A whole system approach to increasing children's physical activity in a multi-ethnic UK city: a process evaluation protocol.
Engaging in regular physical activity requires continued complex decision-making in varied and dynamic individual, social and structural contexts. Widespread shortfalls of physical activity interventions suggests the complex underlying mechanisms of change are not yet fully understood. More insightful process evaluations are needed to design and implement more effective approaches. This paper describes the protocol for a process evaluation of the JU:MP programme, a whole systems approach to increasing physical activity in children and young people aged 5-14 years in North Bradford, UK. This process evaluation, underpinned by realist philosophy, aims to understand the development and implementation of the JU:MP programme and the mechanisms by which JU:MP influences physical activity in children and young people. It also aims to explore behaviour change across wider policy, strategy and neighbourhood systems. A mixed method data collection approach will include semi-structured interview, observation, documentary analysis, surveys, and participatory evaluation methods including reflections and ripple effect mapping. This protocol offers an innovative approach on the use of process evaluation feeding into an iterative programme intended to generate evidence-based practice and deliver practice-based evidence. This paper advances knowledge regarding the development of process evaluations for evaluating systems interventions, and emphasises the importance of process evaluation.


Langerhans cell histiocytosis in the maxillofacial area in adults. Report of three cases.
Langerhans cell histiocytosis (LCH) is a disease of unknown etiology, characterized by proliferation of pathological Langerhans cells within different organs. It mainly affects children, but adult cases also occur, with an incidence rate of one to two per million. The head and neck are affected in almost 90% of cases. Diagnosis is made by means of histopathological analysis, and imaging studies are necessary in order to determine extent of the disease. There are no controlled trials proposing an optimal treatment protocol for LCH. Prognosis in adults is generally good due to the slow evolution of the disease and its favourable response to treatment. In our report, we present three cases of LCH in patients aged 16, 24, and 28 years respectively, with primary manifestation in the maxillofacial area. A literature review was also conducted.


Heterologous expression of IbMYB1a by different promoters exhibits different patterns of anthocyanin accumulation in tobacco.
We previously reported that the transient and stable expression of IbMYB1a produced anthocyanin pigmentation in tobacco leaves and transgenic Arabidopsis plants, respectively. To further determine the effects of different promoters on the expression of IbMYB1a and anthocyanin production, we generated and characterized stably transformed tobacco (Nicotiana tabacum SR1) plants expressing IbMYB1a under the control of three different promoters. We compared the differences in anthocyanin accumulation patterns and phenotypic features of the leaves of these transgenic tobacco plants during growth. Expression of IbMYB1a under the control of these three different promoters led to a remarkable variation in anthocyanin pigmentation in tobacco leaves. The anthocyanin contents of the leaves of the SPO-IbMYB1a-OX (SPO-M) line were higher than those of the SWPA2-IbMYB1a-OX (SPA-M) and 35S-IbMYB1a-OX (35S-M) lines. High levels of anthocyanin pigments negatively affected plant growth in the SPO-M lines, resulting delayed growth and, occasionally, a stunted phenotype. Furthermore, HPLC analysis revealed that transcriptional regulation of IbMYB1a led to the production of cyanidin-based anthocyanins in the tobacco plants. In addition, RT-PCR analysis revealed that IbMYB1a expression induced the up-regulation of several structural genes in the anthocyanin biosynthetic pathway, including DFR and ANS. Differential expression levels of IbMYB1a under the control of different promoters were highly correlated with the expression levels of the structural genes, thereby affecting anthocyanin production levels. These results indicate that IbMYB1a positively controls the expression of multiple anthocyanin biosynthetic genes and anthocyanin accumulation in heterologous tobacco plants.


Facilitated percutaneous coronary intervention versus primary percutaneous coronary intervention: design and rationale of the Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events (FINESSE) trial.
Percutaneous coronary intervention (PCI) has emerged as the strategy of choice in reestablishing effective flow in occluded infarct-related arteries in patients with acute myocardial infarction (MI) if it can be administered in a timely fashion. Patients who enter the catheterization laboratory with Thrombolysis In Myocardial Infarction (TIMI) grade 3 blood flow in the infarct-related vessel have better clinical outcomes than patients presenting with impaired flow. We hypothesize that a strategy of early pharmacologic reperfusion therapy with abciximab alone or in conjunction with reduced-dose reteplase, followed by PCI will improve the outcome of patients eligible for primary PCI. The Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events (FINESSE) study is a 3000-patient, prospective, multicenter, randomized, double-blind, placebo-controlled trial. The study is designed to compare the efficacy and safety of early administration of reduced-dose reteplase and abciximab combination therapy or abciximab alone followed by PCI with abciximab alone administered just before PCI for acute MI. Patients will be randomized to one of these 2 facilitated PCI treatments or primary PCI in a 1:1:1 fashion. The primary efficacy end point of FINESSE is the composite of all-cause mortality or post-MI complications within 90 days of randomization. The primary safety outcome assessment will be Thrombolysis In Myocardial Infarction (TIMI) major bleeding. The FINESSE study will answer important questions regarding the efficacy and safety of "upstream" medical therapy followed by planned intervention for patients with ST-elevation MI, potentially expanding the population eligible for a primary PCI approach. This study will also provide insight as to which facilitated regimen (reteplase/abciximab combination therapy or abciximab monotherapy) provides the best balance of efficacy and safety.


Respiratory-related displacement of the trachea in obstructive sleep apnea.
Tracheal displacement is thought to be the primary mechanism by which changes in lung volume influence upper airway patency. Caudal tracheal displacement during inspiration may help preserve the integrity of the upper airway in response to increasing negative airway pressure by stretching and stiffening pharyngeal tissues. However, tracheal displacement has not been previously quantified in obstructive sleep apnea (OSA). Accordingly, we aimed to measure tracheal displacements in awake individuals with and without OSA. The upper head and neck of 34 participants [apnea-hypopnea index (AHI) = 2-74 events/h] were imaged in the midsagittal plane using dynamic magnetic resonance imaging (MRI) during supine awake quiet breathing. MRI data were analyzed to identify peak tracheal displacement and its timing relative to inspiration. Epiglottic pressure was measured separately for a subset of participants (n = 30) during similar experimental conditions. Nadir epiglottic pressure and its timing relative to inspiration were quantified. Peak tracheal displacement ranged from 1.0-9.6 mm, with a median (25th-75th percentile) of 2.3 (1.7-3.5) mm, and occurred at 89 (78-99)% of inspiratory time. Peak tracheal displacement increased with increasing OSA severity (AHI) (R2 = 0.28, P = 0.013) and increasing negative nadir epiglottic pressure (R2 = 0.47, P = 0.023). Relative inspiratory timing of peak tracheal displacement also correlated with OSA severity, with peak displacement occurring earlier in inspiration with increasing AHI (R2 = 0.36, P = 0.002). Tracheal displacements during quiet breathing are larger in individuals with more severe OSA and tend to reach peak displacement earlier in the inspiratory cycle. Increased tracheal displacement may contribute to maintenance of upper airway patency during wakefulness in OSA, particularly in those with severe disease.NEW & NOTEWORTHY Tracheal displacement is thought to play an important role in stabilizing the upper airway by stretching/stiffening the pharyngeal musculature. Using dynamic magnetic resonance imaging, this study shows that caudal tracheal displacement is more pronounced during inspiration in obstructive sleep apnea (OSA) compared with healthy individuals. Softer pharyngeal muscles and greater inspiratory forces in OSA may underpin greater tracheal excursion. These findings suggest that tracheal displacement may contribute to maintenance of pharyngeal patency during wakefulness in OSA.


Clinical practitioners' knowledge of ionizing radiation doses in diagnostic radiology examinations in Calabar.
Observation has shown a preponderance of irrelevant, unjustified and perhaps unnecessary radiological requests in the study area. The consequences of this on the patients' doses and population collective dose may be dire. To assess Clinicians/Referrers' knowledge of radiation doses of patients undergoing radiological examinations. A prospective, non-experimental, cross-sectional survey of clinicians (except radiologists) in various hospitals in Calabar metropolis, Cross River State, Nigeria, was conducted. A pretested and validated questionnaire was designed to extract responses on rating of effective doses for commonly requested imaging examinations, using the value for the posterior-anterior (PA) chest x-ray as reference. Questions on radiosensitivity of different organs, imaging modalities that use ionizing radiation and considerations for the choice of ionizing radiation (IR) based examinations were included. Participants were also asked for their preferred methods of filling any knowledge gap on IR issues. Responses were presented in simple percentages. A total of 104 respondents, made up of 63.5% males and 36.5% females participated in the study. At least 70% and 42% of the respondents, respectively, were aware that Ultrasound and Magnetic Resonance Imaging were not IR based modalities. About 67.3% of the respondents did not know the doses of commonly requested radiological examinations. This result was not dependent on clinicians' demography. A total of 61.5% of the respondents referred patients for IR examinations even when the result was unlikely to alter their diagnosis or treatment; but to reassure the patient (98.8% ), meet expectations of patients (35%) or to give the patient the feeling of being taken seriously (75%). Participating Clinicians in this study have showed poor knowledge of radiation doses of commonly requested radiological examinations. Most participants suggested improvement of their knowledge of radiation doses through continuous medical education and by the provision of referral guidelines.


