Incident users of antipsychotic agents and future use of cholesterol-lowering drugs: an observational, pharmacoepidemiologic study.
Antipsychotic agents have serious metabolic adverse effects, among them dyslipidemia, which may necessitate secondary prophylaxis with cholesterol-lowering drugs. Second-generation antipsychotics (SGAs), particularly clozapine and olanzapine, are known to confer a higher risk of metabolic adverse effects than first-generation antipsychotics (FGAs). However, little is known regarding the real-life number of antipsychotic-treated patients receiving statins. By extracting data from the Norwegian prescription database, all patients 18-69 years old that started treatment with an antipsychotic during 2004-2012 formed the basis for analysis (n = 301,713). The primary outcome measure was the proportion of FGA and SGA users prescribed with cholesterol-lowering agent during the same period. We used Cox proportional hazards regression to evaluate the risk of redeeming a cholesterol-lowering drug for formerly antipsychotic drug-naive patients (n = 147,218). Statin prescription rates in patients receiving antipsychotic agents were lower (5.3%) than comparable rates in studies covering the general population (34%) and lower than would be expected based on the recognized negative impact of antipsychotics on serum lipids. Statin prescription rates were affected by patient age, antipsychotic dose, and the number of antipsychotic agents prescribed, but rates were only 5% elevated in patients receiving SGAs compared to patients receiving FGAs (P = .048). Our results may support the notion that patients treated with antipsychotic agents receive suboptimal care with regard to metabolic adverse effects.


Methylation status of genes in non-neoplastic mucosa from patients with ulcerative colitis-associated colorectal cancer.
Patients with ulcerative colitis (UC) are at increased risk for developing colorectal cancer (CRC). Surveillance in this at-risk population remains challenging. We assessed the methylation status of genes in the non-neoplastic mucosa of UC-CRC patients and controls to identify potential biomarkers of CRC. We evaluated the methylation status of 10 genes (p16, p14, runt-related transcript factor-3 (RUNX3), cyclooxygenase-2 (COX-2), E-cadherin, methylated-in-tumor-1 (MINT1), MINT31, HPP1, estrogen receptor, SLC5A8) in UC-CRC tumors and non-neoplastic sections from both UC-CRC cases and UC controls (n=114 for each) using methylation-specific PCR. Amplification was successful for 96 UC controls, 83 tumors, and 66 non-adjacent, non-neoplastic samples. The prevalence of methylation was significantly greater in UC-CRC tumors for p16, RUNX3, MINT1, MINT31, and HPP1. Methylation of COX-2 and E-cadherin was greater in UC controls than in tumors. Univariate testing of these genes using non-adjacent, non-neoplastic sections from UC-CRC cases indicated that associations between p16, RUNX3, MINT1, MINT31, E-cadherin, and COX-2 and UC-CRC remained significant. In multivariable analysis of the six genes, only RUNX3, MINT1, and COX-2 remained significantly associated with the UC-CRC cases (odds ratio=12.6, 9.0, and 0.2, respectively). The results remained unaffected by the presence of PSC or severity of inflammation. Logistic regression modeling with the three genes showed interactions that increased the odds ratio for each gene. RUNX3, MINT1, and COX-2 are potential biomarkers for detecting the presence of CRC in patients with UC. These genes should be evaluated as biomarkers for colorectal dysplasia.


Combination of arginine, glutamine, and omega-3 fatty acid supplements for perioperative enteral nutrition in surgical patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST): A prospective, randomized, double-blind study.
Perioperative enteral nutrition (EN) enriched with immune-modulating substrates is preferable for patients undergoing major abdominal cancer surgery. In this study, perioperative EN enriched with immune-modulating nutrients such as arginine, glutamine, and omega-3 fatty acids was evaluated for its anti-inflammatory efficacy in patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST) receiving curative surgery. This prospective, randomized, double-blind study recruited 34 patients with gastric adenocarcinoma or gastric GIST undergoing elective curative surgery. These patients were randomly assigned to the study group, receiving immune-modulating nutrient-enriched EN, or the control group, receiving standard EN from 3 days before surgery (preoperative day 3) to up to postoperative day 14 or discharge. Laboratory and inflammatory parameters were assessed on preoperative day 3 and postoperative day 14 or at discharge. Adverse events (AEs) and clinical outcomes were documented daily and compared between groups. No significant differences were observed between the two groups in selected laboratory and inflammatory parameters, or in their net change, before and after treatment. AEs and clinical outcomes, including infectious complications, overall complications, time to first bowel action, and length of hospital stay after surgery, were comparable between treatment groups (all P > 0.05). Immune-modulating nutrient-enriched EN had no prominent immunomodulation effect compared with that of standard EN.


Mount st. Helens ash from the 18 may 1980 eruption: chemical, physical, mineralogical, and biological properties.
Samples of ash from the 18 May 1980 eruption of Mount St. Helens were collected from several locations in eastern Washington and Montana. The ash was subjected to a variety of analyses to determine its chemical, physical, mineralogical, and biological characteristics. Chemically, the ash samples were of dacitic composition. Particle size data showed bimodal distributions and differed considerably with location. However, all samples contained comparable amounts of particles less than 3.5 micrometers in diameter (respirable fraction). Mineralogically, the samples ranged from almost totally glassy to almost totally crystalline. Crystalline samples were dominated by plagioclase feldspar (andesine) and orthopyroxene (hypersthene), with smaller amounts of titanomagnetite and hornblende. All but one of the samples contained from less than 1 percent to 3 percent free crystalline silica (quartz, trydimite, or cristobalite) in both the bulk samples and 1 to 2 percent in the fractions smaller than 3.5 micrometers. The long-lived natural radionuclide content of the ash was comparable to that of crustal material; however, relatively large concentrations of short-lived radon daughters were present and polonium-210 content was inversely correlated with particle size. In vitro biological tests showed the ash to be nontoxic to alveolar macrophages, which are an important part of the lungs' natural clearance mechanism. On the basis of a substantial body of data that has shown a correlation between macrophage cytotoxicity and fibrogenicity of minerals, the ash is not predicted to be highly fibrogenic.


Long-term clinical and angiographic follow-up results of the dual-layer flow diverter device (FRED) for the treatment of intracranial aneurysms in a multicenter study.
Our aim was to determine the long-term safety and efficacy of the Flow Re-Direction Endoluminal Device (FRED) in this multicenter study with prospective design. This study included 136 consecutive patients with 155 aneurysms treated between March 2013 and June 2016 in 10 centers. Twenty-two (16.2%) patients presented with rupture of the index aneurysm. Large/giant aneurysms comprised 1/3 of the cohort. Adjuvant coil use during the treatment was 15.5%. The effectiveness measure in the study was the percentage of aneurysms with stable occlusion at follow-up. Vascular imaging follow-up was performed at least once in 131/136 (96.3%) patients with 148/155 (95.5%) aneurysms up to 75 months (mean: 37.3 months; median: 36 months according to latest follow-up), and 102/155(65.8%) aneurysms in 90/136 (66.2%) patients had ≥ 24-month control. According to the latest controls, the overall stable occlusion rate was 91.9% (95% CI, 87.5 to 96.3%). Three out of 148 aneurysms with follow-up were retreated (2%, 95% CI 0.0 to 4.3%). Adverse events were noted in 19/136 (14%, 95% CI, 9 to 21%) patients with a morbidity of 1.5% (95% CI, 0.0 to 3.5%). Mortality was 1/136 (0.7%, 95% CI, 0.02 to 2.2%) and was unrelated to aneurysm treatment. In-stent stenosis (ISS) was detected in 10/131 of the patients with follow-up (7.6%, 95% CI; 3.1 to 12.2%), only one being symptomatic. No adverse events have occurred in any of the patients with follow-up after 24 months, except the one resulting from ISS. In the treatment of cerebral aneurysms which were candidates for flow diversion technique, this study showed long-term efficacy of FRED with good safety and occlusion rates.


Dark solitons with Majorana fermions in spin-orbit-coupled Fermi gases.
We show that a single dark soliton can exist in a spin-orbit-coupled Fermi gas with a high spin imbalance, where spin-orbit coupling favors uniform superfluids over nonuniform Fulde-Ferrell-Larkin-Ovchinnikov states, leading to dark soliton excitations in highly imbalanced gases. Above a critical spin imbalance, two topological Majorana fermions without interactions can coexist inside a dark soliton, paving a way for manipulating Majorana fermions through controlling solitons. At the topological transition point, the atom density contrast across the soliton suddenly vanishes, suggesting a signature for identifying topological solitons.


Dissociation in plasma renin and adrenal ANG II and aldosterone responses to sodium restriction in rats.
In rats, plasma renin activity (PRA) increases sharply, reaching a plateau within hours of sodium restriction. Plasma aldosterone increases gradually, not reaching a plateau for 1-2 days. To determine whether this dissociation is secondary to the time needed to modify adrenal sensitivity to angiotensin II (ANG II) and to assess the role of locally produced ANG II in this process, rats were salt restricted for 0-120 h. Plasma hormone levels were assessed, adrenal ANG II was measured, and basal and ANG II (1 x 10(-8) M)-stimulated steroidogenesis were determined in vitro. Although PRA attained an elevated plateau within 8 h, plasma aldosterone did not peak until after 48 h of sodium depletion. The in vitro aldosterone sensitivity to exogenous ANG II was not apparent until rats had been salt restricted for 16 h. A plateau (4-fold increase above the ANG II response on high salt) was achieved between 24 and 48 h. Adrenal ANG II also exhibited a similar delayed response that correlates significantly with changes in aldosterone biosynthesis and late pathway activity. Thus the dissociation between PRA and plasma aldosterone may be secondary to a lag in the zona glomerulosa's (ZG) steroidogenic response to ANG II as well as a parallel lag in tissue ANG II production, suggesting that changes in tissue ANG II may mediate ZG sensitivity to ANG II during sodium deprivation.


Summarizing Implementation Support for School-Based COVID-19 Testing Programs in Southwest American Indian Communities.
American Indian communities have been disproportionately affected by the COVID-19 pandemic, with school closures exacerbating health and education disparities. Project SafeSchools' COVID-19 school-based testing program utilized federal and state funding to provide weekly pooled testing with follow-up rapid antigen testing to students and staff from the White Mountain Apache Tribe and Navajo Nation. The project provided partner schools with training and continual logistical and technical support to aid in school-based testing and adherence to state and local reporting requirements. Using the EPIS (Exploration, Preparation, Implementation, and Sustainment) framework, we identified facilitators and barriers to successful program function. While community support and buy-in were essential for successfully implementing school-based testing in these communities, communication, school staff turnover, and funding are among the most significant challenges. Community partnerships in American Indian communities involving schools and local health authorities can successfully implement testing protocols by remaining flexible and working together to maintain strong lines of communication.


