Linea alba 3D morphometric variability by CT scan exploration.

PURPOSE: The width of the Linea alba, which is often gauged by inter-rectus distance, is a key risk factor for incisional hernia and recurrence. Previous studies provided limited descriptions with no consideration for width, location variability, or curvature. We aimed to offer a comprehensive 3D anatomical analysis of the Linea alba, emphasizing its variations across diverse demographics. METHODS: Using open source software, 2D sagittal plane and 3D reconstructions were performed on 117 patients' CT scans. Linea alba length, curvature assessed by the sagitta (the longest perpendicular segment between xipho-pubic line and the Linea alba), and continuous width along the height were measured. RESULTS: The Linea alba had a rhombus shape, with a maximum width at the umbilicus of 4.4 ± 1.9 cm and a larger width above the umbilicus than below. Its length was 37.5 ± 3.6 cm, which increased with body mass index (BMI) (p < 0.001), and was shorter in women (p < 0.001). The sagitta was 2.6 ± 2.2 cm, three times higher in the obese group (p < 0.001), majorated with age (p = 0.009), but was independent of gender (p = 0.212). Linea alba width increased with both age and BMI (p < 0.001-p = 0.002), being notably wider in women halfway between the umbilicus and pubis (p = 0.007). CONCLUSION: This study provides an exhaustive 3D description of Linea alba's anatomical variability, presenting new considerations for curvature. This method provides a patient-specific anatomy description of the Linea alba. Further studies are needed to determine whether 3D reconstruction correlates with pathologies, such as hernias and diastasis recti.

Effect of antibiotics on mechanical properties of Bordetella pertussis examined by atomic force microscopy.

In recent years, the coevolution of microorganisms with current antibiotics has increased the mechanisms of bacterial resistance, generating a major health problem worldwide. Bordetella pertussis is a bacterium that causes whooping cough and is capable of adopting different states of virulence, i.e. virulent or avirulent states. In this study, we explored the nanomechanical properties of both virulent and avirulent B. pertussis as exposed to various antibiotics. The nanomechanical studies highlighted that only virulent B. pertussis cells undergo a decrease in their cell elastic modulus and height upon antimicrobial exposure, whereas their avirulent counterparts remain unaffected. This study also permitted to highlight different mechanical properties of individual cells as compared to those growing in close contact with other individuals. In addition, we analyzed the presence on the bacterial cell wall of Filamentous hemagglutinin adhesin (FHA), the major attachment factor produced by virulent Bordetella spp., under different virulence conditions by Force Spectroscopy.

The Impact of HIV-Associated Neurocognitive Impairment on Driving Performance in Commercial Truck Drivers.

Driving ability can be diminished amongst people with HIV with associated neurocognitive impairment (NCI). We explore the relationship between HIV status, NCI and driving ability in professional truck drivers. Forty male professional drivers (20 HIV-positive; mean age = 39.20 ± 7.05) completed a neuropsychological test battery, two driving simulator tasks that assessed driving ability, and a driving history and habits questionnaire. A higher proportion of HIV-positive drivers exhibited impaired overall cognitive performance (p ≤ 0.001). Overall, drivers with NCI (defined as z ≤ 1.00) were more likely than those without NCI to crash (p = 0.002). There were no significant between-group (HIV-positive versus HIV-negative) differences with regard to self-reported on-road driving events. Professional drivers with NCI, as measured on a driving simulator, are at increased risk of making driving errors under high-risk conditions compared to their neurocognitively normal counterparts. These data should inform driver health management with regard to annual medical screening and surveillance.

