Hs27 fibroblast response to contact guidance cues.

Contact guidance is the phenomena of how cells respond to the topography of their external environment. The morphological and dynamic cell responses are strongly influenced by topographic features such as lateral and vertical dimensions, namely, ridge and groove widths and groove depth ([Formula: see text], respectively). However, experimental studies that independently quantify the effect of the individual dimensions as well as their coupling on cellular function are still limited. In this work, we perform extensive parametric studies in the dimensional space-well beyond the previously studied range in the literature-to explore topographical effects on morphology and migration of Hs27 fibroblasts via static and dynamic analyses of live cell images. Our static analysis reveals that the [Formula: see text] is most significant, followed by the [Formula: see text]. The fibroblasts appear to be more elongated and aligned in the groove direction as the [Formula: see text] increases, but their trend changes after 725 nm. Interestingly, the cell shape and alignment show a very strong correlation regardless of [Formula: see text]. Our dynamic analysis confirms that directional cell migration is also strongly influenced by the [Formula: see text], while the effect of the [Formula: see text] and [Formula: see text] is statistically insignificant. Directional cell migration, as observed in the static cell behavior, shows the statistically significant transition when the [Formula: see text] is 725 nm, showing the intimate links between cell morphology and migration. We propose possible scenarios to offer mechanistic explanations of the observed cell behavior.

YB-1 is elevated in medulloblastoma and drives proliferation in Sonic hedgehog-dependent cerebellar granule neuron progenitor cells and medulloblastoma cells.

Postnatal proliferation of cerebellar granule neuron precursors (CGNPs), proposed cells of origin for the SHH-associated subgroup of medulloblastoma, is driven by Sonic hedgehog (Shh) and insulin-like growth factor (IGF) in the developing cerebellum. Shh induces the oncogene Yes-associated protein (YAP), which drives IGF2 expression in CGNPs and mouse Shh-associated medulloblastomas. To determine how IGF2 expression is regulated downstream of YAP, we carried out an unbiased screen for transcriptional regulators bound to IGF2 promoters. We report that Y-box binding protein-1 (YB-1), an onco-protein regulating transcription and translation, binds to IGF2 promoter P3. We observed that YB-1 is upregulated across human medulloblastoma subclasses as well as in other varieties of pediatric brain tumors. Utilizing the cerebellar progenitor model for the Shh subgroup of medulloblastoma in mice, we show for the first time that YB-1 is induced by Shh in CGNPs. Its expression is YAP-dependent and it is required for IGF2 expression in CGNPs. Finally, both gain-of function and loss-of-function experiments reveal that YB-1 activity is required for sustaining CGNP and medulloblastoma cell (MBC) proliferation. Collectively, our findings describe a novel role for YB-1 in driving proliferation in the developing cerebellum and MBCs and they identify the SHH:YAP:YB1:IGF2 axis as a powerful target for therapeutic intervention in medulloblastomas.

A protein complex of SCRIB, NOS1AP and VANGL1 regulates cell polarity and migration, and is associated with breast cancer progression.

By analyzing public data sets of gene expression in human breast cancers we observed that increased levels of transcripts encoding the planar cell polarity (PCP) proteins SCRIB and VANGL1 correlate with increased risk of patient relapse. Experimentally, we found that reducing expression of SCRIB by short-hairpin RNAs (shRNAs) reduces the growth of human breast cancer cells in xenograft assays. To investigate SCRIB-associated proteins that might participate in the responses of breast cancer cells to altered levels of SCRIB, we used mass spectrometry and confocal microscopy. These studies reveal that SCRIB is present in at least two unique protein complexes: (1) a complex of SCRIB, ARHGEF, GIT and PAK (p21-activated kinase), and (2) a complex of SCRIB, NOS1AP and VANGL. Focusing on NOS1AP, we observed that NOS1AP colocalizes with both SCRIB and VANGL1 along cellular protrusions in metastatic breast cancer cells, but does not colocalize with either SCRIB or VANGL1 at cell junctions in normal breast cells. We investigated the effects of shRNA-mediated knockdown of NOS1AP and SCRIB in vitro, and found that reducing NOS1AP and SCRIB slows breast cancer cell migration and prevents the establishment of leading-trailing polarity. We also find that reduction of NOS1AP enhances anchorage-independent growth. Collectively these data point to the relevance of NOS1AP and SCRIB protein complexes in breast cancer.

