Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 433
Filtrar
1.
Transl Psychiatry ; 11(1): 171, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33723209

RESUMEN

Obsessive-compulsive disorder (OCD) is a chronic and severe psychiatric disorder for which effective treatment options are limited. Structural and functional neuroimaging studies have consistently implicated the orbitofrontal cortex (OFC) and striatum in the pathophysiology of the disorder. Recent genetic evidence points to involvement of components of the excitatory synapse in the etiology of OCD. However, the transcriptional alterations that could link genetic risk to known structural and functional abnormalities remain mostly unknown. To assess potential transcriptional changes in the OFC and two striatal regions (caudate nucleus and nucleus accumbens) of OCD subjects relative to unaffected comparison subjects, we sequenced messenger RNA transcripts from these brain regions. In a joint analysis of all three regions, 904 transcripts were differentially expressed between 7 OCD versus 8 unaffected comparison subjects. Region-specific analyses highlighted a smaller number of differences, which concentrated in caudate and nucleus accumbens. Pathway analyses of the 904 differentially expressed transcripts showed enrichment for genes involved in synaptic signaling, with these synapse-associated genes displaying lower expression in OCD subjects relative to unaffected comparison subjects. Finally, we estimated that cell type fractions of medium spiny neurons were lower whereas vascular cells and astrocyte fractions were higher in tissue of OCD subjects. Together, these data provide the first unbiased examination of differentially expressed transcripts in both OFC and striatum of OCD subjects. These transcripts encoded synaptic proteins more often than expected by chance, and thus implicate the synapse as a vulnerable molecular compartment for OCD.

2.
Lancet Infect Dis ; 2021 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-33676595

RESUMEN

BACKGROUND: To address the increasing incidence of gonorrhoea and antimicrobial resistance, we compared the efficacy of Listerine and Biotène mouthwashes for preventing gonorrhoea among men who have sex with men (MSM). METHODS: The OMEGA trial was a multicentre, parallel-group, double-blind randomised controlled trial among MSM, done at three urban sexual health clinics and one general practice clinic in Australia. Men were eligible if they were diagnosed with oropharyngeal gonorrhoea by nucleic acid amplification test (NAAT) in the previous 30 days or were aged 16-24 years. They were randomly assigned to receive Listerine (intervention) or Biotène (control) via a computer-generated sequence (1:1 ratio, block size of four). Participants, clinicians, data collectors, data analysts, and outcome adjudicators were masked to the interventions after assignment. Participants were instructed to rinse and gargle with 20 mL of mouthwash for 60 s at least once daily for 12 weeks. Oropharyngeal swabs were collected by research nurses every 6 weeks, and participants provided saliva samples every 3 weeks, to be tested for Neisseria gonorrhoeae with NAAT and quantitative PCR. The primary outcome was proportion of MSM diagnosed with oropharyngeal N gonorrhoeae infection at any point over the 12-week period, defined as a positive result for either oropharyngeal swabs or saliva samples by NAAT, and the cumulative incidence of oropharyngeal gonorrhoea at the week 12 visit. A modified intention-to-treat analysis for the primary outcome was done that included men who provided at least one follow-up specimen over the 12-week study period. The trial was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12616000247471). FINDINGS: Between March 30, 2016, and Oct 26, 2018, 786 MSM were screened and 256 were excluded. 264 MSM were randomly assigned to the Biotène group and 266 to the Listerine group. The analysis population included 227 (86%) men in the Biotène group and 219 (82%) in the Listerine group. Oropharyngeal gonorrhoea was detected in ten (4%) of 227 of MSM in the Biotène group and in 15 (7%) of 219 in the Listerine group (adjusted risk difference 2·5%, 95% CI -1·8 to 6·8). The cumulative incidence of oropharyngeal gonorrhoea at the week 12 visit did not differ between the two mouthwash groups (adjusted risk difference 3·1%, 95% CI -1·4 to 7·7). INTERPRETATION: Listerine did not reduce the incidence of oropharyngeal gonorrhoea compared with Biotène. However, previous research suggests that mouthwash might reduce the infectivity of oropharyngeal gonorrhoea; therefore, further studies of mouthwash examining its inhibitory effect on N gonorrhoeae are warranted to determine if it has a potential role for the prevention of transmission. FUNDING: Australian National Health and Medical Research Council.

