Clinical outcomes of combined surgical treatment of medial epicondylitis and cubital tunnel syndrome.

Surgical results for treatment of medial epicondylitis and cubital tunnel syndrome are generally satisfactory when performed alone. However, our experience suggests a combined procedure is associated with inferior outcomes. A retrospective review was conducted of consecutive surgical cases of medial epicondylectomy/debridement and ulnar nerve decompression during a single operation at our institution from March 2008 to February 2017 using CPT codes. Thirty combined procedures were identified in 29 patients. Fourteen patients and 15 elbows returned to clinic for evaluation at average 4.3 years after surgery (8 men, 6 women, mean age 45.1 years). A Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, visual analogue pain scale (VAS), and physical examination were performed. The data was stratified by type of ulnar nerve procedure and analyzed. Three of fifteen elbows underwent in situ ulnar nerve decompression, and twelve of 15 had transposition, five subcutaneous and seven submuscular. The mean DASH score for in situ decompression was significantly higher than that of transposition (68.2 vs. 13.1). The average visual pain score for patients whom underwent in situ decompression was significantly higher than that of those with ulnar nerve transposition (8.0 vs. 1.2). All other physical exam measures demonstrated no significant difference between the two groups. In situ ulnar nerve decompression in the setting of medial epicondylectomy/debridement may be associated with inferior clinical outcomes in comparison to ulnar nerve transposition. Further studies are needed to validate the results of our study and inform management.

Oral Sciences PhD Program Enrollment, Graduates, and Placement: 1994 to 2016.

For decades, dental schools in the United States have endured a significant faculty shortage. Studies have determined that the top 2 sources of dental faculty are advanced education programs and private practice. Those who have completed both DDS and PhD training are considered prime candidates for dental faculty positions. However, there is no national database to track those trainees and no evidence to indicate that they entered academia upon graduation. The objective of this study was to assess outcomes of dental school-affiliated oral sciences PhD program enrollment, graduates, and placement between 1994 and 2016. Using the American Dental Association annual survey of advanced dental education programs not accredited by the Commission on Dental Accreditation and data obtained from 22 oral sciences PhD programs, we assessed student demographics, enrollment, graduation, and placement. Based on the data provided by program directors, the average new enrollment was 33, and graduation was 26 per year. A total of 605 graduated; 39 did not complete; and 168 were still in training. Among those 605 graduates, 211 were faculty in U.S. academic institutions, and 77 were faculty in foreign institutions. Given that vacant budgeted full-time faculty positions averaged 257 per year during this period, graduates from those oral sciences PhD programs who entered academia in the United States would have filled 9 (3.6%) vacant faculty positions per year. Therefore, PhD programs have consistently generated only a small pipeline of dental school faculty. Better mentoring to retain talent in academia is necessary. Stronger support and creative funding plans are essential to sustain the PhD program. Furthermore, the oral sciences PhD program database should be established and maintained by dental professional organizations to allow assessments of training models, trends of enrollment, graduation, and placement outcomes.

Bupropion and naltrexone for smoking cessation: A double-blind randomized placebo-controlled clinical trial.

Combination of non-nicotine pharmacotherapies has been underexamined for cigarette smoking cessation. A randomized, double-blind, parallel-group double-dummy study evaluated two medications, bupropion (BUP) and naltrexone (NTX), in treatment-seeking cigarette smokers (N = 121) over a 7-week treatment intervention with 6-month follow-up. Smokers were randomized to either BUP (300 mg/day) + placebo (PBO) or BUP (300 mg/day) + NTX (50 mg/day). The primary outcome was biochemically verified (saliva cotinine, carbon monoxide) 7-day, point-prevalence abstinence. BUP + NTX was associated with significantly higher point-prevalence abstinence rates after 7-weeks of treatment (BUP + NTX, 54.1%; BUP + PBO, 33.3%), P = 0.0210, but not at 6-month follow-up (BUP + NTX, 27.9%; BUP + PBO, 15.0%), P = 0.09. Continuous abstinence rates did not differ, P = 0.0740 (BUP + NTX, 26.2%; BUP + PBO, 13.3%). Those receiving BUP + NTX reported reduced nicotine withdrawal, P = 0.0364. The BUP + NTX combination was associated with elevated rates of some side effects, but with no significant difference in retention between the groups.

