The Impact of Melanoma Imaging Biomarker Cues on Detection Sensitivity and Specificity in Melanoma versus Clinically Atypical Nevi.

Incorporation of dermoscopy and artificial intelligence (AI) is improving healthcare professionals' ability to diagnose melanoma earlier, but these algorithms often suffer from a "black box" issue, where decision-making processes are not transparent, limiting their utility for training healthcare providers. To address this, an automated approach for generating melanoma imaging biomarker cues (IBCs), which mimics the screening cues used by expert dermoscopists, was developed. This study created a one-minute learning environment where dermatologists adopted a sensory cue integration algorithm to combine a single IBC with a risk score built on many IBCs, then immediately tested their performance in differentiating melanoma from benign nevi. Ten participants evaluated 78 dermoscopic images, comprised of 39 melanomas and 39 nevi, first without IBCs and then with IBCs. Participants classified each image as melanoma or nevus in both experimental conditions, enabling direct comparative analysis through paired data. With IBCs, average sensitivity improved significantly from 73.69% to 81.57% (p = 0.0051), and the average specificity improved from 60.50% to 67.25% (p = 0.059) for the diagnosis of melanoma. The index of discriminability (d') increased significantly by 0.47 (p = 0.002). Therefore, the incorporation of IBCs can significantly improve physicians' sensitivity in melanoma diagnosis. While more research is needed to validate this approach across other healthcare providers, its use may positively impact melanoma screening practices.

Distribution and habitat use patterns of the endangered Central American clouded oncilla (Leopardus pardinoides oncilla) in Costa Rica.

Montane cloud forests are highly threatened ecosystems that are vulnerable to climate change. These complex habitats harbor many species that suffer the negative consequences of this global phenomenon, such as shifts in their distribution and habitat use. The Central American clouded oncilla (Leopardus pardinoides oncilla) is the smallest and most endangered wild cat in Mesoamerica and is primarily reported in cloud forests throughout its distribution. The species is poorly understood, with no studies conducted in Central America assessing its habitat preferences. To bridge this knowledge gap, we sampled two mountain ranges in Costa Rica with camera traps and conducted an occupancy analysis to understand the anthropogenic and environmental features that influence oncilla habitat use within them. Additionally, we conducted spatial predictions of habitat use across its northern and southern range in Costa Rica to identify priority conservation areas for the species. We found that Central American clouded oncilla habitat use is driven primarily by environmental factors. Our results showed that oncillas select habitats with denser tree cover at high elevations, closer to permanent water sources, which may provide them with high prey density and a favorable habitat structure for their survival. Spatial predictions identified two main regions as conservation priority areas where threat mitigation efforts and monitoring should be implemented: the Caribbean slope of the Talamanca mountains, and the Arenal-Monteverde forest complex. The occupancy modeling approach turned out to be very useful to assess the spatial associations of the species with the environment and mapping the conservation priority areas. Future research and mitigation actions should focus on potential threats that could negatively impact Central American clouded oncilla populations and habitat use, including the role of mesopredators and feral species.

Do Sex and Gender Have Separate Identities?

The largely binary nature of biological sex and its conflation with the socially constructed concept of gender has created much strife in the last few years. The notion of gender identity and its differences and similarities with sex have fostered much scientific and legal confusion and disagreement. Settling the debate can have significant repercussions for science, medicine, legislation, and people's lives. The present review addresses this debate though different levels of analysis (i.e., genetic, anatomical, physiological, behavioral, and sociocultural), and their implications and interactions. We propose a rationale where both perspectives coexist, where diversity is the default, establishing a delimitation to the conflation between sex and gender, while acknowledging their interaction. Whereas sex in humans and other mammals is a biological reality that is largely binary and based on genes, chromosomes, anatomy, and physiology, gender is a sociocultural construct that is often, but not always, concordant with a person' sex, and can span a multitude of expressions.

MicroRNA Transcriptomes Reveal Prevalence of Rare and Species-Specific Arm Switching Events During Zebrafish Ontogenesis.

