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Objectives. We examined sexually transmitted infection (STI), HIV, and hepatitis virus prevalence and risk behaviors among truck drivers. Methods. We asked participants about their risk behaviors, and we screened them for STIs, HIV, and hepatitis infections. We used logistic regression to identify factors associated with outcomes. Results. Of the 652 enrolled participants, 21% reported sex with sex workers or casual partners in the prior year. Driving solo (odds ratio [OR]=15.04; 95% confidence interval [CI]=1.92, 117.53; P=.01), history of injection drug use (IDU; OR=2.69; 95% CI=1.19, 6.12; P=.02), and history of an STI (OR=2.47; 95% CI=1.19, 5.09; P=.01) were independently associated with high-risk sexual behaviors. Fourteen percent of participants reported drug use in the previous year, and 11% reported having ever injected drugs. Participants tested positive as follows: 54 for HCV antibodies (8.5%), 66 for hepatitis B anticore (anti-HBc) antibodies (10.4%), 8 for chlamydia (1.3%), 1 for gonorrhea (0.2%), 1 for syphilis (0.2%), and 1 for HIV (0.2%). History of injecting drugs (OR=26.91; 95% CI=11.61, 62.39; P<.01) and history of anti-HBc antibodies (OR=7.89; 95% CI=3.16, 19.68; P<.01) were associated with HCV infection. Conclusions. Our results suggest a need for hepatitis C screening and STI risk-reduction interventions in this population. [ABSTRACT FROM AUTHOR]

While African Americans in the United States are disproportionately affected by HIV, they are less likely to take antiretroviral therapies. Different first-line antiretroviral therapies are associated with short-term and long-term adverse event (AE) risks. We estimated the willingness of antiretroviral-naïve, HIV-positive African Americans to accept risks of acute AEs with known outcomes and long-term AEs with uncertain outcomes in exchange for virologic suppression. We estimated the relative importance of short-term and long-term AE risks. Two hundred thirty-five subjects were recruited through eight clinics in the United States. One hundred fifty-eight subjects met study inclusion criteria. One hundred fifty-three subjects completed a series of choice-format conjoint trade-off tasks. In each task, subjects were asked to choose between two hypothetical treatments with varying levels of virologic failure, risks of hypersensitivity reaction, decreases in bone mineral density (BMD), and renal impairment, and outcome uncertainty associated with the risks of decreased BMD and renal impairment. Attributes were expressed as probabilities of occurrence. We calculated the relative importance of each AE and the level of risk subjects would accept to reduce the risk of virologic failure. Subjects indicated that short-term AEs with relatively certain outcomes are preferred to long-term AEs with uncertain outcomes. Subjects were strongly averse to the risk of decreased BMD that could not be treated successfully or when the outcome was uncertain and to the risk of renal impairment that could not be treated successfully. Subjects were willing to accept increased risks of AEs in exchange for lower risk of virologic failure. [ABSTRACT FROM AUTHOR]

Reports on the observation of stavudine in clinical trials and cohort studies to be more often complicated in cases of hyperlactatemia than other nucleoside reverse transcriptase inhibitors, possibly because of its relatively greater propensity to induce mitochondrial toxicity. Assessment of changes in serum lactate levels and signs/symptoms of hyperlactatemia after substitution of abacavir or zidovudine in virologically suppressed HIV-infected patients; Results of symptoms of hyperlactatemia in the group elevated lactate at baseline.

Attracting more minorities to the health, physical education, recreation and dance (HPERD) profession is a call for urgent concern. In education, there is a critical shortage of minorities at all teaching levels. In the HPERD fields, there is an even greater need for the recruitment of minority professionals. For example, the number of black American students enrolled in the U.S. schools has continued to increase, while the number of black educators has declined significantly. One effective strategy to increase minority professionals involves finding areas where potential educators and professionals frequently convene. This could mean attending social club functions, such as fraternity and sorority meetings, church gatherings and other settings.

Anodic aluminum oxide (AAO) membranes were used as templates to control orientation of an ion-channel forming columnar mesophase obtained by self assembly of a wedge-shaped sulfonate molecule. Inside the AAO structure, the director vector of the mesophase is oriented parallel to the pore axis due to the confinement effect. The molecular arrangement induced by the spatial confinement within the pores is extended over several microns into the remnant film on the AAO surface. The homeotropic alignment of the channels promotes unidimensional ion conduction through the film plane, which is manifested by a considerable increase in conductivity relative to isotropic samples.

