The Alpine ibex (Capra ibex) gut microbiome, seasonal dynamics, and potential application in lignocellulose bioconversion.

Aiming to shed light on the biology of wild ruminants, we investigated the gut microbiome seasonal dynamics of the Alpine ibex (Capra ibex) from the Central Italian Alps. Feces were collected in spring, summer, and autumn during non-invasive sampling campaigns. Samples were analyzed by 16S rRNA amplicon sequencing, shotgun metagenomics, as well as targeted and untargeted metabolomics. Our findings revealed season-specific compositional and functional profiles of the ibex gut microbiome that may allow the host to adapt to seasonal changes in available forage, by fine-tuning the holobiont catabolic layout to fully exploit the available food. Besides confirming the importance of the host-associated microbiome in providing the phenotypic plasticity needed to buffer dietary changes, we obtained species-level genome bins and identified minimal gut microbiome community modules of 11-14 interacting strains as a possible microbiome-based solution for the bioconversion of lignocellulose to high-value compounds, such as volatile fatty acids.

Resistance to freezing conditions of endemic Antarctic polychaetes is enhanced by cryoprotective proteins produced by their microbiome.

The microbiome plays a key role in the health of all metazoans. Whether and how the microbiome favors the adaptation processes of organisms to extreme conditions, such as those of Antarctica, which are incompatible with most metazoans, is still unknown. We investigated the microbiome of three endemic and widespread species of Antarctic polychaetes: Leitoscoloplos geminus, Aphelochaeta palmeri, and Aglaophamus trissophyllus. We report here that these invertebrates contain a stable bacterial core dominated by Meiothermus and Anoxybacillus, equipped with a versatile genetic makeup and a unique portfolio of proteins useful for coping with extremely cold conditions as revealed by pangenomic and metaproteomic analyses. The close phylosymbiosis between Meiothermus and Anoxybacillus and these Antarctic polychaetes indicates a connection with their hosts that started in the past to support holobiont adaptation to the Antarctic Ocean. The wide suite of bacterial cryoprotective proteins found in Antarctic polychaetes may be useful for the development of nature-based biotechnological applications.

The endocrine disruptor vinclozolin causes endothelial injury via eNOS/Nox4/IRE1α signaling.

Vinclozolin (VCZ) is a common dicarboximide fungicide used to protect crops from diseases. It is also an endocrine disruptor, and its effects on various organs have been described but its influence on vasculature has not yet been addressed. This study focuses on the potential mechanism of VCZ-induced vascular injury. The effect of VCZ on vascular function in terms of relaxing and contracting response was evaluated in mice aorta. A short exposure to VCZ affected the endothelial but not the smooth muscle component. Specifically, it caused a disruption of the eNOS/NO signaling. In line, a short exposure to VCZ in bovine aortic endothelial cells promoted eNOS uncoupling resulting in a reduction of NO bioavailability and eNOS dimer/monomer ratio, and in turn an increase of nitro-tyrosine levels and ROS formation. Prolonging the exposure to VCZ (3 and 6h) an up-regulation of Nox4, enzyme-generating ROS constitutively expressed in endothelial cells, and an increase in ROS and malondialdehyde content coupled with a reduction in NO levels were found. These events were strictly linked to endoplasmic reticulum stress as demonstrated by the phosphorylation of inositol-requiring transmembrane kinase endoribonuclease 1α (IRE1α), a stress sensor and its reversion by using a selective inhibitor. Collectively, these results demonstrated that VCZ provokes endothelial dysfunction by oxidative stress involving eNOS/Nox4/IRE1α axis. The rapid exposure affected the endothelial function promoting eNOS uncoupling while a post-transcriptional modification, involving Nox4/IRE1α signaling, occurred following prolonged exposure. Thus, exposure to VCZ could contribute to the onset and/or progression of cardiovascular diseases associated with endothelial dysfunction.

Suicide Ideation Among Transgender and Gender Diverse Adolescents: The Role of Parental Invalidation of Adolescents' Gender Identity.

