Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection

HIV type 1 (HIV-1) persists within resting CD4(+) T cells despite antiretroviral therapy (ART). To better understand the kinetics by which resting cell infection (RCI) is established, we developed a mathematical model that accurately predicts (r = 0.65, P = 2.5 × 10(-4)) the initial frequency of RCI measured about 1 year postinfection, based on the time of ART initiation and the dynamic changes in viremia and CD4(+) T cells. In the largest cohort of patients treated during acute seronegative HIV infection (AHI) in whom RCI has been stringently quantified, we found that early ART reduced the generation of latently infected cells. Although RCI declined after the first year of ART in most acutely infected patients, there was a striking absence of decline when initial RCI frequency was less than 0.5 per million. Notably, low-level viremia was observed more frequently as RCI increased. Together these observations suggest that (i) the degree of RCI is directly related to the availability of CD4(+) T cells susceptible to HIV, whether viremia is controlled by the immune response and/or ART; and (ii) that two pools of infected resting CD4(+) T cells exist, namely, less stable cells, observable in patients in whom viremia is not well controlled in early infection, and extremely stable cells that are established despite early ART. These findings reinforce and extend the concept that new approaches will be needed to eradicate HIV infection, and, in particular, highlight the need to target the extremely small but universal, long-lived latent reservoir.     

Evaluating Auditory Pathway by Electrical Auditory Middle Latency Response and Postoperative Hearing Rehabilitation

ABSTRACT

Objective: To establish an effective detection method to evaluate auditory pathway in patients by electrical evoked middle latency response (EMLR) before artificial cochlear implantation, and to analyze the relationship between postoperative hearing rehabilitation and auditory cortex functions. Methods: Twenty-three patients with artificial cochlear implant were recruited. EMLR was measured after adjusting the depth of anesthesia. The electrical auditory brainstem response (EABR) mode with monopolar stimulation and two-phase alternating current square waves was selected. The parameters of EMLR waveforms were recorded by the EABR measurement system. Nerve response telemetry (NRT) was examined by measuring threshold level (T value) and comfortable level (C value) 1 month after power-on, and hearing and speech development was followed up 12 months later.Results: The detection rate of EMLR was 95.65%. The waveforms of EMLR were comparable to those of auditory middle latency response (AMLR), showing decreased latency and interval but similar amplitude. The induction rate of NRT was 69.23%, which was much lower than that of EMLR. The EMLR thresholds were significantly correlated to the T and C values, and were comparable to the T values numerically. The Spearman's r value between EMLR waveforms and CAP scores after using the cochlear implant for 12 months was 0.673 (P < 0.01). Conclusion: An effective detection method to measure EMLR before artificial cochlear implant was established. The thresholds of EMLR were lower than those of NRT. The method can be useful for objective evaluation of auditory cortex functions and postoperative hearing rehabilitation.     

Contralateral electrodiagnosis in patients with abnormal median distal sensory latency

Background

We hypothesized that electrodiagnostic evidence of carpal tunnel syndrome (CTS) on the contralateral, less-severe side correlates with disease severity.

Methods

We retrospectively reviewed 285 adults that had bilateral electrodiagnostic testing and a median distal sensory latency (DSL) greater than 3.6 ms on at least one side. Variables associated with abnormal contralateral median DSL were analyzed in bivariable and multivariable analysis.

Results

Patients with a nonrecordable median DSL on the worst side were significantly more likely to have electrodiagnostic evidence of contralateral CTS compared to patients with a prolonged DSL on the worst side (90 versus 65 %, respectively; p < 0.001). Bilateral symptoms were reported by 75 % of patients. The best logistic regression model for electrodiagnostic evidence of contralateral CTS included nonrecordable median DSL of the worst side and polyneuropathy (p < 0.001 and p = 0.14, respectively).

Conclusions

The finding that disease severity relates to the probability of contralateral abnormalities is consistent with the concept that CTS is typically bilateral. Patients with CTS on one side should be advised of the likelihood that it can be present or may develop on the other side.     

Undiagnosed and comorbid disorders in patients with presumed chronic fatigue syndrome

Objective

To assess undiagnosed and comorbid disorders in patients referred to a tertiary care center with a presumed diagnosis of chronic fatigue syndrome (CFS).

Methods

Patients referred for chronic unexplained fatigue entered an integrated diagnostic pathway, including internal medicine assessment, psychodiagnostic screening, physiotherapeutic assessment and polysomnography + multiple sleep latency testing. Final diagnosis resulted from a multidisciplinary team discussion. Fukuda criteria were used for the diagnosis of CFS, DSM-IV-TR criteria for psychiatric disorders, ICSD-2 criteria for sleep disorders.

Results

Out of 377 patients referred, 279 (74.0%) were included in the study [84.9% female; mean age 38.8 years (SD 10.3)].A diagnosis of unequivocal CFS was made in 23.3%. In 21.1%, CFS was associated with a sleep disorder and/or psychiatric disorder, not invalidating the diagnosis of CFS. A predominant sleep disorder was found in 9.7%, 19.0% had a psychiatric disorder and 20.8% a combination of both. Only 2.2% was diagnosed with a classical internal disease.In the total sample, a sleep disorder was found in 49.8%, especially obstructive sleep apnea syndrome, followed by psychophysiologic insomnia and periodic limb movement disorder. A psychiatric disorder was diagnosed in 45.2%; mostly mood and anxiety disorder.

