CLADIN- CLADribine and INnate immune response in multiple sclerosis - A phase IV prospective study.

Cladribine (Mavenclad®) is an oral treatment for relapsing remitting MS (RRMS), but its mechanism of action and its effects on innate immune responses in unknown. This study is a prospective Phase IV study of 41 patients with RRMS, and aims to investigate the mechanism of action of cladribine on peripheral monocytes, and its impact on the P2X7 receptor. There was a significant reduction in monocyte count in vivo at week 1 post cladribine administration, and the subset of cells being most impacted were the CD14lo CD16+ 'non-classical' monocytes. Of the 14 cytokines measured in serum, CCL2 levels increased at week 1. In vitro, cladrabine induced a reduction in P2X7R pore as well as channel activity. This study demonstrates a novel mechanism of action for cladribine. It calls for studying potential benefits of cladribine in progressive forms of MS and other neurodegenerative diseases where innate immune related inflammation is implicated in disease pathogenesis.

Formal Ethics Consultation in Extracorporeal Membrane Oxygenation Patients: A Single-Center Retrospective Cohort of a Quaternary Pediatric Hospital.

OBJECTIVE: To examine characteristics associated with formal ethics consultation (EC) referral in pediatric extracorporeal membrane oxygenation (ECMO) cases, and document ethical issues presented. DESIGN: Retrospective cohort study using mixed methods. SETTING: Single-center quaternary pediatric hospital. PATIENTS: Patients supported on ECMO (January 2012 to December 2021). INTERVENTIONS: We compared clinical variables among ECMO patients according to the presence of EC. We defined optimal cutoffs for EC based on run duration, ICU length of stay (LOS), and sum of procedures or complications. To identify independent explanatory variables for EC, we used a forward stepwise selection multivariable logistic regression model. EC records were thematically characterized into ethical issues. MEASUREMENTS AND MAIN RESULTS: Of 601 ECMO patients and 225 patients with EC in 10 years, 27 ECMO patients received EC (4.5% of ECMO patients, 12% of all ECs). On univariate analysis, use of EC vs. not was associated with multiple ECMO runs, more complications/procedures, longer ICU LOS and ECMO duration, cardiac admissions, decannulation outcome, and higher mortality. Cutoffs for EC were ICU LOS >52 days, run duration >160 hours, and >6 complications/procedures. Independent associations with EC included these three cutoffs and older age. The model showed good discrimination (area under the curve 0.88 [0.83, 0.93]) and fit. The most common primary ethical issues were related to end-of-life, ECMO discontinuation, and treatment decision-making. Moral distress was cited in 22 of 27 cases (82%). CONCLUSION: EC was used in 4.5% of our pediatric ECMO cases, with most ethical issues related to end-of-life care or ECMO discontinuation. Older age, longer ICU LOS, prolonged runs, and multiple procedures/complications were associated with greater odds for EC requests. These data highlight our single-center experience of ECMO-associated ethical dilemmas. Historical referral patterns may guide a supported decision-making framework. Future work will need to include quality improvement projects for timely EC, with evaluation of impacts on relevant endpoints.

Entorhinal-Hippocampal Circuit Integrity Is Related to Mnemonic Discrimination and Amyloid-ß Pathology in Older Adults.

