HIV Neuropathogenesis in the Presence of a Disrupted Dopamine System

Antiretroviral therapy (ART) has transformed HIV into a chronic condition, lengthening and improving the lives of individuals living with this virus. Despite successful suppression of HIV replication, people living with HIV (PLWH) are susceptible to a growing number of comorbidities, including neuroHIV that results from infection of the central nervous system (CNS). Alterations in the dopaminergic system have long been associated with HIV infection of the CNS. Studies indicate that changes in dopamine concentrations not only alter neurotransmission, but also significantly impact the function of immune cells, contributing to neuroinflammation and neuronal dysfunction. Monocytes/macrophages, which are a major target for HIV in the CNS, are responsive to dopamine. Therefore, defining more precisely the mechanisms by which dopamine acts on these cells, and the changes in cellular function elicited by this neurotransmitter are necessary to develop therapeutic strategies to treat neuroHIV. This is especially important for vulnerable populations of PLWH with chemically altered dopamine concentrations, such as individuals with substance use disorder (SUD), or aging individuals using dopamine-altering medications. The specific neuropathologic and neurocognitive consequences of increased CNS dopamine remain unclear. This is due to the complex nature of HIV neuropathogenesis, and logistical and technical challenges that contribute to inconsistencies among cohort studies, animal models and in vitro studies, as well as lack of demographic data and access to human CNS samples and cells. This review summarizes current understanding of the impact of dopamine on HIV neuropathogenesis, and proposes new experimental approaches to examine the role of dopamine in CNS HIV infection.

HIV Neuropathogenesis in the Presence of a Disrupted Dopamine System. Both substance abuse disorders and the use of dopaminergic medications for age-related diseases are associated with changes in CNS dopamine concentrations and dopaminergic neurotransmission. These changes can lead to aberrant immune function, particularly in myeloid cells, which contributes to the neuroinflammation, neuropathology and dysfunctional neurotransmission observed in dopamine-rich regions in HIV+ individuals. These changes, which are seen despite the use antiretroviral therapy (ART), in turn lead to further dysregulation of the dopamine system. Thus, in individuals with elevated dopamine, the bi-directional interaction between aberrant dopaminergic neurotransmission and HIV infection creates a feedback loop contributing to HIV associated neurocognitive dysfunction and neuroHIV. However, the distinct contributions and interactions made by HIV infection, inflammatory mediators, ART, drugs of abuse, and age-related therapeutics are poorly understood. Defining more precisely the mechanisms by which these factors influence the development of neurological disease is critical to addressing the continued presence of neuroHIV in vulnerable populations, such as HIV-infected older adults or drug abusers. Due to the complexity of this system, understanding these effects will require a combination of novel experimental modalities in the context of ART. These will include more rigorous epidemiological studies, relevant animal models, and in vitro cellular and molecular mechanistic analysis.

     

鼻塞式同步间歇正压通气(NIPPV)联合布地奈德雾化治疗新生儿急性呼吸窘迫综合征疾病的临床应用研究

目的:分析鼻塞式同步间歇正压通气(NIPPV)联合布地奈德雾化治疗ARDS(新生儿急性呼吸窘迫综合征)疾病的临床应用效果。方法:纳入病例是2017年5月—2019年11月收治的104例ARDS新生儿,随机平均分为两组。参照组52例采纳CPAP(持续气道正压通气通气)治疗,实验组52例采纳NIPPV+布地奈德雾化治疗,对比两组呼吸机通气时间、用氧时间、住院时间、血气指标以及并发症发生情况。结果:实验组呼吸机通气时间、用氧时间、住院时间均明显短于参照组,差异有统计学意义P<0.05;实验组治疗3 d后PaCO2明显低于参照组,实验组治疗3 d后PH以及PaO2明显高于参照组,差异有统计学意义P<0.05;实验组并发症发生率(3.85%,2/52)明显低于参照组(21.15%,11/52),差异有统计学意义P<0.05。结论:NIPPV+布地奈德雾化可有效缩短ARDS患者机械通气时间,改善血气指标,降低并发症发生率,值得借鉴。     

Low bone mineral density in ambulatory persons with cerebral palsy? A systematic review

Purpose: Non-ambulatory persons with cerebral palsy are prone to low bone mineral density. In ambulatory persons with cerebral palsy, bone mineral density deficits are expected to be small or absent, but a consensus conclusion is lacking. In this systematic review bone mineral density in ambulatory persons with cerebral palsy (Gross Motor Function Classification Scales I–III) was studied.

Materials and methods: Medline, Embase, and Web of Science were searched. According to international guidelines, low bone mineral density was defined as Z-score?≤??2.0. In addition, we focused on Z-score?≤??1.0 because this may indicate a tendency towards low bone mineral density.

Results: We included 16 studies, comprising 465 patients aged 1–65?years. Moderate and conflicting evidence for low bone mineral density (Z-score?≤??2.0) was found for several body parts (total proximal femur, total body, distal femur, lumbar spine) in children with Gross Motor Function Classification Scales II and III. We found no evidence for low bone mineral density in children with Gross Motor Function Classification Scale I or adults, although there was a tendency towards low bone mineral density (Z-score?≤??1.0) for several body parts.

Conclusions: Although more high-quality research is needed, results indicate that deficits in bone mineral density are not restricted to non-ambulatory people with cerebral palsy.

• Implications for Rehabilitation

• Although more high-quality research is needed, including adults and fracture risk assessment, the current study indicates that deficits in bone mineral density are not restricted to non-ambulatory people with CP.

• Health care professionals should be aware that optimal nutrition, supplements on indication, and an active lifestyle, preferably with weight-bearing activities, are important in ambulatory people with CP, also from a bone quality point-of-view.

• If indicated, medication and fall prevention training should be prescribed.