Predicting blood pressure response after renal artery stenting.
Although technical success of renal artery stenting (RAS) is high and adverse events are infrequent, clinical success (improved blood pressure and renal function) and durability have been less predictable. Identifying those patients who will respond to RAS could improve overall outcomes of the procedure. This was a retrospective analysis of all patients who underwent RAS for treatment of renovascular hypertension (RVH) between 2001 and 2007 at Dartmouth-Hitchcock Medical Center. The primary outcome measure was blood pressure improvement or cure as judged by American Heart Association criteria. Estimated glomerular filtration rate (eGFR), number of antihypertensive medications, and survival were evaluated as secondary outcomes. Univariate and multivariate analyses were performed to identify factors associated with blood pressure improvement at the last follow-up. During the 6-year period, 129 patients (179 renal arteries) underwent stent placement for RVH. Procedural complications occurred nine patients (7.0%). Average length follow-up was 1.5 years. Follow-up data were obtained in 122 patients (95%). At last follow-up, there were significant improvements in systolic blood pressure (161 vs 144 mm Hg, P < .001), diastolic blood pressure (80 vs 73 mm Hg, P < .001), and number of antihypertensive medications (3.1 vs 2.8, P = .034). The eGFR was improved in 16% of patients, stable in 60%, and worse in 24%. By multivariate analysis, a baseline eGFR <40 mL/min/1.73 m2 (odds ratio, 1.6; 95% confidence interval [CI], 1.0-2.9; P = .02) and female gender (OR, 1.3; 95% CI, 1.0-2.1; P = .04) were independent predictors of failure to achieve blood pressure improvement. By 2 and 4 years of follow-up, sustained blood pressure improvement was present in 67% of patients with a baseline eGFR of > or = 40 mL/min/1.73 m2 and in 31% of patients with a baseline eGFR <40 mL/min/1.73 m2. During 2 years of follow-up, survival was similar between patients with sustained blood pressure response and those without. Patients treated for RVH who have a baseline eGFR of > or = 40 mL/min/1.73 m2 demonstrate a better response to RAS at each follow-up interval, with a significant difference at 2 to 4 years, compared with patients with an eGFR <40 mL/min/1.73 m2.


The timing of upper-layer neurogenesis is conferred by sequential derepression and negative feedback from deep-layer neurons.
The prevailing view of upper-layer (UL) neurogenesis in the cerebral cortex is that progenitor cells undergo successive rounds of asymmetric cell division that restrict the competence and production of UL neurons later in development. However, the recent discovery of UL fate-committed early progenitors raises an alternative perspective concerning their ontogeny. To investigate the emergence of UL progenitors, we manipulated the timing and extent of cortical neurogenesis in vivo in mice. We demonstrated that UL competence is tightly linked to deep-layer (DL) neurogenesis and that this sequence is determined primarily through derepression of Fezf2 by Foxg1 within a closed transcriptional cascade. We further demonstrated that the sequential acquisition of UL competence requires negative feedback, which is propagated from postmitotic DL neurons. Thus, neocortical progenitors integrate intrinsic and extrinsic cues to generate UL neurons through a system that controls the sequence of DL and UL neurogenesis and to scale the production of intracortical projection neurons based on the availability of their subcortical projection neuron counterparts during cortical development and evolution.


[Faculty development for clinicaI teachers in medicine].
Effective clinical teaching is an imperative of medical education. Clinical teachers and faculty development initiatives as well as Medical Schools, need to focus their efforts to pursue common outcomes: effective learning in students, future competent physicians and healthy patients. Excellence in quality of teaching needs scholars in education. To achieve this objective, institutions must recruit a core of medical faculty according to its mission, define the attributes and teaching competences, implement faculty development programs, and finally, support academic vitality. This article describes the three main issues of medical teaching: faculty, faculty development and its organization.


Leveraging Radiation-triggered Metal Prodrug Activation Through Nanosurface Energy Transfer for Directed Radio-chemo-immunotherapy.
Metal-based drugs currently dominate the field of chemotherapeutic agents; however, achieving the controlled activation of metal prodrugs remains a substantial challenge. Here, we propose a universal strategy for the radiation-triggered activation of metal prodrugs via nanosurface energy transfer (NSET). The core-shell nanoplatform (Ru-GNC) is composed of gold nanoclusters (GNC) and ruthenium (Ru)-containing organic-inorganic hybrid coatings. Upon X-ray irradiation, chemotherapeutic Ru (II) complexes were released in a controlled manner through a unique NSET process involving the transfer of photoelectron energy from the radiation-excited Ru-GNCs to the Ru-containing hybrid layer. In contrast to the traditional radiation-triggered activation of prodrugs, such an NSET-based system ensures that the reactive species in the tumor microenvironment are present in sufficient quantity and are not easily quenched. Additionally, ultrasmall Ru-GNCs preferably target mitochondria and profoundly disrupt the respiratory chain upon irradiation, leading to radiosensitization by generating abundant reactive oxygen species. Consequently, Ru-GNC-directed radiochemotherapy induces immunogenic cell death, resulting in significant therapeutic outcomes when combined with the programmed cell death-ligand 1 (PD-L1) checkpoint blockade. This NSET strategy represents a breakthrough in designing radiation-triggered nanoplatforms for metal-prodrug-mediated cancer treatment in an efficient and controllable manner.


Cross-sectional geometry, bone strength, and bone mass in the proximal femur in black and white postmenopausal women.
Osteoporosis is characterized by both a low bone mass and a disruption of the architectural arrangement of bone tissue, leading to decreased skeletal strength and increased fracture risk. Although there are well-known ethnic differences in bone mass and fracture risk, little is known about possible ethnic differences in bone structure. Therefore, we studied cross-sectional geometry in the hip in a sample of postmenopausal black and white women in order to investigate ethnic differences that might contribute to differences in bone strength and ultimately hip fracture risk. We recruited 371 postmenopausal black and white women who were entering the Women's Health Initiative (WHI) clinical trials in Detroit. Bone density measurements of the proximal femur were done by dual-energy X-ray absorptiometry (DXA) using a Hologic 1000 Plus bone densitometer. The DXA data were used for hip structure analysis, which treats the entire proximal femur as a continuous curved beam from the proximal shaft to the femoral neck. This permits the analysis of cross-sectional geometric properties in two narrow regions corresponding to thin (5 mm) cross-sectional slabs seen on edge. The results indicate significant ethnic differences in bone density, cross-sectional geometry, and dimensional variables. Specifically, the black women have a significantly higher bone density in both locations (10.1% and 4.1% for the neck and shaft, respectively); greater cross-sectional geometric properties in the neck (ranging from 6.1% to 11.6%), but a smaller endocortical diameter in the neck (3.6%). There are fewer significant differences in cross-sectional geometry in the shaft location. Our data suggest that the spatial distribution of bone is arranged in the femoral neck to resist greater loading in black women compared with white women.


Improved Opacification of a Suboptimally Enhanced Pulmonary Artery in Chest CT: Experience Using a Dual-Layer Detector Spectral CT.
The objective of our study was to evaluate the quality of virtual monoenergetic imaging (VMI) from dual-layer detector spectral CT and the effect of virtual monoenergetic images obtained at low energies on the detection of pulmonary embolism (PE) in patients with a suboptimally enhanced pulmonary artery on chest CT. Of 1552 consecutive chest CT examinations performed with dual-layer detector spectral CT using a routine protocol with a tube voltage of 120 kVp, 79 examinations with suboptimal enhancement of the pulmonary artery (i.e., mean attenuation of pulmonary artery ≤ 180 HU) were included. The mean attenuation of the pulmonary artery, noise, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) of virtual monoenergetic images obtained at 40-200 keV were compared with those of the conventional 120-kVp images. The virtual monoenergetic images with the best CNR were compared with the 120-kVp images with regard to subjective image quality and diagnostic accuracy for detecting PE. Sufficient attenuation of the pulmonary artery (> 180 HU) was obtained using VMI for 78 of the 79 examinations. The noise levels of the virtual monoenergetic images were gradually increased with decreasing energy level (i.e., kiloelectron volt setting). The CNR and SNR of virtual monoenergetic images at 40-65 keV were significantly higher (both, p < 0.001) than the CNR and SNR of the 120-kVp images. The CNR was the highest at 40 keV for all cases. Diagnostic accuracy for detecting PE was significantly higher for 40-keV images (reader 1: AUC = 0.992, p = 0.033; reader 2: AUC = 0.986, p = 0.043) than for 120-kVp images (reader 1, AUC = 0.911; reader 2, AUC = 0.933). The subjective quality was not different between these two images. In chest CT examinations in which the pulmonary artery is suboptimally enhanced, obtaining virtual monoenergetic images at a low energy setting using dual-layer detector spectral CT allows sufficient attenuation of the pulmonary artery to be achieved while preserving image quality and increasing diagnostic performance for detecting PE.


Educational programs in US medical schools, 1996-1997.
We use data from the 1996-1997 Liaison Committee on Medical Education Annual Medical School Questionnaire, which had a 100% response rate, to describe medical education programs in the United States. In the 1996-1997 academic year, there were 95 568 full-time medical school faculty members, a 4.5% increase from 1995-1996. In clinical departments, the largest increases were in emergency medicine (a 29% increase from 1995-1996) and family medicine (a 13% increase). Of all full-time faculty members in clinical departments, 76.9% have an MD or DO as the highest degree, 4.5% have both an MD and PhD, 13.9% have a PhD, and 4.7% have an academic or professional bachelor's or master's degree as their final degree. The total number of applicants for the class entering in 1996 was 46968 (0.8% increase from 1995), while the number of first-time applicants decreased 1% from 1995. First-year medical students who were members of underrepresented minority groups numbered 2236, a 4% decrease from 1995. In 1996-1997, the total number of medical students was 66712 (0.3% less than in 1995-1996). For students graduating during the 1995-1996 academic year, 13% took longer than 4 years to complete the program. There were 47 medical schools that reported that 1 or more hospitals used for required clinical clerkships had changed ownership, merged, or closed during 1996. Medical schools used an average of 6 (range, 1-36) hospitals for core clinical clerkship. Ninety-five schools required a passing grade on Step 1 of the US Medical Licensing Examination (USMLE) for promotion or graduation; 54 schools required a passing grade on Step 2 of the USMLE.


