The impact of anxiety on postoperative pain following pelvic reconstructive surgery.

INTRODUCTION AND HYPOTHESIS: Despite the prevalence of anxiety, its impact on postoperative pain remains poorly characterized. The present study was aimed at assessing the impact of preoperative anxiety on postoperative pain in patients undergoing pelvic reconstructive surgery. We hypothesized that greater anxiety would be associated with increased postoperative pain for patients undergoing pelvic reconstructive surgery. METHODS: This was a prospective multi-center observational study in Baltimore between September 2018 and June 2019. The Beck Anxiety Inventory was used to assess preoperative anxiety and the validated Surgical Pain Scale instrument was used to assess pain in the postoperative period. The association between anxiety and postoperative pain was analyzed using multivariate logistic regression, adjusting for relevant confounders. RESULTS: A total of 149 patients undergoing pelvic reconstructive surgery completed preoperative surveys. The median age of the study population was 59. The prevalence of preoperative anxiety (anxiety score > 9) in our study population was 26.8% (95% CI 19.7-34.0%). Women with preoperative anxiety reported higher postoperative pain on days 1-2 (relative odds 1.05, 95% confidence interval 1.01-1.10) and day 14 (relative odds 1.53, 95% confidence interval 1.00-2.34). CONCLUSIONS: A large fraction of women undergoing pelvic reconstructive surgery have moderate to severe preoperative anxiety. Women with preoperative anxiety appear to have greater odds of increased postoperative pain. Understanding this association may help surgeons with preoperative counseling and expectations regarding postoperative pain.

Prolapse and mesh reoperations following sacrocolpopexy: comparing supracervical hysterectomy, total hysterectomy, and no hysterectomy.

INTRODUCTION AND HYPOTHESIS: Sacrocolpopexy is effective for apical prolapse repair and is often performed with hysterectomy. It is unknown whether supracervical or total hysterectomy at time of sacrocolpopexy influences prolapse recurrence and mesh complications. The primary objective of this study is to compare reoperations for recurrent prolapse after sacrocolpopexy with either supracervical hysterectomy or total hysterectomy, or without concomitant hysterectomy. We also sought to compare these three groups for the incidence of mesh complications and describe cervical interventions following supracervical hysterectomy. METHODS: A retrospective cohort study of sacrocolpopexy was performed using the MarketScan® Research Database. Women > 18 years who underwent sacrocolpopexy between 2010 to 2014 were identified. Utilizing diagnostic and procedural codes, reoperations for prolapse and mesh complications were identified. Women with < 2 years of follow-up were excluded. RESULTS: From 2010 to 2014, 3463 women underwent sacrocolpopexy with at least 2 years of follow-up, 910 (26.3%) with supracervical hysterectomy, 1243 (35.9%) with total hysterectomy, and 1310 (37.8%) without hysterectomy. Reoperations for prolapse were similar after supracervical hysterectomy (1.5%), after total hysterectomy (1.1%, p = 0.40), and without hysterectomy (1.5%, p = 0.98). Mesh complications after sacrocolpopexy were similar after supracervical hysterectomy (1.8%), after total hysterectomy (1.5%, p = 0.68), and without hysterectomy (2.8%, p = 0.11). Following supracervical hysterectomy, 0.9% underwent cervical procedures. CONCLUSIONS: When comparing supracervical and total hysterectomy at time of sacrocolpopexy, there were no significant differences in reoperations for recurrent prolapse, reoperations for mesh complications, or mesh complication diagnoses. This study shows that surgeons can be reassured on performing hysterectomy with sacrocolpopexy.

Obstructed defecation syndrome in the first week after pelvic reconstructive surgery.