Transgender and gender diverse (TGD) youth experience chronic and acute stress associated with their gender identity contributing to their increased risk of suicide and suicide ideation (SI) compared to non-TGD peers. This study examined how invalidating and accepting gender-related experiences with a parent impact SI severity among TGD adolescents cross-sectionally and longitudinally, within-person. Participants were 15 TGD adolescents with past month SI recruited across community and clinical settings. Adolescents completed a baseline assessment of validated interviews and self-report measures on parental invalidation and SI severity. Over a 14-day follow-up period, adolescents reported instances of parental gender invalidation and acceptance, relative stress of those experiences, and SI severity multiple times/day via ecological momentary assessment (EMA). Bivariate associations of parental invalidation and acceptance with SI were examined at baseline, while multilevel models examined the relationship within-person over follow-up. Cross-sectionally, greater perceived invalidation and non-affirmation by their parents was associated with more severe SI. Over the follow up, instances of perceived parental invalidation were associated with passive SI within-person. Findings partially support the minority stress theory and social safety perspective by showing that perceived gender-invalidation from parents affects SI in TGD adolescents, both cross-sectionally and longitudinally. Further research is needed to identify specific emotional and cognitive factors, such as perceived stress, that contribute to the risk of SI among TGD youth and inform the development of targeted interventions for this vulnerable population.

Active surveillance of antimicrobial resistance in companion animals: A pilot study in a Spanish Veterinary Teaching Hospital.

The role of small animal veterinary hospitals in the onset and dissemination of antimicrobial-resistant organisms (AMROs) is still not clear, and the implementation of an internal surveillance systems is a cost-effective tool to better understand their impact. The aim of this study was to describe a pilot program of active surveillance in a Spanish Veterinary Teaching Hospital, developed to estimate the detection frequency of AMROs in the commensal flora of patients and in the environment. Surveillance was focused on Methicillin-resistant Staphylococci (MRS), third generation cephalosporins resistant gram-negative bacteria (3GCR-GNB), and carbapenems-resistant gram-negative bacteria (CR-GNB). Oral and perirectal swabs were collected in the same dogs and cats hospitalized > 48 h, at their admission and before their discharge. Out of 50 patients sampled, 24% (12/50) were carriers at admission of at least one of the three investigated AMROs. Twenty-eight percent of patients (14/50) acquired at least one AMRO during the hospital stay. MRS detection frequency at admission was 12% (6/50), while acquisition was 6% (3/50). 3GCR-GNB detection frequency was 14% at admission (7/50) and acquisition 22% (11/50), while CR-GNB detection frequency was 2% at admission (1/50) and acquisition 2% (1/50). Environmental surveillance (98 samples) showed a total detection frequency of 22.4% for MRS (22/98), 2% for 3GCR-GNB and CR-GNB (2/98). Clinical staff' shoe soles showed high detection frequency for MRS (50%). 3GCR Escherichia coli was the most isolated species in patients (n = 17). The results show how active surveillance can be used as a tool to assess the impact of AMROs in veterinary hospitals to subsequently build up tailored control plans based on specific issues.

Fingerprick volumetric absorptive microsampling for therapeutic drug monitoring of antiseizure medications: Reliability and real-life feasibility in epilepsy patients.

Volumetric absorptive microsampling (VAMS) is increasingly proposed as a clinically reliable therapeutic drug monitoring (TDM) sampling methodology. The study aimed to establish the reliability and real-life feasibility of patient self-collected capillary VAMS for TDM of antiseizure medication (ASMs), using plasma ASMs concentrations from venous blood as a reference standard. Nurses collected venous and capillary blood samples using VAMS. Afterward, persons with epilepsy (PWE) performed VAMS sampling by themselves. All samples were analyzed by UHPLC-MS/MS. We performed a cross-validation study, comparing ASMs concentrations obtained by VAMS nurses and patients' self-collected versus plasma through Bland-Altman analysis and Passing-Bablok regression. We enrolled 301 PWE (M: F 42.5%:57.5%; mean age 44±16 years), treated with 13 ASMs, providing a total of 464 measurements. Statistical analysis comparing VAMS self-collected versus plasma ASMs concentrations showed a bias close to zero and slope and intercept values indicating a good agreement for CBZ, LCS, LEV, LTG, OXC, PB, and PHT, while a systematic difference between the two methods was found for VPA, PMP, TPM and ZNS. This is the first study showing the reliability and feasibility of the real-world application of PWE self-collected VAMS for most of the ASMs considered, giving a promising basis for at-home VAMS applications.

