Glucocorticoid response to naturalistic interactions between children and dogs.

Although research has shown that pets appear to provide certain types of social support to children, little is known about the physiological bases of these effects, especially in naturalistic contexts. In this study, we investigated the effect of free-form interactions between children (ages 8-10 years) and dogs on salivary cortisol concentrations in both species. We further investigated the role of the child-dog relationship by comparing interactions with the child's pet dog to interactions with an unfamiliar dog or a nonsocial control condition, and modeled associations between survey measures of the human-animal bond and children's physiological responses. In both children and dogs, salivary cortisol decreased from pre- to post-interaction; the effect was strongest for children interacting with an unfamiliar dog (compared to their pet dog) and for the pet dogs (compared to the unfamiliar dog). We found minimal evidence for associations between cortisol output and behaviors coded from video, but children scoring higher on survey measures of the human-animal bond exhibited the greatest reductions in cortisol when interacting with dogs. Self-reported loneliness was not related to cortisol or the human-animal bond, but measures of both loneliness and the human-animal bond were higher among children who participated after the onset of the COVID-19 pandemic, relative to those who participated before the pandemic. This study builds on previous work that investigated potential stress-buffering effects of human-animal interaction during explicit stressors and demonstrates important physiological correlates of naturalistic interactions between children and dogs, similar to those that occur in daily life.

Diurnal fecal glucocorticoid metabolite rhythms in a cathemeral primate, the red-bellied lemur (Eulemur rubriventer), and across mammalian species.

Measuring glucocorticoids is one of the most reliable and widely used techniques to monitor stress responses, however invasive techniques to collect plasma samples may not be applicable for wild populations. Monitoring excreted glucocorticoids is an effective noninvasive technique that researchers have used increasingly over the past two decades, and it has allowed the investigation of glucocorticoids in a variety of species with a range of activity patterns. Many species exhibit predictable circadian patterns of glucocorticoid secretion in accordance with their daily activity pattern. There remains a gap in our understanding of how excreted glucocorticoid metabolites vary throughout the day and across species, despite the utility of this information when developing sampling protocols and analyzing data. We investigated circadian patterns of glucocorticoid excretion in a cathemeral primate species, Eulemur rubriventer (red-bellied lemur), in Ranomafana National Park, Madagascar. We collected fecal samples from 10 individuals throughout the day and analyzed fecal glucocorticoid levels across three time points (Early, Midday, and Late), and again across two time points (Morning and Afternoon). We also investigated whether activity pattern, sex (as a control variable), and other traits associated with gut passage rate (diet, body mass) could help predict the presence and timing of circadian patterns of fecal glucocorticoid metabolites across mammal species. We found that fecal glucocorticoid metabolite levels in E. rubriventer fluctuate throughout the day, with lowest levels in the morning and peak levels in the afternoon. None of the variables that we tested predicted whether daily fecal glucocorticoid metabolites changed significantly throughout the day, nor when levels were likely to peak, across species. We stress the importance of controlling for sampling time and reporting these results as standard practice in studies of fecal glucocorticoid metabolites.

Changes in membrane elasticity caused by the hydrophobic surfactant proteins correlate poorly with adsorption of lipid vesicles.

To establish how the hydrophobic surfactant proteins, SP-B and SP-C, promote adsorption of lipids to an air/water interface, we used X-ray diffuse scattering (XDS) to determine an order parameter of the lipid chains (Sxray) and the bending modulus of the lipid bilayers (KC). Samples contained different amounts of the proteins with two sets of lipids. Dioleoylphosphatidylcholine (DOPC) provided a simple, well characterized model system. The nonpolar and phospholipids (N&PL) from extracted calf surfactant provided the biological mix of lipids. For both systems, the proteins produced changes in Sxray that correlated well with KC. The dose-response to the proteins, however, differed. Small amounts of protein generated large decreases in Sxray and KC for DOPC that progressed monotonically. The changes for the surfactant lipids were erratic. Our studies then tested whether the proteins produced correlated effects on adsorption. Experiments measured the initial fall in surface tension during adsorption to a constant surface area, and then expansion of the interface during adsorption at a constant surface tension of 40 mN m-1. The proteins produced a sigmoidal increase in the rate of adsorption at 40 mN m-1 for both lipids. The results correlated poorly with the changes in Sxray and KC in both cases. Disordering of the lipid chains produced by the proteins, and the softening of the bilayers, fail to explain how the proteins promote adsorption of lipid vesicles.