Remplissage reduced sense of apprehension and increased the rate of return to sports at preinjury level of elite overhead athletes with on-track anterior shoulder instability.
The purpose of this study was to compare the results of arthroscopic isolated Bankart repair (B) with Bankart repair plus Remplissage (B + R) procedure in contact overhead athletes with on-track anterior shoulder instability. A total of 64 athletes playing basketball, volleyball and handball in elite professional level who underwent arthroscopic isolated Bankart repair (34 patients) or Bankart repair plus Remplissage procedure (30 patients) with the diagnosis of recurrent anterior shoulder instability between 2017 and 2020, were retrospectively reviewed. Radiologically all patients had on-track Hill-Sachs defects and minimal or subcritical glenoid bone loss (< 13.5%). Patients were evaluated using pre- and postoperative pVAS, SANE, ASES, ROWE, WOSI scores and postoperative active ROM assessment. Patients were also asked for the frequency of any subjective apprehension and satisfaction with the surgery in four grades. The mean ages of the groups B and B + R were 26.8 and 26 years (SD = 3.22), respectively; the mean follow-up times were 37.8 and 36.2 months (SD = 11.19). Compared with the preoperative status, there was a statistically significant improvement of all 5 postoperative outcome scores in both groups (P < 0.001). However, significant difference between the improvement of the groups were only found for the SANE (B: 22.3 ± 4.1, B + R: 26.3 ± 4.3; P = 0.0004), ASES (B: 26.1 ± 2.6, B + R: 30.2 ± 3.6; P < 0.001) and ROWE (B: 42 ± 3.7, B + R: 47.7 ± 2.8; P < 0.001) scores in favor of the group B + R. The loss of internal and external rotation of the adducted arm in group B + R was found to be approximately 5 degrees compared to the group B (P < 0.001). More than 80% of group B + R showed no apprehension in sports activities and almost completely returned to pre-injury athletic level, depicting statistically significant improvement compared to group B athletes (P = 0.002 and 0.036, respectively). 3 patients developed re-dislocation after isolated Bankart repair, whereas no re-dislocation occurred in the B + R group. Adding Remplissage procedure to the Bankart repair provided an advantage in terms of both return to sport at preinjury level and the frequency of apprehension sensation during sports activity. III.


Evaluation of a new rapid D-dimer assay for clinically suspected deep venous thrombosis (Liatest D-dimer).
In previous studies, enzyme-linked immunosorbent assays (ELISA) for plasma D-dimer analysis have demonstrated high sensitivity, suggesting their potential usefulness in excluding deep venous thrombosis (DVT). We evaluated the usefulness of a new D-dimer test (Liatest D-dimer) for suspected DVT in a prospective study of patients admitted to the hospital because of recent (not exceeding 1 week before admission) clinical signs. Contrast venography or compression ultrasonography or both were performed within 24 hours of admission. A new quantitative determination of D-dimer concentration using a suspension of microlatex particles coated with specific antibodies was tested. A standard plasma D-dimer ELISA measurement was also performed. Of 464 patients, 276 had a proven DVT (distal, 74; proximal, 202). For a cutoff level of 400 ng/mL, sensitivity of the Liatest method in the diagnosis of overall DVT was 94.6% (95% confidence interval, 92.0%-97.0%), and the specificity was 35% (95% confidence interval, 28%-42%). The sensitivity and negative predictive value were 98.5% and 95.6%, respectively, in the diagnosis of proximal DVT, but only 83.8% and 84.6%, respectively, in the diagnosis of distal DVT. This new rapid Liatest D-dimer assay seems to be highly sensitive and could replace the ELISA method in excluding patients with proximal DVT. Both methods provide lower sensitivity for distal DVT.


Clinical definitions of pertussis: Summary of a Global Pertussis Initiative roundtable meeting, February 2011.
Existing clinical case definitions of pertussis are decades old and based largely on clinical presentation in infants and children, yet an increasing burden is borne by adolescents and adults who may manifest distinct signs/symptoms. Therefore, a "one-size-fits-all" clinical case definition is no longer appropriate. Seeking to improve pertussis diagnosis, the Global Pertussis Initiative (GPI) developed an algorithm that delineates the signs/symptoms of pertussis most common to 3 age groups: 0-3 months, 4 months to 9 years, and ≥10 years. These case definitions are based on clinical presentation alone, but do include recommendations on laboratory diagnostics. Until pertussis can be accurately diagnosed, its burden will remain underestimated, making the introduction of epidemiologically appropriate preventive strategies difficult. The proposed definitions are intended to be widely applicable and to encourage the expanded use of laboratory diagnostics. Determination of their utility and their sensitivity and/or specificity versus existing case definitions is required.


Enhancing Hybrid Upconversion Nanosystems via Synergistic Effects of Moiety Engineered NIR Dyes.
Hybrid upconversion nanosystems have been reported to improve the low absorption efficiency of lanthanide-doped upconversion nanoparticles (UCNPs). However, the low quantum yield and poor photostability of NIR dyes pose challenges for practical uses. Here, we introduce a bulky moiety, 4-(1,2,2-triphenylvinyl)-1,1'-biphenyl (TPEO), to enhance its quantum yield by suppressing the bond rotation and improve the stability by deactivating the photoinduced oxidization. Compared with the conventional IR806, the formed NIR dye, TPEO-Cy, has been characterized to deliver three times higher quantum yield and seven times better photostability. Moreover, we take advantage of the strong affinity of sulfonate chains on the TPEO-Cy to bind to the surface of UCNPs. Taking together the synergistic effect, we have achieved a 242-fold upconversion emission enhancement over the benchmark of IR806-sensitized system and an ∼800 000-fold increase than the bare UCNPs. Our design of the NIR dyes suggests a new scope to search for more efficient upconversion nanohybrids.


Implementer and recipient perspectives of community-wide mass drug administration for soil-transmitted helminths in Kwale County, Kenya.
Soil-transmitted helminthiases (STH) are one of 17 neglected tropical diseases (NTDs) earmarked for control or elimination by 2020 in the WHO's Roadmap on NTDs. Deworming programs for STH have thus far been focused on treating pre-school and school-aged children; however, there is a growing consensus that to achieve elimination of STH transmission, programs must also target adults, potentially through community-wide mass drug administration (MDA). There is currently a gap in the literature on what components are required to deliver community-wide MDA for STH in order to achieve high intervention reach and uptake. Nested within the TUMIKIA Project, a cluster randomized trial in Kenya evaluating the effectiveness of school-based deworming versus community-wide MDA, we collected qualitative data from program implementers and recipients in eight clusters where community-wide MDA was delivered. Data collection included semi-structured in-depth interviews (n = 72) and focus group discussions (n = 32). A conceptual framework for drug distribution was constructed to help build an analysis codebook. Case memos were developed for each top-level theme. Community-wide MDA for STH was perceived as a complex intervention with key administrative and social mobilization domains. Key actionable themes included: (1) developing an efficient strategy to allocate reasonable workload for implementers to cover all targeted households; (2) maximizing community drug distributors' motivation through promoting belief in the effectiveness of the intervention and providing sufficient financial incentives; (3) developing effective capacity building strategies for implementers; and (4) implementing a context-adapted community engagement strategy that leverages existing community structures and takes into consideration past community experiences of MDAs. Transitioning from STH control to elimination goals requires significant planning and action to ensure community-wide MDA is delivered with sufficient reach and uptake. We present findings that can inform national deworming programs to increase intervention delivery capacity.


Cerebral infarction in the Mongolian gerbil exacerbated by phenoxybenzamine treatment.
In a double-blind study, the effects of a large dose (20 mg per kilogram) of phenoxybenzamine (PBZ) on cerebral infarction were evaluated in 120 Mongolian gerbils. The left common carotid artery was ligated in 100 animals; a sham operation was done in 20 animals. One hour later, 25 animals were given 2 mg per kilogram of PBZ, 25 animals were given 20 mg per kilogram of phenoxybenzamine, and 50 animals were given 0.5 cc of nomal saline, all doses being repeated at 24, 48, and 72 hours. Five sham-operated animals were given 2 mg per kilogram of phenoxybenzamine, five were given 20 mg per kilogram of phenoxybenzamine and ten were given 0.5 cc of normal saline on the same treatment schedule. Morbidity and mortality were recorded for one week and then all surviving animals wer killed. All brains were studied for signs of infarction. Of the saline-treated animals, 32% had cerebral infarction and 81% of these died. Of the animals treated with phenoxybenzamine, 36% of those receiving 2 mg per kilogram and 68% (p less than 0.05) of those receiving 20 mg per kilogram had cerebral infarction and all of those with infarction died during the observation period. The animals receiving phenoxybenzamine had a larger stroke index than those treated with saline. The authors concluded that phenoxybenzamine is harmful in postischemic treatment of strokes.


Comparison of dimensional accuracy of four different die materials before and after disinfection of the impression: an in vitro study.
This study was conducted to compare the linear dimensional accuracy of die materials before and after disinfection of the impression. Type IV and V conventional dental stone, type IV-resin impregnated and copper-plated die materials were studied. A stainless-steel master die analogs to a complete veneer crown preparation with three scribed lines (I: vertical, II and III: horizontal) was machined and measurements were made from these scribed reference lines. Impressions were made with monophase addition silicone impression material for each of the specimens. 2% glutaraldehyde was used as a disinfectant. The fabricated dies were measured to the nearest 0.0001 mm. ANOVA and post hoc was carried out using Scheffe multiple comparison test at significance level of 0.05. Type IV resin-impregnated dental stone and copperplated dies approximated the dimensions of the master die. Type IV and V conventional dental stone dies showed greater variation in measurements. Statistically significant differences were observed for type IV resin-impregnated and copper-plated dies in dimension I and III. For dimension II no significant differences were found for dies fabricated from four die materials. A one-way analysis of variance indicated no statistical significant differences among the two groups of dies fabricated from disinfectant treated impressions and those fabricated from nondisinfectant treated impressions. Type IV resin-impregnated dental stone and copper-plated dies are dimensionally more accurate than type IV and V conventional dental stone die materials. No significant linear distortion in the dies fabricated from the disinfected impressions was observed.


Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway.
Although activating mutations in RAS oncogenes are known to result in aberrant signaling through multiple pathways, the role of microRNAs (miRNAs) in the Ras oncogenic program remains poorly characterized. Here we demonstrate that Ras activation leads to repression of the miR-143/145 cluster in cells of human, murine, and zebrafish origin. Loss of miR-143/145 expression is observed frequently in KRAS mutant pancreatic cancers, and restoration of these miRNAs abrogates tumorigenesis. miR-143/145 down-regulation requires the Ras-responsive element-binding protein (RREB1), which represses the miR-143/145 promoter. Additionally, KRAS and RREB1 are targets of miR-143/miR-145, revealing a feed-forward mechanism that potentiates Ras signaling.


