The spectrum of substance use in mood and anxiety disorders

This study evaluates the prevalence of threshold and subthreshold use of substances among patients with psychiatric disorders and 2 comparison groups. Participants were outpatients and inpatients with mood and anxiety disorders, subjects with opiate dependence, and a comparison group of individuals not undergoing treatment for psychiatric disorders. Assessments included the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition , Axis I Disorders, an interview exploring the spectrum of substance use (Structured Clinical Interview for the Spectrum of Substance Use), and a self-report instrument exploring the spectrum of 5 psychiatric disorders (General 5-Spectrum Measure). The overall frequency of substance use disorder (SUD) and that of subthreshold use were 46% and 8% in patients with bipolar disorder, 4% and 26% in those with panic disorder, 8% and 26% in those with obsessive-compulsive disorder, and 6% and 10% in the control group, respectively ( Idouble dagger 2 = 51.6, P < .001). Inspection of standardized residuals indicated that alcohol use disorder and SUD were significantly ( P < .05) more frequent in subjects with bipolar disorder than among those with obsessive-compulsive disorder or panic disorder. The latter showed a significantly higher subthreshold use of substances than control subjects. The pattern of motivations for use varied according to the psychiatric disorder. Our results suggest that the well-established relationship between SUDs and psychiatric disorders might be the end point of a process that starts from increased proneness to substance use, which first leads to self-medication and then may eventually develop into substance abuse or dependence, among subjects with psychiatric symptoms.     

Mouse plasmacytoid cells: long-lived cells,heterogeneous in surface phenotype and function,that differentiate into CD8(+) dendritic cells only after microbial stimulus

The CD45RA(hi)CD11c(int) plasmacytoid predendritic cells (p-preDCs) of mouse lymphoid organs, when stimulated in culture with CpG or influenza virus, produce large amounts of type I interferons and transform without division into CD8(+)CD205(-) DCs. P-preDCs express CIRE, the murine equivalent of DC-specific intercellular adhesion molecule 3 grabbing nonintegrin (DC-SIGN). P-preDCs are divisible by CD4 expression into two subgroups differing in turnover rate and in response to Staphylococcus aureus. The kinetics of bromodeoxyuridine labeling and the results of transfer to normal recipient mice indicate that CD4(-) p-preDCs are the immediate precursors of CD4(+) p-preDCs. Similar experiments indicate that p-preDCs are normally long lived and are not the precursors of the short-lived steady-state conventional DCs. However, in line with the culture studies on transfer to influenza virus-stimulated mice the p-preDCs transform into CD8(+)CD205(-) DCs, distinct from conventional CD8(+)CD205(+) DCs. Hence as well as activating preexistant DCs, microbial infection induces a wave of production of a new DC subtype. The functional implications of this shift in the DC network remain to be determined.     

A qualitative study of patient experiences of decentralized acute healthcare services

Objective: Municipality acute wards (MAWs) have recently been launched in Norway as an alternative to hospitalizations, and are aimed at providing treatment for patients who otherwise would have been hospitalized. The objective of this study was to explore how patients normally admitted to hospitals perceived the quality and safety of treatment in MAWs.

Design: The study had a qualitative design. Thematic analysis was used to analyze the data.

Setting: The study was conducted in a county in south-eastern Norway and included five different MAWs.

Patients: Semi-structured interviews were conducted with 27 participants who had required acute health care and who had been discharged from the five MAWs.

Results: Three subthemes were identified that related to the overarching theme of hospital-like standards (“almost a hospital, but…”), namely (a) treatment and competence, (b) location and physical environment, and (c) adequate time for care. Participants reported the treatment to be comparable to hospital care, but they also experienced limitations. Participants spoke positively about MAW personnel and the advantages of having a single patient room, a calm environment, and proximity to home.

Conclusions: Participants felt safe when treated at MAWs, even though they realized that the diagnostic services were not similar to that in hospitals. Geographical proximity, treatment facilities and time for care positively distinguished MAWs from hospitals, while the lack of diagnostic resources was stressed as a limitation.

