Caregiver experiences of hospice dementia care: a systematic review and meta-ethnography.

OBJECTIVES: Hospices are regarded as gold standard providers of end-of-life care. The term hospice, however, is broadly used, and can describe a type of care offered in a variety of health care services (e.g. nursing homes). It thus becomes complex for families to decide between services. We aimed to review the evidence around the experience of family carers of people with dementia accessing in-patient hospice settings for end-of-life care. METHOD: We registered the review protocol on PROSPERO. We used PerSPE(C)TiF to systematically organise our search strategy. The evidence was reviewed across six databases: PubMed, EMBASE, PsycINFO, ASSIA, ISI Web, and CINAHL. We used meta-ethnography as per the eMERGe guidance for data interpretation. RESULTS: Four studies were included. Two third-order constructs were generated through meta-ethnography: expectations of care and barriers to quality of care. We found that carers had expectations of care, and these could change over time. If discussion was not held with hospice staff early on, the carers could experience reduced care quality due to unmatched expectations. Unmatched expectations acted as barriers to care and these were found in terms of carers not feeling adequately supported, and/or having the person discharged from hospice, which would entail increased care responsibility for carers. CONCLUSION: In view of an increase in new dementia cases over time and with hospice services being under pressure, integrating palliative care services within community-based models of care is key to reducing the risk of having inadequate and under resourced services for people with dementia.

Clinical Study Demonstrates that Electromagnetic Muscle Stimulation Does Not Cause Injury to Fat Cells.

BACKGROUND AND OBJECTIVES: A previous pre-clinical study on electromagnetic muscle stimulation (EMMS) suggested that fat cell apoptosis occurs following treatment in a porcine model. While EMMS can induce changes in muscle, the effect on fat tissue is not established. This clinical study sought to assess adipose tissue response to EMMS in comparison to cryolipolysis treatment. STUDY DESIGN/MATERIALS AND METHODS: Study subjects were recruited prior to abdominoplasty to receive body contouring treatments and subsequently to obtain tissue for histological analysis. Non-invasive abdominal treatments were delivered using a commercially available (n = 6) or prototype (n = 3) EMMS system or a cryolipolysis system (n = 2). Subjects received a single EMMS treatment (100% intensity for 30 minutes) or a single cryolipolysis treatment (-11°C for 35 minutes) to the abdomen. Superficial and deep (i.e., adjacent to muscle layer) subcutaneous adipose tissue was harvested at set timepoints post-treatment. The presence or absence of an inflammatory response was evaluated using standard hematoxylin and eosin (H&E) staining. As adipocytes that are destined to become apoptotic cannot be distinguished by traditional H&E staining during the early phases of injury, irreversible fat cell injury was assessed using perilipin immunofluorescence. RESULTS: Following H&E histological analysis at 3, 10, 11, and 17 days post-treatment, no EMMS-treated samples showed an inflammatory response in either the superficial or deep subcutaneous adipose tissue. For the cryolipolysis-treated adipose tissue, however, the H&E staining revealed a marked inflammatory response with an influx of neutrophils, lymphocytes, and macrophages at timepoints consistent with previous histological studies. Further, loss of perilipin staining provided clear visual evidence of irreversible fat cell injury in the cryolipolysis-treated adipose tissue. In contrast, the electromagnetic muscle stimulation-treated samples showed persistence of perilipin staining of adipose tissue indicating that all fat cells were viable. CONCLUSION: This study failed to demonstrate either fat cell injury or inflammatory response following EMMS treatment. While electromagnetic muscle stimulation may non-invasively induce muscle changes, this clinical study found no evidence of an impact injurious or otherwise on subcutaneous fat. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

Low-Avidity Autoantibodies against Bactericidal/Permeability-Increasing Protein Occur in Gram-Negative and Gram-Positive Bacteremia.

