Identifying food deserts and swamps based on relative healthy food access: a spatio-temporal Bayesian approach.
Obesity and other adverse health outcomes are influenced by individual- and neighbourhood-scale risk factors, including the food environment. At the small-area scale, past research has analysed spatial patterns of food environments for one time period, overlooking how food environments change over time. Further, past research has infrequently analysed relative healthy food access (RHFA), a measure that is more representative of food purchasing and consumption behaviours than absolute outlet density. This research applies a Bayesian hierarchical model to analyse the spatio-temporal patterns of RHFA in the Region of Waterloo, Canada, from 2011 to 2014 at the small-area level. RHFA is calculated as the proportion of healthy food outlets (healthy outlets/healthy + unhealthy outlets) within 4-km from each small-area. This model measures spatial autocorrelation of RHFA, temporal trend of RHFA for the study region, and spatio-temporal trends of RHFA for small-areas. For the study region, a significant decreasing trend in RHFA is observed (-0.024), suggesting that food swamps have become more prevalent during the study period. For small-areas, significant decreasing temporal trends in RHFA were observed for all small-areas. Specific small-areas located in south Waterloo, north Kitchener, and southeast Cambridge exhibited the steepest decreasing spatio-temporal trends and are classified as spatio-temporal food swamps. This research demonstrates a Bayesian spatio-temporal modelling approach to analyse RHFA at the small-area scale. Results suggest that food swamps are more prevalent than food deserts in the Region of Waterloo. Analysing spatio-temporal trends of RHFA improves understanding of local food environment, highlighting specific small-areas where policies should be targeted to increase RHFA and reduce risk factors of adverse health outcomes such as obesity.


Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy.
Neonatal encephalopathy (NE) is the clinical manifestation of disordered neonatal brain function. Lack of universal agreed definitions of NE and the sub-group with hypoxic-ischaemia (HIE) makes the estimation of incidence and the identification of risk factors problematic. NE incidence is estimated as 3.0 per 1000 live births (95%CI 2.7 to 3.3) and for HIE is 1.5 (95%CI 1.3 to 1.7). The risk factors for NE vary between developed and developing countries with growth restriction the strongest in the former and twin pregnancy in the latter. Potentially modifiable risk factors include maternal thyroid disease, receipt of antenatal care, infection and aspects of the management of labour and delivery, although indications for some interventions were not reported and may represent a response to fetal compromise rather than the cause. It is estimated that 30% of cases of NE in developed populations and 60% in developing populations have some evidence of intrapartum hypoxic-ischaemia.


Animal model of isolated gonadotropin deficiency. I. Hormonal responses to LHRH immunoneutralization.
Five intact male mongrel dogs, characterized by an episodic secretory pattern of LH and normal serum testosterone concentrations, were actively immunized against LHRH by subcutaneous injections of 200 micrograms of a LHRH-human serum albumin conjugate at 0, 4, and 8 weeks. After 12 weeks, two dogs having the highest antibody titers to LHRH (25% and 51% binding of 125I-LHRH in serum diluted 1:1000 B/Bo) had low to nondetectable serum concentrations of LH and testosterone, whereas serum FSH concentrations were significantly reduced in only one of these dogs. Immunocytochemical techniques showed that the pituitaries of these same two dogs had smaller and fewer LH immunoreactive gonadotropes than did the pituitaries of another three immunized-nonaffected dogs or of the five nonimmunized control dogs. The two LHRH-immunized dogs characterized by hypogonadotropism also had reduced testis (4.0 and 4.0 g) and prostate (2.1 and 1.7 g) weights when compared to control dogs (testis: 12.1 +/- 1.0 g and prostate: 9.2 +/- 1.9 g). LHRH antibody titers in three immunized dogs were demonstrable (8.1, 9.8, and 14.2% B/Bo), but effects on LH, FSH, and testosterone concentrations, pituitary gonadotropes, and reproductive tissue weights were not apparent. The similarity in hormonal and tissue responses observed between dogs effectively immunized against LHRH and men with isolated gonadotropin deficiency suggests that the LHRH-immunized dog may provide a suitable experimental model for the study of patients with isolated gonadotropin deficiency.


Epidemiological Characteristics and Clinical Features of Patients Infected With the COVID-19 Virus in Nanchang, Jiangxi, China.
Objectives: The 2019 novel coronavirus disease (COVID-19) pandemic is the biggest public health crises in the 21st century. While most patients infected with the COVID-19 virus have no to moderate symptoms, there is currently limited clinical information about these patients. Methods: In this study, we retrospectively investigated 41 patients infected with the COVID-19 virus in Nanchang, Jiangxi province, China, from February 4 to March 2, 2020. Nanchang is about 260 km southeast of Wuhan, the initial epicenter of the COVID-19 pandemic. We retrieved information on patient demographics, physical examination results, epidemiology, clinical manifestations, underlying conditions, laboratory analyses, radiological images, and treatment outcomes. Results: Most patients (70.7%) had a history of close contact with patients with confirmed COVID-19, and 16 patients (39.0%) showed a high degree of family clustering. All 41 patients had no to moderate symptoms. The median age was 39.9 years and common symptoms of illness were fever (69.2%), cough (65.4%), and fatigue (19.2%). The dominant patient group was middle-aged women, with hypertension (14.6%) and chronic liver disease (12.2%) as the most frequent underlying conditions. All patients recovered, with the mean time of viral nucleic acid clearance at 10.6 days. Chest CT scans presented ground-glass opacities in 53.7% of patients while 26.8% had normal CT images. Laboratory results showed that lymphocyte counts, lymphocyte percentages, ESR, CRP, IgG, Fib, and cytokines were correlated to patients' conditions. Approximately 60-90% of patients had abnormally high levels of cytokines IL-4, IL-6, IL-10, and/or TNF-α. Conclusions: Our results showed variable clinical and laboratory presentations among this group of patients infected with the COVID-19 virus. Though all 41 patients recovered, our results suggest that cytokine levels and other biochemical indicators should be monitored for patients infected with the COVID-19 virus showing no to moderate symptoms to ensure quick access for critical medical attention, if needed.


Effectiveness of different intracanal irrigation techniques in removing intracanal paste medicaments.
This study aimed to compare the effectiveness of different intracanal irrigation techniques in removing intracanal medicaments prior to obturation. A total of 168 single roots were prepared with ProTaper® rotary files and medicament pastes applied (Ledermix®, Odontopaste®, Doxypaste and Pulpdent®), left in for 2 weeks, then removed using filing followed by one of four methods: irrigation with an open-ended notched irrigation needle (Appli-Vac) either at the working length or 5 mm from the canal orifice, or the Max-I-probe or EndoActivator® at the working length. Following the removal of medicaments, the roots were split into two and the internal surfaces photographed, for digital image analysis of the overall percentage of residual medicament. With the exception of canals irrigated 5 mm apical to the root canal orifice, all four irrigation techniques achieved an average of 95% for removal of Ledermix®, Odontopaste® and Doxypaste. Calcium hydroxide paste was the most difficult medicament to remove, with no difference between irrigation techniques. Up to 27% of the Pulpdent® material remained after irrigation. No irrigation technique could completely remove all traces of medicaments. The position of the irrigational needle and the type of medicament used are key factors, which influence the effectiveness of irrigation in removing medicaments.


Jet spectroscopy of buckybowl: electronic and vibrational structures in the S0 and S1 states of triphenylene and sumanene.
Sumanene is a typical buckybowl molecule with C3v symmetry. We observed a fluorescence excitation spectrum and a dispersed fluorescence spectrum of sumanene in a supersonic jet. Bowl effects were clarified by comparing the spectra with those of triphenylene (D3h symmetry), which is a planar prototype of nonplanar sumanene. The S1 (1)A1 ← S0 (1)A1 transition is symmetry allowed. We found the 0(0)(0) band in the fluorescence excitation spectrum at 357.78 nm; this band was missing in the forbidden S1 (1)A1(') ← S0 (1)A1(') transition of triphenylene. The transition moment was shown to be along the oblate symmetric top axis (out of plane) by the observed rotational contour. A large number of vibronic bands were observed, unlike in triphenylene. Some were considered to be out-of-plane vibrational modes, which lead to a bowl-to-bowl inversion reaction assisted by in-plane vibrations. We found that the vibronic bands were markedly weak in the high energy region of triphenylene-d12. This indicates that the fluorescence quantum yield is very low at the high vibrational levels in the S1 state due to the rapid radiationless transition. The main process is considered to be internal conversion to the S0 state. The nonplanar structural distortion may also enhance radiationless transitions. We could not, however, observe weakening of the vibronic bands in the fluorescence excitation spectrum of sumanene.


Effectiveness of a fixed-dose combination injectable (0.2 mg/kg doramectin + 6.0 mg/kg levamisole hydrochloride) against Rhipicephalus microplus and sucking lice infesting cattle.
Unmanaged tick and sucking lice infestations negatively impact the health and production potential of cattle. Described herein are two non-interference dose confirmation studies evaluating the efficacy of a single administration of a new fixed-dose combination injectable (FDCI) endectocide consisting of 0.2 mg/kg doramectin + 6.0 mg/kg levamisole hydrochloride, against either laboratory-induced Rhipicephalus microplus infestations in Australia or naturally acquired sucking lice (Linognathus vituli) infestations in the US. This FDCI is available as Dectomax V® in Australia and New Zealand and as Valcor® in the United States. To evaluate therapeutic efficacy against R. microplus, 12 calves were each exposed to 10 infestations of ∼5000 larvae per infestation between Days -24 and -2. Calves were either treated on Day 0 with the FDCI or left untreated (control). Additional R. microplus infestations of ∼5000 larvae were conducted on Day 2 and then three times weekly to also evaluate persistent efficacy of the FDCI. Tick collections were conducted daily from Day -3. Group mean live tick counts, egg production, and egg viability were analyzed for significant differences between the two groups. To determine efficacy of the FDCI against lice, 24 cattle with active sucking lice infestations based on Day -7 counts were allocated to two groups and treated on Day 0 with either saline (control) or the FDCI. Lice counts were conducted weekly from Day 14 through 42 and again on Day 56. Mean group lice counts on each count day were compared between treatment groups. In the R. microplus study presented here, cattle in Queensland, Australia treated with the FDCI (Dectomax V®) showed > 90 % reduction in tick counts based on arithmetic means within 48 h of treatment when compared to untreated cattle, and counts were > 95 % reduced from post-treatment Day 5 through Day 30. In the sucking lice study conducted in the US, the FDCI (Valcor®) displayed 100 % efficacy against sucking lice infestations (L. vituli) from first count day (Day 14 post-treatment) through Day 35 and then 99.9 % efficacy through Day 56 post-treatment. No treatment-related adverse events were reported for cattle in either study. Using R. microplus and sucking lice as representative ectoparasites, these studies demonstrate the ectoparasite activity of doramectin is retained in the new FDCI.