Can vaccines interact with drug metabolism?
Vaccines are safe and efficacious in reducing the burden of several serious infections affecting children and adults. Due to their efficacy, vaccines are often administered in patients with chronic diseases, likely to be under poly-therapy. Because of several case reports indicating changes in drug metabolism after vaccination, the hypothesis of an interaction between vaccines and specific drugs has been put forward. These interactions are conceivably of great concern, especially in patients treated with molecules characterised by a narrow therapeutic index. Herein, we review and systematise the available evidence on vaccine-drug interactions. The picture that emerges indicates that reduction in the activity of specific CYPs following vaccination may occur, most likely via interferon γ overproduction, and for specific drugs such as anticonvulsivant and theophylline may have significant clinical relevance. Clinical interaction between vaccines and drugs that are metabolised by cytochromes uninfluenced by INFγ levels, such as warfarin, are instead unlikely to happen. Further studies are however needed to gain a complete picture of vaccine-drug interactions and define their relevance in terms of possible negative clinical impact.


Restoration of femoral anatomy in TKA with unisex and gender-specific components.
Recent modifications in total knee prosthesis design theoretically better accommodate the anatomy of the female femur and thereby have the theoretical potential to improve clinical results in TKA by more accurately restoring femoral posterior condylar offset, reducing femoral notching, reducing femoral component flexion, and reducing component overhang. First, we radiographically evaluated whether a contemporary unisex prosthesis would accommodate female anatomy equally as well as male anatomy. Next, we radiographically evaluated female knees in which a gender-specific prosthesis was used. Pre- and postoperative radiographs of 122 knees (42 female unisex, 41 male unisex, 39 female gender-specific) were reviewed. In the unisex groups, there were no differences in femoral notching or femoral component flexion. Posterior femoral offset increased in both groups. However, femoral component overhang was worse in female knees (17%) than in male knees (0%). In the gender-specific female group, the incidence of component overhang was similar to that in the unisex female group. Unisex femoral components of this specific design do not equally match the native anatomy male and female knees. In some women, a compromise was required in sizing.


A higher PSA-density cut-off level in patients with intermediate PSA values for the early detection of prostate cancer.
The use of PSA-density (PSAD) as an indicator for prostate biopsy at intermediate PSA values has generated controversy. There are investigators who consider that the determination of PSAD is futile, and that it is better to do a prostate biopsy based on PSA values alone, TRUS (Transrectal Ultrasound) findings and/or DRE examinations. Asian countries, especially in the Far East, are considered to have a low incidence of prostate cancer (PCa). However, based on western references, we still measure PSA-density with a cut-off level of 0.15 to promote prostate biopsy in patients with intermediate PSA values (4.1-10.0 ng/ml). Our study aims to evaluate the usefulness of PSAD as an indication for biopsy in patients with intermediate serum PSA values. To evaluate the usefulness of this indicator, we conducted a retrospective study of 132 uncatheterized (to minimize potential bias) BPH and PCa cases that were hospitalized in our department between 1995-1997 (3 years). This group comprised 127 BPH and 5 PCa patients. Mean age was 66.1 +/- 7.69 years; mean PSA was 7.92 +/- 9.289 ng/ml; mean prostate volume was 54.1 +/- 26.72 cc; mean PSAD was 0.15 +/- 0.185. More specifically, there were 49 patients with intermediate PSA values (47 BPH & 2 PCa). The receiver operator characteristic (ROC) curve revealed an optimum cut-off level of 0.19. At this level of PSA density, the measured sensitivity was 100% with a specificity of 79%. We concluded that, in our uncatheterized patients (without retention) series, the PSAD cut-off level for prostate biopsy (0.19) was higher than that in the western world (0.12 or 0.15).


Postsynthetic and Selective Control of Lead Halide Perovskite Microlasers.
The control of photoluminescence and absorption of lead halide perovskites plays a key role in their applications in micro- and nano-sized light emission devices and photodetectors. To date, the wavelength controls of lead halide perovskite microlasers are mostly realized by changing the halide mixture in solution. Herein, we report the postsynthetic and selective control of the optical properties of lead halide perovskites with conventional semiconductor technology. By selectively exposing a CH3NH3PbBr3 microstructure with chlorine in inductively coupled plasma, we find that the wavelengths of absorption, photoluminescence, and laser emissions of exposed structures are blue-shifted around 50 nm. Most importantly, the device characteristics such as the photoluminescence intensities and laser thresholds are well maintained during the reaction process. We believe our finding will significantly boost the practical applications of lead halide perovskite based optoelectronics.


From allo- to egocentric spatial ability in early Alzheimer's disease: a study with virtual reality spatial tasks.
The ability to orient in space constitutes a main sign of cognitive impairment in Alzheimer's disease (AD). Presently, a peculiar aspect of topographical disorientation in AD linked with spatial reference frame congruence appears to have been only minimally investigated. We aim to study whether there is a decline in performing the allo- to egocentric translation of spatial knowledge during different types of wayfinding in AD patients. We introduced two virtual reality tasks, the VR-Maze and VR-Road Map tasks, in which we compared 26 AD and 26 healthy, elderly subjects. The results emphasize that there is a specific reduction in performing allo- to egocentric spatial tasks in AD, whereas this reduction is not as evident in equivalent allocentric spatial tasks. The data are consistent with the neurological results regarding the early degeneration of the hippocampus and retrosplenial cortex in AD, which underlies the ability to translate between these two reference frames.


Effect of ellagic acid and hydroxylated flavonoids on the tumorigenicity of benzo[a]pyrene and (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene on mouse skin and in the newborn mouse.
Ellagic acid, quercetin and robinetin were tested for their ability to antagonize the tumor-initiating activity of benzo[a]pyrene (B[a]P) and (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P 7,8-diol-9,10-epoxide-2), the ultimate carcinogenic metabolite of benzo[a]-pyrene. Ellagic acid, robinetin or quercetin (2500 nmol) had no tumor-initiating activity on mouse skin, but the topical application of 2500 nmol of ellagic acid 5 min before a tumor-initiating dose of 200 nmol of B[a]P 7,8-diol-9,10-epoxide-2 caused a 59-66% inhibition in the number of skin tumors per mouse that were observed after 15-20 weeks of promotion with 12-O-tetradecanoylphorbol-13-acetate. Similar treatment with 2500 nmol of robinetin or quercetin caused a statistically insignificant 16-24% inhibition in the tumor-initiating activity of 200 nmol of B[a]P 7,8-diol-9,10-epoxide-2 applied 5 min later. Treatment of mice with 2500 nmol of ellagic acid 5 min before the application of 50 nmol of B[a]P inhibited the mean number of skin tumors per mouse by 28-33% after 15-20 weeks of promotion, but these decreases were not statistically significant. Robinetin and quercetin had little or no effect on the tumor-initiating activity of B[a]P on mouse skin. Treatment of preweanling mice with 1/7, 2/7 and 4/7 of the total dose of ellagic acid (300 nmol), robinetin (1400 nmol), myricetin (1400 nmol) or quercetin (1400 nmol) i.p. on their first, eighth and fifteenth day of life, respectively, did not cause the formation of tumors in animals that were killed 9-11 months later. Similar treatment of preweanling mice with the above doses of the phenolic compounds 10 min before the i.p. injection of a total dose of 30 nmol of B[a]P 7,8-diol-9,10-epoxide-2 during the animal's first 15 days of life caused a 44-75% inhibition in the number of diol-epoxide-induced pulmonary tumors per mouse. Similar treatment with these plant phenols had little or no effect on B[a]P-induced pulmonary tumors.


Antixenosis and antibiosis of common beans to Thrips palmi Karny (Thysanoptera: Thripidae).
Antixenosis and antibiosis in the resistance of common beans (Phaseolus vulgaris L.) to the melon thrips, Thrips palmi Karny, were investigated under laboratory and field conditions. Experiments were conducted for four moderately resistant genotypes ('Brunca', BH-130, EMP 486, and FEB 115) in comparison with one susceptible genotype (APN 18). Multiple-choice tests recorded most thrips on EMP 486 and least on FEB 115. Dual-choice tests conducted in both laboratory and field confirmed the antixenotic effect of FEB 115 and the attractant effect of EMP 486 on thrips. These results demonstrate the significance of antixenosis in the resistance of common beans to T. palmi. Life-table studies showed significant differences in egg duration, immature and adult survivorship, female body length and longevity, daily oviposition rate, and total fecundity among the bean genotypes. The intrinsic rate of natural increase (r(m)) and its associated population parameters varied significantly with the bean genotype on which T. palmi cohorts were reared. Based on mean r(m) values, the five bean genotypes can be divided into two groups, with BH-130 and 'Brunca' being less favorable for the population growth of thrips than EMP 486 and FEB 115; the latter were comparable to the susceptible genotype APN 18. These life-table results indicate the role of antibiosis in enhancing the resistance of common beans to T. palmi.


A Novel Continuous Blood Pressure Estimation Approach Based on Data Mining Techniques.
Continuous blood pressure (BP) estimation using pulse transit time (PTT) is a promising method for unobtrusive BP measurement. However, the accuracy of this approach must be improved for it to be viable for a wide range of applications. This study proposes a novel continuous BP estimation approach that combines data mining techniques with a traditional mechanism-driven model. First, 14 features derived from simultaneous electrocardiogram and photoplethysmogram signals were extracted for beat-to-beat BP estimation. A genetic algorithm-based feature selection method was then used to select BP indicators for each subject. Multivariate linear regression and support vector regression were employed to develop the BP model. The accuracy and robustness of the proposed approach were validated for static, dynamic, and follow-up performance. Experimental results based on 73 subjects showed that the proposed approach exhibited excellent accuracy in static BP estimation, with a correlation coefficient and mean error of 0.852 and -0.001 ± 3.102 mmHg for systolic BP, and 0.790 and -0.004 ± 2.199 mmHg for diastolic BP. Similar performance was observed for dynamic BP estimation. The robustness results indicated that the estimation accuracy was lower by a certain degree one day after model construction but was relatively stable from one day to six months after construction. The proposed approach is superior to the state-of-the-art PTT-based model for an approximately 2-mmHg reduction in the standard derivation at different time intervals, thus providing potentially novel insights for cuffless BP estimation.