Intra and interobserver variability of preoperative planning for surgical instrumentation in adolescent idiopathic scoliosis.

Surgical instrumentation planning for the correction of scoliosis involves many difficult decisions, especially with the introduction of multi-segmental and other instrumentation technologies. A preliminary study has shown a high variability in planning among a small group of surgeons. The purpose of this paper was to evaluate and analyze the selection of fusion levels and instrumentation choices among a more extended group of scoliosis surgeons. Thirty-two experienced spinal deformity surgeons were asked to provide their preferred posterior instrumentation planning for five patients with adolescent idiopathic scoliosis (AIS) using a graphical worksheet and the usual preoperative X-rays. Overall, the number of implants used ranged from 8 to 30 per patient (mean 16; SD 6): 71% of these were mono-axial screws, 20% multi-axial screws, and 9% hooks. The selected superior and inferior instrumented vertebrae varied up to six levels. The following significant groups of strategies were identified: A- "All Pedicle Screws Constructs" [N(A) = 103; 66%]; B- "All Hooks constructs" [N(B) = 5; 3%]; C- "Hybrid Constructs" [N(C) = 48; 31%]. A top-to-bottom attachment sequence was selected in 49% of all cases, a bottom-up in 46%, and an alternate order in 4%. A large variability in preoperative instrumentation strategy exists in AIS within an experienced group of orthopedic spine surgeons. The impact of such choices on the resulting correction is questioned and will need to be determined with adequate clinical, biomechanical, and computer simulation prospective studies.

Substrate source utilization during moderate intensity exercise with glucose ingestion in Type 1 diabetic patients.

Substrate oxidation and the respective contributions of exogenous glucose, glucose released from the liver, and muscle glycogen oxidation were measured by indirect respiratory calorimetry combined with tracer technique in eight control subjects and eight diabetic patients (5 men and 3 women in both groups) of similar age, height, body mass, and maximal oxygen uptake, over a 60-min exercise period on cycle ergometer at 50.8% (SD 4.0) maximal oxygen uptake [131.0 W (SD 38.2)]. The subjects and patients ingested a breakfast (containing approximately 80 g of carbohydrates) 3 h before and 30 g of glucose (labeled with 13C) 15 min before the beginning of exercise. The diabetic patients also received their usual insulin dose [Humalog = 9.1 U (SD 0.9); Humulin N = 13.9 U (SD 4.4)] immediately before the breakfast. Over the last 30 min of exercise, the oxidation of carbohydrate [1.32 g/min (SD 0.48) and 1.42 g/min (SD 0.63)] and fat [0.33 g/min (SD 0.10) and 0.30 g/min (SD 0.10)] and their contribution to the energy yield were not significantly different in the control subjects and diabetic patients. Exogenous glucose oxidation was also not significantly different in the control subjects and diabetic patients [6.3 g/30 min (SD 1.3) and 5.2 g/30 min (SD 1.6), respectively]. In contrast, the oxidation of plasma glucose and oxidation of glucose released from the liver were significantly lower in the diabetic patients than in control subjects [14.5 g/30 min (SD 4.3) and 9.3 g/30 min (SD 2.8) vs. 27.9 g/30 min (SD 13.3) and 21.6 g/30 min (SD 12.8), respectively], whereas that of muscle glycogen was significantly higher [28.1 g/30 min (SD 15.5) vs. 11.6 g/30 min (SD 8.1)]. These data indicate that, compared with control subjects, in diabetic patients fed glucose before exercise, substrate oxidation and exogenous glucose oxidation overall are similar but plasma glucose oxidation is lower; this is associated with a compensatory higher utilization of muscle glycogen.

Identical clonal types of Porphyromonas gingivalis or Prevotella nigrescens recovered from infected root canals and subgingival plaque.

