Did the exposure of coacervate droplets to rain make them the first stable protocells?

Membraneless coacervate microdroplets have long been proposed as model protocells as they can grow, divide, and concentrate RNA by natural partitioning. However, the rapid exchange of RNA between these compartments, along with their rapid fusion, both within minutes, means that individual droplets would be unable to maintain their separate genetic identities. Hence, Darwinian evolution would not be possible, and the population would be vulnerable to collapse due to the rapid spread of parasitic RNAs. In this study, we show that distilled water, mimicking rain/freshwater, leads to the formation of electrostatic crosslinks on the interface of coacervate droplets that not only suppress droplet fusion indefinitely but also allow the spatiotemporal compartmentalization of RNA on a timescale of days depending on the length and structure of RNA. We suggest that these nonfusing membraneless droplets could potentially act as protocells with the capacity to evolve compartmentalized ribozymes in prebiotic environments.

Biocontrol mechanisms of the Antarctic yeast Debaryomyces hansenii UFT8244 against post-harvest phytopathogenic fungi of strawberries.

The use of yeasts has been explored as an efficient alternative to fungicide application in the treatment and prevention of post-harvest fruit deterioration. Here, we evaluated the biocontrol abilities of the Antarctic yeast strain Debaryomyces hansenii UFT8244 against the post-harvest phytopathogenic fungi Botrytis cinerea and Rhizopus stolonifer for the protection and preservation of strawberry fruit. The strongest inhibition of germination of B. cinerea (57%) was observed at 0 °C, followed by 40% at 25 °C. In addition, germ tubes and hyphae of B. cinerea were strongly surrounded and colonized by D. hansenii. Production of the enzymes ß-1,3-glucanase, chitinase and protease by D. hansenii was detected in the presence of phytopathogenic fungus cell walls. The activity of ß-1,3-glucanase was highest on day 12 of incubation and remained high until day 15. Chitinase and protease activities reached their highest levels on the day 15 of incubation. D. hansenii additionally demonstrated the ability to resist oxidative stress. Our data demonstrated that the main biocontrol mechanisms displayed by D. hansenii were the control of phytopathogenic fungal spore germination, production of antifungal enzymes and resistance to oxidative stress. We conclude that isolate D. hansenii UFT8422 should be further investigated for use at commercial scales at low temperatures.

Expression of the non-coding RNA nc886 facilitates the development of tyrosine kinase inhibitor resistance in EGFR-mutated non-small-cell lung cancer cells.

Treatment of non-small-cell lung cancer (NSCLC) patients possessing EGFR-activating mutations with tyrosine kinase inhibitors (TKIs) can confer an initial promising response. However, TKI resistance inevitably arises. Numerous TKI resistance mechanisms are identified including EGFR secondary mutations, bypass receptor tyrosine kinase (RTK) signaling, and cellular transition e.g. epithelial-mesenchymal transition (EMT). To increase the knowledge of TKI resistance we performed an epigenetic screen to identify small non-coding (nc) genes with DNA methylation alterations in HCC827 NSCLC EGFR-mutated cells with acquired TKI resistance. We analyzed Infinium Methylation EPIC 850K Array data for DNA methylation changes present in both TKI-resistant HCC827 cells with EMT and MET-amplification. Hereby, we identified that the polymorphic maternal imprinted gene nc886 (vtRNA2-1) has a decrease in promoter DNA methylation in TKI-resistant cells. This epigenetic change was associated with an increase in the expression of nc886. The induction of EMT did not affect nc886 expression. CRISPR/Cas9-mediated distortion of the nc886 sequence increased the sensitivity of HCC827 cells towards TKI. Finally, nc886 sequence distortion hindered MET RTK activation and instead was EMT the endpoint TKI resistance mechanism. In conclusion, the expression of nc886 contributes to TKI resistance in the HCC827 NSCLC cell line by supporting cell survival and selection of the endpoint TKI resistance mechanism. We propose DNA methylation and expression changes for nc886 to constitute a novel TKI resistance contributing mechanism in NSCLC.

Endolithic Fungal Diversity in Antarctic Oligocene Rock Samples Explored Using DNA Metabarcoding.