Searching for Novel Sources of Hydrogen Sulfide Donors: Chemical Profiling of Polycarpa aurata Extract and Evaluation of the Anti-Inflammatory Effects.

Hydrogen sulfide (H2S) is a signaling molecule endogenously produced within mammals' cells that plays an important role in inflammation, exerting anti-inflammatory effects. In this view, the research has shown a growing interest in identifying natural H2S donors. Herein, for the first time, the potential of marine extract as a source of H2S-releasing agents has been explored. Different fractions obtained by the Indonesian ascidian Polycarpa aurata were evaluated for their ability to release H2S in solution. The main components of the most active fraction were then characterized by liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and NMR spectroscopy. The ability of this fraction to release H2S was evaluated in a cell-free assay and J774 macrophages by a fluorimetric method, and its anti-inflammatory activity was evaluated in vitro and in vivo by using carrageenan-induced mouse paw edema. The anti-inflammatory effects were assessed by inhibiting the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), and interleukin-6 (IL-6), coupled with a reduction in nitric oxide (NO) and IL-6 levels. Thus, this study defines the first example of a marine source able to inhibit inflammatory responses in vivo through the release of H2S.

Biphasic inflammatory response induced by intra-plantar injection of L-cysteine: Role of CBS-derived H2S and S1P/NO signaling.

This study investigates the inflammatory response to intra-plantar injection of L-cysteine in a murine model. L-cysteine induces a two-phase response: an early phase lasting 6 h and a late phase peaking at 24 h and declining by 192 h. The early phase shows increased neutrophil accumulation at 2 h up to 24 h, followed by a reduction at 48 h. On the other hand, the late phase exhibits increased macrophage infiltration peaking at 96 h. Inhibition of cystathionine ß-synthase (CBS), the first enzyme in the transsulfuration pathway, significantly reduces L-cysteine-induced edema, suggesting its dependence on CBS-derived hydrogen sulfide (H2S). Sequential formation of sphingosine-1-phosphate (S1P) preceding nitric oxide (NO) generation suggests the involvement of a CBS/S1P/NO axis in the inflammatory response. Inhibition of de novo sphingolipid biosynthesis, S1P1 receptor, and endothelial NO synthase (eNOS) attenuates L-cysteine-induced paw edema. These findings indicate a critical role of the CBS/H2S/S1P/NO signaling pathway in the development and maintenance of L-cysteine-induced inflammation. The co-presence of H2S and NO is necessary for inducing and sustaining the inflammatory response, as NaHS or L-arginine alone do not replicate the marked and prolonged inflammatory effect observed with L-cysteine. This study enhances our understanding of the complex molecular mechanisms of the interplay between NO and H2S pathways in inflammation and identifies potential therapeutic targets for inflammatory disorders.

Hydrogen sulfide regulates the redox state of soluble guanylate cyclase in CSE-/- mice corpus cavernosum microcirculation.

The corpus cavernosum (CC) is a highly vascularized tissue and represents an excellent example of microcirculation. Indeed, erectile dysfunction is considered an early index of cardiovascular disease. Hydrogen sulfide (H2S) at the vascular level is endogenously produced from L-cysteine mainly by the action of cystathionine-γ-lyase (CSE) and plays a role in CC vascular homeostasis. Here we have evaluated the involvement of the endogenous H2S in the regulation of the soluble guanylate cyclase (sCG) redox state. The lack of CSE-derived endogenous H2S, in CSE-/- mice, disrupted the eNOS/NO/sGC/PDE pathway. Indeed, the absence of CSE-derived endogenous H2S caused a significant reduction of the relaxant response to riociguat, an sGC redox-dependent stimulator. Conversely, the response to cinaciguat, an sGC redox-independent activator, was not modified. The relevance of the role played at the redox level of the endogenous H2S was confirmed by the findings that in CC harvested from CSE-/- mice there was a significant reduction of GCß1 expression coupled with a decrease in CYP5R3, a reductase involved in the regulation of the redox state of sGC. These molecular changes driven by the lack of endogenous H2S translate into a significant reduction in cGMP levels. The replenishment of the lack of H2S with an H2S donor rescued the relaxant response to riociguat in CC of CSE-/- mice. In conclusion, the endogenous CSE-derived H2S plays a physiological key role in the regulation of the redox state of sGC in CC microcirculation.