RESUMEN: La capacidad de conducción puede verse disminuida entre las personas con VIH con deterioro neurocognitivo asociado (neurocognitive impairment, NCI). Exploramos la relación entre la situación frente al VIH, el NCI y la capacidad de conducción en conductores profesionales de camiones. Cuarenta conductores profesionales masculinos (20 seropositivos, edad media = 39.20 ± 7.05) completaron una batería de pruebas neuropsicológicas, dos tareas de simulador de conducción que evaluaron la capacidad de conducción y un cuestionario de hábitos y antecedentes de conducción. Una mayor proporción de conductores VIH positivos exhibió un desempeño cognitivo general deficiente (p ≤ 0.001). En general, los conductores con NCI (definido como z ≤ 1.00) tenían más probabilidades de chocar que aquellos sin NCI (p = 0.002). No hubo diferencias significativas entre los grupos (VIH positivo frente a VIH negativo) con respecto a los eventos autoinformados de conducción en carretera. Los conductores profesionales con NCI, según lo medido en un simulador de conducción, tienen un mayor riesgo de cometer errores de conducción en condiciones de alto riesgo en comparación con sus homólogos neurocognitivamente normales. Estos datos deberían informar a la gestión de la salud del conductor en lo que respecta a la vigilancia y los exámenes médicos anuales.

Mechanical effects of load speed on the human colon.

The aim of this study was to examine the mechanical behavior of the colon using tensile tests under different loading speeds. Specimens were taken from different locations of the colonic frame from refrigerated cadavers. The specimens were submitted to uniaxial tensile tests after preconditioning using a dynamic load (1 m/s), intermediate load (10 cm/s), and quasi-static load (1 cm/s). A total of 336 specimens taken from 28 colons were tested. The stress-strain analysis for longitudinal specimens indicated a Young's modulus of 3.17 ±â€¯2.05 MPa under dynamic loading (1 m/s), 1.74 ±â€¯1.15 MPa under intermediate loading (10 cm/s), and 1.76 ±â€¯1.21 MPa under quasi-static loading (1 cm/s) with p < 0.001. For the circumferential specimen, the stress-strain curves indicated a Young's modulus of 3.15 ±â€¯1.73 MPa under dynamic loading (1 m/s), 2.14 ±â€¯1.3 MPa under intermediate loading (10 cm/s), and 0.63 ±â€¯1.25 MPa under quasi-static loading (1 cm/s) with p < 0.001. The curves reveal two types of behaviors of the colon: fast break behavior at high speed traction (1 m/s) and a lower break behavior for lower speeds (10 cm/s and 1 cm/s). The circumferential orientation required greater levels of stress and strain to obtain lesions than the longitudinal orientation. The presence of taeniae coli changed the mechanical response during low-speed loading. Colonic mechanical behavior varies with loading speeds with two different types of mechanical behavior: more fragile behavior under dynamic load and more elastic behavior for quasi-static load.

Influence of gender, age, shelf-life, and conservation method on the biomechanical behavior of colon tissue under dynamic solicitation.

BACKGROUND: Data from biomechanical tissue sample studies of the human digestive tract are highly variable. The aim of this study was to investigate 4 factors which could modify the mechanical response of human colonic specimens placed under dynamic solicitation until tissue rupture: gender, age, shelf-life and conservation method. METHODS: We performed uniaxial dynamic tests of human colonic specimens. Specimens were taken according to three different protocols: refrigerated cadavers without embalming, embalmed cadavers and fresh colonic tissue. A total of 143 specimens were subjected to tensile tests, at a speed of 1 m s-1. FINDINGS: Young's modulus of the different conservation protocols are as follows: embalmed, 3.08 ±â€¯1.99; fresh, 2.97 ±â€¯2.59; and refrigerated 3.17 ±â€¯2.05. The type of conservation does not modify the stiffness of the tissue (p = 0.26) but does modify the stress necessary for rupture (p < 0.001) and the strain required to obtain lesions of the outer layer and the inner layer (p < 0.001 and p < 0.05, respectively). Gender is also a factor responsible for a change in the mechanical response of the colon. The age of the subjects and the shelf-life of the bodies did not represent factors influencing the mechanical behavior of the colon (p > 0.05). INTERPRETATION: The mechanical response of the colon tissue showed a biphasic injury process depending on gender and method of preservation. The age and shelf-life of anatomical subjects do not alter the mechanical response of the colon.

Metaplastic woven bone in bone metastases: A Fourier-transform infrared analysis and imaging of bone quality (FTIR).

