Choice of antiretroviral therapy has low impact on weight gain.

Objective: Antiretroviral therapy (ART) containing integrase inhibitors (INSTIs) and/or tenofovir alafenamide (TAF) has been associated with greater weight gain. Yet few studies have delineated between exposure to 'anchor' drugs [protease inhibitors (PI), nonnucleoside reverse transcriptase inhibitors (NNRTI) or INSTIs] and exposure to nucleoside reverse transcriptase inhibitors (NRTIs).

Design: In this cohort of antiretroviral drug-naive patients who initiated ART from 2008-2022, we analyzed BMI gain for eight contemporary 'anchor' drugs and three contemporary NRTIs during the first 3 years of ART.

Triggered contraction of self-assembled micron-scale DNA nanotube rings.

Contractile rings are formed from cytoskeletal filaments during cell division. Ring formation is induced by specific crosslinkers, while contraction is typically associated with motor protein activity. Here, we engineer DNA nanotubes and peptide-functionalized starPEG constructs as synthetic crosslinkers to mimic this process.

Impact of an Educational and Laboratory Stewardship Intervention on Inpatient COVID-19 Therapeutics at a Veterans Affairs Medical Center.

Background: Accurate and timely prescriptions of COVID-19 therapeutics, laboratory testing, and antimicrobial stewardship have been a challenge throughout the pandemic as new evidence emerges. While universal consultation with infectious disease specialists on patients admitted with COVID-19 is desirable, it is not always feasible due to limited resources.

Observations: In this single-center study, we implemented a combined educational and laboratory stewardship intervention geared toward hospitalist practitioners resulting in improved accuracy of remdesivir and dexamethasone prescriptions, reduced laboratory use of blood cultures, interleukin 6 assay, and sputum cultures, and a decrease in antibiotic use for patients with mild-to-moderate oxygen requirements over 6 months.

Fabrication of High Aspect Ratio Gold Nanowires within the Microtubule Lumen.

Gold nanowires have great potential use as interconnects in electronic, photonic, and optoelectronic devices. To date, there are various fabrication strategies for gold nanowires, each one associated with particular drawbacks as they utilize high temperatures, toxic chemicals, or expensive compounds to produce nanowires of suboptimal quality. Inspired by nanowire fabrication strategies that used higher-order biopolymer structures as molds for electroless deposition of gold, we here report a strategy for the growth of gold nanowires from seed nanoparticles within the lumen of microtubules.

CENP-V is required for proper chromosome segregation through interaction with spindle microtubules in mouse oocytes.

Proper chromosome segregation is essential to avoid aneuploidy, yet this process fails with increasing age in mammalian oocytes. Here we report a role for the scarcely described protein CENP-V in oocyte spindle formation and chromosome segregation. We show that depending on the oocyte maturation state, CENP-V localizes to centromeres, to microtubule organizing centers, and to spindle microtubules.

The ALS-Associated FUS (P525L) Variant Does Not Directly Interfere with Microtubule-Dependent Kinesin-1 Motility.

Deficient intracellular transport is a common pathological hallmark of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Mutations in the fused-in-sarcoma (FUS) gene are one of the most common genetic causes for familial ALS. Motor neurons carrying a mutation in the nuclear localization sequence of FUS (P525L) show impaired axonal transport of several organelles, suggesting that mislocalized cytoplasmic FUS might directly interfere with the transport machinery.

Consistent use of lipid lowering therapy in HIV infection is associated with low mortality.

Background: In people living with HIV (PLWH), statins may be disproportionately effective but remain underutilized. A large prospective trial in patients with low to moderate cardiovascular (ASCVD) risk will reveal whether they should be considered in all PLWH. But its effect size may not apply to real-world PLWH with higher ASCVD and mortality risk.

Multivalent electrostatic microtubule interactions of synthetic peptides are sufficient to mimic advanced MAP-like behavior.

Microtubule-associated proteins (MAPs) are a functionally highly diverse class of proteins that help to adjust the shape and function of the microtubule cytoskeleton in space and time. For this purpose, MAPs structurally support microtubules, modulate their dynamic instability, or regulate the activity of associated molecular motors. The microtubule-binding domains of MAPs are structurally divergent, but often depend on electrostatic interactions with the negatively charged surface of the microtubule.

