Associations of current marital status and living arrangements with HIV and syphilis risk: findings from a community-based sample of men who have sex with men in China

Chinese men who have sex with men (MSM) are disproportionally affected by HIV and sexually transmitted infections (STIs), but little is known about the role of current marital status and living arrangements in shaping their HIV/syphilis risk. A cross-sectional study was conducted among MSM in Beijing, China to assess their sociodemographic/behavioral characteristics between married and single MSM, and test the hypothesis that currently married MSM have a lower odds of being HIV- and/or syphilis-infected. Participants were recruited via short message services, peer referral, internet, and community outreach. Data collection was based on a questionnaire survey and self-report. Infection status was lab-confirmed. Multivariable logistic regression modeling was used to assess the association of marital status and living arrangement with HIV/syphilis risk. Of the 3588 MSM, infection prevalence was high (HIV?=?12.7%; syphilis?=?7.5%). Compared to single MSM living with their boyfriends or male sex partners, single/alone MSM and married MSM living with wives were less likely to practice condomless insertive (CIAI) or receptive (CRAI) anal intercourse with men; while married MSM living with boyfriends or male sex partner were more likely to practice CIAI and CRAI, and married MSM were more likely to practice condomless vaginal sex. Compared to men living with boyfriends/sexual partners, significantly reduced odds of being HIV-positive were seen among married MSM who were living alone (aOR: 0.52; 95%CI: 0.28, 0.94) or living with their wives (aOR: 0.53; 95%CI: 0.31, 0.89). Similarly, single MSM living alone (aOR: 0.67; 95%CI: 0.48, 0.95) and married MSM living with their wives were comparatively less likely to be syphilis-infected (aOR: 0.43; 95%CI: 0.23, 0.79). Future efforts should consider characteristics of marital status and living arrangements for designing subgroup-specific risk reduction strategies among Chinese MSM.     

Gating of steering signals through phasic modulation of reticulospinal neurons during locomotion

The neural control of movements in vertebrates is based on a set of modules, like the central pattern generator networks (CPGs) in the spinal cord coordinating locomotion. Sensory feedback is not required for the CPGs to generate the appropriate motor pattern and neither a detailed control from higher brain centers. Reticulospinal neurons in the brainstem activate the locomotor network, and the same neurons also convey signals from higher brain regions, such as turning/steering commands from the optic tectum (superior colliculus). A tonic increase in the background excitatory drive of the reticulospinal neurons would be sufficient to produce coordinated locomotor activity. However, in both vertebrates and invertebrates, descending systems are in addition phasically modulated because of feedback from the ongoing CPG activity. We use the lamprey as a model for investigating the role of this phasic modulation of the reticulospinal activity, because the brainstem–spinal cord networks are known down to the cellular level in this phylogenetically oldest extant vertebrate. We describe how the phasic modulation of reticulospinal activity from the spinal CPG ensures reliable steering/turning commands without the need for a very precise timing of on- or offset, by using a biophysically detailed large-scale (19,600 model neurons and 646,800 synapses) computational model of the lamprey brainstem–spinal cord network. To verify that the simulated neural network can control body movements, including turning, the spinal activity is fed to a mechanical model of lamprey swimming. The simulations also predict that, in contrast to reticulospinal neurons, tectal steering/turning command neurons should have minimal frequency adaptive properties, which has been confirmed experimentally.In many vertebrate and invertebrate motor systems, a phasic modulation occurs in the descending control system determining the level of activity (1–3) during rhythmic movements. The physiological role of this modulation has remained enigmatic, because it has been shown that tonic activity is sufficient to effectively drive motor activity like locomotion. One example is the reticulospinal neurons in the brainstem that serve as the major interface between higher level commands and the networks in the spinal cord in all vertebrates from lamprey to primates (4–6). In this study, we investigate the motor system of the lamprey, belonging to the most ancient group of vertebrates that has been investigated in considerable detail not only at the brainstem–spinal cord level but also with regard to the forebrain systems underlying the control of action (2, 7, 8). A bilateral symmetric activation of reticulospinal neurons will activate the locomotor networks in the spinal cord, resulting in coordinated swimming movements (2, 9–11). The reticulospinal neurons act on the excitatory and inhibitory network interneurons in the spinal cord through NMDA and AMPA receptors (12). Most reticulospinal neurons can be involved in several motor patterns (13). Whereas a bilaterally symmetric activation leads to locomotion, a unilateral addition of excitation to one side will enhance motor activity on this side and result in turning. This is the basis of steering during locomotion (14).The phasic modulation of reticulospinal neurons is most pronounced in the fastest-conducting group involved in steering (15). It results from feedback from the network neurons in the rostral segments of the spinal cord during locomotor movements, so that the reticulospinal neurons become active in phase with those segments, and during the inactive period they are instead inhibited (15–19). This feedback is conveyed to reticulospinal neurons via ascending spinobulbar neurons (15–20) that provide an “efference copy” regarding the cycle-to-cycle activity in the locomotor network. Spinobulbar neurons (21) provide the excitatory and inhibitory drive to reticulospinal neurons, resulting in modulation of their activity in phase with the ipsilateral rostral parts of the spinal cord (21, 22) and this forms a closed spino-reticulo-spinal loop (17).Visuomotor coordination (23) and steering results from activation of tectal output neurons that monosynaptically activate reticulospinal neurons (24, 25), which represent the interface between tectum and the spinal cord networks. Here, we focus on the role of the phasic modulation of the reticulospinal neurons. We show that the phasic modulation of the reticulospinal cells is advantageous in that the steering commands from tectum become gated and thereby arrive in the correct phase of the locomotor cycle. The tectal commands, therefore, need not be timed very precisely in relation to the locomotor cycle. The reticulospinal modulation ascertains that the command signal will be accurately timed provided that the tectal command signal itself remains constant and thus has a limited spike-frequency adaptation, which indeed applies to the tectal output neurons as shown here experimentally (25). We explore the effect of steering signals through a combined simulation-experimental approach. Biologically detailed lamprey spinal cell models (26) are used in large-scale simulations of the locomotor network (7) to replicate electric activity in command centers and the spinal cord. A mechanical model of swimming (27, 28) is used for a quantitative evaluation of the locomotor response.     