Most osteolytic tumors are in fact mixed and contain an osteoblastic component associated with the predominant osteolytic areas. This metaplastic woven bone is always evidenced by histological analysis even in the absence of radiological expression. Metaplastic bone formation reflects the activation of new osteoblasts coming from the stimulation of the dormant lining cells. Twelve patients with secondary metastases of the iliac crest evidenced by hot spots on a 99Tc-MBP san were diagnosed by histomorphometry on bone biopsies. Fourier Transformed InfraRed analysis and Imaging (FTIRI) was used on 4µm thick sections of undecalcified bone. The mineralization degree, carbonate substitution, crystallinity and the cross-links ratio of collagen (1660/1690cm-1 bands) were determined. The matrix characteristics were analyzed and imaged in the pre-existing residual bone and in the metaplastic woven bone in the vicinity of the tumor cells. FTIRI provided images of the phosphate, amide and combination of peak ratio after having selected the peaks of interest. In addition, the matrix properties can be measured and compared between the old and newly-formed bones. Woven bone appeared poorly calcified with a low phosphate/amide ratio (P=0.03) crystallinity (P<0.0001) and carbonate substitution (P=0.003). Collagen was less mature as evidenced by lower cross-links (P=0.01). Woven bone associated with bone metastasis appears poorly mineralized and rapidly elaborated by osteoblasts. The collagenous phase of the bone matrix has a low level of reticulation. FTIRI is a powerful tool to measure and visualize the various components of the bone matrix in human diseases.

Novel mutations in DNAJB6 cause LGMD1D and distal myopathy in French families.

BACKGROUND AND PURPOSE: The aim was to determine the genetic background of unknown muscular dystrophy in five French families. METHODS: Twelve patients with limb girdle muscular dystrophy or distal myopathy were clinically evaluated. Gene mutations were identified using targeted exon sequencing and mutated DNAJB6 was tested in vitro. RESULTS: Five patients presented with distal lower limb weakness whilst others had proximal presentation with a variable rate of progression starting at the mean age of 38.5 years. Two novel mutations (c.284A>T, p.Asn95Ile, two families; and c.293_295delATG, p.Asp98del, one family) as well as the previously reported c.279C>G (p.Phe93Leu, two families) mutation in DNAJB6 were identified. All showed a reduced capacity to prevent protein aggregation. CONCLUSIONS: The mutational and phenotypical spectrum of DNAJB6-caused muscle disease is larger than previously reported, including also dysphagia. The originally reported c.279C>G (p.Phe93Leu) mutation is now identified in four different populations and appears to be a mutational hotspot. Our report confirms that some DNAJB6 mutations cause distal-onset myopathy and hence DNAJB6 defects should be considered broadly in dominant muscular dystrophy families.

Narrow hybrid zones in spite of very low population differentiation in neutral markers in an island bird species complex.

Patterns of phenotypic and genic frequencies across hybrid zones provide insight into the origin and evolution of reproductive isolation. The Reunion grey white-eye, Zosterops borbonicus, exhibits parapatrically distributed plumage colour forms across the lowlands of the small volcanic island of Reunion (Mascarene archipelago). These forms meet and hybridize in regions that are natural barriers to dispersal (rivers, lava fields). Here, we investigated the relationship among patterns of differentiation at neutral genetic (microsatellite) markers, phenotypic traits (morphology and plumage colour) and niche characteristics across three independent hybrid zones. Patterns of phenotypic divergence revealed that these hybrid zones are among the narrowest ever documented in birds. However, the levels of phenotypic divergence stand in stark contrast to the lack of clear population neutral genetic structure between forms. The position of the hybrid zones coincides with different natural physical barriers, yet is not associated with steep changes in vegetation and related climatic variables, and major habitat transitions are shifted from these locations by at least 18 km. This suggests that the hybrid zones are stabilized over natural dispersal barriers, independently of environmental boundaries, and are not associated with niche divergence. A striking feature of these hybrid zones is the very low levels of genetic differentiation in neutral markers between forms, suggesting that phenotypic divergence has a narrow genetic basis and may reflect recent divergence at a few linked genes under strong selection, with a possible role for assortative mating in keeping these forms apart.

5B9, a monoclonal antiplatelet factor 4/heparin IgG with a human Fc fragment that mimics heparin-induced thrombocytopenia antibodies.