This paper presents an approach to integrate tire wear buildup and rainfall-runoff models to simulate tire wear buildup on road surfaces and its subsequent transport in stormwater runoff events. To do so, a buildup model is presented based on vehicle kilometers traveled, vehicle type, vehicle speed, and road roughness within a watershed. This buildup model was integrated into an EPA SWMM model that simulated the runoff of tire wear particles in twelve watersheds in the San Francisco, CA bay area. Results demonstrate that tire wear particle buildup within the watersheds ranged between 0.4 and 0.51 (kg/km 2 ) per hour. Applied to the SWMM model, total event mean tire wear concentrations ranged between 0.5 and 67 μg/L. These concentrations were linearly correlated to depth-integrated samples collected at the outlet of each of the watersheds (R 2  = 0.66). The proposed modeling approach can ultimately be applied to create solutions to an emerging stormwater contaminant., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The number of individuals with upper or lower extremities dysfunction (ULED) has considerably increased in the past few decades, resulting in a high economic burden for their families and society. Individuals with ULEDs require assistive robots to fulfill all their activities of daily living (ADLs). However, a theory for the optimal design of assistive robots that reduces energy consumption while increasing the workspace is unavailable. Thus, this research presents an algorithm for the optimal link length selection of an assistive robot mounted on a wheelchair to minimize the torque demands of each joint while increasing the workspace coverage. For this purpose, this research developed a workspace to satisfy a list of 18 ADLs. Then, three torque indices from the literature were considered as performance measures to minimize; the three torque measures are the quadratic average torque (QAT), the weighted root square mean (WRMS), and the absolute sum of torques (AST). The proposed algorithm evaluates any of the three torque measures within the workspace, given the robot dimensions. This proposed algorithm acts as an objective function, which is optimized using a genetic algorithm for each torque measure. The results show that all tree torque measures are suitable criteria for assistance robot optimization. However, each torque measures yield different optimal results; in the case of the QAT optimization, it produces the least workspace with the minimum overall torques of all the joints. Contrarily, the WRMS and AST optimization yield similar results generating the maximum workspace coverage but with a greater overall torque of all joints. Thus, the selection between the three methods depends on the designer's criteria. Based on the results, the presented methodology is a reliable tool for the optimal dimensioning of assistive robots.

Hepatitis C virus-induced liver damage, chronic liver damage due to alcohol, and non-alcoholic liver disease-induced cellular alterations promote fibrosis, cirrhosis, and/or hepatocellular carcinoma. The recommended therapeutic option for advanced liver damage is liver transplantation. Extracellular matrix scaffolds have been evaluated as an alternative for tissue restoration. Studies on the biocompatibility and rejection of synthetic and natural scaffolds as an alternative to organ transplantation have been evaluated. Our group has recently described the xenoimplant of collagen matrix scaffold (CMS) in a rat model. However, no complete macroscopic and histological description of the liver parenchyma at the initial (day 3), intermediate (day 14), and advanced (day 21) stages has been obtained. In this study, we described and compared liver tissue from the CMS zone (CZ, CMS, and liver parenchyma), liver tissue from the normal zone (liver parenchyma close to the CMS), and basal tissue (resected tissue from the CMS implantation site). Our data strongly suggest that the collagen matrix xenoimplant is a good niche for hepatocytes, with no rejection, and does not affect liver function tests. The liver can regenerate after damage, but this capacity is inhibited in a chronic injury. At present, the use of CMS after liver damage has not been reported. This biomaterial could be a novel alternative in the field of regenerative medicine for liver diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Martinez-Castillo, León-Mancilla, Ramírez-Rico, Alfaro, Pérez-Torres, Díaz-Infante, García-Loya, Medina-Avila, Sanchez-Hernandez, Piña-Barba and Gutierrez-Reyes.)