INTRODUCTION AND HYPOTHESIS: Research shows that patients are concerned about postoperative bowel function after pelvic reconstructive surgery. The objectives of this study were to estimate the proportion of patients with obstructed defecation syndrome (ODS), a subtype of constipation, in the week after surgery, to identify associated patient-level and perioperative characteristics and the associated bother. METHODS: Women completed a preoperative and postoperative ODS questionnaire and postoperative bowel diary. Characteristics of women with and without postoperative ODS were compared. Chi-squared or Fisher's exact tests compared categorical variables. Student's t test or Wilcoxon rank-sum tests compared continuous variables. Multivariate logistic regression was assessed for independent effects. Wilcoxon rank-sum tests compared the groups with regard to bother. Spearman correlation coefficients described the relationship among bother, postoperative ODS score, and bowel diary variables. RESULTS: Of the 186 participants enrolled, 165 completed the postoperative ODS questionnaire. Of these, 39 women (23.6%, 95% CI 17.2-30.1) had postoperative ODS. Postoperative ODS was significantly associated with preoperative ODS (p < 0.001), posterior colporrhaphy (p = 0.03), surgery type (p = 0.01), and longer duration of surgery (p = 0.03). Using multivariate logistic regression controlling for age, only preoperative ODS was significantly associated with postoperative ODS (OR 2.68, 95% CI 1.73-4.17). Women with postoperative ODS reported more bother with their defecatory symptoms (p < 0.001). The degree of bother was significantly associated with postoperative ODS score (p < 0.001). CONCLUSION: Using a validated disease-specific questionnaire to identify ODS, this complication was identified in 23.6% of patients in the week after pelvic reconstructive surgery. Preoperative ODS was a significant and important risk factor for this complication.

Phase 2 of family-based treatment: an exploratory assessment of clinician practices.

PURPOSE: In manualized family-based treatment (FBT) for eating disorders, phase 1 of the 3-phase treatment-during which parents are put in control of eating-related issues-is perhaps the most critical phase, and is comprehensively addressed in the manual. Phase 2, during which control over eating is gradually returned to the patient, is more variable and the manual dedicates less space to this phase. The purpose of the current exploratory study was to assess Phase 2 practices of clinicians providing FBT and to compare these practices to the guidance offered in the manual. METHODS: In the current study, a survey assessing Phase 2 practices was sent to clinicians. Twenty-seven providers responded. Two providers reported that they did not provide FBT in an outpatient setting. One reported not currently providing outpatient FBT but had in the past. The remaining providers were currently providing FBT in an outpatient setting. RESULTS: No items addressing the core interventions of Phase 2, including encouraging age-appropriate independent eating, were endorsed by 100% of respondents as being addressed 100% of the time in Phase 2. CONCLUSION: Responses reflected some adherence to the manual, along with examples of therapist drift and incorporation of therapeutic interventions that are not described in the FBT manual. Adherence to manualized treatments may improve outcome for some patients, while allowing for flexibility to address clinical situations that are not addressed in the manual. LEVEL OF EVIDENCE: V. Opinions of respected authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.

Understanding the biology, morbidity and social contexts of adolescent tuberculosis: a prospective observational cohort study protocol (Teen TB).

INTRODUCTION: A considerable burden of the tuberculosis (TB) epidemic is found in adolescents. The reasons for increased susceptibility to TB infection and higher incidence of TB disease in adolescence, compared with the 5-10 years old age group, are incompletely understood. Despite the pressing clinical and public health need to better understand and address adolescent TB, research in this field remains limited. METHODS AND ANALYSIS: Teen TB is an ongoing prospective observational cohort study that aims to better understand the biology, morbidity and social context of adolescent TB. The study plans to recruit 50 adolescents (10-19 years old) with newly diagnosed microbiologically confirmed pulmonary TB disease and 50 TB-exposed controls without evidence of TB disease in Cape Town, South Africa, which is highly endemic for TB. At baseline, cases and controls will undergo a detailed clinical evaluation, chest imaging, respiratory function assessments and blood collection for viral coinfections, inflammatory cytokines and pubertal hormone testing. At 2 weeks, 2 months and 12 months, TB disease cases will undergo further chest imaging and additional lung function testing to explore the patterns of respiratory abnormalities. At week 2, cases will complete a multicomponent quantitative questionnaire about psychological and social impacts on their experiences and longitudinal, in-depth qualitative data will be collected from a nested subsample of 20 cases and their families. ETHICS AND DISSEMINATION: The study protocol has received ethical approval from the Stellenbosch University Health Research Ethics Committee (N19/10/148). The study findings will be disseminated through peer-reviewed publications, academic conferences and formal presentations to health professionals. Results will also be made available to participants and caregivers.

