B7-H3: a robust target for immunotherapy in prostate cancer.

B7-H3, an immune checkpoint glycoprotein, facilitates immune evasion and the promotion of tumors and is highly expressed on the surface of prostate cancer (PCa) cells, which makes it a feasible and robust candidate for immunotherapies against advanced prostate cancer. Here, we summarize and discuss recent findings on the suitability of targeting B7-H3 in PCa treatment.

Decoding LINC00052 role in breast cancer by bioinformatic and experimental analyses.

LncRNA is a group of transcripts with a length exceeding 200 nucleotides that contribute to tumour development. Our research group found that LINC00052 expression was repressed during the formation of breast cancer (BC) multicellular spheroids. Intriguingly, LINC00052 precise role in BC remains uncertain. We explored LINC00052 expression in BC patients` RNA samples (TCGA) in silico, as well as in an in-house patient cohort, and inferred its cellular and molecular mechanisms. In vitro studies evaluated LINC00052 relevance in BC cells viability, cell cycle and DNA damage. Results. Bioinformatic RNAseq analysis of BC patients showed that LINC00052 is overexpressed in samples from all BC molecular subtypes. A similar LINC00052 expression pattern was observed in an in-house patient cohort. In addition, higher LINC00052 levels are related to better BC patient´s overall survival. Remarkably, MCF-7 and ZR-75-1 cells treated with estradiol showed increased LINC00052 expression compared to control, while these changes were not observed in MDA-MB-231 cells. In parallel, bioinformatic analyses indicated that LINC00052 influences DNA damage and cell cycle. MCF-7 cells with low LINC00052 levels exhibited increased cellular protection against DNA damage and diminished growth capacity. Furthermore, in cisplatin-resistant MCF-7 cells, LINC00052 expression was downregulated. Conclusion. This work shows that LINC00052 expression is associated with better BC patient survival. Remarkably, LINC00052 expression can be regulated by Estradiol. Additionally, assays suggest that LINC00052 could modulate MCF-7 cells growth and DNA damage repair. Overall, this study highlights the need for further research to unravel LINC00052 molecular mechanisms and potential clinical applications in BC.

Impact of a geriatric intervention based on the Comprehensive Geriatrics Assessment on avoidable admissions in older patients at risk evaluated in the Emergency Department.

OBJECTIVE: To know the impact of a geriatric intervention based on the Comprehensive Geriatric Assessment (CGA) on avoidable admissions in older patients at risk evaluated in the Emergency Department. METHOD: Prospective observational unicenter study. We included patients, from October 1, 2018 to January 31, 2020, over 75 years who were attended at the Emergency Department with a Triage Risk Screening Tool (TRST) score≥2. All patients were evaluated by a geriatrician through the CGA. The reasons for going to the Emergency room were collected and also the main intervention carried out by Geriatrics, whether admission or discharge was indicated and whether the admission was avoidable. We did a cost analysis calculating this by (bed/day×average stay×number of admissions avoided). RESULTS: We included 260 patients, 66% were women and the mean age was 86 years. 73.5% patients had polypharmacy, the mean Charlson index was 2.5 (5.6). 63.3% were independent for walking and 20.8% independent for basic activities of daily living. 59% had cognitive impairment. 91.5% lived at home. The most frequent reason for visiting the Emergency room was decline of general state in 22% and the most frequent intervention carried out by Geriatrics was assistance in the decision making process in 35.4% followed by referral to a preferential outpatient geriatric care circuit in 32.7%. Other interventions carried out by Geriatrics was assistance in clarifying diagnosis (4.2%), assistance in pharmacological adjustment (8.5%), referral to a standard geriatric care pathway (13.1%), telephone follow-up (4.2%) and/or coordination with Social Services for care planning (11.2%). Including all patients, 29.2% required hospital admission and 70.8% were discharged. 40% admissions were avoided, which meant more than 540 thousand euros saved. CONCLUSIONS: A standardized CGA coordinated by Geriatrics in older patients at risk of suffering adverse events in the Emergency room reduces admissions and costs, so it should therefore be established as a recommendation of good clinical practice.