Conclusions

A multidisciplinary approach to presumed CFS yields unequivocal CFS in only a minority of patients, and reveals a broad spectrum of exclusionary or comorbid conditions within the domains of sleep medicine and psychiatry. These findings favor a systematic diagnostic approach to CFS, suitable to identify a wide range of diagnostic categories that may be subject to dedicated care.     

Hippocampal negative event‐related potential recorded in humans during a simple sensorimotor task occurs independently of motor execution

A hippocampal‐prominent event‐related potential (ERP) with a peak latency at around 450 ms is consistently observed as a correlate of hippocampal activity during various cognitive tasks. Some intracranial EEG studies demonstrated that the amplitude of this hippocampal potential was greater in response to stimuli requiring an overt motor response, in comparison with stimuli for which no motor response is required. These findings could indicate that hippocampal‐evoked activity is related to movement execution as well as stimulus evaluation and associated memory processes. The aim of the present study was to investigate the temporal relationship between the hippocampal negative potential latency and motor responses. We analyzed ERPs recorded with 22 depth electrodes implanted into the hippocampi of 11 epileptic patients. Subjects were instructed to press a button after the presentation of a tone. All investigated hippocampi generated a prominent negative ERP peaking at ～420 ms. In 16 from 22 cases, we found that the ERP latency did not correlate with the reaction time; in different subjects, this potential could either precede or follow the motor response. Our results indicate that the hippocampal negative ERP occurs independently of motor execution. We suggest that hippocampal‐evoked activity, recorded in a simple sensorimotor task, is related to the evaluation of stimulus meaning within the context of situation. © 2013 Wiley Periodicals, Inc.     

F波各参数对糖尿病周围神经病的诊断敏感性

 目的 探讨F波各参数中对诊断糖尿病周围神经病(diabetic peripheral neuropathy,DPN)的敏感指标。方法 随机选取81例2型糖尿病患者,检测其正中神经、尺神经、胫神经神经的传导速度(nerve conduction velocity,NCV)、F波。根据NCV结果分为NCV正常组和NCV异常组,比较两组同名神经各参数指标,比较NCV异常组各神经的F波与MCV异常率。结果 糖尿病患者各神经F波最长潜伏期总异常率高于最短潜伏期、平均潜伏期、F波出现率、F波最大传导速度的总异常率,差异有统计学意义(P<0.05)。与NCV正常组比较,NCV异常组正中神经F波的最短潜伏期、最长潜伏期、平均潜伏期、最大速度差异有统计学意义(P<0.05),两组其他同名神经参数比较均无统计学差异。NCV异常组胫神经、正中神经、尺神经F波异常率明显高于同一神经的运动神经传导速度(motor nerve conduction velocity,MCV)异常率,差异有统计学意义(P<0.05)。结论 F波最长潜伏期对DPN的诊断较敏感,NCV联合F波可以提高DPN的检出率。     

超声测量羊水指数和宫颈管长度预测未足月胎膜早破患者分娩潜伏期的价值

目的:探讨超声测量羊水指数(AFI)和宫颈管长度(CL)预测未足月胎膜早破(PPROM)患者分娩潜伏期的价值。方法:选择2009年10月至2014年10月我院收治的198例PPROM患者,入院后6h内超声检查测量AFI和CL。根据分娩潜伏期分为7日内分娩组和7日后分娩组,比较两组的病史、临床特点及超声指标,评估CL及AFI预测PPROM患者7日内分娩的特异性及敏感性。结果:(1)7日内分娩组患者破膜时伴阴道流血率、破膜时伴有宫缩率和新生儿转NICU率均高于7日后分娩组,差异有统计学意义(P0.05);(2)7日内分娩组患者的AFI、CL和分娩潜伏期均小于7日后分娩组患者,差异有统计学意义(P0.05);(3)CL≤2cm联合AFI≤5cm预测PPROM患者7日内分娩具有较高的敏感性及特异性(灵敏度82%,特异度51%);(4)以破膜后7日内是否分娩为应变量,经二分类logistic回归分析显示,破膜时伴阴道流血、破膜时伴有宫缩、CL≤2cm、AFI≤5cm是PPROM后7日内分娩的有效自变量(P0.05)。结论:超声测量AFI和CL对预测PPROM患者7日内是否分娩有一定价值,TVCL≤2cm联合AFI≤5cm能提高预测PPROM患者7日内分娩的敏感性及特异性。     

HIV-1 integrates into resting CD4+ T cells even at low inoculums as demonstrated with an improved assay for HIV-1 integration

Human Immunodeficiency Virus Type 1 (HIV-1) establishes a latent reservoir early in infection that is resistant to the host immune response and treatment with highly active antiretroviral therapy (HAART). The best understood of these reservoirs forms in resting CD4(+) T cells. While it remains unclear how reservoirs form, a popular model holds that the virus can only integrate in activated CD4(+) T cells. Contrary to this model, our previous results suggest that HIV-1 can integrate directly into the genomes of resting CD4(+) T cells. However, a limitation of our previous studies was that they were conducted at high viral inoculum and these conditions may lead to cellular activation or saturation of restriction factors. In the present study, we tested if our previous findings were an artifact of high inoculum. To do this, we enhanced the sensitivity of our integration assay by incorporating a repetitive sampling technique that allowed us to capture rare integration events that occur near an Alu repeat. The new technique represents a significant advance as it enabled us to measure integration accurately down to 1 provirus/well in 15,000 genomes--a 40-fold enhancement over our prior assay. Using this assay, we demonstrate that HIV can integrate into resting CD4(+) T cells in vitro even at low viral inoculum. These findings suggest there is no threshold number of virions required for HIV to integrate into resting CD4(+) T cells.