Selectivity of upper limb posterior root muscle reflexes via cervicothoracic spinal cord stimulation.

Recent studies have reported that transcutaneous spinal stimulation (tSCS) may facilitate improved upper limb motor function in those with incomplete tetraplesia. However, little is known about how tSCS engages upper limb motor pools. This study aimed to explore the extent to which discrete upper limb motor pools can be selectively engaged via altering stimulus location and intensity. 14 participants with intact nervous systems completed two test visits, during which posterior root-muscle reflexes (PRMR) were evoked via a 3x3 cathode matrix applied over the cervicothoracic spine. An incremental recruitment curve at C7 vertebral level was initially performed to attain minimal threshold intensity (MTI) in each muscle. Paired pulses (1ms square monophasic with inter-pulse interval of 50ms) were subsequently delivered at a frequency of 0.25Hz at two intensities (MTI and [Formula: see text]) across all nine locations. in a random order. Evoked response to the 1st (PRMR1) and 2nd (PRMR2) stimuli were recorded from four upper limb muscles. A significant effect of spinal level was observed in all muscles for PRMR1 with greater responses recorded more caudally. Unexpectedly, contralateral cathode placement significantly increased PRMR1 in Biceps Brachii (P=0.012), Flexor Carpi Radialis (P=0.035) and Abductor Pollicis Brevis (P=0.001). Post-activation depression (PAD) was also significantly increased with contralateral cathode placement in Biceps Brachii (P=0.001), Triceps Brachii (P=0.012) and Flexor Carpi Radialis (P=0.001). These results suggest that some level of unilateral motor pool selectivity may be attained via altering stimulus intensity and location during cervicothoracic tSCS.

Effect of Initial Knee angle and Arm Facilitation on biomechanics of the Sit-to-Stand movement.

Spinal cord injuries cause loss of muscle function and subsequently reduce independence. Therapeutic interventions such as transcutaneous spinal cord stimulation are increasingly being used to help improve motor functioning however, a comprehensive understanding of the biomechanical elements of movement may help optimize stimulation protocols. Twenty healthy participants completed five sit-to-stand (STS) transitions while initial knee angle and arm facilitation were altered. Electromyography (EMG) activation of four lower limb muscles and centre of pressure dynamics were recorded. Acute initial knee angles resulted in a change in duration of phases within the STS, and restrictive arm positioning caused the time to completion to increase (p=0.04). Muscle activation patterns across phases were compared and showed significant differences between phases in both the Tibialis Anterior and Rectus Femoris (p<0.006). Acute initial knee angles were also found to significantly increase Biceps Femoris activation across multiple phases (p=0.034). Altering the starting position and limb movement result in vastly different temporal and muscular strategies to complete the STS. Thus, joint angle and upper limb facilitation should be considered when designing rehabilitative interventions for clinical cohorts.

Screw-actuated displacement micropumps for thermoplastic microfluidics.

The fabrication of on-chip displacement pumps integrated into thermoplastic chips is explored as a simple and low cost method for achieving precise and programmable flow control for disposable microfluidic systems. The displacement pumps consist of stainless steel screws inserted into threaded ports machined into a thermoplastic substrate which also serve as on-chip reagent storage reservoirs. Three different methods for pump sealing are investigated to enable high pressure flows without leakage, and software-defined control of multiple pumps is demonstrated in a self-contained platform using a compact and self-contained microcontroller for operation. Using this system, flow rates ranging from 0.5-40 µl min-1 are demonstrated. The pumps are combined with on-chip burst valves to fully seal multiple reagents into fabricated chips while providing on-demand fluid distribution in a downstream microfluidic network, and demonstrated for the generation of size-tunable water-in-oil emulsions.

Quality of life after radical trachelectomy for early-stage cervical cancer: A 5-year prospective evaluation.