Antibody autoreactivity against bactericidal/permeability-increasing protein (BPI) is strongly associated with Pseudomonas aeruginosa infection in cystic fibrosis (CF), non-CF bronchiectasis (BE), and chronic obstructive pulmonary disease (COPD). We examined the pathogen-specific nature of this autoreactivity by examining antibodies to BPI in bacteremia patients. Antibodies to BPI and bacterial antigens were measured in sera by ELISA from five patient cohorts (n = 214). Antibody avidity was investigated. Bacteremic patient sera (n = 32) exhibited IgG antibody autoreactivity against BPI in 64.7% and 46.7% of patients with positive blood cultures for P. aeruginosa and Escherichia coli, respectively. Autoantibody titers correlated with IgG responses to bacterial extracts and lipopolysaccharide (LPS). A prospective cohort of bacteremic patient sera exhibited anti-BPI IgG responses in 23/154 (14.9%) patients with autoreactivity present at the time of positive blood cultures in patients with Gram-negative and Gram-positive bacteria, including 8/60 (13.3%) patients with Staphylococcus aureus Chronic tissue infection with S. aureus was associated with BPI antibody autoreactivity in 2/15 patients (13.3%). Previously, we demonstrated that BPI autoreactivity in CF patient sera exhibits high avidity. Here, a similar pattern was seen in BE patient sera. In contrast, sera from patients with bacteremia exhibited low avidity. These data indicate that low-avidity IgG responses to BPI can arise acutely in response to bacteremia and that this association is not limited to P. aeruginosa This is to be contrasted with chronic respiratory infection with P. aeruginosa, suggesting that either the chronicity or the site of infection selects for the generation of high-avidity responses, with biologic consequences for airway immunity.

Adjustable Depth Fractional Radiofrequency Combined With Bipolar Radiofrequency: A Minimally Invasive Combination Treatment for Skin Laxity.

Increasingly, patients are seeking minimally invasive methods to tighten skin and remodel adipose tissue. A large treatment gap exists among 3 types of patients: (1) the younger demographic, who increasingly desire soft tissue tightening without traditional operations, scars, and downtime; (2) patients with soft tissue laxity who are not "severe enough" to justify an excisional procedure, but not "mild enough" to rely on liposuction with soft tissue contraction alone; and (3) those with recurrent laxity who already underwent traditional excisional procedures. In these populations, plastic surgeons risk under- or overtreating with traditional methods. The purpose of this supplement is to describe the utility of radiofrequency (RF) microneedling (Fractora modified to Morpheus8 InMode Aesthetic Solutions, Lake Forest, CA) in combination with bipolar RF (FaceTite/BodyTite, InMode Aesthetic Solutions). By combining these procedures, the aforementioned treatment gap can be addressed. The RF microneedling allows for subdermal adipose remodeling and skin tightening. Addition of bipolar RF also tightens the skin by contraction of the underlaying fibroseptal network in addition to induction of neocollagenesis, elastogenesis, and angiogenesis at skin surface temperatures of 40° to 50°C. In our experience, these technologies have been effective and safe in these patient populations. Level of Evidence: 4.

Transmission of a common intestinal neoplasm in zebrafish by cohabitation.

Intestinal neoplasms are common in zebrafish (Danio rerio) research facilities. These tumours are most often seen in older fish and are classified as small cell carcinomas or adenocarcinomas. Affected fish populations always contain subpopulations with preneoplastic lesions, characterized by epithelial hyperplasia or inflammation. Previous observations indicated that these tumours are unlikely caused by diet, water quality or genetic background, suggesting an infectious aetiology. We performed five transmission experiments by exposure of naïve fish to affected donor fish by cohabitation or exposure to tank effluent water. Intestinal lesions were observed in recipient fish in all exposure groups, including transmissions from previous recipient fish, and moribund fish exhibited a higher prevalence of neoplasms. We found a single 16S rRNA sequence, most similar to Mycoplasma penetrans, to be highly enriched in the donors and exposed recipients compared to unexposed control fish. We further tracked the presence of the Mycoplasma sp. using a targeted PCR test on individual dissected intestines or faeces or tank faeces. Original donor and exposed fish populations were positive for Mycoplasma, while corresponding unexposed control fish were negative. This study indicates an infectious aetiology for these transmissible tumours of zebrafish and suggests a possible candidate agent of a Mycoplasma species.

Safety and efficacy of cryolipolysis for non-invasive reduction of submental fat.