Statin use and medically attended acute respiratory illness among influenza vaccine recipients.

Background: Previous studies have suggested that statins decrease influenza vaccine effectiveness and increase risk of medically attended acute respiratory illness (MAARI).

Objectives: To examine the association of incident statin use and MAARI in a cohort of influenza vaccine recipients.

Methods: This retrospective cohort study evaluated influenza vaccine recipients within the Tricare population.

Skin disease prevalence study in schoolchildren in rural Côte d'Ivoire: Implications for integration of neglected skin diseases (skin NTDs).

Background: Early detection of several skin-related neglected tropical diseases (skin NTDs)-including leprosy, Buruli ulcer, yaws, and scabies- may be achieved through school surveys, but such an approach has seldom been tested systematically on a large scale in endemic countries. Additionally, a better understanding of the spectrum of skin diseases and the at-risk populations to be encountered during such surveys is necessary to facilitate the process.

Methods: We performed a school skin survey for selected NTDs and the spectrum of skin diseases, among primary schoolchildren aged 5 to 15 in Côte d'Ivoire, West Africa.

Kif15 functions as an active mechanical ratchet.

Kif15 is a kinesin-12 that contributes critically to bipolar spindle assembly in humans. Here we use force-ramp experiments in an optical trap to probe the mechanics of single Kif15 molecules under hindering or assisting loads and in a variety of nucleotide states. While unloaded Kif15 is established to be highly processive, we find that under hindering loads, Kif15 takes <∼10 steps.

The Enterohemorrhagic Escherichia coli Effector EspW Triggers Actin Remodeling in a Rac1-Dependent Manner.

Enterohemorrhagic (EHEC) is a diarrheagenic pathogen that colonizes the gut mucosa and induces attaching-and-effacing lesions. EHEC employs a type III secretion system (T3SS) to translocate 50 effector proteins that hijack and manipulate host cell signaling pathways, which allow bacterial colonization and subversion of immune responses and disease progression. The aim of this study was to characterize the T3SS effector EspW.

Mps1 Regulates Kinetochore-Microtubule Attachment Stability via the Ska Complex to Ensure Error-Free Chromosome Segregation.

The spindle assembly checkpoint kinase Mps1 not only inhibits anaphase but also corrects erroneous attachments that could lead to missegregation and aneuploidy. However, Mps1's error correction-relevant substrates are unknown. Using a chemically tuned kinetochore-targeting assay, we show that Mps1 destabilizes microtubule attachments (K fibers) epistatically to Aurora B, the other major error-correcting kinase.

Current use of statins reduces risk of HIV rebound on suppressive HAART.

Background: Despite compelling evidence for activity against HIV-1 in vitro, a virologic effect of statins has not been shown in clinical studies. Given their short plasma half-lives, such an effect may be transient and only apparent during ongoing exposure.

Methods: We studied all HIV infected US-Veterans who started HAART 1995-2011, had a documented HIV viral load (VL) >1000 copies/mL, reached an undetectable VL on HAART, and had ≥1 follow-up VL within 13 months.

Kinesin-12 motors cooperate to suppress microtubule catastrophes and drive the formation of parallel microtubule bundles.

Human Kinesin-12 (hKif15) plays a crucial role in assembly and maintenance of the mitotic spindle. These functions of hKif15 are partially redundant with Kinesin-5 (Eg5), which can cross-link and drive the extensile sliding of antiparallel microtubules. Although both motors are known to be tetramers, the functional properties of hKif15 are less well understood.

Mechanisms of bone disease in HIV and hepatitis C virus: impact of bone turnover, tenofovir exposure, sex steroids and severity of liver disease.

Objective: Both HIV and hepatitis C virus (HCV) infections are associated with higher osteoporotic fracture risk. Increased bone turnover, liver fibrosis, tenofovir (TDF) use or hormonal imbalances are possible underlying mechanisms.

Design: This prospective, cross-sectional study assessed 298 male volunteers with either virologically suppressed HIV or untreated HCV mono-infections, HIV/HCV co-infection and noninfected controls.

Yeast GSK-3 kinase regulates astral microtubule function through phosphorylation of the microtubule-stabilizing kinesin Kip2.