Dysregulated Provision of Oxidisable Substrates to the Mitochondria in ME/CFS Lymphoblasts.

Although understanding of the biomedical basis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is growing, the underlying pathological mechanisms remain uncertain. We recently reported a reduction in the proportion of basal oxygen consumption due to ATP synthesis by Complex V in ME/CFS patient-derived lymphoblast cell lines, suggesting mitochondrial respiratory inefficiency. This was accompanied by elevated respiratory capacity, elevated mammalian target of rapamycin complex 1 (mTORC1) signaling activity and elevated expression of enzymes involved in the TCA cycle, fatty acid ß-oxidation and mitochondrial transport. These and other observations led us to hypothesise the dysregulation of pathways providing the mitochondria with oxidisable substrates. In our current study, we aimed to revisit this hypothesis by applying a combination of whole-cell transcriptomics, proteomics and energy stress signaling activity measures using subsets of up to 34 ME/CFS and 31 healthy control lymphoblast cell lines from our growing library. While levels of glycolytic enzymes were unchanged in accordance with our previous observations of unaltered glycolytic rates, the whole-cell proteomes of ME/CFS lymphoblasts contained elevated levels of enzymes involved in the TCA cycle (p = 1.03 × 10-4), the pentose phosphate pathway (p = 0.034, G6PD p = 5.5 × 10-4), mitochondrial fatty acid ß-oxidation (p = 9.2 × 10-3), and degradation of amino acids including glutamine/glutamate (GLS p = 0.034, GLUD1 p = 0.048, GOT2 p = 0.026), branched-chain amino acids (BCKDHA p = 0.028, BCKDHB p = 0.031) and essential amino acids (FAH p = 0.036, GCDH p = 0.006). The activity of the major cellular energy stress sensor, AMPK, was elevated but the increase did not reach statistical significance. The results suggest that ME/CFS metabolism is dysregulated such that alternatives to glycolysis are more heavily utilised than in controls to provide the mitochondria with oxidisable substrates.

Blood Mercury in Three Populations of Endangered Whooping Crane (Grus americana).

We investigated concentrations of blood total mercury (THg) in three extant populations of endangered Whooping Crane (Grus americana). Blood THg was greater in cranes reintroduced during 2001-2008 that range in the eastern US (median = 0.31 ug/g ww) than both wild cranes in central North America (median = 0.11 ug/g ww) and from captivity (median = 0.01 ug/g ww). The median THg blood concentrations in the two free-ranging populations of Whooping Cranes were low compared to reproductive toxic thresholds suggested for other large bird species (> 4.3 ug/g ww), but a singular elevated concentration was observed in one crane (1.04 ug/g ww; 6% of samples from the reintroduced population). These results likely reflect variable dietary Hg exposure among these populations, but should prompt additional biomonitoring to discern risk of greater Hg exposure nearer to the time of breeding and potential effects on productivity.

Catalytic Detoxification of Organophosphorus Nerve Agents by Butyrylcholinesterase-Polymer-Oxime Bioscavengers.

Organophosphorus nerve agents (OPNAs), used in chemical warfare, irreversibly inhibit essential cholinesterases (ChEs) in the cholinergic neurotransmission system. Several potent nucleophilic oximes have been approved for the treatment of acute poisoning by OPNAs, but they are rapidly cleared from blood circulation. Butyrylcholinesterase (BChE) stoichiometrically binds nerve agents, but because the molecular weight of a nerve agent is about 500-fold less than the enzyme, the bioscavenger has had limited utility. We synthesized BChE-polymer-oxime conjugates using atom transfer radical polymerization (ATRP) and azide-alkyne "click" chemistry. The activity of the BChE-polymer-oxime conjugates was dependent on the degree of oxime loading within the copolymer side chains. The covalent modification of oxime-containing copolymers prolonged the activity of BChE in the presence of the VX- and cyclosarin-fluorogenic analogues EMP-MeCyC and CMP-MeCyC, respectively. After complete inactivation by VX and cyclosarin fluorogenic analogues, the conjugates demonstrated efficient self-reactivation of up to 80% within 3-6 h. Repeated inhibition and high-level self-reactivation assays revealed that the BChE-polymer-oxime conjugates were excellent reactivators of OPNA-inhibited BChE. Recurring self-reactivation of BChE-polymer-oxime conjugates following repeated BChE inhibition by fluorogenic OPNAs (Flu-OPNAs) opens the door to developing the next generation of nerve agent "catalytic" bioscavengers.

