Center of pressure characteristics differ during single leg stance throughout pregnancy and compared to nulligravida individuals.

BACKGROUND: Falls are common during pregnancy and present potential for injury to the pregnant individual and the baby. RESEARCH QUESTION: Do center of pressure characteristics during single leg stance differ between participants during and after pregnancy and nulligravida participants in the presence and absence of visual input? METHODS: Nineteen pregnant participants completed testing during the second trimester, the third trimester, and 4-6 months post-partum. Matched, nulligravida females completed testing once. All participants performed single leg stance on a force platform on each limb for up to 20 s with eyes open and with eyes closed. Center of pressure characteristics were compared between pregnant and nulligravida females using three separate 2 × 2 mixed way ANOVAs, one for each pregnancy time point (second trimester, third trimester, and post-partum) with Bonferroni correction. RESULTS: Pregnant females demonstrated smaller single leg stance time with eyes closed during the third trimester. During the second and third trimester, pregnant participants demonstrated smaller sway and sway velocity across eyes open and eyes closed conditions. During the third trimester and post-partum, pregnant participants demonstrated greater median frequency of the center of pressure data. Pregnant participants also demonstrated smaller sample entropy in the anteroposterior direction during the second and third trimesters and in the mediolateral direction during the second trimester. SIGNIFICANCE: The decreased total sway and sway velocity observed during pregnancy may reflect rigidity or a protective strategy during single limb stance. Additionally, center of pressure data were less smooth and more repetitive during pregnancy indicating robust differences in postural control strategies and potentially increased fall risk. Because single limb stance is a component of many activities of daily living, the single limb stance task may have clinical utility for testing or training balance in this population with a goal of decreasing falls.

An exploratory analysis of gait biomechanics and muscle activation in pregnant females with high and low scores for low back or pelvic girdle pain during and after pregnancy.

BACKGROUND: The purpose of this study was to compare gait kinematics, kinetics, and muscle activation between pregnant females with high and low scores for low back and/or pelvic girdle pain during and after pregnancy. METHODS: Twenty participants tested during second trimester, third trimester, and again post-partum. At each session, motion capture, force plates, and surface electromyography data were captured during self-selected velocity over-ground walking. Participants completed the Quebec Back Pain Disability Scale (QBPDS) and were assigned to high (QBPDS ≥15) or low pain groups (QBPDS <15) based on third trimester scores. Two-way mixed model ANOVAs were used to compare high and low pain groups over time. FINDINGS: Nine participants met the high pain group criteria and 11 were low pain. During second trimester the high pain group compared to the low pain group demonstrated smaller peak hip flexor moments, total hip work, percent hip contribution to work, and larger percent ankle contribution to work. Pregnant females demonstrated greater hip, knee, and ankle moments, ankle work, and gluteus maximus muscle activation third trimester than second trimester. INTERPRETATION: Reduced hip and greater ankle contribution to work in the high pain group during second trimester could indicate decreased hip utilization early in pregnancy and may contribute to disability as pregnancy progresses. It is also possible kinetic differences during second trimester reflect an early strategy to reduce pain by avoiding hip joint loading. Increased moments and work during third trimester indicate a clinical imperative to better prepare pregnant females to accommodate increased joint loading and muscular demand.

Lower extremity kinetics and muscle activation during gait are significantly different during and after pregnancy compared to nulliparous females.

BACKGROUND: Low back, pelvic, and lower extremity pain are common during and after pregnancy. Understanding differences in mechanics between pregnant and non-pregnant females is a first step toward identifying potential pathological mechanisms. The primary purpose of this study was to compare joint kinetics and muscle activation during gait between females during and after pregnancy to nulliparous females. METHODS: Twenty pregnant females completed testing on three occasions (second trimester, third trimester, and post-partum), while 20 matched, nulliparous controls were tested once. Motion capture, force data, and surface electromyography were averaged across seven trials during gait. Lower extremity kinematics, lower extremity moments and work normalized to pre-pregnancy body mass, work distribution, and peak and average muscle activation amplitude were calculated. Independent t-tests were conducted between pregnant and nulliparous females at each time point. RESULTS: Compared to controls, peak hip abductor moments were greater throughout and after pregnancy. Females in second trimester also demonstrated greater sagittal negative ankle work and greater percent contribution of the ankle and smaller percent contribution of the hip to negative work. Compared to controls, during third trimester there were greater knee abductor, ankle plantarflexor, and ankle dorsiflexor moments and greater work at the ankle and total work. Several moment and work variables continued to be elevated post-partum compared to controls. Gluteus maximus muscle activation amplitude was smaller in second trimester and post-partum compared to controls. SIGNIFICANCE: While overall joint demands were greater during and after pregnancy, there was a smaller relative sagittal utilization of the hip early in pregnancy and smaller gluteus maximus muscle amplitude during second trimester and post-partum. Because the gluteus maximus muscle contributes to force closure and dynamic stability of the low back and pelvis, relative gluteus maximus disuse, concurrent with increased joint loads, could potentially contribute to pain during and after pregnancy.