Background: A male predominance in Brugada syndrome (BrS) has been widely reported, but scarce information on female patients with BrS is available., Objective: The purpose of this study was to investigate the clinical characteristics and long-term prognosis of women with BrS., Methods: A multicenter retrospective study of patients diagnosed with BrS and previous electrophysiological study (EPS) was performed., Results: Among 770 patients, 177 (23%) were female. At presentation, 150 (84.7%) were asymptomatic. Females presented less frequently with a type 1 electrocardiographic pattern (30.5% vs 55.0%; P <.001), had a higher rate of family history of sudden cardiac death (49.7% vs 29.8%; P <.001), and had less sustained ventricular arrhythmias (VAs) on EPS (8.5% vs 15.1%; P = .009). Genetic testing was performed in 79 females (45% of the sample) and was positive in 34 (19%). An implantable cardioverter-defibrillator was inserted in 48 females (27.1%). During mean (± SD) follow-up of 122.17 ± 57.28 months, 5 females (2.8%) experienced a cardiovascular event compared to 42 males (7.1%; P = .04). On multivariable analysis, a positive genetic test (18.71; 95% confidence interval [CI] 1.82-192.53; P = .01) and atrial fibrillation (odds ratio 21.12; 95% CI 1.27-350.85; P = .03) were predictive of arrhythmic events, whereas VAs on EPS (neither with 1 or 2 extrastimuli nor 3 extrastimuli) were not., Conclusion: Women with BrS represent a minor fraction among patients with BrS, and although their rate of events is low, they do not constitute a risk-free group. Neither clinical risk factors nor EPS predicts future arrhythmic events. Only atrial fibrillation and positive genetic test were identified as risk factors for future arrhythmic events., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The development of new active biocompatible materials and devices is a current need for their implementation in multiple fields, including the fabrication of implantable devices for biomedical applications and sustainable devices for bio-optics and bio-optoelectronics. This paper describes a simple strategy to use designed proteins to develop protein-based functional materials. Using simple proteins as self-assembling building blocks as a platform for the fabrication of new optically active materials takes previous work one step further towards the design of materials with defined structures and functions using naturally occurring protein materials, such as silk. The proposed fabrication strategy generates thin and flexible nanopatterned protein films by letting the engineered protein elements self-assemble over the surface of an elastomeric stamp with nanoscale features. These nanopatterned protein films are easily transferred onto 3D objects (flat and curved) by moisture-induced adhesion. Additionally, flexible nanopatterned protein films are prepared by incorporating a thin polymeric layer as a back support. Finally, taking advantage of the tunability of the selected protein scaffold, the flexible protein-based surfaces are endowed with optical functions, achieving efficient lasing features. As such, this work enables the simple and cost-effective production of flexible and nanostructured, protein-based, optically active biomaterials and devices over large areas toward emerging applications., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Collection of blood samples from veterinary and wildlife patients is often challenging because the samples have to be collected on farm or in the wild under various environmental conditions. This poses many technical problems associated with venipuncture materials, their safe use and disposal, transportation and processing of collected samples. Dried blood spot (DBS) sample collection techniques offer a simple and practical alternative to traditional blood collection methods to obtain blood samples from animals for parasite antibody evaluation. The DBS collection devices are compact, simple to use, and are particularly useful for large number of samples. Additionally, DBS samples take up less space and they are easier to transport than traditional venipuncture-collected blood samples. Visceral leishmaniasis (VL) is a potentially fatal parasitic disease of dogs and humans and it is frequently diagnosed by antibody tests. Immunochromatographic tests (ICT) for antibodies to Leishmania infantum are commercially available for dogs and they produce qualitative results in minutes. Measurement of canine antibodies to L. infantum with the ICT using traditional venipuncture has been validated previously, but the use of DBS samples has not been evaluated using this method. The purpose of the present study was to determine the ability of DBS samples to detect antibodies to L. infantum in dogs using a commercial ICT assay. One hundred plasma samples from dogs experimentally infected with the LIVT-1 strain of L. infantum were collected by venipuncture and frozen. Individual samples were thawed, and then 80 μl plasma (2 drops) was aliquotted onto the 8-spoked disk pad on individual DBS sample collection devices (HemaSpot™, Spot-On Sciences, Austin, TX), dried, and stored in the dark at room temperature. After one month and six months, respectively, 2 spokes of the 8 spokes of the disk pad of each DBS sample were removed and eluted in 200 μl PBS. The eluate was used to test for antibodies in the ICT and compared to ICT results using thawed plasma (same initial source). Sensitivity and specificity of the ICT using DBS were determined by using ICT results from traditional blood collection samples for comparison. After 1 month, DBS samples showed 100% sensitivity and specificity when compared to ICT results on thawed plasma samples collected by traditional venipuncture. After six months storage at room temperature, DBS samples demonstrated 79% sensitivity and 100% specificity compared to traditional blood collection. Results from this study indicate that dried blood spot collection may be a useful tool for screening dogs for antibodies to L. infantum with the ICT assay., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A microelectromechanical-systems-based calorimeter designed for use on a synchrotron nano-focused X-ray beamline is described. This instrument allows quantitative DC and AC calorimetric measurements over a broad range of heating/cooling rates (≤100000 K s(-1)) and temperature modulation frequencies (≤1 kHz). The calorimeter was used for high-resolution thermal imaging of nanogram-sized samples subjected to X-ray-induced heating. For a 46 ng indium particle, the measured temperature rise reaches ∼0.2 K, and is directly correlated to the X-ray absorption. Thermal imaging can be useful for studies of heterogeneous materials exhibiting physical and/or chemical transformations. Moreover, the technique can be extended to three-dimensional thermal nanotomography.