SOCS2 inhibits hepatoblastoma metastasis via downregulation of the JAK2/STAT5 signal pathway.
Metastasis of hepatoblastoma (HB) is a key factor that impairs the prognosis and treatment of children. The suppressor of cytokine signaling 2 (SOCS2) is a classical negative feedback protein that regulates cytokine signal transduction and has been known to be downregulated in several tumor, but the molecular mechanisms of its involvement in HB metastasis are unknown. We found that SOCS2 was a gene down-regulated in hepatoblastoma and associated with HB metastasis through bioinformatics. The qRT-PCR, Western blot and IHC showed that SOCS2 was significantly lower in HB tissues. Clinicopathological correlation analysis revealed that low expression of SOCS2 was significantly correlated with tumor metastasis (P = 0.046) and vascular invasion (P = 0.028), associated with poor prognosis. Overexpression of SOCS2 inhibited the migration and invasion of hepatoblastoma cells, while knockdown of SOCS2 expression promoted these malignant phenotypes. In vivo studies revealed overexpression of SOCS2 inhibited the formation of lung metastasis. Up-regulation of SOCS2 in HB cell inhibited EMT and JAK2/STAT5. Conversely, down-regulation of SOCS2 promoted EMT and JAK2/STAT5. The addition of the JAK2 inhibitor Fedratinib partially reversed the effects of si-SOCS2 on HB cells. SOCS2 may inhibit the migration and invasion of HB cells by inhibiting the JAK2/STAT5 signaling pathway. These results may provide guiding significance for the clinical treatment of HB.


The Dutch DAPP-BQ: improvements, lower- and higher-order dimensions, and relationship with the 5DPT.
After modifying 53 items in a previous Dutch translation of the Dimensional Assessment of Personality Pathology-Basic Questionnaire (DAPP-BQ; Livesley & Jackson, 2002), the present DAPP-BQ scales (with or without Self-Harm included) were subjected to a principal components analysis with oblimin or varimax rotation in a general population sample of 478 subjects, retaining four factors. All four (higherorder) factors (Emotional Dysregulation, Dissocial, Inhibition, and Compulsivity) proved identical to the factors originally derived in Canada, with Tucker coefficients of factor similarity approaching unity. Particularly the (unexpected) finding that the present Dutch version of the DAPP-BQ also resulted in an Inhibition factor (and not, like the former Dutch version, in an Intimacy Problems factor) was considered positive. In addition, a principal components analysis with oblimin rotation was conducted on the 282 items contained in the 18 DAPP-BQ scales, investigating the lower-order structure of the DAPP-BQ; in this case, 18 factors were retained. Although the structure originally derived by Livesley and colleagues could not be recovered completely, the degree of similarity was of such a magnitude that the 18 DAPP-BQ scales were considered to give a dependable account of the "true" lower-order structure of disordered personality. Moreover, based on the finding that the 18 scales are sufficiently reliable (Cronbach's alpha) and correlate as predicted in a subsample of 284 subjects with the normal personality scales of Van Kampen's 5DPT (or, Five-Dimensional Personality Test), the DAPP-BQ appears to be a valuable instrument.


Overexpression of a mutant form of TGFBI/BIGH3 induces retinal degeneration in transgenic mice.
Despite ubiquitous expression of the keratoepithelin (KE) protein encoded by the transforming growth factor beta induced/beta induced gene human clone 3 (TGFBI/BIGH3) gene, corneal dystrophies are restricted to the cornea, and no other tissues are affected. We investigated the role of TGFBI/BIGH3 in Groenouw corneal dystrophies by generating transgenic mice overexpressing TGFBI/BIGH3 containing the R555W mutation. Transgenic animals expressing the Groenouw mutation of human TGFBI/BIGH3 were generated using lentiviral vectors. The line expressed TGFBI/BIGH3 containing the R555W mutation under the control of the phosphoglycerate kinase (PGK) promoter. Expression of the transgene was monitored by Southern and western blotting and by RT-PCR. Electroretinogram analysis was performed and four mice were subjected to complete necroscopy. Transgene expression was observed in different organs although without specific expression in the cornea. The overall morphology of the transgenic animals was not severely affected by KE overexpression. However, we observed an age-dependent retinal degeneration both functionally and histologically. Female-specific follicular hyperplasia in the spleen and increased levels of lipofuscin in the adrenal gland were also seen in transgenic animals. Cellular degeneration in the retina of transgenic animals suggest that perturbation of the transforming growth factor beta (TGFbeta) family regulation may affect photoreceptor survival and may induce possible accelerated aging in several tissues. No corneal phenotype could be observed, probably due to the lack of transgene expression in this tissue.


Assisted reproductive technologies and metabolic syndrome complications: medico-legal reappraisal.
In the last 40 years, the number of elderly patients that require Assisted Reproductive Technologies (ART) has risen enormously, especially after heterolougus fertilization techniques have become available. In recent years, the incidence of peripartum cardiomyopathy (PPCM) has substantially grown, as a consequence of the combined effect of increased maternal age, consequent high prevalence of hypertension and metabolic syndrome (MS). That cohort of women may be exposed to a greater number of cardiac, obstetric and anesthesio-logical complications, therefore the incidence of medico-legal issues, litigation, liabilities and claims over the past years has significantly risen. Cardiovascular and hormonal changes during pregnancy can challenge even the healthiest of individuals, and in that pregnant population the risk is even greater. These patients should be monitored before the ART, during pregnancy, delivery and puerperium, to avoid heart failure, thrombotic problems, embolic complications, stroke and death. Management issues regarding pregnancy and delivery are elaborate, including anesthesia considerations. This new population of women needs an accurate cardiac risk stratification with a thorough cardiovascular history and examination, 12 lead ECG, and transthoracic echocardiogram. Therefore, a comprehensive multidisciplinary assessment and management can provide the best opportunity to improve maternal and neonatal outcomes.


Stein and Leventhal: 80 years on.
Eighty years ago a publication in the Journal proved to be seminal and transformative. The report by Irving Freiler Stein and Michael Leventhal titled, "Amenorrhea associated with polycystic ovaries," has proven to be a remarkably lasting and influential publication. The growth in related literature has been increasing exponentially: the 50 years between 1950 and 2000 saw a little more than 8000 publications on the topic, whereas the 15 year period between 2001 and 2015 (so far) has seen more than 20,000 related publications, a greater than 8-fold increase in the publication rate after 2000. As we commemorate the 80th anniversary year of the publication of the report by Stein and Leventhal, it is important to ask ourselves, "Was this publication truly as seminal as it is generally assumed to be? And why did it gain such a strong foothold on the medical psyche?" To the first question, a review of the antecedent medical literature makes it clear that the report of Drs Stein and Leventhal in 1935, although not flawless, was both seminal and transformative. In fact, it was the first report to describe a series of patients, rather than isolated cases, who demonstrated the triad of polycystic ovaries, hirsutism, and oligo/amenorrhea, connecting what had previously been disparate features of polycystic ovaries and menorrhagia, and hirsutism and oligo/amenorrhea. Second, the facts that Dr Stein and his collaborators were relatively prolific writers, consistent and clear in their message and descriptions; that a possible therapy (bilateral ovarian wedge resection) had been conveniently included in the report; and that the disorder was (is) relatively prevalent, permitted what would eventually be called the Stein-Leventhal syndrome to gain a strong foothold in contemporary medical practice. Overall, we in the field of medicine have much to celebrate, as we commemorate the 80th anniversary of the publication of the report by Stein and Leventhal in 1935, for a new disorder was described, one that we know today affects, in its various forms, 1 in every 7-17 women worldwide.


A prey-type dependent hypoglossal feedback system in the frog Rana pipiens.
Nerve transection experiments combined with high-speed videography and electromyography were used to characterize a prey-type dependent hypoglossal feedback system which coordinates mouth opening and tongue protraction in the common leopard frog, Rana pipiens. When feeding on small prey, sensory feedback from the tongue through the hypoglossal nerve is necessary to trigger mouth opening. If sensory feedback is prevented from reaching the brain by transection of the hypoglossal nerve, then the mouth fails to open although the feeding behavior appears otherwise normal. However, when feeding on large prey, the mouth opens normally even after the hypoglossal nerve has been transected. Thus, peripheral feedback is not necessary to trigger mouth opening when feeding on large prey, and presumably a central coordination mechanism is used. In Rana pipiens, the evolution of a new tongue morphology and a new motor pattern for feeding on small prey has been accompanied by the evolution of a novel, peripheral mechanism for coordinating tongue protraction and mouth opening. However, the primitive motor pattern for feeding on large prey and the primitive coordinating mechanism have been retained. These results imply that the neural circuits producing the different motor patterns for large and small prey are anatomically distinct at some level in the central nervous system. If they are not anatomically distinct, then sensory feedback should be necessary to trigger mouth opening regardless of which motor pattern is being expressed. While the anatomy of these distinct pathways remains to be elucidated, these results suggest that novel neural circuits may in fact underlie different behaviors even when they seem, superficially, to be relatively similar.


Improving diabetes self-care with a PDA in ambulatory care.
Use of information technology in diabetes management has been shown to improve self-care. We determined whether enhancing type 2 diabetes (T2DM) self-care with a personal digital assistant (PDA) by patients in the ambulatory setting would improve glycemic control. A pretest/posttest intervention study was conducted in four family practice clinics in a large multispecialty group practice associated with an 186,000-member Health Maintenance Organization. Adults with T2DM and last measured glycosylated hemoglobin (HbA1c) of > or = 8.00% received one-on-one training on the use of a loaned PDA pre-installed with "Diabetes Pilot." Changes in HbA1c and other outcomes were assessed at 6 months from baseline for all participants and by participant-reported PDA use patterns, dichotomized into high PDA users (> or =3 days in past 7) and low PDA users (< 3 days). Of 43 subjects enrolled, 18 (41.90%) completed the 6-month intervention. Their mean HbA1c decreased 17.50% from 9.70% at baseline to 8.00%, a significant mean HbA1c change of -1.7% (95% CI = -2.60 to -0.90). The mean HbA1c change was higher among reported high PDA users (n = 9, mean difference = -1.90, 95% CI = -3.20 to -0.50) than among reported low PDA users (n = 9, mean difference = -1.50, 95% CI = -2.80 to -0.30). Significant increases were reported for the foot care and general diet subscales of the Summary of Diabetes Self-Care Activities from 3 to 6 months. Enhancing T2DM self-care by adults with a PDA was associated with significant reductions in HbA1c; the reductions were greater among reported high PDA users.


