leap forward in our knowledge of sexual commitment in Plasmodium. We will further propose a model for the mechanism triggering the switch to sexual development, constructed around the proteins currently known to regulate this process. Further insight into sexual commitment and gametocyte development will help identify targets for the development of transmission-blocking malaria therapies.

Making molehills out of a mountain: experience with a new scheduling strategy to diminish workload variations in response to increased treatment demands.

PURPOSE: A new scheduling strategy was implemented. Before implementation, treatments and planning computed tomography (ct) imaging were both scheduled at the same time. Maximal wait times for treatment are defined by the Quebec Ministry of Health's plan of action according to treatment aim and site. After implementation, patients requiring rapid treatment (priorities 0-3) continued to have their treatments scheduled at the same time as their planning ct; treatments for priority 4 (P4) patients were scheduled only after the treatment plan was approved. That approach aims to compensate for unexpected increases in planning workload by relocating less delay-sensitive cases to other time slots. We evaluated the impact on the patient experience, workload in various sectors, the care team's perception of care delivery, access to care, and the department's efficiency in terms of hours worked per treatment delivered. METHODS: Three periods were defined for analysis: the pre-transitional phase, for baseline evaluation; the transitional phase, during which there was an overlap in the way patients were being scheduled; and the post-transitional phase. Wait times were calculated from the date that patients were ready to treat to the date of their first treatment. Surveys were distributed to pre- and post-transitional phase patients. Care team members were asked to complete a survey evaluating their perception of how the change affected workload and patient care. Operational data were analyzed. RESULTS: We observed a 24% increase in the number of treatments delivered in the post-transitional phase. Before implementation, priority 0-3 patients waited a mean of 7.9 days to begin treatments (n = 241); afterward, they waited 6.3 days (n = 340, p = 0.006). Before implementation, P4 patients waited a mean 15.1 days (n = 233); after implementation, they waited 16.1 days (n = 368, p = 0.22). Surveys showed that patients felt that the time it took to inform them of treatment appointments was acceptable in both phases. No significant change in overtime hours occurred in dosimetry (p = 0.7476) or globally (p = 0.4285) despite the increased number of treatments. However, departmental efficiency improved by 16% (p = 0.0001). CONCLUSIONS: This new scheduling strategy for P4 cases resulted in improved access to care for priority 0-3 patients. Departmental efficiency was improved, and overtime hours did not increase. Patient satisfaction remained high.

The effect of follow-up inspections on critical violations identified during restaurant inspections.

Follow-up inspections are recommended by the Food and Drug Administration as a tool to verify corrections to violations cited during restaurant inspections. The effectiveness of follow-up inspections as a tool in reducing critical violations is unknown, however. The purpose of the authors' study was to assess whether a serious violation that leads to a follow-up inspection reduces the probability of specific critical violations occurring during the next routine inspection. Outcome measures included poor personal hygiene, improper holding temperatures, substandard equipment cleanliness, potential cross contamination, and improper sanitizer concentration. The risk of having a violation increased for all targeted critical violations during inspections conducted after a follow-up inspection compared to restaurant inspections without a prior follow-up, when adjusting for restaurant type, inspector experience, and season.

Characterization of a novel oil-in-water emulsion adjuvant for swine influenza virus and Mycoplasma hyopneumoniae vaccines.

Vaccines consisting of subunit or inactivated bacteria/virus and potent adjuvants are widely used to control and prevent infectious diseases. Because inactivated and subunit antigens are often less antigenic than live microbes, a growing need exists for the development of new and improved vaccine adjuvants that can elicit rapid and long-lasting immunity. Here we describe the development and characterization of a novel oil-in-water emulsion, OW-14. OW-14 contains low-cost plant-based emulsifiers and was added to antigen at a ratio of 1:3 with simple hand mixing. OW-14 was stable for prolonged periods of time at temperatures ranging from 4 to 40°C and could be sterilized by autoclaving. Our results showed that OW-14 adjuvanted inactivated swine influenza viruses (SIV; H3N2 and H1N1) and Mycoplasma hyopneumoniae (M. hyo) vaccines could be safely administered to piglets in two doses, three weeks apart. Injection sites were monitored and no adverse reactions were observed. Vaccinated pigs developed high and prolonged antibody titers to both SIV and M. hyo. Interestingly, antibody titers were either comparable or greater than those produced by commercially available FluSure (SIV) or RespiSure (M. hyo) vaccines. We also found that OW-14 can induce high antibody responses in pigs that were vaccinated with a decreased antigen dose. This study provides direct evidence that we have developed an easy-to-use and low-cost emulsion that can act as a powerful adjuvant in two common types of swine vaccines.

Delirium affects length of hospital stay after lung transplantation.

