The long-term effectiveness of generic adult fixed-dose combination antiretroviral therapy for HIV-infected Ugandan children

Background

Access to pediatric antiretroviral formulations is increasing in resource-limited countries, however adult FDCs are still commonly used by antiretroviral therapy (ART) programs.

Objective

To describe long-term effectiveness of using adult FDC of d4T+3TC+NVP (Triomune) in children for HIV treatment.

Methods

Clinical, immunologic, and virologic outcomes of HIV-infected ART-naïve children aged six months to 12 years, were evaluated up to 96 weeks post-ART initiation.

Results

From March 2004 to June 2006, 104 children were followed with a median age of 5.4 years, median CD4 cell percent and HIV-1 RNA were 11.0% (IQR 6.7–13.9) and 348,846copies/mL (IQR 160,941–681,313) respectively at baseline. Using Kaplan-Meir estimates, 75% of children had undetectable viral loads (<400copies/mL) at 96weeks of ART. Children with a baseline CD4 cell percent >15% were 3 times more likely to achieve viral load <400copies/mL than those with baseline CD4 cell percent <5% after adjusting for baseline age {aHR = 3.03 (1.10–8.32), p=0.03}; no difference was found among those with CD4 cell percent >5–14.9% and <5%.

Conclusion

Treatment with generic adult FDC for HIV-infected Ugandan children led to sustained clinical, immunologic and virologic response during 96 weeks of ART. Early initiation of ART is key to achieving virological success.     

The Next Wave: Confexting

Radiology conferences enable participants the opportunity to ask experts questions through question and answer (Q and A) sessions or individually. Given the time limitations and intimidating circumstances, we incorporated conference text messaging (confexting) as a method of increasing interactivity between the audience and speakers. During a 5-day radiology conference, text messaging was utilized for anonymous interactivity between the audience and speakers during Q and A sessions. There were 324 text messages; 76 of these were either follow-up statements or questions related to earlier text messages. Forty-two questions were submitted via paper notes. There was a general trend of an increasing number of text messages and a decreasing number of paper notes. The anonymous text messaging system was found to be an effective method for interactivity between the audience and the speakers. The questions and answers could be presented in a PowerPoint format at the formal Q and A sessions. Questions texted to the authors during their talks could be immediately answered or addressed in subsequent talks. Although difficult for some individuals to embrace technology, confexting allows for interactivity and prompts discussion. Confexting is an effective method for interactivity between the audience and speakers not previously utilized in a conference setting. The anonymity and asynchronous communication enable conference participants to submit more questions than in the traditional setting. The speakers may be able to explain more thoroughly difficult concepts more thoroughly with additional slides at Q and A sessions or may immediately answer texted questions during their talks.     

In vivo demonstration that alpha-synuclein oligomers are toxic

The aggregation of proteins into oligomers and amyloid fibrils is characteristic of several neurodegenerative diseases, including Parkinson disease (PD). In PD, the process of aggregation of α-synuclein (α-syn) from monomers, via oligomeric intermediates, into amyloid fibrils is considered the disease-causative toxic mechanism. We developed α-syn mutants that promote oligomer or fibril formation and tested the toxicity of these mutants by using a rat lentivirus system to investigate loss of dopaminergic neurons in the substantia nigra. The most severe dopaminergic loss in the substantia nigra is observed in animals with the α-syn variants that form oligomers (i.e., E57K and E35K), whereas the α-syn variants that form fibrils very quickly are less toxic. We show that α-syn oligomers are toxic in vivo and that α-syn oligomers might interact with and potentially disrupt membranes.     

Wide turn diversity in protein transmembrane helices implications for G-protein-coupled receptor and other polytopic membrane protein structure and function

Previously, we showed that perturbations of protein transmembrane helices are manifested as one of three types of noncanonical structures (wide turns, tight turns, and kinks), which, compared with alpha-helices, are evident by distinctive Calpha(i)-->Calpha(x) distances. In this study, we report the analysis of more than 3000 transmembrane helices in 244 crystal structures from which we identified 70 wide turns (29 proline- and 41 nonproline-induced). Based on differences in the Calpha(i)-->Calpha(i)(-4) and Calpha(i)-->Calpha(i)(-5) profiles, we show that wide turns can be subclassified into three distinct subclasses (W(1), W(2), and W(3)) that differ with regard to the number and position of backbone i --> i-5 H-bonds formed N-terminal to the perturbing or signature proline or nonproline residue. Although wide turns generally produce changes in helical direction of 20 degrees to 30 degrees and a lateral shift in the helical axis, some of the W(3) subclass are associated with changes of <5 degrees . We also show that the distinct architectural features of wide turns allow the carbonyl bond of the i-4th residue, which is located on the widened loop of a wide turn, to be directed away from the helical axis. This provides regions of flexibility within helical regions allowing, for example, unique opportunities for interhelical H-bonding, including interactions with glycine zipper motifs, and for ion and cofactor binding. Furthermore, differences in wide-turn subtype usage by related protein family members, such as the G-protein-coupled receptors rhodopsin and the beta2-adrenergic receptor, can significantly affect the orientation and position of residues critical for ligand binding and receptor activation.     

