The Interactions of Anti-HIV Pronucleotides with a Model Phospholipid Membrane.

Pronucleotides, after entering the cell, undergo chemical or enzymatic conversion into nucleotides with a free phosphate residue, and the released nucleoside 5'-monophosphate is then phosphorylated to the biologically active form, namely nucleoside 5'-triphosphate. The active form can inhibit HIV virus replication. For the most effective therapy, it is necessary to improve the transport of prodrugs into organelles.

Association Between Longitudinal Changes in Patellar Tendon Abnormality and Land-Jump Biomechanics in Male Collegiate Basketball Players.

Background: The relationship between self-reported symptoms and the severity of patellar tendon abnormality (PTA) as seen on magnetic resonance imaging and ultrasound is unclear, but biomechanical testing may resolve this.

Purpose: To (1) compare land-jump limb biomechanics between pre- and postseason timepoints, (2) assess whether seasonal changes in biomechanics are associated with seasonal changes in PTA and symptom severity, and (3) explore models that identify seasonal changes in PTA and symptoms with seasonal changes in biomechanics in collegiate basketball players.

Study Design: Cohort study; Level of evidence, 2.

Association Between Patellar Tendon Abnormality and Land-Jump Biomechanics in Male Collegiate Basketball Players During the Preseason.

Background: Patellar tendinopathy is a degenerative condition that predominantly affects jumping athletes. Symptoms may be subtle or nonexistent at preseason, but structural abnormalities may be present. Assessing patellar tendon abnormality (PTA) through magnetic resonance imaging (MRI) and ultrasound (US) and classifying symptoms using the Victorian Institute for Sport Assessment-Patellar tendon (VISA-P) may provide useful insights if combined with biomechanics measurements.

Assessment of a two-mass ground reaction force model applied to indoor overground running in adult recreational runners.

Outdoor running kinetic measurements like vertical ground reaction force (vGRF) need simple and accurate models. A previous study assessed a two mass model (2MM) on an athletic adult population during treadmill running, but not recreational adults during overground running. The objectives were to compare accuracy of the overground 2MM and an optimized version to the reference study and force platform (FP) measurements.

Body mass affects kinetic symmetry and inflammatory markers in adolescent knees during gait.

Background: Early-onset osteoarthritis has been attributed to pro-inflammatory factors and biomechanical changes in obesity. However, research has yet to explore whether knee joint moments are asymmetrical in children with obesity and could precede the onset of knee osteoarthritis. The present study compares knee moment asymmetry between adolescents with and without obesity and examines the relationship between asymmetries and inflammatory biomarkers.

Knee Kinetics and Kinematics in Patients With Ankle Arthroplasty and Ankle Arthrodesis.

: Previous literature suggests that patients treated with total ankle arthroplasty (TAA) versus ankle arthrodesis (AA) may have better function and lower risk for adjacent joint arthritis in the foot. Little is known on how these interventions affect proximal joints such as the knee. : We sought to assess whether patients with TAA and AA exhibited altered biomechanics linked to the onset and progression of knee osteoarthritis (KOA).

Dynamic Assessment of Femoroacetabular Impingement Syndrome Hips.

Purpose: The purpose of our study was to compare lower extremity rotational kinematics and kinetics (angles, torques, and powers) and hip muscle electromyography (EMG) activity between cam-type femoroacetabular impingement syndrome (FAIS) and age- and sex-matched controls during walking, fast walking, stair ascent, stair descent, and sit-to-stand.

Methods: This study included 10 males with unilateral FAIS and 10 control males with no FAIS. We measured kinematics, kinetics, and electromyographic signals during stair ascent/descent, sit-to-stand, self-selected walk, and fast walk.

H-Phosphonate Chemistry in the Synthesis of Electrically Neutral and Charged Antiviral and Anticancer Pronucleotides.

In this review a short account of our work on the synthesis and biological activity of electrically neutral and charged anti-HIV and anticancer pronucleotides, presented on the background of the contemporary research in this area, is given.

Differences in Gait and Stair Ascent After Total Ankle Arthroplasty and Ankle Arthrodesis.

Background: Ankle arthrodesis has historically been the standard of care for end-stage ankle arthritis; however, total ankle arthroplasty (TAA) is considered a reliable alternative. Our objective was to compare 3-dimensional foot and ankle kinetics and kinematics and determine the ankle power that is generated during level walking and stair ascent between TAA and ankle arthrodesis patients.

Methods: Ten patients who underwent TAA with a modern fixed-bearing ankle prosthesis and 10 patients who previously underwent ankle arthrodesis were recruited.