In metazoans, microRNAs (miRNAs) are essential regulators of gene expression, affecting critical cellular processes from differentiation and proliferation, to homeostasis. During miRNA biogenesis, the miRNA strand that loads onto the RNA-induced Silencing Complex (RISC) can vary, leading to changes in gene targeting and modulation of biological pathways. To investigate the impact of these "arm switching" events on gene regulation, we analyzed a diverse range of tissues and developmental stages in zebrafish by comparing 5p and 3p arms accumulation dynamics between embryonic developmental stages, adult tissues, and sexes. We also compared variable arm usage patterns observed in zebrafish to other vertebrates including arm switching data from fish, birds, and mammals. Our comprehensive analysis revealed that variable arm usage events predominantly take place during embryonic development. It is also noteworthy that isomiR occurrence correlates to changes in arm selection evidencing an important role of microRNA distinct isoforms in reinforcing and modifying gene regulation by promoting dynamics switches on miRNA 5p and 3p arms accumulation. Our results shed new light on the emergence and coordination of gene expression regulation and pave the way for future investigations in this field.

Microbiomes of Thalassia testudinum throughout the Atlantic Ocean, Caribbean Sea, and Gulf of Mexico are influenced by site and region while maintaining a core microbiome.

Plant microbiomes are known to serve several important functions for their host, and it is therefore important to understand their composition as well as the factors that may influence these microbial communities. The microbiome of Thalassia testudinum has only recently been explored, and studies to-date have primarily focused on characterizing the microbiome of plants in a single region. Here, we present the first characterization of the composition of the microbial communities of T. testudinum across a wide geographical range spanning three distinct regions with varying physicochemical conditions. We collected samples of leaves, roots, sediment, and water from six sites throughout the Atlantic Ocean, Caribbean Sea, and the Gulf of Mexico. We then analyzed these samples using 16S rRNA amplicon sequencing. We found that site and region can influence the microbial communities of T. testudinum, while maintaining a plant-associated core microbiome. A comprehensive comparison of available microbial community data from T. testudinum studies determined a core microbiome composed of 14 ASVs that consisted mostly of the family Rhodobacteraceae. The most abundant genera in the microbial communities included organisms with possible plant-beneficial functions, like plant-growth promoting taxa, disease suppressing taxa, and nitrogen fixers.

Cohabitation with receptive females under D2-type agonism in adulthood restores partner preference and brain dimorphism in the SDN-POA following neonatal gonadectomy in male rats.

Perinatal testosterone, or its metabolite estradiol, organize the brain toward a male phenotype. Male rodents with insufficient testosterone during this period fail to display sexual behavior and partner preference for receptive females in adulthood. However, cohabitation with non-reproductive conspecifics under the influence of a D2 agonist facilitates the expression of conditioned partner preference via Pavlovian learning in gonadally intact male rats. In the present experiment, three groups of neonatal PD1 males (N = 12/group) were either gonadectomized (GDX), sham-GDX, or left intact and evaluated for social preferences and sexual behaviors as adults. We then examined whether the effects of GDX could be reversed by conditioning the males via cohabitation with receptive females under the effects of the D2 agonist quinpirole (QNP) or saline, along with the size of some brain regions, such as the sexually dimorphic nucleus of the preoptic area (SDN-POA), suprachiasmatic nucleus (SCN), posterior dorsal medial amygdala (MeApd) and ventromedial hypothalamus (VMH). Results indicated that neonatal GDX resulted in the elimination of male-typical sexual behavior, an increase in same-sex social preference, and a reduction of the area of the SDN-POA. However, GDX-QNP males that underwent exposure to receptive females in adulthood increased their social preference for females and recovered the size in the SDN-POA. Although neonatal GDX impairs sexual behavior and disrupts partner preference and brain dimorphism in adult male rats, Pavlovian conditioning under enhanced D2 agonism ameliorates the effects on social preference and restores brain dimorphism in the SDN-POA without testosterone.

A Qualitative Analysis of the Perceptions of Stakeholders Involved in Vector Control and Vector-Borne Disease Research and Surveillance in Orinoquia, Colombia.

