Structured Long Interview and Clinical Examination (SLICE) as Formative Assessment Tool in Clinical Clerkship: Medical Students Perspective.
To evaluate medical students' views about undertaking structured long interview and clinical examination as a formative assessment. The qualitative, exploratory study was conducted from February to July 2019 at the Islamic International Medical College, Riphah International University, Islamabad, Pakistan, and comprised final year medical students having undertaken formative assessment through structured long interview and clinical examination during their clerkship rotation in Paediatrics, General Medicine, General Surgery and Gynaecology and Obstetrics. Four sets of focus group discussions were conducted according to the relevant clerkship module. Each recorded FGD was transcribed verbatim. Thematic analysis was conducted manually. Of the 32 students, there were 8(25%) in each of the four groups. Five major themes and five-sub-themes emerged, with the main themes being: Purpose, Learning, Timing, Relevancy and Fairness of the structured long interview and clinical examination. The students generally thought that the structured long interview and clinical examination was effective in enhancing their clinical skills learning and should be conducted more frequently with minor adjustments.


Patterns of Esophageal Cancer in the National Cancer Institute at the University of Gezira, in Gezira State, Sudan, in 1999-2012.
Esophageal cancer (EC) is among the most common malignancies in Eastern Africa, but the occurrence of EC in Sudan has rarely been described in the scientific literature. This paper reports the results of a consecutive case series of all EC patients who visited one of the two public cancer treatment centers in the country in 1999-2012, providing a first description of this disease in a treatment center located in central Sudan. Clinical and demographic data for all EC patients who visited the Department of Oncology of the National Cancer Institute at the University of Gezira (NCI-UG) from 1999 to the end of 2012 were abstracted and tabulated by sex, tumor type and other characteristics. A total of 448 EC patients visited NCI-UG in 1999-2012, and the annual number of EC cases increased steadily from 1999. Squamous cell carcinoma (SCC) was the predominant EC tumor type (90%), and adenocarcinoma (ADC) was reported in 9.4% of the EC cases. The overall male-to-female ratio for EC was 1:1.8, but the ratio was tumor type-dependent, being 1:2 for SCC and 2:1 for ADC. Only 20% of EC patients reported having ever used tobacco and/or alcohol, and the vast majority of these patients were male. At the time of EC diagnosis, 47.3% of the patients resided in Gezira State. Some EC patients from Gezira State seek out-of-state treatment in the national capital of Khartoum instead of visiting NCI-UG. The annual number of EC patients visiting NCI-UG has increased in recent years, approximately half of these patients being from Gezira State. Although this consecutive series of EC patients who visited NCI-UG was complete, it did not capture all EC patients from the state. A population- based cancer registry would provide more complete data required to better understand EC patterns and risk factors.


Serum immunoglobulin M concentrations following bowel resection in chronic inflammatory bowel disease.
Serum immunoglobulin alterations were characterized in 20 patients with chronic inflammatory bowel disease (CIBD) undergoing bowel resection and in 11 control subjects undergoing intra-abdominal operations. Serum immunoglobulin M (IgM) values became elevated during the 2nd week in both groups with individual serum IgM concentrations reaching as high as 9 times preoperative values. The IgM increment, which was 19 S polyclonal immunoglobulin, was significantly greater in the CIBD group than in controls. Because of a recent suggestion that this IgM rise might be related to the pathogenesis of CIBD, the affinity of this IgM for colon was studied in two ways. Serum anticolon antibody titers did not change after surgery nor did IgM, isolated from serum after surgery and labeled with 125I, bind to homogenates of normal or CIBD colon. Titers of heterophile antibody and antibodies directed against Escherichia coli, Bacteroides, and blood group antigens increased in many patients. In most instances, these increments were shown to be antibody of the IgM class by reduction with 2-mercaptoethanol. These data indicate that the IgM changes after abdominal surgery (1) are not specific for CIBD patients, (2) do not represent antibody directed against colon antigens, and (3) include increased titers of several IgM antibodies. These findings might be explained by a response to bacterial or tissue antigens released at or after the time of surgery.


