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.

Cicatricial changes in ocular pemphigus.

PURPOSE: To describe the clinical characteristics of ocular involvement in patients with pemphigus at an ophthalmological referral center. METHODS: A retrospective review was conducted on patients with the immunopathological diagnosis of pemphigus examined between 1 January 2000 and 1 April 2010. Uncorrected distance visual acuity (UDVA), best corrected distance visual acuity (BCVA), ocular symptoms, and ocular surface inflammatory and scarring changes were assessed. RESULTS: A total of 15 patients were identified, with a mean age of 68.27 ± 14.35 years, and 80% (n=12) were female. Extraocular involvement was reported in one patient. All of the eyes showed cicatricial changes in the conjunctiva. In all, 6 eyes (20%) were classified as stage I; 12 eyes (40%) as stage II; 10 eyes (33%) as stage III; and 2 eyes (7%) as stage IV. A statistically significant association was found between BCVA and the severity of ocular involvement. The mean BCVA logMAR was 1.66 (20/914), with a range from logMAR 0 (20/20) to logMAR 4 (NLP). Other ocular diseases were found in 8 (53.3%), systemic diseases in 10 (66.7%), and the use of pemphigus-inducing drugs in 10 patients (66.7%). CONCLUSIONS: The present report represents the largest series of ocular involvement in pemphigus confirmed by immunopathology. The clinical manifestations varied from conjunctival hyperemia to corneal scarring and perforation. There was a strong association between scarring changes and low BCVA. Ocular and systemic diseases as well as the use of pemphigus-inducing drugs may predispose to ocular cicatricial changes observed in this series.

An imbalance between frequency of CD4+CD25+FOXP3+ regulatory T cells and CCR4+ and CCR9+ circulating helper T cells is associated with active perennial allergic conjunctivitis.

Allergic conjunctivitis (AC) is one of the most common eye disorders in ophthalmology. In mice models, it has been suggested that control of allergic conjunctivitis is a delicate balance between Tregs and inflammatory migrating effector cells. Our aim was to evaluate the frequency of Tregs and the frequency of homing receptors expressing cells in peripheral blood mononuclear cells (PBMC) from patients with perennial allergic conjunctivitis (PAC). The analyses of phenotypic markers on CD4+ T cells and both soluble or intracellular cytokines were performed by flow cytometry. CD4+CD25+ cells were 15 times more frequent in PBMC from patients than HC; the vast majority of these CD4+CD25+ cells were FOXP3-, and most of CD4+ T cells were CCR4+ and CCR9+ cells. Upon allergen-stimulation, no significant changes were observed in frequency of Treg; however, an increased frequency of CD4+CCR4+CCR9+ cells, CD4+CD103+ cells and CD4+CD108+ cells with increased IL-5, IL-6, and IL-8 production was observed. These findings suggest an immune dysregulation in PAC, characterized by diminished frequency of Tregs and increased frequency of circulating activated CD4+ T cells; upon allergen-stimulation, these cells were expressing cell-surface molecules related to mucosa homing and were able to trigger an inflammatory microenvironment.

Overexpression of peroxiredoxin 2 in pterygium. A proteomic approach.

Pterygium is one of the most frequent pathologies in ophthalmology, and is a benign, fibrovascular lesion originating from the bulbar conjunctiva. It is composed of an epithelium and highly vascular, subepithelial, loose connective tissue. The etiology of pterygium is not clearly understood; the most widely recognized originating factor is ultraviolet radiation. It has been proposed that pterygium and neoplasia have common features, raising the possibility that pterygium is a neoplastic-like growth disorder. In this study, proteomic analysis was performed to show that peroxiredoxin 2 is overexpressed in pterygia compared to healthy conjunctivas. Twelve pterygium specimens were obtained together with healthy conjunctival tissue from the same eyes. Total proteins of pterygia and healthy conjunctivas were analyzed in SDS-PAGE. This analysis showed protein bands expressed exclusively in pterygium samples at the range of 20-25 kDa. After this, 2D electrophoresis was performed for the separation of total proteins; differential spots expressed in pterygium were excised and sequenced. Mass spectrometry (MS) data were searched in the NCBInr and EST databases using the MASCOT program. The spot was identified as peroxiredoxin 2. Real-time PCR, western blot and immunohistochemistry showed that peroxiredoxin 2 was increased in pterygium compared to healthy conjunctiva. Although, these results suggest that overexpression of peroxiredoxin 2 in pterygium could protect the cell against oxidative stress-induced apoptosis, further studies are required to establish the functional role of peroxiredoxin 2 in pterygium to determine its role in peroxidation and apoptosis in this pathology.