OBJECTIVES: To longitudinally assess quality of life (QOL) in women undergoing radical trachelectomy for early-stage cervical cancer. METHODS: We prospectively enrolled patients with stage IA1-IB1 cervical cancer prior to undergoing radical trachelectomy to complete validated QOL instruments. These instruments included the General Health-Related QOL (SF-12), Functional Assessment of Cancer Therapy-Cervix (FACT-Cx), MD Anderson Symptom Inventory (MDASI), Female Sexual Functioning Index (FSFI), and Satisfaction with Decision scale (SWD). Instruments were filled out at baseline, postoperatively at 6weeks, 6months, 1year, and annually thereafter for 4years. RESULTS: Thirty-nine patients enrolled in the study, and 32 patients were evaluable. The scores for FSFI-arousal (p=0.0002), lubrication (p<0.0001), orgasm (p=0.006), pain (p=0.01), satisfaction (p=0.03) and total score (p=0.004) showed a significant decline at 6weeks then returned to baseline levels by 6 months. The scores for FACT-Cx functional well-being (p=0.02) and physical well-being (p<0.0001), SF-12 bodily pain (p<0.0001), physical functioning (p<0.0001), role physical (p<0.0001), role emotional (p=0.03), social functioning (p=0.002), and MDASI total (p=0.04) showed significantly worsened symptoms at 6weeks then returned to baseline by 6months. The scores for FACT-Cx emotional well-being showed significant worsening of symptoms that persisted at 6-weeks (p=0.004), 6months (p=0.007), 1year (p=0.001), 2years (p=0.002), and 4 years (p=0.03). There was no difference in SWD. CONCLUSIONS: Several quality of life assessments decline immediately postoperatively after radical trachelectomy, however, return to baseline thereafter. The long-term emotional impact of this surgery highlights a need for perioperative counseling in these patients.

Does the North American Society for Pediatric and Adolescent Gynecology Short Curriculum Increase Resident Knowledge in Pediatric and Adolescent Gynecology?

STUDY OBJECTIVE: To determine if the North American Society for Pediatric and Adolescent Gynecology (NASPAG) Short Curriculum improves self-reported knowledge in pediatric and adolescent gynecology (PAG) among obstetrics and gynecology (Ob/Gyn) residents, at programs without PAG-trained faculty. DESIGN: Prospective, cross-sectional exposure to the NASPAG short curriculum with a follow-up questionnaire. SETTING: Ob/Gyn residency training programs without PAG faculty. PARTICIPANTS: Ob/Gyn residents in training from February 2015 to June 2015. INTERVENTIONS: Exposure to the NASPAG Short Curriculum. MAIN OUTCOME MEASURES: Improvement in self-perceived knowledge after completion of curriculum. RESULTS: Two hundred twenty-seven residents met inclusion criteria; 34 completed the study (15% response). Less than 50% of residents reported adequate knowledge in the areas of prepubertal vaginal bleeding, vulvovaginitis, precocious and delayed puberty, Home environment, Education and Employment, Eating, peer-related Activities, Drugs, Sexuality, Suicide/depression, Safety from injury and violence (HEEADSSS) interview, pelvic pain, and bleeding management in teens with developmental delay. After completion of the curriculum, self-reported knowledge improved in 8 of 10 learning objectives, with no significant improvement in bleeding disorders or Müllerian anomalies. There was no association between pretest knowledge and level of residency training, type of residency program, previous exposure to PAG lectures, and previous exposure to patients with PAG complaints. CONCLUSION: Significant deficiencies exist regarding self-reported knowledge of core PAG topics among Ob/Gyn residents at programs without PAG-trained faculty. Use of the NASPAG Short Curriculum by residents without access to PAG-trained faculty resulted in improved self-reported knowledge in PAG.

The Δ133p53 isoform and its mouse analogue Δ122p53 promote invasion and metastasis involving pro-inflammatory molecules interleukin-6 and CCL2.

A number of naturally occurring isoforms of the tumour suppressor protein p53 have been discovered, which appear to have differing roles in tumour prevention or promotion. We are investigating the tumour-promoting activities of the Δ133p53 isoform using our mouse model of Δ133p53 (Δ122p53). Here, we report that tumours from Δ122p53 homozygous mice show evidence of invasion and metastasis and that Δ122p53 promotes migration though a 3-dimensional collagen matrix. We also show that Δ122p53 and Δ133p53 promote cell migration in scratch wound and Transwell assays, similar to the 'gain-of-function' phenotypes seen with mutant p53. Using the well-defined B16 mouse melanoma metastatic model, we show that Δ122p53 leads to faster generation of lung metastases. The increased migratory phenotypes are dependent on secreted factors, including the cytokine interleukin-6 and the chemokine CCL2. We propose that Δ122p53 (and Δ133p53) acts in a similar manner to 'gain-of-function' mutant p53 proteins to promote migration, invasion and metastasis, which may contribute to poor survival in patients with Δ133p53-expressing tumours.

Acute response to barefoot running in habitually shod males.

