Accuracy of Primary Care Medical Home Designation in a Specialty Mental Health Clinic.

To assess whether primary care medical homes (PCMHs) are accurately identified for patients receiving care in a specialty mental health clinic within an integrated public delivery system. This study reviewed the electronic records of patients in a large urban mental health clinic. The study defined 'matching PCMH' if the same primary care clinic was listed in both the mental health and medical electronic records. This study designated all others as 'PCMH unknown.' This study assessed whether demographic factors predicted PCMH status using chi-square tests. Among 229 patients (66% male; mean age 49; 36% White, 30% Black, and 17% Asian), 72% had a matching PCMH. Sex, age, race, psychiatric diagnosis, and psychotropic medication use were not associated with matching PCMH. To improve care coordination and health outcomes for people with severe mental illness, greater efforts are needed to ensure the accurate designation of PCMHs in all mental health patient electronic records.

Unmet Mental Health Need Among Chinese and Latino Primary Care Patients: Intersection of Ethnicity, Gender, and English Proficiency.

BACKGROUND: Ethnic minorities who present with mental health symptoms in primary care are less likely to receive treatment than non-Hispanic whites; language barriers may magnify this disparity. OBJECTIVE: We examined the contributions of ethnicity, gender, and English proficiency to unmet mental health need. DESIGN: Cross-sectional study. PARTICIPANTS: Chinese and Latino primary care patients with a preferred language of English, Cantonese, Mandarin, or Spanish. MAIN MEASURES: Participants were interviewed within 1 week of a primary care visit and asked whether in the prior year they (1) needed help with emotional or mental health symptoms and (2) had seen a primary care physician or a mental health professional for these symptoms. Among those who reported "mental health need," we defined "unmet mental health need" as no reported use of services for these symptoms. Regression models explored independent and interaction effects among ethnicity, gender, and English proficiency, on the two outcomes. KEY RESULTS: Among 1149 participants (62% women; 262 Chinese, with English proficiency [EP], 532 Chinese, with limited English proficiency [LEP], 172 Latino with EP; and 183 Latino with LEP), 33% reported mental health need. Among Chinese, but not Latino, participants, those with LEP were more likely than those with EP to report mental health need (AOR 2.55, 95% CI 1.73-3.76). Women were more likely to report mental health need than men (AOR 1.35, 1.03-1.79) regardless of ethnicity or English proficiency. Among participants reporting mental health need, 41% had unmet mental health need. Men with LEP, compared with those with EP, were more likely to have unmet mental health need regardless of ethnicity (AOR 2.53, 1.06-6.04). CONCLUSIONS: We found high levels of mental health symptoms and unmet mental health need in both Chinese and Latino primary care patients. These results affirm the need to implement depression screening and targeted treatment interventions for patient subgroups at highest risk of untreated symptoms, such as men with LEP.

Inhibition of transcription and translation in dorsal hippocampus does not interfere with consolidation of memory of intense training.

Findings of several experiments indicate that many treatments that typically interfere with memory consolidation are ineffective in preventing or attenuating memory induced by intense training. As extensive evidence suggests that the consolidation of newly acquired memories requires gene expression and de novo protein synthesis the present study investigated whether intense training prevents consolidation impairment induced by blockers of mRNA and protein synthesis. Rats were given a single inhibitory training trial using a moderate (1.0 mA) or a relatively intense (2.0 mA) foot-shock. Bilateral hippocampal infusions of the mRNA synthesis blocker DRB (10, 40 or 80 ng/0.5 µL/hemisphere) or the protein synthesis inhibitor anisomycin (ANI), an inhibitor de novo protein synthesis (15.62, 31.25, or 62.50 µg/0.5 µL/hemisphere) were administered 15 min prior to training. Retention was measured at 30 min or 48 h following training. DRB and ANI impaired memory of moderate training in a dose-dependent manner without affecting short-term memory. In contrast, memory consolidation was not impaired in the groups trained with 2.0 mA. The findings showed that: (1) inhibitors of transcription and translation in the hippocampus impair the consolidation of memory of inhibitory avoidance learning induced by moderate levels of aversive stimulation and (2) blocking of mRNA and protein synthesis does not prevent the consolidation of memory induced by relatively high levels of aversive stimulation. These findings do not support the hypothesis that gene expression and de novo protein synthesis are necessary steps for long-term memory formation as memory was not impaired if intense foot-shock was used in training.