3.
Artículo en Inglés | MEDLINE | ID: mdl-33632090

RESUMEN

Abstract: The key issues with Neisseria gonorrhoeae infections, in Australia and elsewhere, are coincident increases in disease rates and in antimicrobial resistance (AMR), although these factors have not been shown to be correlated. Despite advances in diagnosis, control of this disease remains elusive, and incidence in Australia continues to increase. Of the Australian jurisdictions, New South Wales (NSW) has the highest N. gonorrhoeae notifications, and over the five-year period 2015-2019, notifications in NSW have increased above the national average (by 116% versus 85%, respectively). Gonococcal disease control is reliant on effective antibiotic regimens. However, escalating AMR in N. gonorrhoeae is a global health priority, as the collateral injury of untreated infections has substantive impacts on sexual and newborn health. Currently, our first-line therapy for gonorrhoea is also our last line, with no ideal alternative identified. Despite some limitations, gentamicin is licensed and readily available in Australia, and is proposed for treatment of resistant N. gonorrhoeae in national guidelines; however, supportive published microbiological data are lacking. Analysis of gonococcal resistance patterns within Australia for the period 1991-2019, including 35,000 clinical isolates from NSW, illustrates the establishment and spread of population-level resistance to all contemporaneous therapies. An analysis of gentamicin susceptibility on 2,768 N. gonorrhoeae clinical isolates from NSW, for the period 2015-2020, demonstrates that the median minimum inhibitory concentration (MIC) for gentamicin in NSW has remained low, at 4.0 mg/L, and resistance was not detected in any isolate. There has been no demonstration of MIC drift over time (p = 0.91, Kruskal-Wallis test), nor differences in MIC distributions according to patients' sex or site of specimen collection. This is the first large-scale evaluation of gentamicin susceptibility in N. gonorrhoeae in Australia. No gentamicin resistance was detected in clinical isolates, 2015-2020, hence this is likely to be an available treatment option for resistant gonococcal infections in NSW.


Asunto(s)
Gentamicinas/uso terapéutico , Gonorrea/tratamiento farmacológico , Neisseria gonorrhoeae/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Femenino , Gentamicinas/farmacología , Gonorrea/microbiología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Nueva Gales del Sur , Factores Sexuales
4.
Curr Opin HIV AIDS ; 16(2): 115-120, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33625042

RESUMEN

PURPOSE OF REVIEW: This review considers the potential and demonstrated impacts of SARS-CoV-2 on the sexually transmissible infection (STI)/HIV transmission. RECENT FINDINGS: COVID-19 increases the vulnerability of those at highest risk of acquiring STI/HIV. Altered health-seeking behaviour, reductions in STI/HIV clinic capacity, service disruptions and redeployment of human resources to assist COVID-19 control efforts have impacted on STI/HIV control programmes. Reports of reduced STI incidence are emerging, but it is hard to determine whether this is real or due to decreased testing during COVID-19 lockdown periods. Fear of COVID-19 and implemented control measures have altered STI/HIV transmission dynamics. Sexual health services adapted to the pandemic by reducing face-to-face patient encounters in favour of telehealth and mail-based initiatives as well as more stringent triage practice. Many sexual health and HIV treatment services now operate at reduced capacity and experience ongoing service disruptions, which necessarily translates into poorer outcomes for patients and their communities. SUMMARY: In the short-term, COVID-19 related sexual behaviour change is driving STI/HIV transmission downwards. However, the impacts of the global COVID-19 response on sexual health-seeking behaviour and STI/HIV services threaten to drive STI/HIV transmission upwards. Ultimately, the expected rebound in STI/HIV incidence will require an appropriate and timely public health response. VIDEO ABSTRACT: http://links.lww.com/COID/A31.