Directed evolution is an approach that mimics natural evolution in the laboratory with the goal of modifying existing enzymatic activities or of generating new ones. The identification of mutants with desired properties involves the generation of genetic diversity coupled with a functional selection or screen. Genetic diversity can be generated using PCR or using in vivo methods such as chemical mutagenesis or error-prone replication of the desired sequence in a mutator strain. In vivo mutagenesis methods facilitate iterative selection because they do not require cloning, but generally produce a low mutation density with mutations not restricted to specific genes or areas within a gene. For this reason, this approach is typically used to generate new biochemical properties when large numbers of mutants can be screened or selected. Here we describe protocols for an advanced in vivo mutagenesis method that is based on error-prone replication of a ColE1 plasmid bearing the gene of interest. Compared to other in vivo mutagenesis methods, this plasmid-targeted approach allows increased mutation loads and facilitates iterative selection approaches. We also describe the mutation spectrum for this mutagenesis methodology in detail, and, using cycle 3 GFP as a target for mutagenesis, we illustrate the phenotypic diversity that can be generated using our method. In sum, error-prone Pol I replication is a mutagenesis method that is ideally suited for the evolution of new biochemical activities when a functional selection is available.

Radial symmetry is essential for the conventional view of the polymer spherulite microstructure. Typically it is assumed that, in the course of the spherulite morphogenesis, the lamellar crystals grow radially. Using submicron X-ray diffraction, it is shown that in banded spherulites of poly(propylene adipate) the crystals have the shape of a helix with flat-on crystals winding around a virtual cylinder of about 6 µm in diameter. The helix angle of 30° implies that the crystal growth direction is tilted away from the spherulite radius by this angle. The implications of the helical crystal shape contradict the paradigm of the spherulitic microstructure. The radial growth rate of such spherulites does not correspond to the crystal growth rate, but to the propagation rate of the virtual cylinder the ribbons wind around., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A novel wedge-shaped compound containing two diacetylene tails, namely, methyl 3,5-bis(trideca-2,4-diyn-1yloxyl)benzoate (DDABM), was synthesized. As shown by UV/Vis spectroscopy this compound can be polymerized under UV irradiation. The crystalline structure of DDABM was investigated by grazing-incidence wide-angle X-ray diffraction on oriented crystalline films deposited on PTFE-rubbed silicon wafer substrates. Furthermore, the spherulites formed in thicker films were analyzed by wide-angle X-ray diffraction. A molecular packing model of DDABM based on the X-ray diffraction data is proposed. The diacetylene units are oriented along a defined lattice direction with a reticular distance of 4.85 Å, which fulfills the requirements for topochemical polymerization. It was observed that UV polymerization does not affect the phase behavior of the compound, but mainly alters its optical properties., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Recognizing that GLBTI individuals are often barred from visiting their partners in hospitals or from acting as health care surrogates for incapacitated partners, President Obama directed the Department of Health and Human Services to address these issues. In response, the department amended its rules to prohibit hospitals from restricting, limiting, or denying visitation privileges on the basis of gender identity or sexual orientation. But the changes do not affect the designation of a health care surrogate, a matter largely governed by state law. Therefore, subject to state law, same-sex partners can still be legally barred from making health care decisions for their incapacitated partners, and it remains essential that they execute advance directives and appoint one another as their health care proxies.