The aim of this study was to examine the immediate effects of barefoot (BF) running on lower limb kinematics and muscle activity in a group of habitually shod runners. Ten male runners with no prior BF or minimalist running experience performed 1-min bouts of treadmill running at 3 velocities in both shod and BF conditions. 2D video data were recorded in order to quantify ankle, knee and hip kinematics. Synchronous kinetic data were recorded from a force plate supporting the treadmill in order to quantify spatiotemporal variables. EMG data were collected from 6 lower limb muscles, quantifying recruitment patterns during discrete phases of the gait cycle. BF running resulted in significantly higher stride frequency and shorter ground contact times (P < .001). Additionally, BF running significantly reduced knee and hip range of motion but increased ankle range of motion during the absorptive phase of the stance. Alterations in ankle kinematics during BF running resulted from increased pre-activation of the medial (P < .05) and lateral (P < .01) gastrocnemius in addition to reductions in pre-activation of the tibialis anterior (P < .05). The results highlight that recruitment patterns and kinematics can change in as little as 30-s of BF running in individuals with no previous BF running experience.

Internalizing disorders and leukocyte telomere erosion: a prospective study of depression, generalized anxiety disorder and post-traumatic stress disorder.

There is evidence that persistent psychiatric disorders lead to age-related disease and premature mortality. Telomere length has emerged as a promising biomarker in studies that test the hypothesis that internalizing psychiatric disorders are associated with accumulating cellular damage. We tested the association between the persistence of internalizing disorders (depression, generalized anxiety disorder and post-traumatic stress disorder) and leukocyte telomere length (LTL) in the prospective longitudinal Dunedin Study (n=1037). Analyses showed that the persistence of internalizing disorders across repeated assessments from ages 11 to 38 years predicted shorter LTL at age 38 years in a dose-response manner, specifically in men (ß=-0.137, 95% confidence interval (CI): -0.232, -0.042, P=0.005). This association was not accounted for by alternative explanatory factors, including childhood maltreatment, tobacco smoking, substance dependence, psychiatric medication use, poor physical health or low socioeconomic status. Additional analyses using DNA from blood collected at two time points (ages 26 and 38 years) showed that LTL erosion was accelerated among men who were diagnosed with internalizing disorder in the interim (ß=-0.111, 95% CI: -0.184, -0.037, P=0.003). No significant associations were found among women in any analysis, highlighting potential sex differences in internalizing-related telomere biology. These findings point to a potential mechanism linking internalizing disorders to accelerated biological aging in the first half of the life course, particularly in men. Because internalizing disorders are treatable, the findings suggest the hypothesis that treating psychiatric disorders in the first half of the life course may reduce the population burden of age-related disease and extend health expectancy.

12 weeks of simulated barefoot running changes foot-strike patterns in female runners.

To investigate the effect of a transition program of simulated barefoot running (SBR) on running kinematics and foot-strike patterns, female recreational athletes (n=9, age 29 ± 3 yrs) without SBR experience gradually increased running distance in Vibram FiveFingers SBR footwear over 12 weeks. Matched controls (n=10, age 30 ± 4 yrs) continued running in standard footwear. A 3-D motion analysis of treadmill running at 12 km/h(-1) was performed by both groups, barefoot and shod, pre- and post-intervention. Post-intervention data indicated a more-forefoot strike pattern in the SBR group compared to controls; both running barefoot (P>0.05), and shod (P<0.001). When assessed barefoot, there were significant kinematic differences across time in the SBR group for ankle flexion angle at toe-off (P<0.01). When assessed shod, significant kinematic changes occurred across time, for ankle flexion angles at foot-strike (P<0.001) and toe-off (P<0.01), and for range of motion (ROM) in the absorptive phase of stance (P<0.01). A knee effect was recorded in the SBR group for flexion ROM in the absorptive phase of stance (P<0.05). No significant changes occurred in controls. Therefore, a 12-week transition program in SBR could assist athletes seeking a more-forefoot strike pattern and "barefoot" kinematics, regardless of preferred footwear.

Tubo-ovarian abscess in virginal adolescent females: a case report and review of the literature.

BACKGROUND: A tubo-ovarian abscess (TOA) is a serious complication of pelvic inflammatory disease (PID), predominantly polymicrobial and present in sexually active women. TOA in virginal adolescent females are extremely rare but have serious and lifelong consequences. CASE: A 13 y.o. virginal female presented to the Emergency Room of a tertiary care pediatric hospital with abdominal pain and vomiting. Imaging suggested bowel compromise with potential perforation. An exploratory laparotomy revealed TOA which grew Escherichia Coli. This is the first reported case of Escherichia Coli TOA due to suspected bowel translocation. CONCLUSION: Review of the literature identified 8 cases of TOA in virginal adolescents. Given the severity of outcomes following TOA, this pathology should be considered in the differential diagnosis of virginal adolescents who present with fever and abdominal pain. If suspected, a prompt gynecology consult should be initiated, followed by a first line antibiotic therapy and when indicated, surgical drainage.

