Documentation of Psychiatric Disorders and Related Factors in a Large Sample Population of HIV-Positive Patients in California

This retrospective cohort study examined electronic medical records of HIV-positive patients in California (N = 7,834) to find the prevalence of any psychiatric condition and the associations between several factors and the likelihood of these disorders. Approximately 53 % of the patients in this study had a documented psychiatric condition, including 23 % who had a mood disorder, 19 % who had a substance-related disorder, and 16 % who had an anxiety disorder. After controlling for potential confounders, significant positive associations (p < 0.001) were found between female gender and the presence of any mood disorder (adjusted odds ratio [95 % confidence interval, 95 %CI] = 1.58 [1.26–1.99]) or anxiety disorder (AOR = 1.54 [1.18–2.02]) and between homosexual orientation and the presence of any psychiatric condition (AOR = 1.33 [1.15–1.55]), mood disorder (AOR = 1.71 [1.42–2.07]), or anxiety disorder (AOR = 1.41 [1.22–1.88]). There were also significant negative associations between African-American race and the presence of any psychiatric condition (AOR = 0.68 [0.60–0.77]), mood disorder (AOR = 0.74 [0.64–0.86]), anxiety disorder (AOR = 0.43 [0.36–0.52]), or substance-related disorder (AOR = 0.78 [0.67–0.91]) and between state/federal insurance and the presence of any psychiatric condition (AOR = 0.70 [0.62–0.79]), mood disorder (AOR = 0.71 [0.62–0.80]), or anxiety disorder (AOR = 0.77 [0.66–0.89]).     

The impact of chemokine receptor CX3CR1 deficiency during respiratory infections with Mycobacterium tuberculosis or Francisella tularensis

Recruitment of immune cells to infection sites is a critical component of the host response to pathogens. This process is facilitated partly through interactions of chemokines with cognate receptors. Here, we examine the importance of fractalkine (CX3CL1) receptor, CX3CR1, which regulates function and trafficking of macrophages and dendritic cells, in the host''s ability to control respiratory infections with Mycobacterium tuberculosis or Francisella tularensis. Following low-dose aerosol challenge with M. tuberculosis, CX3CR1^−/− mice were no more susceptible to infection than wild-type C57BL/6 mice as measured by organ burden and survival time. Similarly, following inhalation of F. tularensis, CX3CR1^−/− mice displayed similar organ burdens to wild-type mice. CX3CR1^−/− mice had increased recruitment of monocytes and neutrophils in the lung; however, this did not result in increased abundance of infected monocytes or neutrophils. We conclude that CX3CR1-deficiency affects immune-cell recruitment; however, loss of CX3CR1 alone does not render the host more susceptible to M. tuberculosis or F. tularensis.     

Vascular endothelial growth factor receptor-1 regulates postnatal angiogenesis through inhibition of the excessive activation of Akt

Vascular endothelial growth factor (VEGF) binds both VEGF receptor-1 (VEGFR-1) and VEGF receptor-2 (VEGFR-2). Activation of VEGFR-2 is thought to play a major role in the regulation of endothelial function by VEGF. Recently, specific ligands for VEGFR-1 have been reported to have beneficial effects when used to treat ischemic diseases. However, the role of VEGFR-1 in angiogenesis is not fully understood. In this study, we showed that VEGFR-1 performs "fine tuning" of VEGF signaling to induce neovascularization. We examined the effects of retroviral vectors expressing a small interference RNA that targeted either the VEGFR-1 gene or the VEGFR-2 gene. Deletion of either VEGFR-1 or VEGFR-2 reduced the ability of endothelial cells to form capillaries. Deletion of VEGFR-1 markedly reduced endothelial cell proliferation and induced premature senescence of endothelial cells. In contrast, deletion of VEGFR-2 significantly impaired endothelial cell survival. When VEGFR-1 expression was blocked, VEGF constitutively activated Akt signals and thus induced endothelial cell senescence via a p53-dependent pathway. VEGFR-1(+/-) mice exhibited an increase of endothelial Akt activity and showed an impaired neovascularization in response to ischemia, and this impairment was ameliorated in VEGFR-1(+/-) Akt1(+/-) mice. These results suggest that VEGFR-1 plays a critical role in the maintenance of endothelial integrity by modulating the VEGF/Akt signaling pathway.     

Evolution of the NBOMes: 25C- and 25B- Sold as 25I-NBOMe

Introduction

The NBOMes (N-benzyl-oxy-methyl derivatives of known 2C phenylethylamines) are a new and growing class of potent synthetic stimulants. Case reports provide the bulk of available safety and clinical data for clinicians. We report two cases of NBOMe intoxication with 25C-NBOMe (the first lab-confirmed US case) and 25B-NBOMe, respectively, both confirmed via triple quadrapole mass spectrometry.

Case Reports

Case 1: A 16-year-old girl had a generalized seizure after reported use of 25I-NBOMe. She presented with altered mental status, lower extremity rigidity, and elevated CPK (6042 U/L). Despite treatment with benzodiazepines, her lower extremity rigidity persisted and CPK peaked at 47,906 U/L. She was discharged on hospital day 8. Serum and urine specimens confirmed presence of 25C-NBOMe. Case 2: A 15-year-old boy developed bizarre behavior after reported use of 25I-NBOMe. In the ED, he had two generalized seizures and persistent muscle rigidity. CPK peaked at 429 U/L. Seizures were managed with benzodiazepines, and he was discharged within 24 h. Serum specimens revealed 25B-NBOMe.

Discussion

NBOMes are amphetamine derivatives and highly potent 5-HT_2A receptor agonists. Clinical manifestations are a product of enhanced central sympathetic and serotonergic tone. We report two cases of NBOMe intoxication in patients who believed they used 25I-NBOME, while lab confirmation proved otherwise. Whether unique clinical manifestations are specific to the NBOMe variant, dose, route of administration, or other factors is unknown. Laboratory confirmation may play a role in identifying unexpected NBOMe variants, while contributing to the epidemiologic data on these novel substances.     

Shortened Telomere Length in Sputum Cells of Bronchiectasis Patients is Associated with Dysfunctional Inflammatory Pathways

Telomere attrition is an established ageing biomarker and shorter peripheral blood leukocyte telomere length has been associated with increased risks of respiratory diseases. However, whether telomere length in disease-relevant sputum immune cells of chronic respiratory disease patients is shortened and which pathways are dysfunctional are not clear. Here we measured telomere length from sputum samples of bronchiectasis and asthmatic subjects and determined that telomere length in sputum of bronchiectasis subjects was significantly shorter (Beta?=????1.167, P_Adj?=?2.75?×?10^?4). We further performed global gene expression analysis and identified genes involved in processes such as NLRP3 inflammasome activation and regulation of adaptive immune cells when bronchiectasis sputum telomere length was shortened. Our study provides insights on dysfunctions related to shortened telomere length in sputum immune cells of bronchiectasis patients.

     

Early identification of axial spondyloarthritis in a multi-ethnic Asian population

Clinical Rheumatology - To address the diagnostic delay in axial spondyloarthritis (axSpA), we have cross-culturally adapted the Hamilton axSpA questionnaire, a self-administered screening...