Colombia has a tropical climate and environmental conditions that favour the circulation of most of the known vector-borne diseases (VBDs). Protocols have been established and implemented to address the threats of these diseases, but they are for country-wide use and do not take into consideration the nuances of the different environments of the country. Almost the entire population is vulnerable to infection with one or more VBD. This study aims to characterise the perceptions and experiences of stakeholders involved in vector control and VBDs in the Orinoquia region in Colombia. Two panel discussions, and 12 semi-structured interviews, were conducted. Experts from the Colombian National Health Institute (INS), health secretaries from Meta, Guaviare and Vichada Departments, academic researchers, and individuals from private vector control companies participated. All sessions were recorded, transcribed, and translated, and then subject to thematic analysis. Three major themes emerged: involvement, limitations, and recommendations. Results showed that participants are engaged in vector surveillance activities, education, and vector control research. Participants focused on problems of disjointed efforts towards VBD control between health secretaries and the health ministry, as well as societal issues, such as socioeconomic, cultural, and political issues, which became the rationale for the lack of vector control resources. Responses in the panel discussions and interviews overlapped in opinions, and suggested that vector control could be improved through better communication between vector control bodies, strengthened engagement with vulnerable communities, more collaborative actions, and a more balanced distribution of resources.

Cost-effectiveness of a police education program on HIV and overdose among people who inject drugs in Tijuana, Mexico.

Background: Incarceration is associated with drug-related harms among people who inject drugs (PWID). We trained >1800 police officers in Tijuana, Mexico on occupational safety and HIV/HCV, harm reduction, and decriminalization reforms (Proyecto Escudo). We evaluated its effect on incarceration, population impact and cost-effectiveness on HIV and fatal overdose among PWID. Methods: We assessed self-reported recent incarceration in a longitudinal cohort of PWID before and after Escudo. Segmented regression was used to compare linear trends in log risk of incarceration among PWID pre-Escudo (2012-2015) and post-Escudo (2016-2018). We estimated population impact using a dynamic model of HIV transmission and fatal overdose among PWID, with incarceration associated with syringe sharing and fatal overdose. The model was calibrated to HIV and incarceration patterns in Tijuana. We compared a scenario with Escudo (observed incarceration declines for 2 years post-Escudo among PWID from the segmented regression) compared to a counterfactual of no Escudo (continuation of stable pre-Escudo trends), assessing cost-effectiveness from a societal perspective. Using a 2-year intervention effect and 50-year time horizon, we determined the incremental cost-effectiveness ratio (ICER, in 2022 USD per disability-adjusted life years [DALYs] averted). Findings: Compared to stable incarceration pre-Escudo, for every three-month interval in the post-Escudo period, recent incarceration among PWID declined by 21% (adjusted relative risk = 0.79, 95% CI: 0.68-0.91). Based on these declines, we estimated 1.7% [95% interval: 0.7%-3.5%] of new HIV cases and 12.2% [4.5%-26.6%] of fatal overdoses among PWID were averted in the 2 years post-Escudo, compared to a counterfactual without Escudo. Escudo was cost-effective (ICER USD 3746/DALY averted compared to a willingness-to-pay threshold of $4842-$13,557). Interpretation: Escudo is a cost-effective structural intervention that aligned policing practices and human-rights-based public health practices, which could serve as a model for other settings where policing constitutes structural HIV and overdose risk among PWID. Funding: National Institute on Drug Abuse, UC MEXUS CONACyT, and the San Diego Center for AIDS Research (SD CFAR).

Participation of the nitric oxide pathway in lordosis induced by apelin-13 in female rats.

The present study investigated the participation of the nitric oxide pathway in facilitating lordosis behavior induced by intrahypothalamic administration of apelin-13 in ovariectomized rats primed with estradiol benzoate (EB). The experiments involved the administration of a nitric oxide synthase inhibitor (L-NAME) or a nitric oxide-dependent, soluble guanylyl cyclase inhibitor (ODQ), and an inhibitor of protein kinase G (KT5823) to the ventromedial hypothalamus (VMH) of EB-primed rats 30 min before infusion of apelin-13 (0.75 µg/µl). This dose of apelin-13 consistently induces lordosis behavior at 30 min, 120 min, and 240 min following infusion. Results showed that injections of either L-NAME or KT5823 significantly reduced the lordosis induced by apelin at 120 and 240 min. However, VMH infusion of ODQ 30 min before apelin-13 infusion reduced but did not significantly inhibit, the lordosis elicited by this peptide at the same time points. We conclude that the nitric oxide pathway in the VMH plays an important role in lordosis induced by apelin-13 in EB-primed rats.