BACKGROUND: Delirium is relatively common after lung transplantation, although its prevalence and prognostic significance have not been systematically studied. The purpose of the present study was to examine pretransplant predictors of delirium and the short-term impact of delirium on clinical outcomes among lung transplant recipients. METHODS: Participants underwent pretransplant cognitive testing using the Repeatable Battery for the Assessment of Neuropsychological Status and the Trail Making Test. After transplant, delirium was assessed using the Confusion Assessment Method until discharge. RESULTS: Sixty-three patients were transplanted between March and November 2013, of which 23 (37%) developed delirium. Among transplanted patients, 48 patients completed pretransplant cognitive testing. Better pretransplant cognitive function was associated with lower risk of delirium (odds ratio, 0.69 [95% confidence interval 0.48, 0.99], P = .043); and demographic and clinical features including native disease (P = .236), the Charlson comorbidity index (P = .581), and the lung allocation score (P = .871) were unrelated to risk of delirium, although there was a trend for women to experience delirium less frequently (P = .071). The presence (P = .006) and duration (P = .027) of delirium were both associated with longer hospital stays. CONCLUSION: Delirium occurs in more than one-third of patients after lung transplantation. Delirium was associated with poorer pretransplant cognitive functioning and longer hospital stays, after accounting for other medical and demographic factors.

Motivational interviewing at the intersections of depression and intimate partner violence among African American women.

This article focuses on design, training, and delivery of a culturally tailored, multi-faceted intervention that used motivational interviewing (MI) and case management to reduce depression severity among African American survivors of intimate partner violence (IPV). We present the details of the intervention and discuss its implementation as a means of creating and providing culturally appropriate depression and violence services to African American women. We used a community-based participatory research approach to develop and evaluate the multi-faceted intervention. As part of the evaluation, we collected process measures about the use of MI, assessed MI fidelity, and interviewed participants about their experiences with the program.

Biased attention to threat in paediatric anxiety disorders (generalized anxiety disorder, social phobia, specific phobia, separation anxiety disorder) as a function of 'distress' versus 'fear' diagnostic categorization.

BACKGROUND: Structural models of emotional disorders propose that anxiety disorders can be classified into fear and distress disorders. Sources of evidence for this distinction come from genetic, self-report and neurophysiological data from adults. The present study examined whether this distinction relates to cognitive processes, indexed by attention bias towards threat, which is thought to cause and maintain anxiety disorders. METHOD: Diagnostic and attention bias data were analysed from 435 children between 5 and 13 years of age; 158 had principal fear disorder (specific phobia, social phobia or separation anxiety disorder), 75 had principal distress disorder (generalized anxiety disorder, GAD) and 202 had no psychiatric disorder. Anxious children were a clinic-based treatment-seeking sample. Attention bias was assessed on a visual-probe task with angry, neutral and happy faces. RESULTS: Compared to healthy controls, children with principal distress disorder (GAD) showed a significant bias towards threat relative to neutral faces whereas children with principal fear disorder showed an attention bias away from threat relative to neutral faces. Overall, children displayed an attention bias towards happy faces, irrespective of diagnostic group. CONCLUSIONS: Our findings support the distinction between fear and distress disorders, and extend empirically derived structural models of emotional disorders to threat processing in childhood, when many anxiety disorders begin and predict lifetime impairment.

Examination of the association between announced inspections and inspection scores.

In 2010 the Salt Lake Valley Health Department conducted a pilot of an announced inspection program utilizing a randomized assignment of restaurants to an intervention group with announced inspections and a control group that remained on the usual schedule of unannounced inspections. After adjusting for food type, visible kitchen, outside quality assurance, season, and standardized inspector, significant reductions were found in the odds ratios of personal hygiene (adjusted odds ratios [aOR] = 0.11, p = .00) and equipment cleanliness (aOR = 0.19, p = .00) violations. In the models for the control group, none of the odds ratios were statistically different from one, indicating no change in the postintervention time period as compared to the preintervention period.

Impact of internet posting of restaurant inspection scores on critical violations.

Posting restaurant inspection scores on the Internet as a tool for improving food safety is becoming more common. The purpose of the study described in this article was to evaluate the association between Internet posting of restaurant inspection scores and the five most frequently cited critical violations in Salt Lake County, Utah. The study examined 2,995 inspections conducted at 796 full service and fast food restaurants for a one-year period before and after launch of a restaurant inspection Web site. Critical violations decreased significantly after the Web site launch compared to before-launch levels. The greatest improvements were found in temperature holding violations (odds ratio = 0.75, p < .001), hygiene practices violations (odds ratio = 0.68, p < .001) and equipment cleanliness violations (odds ratio = 0.58, p < .001). Restaurant type (full service, fast food), inspector experience, and season were significantly associated with the decrease in violations.

Assessing aluminium toxicity in streams affected by acid mine drainage.