BACKGROUND AND OBJECTIVES: Cryolipolysis has previously received FDA clearance for fat reduction in the abdomen, flanks, and thighs. There is also interest in small volume fat reduction for areas such as the chin, knees, and axilla. This article reports the results of a cryolipolysis pivotal IDE study for reduction of submental fullness. STUDY DESIGN/MATERIAL AND METHODS: A prototype small volume vacuum applicator (CoolMini applicator, CoolSculpting System, ZELTIQ Aesthetics) was used to treat 60 subjects in the submental area. At each treatment visit, a single treatment cycle was delivered at -10°C for 60 minutes, the same temperature and duration used in current commercially-available cryolipolysis vacuum applicators. At the investigator's discretion, an optional second treatment was delivered 6 weeks after the initial treatment. The primary efficacy endpoint was 80% correct identification of baseline photographs by independent physician review. The primary safety endpoint was monitoring incidence of device- and/or procedure-related serious adverse events. Secondary endpoints included assessment of fat layer thickness by ultrasound and subject satisfaction surveys administered 12 weeks after final cryolipolysis treatment. RESULTS: Independent photo review from 3 blinded physicians found 91% correct identification of baseline clinical photographs. Ultrasound data indicated mean fat layer reduction of 2.0 mm. Patient questionnaires revealed 83% of subjects were satisfied, 80% would recommend submental cryolipolysis to a friend, 77% reported visible fat reduction, 77% felt that their appearance improved following the treatment, and 76% found the procedure to be comfortable. No device- or procedure-related serious adverse events were reported. CONCLUSION: The results of this clinical evaluation of 60 patients treated in a pivotal IDE study demonstrate that submental fat can be reduced safely and effectively with a small volume cryolipolysis applicator. Patient surveys revealed that submental cryolipolysis was well-tolerated, produced visible improvement in the neck contour, and generated high patient satisfaction. These study results led to FDA clearance of cryolipolysis for submental fat treatment.

A Multicenter Study for Cellulite Treatment Using a 1440-nm Nd:YAG Wavelength Laser with Side-Firing Fiber.

BACKGROUND: Treatment of cellulite using a 1440-nm YAG wavelength laser with side-firing fiber has proven safe and effective, lasting at least 6 months. OBJECTIVES: The authors evaluate the safety and efficacy of a single, subdermal procedure to treat the underlying structure of cellulite for at least 1 year. METHODS: Fifty-seven patients underwent a 3-step cellulite treatment with a 1440-nm Nd:YAG laser with a side-firing fiber and temperature-sensing cannula. Efficacy was measured by the blinded evaluators to distinguish baseline photos from those taken at 12 months posttreatment, with results on a 5-point, 2-category ordinal photonumeric scale when comparing baseline photos to 12 months posttreatment. Subject and physician satisfaction was assessed based on completion of a satisfaction survey. Adverse events (AE) were recorded throughout the study. Twelve month data were analyzed and compared to 6 month data. RESULTS: Evaluators chose baseline photographs 97% on average from 6 (-1, +2) months and 91% from the 12 (-3, +2) months posttreatment photographs. At 6 (-1, +2) months, the average improvement score was 1.7 for dimples and 1.1 for contour irregularities. At 12 (-3, +2) months, the average improvement score was 1.4 for dimples and 1.0 for contour irregularities. The average satisfaction score for the physician was 5.6 and the patient was 5.3 on a 6-point scale. CONCLUSIONS: A single, 3-step, minimally invasive laser treatment using a 1440-nm Nd:YAG laser, side-firing fiber, and temperature-sensing cannula to treat the underlying structure of cellulite proved to be safe and maintained effectiveness at least 1 year post treatment. LEVEL OF EVIDENCE 2: Therapeutic.

Measured removal rates of chrysotile asbestos fibers from air and comparison with theoretical estimates based on gravitational settling and dilution ventilation.

CONTEXT: Industrial hygiene assessments often focus on activity-based airborne asbestos concentration measurements, but few empirical data exist regarding the fiber removal rate from air after activities cease. OBJECTIVE: Grade 7T chrysotile indoor fiber settling (FS) rates were characterized using air sampling (NIOSH Method 7402). MATERIALS AND METHODS: Six replicate events were conducted in a 58 m(3) study chamber (ventilation 3.5 ACH), in which chrysotile-contaminated work clothing was manipulated for 15 min followed by 30 min of no activity. The fiber concentration decay constant and removal rate were characterized using an exponential decay model based on the measurements. RESULTS: Breathing zone airborne chrysotile concentrations decreased by 86% within 15-30 min after fiber disturbance, compared to concentrations during active disturbance (p < 0.05). Estimated mean time required for 99% of the phase contrast microscopy-equivalent (PCME) fibers to be removed from air was approximately 30 min (95% CI: 22-57 min). The observed effective FS velocity was 0.0034 m/s. This settling velocity was between 4.5-fold and 180-fold faster than predicted by two different particulate gravitational settling models. Additionally, PCME concentrations decreased approximately 2.5-fold faster than predicted due to air exchange alone (32 versus 79 min to 99% decrease in concentration). DISCUSSION: Other measurement studies have reported similar airborne fiber removal rates, supporting the finding that factors other than gravitational settling and dilution ventilation contribute measurably to PCM fiber removal from air (e.g. impaction, agglomeration). CONCLUSION: Overall, the scientific weight of evidence indicates that the time necessary for removal of 99% of fibers greater than 5 µm in length (with aspect ratios greater than 3:1) is approximately 20-80 min.