In this study, we evaluated the fungal diversity present associated with cores of Oligocene rocks using a DNA metabarcoding approach. We detected 940,969 DNA reads grouped into 198 amplicon sequence variants (ASVs) representing the phyla Ascomycota, Basidiomycota, Mortierellomycota, Chytridiomycota, Mucoromycota, Rozellomycota, Blastocladiomycota, Monoblepharomycota, Zoopagomycota, Aphelidiomycota (Fungi) and the fungal-like Oomycota (Stramenopila), in rank abundance order. Pseudogymnoascus pannorum, Penicillium sp., Aspergillus sp., Cladosporium sp., Aspergillaceae sp. and Diaporthaceae sp. were assessed to be dominant taxa, with 22 fungal ASVs displaying intermediate abundance and 170 being minor components of the assigned fungal diversity. The data obtained displayed high diversity indices, while rarefaction indicated that the majority of the diversity was detected. However, the diversity indices varied between the cores analysed. The endolithic fungal community detected using a metabarcoding approach in the Oligocene rock samples examined contains a rich and complex mycobiome comprising taxa with different lifestyles, comparable with the diversity reported in recent studies of a range of Antarctic habitats. Due to the high fungal diversity detected, our results suggest the necessity of further research to develop strategies to isolate these fungi in culture for evolutionary, physiological, and biogeochemical studies, and to assess their potential role in biotechnological applications.

Plant-Based Diets and Disease Progression in Men With Prostate Cancer.

Importance: Plant-based diets are associated with many health and environmental benefits, including primary prevention of fatal prostate cancer, but less is known about postdiagnostic plant-based diet patterns in individuals with prostate cancer. Objective: To examine whether postdiagnostic plant-based dietary patterns are associated with risk of prostate cancer progression and prostate cancer-specific mortality. Design, Setting, and Participants: This longitudinal observational cohort study included men with biopsy-proven nonmetastatic prostate cancer (stage ≤T3a) from the diet and lifestyle substudy within the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) enrolled at 43 urology practices across the US from 1999 to 2018. Participants completed a comprehensive diet and lifestyle questionnaire (including a validated food frequency questionnaire [FFQ]) between 2004 and 2016. Data were analyzed from August 2022 to April 2023. Exposures: Overall plant-based diet index (PDI) and healthful plant-based diet index (hPDI) scores were calculated from the FFQ. Main Outcomes and Measures: The primary outcome was prostate cancer progression (recurrence, secondary treatment, bone metastases, or prostate cancer-specific mortality). The secondary outcome was prostate cancer-specific mortality. Results: Among 2062 participants (median [IQR] age, 65.0 [59.0-70.0] years), 61 (3%) identified as African American, 3 (<1%) identified as American Indian or Alaska Native, 9 (<1%) identified as Asian or Pacific Islander, 15 (1%) identified as Latino, and 1959 (95%) identified as White. Median (IQR) time from prostate cancer diagnosis to FFQ was 31.3 (15.9-62.0) months after diagnosis. During a median (IQR) follow-up of 6.5 (1.3-12.8) years after the FFQ, 190 progression events and 61 prostate cancer-specific mortality events were observed. Men scoring in the highest vs lowest quintile of PDI had a 47% lower risk of progression (HR, 0.53; 95% CI, 0.37-0.74; P for trend = .003). The hPDI was not associated with risk of progression overall. However, among 680 individuals with Gleason grade 7 or higher at diagnosis, the highest hPDI quintile was associated with a 55% lower risk of progression compared with the lowest hPDI quintile (HR 0.45; 95% CI, 0.25-0.81; P for trend = .01); no association was observed in individuals with Gleason grade less than 7. Conclusions and Relevance: In this cohort study of 2062 men with prostate cancer, higher intake of plant foods after prostate cancer diagnosis was associated with lower risk of cancer progression. These findings suggest nutritional assessment and counseling may be recommended to patients with prostate cancer to help establish healthy dietary practices and support well-being and overall health.

Statine-based peptidomimetic compounds as inhibitors for SARS-CoV-2 main protease (SARS-CoV­2 Mpro).