Wheatstone bridge configuration for evaluation of plasmonic energy transfer.

We propose an internal (on-chip) Wheatstone bridge configuration to evaluate the efficiency of near-field transducers (NFT) as used in heat-assisted magnetic recording (HAMR). The electric field enhancement between the transducer and the image plane is monitored by measuring the resistance of metal electrodes composing the image plane. The absorption of the enhanced electric field causes an increase in the metal temperature, and thereby, in its resistance whose variation is monitored with an internal Wheatstone bridge which is accurately balanced in the absence of the electric field.

Mifepristone-inducible transgene expression in neural progenitor cells in vitro and in vivo.

Numerous gene and cell therapy strategies are being developed for the treatment of neurodegenerative disorders. Many of these strategies use constitutive expression of therapeutic transgenic proteins, and although functional in animal models of disease, this method is less likely to provide adequate flexibility for delivering therapy to humans. Ligand-inducible gene expression systems may be more appropriate for these conditions, especially within the central nervous system (CNS). Mifepristone's ability to cross the blood-brain barrier makes it an especially attractive ligand for this purpose. We describe the production of a mifepristone-inducible vector system for regulated expression of transgenes within the CNS. Our inducible system used a lentivirus-based vector platform for the ex vivo production of mifepristone-inducible murine neural progenitor cells that express our transgenes of interest. These cells were processed through a series of selection steps to ensure that the cells exhibited appropriate transgene expression in a dose-dependent and temporally controlled manner with minimal background activity. Inducible cells were then transplanted into the brains of rodents, where they exhibited appropriate mifepristone-inducible expression. These studies detail a strategy for regulated expression in the CNS for use in the development of safe and efficient gene therapy for neurological disorders.

Transforming Growth Factor-ß3 Therapy Delays Postoperative Reossification and Improves Craniofacial Growth in Craniosynostotic Rabbits.

Postoperative reossification is a common clinical correlate following surgery. It has been suggested that an underexpression of transforming growth factor-ß3 (TGF-ß3) may be related to craniosynostosis and postoperative reossification. Adding TGF-ß3 may delay reossification and improve postoperative growth. The present study was designed to test this hypothesis. Thirty 10-day-old New Zealand white rabbits with hereditary coronal suture synostosis were divided into three groups: (1) suturectomy controls (n = 14), (2) suturectomy treated with bovine serum albumin (n = 8), and (3) suturectomy treated with TGF-ß3 protein (n = 8). At 10 days of age, a 3-mm × 15-mm coronal suturectomy was performed, and serial three-dimensional (3D) computed tomography (CT) scans and cephalographs were taken at 10, 25, 42, and 84 days of age. Calvaria were harvested at 84 days of age for histomorphometric analysis. Mean differences were analyzed using a group by age analysis of variance. Analysis of the 3D CT scan data revealed that sites treated with TGF-ß3 had significantly (P < .05) greater defect areas and significantly (P < .05) greater intracranial volumes through 84 days of age compared with controls. Histomorphometry showed that sites treated with TGF-ß3 had patent suturectomy sites and significantly (P < .001) less new bone in the suturectomy site compared with controls. Serial radiograph data revealed significant (P < .05) differences in craniofacial growth from 25 to 84 days in TGF-ß3-treated rabbits compared with controls. Data show that TGF-ß3 administration delayed reossification and improved craniofacial growth in this rabbit model. These findings also suggest that this molecular-based therapy may have potential clinical use.

Geophysical investigation of seepage beneath an earthen dam.

