Cyberbullying and Suicidal Behavior, Self-Harm, and Nonsuicidal Self-Injury: A Systematic Review of Longitudinal Studies.

Aim: Identify and systematically review cohort studies examining the association between cyberbullying (CB) and suicidal ideation, attempted suicide, self-harm, and nonsuicidal self-injury (NSSI). Methods: Systematic literature review following PRISMA guidelines. Searches for relevant literature were conducted in Scopus, Web of Science, PubMed, PsyINFO, CINAHL, Embase, and Cochrane up until July 2023. Cohort studies were included that provided information regarding the association between CB and different dimensions pertaining to self-injurious thoughts and behaviors (SITB) separately. Gathered information included data on study characteristics, sample characteristics, prevalence, and associations between CB and variables pertaining to SITB. Findings were synthesized, and grouping studies as a function of the outcome variable was analyzed. Results: A total of 19 studies were included. Suicidal ideation was analyzed in 11 studies, with the majority (n = 8) reporting statistically significant positive associations (aOR = 1.88 [1.08, 3.29], ß = 0.08 to 0.47). Only a single study conducted independent analysis of attempted suicide, finding a statistically significant association (aOR 1.88 [1.08, 3.29]). Outcomes regarding the self-harm variable were equivocal, with only two out of five studies finding a statistically significant association and one of these, which conducted a gender differentiated analysis, only finding a significant association in females. Studies that considered the NSSI dimension were also inconclusive, with only a limited number of studies (n = 5) producing contradictory outcomes. Conclusion: There is a need to continue exploring the relationship between CB and different dimensions within the spectrum of SITB through longitudinal studies. It is recommended that analyses adopt a new perspective in which short-term follow-up is prioritized or individualized follow-up periods are considered, given the rapidly changing nature of suicidal tendencies. It would be interesting to analyze the frequency, persistence, or severity of CB events and broaden research to include all age ranges. Special attention should also be given to potential gender differences and possible mediators or moderators.

Is a vegetarian diet beneficial for bipolar disorder? Relationship between dietary patterns, exercise and pharmacological treatments with metabolic syndrome and course of disease in bipolar disorder.

BACKGROUND: Lifestyle factors are being increasingly studied in bipolar disorder (BD) due to their possible effects on both course of disease and physical health. The aim of this study was to jointly describe and explore the interrelations between diet patterns, exercise, pharmacological treatment with course of disease and metabolic profile in BD. METHODS: The sample consisted of 66 euthymic or mild depressive individuals with BD. Clinical and metabolic outcomes were assessed, as well as pharmacological treatment or lifestyle habits (diet and exercise). Correlations were explored for different interrelations and a factor analysis of dietary patterns was performed. RESULTS: Adherence to the Mediterranean diet was low, seen in 37.9% of the patients and was positively associated with perceived quality of life. The amount of exercise was negatively associated with cholesterol levels, with 32.8% of participants rated as low active by International Physical Activity Questionnaire. There was a high prevalence of obesity (40.6%) and metabolic syndrome (29.7%). Users of lithium showed the best metabolic profile. Interestingly, three dietary patterns were identified: "vegetarian," "omnivore" and "Western." The key finding was the overall positive impact of the "vegetarian" pattern in BD, which was associated with reduced depression scores, better psychosocial functioning, and perceived quality of life, decreased body mass index, cholesterol, LDL and diastolic blood pressure. Nuts consumption was associated with a better metabolic profile. CONCLUSIONS: A vegetarian diet pattern was associated with both, better clinical and metabolic parameters, in patients with BD. Future studies should prioritize prospective and randomized designs to determine causal relationships, and potentially inform clinical recommendations.

SARS-CoV-2 S Protein Reduces Cytoprotective Defenses and Promotes Human Endothelial Cell Senescence.