Microbial diversity, genomics, and phage-host interactions of cyanobacterial harmful algal blooms.

The occurrence of cyanobacterial harmful algal blooms (cyanoHABs) is related to their physical and chemical environment. However, less is known about their associated microbial interactions and processes. In this study, cyanoHABs were analyzed as a microbial ecosystem, using 1 year of 16S rRNA sequencing and 70 metagenomes collected during the bloom season from Lake Okeechobee (Florida, USA). Biogeographical patterns observed in microbial community composition and function reflected ecological zones distinct in their physical and chemical parameters that resulted in bloom "hotspots" near major lake inflows. Changes in relative abundances of taxa within multiple phyla followed increasing bloom severity. Functional pathways that correlated with increasing bloom severity encoded organic nitrogen and phosphorus utilization, storage of nutrients, exchange of genetic material, phage defense, and protection against oxidative stress, suggesting that microbial interactions may promote cyanoHAB resilience. Cyanobacterial communities were highly diverse, with picocyanobacteria ubiquitous and oftentimes most abundant, especially in the absence of blooms. The identification of novel bloom-forming cyanobacteria and genomic comparisons indicated a functionally diverse cyanobacterial community with differences in its capability to store nitrogen using cyanophycin and to defend against phage using CRISPR and restriction-modification systems. Considering blooms in the context of a microbial ecosystem and their interactions in nature, physiologies and interactions supporting the proliferation and stability of cyanoHABs are proposed, including a role for phage infection of picocyanobacteria. This study displayed the power of "-omics" to reveal important biological processes that could support the effective management and prediction of cyanoHABs. IMPORTANCE: Cyanobacterial harmful algal blooms pose a significant threat to aquatic ecosystems and human health. Although physical and chemical conditions in aquatic systems that facilitate bloom development are well studied, there are fundamental gaps in the biological understanding of the microbial ecosystem that makes a cyanobacterial bloom. High-throughput sequencing was used to determine the drivers of cyanobacteria blooms in nature. Multiple functions and interactions important to consider in cyanobacterial bloom ecology were identified. The microbial biodiversity of blooms revealed microbial functions, genomic characteristics, and interactions between cyanobacterial populations that could be involved in bloom stability and more coherently define cyanobacteria blooms. Our results highlight the importance of considering cyanobacterial blooms as a microbial ecosystem to predict, prevent, and mitigate them.

Gummatous neurosyphilisin an HIV-negative patient: Case report.

Syphilis is a chronic infectious disease, which dates back to the XV century and is caused by the spirochete treponema pallidum, capable of invading the central nervous system in any of its stages- Its incidence has increased in parallel to the HIV/AIDS pandemic, and the synergism between both pathologies is such. that it has become a public health problem in recent years. Here we present the case of a 31-year-old female patient, who consulted for headache associated with decreased visual acuity and provided an unenhanced head CT showing hypodense lesions in both thalamic regions, serological tests for syphilis were reactive and those for HIV were not reactive. The brain MRI with spectroscopy was reported in favor of cerebral toxoplasmosis, which was later ruled out with a study of cerebrospinal fluid. Management with penicillin G sodium IV for 6 weeks was indicated, achieving complete imaging resolution of her lesions.

Participation of kisspeptin, progesterone, and GnRH receptors on lordosis behavior induced by kisspeptin.