COVID-19 is a multisystemic disease caused by the SARS-CoV-2 airborne virus, a member of the Coronaviridae family. It has a positive sense single-stranded RNA genome and encodes two non-structural proteins through viral cysteine-proteases processing. Blocking this step is crucial to control virus replication. In this work, we reported the synthesis of 23 statine-based peptidomimetics to determine their ability to inhibit the main protease (Mpro) activity of SARS-CoV-2. Among the 23 peptidomimetics, 15 compounds effectively inhibited Mpro activity by 50% or more, while three compounds (7d, 8e, and 9g) exhibited maximum inhibition above 70% and IC50 < 1 µM. Compounds 7d, 8e, and 9g inhibited roughly 80% of SARS-CoV-2 replication and proved no cytotoxicity. Molecular docking simulations show putative hydrogen bond and hydrophobic interactions between specific amino acids and these inhibitors. Molecular dynamics simulations further confirmed the stability and persisting interactions in Mpro's subsites, exhibiting favorable free energy binding (ΔGbind) values. These findings suggest the statine-based peptidomimetics as potential therapeutic agents against SARS-CoV-2 by targeting Mpro.

Comorbid substance use disorder, major depression, and associated disability in a nationally representative sample.

BACKGROUND: Major depressive disorders (MDD) and substance use disorders (SUDs) are commonly linked to disability, but there is a lack of research on the risk of disability among individuals who have both SUDs and MD in the general population. This study aimed to investigate the associated risk of disability in people with comorbid SUDs- specifically cannabis use disorder, alcohol use disorder, other drug (except cannabis) use disorder, and a major depressive episode using a nationally representative sample. METHODS: The 2012 Canadian Community Health Survey- Mental Health (CCHS-MH) data were analyzed using multilevel logistic regression models. The survey included a nationally representative sample of Canadians aged 15 years and older (n = 25,113) residing in the ten Canadian provinces from January to December 2012. The diagnoses of major depressive episodes (MDE) and the SUDs were derived from the DSM-IV diagnostic criteria using a modified WHO-CIDI instrument, while disability was assessed using the World Health Organization Disability Assessment Score (WHODAS) 2.0. RESULTS: The strongest predictor of disability was found to be comorbidity. Individuals diagnosed with both a SUD and MDE were 4 to 9 times more likely to experience disability, depending on the substance used, compared to those without either diagnosis. LIMITATIONS: The study's cross-sectional design limits causal inferences. CONCLUSIONS: Our research discovered that individuals who have both SUD and MDE are at a significantly higher risk of experiencing disability. This highlights the importance of integrating mental health and addiction services to mitigate the risk of disability and improve overall treatment outcomes.

Contrastsing synaptic roles of MDGA1 and MDGA2.

Neurodevelopmental disorders are frequently linked to mutations in synaptic organizing molecules. MAM domain containing glycosylphosphatidylinositol anchor 1 and 2 (MDGA1 and MDGA2) are a family of synaptic organizers suggested to play an unusual role as synaptic repressors, but studies offer conflicting evidence for their localization. Using epitope-tagged MDGA1 and MDGA2 knock-in mice, we found that native MDGAs are expressed throughout the brain, peaking early in postnatal development. Surprisingly, endogenous MDGA1 was enriched at excitatory, but not inhibitory, synapses. Both shRNA knockdown and CRISPR/Cas9 knockout of MDGA1 resulted in cell-autonomous, specific impairment of AMPA receptor-mediated synaptic transmission, without affecting GABAergic transmission. Conversely, MDGA2 knockdown/knockout selectively depressed NMDA receptor-mediated transmission but enhanced inhibitory transmission. Our results establish that MDGA2 acts as a synaptic repressor, but only at inhibitory synapses, whereas both MDGAs are required for excitatory transmission. This nonoverlapping division of labor between two highly conserved synaptic proteins is unprecedented.

A Comprehensive Review of Myocardial Bridging: Exploring Diagnostic and Treatment Modalities.