[Heart failure: the importance of a disease management program].
Heart failure remains a growing public health problem, hospitalizations represent the main cost component of heart failure care and the poor quality of life of patients is often worsened by frequent admissions. A multidisciplinary approach and specific disease management programs are a potentially useful instrument to reducing hospitalizations in heart failure patients. These concepts have recently been discussed in a consensus document by all the Scientific Societies involved in the care of heart failure patients. The effectiveness of intervention programs delivering continuity of care by a multidisciplinary team achieved a promising reduction in admissions, but the results of the studies have not been univocal for category of strategies and about the effect on survival. Telephone intervention significantly decreased heart failure admissions but not all-cause admissions and mortality. The multicenter randomized DIAL study, comparing a centralized telephone intervention program delivering continuity of care by a multidisciplinary team with usual care in patients with heart failure, confirms these findings. After a mean 16-month follow-up, there was a benefit mostly due to a significant reduction in admissions for heart failure, but mortality was similar in both groups. Data on 9000 patients from the IN-CHF registry show that hospitalizations are a serious problem in Italy: 44% of the patients had at least one hospitalization for heart failure in the year prior to the entry visit and this is the most powerful independent predictor of rehospitalization during the follow-up. Nearly a quarter of the population with follow-up data availability (92%) has been rehospitalized in the year after enrollment; patients in advanced functional class (32.1% hospitalization rate) and with ischemic etiology (25.0%) are more likely to be hospitalized than those in NYHA class I-II and without ischemic etiology. In a survey carried out recently in Italy, in 1152 patients admitted for decompensated heart failure, readmission rate was even higher: more than 40% of patients have been readmitted once in the 6 months after discharge and 7.2% had two or more admissions.


Excited-state dynamics and dye-dye interactions in dye-coated gold nanoparticles with varying alkyl spacer lengths.
Gold nanoparticles (ca. 3 nm in diameter) coated with bis(diarylamino)biphenyl-based thiols with two different alkyl spacers (propyl and dodecyl) between the chromophore and the surface-anchoring thiol group have been prepared and characterized with a variety of techniques. The excited-state dynamics of the dyes in close proximity to the nanoparticle surface were studied using the time-correlated single-photon counting technique and near-IR fs transient absorption spectroscopy. The excited states of the dyes in the hybrid metal/organic systems exhibit an ultrafast (<5 ps) deactivation as evidenced by the fs transient absorption measurements. The length of the alkyl spacer between the dye and the thiol group has a profound effect on the ultrafast dynamics of the photoexcited systems. An ultrafast formation (ca. 0.5 ps) of a cation-like species has been recorded for the system incorporating the propyl spacer but not for the dodecyl-linker system. The formation of the cation-like species has been shown to be less efficient in a mixed-ligand system in which the bis(diarylamino)biphenyl-based thiol was diluted on the surface with dodecanethiol. Additionally, the ultrafast formation (ca. 1 ps) of a cation-like species with a similar spectroscopic signature has been observed in the solid state of the dye. A combination of the ultrafast dynamics and (1)H NMR spectroscopic data has been used to discuss the observed behavior in terms of dye-dye interactions in the nanoparticle systems. Due to the surface curvature of the nanoparticle, the propyl spacer imposes a closer dye-dye distance than the dodecyl spacer, thus facilitating dye-dye interactions that lead to the formation of a charge-transfer species involving two or more dye molecules.


Inpatient resource use and costs associated with switching from oral antipsychotics to aripiprazole once-monthly for the treatment of schizophrenia.
Schizophrenia is associated with high direct healthcare costs due to progression of disease and frequent occurrence of relapses. Aripiprazole once-monthly (AOM) has been shown to reduce total psychiatric hospitalizations among patients who switched from oral standard of care (SOC) therapy to AOM in a multicenter, open-label, mirror-image study of patients with schizophrenia. Because of the increasing need to improve patient outcomes while containing costs, it is important to understand the impact of AOM treatment initiation on medical costs associated with psychiatric hospitalizations and antipsychotic pharmacy costs. In the current study, an economic model was developed using data from the AOM mirror-image study to evaluate the psychiatric hospitalization-related medical costs and antipsychotic pharmacy costs during a 6-month period before (retrospective period) and after (prospective period) the AOM treatment initiation. The economic model evaluated cost-saving potential of AOM among all patients (n=433) as well as a subset of patients with ≥1 prior hospitalization (n=165) who switched from oral SOC to AOM. Unit cost data were obtained from publicly available sources. Both hospitalizations and hospital days were reduced following a switch from oral SOC to AOM. As a result, psychiatric hospitalization-related costs were lower during the prospective period when compared with the retrospective period. Furthermore, the increase in antipsychotic pharmacy costs due to switching from oral SOC to AOM was offset by a reduction in psychiatric hospitalization-related medical costs. Per-patient costs were reduced by $1,046 (USD) in the overall population and by $20,353 in a subset of patients who had at least 1 psychiatric hospitalization during the retrospective period. Results were most sensitive to changes in hospitalization costs. AOM is associated with reducing the risk of relapse among patients with schizophrenia. The increase in antipsychotic pharmacy costs due to switching from oral SOC to AOM was offset by a reduction in costs associated with psychiatric hospitalizations, thereby presenting a cost-saving opportunity for health plans.


Liver resection for primary intrahepatic stones: a single-center experience.
Primary intrahepatic lithiasis occurs frequently in East Asia but is rare in Western countries. Biliary pain and episodes of cholangitis are the most common presenting symptoms, whereas intrahepatic cholangiocarcinoma represents a long-term unfavorable complication of the disease. When a single liver lobe or segment is involved, partial hepatectomy may be regarded today as an effective method of treatment. Retrospective study. Hepatobiliary unit in a tertiary care hospital. The clinical records of 35 patients treated for primary intrahepatic lithiasis between January 1, 1992, and December 31, 2005, were reviewed and clinical data, cholangiograms, operative procedures, and early and late results were examined. Thirty-four patients underwent liver resection; left hepatectomy (18 patients) and left lateral segmentectomy (10 patients) were the most frequently performed procedures. A cholangiocarcinoma was found in 3 patients (8.6%): 2 underwent liver resection and 1, who was found unresectable at surgery, underwent only explorative laparotomy. Survival, quality of life, laboratory data, and need for further treatments. There was no postoperative mortality. Morbidity was 20.0% with a prevalence of infectious complications related to bile leakage. Long-term results, assessed in 26 patients with follow-up longer than 12 months (range, 12-170 months; mean, 63 months), were good or fair in 24 patients (92.3%), including 3 patients who needed subsequent endoscopic removal of biliary stones. Primary intrahepatic lithiasis more commonly involves 1 single liver segment or lobe. Partial hepatectomy is a safe and effective procedure, allowing definitive treatment of the disease and prevention of cancer.


An evaluation of commissioning arrangements for intrauterine and subdermal contraception services from general practitioners in London, UK.
General practitioners (GPs) in the UK may be commissioned to provide long-acting reversible contraception (LARC), which may have a role in reducing rates of abortion and unintended pregnancies. Primary care trusts (PCTs) in England had commissioning arrangements with GPs to provide LARC but little is known about such contractual arrangements. We studied the commissioning arrangements in some London PCTs to evaluate the cost and clinical governance of these contracts. We requested commissioning contract specifications and activities for intrauterine contraception (IUC) and subdermal implants (SDI) from responsible officers in each PCT in London relating to activities in three financial years, namely 2009/2010 to 2011/2012. We evaluated each contract using a structure, process and outcome approach. Half (15/31) the PCTs responded and submitted 20 contracts used to commission their GPs to provide IUC, SDI or a combination of these with testing for sexually transmitted infections. The information regarding service activity was inadequate and inconsistent so had to be abandoned. Information from 20 contracts suggested there was a variation in clinical governance and quality assurance mechanisms; there was also a range in the reimbursement for IUC insertion (£77.50 to £105.00), SDI insertion (£25.00 to £81.31) and SDI removal (£30.00 to £100.00) at 2011 prices. It was not clear from non-responders if these PCTs had a service in place. Of those that did commission IUC and SDI services, some specifications were lacking in detail regarding aspects of clinical governance. New commissioners should make explicit references to quality and safety criteria as poor-quality specifications can give rise to serious untoward incidents and litigation.


The Bambuí health and ageing study (BHAS): methodological approach and preliminary results of a population-based cohort study of the elderly in Brazil.
A cohort study has been designed to identify predictors of adverse health events in the elderly. The methodology of the study and preliminary descriptive results are presented. The study population comprises all residents of Bambuí (Minas Gerais, Brazil), aged 60 or more years (n=1.742). From these, 92.2% were interviewed and 85.9% underwent clinical examination, consisting of haematological and biochemical tests, serology for Trypanosoma cruzi, anthropometric and blood pressure measures and electrocardiogram. Aliquots of serum, plasma and DNA were stored for future investigations. The baseline interview included sociodemographic characteristics, self-referred health condition and history of selected diseases, medication use, health service use, source of medical care, physical activities, smoking, drinking and eating habits, reproductive history, physical functioning, life events, social support and mental health. Individuals are being followed up annually. The following characteristics predominated among participants: women (60,0%), married (48.9%) or widowed (35.4%), people living in households with up to 2 residents (73.8%), heads of family (76.7%), people with monthly income between 1.00 and 2.99 Brazilian minimum wages (62.0%) and people with up to 4 years of schooling (89.1%). The median age was 68 years. Among the cohort members, only 1.7% were lost in the first follow-up. In general, the characteristics of the study population were very similar to those from other epidemiological studies of the elderly based on large Brazilian cities. The small number of losses to follow-up indicates that the choice of Bambuí was adequate, assuring the feasibility of a long term cohort study.


A physicochemical model of crystalloid infusion on acid-base status.
The objective of this study is to develop a physicochemical model of the projected change in standard base excess (SBE) consequent to the infused volume of crystalloid solutions in common use. A clinical simulation of modeled acid-base and fluid compartment parameters was conducted in a 70-kg test participant at standard physiologic state: pH =7.40, partial pressure of carbon dioxide (PCO2) = 40 mm Hg, Henderson-Hasselbalch actual bicarbonate ([HCO3]HH) = 24.5 mEq/L, strong ion difference (SID) = 38.9 mEq/L, albumin = 4.40 g/dL, inorganic phosphate = 1.16 mmol/L, citrate total = 0.135 mmol/L, and SBE =0.1 mEq/L. Simulations of multiple, sequential crystalloid infusions up to 10 L were conducted of normal saline (SID = 0), lactated Ringer's (SID = 28), plasmalyte 148 (SID = 50), one-half normal saline þ 75 mEq/L sodium bicarbonate (NaHCO3; SID = 75), 0.15 mol/L NaHCO3 (SID = 150), and a hypothetical crystalloid solution whose SID = 24.5 mEq/L, respectively. Simulations were based on theoretical completion of steady-state equilibrium and PCO2 was fixed at 40 mm Hg to assess nonrespiratory acid-base effects. A crystalloid SID equivalent to standard state actual bicarbonate (24.5 mEq/L) results in a neutral metabolic acid-base status for infusions up to 10 L. The 5 study solutions exhibited curvilinear relationships between SBE and crystalloid infusion volume in liters. Solutions whose SID was greater than 24.5 mEq/L demonstrated a progressive metabolic alkalosis and less, a progressive metabolic acidosis. In a human model system, the effects of crystalloid infusion on SBE are a function of the crystalloid and plasma SID, volume infused, and nonvolatile plasma weak acid changes. A projection of the impact of a unit volume of various isotonic crystalloid solutions on SBE is presented. The model's validation, applications, and limitations are examined.


