Nitrous Oxide Alters Functional Connectivity in Medial Limbic Structures in Treatment-Resistant Major Depression.

While nitrous oxide (N 2 O) has demonstrated antidepressant properties in treatment-resistant major depression (TRD), little is known about neural mechanisms mediating these effects. Employing serial resting-state functional magnetic resonance imaging (rs-fMRI), we compared spatiotemporal effects of inhaled N 2 O on brain functional connectivity in TRD patients (n=14) and non-depressed healthy controls (n=16, CNTL). Participants received sequential, one-hour inhalations of either 50% N 2 O/oxygen or air/oxygen (placebo), with sessions separated by at least one month in random cross-over order. BOLD-contrast rs-fMRI scans were acquired at three time points: pre-inhalation, 2 hours post-inhalation, and 24 hours post-inhalation. For the rs-fMRI functional connectivity analyses, five a priori seeds in medial limbic structures targeted cortical networks implicated in major depression - the salience, anterior and posterior default mode, reward, and cingulo-opercular networks - and a nexus in the dorsal paracingulate region previously identified in MDD ("dorsal nexus"). Depression, dissociation, and psychosis assessments were made before and after inhalations. In TRD patients, functional connectivity was reduced in all seeded networks and the voxel-wise global analysis after N 2 O exposure. N 2 O progressively decreased connectivity in patients with TRD but increased connectivity in healthy controls. In TRD patients, each seeded network demonstrated post-inhalation functional connectivity reductions in the dorsal paracingulate gyrus ("dorsal nexus"). This study further elucidates neural mechanisms underlying the antidepressant properties of N 2 O, supporting the notion that N 2 O specifically alters mood-associated brain regions in the depressed brain state by reducing functional connectivity within these brain networks. The trial was registered at ClinicalTrials.gov ( NCT02994433 ). One sentence summary: Nitrous oxide reduces long-range functional brain connectivity in treatment-resistant major depression, which may underlie its antidepressant action.

Immunogenicity, Efficacy, and Safety of Biosimilar Insulin Glargine (Gan & Lee Glargine) Compared With Originator Insulin Glargine (Lantus) in Patients With Type 1 Diabetes After 26 Weeks Treatment.

OBJECTIVE: To compare the immunogenicity, safety, and efficacy of Gan & Lee insulin glargine (GL Glargine) with that of the originator insulin glargine (Lantus) in patients with type 1 diabetes mellitus (T1DM). METHODS: This was a phase 3, multicenter, randomized, open-label, equivalence study. Five hundred seventy-six subjects with T1DM were randomized 1:1 to receive either GL Glargine or Lantus treatment for 26 weeks. The primary end point was the percentage of subjects in each treatment group who developed treatment-induced anti-insulin antibody after baseline and up to visit week 26, which was evaluated using a country-adjusted logistic regression model. The study also compared the changes in glycated hemoglobin, and adverse events including hypoglycemia. RESULTS: The percentage of subjects positive for treatment-induced anti-insulin antibody by Week 26 was 25.8% in the GL Glargine treatment group and 25.3% in the Lantus treatment group, with a 90% confidence interval (-5.4, 6.5) of the difference in proportions that fell completely between the similarity margins (-11.3, 11.3). The least squares mean difference between treatment groups for changes in glycated hemoglobin was -0.08 (90% confidence interval: -0.23, 0.06), and the other immunogenicity and safety profiles were comparable. CONCLUSION: GL Glargine demonstrated similar immunogenicity, efficacy, and safety compared to Lantus over 26 weeks in patients with T1DM.

Diversity of 'Candidatus Liberibacter asiaticus' Strains in Texas Revealed by Prophage Sequence Analyses.

Prophages/phages are important components of the genome of 'Candidatus Liberibacter asiaticus' (CLas), an unculturable alphaproteobacterium associated with citrus huanglongbing (HLB) disease. Phage variations have significant contributions to CLas strain diversity research, which provide critical information for HLB management. In this study, prophage variations among selected CLas strains from southern Texas were studied. The CLas strains were collected from three different CLas inhabitant environments: citrus leaf, citrus root, and Asian citrus psyllid (ACP), the vector of CLas. Regardless of the different habitats and time span, more than 80% of CLas strains consistently had both Type 1 and Type 2 prophages, the same prophage type profile as in CLas strains from Florida but different to those reported in California and China. Further studies were performed on prophage type diversity. Analyses on Type 1-specific PCR amplicon sequences (encoding an endolysin protein) revealed the presence of two groups: Type 1-A, clustered around prophage SC1 originating from Florida, and Type 1-B, clustered with prophage P-SGCA5-1 originating in California. Type 1-B strains were mostly from ACP of nearby citrus orchards. On the other hand, analyses on Type 2-specific PCR amplicon sequences (encoding a putative hypothetical protein) showed a single group clustering around prophage SC2 originated from Florida, although a different Type 2 prophage has been reported in California. The presence of two distinct Type 1 prophage groups suggested the possibility of two different CLas introductions in southern Texas. The results from this study provide an initial baseline of information on genomic and population diversity of CLas in Texas.