Immunophenotyping in peripheral blood mononuclear cells, aqueous humour and vitreous in a Blau syndrome patient caused by a novel NOD2 mutation.

The genetic and immunophenotypic characteristics of a 3-year-old patient with Blau syndrome (BS), an early onset sarcoidosis caused by mutations in NOD2, were investigated. Molecular analysis of NOD2 gene was achieved by PCR and direct nucleotide sequencing. Immunophenotyping included cytometric analysis of memory-effector markers on T-cells, and cytokine in serum, aqueous humour and vitreous. A novel M513R mutation in NOD2 was demonstrated. Immunophenotyping revealed higher frequency of CCR4+ cells and CCR9+ cells on CD4+ cells; most CD8+ cells were CCR7- and CCR9+. IL6 and IL-8 were detected in a gradient manner: vitreous humour>aqueous humour>serum. The immunophenotype in this patient was characterized by a differential expression of chemokine receptors on T cells and by a particular ocular microenvironment enriched in IL-6 and IL-8. To our knowledge, this is the first study analysing the immunological features of BS at aqueous humour, vitreous and blood levels. Our results expand the knowledge of the genetic and immunopathological basis of BS.

Some questions provoked by a chronic headache (with mixed migraine and cluster headache features) in a woman with a pineal cyst. Answers from a literature review.

The main known function of the pineal gland in humans is the production of melatonin. Benign cysts of the gland have been related to headache, although the mechanism of production of this assumed clinical manifestation has not been clearly determined, due to the lack of large prospective studies. The question is complicated by the fact that pineal cysts are frequently found on brain magnetic resonance imaging. Much has been published about the possible role of benign pineal cysts in the pathophisiology of headaches and the potential of melatonin in headache therapy, as well as in other disorders. The aim of this article is to review the current state of the subject. We have tried to place accurately the relation between headache and pineal cysts based on the available evidence, as well as the actual role of melatonin in physiology and pharmacology, more specifically in headache therapy. We include a clinical case to illustrate the subject.

[Immunological characteristics of limbal epithelial cells: in vitro analysis of TLR4 function]. / Características inmunológicas de las células epiteliales limbales: análisis in vitro de la función del TLR4.

OBJECTIVE: The aim of the present study was to determine the expression of TLR4 on human limbal epithelial cells cultivated in vitro, and to determine its cellular function after stimulation with lipopolysaccharide (LPS). METHODS: Limbal epithelial cells were isolated from sclera-corneal rims and stimulated for 24 hours with different doses of LPS from E. coli and from Pseudomonas. After stimulation, the cells were harvested, stained with antibodies against human TLR4 and analysed by flow cytometry. mRNA was obtained and RT-PCR was performed for the identification of TLR4. Secretion of TNF-alpha by these cells was evaluated by ELISA of the supernatant. RESULTS: Limbal epithelial cells expanded in vitro constitutively expressed the TLR4 molecule. After stimulation of cells with LPS the average fluorescence intensity increased, indicating that the expression of extracellular TLR4 was augmented. The expression of TLR4 mRNA was also increased with LPS stimulation, with maximum expression measured at 10 ng/ml LPS. The level of TNF-alpha in the supernatant was not different between the stimulated and the non-stimulated cells. CONCLUSIONS: Although stimulation of in vitro limbal epithelial cells with LPS up-regulates the extracellular expression of TLR4, the function of TLR4 does not seem to be associated with the secretion of TNF-alpha by these cells. These results are consistent with the proposal that the corneal epithelium is an immunosilent site in the eye.

[Expression of B7 molecules and TLR-9 on corneal epithelial cells infected with adenovirus: clinico-pathological implications in viral keratoconjunctivitis]. / Expresión de moléculas B7 y TLR:9 en células epiteliales corneales infectadas con adenovirus: implicaciones clínico-patológicas en la queratoconjuntivitis viral.