Immunochemical studies to purify rabbit and chicken immunoglobulin G antibody by protein A-Sepharose chromatography.
The immunoglobulin (Ig) G binding properties of protein A made affinity chromatography with protein A an acceptable method for isolation of IgG in mammals. Rabbit IgG was isolated by fractionation of serum on a column containing protein A coupled to Sepharose. The IgG molecules of subclasses 1, 2, and 4 and their fragments containing the Fc region had this affinity, but not IgG-3. The second peak, after washing with 1M acetic acid eluate (pH 7.0) as shown in the Ouchterlony agar immunodiffusion test, was the IgG fraction. Similar studies on normal and hyperimmune chicken sera indicated that chicken IgG does not bind to protein A molecules. Further studies indicated that chicken plasminogen did not bind covalently to protein A molecules and subsequently did not interfere in the affinity of protein A to bind to IgG molecules. The inhibition of binding of chicken IgG to protein A molecule is still unknown.


Dual enhancement of electroluminescence efficiency and operational stability by rapid upconversion of triplet excitons in OLEDs.
Recently, triplet harvesting via a thermally activated delayed fluorescence (TADF) process has been established as a realistic route for obtaining ultimate internal electroluminescence (EL) quantum efficiency in organic light-emitting diodes (OLEDs). However, the possibility that the rather long transient lifetime of the triplet excited states would reduce operational stability due to an increased chance for unwarranted chemical reactions has been a concern. Herein, we demonstrate dual enhancement of EL efficiency and operational stability in OLEDs by employing a TADF molecule as an assistant dopant and a fluorescent molecule as an end emitter. The proper combination of assistant dopant and emitter molecules realized a "one-way" rapid Förster energy transfer of singlet excitons from TADF molecules to fluorescent emitters, reducing the number of cycles of intersystem crossing (ISC) and reverse ISC in the TADF molecules and resulting in a significant enhancement of operational stability compared to OLEDs with a TADF molecule as the end emitter. In addition, we found that the presence of this rapid energy transfer significantly suppresses singlet-triplet annihilation. Using this finely-tuned rapid triplet-exciton upconversion scheme, OLED performance and lifetime was greatly improved.


Involvement of CD4+ cells in the protection of C58 mouse against polioencephalomyelitis induced by lactate dehydrogenase-elevating virus.
Immunosuppression, occurring naturally with aging, or experimentally after cyclophosphamide treatment or irradiation, is required for the development in C58 mice infected with lactate dehydrogenase-elevating virus (LDV) of a severe polioencephalomyelitis that is caused by viral destruction of anterior horn neurons. Here it is shown that depletion of T helper lymphocytes by administration of an anti-CD4 antibody was followed by a progressive paralysis typical of polioencephalomyelitis in C58/J mice inoculated with a neurovirulent strain of LDV. Although it was clear that other cell subsets are also required to assure complete protection of genetically-susceptible mice, our results show that T helper lymphocytes play a major role in the prevention of LDV-induced polioencephalomyelitis. The mechanisms by which these cells confer this protection remain however to be determined.


A comparison of essential oils obtained from lavandin via different extraction processes: Ultrasound, microwave, turbohydrodistillation, steam and hydrodistillation.
A total of eight extraction techniques ranging from conventional methods (hydrodistillation (HD), steam distillation (SD), turbohydrodistillation (THD)), through innovative techniques (ultrasound assisted extraction (US-SD) and finishing with microwave assisted extraction techniques such as In situ microwave-generated hydrodistillation (ISMH), microwave steam distillation (MSD), microwave hydrodiffusion and gravity (MHG), and microwave steam diffusion (MSDf)) were used to extract essential oil from lavandin flowers and their results were compared. Extraction time, yield, essential oil composition and sensorial analysis were considered as the principal terms of comparison. The essential oils extracted using the more innovative processes were quantitatively (yield) and qualitatively (aromatic profile) similar to those obtained from the conventional techniques. The method which gave the best results was the microwave hydrodiffusion and gravity (MHG) method which gave reduced extraction time (30min against 220min for SD) and gave no differences in essential oil yield and sensorial perception.


The Dean's Certificate of Distinction in Native Hawaiian Health.
Certificates of Distinction at USA medical schools are given to students who have shown additional commitment and effort in areas such as global health and social justice. In 2014, the Dean's Certificate of Distinction in Native Hawaiian Health (COD-NHH), at the John A. Burns School of Medicine (JABSOM), was designed to offer more experience and knowledge in Native Hawaiian health, as well as directly benefiting Native Hawaiian communities through personal and cultural growth, service learning and scholarly projects. The COD-NHH utilises the Department of Native Hawaiian Health 'na pou kihi' framework represented by a hale (house). This framework embodies the Native Hawaiian holistic view of health and incorporates traditional values and cultural strengths, critical to ensure that students can work comfortably and effectively in our communities. Activities focus on four 'pou kihi' (pillars): (1) cultural knowledge and space; (2) community/environmental stewardship; (3) knowledge advancement and dissemination; and (4) social justice. The first cohort received their COD-NHH in May 2017. Interest among JABSOM students is expanding. The COD-NHH, though well received, has required some modification including new technology for data collection of requirements. Feedback from the community is positive and continued community partnerships allow for opportunities of engagement with the student.


Protection of large predators in a marine reserve alters size-dependent prey mortality.
Where predator-prey interactions are size-dependent, reductions in predator size owing to fishing has the potential to disrupt the ecological role of top predators in marine ecosystems. In southern California kelp forests, we investigated the size-dependence of the interaction between herbivorous sea urchins and one of their predators, California sheephead (Semicossyphus pulcher). Empirical tests examined how differences in predator size structure between reserve and fished areas affected size-specific urchin mortality. Sites inside marine reserves had greater sheephead size and biomass, while empirical feeding trials indicated that larger sheephead were required to successfully consume urchins of increasing test diameter. Evaluations of the selectivity of sheephead for two urchin species indicated that shorter-spined purple urchins were attacked more frequently and successfully than longer-spined red urchins of the same size class, particularly at the largest test diameters. As a result of these size-specific interactions and the higher biomass of large sheephead inside reserves, urchin mortality rates were three times higher inside the reserve for both species. In addition, urchin mortality rates decreased with urchin size, and very few large urchins were successfully consumed in fished areas. The truncation of sheephead size structure that commonly occurs owing to fishing will probably result in reductions in urchin mortality, which may reduce the resilience of kelp beds to urchin barren formation. By contrast, the recovery of predator size structure in marine reserves may restore this resilience, but may be delayed until fish grow to sizes capable of consuming larger urchins.


Cytotoxic and apoptotic effects of bortezomib and gefitinib compared to alkylating agents on human glioblastoma cells.
Glioblastoma is a malignant astrocytic tumor with a median survival of about 12 months for which new therapeutic strategies are required. We therefore examined the cytotoxicity of anticancer drugs with different mechanisms of action on two human glioblastoma cell lines expressing various levels of EGFR (epidermal growth factor receptor). Apoptosis induced by these anticancer agents was evaluated by flow cytometry. The cytotoxicity of alkylating drugs followed a dose-effect curve and cytotoxicity index values were lower with carboplatin than with BCNU and temozolomide. Anti-EGFR gefitinib (10 microM) cytotoxicity on DBTRG.05-MG expressing high levels of EGFR was significantly higher than on U87-MG expressing low levels of EGFR. Carboplatin and temozolomide cytotoxicity was potentiated with the addition of gefitinib on DBTRG.05-MG. Among the anticancer agents tested, the proteasome inhibitor bortezomib was the most cytotoxic with very low IC50 on the two cell lines. Moreover, all anticancer drugs tested induced apoptosis in a concentration-dependent manner. Bortezomib proved to be a more potent inductor of apoptosis than gefitinib and alkylating agents. These results show the efficacy of bortezomib and of the association between conventional chemotherapy and gefitinib on glioblastoma cells and therefore suggest the interest of these molecules in the treatment of glioblastoma.


Greater agreement is required to harness the potential of health intelligence: a critical interpretive synthesis.
To synthesize existing knowledge on the features of, and approaches to, health intelligence, including definitions, key concepts, frameworks, methods and tools, types of evidence used, and research gaps. We applied a critical interpretive synthesis methodology, combining systematic searching, purposive sampling, and inductive analysis to explore the topic. We conducted electronic and supplementary searches to identify records (papers, books, websites) based on their potential relevance to health intelligence. The key themes identified in the literature were combined under each of the compass subquestions and circulated among the research team for discussion and interpretation. Of the 290 records screened, 40 were included in the synthesis. There is no clear definition of health intelligence in the literature. Some records describe it in similar terms as public health surveillance. Some focus on the use of artificial intelligence, while others refer to health intelligence in a military or security sense. And some authors have suggested a broader definition of health intelligence that explicitly includes the concepts of synthesis of research evidence for informed decision making. Rather than developing a new or all-encompassing definition, we suggest incorporating the concept and scope of health intelligence within the evidence ecosystem.


Minactivin expression in human monocyte and macrophage populations.
Adherent monolayer cultures of human blood monocytes, peritoneal macrophages, bone marrow macrophages, and colonic mucosa macrophages were examined for their ability to produce and secrete minactivin, a specific inactivator of urokinase-type plasminogen activator. All except colonic mucosa macrophages produced and secreted appreciable amounts of minactivin, but only blood monocytes were stimulated by muramyl dipeptide (adjuvant peptide) to increase production. The minactivin from each of these populations could be shown to preferentially inhibit urokinase-type plasminogen activator and not trypsin, plasmin, or "tissue"-type plasminogen activator (HPA66). A plasminogen-activating enzyme present in monocyte cultures appeared unaffected by the presence of minactivin and could be shown to be regulated independently by dexamethasone.


