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The channel-forming glycoprotein PANX3 functions in cutaneous wound healing and keratinocyte differentiation, but its role in maintaining skin homeostasis through aging is not yet understood. We found that PANX3 is absent in newborn skin but becomes upregulated with age. We characterized the skin of global Panx3-knockout (KO) mice and found that KO dorsal skin showed sex differences at different ages but generally had reduced dermal and hypodermal areas compared with age-matched controls. Transcriptomic analysis of the KO epidermis revealed reduced E-cadherin stabilization and Wnt signaling compared with that of wild-type, consistent with the inability of primary KO keratinocytes to adhere in culture and diminished epidermal barrier function in KO mice. We also observed increased inflammatory signaling in the KO epidermis and a higher incidence of dermatitis in aged KO mice compared with that in wild-type controls. These findings suggest that during skin aging, PANX3 is critical in the maintenance of dorsal skin architecture, keratinocyte cell-cell and cell-matrix adhesion, and inflammatory skin responses., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with pure native aortic regurgitation (AR) have been excluded from transcatheter aortic valve replacement (TAVR) trials. We sought to examine midterm outcomes with TAVR in AR compared with surgical AVR (SAVR) in a contemporary cohort., Methods: Medicare beneficiaries who underwent elective TAVR or SAVR for pure AR from 2016 to 2019 were identified. Patients with concomitant aortic stenosis and who underwent a valve-in-valve intervention or concomitant mitral valve or ascending aorta operation were excluded. The primary outcome was all-cause mortality in the longest follow-up. Secondary outcomes included stroke, endocarditis, and redo AVR. Overlap propensity score weighting was used to adjust for confounders., Results: During the study period, 11,027 patients with pure AR underwent elective AVR (TAVR, n = 1147; SAVR, n = 9880). SAVR patients were younger, with fewer comorbidities and less frailty compared with TAVR patients. TAVR was associated with adjusted 30-day mortality comparable to SAVR. After a median follow-up of 31 months (interquartile range, 18-44 months), TAVR was associated with higher adjusted risk of death (hazard ratio [HR], 1.41; 95% CI, 1.03-1.93; P = .02) and need for redo-AVR (HR, 2.13; 95% CI, 1.05-4.34; P = .03) compared with SAVR. The risk of stroke (HR, 1.65; 95% CI, 0.95-2.87; P = .07) and endocarditis (HR, 2.60; 95% CI, 0.92-7.36; P = .07) was numerically higher with TAVR., Conclusions: In Medicare patients with pure native AR, TAVR with the current commercially available transcatheter valves has comparable short-term outcomes. Although long-term outcomes were inferior to SAVR, the possibility of residual confounding, biasing long-term outcomes, given older and frailer TAVR patients, cannot be excluded., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA in wastewater can be used as an indicator of the presence of SARS-CoV-2 infection in specific catchment areas. We conducted a hospital-based study to explore wastewater management in healthcare facilities and analyzed SARS-CoV-2 RNA in the hospital wastewater in Dhaka city during the Coronavirus disease (COVID-19) outbreak between September 2020-January 2021. We selected three COVID-hospitals, two non-COVID-hospitals, and one non-COVID-hospital with COVID wards, conducted spot-checks of the sanitation systems (i.e., toilets, drainage, and septic-tank), and collected 90 untreated wastewater effluent samples (68 from COVID and 22 from non-COVID hospitals). E. coli was detected using a membrane filtration technique and reported as colony forming unit (CFU). SARS-CoV-2 RNA was detected using the iTaq Universal Probes One-Step kit for RT-qPCR amplification of the SARS-CoV-2 ORF1ab and N gene targets and quantified for SARS-CoV-2 genome equivalent copies (GEC) per mL of sample. None of the six hospitals had a primary wastewater treatment facility; two COVID hospitals had functional septic tanks, and the rest of the hospitals had either broken onsite systems or no containment of wastewater. Overall, 100 % of wastewater samples were positive with a high concentration of E. coli (mean = 7.0 log 10 CFU/100 mL). Overall, 67 % (60/90) samples were positive for SARS-CoV-2. The highest SARS-CoV-2 concentrations (median: 141 GEC/mL; range: 13-18,214) were detected in wastewater from COVID-hospitals, and in non-COVID-hospitals, the median SARS-CoV-2 concentration was 108 GEC/mL (range: 30-1829). Our results indicate that high concentrations of E. coli and SARS-CoV-2 were discharged through the hospital wastewater (both COVID and non-COVID) without treatment into the ambient water bodies. Although there is no evidence for transmission of SARS-CoV-2 via wastewater, this study highlights the significant risk posed by wastewater from health care facilities in Dhaka for the many other diseases that are spread via faecal oral route. Hospitals in low-income settings could function as sentinel sites to monitor outbreaks through wastewater-based epidemiological surveillance systems. Hospitals should aim to adopt the appropriate wastewater treatment technologies to reduce the discharge of pathogens into the environment and mitigate environmental exposures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

By the time a Drosophila egg is laid, both major body axes have already been defined and it contains all the nutrients needed to develop into a free-living larva in 24 h. By contrast, it takes almost a week to make an egg from a female germline stem cell, during the complex process of oogenesis. This review will discuss key symmetry-breaking steps in Drosophila oogenesis that lead to the polarisation of both body axes: the asymmetric divisions of the germline stem cells; the selection of the oocyte from the 16-cell germline cyst; the positioning of the oocyte at the posterior of the cyst; Gurken signalling from the oocyte to polarise the anterior-posterior axis of the somatic follicle cell epithelium around the developing germline cyst; the signalling back from the posterior follicle cells to polarise the anterior-posterior axis of the oocyte; and the migration of the oocyte nucleus that specifies the dorsal-ventral axis. Since each event creates the preconditions for the next, I will focus on the mechanisms that drive these symmetry-breaking steps, how they are linked and the outstanding questions that remain to be answered., (Copyright © 2023. Published by Elsevier Inc.)

