Trapeziometacarpal (TMC) arthroplasty under Wide Awake Local Anesthesia with No Tourniquet (WALANT) versus Local Anesthesia with peripheral nerve blocks (LAPNV): Perioperative pain and early functional results in 30 patients.

We hypothesized that WALANT would provide similar perioperative analgesic comfort compared to local anesthesia with peripheral nerve blocks (LAPNV). We analyzed whether the patient's active participation during surgery would improve its early functional results. We did a retrospective, single study in an outpatient surgery unit, comparing two types of surgery: trapeziometacarpal arthroplasty (TMCA) under LAPNV and TMCA under WALANT. Fifteen patients were included per group. Pain levels were determined during anesthesia induction, intraoperatively, postoperatively, at rest and during activity at the last follow-up visit. The overall satisfaction with the surgery and time to resume daily activities and work were documented. The statistical analysis was performed on SAS software with an ANOVA. The significance threshold was set at 0.05. The groups were comparable on age, sex, dominant side, and operated side. No patients were lost to follow-up. The mean follow-up was 4 months (2.3-11). The QuickDASH score was 4.93 for TMCA under WALANT vs. 13.47 for TMCA under LAPNV (p = 0.01). There was no loosening, dislocation, or major complication. Our study showed that TMCA performed with WALANT yields similar results to the same procedure with LAPNV for perioperative pain relief without additional complications. Functional scores seem to be slightly improved with WALANT compared to LAPNV, but these results should be confirmed with longer follow up.

Strategic methodology to set priorities for sustainable hydropower development in a biodiversity hotspot.

Massive exploitation of freshwater systems for hydropower generation in developing countries is challenging sustainability due to cumulative environmental impacts in regions with high endemism. Habitat fragmentation is recognized as a major impact on river ecosystems. The nature and magnitude of connectivity loss depend on characteristics of the hydropower projects, and of the threatened fish communities. In areas where appropriate mitigation technology is lacking, there is a need to identify the fish species that are most at risk to better concentrate efforts. This paper aimed to set conservation priorities for sustainable hydropower development by analyzing native fish species and project characteristics. The Chilean ichthyogeographic province, an ecoregion with high endemism and massive hydropower projects development, has been considered as a case study. By using overlapping information on the characteristics of 1124 hydropower projects and distribution of native fish species, we identified three project categories of projects based on their need for mitigation. These were projects where mitigation was considered: a) not required (15%), b) required and feasible (35%), and c) required but challenging (50%). Projects where mitigation was not required were located at sites where native fish were absent and/or where water intakes allowed fish to pass. Interestingly, projects where mitigation was feasible were inhabited by a species assemblage that comprised the genus Trichomycterus, Diplomystes and Percilia, and the species Ch. pisciculus and B. maldonadoi. This finding emphasizes the need to develop a multispecific fishway that can accommodate this group. Projects where mitigation would be difficult to achieve were located at sites with a variety of different assemblages, thus making a standard fish pass solution challenging and site-specific. This study advances understanding for the need to develop mitigation strategies and technologies in ecoregions of high endemism threatened by hydropower and to prioritize the construction of planned projects.

Ameloblastoma of the jaws: Management and recurrence rate.

INTRODUCTION: Ameloblastoma is a rare, benign odontogenic tumour associated with a high recurrence rate. It accounts for 1% of all tumours of the jaws. The purpose of this study was to compare the ameloblastoma recurrence rate according to the type of treatment: radical or conservative. PATIENTS AND METHODS: All patients with a diagnosis of ameloblastoma between 1991 and 2013 were retrospectively identified in order to extract topographic, radiological, and histological data and the type of treatment: conservative (marsupialization, enucleation, curettage) or radical (segmental resection) and to compare the recurrence rate according to the type of treatment. RESULTS: Twenty-seven patients were included, managed by conservative treatment (CT) in 22 cases and radical treatment (RT) in 14 cases. The recurrence rate was 90.9% in the CT group and 9.1% in the RT group (P=0.025) with a mean follow-up of 56.2 months. DISCUSSION: The recurrence rate after conservative treatment was higher than that after radical treatment. These results are similar to those reported in the literature. The choice of treatment must be adapted to the macroscopic and histological characteristics of each tumour and to the patient.

Development of a lab-on-chip electrochemical biosensor for water quality analysis based on microalgal photosynthesis.

