A cross-sectional study on the risk factors for erosive esophagitis in young adults.
To investigate the impact of metabolic and lifestyle factors on erosive esophagitis in young adults. A total of 5,069 people under the age of 40 years old were enrolled in a medical survey at our institute. People with a previous history of upper gastrointestinal tract surgery were excluded, as were individuals taking medication for reflux symptoms, peptic ulcers, or malignancies. Independent and significant predictors affecting the presence of erosive esophagitis were determined by multivariate analysis. A total of 4,990 participants (male/female; 3,871/1,119, age; 33.9±3.9 years) were eligible. A total of 728 participants (14.6%) had erosive esophagitis. Male gender and increasing age were independent predictors for increased prevalence of erosive esophagitis (odds ratio=2.242 and 1.045. 95% confidence interval=1.613-3.117 and 1.019-1.072; p<0.001 and 0.001, respectively). Moderate-to-heavy alcohol consumption, light-to-moderate-to-heavy smoking, hypertension, hyperglycemia, and hiatal hernia each significantly and independently increased the risk for erosive esophagitis (odds ratio=1.499, 1.398, 1.353, 1.570, 1.884, 1.297, 1.562, and 3.213. 95% confidence interval=1.181-1.903, 1.040-1.880, 1.094-1.675, 1.250-1.971, 1.307-2.716, 1.074-1.566, 1.063-2.295, and 2.712-3.807; p=0.001, 0.027, 0.005, <0.001, 0.001, <0.001, 0.007, 0.023, and <0.001 respectively). Helicobacter pylori infection decreased the risk for erosive esophagitis (odds ratio=0.575, 95% confidence interval =0.436-0.759 p<0.001). Neither body mass index nor waist girth conferred increased risk of erosive esophagitis after adjusting for potential confounding factors. Risk of erosive esophagitis in Japanese young adults was not increased by obesity, but it was increased by hiatal hernia and metabolic and lifestyle profiles including hypertension, hyperglycemia, alcohol consumption and smoking.


Expression, subcellular localization and protein-protein interaction of four isoforms of EcR/USP in the common cutworm.
Ecdysone receptor (EcR) and ultraspiracle (USP) form heterodimers to mediate ecdysteroid signaling during molting and metamorphosis. Various EcR/USP heterodimers have been reported. However, it is unclear what kind of EcR/USP combination is adopted by lepidopteran insects during the larval-pupal metamorphosis and whether the EcR/USP heterodimer varies among different tissues. To address these questions, two isoforms of each EcR and USP were cloned from the common cutworm, their messenger RNA expression patterns were examined by real-time quantitative polymerase chain reaction in different tissues during the larval-pupal metamorphosis and in the midgut in response to hormonal induction. Furthermore, their subcellular localization and protein-protein interaction were explored by transient expression and far-western blotting, respectively. All the four genes were significantly up-regulated in prepuae and/or pupae. The expression profiles of EcRB1 and USP1 were nearly identical to each other in the epidermis, fat body and midgut, and a similar situation also applied to EcRA and USP2. The three genes responded to 20-hydroxyecdysone (20E) induction except for USP2, and USP1 could be up-regulated by both 20E and juvenile hormone. The four proteins mainly localized in the nucleus and the nuclear localization was promoted by 20E. The protein-protein interaction between each EcR and USP was found in vitro. These results suggest that two types of EcR/USP heterodimer (EcRA/USP2 and EcRB1/USP1) may exist simultaneously in the common cutworm, and the latter should play more important roles during the larval-pupal metamorphosis. In addition, the types of EcR/USP heterodimer do not vary in the tissues which undergo histolysis and regeneration during metamorphosis.


The usefulness of monomeric periostin as a biomarker for idiopathic pulmonary fibrosis.
The natural course of idiopathic pulmonary fibrosis (IPF) is variable. Predicting disease progression and survival in IPF is important for treatment. We previously demonstrated that serum periostin has the potential to be a prognostic biomarker for IPF. Our aim was to use monomeric periostin in a multicenter study to evaluate its efficacy in diagnosing IPF and predicting its progression. To do so, we developed a new periostin kit to detect only monomeric periostin. The subjects consisted of 60 IPF patients in a multicenter cohort study. We applied monomeric periostin, total periostin detected by a conventional kit, and the conventional biomarkers-KL-6, SP-D, and LDH-to diagnose IPF and to predict its short-term progression as estimated by short-term changes of %VC and % DL, CO. Moreover, we compared the fraction ratios of monomeric periostin to total periostin in IPF with those in other periostin-high diseases: atopic dermatitis, systemic scleroderma, and asthma. Monomeric periostin showed the greatest ability to identify IPF comparable with KL-6 and SP-D. Both monomeric and total periostin were well correlated with the decline of %VC and % DL, CO. Clustering of IPF patients into high and low periostin groups proved useful for predicting the short-term progression of IPF. Moreover, the relative ratio of monomeric periostin was higher in IPF than in other periostin-high diseases. Measuring monomeric periostin is useful for diagnosing IPF and predicting its short-term progression. Moreover, the ratio of monomeric periostin to total periostin is elevated in IPF compared to other periostin-high diseases.


Results of the 2005 national resident matching program: family medicine.
The results of the 2005 National Resident Matching Program (NRMP) reflect a currently stable level of student interest in family medicine residency training in the United States. Compared with the 2004 Match, 19 more positions (66 fewer US seniors) were filled in family medicine residency programs through the NRMP in 2005, at the same time as four fewer (18 fewer US seniors) in primary care internal medicine, seven more in pediatrics-primary care (three fewer US seniors), and 12 fewer (21 fewer US seniors) in internal medicine-pediatrics programs. In comparison, 25 more positions (four more US seniors) were filled in anesthesiology but two fewer (14 fewer US seniors) in diagnostic radiology, two "marker" disciplines that have shown increases over the past several years. Many different forces, including student perspectives of the demands, rewards, and prestige of the specialty, the turbulence and uncertainty of the health care environment, lifestyle issues, and the impact of faculty and resident role models, continue to influence medical student career choices. Seven more positions (57 more US seniors) were filled in categorical internal medicine while 48 more positions (68 more US seniors) were filled in categorical pediatrics programs, where trainees perceive options for either practicing as generalists or entering subspecialty fellowships, depending on the market. With the needs of the nation, especially for rural and underserved populations, continuing to offer opportunities for family physicians, family medicine experienced another slight increase through the 2005 NRMP. The 2005 NRMP results suggest that interest in family medicine and primary care careers continues to be stable.


Preliminary Comparative Effectiveness of Robotic Versus Open Radical Cystectomy in Elderly Patients.
Treatment for muscle-invasive bladder cancer (MIBC) remains highly morbid despite improving surgical techniques. As the median age of diagnosis is 73, many patients are elderly at the time of cystectomy. We compare perioperative surgical outcomes in elderly patients undergoing robotic vs open radical cystectomy (RC). Patients >75 years at time of RC were identified. Demographic, clinicopathologic, and perioperative variables were examined. Estimated blood loss (EBL) and length of stay (LOS) data were collected with multivariate linear regression analysis performed to assess whether technique was independently associated with outcomes. Eighty-seven patients >75 years of age underwent cystectomy for MIBC (58 open, 29 robotic). Mean age was 79.6 (±3.2) and 79.2 (±3.5) for open and robotic groups, respectively (p = 0.64). There were no significant differences in baseline comorbidities, clinical or pathologic stage, or use of neoadjuvant chemotherapy. The mean number of lymph nodes removed was similar (p = 0.08). Robotic cystectomy had significantly longer mean OR times (p < 0.001). On multivariate analyses, robotic surgery was associated with -389cc less EBL (95% CI -547 to -230, p < 0.001) and a -1.5-day-shortened LOS (95%CI -2.9 to -0.2, p = 0.02) compared with open surgery. There were no significant differences in surgical complications or 90-day readmission rates between the two groups. Robotic cystectomy is safe and feasible in an elderly population. We observed longer OR times with robotic surgery, but with decreased EBL, shorter hospital stays, and comparable complication and readmission rates with open RC. Larger prospective studies are required to confirm these findings.


Preparation, electrochemical and spectral properties of N-methyl-pyridylethynyl nickel porphyrins.
A series of nickel N-methyl-pyridylethynylporphines were synthesized and their electrochemical and absorption properties were studied. UV-visible spectra of these complexes show that the absorption red-shifts of the nickel porphyrins are as significant as the zinc analogues. Although the reduction potential shifts caused by the electron-withdrawing substituents are not as large as the zinc complexes, the first reduction potentials of the nickel porphyrins are more positive than those of the zinc counterparts. In addition, the redox behaviors of these nickel porphyrins are similar to those of the zinc analogues.


C–H arylation of unsubstituted furan and thiophene with acceptor bromides: access to donor–acceptor–donor-type building blocks for organic electronics.
Pd-catalyzed direct arylation (DA) reaction conditions have been established for unsubstituted furan (Fu) and thiophene (Th) with three popular acceptor building blocks to be used in materials for organic electronics, namely 4,7-dibromo-2,1,3-benzothiadiazole (BTBr2), N,N′-dialkylated 2,6-dibromonaphthalene-1,4,5,8-bis(dicarboximide) (NDIBr2), and 1,4-dibromotetrafluorobenzene (F4Br2). Reactions with BTBr2, F4Br2, and NDIBr2 require different solvents to obtain high yields. The use of dimethylacetamide (DMAc) is essential for the successful coupling of BTBr2 and F4Br2, but detrimental for NDIBr2, as the electron-deficient NDI core is prone to nucleophilic core substitution in DMAc as solvent but not in toluene. NDIFu2 is much more planar compared to NDITh2, resulting in an enhanced charge-transfer character, which makes it an interesting building block for conjugated systems designed for organic electronics. This study highlights direct arylation as a simple and inexpensive method to construct a series of important donor–acceptor–donor building blocks to be further used for the preparation of a variety of conjugated materials.


[Evaluation of the mutagenicity of detergents by tests on bacteria, plant cells and human leucocytes.].
The aim of this study was to evaluate the mutagenicity of several traditional detergents and that of newer more biodegradable detergents, by using a bacterial test (Ames test), a plant cell test (Allium cepa micronuclei test) and a human leucocyte test (Comet test). All tests were conducted using a wide range of doses (1-2000 mg/l). None of the examined detergents induced mutations in S.typhimurium. One traditional detergent showed a genotoxic effect with the A. cepa test, while all newer detergents and one traditional detergent were shown by the Comet test to be capable of inducing DNA damage.