Structure-based methods to predict mutational resistance to diarylpyrimidine non-nucleoside reverse transcriptase inhibitors.

Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) is a leading cause of HIV treatment failure. Often included in antiviral therapy, NNRTIs are chemically diverse compounds that bind an allosteric pocket of enzyme target reverse transcriptase (RT). Several new NNRTIs incorporate flexibility in order to compensate for lost interactions with amino acid conferring mutations in RT. Unfortunately, even successful inhibitors such as diarylpyrimidine (DAPY) inhibitor rilpivirine are affected by mutations in RT that confer resistance. In order to aid drug design efforts, it would be efficient and cost effective to pre-evaluate NNRTI compounds in development using a structure-based computational approach. As proof of concept, we applied a residue scan and molecular dynamics strategy using RT crystal structures to predict mutations that confer resistance to DAPYs rilpivirine, etravirine, and investigational microbicide dapivirine. Our predictive values, changes in affinity and stability, are correlative with fold-resistance data for several RT mutants. Consistent with previous studies, mutation K101P is predicted to confer high-level resistance to DAPYs. These findings were further validated using structural analysis, molecular dynamics, and an enzymatic reverse transcription assay. Our results confirm that changes in affinity and stability for mutant complexes are predictive parameters of resistance as validated by experimental and clinical data. In future work, we believe that this computational approach may be useful to predict resistance mutations for inhibitors in development.

Review of Lisdexamfetamine Dimesylate in Adults With Attention-Deficit/Hyperactivity Disorder.

Lisdexamfetamine dimesylate (LDX) is the first prodrug stimulant used for the treatment of attention-deficit/hyperactivity disorder (ADHD) dosed once daily. Due to its long-acting properties, LDX remains pharmacologically inactive until an enzymatic process predominantly associated with red blood cells converts it to the active ingredient, d-amphetamine and the amino acid lysine. The efficacy of LDX over placebo has been demonstrated in several studies in adults with moderate to severe ADHD with significant improvements noted in ADHD rating scales, Clinical Global Improvement scores, and assessments of executive function, for all doses of LDX (30-70 mg daily). Lisdexamfetamine dimesylate has demonstrated efficacy at 14 hours post dose in adults and may be used as a long-acting stimulant for managing ADHD symptoms, which may extend late into the day. Lisdexamfetamine dimesylate has demonstrated a safety profile consistent with long-acting stimulants use. Relevant English language articles were identified through computerized searches of MEDLINE (PubMed and EMBASE) from 1995 to 2016 using the following search terms: lisdexamfetamine dimesylate, attention-deficit hyperactivity disorder, NRP104, and Vyvanse.

Human papillomavirus vaccination guideline update: American Cancer Society guideline endorsement.

Answer questions and earn CME/CNE The American Cancer Society (ACS) reviewed and updated its guideline on human papillomavirus (HPV) vaccination based on a methodologic and content review of the Advisory Committee on Immunization Practices (ACIP) HPV vaccination recommendations. A literature review was performed to supplement the evidence considered by the ACIP and to address new vaccine formulations and recommendations as well as new data on population outcomes since publication of the 2007 ACS guideline. The ACS Guideline Development Group determined that the evidence supports ACS endorsement of the ACIP recommendations, with one qualifying statement related to late vaccination. The ACS recommends vaccination of all children at ages 11 and 12 years to protect against HPV infections that lead to several cancers and precancers. Late vaccination for those not vaccinated at the recommended ages should be completed as soon as possible, and individuals should be informed that vaccination may not be effective at older ages. CA Cancer J Clin 2016;66:375-385. © 2016 American Cancer Society.