Validation of a Spanish Version of the Prolapse and Incontinence Knowledge Questionnaire.

OBJECTIVE: The objective of this study was to validate a Spanish version of the Prolapse and Incontinence Knowledge Questionnaire (PIKQ). METHODS: Validation and reliability testing of the Spanish version of the PIKQ was conducted in 2 phases. In the first phase, a translation-back-translation method by 6 bilingual researchers was utilized to generate a final Spanish translation. In the second phase, bilingual women were randomized to complete the Spanish or English version first, followed by the alternate language. Agreement between individual items from English and Spanish versions was assessed by percent agreement and κ statistics. Intraclass correlation coefficients compared overall PIKQ scores and pelvic organ prolapse (POP) and urinary incontinence (UI) subscores. To establish test-retest reliability, we calculated Pearson correlation coefficients. In order to have a precision of 10% for 90% agreement, so that the lower 95% confidence interval would not be less than 80% agreement, 50 bilingual participants were required. RESULTS: Fifty-seven bilingual women were randomized and completed both versions of the PIKQ. Individual items showed 74%-97% agreement, good to excellent agreement (κ = 0.6-0.89) for 9 items and moderate agreement (κ = 0.4-0.59) for 14 items between English and Spanish PIKQ versions. Intraclass correlation coefficients of the overall score and POP and UI subscores showed excellent agreement (intraclass correlation coefficient = 0.81-0.91). Pearson correlation coefficients between initial and repeat Spanish scores were high: overall (r = 0.87) and for POP (r = 0.81) and UI subscores (r = 0.77). CONCLUSIONS: A valid and reliable Spanish version of the PIKQ has been developed to assess patient knowledge about UI and POP.

Examining the association between meal context and diet quality: an observational study of meal context in older adults.

BACKGROUND: Though a healthy diet is widely associated with reduced risks for chronic disease and mortality, older adults in the U.S. on average do not meet dietary recommendations. Given that few studies have examined the association between meal context on older adult diet quality, the aims of this study were (1) to compare the dietary quality of foods consumed in different meal contexts, as measured by the Healthy Eating Index 2015 (HEI-2015): meal location, the presence of others, and the use of electronic screens; and (2) to examine which components of the HEI-2015 drove differences in HEI-2015 total scores by meal context. METHODS: Interactive Diet and Activity Tracking in AARP study participants (50-74 years) completed the Automated Self-Administered 24-h Dietary Assessment tool (ASA24, version 2011) that included foods and beverages consumed and three meal contexts: "at home" versus "away from home," "alone" versus "with company," and "with screen time" versus "without screen time." A population ratio approach was used to estimate HEI-2015 total and component scores for all food items consumed by meal context. Mean HEI-2015 scores (range: 0-100) for the three meal context variables were compared using t-tests. Where there were significant differences in total scores, additional t-tests were used to explore which HEI-2015 components were the primary drivers. All tests were stratified by sex and adjusted for multiple comparisons. RESULTS: HEI-2015 scores were lower for meals consumed away vs. at home (mean difference (SE), males: - 8.23 (1.02); females: - 7.29 (0.93); both p < 0.0001) and for meals eaten with vs. without company (mean difference (SE), males: - 6.61 (1.06); females: - 7.34 (1.18); both p < 0.0001). There was no difference comparing with vs. without screen time. When HEI-2015 component scores were examined, fewer total fruits, whole grains, and dairy were consumed away from home or with company; more total vegetables and greens and beans, and less added sugars were consumed with company. CONCLUSIONS: Our findings suggest an association between the behavior cues of meal location and companions and dietary choices among older adults. Future studies can explore the individual and interactive effects of meal context on diet quality and subsequent health outcomes.

Opportunities for Mobile App-Based Adherence Support for Children With Tuberculosis in South Africa.