PURPOSE: B7 molecules are a family of proteins that co-stimulate T cells during immune activation. Normally the corneal epithelial cells (CEC) do not express these molecules on their cell surface. Toll-like receptors play an important role in the innate immune response to invading pathogens and recently have been demonstrated to be expressed on mice cornea. The objective of this study was to determine whether adenoviral infection induces B7 molecules and TLR9 on human CEC. METHODS: CEC were isolated from human corneas treated with dispase-II, and grown in the presence of supplemented hormonal epithelial medium until confluence. Then CEC were then infected with adenovirus 5 (Ad5) and cultured for different times. The CEC were then recovered and stained against human CD80, CD86, TLR-9 and cytokeratin. All cells were analyzed by flow cytometry. RESULTS: Ad5 infection of CEC induced the expression of B7 molecules and TLR-9 after 24 hours in culture, rising to maximum levels at 72 hours. B7 expression at 72 hours was as follows: CD80 expression on infected CEC was 62% (standard error [SE] 2.6) versus 3% (SE 1.2) on non-infected CEC (p<0.001); CD86 expression on infected CEC was 95% (SE 2.1) versus 5% (SE 1.2) on non-infected CEC (p<0.001). TLR-9 expression at 72 hours was 80% (SE 1.2) on infected CEC versus 5% (SE 1) on non-infected CEC (p<0.001). CONCLUSIONS: Ad5 infection induced the expression of B7 molecules and TLR-9 on CEC.

Expresión de moléculas B7 y TLR:9 en células epiteliales corneales infectadas con adenovirus: implicaciones clínico-patológicas en la queratoconjuntivitis viral / Expression of B7 molecules and TLR-9 on corneal epithelial cells infected with adenovirus: clinico-pathological implications in viral keratoconjunctivitis

Objetivo: Las moléculas B7 son una familia deproteínas que coestimulan al linfocito T durante laactivación inmunitaria, normalmente las célulasepiteliales corneales (CEC) no expresan estas moléculasen superficie. Los receptores tipo Toll jueganun papel importante en la respuesta inmune innatahacia patógenos invasores y recientemente sedemostró su expresión en córneas de ratón. El objetivodel presente estudio fue determinar si la infecciónviral induce moléculas B7 y TLR9 en CEChumanas.Métodos: Las CEC fueron obtenidas de corneashumanas tratadas con dispasa II y crecidas en presenciade medio hormonal epitelial suplementadohasta su confluencia. Posteriormente las células fueron infectadas con adenovirus 5 (Ad5) y cultivadasa diferentes tiempos. Las CEC fueron recuperadasy marcadas contra CD80, CD86, TLR-9 y citoqueratina.Todas las células fueron analizadas porcitometría de flujo.Resultados: La infección de CEC con Ad5 indujola expresión de moléculas B7 y TLR-9 desde las 24h, alcanzando su máximo nivel a las 72 h. La expresiónde moléculas B7 a las 72 h fue como sigue,expresión de CD80 en CEC infectadas 62% errorestándar (ES) 2.6 versus 3 ES 1.2 (p < 0,001) enCEC no infectadas; expresión de CD86 en CECinfectadas 95% ES 2.1 versus 5% ES 1.2 (p <0,001) en CEC no infectadas. La expresión de TLR-9 a las 72 h fue de 80% ES 1.2 en CEC infectadasversus 5% ES 1 en CEC no infectadas (p < 0,001).Conclusiones: La infección por Ad5 induce laexpresión de moléculas B7 y TLR-9 en CEC

