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Background: Many pregnant individuals with opioid use disorder (OUD) spend time in jail, yet access to standard of care medications for OUD (MOUD) in jail is limited. Though qualitative studies of non-incarcerated pregnant and non-pregnant incarcerated individuals with OUD demonstrate complexities that must be considered in delivering effective care, studies with pregnant, incarcerated patients with OUD are lacking. Methods: We conducted semi-structured qualitative interviews from October 2020–November 2021 with pregnant and postpartum people with OUD who were currently or previously in jail in Florida, Maryland, Ohio, and Virginia. Interview guides incorporated understandings of the power dynamics of incarceration and gendered expectations of motherhood. We analyzed transcripts using descriptive phenomenology to identify themes around experiences of treatment or withdrawal in jail and upon release. Results: We interviewed 32 women, 23 pregnant and nine postpartum. Some received MOUD in jail and others endured withdrawal. All participants expressed concern for their babies. Five themes emerged: 1)lack of counseling or accurate information about MOUD in pregnancy; 2)absent, delayed, or coercive care in jail; 3)experiences of stigma and discrimination from staff and caregivers; 4)structural barriers to safe transitions and continuing MOUD; and 5)the destructive presence of child protective services for care continuity. These factors all influenced their ability to recover. Conclusions: Jails must provide OUD care that is attentive to pregnancy physiology, pregnancy-stigma, reentry needs, and patients’ fetal-newborn concerns. Tailoring care specific to pregnancy and postpartum context can improve recovery success, reduce overdose, and promote intergenerational equity.

Summary: N-methyl-D-aspartate (NMDA)-type ionotropic glutamate receptors have essential roles in neurotransmission and synaptic plasticity. Previously, we identified an evolutionarily conserved protein, NRAP-1, that is required for NMDA receptor (NMDAR) function in C. elegans. Here, we demonstrate that NRAP-1 was sufficient to gate NMDARs and greatly enhanced glutamate-mediated NMDAR gating, thus conferring coincident activation properties to the NMDAR. Intriguingly, vertebrate NMDARs—and chimeric NMDARs where the amino-terminal domain (ATD) of C. elegans NMDARs was replaced by the ATD from vertebrate receptors—were spontaneously active when ectopically expressed in C. elegans neurons. Thus, the ATD is a primary determinant of NRAP-1- and glutamate-mediated gating of NMDARs. We determined the crystal structure of NRAP-1 at 1.9-Å resolution, which revealed two distinct domains positioned around a central low-density lipoprotein receptor class A domain. The NRAP-1 structure, combined with chimeric and mutational analyses, suggests a model where the three NRAP-1 domains work cooperatively to modify the gating of NMDARs.

Summary: Neurons require large amounts of energy, but whether they can perform glycolysis or require glycolysis to maintain energy remains unclear. Using metabolomics, we show that human neurons do metabolize glucose through glycolysis and can rely on glycolysis to supply tricarboxylic acid (TCA) cycle metabolites. To investigate the requirement for glycolysis, we generated mice with postnatal deletion of either the dominant neuronal glucose transporter (GLUT3cKO) or the neuronal-enriched pyruvate kinase isoform (PKM1cKO) in CA1 and other hippocampal neurons. GLUT3cKO and PKM1cKO mice show age-dependent learning and memory deficits. Hyperpolarized magnetic resonance spectroscopic (MRS) imaging shows that female PKM1cKO mice have increased pyruvate-to-lactate conversion, whereas female GLUT3cKO mice have decreased conversion, body weight, and brain volume. GLUT3KO neurons also have decreased cytosolic glucose and ATP at nerve terminals, with spatial genomics and metabolomics revealing compensatory changes in mitochondrial bioenergetics and galactose metabolism. Therefore, neurons metabolize glucose through glycolysis in vivo and require glycolysis for normal function.

