Disparities in Reported Reasons for Not Initiating or Stopping Antiretroviral Treatment Among a Diverse Sample of Persons Living with HIV

BACKGROUND  Disparities in the use of antiretroviral therapy (ART) for HIV disease have been documented across race, gender, and substance use groups. OBJECTIVE  The current analysis compares self-reported reasons for never taking or stopping ART among a diverse sample of men and women living with HIV. DESIGN  Cross-sectional interview. PARTICIPANTS  HIV + (N = 3,818) adults, 968 of whom reported discontinuing or never using ART. MEASUREMANTS  Computerized self-administered and interviewer-administered self-reported demographic and treatment variables, including gender, race, ethnicity, CD4 count, detectable viral load, and reported reasons for not taking antiretroviral therapy. RESULTS  Despite equivalent use of ART in the current sample, African-American respondents were 1.7 times more likely to report wanting to hide their HIV status and 1.7 times more likely to report a change in doctors/clinics as reasons for stopping ART (p = .049, and p = .042) and had odds 4.5 times those of non-African Americans of reporting waiting for viral marker counts to worsen (p = < .0001). There was a lower tendency (OR = 0.4) for women to endorse concerns of keeping their HIV status hidden as a reason for stopping ART compared to men (p = .003). Although those with an IDU history were less likely to be on ART, no differences in reasons for stopping or never initiating ART were found between those with and without an IDU history. CONCLUSIONS  A desire to conceal HIV status as well as a change in doctors/clinics as reasons for discontinuing ART were considerably more common among African Americans, suggesting that perceived HIV/AIDS stigma is an obstacle to maintenance of treatment. Findings also indicate differences in reasons for stopping ART by gender and a perceived desire to wait for counts to worsen as a reason for not taking ART by African Americans, regardless of detectable viral load, CD4 count, age, education, employment, sexual orientation, and site.     

The mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibitor PD184352 (CI-1040) selectively induces apoptosis in malignant schwannoma cell lines

Type 1 neurofibromatosis (NF1) is a common autosomal dominant disorder that results in neuroectodermal tumors. The NF1 tumor-suppressor gene encodes neurofibromin, which includes a GTPase-activating domain for Ras inactivation. Affinity purification showed N-Ras to be the predominant activated isoform of Ras in two independent neurofibrosarcoma cell lines from NF1 patients (lines ST88-14 and NF90-8). These NF1 cells also demonstrated increased constitutive activity of the extracellular signal-regulated kinases 1 and 2 (ERK1,2) mitogen-activated protein (MAP) kinases compared with a sporadic malignant schwannoma cell line that maintains neurofibromin expression (STS-26T). Thus, MAP kinase kinase (MEK) inhibitors may be a rational approach to NF1 therapy. The MEK inhibitors PD98059 [2'-amino-3'-methoxyflavone], PD184352 (also called CI-1040) [2-(2-chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzamide], and U0126 [1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene] all produced concentration-dependent suppression of the proliferation of the three cell lines. Individual MEK inhibitors had similar effects in all three cell lines. However, only the antiproliferative effects of PD184352 correlated closely with the elimination of ERK1,2 MAP kinase activities. PD98059 was primarily cytostatic, whereas U0126 and PD184352 were cytotoxic. Only PD184352 induced apoptosis in all three lines, as indicated by morphology, activation of DEVDase, procaspase-3 cleavage, and the appearance of populations having sub-G(0)/G(1) DNA contents. The differential effects of the MEK inhibitors on cell survival were not dependent on p53 status or effects on the ERK5 pathway. PD184352 was also proapoptotic to primary rat Schwann cells. Hence, although PD184352 effectively killed neurofibrosarcoma cells, its effects on normal Schwann cells may limit its usefulness in the clinic.     