Fine needle aspiration diagnosis of isolated pancreatic tuberculosis. A case report and review of literature.
Tuberculosis is a common disease in the developing world and its incidence is slowly increasing in developed countries where a resurgence has been seen subsequent to the AIDS epidemic. Tuberculosis, in its extrapulmonary form, though emerging as a clinical problem, rarely affects the pancreas. The pancreas is biologically protected from being infected by Mycobacterium tuberculosis. Pancreatic tuberculosis presents with a wide spectrum of symptoms such as abdominal pain, constitutional symptoms, obstructive jaundice, iron deficiency anemia, pancreatic abscess, massive gastro-intestinal bleeding, acute/chronic pancreatitis, secondary diabetes, splenic vein thrombosis and a pancreatic mass mimicking malignancy. It should be suspected clinically in patients having a pancreatic mass, particularly if the patient is young, not jaundiced, coming from an area of high tuberculosis endemicity and having a normal endoscopic retrograde cholangio-pancreatography. Its indolent course and vague symptomatology along with non-specific laboratory and radiological findings call for greater vigilance. We report a case of pancreatic tuberculosis which presented with pancreatic pain. Imaging techniques revealed a mass located in the head of the pancreatic gland. Fine needle aspiration cytology revealed caseating granulomas. The diagnosis of pancreatic tuberculosis was made and the patient was put on anti-tubercular therapy. Five months later, a repeat CT scan of the abdomen revealed resolution of the pancreatic lesion. The diagnosis of pancreatic tuberculosis is usually not suspected prior to laparotomy. Most patients have been diagnosed at laparotomy, thus fine needle aspiration cytology/biopsy is useful in obviating the need for major surgery with its accompanying morbidity. Exploratory laparotomy may be required in technically difficult cases due to risk of injury to the vessels in the vicinity of the mass.


Medically assisted suicide in Italy: Recent legal developments on a controversial topic.
On 16th June 2022, the first case of lawful 'medically assisted suicide' took place on Italian soil. This event is a result of decade-long debates on informed consent and end-of-life care stimulated by medical jurisprudence. The authors first retrace the crucial moments that allowed this to happen and underline the problems still to be solved. The cases of DJ Fabo, Davide Trentin, Mario and Fabio Ridolfi are discussed, signalling how they influenced the path implemented by Italian jurisprudence.


Inflammatory myofibroblastic tumor of the larynx: report of a case and review of the literature.
Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm, most commonly seen in children and adolescents. It can occur in nearly every part of the body. Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm mostly seen in the lungs, but also in extrapulmonary sites. But it may rarely be seen in the vical cord. We report a case of a 73-year-old men presented with hoarseness and cough. Laryngoscopy reveals a large non-ulcerated, red subepithelial mass arising from the right vical cord. Magnetic resonance imaging (MRI) scan revealed a mass in the right vical cord, and magnetic resonance imaging (MRI) enhanced scan showed the mass of the right vical cord inhomogeneous enhancement. The patient underwent right cordectomy with KTP laser, and further assessment of the tissue demonstrated a pathologic diagnosis of IMT.


A Comparative Study of Shock Absorption Capacities of Custom Fabricated Mouthguards using a Triangulation Sensor.
This in-vitro study compares the shock absorption qualities of five mouthguard designs measured with a triangulation laser sensor during small hard object collisions. The aim was to investigate the impact of different labial designs on mouthguard performance. Five different custom-fabricated ethylene vinyl acetate (EVA) types of mouthguards with varying thickness and different labial inserts (polyethylene terephthalate glycol-modified (PETG), nylon mesh, air space) were tested with a triangulation laser sensor during different energy blows, generated with a pendulum testing device. The pendulum hits were applied to the center of a pivoted tooth crown in a custom-built upper jaw model. Measurements were executed with the mouthguards on the model and with no mouthguard as a negative control. Tooth deflection was reduced with all mouthguards in comparison to no mouthguard. Increasing mouthguard thickness improved the mouthguards' shock absorption capacities. Also, adding labial inserts increased their preventive qualities in ascending order: Mouthguard with a soft insert (nylon mesh), a hard insert (PETG), air space plus a hard insert (PETG). Increasing EVA foil thickness of a mouthguard, increasing labial thickness, and adding labial inserts (soft, stiff and air space) improve mouthguard shock absorption capabilities during small hard object collisions, thereby improving dental trauma prevention.


Voltage-dependent modulation of Ca channel current in heart cells by Bay K8644.
We have investigated the voltage-dependent effects of the dihydropyridine Bay K8644 on Ca channel currents in calf Purkinje fibers and enzymatically dispersed rat ventricular myocytes. Bay K8644 increases the apparent rate of inactivation of these currents, measured during depolarizing voltage pulses, and shifts both channel activation and inactivation in the hyperpolarizing direction. Consequently, currents measured after hyperpolarizing conditioning pulses are larger in the presence of drug compared with control conditions, but are smaller than control if they are measured after positive conditioning pulses. Most of our experimental observations on macroscopic currents can be explained by a single drug-induced change in one rate constant of a simple kinetic model. The rate constant change is consistent with results obtained by others with single channel recordings.


miR-34c plays a role of tumor suppressor in HEC‑1-B cells by targeting E2F3 protein.
Endometrial carcinoma (EC) is a common malignancy of the female genital tract with a poor prognosis. It has been reported that miR-34c is significantly reduced in EC, but research concerning its function in EC is rare. In the present study, the expression of miR-34c was upregulated in the EC cell line, HEC-1-B, by transfecting the cells with hsa-miR-34c-5p mimics. Then, after determining the transfection efficiency by RT-qPCR, we analyzed the effects of miR-34c on the HEC-1-B cells. We found that overexpression of miR-34c significantly inhibited cell proliferation, colony formation, migration and invasion and induced cell cycle arrest and apoptosis. Finally, western blot analysis demonstrated that the expression of E2F3 was reduced after upregulation of the expression of miR-34c in the HEC-1-B cells, and the effects of miR-34c are likely associated with the reduction in E2F3 protein. In conclusion, our study demonstrated that miR-34c plays a role of tumor suppressor in HEC-1-B cells, and E2F3 protein may be a target of miR-34c.


Spinal cord motion: influence of respiration and cardiac cycle.
To assess physiological spinal cord motion during the cardiac cycle compared with the influence of respiration based on magnetic resonance imaging (MRI) measurements. Anterior-posterior spinal cord motion within the spinal canal was assessed in 16 healthy volunteers (median age, 25 years) by cardiac-triggered and cardiac-gated gradient echo pulse sequence MRI. Image acquisition was performed during breath-holding, normal breathing, and forced breathing. Normal spinal cord motion values were computed using descriptive statistics. Breathing-dependent differences were assessed using the Wilcoxon signed-rank test and compared with the cardiac-based cord motion. A normal value table was set up for the spinal cord motion of each vertebral cervico-thoracic-lumbar segment. Significant differences in cord motion were found between cardiac-based motion while breath-holding and the two breathing modalities (P < 0.01 each). Spinal cord motion was found to be highest during forced breathing, with a maximum in the lower cervical spinal segments (C5; mean, 2.1 mm ± 1.17). Image acquisition during breath-holding revealed the lowest motion. MRI permits the demonstration and evaluation of cardiac and respiration-dependent spinal cord motion within the spinal canal from the cervical to lumbar segments. Breathing conditions have a considerably greater impact than cardiac activity on spinal cord motion. • Cardiac-triggered and ECG-gated MRI allows for demonstration of the smallest spinal cord motions.• Respiratory influences seem to have the highest impact on spine motion.• In contrast, the influence of the cardiac cycle seems to be small.• The smallest spinal cord motions were measured during breath-hold.


Regulation of Tendon Stem Cell Behavior by Designed Nanoporous Topography of Microfibers.
Nano scale topography scaffold is more bioactive and biomimetic than smooth fiber topographies. Tendon stem cells (TSCs) play important roles in the tendinogenesis of tendon tissue engineering, but the effects and mechanisms of nano topography on TSC behavior are still unclear. This study determined whether the morphology, proliferation, cytoskeleton, and differentiation of TSCs are affected by topography of scaffold in vitro. The porous PA56 scaffolds were prepared with different concentration ratios of glycerol as the molecular template by electrospinning. Its topological characteristics, hydrophilicity, and degradation properties varied with glycerol proportion and movement rate of the receiving plate. Porous fibers promoted the proliferation of TSCs and the number of TSCs varied with topography. Although there was no significant difference due to the small sample size, the number of pseudopodia and cell polarizability still showed differences among different topographies. The morphology of actin cytoskeleton of TSCs showed difference among cultured on porous fibers, smooth fibers, and in culture media with no fiber, suggesting the orientation growth of cells on porous fiber. Moreover, porous fibers promoted teno-lineage differentiation of TSCs by upregulating tendon-specific gene expression. These findings provide evidence that nano porous topography scaffold promotes TSC proliferation, cytoskeleton orientation, and tenogenic differentiation.


Acute heart failure due to COVID-19 related myocardial injury and de novo hypertensive cardiomyopathy: a challenging diagnosis.
We report a COVID-19 case with acute heart and kidney failure in a healthy young male. Echocardiography showed severe systolic and diastolic left ventricle dysfunction, with diffuse myocardial thickening. Cardiac MRI showed aspects of focal myocarditis, and hypertensive cardiomyopathy. Renal biopsy demonstrated limited acute tubular injury, and hypertensive kidney disease. Coronary angiography excluded critical stenoses. Unlike what we initially suspected, myocardial inflammation had a limited extent in our patient; severe hypertension causing cardiomyopathy and multi-organ damage, not diagnosed before, was primarily responsible for severe illness. Correct diagnosis and guidelines-directed treatment allowed a favorable course.