Computational fluid dynamic modelling of the effect of ventilation mode and tracheal tube position on air flow in the large airways.

We have used computational fluid dynamic modelling to study the effects of tracheal tube size and position on regional gas flow in the large airways. Using a three-dimensional mathematical model, we simulated flow with and without a tracheal tube, replicating both physiological and artificial breathing. Ventilation through a tracheal tube increased proportional flow to the left lung from 39.5% with no tube to 43.1-47.2%, depending on tube position. Ventilation mode and tube distance from the carina had no effect on flow. Lateral displacement and deflection of the tube increased ventilation to the ipsilateral lung; for example, when deflected 10° to the left of centre, flow to the left lung increased from 43.8 to 53.7%. Because of the small diameter of a tracheal tube relative to the trachea, gas exits a tube at high velocity such that regional ventilation may be affected by changes in the position and angle of the tube.

Cryolipolysis for safe and effective inner thigh fat reduction.

BACKGROUND AND OBJECTIVES: While cryolipolysis initially received FDA clearance for fat reduction in the abdomen and flanks, there was significant interest in non-surgical fat reduction for other sites, such as the inner and outer thighs. This article reports the results of an inner thigh study which contributed to FDA clearance of cryolipolysis for treatment of thighs. STUDY DESIGN/MATERIAL AND METHODS: A flat cup vacuum applicator (CoolFit applicator, CoolSculpting System) was used to treat 45 subjects bilaterally in the inner thighs. Single cycle treatments were delivered at Cooling Intensity Factor (CIF) 41.6 for 60 minutes followed by 2 minutes of manual massage. Follow-up visits were conducted at 8 and 16 weeks. Efficacy was assessed by ultrasound imaging, circumference measurements, and photographs. Safety was assessed by monitoring adverse events. Patient satisfaction was evaluated by questionnaire. RESULTS: Data is presented for n = 42 patients that completed the 16 week study follow-up and maintained their weight within 5 lbs. of baseline. Independent photo review from three blinded physicians found 91% correct identification of baseline clinical photographs. Ultrasound data indicate fat layer reduction of 2.8 mm. Circumferential measurements indicate mean reduction of 0.9 cm. Patient questionnaires reveal 93% were satisfied with the CoolSculpting procedure; 84% noticed visible fat reduction; 89% would recommend to a friend; and 91% were likely to have a second treatment. There were no device- or procedure-related serious adverse events. CONCLUSION: The CoolFit flat cup vacuum applicator was found to deliver safe and effective cryolipolysis treatment to reduce inner thigh fat. Completed 16-week data from 42 subjects show 2.8 mm reduction in fat thickness and 0.9 cm reduction in circumference. Assessment of clinical photographs found 91% correct identification of baseline images. The results of this prospective, multi-center, interventional clinical study contributed to FDA clearance of cryolipolysis for treatment of thighs in April 2014.

A Prospective, Randomized, Multicenter Trial Assessing a Novel Lysine-Derived Urethane Adhesive in a Large Flap Surgical Procedure without Drains.

OBJECTIVE: To evaluate the safety and effectiveness of a lysine-derived urethane adhesive as a noninvasive alternative to closed suction drains in a commonly performed large flap surgical procedure. METHODS: One hundred thirty subjects undergoing abdominoplasty at five centers were prospectively randomized to standard flap closure with surgical drains (Control group) or a lysine-derived urethane adhesive (Treatment group) without drains. The primary outcome measured was the number of post-operative procedures, including drain removals (as the event marking the use of a surgical drain) and needle aspirations. Secondary endpoints included total wound drainage, cumulative days of treatment, and days to drain removal. A patient questionnaire evaluating quality of life measures was also administered. RESULTS: Subjects in the Treatment group required significantly fewer post-operative procedures compared to the Control group (1.8 ± 3.8 vs. 2.4 ± 1.2 procedures; p < 0.0001) and fewer cumulative days of treatment (1.6 ± 0.4 vs. 7.3 ± 3.3; p < 0.0001). A procedure to address fluid accumulation was required for only 27.3 % of the subjects in the Treatment group versus 100 % of Control group, which by study design required the use of drains. The mean duration of use of indwelling surgical drains for the Control group was 6.9 ± 3.3 days. All fluid collections treated with percutaneous aspiration were resolved and there were no unanticipated adverse events. CONCLUSION: The results of the study support that the use of a lysine-derived urethane adhesive is a safe and effective alternative to drains in patients undergoing a common large flap surgical procedure.

