Global cross-cultural validation of a brief measure for identifying potential suicide risk in 42 countries.

OBJECTIVES: This study aimed to examine the psychometric properties of the P4 suicide screener in a multinational sample. The primary goal was to evaluate the reliability and validity of the scale and investigate its convergent validity by analyzing its correlation with depression, anxiety, and substance use. STUDY DESIGN: The study design is a cross-sectional self-report study conducted across 42 countries. METHODS: A cross-sectional, self-report study was conducted in 42 countries, with a total of 82,243 participants included in the final data set. RESULTS: The study provides an overview of suicide ideation rates across 42 countries and confirms the structural validity of the P4 screener. The findings indicated that sexual and gender minority individuals exhibited higher rates of suicidal ideation. The P4 screener showed adequate reliability, convergence, and discriminant validity, and a cutoff score of 1 is recommended to identify individuals at risk of suicidal behavior. CONCLUSIONS: The study supports the reliability and validity of the P4 suicide screener across 42 diverse countries, highlighting the importance of using a cross-cultural suicide risk assessment to standardize the identification of high-risk individuals and tailoring culturally sensitive suicide prevention strategies.

Radiant Exitance of Old, New, and Damaged LED Light Curing Units.

PURPOSE: This study aimed to determine the radiant exitance of new, damaged, and 16-year-old light-curing units (LCUs) with and without infection control barriers, and before and after removal of any debris. METHODS AND MATERIALS: Old LCUs consisted of 62 SmartLite iQ2 lights (Dentsply Sirona, York, PA). New LCUs consisted of 58 SmartLite Focus (Dentsply Sirona) and 58 Valo Grand (Ultradent, South Jordan, UT, USA) LCUs. Each LCU was examined for damage and debris on its tip. A handheld radiometer (CheckUp with BlueLight Analytics app, Halifax, Nova Scotia, Canada ) was used to measure the radiant exitance using a 10-second exposure time. Measurements were made with and without infection control barriers. If debris was present, the radiant exitance was measured before and after removal of debris with and without the barriers. All measurements were repeated three times. The means of the measurements were used for statistical analyses, which consisted of paired t-tests, analysis of variance (ANOVA), and Tukey post-hoc analyses conducted with a 0.05 level of significance. RESULTS: Infection control barriers significantly reduced the radiant exitance of all LCUs, ranging from 4.35% to 6.91% depending upon the LCU and the presence of debris or damage. Clean undamaged SmartLite Focus (907 mW/cm2) and Valo Grand (Ultradent) LCUs (883 mW/cm2) with barriers had statistically higher radiant exitance than older clean undamaged SmartLite iQ2 (Dentsply Sirona) LCUs (719 mW/cm2) with barriers. All LCUs exceeded the recommended 400 mW/cm2 radiant power to cure 2 mm of Filtek Supreme Ultra shade A2 composite resin (3M ESPE, St Paul MN, USA). CONCLUSION: Infection control barriers, debris, damage, and age all significantly reduced radiant exitance of the lights.

Current level of technology use, health and eHealth literacy in older Canadians with a recent fracture-a survey in orthopedic clinics.

Among older adults who have recently sustained a fracture, there is substantial adoption of mobile technology. Furthermore, health and eHealth literacy level reported by participants supports the development of interactive eHealth interventions toward fostering better patient engagement in skeletal health management. INTRODUCTION: Electronic health resources are increasingly used in the self-management of medical conditions. We aimed to identify the current level of technology adoption, health, and eHealth literacy among older adults with a recent fracture, to determine if the use of electronic interventions would be feasible and acceptable in this population. METHODS: Adults ≥ 50 years with recent fractures were invited to complete a self-administered survey composed of 21 questions, including an 8-item perceived eHealth literacy scale. RESULTS: A total of 401 participants completed the survey (women, 64%; ≥ 65 years, 59%; university education, 32%). Most participants reported no difficulty in reading printed health material (67%) and felt confident in filling out medical forms (65%). Younger age and higher levels of education were associated with higher health literacy. Most respondents (81%) owned at least one mobile device (smartphone, 49%; tablet, 45%). eHEALS scores were similar among men (29, IQR 24-32) and women (29, IQR 25-33), and between younger age group categories (50-64 years, 30; IQR 26-33; and 65-74 years, 29; IQR 25-32), but lower in the oldest age group (≥ 75 years, 24; IQR 21-29; p < 0.05). Compared with the youngest group, those ≥ 75 years had higher odds of an eHEALS < 26 (odds ratio, 4.2; 95% confidence interval 2.0-8.9) after adjusting for sex and education level. CONCLUSION: There is significant adoption of mobile technology among older adults. Health and eHealth literacy reported by this study population supports the development of interactive eHealth interventions toward fostering better patient engagement in skeletal health management.