General anesthesia complicated by perioperative iatrogenic splenic rupture.
Patients with splenomegaly often present with diverse coexisting medical disease and thus offer a variety of anesthetic considerations. The challenges that come with splenectomy have also become increasingly common to the anesthesiologist, given the growing number of indications for surgical intervention including both benign and malignant disease. Removal of the spleen is associated with numerous intraoperative and postoperative risks, including massive intraoperative hemorrhage, perioperative coagulation abnormalities, and post-splenectomy infection. When caring for the patient with an enlarged spleen scheduled for splenectomy, the anesthetic plan must address both patient and procedure specific concerns. We present a medically challenging case of a 28 year old man with splenomegaly secondary to lymphoma, who underwent elective splenectomy, which was complicated by perioperative splenic rupture and hemorrhage.


Differential Translocation of Host Cellular Materials into the Chlamydia trachomatis Inclusion Lumen during Chemical Fixation.
Chlamydia trachomatis manipulates host cellular pathways to ensure its proliferation and survival. Translocation of host materials into the pathogenic vacuole (termed 'inclusion') may facilitate nutrient acquisition and various organelles have been observed within the inclusion, including lipid droplets, peroxisomes, multivesicular body components, and membranes of the endoplasmic reticulum (ER). However, few of these processes have been documented in living cells. Here, we survey the localization of a broad panel of subcellular elements and find ER, mitochondria, and inclusion membranes within the inclusion lumen of fixed cells. However, we see little evidence of intraluminal localization of these organelles in live inclusions. Using time-lapse video microscopy we document ER marker translocation into the inclusion lumen during chemical fixation. These intra-inclusion ER elements resist a variety of post-fixation manipulations and are detectable via immunofluorescence microscopy. We speculate that the localization of a subset of organelles may be exaggerated during fixation. Finally, we find similar structures within the pathogenic vacuole of Coxiella burnetti infected cells, suggesting that fixation-induced translocation of cellular materials may occur into the vacuole of a range of intracellular pathogens.


Evaluation of the effect of a health education campaign of HIV by using an analytical hierarchy process method.
This study was designed to understand the status of HIV/AIDS knowledge, attitude and practice (KAP) among different populations and to provide scientific evidences for further health education. Three rounds of questionnaires were administered among service industry workers who were selected through stratified cluster sampling. Study subjects included hotel attendants, employees of beauty parlors and service workers of transportation industry. Data were analyzed using the analytical hierarchy process. All demonstrated high KAP overall. Synthetic scoring indexes of the three surveys were above 75%. However, the correct response rate on questions whether mosquito bite can transmit HIV/AIDS and what is the relationship between STD with HIV was unsatisfactory (lower than expected); and their attitudes towards people living with HIV and AIDS need to be improved. Moreover, the effect of health education on these groups was unclear. In conclusion, analytical hierarchy process is a valid method in estimating overall effect of HIV/AIDS health education. Although the present status of HIV/AIDS KAP among the service industry workers was relatively good, greater efforts should be made to improve their HIV transmission knowledge, attitude and understanding of the relationship between STDs and HIV.


"Standing alone": understanding the self-management of family caregivers of persons post-stroke at the time of acute care.
To support family caregivers of persons post-stroke adequately from the start and to develop self-management interventions, we aim to gain a better understanding of family caregivers experiences at the time of acute care and therefore achieve a better understanding of how they manage their new situation. We chose a qualitative descriptive methodology using individual semi-structured interviews with eleven family caregivers of persons post-stroke. We conducted interviews retrospectively, between 2 and 10 months post-stroke, and analysed transcripts using thematic analysis. The themes (1) being in survival mode, (2) feeling supported by family and friends, (3) feeling left alone by the treatment team and (4) insisting on information emerged from the data. During acute care, many self-management skills are required from family caregivers but are just starting to be developed. This development can first be observed as co-management with the social network and is often combined with shared decision-making. Information-sharing, foundational for developing self-management, is essential for family caregivers and should be supported proactively by health professionals from the beginning. Further, from the start, health professionals should raise awareness about role changes and imbalances of activities among family caregivers to prevent negative influences on their health.


Evaluation of lithium response in episodic cluster headache: a retrospective case series.
In this study, we attempted to evaluate the response to lithium treatment and its tolerability in the prevention of episodic cluster headache (CH) and to identify clinical predictors of response. Verapamil and lithium are the most widely used drugs in the prevention of CH attacks. Lithium is considered a second-line treatment in part because of its potentially severe adverse drug reactions (ADRs). Evidence for the efficacy of lithium in CH prevention is greater in chronic than in episodic patients. In addition, because of its narrow therapeutic window and ADRs (which can be significantly reduced with proper periodical monitoring of blood levels), lithium is recommended only in chronic CH, when other drugs are ineffective or potentially harmful. Our primary aim was to determine whether lithium reduced the number of attacks per day (attack frequency). We compared attack frequency in 3 periods: run-in, the first, and the second week of lithium treatment. Responders were defined as patients showing at least a 50% reduction in attack frequency. Lithium response was evaluated in 26 patients. Treatment led to a significant reduction in attack frequency within 2 weeks in a percentage of 77% of responders and 23% of nonresponders. Responders and nonresponders did not differ in terms of demographic and clinical characteristics. Only 15% of patients experienced mild ADRs. Our study provides additional evidence on the effectiveness of lithium in the prevention of episodic CH. It also shows the tolerability of lithium, given the short duration of treatment and low dosage.


Kerr nonlinearity mitigation in 5 × 28-GBd PDM 16-QAM signal transmission over a dispersion-uncompensated link with backward-pumped distributed Raman amplification.
We present experimental and numerical investigations of Kerr nonlinearity compensation in a 400-km standard single-mode fiber link with distributed Raman amplification with backward pumping. A dual-pump polarization-independent fiber-based optical parametric amplifier is used for mid-link spectral inversion of 5 × 28-GBd polarization-multiplexed 16-QAM signals. Signal quality factor (Q-factor) improvements of 1.1 dB and 0.8 dB were obtained in the cases of a single-channel and a five-channel wavelength-division multiplexing (WDM) system, respectively. The experimental results are compared to numerical simulations with good agreement. It is also shown with simulations that a maximum transmission reach of 2400 km enabled by the optical phase conjugator is possible for the WDM signal.


Effect of Scurrula atropurpurea on nitric oxide, endothelial damage, and endothelial progenitor cells of DOCA-salt hypertensive rats.
To know whether Scurrula atropurpurea is able to modulate total plasma nitrate/nitrite levels, decrease endothelial damage, and increase endothelial progenitor cells (EPCs) in hypertensive rats. The rats were divided in 5 groups: control (normotensive) group, Desoxy cortico sterone (DOCA)-salt hypertensive group, and three DOCA-salt hypertensive groups. All 5 groups received methanolic extract of S. atropurpurea (MESA) at a dosage of 50; 100; and 200 mg/KgBW. Serum nitric oxide (NO) was assayed by colorimetric. Circulating endothelial cells (CECs) and EPCs were assayed using flow cytometry. The administration of MESA100 and MESA200 elevated the total plasma nitrate/nitrite levels but cannot reach the level in control group. MESA100 and MESA200 also elevated the EPCs number compared with hypertensive group. The administration of MESA significantly (P< 0.05) decreased the CECs number compared to hypertensive groups. Methanolic extract of S. atropurpurea is able to modulate total plasma nitrate/nitrite levels and diminish endothelial damage via increasing EPCs.


A need for more psychophysiological research in australia.
Western communities are becoming increasingly more interested in altered states of consciousness such as hypnosis, meditation and other states associated with certain "brain wave" patterns. In the United States of America especially, psychophysiological research is beginning to lead to an understanding of some of the basic mechanisms underlying certain mental phenomena and their therapeutic uses. In Australia, on the other hand, experimental investigations in this area are negligible. It is important to begin intensive psychophysiological research now.


High Frequency of ASXL1 and IDH Mutations in Young Acute Myeloid Leukemia Egyptian Patients.
Prognostication of AML patients depends on association of genetic and epigenetic abnormalities. We aimed to evaluate the frequency and prognostic significance of Additional Sex comb's Like1 (ASXL1), Isocitrate Dehydrogenase (IDH) and Casitas B- lineage Lymphoma (CBL) mutations in AML assessing their association with different cytogenetic risk category. We used High Resolution Melting (HRM) technology that detects small differences in PCR amplified sequences by direct melting using EvaGreen saturating dye to analyze epigenetic mutations in 70 denovo AML patients. Median age of AML patients was 39.5 years (18-75). ASXL1, IDH and CBL mutations were detected in 14 (20%), 10 (14%) and 5 (7%) patients, respectively. Mean age of ASXL1 and IDH mutants vs. wild type was 35.9±14.6 years and 42.9±14.4 years (p=0.114) and 46.7±15.2 years vs. 40.6±14.5 years (p=0.290), respectively. AML cytogenetic risk groups included low (25/70, 36%), intermediate (33/70, 47%) and high-risk (12/70, 17%). Nine/14 (64%) ASXL1 and 8/10 (80%) IDH mutants were classified as intermediate risk and 9 ASXL1 positive (64%) were adolescent and young adults (AYA). Overall survival (OS) of mutant ASXL1 vs. wild type was 1.1 years (95% CI 0.83-1.4) vs. 1.9 years (95% CI 0.71-7.51), respectively (p=0.056). OS of mutant IDH vs. wild type was 1.25 years (95% CI 0.85-1.6) vs. 1.8 years (95% CI 1.2-6.7), respectively (p=0.020). In intermediate risk cytogenetic group, ASXL1 and IDH mutants had shorter OS than wild type; 1.1 years (95% CI 0.97-1.2) vs. 2.1 years (95% CI 0.14-10.8) (p=0.002) and 1.8 years (95% CI 0.69-3.15) vs. 2.3 years (95% CI 1.1-5.5) (p=0.05), respectively. ASXL1 and IDH mutations occur at a high incidence among young Egyptian AML patients with intermediate risk cytogenetics and confer a poorer outcome. Integration of mutations into risk profiling may predict outcome and impact therapeutic approach of young AML patient with uncertain prognosis.