Tuberculosis is the number one infectious cause of death globally. Young children, generally those younger than 5 years, are at the highest risk of progressing from tuberculosis infection to tuberculosis disease and of developing the most severe forms of tuberculosis. Most current tuberculosis drug formulations have poor acceptability among children and require consistent adherence for prolonged periods of time. These challenges complicate children's adherence to treatment and caregivers' daily administration of the drugs. Rapid developments in mobile technologies and apps present opportunities for using widely available technology to support national tuberculosis programs and patient treatment adherence. Pilot studies have demonstrated that mobile apps are a feasible and acceptable means of enhancing children's treatment adherence for other chronic conditions. Despite this, no mobile apps that aim to promote adherence to tuberculosis treatment have been developed for children. In this paper, we draw on our experiences carrying out research in clinical pediatric tuberculosis studies in South Africa. We present hypothetical scenarios of children's adherence to tuberculosis medication to suggest priorities for behavioral and educational strategies that a mobile app could incorporate to address some of the adherence support gaps faced by children diagnosed with tuberculosis. We argue that a mobile app has the potential to lessen some of the negative experiences that children associate with taking tuberculosis treatment and to facilitate a more positive treatment adherence experience for children and their caregivers.

Seasonal asthma in Melbourne, Australia, and some observations on the occurrence of thunderstorm asthma and its predictability.

We examine the seasonality of asthma-related hospital admissions in Melbourne, Australia, in particular the contribution and predictability of episodic thunderstorm asthma. Using a time-series ecological approach based on asthma admissions to Melbourne metropolitan hospitals, we identified seasonal peaks in asthma admissions that were centred in late February, June and mid-November. These peaks were most likely due to the return to school, winter viral infections and seasonal allergies, respectively. We performed non-linear statistical regression to predict daily admission rates as functions of the seasonal cycle, weather conditions, reported thunderstorms, pollen counts and air quality. Important predictor variables were the seasonal cycle and mean relative humidity in the preceding two weeks, with higher humidity associated with higher asthma admissions. Although various attempts were made to model asthma admissions, none of the models explained substantially more variation above that associated with the annual cycle. We also identified a list of high asthma admissions days (HAADs). Most HAADs fell in the late-February return-to-school peak and the November allergy peak, with the latter containing the greatest number of daily admissions. Many HAADs in the spring allergy peak may represent episodes of thunderstorm asthma, as they were associated with rainfall, thunderstorms, high ambient grass pollen levels and high humidity, a finding that suggests thunderstorm asthma is a recurrent phenomenon in Melbourne that occurs roughly once per five years. The rarity of thunderstorm asthma events makes prediction challenging, underscoring the importance of maintaining high standards of asthma management, both for patients and health professionals, especially during late spring and early summer.

Adherence as a predictor of weight loss in a commonly used smartphone application.

As adherence to weight loss interventions has been shown in prior research to be crucial in achieving weight reduction, we were interested in examining whether this held true for individuals attempting to lose weight using smartphone applications. Archived data from an international community sample of 7633 overweight men and women using Noom, a smartphone-based behavioural weight loss program, were used to test the hypotheses that there would be significant weight loss after using the application for three months and that greater self-monitoring adherence would be positively associated with weight loss outcomes. An average 1.92 BMI points were lost after using Noom for three months, and for every 10% increase in adherence there was a decrease of 2.59 BMI points (ß=-1.36kg, SE=.24, p<.001). Our results provide preliminary evidence suggesting that smartphone application use is linked to significant short-term weight loss and that this weight loss is associated with adherence.

Adult forebrain NMDA receptors gate social motivation and social memory.

Motivation to engage in social interaction is critical to ensure normal social behaviors, whereas dysregulation in social motivation can contribute to psychiatric diseases such as schizophrenia, autism, social anxiety disorders and post-traumatic stress disorder (PTSD). While dopamine is well known to regulate motivation, its downstream targets are poorly understood. Given the fact that the dopamine 1 (D1) receptors are often physically coupled with the NMDA receptors, we hypothesize that the NMDA receptor activity in the adult forebrain principal neurons are crucial not only for learning and memory, but also for the proper gating of social motivation. Here, we tested this hypothesis by examining sociability and social memory in inducible forebrain-specific NR1 knockout mice. These mice are ideal for exploring the role of the NR1 subunit in social behavior because the NR1 subunit can be selectively knocked out after the critical developmental period, in which NR1 is required for normal development. We found that the inducible deletion of the NMDA receptors prior to behavioral assays impaired, not only object and social recognition memory tests, but also resulted in profound deficits in social motivation. Mice with ablated NR1 subunits in the forebrain demonstrated significant decreases in sociability compared to their wild type counterparts. These results suggest that in addition to its crucial role in learning and memory, the NMDA receptors in the adult forebrain principal neurons gate social motivation, independent of neuronal development.