Purpose: B7 molecules are a family of proteins that co-stimulate T cells during immune activation. Normally the corneal epithelial cells (CEC) do not express these molecules on their cell surface. Tolllike receptors play an important role in the innate immune response to invading pathogens and recently have been demonstrated to be expressed on mice cornea. The objective of this study was to determine whether adenoviral infection induces B7 molecules and TLR9 on human CEC. Methods: CEC were isolated from human corneas treated with dispase-II, and grown in the presence of supplemented hormonal epithelial medium until confluence. Then CEC were then infected with adenovirus 5 (Ad5) and cultured for different times. The CEC were then recovered and stained against human CD80, CD86, TLR-9 and cytokeratin. All cells were analyzed by flow cytometry. Results: Ad5 infection of CEC induced the expression of B7 molecules and TLR-9 after 24 hours in culture, rising to maximum levels at 72 hours. B7 expression at 72 hours was as follows: CD80 expression on infected CEC was 62% (standard error [SE] 2.6) versus 3% (SE 1.2) on non-infected CEC (p<0.001); CD86 expression on infected CEC was 95% (SE 2.1) versus 5% (SE 1.2) on non-infected CEC (p<0.001). TLR-9 expression at 72 hours was 80% (SE 1.2) on infected CEC versus 5% (SE 1) on non-infected CEC (p<0.001). Conclusions: Ad5 infection induced the expression of B7 molecules and TLR-9 on CEC

Differential expression of a 70 kDa O-glycoprotein on T cells: a possible marker for naive and early activated murine T cells.

We purified a 70 kDa O-glycoprotein that binds to the GalNAc specific lectin from Amaranthus leucocarpus (ALLr) and determined its expression pattern on T lymphocytes from different murine lymphoid organs. High level of ALLr expression was demonstrated in 95-98% of both CD4(+)8(+) and CD4(-)8(+) thymocytes, and in 80-95% of CD8(+) T cells from peripheral blood, lymph nodes, and spleen, whereas a minor fraction of CD4(+)8(-) thymocytes (46-67%) and peripheral CD4(+) T cells (9-40%) showed low ALLr expression. Peripheral CD19(+) B cells were ALLr negative and most of the peripheral ALL(+) T cells showed a CD62L(hi)CD45RB(hi)CD44(lo/-) phenotype, indicating features of naive cells. Mitogenic activation of peripheral T cells increased 3-fold the number of ALL(+)CD4(+) T cells 24 h after stimulation, as opposed to a >80% decrease in CD8(+) T cells 72 h after stimulation. Our results suggest that ALL detects a non-described surface O-glycoprotein selectively expressed by naive CD8(+) T cells and by early activated CD4(+) T cells.

Connectivity patterns in tuberculosis and leprosy patients are indistinguishable from that of healthy donors.

Connectivity, the self-defined interactions between antigen-recognising molecules in a network system can in part be assessed by measuring the reactivity of a given serum against an ordered set of immunoglobulin (Ig)G F(ab')2 fractions, separated by means of isoelectric focusing so that, the serum reactivity against the whole set of fractions defines a characteristic pattern of connectivity. Deviations from the normal condition (healthy donors) have so far been documented for two autoimmune diseases: systemic lupus erythematosus (SLE) and pemphigus vulgaris, as well as for human immunodeficiency virus (HIV)-1 infection. We tested here if bacterial infections lead to alterations in connectivity. In addition, we wanted to test if two antigenically related bacteria would produce similar or otherwise distinctive connectivity patterns. Connectivity analysis was applied on the sera from tuberculosis and leprosy patients and the sera from healthy donors were used as control. No statistically significant differences between the three groups studied were found. These results have implications for theories that set the origin of autoimmune diseases in microbial infections. To the best of our knowledge, this is the first attempt to analyze the connectivity status in bacterial infections.

[Cell surface markers in patients with allergic rhinitis versus Der p and Der f challenge]. / Estudio de marcadores de superficie celular en pacientes con rinitis alérgica frente a reto con Der p y Der f.

The allergic condition is determined genetically and they affect of the general population's 20-30% in developed countries, in the last decade have been increased the prevalence. Inside the imbalance that is manifested in the atopic patients it is on one hand the antigen-presenting cells (monocytes and B cells) and on the other hand, the lymphocytes T CD4+. The association of molecules like CD80, CD 86 (co-stimulatory molecules) in monocytes and B cells and CD30, CD62L, ALL, CD11a, CD28, CD124 and CD152 in CD4+, they have shown to be of particular interest in allergic sufferings. However we don't find a difference statistically significant among patient and controls and among nasal challenges with saline solution with specific allergen. For what we suggest that the changes in the activation, proliferation and cooperation are given in the les ion place, without an apparent repercussion in cells of peripheral blood.