THE IMPACT OF DEPRESSION ON MATERNAL RESPONSES TO INFANT FACES IN PREGNANCY.

Research has suggested that prenatal depression may be associated with disrupted maternal responses to infant stimuli, with depressed pregnant women not showing the bias toward distressed infants as that observed in nondepressed pregnant women. The current study examined the effects of depression on self- reported responses to infant stimuli, in early pregnancy. Women with clinical depression (n = 38), and nondepressed women (n = 67) were recruited from a wider cognitive behavioral therapy trial. They completed Maternal Response Scales in which they were presented with images of distressed, neutral, and happy infant faces, with no time limit. The women rated their responses to these images along three dimensions--wanting to comfort, wanting to turn away, and feelings of anxiety--using Likert scales via a computerized task. There was evidence that women with depression in pregnancy showed different responses than did women without depression. Women with depression were substantially more likely to be in the highest quartile for ratings of wanting to turn away, odds (OR) ratio = 4.15, 95% confidence intervals (CIs) = 1.63-10.5, p = .003, and also were substantially less likely to be in the highest quartile for wanting to comfort a distressed infant face, OR = 0.22, 95% CIs = 0.09-0.54, p < .001. Findings are consistent with there being both a heightened avoidant and a reduced comforting response toward distressed infants in depressed pregnant women, providing some support that depression disrupts maternal preparations at a conscious level.

Nutritional enhancement of leaves by a psyllid through senescence-like processes: insect manipulation or plant defence?

Some herbivores can modify the physiology of plant modules to meet their nutritional requirements. Induction of premature leaf senescence could benefit herbivores since it is associated with the mobilisation of nutrients. We compared the effects of nymphal feeding by Cardiaspina near densitexta on Eucalyptus moluccana with endogenous processes associated with senescence to assess the relative merits of an insect manipulation or plant defence interpretation of responses. Evidence supporting insect manipulation included increased size of fourth and fifth instar nymphs (in the latter the effect was restricted to forewing pad length of females) on leaves supporting high numbers of conspecifics and feeding preventing leaf necrosis. Intra-specific competition negated greater performance at very high densities. High and very high abundances of nymphs were associated with increased concentrations of amino acid N but only very high abundances of nymphs tended to be associated with increased concentrations of six essential amino acids. Contrary to the insect manipulation interpretation, feeding by very high abundances of nymphs was associated with significant reductions in chlorophyll, carotenoids and anthocyanins. Evidence supporting plant defence included the severity of chlorosis increasing with the abundance of nymphs. Leaf reddening did not develop because ambient conditions associated with photoinhibition (high irradiance and low temperature) were not experienced by leaves with chlorotic lesions. Leaf reddening (from anthocyanins) alone is not expected to adversely affect nymphal survival; only leaf necrosis would kill nymphs. For senescence-inducing psyllids, nutritional enhancement does not fit neatly into either an insect manipulation or plant defence interpretation.

Pulmonary arterial hypertension associated with the use of interferon therapy for chronic hepatitis C infection complicated by extrinsic left main coronary artery compression.

Interferon-alpha treatment is a rare cause of pulmonary arterial hypertension (PAH). We report a case of a 43-year-old man treated for chronic hepatitis C infection complicated by decompensated right heart failure diagnosed with PAH and external coronary artery compression secondary to a dilated pulmonary trunk. The novel complication of extrinsic coronary artery compression should be considered in PAH patients presenting with chest pain or acute coronary syndrome. Establishing a diagnosis has clinical value as pulmonary vasodilator therapy may improve symptoms.

High-intensity focused ultrasound for the reduction of subcutaneous adipose tissue using multiple treatment techniques.