Brain Computation Is Organized via Power-of-Two-Based Permutation Logic.

There is considerable scientific interest in understanding how cell assemblies-the long-presumed computational motif-are organized so that the brain can generate intelligent cognition and flexible behavior. The Theory of Connectivity proposes that the origin of intelligence is rooted in a power-of-two-based permutation logic (N = 2 i -1), producing specific-to-general cell-assembly architecture capable of generating specific perceptions and memories, as well as generalized knowledge and flexible actions. We show that this power-of-two-based permutation logic is widely used in cortical and subcortical circuits across animal species and is conserved for the processing of a variety of cognitive modalities including appetitive, emotional and social information. However, modulatory neurons, such as dopaminergic (DA) neurons, use a simpler logic despite their distinct subtypes. Interestingly, this specific-to-general permutation logic remained largely intact although NMDA receptors-the synaptic switch for learning and memory-were deleted throughout adulthood, suggesting that the logic is developmentally pre-configured. Moreover, this computational logic is implemented in the cortex via combining a random-connectivity strategy in superficial layers 2/3 with nonrandom organizations in deep layers 5/6. This randomness of layers 2/3 cliques-which preferentially encode specific and low-combinatorial features and project inter-cortically-is ideal for maximizing cross-modality novel pattern-extraction, pattern-discrimination and pattern-categorization using sparse code, consequently explaining why it requires hippocampal offline-consolidation. In contrast, the nonrandomness in layers 5/6-which consists of few specific cliques but a higher portion of more general cliques projecting mostly to subcortical systems-is ideal for feedback-control of motivation, emotion, consciousness and behaviors. These observations suggest that the brain's basic computational algorithm is indeed organized by the power-of-two-based permutation logic. This simple mathematical logic can account for brain computation across the entire evolutionary spectrum, ranging from the simplest neural networks to the most complex.

Paraurethral Leiomyoma in a 20 Year-old Woman: A Case Report.

We present the case of a 20 year-old woman with a vulvar mass, found to be a paraurethral leiomyoma. She subsequently underwent supermedial-approach paraurethral mass excision, distal urethral reconstruction and cystourethroscopy. Paraurethral leiomyoma make up approximately five percent of urethral tumors. This case depicts the presentation and treatment of a paraurethral leiomyoma in one of the youngest women reported in the literature.

Importance of the GluN2B carboxy-terminal domain for enhancement of social memories.

The N-methyl-D-aspartate (NMDA) receptor is known to be necessary for many forms of learning and memory, including social recognition memory. Additionally, the GluN2 subunits are known to modulate multiple forms of memory, with a high GluN2A:GluN2B ratio leading to impairments in long-term memory, while a low GluN2A:GluN2B ratio enhances some forms of long-term memory. Here, we investigate the molecular motif responsible for the differences in social recognition memory and olfactory memory in the forebrain-specific transgenic GluN2A overexpression mice and the forebrain-specific transgenic GluN2B overexpression mice by using two transgenic mouse lines that overexpress chimeric GluN2 subunits. The transgenic chimeric GluN2 subunit mice were tested for their ability to learn and remember fruit scents, male juveniles of the same strain, females of the same strain, male juveniles of another strain, and rodents of another species. The data presented here demonstrate that the GluN2B carboxy-terminal domain is necessary for enhanced social recognition memory in GluN2B transgenic overexpression mice. Furthermore, the GluN2A carboxy-terminal domain is responsible for the impaired long-term olfactory and social memory observed in the GluN2A overexpression mice.

Heat stress during the Black Saturday event in Melbourne, Australia.