The neuropeptide kisspeptin (Kiss) is crucial in regulating the hypothalamic-pituitary-gonadal axis. It is produced by two main groups of neurons in the hypothalamus: the rostral periventricular region around the third ventricle and the arcuate nucleus. Kiss is the peptide product of the KiSS-1 gene and serves as the endogenous agonist for the GPR54 receptor. The Kiss/GPR54 system functions as a critical regulator of the reproductive system. Thus, we examined the effect of intracerebroventricular administration of 3 µg of Kiss to the right lateral ventricle of ovariectomized rats primed with a dose of 5 µg subcutaneous (sc) of estradiol benzoate (EB). Kiss treatment increased the lordosis quotient at all times tested. However, the lordosis reflex score was comparatively lower yet still significant compared to the control group. To investigate receptor specificity and downstream mechanisms on lordosis, we infused 10 µg of GPR54 receptor antagonist, Kiss-234, 5 µg of the progestin receptor antagonist, RU486, or 3 µg of antide, a gonadotropin-releasing hormone-1 (GnRH-1) receptor antagonist, to the right lateral ventricle 30 min before an infusion of 3 µg of Kiss. Results demonstrated a significant reduction in the facilitation of lordosis behavior by Kiss at 60 and 120 min when Kiss-234, RU486, or antide were administered. These findings suggest that Kiss stimulates lordosis expression by activating GPR54 receptors on GnRH neurons and that Kiss/GPR54 system is an essential intermediary by which progesterone activates GnRH.

Systemic cellular migration: The forces driving the directed locomotion movement of cells.

Directional motility is an essential property of cells. Despite its enormous relevance in many fundamental physiological and pathological processes, how cells control their locomotion movements remains an unresolved question. Here, we have addressed the systemic processes driving the directed locomotion of cells. Specifically, we have performed an exhaustive study analyzing the trajectories of 700 individual cells belonging to three different species (Amoeba proteus, Metamoeba leningradensis, and Amoeba borokensis) in four different scenarios: in absence of stimuli, under an electric field (galvanotaxis), in a chemotactic gradient (chemotaxis), and under simultaneous galvanotactic and chemotactic stimuli. All movements were analyzed using advanced quantitative tools. The results show that the trajectories are mainly characterized by coherent integrative responses that operate at the global cellular scale. These systemic migratory movements depend on the cooperative nonlinear interaction of most, if not all, molecular components of cells.

Removal of endothelial surface-associated von villebrand factor suppresses accelerate datherosclerosis after myocardial infarction.

BACKGROUND: Thromboinflammation involving platelet adhesion to endothelial surface-associated von Willebrand factor (VWF) has been implicated in the accelerated progression of non-culprit plaques after MI. The aim of this study was to use arterial endothelial molecular imaging to mechanistically evaluate endothelial-associated VWF as a therapeutic target for reducing remote plaque activation after myocardial infarction (MI). METHODS: Hyperlipidemic mice deficient for the low-density lipoprotein receptor and Apobec-1 underwent closed-chest MI and were treated chronically with either: (i) recombinant ADAMTS13 which is responsible for proteolytic removal of VWF from the endothelial surface, (ii) N-acetylcysteine (NAC) which removes VWF by disulfide bond reduction, (iii) function-blocking anti-factor XI (FXI) antibody, or (iv) no therapy. Non-ischemic controls were also studied. At day 3 and 21, ultrasound molecular imaging was performed with probes targeted to endothelial-associated VWF A1-domain, platelet GPIbα, P-selectin and vascular cell adhesion molecule-1 (VCAM-1) at lesion-prone sites of the aorta. Histology was performed at day 21. RESULTS: Aortic signal for P-selectin, VCAM-1, VWF, and platelet-GPIbα were all increased several-fold (p < 0.01) in post-MI mice versus sham-treated animals at day 3 and 21. Treatment with NAC and ADAMTS13 significantly attenuated the post-MI increase for all four molecular targets by > 50% (p < 0.05 vs. non-treated at day 3 and 21). On aortic root histology, mice undergoing MI versus controls had 2-4 fold greater plaque size and macrophage content (p < 0.05), approximately 20-fold greater platelet adhesion (p < 0.05), and increased staining for markers of platelet transforming growth factor-ß1 signaling. Accelerated plaque growth and inflammatory activation was almost entirely prevented by ADAMTS13 and NAC. Inhibition of FXI had no significant effect on molecular imaging signal or plaque morphology. CONCLUSIONS: Plaque inflammatory activation in remote arteries after MI is strongly influenced by VWF-mediated platelet adhesion to the endothelium. These findings support investigation into new secondary preventive therapies for reducing non-culprit artery events after MI.

Comparative clinicopathological study of the main anatomic locations of oral squamous cell carcinoma.