A Fischer rat substrain deficient in dipeptidyl peptidase IV activity makes normal steady-state RNA levels and an altered protein. Use as a liver-cell transplantation model.
Dipeptidyl peptidase IV (DPPIV) is a serine exoproteinase expressed at high levels in epithelial cells of kidney, liver and small intestine. Recently Watanabe, Kohima & Fujimoto [(1987) Experientia 43, 400-401] and Gossrau et al. [(1990) Histochem. J. 22, 172-173] reported that Fischer 344 rats are deficient in this enzyme. We have examined DPPIV expression in Fischer 344 rats available from U.S. and German suppliers and find that livers of the U.S. Fischer rats, in contrast with their German counterparts, express active DPPIV (D+). Northern analysis of liver RNA showed comparable levels of 3.4 kb and 5.6 kb DPPIV transcripts in both D+ rats from the U.S. and German (D-) rats. Monoclonal antibody (MAb) 236.3 to DPPIV immunoprecipitated at 150 kDa enzymically active (105 kDa, denatured) protein from surface-labelled D+ hepatocytes and reacted with canalicular and sinusoidal membranes (as shown by immunofluorescence microscopy). MAb 236.3 failed to immunoprecipitate a labelled peptide from D- cell extract or to stain D- liver sections. Polyclonal antibody (PAb) specific for DPPIV immunoprecipitated an enzymically active peptide from D+ hepatocyte extracts and a smaller, inactive peptide from D- hepatocyte extracts. Peptide maps of DPPIV immunoprecipitated from D+ extracts with MAb 236.3 and PAb were identical, but differed from that of the D- hepatocyte component recognized by PAb. The molecular basis of the DPPIV deficiency in the D- rats thus appears to be the translation of an enzymically inactive protein missing the epitope recognized by MAb 236.3. We have exploited these D- rats as hosts for syngeneic transplantation of liver cells from D+ Fischer rats. DPPIV expression is stable in the transplanted cells and allows them to be readily distinguished from the surrounding D- tissue.


[Prevention of viral hepatitis in children with concentrated human leukocyte interferon].
Concentrated human leukocytic interferon, introduced electrophoretically in small doses for preventive purposes, reduces morbidity rate in hepatitis foci 6 times, probably due to an increase in the production of endogenous interferon. Interferon is introduced once in 7-10 days, taking into account the minimal time of the preservation of the preparation in the musculocutaneous depot. The application of a rubber bandage and the creation of the zone of congestive hyperemia leads to deeper penetration of interferon and to the increased therapeutic effectiveness of the preparation. The absence of significant differences in a number of immunological characteristics may be attributed to the use of interferon for the prophylaxis of healthy children having had contacts with viral hepatitis patients rather than children, actually having the disease.


Pilot study of dietary phosphorus restriction and phosphorus binders to target fibroblast growth factor 23 in patients with chronic kidney disease.
High levels of fibroblast growth factor 23 (FGF23) are associated with mortality and progression of chronic kidney disease (CKD). Reducing dietary phosphorus intake lowers FGF23 secretion in healthly individuals, but there is little data on its effects in patients with pre-dialysis CKD. Using a 2×2 factorial design, we randomly assigned 16 normophosphataemic CKD stage 3-4 patients to receive a 2-week treatment with either lanthanum carbonate 1000 mg three times daily or placebo, and to ingest a tightly controlled diet containing 750 or 1500 mg of dietary phosphorus daily. We analysed serial measurements of FGF23, parathyroid hormone, serum phosphate and calcium, and 24-h urinary phosphate and calcium excretion using repeated-measures analyses. Compared with the 1500-mg phosphorus diet, patients assigned to the 750-mg diet had greater reduction in 24-h urinary phosphate excretion (66% vs. 29%; P<0.0001). Lanthanum-treated patients experienced a significant reduction in 24-h urinary phosphate excretion compared with baseline (64%; P<0.0001), but the difference compared with placebo did not reach significance (64% vs. 31%). Despite the significant reductions in 24-h urinary phosphate excretion, no group demonstrated a significant reduction in FGF23 levels; FGF23 levels actually increased significantly in the 1500-mg diet plus placebo group, suggesting dietary phosphorus loading. Although dietary phosphorus restriction and lanthanum lowered urinary phosphate excretion consistent with a rapid decrease in phosphorus absorption, inducing a reduction in FGF23 levels in CKD patients may require interventions with a longer duration than in healthy volunteers.


[The convergence angle of crown preparations with clinically satisfactory retention].
A method was developed to measure the convergence angle on dies of complete crown preparations. The 132 dies measured revealed a surprising range in the convergence angles (15.5 to 30.2 degrees). The mandibular molar preparations had the greatest convergence angle. The design of mandibular molar preparations should be the subject of additional research.


Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system.
In an active, self-ubiquitinated state, the Ring1B ligase monoubiquitinates histone H2A playing a critical role in Polycomb-mediated gene silencing. Following ubiquitination by external ligases, Ring1B is targeted for proteosomal degradation. Using biochemical data and computational modeling, we show that the Ring1B ligase can exhibit abrupt switches, overshoot transitions and self-perpetuating oscillations between its distinct ubiquitination and activity states. These different Ring1B states display canonical or multiply branched, atypical polyubiquitin chains and involve association with the Polycomb-group protein Bmi1. Bistable switches and oscillations may lead to all-or-none histone H2A monoubiquitination rates and result in discrete periods of gene (in)activity. Switches, overshoots and oscillations in Ring1B catalytic activity and proteosomal degradation are controlled by the abundances of Bmi1 and Ring1B, and the activities and abundances of external ligases and deubiquitinases, such as E6-AP and USP7.


Microstructured Polyfluoroacrylate Elastomeric Dielectric Layer for Highly Stretchable Wide-Range Capacitive Pressure Sensors.
Capacitive pressure sensors capable of replicating human tactile senses have garnered tremendous attention. Introducing microstructures into the dielectric layer is an effective approach to improve the sensitivity of the sensors. However, most reported processes to fabricate microstructured dielectric layers are complicated and time-consuming and usually have adverse effects on the mechanical properties. Herein, we report a mechanically strong and highly stretchable dielectric layer fabricated from a microstructured fluorinated elastomer with a high dielectric constant (5.8 at 1000 Hz) via a simple and low-cost thermal decomposition process. Capacitive pressure sensors based on this microstructured fluorinated elastomer dielectric layer and soft ionotronic electrodes illustrate an impressing stretchability (>300%), a high pressure sensitivity (17 MPa-1), a wide detection range (70 Pa-800 kPa), and a fast response time (below 300 ms). Moreover, the multipixel capacitive pressure sensors sensing array maintains the unique spatial tactile sensing performance even under significant tensile deformation. It is believed that our microstructured fluorinated elastomer dielectric layer might find wide applications in stretchable ionotronic devices.


Differential expression of genes in potato tubers after wounding.
Tubers of a common tetraploid species of Solanum tuberosum (Granola) were mechanically wounded by slicing. After 18 hr only small differences were detectable in the pattern of the steady-state protein extracted from wounded versus unwounded tubers. In contrast the protein pattern obtained by in vitro translation of mRNA isolated from wounded and unwounded tubers differed significantly. A cDNA library was established and screened for wound-induced cDNA clones by differential hybridization. Two clones, wun-1 and wun-2, were found that corresponded to genes that were highly expressed in wounded potato tubers but were not expressed in unwounded tubers. The expression of the gene corresponding to wun-1 is detectable 30 min after wounding; the expression of the gene corresponding to wun-2 is detectable 4 hr after wounding. The expression of both genes (hereafter referred to as wun-1 and wun-2) remains constant for up to 24 hr after wounding. Interestingly the RNA corresponding to patatin, a major storage protein of potato tubers, behaves in the opposite way; it decreases dramatically in tubers within 30 min after wounding. The low level of patatin mRNA observed in unwounded roots and stems also disappears after wounding. Run-off transcription experiments, performed with isolated nuclei, indicate that the activation of the wound-induced genes as well as the inhibition of the patatin gene are controlled at the transcriptional level.


Lamb survival in Australian Merino sheep: a genetic analysis.
Direct and maternal components of variance for lamb survival to birth, 7 d, and weaning (110 d) were estimated by REML procedures in a flock of Australian Merino sheep. A total of 14,142 lambs, the progeny of 421 sires and 3,666 dams, born between 1975 and 1983 were available for analysis. The study has produced some of the most precise estimates of genetic parameters for lamb survival in the Australian Merino. Very low heritabilities for lamb viability (0.03) and the performance of the dam or ewe rearing ability (0.07) suggest that genetic solutions to lamb survival are unlikely to be significant. But, despite the low heritabilities, there is still potential for improvement through selective breeding. The estimated repeatability of at least 0.10 shows that multiple records on the rearing ability of a ewe over its lifetime can increase selection accuracy. More importantly, such repeatabilities indicate that current generation improvement can be achieved by culling ewes from the breeding flock with poor rearing ability. Despite maternal bond score and lamb birth weight being highly repeatable and moderately heritable traits, correlations with lamb survival were essentially zero. These traits therefore have no value as indirect selection criteria for Merino lamb survival.


Multi-stage optimization of a deep model: A case study on ground motion modeling.
In this study, a multi-stage optimization procedure is proposed to develop deep neural network models which results in a powerful deep learning pipeline called intelligent deep learning (iDeepLe). The proposed pipeline is then evaluated by a challenging real-world problem, the modeling of the spectral acceleration experienced by a particle during earthquakes. This approach has three main stages to optimize the deep model topology, the hyper-parameters, and its performance, respectively. This pipeline optimizes the deep model via adaptive learning rate optimization algorithms for both accuracy and complexity in multiple stages, while simultaneously solving the unknown parameters of the regression model. Among the seven adaptive learning rate optimization algorithms, Nadam optimization algorithm has shown the best performance results in the current study. The proposed approach is shown to be a suitable tool to generate solid models for this complex real-world system. The results also show that the parallel pipeline of iDeepLe has the capacity to handle big data problems as well.


Inference of human continental origin and admixture proportions using a highly discriminative ancestry informative 41-SNP panel.
Accurate determination of genetic ancestry is of high interest for many areas such as biomedical research, personal genomics and forensics. It remains an important topic in genetic association studies, as it has been shown that population stratification, if not appropriately considered, can lead to false-positive and -negative results. While large association studies typically extract ancestry information from available genome-wide SNP genotypes, many important clinical data sets on rare phenotypes and historical collections assembled before the GWAS area are in need of a feasible method (i.e., ease of genotyping, small number of markers) to infer the geographic origin and potential admixture of the study subjects. Here we report on the development, application and limitations of a small, multiplexable ancestry informative marker (AIM) panel of SNPs (or AISNP) developed specifically for this purpose. Based on worldwide populations from the HGDP, a 41-AIM AISNP panel for multiplex application with the ABI SNPlex and a subset with 31 AIMs for the Sequenome iPLEX system were selected and found to be highly informative for inferring ancestry among the seven continental regions Africa, the Middle East, Europe, Central/South Asia, East Asia, the Americas and Oceania. The panel was found to be least informative for Eurasian populations, and additional AIMs for a higher resolution are suggested. A large reference set including over 4,000 subjects collected from 120 global populations was assembled to facilitate accurate ancestry determination. We show practical applications of this AIM panel, discuss its limitations for admixed individuals and suggest ways to incorporate ancestry information into genetic association studies. We demonstrated the utility of a small AISNP panel specifically developed to discern global ancestry. We believe that it will find wide application because of its feasibility and potential for a wide range of applications.