Phytochemical Findings Evidencing Botanical Origin of New Propolis Type from North-West Argentina.

Propolis samples from north-west Argentina (Amaicha del Valle, Tucumán) were evaluated by palynology, FT-IR spectra, and RP-HPTLC. In addition, the volatile fraction was studied by HS-SPME-GC/MS. The botanical species most visited by Apis mellifera L. near the apiaries were collected and their RP-HPTLC extracts profiles were compared with propolis samples. In addition, GC/MS was performed for volatile compounds from Zuccagnia punctata Cav. (Fabaceae). FT-IR spectra and RP-HPTLC fingerprints of propolis samples showed similar profiles. In RP-HPTLC analyses, only Z. punctata presented a similar fingerprint to Amaicha propolis. The major volatile compounds present in both were trans-linalool oxide (furanoid), 6-camphenone, linalool, trans-pinocarveol, p-cymen-8-ol, and 2,3,6-trimethylbenzaldehyde. Potential variations for the Amaicha del Valle propolis volatile fraction as consequence of propolis sample preparation were demonstrated.

Collaborative Care for Depression among Patients with Limited English Proficiency: a Systematic Review.

BACKGROUND: Patients with limited English proficiency (LEP) have high rates of depression, yet face challenges accessing effective care in outpatient settings. We undertook a systematic review to investigate the effectiveness of the collaborative care model for depression for LEP patients in primary care. METHODS: We queried online PubMed, PsycINFO, CINAHL and EMBASE databases (January 1, 2000, to June 10, 2017) for quantitative studies comparing collaborative care to usual care to treat depression in adults with LEP in primary care. We evaluated the impact of collaborative care on depressive symptoms or on depression treatment. Two reviewers independently extracted key data from the studies and assessed risk of bias using the Cochrane bias and quality assessment tool (RCTs) and the Newcastle-Ottawa Quality Assessment Scale (non-RCTs). RESULTS: Of 86 titles identified, 15 were included (representing 9 studies: 5 RCTs, 3 cohort studies, and 1 case-control study). Studies included 4859 participants; 2679 (55%) reported LEP. The majority spoke Spanish (93%). The wide variability in study design and outcome definitions precluded performing a meta-analysis. Follow-up ranged from 3 months to 2 years. Three of four high-quality RCTs reported that 13-25% more patients had improved depressive symptoms when treated with culturally tailored collaborative care compared to usual care; the last had high treatment in the control arm and found equal improvement. Two non-RCT studies suggest that Spanish-speaking patients may benefit as much as, if not more than, English-speaking patients treated with collaborative care. The remaining studies reported increased receipt of preferred depression treatment (therapy vs. antidepressants) in the intervention groups. Eight of nine studies used bilingual providers to deliver the intervention. DISCUSSION: While limited by the number and variability of studies, the available research suggests that collaborative care for depression delivered by bilingual providers may be more effective than usual care among patients with LEP. Implementation studies of collaborative care, particularly among Asian and non-Spanish-speakers, are needed.

Which Complex Patients Should Be Referred for Intensive Care Management? A Mixed-Methods Analysis.