Essentials No humanized monoclonal antibody was available to study heparin-induced thrombocytopenia (HIT). We developed the first anti-platelet factor 4 (PF4)/heparin antibody with a human Fc fragment. This antibody (5B9) fully mimics the effects of human HIT antibodies. 5B9 binds two regions within PF4 that may be critical for the pathogenicity of HIT antibodies. SUMMARY: Background The diagnosis of heparin-induced thrombocytopenia (HIT) is based on clinical and biological criteria, but a standard is lacking for laboratory assays. Moreover, no humanized HIT antibody is available for pathophysiological studies. Objective To characterise 5B9, a chimeric monoclonal antibody, which fully mimics the effects of human HIT antibodies. Methods/Results 5B9, a chimeric anti-platelet factor 4/heparin complexes IgG1 antibody, was obtained after immunizing specific transgenic mice. 5B9 induced heparin FcγRIIA-dependent platelet aggregation and tissue factor mRNA synthesis in monocytes. It also induced significant thrombocytopenia and thrombin generation in mice expressing human PF4 and FcγRIIA receptors. The binding of 5B9 to PF4/H complexes was inhibited by 15 of 25 HIT plasma samples and only three of 25 samples containing non-pathogenic anti-PF4/H antibodies. KKO, a murine IgG2b HIT antibody, also inhibited the binding of 5B9 to PF4/H, suggesting that epitopes recognized by both antibodies are close. A docking analysis based on VH and VL sequences of 5B9 showed that binding of 5B9 Fab to PF4 involved 12 and 12 residues in B and D monomers, respectively, including seven previously identified as critical to the formation of a PF4/KKO complex. Two regions (Asp-7 to Thr-15 and Ala-32 to Thr-38) therefore appeared important for the binding of 5B9 and KKO on PF4 modified by heparin. Conclusions 5B9 is the first anti-PF4/H monoclonal antibody with a human Fc fragment, which induces similar cellular activation as HIT antibodies. Moreover, 5B9 binds epitopes within PF4 that are likely to be critical for the pathogenicity of HIT antibodies.

Chondrodysplasia with multiple dislocations: comprehensive study of a series of 30 cases.

The group of chondrodysplasia with multiple dislocations includes several entities, characterized by short stature, dislocation of large joints, hand and/or vertebral anomalies. Other features, such as epiphyseal or metaphyseal changes, cleft palate, intellectual disability are also often part of the phenotype. In addition, several conditions with overlapping features are related to this group and broaden the spectrum. The majority of these disorders have been linked to pathogenic variants in genes encoding proteins implicated in the synthesis or sulfation of proteoglycans (PG). In a series of 30 patients with multiple dislocations, we have performed exome sequencing and subsequent targeted analysis of 15 genes, implicated in chondrodysplasia with multiple dislocations, and related conditions. We have identified causative pathogenic variants in 60% of patients (18/30); when a clinical diagnosis was suspected, this was molecularly confirmed in 53% of cases. Forty percent of patients remain without molecular etiology. Pathogenic variants in genes implicated in PG synthesis are of major importance in chondrodysplasia with multiple dislocations and related conditions. The combination of hand features, growth failure severity, radiological aspects of long bones and of vertebrae allowed discrimination among the different conditions. We propose key diagnostic clues to the clinician.

Head impact in a snowboarding accident.

To effectively prevent sport traumatic brain injury (TBI), means of protection need to be designed and tested in relation to the reality of head impact. This study quantifies head impacts during a typical snowboarding accident to evaluate helmet standards. A snowboarder numerical model was proposed, validated against experimental data, and used to quantify the influence of accident conditions (speed, snow stiffness, morphology, and position) on head impacts (locations, velocities, and accelerations) and injury risk during snowboarding backward falls. Three hundred twenty-four scenarios were simulated: 70% presented a high risk of mild TBI (head peak acceleration >80 g) and 15% presented a high risk of severe TBI (head injury criterion >1000). Snow stiffness, speed, and snowboarder morphology were the main factors influencing head impact metrics. Mean normal head impact speed (28 ± 6 km/h) was higher than equivalent impact speed used in American standard helmet test (ASTM F2040), and mean tangential impact speed, not included in standard tests, was 13.8 (±7 km/h). In 97% of simulated impacts, the peak head acceleration was below 300 g, which is the pass/fail criteria used in standard tests. Results suggest that initial speed, impacted surface, and pass/fail criteria used in helmet standard performance tests do not fully reflect magnitude and variability of snowboarding backward-fall impacts.