Acid mine drainage (AMD) has degraded water quality and ecology in streams on the Stockton Plateau, the site of New Zealand's largest open-cast coal mining operation. This has previously been attributed largely to the effects of acidity and elevated aluminium (Al) concentrations. However, the toxicity of dissolved Al is dependent on speciation, which is influenced by pH which affects Al hydrolysis, as well as the concentrations of organic carbon and sulphate which complex Al. Methods for the assessment of the toxic fraction of Al, by chemical analysis and geochemical modelling, have been investigated in selected streams on the Stockton Plateau, where dissolved Al concentrations ranged from 0.034 to 27 mg L(-1). Modelling using PHREEQC indicated that between 0.2 and 85% of the dissolved Al was present as the free ion Al(3+), the most toxic Al species, which dominated in waters of pH = 3.8-4.8. Al-sulphate complexation reduced the Al(3+) concentration at lower pH, while Al-organic and -hydroxide complexes dominated at higher pH. Macroinvertebrate richness in the streams identified an Al(3+) 'threshold' of approximately 0.42 mg/L, above which taxa declined rapidly. Colorimetric 'Aluminon' analysis on unpreserved, unfiltered waters provided a better estimation of Al(3+) concentrations than inductively couple plasma-mass spectrometry (ICP-MS) on filtered, acidified waters. The Aluminon method does not react with particulate Al or strong Al complexes, often registering as little as 53% of the dissolved Al concentration determined by ICP-MS.

The management of recurrent croup in children.

OBJECTIVE: To review the aetiology, investigation, diagnosis, treatment and clinical outcome of children with recurrent croup. METHOD: Retrospective case note review of all children with recurrent croup referred to the otolaryngology service at our hospital from November 2002 to March 2011. RESULTS: Ninety children with recurrent croup were identified. Twenty-five children (28 per cent) had anatomical airway abnormalities, of which 16 (18 per cent) demonstrated degrees of subglottic stenosis. Twenty-three children (26 per cent) had positive microlaryngobronchoscopy findings suggestive of reflux. Eleven children were treated for gastroesophageal reflux disease, 10 (91 per cent) of whom responded well to anti-reflux medication (p = 0.006). No cause was identified for 41 (45 per cent) of the children; this was the group most likely to continue having episodes of croup at follow up. One death occurred in this group. CONCLUSION: Airway anomalies are common in children that present with recurrent croup. Laryngobronchoscopy allows identification of the cause of croup and enables a more accurate prognosis. In the current study, laryngobronchoscopy findings that indicated reflux were predictive of benefit from anti-reflux medications, whereas the clinical presentation of reflux was not. Routine measurement of immunoglobulin E and complement proteins did not appear to be helpful.

Seven years' experience of Mohs micrographic surgery in a UK centre, and development of a UK minimum dataset and audit standards.

BACKGROUND: Mohs micrographic surgery (MMS) is the gold-standard treatment for high-risk basal cell carcinomas and a variety of other cutaneous tumours, including dermatofibromasarcoma protuberans and microcystic adnexal carcinoma. Previous large-scale case series, audits and reviews have allowed evaluation of MMS outcomes, such as BCC recurrence rates. However, to date there has been no systematic UK MMS audit, and certain important aspects of care, such as postoperative functional outcomes, have not yet been subject to scrutiny. AIMS: To review audit data from our centre, and from this to develop a minimum dataset and audit standards for UK MMS centres, on behalf of the British Society of Dermatological Surgery (BSDS). METHODS: An MMS database was developed locally and modified in response to repeated audit cycles since the introduction of the MMS service. A minimum dataset was developed using this experience. RESULTS: In our department, primary BCC recurrence rates are reassuringly low at 0.3%, at both 2 and 5 years. Histopathological discordance is < 2%, and aesthetic and functional outcomes at 3 months are good. CONCLUSIONS: The collation of audit data has been simplified by use of the minimum dataset, which we propose for all UK MMS centres, on behalf of the BSDS.

The Interconnections Project: development and evaluation of a community-based depression program for African American violence survivors.

BACKGROUND: Multi-faceted depression care programs based within the healthcare system have been found to be effective, but may not fully address the needs of African American Intimate Partner Violence (IPV) survivors, many of whom are not seeking depression care in healthcare settings. OBJECTIVES: To develop and evaluate a multifaceted, community-based depression care program (the Interconnections Project) for African American women with a history of IPV. METHODS: We used a community-based participatory research (CBPR) approach to develop, implement, and evaluate the intervention. Participants were African American women who had current depressive symptoms and a lifetime history of IPV. They participated in a 6-month intervention where a peer advocate provided education, skills training, and case management services, and used Motivational Interviewing to support self-management behaviors. We conducted pre-intervention and post-intervention assessments using quantitative and qualitative data. RESULTS: Fifty-nine women participated, with 92 % attending any sessions and 51 % attending at least 6 h of intervention activities. Intervention changes made to better accommodate participants' unpredictable schedules improved participation rates. Participants noted high levels of satisfaction with the program. There were significant improvements in depression severity (PHQ-9 13.9 to 7.9, p < 0.001), self-efficacy, self-management behaviors, and self-esteem (all p < 0.001), but no increase in use of antidepressants. Common themes related to why the program was helpful included that the program was by and for African American women, that it fostered trust, and that it taught self-management strategies with practical, lasting value. CONCLUSION: Culturally specific, community-based interventions led by peer advocates may be a promising way to help African American IPV survivors effectively address depression.