Clinical samples from 10 infected root canals and from subgingival plaque in 10 patients were screened by anaerobic culture for black-pigmented anaerobes. A total of 17 Porphyromonas gingivalis and 9 Prevotella nigrescens were obtained from four patients and were identified by species-specific polymerase chain reaction (PCR) amplification. The arbitrarily primed PCR reaction used to examine the genetic diversity of the isolates revealed that the P. gingivalis or P. nigrescens simultaneously present in the root canal system and in subgingival plaque of all four patients were genotypically indistinguishable. These data indicate that the endodontium and the periodontium can be colonized by the same clonal types of black-pigmented anaerobes.

Treatment of mild-to-moderate hypertension: comparison between a calcium-channel blocker and a potassium-sparing diuretic.

In a multicenter study, 61 patients, 18-70 years of age, with mild-to-moderate hypertension [diastolic blood pressure (DBP) 95/114] completed a 28-week treatment. After initial placebo washout, patients were randomly allocated either to diltiazem or hydrochlorothiazide/triamterene. At the end of 12 weeks, the patients continued on the same medication if their goal blood pressure achieved (DBP less than 90; or 10 mm Hg below baseline). If not, the alternate agent was added (either diltiazem + hydrochlorothiazide/triamterene or hydrochlorothiazide/triamterene + diltiazem). At the end of 28 weeks, the intent-to-treat analysis showed that 90% on diltiazem alone, 73.7% on hydrochlorothiazide/triamterene alone, 71.4% on (diltiazem + hydrochlorothiazide/triamterene), and 57.1% on (hydrochlorothiazide/triamterene + diltiazem) achieved goal BP. End point mean values of BP and heart rate after adjusting for sex, baseline values, age, and weight showed no significant difference between groups. Forty-six percent on hydrochlorothiazide/triamterene alone and 24% on diltiazem alone reported one or more adverse events, possibly related to study medication. Patients with diltiazem as the first choice had better BP control than those on hydrochlorothiazide/triamterene alone (81.5% vs. 69.7%). Furthermore, among non-goal achievers at week 12, there was a greater response in the group when hydrochlorothiazide/triamterene was added to diltiazem than when diltiazem was added to hydrochlorothiazide/triamterene. This study suggests that in mild-to-moderate hypertension, diltiazem is better than hydrochlorothiazide/triamterene as first line therapy.

[Multifocal fractures of the mandibular symphysis. Apropos of 3 cases]. / Les fractures pluri-focales de la symphyse mandibulaire. A propos de trois cas.

Three patients presented with multiple site fractures of mandibular symphysis, associated in two cases with a bilateral subcondylar fracture. Treatment was by multiple solid osteosynthesis of mandibular body combining miniaturized screw plates and steel wire osteosynthesis. Emphasis is placed on the interest of a stable solid osteosynthesis of mandibular symphysis by screw plate, combined with osteosynthesis using a steel wire passing through the hole of a plate and into the small basilar bone fragment, allowing in this way the restitution of a perfect morphology of symphysis.

[Oh! Grandmother, what big teeth you have!]. / Oh! Mère-grand, comme vous avez de grandes dents!?...

The Association of Health and Security at Work, as part of the Social Affairs' Sector, has tried to define the existence, the scope, causes and solutions of the problem of violence that afflicts the employees of the reception centers at the hands of the residents that they care for. According to information obtained, it seems that the problem exists eventhough the physical danger is minimal. However, the impact on the workers' morale should be considered. The causes and therefore the solutions are concerned with the beneficiaries' living conditions and the working conditions offered to employees. Other factors include the service plans adapted to the residents' needs, the training, the abilities and the organization of the personnel, the quality of the functional communications as well as the ability of the establishment to diagnose and resolve the problems of administration and aggression that arise.

[Mental health services and therapists.]. / Services en santé mentale et thérapeutes.

This article describes how sectorial teams function, their realizations, difficulties and projects. The tool used is a questionnaire answered by participants of the first symposium on sectorial psychiatry.

[Sectorial psychiatry : 10 years later.]. / Psychiatrie de secteur : 10 ans après.

This article presents discussions held in workshops during the first symposium on sectorial psychiatry. The themes are : continuity in care, team work ; the use of para/professionals ; education ; consultation ; the place of the ill in society ; prevention.