BACKGROUND: High-intensity focused ultrasound (HIFU) is a noninvasive alternative to traditional invasive body sculpting procedures. OBJECTIVE: To assess the effectiveness and tolerability of HIFU treatment using high and low fluence settings with 2 treatment techniques, grid repeat (GR) and site repeat (SR). MATERIALS AND METHODS: Two multicenter studies were conducted. Subjects underwent 1 HIFU treatment with 1 of 5 treatment protocols (total fluence, 150-180 J/cm). Primary end point was change from baseline in waist circumference (CBWC) at 12 weeks. Secondary end points included CBWC at 4 and 8 weeks and investigator- and subject-assessed clinical improvement. Adverse events were monitored throughout the study. RESULTS: In the intent-to-treat (ITT) population, all subjects had a statistically significant mean circumferential reduction of -2.3 ± 2.9 cm (p < .0001) from baseline at 12 weeks, with no significant differences among the 5 treatment groups (ITT: p = .153). Analysis of secondary end points in the ITT population demonstrated a significant circumferential reduction starting as early as 4 weeks in all subjects (-1.1 ± 1.9 cm, p < .0001). Most subjects in all treatment groups showed improvements at 12 weeks as rated by the investigators and subjects. CONCLUSION: High-intensity focused ultrasound treatment using either a low or high fluence setting in a GR or SR method is effective for circumferential waist reduction, resulting in statistically significant CBWC in all treatment groups.

Spinal cord essentials: The development of an individualized, handout-based patient and family education initiative for people with spinal cord injury.

STUDY DESIGN: Mixed (environmental scan, qualitative and semiquantitative). OBJECTIVES: To develop a customizable patient and family education resource for people with spinal cord injury (SCI). SETTING: SCI rehabilitation center (Canada). METHODS: An environmental scan was conducted and stakeholder input sought to generate a list of potential handouts and inform content development. Staff members were recruited to draft handouts, which were later edited and finalized by the project team. Hardcopies of handouts were placed in cabinets throughout the rehabilitation center. Staff members were also trained/coached to facilitate and promote usage; which was then tracked for 2 years. RESULTS: One hundred and fifty-six potential handouts were identified; 83 deemed high priority. Seventy-two handouts addressing patient organization, self-management and community integration were finalized for phase 1. At inpatient admission, patients receive a binder containing base materials. The binder is then customized and populated with pertinent handouts throughout the rehabilitation admission, and taken home at discharge for future reference. Handouts with the highest usage covered medical management (for example, bladder, bowel and pressure ulcers), mobility and activities of daily living. Handouts were also helpful for staff training and orientation, as well as increasing the confidence of staff providing education outside their immediate area of expertise. CONCLUSION: Spinal Cord Essentials is a novel patient and family education initiative comprised of practical handouts that address many important aspects of SCI management. Handouts can be downloaded for free in four languages (English, French, Chinese and Farsi) at www.spinalcordessentials.ca. Additional handouts are planned for subsequent phases of the project.

ATP5PO levels regulate enteric nervous system development in zebrafish, linking Hirschsprung disease to Down Syndrome.

Hirschsprung disease (HSCR) is a complex genetic disorder characterized by the absence of enteric nervous system (ENS) in the distal region of the intestine. Down Syndrome (DS) patients have a >50-fold higher risk of developing HSCR than the general population, suggesting that overexpression of human chromosome 21 (Hsa21) genes contribute to HSCR etiology. However, identification of responsible genes remains challenging. Here, we describe a genetic screening of potential candidate genes located on Hsa21, using the zebrafish. Candidate genes were located in the DS-HSCR susceptibility region, expressed in the human intestine, were known potential biomarkers for DS prenatal diagnosis, and were present in the zebrafish genome. With this approach, four genes were selected: RCAN1, ITSN1, ATP5PO and SUMO3. However, only overexpression of ATP5PO, coding for a component of the mitochondrial ATPase, led to significant reduction of ENS cells. Paradoxically, in vitro studies showed that overexpression of ATP5PO led to a reduction of ATP5PO protein levels. Impaired neuronal differentiation and reduced mitochondrial ATP production, were also detected in vitro, after overexpression of ATP5PO in a neuroblastoma cell line. Finally, epistasis was observed between ATP5PO and ret, the most important HSCR gene. Taken together, our results identify ATP5PO as the gene responsible for the increased risk of HSCR in DS patients in particular if RET variants are also present, and show that a balanced expression of ATP5PO is required for normal ENS development.