Screening of binge drinking among patients on an emergency surgical ward.

In a sample of 149 emergency surgical patients, binge drinking was assessed through interviews. Sensitivity, specificity, and positive and negative predictive values were calculated for three questionnaires-the Malm? modification of brief MAST (Mm-MAST), CAGE, and the Trauma Scale-and two biological markers-carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GGT). Binge drinking was reported by 42% of male patients, aged 16-29 years; 66% of female patients, aged 16-29 years; 27% of male patients, aged 30-73 years; and 16% of female patients, aged 30-73 years. All alcohol biomarkers had low sensitivity to binge drinking among women. Mm-MAST alone and CAGE and CDT combined were sensitive to identifying binge drinking among men aged 30-73 years. The three questionnaires combined had a sensitivity of 0.82 to binge drinking among men aged 16-29 years.     

Quantitation of circumferential subpixel vessel wall position and wall shear stress by multiple sectored three-dimensional paraboloid modeling of velocity encoded cine MR

Methods are lacking for accurate, noninvasive circumferential edge detection and wall shear stress calculation. Using stan dard MR phase contrast sequences, parts of the velocity pro files were fitted to a multiple sectored three-dimensional pa raboloid model enabling exact calculation of vessel wall position and wall shear stress in 24 locations evenly distrib uted around the luminal vessel wall. The model was evaluated by in vitro scans and computer simulations and applied to the common carotid artery of humans. In vitro, the luminal area of a glass tube was assessed with an error of 0.9%. Computer simulations of peak systolic data revealed errors of ±0.9% (vessel area) and ±3.25% (wall shear stress). The in vivo results showed substantial difference between anterior and posterior wall shear stress values due to skewed velocity profiles. A new noninvasive method for highly accurate mea surement of circumferential subpixel vessel wall position and wall shear stress has been developed.     

Cardiovascular Actions of Chronic Intracerebroventricular Administration of Metformin in Normotensive Rats

Abstract: Acute intracerebroventricular administration of the antihyperglycaemic agent metformin (0.25–1 mg) elicits sympathoinhibitory responses in spontaneously hypertensive rats. However, cardiovascular actions of chronic intracerebroventricular metformin administration are unknown. To define the dose-response relationship during chronic intracerebroventricular metformin administration, mean arterial pressure, heart rate, and locomotor activity were measured continuously by radiotelemetry in 40 normotensive rats. After a 10 day control period, an intracerebroventricular cannula was implanted and connected to an osmotic minipump which delivered metformin in the following doses: 0 [saline], 0.01, 0.1, 1, and 10 mg/day. LD₅₀ was 1.5 mg/day. Metformin, 1 mg/day attenuated the nocturnal, physiological increase in mean arterial pressure (-7.3+1.6% versus before metformin), produced behavioural changes and tended to increase locomotor activity. Lower doses of intracerebroventricular metformin (0.1 and 0.01 mg/day) did not affect mean arterial pressure, heart rate or locomotor activity. In conclusion, chronic intracerebroventricular administration of high dose metformin (1.0 mg/day) attenuates the nocturnal, physiological increase in mean arterial pressure. These findings are compatible with a toxic, sympathoinhibitory action of high doses of metformin intracerebroventricularly.     