Background: Transient thyrotoxicosis has been documented in the setting of hyperemesis gravidarum (HG) with elevated human chorionic gonadotropin (hCG) levels. Thyroid storm in pregnancy is rarer and typically associated with autoimmune hyperthyroidism. We described thyroid storm in a primigravid 18-year-old patient due to hCG level elevation secondary to HG, which resolved in the second trimester of pregnancy. Case Report: Our patient presented with vomiting, hyperthyroidism, and cardiac and renal dysfunction at 16 weeks’ gestation. She was clinically found to have a thyroid storm, with undetectable thyroid-stimulating hormone (TSH) and a free thyroxine level of >6.99 ng/dL. The hCG level was elevated at 246 030 mIU/L (9040-56 451 mIU/L). She was treated with methimazole, saturated solution potassium iodide, and propranolol. Because thyroid autoantibodies were absent, thyroid ultrasound yielded normal results, and thyroid function testing results rapidly improved as the hCG level decreased, the medications were tapered and ultimately discontinued by day 10 of hospitalization. The thyroid function remained normal after discharge. Discussion: Because hCG and TSH have identical alfa subunits and similar beta subunits, hCG can bind to the TSH receptor and stimulate thyroxine production. The hCG level peaks at around 8-14 weeks of gestation, correlating with decreased TSH levels in this same time frame. This case emphasizes the relevant physiology and importance of timely and thorough evaluation to determine the appropriate management, prognosis, and follow-up for patients with thyroid storm in the setting of HG. Conclusion: Although transient thyrotoxicosis is documented in patients with HG, thyroid storm is rare, and our case illustrates a severe example of these comorbidities.

Background: Specific clinical and radiographic risk factors for medial unicompartmental knee arthroplasty (UKA) failure are incompletely understood. The purpose of this study was to perform a midterm survivorship analysis of medial UKA from a single, nondesigner surgeon. Based on observations from clinical practice, we hypothesized that the presence of a lateral trochlear osteophyte on preoperative Merchant radiographs may be predictive of medial UKA failure secondary to progressive osteoarthritis (OA). Methods: Patients who underwent a mobile-bearing medial UKA by a single surgeon with minimum 24 months of clinical follow-up from 2008 to 2019 were retrospectively identified. Radiographic parameters, including the presence of a lateral trochlear osteophyte, were measured. Kaplan-Meier survivorship analyses were performed. Cox proportional hazards models were used to evaluate variables as risk factors for UKA failure, defined as reoperation or component revision. Results: A total of 233 UKAs were included. The mean age was 60 years, mean BMI 32 kg/m2, and 53% of patients were male. The mean follow-up duration was 5.7 years (range, 2.0-13.1 years). Using any reoperation as an endpoint, the 10-year survival was 91%. Using any component revision as an endpoint, the 10-year survival was 93%. Using revision due to progressive OA as an endpoint, the 10-year survival was 95%. The presence of a lateral trochlear osteophyte was associated with an increased risk of any reoperation (hazard ratio 3.6; 95% confidence interval 1.3-9.5) and increased risk of revision due to progressive OA (hazard ratio 9.8; 95% confidence interval 2.9-32.7). Conclusions: The presence of a lateral trochlear osteophyte on preoperative Merchant view radiographs was associated with an increased risk of medial UKA failure.

Background: The current and future harms caused by climate change are highly distressing. Different theoretical models suggest diverse impacts of distress on behavior. We examined how psychological distress, climate change distress, and social norms may foster or impede climate change activism. Methods: As part of an ongoing online longitudinal study in the US beginning in March 2020, respondents were assessed on their depressive symptoms (CES-D 10), climate change distress, climate change mitigation social norms, and six outcomes of the climate change activism behaviors of writing letters, e-mailing, or phoning government officials; voting for candidates who support measures to reduce climate change; signing petitions; volunteering with organizations; donating money to organizations; and attending protests. Results: Of the 775 respondents, 53% were female, 72% white, 12% Black, 7% Hispanic, and 6% Asian. Climate change social norms predicted all six climate change actions in the bivariate and multivariable cross-sectional logistic regression models. A similar finding was observed with the brief climate change distress scale (BCCDS), except it was not associated with volunteering in the multivariable model. Depressive symptoms were associated with greater odds of contacting government officials and signing petitions in the bivariate models but did not retain significance in the multivariable models. Longitudinal models indicated a weak association between depressive symptoms and climate change activism. Conclusions: Climate change distress and social norms are positively associated with climate change activism. Although climate change distress may not usually impede climate change activism, organizations addressing climate change should consider providing social support to members and assisting those with high levels of psychological and climate change distress. Social norms around climate change activism should be fostered.