Mnemonic discrimination, a cognitive process that relies on hippocampal pattern separation, is one of the first memory domains to decline in aging and preclinical Alzheimer's disease. We tested whether functional connectivity (FC) within the entorhinal-hippocampal circuit, measured with high-resolution resting state fMRI, is associated with mnemonic discrimination and amyloid-ß (Aß) pathology in a sample of 64 cognitively normal human older adults (mean age, 71.3 ± 6.4 years; 67% female). FC was measured between entorhinal-hippocampal circuit nodes with known anatomical connectivity, as well as within cortical memory networks. Aß pathology was measured with 18F-florbetapir-PET, and neurodegeneration was assessed with subregional volume from structural MRI. Participants performed both object and spatial versions of a mnemonic discrimination task outside of the scanner and were classified into low-performing and high-performing groups on each task using a median split. Low object mnemonic discrimination performance was specifically associated with increased FC between anterolateral entorhinal cortex (alEC) and dentate gyrus (DG)/CA3, supporting the importance of this connection to object memory. This hyperconnectivity between alEC and DG/CA3 was related to Aß pathology and decreased entorhinal cortex volume. In contrast, spatial mnemonic discrimination was not associated with altered FC. Aß was further associated with dysfunction within hippocampal subfields, particularly with decreased FC between CA1 and subiculum as well as reduced volume in these regions. Our findings suggest that Aß may indirectly lead to memory impairment through entorhinal-hippocampal circuit dysfunction and neurodegeneration and provide a mechanism for increased vulnerability of object mnemonic discrimination.SIGNIFICANCE STATEMENT Mnemonic discrimination is a critical episodic memory process that is performed in the dentate gyrus (DG) and CA3 subfield of the hippocampus, relying on input from entorhinal cortex. Mnemonic discrimination is particularly vulnerable to decline in older adults; however, the mechanisms behind this vulnerability are still unknown. We demonstrate that object mnemonic discrimination impairment is related to hyperconnectivity between the anterolateral entorhinal cortex and DG/CA3. This hyperconnectivity was associated with amyloid-ß pathology and neurodegeneration in entorhinal cortex, suggesting aberrantly increased network activity is a pathological process. Our findings provide a mechanistic explanation of the vulnerability of object compared to spatial mnemonic discrimination in older adults and has translational implications for choice of outcome measures in clinical trials for Alzheimer's disease.

Current attitudes toward drug checking services and a comparison of expected with actual drugs present in street drug samples collected from opioid users.

BACKGROUND: The opioid epidemic continues to be associated with high numbers of fatalities in the USA and other countries, driven mainly by the inclusion of potent synthetic opioids in street drugs. Drug checking by means of various technologies is being increasingly implemented as a harm reduction strategy to inform users about constituent drugs in their street samples. We assessed how valued drug checking services (DCS) would be for opioid street drug users given the ubiquity of fentanyl and related analogs in the drug supply, the information they would most value from drug checking, and compared expected versus actual constituent drugs in collected samples. METHODS: A convenience sample of opioid street drug users (N = 118) was recruited from two syringe service exchange programs in Chicago between 2021 and 2022. We administered brief surveys asking about overdose history, whether fentanyl was their preferred opioid, and interest in DCS. We also collected drug samples and asked participants what drug(s) they expected were in the sample. Provided samples were analyzed using LC-MS technology and the results compared to their expected drugs. RESULTS: Participants reported an average of 4.4 lifetime overdoses (SD = 4.8, range = 0-20) and 1.1 (SD = 1.8, range = 0-10) past-year overdoses. A majority (92.1%) believed they had recently used drugs containing fentanyl whether intentionally or unintentionally. Opinions about the desirability of fentanyl were mixed with 56.1% indicating they did not and 38.0% indicating they did prefer fentanyl over other opioids, mainly heroin. Attitudes toward DCS indicated a general but not uniform receptiveness with a majority indicating interest in DCS though sizeable minorities believed DCS was "too much trouble" (25.2%) or there was "no point" in testing (35.4%). Participants were especially inaccurate identifying common cutting agents and potentiating drugs such as diphenhydramine in their samples (sensitivity = .17). CONCLUSIONS: Results affirmed street drug users remain interested in using DCS to monitor their drugs and such services should be more widely available. Advanced checking technologies that provide information on the relative quantities and the different drugs present in a given sample available at point-of-care, would be most valuable but remain challenging to implement.

Extracorporeal Membrane Oxygenation Candidacy Decisions: An Argument for a Process-Based Longitudinal Approach.