Synthesis and Antiproliferative Insights of Lipophilic Ru(II)-Hydroxy Stearic Acid Hybrid Species.

Metallodrugs represent a combination of multifunctionalities that are present concomitantly and can act differently on diverse biotargets. Their efficacy is often related to the lipophilic features exhibited both by long carbo-chains and the phosphine ligands. Three Ru(II) complexes containing hydroxy stearic acids (HSAs) were successfully synthesized in order to evaluate possible synergistic effects between the known antitumor activity of HSA bio-ligands and the metal center. HSAs were reacted with [Ru(H)2CO(PPh3)3] selectively affording O,O-carboxy bidentate complexes. The organometallic species were fully characterized spectroscopically using ESI-MS, IR, UV-Vis, and NMR techniques. The structure of the compound Ru-12-HSA was also determined using single crystal X-ray diffraction. The biological potency of ruthenium complexes (Ru-7-HSA, Ru-9-HSA, and Ru-12-HSA) was studied on human primary cell lines (HT29, HeLa, and IGROV1). To obtain detailed information about anticancer properties, tests for cytotoxicity, cell proliferation, and DNA damage were performed. The results demonstrate that the new ruthenium complexes, Ru-7-HSA and Ru-9-HSA, possess biological activity. Furthermore, we observed that the Ru-9-HSA complex shows increased antitumor activity on colon cancer cells, HT29.

Two cases of bloodstream infections associated with opportunistic bacterial species (Enterococcus hirae and Enterobacter xiangfangensis) in companion animals.

BACKGROUND: Bloodstream infections are a matter of concern in small animal veterinary practice. Few reports are avaiable, especially regarding the role of opportunistic bacteria in becoming infectious. This report aims to add to the current veterinary literature on two opportunistic bacterial species (Enterococcus hirae and Enterobacter xiangfangensis) associated with bloodstream infections in small animals admitted to the Bologna University Veterinary Hospital. CASE PRESENTATION: In the first case, a 15-year-old, immunocompromised, cardiopathic dog was admitted to the hospital for anorexia and diarrhea. The patient had a history of previous surgery and hospitalization. After three days, hyperthermia, leukopenia and hyperlactatemia were recorded, and blood culture revealed positivity for Enterococcus hirae, identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The patient's general conditions progressively worsened, and the patient was euthanized. In the second case, a 2-year-old cat with chronic ocular herpesvirus infection and hypertrophic cardiomyopathy was admitted to the hospital for anorexia and hyperthermia. The cat was hospitalized one week before and received antimicrobial treatment for urinary tract infection by Staphylococcus felis. Hypokalemia and lymphopenia were also diagnosed. The patient progressively improved and was discharged after three days. On the same day, blood culture taken at admission revealed positivity for Enterobacter xiangfangensis, identified using MALDI-TOF MS. After five days, the patient returned with neurological symptoms, hypothermia and bradycardia, and was euthanized. CONCLUSIONS: In small animal veterinary practice, the impact of opportunistic bacterial agents (such as E.hirae and E.xiangfangensis) on bloodstream infections remains unclear. As in human medicine, they can be contracted in every healthcare setting and considered hospital-acquired infections. In this report, we highlighted the threat they pose especially in patients with multiple risk factors. Rapid and accurate diagnostic tools (such as MALDI-TOF MS) could be particularly important for reducing the severity of the infections.

Case report: First isolation of Yersinia pseudotuberculosis from the blood of a cat.

A 14-year-old female domestic short-haired cat with a diagnosed diabetes mellitus and acromegaly was presented for lethargy and dysorexia. On clinical presentation, the patient showed hyperglycemia, hyperthermia, dull mentation, and dehydration. With the suspicion of an inflammatory or infectious complication of diabetes, she was hospitalized with constant rate infusion of insulin, and empirical ampicillin sulbactam was started. Blood culture revealed positivity for Yersinia pseudotuberculosis and the septic picture was confirmed by blood analysis, with leukocytosis, neutrophilia, and an increased serum amyloid A concentration. The isolated Y. pseudotuberculosis strain showed susceptibility to every antimicrobial tested. During the second day of hospitalization, the onset of hypoglycemia and hypotension was treated with norepinephrine and glucose in fluid therapy. The cat recovered well and was discharged with insulin and amoxicillin-clavulanate. This is the first case of septicemia associated with Y. pseudotuberculosis in a cat, suspected of developing the infection after contact with natural reservoirs such as rodents or birds. This route of transmission should be highlighted especially in relation to the zoonotic potential of the bacteria.