ABSTRACT: The COVID-19 pandemic and climate change are two current global threats. This study examined the relationship between climate change attitudes and COVID-19 behaviors and risk perceptions. Drivers of climate change attitudes and COVID-19 behaviors were also assessed. Study participants were an online sample of 520 respondents from a longitudinal study of COVID-19 and well-being in the US. Logistic regression models were used to examine the outcomes of climate change opinions and COVID-19 perceptions and prevention behaviors (perceived COVID-19 risk, mask wearing, social distancing, and vaccine intentions). Covariates included political ideology, conspiracy beliefs, and trust in scientific information about COVID-19. In the multivariable models of COVID-19 perceptions and prevention behaviors, climate change opinions were also included as a covariate. In these models, climate change attitudes were significantly associated with perceived risk of COVID-19, always wearing masks, decreased time spent with others due to COVID-19, and intention to get a COVID-19 vaccine. In adjusted models, the odds of wearing a mask increased 41% (CI: 1.11–1.78) for every 1-point increase on the climate attitude scale and decreased 13% (CI: 0.79–0.96) if the participant distrusted COVID-19 information. Those who reported distrust of COVID-19 information (aOR: 1.61, CI: 1.40–1.85), politically conservative ideology (aOR: 1.24, CI: 1.04–1.47), lower concern about climate change (aOR: 0.71, CI: 0.53–0.97), female sex (aOR: 2.39 CI: 1.38–4.13), and lower disbelief in conspiracy theories (aOR: 0.63, CI: 0.51–0.80) had higher odds of not intending to be vaccinated. These findings suggest that climate change attitudes are linked to COVID-19 behaviors and perceptions, which are not completely driven by political ideology or trust in scientific information.

Unprecedented global efforts in vaccine development have resulted in effective vaccines for COVID-19. The pandemic response in the US has been highly politicized, resulting in significant opposition to public health efforts, including vaccines. We aimed to understand patterns of attitudes and beliefs about the COVID-19 vaccine to inform vaccination campaigns.583 English speaking United States adults were surveyed November 18–29, 2020. Participants answered 11 questions about their attitudes and beliefs about a COVID-19 vaccine, including perceived vaccine effectiveness, likelihood of getting vaccinated, and concerns that vaccine development was rushed/influenced by politics. We conducted a latent class analysis to identify profiles of attitudes/beliefs about a COVID-19 vaccine. We identified four classes of COVID-19 vaccine beliefs. The pro-vaccine class (28.8%) was willing to get vaccinated and had broadly positive beliefs about the vaccine. The development concerns class (27.8%) was willing to get vaccinated but was concerned about the development process. The third class (22.6%) was largely unsure if they would get vaccinated and if their peer groups would be vaccinated. The forth class (anti-vaccine, 20.8%) was dominated by an unwillingness to get vaccinated, vaccine distrust, vaccine development concerns, and peers groups with negative vaccine intentions. Given the large proportion of individuals who were concerned about the COVID-19 vaccine development process, messaging about rigor and approval processes may be critical to securing this group’s commitment to vaccination. Having scientific and cultural leaders endorse vaccination may also be influential.

Bacterial biofilms, often associated with chronic infections, respond poorly to antibiotic therapy and frequently require surgical intervention. Biofilms harbor persister cells, metabolically indolent cells, which are tolerant to most conventional antibiotics. In addition, the biofilm matrix can act as a physical barrier, impeding diffusion of antibiotics. Novel therapeutic approaches frequently improve biofilm killing, but usually fail to achieve eradication. Failure to eradicate the biofilm leads to chronic and relapsing infection, is associated with major financial healthcare costs and significant morbidity and mortality. We address this problem with a two-pronged strategy using 1) antibiotics that target persister cells and 2) ultrasound-stimulated phase-change contrast agents (US-PCCA), which improve antibiotic penetration.We previously demonstrated that rhamnolipids, produced by Pseudomonas aeruginosa, could induce aminoglycoside uptake in gram-positive organisms, leading to persister cell death. We have also shown that US-PCCA can transiently disrupt biological barriers to improve penetration of therapeutic macromolecules. We hypothesized that combining antibiotics which target persister cells with US-PCCA to improve drug penetration could improve treatment of methicillin resistant S. aureus (MRSA) biofilms. Aminoglycosides alone or in combination with US-PCCA displayed limited efficacy against MRSA biofilms. In contrast, the anti-persister combination of rhamnolipids and aminoglycosides combined with US-PCCA dramatically improved biofilm killing. This novel treatment strategy has the potential for rapid clinical translation as the PCCA formulation is a variant of FDA-approved ultrasound contrast agents that are already in clinical practice and the low-pressure ultrasound settings used in our study can be achieved with existing ultrasound hardware at pressures below the FDA set limits for diagnostic imaging.