Background: Owing to the opioid epidemic, more cardiac surgery patients present with opioid use disorder (OUD). A better understanding of national readmissions among these patients is necessary to improve outcomes and optimize resource utilization. We sought to examine the effect of OUD on readmission after cardiac surgery., Methods: Of 555 394 cardiac surgery patients from 2016 to 2017 in the Nationwide Readmissions Database, 6082 (1.1%) presented with OUD. These patients were assessed at 30, 90, and 180 days after discharge. The OUD patients and non-OUD patients were propensity score matched for patient- and procedure-level characteristics. Kaplan-Meier curves were compared using the log rank test., Results: First-time readmissions were significantly higher among patients with OUD (30 days 19.7% vs 15.7%, P = .04; 90 days 31.8% vs 24.2%, P < .0001; and 180 days 42.3% vs 30.6%, P < .0001). There was a trend toward higher reoperation by 180 days, with 90% of those being isolated valve surgery. By 180 days, significantly more OUD patients had three or more readmissions (7.8% vs 4.5%) compared with non-OUD patients. Yet, only 2.4% of OUD patients received any counseling or treatment for substance abuse during the index admission. The most common readmitting diagnosis was infection (55% vs 41%, P < .0001) including endocarditis, prosthetic infections, and skin or subcutaneous infections. Respiratory failure, opioid overdose, and acute pain were also more common among patients with OUD., Conclusions: Cardiac surgery patients with OUD have multiple readmissions but are rarely provided adequate addiction management during their index admission. Greater emphasis on multidisciplinary management is necessary to limit costs and morbidity associated with readmission or reoperation., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: The aims of this study were to characterize the interplay between mixed aortic valve disease (MAVD) phenotypes (defined by concomitant severities of aortic stenosis and aortic regurgitation) and left ventricular global longitudinal strain (LV-GLS), and to assess the prognostic utility of LV-GLS in MAVD., Background: Little is known about the way LV-GLS separates MAVD phenotypes and if it is associated with their outcomes., Methods: This observational cohort study evaluated 783 consecutive adult patients with left ventricular ejection fraction ≥50% and MAVD, which was defined as coexisting with at least moderate aortic stenosis and at least moderate aortic regurgitation. We measured the conventional echocardiographic variables and average LV-GLS from apical long, 2- and 4-chamber views. The primary endpoint was all-cause mortality., Results: Mean age of patients was 69 ± 15 years, and 58% were male. Mean LV-GLS was -14.7 ± 2.9%. In total, 458 patients (59%) underwent aortic valve replacement at a median period of 50 days (25th to 75th percentile range: 6 to 560 days). During a median follow-up period of 5.6 years (25th to 75th percentile range: 1.8 to 9.4 years), 391 patients (50%) died. When stratified patients into tertiles according to LV-GLS values, patients with worse LV-GLS had worse outcomes (p < 0.001). LV-GLS was independently associated with mortality (hazard ratio: 1.09; 95% confidential intervals: 1.04 to 1.14; p < 0.001), with the relationship between LV-GLS and mortality being linear., Conclusions: LV-GLS is associated with all-cause mortality. LV-GLS may be useful for risk stratification in patients with MAVD., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Failure to rescue (FTR) is gaining popularity as a quality metric. The relationship between patient frailty and FTR after cardiovascular surgery has not been fully explored. This study aimed to utilize a national database to examine the impact of patient frailty on FTR., Methods: Of 5,199,534 patients undergoing cardiovascular surgery between 2000 and 2014, 75,851 (1.5%) were identified from the Nationwide Inpatient Sample database as frail based on the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnoses indicator. Propensity-score matching was used to adjust for patient- and hospital-level characteristics and comorbidities when comparing frail and nonfrail patients., Results: Frail patients were on average older (68 ± 12 years vs 65 ± 12 years; P < .001) and had more comorbidities including heart failure, and chronic lung, liver, or renal disease. Among 68,472 matched pairs, frail patients had significantly higher rates of FTR (13.4% vs 11.9%; P < .001). This contributed to a $39,796 increase in cost per hospitalization (P < .001). Renal failure, respiratory failure, pneumonia, and sepsis were most commonly associated with FTR in frail patients. When hospitals were stratified by risk-adjusted mortality, low-mortality (1st quintile) centers had significantly lower FTR rates and costs among frail patients when compared to high-mortality (5th quintile) centers., Conclusions: Frailty contributes significantly to FTR after cardiovascular surgery. Frail patients can expect better outcomes with lower costs at cardiac surgical centers of excellence that can adequately manage postoperative outcomes. Preoperative assessment of frailty may better guide risk estimation and identification of patients who would benefit from appropriate prehabilitative interventions to optimize outcomes., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare that they have no conflicts of interest.

Introduction: Cryptorchidism is one of the most common referral diagnoses to pediatric urologists. It is well recognized in the urologic community that diagnostic imaging is unnecessary in the work-up of these patients, and the Choosing Wisely® recommendation (CWR) on this subject re-emphasized this in 2013. Many boys, however, still are sent for testing prior to referral., Objective: The purpose of our study was dual in nature. We pursued, first, to identify any factors that make patients more likely to be sent for imaging prior to referral, and second, to determine if rates of diagnostic imaging for cryptorchidism decreased after the release of the CWR., Study Design: We included all boys who had surgery for cryptorchidism by Urology at our institution between January 2007 and August 2018. Demographics and clinical data were collected including height, weight, race, insurance type, pre-referral imaging status, testis location at time of surgery, and distance from our medical center. Chi-squared analysis was utilized to compare imaging use before and after CWR. Influence of other clinical and socioeconomic factors on imaging utilization was also evaluated using chi-squared and two-sample t tests. Those found to be significant at the 0.2 level were analyzed in multivariate logistic regression. Significance was set at 0.05., Results: 1010 boys were available for analysis. Of the 256 patients (25.3%) with pre-referral studies, 7 had axial exams (CT or MRI), and the remainder underwent ultrasounds. Children living closer to the medical center were more likely to undergo imaging (p < 0.01) as were boys with testes not found in the inguinal canal at the time of surgery (p = 0.007). Race, insurance status, age at first visit, and increased body mass index were not found to be influential. Similarly, the release of CWR had no impact on the imaging usage (p = 0.61)., Conclusion: Utilization of pre-referral diagnostic imaging remains inappropriately high despite evidence demonstrating the ineffectiveness of the studies. Boys living closer to the medical center and those with non-inguinal testes are more likely to undergo these studies, but no other factors were found to have an effect. Further, the Choosing Wisely® recommendation has not improved rates of inappropriate imaging use in boys with cryptorchidism in our referral area. Our findings indicate the need for increased efforts to disseminate this evidence-based guideline more widely to primary care providers in order to promote more cost-effective and timely care of boys with undescended testes., Competing Interests: Conflicts of interest/funding None of the authors have any financial or personal conflicts to disclose., (Copyright © 2020 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Background: The Food and Drug Administration recommends that retrievable inferior vena cava filters (IVCFs) be removed 29-54 days postinsertion. Nationally, the retrieval rate is around 23-25%. The objectives of this study are to assess the effect of a plan for IVCF retrieval and access to an office endovascular center (OEC) on filter removal rates and to assess the safety of the procedure in an OEC., Methods: In this institutional review board-exempt retrospective study, the medical records of all patients who had an IVCF placed or removed in the hospital and OEC setting by one group of vascular surgeons between January 2011 and February 2017 were analyzed. Informed consent was not required for this retrospective chart review. The following data were abstracted: filter model, procedure site, retrieval plan, number of removal attempts, complications attributed to removal, success of removal, and the duration that the filter was in place. Anticoagulation was not discontinued before filter retrieval. Filters were removed under local anesthesia with or without mild conscious sedation., Results: IVCF removal was attempted in all eligible patients, 120 of 191 with IVCFs, whereas 71 patients were lost to follow-up (46), died (19), or the indication changed (6). Of the patients who had filters placed in the hospital (n = 161), 62% were removed (n = 101), of which 86% had a removal attempt in the OEC, whereas 14% had the filter removed in the hospital. Sixty-three percent of patients who had filters placed in the OEC (n = 30) had the filter removed in the OEC (n = 19). All patients with a newly placed filter were given an office appointment with a vascular surgeon for evaluation and removal planning. Of patients who had their filter removed at the OEC, all were removed via the jugular approach, resulting in 103 of 106 (97%) successful removals in the OEC. Visipaque (GE Healthcare, Chicago, IL) contrast was used during filter removal. Intravascular ultrasound was not used because the study predates the insurance coverage of this technology in the office laboratory. There was no mortality related to filter removal. In addition, there were no bleeding complications, despite patients remaining on anticoagulant therapy during the removal. In 4% of patients, the filter was removed in less than 3 weeks, 30% of patients between 3 and 6 weeks, 26% of patients between 6 weeks and 3 months, and 40% of patients after 3 months., Conclusions: Having access to both an OEC and a documented retrieval plan increases the frequency of IVCF removal in a community compared with national rates. Retrievable filters can be safely removed in an OEC with extremely high success and safety. Anticoagulation therapy can be continued during retrieval attempt without increased risk of bleeding., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Lungs of donors with high body mass index (BMI) have more atelectasis and a lower PaO 2 /FiO 2 (P/F) ratio than those with normal BMI. This study prospectively evaluated outcomes of a new approach for these lungs in our lung transplant program., Methods: From February 2016 to December 2018, 336 lung transplants were performed at Cleveland Clinic. Of these, 58 met criteria for our aggressive approach to donors with a P/F ratio of less than 300 mm Hg at offer and BMI of 25 kg/m 2 or greater. In the donor operating room, lung recruitment was performed by positive end-respiratory pressure of 25 to 30 cmH 2 O for 30 seconds and lungs were converted to either straight transplantation or ex vivo lung perfusion (EVLP). Postoperative outcomes of the low P/F-high BMI group were compared with those of recipients receiving lungs meeting standard criteria., Results: Of the 58 donors, 33 were converted to straight lung transplantation because they demonstrated significant improvement in the P/F ratio after lung recruitment compared with the P/F ratio at lung offer (median, 278 versus 420 mm Hg; P < .01). Seventeen lungs with a persistently low P/F ratio underwent EVLP, 8 of which were transplanted. There was no significant difference in primary graft dysfunction grade 3 at 72 hours (n = 3 of 41 [7.5%] versus 31 of 247 [13%]; P = .79) or in 30-day survival (100% versus 97%; P = .60) between low P/F-high BMI and standard groups., Conclusions: These data suggest that atelectasis in high-BMI donors contributes to P/F ratios less than 300 mm Hg and that intraoperative lung recruitment or EVLP can allow the use of lungs from these donors with good outcomes., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the safety and effectiveness of infrainguinal artery revascularization via atherectomy supplemented with other endovascular techniques in an office endovascular center (OEC) setting., Methods: A retrospective study was conducted examining 352 lower extremity atherectomy revascularization procedures between 2011 and 2016 at an OEC by five board-certified vascular surgeons. Patients received laser atherectomy or orbital atherectomy followed by angioplasty or angioplasty and stent placement as needed. Reintervention was indicated based on evidence of clinical symptoms and imaging studies. Demographics, vessel-specific data, treatment information, and outcome of procedures were recorded. Data analysis was carried out using Kaplan-Meier survival curves., Results: Lower extremity atherectomy was carried out in 282 patients in 352 limbs with average age of 69 ± 11 years. Technical success of <30% residual stenosis by angiogram was achieved in 571/594 vessels treated. Within 30 days of procedure, 23/352 limbs required major amputation resulting from pre-existing disease, ranging from 3 Rutherford class 4, 17 Rutherford class 5, to 3 Rutherford class 6 limbs. No 30-day mortality was noted. The primary patency of the 571 treated vessels at 12 months was 90%, and 84% at 29 months. The patency of treated vessels that reached >50% stenosis on follow-up and required reintervention (51/571 vessels) or did not require reintervention (79/571) was 72% and 87% at 23 months' follow-up, respectively, with no difference in risk of occlusion identified (P = .181). There was a significantly increased risk of occlusion for vessels treated with laser atherectomy as compared with orbital atherectomy (odds ratio, 2.552; 95% confidence interval, 1.375-4.735; P = .003). No significant difference in risk of occlusion was found between treatment with atherectomy and angioplasty (466/571 vessels) compared with atherectomy, angioplasty, and stenting (102/571) with secondary patency of 90% and 85% at 6 months' follow-up, respectively. There was no difference in patency between claudicants and patients with critical limb ischemia., Conclusions: Atherectomy in conjunction with angioplasty and/or stenting has satisfactory patency with minimal complications when the procedure is carried out in an OEC. Asymptomatic >50% restenosis of treated vessels does not warrant reintervention unless the patient presents with clinical symptoms. Various atherectomy devices may result in different outcomes., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to evaluate the safety and efficacy of a retrograde tibial approach in revascularization of lower extremities for treatment of ischemia in anatomically challenging patients., Methods: This is a retrospective study of 57 procedures performed between 2012 and 2016 using the retrograde approach to treat patients with flush occlusion, inability to cross the lesion, failed bypass, or hostile groin. Demographic data, Rutherford classes, vessels treated, and approach were noted. Type of procedure, complications, amputations, deaths, and patency of access tibial vessels and treated vessels were recorded. Ultrasound-guided tibial access was achieved through the anterior tibial artery, posterior tibial artery, or peroneal artery. Technical success was defined as residual stenosis of <30%. Restenosis was defined as two times increase in velocity at the site of treatment. In follow-up, access vessel patency and treated vessel patency were evaluated by physical examination and ultrasound. Kaplan-Meier survival curves were used to assess proportional hazards before using the marginal Cox model to determine statistical significance in risk of postintervention occlusion., Results: In 53 patients (32 men) with an average age of 67 ± 10.6 years, Rutherford categories were as follows: class 2, n = 1; class 3, n = 37; class 4, n = 5; class 5, n = 12; and class 6, n = 2. Tibial arteries were successfully accessed in all limbs. Lesions were crossed in 56 of 57 limbs. One procedure was terminated because of local arterial dissection. Revascularization was achieved in 55 of 57 limbs. Within 30 days of the procedure, 2 of 2 Rutherford class 6 patients and 1 of 12 class 5 patients needed major amputation because of pre-existing disease. There was no 30-day mortality. Of 103 vessels treated, technical success was achieved in 97 (94%). Secondary patency for 103 vessels was 79% with mean follow-up of 6.66 ± 5.4 months. The primary patency was 90% compared with a primary assisted patency of 51%. There was no statistically significant difference in access vessel primary patency in follow-up: 86% (30/35) for anterior tibial artery, 80% (16/20) for posterior tibial artery, and 100% (2/2) for peroneal artery. In addition, in follow-up, there was no significant difference in incidence of occlusion of target vessels based on choice of access vessel used (P = .109)., Conclusions: In this group of anatomically challenging patients, a retrograde tibial approach was safely used. Accessing the tibial artery does not usually cause access vessel occlusion and resulted in no adverse outcomes. The majority of access vessels remained patent for future bypass if necessary., (Copyright © 2018 Society for Vascular Surgery. All rights reserved.)