A hydrogeophysical survey is performed at small earthen dam that overlies a confined aquifer. The structure of the dam has not shown evidence of anomalous seepage internally or through the foundation prior to the survey. However, the surface topography is mounded in a localized zone 150 m downstream, and groundwater discharges from this zone periodically when the reservoir storage is maximum. We use self-potential and electrical resistivity tomography surveys with seismic refraction tomography to (1) determine what underlying hydrogeologic factors, if any, have contributed to the successful long-term operation of the dam without apparent indicators of anomalous seepage through its core and foundation; and (2) investigate the hydraulic connection between the reservoir and the seepage zone to determine whether there exists a potential for this success to be undermined. Geophysical data are informed by hydraulic and geotechnical borehole data. Seismic refraction tomography is performed to determine the geometry of the phreatic surface. The hydro-stratigraphy is mapped with the resistivity data and groundwater flow patterns are determined with self-potential data. A self-potential model is constructed to represent a perpendicular profile extending out from the maximum cross-section of the dam, and self-potential data are inverted to recover the groundwater velocity field. The groundwater flow pattern through the aquifer is controlled by the bedrock topography and a preferential flow pathway exists beneath the dam. It corresponds to a sandy-gravel layer connecting the reservoir to the downstream seepage zone.

Improvement in aortic valve area using a new "hour glass" shaped valvuloplasty balloon compared with standard cylindrical balloons in severe aortic stenosis patients.

AIM: Balloon aortic valvuloplasty (BAV) has reemerged with transcatheter valve therapy. Cylindrical balloons have been the device of choice despite limitations. An hour glass shaped balloon may permit enhanced fixation and broader leaflet opening without annular compromise. METHODS: We report our initial BAV experience using the V8 balloon (InterValve Inc.) in 20 consecutive patients compared to 20 patients from a 403-patient BAV database using cylindrical balloons. Patients were propensity matched on a 1:1 basis by age, gender, left ventricular ejection fraction (LVEF), baseline aortic valve area (AVA) and Society of Thoracic Surgery (STS) mortality risk score. End points included change in AVA and aortic insufficiency (AI) by echocardiography. New atrioventricular conduction defects (AVCD), need for post procedure pacemaker were documented. Major adverse events (MAE) included procedure related death, emergency surgery or stroke. RESULTS: V8 and cylindrical balloon groups were similar across age, gender, LVEF, AVA and STS score. The change in AVA from baseline to post-procedure strongly trended towards being larger in the V8 group than cylindrical balloon group (mean [SD]; 0.30±0.23 cm2 vs. 0.17±0.21 cm2; P=0.063). There were no differences in outcomes for degree of AI, AVCD, need for pacemaker or MAE. CONCLUSION: Preliminary findings in this small experience suggest an advantage for enhancing AVA when using the V8 compared with cylindrical balloons. Additionally, there was no evidence of increased AI, AVCD or MAE.

Characterization of focused seepage through an earthfill dam using geoelectrical methods.

Resistivity and self-potential tomography can be used to investigate anomalous seepage inside heterogeneous earthen dams. The self-potential (SP) signals provide a unique signature to groundwater flow because the source current density responsible for the SP signals is proportional to the Darcy velocity. The distribution of the SP signals is also influenced by the distribution of the resistivity; therefore, resistivity and SP need to be used in concert to elucidate groundwater flow pathways. In this study, a survey is conducted at a small earthen dam in Colorado where anomalous seepage is observed on the downstream face at the dam toe. The data reveal SP and direct current resistivity anomalies that are used to delineate three anomalous seepage zones within the dam and to estimate the source of the localized seepage discharge. The SP data are inverted in two dimensions using the resistivity distribution to determine the distribution of the Darcy velocity responsible for the observed seepage. The inverted Darcy velocity agrees with an estimation of the Darcy velocity from the hydraulic conductivity obtained from a slug test and the observed head gradient.

Colour of fat, and colour, fatty acid composition and sensory characteristics of muscle from heifers offered alternative forages to grass silage in a finishing ration.

The effect of type of silage offered to beef heifers during the finishing period on aspects of beef quality was determined. In two experiments, a diet based on grass silage (GS) was compared with a diet based on maize silage (MS) or whole-crop wheat silage (WCW). Compared to the GS-based diet, increasing the amount of MS linearly increased fat whiteness while the increase in fat whiteness due to WCW was dependent on the stage of crop maturity at harvesting. There was no effect of diet on muscle colour or on muscle pH measured at 48h post-mortem, drip loss, taste panel traits after 14days ageing or shear force values at 2, 7 or 14days ageing. The alternative silages decreased the n-3 polyunsaturated fatty acid proportion and increased the linoleic:linolenic acid ratio in intramuscular lipid. It is concluded that type of silage affects fat colour and fatty acid composition of muscle but not the other muscle characteristics examined.