• Key points

• Municipality acute wards (MAWs) have been implemented across Norway. Research on patient perspectives on the decentralization of acute healthcare in MAWs is lacking.

• ??Patients perceive decentralized acute healthcare and treatment as being comparable to the quality they would have expected in hospitals.

• ??Geographical proximity, a home-like atmosphere and time for care were aspects stressed as positive features of the decentralized services.

• ??Lack of diagnostic resources was seen as a limitation.

     

Significance of Lymph Node Sampling in Epithelial Carcinoma of the Ovary

From 1979 to 1984, 127 patients operated on for ovarian cancer underwent pelvic, para-aortic, or pelvic and para-aortic lymph node sampling. Forty-seven patients proved to be stage I (14 IA and 33 IC), 14 were stage II (3 IIA, 8 IIB, and 3 IIC), 58 were stage III (7 IIIA, 13 IIIB, and 38 IIIC), and 8 were stage IV. Positive lymph nodes were found in 4.2% of patients at stage I, 35.7% at stage II, 41.3% at stage III, and 87.5% at stage IV. With regard to grading, positive lymph nodes were found in 4.4% of G1, in 21.6% of G2, and in 49.1% of G3. A significant increase in survival (P= 0.04) was found for patients classified as stage IIIC only according to lymph node involvement compared to patients in peritoneal stage IIIC with positive lymph nodes (3-year survival: 46% vs 12%). A small increase in survival was observed for N− patients compared to N+ patients, at both stage III and IV, even with same residual tumor size, but the difference is not statistically significant. All other things being equal, because the prevalence of lymph node positivity depends closely on the number of lymph nodes removed and examined (OR = 3.9 for >10 lymph nodes removed compared to 1–5 lymph nodes removed), lymph node sampling does not seem to be a reliable method for evaluating the retroperitoneal status. With regard to the therapeutic role of systematic lymphadenectomy, few data in literature are available and, most important, are not derived from experimental studies. Probably, only randomized studies with a large number of patients will provide useful answers.     

Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli

SUMOylation is an essential ubiquitin-like modification involved in important biological processes in eukaryotic cells. Identification of small ubiquitin-related modifier (SUMO)-conjugated residues in proteins is critical for understanding the role of SUMOylation but remains experimentally challenging. We have set up a powerful and high-throughput method combining quantitative proteomics and peptide immunocapture to map SUMOylation sites and have analyzed changes in SUMOylation in response to stimuli. With this technique we identified 295 SUMO1 and 167 SUMO2 sites on endogenous substrates of human cells. We further used this strategy to characterize changes in SUMOylation induced by listeriolysin O, a bacterial toxin that impairs the host cell SUMOylation machinery, and identified several classes of host proteins specifically deSUMOylated in response to this toxin. Our approach constitutes an unprecedented tool, broadly applicable to various SUMO-regulated cellular processes in health and disease.Posttranslational modifications (PTMs) are key mechanisms used by both prokaryotes and eukaryotes to regulate protein activity specifically, locally, and temporally. Ubiquitin and ubiquitin-like proteins (UBLs) constitute a specific class of small protein modifiers that can be covalently attached to a target protein via the formation of an isopeptide bond in a reversible manner. Small ubiquitin-related modifier (SUMO), one of these UBLs, is an essential PTM in eukaryotic cells that is involved in various cellular functions including gene expression regulation, DNA repair, intracellular transport, and response to viral and bacterial infections (1–5). The human genome encodes three different functional SUMO isoforms (SUMO1, SUMO2, and SUMO3) that are conjugated to distinct but overlapping sets of target proteins (1, 2, 6). Conjugation of SUMO to its targets in humans requires an E1-activating enzyme (the SAE1/SAE2 heterodimer), an E2-conjugating enzyme (Ubc9), and several E3 SUMO enzymes. Once conjugated to its target, SUMO can be deconjugated by several different SUMO isopeptidases that tightly regulate the SUMOylation levels of proteins (7).Since the discovery of SUMO two decades ago, much effort has been dedicated to the identification of SUMO-conjugated proteins in different organisms including yeast, plants, and mammals (8). However, isolation of SUMOylated proteins has proven to be challenging. Indeed, for most SUMO substrates, only a small proportion of the total amount of protein is SUMO-modified. In addition, the high activity of SUMO isopeptidases in cell lysates results in the rapid loss of SUMO conjugation in the absence of appropriate inhibitors. Thus, the most common approach used to isolate SUMOylated proteins is based on the expression of His-tagged versions of SUMO allowing the purification of SUMO-conjugated proteins by nickel chromatography under denaturing conditions (8, 9). Denaturing conditions inactivate SUMO isopeptidases and also prevent contamination by proteins interacting noncovalently with SUMO via specific domains such as SUMO-interacting motifs (SIMs) (2). Once SUMOylated proteins have been isolated, their analysis by mass spectrometry (MS) has been widely used to identify SUMO-modified proteins and, albeit less successfully, SUMO-conjugation sites.Mapping the exact lysine residue to which SUMO is attached in modified proteins is a critical step to get further insight into the function of SUMOylation. Indeed, the identification of SUMO sites allows the generation of non-SUMOylatable mutants and the study of associated phenotypes. Identification of SUMO sites by MS is not straightforward (8). Unlike ubiquitin, which leaves a small diglycine (GG) signature tag on the modified lysine residue after trypsin digestion, SUMO leaves a larger signature that severely hampers the identification of modified peptides.In addition to the identification of the SUMO site per se, a comparison of the SUMOylation status of sites in different cell-growth conditions is critical for better characterizing the biological implications of SUMOylation. For example, analysis of SUMOylation changes induced after heat shock, arsenic treatment, inhibition of the proteasome, or during the cell cycle has led to numerous insights into the role of SUMOylation in cell physiology (refs. 10–14 and reviewed in ref. 2). Here, we devised a performant approach which combines the use of SUMO variants, peptide immunocapture, and quantitative proteomics for high-throughput identification of SUMO sites. We then show that our approach is able to characterize global changes in the cell SUMOylome in response to a given stimulus, such as exposure to a bacterial toxin, listeriolysin O (LLO).     