Quality of life as a mediator of leisure activity and perceived health among older women.

Despite consistent evidence to suggest that participating in leisure is associated with perceived health status among older adults, there have been few attempts to determine the possible underlying mechanisms in this relationship, including the role of quality of life (QoL). This study examined the role of perceived quality of life in the relationship between leisure and perceived health in older women. Correlations, regression, and mediation analysis were conducted on data from the Woman's College Alumnae Women's Health Study. Results indicate that QoL partially mediates the relationship between leisure and perceived health in older women. Findings further establish the link between leisure and perceived health with QoL playing an important role in the relationship.

Effect of defibrillation threshold testing on effectiveness of the subcutaneous implantable cardioverter defibrillator.

BACKGROUND: Defibrillation threshold (DFT) testing is recommended with the subcutaneous implantable cardioverter defibrillator (SICD). OBJECTIVE: To describe first shock efficacy for appropriate SICD therapies stratified by the presence of implant DFT testing. METHODS: We reviewed all patients receiving SICDs at our institution and stratified them based on whether implant DFT testing was performed. Appropriate shocks were reviewed to see if ventricular tachycardia/ventricular fibrillation (VT/VF) terminated with a single shock. First shock efficacy was stratified by implant DFT status. RESULTS: 178 patients implanted with SICDs and followed in our center were included in this study. Of these, 135 (76%) underwent DFT testing (DFT (+) group). In the DFT (+), 80 appropriate shocks were needed to treat 69 episodes of VT/VF. The first shock was effective in 61 out of 69 episodes (88.4%), whereas multiple shocks were required to terminate VT/VF in the remaining eight episodes. Among 43 patients without implant DFT testing (DFT (-) group), 20 appropriate shocks to treat 17 episodes of VT/VF occurred in seven patients. VT/VF was successfully terminated with the first shock in 16 out of 17 episodes (first shock efficacy 94.1 %). There was no significant difference in first shock effectiveness between those with and without implant DFT testing (P  =  0.97). CONCLUSION: A strategy that omits DFT testing at implant did not appear to compromise the effectiveness of the SICD. These data suggest that routine DFT testing at SICD implant might not be necessary. Randomized trials are needed to confirm this finding.

Gender and national origin differences in healthcare utilization among U.S. Immigrants from Mexico, China, and India.

OBJECTIVES: To examine gender and national origin differences in the healthcare utilization of immigrants from the three largest populations in the U.S. today (Mexico, China, and India) and to determine if barriers to utilization operate similarly across groups. METHODS: The analysis uses nationally-representative data from the 2003 New Immigrant Survey (NIS) to compare utilization behaviors among legal permanent residents from Mexico, China, and India (n = 2244). Conceptually, the study draws on Andersen's Behavioral Model to hypothesize gender and national origin differences in utilization based on factors that might predispose, enable, or necessitate healthcare. Multivariate logistic regression models are used to predict the odds of having seen a doctor in the past year and to test whether obstacles to utilization differ across immigrant groups. RESULTS: Chinese immigrants are less likely than Mexican and Indian immigrants to have seen a doctor in the past year, a finding that is largely driven by a lack of health insurance. Female immigrants are more likely than males to have done so, despite having fewer resources that enable access to care (e.g. income, English proficiency). Moreover, the relationship between gender and utilization is moderated by English language proficiency: among immigrants with low levels of proficiency, women are significantly more likely than men to have seen a doctor in the past year, while no difference exists between men and women who are proficient in English. This pattern is most evident among Mexican, and to a lesser extent, Indian immigrants. CONCLUSIONS: Barriers to immigrant healthcare utilization vary by gender and national origin. Research will need to continue documenting such variation in order to better inform policy makers and health practitioners of potential solutions for improving health outcomes in increasingly diverse immigrant communities.

Management of New-Onset Postoperative Atrial Fibrillation Utilizing Insertable Cardiac Monitor Technology to Observe Recurrence of AF (MONITOR-AF).