Link N suppresses interleukin-1ß-induced biological effects on human osteoarthritic cartilage.

Osteoarthritis (OA) is a disease of diarthrodial joints associated with extracellular matrix proteolytic degradation under inflammatory conditions, pain and disability. Currently, there is no therapy to prevent, reverse or modulate the disease course. The present study aimed at evaluating the regenerative potential of Link N (LN) in human OA cartilage in an inflammatory milieu and determining if LN could affect pain-related behaviour in a knee OA mouse injury model. Osteo-chondro OA explants and OA chondrocytes were treated with LN in the presence of interleukin-1ß (IL-1ß) to simulate an osteoarthritic environment. Quantitative von Frey polymerase chain reaction and Western blotting were performed to determine the effect of LN on matrix protein synthesis, catabolic enzymes, cytokines and nerve growth factor expression. Partial medial meniscectomy (PMM) was performed on the knee of C57BL/6 mice and, 12 weeks post-surgery, mice were given a 5 µg intra-articular injection of LN or phosphate-buffered saline. A von Frey test was conducted over 24 h to measure the mechanical allodynia in the hind paw. LN modulated proteoglycan and collagen synthesis in human OA cartilage through inhibition of IL-1ß-induced biological effects. LN also supressed IL-1ß-induced upregulation of cartilage-degrading enzymes and inflammatory molecules in OA chondrocytes. Upon investigation of the canonical signalling pathways IL-1ß and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), LN resulted to significantly inhibit NF-κB activation in a dose-dependent manner. In addition, LN suppressed mechanical allodynia in an OA PMM mouse model. Results supported the concept that LN administration could provide therapeutic potential in OA.

In Vitro Chromatin Assembly: Strategies and Quality Control.

Chromatin accessibility is modulated by structural transitions that provide timely access to the genetic and epigenetic information during many essential nuclear processes. These transitions are orchestrated by regulatory proteins that coordinate intricate structural modifications and signaling pathways. In vitro reconstituted chromatin samples from defined components are instrumental in defining the mechanistic details of such processes. The bottleneck to appropriate in vitro analysis is the production of high quality, and quality-controlled, chromatin substrates. In this chapter, we describe methods for in vitro chromatin reconstitution and quality control. We highlight the strengths and weaknesses of various approaches and emphasize quality control steps that ensure reconstitution of a bona fide homogenous chromatin preparation. This is essential for optimal reproducibility and reliability of ensuing experiments using chromatin substrates.

Gsx1 expression defines neurons required for prepulse inhibition.

In schizophrenia, cognitive overload is thought to reflect an inability to suppress non-salient information, a process which is studied using prepulse inhibition (PPI) of the startle response. PPI is reduced in schizophrenia and routinely tested in animal models and preclinical trials of antipsychotic drugs. However, the underlying neuronal circuitry is not well understood. We used a novel genetic screen in larval zebrafish to reveal the molecular identity of neurons that are required for PPI in fish and mice. Ablation or optogenetic silencing of neurons with developmental expression of the transcription factor genomic screen homeobox 1 (gsx1) produced profound defects in PPI in zebrafish, and PPI was similarly impaired in Gsx1 knockout mice. Gsx1-expressing neurons reside in the dorsal brainstem and form synapses closely apposed to neurons that initiate the startle response. Surprisingly, brainstem Gsx1 neurons are primarily glutamatergic despite their role in a functionally inhibitory pathway. As Gsx1 has an important role in regulating interneuron development in the forebrain, these findings reveal a molecular link between control of interneuron specification and circuits that gate sensory information across brain regions.

Antibody colocalization microarray: a scalable technology for multiplex protein analysis in complex samples.