Asunto(s)
/epidemiología , Infecciones por VIH/epidemiología , Enfermedades de Transmisión Sexual/epidemiología , Infecciones por VIH/transmisión , Humanos , Incidencia , Conducta Sexual , Parejas Sexuales , Enfermedades de Transmisión Sexual/transmisión
5.
ChemSusChem ; 2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33634605

RESUMEN

An insulating composite was made from the sustainable building blocks wool, sulfur, and canola oil. In the first stage of the synthesis, inverse vulcanization was used to make a polysulfide polymer from the canola oil triglyceride and sulfur. This polymerization benefits from complete atom economy. In the second stage, the powdered polymer was mixed with wool, coating the fibers through electrostatic attraction. The polymer and wool mixture were then compressed with mild heating to provoke S-S metathesis in the polymer, which locks the wool in the polymer matrix. The wool fibers imparted tensile strength, insulating properties, and reduced the flammability of the composite. All building blocks are sustainable or derived from waste and the composite is a promising lead on next-generation insulation for energy conservation.

6.
Schizophr Bull ; 2021 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-33442739

RESUMEN

Schizophrenia (SCZ) and bipolar disorder (BP) share a number of features. For example, multiple transcriptome analyses have reported molecular alterations common to both diagnoses, findings supported by the considerable overlap in the genetic risk for each disorder. These molecular similarities may underlie certain clinical features that are frequently present in both disorders. Indeed, many individuals with BP exhibit psychosis, and some individuals with SCZ have prominent mood symptoms that warrant the diagnosis of schizoaffective disorder (SA). To explore the potential relationships between molecular alterations and certain clinical features among subjects with these diagnoses, we analyzed RNA sequencing data from the dorsolateral prefrontal and anterior cingulate cortices, provided by the CommonMind Consortium, in subjects from the University of Pittsburgh Brain Tissue Donation Program. Relative to unaffected comparison subjects, in each brain region, robust differential gene expression was present only in SCZ, including a lower expression of genes involved in mitochondrial function and an elevated expression of immune-related genes. However, correlation analyses showed that BP subjects had similar, although less pronounced, gene expression alterations. Comparisons across subgroups of subjects revealed that the similarities between SCZ and BP subjects were principally due to the BP subjects with psychosis. Moreover, the gene expression profile in BP subjects with psychosis was more similar to "pure" SCZ and SA subjects than to BP subjects without psychosis. Together, these analyses suggest that similarities in gene expression between SCZ and BP are at least partially related to the presence of psychosis in some BP subjects.

8.
Transl Psychiatry ; 11(1): 40, 2021 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-33436571

RESUMEN

Bipolar disorder and schizophrenia have multiple clinical and genetic features in common, including shared risk associated with overlapping susceptibility loci in immune-related genes. Higher activity of the nuclear factor-κB (NF-κB) transcription factor complex, which regulates the transcription of multiple immune markers, has been reported to contribute to immune activation in the prefrontal cortex in schizophrenia. These findings suggest the hypothesis that elevated NF-κB activity is present in the prefrontal cortex in bipolar disorder in a manner similar to that seen in schizophrenia. Therefore, we quantified levels of NF-κB-related mRNAs in the prefrontal cortex of 35 matched pairs of bipolar disorder and unaffected comparison subjects using quantitative PCR. We found that transcript levels were higher in the prefrontal cortex of bipolar disorder subjects for several NF-κB family members, NF-κB activation receptors, and NF-κB-regulated mRNAs, and were lower for an NF-κB inhibitor. Transcript levels for NF-κB family members, NF-κB activation receptors, and NF-κB-regulated mRNAs levels were also highly correlated with each other. This pattern of elevated transcript levels for NF-κB-related markers in bipolar disorder is similar to that previously reported in schizophrenia, suggesting that cortical immune activation is a shared pathophysiological feature between the two disorders.