Inoculation of Tomato With Plant Growth Promoting Rhizobacteria Affects the Tomato-Potato Psyllid-Candidatus Liberibacter Solanacearum Interactions.

The Rio Grande Valley (RGV) in southern Texas is well-suited for vegetable production due to its relatively mild/warm weather conditions in the fall and winter. Consequently, insects inflict year-round, persistent damage to crops in the RGV and regions with similar climate. Bactericera cockerelli (Sulc) (Hemiptera: Triozidae), commonly known as the potato psyllid, is a known vector of Candidatus Liberibacter solanacearum (CLso) (Hyphomicrobiales: Rhizobiaceae), a fastidious phloem-limited bacterium associated to vein-greening in tomatoes and Zebra Chip in potatoes. Vector control is the primary approach of integrated pest management (IPM) strategies that aim to prevent plant diseases in commercial agricultural systems. However, resistance-selective pressures that decrease the effectiveness of chemical control (insecticide) applications over time are of increasing concern. Therefore, we explore an ecological approach to devising alternative IPM methodologies to manage the psyllid-transmitted CLso pathogen to supplement existing chemical products and application schedules without increasing resistance. In this study, our objective was to examine the effects of plant-growth promoting rhizobacteria (PGPR) on host-vector-pathogen interactions. Soil-drench applications of PGPRs to Solanum lycopersicum (Solanales: Solanaceae) seedlings revealed structural and possible physiological changes to the plant host and indirect changes on psyllid behavior: host plants had increased length and biomass of roots and exhibited delayed colonization by CLso, while psyllids displayed changes in parental (F0) psyllid behavior (orientation and oviposition) in response to treated hosts and in the sex ratio of their progeny (F1). Based on our results, we suggest that PGPR may have practical use in commercial tomato production.

Target receptor identification and subsequent treatment of resected brain tumors with encapsulated and engineered allogeneic stem cells.

Cellular therapies offer a promising therapeutic strategy for the highly malignant brain tumor, glioblastoma (GBM). However, their clinical translation is limited by the lack of effective target identification and stringent testing in pre-clinical models that replicate standard treatment in GBM patients. In this study, we show the detection of cell surface death receptor (DR) target on CD146-enriched circulating tumor cells (CTC) captured from the blood of mice bearing GBM and patients diagnosed with GBM. Next, we developed allogeneic "off-the-shelf" clinical-grade bifunctional mesenchymal stem cells (MSCBif) expressing DR-targeted ligand and a safety kill switch. We show that biodegradable hydrogel encapsulated MSCBif (EnMSCBif) has a profound therapeutic efficacy in mice bearing patient-derived invasive, primary and recurrent GBM tumors following surgical resection. Activation of the kill switch enhances the efficacy of MSCBif and results in their elimination post-tumor treatment which can be tracked by positron emission tomography (PET) imaging. This study establishes a foundation towards a clinical trial of EnMSCBif in primary and recurrent GBM patients.

Nitrous Oxide: an emerging novel treatment for treatment-resistant depression.

Stemming from the results of the historic STAR-D trial, it is evident that a significant subset of individuals (20-25%) with major depressive disorder (MDD) do not respond to conventional antidepressant medications. As a result, an emphasis has been placed on the development of novel therapeutics for MDD over the last two decades. Recently, substantial research efforts have been focused on the use of ketamine as an antidepressant whose mechanism of action is via the N-methyl-d-aspartate (NMDA) receptor. Another potential therapeutic compound of interest is nitrous oxide, which has been utilized for more than a century in multiple fields of medicine for its analgesic and anesthetic properties. Recent clinical studies suggest that nitrous oxide may be effective for treatment-resistant depression. In this review, we will discuss the administration of nitrous oxide as a psychiatric intervention, current use in psychiatry, putative mechanisms of action, and future directions highlighting knowledge gaps and other potential utilities in the field of psychiatry.

Effects of musical improvisation as a cognitive and motor intervention for the elderly / Efeitos da improvisação musical como intervenção cognitiva e motora para idosos

Music has been debated as a positive factor for the health of elderly people. In a randomized study, the researchers compared an intervention based on percussion and musical improvisation with a choir activity. The objective was to investigate whether improvisation would influence the executive functioning and motor skills of healthy elderly people. A set of instruments for psychological and motor assessment was used before and after the procedure. Differences were found in the performance of the participants of the improvisation group in the Clock Drawing Test suggesting possible gains in executive function. There were gains, regardless of the group, in part A of the Trail Making Test, which indicates a sustained attention. No evidence of motor effects was found in this study. The results suggest that musical activities can contribute to the prevention of cognitive decline caused by aging.