OBJECTIVE: To analyze the clinicopathological and evolutionary profile of the main locations of oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: This is a retrospective study on 133 patients treated for OSCC. The group was composed of 48 women and 85 men, with a mean age 63.9 ± 12.73 years. Most cases involved the lingual border of tongue (63), followed by the gingiva (36) and the floor of mouth (34). A comparative analysis was performed using multinomial regression. RESULTS: There were significant differences regarding age, sex, tobacco and alcohol consumption, liver pathology, oral potentially malignant disorders, and bone and perineural invasion. In multivariate regression, tobacco consumption, and bone invasion remained significant. There were no significant differences in relation to prognosis. CONCLUSION: The location of OSCC is an important factor in the clinicopathological assessment of this neoplasm. The main locations of OSCC show differential etiopathogenic and clinicopathological aspects. Tobacco consumption has a great relevance in the floor of mouth; nonetheless, it is less important in the tongue border and the gum, which suggests other pathogenic factors. It is necessary to consider the anatomical location of OSCC in preventive protocols, with the aim of reducing its high mortality.

Versatility of the medial corticoperiosteal flap: from recalcitrant non-unions up to large bony defects.

BACKGROUND: Reconstructive microsurgery techniques using vascularized bone grafts have revolutionized the treatment of complex cases associated with recalcitrant non-unions or osteomyelitis. The medial femoral corticoperiosteal flap (MFCP flap) has emerged as a valuable option in bone reconstruction. Its clinical applications have been extended over the years considering this flap from non-unions with minimal bone lost, up to large intercalary defects of the upper and lower extremities. This article aims to present the clinical applications and outcomes of the MFCP flap in various reconstructive scenarios. METHODS: Seventy-nine patients with persistent non-union and bone defects of the upper and lower limb were evaluated from June 2008 to October 2020. All of them were reconstructed with a corticoperiosteal flap from the medial femoral condyle in our hospital. Previous procedures, bone gap and type of flap used were recorded. Postoperative functional status was assessed with time of bone healing, complications and clinical final outcome. RESULTS: Radiological evidence of bone union was observed at 4.09 months (range 2-9). Healing rate was 97% with periosteal corticocancellous flaps (PCC flaps) and 93% with corticoperiosteal flaps (CP flaps). Average follow-up was 14.5 months (range 5-28). There were no significant donor site complications. CONCLUSIONS: The MFCP flap offers a versatile and reliable option for bone reconstruction. Its ability to provide vascularized bone tissue with low morbidity enhances the healing process and improves outcomes. The MFCP flap has been increasing its applications and it serves as a valuable option in the treatment of recalcitrant non-unions or bony defects irrespective of site and size up to 5 cm in the upper and lower extremities.

Transposon DNA sequences facilitate the tissue-specific gene transfer of circulating tumor DNA between human cells.

The exchange of genes between cells is known to play an important physiological and pathological role in many organisms. We show that circulating tumor DNA (ctDNA) facilitates cell-specific gene transfer between human cancer cells and explain part of the mechanisms behind this phenomenon. As ctDNA migrates into the nucleus, genetic information is transferred. Cell targeting and ctDNA integration require ERVL, SINE or LINE DNA sequences. Chemically manufactured AluSp and MER11C sequences replicated multiple myeloma (MM) ctDNA cell targeting and integration. Additionally, we found that ctDNA may alter the treatment response of MM and pancreatic cancer models. This study shows that retrotransposon DNA sequences promote cancer gene transfer. However, because cell-free DNA has been detected in physiological and other pathological conditions, our findings have a broader impact than just cancer. Furthermore, the discovery that transposon DNA sequences mediate tissue-specific targeting will open up a new avenue for the delivery of genes and therapies.

Breaking Barriers: Advancing the Mission of The Equity in Heart Transplant Project.