Premature vascular aging and endothelial cell senescence are major risk factors for cardiovascular diseases and atherothrombotic disturbances, which are main complications of both acute and long COVID-19. The S protein of SARS-CoV2, which acts as the receptor binding protein for the viral infection, is able to induce endothelial cells inflammation and it has been found as an isolated element in the circulation and in human tissues reservoirs months after infection. Here, we investigated whether the S protein is able to directly induce endothelial cell senescence and deciphered some of the mechanisms involved. In primary cultures of human umbilical vein endothelial cells (HUVEC), SARS-CoV-2 S protein enhanced in a concentration-dependent manner the cellular content of senescence and DNA damage response markers (senescence-associated-ß galactosidase, γH2AX), as well as growth-arrest effectors (p53, p21, p16). In parallel, the S protein reduced the availability of cytoprotective proteins, such as the anti-aging protein klotho, Nrf2 or heme oxygenase-1, and caused functional harm by impairing ex vivo endothelial-dependent vasorelaxation in murine microvessels. These effects were prevented by the pharmacological inhibition of the NLRP3 inflammasome with MCC950. Furthermore, the supplementation with either recombinant klotho or angiotensin-(1-7), equally protected against the pro-senescence, pro-inflammatory and pro-oxidant action of the S protein. Globally, this study proposes novel mechanisms of disease in the context of COVID-19 and its vascular sequelae and provides pharmacological clues in order to prevent such complications.

Trans-[Pt(amine)Cl2(PPh3)] Complexes Target Mitochondria and Endoplasmic Reticulum in Gastric Cancer Cells.

Gastric cancer prognosis is still notably poor despite efforts made to improve diagnosis and treatment of the disease. Chemotherapy based on platinum agents is generally used, regardless of the fact that drug toxicity leads to limited clinical efficacy. In order to overcome these problems, our group has been working on the synthesis and study of trans platinum (II) complexes. Here, we explore the potential use of two phosphine-based agents with the general formula trans-[Pt(amine)Cl2(PPh3)], called P1 and P2 (with dimethylamine or isopropylamine, respectively). A cytotoxicity analysis showed that P1 and especially P2 decrease cell viability. Specifically, P2 exhibits higher activity than cisplatin in gastric cancer cells while its toxicity in healthy cells is slightly lower. Both complexes generate Reactive Oxygen Species, produce DNA damage and mitochondrial membrane depolarization, and finally lead to induced apoptosis. Thus, an intrinsic apoptotic pathway emerges as the main type of cell death through the activation of BAX/BAK and BIM and the degradation of MCL1. Additionally, we demonstrate here that P2 produces endoplasmic reticulum stress and activates the Unfolded Protein Response, which also relates to the impairment observed in autophagy markers such as p62 and LC3. Although further studies in other biological models are needed, these results report the biomolecular mechanism of action of these Pt(II)-phosphine prototypes, thus highlighting their potential as novel and effective therapies.

Diet shapes the metabolite profile in the intact human ileum, which affects PYY release.

The human ileum contains a high density of enteroendocrine L-cells, which release the appetite-suppressing hormones glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) in response to food intake. Recent evidence highlighted the potential role of food structures in PYY release, but the link between food structures, ileal metabolites, and appetite hormone release remains unclear owing to limited access to intact human ileum. In a randomized crossover trial (ISRCTN11327221; isrctn.com), we investigated the role of human ileum in GLP-1 and PYY release by giving healthy volunteers diets differing in fiber and food structure: high-fiber (intact or disrupted food structures) or low-fiber disrupted food structures. We used nasoenteric tubes to sample chyme from the intact distal ileum lumina of humans in the fasted state and every 60 min for 480 min postprandially. We demonstrate the highly dynamic, wide-ranging molecular environment of the ileum over time, with a substantial decrease in ileum bacterial numbers and bacterial metabolites after food intake. We also show that high-fiber diets, independent of food structure, increased PYY release compared with a low-fiber diet during 0 to 240 min postprandially. High-fiber diets also increased ileal stachyose, and a disrupted high-fiber diet increased certain ileal amino acids. Treatment of human ileal organoids with ileal fluids or an amino acid and stachyose mixture stimulated PYY expression in a similar profile to blood PYY concentrations, confirming the role of ileal metabolites in PYY release. Our study demonstrates the diet-induced changes over time in the metabolite environment of intact human ileum, which play a role in PYY release.