DNA microarrays were rapidly scaled up from 256 to 6.5 million targets, and although antibody microarrays were proposed earlier, sensitive multiplex sandwich assays have only been scaled up to a few tens of targets. Cross-reactivity, arising because detection antibodies are mixed, is a known weakness of multiplex sandwich assays that is mitigated by lengthy optimization. Here, we introduce (1) vulnerability as a metric for assays. The vulnerability of multiplex sandwich assays to cross-reactivity increases quadratically with the number of targets, and together with experimental results, substantiates that scaling up of multiplex sandwich assays is unfeasible. We propose (2) a novel concept for multiplexing without mixing named antibody colocalization microarray (ACM). In ACMs, both capture and detection antibodies are physically colocalized by spotting to the same two-dimensional coordinate. Following spotting of the capture antibodies, the chip is removed from the arrayer, incubated with the sample, placed back onto the arrayer and then spotted with the detection antibodies. ACMs with up to 50 targets were produced, along with a binding curve for each protein. The ACM was validated by comparing it to ELISA and to a small-scale, conventional multiplex sandwich assay (MSA). Using ACMs, proteins in the serum of breast cancer patients and healthy controls were quantified, and six candidate biomarkers identified. Our results indicate that ACMs are sensitive, robust, and scalable.

Comparison between transcatheter and surgical prosthetic valve implantation in patients with severe aortic stenosis and reduced left ventricular ejection fraction.

BACKGROUND: Patients with severe aortic stenosis and reduced left ventricular ejection fraction (LVEF) have a poor prognosis with conservative therapy but a high operative mortality when treated surgically. Recently, transcatheter aortic valve implantation (TAVI) has emerged as an alternative to surgical aortic valve replacement (SAVR) for patients considered at high or prohibitive operative risk. The objective of this study was to compare TAVI and SAVR with respect to postoperative recovery of LVEF in patients with severe aortic stenosis and reduced LV systolic function. METHODS AND RESULTS: Echocardiographic data were prospectively collected before and after the procedure in 200 patients undergoing SAVR and 83 patients undergoing TAVI for severe aortic stenosis (aortic valve area ≤1 cm(2)) with reduced LV systolic function (LVEF ≤50%). TAVI patients were significantly older (81±8 versus 70±10 years; P<0.0001) and had more comorbidities compared with SAVR patients. Despite similar baseline LVEF (34±11% versus 34±10%), TAVI patients had better recovery of LVEF compared with SAVR patients (ΔLVEF, 14±15% versus 7±11%; P=0.005). At the 1-year follow-up, 58% of TAVI patients had a normalization of LVEF (>50%) as opposed to 20% in the SAVR group. On multivariable analysis, female gender (P=0.004), lower LVEF at baseline (P=0.005), absence of atrial fibrillation (P=0.01), TAVI (P=0.007), and larger increase in aortic valve area after the procedure (P=0.01) were independently associated with better recovery of LVEF. CONCLUSION: In patients with severe aortic stenosis and depressed LV systolic function, TAVI is associated with better LVEF recovery compared with SAVR. TAVI may provide an interesting alternative to SAVR in patients with depressed LV systolic function considered at high surgical risk.

Primary cardiac Burkitt-like lymphoma of the right atrium.

A 74-year-old man presented for shortness of breath. Echocardiography revealed the presence of a large pericardial effusion with signs of tamponade. A right atrial mass was suspected and later confirmed by transesophageal echocardiography. The mass was attached to the right side of the interatrial septum. Surgical resection was performed. Histology was compatible with a diagnosis of undifferentiated B-cell non-Hodgkin's (Burkittlike) primary cardiac lymphoma. The present report provides the first description of a Burkitt-like primary cardiac lymphoma. The presence of a mass in the right atria should raise the possibility of a malignant cardiac tumour. Transesophageal echocardiography should be considered as the initial diagnostic procedure to be performed. Rapid histological diagnosis is important because systemic therapy can influence prognosis in the presence of a primary cardiac lymphoma.

[Treatment of exacerbation of asthma: what are today's issues?]. / Traitement de la crise d'asthme: où sont aujourd'hui les enjeux?