BACKGROUND: New-onset postoperative atrial fibrillation (POAF) occurs in up to 30% of patients undergoing coronary artery bypass grafting (CABG). POAF is associated with short- and long-term mortality. METHODS: To identify the true incidence and time course of recurrent atrial fibrillation (AF) in patients with POAF, we prospectively assigned 23 patients with POAF to receive an implantable loop recorder (ILR; Medtronic Inc., Minneapolis, MN, USA) for the detection of recurrent AF. Two electrophysiologists independently adjudicated monthly ILR transmissions to classify recurrent AF. We defined AF as any episode lasting ≥6 minutes. RESULTS: The cohort included 23 subjects averaging 69.1 ± 7.2 years of age. Their mean CHADS2 score averaged 1.9 ± 0.8. Note that 26.1% underwent direct current cardioversion prior to discharge; 95.7% left the hospital taking amiodarone and 26.1% warfarin. A total of 14 patients (60.9%) experienced recurrent AF. AF first recurred within 3 months in nine patients (39.1%), and in 10 patients AF emerged or continued beyond 3 months. Eight of 17 (47.1%) patients followed for at least 1 year experienced AF recurrence beyond 1 year of CABG. The time from surgery to first AF episode averaged 143 ± 22.5 days. Long-term monitoring shows that 60.9% of patients with POAF develop recurrent AF. CONCLUSION: POAF may represent a propensity for recurrent paroxysmal atrial fibrillation, and not simply a transient consequence of postoperative stress and inflammation. Better detection of recurrent AF might identify patients at risk for stroke who would benefit from continuing anticoagulation.

Effects of human-animal interaction on salivary and urinary oxytocin in children and dogs.

Oxytocin pathways are hypothesized to play important roles in human-animal interactions and may contribute to some benefits of these interspecific social relationships. We explored the effects of naturalistic interactions between children and dogs on oxytocin release in both species, as well as associations between methylation of the oxytocin receptor gene (OXTRm), social behavior, and oxytocin response in this context. Children (N = 55) participated in a within-subjects design involving a) interaction with their pet dog, b) interaction with an unfamiliar dog, and c) a nonsocial control condition (solitary play). We used immunoassays to measure salivary and urinary oxytocin in both the children and dogs, behavioral coding to characterize dog-child interactions, and bisulfite sequencing to quantify methylation of the oxytocin receptor gene (N = 32 children). Child salivary oxytocin decreased moderately across time in all conditions, but the extent of this effect varied between conditions, with greater oxytocin output during interactions with dogs than the control condition. In the pet dog condition, children's salivary oxytocin response was positively associated with the duration of visual co-orientation between the child and dog. Child urinary oxytocin did not deviate substantially from baseline in any condition. Children with higher levels of OXTRm had greater oxytocin output during interactions with their pet dogs, but lower oxytocin output in the control condition, and engaged in lower levels of affectionate interaction with dogs across conditions. Children's pet dogs exhibited increases in salivary oxytocin, but we observed the opposite pattern in the unfamiliar dog, who exhibited decreases in both urinary and salivary oxytocin on average. Collectively, our results support the hypothesis that oxytocin pathways may shape and respond to social interactions between children and dogs, highlighting an important role for companion animals in child development.

Mechanisms of the different effects of sucrose, glucose, fructose, and a glucose-fructose mixture on wheat starch gelatinization, pasting, and retrogradation.

The gelatinization, pasting, and retrogradation of starch influence texture, quality, and shelf-life attributes of many foods. The purpose of this work was to document the effects of a 50:50 glucose:fructose (glc:fru) mixture and sucrose solutions on these starch traits to provide a fundamental basis to explain the different texture and shelf-life attributes of baked goods formulated with these sugars. Differential scanning calorimetry, rapid visco analyzer, and oscillatory rheometry were used to quantify the effects of glucose, fructose, glc:fru mixture, and sucrose at different concentrations (0% to 60% w/w), on the gelatinization temperature, pasting, and retrogradation properties of wheat starch. Distinct differences were found between the effects of sucrose and those of the monosaccharides including the glc:fru mixture. Sucrose elevated Tgel and pasting temperature most and decreased other RVA parameters compared to the monosaccharides as concentration increased. Fructose and the glc:fru mixture promoted amylopectin retrogradation, while retrogradation was inhibited in sucrose and glucose solutions. The glc:fru mixture had similar effects on starch properties compared to fructose under static measurement conditions (DSC), and the effects were in between those of glucose and fructose under dynamic conditions when shear was applied (RVA and rheology). These effects are explained by the phase separation and/or solute partitioning of the monosaccharide constituents of the glc:fru mixture. Sugar solution physicochemical properties correlated strongly with starch gelatinization and retrogradation. The results substantiate the important relationship between sugar physicochemical properties and solution dynamics with starch thermal properties, which in turn affect the texture and structure of starch-containing food products. PRACTICAL APPLICATION: The quality attributes of starch-containing baked goods are influenced by how different amounts and types of sugars affect starch cooking properties. The underlying mechanisms of the different sugar effects involve solution viscosity, intermolecular hydrogen bonding, and phase separation. Substituting one sugar for another has less effect on these starch properties in products with lower sugar concentrations than in products with more sugar. Mixtures of sugars behave differently than single sugars in different conditions due to phase separation. Baked goods made with glucose:fructose mixtures in place of sucrose likely have higher amounts of gelatinized starch and increased firmness (i.e., staling or retrogradation) over time.