Dynamic biomechanical characterization of colon tissue according to anatomical factors.

INTRODUCTION: The aim of this study was to determine the mechanical response of colonic specimens retrieved from the entire human colon and placed under dynamic solicitation until the tissue ruptured. MATERIAL AND METHODS: Specimens were taken from 20 refrigerated cadavers from different locations of the colonic frame (ascending, transverse, descending and sigmoid colon) in two different directions (longitudinal and circumferential), with or without muscle strips (taenia coli). A total of 120 specimens were subjected to tensile tests, after preconditioning, at the speed of 1m/s. RESULTS: High-speed video analysis showed a bilayer injury process with an initial rupture of the serosa / external muscular layer followed by a second rupture of the inner layer consisting of the internal muscle / submucosa / mucosa. The mechanical response was biphasic, with a first point of initial damage followed by a complete rupture. The levels of stress and strain at the failure site were statistically greater in terms of circumferential stress (respectively 69±22% and 1.02±0.50MPa) than for longitudinal stress (respectively 55±32% and 0.70±0.34MPa). The difference between longitudinal and circumferential stress was not statistically significant (3.17±2.05MPa for longitudinal stress and 3.15±1.73MPa for circumferential stress). The location on colic frame significantly modified the mechanical response both longitudinally and circumferentially, whereas longitudinal taenia coli showed no mechanical influence. CONCLUSION: The mechanical response of the colon specimen under dynamic uniaxial solicitation showed a bilayer and biphasic injury process depending on the direction of solicitation and colic localization. Furthermore these results could be integrated into a numeric model reproducing abdominal trauma to better understand and prevent intestinal injuries.

Fibrodysplasia ossificans progressiva. A case report and focus on the BMP signaling pathway.

Fibrodysplasia ossificans progressiva is a very rare heritable disease characterized by a progressive heterotopic endochondal ossification, occurring in the first decade of life, and leading thereafter to a severe ankylosis of the spine, limbs and jaw, with a progressive and severe functional disability. To date the cause of the disease remains unknown and no medical treatment has been proved efficient. It has recently been shown that a recurrent mutation in activation domain of the activin-receptor IA (ACVR1), a BMP receptor, could lead to an abnormal signalling pathway of BMP-4 and contribute to the occurrence of the devastating lesions characteristic of the disease.

Cysteinyl leukotriene receptor (CysLT) antagonists decrease pentylenetetrazol-induced seizures and blood-brain barrier dysfunction.