Age-associated differences in gene expression in response to delayed anesthetic preconditioning.

Evidence suggests that the protective benefits of anesthetic preconditioning (APC) are significantly attenuated in the aged myocardium. In this study, we investigated the effect of aging on gene expression in delayed APC. Hearts from Fischer 344 rats, age 4 or 24 months, were divided into five groups: control; ischemia/reperfusion (I/R); and delayed APC at 6, 12, and 24 h. Whole-genome array was studied using Affymetrix Rat Genome 230 2.0 array. Data were analyzed for significant ≥2.0-fold changes in gene expression. Microarray results were confirmed by quantitative real-time reverse transcription-polymerase chain reaction. Of the 28,000 genes represented on the Affymetrix Rat Genome 230 2.0 Microarray chip, 24 transcripts in 6 h APC, 28 in 12 h APC, and 28 in 24 h APC group displayed significant up-regulation in mRNA levels, and 70 transcripts in 6 h APC, 101 in 12 h APC, and 82 in 24 h APC displayed significant down-regulation in young rat hearts. These altered genes fall into functional categories of cell defense/death, cell structure, gene expression/protein synthesis, inflammatory response/growth/remodeling, and signaling/communication. Although alterations for some genes were in common, the numbers of changed genes in old rats were markedly and consistently lower than the young rats. Twenty-four hour delayed APC also significantly reduced infarct size and improved myocardial left ventricular function in young hearts, effects that were not observed in old rat hearts. We concluded that delayed APC profoundly and differentially affected gene expression profiles of the cardiomyocyte in an age-associated pattern. The impaired genomic response to delayed APC could underlie the loss of the protective benefits of preconditioning in aged hearts.

Feasibility study of a smart pen for autonomous detection of concentration lapses during reading.

We implemented a portable smart pen system capable of detecting lapses in concentration during reading. An accelerometer and a microcontroller are embedded within a pen casing to record data as a user reads sections of text using the pen as a pointer. When a substantial pause in reading is detected, the system generates an appropriate warning or alarm. An accompanying software program can communicate with the pen through a USB interface to customize system parameters, record relevant data, and graph collected data over time. The overall effectiveness of a prototype system was tested on 11 normal volunteers and 3 persons with attention deficit disorder (ADD). The prototype system had probability of false alarm of 19%, and sensitivity of 82%. With further refinement, this system could enable patients with attention deficit/hyperactivity disorder maintain concentration during reading in a variety of environments.

Isolated transient neonatal clitoromegaly with hyperandrogenism of unknown etiology.

BACKGROUND: Neonatal clitoromegaly is usually attributed to androgen stimulation secondary to congenital adrenal hyperplasia or in utero androgen exposure. We present a unique case of transient, isolated neonatal clitoromegaly, associated with increased androgen levels of unidentifiable cause, which spontaneously resolved when the androgen levels normalized. This is the first report where, despite an exhaustive workup, the cause of hyperandrogenism remains unknown. CASE: A female infant was delivered at 25 + 5 weeks gestational age. Clitoromegaly was first documented at 3 months of age (18 mm long, |13 mm wide). There was no other evidence of virilization. There was no neonatal history of transfusions or androgen-medication exposure. Initial bloodwork documented extremely high levels of free testosterone (117 pmol/L) and dehydroepiandrosterone sulfate (DHEAS). Further tests ruled out the following diagnoses: 21-hydroxylase deficiency, 11-betahydroxylase deficiency, testicular feminization, presence of ovotesticular tissue, and androgen-secreting tumors. Maternal history ruled out in utero androgen exposure, maternal drug use, hyperandrogenism, or virilization during pregnancy, and antenatal imaging had not detected a maternal ovarian mass or adrenal tumor. The infant's androgen levels spontaneously declined, and by 4 months of age had normalized without therapy (free testosterone 8 pmol/L). At 5 months of age, the clitoral measurements normalized (10mm long, 5mm wide). CONCLUSION: In this case of a premature female infant, hyperandrogenism and clitoromegaly resolved spontaneously. Only 1 other case of hyperandrogenism and clitoromegaly that resolved spontaneously in a preterm infant has been reported. In that case, the clitoromegaly and high testosterone levels were attributed to repeated blood transfusions from an adult male. The etiology of the hyperandrogenism and resultant clitoromegaly in our case is not known.