DNA methylation and stroke prognosis: an epigenome-wide association study.

BACKGROUND AND AIMS: Stroke is the leading cause of adult-onset disability. Although clinical factors influence stroke outcome, there is a significant variability among individuals that may be attributed to genetics and epigenetics, including DNA methylation (DNAm). We aimed to study the association between DNAm and stroke prognosis. METHODS AND RESULTS: To that aim, we conducted a two-phase study (discovery-replication and meta-analysis) in Caucasian patients with ischemic stroke from two independent centers (BasicMar [discovery, N = 316] and St. Pau [replication, N = 92]). Functional outcome was assessed using the modified Rankin Scale (mRS) at three months after stroke, being poor outcome defined as mRS > 2. DNAm was determined using the 450K and EPIC BeadChips in whole-blood samples collected within the first 24 h. We searched for differentially methylated positions (DMPs) in 370,344 CpGs, and candidates below p-value < 10-5 were subsequently tested in the replication cohort. We then meta-analyzed DMP results from both cohorts and used them to identify differentially methylated regions (DMRs). After doing the epigenome-wide association study, we found 29 DMPs at p-value < 10-5 and one of them was replicated: cg24391982, annotated to thrombospondin-2 (THBS2) gene (p-valuediscovery = 1.54·10-6; p-valuereplication = 9.17·10-4; p-valuemeta-analysis = 6.39·10-9). Besides, four DMRs were identified in patients with poor outcome annotated to zinc finger protein 57 homolog (ZFP57), Arachidonate 12-Lipoxygenase 12S Type (ALOX12), ABI Family Member 3 (ABI3) and Allantoicase (ALLC) genes (p-value < 1·10-9 in all cases). DISCUSSION: Patients with poor outcome showed a DMP at THBS2 and four DMRs annotated to ZFP57, ALOX12, ABI3 and ALLC genes. This suggests an association between stroke outcome and DNAm, which may help identify new stroke recovery mechanisms.

Selective decontamination of the digestive tract in a burns unit reduces the incidence of hospital-acquired infections: A retrospective before-and-after cohort study.

OBJECTIVE: To evaluate the effect of selective decontamination of the digestive tract (SDD) on hospital-acquired infections (HAIs) in patients with acute burn injury requiring admission to a Burns Unit (BU). DESIGN: Retrospective before-and-after cohort study, between January 2017 and June 2023. SDD was implemented in March 2019, dividing patients into two groups. SETTING: Four-bed BU, in a referral University Hospital in Spain. PATIENTS: All the patients admitted during the study period were eligible for analysis. Patients who died or were discharged within 48hours of admission, and patients with an estimated survival less than 10% not considered for full escalation of therapy were excluded. INTERVENTION: SDD comprised the administration of a 4-day course of an intravenous antibiotic, and an oral suspension and oral topical paste of non-absorbable antibiotics during the stay in the BU. MAIN VARIABLE OF INTEREST: Incidence of HAIs during the stay in the BU. SECONDARY OUTCOMES: incidence of specific types of infections by site (bacteremia, pneumonia, skin and soft tissue infection) and microorganism (Gram-positive, Gram-negative, fungi), and safety endpoints. RESULTS: We analyzed 72 patients: 27 did not receive SDD, and 45 received SDD. The number of patients who developed HAIs were 21 (77.8%) and 21 (46.7%) in the non-SDD and the SDD groups, respectively (p=0.009). The number of hospital-acquired infectious episodes were 2.52 (1.21-3.82) and 1.13 (0.54-1.73), respectively (p=0.029). CONCLUSIONS: SDD was associated with a reduced incidence of bacterial HAIs and a decrease in the number of infectious episodes per patient.

Complementary and Alternative Medicine to Treat Fibromyalgia Symptoms. A Systematic Review.