Identification of Voxels Confounded by Venous Signals Using Resting-State fMRI Functional Connectivity Graph Community Identification.
Identifying venous voxels in fMRI datasets is important to increase the specificity of fMRI analyses to microvasculature in the vicinity of the neural processes triggering the BOLD response. This is, however, difficult to achieve in particular in typical studies where magnitude images of BOLD EPI are the only data available. In this study, voxelwise functional connectivity graphs were computed on minimally preprocessed low TR (333 ms) multiband resting-state fMRI data, using both high positive and negative correlations to define edges between nodes (voxels). A high correlation threshold for binarization ensures that most edges in the resulting sparse graph reflect the high coherence of signals in medium to large veins. Graph clustering based on the optimization of modularity was then employed to identify clusters of coherent voxels in this graph, and all clusters of 50 or more voxels were then interpreted as corresponding to medium to large veins. Indeed, a comparison with SWI reveals that 75.6±5.9% of voxels within these large clusters overlap with veins visible in the SWI image or lie outside the brain parenchyma. Some of the remaining differences between the two modalities can be explained by imperfect alignment or geometric distortions between the two images. Overall, the graph clustering based method for identifying venous voxels has a high specificity as well as the additional advantages of being computed in the same voxel grid as the fMRI dataset itself and not needing any additional data beyond what is usually acquired (and exported) in standard fMRI experiments.


Development and Validation of an Analytical Method for Quantitation of Sulfolane in Rat and Mouse Plasma by GC-MS.
Sulfolane is an industrial solvent commonly used for extraction of aromatic hydrocarbons in the oil refining process, as well in the purification of natural gas. Its wide use and high solubility in water has led to contamination of groundwater. The objective of this work was to develop and validate an analytical method to quantitate sulfolane in rodent plasma in support of the National Toxicology Program toxicology and toxicokinetic studies of sulfolane. The method uses extraction of plasma with ethyl acetate and analysis by gas chromatography-mass spectrometry with electron ionization. The method was validated in male Sprague Dawley (SD) rat plasma over the concentration range of 20-100,000 ng/mL. The method was linear (r ≥ 0.99), accurate (mean relative error (RE) ≤ ±5.1%) and precise (relative standard deviation (RSD) ≤ 2.9%). The absolute recovery was ≥74%. The limit of detection was 0.516 ng/mL. Standards as high as ~2.5 mg/mL could be successfully diluted into the calibration range (mean %RE ≤ ±4.5; %RSD ≤ 4.6). Extracted samples were stable for at least 3 days at ambient and refrigerated temperatures, and freeze/thaw stability in matrix was demonstrated after three cycles over 3 days (calculated concentrations within 90.8-102% of Day 0 concentrations). Sulfolane was stable in frozen plasma for at least 75 days at -80°C (calculated concentrations within 93.0-98.1% of Day 0 concentrations). Matrix evaluation was performed for sulfolane in female SD rat plasma and male and female B6C3F1 mouse plasma (mean %RE ≤ ±4.9; %RSD ≤ 3.3). These data demonstrate that the method is suitable for determination of sulfolane in rodent plasma.


Endocannabinoid regulation of spinal nociceptive processing in a model of neuropathic pain.
Models of neuropathic pain are associated with elevated spinal levels of endocannabinoids (ECs) and altered expression of cannabinoid receptors on primary sensory afferents and post-synaptic cells in the spinal cord. We investigated the impact of these changes on the spinal processing of sensory inputs in a model of neuropathic pain. Extracellular single-unit recordings of spinal neurones were made in anaesthetized neuropathic and sham-operated rats. The effects of spinal administration of the cannabinoid CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) and the cannabinoid receptor type 2 (CB(2)) receptor antagonist N-[(1S)-endo-1,3,3-trimethylbicycloheptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528) on mechanically-evoked responses of spinal neurones were determined. The effects of spinal administration of (5Z,8Z11Z,14Z)-N-(3-furanylmethyl)-5,8,11,14-eicosatetraenamide (UCM707), which binds to CB(2) receptors and alters transport of ECs, on evoked responses of spinal neurones and spinal levels of ECs were also determined. The cannabinoid CB(1) receptor antagonist AM251, but not the CB(2) receptor antagonist, significantly facilitated 10-g-evoked responses of spinal neurones in neuropathic, but not sham-operated, rats. Spinal administration of UCM707 did not alter spinal levels of ECs but did significantly inhibit mechanically-evoked responses of neurones in neuropathic, but not sham-operated, rats. Pharmacological studies indicated that the selective inhibitory effects of spinal UCM707 in neuropathic rats were mediated by activation of spinal CB(2) receptors, as well as a contribution from transient receptor potential vanilloid 1 (TRPV1) channels. This work demonstrates that changes in the EC receptor system in the spinal cord of neuropathic rats influence the processing of sensory inputs, in particular low-weight inputs that drive allodynia, and indicates novel effects of drugs acting via multiple elements of this receptor system.


Fibrillin 2 gene knockdown inhibits invasion and migration of lung cancer cells.
To investigate the effect of Fibrillin 2 (FBN2) expression on the invasion and migration of lung cancer cells, and the underlying mechanism. Protein and mRNA expressions of FBN2 were assayed. The relationship between FBN2 protein expression and clinical characteristics of lung cancer patients was analyzed. Correlation between FBN2 expression level and patient survival time was analyzed. Moreover, the mRNA and protein expression of FBN2 in lung cancer cells and human normal lung epithelial cells were assayed. After constructing low-expressing FBN2 cells, the cell proliferation, clone formation, migration and invasion capabilities were tested. Lung cancer cells proliferation with low FBN2 expression in nude mice was measured with a nude mouse tumorigenic experiment. The mRNA and protein expressions of FBN2 in lung cancer tissues were significantly higher than those in para-cancerous tissues (p<0.05). FBN2 protein expression was significantly correlated with TNM stage, lymph node metastasis and histological type (p<0.05). Survival time was markedly reduced in patients with high FBN2 expression (p<0.001). The expressions of FBN2 mRNA and protein were markedly higher in lung cancer cells than in human normal lung epithelial cells. The proliferation, migration and invasion of lung cancer cells were significantly inhibited by FBN2 knockdown. The FBN2 knockdown significantly inhibited the protein expressions of p-FAK, p-MEK and p-ERK. FBN2 is highly expressed in lung cancer tissues, and as an oncogene, it affects the pathogenesis of lung cancer. The knockdown of the expression of FBN2 significantly inhibits the proliferation, invasion and migration abilities of lung cancer cells.


Allium hookeri Extracts Improve Scopolamine-Induced Cognitive Impairment via Activation of the Cholinergic System and Anti-Neuroinflammation in Mice.
Allium hookeri (AH) is a medicinal food that has been used in Southeast Asia for various physiological activities. The objective of this study was to investigate the activation of the cholinergic system and the anti-neuroinflammation effects of AH on scopolamine-induced memory impairment in mice. Scopolamine (1 mg/kg body weight, i.p.) impaired the performance of the mice on the Y-maze test, passive avoidance test, and water maze test. However, the number of error actions was reduced in the AH groups supplemented with leaf and root extracts from AH. AH treatment improved working memory and avoidance times against electronic shock, increased step-through latency, and reduced the time to reach the escape zone in the water maze test. AH significantly improved the cholinergic system by decreasing acetylcholinesterase activity, and increasing acetylcholine concentration. The serum inflammatory cytokines (IL-1β, IL-6, and IFN-γ) increased by scopolamine treatment were regulated by the administration of AH extracts. Overexpression of NF-κB signaling and cytokines in liver tissue due to scopolamine were controlled by administration of AH extracts. AH also significantly decreased Aβ and caspase-3 expression but increased NeuN and ChAT. The results suggest that AH extracts improve cognitive effects, and the root extracts are more effective in relieving the scopolamine-induced memory impairment. They have neuroprotective effects and reduce the development of neuroinflammation.


Moving beyond the lab: investigating empathy through the Empirical 5E approach.
Empathy is a complex and multifaceted phenomenon that plays a crucial role in human social interactions. Recent developments in social neuroscience have provided valuable insights into the neural underpinnings and bodily mechanisms underlying empathy. This methodology often prioritizes precision, replicability, internal validity, and confound control. However, fully understanding the complexity of empathy seems unattainable by solely relying on artificial and controlled laboratory settings, while overlooking a comprehensive view of empathy through an ecological experimental approach. In this article, we propose articulating an integrative theoretical and methodological framework based on the 5E approach (the "E"s stand for embodied, embedded, enacted, emotional, and extended perspectives of empathy), highlighting the relevance of studying empathy as an active interaction between embodied agents, embedded in a shared real-world environment. In addition, we illustrate how a novel multimodal approach including mobile brain and body imaging (MoBi) combined with phenomenological methods, and the implementation of interactive paradigms in a natural context, are adequate procedures to study empathy from the 5E approach. In doing so, we present the Empirical 5E approach (E5E) as an integrative scientific framework to bridge brain/body and phenomenological attributes in an interbody interactive setting. Progressing toward an E5E approach can be crucial to understanding empathy in accordance with the complexity of how it is experienced in the real world.


Genomic code for Sox2 binding uncovers its regulatory role in Six3 activation in the forebrain.
The SRY-related HMG box transcription factor Sox2 plays critical roles throughout embryogenesis. Haploinsufficiency for SOX2 results in human developmental defects including anophthalmia, microphthalmia and septo-optic dysplasia, a congenital forebrain defect. To understand how Sox2 plays a role in neurogenesis, we combined genomic and in vivo transgenic approaches to characterize genomic regions occupied by Sox2 in the developing forebrain. Six3, a homeobox gene associated with holoprosencephaly, a forebrain midline defect, was identified as a Sox2 transcriptional target. This study shows that Sox2 directly regulates a previously unidentified long-range forebrain enhancer to activate Six3 expression in the rostral diencephalon. Further biochemical and genetic evidences indicated a direct regulatory link between Sox2 and Six3 during forebrain development, providing a better understanding of a common molecular mechanism underlying these forebrain defects.