During past decades, major progress has been accomplished in the management of acute asthma. Most recent recommendations include evidence-based rationale. The improved quality of clinical guidelines makes them efficient models for medical education. The pediatric pharmacopoeia provides a great variety of choices of drugs as well as for asthma medical devices. These innovations dramatically facilitated the medical management of asthmatic children, but they did not solve all problems. Physicians now use higher doses of salbutamol, but the early prescription of systemic glucocorticoids for moderate exacerbation of asthma is still underused, given the most recent clinical guidelines and meta-analysis. Furthermore, repeated emergency department visits to the wards and lack of primary care physician should systematically be appraised when evaluating severity, as they are both major risk factors for severe exacerbations, even though they are not considered in acute asthma severity scores. Finally, initiating (or reinforcing) patient education at the time of exacerbation also presents important challenges, as emergency visits are a favorable moment to commence the therapeutic education of the child and his family. Indeed, framing the controller medications and educating families about how to manage the disease and to improve their domestic environment are the genuine tools available for the prevention of asthma exacerbations, and particularly those most severe.

The endocarditis that was not: an unusual case of heparin-induced thrombocytopenia with unusual complications.

The complications of heparin-induced thrombocytopenia have been well described previously. However, evidence of the possibility that heparin-induced thrombocytopenia can trigger a thyroid storm has never been published before. A catastrophic evolution of a man referred with a high endocarditis suspicion previously treated with heparin, who successively developed arterial thrombosis and thyroid storm, is described.

Vulvar vestibulitis syndrome: reliability of diagnosis and evaluation of current diagnostic criteria.

OBJECTIVE: To assess the reliability of the diagnosis of vulvar vestibulitis as defined by Friedrich and to evaluate the usefulness of Friedrich's criteria in the diagnostic process. METHODS: In a university hospital, 146 women with dyspareunia had two sets of gynecologic examinations involving vulvar pain ratings, took part in structured interviews, and completed the McGill-Melzack Pain Questionnaire. RESULTS: Kappa values for the vulvar vestibulitis diagnosis ranged from 0.66 to 0.68 for inter-rater agreement and from 0.49 to 0.54 for test-retest reliability. Mean vestibular pain ratings ranged from 2.45 at the 12 o'clock site to 7.58 at the 9-12 o'clock site; ratings for all sites correlated significantly between gynecologists. Pain in the labia majora and labia minora was minimal for both sets of examinations, with mean participant pain ratings ranging from 0 to 1.49. Gynecologists' erythema ratings did not correlate significantly with respect to either inter-rater agreement or test-retest reliability. Of Friedrich's three diagnostic criteria, only tenderness to pressure within the vulvar vestibule differentiated dyspareunia patients with and without vulvar vestibulitis. In reference to their coital pain, 88.1% of women with vulvar vestibulitis chose adjectives from the McGill-Melzack Pain Questionnaire describing a thermal quality, and 86.6% chose adjectives describing an incisive pressure sensation. CONCLUSION: Vulvar vestibulitis can be reliably diagnosed in women with dyspareunia. Pain is limited to the vulvar vestibule and can be rated and described in a consistent fashion by these women. Erythema does not appear to be a useful diagnostic criterion.

A phase I clinical, pharmacological, and biological trial of interleukin 6 plus granulocyte-colony stimulating factor after ifosfamide, carboplatin, and etoposide in children with recurrent/refractory solid tumors: enhanced hematological responses but a high incidence of grade III/IV constitutional toxicities.

A Phase I trial was conducted to determine the safety, biological activity, and hematopoietic recovery by the combination of interleukin 6 (IL-6) and granulocyte-colony stimulating factor (G-CSF) after myelosuppressive chemotherapy in children. Patients <22 years of age at diagnosis with either recurrent or refractory solid tumors received ifosfamide 1,800 mg/m2/day x 5 days, carboplatin 400 mg/m2/ day x 2 days, and etoposide 100 mg/m2/day x 5 days, followed by daily s.c. G-CSF (5 microg/kg/day) and IL-6 (2.5, 3.75, or 5.0 microg/kg/day). Pharmacokinetic, proinflammatory mediator levels, hematopoietic colony assays, and cytokine receptor expression studies were performed during course one. Nineteen patients were evaluable for toxicity and received IL-6 at doses of 2.5 (n = 8), 3.75 (n = 5), or 5.0 (n = 6) microg/kg/day. Dose-limiting constitutional toxicity occurred in two of six patients at 5.0 microg/kg/day, two of five patients at 3.75 microg/kg/day, and two of eight patients at 2.5 microg/kg/day. The maximum tolerated dose (MTD) exceeded the lowest dose tested. Because of lack of drug availability, an MTD was not established. The maximum concentration of IL-6 (2.5 microg/kg/day) was 0.799 +/- 1.055 ng/ml (mean +/- SD). During the first course, the median time to absolute neutrophil count > or = 1,000/mm3 and platelets > or = 100,000 mm3 was estimated at 19 and 23 days, respectively. Peripheral blood progenitor cells expressing receptors to IL-3, IL-6, and G-CSF increased significantly over baseline (P < 0.05). After the first dose of IL-6, IFN-gamma levels were abnormal in 13 patients, and IL-1beta levels were abnormal in 10 patients. IL-6 has a high incidence of constitutional toxicity and a lower MTD in children compared with adults. In vivo use of IL-6 in children after chemotherapy remains limited. However, IL-6 may be more optimally investigated in children under ex vivo conditions.