Are all children extracorporeal membrane oxygenation (ECMO) candidates? Navigating ECMO decisions represents an enormous challenge in pediatric critical care. ECMO cannulation should not be a default option as it will not confer benefit for "all" critically ill children; however, "all" children deserve well-considered decisions surrounding their ECMO candidacy. The complexity of the decision demands a systematic, "well-reasoned" and "dynamic" approach. Due to clinical urgency, this standard cannot always be met prior to initiation of ECMO. We challenge the paradigm of "candidacy" as a singular decision that must be defined prior to ECMO initiation. Rather, the determination as to whether ECMO is in the patient's best interest is applicable regardless of cannulation status. The priority should be on collaborative, interdisciplinary decision-making processes aligned with principles of transparency, relevant reasoning, accountability, review, and appeal. To ensure a robust process, it should not be temporally constrained by cannulation status. We advocate that this approach will decrease both the risk of not initiating ECMO in a patient who will benefit and the risk of prolonged, nonbeneficial support. We conclude that to ensure fair decisions are made in a patient's best interest, organizations should develop procedurally fair processes for ECMO decision-making that are not tied to a particular time point and are revisited along the management trajectory.

Ethical climate in contemporary paediatric intensive care.

Ethical climate (EC) has been broadly described as how well institutions respond to ethical issues. Developing a tool to study and evaluate EC that aims to achieve sustained improvements requires a contemporary framework with identified relevant drivers. An extensive literature review was performed, reviewing existing EC definitions, tools and areas where EC has been studied; ethical challenges and relevance of EC in contemporary paediatric intensive care (PIC); and relevant ethical theories. We surmised that existing EC definitions and tools designed to measure it fail to capture nuances of the PIC environment, and sought to address existing gaps by developing an EC framework for PIC founded on ethical theory. In this article, we propose a Paediatric Intensive Care Ethical Climate (PICEC) conceptual framework and four measurable domains to be captured by an assessment tool. We define PICEC as the collective felt experience of interdisciplinary team members arising from those factors that enable or constrain their ability to navigate ethical aspects of their work. PICEC both results from and is influenced by how well ethical issues are understood, identified, explored, reflected on, responded to and addressed in the workplace. PICEC encompasses four, core inter-related domains representing drivers of EC including: (1) organisational culture and leadership; (2) interdisciplinary team relationships and dynamics; (3) integrated child and family-centred care; and (4) ethics literacy. Future directions involve developing a PICEC measurement tool, with implications for benchmarking as well as guidance for, and evaluation of, targeted interventions to foster a healthy EC.

Syringe service program-based telemedicine linkage to opioid use disorder treatment: protocol for the STAMINA randomized control trial.

BACKGROUND: A key strategy for mitigating the current opioid epidemic is expanded access to medications for treating opioid use disorder (MOUD). However, interventions developed to expand MOUD access have limited ability to engage opioid users at higher levels of overdose risk, such as those who inject opioids. This paper describes the study protocol for testing STAMINA (Syringe Service Telemedicine Access for Medication-assisted Intervention through NAvigation), an intervention that engages high-risk opioid users at community-based syringe service programs (SSP) and quickly links them to MOUD using a telemedicine platform. METHODS: This randomized control trial will be conducted at three SSP sites in Chicago. All participants will complete an initial assessment with a provider from a Federally Qualified Health Center who can prescribe or refer MOUD services as appropriate. The control arm will receive standard referral to treatment and the intervention arm will receive immediate telemedicine linkage to the provider and (depending on the type of MOUD prescribed) provided transportation to pick up their induction prescription (for buprenorphine or naltrexone) or attend their intake appointment (for methadone). We aim to recruit a total of 273 participants over two years to provide enough power to detect a difference in our primary outcome of MOUD treatment linkage. Secondary outcomes include treatment engagement, treatment retention, and non-MOUD opioid use. Data will be collected using structured interviews and saliva drug tests delivered at baseline, three months, and six months. Fixed and mixed effects generalized linear regression analyses and survival analysis will be conducted to compare the probabilities of a successful treatment linkage between the two arms, days retained in treatment, and post-baseline opioid and other drug use. DISCUSSION: If successful, STAMINA's telemedicine approach will significantly reduce the amount of time between SSP clients' initial indication of interest in the medication and treatment initiation. Facilitating this process will likely lead to stronger additional treatment- and recovery-oriented outcomes. This study is also timely given the need for more rigorous testing of telemedicine interventions in light of temporary regulatory changes that have occurred during the COVID-19 pandemic. TRIAL REGISTRATION: ClinicalTrials.gov (Clinical Trials ID: NCT04575324 and Protocol Number: 1138-0420). Registered 29 September 2020. The study protocol is also registered on the Open Science Framework (DOI 10.17605/OSF.IO/4853 M).