9.
BMJ Case Rep ; 14(1)2021 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-33431534

RESUMEN

A man in his late 30s presented with a several-day history of rectal pain, discharge and bleeding associated with systemic upset. Sexual history revealed receptive anal sex with several male partners in the 2 weeks preceding his clinic visit. Examination of the perianal area was unremarkable. Proctoscopy showed evidence of non-ulcerative proctitis. Microscopy for Gram stain showed pus cells plus extracellular Gram-negative diplococci. The patient was treated for presumptive gonorrhoea and chlamydial infection with ceftriaxone, azithromycin and doxycycline. The patient failed to improve with this treatment regimen. Rectal swab results at 48 hours confirmed the causative agent to be herpes simplex virus (HSV) type 2. The patient was recalled and treated successfully with valaciclovir. This case serves as a useful reminder to clinicians to consider HSV in the differential diagnosis of sexually transmitted proctitis, in the absence of perianal or anorectal ulceration.


Asunto(s)
Herpes Simple/diagnóstico , Herpesvirus Humano 2/aislamiento & purificación , Proctitis/diagnóstico , Enfermedades de Transmisión Sexual/diagnóstico , Adulto , Antivirales/uso terapéutico , ADN Viral/aislamiento & purificación , Diagnóstico Diferencial , Gonorrea/diagnóstico , Herpes Simple/tratamiento farmacológico , Herpes Simple/transmisión , Herpes Simple/virología , Herpesvirus Humano 2/genética , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Mucosa Intestinal/virología , Masculino , Proctitis/tratamiento farmacológico , Proctitis/virología , Recto/virología , Conducta Sexual , Enfermedades de Transmisión Sexual/tratamiento farmacológico , Enfermedades de Transmisión Sexual/transmisión , Enfermedades de Transmisión Sexual/virología , Valaciclovir/uso terapéutico
10.
Curr Opin Infect Dis ; 34(1): 56-61, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33315752

RESUMEN

PURPOSE OF REVIEW: This review considers the potential and demonstrated impacts of SARS-CoV-2 on the sexually transmissible infection (STI)/HIV transmission. RECENT FINDINGS: COVID-19 increases the vulnerability of those at highest risk of acquiring STI/HIV. Altered health-seeking behaviour, reductions in STI/HIV clinic capacity, service disruptions and redeployment of human resources to assist COVID-19 control efforts have impacted on STI/HIV control programmes. Reports of reduced STI incidence are emerging, but it is hard to determine whether this is real or due to decreased testing during COVID-19 lockdown periods. Fear of COVID-19 and implemented control measures have altered STI/HIV transmission dynamics. Sexual health services adapted to the pandemic by reducing face-to-face patient encounters in favour of telehealth and mail-based initiatives as well as more stringent triage practice. Many sexual health and HIV treatment services now operate at reduced capacity and experience ongoing service disruptions, which necessarily translates into poorer outcomes for patients and their communities. SUMMARY: In the short-term, COVID-19 related sexual behaviour change is driving STI/HIV transmission downwards. However, the impacts of the global COVID-19 response on sexual health-seeking behaviour and STI/HIV services threaten to drive STI/HIV transmission upwards. Ultimately, the expected rebound in STI/HIV incidence will require an appropriate and timely public health response. VIDEO ABSTRACT: http://links.lww.com/COID/A31.