BACKGROUND: A large and increasing proportion of health care costs are spent caring for a small segment of medically and socially complex patients. To date, it has been difficult to identify which patients are best served by intensive care management. OBJECTIVE: To characterize factors that best identify which complex patients are most suited for intensive care management. DESIGN: We conducted a mixed-methods study involving 35 care managers (CMs; 10 licensed social workers and 25 registered nurses) working in intensive care management programs within Kaiser Permanente Northern California (KPNC) outpatient medical centers. We asked CMs to review a randomly selected list of up to 50 patients referred to them in the prior year and to categorize each patient as either (1) "good candidates" for care management, (2) "not needing" intensive care management, or (3) "needing more" than traditional care management could provide. We then conducted semi-structured interviews to understand how CMs separated patients into these three groups. RESULTS: CMs assigned 1178 patients into the 3 referral categories. Less than two thirds (62%, n = 736) of referred patients were considered good candidates, with 18% (n = 216) categorized as not needing care management and 19% (n = 226) as needing more. Compared to the other two categories, good candidates were older (76.2 years vs. 73.2 for not needing and 69.8 for needing more, p < 0.001), prescribed more medications (p = 0.02) and had more prior year outpatient visits (p = 0.04), while the number of prior year hospital and emergency room admissions were greater than not needing but less than needing more (p < 0.001). A logistic regression model using available electronic record data predicted good candidate designation with a c statistic of 0.75. Several qualitative themes emerged that helped define appropriateness for referral, including availability of social support, patient motivation, non-medical transitions, recent trajectory of medical condition, and psychiatric or substance use issues. CONCLUSION: Many apparently complex patients are not good candidates for intensive care management. Current electronic medical records do not capture several of the most salient characteristics that determine appropriateness for care management. Our findings suggest that systematic collection of social support, patient motivation, and recent non-medically related life change information may help identify which complex patients are most likely to benefit from care management.

[Antimicrobial susceptibility of Helicobacter pylori strains isolated from gastric lesions]. / Sensibilidad a los antimicrobianos de aislamientos de Helicobacter pylori aislados de lesiones gástricas.

Antimicrobial susceptibility was evaluated by two diffusion methods: E-test strips to determine minimum inhibitory concentration (MIC) and disk diffusion for amoxicillin, clarithromycin, metronidazole and ciprofloxacin in 30 Helicobacter pylori strains isolated from gastric biopsies. No strains were resistant to amoxicillin, 17% (5/30) were resistant to clarithromycin, 20% (6/30) ciprofloxacin by both methods, and 37% (11/30) to metronidazole by the E-test. Although the number of strains studied was reduced, there was a single mismatch in interpreting susceptibility when both methods were compared; the same mismatch was observed for metronidazole, being categorized as sensitive by the E-test and as intermediate by disk diffusion. No association between the histological type of lesion and the resistance pattern found could be determined.

Association of maternal depression and infant nutritional status among women living with HIV in Tanzania.

Antenatal and post-natal depression has demonstrated a significant burden in sub-Saharan Africa, with rates ranging from 10% to 35%. However, perinatal women living with HIV in Tanzania have reported an even greater prevalence of depression (43-45%). The primary goal of this study was to examine the relationship between maternal depression and infant malnutrition among women living with HIV. The design was a retrospective cohort study within the context of a randomised controlled trial among women living with HIV and their infants. Within this trial, 699 mother-child pairs were analysed for the present study. Although antenatal depression was not associated with infant malnutrition and post-natal depression was negatively associated [relative risk (RR = 0.80, P = 0.04], cumulative depression demonstrated a positive association with infant wasting (RR = 1.08, P < 0.01) and underweight (RR = 1.03, P < 0.01) after controlling for confounding factors. Variation in the association between depression and infant nutritional status was observed for episodic vs. chronic depression. These findings suggest that providing evidence-based services for persistent depression among women living with HIV may have an effect on infant malnutrition. In addition, other positive outcomes may be related to infant cognitive development as well as HIV disease prognosis and survival among women.

Barriers and facilitators to depression care among Latino men in a primary care setting: a qualitative study.