The present work was dedicated to the development of a lab-on-chip device for water toxicity analysis and more particularly herbicide detection in water. It consists in a portable system for on-site detection composed of three-electrode electrochemical microcells, integrated on a fluidic platform constructed on a glass substrate. The final goal is to yield a system that gives the possibility of conducting double, complementary detection: electrochemical and optical and therefore all materials used for the fabrication of the lab-on-chip platform were selected in order to obtain a device compatible with optical technology. The basic detection principle consisted in electrochemically monitoring disturbances in metabolic photosynthetic activities of algae induced by the presence of Diuron herbicide. Algal response, evaluated through oxygen (O2) monitoring through photosynthesis was different for each herbicide concentration in the examined sample. A concentration-dependent inhibition effect of the herbicide on photosynthesis was demonstrated. Herbicide detection was achieved through a range (blank - 1 µM Diuron herbicide solution) covering the limit of maximum acceptable concentration imposed by Canadian government (0.64 µM), using a halogen white light source for the stimulation of algal photosynthetic apparatus. Superior sensitivity results (limit of detection of around 0.1 µM) were obtained with an organic light emitting diode (OLED), having an emission spectrum adapted to algal absorption spectrum and assembled on the final system.

The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers.

BACKGROUND: The TP53 pathway, in which TP53 and its negative regulator MDM2 are the central elements, has an important role in carcinogenesis, particularly in BRCA1- and BRCA2-mediated carcinogenesis. A single nucleotide polymorphism (SNP) in the promoter region of MDM2 (309T>G, rs2279744) and a coding SNP of TP53 (Arg72Pro, rs1042522) have been shown to be of functional significance. METHODS: To investigate whether these SNPs modify breast cancer risk for BRCA1 and BRCA2 mutation carriers, we pooled genotype data on the TP53 Arg72Pro SNP in 7011 mutation carriers and on the MDM2 309T>G SNP in 2222 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analysed using a Cox proportional hazards model within a retrospective likelihood framework. RESULTS: No association was found between these SNPs and breast cancer risk for BRCA1 (TP53: per-allele hazard ratio (HR)=1.01, 95% confidence interval (CI): 0.93-1.10, P(trend)=0.77; MDM2: HR=0.96, 95%CI: 0.84-1.09, P(trend)=0.54) or for BRCA2 mutation carriers (TP53: HR=0.99, 95%CI: 0.87-1.12, P(trend)=0.83; MDM2: HR=0.98, 95%CI: 0.80-1.21, P(trend)=0.88). We also evaluated the potential combined effects of both SNPs on breast cancer risk, however, none of their combined genotypes showed any evidence of association. CONCLUSION: There was no evidence that TP53 Arg72Pro or MDM2 309T>G, either singly or in combination, influence breast cancer risk in BRCA1 or BRCA2 mutation carriers.

Dermatitis laboral por cromo: a propósito de un caso / Workplace dermatitis due to contact with chromium: a clinical report

Se presenta un caso clínico de dermatitis alérgica de contacto por cromo (DACC) en un paciente con antecedentes de exposición laboral a bicromato de sodio corroborada por test epicutáneo. El caso presentado refleja las características clínicas, cronológicas y evolutivas descritas en la literatura internacional. La dermatits de contacto por cromo es una causa muy frecuente de dermatitis ocupacional aunque no se conoce la prevalencia de estos casos en nuestro país. El diagnóstico de dermatitis alérgica de contacto al cromo de tipo laboral tiene gran importancia por el pronóstico funcional y laboral en los trabajadores afectados.

[Comparison of two electrical stimulation protocols on quadriceps muscle after anterior cruciate ligament surgery. Feasability study]. / Etude comparative de deux protocoles d'électrostimulation du quadriceps après chirurgie du ligament croisé antérieur. Etude de faisabilité.