The Efficacy of Dynamic Contract-Relax Stretching on Delayed-Onset Muscle Soreness Among Healthy Individuals: A Randomized Clinical Trial.
To evaluate the efficacy of dynamic contract-relax stretching on delayed-onset muscle soreness (DOMS) in the calf muscle of healthy individuals. Randomized clinical trial. Research laboratory. Three groups of 16 healthy participants (n = 48) were recruited by convenience sampling. Three sets of resisted bilateral heel-raising exercises until exhaustion were conducted to initiate DOMS. Participants were randomly allocated into control group without any interventions, dynamic contract-relax stretching (DS), or static stretching (SS) groups. Dynamic contract-relax stretching and SS groups performed DS and SS, respectively, on the dominant leg twice a day for 5 consecutive days (before time points of outcome measurements at 24, 48, 72, 96, and 120 hours postexercise, respectively). Muscle soreness, lower leg girth, pressure pain threshold (PPT), range of motion (ROM), and muscle strength were measured before exercise, immediately after, and at 24, 48, 72, 96, and 120 hours postexercise. There was a significant effect of time in all outcome measures including muscle soreness, lower leg girth, PPT, ROM, and muscle strength; however, there were no significant group differences or group by time interactions. The effect of DS on relieving DOMS in the calf muscle is insignificant in this study. Further evidence is needed to prove the efficacy of DS on DOMS. Stretching is commonly recommended before and after exercise; however, this study showed no significant impact of DS or SS in treating DOMS.


Cognitive function in the early phase of Parkinson's disease, a five-year follow-up.
Presence of mild cognitive impairment (MCI) as a predictor for Parkinson's disease dementia (PDD) has been discussed from a clinical perspective. Recently, a Movement Disorder Society (MDS) commissioned Task Force published guidelines for PD-MCI. However, long-term follow-ups of the PD-MCI guidelines for the prediction of PDD have been sparse. In a community-based cohort of PD, the MDS guidelines for PD-MCI and consensus criteria for PDD were applied on 147 subjects. The predictive ability of PD-MCI for PDD was investigated. Additionally, baseline comparisons were conducted between MCI that converted to PDD and those who did not, and evolvement of motor function was investigated. One fourth of the population developed PDD. MCI and age at baseline predicted later occurrence of PDD, and baseline results of tests measuring episodic memory, visuospatial function, semantic fluency, and mental flexibility differed between MCI converters and non-converters. Postural instability/gait (PIGD) phenotype and education did not predict later occurrence of PDD, but increased postural/gait disturbances were shown across time in those developing dementia. The new PD-MCI guidelines are useful to detect patients at risk for developing PDD. The PIGD phenotype at diagnosis was not a predictor of PDD within 5 years, but the study supports a temporal association between postural/gait disturbances and PDD. Older patients with PD-MCI at baseline with decline in episodic memory, semantic fluency, and mental flexibility need to be carefully monitored regarding cognition and likely also for fall risk.


Dynamic changes in corneal topography and its influence on the point-spread function of the eye.
The dynamic changes of the anterior surface of the eye are investigated. A Twyman-Green interferometer is used to record topographic images at 40 ms intervals. A method of analysis of the dynamic changes in topography by use of Zernike polynomials enables a general distinction to be made between dynamic alterations in the shape of the cornea itself and the changes in the layer of the tears. The influence of deviations in the shape of the anterior surface of the eye on the retinal image is estimated.


Identification and molecular mapping of a major quantitative trait locus underlying branch angle in soybean.
A major quantitative trait locus (QTL) modulating soybean (Glycine max) branch angle was identified by linkage analysis using two bi-parental mapping populations with and without pedigree from wild soybean (Glycine soja). Soybean branch angle is a critical architectural trait that affects many other traits of agronomic importance associated with the plant's productivity and grain yield and is thus a vital consideration in soybean breeding. However, the genetic basis for modulating this important trait in soybean and many other crops remain unknown. Previously, we developed a recombinant inbred line (RIL) population derived from a cross between a domesticated soybean (Glycine max) variety, Williams 82, and a wild soybean (Glycine soja) accession, PI 479,752, and observed drastic variation in plant architecture including branch angle among individual RILs. In this study, one of the RILs possessing extremely wide branch angle (WBA) was crossed with an elite soybean cultivar (LD00-3309) possessing narrow branch angle (NBA) to produce an F2 population composed of 147 plants and F2-derived F3 families for inheritance analysis and QTL mapping. We found that branch angle is controlled by a major QTL located on chromosome 19, designated qGmBa1 and that WBA-derived from the wild soybean accession-is dominant over NBA. This locus was also detected as a major one underlying branch angle by QTL mapping using a subset of the soybean nested association mapping (SoyNAM) population composed of 140 RILs, which were derived from a cross between a landrace, PI 437169B, possessing WBA and an elite variety, IA3023, possessing NBA. Molecular markers located in the QTL region defined by both mapping populations can be used for marker-assisted selection of branch angle in soybean breeding.


RUNX3, a novel tumor suppressor, is frequently inactivated in gastric cancer by protein mislocalization.
Loss of RUNX3 expression is suggested to be causally related to gastric cancer as 45% to 60% of gastric cancers do not express RUNX3 mainly due to hypermethylation of the RUNX3 promoter. Here, we examined for other defects in the properties of RUNX3 in gastric cancers that express RUNX3. Ninety-seven gastric cancer tumor specimens and 21 gastric cancer cell lines were examined by immunohistochemistry using novel anti-RUNX3 monoclonal antibodies. In normal gastric mucosa, RUNX3 was expressed most strongly in the nuclei of chief cells as well as in surface epithelial cells. In chief cells, a significant portion of the protein was also found in the cytoplasm. RUNX3 was not detectable in 43 of 97 (44%) cases of gastric cancers tested and a further 38% showed exclusive cytoplasmic localization, whereas only 18% showed nuclear localization. Evidence is presented suggesting that transforming growth factor-beta is an inducer of nuclear translocation of RUNX3, and RUNX3 in the cytoplasm of cancer cells is inactive as a tumor suppressor. RUNX3 was found to be inactive in 82% of gastric cancers through either gene silencing or protein mislocalization to the cytoplasm. In addition to the deregulation of mechanisms controlling gene expression, there would also seem to be at least one other mechanism controlling nuclear translocation of RUNX3 that is impaired frequently in gastric cancer.


Emerging potential of therapeutic targeting of ubiquitin-specific proteases in the treatment of cancer.
The ubiquitin-proteasome system (UPS) has emerged as a therapeutic focus and target for the treatment of cancer. The most clinically successful UPS-active agents (bortezomib and lenalidomide) are limited in application to hematologic malignancies, with only marginal efficacy in solid tumors. Inhibition of specific ubiquitin E3 ligases has also emerged as a valid therapeutic strategy, and many targets are currently being investigated. Another emerging and promising approach in regulation of the UPS involves targeting deubiquitinases (DUB). The DUBs comprise a relatively small group of proteins, most with cysteine protease activity that target several key proteins involved in regulation of tumorigenesis, apoptosis, senescence, and autophagy. Through their multiple contacts with ubiquitinated protein substrates involved in these pathways, DUBs provide an untapped means of modulating many important regulatory proteins that support oncogenic transformation and progression. Ubiquitin-specific proteases (USP) are one class of DUBs that have drawn special attention as cancer targets, as many are differentially expressed or activated in tumors or their microenvironment, making them ideal candidates for drug development. This review attempts to summarize the USPs implicated in different cancers, the current status of USP inhibitor-mediated pharmacologic intervention, and future prospects for USP inhibitors to treat diverse cancers.


An ideal trial to test differential onset of antidepressant effect.
Although various published clinical studies have suggested that some antidepressants may have a more rapid onset of therapeutic effect than others, none of these trials was adequately designed to measure differential time to onset of effect. Thus, existing data do not support claims that one drug reduces the symptoms of depression faster than another. In this article, we propose a study that would be ideal for measuring comparative onset of antidepressant effect. The key features of this ideal trial include (1) a prospective definition of early onset of action, (2) increased frequency of assessment, (3) a data-analytic approach capable of capturing the dynamic nature of symptomatic change, and (4) various strategies to minimize bias and heterogeneity of response.


Mental health care use among children and adolescents in Germany: results of the longitudinal BELLA study.
Data on mental health care use of children and adolescents in Germany is scarce. This study investigates the degree of mental health care use, its trajectories and influencing factors among children and adolescents in Germany, using longitudinal data of the BELLA study. The BELLA study is the mental health module of the representative German National Health Interview and Examination Survey for children and adolescents (KiGGS). Baseline data of N = 2,863 participants aged 7-17 years were collected between 2003 and 2006. The study sample was followed up in three additional measurement points, assessing general mental health problems and impairment, specific mental health problems, and mental health care use. In the current study, we analysed data from the first three measurement points. At baseline, 5.9 % of all participants used mental health care in the past 12 months. Among those with general mental health problems, 29.5 % sought professional help. Only a minority of participants reporting mental health care use at baseline also sought help at the following two measurement points. Analysing a random intercept only model, mental health care use was found to be more likely among participants living in larger communities as well as in the Eastern part of Germany, among those participants with impairment of mental health problems, and signs of externalizing problems. Our results indicate a temporary character of mental health care use. Participants' impairment was identified to be the strongest predictor of mental health care use.


Transforming growth factor-alpha in the adult bovine ovary: identification in growing ovarian follicles.
The pituitary gonadotropins and gonadal steroids are required for normal follicular growth and development but neither has been shown to act directly as a granulosa cell mitogen in vitro. A number of polypeptide growth factors, however, are known to have pronounced mitogenic effects on the cells of the follicle. We have localized transforming growth factor-alpha (TGF-alpha), a potent mitogen, in bovine thecal cells via immunoperoxidase staining using a monoclonal antibody for TGF-alpha that does not cross-react with epidermal growth factor. TGF-alpha staining is most intense in the theca of follicles at the discrete physiological stages known to show rapid granulosa cell growth (small follicles of 0.7-2.0 mm diameter). Staining intensity for TGF-alpha declines in large preovulatory follicles, coincident with the known decline in granulosa cell mitosis. These studies provide further evidence for paracrine interactions in the ovary and show that TGF-alpha may play an important role in the regulation of follicular development in the adult bovine ovary.


Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia.
To gain insight into melanoma pathogenesis, we characterized an insertional mouse mutant, TG3, that is predisposed to develop multiple melanomas. Physical mapping identified multiple tandem insertions of the transgene into intron 3 of Grm1 (encoding metabotropic glutamate receptor 1) with concomitant deletion of 70 kb of intronic sequence. To assess whether this insertional mutagenesis event results in alteration of transcriptional regulation, we analyzed Grm1 and two flanking genes for aberrant expression in melanomas from TG3 mice. We observed aberrant expression of only Grm1. Although we did not detect its expression in normal mouse melanocytes, Grm1 was ectopically expressed in the melanomas from TG3 mice. To confirm the involvement of Grm1 in melanocytic neoplasia, we created an additional transgenic line with Grm1 expression driven by the dopachrome tautomerase promoter. Similar to the original TG3, the Tg(Grm1)EPv line was susceptible to melanoma. In contrast to human melanoma, these transgenic mice had a generalized hyperproliferation of melanocytes with limited transformation to fully malignant metastasis. We detected expression of GRM1 in a number of human melanoma biopsies and cell lines but not in benign nevi and melanocytes. This study provides compelling evidence for the importance of metabotropic glutamate signaling in melanocytic neoplasia.


Continuous monitoring of electromyography (EMG), mechanomyography (MMG), sonomyography (SMG) and torque output during ramp and step isometric contractions.
In this study we simultaneously collected ultrasound images, EMG, MMG from the rectus femoris (RF) muscle and torque signal from the leg extensor muscle group of nine male subjects (mean±SD, age=30.7±.4.9 years; body weight=67.0±8.4kg; height=170.4±6.9cm) during step, ramp increasing, and decreasing at three different rates (50%, 25% and 17% MVC/s). The muscle architectural parameters extracted from ultrasound imaging, which reflect muscle contractions, were defined as sonomyography (SMG) in this study. The cross-sectional area (CSA) and aspect ratio between muscle width and thickness (width/thickness) were extracted from ultrasound images. The results showed that the CSA of RF muscles decreased by 7.25±4.07% when muscle torque output changed from 0% to 90% MVC, and the aspect ratio decreased by 41.66±7.96%. The muscle contraction level and SMG data were strongly correlated (R(2)=0.961, P=0.003, for CSA and R(2)=0.999, P<0.001, for width/thickness ratio). The data indicated a significant difference (P<0.05) in percentage changes for CSA and aspect ratio among step, ramp increasing, and decreasing contractions. The normalized EMG RMS in ramp increasing was 8.25±4.00% higher than step (P=0.002). The normalized MMG RMS of step contraction was significantly lower than ramp increasing and decreasing, with averaged differences of 12.22±3.37% (P=0.001) and 12.06±3.37% (P=0.001), respectively. The results of this study demonstrated that the CSA and aspect ratio, i.e., SMG signals, can provide useful information about muscle contractions. They may therefore complement EMG and MMG for studying muscle activation strategies under different conditions.


Changing the Tone of Clinical Study Design in the Cannabis Industry.
Cannabis (also known as marijuana) is the most frequently used psychoactive substance globally. Cannabis exerts therapeutic functions for many indications and has vast potential as a health and wellness product. Advances in our understanding of the composition and pharmacological properties of cannabis have revealed interactions between cannabis, an individuals' circadian rhythms and and their endocannabinoid signaling. Exogenously administered cannabinoids can bidirectionally entrain central and peripheral clocks that comprise circadian rhythms, and malfunctions in the endocannabinoid system are reported to impact neurological processes. Therefore, it is necessary to account for the circadian rhythm when designing clinical trials examining the pharmacological properties of cannabis-based products for health and wellness to limit its potential confounding impact on results. Consideration of the entrainment capabilities of the endocannabinoid system is warranted when designing clinical trials.


Deep intrinsic decomposition trained on surreal scenes yet with realistic light effects.
Estimation of intrinsic images still remains a challenging task due to weaknesses of ground-truth datasets, which either are too small or present non-realistic issues. On the other hand, end-to-end deep learning architectures start to achieve interesting results that we believe could be improved if important physical hints were not ignored. In this work, we present a twofold framework: (a) a flexible generation of images overcoming some classical dataset problems such as larger size jointly with coherent lighting appearance; and (b) a flexible architecture tying physical properties through intrinsic losses. Our proposal is versatile, presents low computation time, and achieves state-of-the-art results.


Electroconvulsive therapy in 1985--a review.
Electroconvulsive therapy (ECT) has recently been re-examined in randomized, double-blind controlled trials. Although a variable placebo influence has been demonstrated, the effectiveness of ECT in severe depression is now well established. ECT may also have a role in the treatment of resistant schizophrenia. A bilateral convulsion is essential for therapeutic efficiency. Unilateral electrode placement is as effective as bilateral placement and reduces subsequent memory impairment considerably. A reduction in the total electrical energy used to produce the convulsion (with unidirectional squared wave forms and brief pulses) lessens cognitive difficulties after ECT. Long-term memory is not impaired but selective impairment of verbal and non-verbal learning can occur in the short term. Psychopharmacological studies suggest that postsynaptic dopamine transmission may be enhanced by ECT.


Facilitators of and barriers to emergency medical service use by acute ischemic stroke patients: A retrospective survey.
The objective of the study was to identify facilitators and barriers to emergency medical service use among acute ischemic stroke patients in Korea. This paper presents a secondary analysis of a retrospective survey that collected data from questionnaires and medical records. Among 233 acute ischemic stroke patients enrolled in a large-scale study, 160 patients who had arrived at a hospital within 72 h after symptom onset were included in the data analysis. Users of emergency medical services needed a shorter time than non-users to arrive at hospital (140 min vs. 625 min., p = 0.001) and were more likely to arrive at hospital within 3 h of symptom onset (51.9% vs. 31.5%, p = 0.013). For those who first contacted emergency medical service, the facilitators of emergency medical service use were the presence of hemiparesis (p = 0.003), bilateral paralysis (p = 0.040), and loss of balance (p = 0.021). The predominant barrier was the failure to recognize the urgency of symptoms (p = 0.006). The use of emergency medical services reduced prehospital delay and increased the likelihood of patient arrival at hospital within 3 h. Given that experiencing typical stroke symptoms was a facilitator of emergency medical service use yet failure to recognize the urgency of symptoms was a barrier, public awareness should be raised as regards stroke symptoms and the benefits of using emergency medical services.


Resveratrol Derivative-Rich Melinjo Seed Extract Attenuates Skin Atrophy in Sod1-Deficient Mice.
The oxidative damages induced by a redox imbalance cause age-related changes in cells and tissues. Superoxide dismutase (SOD) enzymes play a pivotal role in the antioxidant system and they also catalyze superoxide radicals. Since the loss of cytoplasmic SOD (SOD1) resulted in aging-like phenotypes in several types of murine tissue, SOD1 is essential for the maintenance of tissue homeostasis. Melinjo (Gnetum gnemon Linn) seed extract (MSE) contains trans-resveratrol (RSV) and resveratrol derivatives, including gnetin C, gnemonoside A, and gnemonoside D. MSE intake also exerts no adverse events in human study. In the present studies, we investigated protective effects of MSE on age-related skin pathologies in mice. Orally MSE and RSV treatment reversed the skin thinning associated with increased oxidative damage in the Sod1 (-/-) mice. Furthermore, MSE and RSV normalized gene expression of Col1a1 and p53 and upregulated gene expression of Sirt1 in skin tissues. In vitro experiments revealed that RSV significantly promoted the viability of Sod1 (-/-) fibroblasts. These finding demonstrated that RSV in MSE stably suppressed an intrinsic superoxide generation in vivo and in vitro leading to protecting skin damages. RSV derivative-rich MSE may be a powerful food of treatment for age-related skin diseases caused by oxidative damages.


Structure and bonding in alpha-copper phthalocyanine by electron diffraction.
Energy-filtered quantitative electron diffraction at liquid nitrogen temperature has been used to examine the atomic structure and bonding of metastable alpha-Cu phthalocyanine crystals. Three theoretical methods (kinematic, kinematic with excitation errors and Bloch wave) were employed for the intensity calculations. The Bloch-wave method was found to account for dynamical effects by greatly reducing the residual factor between experimental and simulated results. A new method for calculating electron scattering factors for partially charged ions is proposed and the sensitivity of electron diffraction to charge transfer is discussed. The atomic charge states were analyzed for alpha-Cu phthalocyanine using a charge cloud model in which the Gaussian bond charge is positioned along the bonds. Spot patterns were collected in the Kohler mode at two beam energies to reduce error. Using the best-fitting model, a deformation charge-density map is produced and compared to the neutral-atom model. From this, the main features of atomic charge transfer in the alpha-Cu phthalocyanine structure can be seen in the (010) plane.


[Lesions of target organs in arterial hypertension].
A total of 530 patients with a variety of hypertensive conditions, including 476 patients with labile and stable essential hypertension, 40 with hypertensive chronic diffuse glomerulonephritis and hypertensive chronic pyelonephritis, and 14 with vasorenal hypertension, were investigated. Structure and function of target organs (the heart and the kidneys) were assessed by means of echocardiography (530) and intravital morphologic studies of renal biopsy specimens (89). A heterogeneous nature of hypertrophic developments associated with essential hypertension was demonstrated, with adequate, inadequate, disproportionate and excessive hypertrophy identified, while no correlation could be found between the kind of hypertension and the degree and nature of hypertrophy. Renal morphologic changes were also shown to be heterogeneous in labile and stable arterial hypertension, and early involvement of the renal mechanism presenting as structural changes was found to be possible.


Reducing alcohol-related violence and improving community safety: the Alcohol Linking Program.
Harm associated with the consumption of alcohol on licensed premises is an issue of increasing community concern. This paper reports on a decade-long research initiative that involved the development and implementation of police systems designed to enhance identification of, and police capacity to respond to, premises suggested to be associated with such harms. The outcomes of the Alcohol Linking Program demonstrate enhanced information regarding the occurrence and characteristics of alcohol-related incidents; there are more than 34,000 such incidents each year in rural and regional NSW. Evaluation of the impact of an educational intervention demonstrated reductions of about 15% in the number of alcohol-related incidents linked with such premises. The Program has subsequently been adopted into routine practice on a system-wide basis by the NSW Police and New Zealand Police. Opportunities exist for public health practitioners to contribute to reducing alcohol-related harm in the community through the development of equivalent surveillance systems in emergency departments, monitoring licencee compliance with the Liquor Act, and through injury prevention, health promotion and drug and alcohol practitioners enhancing the capacity of licencees to serve alcohol responsibly.