MidA is a putative methyltransferase that is required for mitochondrial complex I function.

Dictyostelium and human MidA are homologous proteins that belong to a family of proteins of unknown function called DUF185. Using yeast two-hybrid screening and pull-down experiments, we showed that both proteins interact with the mitochondrial complex I subunit NDUFS2. Consistent with this, Dictyostelium cells lacking MidA showed a specific defect in complex I activity, and knockdown of human MidA in HEK293T cells resulted in reduced levels of assembled complex I. These results indicate a role for MidA in complex I assembly or stability. A structural bioinformatics analysis suggested the presence of a methyltransferase domain; this was further supported by site-directed mutagenesis of specific residues from the putative catalytic site. Interestingly, this complex I deficiency in a Dictyostelium midA(-) mutant causes a complex phenotypic outcome, which includes phototaxis and thermotaxis defects. We found that these aspects of the phenotype are mediated by a chronic activation of AMPK, revealing a possible role of AMPK signaling in complex I cytopathology.

Women's status, breastfeeding support, and breastfeeding practices in the United States.

The objective of this study is to examine associations between state-level breastfeeding support and breastfeeding practices, controlling for women's status, in the U.S. We used publicly available data on state-level breastfeeding practices and support (international board-certified lactation consultants (IBCLC), births in Baby-Friendly hospitals, and La Leche League Leaders) for births in 2015 from the CDC Breastfeeding Report Card (2018) and other CDC reported data, and indicators of women's status from the Institute for Women's Policy Research reports (2015). We conducted an ecological study to estimate incidence rate ratios of exclusive breastfeeding at six months and breastfeeding at 12 months with breastfeeding supports using bivariate and multivariable Poisson regression. Political participation, poverty, and employment and earnings were associated with breastfeeding practices, as was each breastfeeding support in bivariate analyses. After controlling for women's status, only IBCLCs were positively associated with rates of exclusive breastfeeding at 6 months and continued breastfeeding at 12 months. For every additional IBCLC per 1000 live births, the rate of exclusive breastfeeding at 6 months increased by 5 percent (95% CI 1.03, 1.07) and the rate of breastfeeding at 12 months increased by 4 percent (95% CI 1.02, 1.06). Political participation, poverty, and employment and earnings were associated with breastfeeding practices, indicating a relationship between women's political and economic status and their breastfeeding practices in the U.S. Given the influence of women's status, increasing the number of IBCLCs may improve breastfeeding practices.

North Carolina LGBTQ Domestic Violence Response Initiative: Building Capacity to Provide Safe, Affirming Services.

Intimate partner violence (IPV) is as prevalent or more so as reported by lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals compared with non-LGBTQ individuals. Yet largely due to prior harmful and nonaffirming experiences with service providers, they are reluctant to seek services from domestic violence service providers (DVSP). These factors, combined with the reality that those who do seek services may not be provided with safe, affirming, and effective responses, exacerbate the impact of IPV on LGBTQ health and recovery. The North Carolina (NC) LGBTQ Domestic Violence Response Initiative (NC Initiative) was developed to increase DVSP capacity to serve LGBTQ survivors. This article describes the first four phases of the Initiative's development: (1) formative focus group research with DVSPs statewide, identifying agencies' interest in improving their responses to LGBTQ survivors; (2) Initiative launch, including funding and identification of partners; (3) development of capacity assessment tools; and (4) review of baseline capacity assessment findings. The development of tools, specifically designed to assess capacity of DVSPs to serve LGBTQ survivors, is a unique contribution as no tools existed to do so. The common capacity-building needs and data-informed recommendations identified provide a starting point for agencies expanding into LGBTQ-focused work, who may not have the benefit of grant funding, tools, or evaluators to assist. Our findings, lessons learned, and tools may be used by agencies to evaluate and inform their own practices, thereby creating safer, more affirming agencies that are capable provide effective care to meet unique needs of LGBTQ survivors.