The effects of testosterone on craniosynostotic calvarial cells: a test of the gene/environmental model of craniofacial anomalies.

INTRODUCTION: The gene-environmental interaction model for craniofacial development proposes that if a genetic predisposition for an anomaly is coupled with an environmental factor that can exacerbate this predisposition, more severe phenotypes will result. Here, we utilize cells derived from our non-syndromic rabbit model of craniosynostosis to test the hypothesis that an insult, testosterone (TP) administration (exogenous source) will alter the osteogenic activity of these cells. DESIGN: Calvarial cells from wild-type (WT) (N=13) or craniosynostotic (CS) rabbits (N=11) were stimulated with TP, an androgen receptor blocker, flutamide, and combined treatments. Proliferation and differentiation assays were conducted after 7 days. anova and t-tests were used to determine differences in stimulation and cell type. RESULTS: The CS cells had significantly greater proliferation after TP administration compared to WT. There were no appreciable changes in differentiation after TP stimulation. Flutamide administration or combined TP and flutamide administration decreased both proliferation and differentiation for both cell types similarly. CONCLUSIONS: Testosterone exposure caused an increase in cell proliferation for CS osteoblast cells. However, a therapy targeted to mitigate this response (flutamide therapy) similarly affected CS and WT cells, suggesting that the administration of flutamide or TP in the presence of flutamide decreases osteogenesis of these cells. Thus, although our data support a mechanism of gene-environmental interaction, these results would not support a therapeutic intervention based on this interaction.

Development of the Lacrimal Apparatus in the Rabbit (Oryctolagus cuniculus) and Its Potential Role as an Animal Model for Humans.

Rabbits have been proposed as a model organism for the human lacrimal apparatus (LA), including the nasolacrimal duct (NLD), based principally on comparative studies of adult morphology; however, little is known about its development. The NLD first appears as an incomplete primordium in the subcutaneous region of the primordial eyelid and subsequently elongates to reach the naris. One posterior and three anterior orbital glands are present fetally although one of the anterior glands is soon lost. The NLD follows a tortuous path and passes through a bony canal consisting of lacrimal, maxilla, and maxilloturbinal bones at different regions. Although early developmental similarities exist to haplorhine primates, the narial opening of the NLD resembles strepsirrhines. This distinction, along with the ductal and glandular differences at the orbital end of the NLD, indicates that rabbits may be a poor model for LA drainage in primates, specifically humans.

New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).

BACKGROUND: Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000, many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to the development of a revised RECIST guideline (version 1.1). Evidence for changes, summarised in separate papers in this special issue, has come from assessment of a large data warehouse (>6500 patients), simulation studies and literature reviews. HIGHLIGHTS OF REVISED RECIST 1.1: Major changes include: Number of lesions to be assessed: based on evidence from numerous trial databases merged into a data warehouse for analysis purposes, the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total (and from five to two per organ, maximum). Assessment of pathological lymph nodes is now incorporated: nodes with a short axis of 15 mm are considered measurable and assessable as target lesions. The short axis measurement should be included in the sum of lesions in calculation of tumour response. Nodes that shrink to <10mm short axis are considered normal. Confirmation of response is required for trials with response primary endpoint but is no longer required in randomised studies since the control arm serves as appropriate means of interpretation of data. Disease progression is clarified in several aspects: in addition to the previous definition of progression in target disease of 20% increase in sum, a 5mm absolute increase is now required as well to guard against over calling PD when the total sum is very small. Furthermore, there is guidance offered on what constitutes 'unequivocal progression' of non-measurable/non-target disease, a source of confusion in the original RECIST guideline. Finally, a section on detection of new lesions, including the interpretation of FDG-PET scan assessment is included. Imaging guidance: the revised RECIST includes a new imaging appendix with updated recommendations on the optimal anatomical assessment of lesions. FUTURE WORK: A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI. It was concluded that, at present, there is not sufficient standardisation or evidence to abandon anatomical assessment of tumour burden. The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression. As is detailed in the final paper in this special issue, the use of these promising newer approaches requires appropriate clinical validation studies.