Background: Recently, the Data collection of Adverse events of Anti-HIV Drugs Group (D:A:D) described results from their international observational cohort of 33,347 HIV-1-infected individuals, suggesting unexpected increased risk of myocardial infarction (MI) associated with abacavir (ABC) therapy [relative rate 1.9, 95% confidence interval (CI): 1.47 to 2.45; P = 0.0001]. To contribute to the scientific question, we summarized GlaxoSmithKline HIV clinical trial data to determine if a similar signal emerged., Methods: We compiled data from GlaxoSmithKline-sponsored clinical trials with > or = 24 weeks of combination antiretroviral therapy comprising 14,174 HIV-infected adults who received ABC (n = 9502; 7641 person-years) or not (n = 4672; 4267 person-years)., Findings: Baseline demographics and HIV disease characteristics, including lipids and glucose values, were similar. MI rates were comparable among subjects exposed [n = 16 (0.168%; CI: 0.096 to 0.273; 2.09 per 1000 person-years)] or not [n = 11 (0.235%; CI: 0.118 to 0.421; 2.57 per 1000 person-years)] to ABC-containing therapy. Results of 12 trials with randomization to ABC or not were consistent (2.15 per 1000 person-years vs. 4.10 per 1000 person-years)., Interpretations: In this pooled summary, we observed few MI events overall and no excess risk of MI with ABC therapy. It is unclear why results from this data set seem discrepant to the Data collection of Adverse events of Anti-HIV Drugs data set, particularly, as the non-ABC MI event rate is similar. Further data are needed to evaluate any association between ABC and increased risk of MI.

Purpose: The purpose of this study was to define a safe angle for suture anchor insertion during acetabular labral repair that will facilitate anchor placement within bone and prevent penetration into the hip joint., Methods: Nine acetabuli were harvested. Anatomic measurements were performed at the anterosuperior quadrant. Electronic calipers were used to measure acetabular bone. "Safe angle" measurements were obtained with suture anchor drills and a protractor. Comparisons between groups were calculated with a 1-way analysis of variance. The Tukey post-hoc analysis was completed for all significant analysis of variance results., Results: Labral insertion point distances and acetabular bone widths at the labral insertion did not statistically differ. Mean "danger angles" ranged from 17.0 degrees to 23.8 degrees. Safe angle measurements ranged from 20.1 degrees to 27.6 degrees., Conclusions: The extracapsular labral insertion, located between 2.3 and 2.6 mm from the rim of the anterosuperior acetabulum, is offered as a starting point for insertion of anchors sized less than 3.0 mm. The danger angle and safe angle of anchor insertion serve as guidelines that may improve fixation in bone and lessen intra-articular penetration. A target angle of 10 degrees is recommended., Clinical Relevance: The danger angle and safe angle may be referenced intraoperatively, during imaging and suture anchor insertion, to assure anchor placement within bone and prevent intra-articular penetration. A target angle of 10 degrees is safe and easily remembered.

Thin films (9-70 nm) of a series of polymers containing in the main chain dibenzo-18-crown-6 ether unit (DB18C6) linked to an aliphatic spacer of different length (10C and 14C) and nature have been prepared, from chloroform solutions, by spin coating on a silicon substrate. The quality and homogeneity of the polymer coatings was revealed by their reflectivity spectra and atomic force microscopy (AFM). The grazing incidence small-angle X-ray scattering (GISAXS) patterns show an out-of-plane structure correlation (interference maximum near the horizon) of scale size related to the polymer repeating unit length. Above this Bragg reflection, the shape of the scattering observed, in the GISAXS pattern, reveals an orientation of the stacked molecular columns in the coated polymer. A thermal treatment of the samples improves the nanostructure by increasing the lamellar coherence size (in y-direction) as well as the vertical orientation of the molecular columns.