What's Fair in Child Welfare? Parent Knowledge, Attitudes, and Experiences.
Parents play a critical role in the progression and outcomes of juvenile dependency (child welfare court) cases. Yet, very little is known about these parents' knowledge, attitudes, and experiences. We examined legal understanding and attitudes among 201 parents involved in ongoing dependency cases in California and Florida via semi-structured, in-person interviews. We expected parents' understanding to be low and attitudes to be negative, particularly among parents of color and low SES parents. We expected greater dependency understanding to be related to more positive justice attitudes, and procedural and distributive justice attitudes to be indistinguishable in this population. Findings partially confirmed expectations. Parents' understanding of the system was low, especially among parents of color and less educated parents. Parents felt less than satisfied about the fairness of procedures and decisions. However, procedural and distributive justice attitudes were distinguishable. Finally, and unexpectedly, parents' knowledge and attitudes were negatively related. The consistently low levels of knowledge across CA and FL suggest the critical need to increase parental knowledge. It is also important to promote fair court procedures and decision-making to improve parents' attitudes about procedural and distributive justice, which were found to be distinct and important factors among parents navigating juvenile dependency cases.


The cytotoxic effect of memantine and its effect on cytoskeletal proteins expression in metastatic breast cancer cell line.
Breast cancer is an important leading cause of death from cancer. Stathmin and tau proteins are regulators of cell motility, and their overexpression is associated with the progression and bad prognosis of breast cancer. Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is the potential inhibitor of tau protein in neurons. This study determines the effect of memantine on breast cancer cell migration and proliferation, tau and stathmin gene expression in cancer cells and its synergistic effect with paclitaxel. The cell proliferation was evaluated by MTT assay and for this purpose, MCF-7 breast cancer cells were treated with various concentration of memantine (2, 20 and 100 μg/ml). Tau and stathmin mRNA expression was evaluated through quantitative real time RT-PCR method. The migration of cancer cells treated with memantine for 24 hr was compared to non-treated cells using an in vitro transmembrane migration assay. Incubation of breast cancer cells with memantine resulted in a dose dependent reduction in cell survival (P=0.0001). Paclitaxel (100 nM) showed synergistic effect with memantine (P=0.0001). Memantine significantly decreased tau and stathmin mRNA expression (by RT-PCR), so that 100 µmol/l of memantine decreased tau and stathmin expression by 46% (P=0.0341) and 33% (P=0.043), respectively. Migration of cells was also decreased by memantine (P=0.0001). The presented data shows that memantine reduced mRNA levels of tau and stathmin proteins and also reduced cellular migration.


Bax-interacting factor-1 expression in prostate cancer.
Bax-interacting factor (Bif)-1 protein is a member of the endophilin B family that binds to and activates the proapoptotic Bax protein in response to apoptotic signals. Loss of Bif-1 suppresses the intrinsic pathway of apoptosis and promotes tumorigenesis. We examined the expression levels of Bif-1 protein in human prostate cancer. Thirty-nine archival tissue specimens of human prostate cancer, and a human prostate cancer tissue microarray containing 19 samples of normal prostate, 26 samples of benign prostatic hyperplasias (BPHs), 30 samples of high-grade prostatic intraepithelial neoplasia (PIN), and 153 samples of prostate cancer, were selected for immunohistochemical staining with Bif-1 antibody. The slides were scored by 2 independent observers. Nontissue microarray samples: moderate to strong Bif-1 staining was identified in 38 of 39 prostate cancer samples. In 32 cases, foci of PIN were identified adjacent to prostate cancer samples. Of these, 29 samples (90.6%) showed strong and diffuse Bif-1 staining. Benign prostatic hyperplasias, identified in 27 cases, was weakly Bif-1 positive in 88.9% of cases. Tissue microarray samples: 38.6% (59 of 153) of prostate cancer samples showed moderate to strong Bif-1 expression, and 21.6% (33 of 153) were Bif-1 negative. Bif-1 expression was moderate to strong in 76.7% (23 of 30) of PIN. Bif-1 was weak to moderate in 53.8% (14 of 26) of BPH and negative in 46.2% (12 of 26) of them. Low to moderate Bif-1 was seen in 89.5% of normal prostate samples. The loss of Bif-1 expression in a subset of prostate cancer samples is in agreement with the proapoptotic function of Bif-1. The significance of the increased Bif-1 in a subgroup of prostate cancer samples and in PIN remains to be determined. It seems that Bif-1 has a role in prostate cancer, providing the rationale for using Bif-1 as a target for prostate anticancer therapy.


Fourier transform infrared spectroscopy with visible light.
Nonlinear interferometers allow spectroscopy in the mid-infrared range by detecting correlated visible light, for which non-cooled detectors with higher specific detectivity and lower dark count rates are available. We present a new approach for the registration of spectral information, which combines a nonlinear interferometer using non-degenerate spontaneous parametric down-conversion (SPDC) with a Fourier-transform spectroscopy concept. In order to increase the spectral coverage, we use broadband non-collinear SPDC in periodically poled LiNbO3. Without the need for spectrally selective detection, continuous spectra with a spectral bandwidth of more than 100 cm-1 are achieved. We demonstrate transmission spectra of a polypropylene sample measured with 6 cm-1 resolution in the spectral range between 3.2 µm to 3.9 µm.


Expanded safety and immunogenicity of a bivalent, oral, attenuated cholera vaccine, CVD 103-HgR plus CVD 111, in United States military personnel stationed in Panama.
To provide optimum protection against classical and El Tor biotypes of Vibrio cholerae O1, a single-dose, oral cholera vaccine was developed by combining two live, attenuated vaccine strains, CVD 103-HgR (classical, Inaba) and CVD 111 (El Tor, Ogawa). The vaccines were formulated in a double-chamber sachet; one chamber contained lyophilized bacteria, and the other contained buffer. A total of 170 partially-immune American soldiers stationed in Panama received one of the following five formulations: (a) CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(7) CFU, (b) CVD 103-HgR at 10(8) CFU plus CVD 111 at 10(6) CFU, (c) CVD 103-HgR alone at 10(8) CFU, (d) CVD 111 alone at 10(7) CFU, or (e) inactivated Escherichia coli placebo. Among those who received CVD 111 at the high or low dose either alone or in combination with CVD 103-HgR, 8 of 103 had diarrhea, defined as three or more liquid stools. None of the 32 volunteers who received CVD 103-HgR alone or the 35 placebo recipients had diarrhea. CVD 111 was detected in the stools of 46% of the 103 volunteers who received it. About 65% of all persons who received CVD 103-HgR either alone or in combination had a fourfold rise in Inaba vibriocidal titers. The postvaccination geometric mean titers were comparable among groups, ranging from 450 to 550. Ogawa vibriocidal titers were about twice as high in persons who received CVD 111 as in those who received CVD 103-HgR alone (600 versus 300). The addition of CVD 111 improved the overall seroconversion rate and doubled the serum Ogawa vibriocidal titers, suggesting that the combination of an El Tor and a classical cholera strain is desirable. While CVD 111 was previously found to be well tolerated in semiimmune Peruvians, the adverse effects observed in this study indicate that this strain requires further attenuation before it can be safely used in nonimmune populations.


Unchanged cardiovascular and respiratory outcomes in healthy C57Bl/6 mice after in utero exposure to ionizing radiation.
Advancements in medical technologies that utilize ionizing radiation have led to improved diagnosis and patient outcomes, however, the effect of ionizing radiation on the patient is still debated. In the case of pregnancy, the potential effects are not only to the mother but also to the fetus. The aim of this study was to determine if exposure from ionizing radiation during pregnancy alters the development of the cardiovascular and respiratory system of the offspring. Pregnant C57Bl/6 mice were whole-body irradiated at gestational day 15 with a 137Cs gamma radiation emitting source at 0 mGy (sham), 50 mGy, 300 mGy, or 1000 mGy. Post weaning weight and blood pressure measurements were taken weekly for both male and female pups until euthanasia at 16-17 weeks postnatal age. Immediately following, the trachea was cannulated, and the lungs and heart excised. The lung was then examined to assess respiratory physiological outcomes. In utero exposures to 1000 mGy caused significant growth reduction compared to sham irradiated, which remained persistent for both male and female pups. Growth restriction was not observed for lower exposures. There was no significant change in any cardiovascular or respiratory outcomes measured. Overall, intrauterine exposures to ionizing radiation does not appear to significantly alter the development of the cardiovascular and respiratory system in C57Bl/6 pups up to 17 weeks postnatal age.


Leaf anatomy of three herbaceous bamboo species.
Fully developed leaves of Cryptochloa capillata (Swallen) Soderstrom, Raddia brasilienses Bertol and Pharus lappulaceus Aublet (Poaceae: Bambusoideae) were collected at Restinga de Jacarepiá, Environment Proctection Area of Massambaba, county of Rio de Janeiro, State of Rio de Janeiro, Brazil, and studied by optical microscope. Leaf anatomy is described in order to contribute to the Poaceae family study. Anatomic features observed in the three studied species such as: midrib with complex vascular system, mesophyll consisting of tabular lobed chlorophyllous elements and fusoid cells, vascular bundles with double sheath, epidermis made up of long cells, short cells, micro-hairs, prickles and silica bodies correspond to the "bambusoid type" of leaf anatomy.


Pharmacological treatment of psychiatric disorders in children and adolescents: focus on guidelines for the primary care practitioner.
This article is a practical review of the current psychopharmacological agents used in the treatment of child and adolescent psychiatric disorders. Psychostimulants such as methylphenidate, dexamphetamine and pemoline are effective in the control of symptoms associated with attention deficit hyperactivity disorder. The controlled release preparations and the adjunctive use of clonidine are helpful to extend stimulant effects and control adverse effects. Tricyclic antidepressants are helpful in individual cases of child and adolescent depression, but adverse effects may limit their use. Clomipramine has been found to be effective for childhood obsessive-compulsive disorder. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) appear to be safer for depression and are also useful in obsessive-compulsive disorder. Buspirone is effective for the treatment of anxiety disorders in children. Newer atypical antipsychotics such as risperidone may have less limiting adverse effects than older antipsychotics in the treatment of psychosis and severe behaviour disorders, but the physician must be vigilant for the emergence of tardive dyskinesia. Drug treatment in children and adolescents must take into account the child's environmental influences and be part of an overall treatment plan where individual, familial and cultural issues are addressed.