Background: Dementia is associated with high health care costs, premature long-term care (LTC) placement, medical complications, reduced quality of life, and caregiver burden. Most health care providers and systems are not yet organized or equipped to provide comprehensive long-term care management for dementia, although a range of effective symptoms and supportive care approaches exist. The Maximizing Independence at Home-Streamlined (MIND-S) is a promising model of home-based dementia care coordination designed to efficiently improve person-centered outcomes, while reducing care costs. This report describes the rationale and design of an NIA-funded randomized controlled trial to test the impact of MIND-S on time to LTC placement, person with dementia outcomes (unmet needs, behavior, quality of life), family caregiver outcomes (unmet needs, burden), and cost offset at 18 (primary end point) and 24 months, compared to an augmented usual care group., Methods: This is a 24-month, parallel group, randomized trial evaluating MIND-S in a cohort of 304 community-living persons with dementia and their family caregivers in Maryland. MIND-S dyads receive 18 months of care coordination by an interdisciplinary team comprised of trained non-clinical community workers (e.g. Memory Care Coordinators), a registered nurse, and a geriatric psychiatrist. Intervention components include in-home dementia-related needs assessments; individualized care planning; implementation of standardized evidence-based care strategy protocols; and ongoing monitoring and reassessment. Outcomes are assessed by blinded evaluators at baseline, 4.5, 9, 13.5, 18, and 24 months., Discussion: Trial results will provide rigorous data to inform innovations in effective system-level approaches to dementia care., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Current bovine pregnancy detection methods are not reliable until at least day 28 post artificial insemination (AI). The bovine estrous cycle is approximately 21 days; consequently, producers miss an opportunity to rebreed at the next estrous event. Therefore, commercial interest exists for the discovery of novel biomarkers of pregnancy which could reliably detect pregnancy status at or before day 21 of pregnancy. The objective of the present study was to use liquid chromatography tandem mass spectrometry (LC-MS/MS) to perform a global, label-free, proteomics study on (i) milk whey and (ii) extracellular vesicle (EV) enriched milk whey samples, from day 21 of pregnancy, compared with day 21 of the estrous cycle, in order to identify potential protein biomarkers of early pregnancy. The estrous cycles of 10 dairy cows were synchronized, they went through one (control) estrous cycle and these cows were artificially inseminated during the following estrus. These cows were confirmed pregnant by ultrasound scanning. Milk whey samples were collected on day 21 of the estrous cycle and on day 21 post AI. Milk whey samples and EV enriched milk whey samples were analyzed by LC-MS/MS and subsequent analyzes of the label-free quantitative data was performed in MaxQuant and Perseus. Four proteins (APOB, SPADH1, PLIN2 and LPO) were differentially expressed between the proteomes of milk whey from day 21 of pregnancy and day 21 of the estrous cycle (P < 0.05). Ten proteins (PIGR, PGD, QSOX1, MUC1, SRPRA, MD2, GAPDH, FOLR1, GPRC5B and HHIPL2) were differentially expressed between the proteomes of EV enriched milk whey from day 21 of pregnancy and day 21 of the estrous cycle (P < 0.05). These proteins are potential milk whey biomarkers of early pregnancy., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

