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Abstract HIV entry occurs via membrane-mediated fusion of virus and target cells. Interactions between gp120 and cellular co-receptors lead to both the formation of fusion pores and release of the HIV genome into target cells. Studies using cell-cell fusion assays have demonstrated that a temperature-arrested state (TAS) can generate a stable intermediate in fusion related events. Other studies with MLV pseudotyped with HIV envelope also found that a temperature sensitive intermediate could be generated as revealed by the loss of a fluorescently labeled membrane. However, such an intermediate has never been analyzed in the context of virus infection. Therefore, we used virus-cell infection with replication competent HIV to gain insights into virus-cell fusion. We find that the TAS is an intermediate in the process culminating in the HIV infection of a target cell. In the virion-cell TAS, CD4 has been engaged, the heptad repeats of gp41 are exposed and the complex is kinetically predisposed to interact with coreceptor to complete the fusion event leading to infection.

HIV entry occurs via membrane-mediated fusion of virus and target cells. Interactions between gp120 and cellular co-receptors lead to both the formation of fusion pores and release of the HIV genome into target cells. Studies using cell-cell fusion assays have demonstrated that a temperature-arrested state (TAS) can generate a stable intermediate in fusion related events. Other studies with MLV pseudotyped with HIV envelope also found that a temperature sensitive intermediate could be generated as revealed by the loss of a fluorescently labeled membrane. However, such an intermediate has never been analyzed in the context of virus infection. Therefore, we used virus-cell infection with replication competent HIV to gain insights into viruscell fusion. We find that the TAS is an intermediate in the process culminating in the HIV infection of a target cell. In the virion-cell TAS, CD4 has been engaged, the heptad repeats of gp41 are exposed and the complex is kinetically predisposed to interact with coreceptor to complete the fusion event leading to infection. [ABSTRACT FROM AUTHOR]

Purpose: Decreased spinal extensor muscle strength in adult spinal deformity (ASD) patients is well-known but poorly understood; thus, this study aimed to investigate the biomechanical and histopathological properties of paraspinal muscles from ASD patients and predict the effect of altered biomechanical properties on spine loading., Methods: 68 muscle biopsies were collected from nine ASD patients at L4-L5 (bilateral multifidus and longissimus sampled). The biopsies were tested for muscle fiber and fiber bundle biomechanical properties and histopathology. The small sample size (due to COVID-19) precluded formal statistical analysis, but the properties were compared to literature data. Changes in spinal loading due to the measured properties were predicted by a lumbar spine musculoskeletal model., Results: Single fiber passive elastic moduli were similar to literature values, but in contrast, the fiber bundle moduli exhibited a wide range beyond literature values, with 22% of 171 fiber bundles exhibiting very high elastic moduli, up to 20 times greater. Active contractile specific force was consistently less than literature, with notably 24% of samples exhibiting no contractile ability. Histological analysis of 28 biopsies revealed frequent fibro-fatty replacement with a range of muscle fiber abnormalities. Biomechanical modelling predicted that high muscle stiffness could increase the compressive loads in the spine by over 500%, particularly in flexed postures., Discussion: The histopathological observations suggest diverse mechanisms of potential functional impairment. The large variations observed in muscle biomechanical properties can have a dramatic influence on spinal forces. These early findings highlight the potential key role of the paraspinal muscle in ASD., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The passive elastic modulus of muscle fiber appears to be size-dependent. The objectives of this study were to determine whether this size effect was evident in the mechanical testing of muscle fiber bundles and to examine whether the muscle fiber bundle cross-section is circular. Muscle fibers and fiber bundles were extracted from lumbar spine multifidus and longissimus of three cohorts: group one (G1) and two (G2) included 13 (330 ± 14 g) and 6 (452 ± 28 g) rats, while Group 3 (G3) comprised 9 degenerative spine patients. A minimum of six muscle fibers and six muscle fiber bundles from each muscle underwent cumulative stretches, each of 10% strain followed by 4 minutes relaxation. For all specimens, top and side diameters were measured. Elastic modulus was calculated as tangent at 30% strain from the stress-strain curve. Linear correlations between the sample cross sectional area (CSA) and elastic moduli in each group were performed. The correlations showed that increasing specimen CSA resulted in lower elastic modulus for both rats and humans, muscle fibers and fiber bundles. The median ratio of major to minor axis exceeded 1.0 for all groups, ranging between 1.15-1.29 for fibers and 1.27-1.44 for bundles. The lower elastic moduli with increasing size can be explained by relatively less collagenous extracellular matrix in the large fiber bundles. Future studies of passive property measurement should aim for consistent bundle sizes and measuring diameters of two orthogonal axes of the muscle specimens., (© 2021. The Author(s).)

Traditional load-control musculoskeletal and finite element (FE) models of the spine fail to accurately predict in vivo intervertebral joint loads due mainly to the simplifications and assumptions when estimating redundant trunk muscle forces. An alternative powerful protocol that bypasses the calculation of muscle forces is to drive the detailed FE models by image-based in vivo displacements. Development of subject-specific models, however, both involves the risk of extensive radiation exposures while imaging in supine and upright postures and is time consuming in terms of the reconstruction of the vertebrae, discs, ligaments, and facets geometries. This study therefore aimed to introduce a remedy for the development of subject-specific FE models by scaling the geometry of an existing detailed FE model of the T12-S1 lumbar spine. Five subject-specific scaled models were driven by their own radiography image-based displacements in order to predict joint loads, ligament forces, facet joint forces, and disc fiber strains during relaxed upright as well as moderate flexion and extension tasks. The predicted intradiscal pressures were found in adequate agreement with in vivo data for upright, flexion, and extension tasks. There were however large intersubject variations in the estimated joint loads and facet forces., (© 2019 John Wiley & Sons, Ltd.)

Surgical management of the carotid disease remains controversial in patients affected with coronary artery atheromatous disease. We report the Montreal Heart Institute experience on the influence of carotid disease on postoperative neurologic events of 501 consecutive patients operated on for coronary revascularization during the period from January 1994 to December 1994. There were 381 men and 114 women averaging 62 +/- 9 years old. Major risk factors were high blood pressure (35%), and smoking habit (48%). Fifty-nine patients presented clinical signs of carotid atheromatosis and among them 21 had significant carotid stenosis (> 80% decrease of cross sectional area). During surgery, the mean duration of extracorporeal circulation (ECC) was 76 +/- 31 minutes and the mean perfusion pressure (MPP) was 70 +/- 11 mmHg. The use of inotropic drugs was mandatory in 26% of the cases and the mean arterial lactate (AL) dosage during ECG was 3.07 +/- 1.35 mM/L. During the perioperative period, 13 (2.5%) patients sustained neurologic disturbances of which 5 (1%) were lateralized. Among them, 8 completely recovered whereas 3 of the 5 with permanent damage died. None of the patients with preoperative stigmata of carotid disease experienced lateralized neurologic deficit. Multivariate regression analysis identified the use of vasopressor drugs and perioperative increase of AL as predictive factors. We conclude that in our series, the incidence of neurologic complications was low. The presence of carotid atheromatosis did not increase the postsurgical risk of cerebrovascular accident, however, the increased incidence of neurologic events associated with inotropic drugs and increased AL suggests a direct link with a systemic oxygen debt. Consequently, we do no recommend concurrent prophylactic surgery during coronary artery revascularization.