Toward a Molecular Understanding of the Impact of Crystal Size and Shape on Punch Sticking.

Punch sticking during tablet manufacturing is a common problem facing the pharmaceutical industry. Using several model compounds, effects of crystal size and shape of active pharmaceutical ingredients (API) on punch sticking propensity were systematically investigated in this work to provide molecular insights into the punch-sticking phenomenon. In contrast to the common belief that smaller API particles aggravate punch sticking, results show that particle size reduction can either reduce or enhance API punch sticking, depending on the complex interplay among the particle surface area, plasticity, cohesive strength, and specific surface functional groups. Therefore, other factors, such as crystal mechanical properties, surface chemistry of crystal facets exposed to the punch face, and choice of excipients in a formulation, should be considered for a more reliable prediction of the initiation and progression of punch sticking. The exposure of strong electronegative groups to the punch face facilitates the onset of sticking, while higher plasticity and cohesive strength aggravate sticking.

Influence of seeing a red face during the male-male encounters of mosquito-specialist spiders.

Males of Evarcha culicivora, an East African jumping spider (Salticidae), have bright red faces. Here, we investigated how seeing a red face might influence a male's behaviour during encounters with another male. We applied black eyeliner to conceal the red on a male's face and measured the spectral properties of male faces with and without the eyeliner. Only the faces without eyeliner reflected in the long-wavelength range corresponding to red. In experiments over 2 days, where eyeliner was absent on the first day and present on the second, we compared how two groups of males responded to their mirror images. Face Group: eyeliner concealed their faces. Head Group: eyeliner was applied to the tops of the males' heads instead of on their faces. The males from both groups displayed to their mirror image as if it were a living same-sex conspecific. However, when they could see a red face, males in the face group escalated to higher levels of aggression to their mirror image and initiated displaying from farther away than when the red had been concealed. We also found that the influence of eyeliner was stronger for the face group than for the head group. These findings suggest that, when seeing a red face, E. culicivora males become more confident that the individual in view is another male.

Fentanyl Exposure and Detection Strategies Utilized by Clinical Trial Participants Seeking Linkage to Opioid Use Disorder Treatment at a Syringe Service Program.

INTRODUCTION: The USA continues to face a fentanyl-driven overdose epidemic. Prior research has demonstrated users of illicit opioids are concerned about fentanyl exposure and overdose, but the strategies they report using to detect fentanyl's presence lack empirical support. This study compares self-report and biologically detected fentanyl use and investigates overdose risk and risk reduction behaviors among a sample of high-risk people who use opioids. METHODS: Structured enrollment interviews conducted as part of a larger clinical trial assessed self-reported fentanyl exposure as well as strategies used to determine believed fentanyl exposure and prevent overdose among 240 participants enrolled at a Chicago, IL syringe service program. Urinalysis measured actual fentanyl exposure. RESULTS: Most participants identified as African American (66.7%) and had considerable overdose experience (76.7% lifetime and 48% in the past year). Most also tested positive for fentanyl (93.75%) despite reporting no past year use of fentanyl or fentanyl-adulterated drugs (64.17%). The most utilized approaches reported for identifying fentanyl exposure were stronger effects of the drug (60.7%), sight or taste (46.9%), and being told by someone using the same drugs (34.2%). Few participants (14%) reported using fentanyl test strips. No significant associations were identified between self-report and urinalysis measures or urinalysis results and risk reduction strategies. CONCLUSION: This study adds to prior fentanyl exposure risk research. The disconnect between participants' fentanyl detection methods and reported overdose experiences supports the need for more research to identify and understand factors driving access and use of overdose prevention resources and strategies.

Improving Health and Reducing Chronic Disease Disparities with Latinx Communities: Evaluating the Role of Documented Community-Based Intervention Participation.