Indolizidine and quinolizidine alkaloids.
This review covers the isolation, structure determination, synthesis, chemical transformations and biological activity of indolizidine and quinolizidine alkaloids. Included in the review are the hydroxylated indolizidines lentiginosine, swainsonine, castanospermine and their analogues; alkaloids from animal sources, including arthropods and amphibians; alkaloids from the genera Polygonatum, Prosopis and Poranthera; phenanthroindolizidine and phenanthroquinolizidine alkaloids; Nuphar alkaloids; lupine alkaloids; and alkaloids from marine sources. 130 references are cited.


Increased transcription of the regulatory subunit of gamma-glutamylcysteine synthetase in rat lung epithelial L2 cells exposed to oxidative stress or glutathione depletion.
gamma-Glutamylcysteine synthetase (GCS) is the initial and rate-limiting enzyme in the glutathione (GSH) de novo synthesis pathway. GCS is composed of a heavy (73-kDa) catalytic subunit and a light (30-kDa) regulatory subunit, which maintains the Km for glutamate near physiologic concentrations. Previous studies have shown that the steady-state mRNA level and gene transcription for the catalytic subunit increased in response to the redox-cycling quinone 2,3-dimethoxy-1,4-naphthoquinone (DMNQ) in rat lung epithelial L2 cells (M. M. Shi, et al., 1994, J. Biol. Chem. 269,26512-26517). The ratio of the catalytic to regulatory subunit mRNAs varies among tissues, and the anticancer drug cisplatin appears to induce only the catalytic subunit, suggesting independent gene regulation of the two subunits. Nonetheless, the present study found that the steady-state mRNA level and the transcription rate of the GCS regulatory subunit also increased under DMNQ-induced oxidative stress. Changes in mRNA followed a pattern similar to that for the catalytic subunit. The mRNA levels of the two subunits of GCS also both increased above the baseline levels in cells treated with BSO, an inhibitor of GCS enzymatic activity. These data suggest that, under conditions of oxidative stress or glutathione depletion, the regulatory subunit is upregulated at the level of mRNA transcription. Along with the elevation of the catalytic subunit, this increase in GCS regulatory subunit transcription contributes to increases in GCS enzymatic activity and cellular GSH content.


Pregnancy and radiation.
The risk of foetal irradiation during pregnancy is discussed. It seems that, due to the low level of X-ray exposure to the foetus, neither diagnostic radiography nor nuclear diagnostic examination justifies termination of pregnancy. Radiotherapy for breast cancer, Hodgkin's disease and cervical cancer in pregnant women is reviewed. Radiation therapy for breast cancer is not an absolute contraindication for pregnancy and the risk-benefit assessment should be discussed with the mother. The risk to the foetus during radiotherapy for supradiaphragmatic Hodgkin's disease appears to be minimal, provided special attention is paid to the treatment techniques and the foetus is adequately shielded. Radiotherapy for the treatment of cervical cancer may be necessary during pregnancy, but the timing should be adjusted taking into consideration gestational age. Offspring of cancer patients who were treated by radiotherapy appear to be at little risk of childhood cancer or birth defects. Cancer patients should not be discouraged from having children and can expect a good outcome of pregnancy. However, in the non-pregnant woman, to further reduce any risk it is advisable to delay pregnancy for 12 months following completion of radiation therapy.


Homozygous transcobalamin II deficiency maintained on oral hydroxocobalamin.
A case of transcobalamin II (TCII) deficiency in which a total absence of TCII was demonstrated both functionally and immunologically is reported. Unlike previously described patients, this child has been maintained on oral hydroxocobalamin, 2 mg daily, without any parenteral supplementation for the last five years. At the age of six years her development is normal and her health is good. Plasma cobalamin levels are in the range of 3,000 ng/L and most of this appears to be bound to a molecule, which on gel filtration, elutes with albumin. In an extended family study, a clear separation of heterozygotes from both the propositus and from normal subjects suggests that the underlying defect in this condition is confined to a single gene.


Switching between TADF and RTP: anion-regulated photoluminescence in organic salts and co-crystals.
Thermally activated delayed fluorescence (TADF) and room temperature phosphorescence (RTP) are two photophysical phenomena which utilize triplet excitons. In this work, we demonstrate how variation of the anion in organic salts with carbazole and phenothiazine-5,5-dioxide donors and pyridinium and quinolinium acceptors may be used to switch between TADF and RTP. These compounds adopt similar molecular structures and packing modes with different anions and exhibit different types of photophysical behavior due to the electronic effects of the anions. With bromide anions, the salts exhibit TADF with some RTP. These compounds show fast reverse intersystem crossing and a short delayed lifetime, which is key to application in efficient and robust OLEDs. With BF4 - and PF6 - anions, RTP with long-lived lifetimes and afterglow are observed by eye. This behavior can be utilized for data encryption and anti-counterfeiting applications. Emission wavelengths and lifetimes are also anion-dependent. These results open up an avenue for developing novel luminescent materials through anion tuning and present a molecular model to understand the interplay of RTP and TADF.


5-Methyltetrahydrofolate and tetrahydrobiopterin can modulate electrotonically mediated endothelium-dependent vascular relaxation.
We have investigated the ability of 5-methyltetrahydrofolate (5-MTHF) and tetrahydrobiopterin (BH(4)) to modulate nitric oxide (NO)-independent vascular relaxations that are mediated by the sequential spread of endothelial hyperpolarization through the wall of the rabbit iliac artery by means of myoendothelial and homocellular smooth muscle gap junctions. Relaxations and subintimal smooth muscle hyperpolarizations evoked by cyclopiazonic acid were depressed by the gap junction inhibitor 2-aminoethoxydiphenyl borate, whose effects were prevented by 5-MTHF and BH(4), but not by their oxidized forms folic acid and 7,8-dihydrobiopterin. Analogously, 5-MTHF and BH(4), but not folic acid or 7,8-dihydrobiopterin, attenuated the depression of subintimal hyperpolarization by a connexin-mimetic peptide targeted against Cx37 and Cx40 ((37,40)Gap 26) and the depression of subadventitial hyperpolarization by a peptide targeted against Cx43 ((43)Gap 26), thus reflecting the known differential expression of Cx37 and Cx40 in the endothelium and Cx43 in the media of the rabbit iliac artery. The inhibitory effects of 2-aminoethoxydiphenyl borate and (37,40)Gap 26 against subintimal hyperpolarization were prevented by catalase, which destroys H(2)O(2). 5-MTHF and BH(4) thus appear capable of modulating electrotonic signaling by means of myoendothelial and smooth muscle gap junctions by reducing oxidant stress, potentially conferring an ability to reverse the endothelial dysfunction found in disease states through mechanisms that are independent of NO.


Prospective randomization of parenteral hyperalimentation for long fusions with spinal deformity: its effect on complications and recovery from postoperative malnutrition.
A prospective randomized study of total parenteral nutrition for long spinal deformity fusions as well as its effect on complications and recovery from postoperative malnutrition was performed. To determine whether the administration of total parenteral nutrition to patients undergoing same-day or staged long spinal fusions has an effect on postoperative nutritional parameter depletion, time for return to preoperative nutritional baseline, and complication rate. Several studies have suggested, but only one has demonstrated, that perioperative administration of total parenteral nutrition to patients undergoing spinal reconstructive surgery may reduce postoperative nutritional depletion, thereby decreasing postoperative complications. In this study, 46 patients undergoing same-day or staged spinal reconstruction surgery (> or = 10 levels) were randomized to receive or not receive total parenteral nutrition after surgery. The nutritional parameters of albumin, prealbumin, transferrin, total protein, and absolute lymphocyte count were obtained before surgery and at regular intervals after surgery until at least four out of five parameters were within 10% of their preoperative baseline value. Perioperative data and complications were tallied. There were no complications related to total parenteral nutrition administration. There was no statistical difference in total complications between those who did and those who did not receive total parenteral nutrition. However, there was a trend (P < 0.073) for the total parenteral nutrition group to return to nutritional baseline quicker. A significant increase in transferrin (P < 0.0082) and prealbumin (P < 0.015) depletion occurred in the patients who did not receive total parenteral nutrition. The anterior/posterior-same-day patients receiving total parenteral nutrition had more major complications (P < 0.033) and significantly more total protein depletion (P < 0.018) than the anterior/posterior-staged patients receiving total parenteral nutrition, possibly because the anterior/posterior-staged group received significantly more days(P < 0.0155) of total parenteral nutrition than the anterior/posterior-same-day group. In controlling for the number of days of total parenteral nutrition, no significant difference between type of surgery and complications was found. The administration of postoperative total parenteral nutrition to patients with spinal deformity is safe. No statistical reduction in complications occurred in the total parenteral nutrition group despite a trend toward more rapid normalization of nutritional parameters and a decrease in postoperative nutritional depletion. The anterior/posterior-staged group with the administration of total parenteral nutrition had a lower overall complication rate and a decreased incidence of postoperative nutritional depletion than the one-stage reconstruction group. The difference in the complication rates between the two groups may relate as much to the staging as to the administration of total parenteral nutrition per se. For certain cases it may be more advisable to stage patients and deliver total parenteral nutrition than to manage the cases in a continuous (i.e., same-day) fashion.


[Dynamic esophageal scintigraphy by a condensed imaging method].
The paper is concerned with preliminary evaluation of a method of condensed imaging during processing of the results of dynamic esophageal scintigraphy to detect motor evacuatory function of the esophagus. Altogether 34 patients (20 patients with primary esophageal cancer and 14 without G. I. tract pathology) were investigated. Comparison of the results of analysis of dynamic esophageal scintigraphy by a method of condensed imaging and standard methods of diagnostic data processing has shown that a condensed image of the esophagus objectively reflects some passage features of a food lump in the organ. Condensed imaging seems superior for analysis of the results of investigation and diagnostic data storage. However, this method must not be regarded as an alternative one ruling out a necessity of analysis of esophageal histograms and calculation of RP transport in the esophagus.