[Characterization method for metallothioneins by reversed-phase liquid chromatography coupled with electrospray ionization mass spectrometry].
Mammalian metallothioneins (MTs) usually have two major isoforms, MT-1 and MT-2, existing in tissues because of the genetic polymorphism. Metallothionein isoforms and sub-isoforms were characterized with a hyphenated technique of reversed-phase liquid chromatography (RPLC) coupled with electrospray ionization mass spectrometry (ESI-MS). The MT-isoform separation was carried out using a C8 narrow-bore column Vydac C8 (250 mm x 2.1 mm i.d., 5 microm, 30 nm). Buffer A was 5 mmol/L ammonium acetate in water (pH 6.0) and buffer B was 5 mmol/L ammonium acetate in methanol-water (1:1, v/v) (pH 6.0). A linear gradient elution was used by increasing buffer B from 10% to 37.5% within 40 min. The flow rate was set at 0.20 mL/min. The tentative formulas of MT isoforms and subisoforms were interpreted with the measured masses at the vicinity of apexes in total ion current chromatogram of ESI-MS and the reference data reported previously. The method was validated with the standard reference materials of MT-1 and MT-2. The results indicated that many MT species interpreted were in good agreement with the reference data reported. The MT sample from rabbit liver was measured with the established method. The results, of which the apo-MT was used by acidification of the sample for simplifying the mass spectra, showed that there were species of MT isoforms and subisoforms in rabbit livers.


Off-label use limitation of the Super Arrow-Flex® sheath introducer in congenital heart disease interventions.
Many interventionists are infatuated by the recent resurgence of the coilwire design with the Super Arrow-Flex® sheath (Teleflex, Inc., NC, United States of America). This exclusive sheath is a highly flexible, durable, conduit intended for use in diagnostic and interventional procedures with several advantages and maximum effectiveness in challenging cases. We report failure to easily advance memory shape occluders through Super Arrow-Flex® sheaths larger than the recommended implant French size. We detail the technical reasons behind this non-previously reported drawback and describe benchside tests as possible solutions.


[Solitary fibrous tumor/hemangiopericytoma of central nervous system: a clinicopathologic analysis of 71 cases].
Objective: As solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) share the same molecular genetics features, the 2016 WHO classification of central nervous system (CNS) tumors had created the combined term SFT/HPC and assigns three grades. This study aims to investigate the clinicopathologic characteristics, diagnosis, differential diagnosis and prognosis of CNS SFT/HPC. Methods: Seventy-one cases of CNS SFT and HPC were retrospectively reclassified and studied. Histopathological, immunohistochemical and imaging features were analyzed. The follow-up data were analyzed. Results: There were 37 male and 34 female patients. The median age was 48 years (range, 3-77 years). Twelve cases (17%) were WHO grade Ⅰ, 26 (37%) were WHO grade Ⅱ and 33 (46%) were WHO grade Ⅲ. Microscopically the tumor could show traditional SFT phenotype, HPC phenotype or mixed phenotype. Immunochemically, 97%(69/71) were positive for STAT6, with 96%(66/69)showing diffuse strong staining. Approximately 90% were diffusely positive for bcl-2, CD99 and vimentin. The expression rate of CD34 decreased with increasing tumor grade, and the mean expression rate was 78%. SSTR2a was variably expressed in 10% (7/71) of cases including one case showing strong cytoplasmic staining. A few cases expressed EMA, CD57 and S-100 focally. The Ki-67 index ranged from 1% to 50%. Thirty four patients were followed up for 8-130 months; 12 patients(35%)had recurrences, and two (6%) had liver metastases. Conclusions: CNS SFT/HPC is relatively uncommon. There was significant morphological overlap or transition between different grades. STAT6 is a specific marker for the diagnosis of this tumor. Surgical resection is the preferred treatment. WHO grade Ⅱ and Ⅲ SFT/HPC show rates of local recurrence and systemic metastasis, with liver being the most common site of extracranial metastasis.


3D nanomolding and fluid mixing in micromixers with micro-patterned microchannel walls.
Microfluidic devices where the microchannel walls were decorated with micro and nanostructures were fabricated using 3D nanomolding. Using 3D molded microfluidic devices with microchannel walls decorated with microscale gratings, the fluid mixing behavior was investigated through experiments and numerical simulation. The use of microscale gratings in the micromixer was predicated by the fact that large obstacles in a microchannel enhances the mixing performance. Slanted ratchet gratings on the channel walls resulted in a helical flow along the microchannel, thus increasing the interfacial area between fluids and cutting down the diffusion length. Increasing the number of walls decorated with continuous ratchet gratings intensified the strength of the helical flow, enhancing mixing further. When ratchet gratings on the surface of the top cover plate were aligned in a direction to break the continuity of gratings from the other three walls, a stack of two helical flows was formed one above each other. This work concludes that the 3D nanomolding process can be a cost-effective tool for scaling-up the fabrication of microfluidic mixers with improved mixing efficiencies.Graphical abstractIn this paper we show that a micromixer with patterned walls can be fabricated using 3D nanomolding and solvent-assisted bonding to manipulate the flow patterns to improve mixing.


[Primers for detecting gene rearrangement in different regions of immunoglobulin heavy chain genes and their application in diagnosis of paraffin-embedded lymphoma tissues].
To analyze and optimize the gene rearrangement primers of different frame regions (FR) of immunoglobulin heavy chain (IgH) genes by bioinformatic methods and explore the application of these primers in the detection of paraffin-embedded lymphoma tissues. Three pairs of primers from IgH FR1, FR2 and FR3 regions (P1c, P2A and P31, respectively) were selected as the B cell gene rearrangement primers after comparison of the gene fragments in 44 IgH variable and 6 joining regions. Using one pair of T cell receptor (TCR) gamma primer as the T cell gene rearrangement primer, 101 histopathologically confirmed lymphoproliferative samples including 80 B cell lymphomas, 14 T cell lymphomas, and 7 reactive proliferative lymph nodes were examined by PCR for gene arrangement. The DNAs from DG75 and Jurkat cell lines were used as the positive controls for B and T cell lymphoma, respectively, with those from reactive proliferative lymph nodes as the negative control. The positivity rates of IgH primers (P1c, P2A and P31) in the 80 B cell lymphomas were 37.5% (30/80), 52.5% (42/80) and 70.0% (56/80), respectively, and only one of the 14 T cell lymphoma cases was positive for the primers, suggesting significant differences in the detection rates of B cell lymphomas by the 3 primers. The detection rate was increased to 83.9% by combining the results by P31 and P2A primers. No positivity was found in the proliferative reaction tissues. Primers from IgH FR3 region genes are more sensitive than that from the FR1 and FR2 regions in the detection of gene rearrangement in paraffin-embedded lymphoma tissues. The detection rates can be increased by combining the results with the primers for IgH FR3 with that of FR2.


Evaluation of pollution susceptibility of Karst aquifers of Rewa Town (Madhya Pradesh) using "DRASTIC" approach.
Pollution susceptibility of groundwater of Rewa town situated on karstified Bhander limestones of the Bhander group is discussed in this paper. Pollution potential of selected localities in the town has been determined using the DRASTIC INDEX methodology. Pollution potential for these localities varied between 162 to 217. Shallow aquifers in karstified limestones having direct access to surface water were found more susceptible to pollution. Accordingly, remedial measures were suggested for minimising pollution.


Microgravity effects on thylakoid, single leaf, and whole canopy photosynthesis of dwarf wheat.
The concept of using higher plants to maintain a sustainable life support system for humans during long-duration space missions is dependent upon photosynthesis. The effects of extended exposure to microgravity on the development and functioning of photosynthesis at the leaf and stand levels were examined onboard the International Space Station (ISS). The PESTO (Photosynthesis Experiment Systems Testing and Operations) experiment was the first long-term replicated test to obtain direct measurements of canopy photosynthesis from space under well-controlled conditions. The PESTO experiment consisted of a series of 21-24 day growth cycles of Triticum aestivum L. cv. USU Apogee onboard ISS. Single leaf measurements showed no differences in photosynthetic activity at the moderate (up to 600 micromol m(-2) s(-1)) light levels, but reductions in whole chain electron transport, PSII, and PSI activities were measured under saturating light (>2,000 micromol m(-2) s(-1)) and CO(2) (4000 micromol mol(-1)) conditions in the microgravity-grown plants. Canopy level photosynthetic rates of plants developing in microgravity at approximately 280 micromol m(-2) s(-1) were not different from ground controls. The wheat canopy had apparently adapted to the microgravity environment since the CO(2) compensation (121 vs. 118 micromol mol(-1)) and PPF compensation (85 vs. 81 micromol m(-2) s(-1)) of the flight and ground treatments were similar. The reduction in whole chain electron transport (13%), PSII (13%), and PSI (16%) activities observed under saturating light conditions suggests that microgravity-induced responses at the canopy level may occur at higher PPF intensity.


Endogenous opioids regulate social threat learning in humans.
Many fearful expectations are shaped by observation of aversive outcomes to others. Yet, the neurochemistry regulating social learning is unknown. Previous research has shown that during direct (Pavlovian) threat learning, information about personally experienced outcomes is regulated by the release of endogenous opioids, and activity within the amygdala and periaqueductal gray (PAG). Here we report that blockade of this opioidergic circuit enhances social threat learning through observation in humans involving activity within the amygdala, midline thalamus and the PAG. In particular, anticipatory responses to learned threat cues (CS) were associated with temporal dynamics in the PAG, coding the observed aversive outcomes to other (observational US). In addition, pharmacological challenge of the opioid receptor function is classified by distinct brain activity patterns during the expression of conditioned threats. Our results reveal an opioidergic circuit that codes the observed aversive outcomes to others into threat responses and long-term memory in the observer.


4J(COCCH) and 4J(CCCCH) as probes of exocyclic hydroxymethyl group conformation in saccharides.
[structure: see text] 1H NMR spectra of aldohexopyranosyl rings containing 13C-enrichment at either C1 or C3 reveal the presence of long-range 4J(C1,H6R/S) and 4J(C3,H6R/S) whose magnitudes depend mainly on the O5-C5-C6-O6 torsion angle. Using theoretical calculations (density functional theory, DFT; B3LYP/6-31G*) and conformationally constrained experimental model compounds, the magnitudes and signs of 4J(C1,H6R/S) and 4J(C3,H6R/S) have been established, and their dependencies on the geometry of the C1-O5-C5-C6-H6R/S and C3-C4-C5-C6-H6R/S coupling pathways, respectively, were determined. The latter dependencies mimic that observed previously for 4J(HH) in aliphatic compounds such as propane. DFT calculations also showed that inclusion of non-Fermi contact terms is important for accurate predictions of 4J(CH) values. Application to methyl alpha- and beta-D-glucopyranosides reveals different rotameric distributions about their hydroxymethyl groups, with the beta-anomer enriched in the gt rotamer, in agreement with recent multi-J redundant coupling analyses. 4J(C1,H6R/S) and 4J(C3,H6R/S) are expected to complement other recently developed J-couplings for the assignment of hydroxymethyl group conformation in oligosaccharides containing 1,6-glycosidic linkages.