Myocardial bridging (MB) is a congenital coronary artery anomaly involving an overlying myocardium's partial or complete encasement of a coronary artery segment. The obstruction can lead to significant cardiac symptoms, resulting in myocardial ischemia, arrhythmia, and sudden cardiac death. Several approaches, including invasive and non-invasive methods, have been proposed to diagnose and manage MB. Invasive modalities, such as intravascular ultrasound (IVUS) and coronary angiography, offer high specificity and sensitivity. In contrast, non-invasive methods like Doppler ultrasound, multislice computed tomography (MSCT), and magnetic resonance imaging (MRI) are advantageous due to their non-invasive nature, high sensitivity and specificity, and cost-effectiveness. Treatment options for MB mainly focus on relieving symptoms and preventing adverse outcomes. The use of pharmacological agents and surgical and percutaneous interventions has been documented in numerous studies. Studies conclude that MB is a treatable cardiac anomaly, and a combined approach of diagnosis, treatment, and follow-up is necessary to reduce the morbidity and mortality associated with this condition.

HLA-G Gene Variability Is Associated with Papillary Thyroid Carcinoma Morbidity and the HLA-G Protein Profile.

Human leukocyte antigen (HLA)-G is an immune checkpoint molecule that is highly expressed in papillary thyroid carcinoma (PTC). The HLA-G gene presents several functional polymorphisms distributed across the coding and regulatory regions (5'URR: 5' upstream regulatory region and 3'UTR: 3' untranslated region) and some of them may impact HLA-G expression and human malignancy. To understand the contribution of the HLA-G genetic background in PTC, we studied the HLA-G gene variability in PTC patients in association with tumor morbidity, HLA-G tissue expression, and plasma soluble (sHLA-G) levels. We evaluated 185 PTC patients and 154 healthy controls. Polymorphic sites defining coding, regulatory and extended haplotypes were characterized by sequencing analyses. HLA-G tissue expression and plasma soluble HLA-G levels were evaluated by immunohistochemistry and ELISA, respectively. Compared to the controls, the G0104a(5'URR)G*01:04:04(coding)UTR-03(3'UTR) extended haplotype was underrepresented in the PTC patients, while G0104a(5'URR)G*01:04:01(coding)UTR-03(3'UTR) was less frequent in patients with metastatic and multifocal tumors. Decreased HLA-G tissue expression and undetectable plasma sHLA-G were associated with the G010102a(5'URR)G*01:01:02:01(coding)UTR-02(3'UTR) extended haplotype. We concluded that the HLA-G variability was associated with PTC development and morbidity, as well as the magnitude of the encoded protein expression at local and systemic levels.

BRAF, TERT and HLA-G Status in the Papillary Thyroid Carcinoma: A Clinicopathological Association Study.

As BRAF, TERT, HLA-G, and microRNAs have been individually associated with papillary thyroid carcinoma (PTC), we aimed to evaluate the individual and collaborative role of these markers in PTC in the same patient cohort. HLA-G and BRAF tumor expression was evaluated by immunohistochemistry. Using molecular methods, BRAFV600E and TERT promoter mutations were evaluated in thyroid fine needle aspirates. MicroRNA tumor profiling was investigated using massively parallel sequencing. We observed strong HLA-G (67.96%) while BRAF (62.43%) staining was observed in PTC specimens. BRAF overexpression was associated with poor response to therapy. The BRAFV600E (52.9%) and TERTC228T (13%) mutations were associated with extrathyroidal extension, advanced-age, and advanced-stage cancer. The TERT rs2853669 CC+TC genotypes (38%) were overrepresented in metastatic tumors. Nine modulated microRNAs targeting the BRAF, TERT, and/or HLA-G genes were observed in PTC and involved with cancer-related signaling pathways. The markers were individually associated with PTC features, emphasizing the synergistic effect of BRAFV600E and TERTC228T; however, their collaborative role on PTC outcome was not fully demonstrated. The differentially expressed miRNAs targeting the BRAF and/or HLA-G genes may explain their increased expression in the tumor milieu.

Investigating the Impact of Community Volunteerism on the Mental Health of Medical Students.