Brief communication: DNA from early Holocene American dog.
We present the oldest genetically identified dog in the Americas, directly dated to 9,260 ± 170 Cal. B.P. The DNA was extracted from an occipital condyle imbedded in a human paleofecal sample from Hinds Cave in southwest Texas. A 368 base pair fragment of the mitochondrial genome control region was sequenced. These data were analyzed with comparable data, which included other ancient dogs and extant dogs, wolves and coyotes from around the world. Compiled with published data, our results characterize ancient American dogs within clades rooted by Eurasian wolves. In the Americas, these data provide no evidence of local interbreeding with wolves. This is a departure from the genetic pattern in other areas of the world where interbreeding with local wolf populations is apparent. Our discovery of domestic dog bone in a human paleofecal sample provides the earliest direct evidence for human consumption of dogs in the New World. These data support the hypothesis that dogs were a food source for early Paleoamericans.


Characteristics in response rates for surveys administered to surgery residents.
Surveys are important research tools that permit the accumulation of information from large samples that would otherwise be impractical to collect. Resident surveys have been used frequently to monitor the quality of postgraduate training. Low response rates threaten the utility of this research tool. The purpose of this study was to determine the standard response rate of surveys administered to surgery residents and identify characteristics associated with achieving greater response rates. A search of peer-reviewed literature published between September 2003 and June 2011 was performed with the use of PubMed with Medical Subject Headings: "internship and residency," "surgery," "data collection," and "questionnaires." For inclusion, articles must have described a survey given to active surgery residents within the United States. Surveys were evaluated based on the following criteria: population size, response rate, incentive use, follow-up use, survey format (online vs paper), and institution versus national. Of 433 initial results, 47 met inclusion criteria with a mean response rate of 65.3%. Surveys administered in paper format had a greater response rate compared with those given electronically (mean 78.6% vs 36.4%, respectively, P < .001). Greatest mean response rates were seen for institutional surveys compared with those given nationally (83.1% vs 42% respectively, P < .001). Our review demonstrated that paper surveys administered at the institutional level and during assemblies integrated into residents' schedules demonstrated enhanced response rates. The validity and generalizability of data collected through such surveys will improve as the aspects which dictate response rate are better understood and implemented.


Interaction Effects Between Aquifer Thermal Energy Storage Systems.
Aquifer thermal energy storage (ATES) is an energy efficient technique to provide heating and cooling to buildings by storage of warm and cold water in aquifers. In regions with large demand for ATES, ATES adoption has lead to congestion problems in aquifers. The recovery of thermal energy stored in aquifers can be increased by reducing the distance between wells of the same temperature while safeguarding individual system performance. Although this approach is implemented in practice, the understanding of how this affects both the recovery efficiency and the needed pumping energy is lacking. In this research, the effect of well placement on the performance of individual systems is quantified, and guidelines for planning and design are developed. Results show an increase in thermal recovery efficiency of individual systems when the thermal zones of wells of the same temperature are combined, which is explained by reduced surface area of the thermal zone over which losses occur. The highest increase of the thermal recovery efficiency is found for systems with a small storage volume and long well screens. The relative increase of the thermal recovery efficiency is 12% for average-sized systems with a storage volume of 250,000 m3 /year, and 25% for small systems (50,000 m3 /year). The optimal distance between wells of the same temperature is 0.5 times the thermal radius, following the trade-off between an increase of the thermal recovery efficiency and the increase in pumping energy. The distance between wells of opposite temperature must be larger than three times the thermal radius to avoid negative interaction.


Strength analysis and comparison of the Teno Fix Tendon Repair System with the two-strand modified Kessler repair in the Achilles tendon.
Various options exist for repair of Achilles tendon ruptures, yet a method that consistently provides sufficient gap resistance to allow early mobilization remains elusive. This study compares the mechanical performance of a modified Kessler repair with that of the Teno Fix Tendon Repair System (Ortheon Medical, LLC) in matched pairs of cadaver Achilles tendons. The two-strand modified Kessler repair was selected as the control construct on the basis of literature review and physician interviews which identified it among the many options as a popular method for repair of acutely ruptured Achilles tendons. Test specimens were harvested from matched pairs of cadaver ankles. The tendons were transected 3.5 cm proximal to the calcaneal insertion and repaired with either the two-strand modified Kessler suture construct or the Teno Fix Tendon Repair System. Assignment to the modified Kessler or Teno Fix group was done randomly for the first member of each pair. All test and control repairs were performed by the same author to reduce variability. Evaluation of the repairs consisted of tensile strength testing and measurement of the gap formation and peak stresses. Gap and peak stress for the two-strand modified Kessler repair were 0.30 +/- 0.15 N/mm2 and 1.03 +/- 0.51 N/mm2, respectively. For the Teno Fix repairs the mean gap and peak stress values were 0.80 +/- 0.46 N/mm2 and 1.19 +/- 0.12 N/mm2, respectively. The mean gap formation stress was significantly higher in the Teno Fix repairs than in the control repairs (p < .0005). There was no significant difference in peak strength between the repairs (p < .10). The Teno Fix repair was superior to the modified Kessler repair. In the Teno Fix repairs, the gap formation stress was 67% of the peak tensile stress. In comparison, in the modified Kessler repairs, the gap formation stress was 29% of the peak stress. This can be correlated to the elastic property of the modified Kessler suture and the initial tightening of the suture around the tendon fibers. The Teno Fix system is nonelastic and is fully tensioned during installation. This lends to a more gap resistant repair.


Socioeconomic and geographic disparities in access to pharmacotherapy for alcohol dependence.
A higher rate of alcohol-attributable morbidity and mortality exists in remote and socioeconomically disadvantaged regions of Australia. This study aimed to explore the dispensing pattern of pharmacotherapy for alcohol dependence across these groups. A retrospective cohort study of patients (aged 15-84) dispensed acamprosate or naltrexone (July 2009-June 2013) was conducted. Observed dispensing rates were obtained for 541 local government areas (LGA) of Australia. Expected dispensing was based on national rates and age standardized to each LGA. Mean dispensing ratios (observed to expected) for each medicine over the period were calculated for remoteness and socioeconomic disadvantaged groups. For both medications, the mean dispensing ratio significantly differed across geographical groups and across socioeconomic groups (p's<0.05). For naltrexone and acamprosate, respectively, the mean dispensing ratio in remote areas was 6 and 9 times less than for the major cities. The mean dispensing ratio for both medications in the most socially disadvantaged areas was approximately 5 times less than that of the most disadvantaged areas. Our data highlight geographical and socioeconomic disparities in Australia regarding access to pharmacological treatment for alcohol use disorder. Targeted strategies aimed at bridging the gap of accessibility for relapse prevention medications are required.


Potassium feeding reduces hyperactive central nervous system pressor responses in Dahl salt-sensitive rats.
Dahl showed that feeding KCl prevents the rise in blood pressure caused by a high NaCl diet in salt-sensitive Dahl "S" rats. Such S rats when normotensive on a low NaCl diet have a 2 to 3 times greater pressor response than Dahl "R" rats to intracerebroventricular hypertonic saline (600 mOsm/liter) or angiotensin II (AII) (500 ng). Does dietary KCl prevent NaCl hypertension in S rats partly by abolishing these hyperactive central nervous system (CNS) pressor responses? The effect of potassium-loading on CNS pressor responses was studied in S rats on a low (0.3%) NaCl diet. Drinking a 2% KCl solution reduced the CNS pressor responses in S rats to both AII and hypertonic saline by 44% (p less than 0.025) and brought them down almost as low as in R rats. KCl added to the low NaCl dry diet also decreased the CNS pressor responses in S rats to AII and to hypertonic saline by 39% (p less than 0.01) and 59% (p less than 0.02) respectively. K-citrate added to the low NaCl diet was generally as effective as KCl in reducing CNS pressor responses. K-citrate reduced the angiotensin pressor response by 44% (p less than 0.001) and the hypertonic saline pressor response by 46% (p less than 0.05). Thus, potassium feeding greatly diminished the hyperactive CNS pressor responses in S rats. This CNS action may well explain a good part of the protective effect of KCl against NaCl hypertension in S rats.


Understanding Patient Attitudes Toward Multifocal Intraocular Lenses in Online Medical Forums Through Sentiment Analysis.
Multifocal intraocular lens implants (IOLs) are a premium option for cataract surgery which patients may purchase to achieve improved spectacle-independence for near vision but may have trade-offs with visual quality. We demonstrate the use of sentiment analysis to evaluate multifocal lenses discussed on MedHelp, a leading online health forum. A search for "multifocal IOL" was performed on MedHelp.org on November 1, 2016, yielding relevant patient posts. Sentiment analysis was performed using IBM's Watson, which extracted 30,066 unique keywords and their associated sentiment scores from 7495 posts written by 1474 unique patient users. Keywords associated with monovision, monofocal, and toric lenses had positive mean sentiment, significantly higher than for keywords associated with multifocals, which had negative mean sentiment (p < 0.001, ANOVA). Many keywords represented complaints and were associated with negative sentiment, including glare, halo, and ghosting. Sentiment analysis can provide insights into patient perspectives towards multifocal lenses by interpreting online patient posts.


Prognostic Value of XIAP Level in Patients with Various Cancers: A Systematic Review and Meta-Analysis.
Background: X-linked inhibitor of apoptosis protein (XIAP) plays an important role in cancer pathogenesis, which has been found to be overexpressed in multiple human cancers and associated with survival rates. Herein, we performed a meta-analysis to explore the predictive value of XIAP level in patients with various solid tumors. Methods: Relevant articles exploring the relationship between XIAP expression and survival of cancer patients were retrieved in PubMed, PMC, EMBASE and Web of Science published from 2001 to 2018. The combined hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the significance. Results: A total of 6554 patients from 40 articles were included in this meta-analysis. It was shown in 37 studies with 4864 cases that the over-expression of XIAP was associated with poorer overall survival (OS) (combined HR=1.61, 95% CI: 1.33-1.96). Meanwhile, 8 studies with 1862 cases revealed that elevated XIAP level predicted shorter disease-free survival (DFS) (HR=2.17, 95% CI: 1.03-4.59). Subgroup analyses showed that higher XIAP detection was related to worse OS in gastric cancer (HR=1.42, 95% CI: 1.18-1.72) and head and neck cancer (HNC) (HR=2.97, 95% CI: 1.97-4.47). Conclusion: Our results suggested that elevated XIAP level seemed to represent an unfavorable prognostic factor for clinical outcomes in cancer patients. However, there were limited studies describing the association between XIAP expression and clinical prognosis in each different type of tumors. Therefore, concrete roles of XIAP in various cancers need to be further explored.