BACKGROUND: In the United States, Latinos face a wide array of cultural and structural barriers to accessing and utilizing mental health care. Latino men specifically are at high risk of receiving inadequate mental health care, possibly due to additional obstacles they experience that are related to masculinity. Among men more generally, greater adherence to emotional control and self-reliance is associated with higher depression severity and less depression help-seeking. Men experience more stigma toward depression and help-seeking and are less likely to be diagnosed with depression than women. However, Latino men's barriers and facilitators to depression care remain largely unexplored. The objective of this study was to examine barriers and facilitators to depression care that are related to masculinity among English- and Spanish-speaking Latino men in a primary care setting. METHODS: We used convenience and purposive sampling to recruit primary care patients who self-identified as Latino men, spoke English or Spanish, and screened positive for depressive symptoms on the Patient Health Questionnaire-2 or had a history of depression. Semi-structured interviews were conducted between December 2020 and August 2021. The interview guide examined views and experiences of depression, masculinity, and barriers and facilitators to engaging in depression care. Utilizing consensual qualitative research and thematic analysis informed by modified grounded theory, barriers and facilitators to depression care were identified. RESULTS: We interviewed thirteen participants who varied in English proficiency, education, income, and country of origin. Barriers and facilitators were placed into three domains-Self-Recognition of Depression, Seeking Help for Depression, and Depression Diagnosis and Treatment. Participants described aspects of masculinity as barriers (emotional control and pressure to provide), facilitators (honesty, courage, collaboration, practicality, and responsibility), or both (self-reliance and autonomy). CONCLUSIONS: Masculinity influences barriers and facilitators for depression care among Latino men at the levels of self-recognition, seeking help, and diagnosis and treatment. Clinicians may promote Latino men's engagement in depression care by understanding patients' values and framing depression care as affirming masculinity. Providing education to primary care physicians and other healthcare professionals on gender and depression and addressing structural barriers are essential to providing access to all who need depression care.

First-generation college graduates have similar depressive symptoms in midlife as multi-generational college graduates.

Purpose: Higher education may protect an individual against depressive symptoms, yet, disadvantaged socioeconomic status (SES) during childhood, often measured by lower parental education, may put them at higher risk for depressive symptoms later in life. This study evaluates if midlife depression is similar for first-generation and multi-generation college graduates. Methods: For US Health and Retirement Study (HRS) participants ages 55-63 (N = 16,752), we defined a 4-category exposure from parents' (highest of mother or father's) and participant's own years of education, with 16 years indicating college completion: multi-gen (both ≥ 16 years: reference); first-gen (parents <16; own ≥ 16); only parent(s) (parents ≥ 16; own <16); and neither (both <16) college graduates across three birth cohorts. We used linear regressions to evaluate relationships between college completion and depressive symptoms measured by an 8-item Center for Epidemiologic Studies - Depression (CES-D) scale. Models pooled over time evaluated differences by sex, race/ethnicity, and birthplace. Results: First-gen and multi-gen college graduates averaged similar depressive symptoms in midlife (ß: 0.01; 95% CI: 0.15, 0.13). Results were similar by sex and race/ethnicity. Conclusion: Consistent with resource substitution theory, college completion may offset the deleterious effects of lower parental education on midlife depressive symptoms for first-generation graduates.

Language Access Systems Improvement initiative: impact on professional interpreter utilisation, a natural experiment.

OBJECTIVES: This study aims to evaluate the Language Access Systems Improvement (LASI) initiative's impact on professional interpreter utilisation in primary care and to explore patient and clinician perspectives on professional interpreter use. DESIGN: Multi methods: Quantitative natural experiment pre-LASI and post-LASI, qualitative semistructured interviews with clinicians and focus groups with patients post-LASI. SETTING: Large, academic primary care practice. PARTICIPANTS: Cantonese, Mandarin, Spanish, English-speaking adult patients and their clinicians. INTERVENTION: LASI initiative: Implementation of a clinician language proficiency test and simultaneous provision of on-demand access to professional interpreters via video medical interpretation. MAIN OUTCOME MEASURES: Quantitative: Proportion of language discordant primary care visits which were professionally interpreted. Qualitative: Salient themes related to professional interpreter use and non-use. RESULTS: The researchers categorised language concordance for 1475 visits with 152 unique clinicians; 698 were not fully language concordant (202 pre-LASI and 496 post-LASI). Professional interpreter utilisation increased (pre-LASI 57% vs post-LASI 66%; p=0.01); the visits with the lowest percentage of profssional interpreter use post-LASI were those in which clinicians and patients had partial language concordance. In inverse probability weighted analysis, restricting to 499 visits with strict estimated propensity score overlap (100% common support), post-LASI visits had higher odds of using a professional interpreter compared with pre-LASI visits (OR 2.39; 95% CI 1.04 to 5.48). Qualitative results demonstrate video interpretation was convenient and well liked by both clinicians and patients. Some partially bilingual clinicians reported frustration with patient refusal of interpreter services; others reported using the video interpreters as a backup during visits. Views of the care-partner role differed for clinicians and patients. Clinicians reported sometimes having family interpret out of convenience or habit, whereas patients reported wanting family members present for support and advocacy, not interpretation. CONCLUSIONS: LASI increased utilisation of professional interpreters; however, this was least prominent for partially language concordant visits. Health systems wishing to implement LASI or similar interventions will need to support clinicians and patients with partial bilingual skills in their efforts to use professional interpreters. TRIAL REGISTRATION NUMBER: HSRP20153367.