All cells in vivo have a primary axis of polarity that controls many aspects of their behaviour, such as the direction of protein secretion and signalling, the orientation of cell division and directed cell movement and morphogenesis. Cell polarise in response to extracellular cues or intracellular landmarks that initiate a signal transduction process that establishes complementary cortical domains of conserved polarity factors. These cortical domains then transmit this polarity to the rest of the cell by regulating the organisation of the cytoskeleton and membrane trafficking systems. Here I review work over the past couple of years that has elucidated many key features of how polarity is established and transduced in different systems, but has also revealed unexpected variations in polarity mechanisms depending on context., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Early-life nutrition affects calf development and thus subsequent performance. The aim of this study was to examine the effect plane of nutrition on growth, feeding behaviour and systemic metabolite concentrations of artificially reared dairy bull calves. Holstein-Friesian (F; n=42) and Jersey (J; n=25) bull calves with a mean±SD age (14±4.7 v. 27±7.2 days) and BW (47±5.5 v. 33±4.7 kg) were offered a high, medium or low plane of nutrition for 8 weeks using an electronic feeding system which recorded a range of feed-related events. Calves were weighed weekly and plasma samples were collected via jugular venipuncture on weeks 1, 4 and 7 relative to the start of the trial period. The calves offered a high plane of nutrition had the greatest growth rate. However, the increased consumption of milk replacer led to a reduction in feed efficiency. Holstein-Friesian calves offered a low plane of nutrition had the greatest number of daily unrewarded visits to the feeder (P<0.001). β-hydroxybutyrate (BHB) concentrations were greater in F calves on a low plane of nutrition (P<0.001). Although there was no effect of plane of nutrition, BHB concentrations in F calves increased before weaning, concomitant with an increase in concentrate consumption. Urea concentrations were unaffected by plane of nutrition within either breed. Jersey calves on a low plane of nutrition tended to have lower triglycerides than those on a high plane (P=0.08), but greater than those on a medium plane (P=0.08). Holstein-Friesian calves offered a high plane of nutrition tended to have greater triglyceride concentrations than those on a medium plane (P=0.08). Triglycerides increased from the start to the end of the feeding period (P<0.05), across both breeds. A medium plane of nutrition resulted in a growth, feeding behaviour and metabolic response comparable with a high plane of nutrition in pre-weaned bull calves of both F and J breeds.

Competing Interests: Notification: No conflicts of interest or disclosures to report for all authors.

Bovine respiratory disease (BRD) complex in calves impairs health and welfare and causes severe economic losses for the Stockperson. Early recognition of BRD should lead to earlier veterinary (antibiotic/anti-inflammatory) treatment interventions thereby reducing the severity of the disease and associated costs. Coughing is one of the clinical manifestations of BRD. It is believed that by automatically and continuously monitoring the sounds within calf houses, and analysing the coughing frequency, early recognition of BRD in calves is possible. Therefore, the objective of the present study was to develop an automated calf cough monitor and examine its potential as an early warning system for BRD in artificially reared dairy calves. The coughing sounds of 62 calves were continuously recorded by a microphone over a three-month period. A sound analysis algorithm was developed to distinguish calf coughs from other sounds (e.g. mechanical sounds). During the sound recording period the health of the calves was assessed and scored periodically per week by a trained human observer. Calves presenting with BRD received antibiotic and/or anti-inflammatory treatment and the dates of treatment were recorded. This treatment date reference served as a comparison for the investigation of whether an increase in coughing frequency could be related to calves developing BRD. The calf cough detection algorithm achieved 50.3% sensitivity, 99.2% specificity and 87.5% precision. Four out of five periods, where coughing frequency was observed to be increased, coincided with the development of BRD in more than one calf. This period of increased coughing frequency was always observed before the calves were treated. Therefore, the calf cough monitor has the potential to identify early onset of BRD in calves., (© 2016 Published by Elsevier B.V.)

Haematological profiles indicate the health status of an animal and can be used to identify sub-clinical stress responses. The objectives of the study were to examine (i) the effect of breed and plane of nutrition, on haematological profiles of artificially reared Holstein-Friesian and Jersey bull calves in response to gradual weaning, and (ii) the effect of breed on immune response genes in bovine whole blood using real-time quantitative PCR. Holstein-Friesian and Jersey bull calves were group housed indoors and individually fed using an automatic feeder. They were allocated to a high, medium or low plane of nutrition, based on milk replacer (MR) and concentrate. The nutrition treatments were calculated using National Research Council guidelines in order to achieve a high, medium or low growth rate for each respective breed. During the weaning phase MR was gradually reduced over a 14-day (d) period (d -13 to d 0). Calves were blood sampled on d -14, -6, -3, 0, 1, 3, 8 and 14 relative to weaning (d 0) for subsequent haematological analysis. On d -14, 1 and 8, a subset of eight Holstein-Friesian calves randomly selected from the medium nutrition treatment and eight Jersey calves randomly selected from the high nutrition treatment, were blood sampled for gene expression profiling, targeting biomarkers of weaning stress. These two treatment groups were chosen to examine the effect of breed on expression of the genes of interest, as energy intake and animal performance were similar. There was no effect of breed×plane of nutrition interaction nor effect of plane of nutrition on any variable measured (P>0.05). Gradual weaning produced differential biological responses in the two breeds evidenced by breed×time interactions for lymphocyte, monocyte and red blood cell number, plasma haemoglobin and haptoglobin concentrations (P<0.05). The typical stress response consisting of neutrophilia and lymphopaenia was not observed for any treatment. An immune response to gradual weaning was observed as the relative gene expression level of the pro-apoptotic gene, Fas, increased on d 1 relative to d -14 (P<0.05). Relative gene expression levels were greater in Jersey calves compared with Holstein-Friesian for the pro-inflammatory cytokine CXCL8 (P=0.05) and the glucocorticoid receptor, GRα (P<0.05). The increased levels of these transcripts suggest that Jersey calves may have a more sensitive immune system compared with Holstein-Friesian.