Cochlear Implant Outcomes in the Chinese-Speaking Adult Population: A Systematic Review.

OBJECTIVE: The purpose of this study is to perform a systematic review of speech perception outcomes in the Chinese-speaking adult cochlear implant (CI) population. DATABASES REVIEWED: PubMed, EMbase, and Scopus. METHODS: A comprehensive English literature search was performed with MeSH search terms, keywords, and phrases. Literature written in a language other than English was not included. Full-text articles were screened by two blinded reviewers and adjudicated by a third. Relevant outcomes and demographic data were extracted. Qualitative summaries were performed of the demographics and assessment tools. Speech perception outcomes were assessed with quantitative measures. RESULTS: Forty-four studies (n = 467) notable for marked heterogeneity in speech perception assessment utilized and reporting of relevant patient demographics were included. Mean duration of deafness among studies reporting this metric was 10.27 years (range, 0.08-49; SD, 7.70; n = 250), with 80% of subjects reporting >5 years' duration of deafness and only 19 subjects (7.6%) with <1 year of deafness preimplantation. A summary of the most commonly used assessments is provided. CONCLUSION: Within the English-language literature, there is marked heterogeneity and lack of standardization regarding speech perception outcomes, tests utilized, and reported patient demographics in the Chinese-speaking adult CI population. Most Chinese-speaking CI users for whom data were available had prolonged duration of deafness before implantation. This study may serve as an initial reference for providers counseling Chinese-language CI candidates and who may be interested in adopting these tests, while highlighting the need for continued efforts to measure speech perception outcomes after CI for tonal language speakers.

Guselkumab More Effectively Neutralizes Psoriasis-Associated Histologic, Transcriptomic, and Clinical Measures than Ustekinumab.

Given the key role of the IL-23/Th17 axis in the pathogenesis of moderate-to-severe plaque psoriasis, several specific inhibitors of the p19 subunit of IL-23 have been approved to treat this chronic inflammatory disease. Clinical data indicate that guselkumab, one such selective IL-23 inhibitor, achieves greater clinical efficacy compared with ustekinumab, which inhibits both IL-12 and IL-23 via binding their shared p40 subunit. To understand mechanisms underlying the enhanced efficacy observed with the p19 subunit of IL-23-specific inhibition, we explored cellular and molecular changes in skin of psoriasis patients treated with ustekinumab or guselkumab and in ustekinumab inadequate responders (Investigator's Global Assessment of psoriasis score ≥ 2) subsequently treated with guselkumab (ustekinumab→guselkumab). Skin biopsies were collected pretreatment and posttreatment to assess histologic changes and molecular responses in ustekinumab- and guselkumab-treated patients. Serum cytokines and skin transcriptomics from the subset of ustekinumab→guselkumab-treated patients were also analyzed to characterize differential treatment effects. Ustekinumab and guselkumab demonstrated differential effects on secretion of pathogenic Th17-related cytokines induced by IL-23 in in vitro assays, which suggest guselkumab is a more potent therapeutic agent. Consistent with these findings, guselkumab elicited a significantly greater reduction in cellular and molecular psoriasis-related disease indicators than ustekinumab. In ustekinumab→guselkumab patients, suppression of serum IL-17A and IL-17F levels and neutralization of molecular scar and psoriasis-related gene markers in skin were significantly greater compared with patients continuing ustekinumab. This comparative study demonstrates that guselkumab inhibits psoriasis-associated pathology, suppresses Th17-related serum cytokines, and normalizes the psoriasis skin gene expression profile more effectively than ustekinumab.

Shotgun Metagenomics of Gastric Biopsies Reveals Compositional and Functional Microbiome Shifts in High- and Low-Gastric-Cancer-Risk Populations from Colombia, South America.