Obeticholic acid treatment of mice to promote fertilization and reproduction.
Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, has been demonstrated to ameliorate the histopathological characteristics of liver damage. Nonetheless, the systemic safety profile of OCA with regard to reproduction and development remains poorly understood. In the present study, we conducted a dose-response experiment by administering OCA at doses of 5 mg/kg, 10 mg/kg, or 20 mg/kg through tube feeding to investigate its effect on reproductive development and fertilization rate in both male and female mice. Furthermore, we evaluated the levels of protein and mitochondrial function in the placenta through western blot, qPCR, and scanning electron microscopy. The results showed that 10 mg/kg and 20 mg/kg OCA doses significantly reduced the rate of placental implantation (P < 0.05). Also, OCA increased maternal body weight. In addition, OCA increased levels of FXR and TGR5 and produced changes in oxidative stress levels (P < 0.05). Mitochondrial activity result found that 10 mg/kg and 20 mg/kg of OCA significantly reduced the mitophagy autosomes/nucleus compared with the normal control group (P < 0.05). What is more, there was no significant difference in sperm count after OCA intervention in either C57BL/10 mice or BALB/c mice. Overall, we demonstrated that OCA treatment protected against placental implantation by suppressing placental oxidative stress and mitochondrial activity.


[Management of exercise therapy for elderly with diabetes].
The number of elderly patients with diabetes have rapidly increased. Elderly patients with diabetes have several risks, such as fall, hypoglycemia and cardiovascular disease. On the other hand, physical activity has beneficial effects for glycemic control, cardiovascular disease, fall, cancer and quality of life. Therefore, we need to carefully treat those patients by exercise to provide more benefits, while avoiding those risks. In this review we described the methods, benefits and contra-indications of exercise and physical activity in elderly patients with diabetes.


Vitamin D/Vitamin D receptor mitigates cisplatin-induced acute kidney injury by down-regulating C5aR.
Cisplatin (DDP) is a potent chemotherapeutic; however, it can also cause acute kidney injury (AKI). Because of the complexity of the toxicity it induces, few effective methods exist for ameliorating any form of DDP-induced AKI. Recent research has suggested that the complement system is a potential molecular target for such amelioration. In the study here, in vivo (male ICR mice) and in vitro (HK-2 cells) models of DDP-induced AKI were established to investigate the potential therapeutic effects of Vitamin D (VD) against this form of AKI. Endpoints assessed in vivo/in vitro included overall renal function, degree of renal damage, and complement receptor C5aR expression using histology, immunohistochemistry, immunofluorescence, RT-PCR, and Western blots. The data indicated that the use of VD treatment could reduce renal pathological damage along with expression of TNFα, IL-1β, IL-18, and C5aR; however, an over-expression of C5aR weakened the protective effects of VD/VD receptor (VDR) against oxidative damage and inflammatory cell infiltration. Using a luciferase reporter gene assay and ChIP analysis, it was demonstrated that C5aR was transcriptionally inhibited by VDR. In conclusion, VD/VDR could delay DDP-induced AKI by inhibiting the expression of C5aR through transcriptional regulation and reducing the production of downstream pro-inflammatory cytokines. The present study revealed the regulatory mechanism of VD/VDR in acute renal inflammation and provides new insights into its therapeutic function in DDP-induced AKI.


Ultrafast Laser Processing of Nanostructured Patterns for the Control of Cell Adhesion and Migration on Titanium Alloy.
Femtosecond laser texturing is a promising surface functionalization technology to improve the integration and durability of dental and orthopedic implants. Four different surface topographies were obtained on titanium-6aluminum-4vanadium plates by varying laser processing parameters and strategies: surfaces presenting nanostructures such as laser-induced periodic surface structures (LIPSS) and 'spikes', associated or not with more complex multiscale geometries combining micro-pits, nanostructures and stretches of polished areas. After sterilization by heat treatment, LIPSS and spikes were characterized to be highly hydrophobic, whereas the original polished surfaces remained hydrophilic. Human mesenchymal stem cells (hMSCs) grown on simple nanostructured surfaces were found to spread less with an increased motility (velocity, acceleration, tortuosity), while on the complex surfaces, hMSCs decreased their migration when approaching the micro-pits and preferentially positioned their nucleus inside them. Moreover, focal adhesions of hMSCs were notably located on polished zones rather than on neighboring nanostructured areas where the protein adsorption was lower. All these observations indicated that hMSCs were spatially controlled and mechanically strained by the laser-induced topographies. The nanoscale structures influence surface wettability and protein adsorption and thus influence focal adhesions formation and finally induce shape-based mechanical constraints on cells, known to promote osteogenic differentiation.


Successful Treatment of Aspergillus Empyema Using Open Window Thoracostomy Salvage Treatment and the Local Administration of an Antifungal Agent.
A 76-year-old woman received long-term immunosuppressive treatment for collagen vascular disease-associated interstitial pneumonia. The patient developed a cavitary mass lesion in the right lower lung field, and both nontuberculous mycobacteria and Aspergillus spp. were isolated after bronchial washing. The patient underwent a right lower lobectomy but developed Aspergillus empyema. Empyema due to Aspergillus spp. is a rare and life-threatening condition; however, the standard therapeutic strategies for treating Aspergillus empyema are not clear. We herein report a case of Aspergillus empyema that was successfully treated with a combination therapy which included open-window thoracostomy and the administration of antifungal agents (systemic micafungin and local amphotericin-B).


Cloning and sequencing of the PIF gene involved in repair and recombination of yeast mitochondrial DNA.
The nuclear gene PIF of Saccharomyces cerevisiae is required for both repair of mitochondrial DNA (mtDNA) and recognition of a recombinogenic signal characterized by a 26-bp palindromic AT sequence in the ery region of mtDNA. This gene has been cloned in yeast by genetic complementation of pif mutants. Its chromosomal disruption does not destroy the genetic function of mitochondria. The nucleotide sequence of the 3.5-kb insert from a complementing plasmid reveals an open reading frame encoding a potential protein of 857 amino acids and Mr = 97,500. An ATP-binding domain is present in the central part of the gene and in the carboxy-terminal region a putative DNA-binding site is present. Its alpha helix-turn-alpha helix motif is found in DNA-binding proteins such as lambda and lactose repressors which recognize symmetric sequences. Significant amino acid homology is observed with yeast RAD3 and E. coli UvrD (helicase II) proteins which are required for excision repair of damaged DNA.


Quality assessment of artisanal cheeses in the northwest region of Paraná.
Artisanal unripened cheeses produced in northwestern Paraná, Brazil, were studied for microbiological quality and sensory quality. The cheeses analyzed showed high counts of aerobic mesophilic microorganisms and S. aureus. However, even with the results showing poor microbiological quality, from a sensory point of view, consumers considered cheeses acceptable (high acceptance index). The results may indicate that there is still a lack of training and knowledge of production procedures to reduce microbiological contamination of artisanal cheese produced in northwestern Paraná.


Microdentistry with Lasers.
Treating infants and young children is a rewarding experience, especially when we guide parents and children down the path of prevention and interception of oral disease. The pediatric dentist has to be updated about the new technologies to treating patients along with basic principles. This article gives a brief discussion on the types, applications, advantages, and limitations of the use of lasers in pediatric dentistry.


Inhibition of spore germination, growth, and toxin activity of clinically relevant C. difficile strains by gut microbiota derived secondary bile acids.
The changing epidemiology of Clostridium difficile infection over the past decades presents a significant challenge in the management of C. difficile associated diseases. The gastrointestinal tract microbiota provides colonization resistance against C. difficile, and growing evidence suggests that gut microbial derived secondary bile acids (SBAs) play a role. We hypothesized that the C. difficile life cycle; spore germination and outgrowth, growth, and toxin production, of strains that vary by age and ribotype will differ in their sensitivity to SBAs. C. difficile strains R20291 and CD196 (ribotype 027), M68 and CF5 (017), 630 (012), BI9 (001) and M120 (078) were used to define taurocholate (TCA) mediated spore germination and outgrowth, growth, and toxin activity in the absence and presence of gut microbial derived SBAs (deoxycholate, isodeoxycholate, lithocholate, isolithocholate, ursodeoxycholate, ω-muricholate, and hyodeoxycholate) found in the human and mouse large intestine. C. difficile strains varied in their rates of germination, growth kinetics, and toxin activity without the addition of SBAs. C. difficile M120, a highly divergent strain, had robust germination, growth, but significantly lower toxin activity compared to other strains. Many SBAs were able to inhibit TCA mediated spore germination and outgrowth, growth, and toxin activity in a dose dependent manner, but the level of inhibition and resistance varied across all strains and ribotypes. This study illustrates how clinically relevant C. difficile strains can have different responses when exposed to SBAs present in the gastrointestinal tract.


Effects of hypoxia on muscle protein synthesis and anabolic signaling at rest and in response to acute resistance exercise.
Chronic reductions in tissue O(2) tension (hypoxia) are associated with muscle atrophy and blunted hypertrophic responses to resistance exercise (RE) training. However, the effect of hypoxia on muscle protein synthesis (MPS) at rest and after RE is unknown. In a crossover study, seven healthy men (21.4 ± 0.7 yr) performed unilateral leg RE (6 × 8 repetitions at 70% 1-repetition maximum) under normoxic (20.9% inspired O(2)) and normobaric hypoxic (12% inspired O(2) for 3.5 h) postabsorptive conditions. Immediately after RE the rested leg was biopsied, and a primed continuous infusion of [1,2-(13)C(2)]leucine was maintained for 2.5 h before final biopsies from both legs to measure tracer incorporation and signaling responses (i.e., ribosomal S6 kinase 1). After 3.5 h of hypoxia, MPS was not different from normoxia in the rested leg (normoxia 0.033 ± 0.016 vs. hypoxia 0.043 ± 0.016%/h). MPS increased significantly from baseline 2.5 h after RE in normoxia (0.033 ± 0.016 vs. 0.104 ± 0.038%/h) but not hypoxia (0.043 ± 0.016 vs. 0.060 ± 0.063%/h). A significant linear relationship existed between MPS 2.5 h after RE in hypoxia and mean arterial blood O(2) saturation during hypoxia (r(2) = 0.49, P = 0.04). Phosphorylation of p70S6K(Thr389) remained unchanged in hypoxia at rest but increased after RE in both normoxia and hypoxia (2.6 ± 1.2-fold and 3.4 ± 1.1-fold, respectively). Concentrations of the hypoxia-responsive mTOR inhibitor regulated in development and DNA damage-1 were unaltered by hypoxia or RE. We conclude that normobaric hypoxia does not reduce MPS over 3.5 h at rest but blunts the increased MPS response to acute RE to a degree dependent on extant SpO(2).