Automated prediction of site and sequence of protein modification with ATRP initiators.

One of the most straightforward and commonly used chemical modifications of proteins is to react surface amino groups (lysine residues) with activated esters. This chemistry has been used to generate protein-polymer conjugates, many of which are now approved therapeutics. Similar conjugates have also been generated by reacting activated ester atom transfer polymerization initiators with lysine residues to create biomacromolecular initiators for polymerization reactions. The reaction between activated esters and lysine amino groups is rapid and has been consistently described in almost every publication on the topic as a "random reaction". A random reaction implies that every accessible lysine amino group on a protein molecule is equally reactive, and as a result, that the reaction is indiscriminate. Nonetheless, the literature contradicts itself by also suggesting that some lysine amino groups are more reactive than others (as a function of pKa, surface accessibility, temperature, and local environment). If the latter assumption is correct, then the outcome of these reactions cannot be random at all, and we should be able to predict the outcome from the structure of the protein. Predicting the non-random outcome of a reaction between surface lysines and reactive esters could transform the speed at which active bioconjugates can be developed and engineered. Herein, we describe a robust integrated tool that predicts the activated ester reactivity of every lysine in a protein, thereby allowing us to calculate the non-random sequence of reaction as a function of reaction conditions. Specifically, we have predicted the intrinsic reactivity of each lysine in multiple proteins with a bromine-functionalised N-hydroxysuccinimide initiator molecule. We have also shown that the model applied to PEGylation. The rules-based analysis has been coupled together in a single Python program that can bypass tedious trial and error experiments usually needed in protein-polymer conjugate design and synthesis.

From hybrid to fully remote clinical trial amidst the COVID-19 pandemic: Strategies to promote recruitment, retention, and engagement in a randomized mHealth trial.

Clinical trials worldwide were disrupted when the COVID-19 pandemic began in early 2020. Most intervention trials moved to some form of remote implementation due to restrictions on in-person research activities. Although the proportion of remote trials is growing, they remain the vast minority of studies in part due to few successful examples. Our team transitioned Goals for Reaching Optimal Wellness (GROWell), an NIH-funded (R01NR017659) randomized control trial (RCT; ClinicalTrials.gov identifier NCT04449432) originally designed as a hybrid intervention, into a fully remote clinical trial. GROWell is a digital dietary intervention for people who enter pregnancy with overweight or obesity. Primary outcomes include gestational weight gain and six-month postpartum weight retention. Strategies that we have tested, refined, and deployed include: (a) use of a HIPAA-compliant, web-based participant recruitment and engagement platform; (b) use of a HIPAA-compliant digital health platform to disseminate GROWell and conduct study visits (c) interconnectivity of these two platforms for seamless recruitment, consent, enrollment, intervention delivery, follow-up, and study team blinding; (d) detailed SMS messages to address initial challenges with protocol adherence; (e) email notifications alerting the study team about missed participant surveys so they can follow-up; (f) remuneration using email gift cards with recipient choice of vendor; and (g) geotargeting social media campaigns to improve participation of Black Indigenous and People of Color Communities. These strategies have resulted in screen failure rates improving by 7%, study task adherence improving by an average of 20-30% across study visits, and study completion rates of 82%. Researchers may consider some or all of these approaches in future remote mHealth trials.

The first responder exposure to contaminating powder on dog fur during intranasal and intramuscular naloxone administration.