Recommendations for the assessment of progression in randomised cancer treatment trials.

Progression-free survival (PFS) is an increasingly important end-point in cancer drug development. However, several concerns exist regarding the use of PFS as a basis to compare treatments. Unlike survival, the exact time of progression is unknown, so progression times might be over-estimated (or under-estimated) and, consequently, bias may be introduced when comparing treatments. In addition, the assessment of progression is subject to measurement variability which may introduce error or bias. Ideally trials with PFS as the primary end-point should be randomised and, when feasible, double-blinded. All patients eligible for study should be evaluable for the primary end-point and thus, in general, have measurable disease at baseline. Appropriate definitions should be provided in the protocol and data collected on the case-report forms, if patients with only non-measurable disease are eligible and/or clinical, or symptomatic progression are to be considered progression events for analysis. Protocol defined assessments of disease burden should be obtained at intervals that are symmetrical between arms. Independent review of imaging may be of value in randomised phase II trials and phase III trials as an auditing tool to detect possible bias.

Plasma biomarker profiling in the detection of growth promoter use in calves.

The detection of illicit growth promoter use during meat production within the European Union is reliant on residue testing which is a limiting factor on the number of animals which can be tested and consequently compromises the efficacy of testing procedures. The present study examined a novel detection strategy based on the profiling of plasma component concentrations in response to growth promoter administrations. Calves subjected to nortestosterone decanoate, 17beta-oestradiol benzoate and dexamethasone were found to have altered urea, aminoterminal propeptide of type III procollagen and sex hormone binding globulin profiles in response to treatments. These findings demonstrate the potential of using the identification of perturbed profiles within a panel of biomarkers which cover a spectrum of biological activity to reveal growth promoter abuse.

Mechanisms underlying the metabolic actions of galegine that contribute to weight loss in mice.

BACKGROUND AND PURPOSE: Galegine and guanidine, originally isolated from Galega officinalis, led to the development of the biguanides. The weight-reducing effects of galegine have not previously been studied and the present investigation was undertaken to determine its mechanism(s) of action. EXPERIMENTAL APPROACH: Body weight and food intake were examined in mice. Glucose uptake and acetyl-CoA carboxylase activity were studied in 3T3-L1 adipocytes and L6 myotubes and AMP activated protein kinase (AMPK) activity was examined in cell lines. The gene expression of some enzymes involved in fat metabolism was examined in 3T3-L1 adipocytes. KEY RESULTS: Galegine administered in the diet reduced body weight in mice. Pair-feeding indicated that at least part of this effect was independent of reduced food intake. In 3T3-L1 adipocytes and L6 myotubes, galegine (50 microM-3 mM) stimulated glucose uptake. Galegine (1-300 microM) also reduced isoprenaline-mediated lipolysis in 3T3-L1 adipocytes and inhibited acetyl-CoA carboxylase activity in 3T3-L1 adipocytes and L6 myotubes. Galegine (500 microM) down-regulated genes concerned with fatty acid synthesis, including fatty acid synthase and its upstream regulator SREBP. Galegine (10 microM and above) produced a concentration-dependent activation of AMP activated protein kinase (AMPK) in H4IIE rat hepatoma, HEK293 human kidney cells, 3T3-L1 adipocytes and L6 myotubes. CONCLUSIONS AND IMPLICATIONS: Activation of AMPK can explain many of the effects of galegine, including enhanced glucose uptake and inhibition of acetyl-CoA carboxylase. Inhibition of acetyl-CoA carboxylase both inhibits fatty acid synthesis and stimulates fatty acid oxidation, and this may to contribute to the in vivo effect of galegine on body weight.

Relationship of premaxillary bone and its sutures to deciduous dentition in nonhuman primates.