A search for natural bioactive compounds in Bolivia through a multidisciplinary approach. Part I. Evaluation of the antimalarial activity of plants used by the Chacobo Indians.

Thirty extracts of plants traditionally used by the Chacobos, a native community living in the Amazonian part of Bolivia, were screened in vitro and/or in vivo for antimalarial activity. Two of the four species designated as antimalarial, Geissospermum laeve and Maquira coriacea, displayed rather good activity, corroborating their traditional uses. However, they did show a rather high toxicity in vivo. Among twelve species used to cure symptoms relevant to malaria, five showed good activity: Apuleia leiocarpa, Bauhinia guianensis, Nectandra cuspidata, Sparattanthelium amazonum, Tanaecium jaroba. Two species, Qualea paraensis and Sclerolobium aff. guianense, used to treat scabies, showed interesting antimalarial activity in vivo; three other species (Iryanthera laevis, Prunus amplifolia, Pterocarpus aff. amazonum) used for various medicinal purposes, apparently not related with a Plasmodium infection, also showed antimalarial activity. Finally, one species (Derris amazonica) used as a piscicide displayed good in vitro activity, in the same way as one Annonaceae, Guatteria aff. schomburgkiana, used for construction purposes.

A Phase I study of granulocyte-macrophage-colony stimulating factor/interleukin-3 fusion protein (PIXY321) following ifosfamide, carboplatin, and etoposide therapy for children with recurrent or refractory solid tumors: a report of the Children's Cancer Group.

BACKGROUND: This Phase I trial was developed to determine the safety, biologic activity, and effects on hematopoietic recovery of PIXY321 following ifosfamide, carboplatin, and etoposide chemotherapy for children with recurrent or refractory solid tumors. METHODS: Children (age < 22 years at diagnosis) received ifosfamide 1800 mg/m2/day x 5 days, carboplatin 400 mg/m2/day x 2 days, and etoposide 100 mg/m2/day x 5 days, followed by daily subcutaneous administration of PIXY321. Dose-limiting toxicity was defined as Grade IV toxicity related to PIXY321. Pharmacokinetic and endogenous cytokine production studies were conducted during Course 1, and peripheral blood (PB) progenitor cell and receptor expression studies were conducted during Course 1 when the white blood cell count recovered to > or=1000/mm3. RESULTS: Twenty-four children received ifosfamide, carboplatin, and etoposide chemotherapy plus PIXY321, the latter at doses of 500 /g/m2/day (n=3), 750 microg/m2/day (n=6), 1000 microg/m2/day (n=9), or 500 microg/m2/twice a day (n=6). PIXY321 was well tolerated, with only 1 dose-limiting toxicity (chills, occurring at a dose of 750 microg/m2/day). The maximum tolerated dose was not reached in this study. The median days to absolute neutrophil count recovery (> or =1000/mm3) and platelet recovery (>100,000/mm3) during Course 1 following PIXY321 (1000 microg/ m2/day) were 22 days (range, 5-33 days) and 20 days (range, 5-31 days), respectively. There was a 2500, 5000, 3000, and 390% increase in PB granulocyte-macrophage colony-forming units, erythrocyte blast-forming units, granulocyte erythrocyte macrophage and megakaryocyte colony-forming units, and CD34+ cells, respectively. CONCLUSIONS: In summary, this pediatric Phase I trial demonstrated that PIXY321 was well tolerated by children and resulted in platelet recovery a median of 20 days after ICE chemotherapy and an increase in the number of PB progenitor cells above baseline. However, based on recent negative results with PIXY321 in randomized Phase II/III trials involving adult subjects, PIXY321 is not currently available for future trials involving children.