A Rare Case of Systemic Lupus Erythematosus with Gastric Ulcer and Acute Pancreatitis: A Case Report and Literature Review.
Systemic lupus erythematosus (SLE) is a chronic inflammatory disease which can manifest in many different organ systems. Gastrointestinal (GI) involvement is common in SLE, but the symptoms are usually mild. More severe GI complications including acute pancreatitis and peptic ulcer bleeding are rare but represent a significant risk of morbidity and mortality. We present a case of a 25-year-old Hispanic female with a severe SLE flare. The initial presentation included symptoms of hematemesis and epigastric abdominal pain secondary to both gastric ulceration and acute pancreatitis, an atypical presentation of an SLE flare. The non-specific symptom of abdominal pain makes both acute pancreatitis and gastric ulcer disease a clinical challenge; however, clinicians need to have a high suspicion for these conditions co-existing at the same time due to higher mortality rates.


Preventing increased intracranial pressure: nursing care can make the difference.
Recent studies show that critical care nurses are instrumental in reducing increased intracranial pressure in patients after pathologic neurologic events. The nursing literature addresses the absence of adequate nursing diagnoses to document the scope of critical care nursing practice and the impact of nursing care on the patient's ultimate outcome. In this article several basic pathophysiologic responses to increased intracranial pressure are reviewed and a comprehensive list of nursing interventions is presented to be used by nurses caring for the patient with this potentially catastrophic illness. Two new nursing diagnoses are proposed: (1) alteration in intracranial pressure: increased: potential, and (2) alteration in intracranial pressure: increased: actual. Use of the diagnoses will aid in the critical care nurse's documentation of nursing's unique contribution to the complex care of these patients.


Total Syntheses of Sparsomycin and Sparoxomycins A1 and A2 via Sulfenate-Anion-Mediated Iterative C-S Bond Formation.
The total synthesis of the pyrimidinylpropenamide antibiotics sparsomycin and sparoxomycins A1 and A2 has been achieved. The synthesis of sparsomycin relies on the iterative nucleophilic attack of sulfenate anions on alkyl halides to construct the dithioacetal monoxide chain with high diastereoselectivity. Subsequently, the reagent-controlled diastereoselective oxidation of the terminal sulfide moiety of sparsomycin directly provides sparoxomycins A1 and A2.


Brain-computer interfaces: military, neurosurgical, and ethical perspective.
Brain-computer interfaces (BCIs) are devices that acquire and transform neural signals into actions intended by the user. These devices have been a rapidly developing area of research over the past 2 decades, and the military has made significant contributions to these efforts. Presently, BCIs can provide humans with rudimentary control over computer systems and robotic devices. Continued advances in BCI technology are especially pertinent in the military setting, given the potential for therapeutic applications to restore function after combat injury, and for the evolving use of BCI devices in military operations and performance enhancement. Neurosurgeons will play a central role in the further development and implementation of BCIs, but they will also have to navigate important ethical questions in the translation of this highly promising technology. In the following commentary the authors discuss realistic expectations for BCI use in the military and underscore the intersection of the neurosurgeon's civic and clinical duty to care for those who serve their country.


Novel Therapeutics for Ovarian Cancer: The 11th Biennial Rivkin Center Ovarian Cancer Research Symposium.
The aim of this study was to summarize developments in novel therapeutics for ovarian cancer presented at the Ovarian Cancer Research Symposium held at the University of Washington. A symposium of the leaders in ovarian cancer research was convened to present and discuss current advances and future directions in ovarian cancer research. The fourth session was held on September 13, 2016, and focused on Novel Therapeutics for Ovarian Cancer. The session featured a keynote presentation on Novel Immunotherapeutics for Ovarian Cancer from Nora Disis and an invited oral presentation from Scott Kaufmann that discussed poly (ADP-ribose) polymerase (PARP) Inhibitor Combinations for the Treatment of Ovarian Cancer. Eight additional oral presentations were selected from abstract submissions. Thirty-eight abstracts were presented as posters highlighting recent advances in tumor immunology, PARP inhibition, chemoresistance, and novel targets for ovarian cancer therapy. PARP inhibitors, immunotherapies, and targeted therapies are but some of the expanding number of treatment options for ovarian cancer patients. Identification of the subsets of patients who will benefit most from these treatments remains the subject of intense preclinical and clinical research. Evidence presented at this symposium suggests that non-BRCA patients also benefit from PARP inhibitor therapies. Improved understanding of the mechanisms of chemoresistance and encouraging preclinical data presented for combinatorial approaches may soon yield new therapies for ovarian cancers that are resistant and refractory to standard treatments.


Identification of an RNA silencing suppressor encoded by a mastrevirus.
Wheat dwarf virus (WDV) is a DNA virus belonging to the genus Mastrevirus of the family Geminiviridae. In this study, we report that the Rep protein encoded by WDV is a RNA silencing supressor as determined by co-infiltration assays using transgenic Nicotiana benthamiana line 16c carrying the GFP reporter gene. The Rep protein was shown to inhibit both local and systemic RNA silencing of the GFP gene as well as the spread of systemic GFP RNA silencing signals. Gel mobility shift assays showed that the Rep protein binds 21 nt and 24 nt small interfering RNA (siRNA) duplexes and single-stranded (ss)-siRNA. To our knowledge, this is the first identification of an RNA silencing suppressor encoded by mastreviruses. Furthermore, deletion mutagenesis indicates that both the N- and C-terminal regions of the Rep protein are not critical for silencing suppression and self-interaction, but the N terminus of Rep is necessary for its pathogenicity.


Bacterial adhesion and colonization differences between zirconia and titanium implant abutments: an in vivo human study.
Several parameters have been described for determining the success or failure of dental implants. The surface properties of transgingival implant components have had a great impact on the long-term success of dental implants. The purpose of this study was to compare the tendency of two periodontal pathogens to adhere to and colonize zirconia abutments and titanium alloys both in hard surfaces and soft tissues. Twelve patients participated in this study. Three months after implant placement, the abutments were connected. Five weeks following the abutment connections, the abutments were removed, probing depth measurements were recorded, and gingival biopsies were performed. The abutments and gingival biopsies taken from the buccal gingiva were analyzed using real-time polymerase chain reaction to compare the DNA copy numbers of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and total bacteria. The surface free energy of the abutments was calculated using the sessile water drop method before replacement. Data analyses used the Mann Whitney U-test, and P-values below 0.05 find statistical significance. The present study showed no statistically significant differences between the DNA copy numbers of A. actinomycetemcomitans, P. gingivalis, and total bacteria for both the titanium and zirconia abutments and the biopsies taken from their buccal gingiva. The differences between the free surface energy of the abutments had no influence on the microbiological findings. Zirconia surfaces have comparable properties to titanium alloy surfaces and may be suitable and safe materials for the long-term success of dental implants.


Quantitative classification of adhesive bondline dimensions using Lamb waves and artificial neural networks.
Adhesive bonding of metal assemblies is gaining acceptance for use with safety critical structures, and there is a need for effective inspection for both quality assurance (QA) and the assessment of condition in service. One aspect of QA is the need for the dimensions of adhesive bondlines to be within tolerance and measurable. This paper describes the application of ultrasonic Lamb waves in the determination of the principal dimensions of two forms of adhered joints (Lap and T-form) between metal plates. Low order Lamb wave modes (s0 and a1) are propagated across adhered bond-lines, and the received signals are transformed to the modulus frequency domain (FD). The FD data are used as input to artificial neural networks (ANNs), which are trained to associate features in the input data with principal bondline dimensions. The performance of different network structures and simplified forms of these is examined, and the technique gives reliable estimates of the required dimensions in bondlines not included in network training. The interconnected weights of simplified networks provide evidence of the features in Lamb wave signals that underlie the successful operation of the method.


Obstetricians on the Coronavirus Disease 2019 (COVID-19) Front Lines and the Confusing World of Personal Protective Equipment.
As health care systems struggle to maintain adequate supplies of personal protective equipment, there is confusion and anxiety among obstetricians and others about how to best protect themselves, their coworkers, and their patients. Although use of personal protective equipment is a critical strategy to protect health care personnel from coronavirus disease 2019 (COVID-19), other strategies also need to be implemented on labor and delivery units to reduce the risk of health care-associated transmission, including screening of all pregnant women who present for care (case identification), placing a mask on and rapidly isolating ill pregnant women, and minimizing the number of personnel who enter the room of an ill patient (physical distancing). Although the mechanism of transmission of COVID-19 is not known with certainty, current evidence suggests that COVID-19 is transmitted primarily through respiratory droplets. Therefore, strict adherence to hand hygiene and consistent use of recommended personal protective equipment are cornerstones for reducing transmission. In addition, it is critical that health care professionals receive training on and practice correct donning (putting on) and doffing (removing) of personal protective equipment and avoid touching their faces as well as their facial protection to minimize self-contamination.


The use of work teams: a help or hindrance to performance?
The use of work teams is a popular topic in business literature. Although there is a growing literature on this topic, the team concept is not new to organizations. The article examines historical developments in the use of teams for performance of work. The use of work teams is discussed in the context of the movement away from hierarchical, bureaucratic management structures and toward participative decision making. The benefits of and problems with self-directed teams, in particular, are explored.


Diagnostic Yield of 8-Hour Video-EEG in Detecting Psychogenic Non-Epileptic Seizures (PNES).
To evaluate the diagnostic yield of the first 8 hours of video-EEG (vEEG) monitoring in detecting Psychogenic Non-Epileptic Seizures (PNES) during the Epilepsy Monitoring Unit (EMU) admission. We performed a retrospective chart review of patients ages ≥4 years who were admitted to the EMU between 2011 and 2018 (n = 616). We calculated the proportion of patients diagnosed with PNES within the first 8 hours of EEG recording and studied the associated risk factors for patients diagnosed with PNES and patients with epileptic seizures (ES). Out of the total 616 patients, 24% (149) patients had an EMU diagnosis of PNES. Of these, 44.3% had at least one typical event within the first 8 hours of vEEG monitoring. A higher incidence was seen within the pediatric subgroup (54.8% had an event within 8 hours). A diagnosis of chronic pain disorder was more common with PNES compared to ES (48.3% versus 16.5%, p < 0.001). A suspicion for PNES documented during an office visit was noted in a high proportion of patients (68.5%) who eventually had a PNES event during EMU. Our study suggests that in a well-selected group of patients (such as a high suspicion of PNES during a physician/neurology office visit), an outpatient 8-hour vEEG could open new avenues for a prompt diagnosis. This could especially be beneficial in hospital settings where there is either a lack of an EMU or a delay in admission to the EMU.