PURPOSE: Limited evidence exists on the impact of participation in community-based chronic disease self-management and prevention programs on health disparities. The purpose of this research was to determine the effects of participation in the Healthy Here Wellness Referral System on existing disparities in glycated hemoglobin (HbA1c), systolic blood pressure (BP), and diastolic BP among Hispanic/Latinx adults compared with non-Hispanic White adults. METHODS: We merged administrative clinical and referral data from 2018 through 2022 for adult patients in six focus ZIP codes in New Mexico resulting in a sample of 1331 patients and used regression models to examine predictors of intervention participation as well as propensity-adjusted impacts of participation on HbA1c and BP outcomes. RESULTS: Non-Hispanic White patients who were referred to community-based programming but did not participate saw statistically significant increases in HbA1c. Hispanic/Latinx patients saw statistically significant decreases in HbA1c with referral alone, with no added benefit from program participation. The impact of participation differed statistically significantly (t(683) = 3.55, p < .001) between these two groups for HbA1c levels, as well as for systolic (t(958) = 2.11, p = .04) and diastolic BP outcomes (t(958) = 2.96, p = .003). CONCLUSIONS: Results of this study support the promise of using centralized referral systems to co-produce health improvement in community settings. Mixed findings highlight the need for further uptake of theory-informed measurement in evaluations seeking to understand heterogeneous program impacts by race and ethnicity.

Results From the POINT Pragmatic Randomized Trial: An Emergency Department-Based Peer Support Specialist Intervention to Increase Opioid Use Disorder Treatment Linkage and Reduce Recurrent Overdose.

BACKGROUND: People with opioid use disorder (OUD) frequently present at the emergency department (ED), a potentially critical point for intervention and treatment linkage. Peer recovery support specialist (PRSS) interventions have expanded in US-based EDs, although evidence supporting such interventions has not been firmly established. METHODS: Researchers conducted a pragmatic trial of POINT (Project Planned Outreach, Intervention, Naloxone, and Treatment), an ED-initiated intervention for harm reduction and recovery coaching/treatment linkage in 2 Indiana EDs. Cluster randomization allocated patients to the POINT intervention (n = 157) versus a control condition (n = 86). Participants completed a structured interview, and all outcomes were assessed using administrative data from an extensive state health exchange and state systems. Target patients (n = 243) presented to the ED for a possible opioid-related reason. The primary outcome was overdose-related ED re-presentation. Key secondary outcomes included OUD medication treatment linkage, duration of medication in days, all-cause ED re-presentation, all-cause inpatient re-presentation, and Medicaid enrollment. All outcomes were assessed at 3-, 6-, and 12-months post-enrollment. Ad hoc analyses were performed to assess treatment motivation and readiness. RESULTS: POINT and standard care participants did not differ significantly on any outcomes measured. Participants who presented to the ED for overdose had significantly lower scores (3.5 vs 4.2, P < .01) regarding readiness to begin treatment compared to those presenting for other opioid-related issues. CONCLUSIONS: This is the first randomized trial investigating overdose outcomes for an ED peer recovery support specialist intervention. Though underpowered, results suggest no benefit of PRSS services over standard care. Given the scope of PRSS, future work in this area should assess more recovery- and harm reduction-oriented outcomes, as well as the potential benefits of integrating PRSS within multimodal ED-based interventions for OUD.

Risk of Cervical Abnormalities for Women With Multiple Sclerosis Treated With Moderate-Efficacy and High-Efficacy Disease-Modifying Therapies.