Among over 5million people in the USA with dementia, neuropsychiatric symptoms (NPS) are almost universal, occurring across disease etiology and stage. If untreated, NPS can lead to significant morbidity and mortality including increased cost, distress, depression, and faster disease progression, as well as heightened burden on families. With few pharmacological solutions, identifying nonpharmacologic strategies is critical. We describe a randomized clinical trial, the Dementia Behavior Study, to test the efficacy of an activity program to reduce significant existing NPS and associated caregiver burden at 3 and 6months compared to a control group intervention. Occupational therapists deliver 8 in-home sessions over 3months to assess capabilities and interests of persons with dementia, home environments, and caregiver knowledge, and readiness from which activities are developed and families trained in their use. Families learn to modify activities for future declines and use strategies to address care challenges. The comparison group controls for time and attention and involves 8 in-home sessions delivered by health educators who provide dementia education, home safety recommendations, and advanced care planning. We are randomizing 250 racially diverse families (person with dementia and primary caregiver dyads) recruited from community-based social services, conferences and media announcements. The primary outcome is change in agitation/aggression at 3 and 6months. Secondary outcomes assess quality of life of persons with dementia, other behaviors, burden and confidence of caregivers, and cost and cost effectiveness. If benefits are supported, this activity intervention will provide a clinically meaningful approach to prevent, reduce, and manage NPS., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Using high-speed imaging we assessed Streptococcus mutans biofilm-fluid interactions during exposure to a 60-ms microspray burst with a maximum exit velocity of 51m/s. S. mutans UA159 biofilms were grown for 72h on 10mm-length glass slides pre-conditioned with porcine gastric mucin. Biofilm stiffness was measured by performing uniaxial-compression tests. We developed an in-vitro interproximal model which allowed the parallel insertion of two biofilm-colonized slides separated by a distance of 1mm and enabled high-speed imaging of the removal process at the surface. S. mutans biofilms were exposed to either a water microspray or an air-only microburst. High-speed videos provided further insight into the mechanical behaviour of biofilms as complex liquids and into high-shear fluid-biofilm interaction. We documented biofilms extremely transient fluid behaviour when exposed to the high-velocity microsprays. The presence of time-dependent recoil and residual deformation confirmed the pivotal role of viscoelasticity in biofilm removal. The air-only microburst was effective enough to remove some of the biofilm but created a smaller clearance zone underlying the importance of water and the air-water interface of drops moving over the solid surface in the removal process. Confocal and COMSTAT analysis showed the high-velocity water microspray caused up to a 99.9% reduction in biofilm thickness, biomass and area coverage, within the impact area., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We evaluated single nucleotide polymorphisms (SNPs) associated with infection risk in children with newly diagnosed acute myeloid leukaemia (AML). We conducted a multicentre, prospective cohort study that included children aged ≤18 years with de novo AML. DNA was isolated from blood lymphocytes or buccal swabs, and candidate gene SNP analysis was conducted. Primary outcome was the occurrence of microbiologically documented sterile site infection during chemotherapy. Secondary outcomes were Gram-positive and -negative infections, viridans group streptococcal infection and proven/probable invasive fungal infection. Interpretation was guided by consistency in risk alleles and microbiologic agent with previous literature. Over the study period 254 children and adolescents with AML were enrolled. Overall, 190 (74.8%) had at least one sterile site microbiologically documented infection. Among the 172 with inferred European ancestry and DNA available, nine significant associations were observed; two were consistent with previous literature. Allele A at IL1B (rs16944) was associated with decreased microbiologically documented infection, and allele G at IL10 (rs1800896) was associated with increased risk of Gram-positive infection. We identified SNPs associated with infection risk in paediatric AML. Genotype may provide insight into mechanisms of infection risk that could be used for supportive-care novel treatments., (Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the osteo-regenerative potential of Titanium (Ti) modified by Light Amplification by Stimulated Emission of Radiation (LASER) beam (Yb-YAG) upon culture with human Skeletal Stem Cells (hSSCs(1))., Methods: Human skeletal cell populations were isolated from the bone marrow of haematologically normal patients undergoing primary total hip replacement following appropriate consent. STRO-1(+) hSSC(1) function was examined for 10 days across four groups using Ti discs: i) machined Ti surface group in basal media (Mb(2)), ii) machined Ti surface group in osteogenic media (Mo(3)), iii) LASER-modified Ti group in basal media (Lb(4)) and, iv) LASER-modified Ti group in osteogenic media (Lo(5)). Molecular analysis and qRT-PCR as well as functional analysis including biochemistry (DNA, Alkaline Phosphatase (ALP(6)) specific activity), live/dead immunostaining (Cell Tracker Green (CTG(7))/Ethidium Homodimer-1 (EH-1(8))), and fluorescence staining (for vinculin and phalloidin) were undertaken. Inverted, confocal and Scanning Electron Microscopy (SEM) approaches were used to characterise cell adherence, proliferation, and phenotype., Results: Enhanced cell spreading and morphological rearrangement, including focal adhesions were observed following culture of hSSCs(1) on LASER surfaces in both basal and osteogenic conditions. Biochemical analysis demonstrated enhanced ALP(6) specific activity on the hSSCs(1)-seeded on LASER-modified surface in basal culture media. Molecular analysis demonstrated enhanced ALP(6) and osteopontin expression on titanium LASER treated surfaces in basal conditions. SEM, inverted microscopy and confocal laser scanning microscopy confirmed extensive proliferation and migration of human bone marrow stromal cells on all surfaces evaluated., Conclusions: LASER-modified Ti surfaces modify the behaviour of hSSCs.(1) In particular, SSC(1) adhesion, osteogenic gene expression, cell morphology and cytoskeleton structure were affected. The current studies show Ti LASER modification can enhance the osseointegration between Ti and skeletal cells, with important implications for orthopaedic application., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background and Objectives: Over the last 6 years, our center has introduced a novel technique combining peripheral nerve blocks (femoral and lateral femoral cutaneous nerves) with sedation using propofol with alfentanil target-controlled infusion for hip fracture surgery. The purpose of this review was to identify if adverse outcomes (of mortality and length of stay) were associated with its introduction compared to spinal or general anesthesia., Methods: Retrospective data collection from hospital fracture database. Data were analyzed using Cox regression (adjusted for age, sex, and American Society of Anesthesiologists grade) to compare survival and length of stay data across the different anesthetic techniques used for hip fracture surgery., Results: This technique was used in 472 (20%) of 2360 hip fractures. There was no significant difference between peripheral nerve blocks with propofol/alfentanil sedation/analgesia for mortality up to 120days (hazard ratio, 0.76; 95% confidence interval, 0.54-1.06; P=.11) and length of stay (hazard ratio, 1.03; 95% confidence interval, 0.91-1.17; P=.63) when compared to the other anesthetic techniques of spinal and general anesthesia., Conclusion: This novel technique does not appear to be associated with adverse mortality or length of stay after hip fracture surgery., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To provide a critical review of a multipronged recruitment approach used to identify, recruit, and enroll a diverse community-based sample of persons with memory disorders into an 18-month randomized, controlled dementia care coordination trial., Methods: Descriptive analysis of a recruitment approach comprised five strategies: community liaison ("gatekeepers") method, letters sent from trusted community organizations, display and distribution of study materials in the community, research registries, and general community outreach and engagement activities. Participants were 55 community organizations and 63 staff of community organizations in Baltimore, Maryland. Participant referral sources, eligibility, enrollment status, demographics, and loss to follow-up were tracked in a relational access database., Results: In total, 1,275 referrals were received and 303 socioeconomically, cognitively, and racially diverse community-dwelling persons with cognitive disorders were enrolled. Most referrals came from letters sent from community organizations directly to clients on the study's behalf (39%) and referrals from community liaison organizations (29%). African American/black enrollees were most likely to come from community liaison organizations., Conclusion: A multipronged, adaptive approach led to the successful recruitment of diverse community-residing elders with memory impairment for an intervention trial. Key factors for success included using a range of evidence-supported outreach strategies, forming key strategic community partnerships, seeking regular stakeholder input through all research phases, and obtaining "buy-in" from community stakeholders by aligning study objectives with perceived unmet community needs., (Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To assess whether MIND at Home, a community-based, multicomponent, care coordination intervention, reduces unmet caregiving needs and burden in informal caregivers of persons with memory disorders., Methods: An 18-month randomized controlled trial of 289 community-living care recipient (CR)-caregiver (informal caregivers, i.e., unpaid individuals who regularly assisted the CR) dyads from 28 postal code areas of Baltimore, Maryland was conducted. All dyads and the CR's primary care physician received the written needs assessment results and intervention recommendations. Intervention dyads then received an 18-month care coordination intervention delivered by nonclinical community workers to address unmet care needs through individualized care planning, referral and linkage to dementia services, provision of caregiver dementia education and skill-building strategies, and care progress monitoring by an interdisciplinary team. Primary outcome was total percent of unmet caregiver needs at 18 months. Secondary outcomes included objective and subjective caregiver burden measures, quality of life (QOL), and depression., Results: Total percent of unmet caregiver needs declined in both groups from baseline to 18 months, with no statistically significant between-group difference. No significant group differences occurred in most caregiver burden measures, depression, or QOL. There was a potentially clinically relevant reduction in self-reported number of hours caregivers spent with the CR for MIND participants compared with control subjects., Conclusion: No statistically significant impacts on caregiver outcomes were found after multiple comparison adjustments. However, MIND at Home appeared to have had a modest and clinically meaningful impact on informal caregiver time spent with CRs., (Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