OBJECTIVE: This study aimed to analyze the impact of community service on the mental health of medical students through their perception of stress. METHODS: The 10-item Perceived Stress Scale was used to measure the stress levels of 82 medical students over a 3-month period. Additional survey questions gauged students' weekly volunteer experiences in clinical and nonclinical settings and their perceived effects on stress and quality of life. RESULTS: Results found an inverse relationship between the number of clinical volunteer hours and perceived stress (P = .0497). Nonclinical and total volunteer hours were correlated with both reduced perceived stress levels (nonclinical P = .0095, total P = .0052) and better quality of life (nonclinical P = .0301, total P = .0136). All individual perceived stress scores fell into the low or moderate stress ranges of the Perceived Stress Scale per the week-to-week analysis. CONCLUSION: The preliminary results raised important research questions about the impact of volunteering on medical student perceived stress. As medical students face higher levels of stress in comparison to the general population, it is exceedingly important to determine methods to decrease their risk of compromising their mental health. This study may aid in decision-making and research in favor of or against offering community service opportunities as part of the core medical education curriculum.

Barriers and confidence among colorectal and prostate cancer survivors participating in two behavioral intervention studies.

PURPOSE: Exercise and healthy diet are key components of cancer survivorship. We sought to explore perceived barriers to engaging in healthy diet and exercise, and whether these barriers change throughout remote-based behavioral interventions. METHODS: Smart Pace (SP) and Prostate 8 (P8) were two 12-week pilot randomized controlled trials (RCTs) among 42 colorectal cancer (CRC) survivors and 76 prostate cancer (PC) survivors, respectively, that encouraged participants to implement exercise (both) and healthy diet (P8 only) through text messaging and wearable fitness monitors; P8 also included web materials. Participants completed surveys on perceived barriers and confidence in their ability to implement healthy behaviors at enrollment and 12 weeks; P8 also included a 52-week assessment. RESULTS: At enrollment, CRC survivors commonly reported a lack of discipline/willpower (36%), time (33%), and energy (31%); PC survivors often reported a lack of knowledge about healthy dietary behaviors (26%). Not having anyone with whom to exercise with was a common barrier among both groups (21% in CRC, 20% in PC). Among the intervention groups in both studies, various enrollment barriers (overall, functional/psychological disability, aversiveness, excuses, and inconveniences) were associated with change in behavior over time. CONCLUSIONS: Among CRC and PC survivors, there are multiple potential barriers related to motivation, time, social support, and lack of knowledge, that can be addressed and overcome to improve healthy behaviors. Tailoring lifestyle interventions to participants' individual barriers and confidence is needed to promote and sustain behavior change long-term.

Aurones: A Promising Scaffold to Inhibit SARS-CoV-2 Replication.

Aurones are a small subgroup of flavonoids in which the basic C6-C3-C6 skeleton is arranged as (Z)-2-benzylidenebenzofuran-3(2H)-one. These compounds are structural isomers of flavones and flavonols, natural products reported as potent inhibitors of SARS-CoV-2 replication. Herein, we report the design, synthesis, and anti-SARS-CoV-2 activity of a series of 25 aurones bearing different oxygenated groups (OH, OCH3, OCH2OCH3, OCH2O, OCF2H, and OCH2C6H4R) at the A- and/or B-rings using cell-based screening assays. We observed that 12 of the 25 compounds exhibit EC50 < 3 µM (8e, 8h, 8j, 8k, 8l, 8m, 8p, 8q, 8r, 8w, 8x, and 8y), of which five presented EC50 < 1 µM (8h, 8m, 8p, 8q, and 8w) without evident cytotoxic effect in Calu-3 cells. The substitution of the A- and/or B-ring with OCH3, OCH2OCH3, and OCF2H groups seems beneficial for the antiviral activity, while the corresponding phenolic derivatives showed a significant decrease in the anti-SARS-CoV-2 activity. The most potent compound of the series, aurone 8q (EC50 = 0.4 µM, SI = 2441.3), is 2 to 3 times more effective than the polyphenolic flavonoids myricetin (2) and baicalein (1), respectively. Investigation of the five more active compounds as inhibitors of SARS-CoV-2 3CLpro based on molecular dynamic calculations suggested that these aurones should detach from the active site of 3CLpro, and, probably, they could bind to another SARS-CoV-2 protein target (either receptor or enzyme).