Background: Numerous large, long-term clinical trials have assessed the safety and efficacy of the two antiretroviral nucleoside analogs lamivudine and abacavir as components of highly active antiretroviral therapy for the treatment of patients with HIV-1 infection. This analysis pools the safety data on multi-drug regimens containing lamivudine/abacavir in combination with a protease inhibitor, non-nucleoside reverse transcriptase inhibitor, or nucleoside reverse transcriptase inhibitor., Methods: Data are presented from 2279 treatment-naive HIV-1-infected patients who were enrolled in one of five clinical trials that assessed the safety and tolerability of lamivudine/abacavir in combination with a third antiretroviral agent. The well characterised combination of lamivudine/zidovudine plus efavirenz was used as the comparator arm. All available safety data (including data beyond 48 weeks) were used in all analyses, which included calculation of treatment emergent laboratory values, adverse events (AEs), serious AEs, fatalities, drug discontinuations and any summaries by study week of safety data., Results: In the total lamivudine/abacavir group, 1585 of 2229 (71%) patients experienced at least one drug-related AE during the study compared with 247 of 325 (76%) patients in the lamivudine/zidovudine/efavirenz treatment group. The most common drug-related AEs reported during the study were diarrhoea (19%), nausea (18%) and dizziness (12%) in patients treated with lamivudine/abacavir plus a third agent, and nausea (31%), dizziness (27%) and headache (16%) in the comparator group. Overall, in the total lamivudine/abacavir group there were only three severe (Division of AIDS 1992 toxicity table grade 3 or 4) AEs that were reported in >1% of subjects: drug hypersensitivity, elevated ALT levels and elevated AST levels. In the lamivudine/zidovudine/efavirenz group, six severe AEs that occurred in >1% of the safety population were reported. The abacavir hypersensitivity reaction rate reported in these five studies was comparable with the previously reported rate. In addition, there were no patient fatalities attributed by investigators to the study drugs., Conclusion: This analysis indicates that the combination of lamivudine/abacavir is generally safe for the majority of patients when used as part of combination therapy.

HIV-1 drug resistance methodologies are being increasingly utilized to guide treatment decisions; however, information comparing the various assays is limited. Duplicate plasma samples from 70 ART-experienced subjects were analyzed by both the Antivirogram and PhenoSense phenotypic assays and the results compared. HIV genotypes were also obtained and analyzed using seven different resistance algorithms. These results were also compared with the phenotypic assay results. Concordances between the phenotypic tests and between each algorithm, and between the two phenotypic assays were calculated and kappa coefficients (KC) determined. Overall agreement between the two phenotypic assays was good (86.9% concordance; KC 0.621). The highest concordance by drug class was seen for protease inhibitors (93.4%; KC 0.679) and the lowest (79.8%; KC 0.549) for nucleoside reverse transcriptase inhibitors. Concordance between the two phenotypic assays, when evaluating individual drugs, was good for all drugs tested except for abacavir, zalcitabine, and indinavir. Agreement between the seven algorithms and each phenotypic assay was variable, though most had good or excellent agreement. The highest overall level of agreement for an individual drug was observed when comparing lamivudine susceptibility to either assay. Concordance for abacavir, didanosine, zalcitabine, and saquinavir was generally problematic when comparing one or more phenotypic assays to the drug resistance predictive algorithms. In conclusion, results comparing these two phenotypic tests were mostly similar, but comparisons of the predictive resistance algorithms for specific drugs, as well as to specific phenotypic assays, were more inconsistent.

The use of a computer navigation system is intended to optimize implant positioning. This study compares prospectively followed total knee arthroplasty (TKA) done with imageless computer-assisted navigation with a cohort of TKA done with manual instruments. Primary TKAs were performed on 147 knees, with 78 in the manual group and 69 in the navigated group. Coronal alignment was determined by postoperative full-length standing radiographs. The 2 groups had similar mean values for radiographic mechanical axis at 0.4 degrees . There was a larger variation in alignment in the manual group, with 58% of the manual group within 2 degrees of neutral compared with 78% of the navigated group (P = .008). The navigation system reproducibly resulted in a more reliable reproduction of the mechanical axis.

Progressive supranuclear palsy (PSP) is a disorder of unknown pathogenesis. Familial clusters of PSP have been reported related to mutations of protein tau. We report the linkage of a large Spanish family with typical autosomal dominant PSP to a new locus in chromosome 1. Four members of this family had typical PSP, confirmed by neuropathology in one case. At least five ancestors had similar disease. Other members of the family have incomplete phenotypes. The power of the linkage analysis was increased by detecting presymptomatic individuals with 18F-fluoro-dopa and 18F-deoxyglucose positron emission tomography. We screened the human genome with 340 polymorphic markers and we enriched the areas of interest with additional markers. The disease status was defined according to the clinical and positron emission tomography data. We excluded linkage to the tau gene in chromosome 17. PSP was linked, in this family, to one area of 3.4 cM in chromosome 1q31.1, with a maximal multipoint < OD score of +3.53. This area contains at least three genes, whose relevance in PSP is unknown. We expect to further define the gene responsible for PSP, which could help to understand the pathogenesis of this disease and to design effective treatment.