Bring It Up: An Adapted Collaborative Care Model for Depression in a Safety-Net Primary Care Clinic.

Objective: Over 90 clinical trials demonstrate the efficacy of the collaborative care model (CoCM) to treat depression in primary care but there is significant variability in real-world CoCM implementation and scalability. This study aimed to determine the feasibility and effectiveness of an adapted CoCM in a safety-net primary care setting. Methods: Bring It Up! (BIU) is a pilot trial comparing an adapted CoCM (intervention group) to usual care (historical controls) for primary care safety-net clinic patients with depression. Inclusion criteria: (1) age ≥18; (2) Patient Health Questionnaire-9 (PHQ-9) score ≥10; and (3) major depressive disorder diagnosis. Patients who completed ≥6 months of treatment upon rolling enrollment (April 1, 2018-October 31, 2019) were included. Historical controls completed ≥6 months of usual care in 2017. BIU included all aspects of CoCM except accountable care and leveraged existing staff rather than a dedicated care manager. The primary outcome was depression remission (PHQ-9 <5) within 6 months. Secondary outcomes included depression response, adherence to treatment guidelines and care coordination process. Data were extracted from the electronic health record. Results: Thirty-six patients received the intervention; 41 controls received usual care. Depression remission was achieved in 33.3% of intervention patients and 0% of controls (p = 0.001). Of intervention patients, 44.4% achieved ≥50% reduction in PHQ-9 compared to 4.9% of controls (p = 0.003). Further, 66.7% of intervention patients had guideline-recommended antidepressant medication titration compared to 26.9% of controls (p = 0.003); 94.4% of intervention patients had PHQ-9 repeated compared to 53.7% of controls (p < 0.001). Conclusions: An adapted CoCM was feasible and improved depression care in a safety-net clinic.

Validity of the Spanish-Language Patient Health Questionnaires 2 and 9: A Systematic Review and Meta-Analysis.

Importance: Reliable screening for major depressive disorder (MDD) relies on valid and accurate screening tools. Objective: To examine the validity, accuracy, and reliability of the Spanish-language Patient Health Questionnaires 2 and 9 (PHQ-2 and PHQ-9) to screen for MDD. Data Sources: PubMed, Web of Science, Embase, and PsycINFO from data initiation through February 27, 2023. Study Selection: English- and Spanish-language studies evaluating the validity of the Spanish-language PHQ-2 or PHQ-9 in screening adults for MDD compared with a standardized clinical interview (gold standard). Search terms included PHQ-2, PHQ-9, depression, and Spanish. Data Extraction and Synthesis: Two reviewers performed abstract and full-text reviews, data extraction, and quality assessment. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Random-effects meta-analyses of sensitivity, specificity, and area under the curve (AUC) were performed. Internal consistency was evaluated using Cronbach α and McDonald ψ. Main Outcomes and Measures: Test accuracy and internal consistency. The PHQ-2 is composed of the first 2 questions of the PHQ-9 (targeting core depression symptoms of depressed mood and anhedonia; a score of 3 or higher (score range, 0-6) is generally considered a positive depression screen. If a patient screens positive with the PHQ-2, a follow-up assessment with the PHQ-9 and a clinical diagnostic evaluation are recommended. Once depression is diagnosed, a PHQ-9 score of 10 or higher (score range, 0-27) is often considered an acceptable threshold for treating depression. Results: Ten cross-sectional studies involving 5164 Spanish-speaking adults (mean age range, 34.1-71.8 years) were included; most studies (n = 8) were in primary care settings. One study evaluated the PHQ-2, 7 evaluated the PHQ-9, and 2 evaluated both the PHQ-2 and PHQ-9. For the PHQ-2, optimal cutoff scores ranged from greater than or equal to 1 to greater than or equal to 2, with an overall pooled sensitivity of 0.89 (95% CI, 0.81-0.95), overall pooled specificity of 0.89 (95% CI, 0.81-0.95), and overall pooled AUC of 0.87 (95% CI, 0.83-0.90); Cronbach α was 0.71 to 0.75, and McDonald ψ was 0.71. For the PHQ-9, optimal cutoff scores ranged from greater than or equal to 5 to greater than or equal to 12, with an overall pooled sensitivity of 0.86 (95% CI, 0.82-0.90), overall pooled specificity of 0.80 (95% CI, 0.75-0.85), and overall pooled AUC of 0.88 (95% CI, 0.87-0.90); Cronbach α was 0.78 to 0.90, and McDonald ψ was 0.79 to 0.90. Four studies were considered to have low risk of bias; 6 studies had indeterminate risk of bias due to a lack of blinding information. Conclusions and Relevance: In this systematic review and meta-analysis, limited available evidence supported the use of the Spanish-language PHQ-2 and PHQ-9 in screening for MDD, but optimal cutoff scores varied greatly across studies, and few studies reported on blinding schemes. These results suggest that MDD should be considered in Spanish-speaking individuals with lower test scores. Given the widespread clinical use of the tools and the heterogeneity of existing evidence, further investigation is needed.