Virilizing luteinized thecoma of the ovary in a 15-year-old female: a case report.

BACKGROUND: Only 30% of luteinized thecomas are found in women under the age of 30, and they are typically benign. Only 11% of luteinized thecomas show clinical signs of androgen production. We present an unusual case of a 15-year-old female who presented with secondary amenorrhea and virilization and was subsequently diagnosed with a benign luteinized thecoma of the ovary. This is the youngest nonmalignant luteinized thecoma reported to date. CASE: A 15-year-old Sri Lankan female presented with increasing hair growth, a hoarse voice, and secondary amenorrhea. On physical examination, there was marked hirsutism and clitoromegaly. Investigations found an elevated free testosterone level and an enlarged, homogenous left ovary with absent normal ovarian architecture. A laparotomy and unilateral salpingo-oophorectomy was performed. The final diagnosis was a luteinized ovarian thecoma, with no evidence of malignancy. Postoperatively, testosterone levels normalized and menstrual cycles resumed. Although laser treatment helped with her hirsutism, her other virilizing symptoms (deepening of voice, clitoromegaly) did not improve postoperatively. CONCLUSION: This case of a virilizing ovarian luteinized thecoma emphasizes the need for timely evaluation, diagnosis, and treatment of patients presenting with symptoms of excess androgen secretion in order to avoid irreversible unwanted effects. Possible ovarian causes of excess androgen secretion should not be overlooked when considering possible causes of hyperandrogenism and secondary amenorrhea.

Oro-facial activities in sleep bruxism patients and in normal subjects: a controlled polygraphic and audio-video study.

To our knowledge, the large spectrum of sleep motor activities (SMA) present in the head and neck region has not yet been systematically estimated in normal and sleep bruxism (SB) subjects. We hypothesized that in the absence of audio-video signal recordings, normal and SB subjects would present a high level of SMA that might confound the scoring specificity of SB. A retrospective analysis of several SMA, including oro-facial activities (OFA) and rhythmic masticatory muscle activities (RMMA), was made from polygraphic and audio-video recordings of 21 normal subjects and 25 SB patients. Sleep motor activities were scored, blind to subject status, from the second night of sleep recordings. Discrimination of OFA included the following types of activities: lip sucking, head movements, chewing-like movements, swallowing, head rubbing and scratching, eye opening and blinking. These were differentiated from RMMA and tooth grinding. The frequency of SMA per hour of sleep was lower in normal subjects in comparison with SB patients (P < 0.001). Up to 85% of all SMA in normal subjects were related to OFA while 30% of SMA in SB patients were related to OFA scoring (P < 0.001). The frequency of RMMA was seven times higher in SB patients than in normal subjects (P < 0.001). Several SMA can be observed in normal and SB subjects. In the absence of audio-video signal recordings, the discrimination of various types of OFA is difficult to achieve and may lead to erroneous estimation of SB-related activities.

Template switching within exons 3 and 4 of KV11.1 (HERG) gives rise to a 5' truncated cDNA.

K(V)11.1 (HERG) channels contribute to membrane potential in a number of excitable cell types. We cloned a variant of K(V)11.1 from human jejunum containing a 171 bp deletion spanning exons 3 and 4. Expression of a full-length cDNA clone containing this deletion gave rise to protein that trafficked to the cell membrane and generated robust currents. The deletion occurred in a G/C-rich region and identical sequence elements of UGGUGG were located at the deletion boundaries. In recent studies these features have been implicated to cause deletions via template switching during cDNA synthesis. To examine this possibility we compared cDNAs from human brain, heart, and jejunum synthesized at lower (42 degrees C) and higher temperatures (70 degrees C). The 171 bp deletion was absent at the higher temperature. Our results suggest that the sequence and secondary structure of mRNA in the G/C rich region leads to template switching producing a cDNA product with a 171 bp deletion.

Congenital imperforate hymen and its life-threatening consequences in the neonatal period.

Imperforate hymen is most commonly an isolated finding and usually remains asymptomatic until puberty. Rarely, symptoms of imperforate hymen manifest antenatally as well as in the neonatal period, requiring surgical correction for life-threatening consequences. We report a 5-day-old infant with a large hydrometrocolpos causing severe renal compromise and abdominal ascites, successfully surgically treated in the neonatal period. Associated polydactyly suggested McKusick-Kaufman syndrome.