This study aims to investigate the current evidence for the use of complementary and alternative medicine (CAM) in fibromyalgia (FM). A systematic review was conducted searching for PubMed, Scopus, CINAHL, PsycInfo, and Web of Science databases. Randomized controlled trials published up to December 2023 in peer-reviewed journals were included. Methodological quality was assessed by the Quality Assessment of Controlled Intervention Studies tool. A total of 216 articles were identified and 15 constituted the final sample. The type of CAM most used was traditional Chinese medicine (60%), and the most common instrument used was the Fibromyalgia Impact Questionnaire (60%). Our review was grouped into four themes based on the origin of the therapies: 1) Traditional Chinese Medicine; 2) Japanese natural harmonization (eg, Reiki); 3) Ayurvedic Medicine; and 4) Other non-drug therapies. Our systematic review showed that there is a wide range of CAMs used to treat FM. Most of the clinical trials have shown significant results for the effectiveness of these interventions in both physical and mental health outcomes of FM as compared to control groups. However, the heterogeneity of the interventions and outcomes warrants further studies on this topic.

Systematic review of healthcare interventions for reducing gender-based violence impact on the mental health of women with disabilities.

PURPOSE: Women with disabilities are more exposed to violence. The health sector has a key role in all three levels of prevention of violence against women. The objective of this paper was to review the interventions for preventing gender-based violence and reducing its impact on the mental health of women with any form of disability. METHOD: Relevant studies were identified through conducting searches in PubMed, Scopus, CINAHL, PsyInfo, Social Services Abstracts, and PILOTS. Two reviewers analyzed and selected studies. A qualitative synthesis was made. RESULTS: 3149 references were obtained, among which eight articles describing nine interventions from the USA and the UK. Most were intended for women with mental/intellectual disability and assessed intimate partner or sexual violence. Only one study showed high methodological quality. They were found to be particularly effective as regards improvement of the skills acquired by participants, but the results as regards improved mental health are not consistent. CONCLUSION: Our review shows very little evidence of effective interventions. Further studies are required with higher internal validity and female sample groups with diverse disabilities. CLINICAL RELEVANCE: Gender-based violence is a highly prevalent problem for women with disabilities, and in addition to being a public health challenge is a violation of human rights. Health care systems and policymakers should take a key role in all three levels of prevention of violence against women with disabilities. Interventions with longer follow-up times are required. It is also important for interventions to be designed in consultation with people with disabilities.

The Association of Cardiometabolic, Diet and Lifestyle Parameters With Plasma Glucagon-like Peptide-1: An IMI DIRECT Study.

CONTEXT: The role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes (T2D) and obesity is not fully understood. OBJECTIVE: We investigate the association of cardiometabolic, diet, and lifestyle parameters on fasting and postprandial GLP-1 in people at risk of, or living with, T2D. METHODS: We analyzed cross-sectional data from the two Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohorts, cohort 1 (n = 2127) individuals at risk of diabetes; cohort 2 (n = 789) individuals with new-onset T2D. RESULTS: Our multiple regression analysis reveals that fasting total GLP-1 is associated with an insulin-resistant phenotype and observe a strong independent relationship with male sex, increased adiposity, and liver fat, particularly in the prediabetes population. In contrast, we showed that incremental GLP-1 decreases with worsening glycemia, higher adiposity, liver fat, male sex, and reduced insulin sensitivity in the prediabetes cohort. Higher fasting total GLP-1 was associated with a low intake of wholegrain, fruit, and vegetables in people with prediabetes, and with a high intake of red meat and alcohol in people with diabetes. CONCLUSION: These studies provide novel insights into the association between fasting and incremental GLP-1, metabolic traits of diabetes and obesity, and dietary intake, and raise intriguing questions regarding the relevance of fasting GLP-1 in the pathophysiology T2D.

Blood DNA Methylation Analysis Reveals a Distinctive Epigenetic Signature of Vasospasm in Aneurysmal Subarachnoid Hemorrhage.