OBJECTIVES: To evaluate the feasibility of a study comparing the effects of two protocols of electrical stimulation of the quadriceps femoris after anterior cruciate ligament surgery. MATERIAL: Seven sportsmen with a mean age of 26 yrs were randomly grouped in two: a 20 Hz stimulated group (4 patients) and a 80 Hz stimulated group (3 patients). After surgery all patients received electrical stimulation of the quadriceps femoris, five days a week, for 12 weeks, and had a standard program of voluntary contractions. The main outcome assessed before and three months after surgery were: quadriceps and hamstring peak torque at 90, 180 and 240 degrees /second, maximal isometric quadriceps at 75 degrees of flexion and muscle and subcutaneous fat volumes of the thigh using MRI. RESULTS: After 12 weeks of rehabilitation, the thigh muscle volume deficit of the operated limb was between 3 and 9% in the 20 Hz stimulated group and between 1 and 2% in the 80 Hz stimulated group. Quadriceps peak torque deficit was less than 30% except for two patients in the 20 Hz stimulated group. Maximal isometric quadriceps deficit of the operated limb was higher than 30% except for two patients in the 20 Hz stimulated group. CONCLUSION: The study showed that comparison of two protocols of electrical stimulation of the quadriceps femoris after anterior cruciate ligament surgery is possible if stimulation period is not more than four weeks.

[3D preliminary analysis gait in stroke patients: knee flexion in compensatory strategies]. / Analyse préliminaire 3D de la marche de l'hémiplégique: rôle de la flexion du genou dans la stratégie de récupération fonctionnelle.

OBJECTIVE: The aim of this preliminary study was to assess strategies of walking a stride in stroke patients with spastic right hemiplegia. MATERIAL AND METHODS: Gait was recorded in 3D in seven patients without other locomotion disorders. Kinematics data were studied only on the sagittal plane. The position and trajectory markers on the right side were studied during the swing phase in comparison with static standing position. Results were confronted with angular data. RESULTS: Three walking models were defined: 1) near normal gait with normal mobility in the knee; 2) gait with hicking while the flexion of the knee was reduced; 3) gait with a "talus" foot without motor recovery necessitating a pendular movement. DISCUSSION: The second pathological group was characterized with insufficient flexion in the knee in lifting the foot from the floor. In this group, patients adopted a compensation strategy with hicking in making the stride without touching the floor. We raised the question of limiting this adaptive strategy in order to enhance their remaining mobility. CONCLUSION: A 3D strategy gait analysis, before therapeutic choices, seems to confirm the value of analysing kinematic data in stroke patients with hemiplegia. The amplitude of knee mobility and hip compensation strategy can be specifically studied to improve the effectiveness of therapeutic strategies (orthesis, selective tibial neurotomy, botulinum toxin).

Effects of two electrical stimulation frequencies in thigh muscle after knee surgery.

The purpose of this study was to compare the effects of two protocols of electrical stimulation combined with voluntary contractions on the recovery of thigh muscles after anterior cruciate ligament (ACL) surgery. Ten sportsmen with a mean age of 26 yrs were randomly assigned into two groups: a 80 Hz stimulated group (5 patients) and a 20 Hz stimulated group (5 patients). All patients received electrical stimulation of the quadriceps femoris, five days a week, for 12 weeks, and had a standard program of voluntary contractions. Muscle and fat volumes of the thigh were assessed using MRI before surgery and after 12 weeks of rehabilitation. Quadriceps and hamstring muscle strength were evaluated by isokinetic measurements. Twelve weeks after surgery, the quadriceps peak torque deficit in the operated limb with respect to the non operated limb at 180 degrees /s and 240 degrees /s was significantly (p < 0.05) less in the 20 Hz group than in the 80 Hz group. This difference was not confirmed when comparing the pre-surgery quadriceps peak torque of the operated limb with the post-surgery one. Subcutaneous fat volume was increased for the two groups at the post-surgery test. This increase was significantly (p < 0.05) greater for the 80 Hz group. Thigh muscle volume deficit was not significantly different between the two groups.

Small molecule peptidomimetics containing a novel phosphotyrosine bioisostere inhibit protein tyrosine phosphatase 1B and augment insulin action.