BACKGROUND AND OBJECTIVES: The impact of immunomodulatory therapies on the risk of cervical pre-cancer and invasive cancer development is important for the health and safety of women with multiple sclerosis (wwMS). We investigate the risk of cervical abnormalities in wwMS treated with disease-modifying therapies (DMTs). METHODS: This is a multicenter cohort study with data collected from 1998 to 2019 in Victoria, Australia. Data linkage was performed using matching records from the MSBase Registry, the National Human Papillomavirus (HPV) Vaccination Program Register, and the Victorian Cervical Cytology Register. The primary outcome was the detection of any type of cervical abnormality as determined by cytology or histology. Survival methods were used to assess the time to cervical abnormality detection on cervical screening tests (CSTs). Crude and adjusted Cox proportional hazards models were used to determine time to and magnitude of association of DMTs with the risk of cervical abnormality. In a sensitivity analysis, we constructed standardized survival curves averaged over the same set of covariates to determine the commensurate population-average (marginal) causal effects. RESULTS: We included 248 wwMS. The incidence of abnormal CSTs was lower (p < 0.001) for women not exposed to moderate-high-efficacy therapy (10.2 per 1,000 patient-years [95% confidence interval (CI) 5.5-14.9]), compared with those exposed (36.6 per 1,000 patient-years [95% CI 21.7-51.6]). Exposure to higher efficacy treatment was associated with a 3.79-fold increased hazard (95% CI 2.02-7.08, p < 0.001) of developing a cervical abnormality relative to those not exposed. When adjusted for vaccination status, smoking, hormonal contraceptive use, and socioeconomic status, the risk remained elevated at 3.79 (95% CI 1.99-7.21, p < 0.001). Marginal hazard ratios declined over time, ranging from 3.90 (95% CI 2.09-7.27) at 20 years of age to 2.06 (95% CI 1.14-3.73) at 70 years of age. DISCUSSION: A greater than three-and-a-half-fold increased risk of cervical abnormalities was found after exposure to moderate-high-efficacy DMTs. This risk persisted despite adjusting for HPV vaccination status, hormonal contraception use, smoking, and socioeconomic status. If confirmed in future studies, we would advocate for wwMS exposed to moderate-high-efficacy DMTs to be treated in line with immune-deficient paradigm in cervical screening and HPV vaccination programs. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that highly active MS therapy compared with less active therapy increases the risk of developing cervical abnormalities among women with MS.

Cerebrovascular pathology mediates associations between hypoxemia during rapid eye movement sleep and medial temporal lobe structure and function in older adults.

Obstructive sleep apnea (OSA) is common in older adults and is associated with medial temporal lobe (MTL) degeneration and memory decline in aging and Alzheimer's disease (AD). However, the underlying mechanisms linking OSA to MTL degeneration and impaired memory remains unclear. By combining magnetic resonance imaging (MRI) assessments of cerebrovascular pathology and MTL structure with clinical polysomnography and assessment of overnight emotional memory retention in older adults at risk for AD, cerebrovascular pathology in fronto-parietal brain regions was shown to statistically mediate the relationship between OSA-related hypoxemia, particularly during rapid eye movement (REM) sleep, and entorhinal cortical thickness. Reduced entorhinal cortical thickness was, in turn, associated with impaired overnight retention in mnemonic discrimination ability across emotional valences for high similarity lures. These findings identify cerebrovascular pathology as a contributing mechanism linking hypoxemia to MTL degeneration and impaired sleep-dependent memory in older adults.

A pathway linking pulse pressure to dementia in adults with Down syndrome.

Adults with Down syndrome are less likely to have hypertension than neurotypical adults. However, whether blood pressure measures are associated with brain health and clinical outcomes in this population has not been studied in detail. Here, we assessed whether pulse pressure is associated with markers of cerebrovascular disease and is linked to a diagnosis of dementia in adults with Down syndrome via structural imaging markers of cerebrovascular disease and atrophy. The study included participants with Down syndrome from the Alzheimer's Disease - Down Syndrome study (n = 195, age = 50.6 ± 7.2 years, 44% women, 18% diagnosed with dementia). Higher pulse pressure was associated with greater global, parietal and occipital white matter hyperintensity volume but not with enlarged perivascular spaces, microbleeds or infarcts. Using a structural equation model, we found that pulse pressure was associated with greater white matter hyperintensity volume, which in turn was related to increased neurodegeneration, and subsequent dementia diagnosis. Pulse pressure is an important determinant of brain health and clinical outcomes in individuals with Down syndrome despite the low likelihood of frank hypertension.

Efficient induction of spawning of northern leopard frogs (Lithobates pipiens) during and outside the natural breeding season.