Synthesis of thia-Michael-Type Adducts between Naphthoquinones and N-Acetyl-L-Cysteine and Their Biological Activity.

A series of naphthoquinones, namely, 1,4-naphthoquinone, menadione, plumbagin, juglone, naphthazarin, and lawsone, were reacted with N-acetyl-L-cysteine, and except for lawsone, which did not react, the related adducts were obtained. After the tuning of the solvent and reaction conditions, the reaction products were isolated as almost pure from the complex reaction mixture via simple filtration and were fully characterized. Therefore, the aim of this work was to evaluate whether the antitumor activity of new compounds of 1,4-naphthoquinone derivatives leads to an increase in ROS in tumor cell lines of cervical carcinoma (HeLa), neuroblastoma (SH-SY5Y), and osteosarcoma (SaOS2, U2OS) and in normal dermal fibroblast (HDFa). The MTT assay was used to assay cell viability, the DCF-DA fluorescent probe to evaluate ROS induction, and cell-cycle analysis to measure the antiproliferative effect. Compounds 8, 9, and 12 showed a certain degree of cytotoxicity towards all the malignant cell lines tested, while compound 11 showed biological activity at higher IC50 values. Compounds 8 and 11 induced increases in ROS generation after 1 h of exposure, while after 48 h of treatment, only 8 induced an increase in ROS formation in HeLa cells. Cell-cycle analysis showed that compound 8 caused an increase in the number of G0/G1-phase cells in the HeLa experiment, while for the U2OS and SH-SY5Y cell lines, it led to an accumulation of S-phase cells. Therefore, these novel 1,4-naphthoquinone derivatives may be useful as antitumoral agents in the treatment of different cancers.

ß3 Relaxant Effect in Human Bladder Involves Cystathionine γ-Lyase-Derived Urothelial Hydrogen Sulfide.

It is now well established that the urothelium does not act as a passive barrier but contributes to bladder homeostasis by releasing several signaling molecules in response to physiological and chemical stimuli. Here, we investigated the potential contribution of the hydrogen sulfide (H2S) pathway in regulating human urothelium function in ß3 adrenoceptor-mediated relaxation. The relaxant effect of BRL 37344 (0.1-300 µM), a selective ß3 adrenoceptor agonist, was evaluated in isolated human bladder strips in the presence or absence of the urothelium. The relaxant effect of BRL 37344 was significantly reduced by urothelium removal. The inhibition of cystathionine-γ-lyase (CSE), but not cystathionine-ß-synthase (CBS), significantly reduced the BRL 37344 relaxing effect to the same extent as that given by urothelium removal, suggesting a role for CSE-derived H2S. ß3 adrenoceptor stimulation in the human urothelium or in T24 urothelial cells markedly increased H2S and cAMP levels that were reverted by a blockade of CSE and ß3 adrenoceptor antagonism. These findings demonstrate a key role for urothelium CSE-derived H2S in the ß3 effect on the human bladder through the modulation of cAMP levels. Therefore, the study establishes the relevance of urothelial ß3 adrenoceptors in the regulation of bladder tone, supporting the use of ß3 agonists in patients affected by an overactive bladder.

Climate change effects on bread wheat phenology and grain quality: A case study in the north of Italy.