Protein tyrosine phosphatase 1B (PTP1B) attenuates insulin signaling by catalyzing dephosphorylation of insulin receptors (IR) and is an attractive target of potential new drugs for treating the insulin resistance that is central to type II diabetes. Several analogues of cholecystokinin(26)(-)(33) (CCK-8) were found to be surprisingly potent inhibitors of PTP1B, and a common N-terminal tripeptide, N-acetyl-Asp-Tyr(SO(3)H)-Nle-, was shown to be necessary and sufficient for inhibition. This tripeptide was modified to reduce size and peptide character, and to replace the metabolically unstable sulfotyrosyl group. This led to the discovery of a novel phosphotyrosine bioisostere, 2-carboxymethoxybenzoic acid, and to analogues that were >100-fold more potent than the CCK-8 analogues and >10-fold selective for PTP1B over two other PTP enzymes (LAR and SHP-2), a dual specificity phosphatase (cdc25b), and a serine/threonine phosphatase (calcineurin). These inhibitors disrupted the binding of PTP1B to activated IR in vitro and prevented the loss of tyrosine kinase (IRTK) activity that accompanied PTP1B-catalyzed dephosphorylation of IR. Introduction of these poorly cell permeant inhibitors into insulin-treated cells by microinjection (oocytes) or by esterification to more lipophilic proinhibitors (3T3-L1 adipocytes and L6 myocytes) resulted in increased potency, but not efficacy, of insulin. In some instances, PTP1B inhibitors were insulin-mimetic, suggesting that in unstimulated cells PTP1B may suppress basal IRTK activity. X-ray crystallography of PTP1B-inhibitor complexes revealed that binding of an inhibitor incorporating phenyl-O-malonic acid as a phosphotyrosine bioisostere occurred with the mobile WPD loop in the open conformation, while a closely related inhibitor with a 2-carboxymethoxybenzoic acid bioisostere bound with the WPD loop closed, perhaps accounting for its superior potency. These CCK-derived peptidomimetic inhibitors of PTP1B represent a novel template for further development of potent, selective inhibitors, and their cell activity further justifies the selection of PTP1B as a therapeutic target.

Synthesis of a series of stromelysin-selective thiadiazole urea matrix metalloproteinase inhibitors.

The synthesis and enzyme inhibition data for a series of thiadiazole urea matrix metalloproteinase (MMP) inhibitors are described. A broad screening effort was utilized to identify several thiadiazoles which were weak inhibitors of stromelysin. Optimization of the thiadiazole leads to include an alpha-amino acid side chain with variable terminal amide substituents provided a series of ureas which were moderately effective stromelysin inhibitors, with Ki's between 0.3 and 1.0 microM. The most effective analogues utilized an L-phenylalanine as the amino acid component. In particular, unsubstituted 46 had a Ki of 710 nM, while the p-fluoro analogue 52 displayed increased potency (100 nM). Stromelysin inhibition was further improved using a pentafluorophenylalanine substituent which resulted in 70, a 14 nM inhibitor. While gelatinase inhibition was generally poor, the use of 1-(2-pyridyl)piperazine as the amide component usually provided for enhanced activity, with 71 inhibiting gelatinase with a Ki of 770 nM. The combination of this heterocycle with a p-fluorophenylalanine substituent provided the only analogue, 69, with collagenase activity (13 microM). The SAR for analogues described within this series can be rationalized through consideration of the X-ray structure recently attained for70 complexed to stromelysin. Uniquely, this structure showed the inhibitor to be completely orientated on the left side of the enzyme cleft. These results suggest that thiadiazole urea heterocycles which incorporate a substituted phenylalanine can provide selective inhibitors of stromelysin. Careful selection of the amide substituent can also provide for analogues with modest gelatinase inhibition.

The constituent tryptophans and bisANS as fluorescent probes of the active site and of a secondary binding site of stromelysin-1 (MMP-3).

The active site of the catalytic domain of stromelysin-1 (matrix metalloproteinase-3, MMP-3) was probed by fluorescence quenching, lifetime, and polarization of its three intrinsic tryptophans and by the environmentally sensitive fluorescent reporter molecule bisANS. Wavelength-dependent acrylamide quenching identified three distinct emitting tryptophan species, only one of which changes its emission and fluorescence lifetime upon binding of the competitive inhibitor Batimastat. Significant changes in the tryptophan fluorescence polarization occur upon binding by any of the three hydroxamate inhibitors Batimastat, CAS108383-58-0, and Celltech CT1418, all of which bind in the P2'-P3' region of the active site. In contrast, the inhibitor CGS27023A, which is thought to bind in the P1-P1' region, does not induce any change in tryptophan fluorescence polarization. The use of the fluorescent probe bisANS revealed the existence of an auxiliary binding site extrinsic to the catalytic cleft. BisANS acts as a competitive inhibitor of stromelysin with a dissociation constant of Ki=22 microM. In addition to this binding to the active site, it also binds to the auxiliary site with a dissociation constant of 3.40+/-0.17 microM. The auxiliary site is open, hydrophobic, and near the fluorescing tryptophans. The binding of bisANS to the auxiliary site is greatly enhanced by Batimastat, but not by the other competitive inhibitors tested.