Along with Helicobacter pylori infection, the gastric microbiota is hypothesized to modulate stomach cancer risk in susceptible individuals. Whole metagenomic shotgun sequencing (WMS) is a sequencing approach to characterize the microbiome with advantages over traditional culture and 16S rRNA sequencing including identification of bacterial and non-bacterial taxa, species/strain resolution, and functional characterization of the microbiota. In this study, we used WMS to survey the microbiome in extracted DNA from antral gastric biopsy samples from Colombian patients residing in the high-risk gastric cancer town Túquerres (n = 10, H. pylori-positive = 7) and low-risk town of Tumaco (n = 10, H. pylori-positive = 6). Kraken2/Bracken was used for taxonomic classification and abundance. Functional gene profiles were inferred by InterProScan and KEGG analysis of assembled contigs and gene annotation. The most abundant taxa represented bacteria, non-human eukaryota, and viral genera found in skin, oral, food, and plant/soil environments including Staphylococus, Streptococcus, Bacillus, Aspergillus, and Siphoviridae. H. pylori was the predominant taxa present in H. pylori-positive samples. Beta diversity was significantly different based on H. pylori-status, risk group, and sex. WMS detected more bacterial taxa than 16S rRNA sequencing and aerobic, anaerobic, and microaerobic culture performed on the same gastric biopsy samples. WMS identified significant differences in functional profiles found between H. pylori-status, but not risk or sex groups. H. pylori-positive samples were significantly enriched for H. pylori-specific genes including virulence factors such as vacA, cagA, and urease, while carbohydrate and amino acid metabolism genes were enriched in H. pylori-negative samples. This study shows WMS has the potential to characterize the taxonomy and function of the gastric microbiome as risk factors for H. pylori-associated gastric disease. Future studies will be needed to compare and validate WMS versus traditional culture and 16S rRNA sequencing approaches for characterization of the gastric microbiome.

High level of novelty under the hood of convergent evolution.

Little is known about the extent to which species use homologous regulatory architectures to achieve phenotypic convergence. By characterizing chromatin accessibility and gene expression in developing wing tissues, we compared the regulatory architecture of convergence between a pair of mimetic butterfly species. Although a handful of color pattern genes are known to be involved in their convergence, our data suggest that different mutational paths underlie the integration of these genes into wing pattern development. This is supported by a large fraction of accessible chromatin being exclusive to each species, including the de novo lineage-specific evolution of a modular optix enhancer. These findings may be explained by a high level of developmental drift and evolutionary contingency that occurs during the independent evolution of mimicry.

Repellent Screening of Selected Plant Essential Oils Against Dengue Fever Mosquitoes Using Behavior Bioassays.

Among the efforts to reduce mosquito-transmitted diseases, such as malaria and dengue fever, essential oils (EOs) have become increasingly popular as natural replacements for the repellant DEET. In this study, seven commercially available plant EOs against Aedes species mosquitoes were evaluated for their complete protection time (CPT, min) in vivo using human-hand in cage tests (GB2009/China and WHO2009). Among the EOs with the highest efficacy in repelling mosquitoes, Aedes albopictus (Skuse) were clove bud oil and patchouli oil. Both were further assessed according to the in vivo method recommended by the WHO, to determine their minimum effective dose and CPT. A comparison of the ED50 values (dose yielding a 50% repellent response) of these two EOs against Aedes aegypti(L.) showed that the ED50 (2.496 µg/cm2) of patchouli oil was 1248 times higher than that of clove bud oil (0.002 µg/cm2), thus demonstrating them greater efficacy of the latter in repelling Ae. aegypti mosquitoes. For the 2 EOs, eugenol was the major component with higher than 80% in relative amount of the clove bud oil. The patchouli oil had more than 30% of character chemical patchouli alcohol along with α-bulnesene (10.962%), α-guaiene (9.227%), and seychellene (7.566%). Clove bud oil was found to confer longer complete protection than patchouli oil against a common species of mosquito. These results suggest use of EOs as safe, highly potent repellents for use in daily life and against mosquito-transmitted diseases, such as malaria and dengue fever.

Smartphone intervention to optimize medication assisted treatment outcomes for opioid use disorder: study protocol for a randomized controlled trial.