A música tem sido discutida como fator promotor da saúde do idoso. Em um estudo randomizado, uma intervenção baseada em exercícios de percussão e improvisação foi comparada a uma atividade de canto coral. O objetivo foi investigar os efeitos sobre o funcionamento executivo e motor de idosos saudáveis. Um conjunto de instrumentos de avaliação psicológica e motora foi aplicado antes e depois da intervenção. Foram encontradas diferenças no desempenho do grupo de improvisação no Teste de Desenho do Relógio sugerindo possíveis ganhos executivos. Houve ganhos independentes de grupo na parte A do Teste de Trilhas, que avalia a atenção sustentada. Não foram verificadas evidências de efeitos motores. Os resultados indicam que atividades musicais podem contribuir na prevenção do declínio cognitivo decorrente do envelhecimento.

Correction to: Prevalence and correlates of transactional sex among women of low socioeconomic status in Portland, OR.

An amendment to this paper has been published and can be accessed via the original article.

Prevalence and correlates of transactional sex among women of low socioeconomic status in Portland, OR.

BACKGROUND: Women who report transactional sex are at increased risk for HIV and other sexually transmitted infections (STIs). However, in the United States, social, behavioral, and trauma-related vulnerabilities associated with transactional sex are understudied and data on access to biomedical HIV prevention among women who report transactional sex are limited. METHODS: In 2016, we conducted a population-based, cross-sectional survey of women of low socioeconomic status recruited via respondent-driven sampling in Portland, Oregon. We calculated the prevalence and, assessed the correlates of, transactional sex using generalized linear models accounting for sampling design. We also compared health outcomes, HIV screening, and knowledge and uptake of HIV pre-exposure prophylaxis (PrEP) between women who did and did not report transactional sex. RESULTS: Of 334 women, 13.6% reported transactional sex (95% confidence interval [CI]: 6.8, 20.5%). Women who reported transactional sex were older, more likely to identify as black, to identify as lesbian or bisexual, to experience childhood trauma and recent sexual violence, and to have been homeless. Six percent (95% CI: 1.8, 10.5%) of women with no adverse childhood experiences (ACEs) reported transactional sex compared to 23.8% (95% CI: 13.0, 34.6%) of women who reported eleven ACEs (P <  0.001). Transactional sex was strongly associated with combination methamphetamine and opiate use as well as condomless sex. Women who reported transactional sex were more likely to report being diagnosed with a bacterial STI and hepatitis C; however, HIV screening and pre-exposure prophylaxis knowledge and use were low. CONCLUSIONS: In a sample of women of low socioeconomic status in Portland, Oregon, transactional sex was characterized by marginalized identities, homelessness, childhood trauma, sexual violence, substance use, and sexual vulnerability to HIV/STI. Multi-level interventions that address these social, behavioral, and trauma-related factors and increase access to biomedical HIV prevention are critical to the sexual health of women who engage in transactional sex.

Diagnóstico ecocardiográfico de disfunción por obstrucción intermitente de prótesis de disco mitral / Echocardiographic diagnosis of obstructive intermittent dysfunction of a mitral disc prosthetic valve

Se describen los hallazgos Ecocardiográficos en seis pacientes con disfunción por obstrucción intermitente de prótesis (DOIP) mecánica de disco en posición mitral. Todos con cuadro clínico de instalación gradual, con disnea progresiva de varias semanas de evolución. Se les practicó ETT con registros Bd y de modo M "orientado" desde apical 4/C y se compararon los hallazgos con un grupo control de 14 pts con prótesis normo-funcionante. En el grupo de DOIP, todos presentaban un retardo variable en la apertura de la prótesis, registrada como un "escalón" protodiastólico en el modo M. En la mitad la disfunción fue por trombos. En dos porpannus. Tres se operaron. Uno se trombolizó. En dos se incrementó el tratamiento con heparina IV y con anticoagulante oral. Ninguno falleció durante el manejo agudo de la disfunción intermitente. Dos fallecieron: uno siete meses después en insuficiencia cardíaca y otro, un año después por retrombosis protésica. En pacientes con prótesis mecánica en posición mitral y disnea progresiva, la presencia de un retardo variable en la apertura de la prótesis, es diagnóstica de DOIP y requiere manejo urgente con trombólisis o cirugía.

Echocardiographic findings in six patients with obstructive intermittent dysfunction of mechanical disc prosthetic mitral valve (OIPD) are described. All with a clinical picture of gradual installation and progressive dyspnea of several weeks of evolution. TTE with Bd recordings were performed in all of them with "oriented" M mode from apical 4/C view. The findings were compared with a control group of 14 patients with normal prosthetic valves. In the group of OIDP, all patients displayed a variable delay in the opening of the prosthetic disc, registered as a "protodiastolic step" in M mode. In three patients, the dysfunction was due to a thrombus. In two, due to pannus. Three were operated. One with thrombolysis. In two, the treatment consisted of heparin and increased oral anticoagulation. None die during the acute handling of the intermittent dysfunction. Two patients died: one seven months later due to cardiac failure and the other a year later due to prosthetic rethrombosis. In patients with mechanical prosthetic valve in mitral valve position and progressive dyspnea, the presence of a variable delay in the opening of the prosthesis is diagnostic of OIDP and requires urgent handling with thrombolysis or surgery. (Arch Cardiol Mex 2005; 75: 141-147).