Psychiatric comorbidity in a population of Parkinson''s disease patients

Behavioural disturbances are frequently observed in Parkinson's disease (PD), including mood and anxiety disorders. The existence of a comorbidity between such psychiatric disorders in PD patients has been suggested only in a few studies. To assess the prevalence of mood and anxiety disturbances, and the rate of comorbidity of such disorders in PD. Secondary aim was to correlate the prevalence of psychiatric disorders in PD with age, sex, laterality of motor symptomatology, clinical features, severity of disease, age of onset and PD duration, and anti-parkinsonian therapy. Ninety consecutive PD outpatients, and 90 age- and sex-matched controls were included. All PD patients enrolled were non-fluctuating (21 de novo, 69 treated with levodopa or dopamine agonists). PD patients and controls with Mini Mental State Examination score <23 were excluded. Psychiatric diagnosis was performed by semistructured interview according with DSM-IV criteria and the severity of depressive and anxious symptoms was rated with clinical rating scales. Major depression was found in 21.1% PD patients vs. 3.3% controls (P < 0.01, chi-square analysis), dystimia in 18.8% PD patients vs. 4.4% controls (P < 0.05), panic disorders in 30% PD patients vs. 5.5% controls (P < 0.01). No difference in the prevalence of other anxiety disorders was observed between the two groups. The comorbidity of mood and anxiety disorders was found in 19.3% PD patients vs. 8.6% controls (P < 0.01). No correlation was reported between the prevalence of behavioural disturbances and any of the demographic, clinical or pharmacological data taken into account. Our findings might suggest the existence of a wide spectrum of psychiatric disorders in PD ranging from pure depressive disorders, comorbid depressive and anxiety disorders, and pure anxiety disorders, presumably linked to the same neurobiological substrate.     