The S. cerevisiae kinesin Kip2 stabilises astral microtubules (MTs) and facilitates spindle positioning through transport of MT-associated proteins, such as the yeast CLIP-170 homologue Bik1, dynein and the adenomatous-polyposis-coli-related protein Kar9 to the plus ends of astral MTs. Here, we show that Kip2 associates with its processivity factor Bim1, the yeast homologue of the plus-end-tracking protein EB1.

The RADAR study: week 48 safety and efficacy of RAltegravir combined with boosted DARunavir compared to tenofovir/emtricitabine combined with boosted darunavir in antiretroviral-naive patients. Impact on bone health.

Background: NRTI-sparing regimens may avoid long-term mitochondrial, bone and renal toxicities and maintain viral suppression.

Methods: In the RADAR study, 85 antiretroviral-naïve HIV-infected patients were randomized to receive either raltegravir (RAL) (n = 42) or tenofovir/emtricitabine (TDF/FTC) (n = 43), each with ritonavir-boosted darunavir (DRV/r). Virologic efficacy was assessed at weeks 24 and 48.

The Kinesin-12 Kif15 is a processive track-switching tetramer.

Kinesin-12 motors are a little studied branch of the kinesin superfamily with the human protein (Kif15) implicated in spindle mechanics and chromosome movement. In this study, we reconstitute full-length hKif15 and its microtubule-targeting factor hTpx2 in vitro to gain insight into the motors mode of operation. We reveal that hKif15 is a plus-end-directed processive homotetramer that can step against loads of up to 3.

CD4 counts and mortality in virologically suppressed US veterans.

We used the Veterans Health Administration (VA) HIV Clinical Case Registry (CCR) to evaluate the association between annual CD4 averages and all-cause mortality in HIV-infected veterans during their initial episode of suppressive highly active antiretroviral therapy (HAART). We observed 1083 deaths in 14 769 patients. Unadjusted mortality rates in the top and bottom CD4 quintiles differed significantly from the mid CD4 strata.

Anti-oxLDL antibodies are clinically insignificant for stroke patients.

Objectives: The question about anti-oxidized low-density lipoprotein antibodies (anti-oxLDL Abs) involvement in the pathogenesis of atherosclerosis-related ischemic stroke is still open. The aim of this study was to determine how anti-oxLDL Abs are involved in the pathogenesis of atherosclerosis-related ischemic stroke and identify the main risk factors for stroke, such as arterial hypertension, diabetes mellitus type 2, dyslipidemia, and atherosclerotic changes in the common and internal carotid arteries.

Material And Methods: A total of 40 stroke patients and 25 age- and sex-matched healthy individuals were included in the study.

CD4⁺CD28⁻ lymphocytes and cerebral ischaemic stroke. Part II: CD4⁺CD28⁻ lymphocytes and carotid artery atherosclerotic plaque characteristics.

Background And Purpose: CD4⁺CD28⁻ lymphocytes can directly contribute to the instability of atherosclerotic plaque. This paper attempts to answer the question of the potential influence of the CD4⁺CD28⁻ lymphocyte population on the ultrasound image of atherosclerotic plaque in the common carotid artery (CCA) wall.

Material And Methods: The study involved a group of 109 patients, aged 45 to 65 years, including 42 patients with first ever ischaemic stroke, experiencing symptoms resulting from disturbances of the anterior area of cerebral circulation, arterial hypertension and/or type 2 diabetes mellitus (group 1).

CD4⁺CD28⁻ lymphocytes and ischaemic stroke. Part I: CD4⁺CD28⁻ lymphocytes and common carotid artery intima-media thickness.

Background And Purpose: More and more data point to the involvement of the CD4⁺CD28⁻ lymphocyte subpopulation in the pathogenesis of ischaemic stroke. This paper attempts to answer the question of whether an increase in the percentage of CD4⁺CD28⁻ lymphocytes in the blood may be associated with carotid artery intima-media thickness (IMT).

Material And Methods: The study involved a group of 109 patients, aged 45 to 65 years, including 42 patients with first-ever ischaemic stroke, experiencing symptoms resulting from disturbances of the anterior area of cerebral circulation, arterial hypertension and/or type 2 diabetes mellitus (group 1).