The post-synaptic translation of localised mRNAs has been postulated to underlie several forms of plasticity at vertebrate synapses, but the mechanisms that target mRNAs to these postsynaptic sites are not well understood. Here we show that the evolutionary conserved dsRNA binding protein, Staufen, localises to the postsynaptic side of the Drosophila neuromuscular junction (NMJ), where it is required for the localisation of coracle mRNA and protein. Staufen plays a well-characterised role in the localisation of oskar mRNA to the oocyte posterior, where Staufen dsRNA-binding domain 5 is specifically required for its translation. Removal of Staufen dsRNA-binding domain 5, disrupts the postsynaptic accumulation of Coracle protein without affecting the localisation of cora mRNA, suggesting that Staufen similarly regulates Coracle translation. Tropomyosin II, which functions with Staufen in oskar mRNA localisation, is also required for coracle mRNA localisation, suggesting that similar mechanisms target mRNAs to the NMJ and the oocyte posterior. Coracle, the orthologue of vertebrate band 4.1, functions in the anchoring of the glutamate receptor IIA subunit (GluRIIA) at the synapse. Consistent with this, staufen mutant larvae show reduced accumulation of GluRIIA at synapses. The NMJs of staufen mutant larvae have also a reduced number of synaptic boutons. Altogether, this suggests that this novel Staufen-dependent mRNA localisation and local translation pathway may play a role in the developmentally regulated growth of the NMJ., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess whether a dementia care coordination intervention delays time to transition from home and reduces unmet needs in elders with memory disorders., Design: 18-month randomized controlled trial of 303 community-living elders., Setting: 28 postal code areas of Baltimore, MD., Participants: Age 70+ years, with a cognitive disorder, community-living, English-speaking, and having a study partner available., Intervention: 18-month care coordination intervention to systematically identify and address dementia-related care needs through individualized care planning; referral and linkage to services; provision of dementia education and skill-building strategies; and care monitoring by an interdisciplinary team., Measurements: Primary outcomes were time to transfer from home and total percent of unmet care needs at 18 months., Results: Intervention participants had a significant delay in time to all-cause transition from home and the adjusted hazard of leaving the home was decreased by 37% (Hazard ratio: 0.63, 95% Confidence Interval: 0.42-0.94) compared with control participants. Although there was no significant group difference in reduction of total percent of unmet needs from baseline to 18 months, the intervention group had significant reductions in the proportion of unmet needs in safety and legal/advance care domains relative to controls. Intervention participants had a significant improvement in self-reported quality of life (QOL) relative to control participants. No group differences were found in proxy-rated QOL, neuropsychiatric symptoms, or depression., Conclusions: A home-based dementia care coordination intervention delivered by non-clinical community workers trained and overseen by geriatric clinicians led to delays in transition from home, reduced unmet needs, and improved self-reported QOL., (Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objectives: To quantify the association between complementary and alternative medicine (CAM) use and quality of life in a population with type 2 diabetes and/or cardiovascular disease, accounting for demographics, socioeconomic status, health and lifestyle factors., Design and Setting: Data are from a purpose-designed survey of 2915 individuals aged 18 years and over, all with type 2 diabetes and/or cardiovascular disease (CVD), collected in 2010. Key variables are compared for comparability with nationally representative data. It was hypothesised that CAM use would be associated with higher quality of life, as measured by the Assessment of Quality of Life-4 dimension (AQoL-4D) instrument. Three key variables are used for CAM use in the previous twelve months. In the robustness analysis, CAM use is further disaggregated into the types of practitioner or product used, the frequency of use, the reason for use and expenditure on CAM., Results: CAM use is not associated with higher QoL for this sub-population, and in fact intensive use of CAM practitioners is associated with significantly lower QoL., Conclusions: It is important not to assume that patients have sufficient information with which to make optimal choices regarding CAM use in the absence of accessible and relevant evidence-based guidance., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: This study was conducted to identify the safety of endovascular procedures in the office endovascular suite and to assess patient satisfaction in this setting., Methods: Between May 22, 2007, and December 31, 2012, 2822 patients underwent 6458 percutaneous procedures in an office-based endovascular suite. Demographics of the patients, complications, hospital transfers, and 30-day mortality were documented in a prospective manner. Follow-up calls were made, and a satisfaction survey was conducted. Almost all dialysis procedures were done under local anesthesia and peripheral arterial procedures under conscious sedation. All patients, except those undergoing catheter removals, received hydrocodone and acetaminophen (5/325 mg), diazepam (5-10 mg), and one dose of an oral antibiotic preprocedure and three doses postprocedure. Patients who required conscious sedation received fentanyl and midazolam. Conscious sedation was used almost exclusively in patients having an arterial procedure. Measurements of blood urea nitrogen, creatinine, international normalized ratio, and partial thromboplastin time were performed before peripheral arteriograms. All other patients had no preoperative laboratory tests. Patients considered high risk (American Society of Anesthesiologists Physical Status Classification 4), those who could not tolerate the procedure with mild to moderate conscious sedation, patients with a previous bad experience, or patients who weighed >400 pounds were not candidates for office based procedures., Results: There were 54 total complications (0.8%): venous, 2.2%; aortogram without interventions, 1%; aortogram with interventions, 2.7%; fistulogram, 0.5%; catheters, 0.3%; and venous filter-related, 2%. Twenty-six patients required hospital transfer from the office. Ten patients needed an operative intervention because of a complication. No procedure-related deaths occurred. There were 18 deaths in a 30-day period. Of patients surveyed, 99% indicated that they would come back to the office for needed procedures., Conclusions: When appropriately screened, almost all peripheral interventions can be performed in the office with minimal complications. For dialysis patients, outpatient intervention has a very low complication rate and is the mainstay of treatment to keep the dialysis access patent. Venous insufficiency, when managed in the office setting, also has a low complication rate. Office-based procedural settings should be seriously considered for percutaneous interventions for arterial, venous, and dialysis-related procedures., (Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

In pediatric acute myeloid leukemia (AML), cytogenetic abnormalities are strong indicators of prognosis. Some recurrent cytogenetic abnormalities, such as t(8;16)(p11;p13), are so rare that collaborative studies are required to define their prognostic impact. We collected the clinical characteristics, morphology, and immunophenotypes of 62 pediatric AML patients with t(8;16)(p11;p13) from 18 countries participating in the International Berlin-Frankfurt-Münster (I-BFM) AML study group. We used the AML-BFM cohort diagnosed from 1995-2005 (n = 543) as a reference cohort. Median age of the pediatric t(8;16)(p11;p13) AML patients was significantly lower (1.2 years). The majority (97%) had M4-M5 French-American-British type, significantly different from the reference cohort. Erythrophagocytosis (70%), leukemia cutis (58%), and disseminated intravascular coagulation (39%) occurred frequently. Strikingly, spontaneous remissions occurred in 7 neonates with t(8;16)(p11;p13), of whom 3 remain in continuous remission. The 5-year overall survival of patients diagnosed after 1993 was 59%, similar to the reference cohort (P = .14). Gene expression profiles of t(8;16)(p11;p13) pediatric AML cases clustered close to, but distinct from, MLL-rearranged AML. Highly expressed genes included HOXA11, HOXA10, RET, PERP, and GGA2. In conclusion, pediatric t(8;16)(p11;p13) AML is a rare entity defined by a unique gene expression signature and distinct clinical features in whom spontaneous remissions occur in a subset of neonatal cases.