Alzheimer's protective A2T mutation changes the conformational landscape of the Aβ₁₋₄₂ monomer differently than does the A2V mutation.
The aggregation of amyloid-β (Aβ) peptides plays a crucial role in the etiology of Alzheimer's disease (AD). Recently, it has been reported that an A2T mutation in Aβ can protect against AD. Interestingly, a nonpolar A2V mutation also has been found to offer protection against AD in the heterozygous state, although it causes early-onset AD in homozygous carriers. Since the conformational landscape of the Aβ monomer is known to directly contribute to the early-stage aggregation mechanism, it is important to characterize the effects of the A2T and A2V mutations on Aβ₁₋₄₂ monomer structure. Here, we have performed extensive atomistic replica-exchange molecular dynamics simulations of the solvated wild-type (WT), A2V, and A2T Aβ₁₋₄₂ monomers. Our simulations reveal that although all three variants remain as collapsed coils in solution, there exist significant structural differences among them at shorter timescales. A2V exhibits an enhanced double-hairpin population in comparison to the WT, similar to those reported in toxic WT Aβ₁₋₄₂ oligomers. Such double-hairpin formation is caused by hydrophobic clustering between the N-terminus and the central and C-terminal hydrophobic patches. In contrast, the A2T mutation causes the N-terminus to engage in unusual electrostatic interactions with distant residues, such as K16 and E22, resulting in a unique population comprising only the C-terminal hairpin. These findings imply that a single A2X (where X = V or T) mutation in the primarily disordered N-terminus of the Aβ₁₋₄₂ monomer can dramatically alter the β-hairpin population and switch the equilibrium toward alternative structures. The atomistically detailed, comparative view of the structural landscapes of A2V and A2T variant monomers obtained in this study can enhance our understanding of the mechanistic differences in their early-stage aggregation.


Effects of serum irisin, neuregulin 4, and weight management on obese adolescent girls with polycystic ovary syndrome.
The study is aimed at investigating the association of serum irisin, neuregulin 4 (NRG4), and anti-müllerian hormone (AMH) with adolescent obesity with polycystic ovary syndrome (PCOS) and the efficacy of weight management interventions. Serum levels of irisin, NRG4, AMH, sex steroid hormone, body mass index (BMI), serum insulin, and C-peptide were measured in 52 obese adolescent girls with PCOS (PCOS group) and 43 obese adolescent girls without PCOS (non-PCOS group). The levels of AMH, NRG4, serum irisin, sex steroid hormones, BMI, serum insulin, and C-peptide were evaluated in obese PCOS girls before and after one year weight management. The levels of AMH, serum insulin, NRG4, and total testosterone of PCOS group were significantly higher than those of non-PCOS group. On the contrary, serum irisin and serum C-peptide in PCOS group were significantly lower than that in non-PCOS group. The levels of fat mass, percent body fat, total testosterone, AMH, NRG4, and serum insulin in the obese girls with PCOS showed significant decreases compared with before weight management intervention. On the contrary, after one year of body weight management intervention, serum irisin and serum C-peptide was significantly increased. Adolescent obesity complicated with PCOS is significantly associated with glucose and lipid metabolism and sex steroid hormone disorders, but the exact pathophysiological and clinical features are highly variable. Weight management intervention can significantly improve the clinical symptoms and hematological indicators, serum irisin and NRG4 can be used as two essential biomarkers for evaluating weight management.


Comfrey root: from tradition to modern clinical trials.
Comfrey (Symphytum officinale L.) has been used over many centuries as a medicinal plant. In particular, the use of the root has a longstanding tradition. Today, several randomised controlled trials have demonstrated the efficacy and safety. Comfrey root extract has been used for the topical treatment of painful muscle and joint complaints. It is clinically proven to relieve pain, inflammation and swelling of muscles and joints in the case of degenerative arthritis, acute myalgia in the back, sprains, contusions and strains after sports injuries and accidents, also in children aged 3 years and older. This paper provides information on clinical trials, non-interventional studies and further literature published on comfrey root till date.


Skin bioelectronics towards long-term, continuous health monitoring.
Skin bioelectronics are considered as an ideal platform for personalised healthcare because of their unique characteristics, such as thinness, light weight, good biocompatibility, excellent mechanical robustness, and great skin conformability. Recent advances in skin-interfaced bioelectronics have promoted various applications in healthcare and precision medicine. Particularly, skin bioelectronics for long-term, continuous health monitoring offer powerful analysis of a broad spectrum of health statuses, providing a route to early disease diagnosis and treatment. In this review, we discuss (1) representative healthcare sensing devices, (2) material and structure selection, device properties, and wireless technologies of skin bioelectronics towards long-term, continuous health monitoring, (3) healthcare applications: acquisition and analysis of electrophysiological, biophysical, and biochemical signals, and comprehensive monitoring, and (4) rational guidelines for the design of future skin bioelectronics for long-term, continuous health monitoring. Long-term, continuous health monitoring of advanced skin bioelectronics will open unprecedented opportunities for timely disease prevention, screening, diagnosis, and treatment, demonstrating great promise to revolutionise traditional medical practices.


The influence of competing perceptual and motor priors in the context of the size-weight illusion.
When lifting objects of identical mass but different sizes, people perceive the smaller objects as weighing more than the larger ones (the 'size-weight' illusion, SWI). While individual's grip and load force rates are rapidly scaled to the objects' actual mass, the magnitude of the force used to lift these SWI-inducing objects is rarely discussed. Here, we show that participants continue to apply a greater loading force to a large SWI-inducing cube than to a small SWI cube, lift after lift. These differences in load force persisted long after initial errors in grip and load force rates had been corrected. Interestingly, participants who showed the largest illusion made the smallest errors in load force. This unexpected relationship suggests that the motor system is consistently biased toward the expectations of heaviness for a particular stimulus in a Bayesian fashion, and that this loading error is subsequently reduced by SWI perceptual errors in the opposite direction.


Disparities in Smokefree and Vapefree Home Rules and Smokefree Policy Attitudes Based on Housing Type and Cigarette Smoking Status, United States, 2019.
This study examined variations in cigarette smoking status, home smoking and vaping rules, and attitudes toward smoking rules among U.S. adults. We analyzed data from the 2019 U.S. Census Bureau's Current Population Survey Supplements (n = 40,296 adults) and calculated weighted prevalence estimates of adult cigarette smoking based on housing type. In 2019, multi-unit housing (MUH) residents who currently smoked were predominantly residents of privately rented housing (66.9%), followed by privately owned (17.6%) and public housing (15.5%). MUH residents who currently smoked had the highest proportions of allowing smoking (26.7%) or vaping (29.1%) anywhere inside their homes and were least likely to support rules allowing smoking inside all MUH apartments or living areas. In the adjusted models, MUH residents with a current smoking status were 92% less likely to have a complete smoking ban. More than one in four MUH residents with a current smoking status allowed all smoking inside the home and supported allowing smoking inside all MUH apartment or living areas, reinforcing how MUH residents may be at higher risk of experiencing secondhand smoke or aerosol exposure, or incursions within their places of residence. Our results can inform the development, implementation, and sustainment of strategies to reduce exposures from tobacco and nicotine products in all living environments.


Kaempferol alleviates ox-LDL-induced apoptosis by up-regulation of autophagy via inhibiting PI3K/Akt/mTOR pathway in human endothelial cells.
Oxidized low-density lipoprotein (ox-LDL) has been reported to induce apoptosis of endothelial cells (ECs) and contribute to the progression of atherosclerosis. Kaempferol has been shown to possess antiatherosclerotic effect. The aim of the present study was to evaluate the effect of kaempferol on ox-LDL-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and its possible molecular basis. The results showed that kaempferol alleviated ox-LDL-induced apoptosis. Kaempferol increased the ratio of LC3-II/I and beclin-1 level in ox-LDL-induced HUVECs. Moreover, the expression of p-Akt and p-mTOR was down-regulated after treatment with kaempferol in ox-LDL-treated HUVECs, which is similar to the effect of PI3K inhibitor (LY294002) or mTOR inhibitor [rapamycin (RAP)]. Besides, autophagy induced by kaempferol was enhanced by LY294002 or RAP, while kaempferol-induced autophagy was attenuated with insulin treatment, the activator of PI3K/Akt/mTOR pathway. Furthermore, insulin also abated the effect of kaempferol on cell viability and apoptosis in ox-LDL-induced HUVECs. The results indicated that kaempferol alleviated ox-LDL-induced cell apoptosis by up-regulation of autophagy via inhibiting PI3K/Akt/mTOR pathway in human ECs.


An alternative synthesis of Vandetanib (Caprelsa™) via a microwave accelerated Dimroth rearrangement.
Vandetanib is an orally available tyrosine kinase inhibitor used in the treatment of cancer. The current synthesis proceeds via an unstable 4-chloroquinazoline, using harsh reagents, in addition to requiring sequential protection and deprotection steps. In the present work, use of the Dimroth rearrangement in the key quinazoline forming step enabled the synthesis of Vandetanib in nine steps (compared to the previously reported 12-14).


Long-term biochemical response after bisphosphonate therapy in Paget's disease of bone. Proposed intervals for monitoring treatment.
To monitor the long-term evolution of Paget's disease activity after treatment with tiludronate by using serum total alkaline phosphatase (TAP) and more sensitive markers such as bone alkaline phosphatase (BAP), procollagen type I N propeptide (PINP) and urinary N-terminal cross-linking telopeptide of type I collagen (NTX); to analyse the predictors of long-term response to therapy; and to study the most appropriate intervals of time for monitoring the response to therapy. Thirty-two patients with Paget's disease were included in the study. All received 400 mg of oral tiludronate daily for 3 months. A total of 21 patients completed the study. In these patients, serum TAP, BAP and PINP and urinary NTX were measured at baseline and at 1, 6, 12 and 24 months after discontinuation of therapy. Quantitative bone scintigraphy was performed at baseline and at 6 and 24 months after the end of treatment, obtaining a scintigraphic activity index (SAI). Patients were classified into two groups depending on the long-term response to treatment: Group 1, patients who presented a persistent and significant decrease in disease activity at this time, n = 12 (57%) and Group 2, patients who presented a relapse in the activity of the disease at 24 months after treatment, n = 9 (43%). The relapse of disease activity was defined as a significant increase of SAI (>13%) between 6 and 24 months after the end of treatment, whereas the response to therapy was defined as a significant reduction in SAI (>13%) at 6 months after the end of treatment. In addition, these results were compared with the biochemical evolution of bone markers. Biochemical markers and SAI decreased significantly after therapy and the nadir response was observed at 6 months. At this time 100% of patients responded to therapy. The persistent long-term response was associated with lower baseline indices of bone turnover (serum BAP<60 ng/ml or TAP<600 IU/l). The intervals of time for monitoring depended on the marker used: no patient from Group 1 presented a biochemical relapse in serum TAP at 1 and 2 yr after the end of treatment whereas 33 and 45% of these patients showed relapsed serum BAP at these time points. Moreover, all patients from Group 2 presented a biochemical relapse of serum BAP at 2 yr whereas in only 33% of these patients did serum TAP relapse at this time. Most of the Pagetic patients treated with tiludronate presented a long-term response, which persisted 2 yr after the end of treatment. The nadir response to treatment was observed 6 months after discontinuation of therapy whereas the relapse of disease activity was already observed 1 yr after the end of therapy and depended on both the baseline disease activity and the bone marker used in the evaluation.