Depleting Rac1 in mouse rod photoreceptors protects them from photo-oxidative stress without affecting their structure or function

In nonphagocytic cells, Rac1 is a component of NADPH oxidase that produces reactive oxygen species [Ushio-Fukai M (2006) Sci STKE 2006:re8]. Rac1 is expressed abundantly in mammalian retinal photoreceptors, where it is activated in response to light stimuli [Balasubramanian N, Slepak VZ (2003) Curr Biol 13:1306–1310]. We used Cre-LoxP conditional gene targeting to knock down Rac1 expression in mouse rod photoreceptors and found protection against light-induced photoreceptor death compared with WT litter-mates. We also found a similar protective effect on rods using apocynin, which inhibits NADPH oxidase activity. These results implicate both neuronal Rac1 and NADPH oxidase in cell death in this model of CNS degeneration. Studies in which dominant-mutants of Rac1 were expressed in transgenic Drosophila species demonstrated that Rac1 is a key regulator of photoreceptor morphogenesis and polarity [Chang HY, Ready DF (2000) Science 290:1978–1980]. However, we found that diminished Rac1 expression in mouse rods had no effect on retinal structure or function examined by light microscopy, electron microscopy, rhodopsin measurement, electroretinogram activity, and visual acuity, indicating rod outer segment morphogenesis proceeded normally in Rac1 conditional knockout mice. The lack of structural or functional effect of Rac1 depletion on photoreceptors, but protection under conditions of stress, indicate that the Rac1 pathway warrants exploration as a target for therapy in retinal neurodegenerative diseases.     

Effects of Perindopril and Hydrochlorothiazide on the Long-Term Progression of Lithium-Induced Chronic Renal Failure in Rats

Abstract: Administration of lithium in the diet to new-born rats induces chronic renal failure associated with hypertension, proteinuria and irreversible tubulo-interstitial morphological changes. In the present study we induced chronic renal failure by administration of lithium for 16 weeks to new-born rats, and examined the spontaneous course of this nephropathy and the effects of antihypertensive treatment with either perindopril (12 mg/kg diet) or hydrochlorothiazide (500–1000 mg/kg diet) during a 24 weeks follow up period without lithium. In the placebo group, progression to terminal uraemia occurred in all rats with severe renal failure (initial P_urea >15 mM) (10 of 18). Rats with mild-moderate renal failure (P_urea 9–15 mM) showed no deterioration in renal function despite persistent systolic hypertension and irreversible structural renal changes. Perindopril normalized the blood pressure in all rats but did not prevent the progression to terminal uraemia (8 of 18). Hydrochlorothiazide partially controlled the hypertension and accellerated the progression of uraemia without increasing the mortality (7 of 17). Irrespective of treatments, the predominant quantitative structural changes (e.g. decreased volume of proximal tubular cells) showed significant correlations with the degree of renal dysfunction, but not with systolic blood pressure in the surviving rats. It is concluded that progression of lithium-induced nephropathy to terminal uraemia occurs when the nephrotoxic insult results in a more than 50% reduction of the glomerular filtration rate, judged from P_urea levels. The failure of effective antihypertensive treatment with an angiotensin-converting enzyme inhibitor to modify the progression suggests that in this model, systemic or glomerular hypertension may not be an important pathophysiological factor. The structural and functional deterioration observed in Li-uraemic rats during treatment with hydrochlorothiazide remains unexplained.     

Bronchial hyper-responsiveness predicts the development of mild clinical asthma within 2 yr in school children with hay-fever

In children with mild asthma, symptoms are not always apparent. Therefore, results of tests play an important role for the diagnosis. First, to investigate whether children with bronchial hyper-responsiveness (BHR) but no symptoms of asthma in 1992 had developed clinical asthma at follow up in 1994. The second aim was to find out the diagnostic properties of tests for asthma/allergic inflammation, using either doctor diagnosed asthma (DDA), self-assessed symptoms of asthma or iso-capnic hyperventilation of cold air (IHCA), as the standard, to diagnose asthma in a group of children with hay fever. Twenty-eight children with pollinosis, 12 of them with a history of asthma for the first time during the season 1992, were studied during the birch pollen season and in the autumn of 1994. During both periods, the bronchial hyper-reactivity was estimated by methacholine bronchial provocation tests (MBPT), bronchial variability by peak expiratory flow rate variability, subjective symptoms of asthma by visual analogue scale (VAS) and bronchial inflammation by serum and urine levels of inflammatory mediators. In 1994 IHCA was added during both seasons. Eight of 16 children with BHR but without clinical asthma in 1992 had developed asthma in 1994, 14 of 16 reacted to IHCA and 13 to MBPT. All 12 children with DDA in 1992 had still asthma in 1994 and 14 children with BHR in 1992 had persistent BHR in 1994. Of 23 children with BHR in 1992, 17 had DDA in 1994 and all maintained their BHR. Furthermore, 20 of them reacted to IHCA in 1994. In 1994, 24 of 28 hay-fever children had a positive IHCA tests and 24 had positive MBPT. In relation to VAS, the sensitivity of IHCA and MBPT to predict present asthma was high, but the specificity low, whereas the specificity of most other tests was high, but based on few individuals. In relation to DDA both the IHCA test (65-80%) and the MBPT test (79-85%) had a high sensitivity and it was three to six times more likely to find a positive test among asthmatics than in non-asthmatics. Children with hay fever without clinical asthma have a high risk of developing asthma within 2 yr. In relation to DDA, inhalation of cold air and the MBPT showed a high sensitivity.     