Making sense of the epithelial barrier: what molecular biology and genetics tell us about the functions of oral mucosal and epidermal tissues.
The epidermis of skin and the oral mucosa are highly specialized stratified epithelia that function to protect the body from physical and chemical damage, infection, dehydration, and heat loss. To maintain this critical barrier, epithelial tissues undergo constant renewal and repair. Epithelial cells (keratinocytes) undergo a program of terminal differentiation, expressing a set of structural proteins, keratins, which assemble into filaments and function to maintain cell and tissue integrity. Two types of cell adhesion structures, desmosomes and hemidesmosomes, function to glue keratinocytes to one another and to the basement membrane, and connect the keratin cytoskeleton to the cell surface. Keratinizing epithelia such as the epidermis and oral gingiva that have to withstand severe physical and chemical forces produce a toughened structure, the cornified cell envelope. This envelope is a major component of the epithelial barrier at the tissue surface. This article summarizes our current understanding of the structure and function of these different cellular components and discusses various genetic and acquired diseases that alter tissue integrity and barrier function. We also highlight recent work demonstrating how loss or attenuation of certain proteases can lead to early onset periodontitis and tooth loss as well as other epithelial abnormalities.


Depressive symptoms in farm women: effects of health status and farming lifestyle characteristics, behaviors, and beliefs.
A multitude of responsibilities, environmental and social influences, and stressors place farm women at high risk for depressive symptoms. This cross sectional survey design study examines demographic, health status, and farm lifestyle characteristics, behaviors and beliefs as risk factors contributing to depressive symptoms among farm women in southeast Louisiana. The study was conducted in a stratified, random sample of 657 women 18 years and older. Factors predictive of depressive symptoms in adjusted logistic regression included those who experience poor health, perceive hazards associated with farming, experience recent farm-related injuries and engage in farming over longer periods of time. These findings help target interventions toward women at risk for depressive symptoms.


Modulation of Circadian Rhythms Affects Corneal Epithelium Renewal and Repair in Mice.
In mammalian corneal epithelium, mitosis shows a distinct circadian pattern. However, how this circadian pattern is maintained, and how it or its disruption influence renewal and regeneration remain unclear. C57BL/6 mice were maintained under 12-hour light/12-hour dark (LD), 12-hour light/12-hour light (LL), 12-hour dark/12-hour dark (DD), or reversed LD (DL, 12-hour dark/12-hour light; jet-lag defined as a shift of 12 hours) conditions. Mitotic cells in corneal epithelium were enumerated and analyzed via immunofluorescence at different zeitgeber times (ZTs). Expression of core clock genes (Clock, Bmal1, Period2, Cry1, and Rev-erbα) was qualified via quantitative RT-PCR. The rate and quality of healing at different ZT times and after administration of two small-molecule modifiers of the circadian clock, KL001 and SR8278, was evaluated. In this study, photic cues were found to influence the 24-hour rhythm of corneal clock gene expression and epithelial cell mitosis in mice. Disruption of the circadian clock by exposure to constant light, constant dark, or jet-lag conditions modified the normal 24-hour patterns of corneal epithelial mitosis and corneal clock gene expression. The time of day of wound occurrence affected the rate and quality of corneal healing, with both of these parameters peaking during the more mitotically active hours of the morning. The two small-molecule modifiers of the circadian clock, KL001 and SR8278, had negative and positive effects on corneal wound healing, respectively. Circadian rhythms significantly influence corneal epithelium renewal and repair in mice. Our findings reveal possible opportunities for biological rhythm-based interventional strategies to control corneal healing and restore corneal homeostasis.


Real-Space Observation of Quantum Tunneling by a Carbon Atom: Flipping Reaction of Formaldehyde on Cu(110).
We present a direct observation of carbon-atom tunneling in the flipping reaction of formaldehyde between its two mirror-reflected states on a Cu(110) surface using low-temperature scanning tunneling microscopy (STM). The flipping reaction was monitored in real time, and the reaction rate was found to be temperature independent below 10 K. This indicates that this reaction is governed by quantum mechanical tunneling, albeit involving a substantial motion of the carbon atom (∼1 Å). In addition, deuteration of the formaldehyde molecule resulted in a significant kinetic isotope effect ( RCH2O/ RCD2O ≈ 10). The adsorption structure, reaction pathway, and tunneling probability were examined by density functional theory calculations, which corroborate the experimental observations.


Uncommon causes of cerebrovascular dementia.
The concept of Binswanger's disease (BD) remains unclear and may not constitute a useful diagnostic category. However, cognitive decline may be present in a proportion of patients with subarachnoid hemorrhages (SAH) or subdural hematomas (SH). We provide a critical review of the concept of BD and summarize the main findings on the association between SAH, SH and cognitive decline. BD was originally identified as a type of dementia different from neurosyphilis and with characteristic white matter atrophy. The phenomenology of BD is currently construed around the concept of frontosubcortical dementia, but the validity of this construct is unclear. Patients with SAH frequently develop a variety of cognitive and behavioral problems that usually result in poor psychosocial adjustment and poor quality of life. SH is a rare cause of progressive cognitive impairment. A proportion of patients (particularly functionally impaired old individuals) are at a high risk for cognitive deficits after surgical drainage of the hematoma.


How to select patients and timing for rectal indomethacin to prevent post-ERCP pancreatitis: a systematic review and meta-analysis.
Acute pancreatitis is a severe complication of endoscopic retrograde cholangiopancreatography (ERCP). Previous meta-analyses have shown that indomethacin effectively prevents this complication; however, the data are limited. We performed a systematic review and meta-analysis to clarify the applications for rectal indomethacin. A systematic search was performed in June 2016. Human prospective, randomized, placebo-controlled trials that compared rectally administered indomethacin with a placebo for the prevention of post-ERCP pancreatitis (PEP) were included. A meta-analysis was performed using a random-effects model to assess the outcomes (PEP) using Review Manager 5.0. Seven randomized controlled trials met the inclusion criteria (n = 3013). The overall incidence of PEP was significantly lower after prophylactic administration of rectal indomethacin than after administration of the placebo (RR, 0.58, 95% CI, 0.40-0.83; P = 0.004). A subgroup analysis was performed for rectal indomethacin administration compared to a placebo in high-risk patients (RR, 0.46; 95% CI, 0.32-0.65; P < 0.00001) and average-risk patients (RR, 0.75; 95% CI, 0.46-1.22; P = 0.25) and for administration before ERCP (RR, 0.56; 95% CI, 0.39-0.79; P = 0.001) and after the procedure (RR, 0.61; 95% CI, 0.26-1.44; P = 0.26). This meta-analysis indicated that prophylactic rectal indomethacin is not suitable for all patients undergoing ERCP but it is safe and effective to prevent PEP in high-risk patients. In addition, rectal indomethacin administration before ERCP is superior to its administration after ERCP for the prevention of PEP.


Shoulder and elbow arthroplasty in younger patients.
Joint arthroplasty is common in elderly patients with arthritis. The success of joint arthroplasty in the elderly population has increased the indications for joint arthroplasty in younger patients. The success and increased indications are due to advances in technology and joint arthroplasty design and materials, as well as to bone-conserving approaches that are more applicable to younger patients. Although most joint arthroplasty procedures are for the hip and knee, the upper extremity (shoulder and elbow) is the fastest-growing segment of joint arthroplasty procedures. This article presents innovative approaches to shoulder and elbow arthroplasty that are designed to treat younger patients with arthritis of the shoulder and elbow.


Studies on dentin. 2. Vestigial lacteal incisor teeth of the rat.
The presence of a vestigial, lacteal incisor tooth is described in the laboratory rat. This tooth is felt to belong to the same dental generation as the other functional teeth. Accordingly, the rat is described as having a monophyodont, first dentition containing two incisor teeth in each quadrant. These vestigial teeth are then compared with other similar mammalian teeth and are defined as transient, partially formed and non-functional. As such, they are differentiated from other transient teeth. The examination of the fossil record suggests that tooth loss is a general phenomenon in rodents, but that this vestigial tooth probably represents a condition present in forms antecedent to rodents. A critical literature review strongly suggests that the teeth of the recent rat are members of the first dental generation. The presence of such a vestigial tooth and of the postincisive diastema in the rat is felt to be an example of phylogenetic reduction and progressive retardation in the sense of de Beer's concepts. These same two phenomena were analyzed with respect to the field theory of Butler and of the Zahnreihen theory of Edmund. Placed within the context of recent data on epithelioectomesenchymal interactions, both theories were supported, and both the vestigial teeth and anodontic diastema were shown to be explicable within these conceptual frameworks.


Measurement of enzyme kinetics using microscale steady-state kinetic analysis.
This paper describes a new technique--microscale steady-state kinetic analysis (microSKA)--that enables the rapid and parallel analysis of enzyme kinetics. Rather than physically defining a microscopic reactor through microfabrication, we show how the relative rates of reaction and transport in a macroscopic flow chamber, where the enzyme is immobilized on one wall of the chamber, results in the confinement of an enzyme-catalyzed reaction to a microscopic reactor volume adjacent to this wall. This volume has linear dimensions that are orders of magnitude smaller than the physical dimensions of the system (i.e., micrometer vs millimeter). Conversion within this volume is monitored at steady state as a function of position, rather than time. In this way, limitations due to reactor dead time and mixing are avoided. We use microSKA to determine kinetic parameters for the alkaline phosphatase-catalyzed de-phosphorylation of nonfluorescent methylumbelliferyl phosphate (MUP) to fluorescent 7-hydroxy-4-methylcoumarin (HMC) at two different values of pH. Kinetic parameters measured with microSKA are in good agreement with values obtained using conventional methods, if one takes into account effects of immobilization on enzyme activity. This technique provides a rapid and simple method for determining enzyme kinetics using small amounts of sample material and may be useful for applications in proteomics, drug discovery, biocatalyst development, and clinical diagnostics.


Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats.
Embryonic stem cells promise to provide a well-characterized and reproducible source of replacement tissue for human clinical studies. An early potential application of this technology is the use of retinal pigment epithelium (RPE) for the treatment of retinal degenerative diseases such as macular degeneration. Here we show the reproducible generation of RPE (67 passageable cultures established from 18 different hES cell lines); batches of RPE derived from NIH-approved hES cells (H9) were tested and shown capable of extensive photoreceptor rescue in an animal model of retinal disease, the Royal College of Surgeons (RCS) rat, in which photoreceptor loss is caused by a defect in the adjacent retinal pigment epithelium. Improvement in visual performance was 100% over untreated controls (spatial acuity was approximately 70% that of normal nondystrophic rats) without evidence of untoward pathology. The use of somatic cell nuclear transfer (SCNT) and/or the creation of banks of reduced complexity human leucocyte antigen (HLA) hES-RPE lines could minimize or eliminate the need for immunosuppressive drugs and/or immunomodulatory protocols.