The Equity in Heart Transplant Project, Inc (TEHTP), a 501(c)(3) public charity founded in 2022, addresses financial and social barriers impeding access to heart transplantation for patients with end-stage heart failure in the United States. Rooted in the World Health Organization's declaration on health as a fundamental right, TEHTP champions equitable care. Financial impediments disproportionately affect minority populations, perpetuating disparities in heart transplant outcomes. Since its inception in 2022, TEHTP has successfully supported 31 patients. Looking ahead, TEHTP aims to influence health policies surrounding insurance coverage through advocacy efforts and expand assistance to posttransplant care. Past accomplishments and future goals exemplify the organization's commitment to eradicating systemic barriers and ensuring that poverty does not become a death sentence for transplant patients.

Clinical impact of remote heart failure management using the multiparameter ICD HeartLogic alert.

INTRODUCTION AND OBJECTIVES: The multiparametric implantable cardioverter-defibrillator HeartLogic index has proven to be a sensitive and timely predictor of impending heart failure (HF) decompensation. We evaluated the impact of a standardized follow-up protocol implemented by nursing staff and based on remote management of alerts. METHODS: The algorithm was activated in HF patients at 19 Spanish centers. Transmitted data were analyzed remotely, and patients were contacted by telephone if alerts were issued. Clinical actions were implemented remotely or through outpatient visits. The primary endpoint consisted of HF hospitalizations or death. Secondary endpoints were HF outpatient visits. We compared the 12-month periods before and after the adoption of the protocol. RESULTS: We analyzed 392 patients (aged 69±10 years, 76% male, 50% ischemic cardiomyopathy) with implantable cardioverter-defibrillators (20%) or cardiac resynchronization therapy defibrillators (80%). The primary endpoint occurred 151 times in 86 (22%) patients during the 12 months before the adoption of the protocol, and 69 times in 45 (11%) patients (P<.001) during the 12 months after its adoption. The mean number of hospitalizations per patient was 0.39±0.89 pre- and 0.18±0.57 postadoption (P<.001). There were 185 outpatient visits for HF in 96 (24%) patients before adoption and 64 in 48 (12%) patients after adoption (P<.001). The mean number of visits per patient was 0.47±1.11 pre- and 0.16±0.51 postadoption (P<.001). CONCLUSIONS: A standardized follow-up protocol based on remote management of HeartLogic alerts enabled effective remote management of HF patients. After its adoption, we observed a significant reduction in HF hospitalizations and outpatient visits.

The genome sequence of the giant clam, Tridacna gigas (Linnaeus, 1758).

We present a chromosomal-level genome assembly from an individual Tridacna gigas (the giant clam; Mollusca; Bivalvia; Veneroida; Cardiidae). The genome sequence is 1,175.9 megabases in span. Most of the assembly is scaffolded into 17 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 25.34 kilobases in length. Gene annotation of this assembly on Ensembl identified 18,177 protein coding genes.

Telomere Length is Associated with the Prevalence, Persistence, and Incidence of Sarcopenia.

BACKGROUND: Telomere length (TL) shortening has been identified as a marker of aging and associated with adverse health outcomes, but evidence of its association with sarcopenia is inconclusive. AIMS: Estimate the cross-sectional and prospective associations between TL and sarcopenia. METHODS: We used data from Waves 3 and 4 (2017, 2021) of the Study on Global Aging and Adult Health in Mexico (SAGE-Mexico). The cross-sectional sample consisted of 1,738 adults aged 50 and older, and the longitudinal sample consisted of 1,437. Relative TL was determined by real-time quantitative polymerase chain reaction (qPCR) on DNA extracted from saliva samples and quantified as the telomere/single-copy gene (T/S) ratio. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People (EWGSOP2). RESULTS: The mean salivary TL was 1.50 T/S units (95% CI: 1.49-1.52). The baseline prevalence of sarcopenia was 13.3% (95% CI: 9.8-16.8%). The incidence and persistence of sarcopenia were 6.8% (95% CI: 5.0-9.5%) and 7.0% (95% CI: 5.1-9.6%), respectively. The results showed that a one standard deviation decrease in TL was cross-sectionally associated with higher odds of sarcopenia (OR = 1.31; 95% CI: 1.03-1.67) and prospectively with a higher incidence (RRR = 1.55; 95% CI: 1.06-2.25) and persistence (RRR = 1.50; 95% CI: 1.01-2.24) of sarcopenia. CONCLUSIONS: Older adults with shorter TL had higher rates of incident and persistent sarcopenia. Implementation of interventions to delay the decline of TL in older adults is warranted. Further translational studies are needed to elucidate the effects of exercise or diet on DNA repair in the telomeric region and their associations with sarcopenia.