"Long Overdue": Nurse and Resident Physician Perspectives on Implementation of Dual-Handset Interpreter Phones in the Inpatient Setting.

Background: Patients with language barriers suffer significant health disparities, including adverse events and poor health outcomes. While remote language services can help improve language access, these modalities remain persistently underused. The objective of this study was to understand clinician experiences and challenges using dual-handset interpreter telephones and to inform recommendations for future language access interventions. Methods: We conducted four focus groups with nurses (N=14) and resident physicians (N=20) to understand attitudes toward dual-handset interpreter telephones in the hospital, including general impressions, effects on communication, situations in which they did and did not use them, and impact on clinical care. Three researchers independently coded all transcripts using a constant comparative approach, meeting repeatedly to discuss coding and to reconcile differences to reach consensus. Results: We identified five salient themes, including increased language access (improved convenience, flexibility, and versatility of phones over in-person or ad hoc interpreters); effects on interpersonal processes of care (improved ability to communicate directly with patients); effects on clinical processes of care (improvements in critical patient care functions, including pain and medication management); impact on time (needing extra time for interpreted encounters and perceived delays impacting future use); and patients for whom, and circumstances in which, the dual-handset interpreter telephone is inadequate (e.g., complex discussions, hands-on instruction, or multiple speakers are present). Conclusions: Our findings indicate that clinicians value dual-handset interpretation in bridging communication barriers and highlight recommendations to guide future implementation interventions to increase the uptake of remote language services in hospital settings.

"How's your mood": Recorded physician mental health conversations with Chinese and Latino patients in routine primary care visits.

OBJECTIVE: Patient-physician communication patterns may influence discussions around depressive symptoms and contribute to engagement in depression care among racial/ethnic minority adults. We examined patient-physician communication about depressive symptoms during routine primary care visits with Chinese and Latino patients with and without language barriers. METHODS: We examined 17 audio-recorded conversations between primary care physicians and Chinese (N = 7) and Latino (N = 10) patients who discussed mental health during their visit and reported depressive symptoms on a post-visit survey. Conversations (in English, Cantonese, Mandarin, Hoisan-wa, Spanish) were transcribed and translated by bilingual/bicultural research assistants and analyzed using inductive and deductive thematic and discourse analysis. RESULTS: Patients initiated mental health discussion in eleven visits. Physicians demonstrated care in word choice and sometimes avoided openly mentioning depression; this could contribute to miscommunication around symptoms and treatment goals. Interpreters had difficulty finding single words to convey terms used by either patients or physicians. CONCLUSION: Patients and doctors appeared willing to discuss mental health; however, variability in terminology presented challenges in mental health discussions in this culturally and linguistically diverse sample. PRACTICE IMPLICATIONS: Further understanding patient preferred terminology about mental health symptoms and interpreter training in these terms could improve patient-physician communication about depressive symptoms and treatment preferences.