Asunto(s)
/epidemiología , Infecciones por VIH/epidemiología , Enfermedades de Transmisión Sexual/epidemiología , Infecciones por VIH/transmisión , Humanos , Incidencia , Conducta Sexual , Salud Sexual , Parejas Sexuales , Enfermedades de Transmisión Sexual/transmisión
11.
Proc Natl Acad Sci U S A ; 118(2)2021 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-33372142

RESUMEN

The human striatum can be subdivided into the caudate, putamen, and nucleus accumbens (NAc). Each of these structures have some overlapping and some distinct functions related to motor control, cognitive processing, motivation, and reward. Previously, we used a "time-of-death" approach to identify diurnal rhythms in RNA transcripts in human cortical regions. Here, we identify molecular rhythms across the three striatal subregions collected from postmortem human brain tissue in subjects without psychiatric or neurological disorders. Core circadian clock genes are rhythmic across all three regions and show strong phase concordance across regions. However, the putamen contains a much larger number of significantly rhythmic transcripts than the other two regions. Moreover, there are many differences in pathways that are rhythmic across regions. Strikingly, the top rhythmic transcripts in NAc (but not the other regions) are predominantly small nucleolar RNAs and long noncoding RNAs, suggesting that a completely different mechanism might be used for the regulation of diurnal rhythms in translation and/or RNA processing in the NAc versus the other regions. Further, although the NAc and putamen are generally in phase with regard to timing of expression rhythms, the NAc and caudate, and caudate and putamen, have several clusters of discordant rhythmic transcripts, suggesting a temporal wave of specific cellular processes across the striatum. Taken together, these studies reveal distinct transcriptome rhythms across the human striatum and are an important step in helping to understand the normal function of diurnal rhythms in these regions and how disruption could lead to pathology.

12.
Cereb Cortex ; 31(5): 2345-2363, 2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33338196

RESUMEN

The functional output of a cortical region is shaped by its complement of GABA neuron subtypes. GABA-related transcript expression differs substantially between the primate dorsolateral prefrontal cortex (DLPFC) and primary visual (V1) cortices in gray matter homogenates, but the laminar and cellular bases for these differences are unknown. Quantification of levels of GABA-related transcripts in layers 2 and 4 of monkey DLPFC and V1 revealed three distinct expression patterns: 1) transcripts with higher levels in DLPFC and layer 2 [e.g., somatostatin (SST)]; 2) transcripts with higher levels in V1 and layer 4 [e.g., parvalbumin (PV)], and 3) transcripts with similar levels across layers and regions [e.g., glutamic acid decarboxylase (GAD67)]. At the cellular level, these patterns reflected transcript- and cell type-specific differences: the SST pattern primarily reflected differences in the relative proportions of SST mRNA-positive neurons, the PV pattern primarily reflected differences in PV mRNA expression per neuron, and the GAD67 pattern reflected opposed patterns in the relative proportions of GAD67 mRNA-positive neurons and in GAD67 mRNA expression per neuron. These findings suggest that differences in the complement of GABA neuron subtypes and in gene expression levels per neuron contribute to the specialization of inhibitory neurotransmission across cortical circuits.

13.
Cereb Cortex ; 2020 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-33279960

RESUMEN

Visuospatial working memory (vsWM) requires information transfer among multiple cortical regions, from primary visual (V1) to prefrontal (PFC) cortices. This information is conveyed via layer 3 glutamatergic neurons whose activity is regulated by gamma-aminobutyric acid (GABA)ergic interneurons. In layer 3 of adult human neocortex, molecular markers of glutamate neurotransmission were lowest in V1 and highest in PFC, whereas GABA markers had the reverse pattern. Here, we asked if these opposite V1-visual association cortex (V2)-posterior parietal cortex (PPC)-PFC gradients across the vsWM network are present in layer 3 of monkey neocortex, when they are established during postnatal development, and if they are specific to this layer. We quantified transcript levels of glutamate and GABA markers in layers 3 and 6 of four vsWM cortical regions in a postnatal developmental series of 30 macaque monkeys. In adult monkeys, glutamate transcript levels in layer 3 increased across V1-V2-PPC-PFC regions, whereas GABA transcripts showed the opposite V1-V2-PPC-PFC gradient. Glutamate transcripts established adult-like expression patterns earlier during postnatal development than GABA transcripts. These V1-V2-PPC-PFC gradients and developmental patterns were less evident in layer 6. These findings demonstrate that expression of glutamate and GABA transcripts differs across cortical regions and layers during postnatal development, revealing potential molecular substrates for vsWM functional maturation.