Comparing First Metatarsophalangeal Joint Flexibility in Hallux Rigidus Patients Pre- and Postcheilectomy Using a Novel Flexibility Device.

Background: Hallux rigidus (HR) is a common pathology of the first metatarsophalangeal (MTP) joint causing pain and stiffness. However, severity of symptoms and radiographic findings are not always concordant. A novel flexibility device, which measures the mobility of the MTP joint through its arc of motion, has been validated.

Biomechanical and Functional Improvements Gained by Proximal Tibia Osteotomy Correction of Genu Varum in Patients with Knee Pain.

Background: Mechanical axis malalignment contributes to abnormal forces across the knee joint. Genu varum, or increased medial mechanical axis deviation (MAD), increases force transmission and contact pressures to the medial compartment. With increasing MAD and femoral-tibial mechanical axis angle (MAA), contact forces within the medial or lateral compartment of the knee significantly increase with increasing deformity.

Aryl H-phosphonates. 19. New anti-HIV pronucleotide phosphoramidate diesters containing amino- and hydroxypyridine auxiliaries.

We have designed a new type of AZT and ddU phosphoramidate diesters containing various combinations of 2-, 3-, 4-aminopyridine and 2-, 3-, 4-hydroxypyridine moieties attached to the phosphorus center, as potential anti-HIV pronucleotides. Depending on the pK values of the aminopyridines and the hydroxypyridines used, alternative synthetic strategies based on H-phosphonate chemistry were developed for their preparation. Synthetic aspects of these transformations and the biological activity of the synthesized compounds are discussed.

What Are the Effects of Capsular Plication on Translational Laxity of the Glenohumeral Joint: A Study in Cadaveric Shoulders.

Background: Surgical treatment for shoulder instability generally involves labral repair with a capsular plication or imbrication. Good results are reported in both open and arthroscopic procedures, but there is no consensus on the amount or location of capsular plication that is needed to achieve stability and anatomic anterior, posterior, and inferior translation of the joint.

Questions/purposes: (1) What are the separate and combined effects of increasing plication magnitude and sequential additive plications in the anterior, posterior, and inferior locations of the joint capsule on glenohumeral joint translation in the anterior, posterior, and inferior directions? (2) What plication location and magnitude restores anterior, posterior, and inferior translation to a baseline level?

Methods: Fourteen cadaveric shoulders were dissected down to the glenohumeral capsule and underwent instrumented biomechanical testing.

Lateralizing Calcaneal Osteotomies and Their Effect on Calcaneal Alignment: A Three-Dimensional Digital Model Analysis.

Background: Few authors have directly compared multiple types of lateralizing calcaneal osteotomies (LCOs) in terms of their ability to achieve deformity correction. The aim of this research was to use a digital model of a varus hindfoot to compare 4 different LCOs in terms of deformity correction and amount of tuberosity lateralization required. The authors hypothesis was that osteotomies involving a wedge resection would achieve greater correction with less lateralization.

New antiglioma zwitterionic pronucleotides with an FdUMP framework.

We have designed and synthesized new 5-fluoro-2'-deoxyuridine 5'-phosphate pronucleotides which can function as potential agents against the glioblastoma multiforme tumor. Their anti-malignant potency has been tested against T98G, U-118 MG, U-87 MG gliomas, HeLa, and Caco-2 cancer cell lines, using MRC-5 healthy cells as a reference. Five of the sixteen compounds (4c, 4f-i) exhibited significant anticancer potency and high selectivity indices (SI 12-66).

Mapping glenohumeral laxity: effect of capsule tension and abduction in cadaveric shoulders.

Background: Shoulder capsular plication aims to restore the passive stabilization of the glenohumeral capsule; however, high reported recurrence rates warrant concern. Improving our understanding of the clinical laxity assessment across 2 dimensions, capsular integrity and shoulder position, can help toward the standardization of clinical tools. Our objectives were to test and describe glenohumeral laxity across 5 capsular tension levels and 4 humeral position levels and describe tension-position interplay.

Measuring Joint Flexibility in Hallux Rigidus Using a Novel Flexibility Jig.

Background: The flexibility of the first metatarsophalangeal (MTP) joint in patients with hallux rigidus (HR) has not been studied. Compared to measuring range of motion alone, measures of joint flexibility provide additional information that may prove useful in the assessment of HR. The purpose of this study was to assess the flexibility of the hallux MTP joint in patients with HR compared to controls using a novel flexibility device.

Synthesis of Aminoglycoside-2'-O-Methyl Oligoribonucleotide Fusions.