Botanical nomenclature in pharmacovigilance and a recommendation for standardisation.

Nomenclature of plants in pharmacology can be presented by pharmaceutical names or scientific names in the form of Linnaean binomials. In this paper, positive and negative aspects of both systems are discussed in the context of the scientific nomenclatural framework and the systems' practical applicability. The Uppsala Monitoring Centre (UMC) runs the WHO Programme for International Drug Monitoring and is responsible for the WHO Adverse Drug Reaction (ADR) database that currently contains 3.6 million records. In order for the UMC to monitor pharmacovigilance through ADRs to herbal medicine products the following nomenclatural criteria are important: (i) the name should indicate only one species of plant; (ii) the source for this name must be authoritative; (iii) the name should indicate which part of the plant is used. Based on these criteria, the UMC investigated four options: (i) adopt main names used in recognised (inter-) national pharmacopoeias or authoritative publications; (ii) adopt option 1, but cite the publication for all names in abbreviated form; (iii) three-part pharmaceutical names consisting of Latinised part name plus Latinised genus name, plus Latinised specific epithet; (iv) scientific binomial names, optionally with author and plant part used. The UMC has chosen the latter option and will at its adoption utilise the scientific botanical nomenclature as defined by the International Code of Botanical Nomenclature. This decision satisfies all criteria set by the UMC and renders the necessity of creating a new system or upgrading an old inconsistent system obsolete. The UMC has also issued an extensive synonymy checklist of vernacular, pharmaceutical and scientific names for the herbals in the WHO ADR database. We strongly recommend the adoption of scientific names to denote plant ingredients in medicine.     

Dose-related changes in retinal function and PKC-alpha expression in rabbits on vigabatrin medication

Background  To investigate, in a rabbit model, the effect of two different doses of vigabatrin (VGB) on retinal function and morphology. Methods  Twenty-nine rabbits of mixed strain were divided into two groups, receiving either high-dose (n = 15) or low-dose (n = 14) oral VGB treatment (cumulative dose 29.8 ± 2.9 g and 14.2 ± 0.6 g respectively). Ten rabbits receiving water served as control animals. The rabbits underwent three baseline ff-ERG measurements before initiation of VGB medication and two ff-ERG registrations during treatment, after 8 and 12–14 weeks respectively. At the end of the study, the expression of protein kinase C-alpha (PKC-alpha), gamma amino butyric acid (GABA) A receptors, vimentin, glial fibrillary acidic protein (GFAP) and peanut agglutinin (PNA) was examined in retinal sections from all rabbits. Results  In animals of the high-dose group, the ff-ERG measurements revealed a significant decrease of isolated rod b-wave amplitudes, combined rod-cone b-wave amplitudes and amplitudes of oscillatory potentials (OPs); OP1, OP2 and OP3. In the low-dose group, the b-wave amplitudes of combined rod-cone responses as well as OP2 and OP3 were significantly reduced. PKC-alpha labeling demonstrated a dose-related translocation of the enzyme in rod bipolar cells, also revealing a significant decline of the number of PKC-alpha labeled rod bipolar cells in treated animals. Vimentin labeling showed a dose-related deviant labeling pattern of Müller cells, with strikingly low labeling intensity in the outer parts of the cells; in the outer limiting membrane (OLM) as well as the outer nuclear layer (ONL). Labeling with antibodies against GABA A receptors and GFAP, as well as PNA staining, revealed no differences between treated animals and controls. Conclusions  In this study, VGB medication was associated, in a dose-related manner, with a decrease of ff-ERG amplitudes as well as with altered protein expression in rod bipolar cells and Müller cells, suggesting alterations of inner retinal function. The dose-related morphological and electrophysiological changes indicate a retinal pathology that may explain the constricted visual fields seen in some patients treated with VGB. The authors have no financial interest in the material presented, and none of the authors has any conflict of interest to disclose. The authors have full control of the primary data, and agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review the data upon request.