Soil Fungal Diversity and Ecology Assessed Using DNA Metabarcoding along a Deglaciated Chronosequence at Clearwater Mesa, James Ross Island, Antarctic Peninsula.

We studied the fungal diversity present in soils sampled along a deglaciated chronosequence from para- to periglacial conditions on James Ross Island, north-east Antarctic Peninsula, using DNA metabarcoding. A total of 88 amplicon sequence variants (ASVs) were detected, dominated by the phyla Ascomycota, Basidiomycota and Mortierellomycota. The uncommon phyla Chytridiomycota, Rozellomycota, Monoblepharomycota, Zoopagomycota and Basidiobolomycota were detected. Unknown fungi identified at higher hierarchical taxonomic levels (Fungal sp. 1, Fungal sp. 2, Spizellomycetales sp. and Rozellomycotina sp.) and taxa identified at generic and specific levels (Mortierella sp., Pseudogymnoascus sp., Mortierella alpina, M. turficola, Neoascochyta paspali, Penicillium sp. and Betamyces sp.) dominated the assemblages. In general, the assemblages displayed high diversity and richness, and moderate dominance. Only 12 of the fungal ASVs were detected in all chronosequence soils sampled. Sequences representing saprophytic, pathogenic and symbiotic fungi were detected. Based on the sequence diversity obtained, Clearwater Mesa soils contain a complex fungal community, including the presence of fungal groups generally considered rare in Antarctica, with dominant taxa recognized as cold-adapted cosmopolitan, endemic, saprotrophic and phytopathogenic fungi. Clearwater Mesa ecosystems are impacted by the effects of regional climatic changes, and may provide a natural observatory to understand climate change effects over time.

Role of the valuation of nervousness in cortisol responses to psychosocial stress task and task performance in European American and East Asian students.

How people perceive and value negative affective states is associated with physiological responses to stressful events and moderates the association between negative feelings and physiological and behavioral outcomes. However, previous studies on valuation of negative affective states have been conducted mostly in Western cultures. Different cultural backgrounds shape how people view negative emotions as well as how people attend to internal emotional states, which may change the effects of valuing negative emotions. The present study thus examined whether valuation of nervousness was associated with the magnitude and duration of cortisol responses to a standardized laboratory stressor and task performance in East Asian and European American students. Two hundred undergraduate students were recruited through a large pool of students taking psychology courses. They engaged in demanding speech and arithmetic tasks as part of the Trier Social Stress Test (TSST). European American participants who had a higher valuation of nervousness showed lower cortisol reactivity. Valuing nervousness was associated with better speech performance in students from both cultural backgrounds, and the strength of this association was moderated by cortisol level. Our findings call attention to the importance of considering whether negative emotions are viewed as beneficial or an impediment, as well as the cultural context when responding to demanding and threatening situations.

Ganglioneuroblastoma in a Child With Neurofibromatosis Type 1: A Case Report and Literature Review.

Neurofibromatosis type 1 (NF1) is a genetic condition commonly associated with a predisposition to tumor development. Affected individuals have an increased risk of benign and malignant tumors of the central and peripheral nervous system. Though pediatric patients with NF1 have an increased risk of tumors such as optic gliomas and neurofibromas during childhood, neuroblastic tumors are less often observed in this population. We report a rare case of a 5-year-old female with ganglioneuroblastoma intermixed and known history of NF1 and review the existing literature on the occurrence of ganglioneuroblastoma in pediatric patients with NF1.

Single Cell RNA Sequencing Reveals Human Tooth Type Identity and Guides In Vitro hiPSC Derived Odontoblast Differentiation (iOB).