Vasospasm is a potentially preventable cause of poor prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH). Epigenetics might provide insight on its molecular mechanisms. We aimed to analyze the association between differential DNA methylation (DNAm) and development of vasospasm. We conducted an epigenome-wide association study in 282 patients with aSAH admitted to our hospital. DNAm was assessed with the EPIC Illumina chip (> 850 K CpG sites) in whole-blood samples collected at hospital admission. We identified differentially methylated positions (DMPs) at the CpG level using Cox regression models adjusted for potential confounders, and then we used the DMP results to find differentially methylated regions (DMRs) and enriched biological pathways. A total of 145 patients (51%) experienced vasospasm. In the DMP analysis, we identified 31 CpGs associated with vasospasm at p-value < 10-5. One of them (cg26189827) was significant at the genome-wide level (p-value < 10-8), being hypermethylated in patients with vasospasm and annotated to SUGCT gene, mainly expressed in arteries. Region analysis revealed 13 DMRs, some of them annotated to interesting genes such as POU5F1, HLA-DPA1, RUFY1, and CYP1A1. Functional enrichment analysis showed the involvement of biological processes related to immunity, inflammatory response, oxidative stress, endothelial nitric oxide, and apoptosis. Our findings show, for the first time, a distinctive epigenetic signature of vasospasm in aSAH, establishing novel links with essential biological pathways, including inflammation, immune responses, and oxidative stress. Although further validation is required, our results provide a foundation for future research into the complex pathophysiology of vasospasm.

Exploring the Integrated Role of miRNAs and lncRNAs in Regulating the Transcriptional Response to Amino Acids and Insulin-like Growth Factor 1 in Gilthead Sea Bream (Sparus aurata) Myoblasts.

In this study, gilthead sea bream (Sparus aurata) fast muscle myoblasts were stimulated with two pro-growth treatments, amino acids (AA) and insulin-like growth factor 1 (Igf-1), to analyze the transcriptional response of mRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) and to explore their possible regulatory network using bioinformatic approaches. AA had a higher impact on transcription (1795 mRNAs changed) compared to Igf-1 (385 mRNAs changed). Both treatments stimulated the transcription of mRNAs related to muscle differentiation (GO:0042692) and sarcomere (GO:0030017), while AA strongly stimulated DNA replication and cell division (GO:0007049). Both pro-growth treatments altered the transcription of over 100 miRNAs, including muscle-specific miRNAs (myomiRs), such as miR-133a/b, miR-206, miR-499, miR-1, and miR-27a. Among 111 detected lncRNAs (>1 FPKM), only 30 were significantly changed by AA and 11 by Igf-1. Eight lncRNAs exhibited strong negative correlations with several mRNAs, suggesting a possible regulation, while 30 lncRNAs showed strong correlations and interactions with several miRNAs, suggesting a role as sponges. This work is the first step in the identification of the ncRNAs network controlling muscle development and growth in gilthead sea bream, pointing out potential regulatory mechanisms in response to pro-growth signals.

Early automated cerebral edema assessment following endovascular therapy: impact on stroke outcome.

BACKGROUND: Cerebral edema (CED) is associated with poorer outcome in patients with acute ischemic stroke (AIS). The aim of the study was to investigate the factors contributing to greater early CED formation in patients with AIS who underwent endovascular therapy (EVT) and its association with functional outcome. METHODS: We conducted a multicenter cohort study of patients with an anterior circulation AIS undergoing EVT. The volume of cerebrospinal fluid (CSF) was extracted from baseline and 24-hour follow-up CT using an automated algorithm. The severity of CED was quantified by the percentage reduction in CSF volume between CT scans (∆CSF). The primary endpoint was a shift towards an unfavorable outcome, assessed by modified Rankin Scale (mRS) score at 3 months. Multivariable ordinal logistic regression analyses were performed. The ∆CSF threshold that predicted unfavorable outcome was selected using receiver operating characteristic curve analysis. RESULTS: We analyzed 201 patients (mean age 72.7 years, 47.8% women) in whom CED was assessable for 85.6%. Higher systolic blood pressure during EVT and failure to achieve modified Thrombolysis In Cerebral Infarction (mTICI) 3 were found to be independent predictors of greater CED. ∆CSF was independently associated with the probability of a one-point worsening in the mRS score (common odds ratio (cOR) 1.05, 95% CI 1.03 to 1.08) after adjusting for age, baseline mRS, National Institutes of Health Stroke Scale (NIHSS), and number of passes. Displacement of more than 25% of CSF was associated with an unfavorable outcome (OR 6.09, 95% CI 3.01 to 12.33) and mortality (OR 6.72, 95% CI 2.94 to 15.32). CONCLUSIONS: Early CED formation in patients undergoing EVT was affected by higher blood pressure and incomplete reperfusion. The extent of early CED, measured by automated ∆CSF, was associated with worse outcomes.