Leber's hereditary optic neuropathy: heteroplasmy is likely to be significant in the expression of LHON in families with the 3460 ND1 mutation.

AIM: To assess the effect of heteroplasmy on the expression of Leber's hereditary optic neuropathy (LHON) in a large family with the 3460 LHON mutation. METHODS: Mutation detection was performed by restriction enzyme digestion of polymerase chain reaction (PCR) products. Heteroplasmy was estimated by quantitation of wild type:mutant product ratios. RESULTS: There is a significant association between levels of mutant mtDNA and manifestation of the disease phenotype. CONCLUSION: As a high proportion of families with the 3460 mutation demonstrate heteroplasmy; this is likely to be a significant factor in disease expression.

Leber's hereditary optic neuropathy: implications of the sex ratio for linkage studies in families with the 3460 ND1 mutation.

Leber's hereditary optic neuropathy (LHON), which is associated with mutations in mitochondrial DNA (mtDNA), is commoner in males than females. A study of over 30 LHON families with a mutation at position 3460 of mtDNA demonstrates a significantly decreased male excess from that generally quoted, with evidence for a marked bias in the ascertainment of males over females. This has implications for the analysis of those factors which give rise to the male bias.

K252a, KT5720, KT5926, and U98017 support paclitaxel (taxol)-dependent cells and synergize with paclitaxel.

We have used paclitaxel-dependent Tax 2-4 cells to screen for compounds that have paclitaxel-like functional activity. The indolocarbazole serine/threonine kinase inhibitor K252a and analogues such as KT5926, KT5720, and K252b partially support the growth of the paclitaxel-dependent cells in the absence of paclitaxel. A novel kinase inhibitor of similar structure, U98017, supports the growth of the dependent cells to 48% of that seen with paclitaxel. Used in combination with paclitaxel, these compounds reduce the amount of paclitaxel required for maximum growth of the dependent cells. Isobologram analysis demonstrates that these compounds also act synergistically with paclitaxel to promote toxicity in wild-type Chinese hamster ovary cells. These selected indolocarbazoles may act at sites distinct from that of paclitaxel and may specifically inhibit kinases that contribute to the destabilization of microtubules. Other indolocarbazoles such as staurosporine and rebeccamycin do not support paclitaxel-dependent cell growth. Structurally unrelated serine/threonine kinase inhibitors such as H-9 and H-7 or tyrosine kinase inhibitors such as lavendustin do not support the growth of these cells. These results define a screen for functional paclitaxel analogues and suggest that it may be useful to investigate the possible synergy of selected indolocarbazoles and paclitaxel in vivo.

Nurses' perceptions of usefulness of laboratory data for nursing practice.

The purpose of this study was to examine nurses' perceptions about the usefulness and barriers to the use of laboratory tests. An investigator-developed questionnaire was given to participants in 20 continuing education workshops. The sample consisted of 536 registered nurses and 40 licensed vocational nurses. Descriptive statistics and content analysis were performed. No significant differences existed in the nurses' reported uses or barriers to using laboratory data by area of practice or length of time since graduation. A significant difference (Fisher's exact P = 0.02) found was the educational level in the reported major usefulness of laboratory data.

Effect of dose and method of administration of endotoxin on cell mediator release in neonatal calves.

The cellular response induced in the host animal by endotoxin contributes greatly to the morbidity and mortality of gram-negative infections in bovine neonates. We characterized the temporal sequence, magnitude, and duration of mediator release during endotoxemia and evaluated the effect of endotoxin dose and method of administration. Thromboxane B2 (TxB2), and 6-keto prostaglandin F1 alpha (PGF1 alpha) concentrations and tumor necrosis factor (TNF), and interleukin-1 beta (IL-1 beta) activities were measured in 34 newborn calves given Escherichia coli endotoxin at dosage of 0 (saline solution), 0.2, 2.0, or 20 micrograms/kg of body weight, either by IV administered bolus or infusion over 50 minutes. In all groups and at each lipopolysaccharide dosage, mediators peaked in this sequence: TxB2 and TNF, followed by PGF1 alpha, then IL-1 beta. Neither dose nor method of administration affected the sequence of mediator release. The magnitude of eicosanoid response to endotoxin was dose-dependent. During induced endotoxemia, duration and/or magnitude of mediator response reflected the dose of endotoxin administered, indicating that the outcome of endotoxemia, in neonatal calves, may be related to the amount of circulating endotoxin.