Bibliometric study of the scientific productivity of the COVID-19 impact on constructs affecting happiness in university students.

COVID-19 has caused a wide range of psychological problems, such as panic disorders, anxiety, and depression. Knowing what others have researched on, what constructs they have focused on, will (a) summarize published information, (b) help identify research gaps, and (c) encourage future research that addresses these gaps. The aim of the study was to analyze the bibliometric indicators of scientific productivity of the impact of COVID-19 on constructs affecting undergraduate happiness. A bibliometric study was conducted. The PubMed database was used. Data summarized were: authors, year of publication, journal name, country, language of publication, and subtopic addressed. A total of 16 English-language studies were identified between April 2022 and December 2022. There were 12 countries that have published on the impact of COVID-19 on constructs affecting college students' happiness. Most of the studies were developed in the United States (n = 4, 25%) and China (n = 2, 12.5%). Thirteen journals publishing these topics were detected. The subtopics considered were organized into nine categories (e.g., a: Psychological impact, b: Adverse childhood experiences, c: Stress, d: Personality traits, e: Perception of the educational environment, f: Spiritual health, g: Distress, h: Uncertainty and socioemotional learning, i: Satisfaction with life). This study suggests that the number of countries and scientific journals that have published on the impact of COVID-19 on constructs affecting college students' happiness is small. In addition, the most discussed subtopics during the pandemic were related to constructs such as psychological impact and stress affecting college students' happiness.

Assessment of the Effects of Physiotherapy on Back Care and Prevention of Non-Specific Low Back Pain in Children and Adolescents: A Systematic Review and Meta-Analysis.

Non-specific low back pain (NSLBP) in children and adolescents has increased in recent years, and the evidence of the physiotherapy interventions in back care needs to be updated. Our main goal was to quantify the effects of preventive physiotherapy interventions on improving behavior and knowledge related to back care and prevention of NSLBP in children and adolescents. Based on two previous meta-analyses, Cochrane Library, MEDLINE, PEDro, Web of Science, LILACS, IBECS, PsycINFO, and IME databases and several journals were searched. Two researchers independently extracted data and assessed the risk of bias in the studies using the RoB2 tool. Data were described according to PRISMA guidelines. A total of 24 studies (28 reports) were included. In the posttest, the behavior variable obtained an overall effect size of d+ = 1.48 (95%CI: 0.40 to 2.56), and the knowledge variable obtained an effect size of d+ = 1.41 (95%CI: 1.05 to 1.76). Physiotherapy has demonstrated beneficial impacts on behavior and knowledge concerning back care and to prevent NSLBP in children and adolescents. Interventions focusing on postural hygiene and exercise should be preferred, especially those that are shorter in number of weeks, more intense, and incorporate as many intervention hours as possible.

ZIF-8@Hydroxyapatite Composite as a High Potential Material for Prolonged Delivery of Agrochemicals.