BACKGROUND: Amphibian declines are now recognized globally. It is also well known that many anurans do not reproduce easily in captivity, especially when held over long periods, or if they require hibernation before breeding. A simple method to induce spawning and subsequent development of large numbers of healthy tadpoles is therefore required to meet research and conservation goals. METHODS: The method is based on simultaneous injection of both female and male leopard frogs, Lithobates pipiens (formerly called Rana pipiens) with a cocktail of a gonadotropin-releasing hormone agonist (GnRH-A) and a dopamine antagonist. We call this the AMPHIPLEX method, which is derived from the combination of the words amphibian and amplexus. Following injection, the animals are thereby induced, and perform amplexus and natural fertilization under captive conditions. RESULTS: We tested combinations of a GnRH agonist with 2 different dopamine antagonists in L. pipiens in the breeding season. The combination of des-Gly(10), D-Ala(6), Pro-NHEt(9)-GnRH (0.4 micrograms/g body weight; GnRH-A) with metoclopramide hydrochloride (10 micrograms/g body weight; MET) or domperidone (DOM) were equally effective, producing 89% and 88% successful spawning, respectively. This yielded more than 44,000 eggs for the 16/18 females that ovulated in the GnRH-A+MET group, and more than 39,000 eggs for the 15/17 females that ovulated in the GnRH-A+DOM group. We further tested the GnRH-A+MET in frogs collected in the wild in late autumn and hibernated for a short period under laboratory conditions, and report a low spawning success (43%). However, GnRH-A priming 24 hours prior to injections of the GnRH-A+MET cocktail in animals hibernated for 5-6 weeks produced out-of-season spawning (89%) and fertilization (85%) comparable to those we observed for in-season spawning. Assessment of age and weight at metamorphosis indicated that L. pipiens tadpoles resulting from out-of-season spawning grew normally and metamorphosed successfully. CONCLUSION: We provide evidence for successful captive breeding of the leopard frog, L. pipiens. This simple protocol can be used to obtain large numbers of eggs in a predictable, timed manner.

Over-the-counter and out-of-control: legal strategies to protect youths from abusing products for weight control.

Abuse of widely available, over-the-counter drugs and supplements such as laxatives and diet pills for weight control by youths is well documented in the epidemiological literature. Many such products are not medically recommended for healthy weight control or are especially susceptible to abuse, and their misuse can result in serious health consequences. We analyzed the government's role in regulating these products to protect public health. We examined federal and state regulatory authority, and referred to international examples to inform our analysis. Several legal interventions are indicated to protect youths, including increased warnings and restrictions on access through behind-the-counter placement or age verification. We suggest future directions for governments internationally to address this pervasive public health problem.

The Prevalence of Domestic Violence in the Lives of Female Heterosexual Partners of Sex Addicts.

This study provides evidence that rates of domestic violence (DV) run considerably higher in the lives of heterosexual women who identify as partners of sex addicts (PSAs) than in the general population. Data collected from 558 survey participants, from a variety of high-income nations, revealed that 92.1% had ever experienced any form of DV perpetrated by their partner and 57.7% had experienced physical and/or sexual intimate partner violence with their partner. The study also tests several hypotheses about sex addiction behaviors and PSA intimate partner violence (IPV), to help those working with these populations understand what factors may be contributing to, or mitigating, these women's experiences of violence.

Applying Principles of Evolutionary Biology to Plastic Surgery at an Organizational Level Predicts an Extinction Event.

As an organized profession, plastic surgery struggles delivering a clear message regarding scope of practice to patients given the diversity of procedures performed. Whereas granting licensure to practice medicine resides with governmental bodies, certification rests with organizations. However, certification is not required to practice plastic surgery. Since plastic surgery operationalizes techniques rather than working within a defined body organ, competition for patients is intense. Mapping territorial interactions between healthcare providers while parsing taxonomy elucidates individual, community, organizational, and governmental levels, creating various selection pressures. Applying evolutionary biology as a framework predicts the termination of plastic surgery over time as a unique specialty. An entirely new domain, Restorative Healthcare, is proposed which circumvents an extinction outcome.