Increasing temperatures, heat waves, and reduction of annual precipitation are all the expressions of climate change (CC), strongly affecting bread wheat (Triticum aestivum L.) grain yield in Southern Europe. Being temperature the major driving force of plants' phenological development, these variations also have effects on wheat phenology, with possible consequences on grain quality, and gluten protein accumulation. Here, through a case study in the Bolognese Plain (North of Italy), we assessed the effects of CC in the area, the impacts on bread wheat phenological development, and the consequences on grain gluten quality. The increasing trend in mean annual air temperature in the area since 1952 was significant, with a breakpoint identified in 1989, rising from 12.7 to 14.1°C, accompanied by the signals of increasing aridity, i.e., increase in water table depth. Bread wheat phenological development was compared in two 15-year periods before and after the breakpoint, i.e., 1952-1966 (past period), and 2006-2020 (present period), the latest characterized by aridity and increased temperatures. A significant shortening of the chronological time necessary to reach the main phenological phases was observed for the present period compared to the past period, finally shortening the whole life cycle. This reduction, as well as the higher temperature regime, affected gluten accumulation during the grain-filling process, as emerged analyzing gluten composition in grain samples of the same variety harvested in the area both before and after the breakpoint in temperature. In particular, the proportion of gluten polymers (i.e., gliadins, high and low molecular weight glutenins, and their ratio) showed a strong and significant correlation with cumulative growing degree days (CGDDs) accumulated during the grain filling. Higher CGDD values during the period, typical of CC in Southern Europe, accounting for higher temperature and faster grain filling, correlated with gliadins, high molecular weight glutenins, and their proportion with low molecular weight glutenins. In summary, herein reported, data might contribute to assessing the effects of CC on wheat phenology and quality, representing a tool for both predictive purposes and decision supporting systems for farmers, as well as can guide future breeding choices for varietal innovation.

Determination of Free Amino Acids in Milk, Colostrum and Plasma of Swine via Liquid Chromatography with Fluorescence and UV Detection.

Amino acids are ubiquitous components of mammalian milk and greatly contribute to its nutritional value. The compositional analysis of free amino acids is poorly reported in the literature even though their determination in the biological fluids of livestock animals is necessary to establish possible nutritional interventions. In the present study, the free amino acid profiles in mature swine milk, colostrum and plasma were assessed using a targeted metabolomics approach. In particular, 20 amino acids were identified and quantified via two alternative and complementary reversed-phase HPLC methods, involving two stationary phases based on core-shell technology, i.e., Kinetex C18 and Kinetex F5, and two detection systems, i.e., a diode array detector (DAD) and a fluorescence detector (FLD). The sample preparation involved a de-proteinization step, followed by pre-chromatographic derivatization with 9-fluorenylmethylchloroformate (FMOC-Cl). The two optimized methods were validated for specificity, linearity, sensitivity, matrix effect, accuracy and precision and the analytical performances were compared. The analytical methods proved to be suitable for free amino acid profiling in different matrices with high sensitivity and specificity. The correlations among amino acid levels in different biological fluids can be useful for the evaluation of physio-pathological status and to monitor the effects of therapeutic or nutritional interventions in humans and animals.

Measuring Adolescents' Self-injurious Thoughts and Behaviors: Comparing Ecological Momentary Assessment to a Traditional Interview.

The purpose of this study was to compare adolescents' reports of self-injurious thoughts and behaviors (SITBs) between ecological momentary assessment (EMA) and a traditional, retrospective interview. Adolescents were recruited following recent discharge from acute psychiatric care for a suicidal crisis (as part of a larger study). Participants completed: (1) EMA surveys assessing SITBs multiple times daily over a 28-day follow-up period, and (2) a follow-up phone interview to evaluate SITBs retrospectively at the end of the same 28-day follow-up period. Forty-one adolescents completed the final follow-up interview (Mage = 14.9 years; 78.0% White; 61.0% female). Adolescents' reports of SITB presence (vs. absence) and frequency, collected via EMA and retrospective interview over follow-up, were compared. Preliminary differences in SITB endorsement (presence/absence) were observed between reporting methods with more adolescents endorsing suicide ideation (SI; n = 30) and nonsuicidal self-injury (NSSI; n = 15) in EMA compared to retrospective interview (SI: n = 17; NSSI: n = 10). Reasons for withholding SITBs from EMA reports (gathered during a final qualitative interview) included not wanting to answer additional EMA questions and concerns about EMA-reporting consequences. There were no statistically significant differences in SITB frequency by report method. Further investigation is warranted in a larger sample to elucidate frequency patterns. Given the growing research using this method, these findings are important to help clarify the utility of EMA methods for studying SITBs in youth.

Feasibility and Acceptability of Ecological Momentary Assessment with High-Risk Suicidal Adolescents Following Acute Psychiatric Care.