Bilateral Spigelian Hernias Robotic Repair: A Novel Approach to a Rare Surgical Entity.

Spigelian hernias are an uncommon protrusion defect noted between the rectus abdominis and the transversus abdominis muscles, at the semilunar line, with a low incidence of approximately 0.12% to 2% of all ventral hernias. Furthermore, the incidence of bilateral cases is noted to be even lower in the general population. They are associated with bowel incarceration and strangulation; hence surgical repair is indicated. Therapeutic alternatives for Spigelian hernias include open repair, however laparoscopic repair stands as the standard of care in these cases. Feasible and successful robotic repair has been reported, with associated advantages in terms of visualization and surgical instrument dexterity. We present the first ever reported cases of bilateral Spigelian hernias repaired using robotic approach. Two female Puerto Rican patients referred to our institution complaining of abdominal pain, where imaging studies found bilateral Spigelian hernias. In both cases, a transabdominal preperitoneal repair was performed using the Da Vinci Surgical System. Both patients were discharged home tolerating oral intake with adequate wound healing. On follow up visits, patients denied abdominal discomfort and had adequate wound healing. Robotic surgery for Spigelian hernias poses an advantage over laparoscopic repair as improved visualization, mobility, and precision in movements allow for more gentle tissue manipulation. Furthermore, this is the first evidence of safe and effective repair in the uncommon entity of bilateral cases, providing a newer alternative in the setting of such presentation.

Stroke-associated pneumonia according to mCDC criteria: impact on prognosis and antibiotic therapy.

Objective: The modified Centers for Disease Control and Prevention (mCDC) criteria have been proposed for diagnosing and managing stroke-associated pneumonia (SAP). The objective was to investigate the impact of SAP on stroke outcome depending on whether or not it conforms to mCDC criteria. Our secondary objective was to identify the responsible factors for antibiotic initiation in stroke patients. Methods: We conducted a prospective, multicenter, observational study of ischemic stroke patients with moderate to severe stroke (NIHSS≥4) admitted within 24 h. For 7 days, mCDC criteria were assessed daily, and infections and antibiotics were recorded. Pneumonias were divided into those fulfilling mCDC criteria (mCDC-SAP) or not (other pneumonias, OPn). The effect of each type of pneumonia on 3-month outcome was evaluated in separated logistic regression models. Factors associated with antibiotic initiation were explored using a random forest analysis. Results: Of the 342 patients studied, infections were diagnosed in 72 (21.6%), including 39 (11.7%) cases of pneumonia. Of them, 25 (7.5%) fulfilled mCDC criteria. Antibiotics were used in 92% of mCDC-SAP and 64.3% of OPn. In logistic regression analysis, mCDC-SAP, but not OPn, was an independent predictor of poor outcome [OR, 4.939 (1.022-23.868)]. The random forest analysis revealed that fever had the highest importance for antibiotic initiation. Interpretation: The mCDC criteria might be useful for detecting clinically relevant SAP, which is associated with poor outcomes. Isolated signs of infection were more important for antibiotic initiation than compliance with pre-defined criteria. Therefore, adherence to mCDC criteria might result in antibiotic saving without compromising clinical outcome.