14.
Neuroscience ; 452: 181-191, 2020 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-33212224

RESUMEN

Activation of specific neural circuits in different layers of the primate dorsolateral prefrontal cortex (DLPFC) is essential for working memory, a core cognitive function. Recurrent excitation between pyramidal neurons in middle and deep layers of the DLPFC contributes to the laminar-specific activity associated with different working memory subprocesses. Excitation between cortical pyramidal neurons is mediated by glutamatergic synapses on dendritic spines, but whether the relative abundance of spines receiving cortical inputs differs between middle and deep cortical layers in human DLPFC is unknown. Additionally, GABAergic inputs to spines sculpt pyramidal neuron activity. Whether dendritic spines that receive a glutamatergic input from a cortical pyramidal neuron are targeted by GABAergic interneurons in the human DLPFC is unknown. Using triple-label fluorescence confocal microscopy, we found that 1) the density of spines receiving an input from a cortical pyramidal neuron is greater in the middle than in the deep laminar zone, 2) dendritic spines dually innervated by a cortical pyramidal neuron and an interneuron are present in the human DLPFC, and 3) the density of spines dually innervated by a cortical pyramidal neuron and an interneuron is also greater in the middle than in the deep laminar zone. Ultrastructural analyses support the presence of spines that receive a cortical pyramidal neuron synapse and an interneuron synapse in human and monkey DLPFC. These data support the notion that the DLPFC middle laminar zone is particularly endowed with a microcircuit structure that supports the gating, integrating and fine-tuning of synaptic information in recurrent excitatory microcircuits.

15.
Am J Psychiatry ; 177(12): 1140-1150, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-33115248

RESUMEN

OBJECTIVE: The shared risk factors and clinical features in schizophrenia and bipolar disorder may be linked via mitochondrial dysfunction. However, the severity of mitochondrial dysfunction, and/or the specific mitochondrial functional pathways affected, may differ between diagnoses, especially at the level of individual cell types. METHODS: Transcriptomic profiling data for a gene set indexing mitochondrial functional pathways were obtained for dorsolateral prefrontal cortex (DLPFC) gray matter and layer 3 and layer 5 pyramidal neurons of subjects with schizophrenia or bipolar disorder. Analyses were conducted using a dual strategy: identification of differentially expressed genes (DEGs) and their functional pathway enrichment, and application of weighted gene coexpression network analysis. These analyses were repeated in monkeys chronically exposed to antipsychotic drugs to determine their effect on mitochondrial-related gene expression. RESULTS: In DLPFC gray matter, 41% of mitochondrial-related genes were differentially expressed in the schizophrenia group, whereas 8% were differentially expressed in the bipolar group. In the schizophrenia group, 83% of DEGs showed lower expression, and these were significantly enriched for three functional pathways, each indexing energy production. DEGs in the bipolar disorder group were not enriched for functional pathways. This disease-related pattern of findings was also identified in pyramidal neurons. None of the gene expression alterations disrupted coexpression modules, and DEGs were not attributable to antipsychotic medications. CONCLUSIONS: Schizophrenia and bipolar disorder do not appear to share similar mitochondrial alterations in the DLPFC. The selective and coordinated down-regulation of energy production genes in schizophrenia is consistent with the effects of chronic reductions in pyramidal neuron firing, and enhancement of this activity may serve as a therapeutic target.