Menstrual cycle affects renal-adrenal and hemodynamic responses during prolonged standing in the postural orthostatic tachycardia syndrome.
Approximately 500,000 American premenopausal women have the postural orthostatic tachycardia syndrome (POTS). We tested the hypothesis that in POTS women during orthostasis, activation of the renin-angiotensin-aldosterone system is greater, leading to better compensated hemodynamics in the midluteal phase (MLP) than in the early follicular phase of the menstrual cycle. Ten POTS women and 11 healthy women (controls) consumed a constant diet 3 days before testing. Hemodynamics and renal-adrenal hormones were measured while supine and during 2-hour standing. We found that blood pressure was similar, heart rate and total peripheral resistance were greater, and cardiac output and stroke volume were lower in POTS subjects than in controls during 2-hour standing. In controls, hemodynamic parameters were indistinguishable between menstrual phases. In POTS subjects, cardiac output and stroke volume were lower and total peripheral resistance was greater in the early follicular phase than MLP after 30 minutes of standing; however, blood pressure and heart rate were similar between phases. Plasma renin activity (9+/-6 [SD] versus 13+/-9 ng/mL per hour; P=0.04) and aldosterone (43+/-22 versus 55+/-25 ng/dL; P=0.02) were lower in the early follicular phase than MLP in POTS subjects after 2 hours of standing. Catecholamine responses were similar between phases. The percentage rate of subjects having presyncope was greater in the early follicular phase than MLP for both groups (chi(2) P<0.01). These results suggest that the menstrual cycle modulates the renin-angiotensin-aldosterone system and affects hemodynamics during orthostasis in POTS. The high estrogen and progesterone in the MLP are associated with greater increases in renal-adrenal hormones and presumably more volume retention, which improve late-standing tolerance in these patients.


Associations of neighborhood concentrated poverty, neighborhood racial/ethnic composition, and indoor allergen exposures: a cross-sectional analysis of los angeles households, 2006-2008.
Although racial/ethnic, socioeconomic, and neighborhood factors have been linked to asthma, and the association between indoor allergens and asthma is well documented, few studies have examined the relationship between these factors and indoor allergens. We examined the frequency of reported indoor allergens and differences by racial/ethnic, socioeconomic, and neighborhood characteristics among a diverse sample of Los Angeles households. Multilevel logistic regression models were used to analyze the data from 723 households from wave 2 of the Los Angeles Family and Neighborhood Survey. The reported presence of rats, mice, cockroaches, mold, pets, and tobacco smoke were the primary outcomes of interest. Hispanic and Asian households had a nearly threefold increase in the odds of reporting cockroaches compared to non-Hispanic Whites (OR, 2.85; 95 % CI 1.38-5.88 and OR, 2.62; 95 % CI 1.02-6.73, respectively) even after adjusting for socioeconomic factors. Primary caregivers who had obtained a high school degree were significantly less likely to report the presence of mice and cockroaches compared to primary caregivers with less than a high school degree (OR, 0.19; 95 % CI 0.08-0.46 and OR, 0.39; 95 % CI 0.23-0.68, respectively). Primary caregivers with more than a high school degree were also less likely to report the presence of rats, mice, and cockroaches within their households, compared to those with less than a high school degree. Compared to renters, home owners were less likely to report the presence of mice, cockroaches, and mold within their households. At the neighborhood level, households located within neighborhoods of high concentrated poverty (where the average poverty rate is at least 50 %) were more likely to report the presence of mice and cockroaches compared to households in low concentrated poverty neighborhoods (average poverty rate is 10 % or less), after adjusting for individual race/ethnicity and socioeconomic characteristics. Our study found evidence in support of neighborhood-level racial/ethnic and socioeconomic influences on indoor allergen exposure, above and beyond individual factors. Future studies should continue to explore individual and neighborhood-level racial/ethnic and socioeconomic differences in household allergen exposures across diverse contexts.


Scalable steady state analysis of Boolean biological regulatory networks.
Computing the long term behavior of regulatory and signaling networks is critical in understanding how biological functions take place in organisms. Steady states of these networks determine the activity levels of individual entities in the long run. Identifying all the steady states of these networks is difficult due to the state space explosion problem. In this paper, we propose a method for identifying all the steady states of Boolean regulatory and signaling networks accurately and efficiently. We build a mathematical model that allows pruning a large portion of the state space quickly without causing any false dismissals. For the remaining state space, which is typically very small compared to the whole state space, we develop a randomized traversal method that extracts the steady states. We estimate the number of steady states, and the expected behavior of individual genes and gene pairs in steady states in an online fashion. Also, we formulate a stopping criterion that terminates the traversal as soon as user supplied percentage of the results are returned with high confidence. This method identifies the observed steady states of boolean biological networks computationally. Our algorithm successfully reported the G1 phases of both budding and fission yeast cell cycles. Besides, the experiments suggest that this method is useful in identifying co-expressed genes as well. By analyzing the steady state profile of Hedgehog network, we were able to find the highly co-expressed gene pair GL1-SMO together with other such pairs. Source code of this work is available at http://bioinformatics.cise.ufl.edu/palSteady.html twocolumnfalse].


Patient Care During the COVID-19 Pandemic: Use of Virtual Care.
Virtual care, the use of videoconferencing technology to connect with patients, has become critical in providing continuing care for patients during the current COVID-19 pandemic. Virtual care has now been adopted by health care providers across the spectrum, including physicians, residents, nurse practitioners, nurses, and allied health care professionals. Virtual care is novel and nuanced compared to in-person care. Most of the health care providers who are delivering or expected to deliver virtual care have little to no prior experience with it. The nuances of virtual care involve regulatory standards, platforms, technology and troubleshooting, patient selection, etiquette, and workflow, all of which comprise critical points in the provision of health care. It is important to consistently deliver high-quality, equitable, and professional virtual care to inspire patients with the trust they need to continue follow-up of their care in these difficult times. We have been adopting virtual care in our clinical practice for over two years. In partnership with Canada Health Infoway, we have assembled a primer for virtual care that can serve as a guide for any health care provider in Canada and globally, with the goal of providing seamless transitions between in-person and virtual care.


Role of yeast cell growth temperature on Candida albicans virulence in mice.
Previous studies have suggested that yeast cell growth temperature may influence the relative virulence of the opportunistic dimorphic fungus Candida albicans. To test this possibility, mice were challenged with C. albicans yeast cells which were grown at either room temperature or 37 degrees C, and their survival was monitored daily. Mice which received room temperature-grown cells died faster. The interaction of glycogen-elicited polymorphonucleated neutrophils (PMNs) with C. albicans yeast cells grown at the two temperatures was examined, because PMNs have been shown to have a critical role in preventing development of candidiasis in normal individuals. In the absence of serum (i.e., nonopsonic conditions), more PMNs conjugated and engulfed C. albicans cells grown at room temperature than those grown at 37 degrees C. However, PMNs were less able to kill cells grown at room temperature than cells grown at 37 degrees C. Cells grown at room temperature also produced abundant germ tubes after engulfment and were thus more likely to escape killing by phagocytes. These results suggest that cells grown at room temperature are more virulent because they are less likely to be killed by phagocytes and are more likely to disseminate. The possibility that expression of cell surface hydrophobicity is involved in these events is discussed.


Apart and back again: Reestablished neuronal connections restore walking after paralysis.
Despite significant strides promoting axon regeneration after spinal cord injury (SCI), meaningful functional recovery remains elusive. Using a combination of approaches, Squair et al.1 elegantly demonstrate that axons damaged after SCI must be reconnected with their natural targets to recover lost neurological functions.


Effects of immunological castration (Improvest) on further processed belly characteristics and commercial bacon slicing yields of finishing pigs.
Objectives were to compare fresh belly characteristics, further processed belly characteristics, and commercial bacon slicing yields of immunologically castrated (IC) barrows, IC barrows fed ractopamine hydrochloride (IC+RAC), physically castrated (PC) barrows, intact males, and gilts. One hundred eighty-eight bellies from pigs housed in single sex pens (n = 48) slaughtered at 130 kg ending live weight were evaluated for flop distance, length, width, thickness, and fatty acid composition. Bellies were injected, thermally processed, and sliced according to standard protocols at a USDA federally inspected facility. Complete slices were sorted by trained plant personnel. Then, sliced bellies were individually packaged to maintain anatomical orientation. The effects of treatments were analyzed as a generalized linear mixed model with pen of pigs serving as the experimental unit for all comparisons. Belly thickness was not different (P ≥ 0.11) in bellies from IC barrows (3.74 cm) compared with bellies from IC+RAC (3.60 cm), PC barrows (3.94 cm), or gilts (3.64 cm); however, bellies were 0.42 cm thicker (P < 0.01) in IC barrows compared with intact males. Iodine value was not different (P ≥ 0.06) in bellies from IC barrows (68.26) compared with bellies from IC+RAC (69.78), PC barrows (67.55), or gilts (69.45); however, iodine value was 2.32 units less (P < 0.01) in IC barrows compared with intact males. Green weight was not different (P ≥ 0.09) in bellies from IC barrows (4.88 kg) compared with bellies from IC+RAC (5.11 kg), PC barrows (5.10 kg), or gilts (4.79 kg); however, green weight was 0.56 kg greater (P < 0.0001) in IC barrows compared with intact males. Pump uptake and cooked yield was not different (P ≥ 0.15) among treatment groups. Slicing yield (as a percentage of green weight) was decreased (P ≤ 0.01) in bellies from IC barrows (93.61%) compared with bellies from PC barrows (98.42%) or gilts (98.19%); however, slicing yield was not different (P ≥ 0.11) among bellies from IC barrows, IC+RAC, or intact males. Overall, fresh belly characteristics of IC barrows were analogous to PC barrows and gilts, but commercial slicing yields of bacon manufactured from IC barrows were less than both PC barrows and gilts.


Salmonella-Mediated Cancer Therapy: An Innovative Therapeutic Strategy.
Bacterial-mediated cancer therapy (BMCT) has become a hot topic in the area of antitumor treatment. Salmonella has been recommended to specifically colonize and proliferate inside tumors and even inhibit tumor growth. Salmonella typhimurium (S. typhimurium) is one of the most promising mediators, which can be easily manipulated. S. typhimurium has been engineered and designed as cancer-targeting therapeutics, and can be improved by combining with other therapeutic methods, e.g. chemotherapy and radiotherapy, which regulate the tumor microenvironment synergistically. In view of all these strengths, the engineered attenuated strains have significant advantages for tumor diagnosis and treatment. This treatment has also been approved by the FDA for clinical trial. In this review, we summarized the recent progress and research in the field of Salmonella -mediated cancer therapy.