Bayesian analysis provides a principled way to quantify uncertainty and incorporate data and prior knowledge into parameter estimates. This paper makes the latest in Bayesian methods easier for others to use with a focus on a stochastic plateau crop production function. Previous studies have used Bayesian techniques to model stochastic plateau functions. No published work provides computation guidelines to estimate stochastic plateau functions using Bayesian approaches using computationally efficient algorithms such as Hamiltonian Monte Carlo (HMC). HMC is the default choice in Stan software, but the learning curve to master the software is steep. We provide HMC estimation instructions for a univariate stochastic plateau function using the R environment's brms and RStan. We also compare HMC estimation results with those using Gibbs sampling via Just Another Gibbs Sampler (JAGS) software using the R Interface R2jags. The programs are relatively compact and are included in the paper. Simulation results from HMC are consistent across different priors and are similar to those generated by a Gibbs sampler. This paper serves as a tutorial on the use of HMC for estimating plateau-type production functions. The code, and method, can be extended to other nonlinear models.

This research note extends Bayesian discriminant analysis procedures to the ordered and multinomial logistic likelihood functions. Use of the procedure is warranted when the researcher desires to identify the membership of individuals randomly drawn from distinct groups or locations in a population, rather than from a random sample of undifferentiated individuals from a population. An empirical application analyzes consumers’ reasons why they choose to support a beef product produced with enhanced pasture management practices.

Multiple Sclerosis (MS) is an immune-mediated disease that results in major locomotor deficits. However, recent studies have revealed that fatigue, slow processing speed, and memory impairment are the top variables impacting employment status for MS patients. These suggest that cognitive effects may have a greater impact on productivity, lifestyle, and quality of life than do disease-related motor deficits. However, these debilitating non-locomotive effects have been largely overlooked in rodent models of the disease, such as experimental autoimmune encephalomyelitis (EAE). We hypothesized that murine EAE can also be used to assess non-locomotive dysfunctions (mood, sociability, muscle strength, and balance), as well as potential biases in these dysfunctions due to sex and/or strain. We actively immunized male and female C57BL/6 (B6) and SJL mice for EAE and evaluated their performance on the Deacon's weight grip test, Kondziela's inverted screen test, Hall's rope grip test, manual von Frey test for somatic nociception, and a three-chamber social preference paradigm. We hypothesized that EAE progression is associated with changes in muscle strength, balance, pain, and sociability and that these variations are linked to sex and/or strain. Our results indicate that strain but not sex influenced differences in muscle strength and balance during EAE, and both sex and strain have an impact on mechanical nociception, regardless of EAE disease status. Furthermore, both sex and strain had complex effects on differences in sociability. In conclusion, testing these additional modalities during EAE helps to unveil other signs and symptoms that could be used to determine the efficacy of a drug or treatment in the modulation of a MS-like behavior.