Occupant kinematics and shoulder belt retention in far-side lateral and oblique collisions: a parametric study.
In far-side impacts, head contact with interior components is a key injury mechanism. Restraint characteristics have a pronounced influence on head motion and injury risk. This study performed a parametric examination of restraint, positioning, and collision factors affecting shoulder belt retention and occupant kinematics in far-side lateral and oblique sled tests with post mortem human subjects (PMHS). Seven PMHS were subjected to repeated tests varying the D-ring position, arm position, pelvis restraint, pre-tensioning, and impact severity. Each PMHS was subjected to four low-severity tests (6.6 g sled acceleration pulse) in which the restraint or position parameters were varied and then a single higher-severity test (14 g) with a chosen restraint configuration (total of 36 tests). Three PMHS were tested in a purely lateral (90° from frontal) impact direction; 4 were tested in an oblique impact (60° from frontal). All subjects were restrained by a 3-point seatbelt. Occupant motion was tracked with a 3D optoelectric high speed motion capture system. For all restraint configurations, the 60° oblique impact angle was associated with greater lateral head excursion than the 90° impact angle. This unexpected result reflects the increased axial rotation of the torso in the oblique impacts, which allowed the shoulder to displace more relative to the shoulder belt and thus the head to displace more relative to the sled buck. Restraint engagement of the torso and shoulder was actually greater in the purely lateral impacts than in the oblique impacts. Pretensioning significantly reduced lateral head excursion (175 mm average in the low-severity tests across all restraint configurations).


Triple targeting of RSK, AKT, and S6K as pivotal downstream effectors of PDPK1 by TAS0612 in B-cell lymphomas.
B-cell lymphomas (BCLs) are the most common disease entity among hematological malignancies and have various genetically and molecularly distinct subtypes. In this study, we revealed that the blockade of phosphoinositide-dependent kinase-1 (PDPK1), the master kinase of AGC kinases, induces a growth inhibition via cell cycle arrest and the induction of apoptosis in all eight BCL-derived cell lines examined, including those from activated B-cell-like diffuse large B-cell lymphoma (DLBCL), double expressor DLBCL, Burkitt lymphoma, and follicular lymphoma. We also demonstrated that, in these cell lines, RSK2, AKT, and S6K, but not PLK1, SGK, or PKC, are the major downstream therapeutic target molecules of PDPK1 and that RSK2 plays a central role and AKT and S6K play subsidiary functional roles as the downstream effectors of PDPK1 in cell survival and proliferation. Following these results, we confirmed the antilymphoma efficacy of TAS0612, a triple inhibitor for total RSK, including RSK2, AKT, and S6K, not only in these cell lines, regardless of disease subtypes, but also in all 25 patient-derived B lymphoma cells of various disease subtypes. At the molecular level, TAS0612 caused significant downregulation of MYC and mTOR target genes while inducing the tumor suppressor TP53INP1 protein in these cell lines. These results prove that the simultaneous blockade of RSK2, AKT, and S6K, which are the pivotal downstream substrates of PDPK1, is a novel therapeutic target for the various disease subtypes of BCLs and line up TAS0612 as an attractive candidate agent for BCLs for future clinical development.


Linkage and association studies of the lipoprotein lipase gene with postheparin plasma lipase activities, body fat, and plasma lipid and lipoprotein concentrations: the HERITAGE Family Study.
Lipoprotein lipase (LPL) is responsible for the hydrolysis of triglyceride (TG)-rich lipoproteins. The aims of the present study were (1) to test for potential linkages (sib-pair method) between postheparin plasma lipase (lipoprotein and hepatic lipase) activities, body fatness, plasma lipid concentrations, and LPL polymorphisms (Ser447Ter and a tetranucleotide repeat) and microsatellite markers flanking the LPL locus (D8S261 and D8S258); and (2) to investigate associations between the LPL Ser447Ter (S447X) polymorphism and these phenotypes. Data on 190 parents and 312 adult offspring from 99 Caucasian families participating in the HERITAGE Family Study were available for this study. Data were adjusted for the effects of age within sex, and lipases, lipid variables, and abdominal visceral fat were further adjusted for fat mass. A suggestive linkage was observed only between the S447X polymorphism and very-low-density (VLDL)-apolipoprotein B (apo B) (332 sib-pairs, P = .013). The S447X polymorphism was not associated with body fat phenotypes or postheparin plasma LPL (PH-LPL) activity (men, P = .19; women, P = .47). In contrast, the X447 allele carriers had lower plasma TG (men and women, P = .01), VLDL-TG (men and women, P = .01), and VLDL-apo B (men and women, P = .009). The relationships between the X447 allele and plasma TG, VLDL-TG, and VLDL-apo B in both genders were observed in obese (body mass index [BMI] > or = 30 kg/m2) but not in normal-weight (BMI < 25 kg/m2) subjects. Thus, the S447X polymorphism of the LPL gene is not associated with body fatness and postheparin plasma lipase activities. However, the obese carriers of the X447 allele have plasma TG, VLDL-TG, and plasma cholesterol/high-density lipoprotein cholesterol (HDL-C) levels equivalent to those of normal-weight sedentary adults.


Contrast-enhanced ultrasound features of hepatocellular carcinoma in dogs.
This study aimed to describe the contrast-enhanced ultrasound (CEUS) features of canine hepatocellular carcinoma (HCC) in relation to cellular differentiation and lesion size. Sixty dogs with a cytological diagnosis of HCC and that underwent a CEUS examination were retrospectively selected. The wash-in and wash-out patterns of contrast enhancement, along with the time to wash-in and the time to wash-out, of each lesion were recorded. A dimensional cut-off value of 3 cm was adopted for classification. Cellular differentiation had a significant influence on both wash-in (chi-squared=16.99; P<0.001) and wash-out (chi-squared=10.9; P=0.004) patterns of contrast enhancement. Lesion size had a lower, but still significant, influence on both wash-in (chi-squared=12.7; P=0.005) and wash-out (chi-squared=7.42; P=0.024) patterns. A homogeneous hyperenhancement in the arterial phase followed by homogeneous wash-out were suggestive of a well-differentiated HCC. The cellular differentiation of lesions with inhomogeneous hyperenhancement or hypoenhancement/no enhancement as well as an inhomogeneous wash-out or no wash-out could not be inferred. No significant difference in the time to wash-in and the time to wash-out in relation to cellular differentiation or lesion size was evident. CEUS has the potential to improve efficiency in the diagnosis of HCCs in dogs.


Cutaneous T-cell lymphoma: a paradigm for biological therapies.
Mycosis Fungoides and Sézary Syndrome are the most common types of cutaneous T-cell lymphomas. There is no current standard of care for Mycosis Fungoides/Sézary Syndrome, with a general tendency to rely on topical interventions for early disease delaying systemic, more toxic therapy until the development of extensive symptoms. Knowledge of the biological characteristics of this disease has allowed for the development of rational interventions and a significant advance in its treatment. Retinoids are active in Mycosis Fungoides/Sézary Syndrome with the newer rexinoids being available in topical and systemic forms. Interferon alpha remains one of the most active therapeutic agents for Mycosis Fungoides/Sézary Syndrome, especially in combination with other agents such as PUVA. The monoclonal antibody alemtuzumab leads to responses in at least half of patients with advanced disease with its side effect profile consisting mainly of immunosupression and infusion reactions. The recombinant IL2-diphteria toxin denileukin diftitox (Ontak) is active in this disease and appears to have a beneficial effect in symptoms relief and quality of life. Extracorporeal photochemotherapy as an immunostimulating intervention seems to be very effective in a subset of patients, but its availability is limited to less than a hundred centers worldwide. Experimental and less studied interventions include autologous and allogeneic peripheral stem cell transplantation, Interleukin-12, the histone-deacetylator depsipeptide and the synthetic deoxynucleotide CpG7909. Cutaneous T-cell lymphoma has served as a paradigm for the development of biological agents. Further knowledge of the signaling pathways in Mycosis Fungoides/Sézary Syndrome will allow for the development of more effective treatment strategies.


Comparison of molecular cytokeratin 19 reverse transcriptase polymerase chain reaction (CK19 RT-PCR) and immunocytochemical detection of micrometastatic breast cancer cells in hematopoietic harvests.
Detection of small numbers of breast cancer cells in patient blood, aphereses, and bone marrow has become increasingly important as data have accumulated showing immunocytochemically (ICC) positive tumor cells in up to 50% of women with stage I and II breast cancer, who were initially thought to be cured of their disease but later relapsed. The ability to rule out the presence of micrometastatic disease at any stage of the clinical management protocol, whether before, during, or after therapy, would provide a useful monitoring and diagnostic tool for both the clinician and the scientist. Monitoring for the presence of minimal residual disease (MRD) is traditionally performed using ICC. A more recently established RT-PCR technique uses a molecular marker (the presence of the cytokeratin 19, CK19, transcript) to identify MRD in patient samples, with a level of sensitivity reported to be one tumor cell in 10(6) nucleated cells. This level of sensitivity is generally higher than that claimed for ICC. Based on the discriminating results of this first study, a number of laboratories have evaluated this technique for its diagnostic potential. Results from several laboratories showed a higher than expected false positive rate due to a variety of identified and unidentified sources. Therefore, the current study was designed to achieve two aims: to establish the level of sensitivity and specificity of the RT-PCR technique and to dissect out the possible variables that may contribute to a false positive result using this molecular approach. To accomplish the first goal, two simulation strategies were used, limited dilution of tumor cells into apheresis harvests and semi-quantitative PCR using stepwise dilutions of extracted RNA from tumor cells in apheresis harvests. The second goal was accomplished by performing sequential blood drawings with variably timed sample processing to identify some of the more common variables (time, anticoagulant, sample sequence) that may contribute to false positive results. Of three variables investigated, including type of blood preservative, sequence of blood tube collection, and time point of sample processing, each may contribute to a false positive result. In addition to these problems, known events involving illegitimate transcription of specific genes nonspecifically in tissue is also a potential source of false positive results. These issues may be further compounded by lack of attention to the more common methodologic problems encountered in any laboratory using the PCR technique. However, recommendations can be developed for the effective application of this technique, whose greatest strength is the demonstration of tumor negativity of the sample.