Bathhouse-based voluntary counseling and testing is feasible and shows preliminary evidence of effectiveness

The goal of this study was to provide evidence for the feasibility and effectiveness of conducting voluntary counseling and testing (VCT) for HIV in a bathhouse setting. Four hundred ninety-two men participated in bathhouse-based VCT offered at a single venue over a 13-month period. A convenience sample of 133 of these testers was assessed at 2 points: immediately before and 3 months after testing. Thirty-eight percent of men in the sample reported unprotected anal intercourse (UAI) with 1 of their 2 most recent partners in the 3 months before testing, and 48% of those men had not otherwise been tested for HIV in the previous 12 months. Results showed that in the months after VCT, men were less likely to engage in UAI, decreased their frequency of engaging in sex while drunk or high, and were more likely to communicate about HIV with their sexual partners. Bathhouse-based VCT seems to be a feasible approach for reaching significant numbers of men at risk for HIV and shows preliminary evidence of effectiveness in changing some specific HIV-related risk and precautionary behaviors.     

4α-phorbol 12,13-didecanoate activates cultured mouse dorsal root ganglia neurons independently of TRPV4

Background and Purpose

The Ca²⁺-permeable cation channel TRPV4 is activated by mechanical disturbance of the cell membrane and is implicated in mechanical hyperalgesia. Nerve growth factor (NGF) is increased during inflammation and causes mechanical hyperalgesia. 4α-phorbol 12,13-didecanoate (4αPDD) has been described as a selective TRPV4 agonist. We investigated NGF-induced hyperalgesia in TRPV4 wild-type (+/+) and knockout (–/–) mice, and the increases in [Ca²⁺]_i produced by 4αPDD in cultured mouse dorsal root ganglia neurons following exposure to NGF.

Experimental Approach

Withdrawal thresholds to heat, von Frey hairs and pressure were measured in mice before and after systemic administration of NGF. Changes in intracellular Ca²⁺ concentration were measured by ratiometric imaging with Fura-2 in cultured DRG and trigeminal ganglia (TG) neurons during perfusion of TRPV4 agonists.

Key Results

Administration of NGF caused a significant sensitization to heat and von Frey stimuli in TRPV4 +/+ and –/– mice, but only TRPV4 +/+ mice showed sensitization to noxious pressure. 4αPDD stimulated a dose-dependent increase in [Ca²⁺]_i in neurons from +/+ and –/– mice, with the proportion of responding neurons and magnitude of increase unaffected by the genotype. In contrast, the selective TRPV4 agonist GSK1016790A failed to stimulate an increase in intracellular Ca²⁺ in cultured neurons. Responses to 4αPDD were unaffected by pretreatment with NGF.

Conclusions and Implications

TRPV4 contributes to mechanosensation in vivo, but there is little evidence for functional TRPV4 in cultured DRG and TG neurons. We conclude that 4αPDD activates these neurons independently of TRPV4, so it is not appropriate to refer to 4αPDD as a selective TRPV4 agonist.     

希—内学习能力测验在中国聋儿中使用的信度和效度

采用经部分修改的希－内学习能力测验（Ｈ－ＮＴＬＡ）量表对全国２１个省、市、自治区１７５８名３－１７岁聋儿逐人测试。样本人群地区分布、家长职业构成与１９９０年全国人口普查资料一致。１７５８名聋儿智商呈现正态分布（ｇ１＝０．０１１Ｐ＞０．０５，ｇ２＝０．０５８Ｐ＞０．０５）。测试员间信度系数０．９８１（Ｎ＝２４），复测信度０．８４１（Ｎ＝１３６），分半信度０．９２７（３－８岁）及０．８５４（９－１７岁）。各分测验得分随年龄增加而增加，小年龄组增加明显，大年龄组增加缓慢。各分测验之间、各分测验和总离差智商之间大多数相关系数有显著统计学意义。智商与学习成绩（语文及数学）相关系数０．２０８（Ｐ＜０．０１Ｎ＝２２４），与教师评语等级相关系数０．４４（Ｐ＜０．０５ｄｆ＝１６），表明经修订的Ｈ－ＮＴＬＡ量表适用于中国听力语言障碍人群进行智力评定。