Nutritional strategies to mitigate the negative effects of heat stress on animal welfare and productivity often involve changes in ration formulation. However, cattle commonly sort their ration in favour of certain components, and it is not clear how feed sorting responds to heat stress. This study investigated the association between heat stress and feed sorting behaviour. Lactating Holstein dairy cows (n = 32; parity = 2.8±1.2; mean±SD) were housed in a free stall barn and milked 3×/day. Cows were fed individually using the Calan Broadbent Feeding System and offered ad libitum access to a total mixed ration (containing on a dry matter basis: 3.3% ryegrass hay, 16.5% ryegrass baleage, 24.7% corn silage, 11.1% brewers grains, 19.7% ground corn, 19.8% concentrate and 4.9% protein/mineral supplement), provided 1×/day. Beginning at 186±60 days in milk, cows were exposed to either: heat stress conditions (HT; n = 15) (average temperature–humidity index: 77.6), or evaporative cooling (CL; n = 17), consisting of misters and fans over the freestall and feed bunks. Data were collected during a 4-day baseline period, and two 4-day experimental periods: starting at 10 days after implementing treatments (defined as acute heat stress for HT cows), and at 62 days after implementing treatments (defined as chronic heat stress for HT cows). Daily feed intake and physiological responses to heat stress (body temperature, respiration rate) were recorded. Samples of fresh and refused feed were collected daily from individual cows for particle size analysis. The particle size separator had three screens (19, 8 and 1.18 mm) and a bottom pan, resulting in 4 fractions (long, medium, short and fine particles). Feed sorting was calculated as the actual intake of each particle size fraction expressed as a percentage of the predicted intake of that fraction. During both heat stress periods, HT cows sorted for long particles more than CL cows (105.0% v. 100.6%; SE = 1.1). During acute heat stress, HT cows sorted to a greater extent than CL cows against medium and short particles, whereas sorting of these fractions did not differ during chronic heat stress. Body temperature and respiration rate were associated across treatments with the extent of sorting for long particles and against short particles during acute heat stress. These results suggest that feed sorting is particularly influenced during acute heat stress, and that sorting for longer particles may increase in heat stress.

Little is known about Immunization Information System (IIS) attitudes and experiences using Centralized IIS-based Reminder/Recall (CI-R/R), an effective approach to increasing immunization rates.To describe among IIS managers as it relates to CI-R/R: 1) past experiences and future plans conducting it; 2) attitudes and barriers, 3) IIS capabilities and polices that influence, and 4) factors that differentiate IIS who have and have not conducted CI-R/R.Electronic Surveys were sent to all IIS managers in July 2018 using a member listserve.Fifty-seven of 62 IIS programs contacted (92%) responded. The majority (61%) had ever conducted CI-R/R; 34% reported they were “very likely” to conduct CI-R/R within 6 months. The majority (64%) were in favor of CI-R/R. Barriers included lack of staff (78%), competing demands (76%), and cost (63%). Thirty percent reported receiving a ≥75% of immunization data via real-time electronic interfaces (HL7). Overall, 49% and 24% of jurisdictions had mandatory immunization reporting from private and public health entities for childhood and adult immunizations, respectively. Differences between IIS that ever and never performed CI-R/R, respectively, included: mandatory reporting from private and public entities for children (65% v 27%, p = 0.006), having a legal mandate for CI-R/R (50% v 19%, p = 0.02), less likely to prefer practice-based R/R to CI-R/R (68% v. 91%, p = 0.04), and not reporting having too many competing demands (29% v 67%, p = 0.007).Most IIS have conducted CI-R/R and have positive attitudes towards it. Given it effectiveness and low cost, efforts to sustain it should be considered.

Global climate change will affect crop productivity, technology adoption, and commodity food and fiber prices. This research investigates the ex-ante effects of climate change on cropping mix and irrigation decisions at a watershed scale by integrating a downscaled General Circulation Model (GCM) projections, a crop growth model, and an economic model of the row crop sector typical of corn, soybean, wheat, and sorghum operations in Tennessee, United States. The downscaled GCM is used to generate weather patterns for Tennessee’s watersheds to 2049, under moderate and high greenhouse gas (GHG) emission assumptions. Crop yields and commodity prices were also estimated under these prevailing climate scenarios. Compared with the moderate emission level scenario, greater GHG emissions decrease dryland crop productivity and cause commodity prices to trend upward. A row crop optimization model was developed under the assumption that producers are profit maximizers who base their cropping decisions on the previous yield performance of a cropping system, commodity prices, and production functions, subject to resource constrains. Results suggest that producers in some watersheds adopt irrigation to minimize variability in net returns if water is available. Dryland and irrigated soybeans, dryland corn, and dryland soybean-wheat double cropping could become the dominant cropping systems in watersheds located in western Tennessee while irrigated and dryland soybeans could become the dominant row crop in watersheds located in middle Tennessee.