Extracorporeal life support for pediatric respiratory failure.
The purposes of this report are to a) describe the University of Michigan experience with venoarterial or venovenous extracorporeal life support for severe pediatric pulmonary rescue therapy, and b) examine survivors and nonsurvivors for differences that might be useful for examination in future, prospective studies. Case series report. Phase I study of safety and effectiveness of extracorporeal life support for pediatric respiratory failure. University of Michigan Medical Center. Non-neonatal pediatric patients treated with extracorporeal life support for severe respiratory failure at the University of Michigan. Extracorporeal life support for pulmonary failure. From November 1982 until May 1991, 25 pediatric patients underwent extracorporeal life support for severe pulmonary failure. Twenty patients were treated in the last 36 months. Sixty percent (15/25 patients) survived their life-threatening respiratory illness, were weaned from mechanical ventilation, and were discharged home. The mean patient age was 4.1 yrs, and mechanical ventilation duration before extracorporeal life support was 5.9 days. Mean blood gas data and mechanical ventilation pressures before extracorporeal life support were: peak inspiratory pressure of 48.6 cm H2O, mean airway pressure of 21.9 cm H2O, positive end-expiratory pressure of 9.7 cm H2O, PaCO2 of 43 torr (5.7 kPa), PaO2 of 69 torr (9.1 kPa), estimated alveolar-arterial oxygen gradient of 563 torr (75 kPa), and FIO2 of 0.98. Variables associated with survival included: age of survivors vs. nonsurvivors, 2.1 vs. 7.1 yrs (p less than .02); peak inspiratory pressure of survivors vs. nonsurvivors, 43.1 vs. 57.9 cm H2O (p less than .03); mean airway pressure of survivors vs. nonsurvivors, 18.4 vs. 27.2 cm H2O (p less than .03); and positive end-expiratory pressure of survivors vs. nonsurvivors, 8.1 vs. 12.1 cm H2O (p less than .01). There were no differences detectable in the blood gas values (PaO2, PaCO2, P[A-a]O2) in survivors and nonsurvivors before extracorporeal life support. The number of days mechanical ventilation was used before extracorporeal life support in survivors and in nonsurvivors was similar. Extracorporeal life support is an effective rescue therapy for pediatric patients with severe respiratory failure (University of Michigan survival rate of 60%).


Addressing the evidence for FDA nicotine replacement therapy label changes: a policy statement of the Association for the Treatment of Tobacco use and Dependence and the Society for Research on Nicotine and Tobacco.
Cigarette smoking creates a substantial public health burden. Identifying new, effective smoking cessation interventions that optimize existing interventions and promoting effective use of approved medications is a priority. When used as directed, nicotine replacement therapy (NRT) aids smoking cessation, but there is opportunity for improving its effectiveness. Until recently, NRT use guidelines advised smokers to begin using NRT on their quit date, only to use 1 NRT formulation at a time, to refrain from using NRT while smoking, and to stop NRT within 3 months regardless of progress. The Food and Drug Administration (FDA) issued a recent announcement allowing for NRT labeling changes with applications from pharmaceutical companies for such changes, and we applaud this decision. Nevertheless, additional revisions are warranted by current research. There is robust evidence that combining a longer-acting form (e.g., patch) with a shorter-acting form (e.g., lozenge) is more effective than NRT monotherapy and is safe. Moreover, extant evidence suggests that NRT use prior to a quit attempt or for smoking reduction as part of a quit attempt is safe and as effective as starting NRT on quit date. Specifically, prequit nicotine patch increases quit rates and may engage additional recalcitrant smokers. Last, NRT use longer than 3 months is safe and may be beneficial for relapse prevention in some smokers. This report summarizes the FDA announcement, reviews the evidence for further revisions to current FDA NRT guidelines, and makes recommendations for over-the-counter (OTC) NRT labeling to allow for (1) combined use of faster-acting NRT medications with nicotine patch, (2) nicotine patch use prior to quit date or NRT for smoking reduction as part of a quit attempt, and (3) prolonged NRT for up to 6 months without healthcare provider consultation.


Changes in cerebral [18F]-FDG uptake induced by acute alcohol administration in a rat model of alcoholism.
Several [18F]-FDG positron emission tomography (PET) studies in alcoholics have consistently reported decreases in overall brain glucose metabolism at rest and following acute alcohol administration. However, changes in cerebral glucose utilization associated with the transition to addiction are not well understood and require longitudinal translational imaging studies in animal models of alcoholism. Here, we studied brain glucose uptake in alcohol drinking rats in order to provide convergent evidence to what has previously been reported in human studies. Brain glucose metabolism was measured by [18F]-FDG microPET imaging in different male Wistar rat groups: short-term drinking (three months), long-term drinking (twelve months) and alcohol-naïve. Global and regional cerebral glucose uptake was measured at rest and following acute alcohol administration. We showed that alcohol significantly reduced the whole-brain glucose metabolism. This effect was most pronounced in the parietal cortex and cerebellum. Alcohol-induced decreases in brain [18F]-FDG uptake was most apparent in alcohol-naïve rats, less intense in short-term drinkers and absent in long-term drinkers. The latter finding indicates the occurrence of tolerance to the intoxicating effects of alcohol in long-term drinking individuals. In contrast, some regions, like the ventral striatum and entorhinal cortex, showed enhanced metabolic activity, an effect that did not undergo tolerance during long-term alcohol consumption. Our findings are comparable to those described in human studies using the same methodology. We conclude that [18F]-FDG PET studies in rat models of alcoholism provide good translation and can be used for future longitudinal studies investigating alterations in brain function during different stages of the addiction cycle.


First attempt recanalization with ADAPT: rate, predictors, and outcome.
The rate of first-attempt recanalization (FAR) with the newer-generation thrombectomy devices, and more specifically with aspiration devices, is not well known. Moreover, the effect of FAR on outcomes after mechanical thrombectomy is not properly understood. To report the rate of FAR using a direct aspiration first pass technique (ADAPT), investigate the association between FAR and outcomes, and identify the predictors of FAR. The ADAPT database was used to identify a subgroup of patients in whom FAR was achieved. Baseline characteristics, procedural, and postprocedural variables were collected. Outcome measures included 90-day modified Rankin scale (mRS) score, mortality, and hemorrhagic complications. Multivariate logistic regression was used to identify FAR predictors. A total of 524 patients was included of whom 178 (34.0%) achieved FAR. More patients in the FAR group than in the non-FAR group received IV tPA (46.6% vs 37.6%; p<0.05). For the functional outcome, higher proportions of patients in the FAR group achieved functional independence (mRS score 0-2; 53% vs 37%; p<0.05). Additionally, we observed lower mortality and hemorrhagic transformation rates in the FAR group than the non-FAR group. Independent predictors of FAR in the anterior circulation were pretreatment IV tPA, non-tandem occlusion, and use of larger reperfusion catheters (Penumbra, ACE 64-68). Independent predictors of FAR in the posterior circulation were diabetes, onset-to-groin time, and cardioembolic etiology. FAR was associated with better functional outcome and lower mortality rate. When ADAPT is used, a larger aspiration catheter and pretreatment IV tPA should be employed when indicated.


Low-Density Lipoprotein Receptor-Related Protein 5-Deficient Rats Have Reduced Bone Mass and Abnormal Development of the Retinal Vasculature.
Humans carrying homozygous loss-of-function mutations in the Wnt co-receptor, low-density lipoprotein receptor-related protein 5 (LRP5), develop osteoporosis and a defective retinal vasculature known as familial exudative vitreoretinopathy (FEVR) due to disruption of the Wnt signaling pathway. The purpose of this study was to use CRISPR-Cas9-mediated gene editing to create strains of Lrp5-deficient rats and to determine whether knockout of Lrp5 resulted in phenotypes that model the bone and retina pathology in LRP5-deficient humans. Knockout of Lrp5 in rats produced low bone mass, decreased bone mineral density, and decreased bone size. The superficial retinal vasculature of Lrp5-deficient rats was sparse and disorganized, with extensive exudates and decreases in vascularized area, vessel length, and branch point density. This study showed that Lrp5 could be predictably knocked out in rats using CRISPR-Cas9, causing the expression of bone and retinal phenotypes that will be useful for studying the role of Wnt signaling in bone and retina development and for research on the treatment of osteoporosis and FEVR.


Compulsory licensing often did not produce lower prices for antiretrovirals compared to international procurement.
Compulsory licensing has been widely suggested as a legal mechanism for bypassing patents to introduce lower-cost generic antiretrovirals for HIV/AIDS in developing countries. Previous studies found that compulsory licensing can reduce procurement prices for drugs, but it is unknown how the resulting prices compare to procurements through the Global Fund to Fight AIDS, Tuberculosis, and Malaria; UNICEF; and other international channels. For this study we systematically constructed a case-study database of compulsory licensing activity for antiretrovirals and compared compulsory license prices to those in the World Health Organization's (WHO's) Global Price Reporting Mechanism and the Global Fund's Price and Quality Reporting Tool. Thirty compulsory license cases were analyzed with 673 comparable procurements from WHO and Global Fund data. Compulsory license prices exceeded the median international procurement prices in nineteen of the thirty case studies, often with a price gap of more than 25 percent. Compulsory licensing often delivered suboptimal value when compared to the alternative of international procurement, especially when used by low-income countries to manufacture medicines locally. There is an ongoing need for multilateral and charitable actors to work collectively with governments and medicine suppliers on policy options.