Ethnomedicinal use of African pangolins by traditional medical practitioners in Sierra Leone.
Pangolins (Manidae) have long been used for traditional medicinal purposes in most parts of sub-Saharan Africa. However, very little is known about the extent of this use, the body parts that are used and the ailments these practices are attempting to cure or alleviate. Pangolin body parts are used extensively and frequently by traditional medical practitioners in Sierra Leone. A total of 63 traditional medical practitioners consented and were interviewed using semi-structured questionnaires on the traditional medicinal use of pangolin body parts. The use value, informant agreement ratio and use agreement value for each pangolin part was calculated to ascertain the most sought after body part, the level of knowledge dissemination among traditional medical practitioners about body parts and the most culturally significant body part. It was found that 22 pangolin parts are used to treat various ailments and conditions under 17 international categories of diseases. The highest use value was recorded for scales while eyes had the highest level of consensus among the traditional medical practitioners. The highest use value and informant agreement ratio for scales were recorded for spiritual ailments. Scales were the most culturally significant body part according to the use agreement value. This study indicates a high importance value for pangolins as part of these communities' spiritual, cultural and medicinal beliefs. However, the numbers of individuals harvested from the wild remains unknown and unregulated even though pangolins have been listed under Schedule 2 of the Wildlife Conservation Act, 1972, of Sierra Leone, which prohibits any person from hunting or being in possession of pangolins. It is likely that this unregulated harvesting and poaching of this threatened species, for medicinal purposes, is unsustainable and there is an urgent need to determine pangolin population abundance within this region to ensure their sustainable harvesting for cultural use and conservation.


Control of membrane permeability by external and internal ATP in 3T6 cells grown in serum-free medium.
Cultures of 3T6 cells were plated in serum-free medium and grown in the presence of insulin (1 microgram/ml) and epidermal growth factor (0.5 ng/ml). External ATP (250 microM) applied to such cultures caused a rapid efflux of acid-soluble pools labeled with [3H]uridine, 2-deoxy[3H]glucose, or 86Rb+ and allowed the entry of p-nitrophenylphosphate. This increase in passive membrane permeability depended on ATP concentration, pH, and time of ATP contact with the cells, and it was not produced by GTP, UTP, or Pi. In the presence of compounds that decrease intracellular ATP, low concentrations of external ATP (40 microM) caused a massive synergistic stimulation of efflux. The efflux of acid-soluble pools was stopped (sealing) by bringing the cultures of 3T6 cells to neutral pH in the presence of Ca2+ and Mg2+. Exposure of 3T6 cells grown in serum-free medium to [gamma-32P]ATP under the conditions of permeabilization led to the selective labeling of a membrane protein with a molecular weight of 44,000 as revealed by NaDodSO4 polyacrylamide gel electrophoresis and autoradiography. The results show that the control of membrane permeability by ATP is completely independent of serum-deprived proteins. Furthermore, the protein band (Mr, 44 x 10(3)) that shows selective labeling by [32P]ATP during permeabilization is not an adsorbed serum component.


Robust Switchable Polarization and Coupled Electronic Characteristics of Magnesium-Doped Zinc Oxide.
Ferroelectrics possess a spontaneous polarization that is switchable by an electric field and is critical for the development of low-energy nanoelectronics and neuromorphic applications. However, apart from a few recent developments, the realization of switchable polarization in metal oxides with simpler structures has been a major challenge. Here, we demonstrate the presence of robust switchable polarization at the level of a single nanocrystallite in magnesium-doped zinc oxide thin films with polar wurtzite crystal structures. Using a combination of high-resolution scanning probe microscopy and spectroscopic techniques, voltage control of the polarization and the coupled electronic transport behavior revealing a giant resistance change of approximately 10000% is unveiled. Time- and frequency-resolved nanoscale measurements provide key insights into the polarization phenomenon and a 9-fold increase in the effective longitudinal piezoelectric coefficient. Our work thus constitutes a crucial step toward validating nanoscale ferroelectricity in polar wurtzites for use in advanced nanoelectronics and memory applications.


Don't forget the posters! Quality and content variables associated with accepted abstracts at a national trauma meeting.
As a primary venue for presenting research results, abstracts selected for presentation at national meetings should be of the highest scientific merit and research quality. It is uncertain to what degree this is achieved as the methodological quality of abstracts submitted to national surgical meetings has not been previously described. The objective of this study was to evaluate abstracts presented at a leading trauma meeting for methodological quality. All abstracts accepted for the 2009 American Association for the Surgery of Trauma meeting were reviewed and scored for methodological quality based on 10 criteria (scores, 0-10; 10 being the highest). Criteria were based on nationally published methodology guidelines. Two independent reviewers who were blinded to institution, region, and author reviewed each abstract. A total of 187 abstracts were accepted for presentation (67 oral and 120 posters). The most frequent clinical topics were shock/transfusion (23%), abdomen (12%), and nervous system (11%). Shock/transfusion abstracts were more common in the oral presentations (31% vs. 19%; p = 0.06). Abstracts from the northeast and south regions were the most common in both oral (26% and 29%) and posters (25% and 24%). Basic science accounted for 12% of accepted studies, while 51% were clinical and 28% were health services/outcomes. Only 8% of abstracts presented randomized data and only 11% reported null findings. Overall abstract scores ranged from 3 to 10 (median, 7; mean, 7.4). Abstracts selected for poster presentation had an overall higher score than those selected for oral presentation (7.4 ± 1.7 vs. 6.8 ± 1.7; p = 0.02). Although oral presentations traditionally receive the most attention and interest, the methodological quality of abstracts accepted for poster presentation equals (and sometimes exceeds) that of oral abstracts. Attendees of these national meetings should reconsider their time spent in viewing and visiting these poster sessions as with the oral presentations. In light of our findings, we highly encourage that all members and guests attend the American Association for the Surgery of Trauma Poster Rounds at each year's scientific assembly.


Diabetes-Related Mechanisms of Action Involved in the Therapeutic Effect of Croton Species: A Systematic Review.
Over the years, ethnopharmacological and phytochemical investigations have been conducted to understand the potential effects of the Croton genus on several diseases. It has been revealed that these terpenoid-rich species traditionally used to treat gastrointestinal diseases, heal wounds, and relieve pain have a wide range of therapeutic effects; however, those used to treat diabetes, as well as their action mechanisms, have not been reviewed so far. Therefore, the main objective of this review was to compile all Croton species that have shown pharmacological effects against diabetes and describe their action mechanisms. Through a search of the literature, 17 species with hypoglycemic, antihyperglycemic, antilipidemic, antihypertensive, antioxidant, and anti-inflammatory effects were found. Among the mechanisms by which they exerted these effects were the inhibition of α-glucosidases, the promotion of insulin secretion, and the increase in glucose uptake. Interestingly, it was found that some of them may have antihyperglycemic properties, although there were no ethnopharmacological reports that support their traditional use. Moreover, others only presented studies on their hypoglycemic effect in fasting, so further works are encouraged to describe the mechanisms involved in lowering fasting blood glucose levels, such as hepatic glucose production, especially for C. cajucara, C. cuneatus, C. gratissimus var. gratissimus, C. guatemalensis, and C. membranaceus. It is expected that this review contributes to the plant science knowledge of the genus, and it can be used in future references on the identification and development of new molecules/phytomedicines that help in the treatment of diabetes.


Sensitive and high throughput metabolite assays for inorganic pyrophosphate, ADPGlc, nucleotide phosphates, and glycolytic intermediates based on a novel enzymic cycling system.
Metabolite assays are required to characterise how metabolism changes between genotypes during development and in response to environmental perturbations. They provide a springboard to identify important regulatory sites and investigate the underlying mechanisms. Due to their small size, Arabidopsis seeds pose a technical challenge for such measurements. A set of assays based on a novel enzymic cycling system between glycerol-3-phosphate dehydrogenase and glycerol-3-phosphate oxidase have been developed and optimised for use with growing Arabidopsis seeds. In combination with existing assays they provide a suite of high throughput, sensitive assays for the immediate precursors for starch (adenine diphosphate glucose) and lipid (acetyl coenzyme A, glycerol-3-phosphate) synthesis, as well as pyrophosphate, ATP, ADP and most of the glycolytic intermediates. A method is also presented to rapidly quench intact siliques, lyophilise them and then manually separate seeds for metabolite analysis. These techniques are used to investigate changes in overall seed metabolite levels during development and maturation, and in response to a stepwise decrease of the external oxygen concentration.


Hierarchical phylogenetics as a quantitative analytical framework for evolutionary developmental biology.
Phylogenetics has inherent utility in evolutionary developmental biology (EDB) as it is an established methodology for estimating evolutionary relationships and for making comparisons between levels of biological organization. However, explicit phylogenetic methods generally have been limited to two levels of organization in EDB-the species and the gene. We demonstrate that phylogenetic methods can be applied broadly to other organizational levels, such as morphological structures or cell types, to identify evolutionary patterns. We present examples at and between different hierarchical levels of organization to address questions central to EDB. We argue that this application of "hierarchical phylogenetics" can be a unifying analytical approach to the field of EDB.


Fabrication and growth mechanism of ZnO nanostructures and their cytotoxic effect on human brain tumor U87, cervical cancer HeLa, and normal HEK cells.
ZnO nanostructures of diverse shape were grown via a solution process with different precursors and conditions. Morphological investigation of the nanostructures was carried out using field emission scanning electron microscopy and transmission microscopy observations and revealed that the nanostructures exhibit a wurtzite phase with an ideal lattice fringe distance of approximately 0.52 nm. The powder crystallinity was examined via X-ray diffraction spectroscopy. Screening results from anticancer studies of the effects on human brain tumor U87, cervical cancer HeLa, and normal HEK cells of ZnO nanostructures of diverse shape were obtained and indicate promising activity that varies with changes in the structure and the size of the particles. Treatment-induced cell death [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and survival assay], growth inhibition, cytogenetic damage (formation of micronuclei), and apoptosis were studied as parameters for the cellular response. Treatment with nanostructures enhanced growth inhibition and cell death in a concentration-dependent manner in both U87 and HeLa cell lines. At higher concentrations (above 15.6 μg/ml) the cytotoxic effects of the nanoparticles were highly synergistic and mainly mediated through apoptosis, implying the possible interactions of lesions caused by the agents. The enhanced cell death due to nanoparticles was accompanied by a significant increase (2-3 fold at 31.25 μg/ml) in the formation of micronuclei in U87 cells. The increase in the formation of micronuclei observed after treatment indicates that these structures may interfere with the rejoining of DNA strand breaks. Among all the nanostructures, nanoparticles and sheets exhibited potent activity against both HeLa and U87 cells. However, despite potent in vitro activity, all nanostructures exhibited diminished cytotoxicity against normal human HEK cells at all effective concentrations.