Background: Longevity as a phenotype entails living longer than average and typically includes living without chronic age-related diseases. Recently, several common genetic components to longevity have been identified. This study aims to identify additional genetic variants associated with longevity using unique and powerful analyses of pedigrees with a statistical excess of healthy elderly individuals identified in the Utah Population Database (UPDB). Methods: From an existing biorepository of Utah pedigrees, six independent cousin pairs were selected from four extended pedigrees that exhibited an excess of healthy elderly individuals; whole exome sequencing (WES) was performed on two elderly individuals from each pedigree who were either first cousins or first cousins once removed. Rare (

Bibliometric studies are important to understand changes and improvement opportunities in academia. This study compared bibliometric trends for two major sports medicine/arthroscopy journals, the American Journal of Sports Medicine® (AJSM®) and Arthroscopy® over the past 30 years. Trends over time and comparisons between both journals were noted for common bibliometric variables (number of authors, references, pages, citations, and corresponding author position) as well as author gender and continental origin. Appropriate statistical analyses were performed. A p < 0.001 was considered statistically significant. One representative year per decade was used. There were 814 manuscripts from AJSM® and 650 from Arthroscopy®. For AJSM® the number of manuscripts steadily increased from 86 in 1986 to 350 in 2016; for Arthroscopy® the number of manuscripts increased from 73 in 1985/1986, to 267 in 2006, but then dropped to 229 in 2016. There were significant increases in all bibliometric variables, except for the number of citations which decreased in Arthroscopy®. There were significant differences in manuscript region of origin by journal (p = 0.000002). Arthroscopy® had a greater percentage of manuscripts from Asia than AJSM® (19.3% vs 11.5%) while AJSM® had a greater percentage from North America (70.3% vs 59.2%); both journals had similar percentages from Europe (18.2% for AJSM® and 21.6% for Arthroscopy®). For AJSM® the average percentage of female first authors was 13.3%, increasing from 4.7% in 1986 to 19.3% in 2016; the average percentage of female corresponding authors was 7.3%. For Arthroscopy®, the average percentage of female first authors was 8.1%, increasing from 2.8% in 1985/1986 to 15.7% in 2016 (p = 0.00007). In conclusion, AJSM® and Arthroscopy® showed an increase in most variables analyzed. Although Arthroscopy® is climbing at a higher rate than AJSM® for female authors, AJSM® has an overall greater percentage of female authors.

Summary: DAPK1 binding to GluN2B was prominently reported to mediate ischemic cell death in vivo. DAPK1 and CaMKII bind to the same GluN2B region, and their binding is mutually exclusive. Here, we show that mutating the binding region on GluN2B (L1298A/R1300Q) protected against neuronal cell death induced by cardiac arrest followed by resuscitation. Importantly, the GluN2B mutation selectively abolished only CaMKII, but not DAPK1, binding. During ischemic or excitotoxic insults, CaMKII further accumulated at excitatory synapses, and this accumulation was mediated by GluN2B binding. Interestingly, extra-synaptic GluN2B decreased after ischemia, but its relative association with DAPK1 increased. Thus, ischemic neuronal death requires CaMKII binding to synaptic GluN2B, whereas any potential role for DAPK1 binding is restricted to a different, likely extra-synaptic population of GluN2B. : Ischemic insults cause excitotoxic neuronal cell death via NMDA receptor overstimulation. Buonarati et al. find that excitotoxic insults cause DAPK1 movement to extra-synaptic NMDA receptors and CaMKII movement to synaptic NMDA receptors; importantly, preventing this CaMKII movement protects neurons from ischemic death. Keywords: CaMKII, DAPK1, GluN2B, ischemia, cardiac arrest, cardiopulmonary resuscitation, excitotoxicity, hippocampus

The death-associated protein kinase 1 (DAPK1) is a potent mediator of neuronal cell death. Here, we find that DAPK1 also functions in synaptic plasticity by regulating the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII). CaMKII and T286 autophosphorylation are required for both long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory, and cognition. T286-autophosphorylation induces CaMKII binding to the NMDA receptor (NMDAR) subunit GluN2B, which mediates CaMKII synaptic accumulation during LTP. We find that the LTP specificity of CaMKII synaptic accumulation is due to its LTD-specific suppression by calcineurin (CaN)-dependent DAPK1 activation, which in turn blocks CaMKII binding to GluN2B. This suppression is enabled by competitive DAPK1 versus CaMKII binding to GluN2B. Negative regulation of DAPK1/GluN2B binding by Ca2+/CaM results in synaptic DAPK1 removal during LTP but retention during LTD. A pharmacogenetic approach showed that suppression of CaMKII/GluN2B binding is a DAPK1 function required for LTD.