Objectives: Lipoatrophy is an important manifestation of the lipodystrophy syndrome and is particularly associated with stavudine exposure. Increased apoptosis has been suggested as a possible mechanism of lipoatrophy. We assessed the degree and reversibility of adipocyte apoptosis in patients with lipoatrophy before and 48 weeks after substituting abacavir or zidovudine for stavudine., Methods: Apoptotic adipocytes were identified using terminal transferase dUTP nick end labeling and quantified using video image analysis., Results: Fat biopsy specimens were obtained from patients before (n = 15) and 48 weeks after (n = 10) switching from stavudine and from 20 HIV-uninfected controls. More apoptotic cells were seen in fat samples from patients with lipoatrophy treated with stavudine than in specimens from controls (P < 0.0001). Forty-eight weeks after switching from stavudine to abacavir or zidovudine, there was a reduction in apoptotic cells per unit area (P = 0.01) and as a proportion of all adipocytes present (P = 0.02) in patient biopsy specimens. Levels of adipocyte apoptosis in the 48-week biopsy specimens were no longer significantly different from those seen in control biopsy specimens (P > 0.1)., Conclusions: Increased apoptosis is present in fat samples from patients with lipoatrophy treated with stavudine. This improves toward normal within 48 weeks of switching from stavudine to abacavir or zidovudine, suggesting a causative role for stavudine in this process.

Objective: To determine if stavudine (alpha4T)-associated mitochondrial toxicity could be reversed by substitution with another nucleoside reverse transcriptase inhibitor. As apoptosis and dysfunction of electron transport chain (ETC) activities may underlie mitochondrial toxicity, these parameters were also evaluated., Design: The 16 participants (on d4T for >3 years; with lipoatrophy and/or hyperlactatemia) substituted abacavir or zidovudine for stavudine in their antiretroviral regimen. Key parameters including dual-energy X-ray absorptiometry (DEXA) scans, fat apoptosis, mitochondrial DNA (mtDNA) content in peripheral blood mononuclear cells (PBMC), skeletal muscle and fat, as well as skeletal muscle mitochondrial ETC activities were evaluated at study entry and at 48 weeks after the substitution., Methods: Quantitative PCR was used to evaluate mtDNA levels and the presence of deletions/rearrangements; CLIA-validated methods for ETC activities; terminal deoxynucleotidyl transferase dUTP-digoxigenin nick-end labeling assays to evaluate adipocyte apoptosis; and DEXA scans to measure changes in body fat., Results: MtDNA was depleted at study entry in muscle, adipose tissue and PBMC but levels rebounded with respective mean increases of 141%, 146%, and 369% at week 48. Corresponding fat improvements were noted with DEXA increases of 21%, 11%, and 16% in arm, leg, and trunk, respectively. Quantitative adipocyte apoptosis were significantly increased at baseline (P < 0.01 versus HIV-negative controls), with a significant reduction at week 48 (P < 0.05 versus baseline). Mean values for seven mitochondrial enzyme activities assays at entry indicated substantial loss of function (48% to 85% of controls) with significant improvement of complex I activity by week 48., Conclusions: Substitution of stavudine with abacavir or zidovudine improves mitochondrial indices and fat apoptosis in the setting of lipoatrophy.

HIV-infected subjects who have lipodystrophy and insulin resistance on prolonged antiretroviral therapy have elevated levels of tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) antigens, markers of impaired thrombolysis that are associated with hyperinsulinemia and increased cardiovascular risk. We studied HIV-infected, protease inhibitor (PI)-naive adults treated with indinavir (n = 11) or amprenavir (n = 14) plus two nucleoside reverse transcriptase inhibitors enrolled in two independent prospective trials. Antiretroviral and immune responses were similar in both studies. Over 8 wk, indinavir was associated with decreased insulin sensitivity, whereas amprenavir was not. Levels of tPA antigen declined by approx 25% with both treatments (p < 0.05 for each); levels of PAI-1 antigen did not change. Levels of the inflammatory marker soluble tumor necrosis factor-alpha receptor II (sTNFr2) correlated positively with tPA antigen (r = 0.33, p = 0.02), and mean (SD) plasma concentrations of sTNFr also declined with treatment (4.44 +/- 1.11 ng/mL pretherapy, 3.75 +/- 1.21 posttherapy, p = 0.007). Short-term improvement in a marker of impaired thrombolysis and increased vascular risk can occur during PI-based antiretroviral therapy, perhaps as a consequence of improvement in HIV-related inflammation. This improvement occurred independent of development of insulin resistance, which occurred only with indinavir.