The role of palliative care in advanced muscular dystrophy and spinal muscular atrophy

OBJECTIVE: This study examines the potential role for palliative care services in the care of individuals with muscular dystrophy and spinal muscular atrophy, and the support of their families. METHODOLOGY: Semistructured interviews were conducted in South Australia with nine bereaved and four current family members of individuals with muscular dystrophy or spinal muscular atrophy. Issues explored during interview included: (i) the family perceptions of the difficulties in caring; (ii) the psychological and physical resources which were available to assist them; and (iii) family recall of the management of the terminal phase of the illness. RESULTS: Significant issues identified included: (i) a lack of coordination of care and access to skilled, competent carers; (ii) a lack of support for siblings; (iii) inadequate bereavement care; and (iv) limited discussion of options of ventilatory support and advance directives. CONCLUSIONS: The terminal care for individuals with muscular dystrophy and spinal muscular atrophy and their families requires improvement. Although many individuals with these conditions will die following an acute event, palliative care services may be appropriate for those who require a period of terminal care at home.     

炎宁冲剂的抗炎与解热作用研究

目的：研究炎宁冲剂的抗炎与解热作用。方法：采用角叉菜胶致大鼠足跖炎性肿胀。二甲苯致小鼠耳毛细血管通透性增高,以及大鼠皮下羧甲基纤维素囊中白细胞出游等急性炎症模型研究炎宁冲剂的抗炎作用。采用啤酒酵母液引起家兔发热的方法研究炎宁冲剂的解热作用。结果：炎宁冲剂对以上实验动物均具有明显的抗炎和解热作用。结论：炎宁冲剂对急性炎症具有明显的抗炎作用。对啤酒酵母液引起家兔发热具有明显解热作用。     

Homeopathy: A State of the Science Review With Recommendations for Practical Therapies in Midwifery Practice

A substantial proportion of adults and children in the United States use complementary and alternative health practices, including homeopathy. Many homeopathic therapies are readily available over the counter, and many individuals access and self-administer these therapies with little or no guidance from health care practitioners. In addition, patients and health care providers are often confused by terminologies associated with complementary practices and may be unable to distinguish homeopathy from naturopathy, herbalism, holistic medicine, Ayurveda, traditional Chinese medicine, or other forms of health care. Compared with European and Asian countries, education in the United States about complementary and alternative health practices is not typically found within traditional nursing, midwifery, or medical education curricula. Given this lack of education and the broad acceptance and popularity of homeopathy, it is necessary for health care practitioners to improve their knowledge regarding similarities and differences among therapies so they can fully inform and make appropriate recommendations to patients. The intent of this article is therefore to examine the state of existing science of homeopathy, distinguish it from other complementary methods, and provide midwives and women's health care providers with an introduction to common homeopathic therapies that may be recommended and safely used by persons seeking midwifery care. This review also presents the evidence base, pharmacology, manufacturing, and regulation of homeopathic therapies. We also consider controversies and misunderstandings regarding safety and efficacy of homeopathic remedies relevant to women and birthing persons. Examples of practical applications of homeopathic therapies for use in midwifery practice are introduced. Implications for practice and sample guidelines are included.     

Pushing attention to one side: Force field adaptation alters neural correlates of orienting and disengagement of spatial attention

Sensorimotor adaptation to wedge prisms can alter the balance of attention between left and right space in healthy adults, and improve symptoms of spatial neglect after stroke. Here we asked whether the orienting of spatial attention to visual stimuli is affected by a different form of sensorimotor adaptation that involves physical perturbations of arm movement, rather than distortion of visual feedback. Healthy participants performed a cued discrimination task before and after they made reaching movements to a central target. A velocity‐dependent force field pushed the hand aside during each reach, and required participants to apply compensatory forces toward the opposite side. We used event‐related potentials (ERPs) to determine whether electroencephalography (EEG) responses reflecting orienting (cue‐locked N1) and disengagement (target‐locked P1) of spatial attention are affected by adaptation to force fields. After adaptation, the cue‐locked N1 was relatively larger for stimuli presented in the hemispace corresponding to the direction of compensatory hand force. P1 amplitudes evoked by invalidly cued targets presented on the opposite side were reduced. This suggests that force field adaptation boosted attentional orienting responses toward the side of hand forces, and impeded attentional disengagement from that side, mimicking previously reported effects of prism adaptation. Thus, remapping between motor commands and intended movement direction is sufficient to bias ERPs, reflecting changes in the orienting of spatial attention in the absence of visuo‐spatial distortion or visuo‐proprioceptive mismatch. Findings are relevant to theories of how sensorimotor adaptation can modulate attention, and may open new avenues for treatment of spatial neglect.