With the growth of contrast-enhanced ultrasound (CEUS) clinically, there are concerns about histologic bioeffects in regards to the implementation of high mechanical index (MI) imaging, such as the imaging sequence used for a specific CEUS technique known as flash-replenishment. The data presented are results from a pilot study, which explored flash-replenishment with high and moderate MI imaging sequences at time points of 24 hours and 2 weeks post imaging. This pilot study was followed by a larger study, which can be found in a journal article entitled “Histological and Blood Chemistry Examination of the Rodent Kidney After Exposure to Flash-Replenishment Ultrasound Contrast Imaging” Nyankima et al., 2019. Keywords: Contrast enhanced ultrasound, Ultrasound contrast agents, Microbubble, Bioeffects

Summary: CaMKIIα is a central mediator of bidirectional synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD). To study how CaMKIIα movement during plasticity is affected by soluble amyloid-β peptide oligomers (Aβ), we used FingR intrabodies to simultaneously image endogenous CaMKIIα and markers for excitatory versus inhibitory synapses in live neurons. Aβ blocks LTP-stimulus-induced CaMKIIα accumulation at excitatory synapses. This block requires CaMKII activity, is dose and time dependent, and also occurs at synapses without detectable Aβ; it is specific to LTP, as CaMKIIα accumulation at inhibitory synapses during LTD is not reduced. As CaMKII movement to excitatory synapses is required for normal LTP, its impairment can mechanistically explain Aβ-induced impairment of LTP. CaMKII movement during LTP requires binding to the NMDA receptor, and Aβ induces internalization of NMDA receptors. However, surprisingly, this internalization does not cause the block in CaMKIIα movement and is observed for extrasynaptic, but not synaptic, NMDA receptors. : Cook et al. used simultaneous live imaging of multiple endogenous proteins to probe LTP- versus LTD-induced CaMKII trafficking to excitatory versus inhibitory synapses. They show that Aβ inhibits LTP by blocking LTP-induced CaMKII trafficking via signaling mechanisms that require CaMKII activity. Keywords: CaMKII, excitatory synapse, inhibitory synapse, trafficking, LTP, LTD, amyloid, FingR, intrabody, NMDA-receptor

Objectives: Many hospitals cannot afford an hCG assay on a central lab analyzer and turn to point of care testing (POCT) solutions. The Radiometer AQT90 FLEX is a small benchtop immunoareement between the AQT90 and comparator methods for samples with hCG ssay analyzer for use in the laboratory or at the patient bedside. This study evaluated the analytical performance of the AQT90's βhCG assay. Methods: Precision was assessed using whole blood patient samples and two levels of quality control. Linearity was assessed by dilution of a high hCG plasma sample. Carryover and hook effect were assessed using high and low hCG samples. Method comparisons were done against Abbott i-STAT Total βhCG, Beckman Coulter Total βhCG (5th IS), and Roche hCG+β. Sample concentrations ranged from20 IU/L, biases were apparent against all three comparator assays (i-STAT: +20%, Roche: +30%, Beckman: +5 to 15%). At ≤20 IU/L, the acceptability of agreement varied according to TAE specifications. Concordance between AQT90 and comparator assays using 5 IU/L as the medical decision level ranged from 69% to 81%. Conclusions: Overall, the AQT90 hCG assay performed well and would be suitable for smaller suburban or rural hospitals. Some limitations have been noted and should be kept in mind during clinical testing. Keywords: hCG, AQT90, method evaluation

AAV9 has emerged as an efficient adeno-associated virus (AAV) serotype for gene transfer to the central nervous system. We have used this technique to study aspects of amyotrophic lateral sclerosis (ALS) by administering AAV encoding the ALS-related gene transactive response DNA binding protein of 43 kDa (TDP-43) to neonatal rats. However, inducing the expression in adult subjects would be preferable to mimic the adult onset of symptoms in ALS. We expressed either green fluorescent protein (GFP) or TDP-43 in adult rats after an intravenous (i.v.) route of administration to attempt wide-scale transduction of the spinal cord for disease modeling. In order to optimize the gene transfer, we made comparisons of efficiency by age, gender, and across several AAV serotypes (AAV1, AAV8, AAV9, and AAV10). The data indicate more efficient neuronal transduction in neonates, with little evidence of glial transduction at either age, no gender-related differences in transduction, and that AAV9 was efficient in adults relative to the other serotypes tested. Based on these data, AAV9 TDP-43 was expressed at three vector doses in adult female rats yielding highly consistent, dose-dependent motor deficits. AAV9 can be delivered i.v. to adult rats to achieve consistent pathophysiological changes and a relevant adult-onset system for disease modeling.