The effect of duration of resistance training interventions in children who are overweight or obese.
The purpose of this study was to investigate the effects of different durations of resistance training on body composition and power in children. The study was a 24-week longitudinal design involving 31 preadolescent children who were overweight or obese (ages 7-12 years), divided into 3 groups and resistance trained 3 times per week. Group 8 (G8) trained for 8 weeks, group 16 (G16) trained for 16 weeks, and group 24 (G24) trained for 24 weeks. All participants were measured at weeks 0, 8, 16, and 24 for body composition and power. Subjects in G8 and G16 continued to be tested during the testing weeks after cessation of their training programs. Body composition and bone mineral content were measured by dual-energy X-ray absorptiometry. Significant improvements in body composition were seen in the initial 8-week training phase, and these improvements were maintained for the subsequent 16 weeks. Significant changes in percent body fat ( approximately 5-7%) were observed at 8 weeks in all 3 groups. Total fat mass decreased significantly at week 8 in G16 and G24 (5.9%). By week 24, total fat mass was significantly reduced by 8.1% in G24. Significant improvements were observed in static jump power, which improved by 10.5% at week 16 in G24. These results suggest that an 8-week resistance training program is sufficient time to significantly change body composition, strength, and power measures in children who are overweight or obese. However, further improvements are realized with longer-duration resistance training programs. On cessation of the training programs, the G8 and G16 groups maintained the benefits of the exercise program until the end of the study period.


[Acute blindness caused by fungal infection in chronic myeloid leukemia].
A 35-year-old man had suffered from leukemia since September 1990. A transplantation of bone marrow was carried out in February 1994. He developed a graft-versus-host disease in November 1995. In December 1995 a keratoplasty was necessary because of a perforated corneal ulcer. 17 days later the patient noted a complete loss of vision, first in the left and one day later in the right eye. The optic nerve head was white and the retina looked ischaemic like in central retinal artery occlusion. A hypodensic area was found in the frontal brain reaching up to the optic chiasm in computer tomography. Inspite of intensive treatment the immunosuppressed patient died 4 days after he had become blind. Autopsy showed a mycotic infiltration by mucormycosis of the brain and the right optic nerve sheath. This human- pathogenic fungal infection belongs to the group of mould as well as aspergillus. Mycosis should be considered in the differential diagnosis of acute visual loss in immunosuppressed patients.


Polysiloxane layers created by sol-gel and photochemistry: ideal surfaces for rapid, low-cost and high-strength bonding of epoxy components to polydimethylsiloxane.
In this article we introduce and compare three techniques for low-cost and rapid bonding of stereolithographically structured epoxy components to polydimethylsiloxane (PDMS). In short, we first create a polysiloxane layer on the epoxy surface via silane surface coupling and polymerization. Afterwards, the modified epoxy surface can be bonded to a PDMS component at room temperature using a handheld corona discharger, which is a commonly used low-cost technique for bonding two PDMS components. Using these methods bonds of desirable strength can be generated within half an hour. Depending on the epoxy resin, we found it necessary to modify the silanization procedure. Therefore, we provide a total of three different silanization techniques that allow bonding of a wide variety of stereolithographically structurable epoxy resins. The first technique is a UV-light induced silanization process which couples a silane that contains an epoxy-ring ((3-glycidoxypropyl)trimethoxysilane (GPTMS)). For surfaces that cannot be modified with this silane we use dimethoxydimethylsilane (DMDMS). This silane can either be coupled to the surface by a sol-gel process or UV-light induced polymerisation. The sol-gel process which is a heat induced surface modification technique results in high bond strengths. Because of the heat which triggers the sol-gel process, this technique is limited to epoxy polymers with high glass transition temperatures. For the majority of stereolithographically structured epoxy resins which typically have glass transition temperatures of around 60 °C the light-induced bonding technique is preferable. For all three techniques we performed DIN EN-conform tensile testing demonstrating maximum bond strengths of up to 350 kPa which is comparable with bond strengths reported for PDMS-to-PDMS bonds. For all bond methods, long-term stability as well as hydrolytic stability was assessed.


Tetracycline sclerosis in the management of malignant pericardial effusion.
Twenty-two patients with malignant pericardial effusion were seen at the Toronto General Hospital between 1979 and 1984. Under ECG monitoring, an indwelling Kifa catheter was inserted into the pericardial sac and then connected to a Hemovac system and allowed to drain for 12 to 24 hours. Xylocaine hydrochloride, 100 mg, was first instilled intrapericardially, followed by tetracycline hydrochloride, 500 to 1,000 mg, dissolved in 20 mL normal saline. The catheter was clamped for one to two hours and then allowed to drain into the Hemovac. This procedure was repeated every 24 to 48 hours until the net drainage was less than 25 mL/24 hours. Nine men and 13 women were treated (median age, 55 years). The primary malignancy included lung in 15 patients, breast in two patients, and carcinoma of the stomach, ovary, pleural mesothelioma, chronic granulocytic leukemia, and adenocarcinoma of unknown primary in one patient each. Twenty patients received one to five instillations of tetracycline. In one patient the catheter could not be inserted into the pericardial sac, and in one patient the catheter clotted before tetracycline instillation. Minor complications included transient arrhythmia in two patients, postinjection pain in four patients, and self-limited temperature elevation greater than 38.5 degrees C in two patients. fifteen patients had good control of their malignant pericardial effusion for more than 30 days (median survival, 160 days; range, 38 to 275 days). Three patients died before 30 days without evidence of effusion, and no patient surviving longer than 30 days developed recurrent effusion or pericardial constriction. Intrapericardial tetracycline instillation is a safe and efficacious treatment for malignant pericardial effusion and should be considered the first treatment modality in this situation.


Personalized Early AAC Intervention to Build Language and Literacy Skills: A Case Study of a 3-Year-Old with Complex Communication Needs.
Personalized AAC intervention refers to an approach in which intervention is tailored to the individual's needs and skills, the needs and priorities of the individual's family and other social environments, the evidence base, and the individual's response to intervention. This approach is especially relevant to AAC intervention for young children with complex communication needs given their unique constellations of strengths and challenges, and the qualitative and quantitative changes that they experience over time as they develop, as well as the diversity of their families, schools, and communities. This paper provides detailed documentation of personalized AAC intervention over a six-month period for a 3-year-old girl with developmental delay and complex communication needs. The paper describes (1) personalization of multimodal AAC supports to provide this child with the tools to communicate; (2) personalized intervention to build semantic and morphosyntactic skills; and, (3) personalized instruction in literacy skills (i.e., letter-sound correspondences, sound blending, decoding, sight word recognition, reading simple stories, reading comprehension, and encoding skills). Specific goals, instructional materials, and procedures are described; data on speech, language, and literacy outcomes are presented.


The myristylated virion proteins of herpes simplex virus type 1: investigation of their role in the virus life cycle.
Herpes simplex virus type 1 (HSV-1) gene UL11 encodes a myristylated virion protein. In this paper we have characterized the UL11 product further and investigated its role in the virus life cycle. Wild-type HSV-1 strain 17syn+ expresses three electrophoretically distinguishable UL11 polypeptide species. Analysis of single plaque isolates demonstrated that two virus populations exist within the 17syn+ stock: a major population encoding only the two higher Mr species, and a minor population encoding the lowest Mr species alone. DNA sequence analysis suggests that the latter polypeptide differs from the former ones at a single amino acid residue only. The UL11 polypeptides are synthesized as delayed early gene products and are phosphorylated in vitro. Following subcellular fractionation of infected cells, they are found predominantly associated with membranes. Within the virus particle, they appear to reside within the tegument. An insertion mutant containing the lacZ gene from Escherichia coli within the UL11 open reading frame is viable in tissue culture, although it gives smaller plaques and is impaired for growth compared to the wild-type parent or revertant viruses; it does not have a temperature-sensitive or host-range phenotype. Thus, although required for efficient replication, the myristylated HSV-1 virion protein, in contrast to those of many other viruses, is not essential for virus growth in tissue culture.


Lifestyle interventions based on the diabetes prevention program delivered via eHealth: A systematic review and meta-analysis.
The objective was to describe Diabetes Prevention Program (DPP)-based lifestyle interventions delivered via electronic, mobile, and certain types of telehealth (eHealth) and estimate the magnitude of the effect on weight loss. A systematic review was conducted. PubMed and EMBASE were searched for studies published between January 2003 and February 2016 that met inclusion and exclusion criteria. An overall estimate of the effect on mean percentage weight loss across all the interventions was initially conducted. A stratified meta-analysis was also conducted to determine estimates of the effect across the interventions classified according to whether behavioral support by counselors post-baseline was not provided, provided remotely with communication technology, or face-to-face. Twenty-two studies met the inclusion/exclusion criteria, in which 26 interventions were evaluated. Samples were primarily white and college educated. Interventions included Web-based applications, mobile phone applications, text messages, DVDs, interactive voice response telephone calls, telehealth video conferencing, and video on-demand programing. Nine interventions were stand-alone, delivered post-baseline exclusively via eHealth. Seventeen interventions included additional behavioral support provided by counselors post-baseline remotely with communication technology or face-to-face. The estimated overall effect on mean percentage weight loss from baseline to up to 15months of follow-up across all the interventions was -3.98%. The subtotal estimate across the stand-alone eHealth interventions (-3.34%) was less than the estimate across interventions with behavioral support given by a counselor remotely (-4.31%), and the estimate across interventions with behavioral support given by a counselor in-person (-4.65%). There is promising evidence of the efficacy of DPP-based eHealth interventions on weight loss. Further studies are needed particularly in racially and ethnically diverse populations with limited levels of educational attainment. Future research should also focus on ways to optimize behavioral support.


14-3-3 sigma associates with cell surface aminopeptidase N in the regulation of matrix metalloproteinase-1.
Matrix metalloproteinases (MMPs) are implicated in the degradation of the extracellular matrix during development and tissue repair, as well as in pathological conditions such as tumor invasion and fibrosis. MMP expression by stromal cells is partly regulated by signals from the neighboring epithelial cells. Keratinocyte-releasable 14-3-3sigma, or stratifin, acts as a potent MMP-1-stimulatory factor in fibroblasts. However, its mechanism of transmembrane signaling remains unknown. Ectodomain biotin labeling, serial affinity purification and mass spectroscopy analysis revealed that the stratifin associates with aminopeptidase N (APN), or CD13, at the cell surface. The transient knockdown of APN in fibroblasts eliminated the stratifin-mediated p38 MAP kinase activation and MMP-1 expression, implicating APN in a receptor-mediated transmembrane signaling event. Stratifin deletion studies implicated its C-terminus as a potential APN-binding site. Furthermore, the dephosphorylation of APN ectodomains reduced its binding affinity to the stratifin. The presence of a phosphorylated serine or threonine residue in APN has been implicated. Together, these findings provide evidence that APN is a novel cell surface receptor for stratifin and a potential target in the regulation of MMP-1 expression in epithelial-stromal cell communication.