A critical appraisal of phloem-mobile signals involved in tuber induction.
The identification of FLOWERING LOCUS T (FT) and several FT homologs as phloem-mobile proteins that regulate flowering has sparked the search for additional homologs involved in the long-distance regulation of other developmental processes. Given that flowering and tuber induction share regulatory pathways, the quest for long-distance tuberization signals has been further stimulated. Several tuberization regulators have been proposed as mobile molecules, including the FT family protein StSP6A, the plant growth regulators gibberellins and the microRNA miR172. Although some of these hypotheses are attractive and plausible, evidence that these molecules are transmissible in potato has yet to be obtained. Two mRNAs encoding transcription factors, StBEL5 and POTATO HOMEOBOX 1 (POTH1), are mobile and correlate with tuber induction. However, evidence that StBEL5 or POTH1 are required for tuberization is not available yet. Therefore, there are several good candidates for long-distance molecules in the tuberization process. Further research should test their role as systemic tuberization signals.


Development of Graft-Site Candidiasis in 3 Solid Organ Transplant Recipients from the Same Donor.
BACKGROUND Graft-site candidiasis rarely develops in solid organ transplant recipients; however, severe life-threatening complications can occur. We report the course of 3 solid organ transplant recipients developing graft-site candidiasis. CASE REPORT All grafts, consisting of 2 kidneys and 1 liver, were procured from a single donor. Patient data were collected from our database. Candida albicans was isolated from a swab taken during multiple-organ recovery. Complications associated with candidiasis occurred in all 3 recipients with preservation of the liver transplant. Both renal transplant recipients had vascular complications, eventually resulting in graft nephrectomy and subsequent return to dialysis. The patients recovered completely without residual effects of their prior fungal infection. CONCLUSIONS Fungal infections in solid organ transplant recipients are rare. Since the sequelae of these infections are serious and usually pertain to more than 1 recipient at a time, antifungal prophylaxis may be warranted in select donors.


Highly enantioselective synthesis of 3,4-dihydropyrans through a phosphine-catalyzed [4+2] annulation of allenones and β,γ-unsaturated α-keto esters.
A phosphine-catalyzed novel [4+2] annulation process was devised employing allene ketones as C2 synthons and β,γ-unsaturated α-keto esters as C4 synthons. In the presence of an L-threonine-derived bifunctional phosphine, 3,4-dihydropyrans were obtained in high yields and with virtually perfect enantioselectivities. The synthetic value of the dihydropyran motif was demonstrated by a concise preparation of an anti-hypercholesterolemic agent.


A review of recent research progress on the astragalus genus.
Astragalus L., is one of the largest genuses of flowering plants in the Leguminosae family. Roots of A. membranaceus Bge. var. mongholicus (Bge.) Hsiao, A. membranaceus (Fisch.) Bge. and its processed products are listed in the China Pharmacopeia for "qi deficiency" syndrome treatment. However, more and more researches on other species of Astragalus have been conducted recently. We summarize the recent researches of Astragalus species in phytochemistry and pharmacology. More than 200 constituents, including saponins and flavonoids, obtained from 46 species of Astragalus genus were collected for this article. In pharmacological studies, crude extracts of Astragalus, as well as isolated constituents showed anti-inflammatory, immunostimulant, antioxidative, anti-cancer, antidiabetic, cardioprotective, hepatoprotective, and antiviral activities. The goal of this article is to provide an overview of chemical and pharmacological studies on the Astragalus species over the last 10 years, which could be of value to new drug or food supplement research and development.


Alcohol cues, approach bias, and inhibitory control: applying a dual process model of addiction to alcohol sensitivity.
Low sensitivity to the acute effects of alcohol is a risk factor for heavy drinking and related problems. However, little research has tested process explanations for such effects. The current study tested the hypothesis that low sensitivity is associated with automatic approach biases for alcohol cues, coupled with deficits inhibiting responses in the presence of such cues. Eighty-five participants varying in alcohol sensitivity completed an Alcohol-Approach Avoidance Task and a Cued Go/No-Go Task while event-related potentials were recorded. Low sensitivity (LS) individuals showed evidence of automatic approach tendencies toward alcohol cues in both tasks, and experienced deficits inhibiting prepotent responses cued by alcohol images. Additionally, the event-related potential data indicated that LS individuals experienced more conflict when attempting to inhibit alcohol-cued responses, but not nonalcohol-cued responses, compared with their high-sensitivity counterparts. Together, these data indicate that alcohol cues elicit an approach bias among LS individuals, translating into greater difficulty inhibiting behavioral responses in the presence of such cues, a pattern generally supportive of dual process models of substance use.


Exercise Protocol With Limited Shoulder Range of Motion for 15 or 30 Days After Conservative Surgery for Breast Cancer With Oncoplastic Technique: A Randomized Clinical Trial.
The objective is to evaluate the effect of limiting shoulder range of motion (ROM) for 15 or 30 days on surgical complications and on shoulder ROM, pain, and upper limb function of breast cancer patients following conservative oncoplastic surgery. A randomized clinical trial was conducted with 60 women with breast cancer who underwent conservative oncoplastic surgery. The day after surgery, all patients started an exercise protocol with shoulder exercises limited to 90 degrees. Two weeks after surgery they were randomized into Free ROM Group (n=30) or Limited ROM Group (n=30). The Free ROM Group was allowed to perform shoulder exercises with unlimited ROM; the Limited ROM Group continued with shoulder movement restricted at 90 degrees until 30 days after surgery, at which time they were also allowed free ROM. The primary outcome was the incidence of postoperative complications (dehiscence, seroma, infection, and necrosis) and secondary outcomes were shoulder ROM, pain, and upper limb function. No difference in the incidence of postoperative scar complications between groups was noted. There was no difference between the groups in shoulder joint amplitude, pain, or upper limb function. The free ROM exercise protocol 15 days post surgery was safe concerning cicatricial complications.


Management of ventricular arrhythmias.
Left ventricular dysfunction and complex VPCs are independent risk factors for subsequent cardiac death in patients with ischemic or nonischemic heart disease. The use of antiarrhythmic drugs during acute myocardial infarction is discussed. Patients with complex VPCs associated with heart disease should be treated with antiarrhythmic drugs. Drug efficacy should be evaluated by a 24-hour ambulatory ECG recording and by a treadmill exercise stress test. Blood drug levels should be measured at appropriate times. Maintenance doses of the various antiarrhythmic drugs are listed. Electrophysiologic testing with induction of ventricular tachycardia by extrastimulation may predict the clinical efficacy of the antiarrhythmic drug or combination of drugs needed for the long-term treatment of ventricular tachyarrhythmias. Electrophysiologic testing must be used for selecting antiarrhythmic drugs in patients who have experienced sustained ventricular tachycardia or ventricular fibrillation but who are free of VPCs during ambulatory ECG monitoring and exercise stress testing. If patients have life-threatening ventricular tachycardia or fibrillation resistant to antiarrhythmic drugs, surgical intervention is indicated. Complex VPCs in asymptomatic patients without heart disease should not be treated with antiarrhythmic drugs.


Transient turbulence in plane Couette flow.
Plane Couette flow, the flow between two parallel plates moving in opposite directions, belongs to the group of shear flows where turbulence occurs while the laminar profile is stable. Experimental and numerical studies show that at intermediate Reynolds numbers turbulence is transient and that the lifetimes are distributed exponentially. However, these studies have remained inconclusive about a divergence in lifetimes above a critical Reynolds number. The extensive numerical results for flow in a box of width 2pi and length 8pi presented here cover observation times up to 12,000 units and show that while the lifetimes increase rapidly with Reynolds number, they do not indicate a divergence and therefore no transition to persistent turbulence.


Significant Disparity of Access to Stroke Treatment Between the Western Parts and Eastern and Northern Parts of Sydney.
Objective To provide an estimate of access times and distances to an endovascular clot retrieval (ECR) service provider for a typical stroke patient in the western part of Sydney and to compare it with the eastern and northern parts. Methods Incidences of stroke were simulated through a population-weighted randomized selection of addresses in the studied western, eastern, and northern areas of Sydney (100,000 times for each). The access times and distances were calculated from those addresses to the closest ECR hub for the eastern and northern parts and to all five ECR hubs, as well as the Nepean Public Hospital (NPH) for the western part. The access times and distance means were compared statistically using ANOVA. Results In the western areas, the estimated average access times and distances to different ECR hubs varied from 38.5 (+/- 15) to 45 (+/- 15) minutes and from 42 (+/- 15.9) to 46.8 (+/- 16) km in working hours and from 45 (+/- 15) to 64 (+/- 15) minutes and 46.8 (+/- 16) to 69.6 (+/- 16) km in after hours. However, the estimated average access times and distances to the local ECR hub were 12.25 (+/- 6) minutes and 9.1 (+/- 5.6) km for northern and 7.5 (+/- 4) minutes and 4.4 (+/- 2.5) km for the eastern areas. The differences between the estimated average access times and distances for a typical stroke patient to an ECR hub in the western areas in comparison with eastern or northern areas were statistically significant (p<0.0001). The average access times and distances in the western part to NPH were 17 (+/- 16) minutes and 15.6 (+/- 16.6) km. Conclusions The patients in the western part of Sydney had significantly longer access times to ECR hubs than those living in comparable areas of the eastern and northern parts. This study supports the Nepean Public Hospital supplying an ECR service to achieve travel times, and, therefore, treatment times for a typical stroke patient in the western parts, similar to patients in the eastern and northern parts of Sydney.


Dickens, Little Dorrit, and soul murder.
The effects of moderate psychological child abuse by parents and parental substitutes on Charles Dicken's life and work are examined.