The modulation of the mechanical properties of monolithic fibers by plasticizing and crosslinking enables the dynamic control of the nano-tensile forces, thereby obtaining optimized Young's modulus and ultimate strain for specialized application in the treatment of periodontal disease. In this work, drug-loaded crosslinked and plasticized alginate fibers (cl-PAFs) were prepared by extrusion-gelification with the aim of designing oradurable biomaterials for placement within the periodontal pocket and provide prolonged drug delivery. Mechanical properties of drug-free cl-PAFs were determined using a nanoTensile™ 5000 instrument and subsequently optimized versus the quantity of plasticizer and crosslinker as formulation variables employing a Box-Behnken experimental design strategy. Mechanically optimized fibers obtained (Young's Modulus=314.04 MPa, yield stress=5.80 MPa, ultimate strength=10.05 MPa, ultimate strain=0.29 MPa and toughness=2.39 J cm(-3)) were loaded with the model drugs ciprofloxacin and diclofenac both individually and simultaneously. The Young's modulus of cl-PAFs loaded with either drug individually exhibited a steep decline. However, in the case of cl-PAFs loaded with both drugs simultaneously, Young's modulus regained the original value which may be attributed to the cohesive energy density, porosity and space filling. The effect of various formulation variables on the drug entrapment and release characteristics of the alginate fibers was elucidated at pH 4.0 and pH 6.8. Furthermore, a previously established atomistic computational model based on energy refinements was employed to mechanistically describe the fiber performance. The effect of varying the plasticizer and crosslinking ion concentration on Young's modulus and ultimate strain of the linear elastic polymer matrix and the performance of the ciprofloxacin and/or diclofenac loaded optimized fiber was elucidated and conceptualized using molecular mechanics energy relationships (MMER) via the geometrical conformation and positioning of the molecular architectures., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The objective was to compare 5-year overall survival (OS) between adolescent and young adult (AYA) patients (age 15-19) with acute lymphoblastic leukemia (ALL) treated at a pediatric versus an adult center., Patients and Methods: This was a population-based analysis using administrative data of Ontario ALL AYA patients diagnosed between 1986-2009. We calculated predicted survival proportions (PSPs) and 95% confidence intervals (CI). We also surveyed sites to determine whether pediatric or adult-based protocols were used in each period., Results: Overall, 290 patients between 15-19 years of age were diagnosed with ALL during the study period; 144 patients (49.7%) were treated at an adult center. When adjusted for gender, age, income quintile and time period, AYA patients treated at a pediatric center did not have a significantly different PSP (0.65, 95% CI: 0.56-0.75) in comparison to those treated at an adult center (0.62, 95% CI 0.52-0.73; P = 0.87). Most AYA patients treated at adult centers received pediatric protocols in the recent periods., Conclusions: Using population-based data, AYA ALL patients had similar outcomes whether treated at a pediatric or an adult center. Early introduction of aggressive treatment protocols in adult centers may have negated differences in outcomes among AYA patients by site of care.

Developing effective clinical decision support (CDS) systems for the highly complex and dynamic domain of clinical medicine is a serious challenge for designers. Poor usability is one of the core barriers to adoption and a deterrent to its routine use. We reviewed reports describing system implementation efforts and collected best available design conventions, procedures, practices and lessons learned in order to provide developers a short compendium of design goals and recommended principles. This targeted review is focused on CDS related to medication prescribing. Published reports suggest that important principles include consistency of design concepts across networked systems, use of appropriate visual representation of clinical data, use of controlled terminology, presenting advice at the time and place of decision making and matching the most appropriate CDS interventions to clinical goals. Specificity and contextual relevance can be increased by periodic review of trigger rules, analysis of performance logs and maintenance of accurate allergy, problem and medication lists in health records in order to help avoid excessive alerting. Developers need to adopt design practices that include user-centered, iterative design and common standards based on human-computer interaction (HCI) research methods rooted in ethnography and cognitive science. Suggestions outlined in this report may help clarify the goals of optimal CDS design but larger national initiatives are needed for systematic application of human factors in health information technology (HIT) development. Appropriate design strategies are essential for developing meaningful decision support systems that meet the grand challenges of high-quality healthcare., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Despite major improvements in outcome over the past decades, acute myeloid leukemia (AML) remains a life-threatening malignancy in children, with current survival rates of ∼70%. State-of-the-art recommendations in adult AML have recently been published in this journal by Döhner et al. The primary goal of an international expert panel of the International BFM Study Group AML Committee was to set standards for the management, diagnosis, response assessment, and treatment in childhood AML. This paper aims to discuss differences between childhood and adult AML, and to highlight recommendations that are specific to children. The particular relevance of new diagnostic and prognostic molecular markers in pediatric AML is presented. The general management of pediatric AML, the management of specific pediatric AML cohorts (such as infants) or subtypes of the disease occurring in children (such as Down syndrome related AML), as well as new therapeutic approaches, and the role of supportive care are discussed.

The development of Clinical Research Networks (CRN) has been central to the work conducted by Health Departments and research funders to promote and support clinical research within the NHS in the UK. In England, the National Institute for Health Research has supported the delivery of clinical research within the NHS primarily through CRN. CRN provide the essential infrastructure within the NHS for the set up and delivery of clinical research within a high-quality peer-reviewed portfolio of studies. The success of the National Cancer Research Network is summarized in Chapter 5. In this chapter progress in five other topics, and more recently in primary care and comprehensively across the NHS, is summarized. In each of the 'topic-specific' networks (Dementias and Neurodegenerative Diseases, Diabetes, Medicines for Children, Mental Health, Stroke) there has been a rapid and substantial increase in portfolios and in the recruitment of patients into studies in these portfolios. The processes and the key success factors are described. The CRN have worked to support research supported by pharmaceutical, biotechnology and medical device companies and there has been substantial progress in improving the speed, cost and delivery of these 'industry' studies. In particular, work to support the increased speed of set up and delivery of industry studies, and to embed this firmly in the NHS, was explored in the North West of England in an Exemplar Programme which showed substantial reductions in study set-up times and improved recruitment into studies and showed how healthcare (NHS) organizations can overcome delays in set up times when they actively manage the process. Seven out of 20 international studies reported that the first patient to be entered anywhere in the world was from the UK. In addition, the CRN have supported research management and governance, workforce development and clinical trials unit collaboration and coordination. International peer reviews of all of the CRN have been positive and resulted in the continuation of the system for a further 5 years in all cases.

The adult form of a multicellular organism is shaped by a series of morphogenetic processes that organise the body into tissues and organs. Most of these events involve the deformation of sheets of epithelial cells that are highly polarised along their apical-basal axes and attached to each other by lateral junctions. Here we discuss the role played by modifications in the apical-basal polarity system in driving morphogenesis, with an emphasis on well-characterised events during Drosophila development. Changing the activity of polarity factors can alter the relative sizes of the apical, lateral and basal domains. This can drive transitions between cuboidal, columnar and squamous epithelial morphologies, to increase or decrease the surface area of an epithelial sheet. These changes can also cause epithelial cells to become wedge-shaped, which can drive tissue bending and invagination. In addition, it has recently emerged that the activity of apical-basal polarity factors can also be modulated in a planar polarised manner. By affecting the contractility of the actomyosin cytoskeleton and the stability of adherens junctions, changes within the plane of the epithelium can cause cell rearrangements that contribute to convergence and extension movements, boundary formation and cell alignment., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Perioperative vasoplegia is associated with increased morbidity. Red blood cell (RBC) transfusion increases plasma concentrations of inflammatory mediators, possibly contributing to the development of vasoplegia. We investigated the prevalence of mild and profound postoperative vasoplegia, identified factors associated with its development, and examined the role of RBC and component transfusion on the occurrence of postoperative vasoplegia., Methods: Between January 1, 2000, and January 1, 2007, 25,960 patients underwent on-bypass cardiac surgical procedures. The incidence of vasoplegia was defined as (1) mild vasoplegia requiring norepinephrine infusion for blood pressure support on the day of operation and postoperative day 1, and (2) profound vasoplegia requiring vasopressin, with or without concomitant norepinephrine infusion, on the day of operation and postoperative day 1. Separate logistic regression models were used to model risk factors for development of mild and profound vasoplegia., Results: RBC transfusion increased risk-adjusted odd ratios (ORs) of developing mild vasoplegia (1.07 [95% confidence limits (CL), 1.05, 1.10]; p<0.001) and profound vasoplegia (1.38 [1.31, 1.46] p<0.001). The risk-adjusted ORs (95% CL) for mild vasoplegia and profound vasoplegia were similarly increased by fresh-frozen plasma (OR, 1.24 [1.10, 1.41], p<0.001; and OR, 1.20 [1.13, 1.29], p<0.001) and platelet transfusion (OR, 1.39 [1.25, 1.54], p<0.001; and OR, 1.22 [1.14, 1.31], p<0.001), respectively., Conclusions: Red blood cells, fresh-frozen plasma, and platelet transfusion increased the prevalence of vasoplegia. RBC transfusion exhibited a dose-dependent response for developing vasoplegia with each RBC unit transfused. Further investigation is necessary to determine whether prophylactic use of vasopressor support in the setting of transfusion can ameliorate risk and effect outcomes., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Brown eggs have gradually entered the traditional white-egg markets as a distinctive mode for packaging specialty eggs. A test was conducted at the Brigham Young University Sensory Laboratory (Provo, UT) to understand how consumers view attributes of the brown egg relative to the white egg. The objectives were to see how the consumer viewed properties of eggs by color and to examine the preference for brown color intensity. The 52 panelists were all women who routinely purchased and consumed eggs. Some women (53.8%) consumed eggs twice weekly, and 40.4% purchased them at least every 2 wk. Purchases included specialty eggs (14.6%) consisting of cage-free (50.0%), organic (28.6%), and n-3 enhanced (21.4%) eggs. The panelists preferred white eggs (90.4%). Though brown-shelled eggs did not exceed white eggs in preference, they were perceived positively (white-shelled %:brown-shelled %) as being more nutritious (65:29), having more flavor (27:14) and n-3 content (62:39), having a farm-flock origin (46:44), and being from organically fed hens (56:31) To test the preference for shade of brown eggs, a set of 6 eggs with varying intensities of brown color was evaluated for accepted appearance using a 9-point hedonic scale. The egg color intensities were measured using a Hunter Colorflex spectrophotometer (Hunter Associates Laboratory, Reston, VA) and the CIE system. The lightness (L*) values ranged from 83.2 for the white egg to 63.6 to 46.5 for the brown eggs. A significant (P < 0.05) preference was found for the 2 lighter shades of brown-shelled eggs (L* 63.6 and 57.5). Using the 9-point scale, panelists then compared brown eggs side by side with white eggs. Again, the 2 most light-tinted brown eggs were found most comparable with the white egg in acceptability and better (P < 0.05) than the darker brown eggs. In conclusion, white eggs were preferred over brown eggs; however, brown eggs gained in acceptance but did not exceed white as likely to be more nutritious or flavorful, fresher, organic, and of cage-free origin. Varying color shades in cartoned eggs was equally as acceptable as uniform colored eggs. Panelists preferred the appearance of the light-tinted brown eggs to that of darker brown eggs.