Over 90% of the U.S. adult population suffers from tooth structure loss due to caries. Most of the mineralized tooth structure is composed of dentin, a material produced and mineralized by ectomesenchyme derived cells known as odontoblasts. Clinicians, scientists, and the general public share the desire to regenerate this missing tooth structure. To bioengineer missing dentin, increased understanding of human tooth development is required. Here we interrogate at the single cell level the signaling interactions that guide human odontoblast and ameloblast development and which determine incisor or molar tooth germ type identity. During human odontoblast development, computational analysis predicts that early FGF and BMP activation followed by later HH signaling is crucial. Application of this sci-RNA-seq analysis generates a differentiation protocol to produce mature hiPSC derived odontoblasts in vitro (iOB). Further, we elucidate the critical role of FGF signaling in odontoblast maturation and its biomineralization capacity using the de novo designed FGFR1/2c isoform specific minibinder scaffolded as a C6 oligomer that acts as a pathway agonist. We find that FGFR1c is upregulated in functional odontoblasts and specifically plays a crucial role in driving odontoblast maturity. Using computational tools, we show on a molecular level how human molar development is delayed compared to incisors. We reveal that enamel knot development is guided by FGF and WNT in incisors and BMP and ROBO in the molars, and that incisor and molar ameloblast development is guided by FGF, EGF and BMP signaling, with tooth type specific intensity of signaling interactions. Dental ectomesenchyme derived cells are the primary source of signaling ligands responsible for both enamel knot and ameloblast development.

Risk of suicide ideation in comorbid substance use disorder and major depression.

BACKGROUND: Suicidal behaviour is commonly associated with major depression (MD) and substance use disorders (SUDs). However, there is a paucity of research on risk for suicide ideation among individuals with comorbid SUDs and MD in the general population. OBJECTIVES: This study investigated the associated risk of suicide ideation in comorbid SUDs-cannabis use disorder (CUD), alcohol use disorder (AUD), drug use disorder (DUD) with major depressive episode (MDE) in a nationally representative sample. METHODS: Multilevel logistic regression models were used to analyze the 2012 Canadian Community Health Survey- Mental Health (CCHS-MH) data. This is a cross-sectional survey of nationally representative samples of Canadians (n = 25,113) aged 15 years and older residing in the ten Canadian provinces between January and December 2012. Diagnoses of MDE, AUD, DUD, and CUD were based on a modified WHO-CIDI, derived from DSM-IV diagnostic criteria. RESULTS: Comorbidity was found to be the strongest predictor of suicide ideation. Compared to those with no diagnosis of either a SUD or MDE, individuals with a comorbid diagnosis of AUD with MDE, CUD with MDE, or DUD with MDE were 9, 11 and 16 times more likely to have 12-month suicide ideation respectively. A diagnosis of MDE was a significant predictor of 12-month suicide ideation with about a 7-fold increased risk compared with individuals not diagnosed with either MDE or a SUD. CONCLUSION: Suicide is a preventable public health issue. Our study found a significantly increased risk of suicide ideation among persons who have comorbid SUD with MD. Effective integration of mental health and addictions services could mitigate the risk of suicide and contribute to better outcomes.

The Evolution of Hypertension Guidelines Over the Last 20+ Years: A Comprehensive Review.

Hypertension is the most common modifiable risk factor for cardiovascular and cerebrovascular diseases. In the last two decades, the guidelines have evolved tremendously from areas with no recommendations for screening or treatment to targeted recommendations for some at-risk groups. We sought to go through the literature that provided guidelines for the management of hypertension at any point in time over the last 22 years from 2000 to 2022. We searched four databases: PubMed, Embase, Google Scholar, and Cochrane, using specified search terms. The keywords used were "hypertension" and "guidelines." We combined them using the Boolean operators (AND, OR) and searched for articles. A total of 2461 publications were initially identified; 348 publications were excluded after screening for full-text availability. The full-text articles were further filtered based on title and abstract screening. Following this, a total of 1443 articles were excluded. The remaining 670 full-text articles were assessed for eligibility. Of the 670 full-text articles, 480 were excluded based on exclusion criteria, and following the full-text article screening, 190 articles met the final inclusion criteria. Most of these guideline evolutions concerned establishing and adjusting thresholds for the subgroups of the elderly population and patients with diabetic kidney disease, chronic kidney disease, and stroke. Furthermore, the medications of choice are now guided by the stage of disease, presence or absence of comorbidities, and other relevant information, as opposed to ethnicity, which was previously a heavy yardstick for medication choice.