17.
Sex Transm Infect ; 2020 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-32912933

RESUMEN

OBJECTIVES: International guidelines recommend Mycoplasma genitalium testing, preferably using an assay to detect macrolide resistance-associated mutations, for men presenting with non-gonococcal urethritis, but there is no specific guidance on such testing for men with gonococcal urethritis. METHODS: This study aimed to estimate the proportion of men with gonococcal urethritis who have coinfection with M. genitalium through a retrospective analysis of cases of symptomatic urethral gonorrhoea at Western Sydney Sexual Health Centre in 2017 and 2018. RESULTS: Fourteen of 184 (7.6%, 95% CI 3.7 to 11.5) men with gonococcal urethritis had M. genitalium detected in the urine at the time of presentation. No demographic or behavioural factors predicted M. genitalium coinfection. Coinfection with urethral Chlamydia trachomatis was detected in 29 of 184 (15.8%, 95% CI 10.5 to 21.1). All five men with macrolide-resistant M. genitalium detected returned for treatment with moxifloxacin at a median of 8 days (range 5-16 days) after presentation and treatment of gonorrhoea; three of five were documented to remain symptomatic at this visit. CONCLUSION: Although M. genitalium coinfection is less common than chlamydia among men with symptomatic gonococcal urethritis, M. genitalium testing, using an assay to detect macrolide resistance, will potentially reduce symptom duration particularly for men with macrolide-resistant infections, but may not be justifiable on cost-benefit analysis.

18.
Chem Sci ; 11(21): 5537-5546, 2020 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-32874497

RESUMEN

Inverse vulcanization is a copolymerization of elemental sulfur and alkenes that provides unique materials with high sulfur content (typically ≥50% sulfur by mass). These polymers contain a dynamic and reactive polysulfide network that creates many opportunities for processing, assembly, and repair that are not possible with traditional plastics, rubbers and thermosets. In this study, we demonstrate that two surfaces of these sulfur polymers can be chemically joined at room temperature through a phosphine or amine-catalyzed exchange of the S-S bonds in the polymer. When the nucleophile is pyridine or triethylamine, we show that S-S metathesis only occurs at room temperature for a sulfur rank > 2-an important discovery for the design of polymers made by inverse vulcanization. This mechanistic understanding of the S-S metathesis was further supported with small molecule crossover experiments in addition to computational studies. Applications of this chemistry in latent adhesives, additive manufacturing, polymer repair, and recycling are also presented.

20.
Mol Psychiatry ; 2020 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-32632206

RESUMEN

Psychiatric disorders are associated with accelerated aging and enhanced risk for neurodegenerative disorders. Brain aging is associated with molecular, cellular, and structural changes that are robust on the group level, yet show substantial inter-individual variability. Here we assessed deviations in gene expression from normal age-dependent trajectories, and tested their validity as predictors of risk for major mental illnesses and neurodegenerative disorders. We performed large-scale gene expression and genotype analyses in postmortem samples of two frontal cortical brain regions from 214 control subjects aged 20-90 years. Individual estimates of "molecular age" were derived from age-dependent genes, identified by robust regression analysis. Deviation from chronological age was defined as "delta age". Genetic variants associated with deviations from normal gene expression patterns were identified by expression quantitative trait loci (cis-eQTL) of age-dependent genes or genome-wide association study (GWAS) on delta age, combined into distinct polygenic risk scores (PRScis-eQTL and PRSGWAS), and tested for predicting brain disorders or pathology in independent postmortem expression datasets and clinical cohorts. In these validation datasets, molecular ages, defined by 68 and 76 age-related genes for two brain regions respectively, were positively correlated with chronological ages (r = 0.88/0.91), elevated in bipolar disorder (BP) and schizophrenia (SCZ), and unchanged in major depressive disorder (MDD). Exploratory analyses in independent clinical datasets show that PRSs were associated with SCZ and MDD diagnostics, and with cognition in SCZ and pathology in Alzheimer's disease (AD). These results suggest that older molecular brain aging is a common feature of severe mental illnesses and neurodegeneration.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...