Ganglioglioma deep transcriptomics reveals primitive neuroectoderm neural precursor-like population.

Gangliogliomas are brain tumors composed of neuron-like and macroglia-like components that occur in children and young adults. Gangliogliomas are often characterized by a rare population of immature astrocyte-appearing cells expressing CD34, a marker expressed in the neuroectoderm (neural precursor cells) during embryogenesis. New insights are needed to refine tumor classification and to identify therapeutic approaches. We evaluated five gangliogliomas with single nucleus RNA-seq, cellular indexing of transcriptomes and epitopes by sequencing, and/or spatially-resolved RNA-seq. We uncovered a population of CD34+ neoplastic cells with mixed neuroectodermal, immature astrocyte, and neuronal markers. Gene regulatory network interrogation in these neuroectoderm-like cells revealed control of transcriptional programming by TCF7L2/MEIS1-PAX6 and SOX2, similar to that found during neuroectodermal/neural development. Developmental trajectory analyses place neuroectoderm-like tumor cells as precursor cells that give rise to neuron-like and macroglia-like neoplastic cells. Spatially-resolved transcriptomics revealed a neuroectoderm-like tumor cell niche with relative lack of vascular and immune cells. We used these high resolution results to deconvolute clinically-annotated transcriptomic data, confirming that CD34+ cell-associated gene programs associate with gangliogliomas compared to other glial brain tumors. Together, these deep transcriptomic approaches characterized a ganglioglioma cellular hierarchy-confirming CD34+ neuroectoderm-like tumor precursor cells, controlling transcription programs, cell signaling, and associated immune cell states. These findings may guide tumor classification, diagnosis, prognostication, and therapeutic investigations.

Ataxia-telangiectasia mutated ( Atm ) disruption sensitizes spatially-directed H3.3K27M/TP53 diffuse midline gliomas to radiation therapy.

Diffuse midline gliomas (DMGs) are lethal brain tumors characterized by p53-inactivating mutations and oncohistone H3.3K27M mutations that rewire the cellular response to genotoxic stress, which presents therapeutic opportunities. We used RCAS/tv-a retroviruses and Cre recombinase to inactivate p53 and induce K27M in the native H3f3a allele in a lineage- and spatially-directed manner, yielding primary mouse DMGs. Genetic or pharmacologic disruption of the DNA damage response kinase Ataxia-telangiectasia mutated (ATM) enhanced the efficacy of focal brain irradiation, extending mouse survival. This finding suggests that targeting ATM will enhance the efficacy of radiation therapy for p53-mutant DMG but not p53-wildtype DMG. We used spatial in situ transcriptomics and an allelic series of primary murine DMG models with different p53 mutations to identify transactivation-independent p53 activity as a key mediator of such radiosensitivity. These studies deeply profile a genetically faithful and versatile model of a lethal brain tumor to identify resistance mechanisms for a therapeutic strategy currently in clinical trials.

Community-Based Workshops to Involve Rural Communities in Wildlife Management Case Study: Bighorn Sheep in Baja California, Mexico.

The description of natural history, and information on the factors threatening conservation, the distribution area, and the status of species population are necessary for proper wildlife management. The objective of this research was to generate such information in two rural communities and to engage residents in bighorn sheep management through a program of three workshops. The first one covered training regarding natural history and management of the species. The second one consisted in the description of the habitat of the species through a dynamic of participatory mapping. The third, include a design of a one strategy to monitor the bighorn sheep population. The workshops were attended by 37 people from the two rural communities. The results suggest the economic element was the main interest of the inhabitants regarding the bighorn sheep. Eleven risk factors were identified to the bighorn sheep in the study sites, a participatory map with relevant information for the management of the species on each community was developed, and a monitoring strategy of the bighorn sheep population was prepared. The workshop program proposed in this research is a tool that can be applied in rural communities to lay the groundwork for a long-term management project of wildlife species.