Background: Opioids accounted for 75% of drug overdoses in the United States in 2020, with rural states particularly impacted by the opioid crisis. While medication assisted treatment (MAT) with Suboxone remains one of the more efficacious treatments for opioid use disorder (OUD), approximately 40% of people receiving Suboxone for outpatient MAT for OUD (MOUD) relapse within the first 6 months of treatment. We developed the smartphone app-based intervention OptiMAT as an adjunctive intervention to improve MOUD outcomes. The aims of this study are to (1) evaluate the efficacy of adjunctive OptiMAT use in reducing opioid misuse among people receiving MOUD; and (2) evaluate the role of specific OpitMAT features in reducing opioid misuse, including the use of GPS-driven just-in-time intervention. Methods: We will conduct a two-arm, single-blind, randomized controlled trial of adults receiving outpatient MOUD in the greater Little Rock AR area. Participants are English-speaking adults ages 18 or older recently enrolled in outpatient MOUD at one of our participating study clinics. Participants will be allocated via 1:1 randomized block design to (1) MOUD with adjunctive use of OptiMAT (MOUD+OptiMAT) or (2) MOUD without OptiMAT (MOUD-only). Our blinded research statistician will evaluate differences between the two groups in opioid misuse (as determined by quantitative urinalysis conducted by clinical lab staff blinded to group membership) during the 6-months following study enrolment. Secondary analyses will evaluate if OptiMAT-usage patterns within the MOUD+OptiMAT group predict opioid misuse or continued abstinence. Discussion: This study will test if adjunctive use of OptiMAT improve MOUD outcomes. Study findings could lead to expansion of OptiMAT into rural clinical settings, and the identification of OptiMAT features which best predict positive clinical outcome could lead to refinement of this and similar smartphone appbased interventions. Trial registration: ClinicalTrials.gov identifier: NCT05336188, registered March 21, 2022, https://clinicaltrials.gov/ct2/show/NCT05336188.

Corticosteroids for patients with vestibular neuritis: An evidence synthesis for guidelines for reasonable and appropriate care in the emergency department.

BACKGROUND: A short course of corticosteroids is among the management strategies considered by specialists for the treatment of vestibular neuritis (VN). We conducted an umbrella review (systematic review of systematic reviews) to summarize the evidence of corticosteroids use for the treatment of VN. METHODS: We included systematic reviews of randomized controlled trials (RCTs) and observational studies that evaluated the effects of corticosteroids compared to placebo or usual care in adult patients with acute VN. Titles, abstracts, and full texts were screened in duplicate. The quality of reviews was assessed with the A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) tool. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) assessment was used to rate certainty of evidence. No meta-analysis was performed. RESULTS: From 149 titles, five systematic reviews were selected for quality assessment, and two reviews were of higher methodological quality and were included. These two reviews included 12 individual studies and 660 patients with VN. In a meta-analysis of two RCTs including a total of 50 patients, the use of corticosteroids (compared to placebo) was associated with higher complete caloric recovery (risk ratio 2.81, 95% confidence interval [CI] 1.32 to 6.00, low certainty). It is very uncertain whether this translates into clinical improvement as shown by the imprecise effect estimates for outcomes such as patient-reported vertigo or patient-reported dizziness disability. There was a wide CI for the outcome of dizziness handicap score (one study, 30 patients, 20.9 points in corticosteroids group vs. 15.8 points in placebo, mean difference +5.1, 95% CI -8.09 to +18.29, very low certainty). Higher rates of minor adverse effects for those receiving corticosteroids were reported, but the certainty in this evidence was very low. CONCLUSIONS: There is limited evidence to support the use of corticosteroids for the treatment of VN in the emergency department.

Adolescent Suicide Risk Screening: A Secondary Analysis of the SHIELD Randomized Clinical Trial.

OBJECTIVE: To evaluate the effectiveness of adolescent suicide risk screening to increase initiation of mental health services via a secondary analysis using data from the SHIELD (Screening in High Schools to Identify, Evaluate and Lower Depression) randomized clinical trial, which evaluated school-based screening for major depressive disorder (MDD). STUDY DESIGN: Students in 14 Pennsylvania high schools were randomized by grade to either the usual school practice of targeted referral for behavior raising a concern for suicide risk or universal screening using the Patient Health Questionnaire-9 (PHQ-9), with any response >0 to item 9 regarding suicide risk considered positive. Students identified in either arm were referred to the Student Assistance Program (SAP), which is mandated in all Pennsylvania schools. The SAP determined follow-up. Study groups were compared using mixed-effects logistic regression. RESULTS: The participants comprised 12 909 students, with 6473 (50.1%) randomized to universal screening. The study group was 46% female and 43% Hispanic or non-Hispanic Black. Adolescents in the universal screening arm had 7.1-fold greater odds (95% CI, 5.7-8.8) of being identified as at risk for suicide, 7.8-fold greater odds (95% CI, 4.6-13.1) of follow-up needs, and 4.0-fold greater odds (95% CI, 2.0-7.9) of initiating mental health treatment. CONCLUSIONS: Although the PHQ-9 is a MDD screening tool, its use in universal screening increased identification and treatment initiation for adolescents at risk for suicide. This confirms the value of universal screening and suggests that a suicide-specific risk assessment would have even greater impact on treatment initiation for identified youth. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03716869.