The Black Saturday bushfire event of February 7, 2009, devastated the state of Victoria, Australia, resulting in 173 deaths. On this day, the maximum temperature in Melbourne (state capital of Victoria, population 4 million people) exceeded 46 °C, there were wind gusts of over 80 km h(-1) and the relative humidity dropped below 5 %. We investigated the severe meteorological conditions of Black Saturday and the risk of heat stress and dehydration for the residents of Melbourne. This was through the analysis of weather station data, air pollution data, the apparent temperature (AT) and the COMfort FormulA human energy budget model. A very strong pressure gradient caused hot and dry air to be advected to Melbourne from the desert interior of Australia creating the extreme weather conditions. The AT showed that on Black Saturday, heat stress conditions were present, though underrepresented due to assumptions in the AT formula. Further investigation into the human energy budget revealed that the conditions required a sweating rate of 1.4 kg h(-1) to prevent heat accumulation into the body. If sweating stopped, hyperthermia could occur in 15 min. Sensitivity tests indicated that the dry air and strong winds on Black Saturday helped to release latent heat, but the required sweating rate was virtually unattainable for an average person and would result in intense dehydration. Air particulates were at dangerous concentrations in Melbourne on Black Saturday, further intensifying the stresses to the human body. In the future, we recommend that the AT is not used as a thermal comfort measure as it underestimates the physical stress people experience.

Molecular and genetic determinants of the NMDA receptor for superior learning and memory functions.

The opening-duration of the NMDA receptors implements Hebb's synaptic coincidence-detection and is long thought to be the rate-limiting factor underlying superior memory. Here, we investigate the molecular and genetic determinants of the NMDA receptors by testing the "synaptic coincidence-detection time-duration" hypothesis vs. "GluN2B intracellular signaling domain" hypothesis. Accordingly, we generated a series of GluN2A, GluN2B, and GluN2D chimeric subunit transgenic mice in which C-terminal intracellular domains were systematically swapped and overexpressed in the forebrain excitatory neurons. The data presented in the present study supports the second hypothesis, the "GluN2B intracellular signaling domain" hypothesis. Surprisingly, we found that the voltage-gated channel opening-durations through either GluN2A or GluN2B are sufficient and their temporal differences are marginal. In contrast, the C-terminal intracellular domain of the GluN2B subunit is necessary and sufficient for superior performances in long-term novel object recognition and cued fear memories and superior flexibility in fear extinction. Intriguingly, memory enhancement correlates with enhanced long-term potentiation in the 10-100 Hz range while requiring intact long-term depression capacity at the 1-5 Hz range.

Targeting the NMDA receptor subunit NR2B for treating or preventing age-related memory decline.

INTRODUCTION: Age-related memory loss is believed to be a result of reduced synaptic plasticity, including changes in the NR2 subunit composition of the NMDA receptor. It is known that endogenous NR2B subunits decrease as the brain ages, whereas transgenic upregulation of NR2B enhances synaptic plasticity and learning and memory in several animal species. Accumulating evidence suggests that elevated brain magnesium levels, via dietary supplementation, can boost NR2B in the brain, consequently reversing memory deficits and enhancing cognitive abilities. AREAS COVERED: This review highlights the convergent molecular mechanisms via the NR2B pathway as a useful strategy for treating age-related memory loss. A dietary approach, via oral intake of a novel compound, magnesium L-threonate (MgT), to boost NR2B expression in the brain is highlighted. EXPERT OPINION: Direct upregulation of the NR2B subunit expression can enhance synaptic plasticity and memory functions in a broad range of behavioral tasks in rodents. Other upregulation approaches, such as targeting the NR2B transporter or surface recycling pathway via cyclin-dependent kinase 5, are highly effective in improving memory functions. A dietary supplemental approach by optimally elevating the [Mg²âº] in the brain is surprisingly effective in upregulating NR2B expression and improving memories in preclinical studies. MgT is currently under clinical trials.

Randomized prospective crossover study of interstim lead wire placement with curved versus straight stylet.