Purpose: To assess efficacy, safety, and adherence with compact quadruple therapy comprising one lamivudine 150-mg/zidovudine 300-mg tablet (COM) twice daily + one abacavir (ABC) 300-mg tablet twice daily + three efavirenz (EFV) 200-mg capsules at bedtime for 24 weeks, followed by one lamivudine 150-mg/zidovudine 300-mg/ABC 300-mg triple nucleoside tablet (TZV) twice daily + three EFV 200-mg capsules at bedtime for 24 weeks., Method: A pilot 48-week, prospective, open-label trial in which 38 antiretroviral-naïve HIV-infected adults (baseline median HIV-1 RNA 5.1 log(10) copies/mL, CD4+ cell count 285/microL) received the above treatment and were monitored regularly with respect to plasma HIV-1 RNA levels, CD4+ cell counts, T-cell receptor excision circles (TRECs), adherence, and adverse events., Results: At Week 48, intent-to-treat, switch-included analysis showed plasma HIV-1 RNA levels <400 copies/mL in 100% (29/29) of patients and <50 copies/mL in 93% (27/29); 59% of patients who achieved <50 copies/mL had <3 copies/mL (16/27). Similar virologic suppression was observed in patients with baseline HIV-1 RNA above or below 100000 copies/mL. HIV-1 RNA and CD4+ cell counts changed from baseline by a median of -3.4 log(10) copies/mL and +172 cells/microL, respectively. One virologic failure occurred at Week 16. Median TRECs/100000 peripheral blood lymphocytes increased 6-fold between baseline and Week 48. Median adherence rates were consistently 100% by self-report and 94% by pill count. Grade 2-4 treatment-related adverse events included dreams (16%), nausea (13%), decreased white cells (8%), dizziness (8%), sleep disorders (8%), and malaise and fatigue (8%). A suspected ABC hypersensitivity reaction occurred in 8% (3/38) of patients., Conclusion: COM/ABC/EFV or TZV/EFV produced potent, durable virologic suppression and immunologic benefits, was associated with high adherence rates, and was generally well tolerated.

Movement disorders are well known features of some dominant hereditary ataxias (HA), specially SCA3/Machado-Joseph disease and dentatorubropallidolusyan atrophy. However, little is known about the existence and classification of movement disorders in other dominant and recessive ataxias. We prospectively studied the presence of movement disorders in patients referred for HA over the last 3 years. Only those patients with a confirmed family history of ataxia were included. We studied 84 cases of HA, including 46 cases of recessive and 38 cases of dominant HA. Thirty out of 46 cases of recessive HA could be classified as: Friedreich ataxia (FA), 29 cases; vitamin E deficiency, 1 case. Twenty-three out of 38 cases of dominant HA could be classified as: SCA 2, 4 cases; SCA 3, 8 cases; SCA 6, 4 cases; SCA 7, 6 cases and SCA 8, 1 case. We observed movement disorders in 20/38 (52%) patients with dominant HA and 25/46 (54%) cases with recessive HA, including 16 patients (16/29) with FA. In general, postural tremor was the most frequent observed movement disorder (27 cases), followed by dystonia (22 cases). Five patients had akinetic rigid syndrome, and in 13 cases, several movement disorders coexisted. Movement disorders are frequent findings in HA, not only in dominant HA but also in recessive HA., (Copyright 2002 Elsevier Science B.V.)

A post hoc analysis of safety data from study protocol NZT40012 assessed the incidence of conditions defined by the Centers for Disease Control and Prevention in 86 zidovudine-naïve, antiretroviral-experienced patients with HIV-1 infection who responded poorly (plasma HIV-1 RNA > 1000 copies/mL) despite at least 4 months' treatment with stavudine-containing regimens. Peripheral neuropathy occurred in 21%; other conditions were seen less frequently (candidiasis [13%], herpes zoster [12%], diarrhea lasting > 1 month [9%], Pneumocystis carinii pneumonia [9%], and wasting syndrome [8%]). The incidence of peripheral neuropathy rose significantly with the number of drugs comprising treatment regimens (> or = 4 vs 1-3; P = .013) and tended to be higher in patients with longer exposure to stavudine (29% with > or = 24 months' exposure vs 13% with < 24 months). Because peripheral neuropathy was observed with such high frequency, vigilance for signs and symptoms of this condition appears warranted if stavudine-containing regimens are to be continued.