[Synthesis of 6-benzyl-1-[(benzyloxy)methyl]-3-hydroxy-5-(hydroxymethyl)pyrimidine-2,4(1H,3H)-dione].
To find the best synthesis method of 6-benzyl-1-[(benzyloxy)methyl]-3-hydroxy-5-(hydroxymethyl) pyrimidine-2,4(1H,3H)-dione e for observing the change of its biological activity after N-3 hydroxylation. After trying some N-hydroxylation methods, the target compound was successfully synthesized via one-pot oxidizing process by sodium hydride (NaH) and 3-chloroperbenzoic acid(m-CPBA); the anti-HIV reverse transcriptase (RT) activity and integrase (IN) activity of the target compound was assayed via enzyme-linked immunesorbent assay (ELISA) and phosphorylation of DNA package method. The target compound could be obtained through the improved m-CPBA oxidative method by only one step, and the yield of the reaction could reach 60%-70%. And the structure of this compound was identified by 1H NMR, 13C NMR and MS; The activity result showed it added the anti-HIV IN activity after N-3 hydroxylation as well as retained the anti-HIV RT activity. The improved m-CPBA oxidative method is a convenient and efficient way to prepare the compound 6-benzyl-1-[(benzyloxy)methyl]-3-hydroxy-5-(hydroxymethyl)pyrimidine-2,4(1H,3H)-dione e which has both anti-HIV RT and IN activity.


Does rural generalist focused medical school and family medicine training make a difference? Memorial University of Newfoundland outcomes.
Rural recruitment and retention of physicians is a global issue. The Faculty of Medicine at Memorial University of Newfoundland, Canada, was established as a rural-focused medical school with a social accountability mandate that aimed to meet the healthcare needs of a sparse population distributed over a large landmass as well as the needs of other rural and remote areas of Canada. This study aimed to assess whether Memorial medical degree (MD) and postgraduate (PG) programs were effective at producing physicians for their province and rural physicians for Canada compared with other Canadian medical schools. This retrospective cohort study included medical school graduates who completed their PG training between 2004 and 2013 in Canada. Practice locations of study subjects were georeferenced and assigned to three geographic classes: Large Urban; Small City/Town; and Rural. Analyses were performed at two levels. (1) Provincial level analysis compared Memorial PG graduates practicing where they received their MD and/or PG training with other medical schools who are the only medical school in their province (n=4). (2) National-level analysis compared Memorial PG graduates practicing in rural Canada with all other Canadian medical schools (n=16). Descriptive and bivariate analyses were performed. Overall, 18 766 physicians practicing in Canada completed Canadian PG training (2004-2013), and of those, 8091 (43%) completed Family Medicine (FM) training. Of all physicians completing Canadian PG training, 1254 (7%) physicians were practicing rurally and of those, 1076 were family physicians. There were 379 Memorial PG graduates and of those, 208 (55%) completed FM training and 72 (19%) were practicing rurally, and of those practicing rurally, 56 were family physicians. At the national level, the percentage of all Memorial PG graduates (19.0%) and FM PG graduates (26.9%) practicing rurally was significantly better than the national average for PG (6.4%, p<0.000) and FM (12.9%, p<0.000). Among 391 physicians practicing in Newfoundland and Labrador (NL), 257 (65.7%) were Memorial PG graduates and 247 (63.2%) were Memorial MD graduates. Of the 163 FM graduates, 148 (90.8%) were Memorial FM graduates and 118 (72.4%) were Memorial MD graduates. Of the 68 in rural practice, 51 (75.0%) were Memorial PG graduates and 31 (45.6%) were Memorial MD graduates. Of the 41 FM graduates in rural practice, 39 (95.1%) were Memorial FM graduates and 22 (53.7%) were Memorial MD graduates. Two-sample proportion tests demonstrated Memorial University provided a larger proportion of its provincial physician resource supply than the other four single provincial medical schools, by medical school MD for FM (72.4% vs 44.3%, p<0.000) and for overall (63.2% vs 43.5% p<0.000), and by medical school PG for FM (90.8 % vs 72.0%, p<0.000). This study found Memorial University graduates were more likely to establish practice in rural areas compared with the national average for most program types as well as more likely to establish practice in NL compared with other single medical schools' graduates in their provinces. This study highlights the impact a comprehensive rural-focused social accountability approach can have at supplying the needs of a population both at the regional and rural national levels.


Resonance-Based Time-Frequency Manifold for Feature Extraction of Ship-Radiated Noise.
In this paper, a novel time-frequency signature using resonance-based sparse signal decomposition (RSSD), phase space reconstruction (PSR), time-frequency distribution (TFD) and manifold learning is proposed for feature extraction of ship-radiated noise, which is called resonance-based time-frequency manifold (RTFM). This is suitable for analyzing signals with oscillatory, non-stationary and non-linear characteristics in a situation of serious noise pollution. Unlike the traditional methods which are sensitive to noise and just consider one side of oscillatory, non-stationary and non-linear characteristics, the proposed RTFM can provide the intact feature signature of all these characteristics in the form of a time-frequency signature by the following steps: first, RSSD is employed on the raw signal to extract the high-oscillatory component and abandon the low-oscillatory component. Second, PSR is performed on the high-oscillatory component to map the one-dimensional signal to the high-dimensional phase space. Third, TFD is employed to reveal non-stationary information in the phase space. Finally, manifold learning is applied to the TFDs to fetch the intrinsic non-linear manifold. A proportional addition of the top two RTFMs is adopted to produce the improved RTFM signature. All of the case studies are validated on real audio recordings of ship-radiated noise. Case studies of ship-radiated noise on different datasets and various degrees of noise pollution manifest the effectiveness and robustness of the proposed method.


Microcrystalline cellulose replacement in cakes and biscuits.
Sensory and physical characteristics of cakes and biscuits with up to 60 per cent of flour replaced, volume for volume, with microcrystalline cellulose were compared with those of the respective controls. High quality products were obtained at replacement levels of 40 and 20 per cent, respectively, in lean-formula cakes and in biscuits. At these replacement levels, caloric density was reduced by 12 and 10 per cent, respectively, in the cakes and biscuits.


A feed-forward measurement scheme for periodic noise suppression in atomic magnetometry.
We present an unshielded, double-resonance magnetometer in which we have implemented a feed-forward measurement scheme in order to suppress periodic magnetic noise arising from, and correlated with, the mains electricity alternating current line. The technique described here uses a single sensor to track ambient periodic noise and feed forward to suppress it in a subsequent measurement. This feed forward technique has shown significant noise suppression of electrical mains-noise features of up to 22 dB under the fundamental peak at 50 Hz, 3 dB at the first harmonic (100 Hz), and 21 dB at the second harmonic (150 Hz). This technique is software based, requires no additional hardware, and is easy to implement in an existing magnetometer.


An integrative review: maternal engagement in the neonatal intensive care unit and health outcomes for U.S.-born preterm infants and their parents.
Hospitals and perinatal organizations recognize the importance of family engagement in the neonatal intensive care unit (NICU). The Agency for Healthcare Research and Quality (AHRQ) defines family engagement as "A set of behaviors by patients, family members, and health professionals and a set of organizational policies and procedures that foster both the inclusion of patients and family members as active members of the health care team and collaborative partnerships with providers and provider organizations." In-unit barriers and facilitators to enhance family engagement are well studied; however, less is known specifically about maternal engagement's influence in the NICU on the health of infants and mothers, particularly within U.S. social and healthcare contexts. In this integrative review, we examine the relationship between maternal engagement in the NICU and preterm infant and maternal health outcomes within the U.S. Results from the 33 articles that met inclusion criteria indicate that maternal engagement in the NICU is associated with infant outcomes, maternal health-behavior outcomes, maternal mental health outcomes, maternal-child bonding outcomes, and breastfeeding outcomes. Skin-to-skin holding is the most studied maternal engagement activity in the U.S. preterm NICU population. Further research is needed to understand what types of engagement are most salient, how they should be measured, and which immediate outcomes are the best predictors of long-term health and well-being.


Phenylketonuria: no specific frontal lobe-dependent neuropsychological deficits of early-treated patients in comparison with diabetics.
Neuropsychologic studies have shown that even phenylketonuric patients treated early suffer from phenylalanine-related deficits in all age periods, from childhood to adulthood. This study was performed to determine whether phenylketonuric children show specific frontal lobe-dependent deficits when compared with diabetic patients. The comparative study included 42 phenylketonuric patients, 10 to 18 y of age [mean 14.7 (years, months), SD 2.9], and 42 diabetic patients matched for sex, age, and socioeconomic status. Patients were assessed for intelligence quotient (Culture Fair Intelligence Test), information processing (Wisconsin Card Sorting Test, Trail-Making Test), and selective (Stroop task) as well as sustained attention (Test d-2). Phenylketonuric patients had significantly poorer results than the diabetic patients. Within all tests, however, this was due to reduced performance speed, not to deficits in specific functions. Patients did not show deficits in insight and learning. The selection abilities and the sustained attention of the phenylketonuric patients were not impaired. Performance speed and blood phenylalanine levels were negatively correlated. Elevated phenylalanine levels may cause an imbalance in neurotransmitter metabolism. However, this seems to refer to a global neurotoxic effect rather than to specific effects on the dopaminergic system, which would affect specifically the activation of the frontal lobes.


Detoxification of hostplant's chemical defence rather than its anti-predator co-option drives β-glucosidase-mediated lepidopteran counteradaptation.
The evolutionary plant-herbivore arms race sometimes gives rise to remarkably unique adaptation strategies. Here we report one such strategy in the lepidopteran herbivore Manduca sexta against its hostplant Nicotiana attenuata's major phytotoxins, 17-hydroxygeranyllinalool diterpene glycoside, lyciumoside IV and its malonylated forms. We show that alkalinity of larval regurgitant non-enzymatically demalonylates the malonylated forms to lyciumoside IV. Lyciumoside IV is then detoxified in the midgut by β-glucosidase 1-catalysed deglycosylation, which is unusual, as typically the deglycosylation of glycosylated phytochemicals by insects results in the opposite: toxin activation. Suppression of deglucosylation by silencing larval β-glucosidase 1 by plant-mediated RNAi causes moulting impairments and mortality. In the native habitat of N. attenuata, β-glucosidase 1 silencing also increases larval unpalatability to native predatory spiders, suggesting that the defensive co-option of lyciumoside IV may be ecologically advantageous. We infer that M. sexta detoxifies this allelochemical to avoid its deleterious effects, rather than co-opting it against predators.


Complications and vascular salvage of free-tissue transfers to the extremities.
Complications were examined in 122 free flaps to lower and upper extremities in 104 patients, and vascular salvage was examined in 182 free flaps to lower and upper extremities in 158 patients. All patients were treated by the same surgeon. The overall survival rate of flaps was 96 percent. Complications occurred in 22 percent of the flaps. Complication rates were lower in patients with one free flap than in patients with two. Flaps had more vascular complications than nonvascular. Accompanying skin islands were found to be necessary to monitor vascularized bone transfers in order to avoid flap failure. Flow in the pedicle was reestablished in all flaps, but a higher percentage of flaps with longer ischemic times were lost. Although vascular compromise occurred frequently (15 percent), prompt surgical exploration and reexploration were thought to have greatly increased free-flap survival.