Although agrochemical practices can enhance agricultural productivity, their intensive application has resulted in the deterioration of ecosystems. Therefore, it is necessary to develop more efficient and less toxic methods against pests and infections while improving crop productivity. Moving toward sustainable development, in this work, we originally described the preparation of a composite (ZIF-8@HA) consisting of the coating of zeolitic-like metal-organic framework (MOF) ZIF-8 (based on Zn, an essential micronutrient in plants with antibacterial, antifungal, and antifouling properties) with hydroxyapatite (HA) nanoparticles (i.e., nanofertilizer). The interaction between the HA and ZIF-8 has been characterized through a combination of techniques, such as microscopic techniques, where the presence of a HA coating is demonstrated; or by analysis of the surface charge with a dramatic change in the Z-potential (from +18.7 ± 0.8 to -27.6 ± 0.7 mV for ZIF-8 and ZIF-8@HA, respectively). Interestingly, the interaction of HA with ZIF-8 delays the MOF degradation (from 4 h for pristine ZIF-8 to 168 h for HA-coated material), providing a slower and gradual release of zinc. After a comprehensive characterization, the potential combined fertilizer and bactericidal effect of ZIF-8@HA was investigated in wheat (Triticum aestivum) seeds and Pseudomonas syringae (Ps). ZIF-8@HA (7.3 ppm) demonstrated a great fertilizer effect, increasing shoot (9.4 %) and root length (27.1 %) of wheat seeds after 11 days at 25 °C under dark conditions, improving the results obtained with HA, ZIF-8, or ZnSO4 or even physically mixed constituents (HA + ZIF-8). It was also effective in the growth inhibition (>80 % of growth inhibition) of Ps, a vegetal pathogen causing considerable crop decline. Therefore, this work demonstrates the potential of MOF@HA composites and paves the way as a promising agrochemical with improved fertilizer and antibacterial properties.

Depressive symptoms in adolescence and adult educational and employment outcomes: a structured life course analysis.

BACKGROUND: Depression is a common mental health disorder that often starts during adolescence, with potentially important future consequences including 'Not in Education, Employment or Training' (NEET) status. METHODS: We took a structured life course modeling approach to examine how depressive symptoms during adolescence might be associated with later NEET status, using a high-quality longitudinal data resource. We considered four plausible life course models: (1) an early adolescent sensitive period model where depressive symptoms in early adolescence are more associated with later NEET status relative to exposure at other stages; (2) a mid adolescent sensitive period model where depressive symptoms during the transition from compulsory education to adult life might be more deleterious regarding NEET status; (3) a late adolescent sensitive period model, meaning that depressive symptoms around the time when most adults have completed their education and started their careers are the most strongly associated with NEET status; and (4) an accumulation of risk model which highlights the importance of chronicity of symptoms. RESULTS: Our analysis sample included participants with full information on NEET status (N = 3951), and the results supported the accumulation of risk model, showing that the odds of NEET increase by 1.015 (95% CI 1.012-1.019) for an increase of 1 unit in depression at any age between 11 and 24 years. CONCLUSIONS: Given the adverse implications of NEET status, our results emphasize the importance of supporting mental health during adolescence and early adulthood, as well as considering specific needs of young people with re-occurring depressed mood.

Chemical profiling and quantification of flavones in several Pseudognaphalium and Gnaphalium species of Mexican gordolobo using UHPLC/PDA/MS.

The inflorescences of the Mexican gordolobo are used as a folk medicine to treat various respiratory diseases. Currently, the botanical species that bear the name Mexican gordolobo belong to the genera Gnaphalium and Pseudognaphalium. Despite a long history of traditional use, most Mexican gordolobo species have never been fully chemically characterized, and the range of constituents in the species has not been comprehensively reported. To establish a quality control and chemical characterization method, a total of 49 samples belonging to 18 species of Pseudognaphalium and four species of Gnaphalium were studied. Nine flavones were quantified using a UPLC-PDA method. The method was validated in terms of linearity (R2 > 0.99), precision (intra- and inter-day: 0.1-3.9%), accuracy (96-103%), detection limit (10 ng/mL), limit of quantification (25 ng/mL) and robustness. 3-Methylquercetin, luteolin, quercetin, 3,5-dihydroxy-6,7,8-trimethoxyflavone, apigenin and gnaphaliin A were present at relatively high levels in most of the samples analyzed. The samples of P. oxyphyllum and P. liebmannii showed the highest content of the 9 compounds analyzed. Whereas the samples of the 5 species of Gnaphalium showed the lowest levels, including non-detectable, of the 9 compounds quantified. This marks an important difference with Pseudognaphalium species. Furthermore, using UHPLC-ESI-QToF data with targeted and non-targeted approaches, 57 compounds, were identified in Mexican gordolobo samples. Flavonoids were the main group of compounds found in Mexican gordolobo.