Building a brain in the gut: development of the enteric nervous system.

The enteric nervous system (ENS), the intrinsic innervation of the gastrointestinal tract, is an essential component of the gut neuromusculature and controls many aspects of gut function, including coordinated muscular peristalsis. The ENS is entirely derived from neural crest cells (NCC) which undergo a number of key processes, including extensive migration into and along the gut, proliferation, and differentiation into enteric neurons and glia, during embryogenesis and fetal life. These mechanisms are under the molecular control of numerous signaling pathways, transcription factors, neurotrophic factors and extracellular matrix components. Failure in these processes and consequent abnormal ENS development can result in so-called enteric neuropathies, arguably the best characterized of which is the congenital disorder Hirschsprung disease (HSCR), or aganglionic megacolon. This review focuses on the molecular and genetic factors regulating ENS development from NCC, the clinical genetics of HSCR and its associated syndromes, and recent advances aimed at improving our understanding and treatment of enteric neuropathies.

An analysis of workplace exposures to benzene over four decades at a petrochemical processing and manufacturing facility (1962-1999).

Benzene, a known carcinogen, can be generated as a by-product during the use of petroleum-based raw materials in chemical manufacturing. The aim of this study was to analyze a large data set of benzene air concentration measurements collected over nearly 40 years during routine employee exposure monitoring at a petrochemical manufacturing facility. The facility used ethane, propane, and natural gas as raw materials in the production of common commercial materials such as polyethylene, polypropylene, waxes, adhesives, alcohols, and aldehydes. In total, 3607 benzene air samples were collected at the facility from 1962 to 1999. Of these, in total 2359 long-term (>1 h) personal exposure samples for benzene were collected during routine operations at the facility between 1974 and 1999. These samples were analyzed by division, department, and job title to establish employee benzene exposures in different areas of the facility over time. Sampling data were also analyzed by key events over time, including changes in the occupational exposure limits (OELs) for benzene and key equipment process changes at the facility. Although mean benzene concentrations varied according to operation, in nearly all cases measured benzene quantities were below the OEL in place at the time for benzene (10 ppm for 1974-1986 and 1 ppm for 1987-1999). Decreases in mean benzene air concentrations were also found when data were evaluated according to 7- to 10-yr periods following key equipment process changes. Further, an evaluation of mortality rates for a retrospective employee cohort (n = 3938) demonstrated that the average personal benzene exposures at this facility (0.89 ppm for the period 1974-1986 and 0.125 ppm for the period 1987-1999) did not result in increased standardized mortality ratio (SMRs) for diseases or malignancies of the lymphatic system. The robust nature of this data set provides comprehensive exposure information that may be useful for assessing human benzene exposures at similar facilities. The data also provide a basis for comparable measured exposure levels and the potential for adverse health effects. These data may also prove beneficial for comparing relative exposure potential for production versus nonproduction operations and the relationship between area and personal breathing zone samples.

Impact of benchmarking and clinical decision making tools on rehabilitation length of stay following spinal cord injury.

STUDY DESIGN: Performance improvement initiative. OBJECTIVES: To improve efficiency of spinal cord rehabilitation by reducing length of stay (LOS) while maintaining or improving patient outcomes. SETTING: Academic hospital in Canada. METHODS: LOS benchmarking was completed using national comparator data from the Canadian Institute for Health Information (CIHI). Clinical decision-making tools were developed to support implementation and sustainability. A standardized 'tentative discharge date' calculator was created to establish objective LOS targets. Defined discharge criteria and an accompanying clinical decision tree were developed to support team decision making and improve transparency. A revised patient census tool was also implemented to improve team communication and facilitate data collection. The initiative was implemented in March 2010 and the following metrics were evaluated: LOS, Functional Independence Measure (FIM) change and FIM efficiency. RESULTS: Outcomes are reported for the 2010/11 fiscal year, and compared with the two prior fiscal years. Mean LOS for individuals undergoing initial inpatient rehabilitation was 71.5 days for 2010/11, a 14 and 17% reduction compared with the 2008/09 and 2009/10 fiscal years, respectively. While LOS decreased, FIM change increased 9 and 16% compared with 2008/09 and 2009/10, respectively. Similarly, FIM efficiency increased 54 and 32% compared with 2008/09 and 2009/10. CONCLUSION: The use of benchmarking and decision support tools improved rehabilitation efficiency while increasing standardization in practice and transparency in LOS determination.