Background: The Geriatric Psychiatry Outreach (GO) Program began in 2005 and provides in-home psychiatric evaluation and treatment for older adults who have difficulty getting to an office-based setting., Method: An initial assessment was conducted on the first 100 patients seen by the program and follow-up treatment was provided as clinically indicated., Results: The mean age of patients seen was 79.7 (SD: 8.2), 74% were women, and the most common psychiatric diagnoses were depression (50%) and dementia (45%), with a mean of 1.4 (SD: 0.6) psychiatric diagnoses per patient. The patients had a mean of 4.8 (SD: 2.9) medical diagnoses and were on a mean of 6.8 (SD: 4.0) prescription and 2.2 (SD: 1.2) nonprescription medications. Patients received a mean of 4.2 (SD: 4.2) in-person visits and a mean of 30.2 (SD: 36.5) additional contacts related to their care, such as phone calls, e-mails, and faxes., Conclusions: Providing psychiatric services at home for older adults with mental illness is a much needed but rarely available service. Such patients typically have a complex combination of medical and psychiatric diagnoses and benefit from contacts in addition to the face-to-face visits.

In regions affected by historic non-coal (principally metal) mining activity, government agencies are often faced with the challenge of deploying limited remedial resources at abandoned mine sites to achieve maximum improvements in the chemical and ecological quality of impacted ground and surface waters. As such, strategies for the defensible allocation of public funds require comprehensive and systematic frameworks by which to identify and prioritise polluting sites for remediation. This paper describes the development and initial findings of such a national initiative in England and Wales which allies catchment-scale environmental impact assessments using existing public archive data, with recognition of the uncertainty in impact appraisals arising from disparities in data availability between sites and regions. The methodology identifies polluting sites and takes account not only of the chemical and ecological impacts of mine water discharges on receiving watercourses, but also of socio-economic factors such as conservation and heritage concerns, which can both impede or complement efforts to remediate mine sites. Using a Geographic Information System database and a suite of spatial analyses employing Boolean operators, both the extent of the pollution problem from abandoned non-coal mines in England and Wales (6% of 7815 surface water bodies are affected nationally) and the insight that can be gleaned from systematic analyses of existing archive data are highlighted. The results of the nationwide survey can be used as a dynamic database to inform future remedial planning, in terms of prioritising impacted river basins and abandoned non-coal mine sites themselves for either remediation or future monitoring efforts. As the assessment framework is built upon existing water quality and ecological data and mine site/geological data, there is considerable scope for the approach to be applied elsewhere where the legacy of historic mining persists through the widespread pollution of the aquatic environment.

Insulin-like growth factor-1 (IGF-1) stimulates proliferation, regulates tissue development, protects against apoptosis, and promotes the malignant phenotype in the breast and other organs. Some epidemiological studies have linked high circulating levels of IGF-1 with an increased risk of breast cancer. To study the role of IGF-1 in mammary tumorigenesis in vivo, we used transgenic mice in which overexpression of IGF-1 is under the control of the bovine keratin 5 (BK5) promoter and is directed to either the myoepithelial or basal cells in a variety of organs, including the mammary gland. This model closely recapitulates the paracrine exposure of breast epithelium to stromal IGF-1 seen in women. Histologically, mammary glands from transgenic mice were hyperplastic and highly vascularized. Mammary glands from prepubertal transgenic mice had significantly increased ductal proliferation compared with wild-type tissues, although this difference was not maintained after puberty. Transgenic mice also had increased susceptibility to mammary carcinogenesis, and 74% of the BK5.IGF-1 mice treated with 7,12-dimethylbenz[a]anthracene (20 microg/day) developed mammary tumors compared with 29% of the wild-type mice. Interestingly, 31% of the vehicle-treated BK5.IGF-1 animals, but none of the wild-type animals, spontaneously developed mammary cancer. The mammary tumors were moderately differentiated adenocarcinomas that expressed functional, nuclear estrogen receptor at both the protein and mRNA levels. These data support the hypothesis that tissue overexpression of IGF-1 stimulates mammary tumorigenesis.

A non-lethal chemically based approach was used to investigate the quality of harbour sediments receiving combined road runoff and sewage effluents. A previous investigation of the behaviour of the amphipod Corophium volutator linked polycyclic aromatic hydrocarbons (PAH) in sediments corresponding to the probable effects levels listed in the sediment quality guidelines of the Canadian Council of the Marine Environment to a sediment avoidance response. Since the amphipods did not biotransform contaminants, bioaccumulation was the only fate pursued to examine the bioavailability of PAH. For five Halifax Harbour sediments, a relationship was established between the threshold effects level representing the amphipods' avoidance response and the bioaccumulation of PAH. A body burden of 0.3-1.1 mumol/kg (wet weight) was determined for the sum of abundant parental PAH in amphipods exposed to sediments that initiated the behavioural effect. PAH were much more available from spiked sediments than from field sediments, with biota-sediment accumulation factors of 2.2-7.8 compared to <0.01-0.3, respectively. Animals exposed to PAH-spiked sediments avoided contaminated sediments when their body burden was up to seven times higher than observed with field sediments. This latter result and two exposures to sediments collected further away from sewage discharges point to a role for unidentified chemicals in the body burden and behaviour relationship. Further research is warranted to develop this promising assessment tool.

Total hip and knee arthroplasties are effective surgical interventions for relieving hip pain and improving physical function caused by arthritis. Although the majority of patients substantially improve, not all report gains or are satisfied after receiving total joint arthroplasty. This article reviews the literature on patient outcomes after total hip and knee arthroplasties for osteoarthritis, and the evidence pertaining to factors that affect these patient-centered outcomes. Mounting evidence suggests that no single patient-related or perioperative factor clearly predicts the amount of pain relief or functional improvement that will occur following total hip or knee arthroplasty.