Current evidence suggests that inflammation plays a role in the pathophysiology of seizures. In line with this view, selected pro-inflammatory arachidonic acid derivatives have been reported to facilitate seizures. Kainate-induced seizures are accompanied by leukotriene formation, and are reduced by inhibitors of LOX/COX pathway. Moreover, LTD4 receptor blockade and LTD4 synthesis inhibition suppress pentylenetetrazol (PTZ)-induced kindling and pilocarpine-induced recurrent seizures. Although there is convincing evidence supporting that blood-brain-barrier (BBB) dysfunction facilitates seizures, no study has investigated whether the anticonvulsant effect of montelukast is associated with its ability to maintain BBB integrity. In this study we investigated whether montelukast and other CysLT receptor antagonists decrease PTZ-induced seizures, as well as whether these antagonists preserve BBB during PTZ-induced seizures. Adult male albino Swiss mice were stereotaxically implanted with a cannula into the right lateral ventricle, and two electrodes were placed over the parietal cortex along with a ground lead positioned over the nasal sinus for electroencephalography (EEG) recording. The effects of montelukast (0.03 or 0.3 µmol/1 µL, i.c.v.), pranlukast (1 or 3 µmol/1 µL, i.c.v.), Bay u-9773 (0.3, 3 or 30 nmol/1 µL, i.c.v.), in the presence or absence of the agonist LTD4 (0.2, 2, 6 or 20 pmol/1 µL, i.c.v.), on PTZ (1.8 µmol/2 µL)-induced seizures and BBB permeability disruption were determined. The animals were injected with the antagonists, agonist or vehicle 30 min before PTZ, and monitored for additional 30 min for the appearance of seizures by electrographic and behavioral methods. BBB permeability was assessed by sodium fluorescein method and by confocal microscopy for CD45 and IgG immunoreactivity. Bay-u9973 (3 and 30 nmol), montelukast (0.03 and 0.3 µmol) and pranlukast (1 and 3 µmol), increased the latency to generalized seizures and decreased the mean amplitude of EEG recordings during seizures. LTD4 (0.2 and 2 pmol) reverted the anticonvulsant effect of montelukast (0.3 µmol). Montelukast (0.03 and 0.3 µmol) prevented PTZ-induced BBB disruption, an effect that was reversed by LTD4 at the dose of 6 pmol, but not at the doses 0.2 and 2 pmol. Moreover, the doses of LTD4 (0.2 and 2 pmol) that reverted the effect of montelukast on seizures did not alter montelukast-induced protection of BBB, dissociating BBB protection and anticonvulsant activity. Confocal microscopy analysis revealed that 1. PTZ increased the number of CD45+ and double-immunofluorescence staining for CD45 and IgG cells in the cerebral cortex, indicating BBB leakage with leukocyte infiltration; 2. while LTD4 (6 pmol) potentiated, montelukast decreased the effect of PTZ on leukocyte migration and BBB, assessed by double-immunofluorescence staining for CD45 and IgG cells in the cannulated hemisphere. Our data do not allow us ruling out that mechanisms unrelated and related to BBB protection may co-exist, resulting in decreased seizure susceptibility by montelukast. Notwithstanding, they suggest that CysLT1 receptors may be a suitable target for anticonvulsant development.

Osteomalacia in a patient with Paget's bone disease treated with long-term etidronate.

A 93 year-old woman with Paget's disease of bone had been treated with etidronate without interruption during 20 years. The daily dose was usual (5mg/kg/day) but this prescription had never been stopped by her physicians. Two fractures had already occurred in pagetic (right tibia) and non pagetic bones (right fibula) within the last 2 years, and she presented rib fractures, another right tibia fracture and right femur fracture during hospitalization time. X-rays films showed major osteolysis of left ulna and right tibia. Blood samples and technetium bone scan brought no evidence for sarcoma or lytic evolution of the disease. A transiliac bone biopsy on non pagetic bone site confirmed the diagnosis of osteomalacia (increased osteoid parameters), with secondary hyperparathyroidism (hook resorption). In Paget's disease of bone, continuous treatment by etidronate may induce generalized osteomalacia, and increase the risk of fracture in both pagetic and non-pagetic bones. Whereas physicians and pharmaceutical industry try to improve the observance of those drugs, this striking observation also points out that a prescription always needs to be updated.

[Criteria of pregnancy termination in women with preeclampsia]. / Critères d'arrêt de la grossesse en cas de prééclampsie.

Few studies establishing clear criteria for the medical interruption of a pregnancy complicated by PE are available today. Most of these studies are either retrospective or observational. When combining an analysis of the available literature together with the experts' opinions, one can propose the following set of criteria for therapeutic interruption of pregnancy in the setting of PE, which apply mainly for the severe forms of the disease. These criteria can be subdivided into maternal and fetal criteria. Maternal criteria are a severe uncontrollable HT, eclampsia, acute pulmonary edema, retro placental haematoma, oligura (<100 ml in 4 hours) resistant to appropriate fluid expansion, persistent signs of imminent eclampsia (headache or visual disturbances), persistent epigastric pain, HELLP syndrome, new-onset renal failure and a gestation time within the first 24 weeks. The fetal criteria are prolonged and variable fetal heart rate (FHR) decelerations, a short term variability in FHR <3 bpm, a Manning score < or =4 on two separate occasions, severe oligohydramnios, an estimated fetal weight below the 5(th) percentile beyond the 32(nd) week of amenorrhea and an inverted diastolic flow in the umbilical artery beyond the 32(nd) week of amenorrhea. In case of non-severe PE beyond the 36(th) week of amenorrhea, interruption of the pregnancy must be considered.