Tissue-specific expression of Ruby in Mexican lime (C. aurantifolia) confers anthocyanin accumulation in fruit.

Tissue specific promoters are important tools for the precise genetic engineering of crop plants. Four fruit-preferential promoters were examined for their ability to confer a novel fruit trait in transgenic Mexican lime (Citrus aurantifolia). The Ruby transcription factor activates fruit anthocyanin accumulation within Moro blood orange and has been shown to function in activating anthocyanin accumulation in heterologous plant species. Although the CitVO1, CitUNK, SlE8, and PamMybA promoters were previously shown to confer strong fruit-preferential expression in transgenic tomato, they exhibited no detectable expression in transgenic Mexican lime trees. In contrast, the CitWax promoter exhibited high fruit-preferential expression of Ruby, conferring strong anthocyanin accumulation within the fruit juice sac tissue and moderate activity in floral/reproductive tissues. In some of the transgenic trees with high levels of flower and fruit anthocyanin accumulation, juvenile leaves also exhibited purple coloration, but the color disappeared as the leaves matured. We show that the CitWax promoter enables the expression of Ruby to produce anthocyanin colored fruit desired by consumers. The production of this antioxidant metabolite increases the fruits nutritional value and may provide added health benefits.

Behavioral, Neural, and Molecular Mechanisms of Conditioned Mate Preference: The Role of Opioids and First Experiences of Sexual Reward.

Although mechanisms of mate preference are thought to be relatively hard-wired, experience with appetitive and consummatory sexual reward has been shown to condition preferences for partner related cues and even objects that predict sexual reward. Here, we reviewed evidence from laboratory species and humans on sexually conditioned place, partner, and ejaculatory preferences in males and females, as well as the neurochemical, molecular, and epigenetic mechanisms putatively responsible. From a comprehensive review of the available data, we concluded that opioid transmission at µ opioid receptors forms the basis of sexual pleasure and reward, which then sensitizes dopamine, oxytocin, and vasopressin systems responsible for attention, arousal, and bonding, leading to cortical activation that creates awareness of attraction and desire. First experiences with sexual reward states follow a pattern of sexual imprinting, during which partner- and/or object-related cues become crystallized by conditioning into idiosyncratic "types" that are found sexually attractive and arousing. These mechanisms tie reward and reproduction together, blending proximate and ultimate causality in the maintenance of variability within a species.

Increased Repellent Effect of DEET on Aedes aegypti (Diptera: Culicidae) Field Population.

Insecticides and repellents are routinely used in Brazil because of the high rates of arbovirus transmission and the nuisance caused by mosquitoes. However, few studies have assessed the effectiveness of repellents against mosquito populations that have been under exposure to xenobiotics, mainly insecticides and repellents. This study investigated the sensitivity of a field population of Aedes aegypti (Linnaeus, 1762) from a dengue-endemic area under high insecticide pressure to N,N-diethylmethylbenzamide (DEET), the active ingredient in common repellent products. The field (Laranjeiras, Sergipe, Brazil) and laboratory (Rockefeller) populations were characterized for the presence of the Val1016Ile kdr mutation, associated with pyrethroid resistance, and locomotor activity. Repellency bioassays were performed to assess the response of the mosquitoes to human odor by exposing them to 10% DEET applied to the skin in ethanol. Samples from the field population showed higher frequency of the kdr mutation, 21.9% homozygous and 21.9% heterozygous, greater locomotor activity and greater sensitivity to DEET than the laboratory population. These results suggest increased sensitivity to DEET in field populations and a possible interaction between insecticide exposure and sensitivity to DEET.