Phosphoramidite building blocks of ribostamycin ( and ), that may be incorporated at any position of the oligonucleotide sequence, were synthesized. The building blocks, together with a previously described neomycin-modified solid support, were applied for the preparation of aminoglycoside-2'--methyl oligoribonucleotide fusions. The fusions were used to clamp a single strand DNA sequence (a purine-rich strand of c-Myc promoter 1) to form triple helical 2'--methyl RNA/DNA-hybrid constructs.

Changes in Lower Extremity Kinematics and Temporal Parameters of Adolescent Baseball Pitchers During an Extended Pitching Bout.

Background: Few studies have investigated detailed 3-dimensional lower extremity kinematics during baseball pitching in adolescent athletes during extended play. Changes in these parameters may affect performance outcomes.

Purpose: To investigate whether adolescent baseball pitchers experience changes in lower extremity kinematics and event timing during a simulated game-length pitching bout.

An Investigation of Structure, Flexibility, and Function Variables that Discriminate Asymptomatic Foot Types.

It has been suggested that foot type considers not only foot structure (high, normal, low arch), but also function (overpronation, normal, oversupination) and flexibility (reduced, normal, excessive). Therefore, this study used canonical regression analyses to assess which variables of foot structure, function, and flexibility can accurately discriminate between clinical foot type classifications. The feet of 61 asymptomatic, healthy adults (18-77 years) were classified as cavus (N = 24), rectus (N = 54), or planus (N = 44) using standard clinical measures.

Searching for anti-glioma activity. Ribonucleoside analogues with modifications in nucleobase and sugar moieties.

Several ribonucleoside analogues with modifications in the nucleobase and sugar moiety have been screened for anti-glioma activity in the T98G glioma cell line using cervical (HeLa) cell line as reference human malignant cells, and lung fibroblast (MCR-5) cell line as non-cancerous reference cells. Among the investigated compounds, ribonucleosides containing 6-chloropurine (3), 7-guanine (5) and a pyrrolopyrimidine (18) as nucleobases, show promising anti-glioma activity with good selectivity indices, and can be considered as lead structures for further anti-cancer studies.

New 3'-O-aromatic acyl-5-fluoro-2'-deoxyuridine derivatives as potential anticancer agents.

New aromatic and aliphatic 3'-O-acyl-5-fluoro-2'-deoxyuridine derivatives were synthesized and evaluated as candidates for prodrugs against various cancer cell lines. As the most promising candidate for antimalignant therapeutics was found a dual-acting acyl derivative 7h, which apparently released not only the known anticancer nucleoside, 5-fluoro-2'-deoxyuridine (FdU), but also an additional active metabolite, acetylsalicylic acid, reinforcing thus therapeutic effect of FdU. Promising therapeutic indices showed also some aromatic dicarboxylic acids derivatives decorated with FdU esters (11 and 12).

Surgical Treatments for Scapholunate Advanced Collapse Wrist: Kinematics and Functional Performance.

Purpose: The purpose of this investigation was to compare kinematic motion and functional performance during 2 tasks in patients following 4-corner fusion (4CF) or proximal row carpectomy (PRC) and to compare these data with those from healthy asymptomatic individuals.

Methods: Twenty men (10 4CFs and 10 PRCs, ages, 43-82 y) were recruited for 3-dimensional wrist motion analysis testing. Kinematic coupling (the ratio of wrist flexion/extension to radial-ulnar deviation), kinematic path length (a measure of total angle distance), clinical measures, and performance measures were collected during 2 tasks: dart throwing and hammering.

Aryl H-Phosphonates 18. Synthesis, properties, and biological activity of 2',3'-dideoxynucleoside (N-heteroaryl)phosphoramidates of increased lipophilicity.

Recently, AZT (N-pyridyl)phosphoramidates were reported as a new type of potential anti-HIV therapeutics. In continuation of that work, here we present new (N-heteroaryl)phosphoramidate derivatives of antiviral 2',3'-dideoxynucleosides containing other types of N-heteroaryl moieties, particularly those with higher lipophilicity. The present studies comprise mechanistic investigations using (31)P NMR correlation analysis, which permitted improvements in the synthetic procedures.

The effect of wrist surgery on the kinematic consistency of joint axis reconstruction in a static posture.

Three-dimensional analysis of wrist motion is a growing focus in orthopedic research, however, our understanding of its validity (accuracy and reliability) remains limited. Nine human cadavers were tested to estimate wrist joint axes alignment in a postural static pose. The objective was to investigate a rater's ability to reliably align three skin- tracked wrist joint coordinate system (WJCS) definitions across baseline and reconstructive wrist states (intact, mid-carpal arthrodesis, and proximal-row carpectomy).