OBJECTIVE: The relationship of the human premaxillary bone (Pmx) to neighboring craniofacial structures is clouded by its embryonic union with the maxillary bone proper. Only humans among all primates have such early fusion of the premaxillomaxillary suture (PS). This study surveyed the relationship of the PS to the upper deciduous dentition in nonhuman primates, and describes the distribution of bone cells along the osseous margins of the Pmx. METHOD: Twenty-eight subadult primates were studied using gross, CT, and histologic observations. Location of the anterior deciduous dentition relative to the PS was assessed. In sections of selected specimens, observations of bone cells on the osseous boundaries of the Pmx were made. Osteopontin (OPN) immunohistochemistry was used to isolate osteoclastic binding sites along the Pmx boundaries. RESULTS: The PS was consistently found between deciduous incisor and canine in strepsirrhines of all ages, whereas the suture passed variably closer to the incisor or canine in haplorhines. In all species, the anterior part of the Pmx was nonarticulating and mostly osteoblastic, except for osteoclastic margins adjacent to dentition and the nasal fossa. Superolaterally, the osteogenic fronts of the PS were osteoblastic, while more inferiorly, at the level of the deciduous canine, the PS was often osteoclastic. Results from OPN immunohistochemistry support the findings on bone cell distribution. CONCLUSION: Bone cell distribution patterns in perinatal nonhuman primates resemble those described for the prenatal human Pmx, suggesting that differences among species relate to magnitude rather than the pattern of osteogenesis.

Energy supply patterns for finishing steers: Feed conversion efficiency, components of bodyweight gain and meat quality.

The objective was to determine the effect of pre-slaughter growth rate on feed efficiency, components of body growth and on the tenderness of longissimus muscle from steers reared to a common age and carcass weight. Sixty Friesian steers were group-housed and offered grass silage ad libitum and 3.5kg concentrates per animal daily for 5 months and then 5kg concentrates and 1kg grass hay for 1month before the experiment began. The animals were then weighed and in a randomised block were assigned to one of 5 groups, for slaughter at the beginning of the experiment or to be offered concentrates and hay (900 and 100g/kg total diet, respectively) to achieve target growths of: 0.72kg/day continuously for 17 weeks, 0.36kg/day for the first 8 weeks and 1.08kg/day for the final 8 weeks (low-high), 1.08kg/day for the first 8 weeks and 0.36 for the final 8 weeks (high-low) or 0.36kg/day for the first 2 weeks, 0.72kg/day during weeks 4 and 14 and 1.08kg/day for the final 2 weeks (pulse). One week was allowed for transition to the different dietary allowances within each energy supply pattern. The mean age at the beginning and end of the study was 18 and 22.5 months, respectively. After slaughter, the weight of the carcass and kidney+channel fat depot were recorded, the pistola hind quarter was dissected into fat, lean and bone and the tenderness of the m. longissimus thoracis et lumborum (LTM) muscle was measured instrumentally and using a trained taste panel after 2, 7 or 14 days ageing. The pattern of energy supply did not affect carcass weight, fat score or kidney+channel fat weight. The pistola hind quarter from animals offered the low-high energy pattern had a similar composition to the continuously-fed animals but contained more muscle than that from animals offered high-low or pulse energy patterns. After 14 days ageing, LTM from the continuously-fed animals was more tender than that from animals offered the other energy supply patterns but shear force did not differ between supply patterns. The data do not support the hypothesis that pre-slaughter growth rate increases tenderness but suggest that energy supply pattern can influence body composition of finishing cattle.

Effect of concentrate feeding pattern in a grass silage/concentrate beef finishing system on performance, selected carcass and meat quality characteristics.

Steers were offered grass silage ad libitum and 6.4 kg concentrates daily for 126 days or silage ad libitum for 35 days, followed by concentrates ad libitum (Experiment 1). Steers were offered grass silage ad libitum and 6 kg concentrates daily for 154 days, concentrates ad libitum or grass silage ad libitum for 112 days followed by concentrates ad libitum (Experiment 2). All treatments received the same total concentrate allowance. In Experiment 1, there was no difference in any measurement of meat quality. In Experiment 2, ad libitum concentrate feeding per se, decreased redness and increased shear force of muscle at 2 days post-mortem. Delaying concentrate feeding decreased fat yellowness, decreased shear force at 7 and 14 days post-mortem and increased muscle redness at 14 days post-mortem. Modifications of the beef production system examined had minor effects on beef quality which are unlikely to be of commercial significance.