Ocular Adnexal Lymphoma: no evidence for bacterial DNA associated with lymphoma pathogenesis

Ocular Adnexal Lymphomas (OALs) are the most common tumors of the eye, the majority being extranodal mucosa-associated lymphoid tissue (MALT) lymphomas. Association with Chlamydia psittaci was described in some geographic areas. OAL response to antibiotic therapy was reported in cases not harboring Chlamydia psittaci DNA, suggesting that other bacterial infection might be implicated in the pathogenesis. We examined 49 MALT OALs for bacterial DNA using two distinct polymerase chain reaction techniques based on universal bacterial primers. No bacterial DNA that could be implicated in OAL pathogenesis was detected, suggesting that bacterial infection is not associated with OAL in South Florida.     

Iron-deficiency anemia as presentation of pouchitis

GOALS: This study sought to describe the percentage and cause of anemia in patients who underwent ileal pouch with anal anastomosis (IPAA) for ulcerative colitis (UC), and to compare the distribution of complications in patients with and without anemia, especially pouchitis, after IPAA. BACKGROUND: IPAA is the surgical procedure of choice for UC. Complications include pouchitis (40%), strictures (30%), small bowel obstruction (10%), pelvic sepsis (<5%), and urinary and sexual dysfunctions (<5%). Few studies have described the prevalence of anemia after IPAA, but no conclusive findings have been reported. STUDY: Patients who had undergone IPAA for UC were recruited from the UPR Inflammatory Bowel Disease Clinic and the Gastroenterology Research Unit. Demographic and medical data were obtained. Anemia was diagnosed using standard hematologic criteria. Serum iron, ferritin, transferrin, folate, vitamin B12, erythropoietin, total iron-binding capacity, reticulocyte count, peripheral smear, and bone marrow aspirate were evaluated in patients with anemia. Data analysis was performed with EPI Info version 6.4d. RESULTS: Iron-deficiency anemia was identified in 55.5% (10/18) of patients and pouchitis was found in 77% (14/18). All 10 patients with anemia had pouchitis, whereas only 4 of the 8 without anemia had pouchitis. In half of the anemic patients, pouchitis was asymptomatic. CONCLUSIONS: Iron-deficiency anemia may be a clinical presenting sign of pouchitis. Hemoglobin levels may be considered as surveillance tools for pouchitis in patients with IPAA.     

Opening of small and intermediate calcium-activated potassium channels induces relaxation mainly mediated by nitric-oxide release in large arteries and endothelium-derived hyperpolarizing factor in small arteries from rat

This study was designed to investigate whether calcium-activated potassium channels of small (SK(Ca) or K(Ca)2) and intermediate (IK(Ca) or K(Ca)3.1) conductance activated by 6,7-dichloro-1H-indole-2,3-dione 3-oxime (NS309) are involved in both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF)-type relaxation in large and small rat mesenteric arteries. Segments of rat superior and small mesenteric arteries were mounted in myographs for functional studies. NO was recorded using NO microsensors. SK(Ca) and IK(Ca) channel currents and mRNA expression were investigated in human umbilical vein endothelial cells (HUVECs), and calcium concentrations were investigated in both HUVECs and mesenteric arterial endothelial cells. In both superior (～1093 μm) and small mesenteric (～300 μm) arteries, NS309 evoked endothelium- and concentration-dependent relaxations. In superior mesenteric arteries, NS309 relaxations and NO release were inhibited by both N(G),N(G)-asymmetric dimethyl-l-arginine (ADMA) (300 μM), an inhibitor of NO synthase, and apamin (0.5 μM) plus 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34) (1 μM), blockers of SK(Ca) and IK(Ca) channels, respectively. In small mesenteric arteries, NS309 relaxations were reduced slightly by ADMA, whereas apamin plus an IK(Ca) channel blocker almost abolished relaxation. Iberiotoxin did not change NS309 relaxation. HUVECs expressed mRNA for SK(Ca) and IK(Ca) channels, and NS309 induced increases in calcium, outward current, and NO release that were blocked by apamin and TRAM-34 or charybdotoxin. These findings suggest that opening of SK(Ca) and IK(Ca) channels leads to endothelium-dependent relaxation that is mediated mainly by NO in large mesenteric arteries and by EDHF-type relaxation in small mesenteric arteries. NS309-induced calcium influx appears to contribute to the formation of NO.