OBJECTIVE: To determine whether first responders delivering naloxone by either the IM or intranasal (IN) route were at risk of contamination with inert powder simulating canine opioid exposure. DESIGN: Prospective, crossover design. SETTING: Research study (university setting). ANIMALS: Ten clinically normal working dogs ranging from 9 to 44 months were enrolled based on training to detect odor and ability to be restrained with minimal stress. All enrolled dogs completed both arms of the study without adverse effects. INTERVENTIONS: Dogs were randomly assigned to fentanyl reversal with either IM or IN naloxone and then the alternate treatment after a 7-day washout period. Prior to reversal, dogs' heads were brushed with an inert glow-in-the-dark powder. First responders (the same 2 individuals for all dogs) performing the reversal were photographed under ultraviolet light prior to and 5 min after administering the medication. Digital photographs were scored by body region for presence of glowing powder by observers blinded to timing of photograph (pre- or postreversal) and route of reversal (IM vs IN). MEASUREMENTS AND MAIN RESULTS: Compared to pretreatment, the inert powder scores were higher after treatment regardless of route of naloxone administration (P < 0.001). IN administration led to higher contamination than IM naloxone, particularly in the chest area (P = 0.012). CONCLUSIONS: Both IN and IM naloxone administration to dogs with clinical signs of opioid exposure result in a risk of first responders becoming contaminated with powder, which could include opioids. Awareness, proper personal protective equipment, and appropriate posttreatment decontamination are important to reduce risk of inadvertent exposure of mucous membranes to these contaminating powders.

Goals for Reaching Optimal Wellness (GROWell): A clinical trial protocol of a digital dietary intervention for pregnant and postpartum people with prenatal overweight or obesity.

BACKGROUND: Excess gestational weight gain (EGWG) is associated with multiple pregnancy complications and health risks for birthing people and their infants. Likewise, postpartum weight retention (PPWR), or not losing all pregnancy weight, has long-term health consequences. EGWG among people who enter pregnancy with overweight or obesity have worse obstetric outcomes and increased PPWR compared to women who gain within Institute of Medicine guidelines. METHODS: This study protocol describes the details of a blinded, randomized clinical trial of GROWell: Goals for Reaching Optimal Wellness, a mHealth tool designed to improve diet quality among people who enter pregnancy with overweight or obese BMIs to help them achieve appropriate GWG and safe postpartum pregnancy weight loss. Individuals with overweight and obesity will be randomly assigned to an attention control or intervention arm. The intervention group will receive personalized, goal-oriented text messages regarding dietary choices, while the attention control group will receive text messages about healthy pregnancy, labor, delivery, and early infancy. Both groups will complete online surveys at baseline, follow up, 3 and 6 months postpartum. RESULTS AND DISCUSSION: Currently, 162 subjects have been enrolled. Outcomes associated with GWG and pregnancy are expected in late 2023, while outcomes on postpartum weight retention GROWell adherence are expected in late 2024. The results of this trial will support the use of an evidence-based mHealth tool to be integrated into clinical practice to reduce EGWG and PPWR among pregnant people with overweight and obese BMIs, a resource that is currently lacking. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04449432. Registered on June 26, 2020.

Microtentacle Formation in Ovarian Carcinoma.

BACKGROUND: The development of chemoresistance to paclitaxel and carboplatin represents a major therapeutic challenge in ovarian cancer, a disease frequently characterized by malignant ascites and extrapelvic metastasis. Microtentacles (McTNs) are tubulin-based projections observed in detached breast cancer cells. In this study, we investigated whether ovarian cancers exhibit McTNs and characterized McTN biology. METHODS: We used an established lipid-tethering mechanism to suspend and image individual cancer cells. We queried a panel of immortalized serous (OSC) and clear cell (OCCC) cell lines as well as freshly procured ascites and human ovarian surface epithelium (HOSE). We assessed by Western blot ß-tubulin isotype, α-tubulin post-translational modifications and actin regulatory proteins in attached/detached states. We studied clustering in suspended conditions. Effects of treatment with microtubule depolymerizing and stabilizing drugs were described. RESULTS: Among cell lines, up to 30% of cells expressed McTNs. Four McTN morphologies (absent, symmetric-short, symmetric-long, tufted) were observed in immortalized cultures as well as ascites. McTN number/length varied with histology according to metastatic potential. Most OCCC overexpressed class III ß-tubulin. OCCC/OSC cell lines exhibited a trend towards more microtubule-stabilizing post-translational modifications of α-tubulin relative to HOSE. Microtubule depolymerizing drugs decreased the number/length of McTNs, confirming that McTNs are composed of tubulin. Cells that failed to form McTNs demonstrated differential expression of α-tubulin- and actin-regulating proteins relative to cells that form McTNs. Cluster formation is more susceptible to microtubule targeting agents in cells that form McTNs, suggesting a role for McTNs in aggregation. CONCLUSIONS: McTNs likely participate in key aspects of ovarian cancer metastasis. McTNs represent a new therapeutic target for this disease that could refine therapies, including intraperitoneal drug delivery.