Objective: The study purpose was to examine the feasibility and acceptability of intensive ecological momentary assessment (EMA) among high-risk adolescents with suicidal thoughts and behaviors following discharge from acute psychiatric care.Method: Fifty-three adolescents, 12-18 years old, and their parents, were recruited following discharge from acute psychiatric care for suicide risk. The study included a baseline assessment (adolescent and parent), 28 days of EMA surveys (5x per day) and wrist actigraphy (adolescent), and an interview at the end of the 28-day monitoring period (adolescent). Adolescents' outpatient clinicians were also surveyed about the study.Results: Study feasibility was indicated by a reasonable enrollment rate, high adherence to wearing the actigraphy device, and good adherence to EMA surveys (highest in the first week with significant drop-off in subsequent weeks). Adolescents reported their overall experience in the study was positive, the questions were understandable, their responses to questions were generally accurate, and the surveys were minimally burdensome. The study procedures did not appear to be iatrogenic; suicide attempts and rehospitalizations were not study related and occurred at a rate comparable to other adolescents at the recruitment site. Adolescents' clinicians reported that the study was somewhat positive and minimally burdensome for them, and somewhat positive for their patients and families.Conclusions: This study demonstrated that intensive EMA designs are feasible and acceptable among high-risk suicidal youth following acute psychiatric care. Specific procedures are provided for keeping adolescents safe during intensive EMA studies, including detailed information about the risk and safety monitoring plan.

Thwarted Belongingness Mediates Interpersonal Stress and Suicidal Thoughts: An Intensive Longitudinal Study with High-risk Adolescents.

OBJECTIVE: Interpersonal negative life events (NLEs) have been linked to risk for suicidal thoughts and behaviors. However, little is known about how this risk is conferred over the short term and the mechanisms linking interpersonal NLEs to suicide risk, particularly in adolescents. This study used an intensive longitudinal design to examine thwarted belongingness with family and friends as potential mechanisms linking interpersonal NLEs to suicidal thoughts. METHOD: Forty-eight adolescents (Mage = 14.96 years; 64.6% female, 77.1% White), who recently received acute psychiatric care for suicide risk, were followed intensely for 28 days after discharge. Smartphone-based ecological momentary assessment was used to measure presence of interpersonal NLEs at the day level, fluctuations in thwarted belongingness with family and friends (separately) within day, and fluctuations in suicidal thoughts within day. A multi-level structural equation model was utilized to examine family thwarted belongingness and friend thwarted belongingness as parallel mediators in the relationship between interpersonal NLEs and next-day suicidal thoughts. RESULTS: Significant direct effects were observed between interpersonal NLEs and family thwarted belongingness, family thwarted belongingness and suicidal thoughts, and friend thwarted belongingness and suicidal thoughts. In addition, family, but not friend, thwarted belongingness significantly mediated the association between interpersonal NLEs and next-day suicidal thoughts. CONCLUSIONS: Interpersonal NLEs predicted greater suicidal thoughts over the short term (next day) in high-risk adolescents. Findings suggest how interpersonal NLEs may confer risk for suicidal thoughts - by reducing feelings of family belongingness. Future research is needed to examine how modifying belongingness may reduce suicide risk in adolescents.

Pilot RCT of the Attempted Suicide Short Intervention Program (ASSIP) adapted for rapid delivery during hospitalization to adult suicide attempt patients with substance use problems.

OBJECTIVE: The Attempted Suicide Short Intervention Program (ASSIP) was adapted for hospital delivery and to address substance use problems as well as evaluated for feasibility, acceptability, and therapist fidelity in a series of preparatory steps (n = 28) and in a pilot randomized controlled trial, RCT (n = 34). METHOD: In the RCT, patients with suicide attempts and substance use problem(s) with sufficient lengths of stay to deliver three ASSIP therapy sessions in hospital were randomized to adapted ASSIP or treatment as usual control. A blinded assessor identified suicide reattempts over 6-month follow-up with the Columbia-Suicide Severity Rating Scale (C-SSRS) and a comprehensive multi-source method. Treatment process measures and the Scale for Suicidal Ideation (SSI) were also administered. RESULTS: Median hospital stay was 13 days. ASSIP subjects reported high satisfaction with the treatment and high therapeutic alliance. Study therapists showed high fidelity to the modified ASSIP intervention. Repetition of suicide attempt was common in both study groups including a combined 9 (26%) subjects with reattempt based on C-SSRS and 13 (38%) subjects with reattempt based on multiple sources. CONCLUSIONS: Adult suicide attempt patients with substance use problems who require lengthy hospitalizations are at exceptionally high risk and may require additional strategies to lower risk.