AIMS: To assess whether InterStim lead wire placement with the curved stylet achieves motor response at lower amplitudes compared to straight stylet use. METHODS: This was a prospective, randomized, crossover study of patients scheduled for InterStim lead wire placement. All patients underwent lead wire testing with both the curved and straight stylets. Patients were randomized to determine stylet order, and then crossed-over to the alternate. Intra-operatively, the amplitude achieving motor response at each electrode was recorded. The stylet with lowest overall amplitudes was used for final placement. Primary outcome measure was amplitude requirement in the two deepest (0 and 1) electrodes. Secondary outcomes included amplitudes at the number 2 and 3 electrodes, combined amplitudes, stylet order, and adverse outcomes. RESULTS: Forty-two patients were enrolled, 40 of whom were included in the final analysis. Mean age was 69 years (SD = 12.8) and mean BMI 27 (SD = 5.6). Indications for placement included: urge urinary incontinence (N = 26), urge/frequency (N = 25), non-obstructive urinary retention (N = 5), and fecal incontinence (N = 10). There were no significant differences between randomized groups. Regardless of order, the curved stylet achieved a motor response at lower amplitudes in the deepest electrodes (P < 0.001). Combined amplitudes of all electrodes were also significantly lower with the curved stylet (P < 0.001). Subsequently, 88% underwent final "optimal" placement with curved stylet (N = 35). CONCLUSIONS: The curved stylet for InterStim lead wire placement consistently achieved motor response at lower amplitudes. A brief intra-operative exchange of stylets represents a minor procedural alteration that could maximize Implantable Pulse Generator battery life and facilitate programming.

A new 'bio-comfort' perspective for Melbourne based on heat stress, air pollution and pollen.

Humans are at risk from exposure to extremes in their environment, yet there is no consistent way to fully quantify and understand the risk when considering more than just meteorological variables. An outdoor 'bio-comfort' threshold is defined for Melbourne, Australia using a combination of heat stress, air particulate concentration and grass pollen count, where comfortable conditions imply an ideal range of temperature, humidity and wind speed, acceptable levels of air particulates and a low pollen count. This is a new approach to defining the comfort of human populations. While other works have looked into the separate impacts of different variables, this is the first time that a unified bio-comfort threshold is suggested. Composite maps of surface pressure are used to illustrate the genesis and evolution of the atmospheric structures conducive to an uncomfortable day. When there is an uncomfortable day due to heat stress conditions in Melbourne, there is a high pressure anomaly to the east bringing warm air from the northern interior of Australia. This anomaly is part of a slow moving blocking high originating over the Indian Ocean. Uncomfortable days due to high particulate levels have an approaching cold front. However, for air particulate cases during the cold season there are stable atmospheric conditions enhanced by a blocking high emanating from Australia and linking with the Antarctic continent. Finally, when grass pollen levels are high, there are northerly winds carrying the pollen from rural grass lands to Melbourne, due to a stationary trough of low pressure inland. Analysis into days with multiple types of stress revealed that the atmospheric signals associated with each type of discomfort are present regardless of whether the day is uncomfortable due to one or multiple variables. Therefore, these bio-comfort results are significant because they offer a degree of predictability for future uncomfortable days in Melbourne.

Safety assessment of myogenic stem cell transplantation and resulting tumor formation.

OBJECTIVES: To assess for stem cell migration to liver and lung after transplantation in injured rat anal sphincters. To evaluate histological findings of unanticipated ectopic foci of growth. METHODS: This is a prospective study involving 33 female virginal Sprague-Dawley rats. Anal sphincters were transected and repaired under sterile technique. Animals received injections of 5.0 × 10 myogenic stem cells (24 rats) or sham control (9 rats) and were killed on day 30. Liver and lung samples were obtained. Upon encountering abnormal foci of growth, further staining protocols were employed. Enzyme-linked immunosorbent assay studies evaluated stem cell media for in vitro growth factor secretion. RESULTS: No evidence of cell migration to liver or lung was found at the time of euthanasia in any study animal. Ectopic foci of growth were noted in 2 transplant rats. Further histological evaluations of these growths were consistent with benign tumors: no nuclear abnormalities and no evidence of proliferation at day 30. Enzyme-linked immunosorbent assay studies demonstrated positive secretion of vascular endothelial growth factor and insulin growth factor into the media of cultured rat myogenic stem cells. CONCLUSIONS: Whereas distant migration was not encountered in the liver or lung, 2 transplanted rats developed abnormal foci of growth, that is, tumors, from the external anal sphincter-raising further safety questions. Additional evaluation of these foci seemed benign. Possible explanations include cell trapping, stem cell overgrowth, and/or paracrine factors. The lack of cell migration supports that future investigation of safety parameters could focus locally.