NLM Medical Library Resource Improvement Grant Program: an evaluation.
The Extramural Programs, NLM, undertook a staff study to evaluate the Medical Library Resource Improvement Grant Program in order to determine impact on hospital library development and to assess factors significant to regional medical library (RML) network development. Initiated in fiscal year 1971, the improvement grant program provides one-year, one-time grant awards of a maximum of $3,000 to assist in establishing a basic collection of books, journals, and other health science information resources for community hospitals and comparable health facilities. Applicants who received grant awards were compared to applicants who did not receive awards and to nonapplicants, using nine dependent variables, four independent variables, and responses to an RML questionnaire. Results show that the applicants who received awards outperformed the other groups, and that the improvement grant program has been successful in stimulating library development. As a result of this study, the improvement grant program will be modified to support consortium arrangements as well as individual institutions, and to extend the period of grant support to two years. Future grant support will be a maximum of $4,000 in the first year, and up to $3,000 with a provision of $1,000 in matching funds from the grantee in the second year.


Preparative purification of the rat mast cell chymase: characterization and interaction with granule components.
The rat mast cell granule chymotrypsinlike enzyme was purified to homogeneity from 1 M NaCl solubilized membrane and granule-rich fractions of concentrated rat peritoneal mast cells by a preparative technique utilizing chromatography on Dowex 1, filtration on Sephadex G-75, and affinity chromatography with D-tryptophan methyl ester. Acid disk gel electrophoresis of the purified chymase disclosed a single stained band with activity being eluted from a replicate sliced gel in the same region. SDS-polyacrylamide gel electrophoresis of purified protein gave a single stained band that did not change in position with reduction and alkylation. Mast cell chymase is thus a cationic protein of 25,000 mol wt composed of a single polypeptide chain. The apparent K(m) of the chymase for BTEE was 1.5 x 10(-3) M and the V(max) was 67.8 mumol/min per mg. The enzyme was inhibited by TPCK and not by TLCK. The chymase complexed with native macromolecular rat mast cell heparin in molar ratios of 12:1 and 16:1, and complete heparin uptake occurred at a 40:1 ratio of chymase to heparin. Chymase activity was partially masked by combination with heparin in the isolated granule or experimental chymase-heparin complex, and soluble purified chymase was inhibited by concentrations of 5-HT comparable to those present in mast cells. It is therefore possible that the active site of chymase in the mast cell granule is largely masked by the combined effects of macromolecular heparin and 5-HT.


Spinal epidural abscess associated with epidural anesthesia: gadolinium-enhanced magnetic resonance imaging and its usefulness in diagnosis and treatment.
A case of spinal epidural abscess following epidural anesthesia is described. Gadolinium-enhanced magnetic resonance images were essential in diagnosis of the abscess without frank pus formation, in defining the extension of the infection, and in assessing the therapeutic effect. The patient was successfully treated non-operatively before neurological symptoms developed and full recovery was achieved.


Laminin and heparan sulfate proteoglycan mediate epithelial cell polarization in organotypic cultures of embryonic lung cells: evidence implicating involvement of the inner globular region of laminin beta 1 chain and the heparan sulfate groups of heparan sulfate proteoglycan.
The extracellular matrix and in particular the basement membrane (BM) play an important role in the induction of organotypic rearrangement of cells in culture. This process involves cell aggregation, sorting into epithelial and mesenchymal components, epithelial cell polarization, and lumen formation. In this study, a combination of laminin (LM) and heparan sulfate proteoglycan (HSPG), two major BM constituents, induced organotypic rearrangement of embryonic mouse lung cells. In the absence of LM/HSPG supplementation, the cells sorted into epithelial and mesenchymal compartments but epithelial cell polarization and lumen formation did not occur. Neither LM nor HSPG alone could trigger this process. Synthetic peptide F-9, representing an amino acid sequence from the inner globular region of the laminin beta1 chain (RYVVLPRPVCFEKGMNYTVR) induced organotypic cell rearrangement when substituted for LM. Exogenous LM as well as peptide F-9 were localized at the epithelial-mesenchymal interface of organotypic cultures, where a BM-like structure is formed de novo. Organotypic cell rearrangement was blocked by heparin, heparan sulfate, or antibodies against peptide F-9. Binding assays indicated that peptide F-9 interacts with HSPG but not with LM or type IV collagen. Preincubation of embryonic lung cells with peptide F-9 resulted in a significant increase in cell attachment to HSPG but not to other major BM constituents. These findings suggest that the interaction between LM and BM HSPG is critical for the development of epithelial cell polarization and lumen formation. This interaction occurs at the epithelial-mesenchymal interface and is mediated by a site in the LM molecule represented by peptide F-9 and the heparan sulfate groups of HSPG.


Laparoscopic splenectomy in beta-thalassemia major patients. Advantages and disadvantages.
Splenectomy is indicated in patients with thalassemia major when they develop hypersplenism with subsequent need for increased transfusions. Extreme splenomegaly is considered a restrictive factor for laparoscopic splenectomy in these patients. Laparoscopic splenectomy was undertaken in 12 beta-thalassemia major patients with massive splenomegaly. The devascularization of the organ was performed with serial ligations of the splenic vessels starting from the lower pole of the organ. The spleen was extracted from the abdominal cavity through a 5-cm incision in the left iliac fossa, which incorporated two port sites. The procedure was concluded laparoscopically in 10 cases, while two patients were converted due to difficulty in controlling bleeding from branches of the splenic vein. The patients tolerated the procedure well and had a postoperative hospital stay of 3-6 days. From our limited initial experience it seems that laparoscopic splenectomy in the difficult setting of thalassemia major patients is feasible, but extreme care is required in order to avoid hemorrhagic complications.


Effect of pregnancy on overall survival after the diagnosis of early-stage breast cancer.
To evaluate the impact of subsequent pregnancy on the prognosis of patients with early breast cancer. One hundred eight patients who became pregnant after diagnosis of early-stage breast cancer were identified in institutions participating in International Breast Cancer Study Group (IBCSG) studies. Fourteen had relapse of breast cancer before their first subsequent pregnancy. The remaining 94 patients (including eight who relapsed during pregnancy) formed the study group reported here. A comparison group of 188 was obtained by randomly selecting two patients, matched for nodal status, tumor size, age, and year of diagnosis from the IBCSG database, who were free of relapse for at least as long as the time between breast cancer diagnosis and completion of pregnancy for each pregnant patient. Survival comparison used Cox proportional hazards regression models. Overall 5- and 10-year survival percentages (+/- SE) measured from the diagnosis of early-stage breast cancer among the 94 study group patients were 92% +/- 3% and 86% +/- 4%, respectively. For the matched comparison group survival was 85% +/- 3% at 5 years and 74% +/- 4% at 10 years (risk ratio, 0.44; 95% confidence interval, 0.21 to 0.96; P =.04). Subsequent pregnancy does not adversely affect the prognosis of early-stage breast cancer. The superior survival seen in this and other controlled series may merely reflect a healthy patient selection bias, but is also consistent with an antitumor effect of the pregnancy.


The Scope of Practice of an Embedded Pediatric Palliative Oncology Clinic.
Pediatric palliative care (PPC) improves end-of-life (EOL) outcomes for children with cancer. Though PPC visits are the 'intervention' in studies focused on EOL care, the content of PPC visits within pediatric oncology is poorly understood. This study aimed to understand the scope of PPC practice during visits for children with cancer and their families. This was a retrospective cohort study of patients 0-27 years with cancer seen in PPC clinic within an academic pediatric oncology center between 2017-2022. During each PPC visit, documenting providers chose the domains discussed or managed (Goals of Care, Symptom Management, and Care Coordination with respective subdomains). Data was abstracted from the electronic health record, PPC clinic database, and Cancer Registry. The differences in frequency and addressed domains were analyzed by demographics, visit type, diagnosis group, and proximity to EOL. Across 351 patients, 1,919 outpatient PPC visits occurred. Median domains were higher in visits <90 days vs. 91+ days from EOL (12.0 vs. 10.0; p<0.0001); pain and hospice collaboration were particularly discussed closer to EOL. Psychological symptoms like anxiety (30.7% vs. 21.1%; p<0.001) were addressed more in follow-ups than initial visits. Compared to brain tumor or leukemia/lymphoma visits, solid tumor visits addressed more symptom management subdomains, especially pain (79.9%; p<0.0001). The scope of PPC practice is broad and varied. Each visit encompasses many subdomains, the most common being care coordination with oncology teams and helping patients/families cope with the disease. More domains were addressed in solid tumor visits and near EOL.


Congenital torticollis and saccular dysfunction: a case report.
This is the first report, to our knowledge, of a child with torticollis due to saccular dysfunction. An 18-month-old infant with torticollis was referred for postural imbalance and observed rotary nystagmus. The infant had undergone physical therapy treatment of left torticollis for nearly 15 months. Cervical vestibular evoked myogenic potentials (cVEMPs) were recorded to assess saccular function and caloric stimulation and positional and rotational testing were performed to evaluate other vestibular receptors. The child demonstrated abnormal cVEMP findings, with a low-amplitude response on the left, which indicated left-sided saccular dysfunction. The patient's rotary-torsional nystagmus suggested positional vertigo secondary to abnormal saccular function. This case highlights that saccular dysfunction should be considered when timely resolution of congenital torticollis is not obtained with physical therapy. Early detection of abnormal saccular function in infants and young children with CPT is necessary to ensure appropriate intervention. Further study needs to be done to confirm our findings.