Using a viral vector for mutant (P301L) tau, we studied the effects of gene transfer to the rat substantia nigra in terms of structural and functional properties of dopaminergic neurons. The mutant tau vector caused progressive loss of pars compacta dopaminergic neurons over time, reduced striatal dopamine content, and amphetamine-stimulated rotational behavior consistent with a specific lesion effect. In addition, structural studies demonstrated neurofibrillary tangles and neuritic pathology. Wild-type tau had similar effects on neuronal loss and rotational behavior. In contrast, mutant α-synuclein vectors did not induce rotational behavior, although α-synuclein filaments formed in nigrostriatal axons. Dopamine neuron function is affected by tau gene transfer and appears to be more susceptible to tau- rather than α-synuclein-related damage in this model. Both tau and α-synuclein are important for substantia nigra neurodegeneration models in rats, further indicating their potential as therapeutic targets for human diseases involving loss of dopamine neurons.

Elderly institutionalized men were assigned at random to two groups, one of which received a conventional diet while the other was fed a diet in which the major modification was substitution of unsaturated for saturated fat. Changes in serum lipids and in adipose tissue over periods up to 5 years are described.In control subjects, mean serum cholesterol rose 4% over the first 20 months, then fell during the next 40 months to a level 10% below the starting concentration. In the experimental group there was an immediate drop, followed by further changes roughly parallel to those in the control subjects. The mean difference between the control and experimental groups was 14.0% of the starting level. Changes in serum total lipid were similar, but the percentage difference between control and experimental groups was only 6.8% of the baseline level.All major esterified serum lipid fractions of experimental subjects contained increased concentrations of linoleic acid. This was most marked in triglyceride, which at 3 years had a composition similar to that of the dietary fat in both groups of subjects.Adipose tissue linoleic acid rose in men on the experimental diet from 11% of total fatty acid at time zero to 32% at 5 years. The rise could be fitted to an exponential function with a half-time of 680 days. The rate of rise during the 1st year was correlated negatively with initial body weight and positively with weight gain; the influence of adherence to the diet was much less pronounced.

In elderly, institutionalized men on a diet of high linoleic acid content, there was little correlation after 1 yr between adipose tissue linoleic acid concentration and dining room attendance. The correlation improved thereafter, with a correlation coefficient of +0.81 after 5 yr and +0.74 after 6 yr.

The evidence for the wider effects of fishing on the marine ecosystem demands that we incorporate these considerations into our management of human activities. The consequences of the direct physical disturbance of the seabed caused by towed bottom-fishing gear have been studied extensively with over 100 manipulations reported in the peer-reviewed literature. The outcome of these studies varies according to the gear used and the habitat in which it was deployed. This variability in the response of different benthic systems concurs with established theoretical models of the response of community metrics to disturbance. Despite this powerful evidence, a recent FAO report wrongly concludes that the variability in the reported responses to fishing disturbance mean that no firm conclusion as to the effects of fishing disturbance can be made. This thesis is further supported (incorrectly) by the supposition that current benthic sampling methodologies are inadequate to demonstrate the effects of fishing disturbance on benthic systems. The present article addresses these two erroneous conclusions which may confuse non-experts and in particular policy-makers.

A new spectrophotofluorometric assay for probenecid is presented based on conversion of the drug to a fluorescent anthranilic acid derivative. The assay is especially applicable with "clean" biological fluids such as cerebrospinal fluid and offers severalfold greater sensitivity than the commonly used UV method.

A sensitive gas chromatographic method for quantitative analysis of ketamine and norketamine in human and animal biological fluids is described. The nitrogen-sensitive detection procedure used is more stable than electron-capture detection and reduced analysis time. The method used bromo-ketamine as an internal standard for quantitation and is linear from 10-25,000 ng/ml. No interferences were shown with drugs commonly associated with cardiac surgery with cardiopulmonary by-pass. This assay is sensitive, specific, using either native or derivatized drugs and can be used for routine analysis of ketamine and norketamine in plasma or urine.