Anti-D administration in pregnancy for preventing Rhesus alloimmunisation.
During pregnancy, a Rhesus negative (Rh-negative) woman may develop antibodies when her fetus is Rhesus positive (Rh-positive). These antibodies may harm Rh-positive babies. To assess the effects of antenatal anti-D immunoglobulin on the incidence of Rhesus D alloimmunisation when given to Rh-negative women without anti-D antibodies. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2012). Randomised trials in Rh-negative women without anti-D antibodies given anti-D after 28 weeks of pregnancy, compared with no treatment, placebo or a different regimen of anti-D. Two review authors independently assessed trial eligibility and risk of bias and extracted the data. Two trials with moderate to high risk of bias, involving over 4500 women, compared anti-D prophylaxis with no anti-D during pregnancy. When women received anti-D at 28 and 34 weeks' gestation, risks of immunisation were not significantly different than for women not given antenatal anti-D: risk ratio (RR) of immunisation during pregnancy was 0.42 (95% confidence interval (CI) 0.15 to 1.17); after the birth of a Rh-positive infant the RR was 0.42 (95% CI 0.15 to 1.17); and within 12 months after birth of a Rh-positive infant the RR was 0.39 (95% CI 0.10 to 1.62).However, women receiving anti-D during pregnancy were significantly less likely to register a positive Kleihauer test (which detects fetal cells in maternal blood) in pregnancy (RR 0.60, 95% CI 0.41 to 0.88) and at the birth of a Rh-positive infant (RR 0.60, 95% CI 0.46 to 0.79). No data were available for the risk of Rhesus D alloimmunisation in a subsequent pregnancy. No significant differences were seen for neonatal jaundice, and no adverse effects were reported in either trial. The risk of Rhesus D alloimmunisation during or immediately after a first pregnancy is about 1%. Administration of 100 µg (500 IU) anti-D to women in their first pregnancy can reduce this risk to about 0.2% without, to date, any adverse effects. Although unlikely to confer benefit in the current pregnancy, fewer women may have Rhesus D antibodies in any subsequent pregnancy, but the effects of this needs to be tested in studies of robust design.


Incidence, Risk Factors, and Outcomes of Pouchitis and Pouch-Related Complications in Patients With Ulcerative Colitis.
Acute pouchitis is the most common non-surgical complication after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). We used validated case-finding definitions for pouchitis to search administrative claims data and determine the incidence of pouchitis in the first 2 years after IPAA. We identified all patients who underwent proctocolectomy with IPAA for UC in the IQVIA Legacy PharMetrics Adjudicated Claims Database, from January 1, 2007 through June 1, 2016. The primary outcome was the development of pouchitis within 2 years after IPAA. Secondary outcomes included isolated acute vs recurrent pouchitis, immunosuppressive therapy, further surgery, and admission to the hospital. Among 594 patients, the cumulative incidence of pouchitis within 2 years of IPAA was 48% (95% CI, 44%-52%). The cumulative incidence of isolated acute pouchitis was 29% (95% CI, 26%-33%). Compared to patients with isolated acute pouchitis, patients who received a diagnosis of recurrent pouchitis (cumulative incidence, 19%: 95% CI, 16%-22%) demonstrated increased outpatient visits, emergency department visits, and inpatient admissions (all P < .001). Patients who developed pouchitis were more likely to have a history of primary sclerosing cholangitis (adjusted odds ratio [aOR], 3.94; 95% CI, 1.05-14.8) and anti-tumor necrosis factor alpha therapy prior to colectomy (aOR 1.63; 95% CI, 1.09-2.45). Among patients with pouchitis, the cumulative frequency of new immunosuppressive therapy was 40% (95% CI, 35%-46%) and the cumulative incidence of pouch excision was 1.0% (95% CI, 0.4%-3.0%). The cumulative incidence of a new diagnosis of Crohn's disease after IPAA for UC was 9.0% (95% CI, 7.2%-11%). In a geographically diverse population, 48% of patients with UC developed pouchitis within the first 2 years after IPAA. Patients with pouchitis had greater use of healthcare resources, indicating a significant burden of disease.


Intussusception in the setting of severe acute respiratory syndrome coronavirus 2 infection following rotavirus vaccination.
Most cases of intussusception are thought to be idiopathic, related to viral infections, structural abnormalities, or certain vaccinations. In this report, we present the development of intussusception in a pediatric patient who was coronavirus 2019 (COVID-19) positive. Although the most common gastrointestinal symptoms of COVID-19 virus are diarrhea and vomiting, there recently have been rare case reports of intussusception in patients throughout the world who are severe acute respiratory syndrome coronavirus 2 positive. This case is only the second known report in the United States and the second case reported globally that required surgical intervention for definitive management.


Keratinocyte growth factor transiently alters pulmonary function in rats.
Keratinocyte growth factor (KGF) is a mitogen for pulmonary epithelial cells. Intratracheal administration of KGF to adult rats results in alveolar epithelial type II and bronchiolar epithelial cell proliferation. While cellular responses to KGF have been intensively studied, functional consequences regarding lung function are unknown. Therefore, in this study, we sought to investigate whether KGF alters pulmonary function variables. Rats received either recombinant human KGF (rHuKGF) (5 mg/kg) or vehicle intratracheally. Before and on days 3 and 7 after treatment, pulmonary function was determined by body plethysmography. Subsequently, lung histological changes were quantified. rHuKGF induced a transient proliferation of alveolar and bronchiolar epithelial cells. The extent of type II cell hyperplasia was significantly correlated with a transient reduction in tidal volume and an increase in breathing frequency. In addition, quasi-static compliance, total lung capacity, and vital capacity were reduced after rHuKGF instillation, suggesting the development of a transitory restrictive lung disorder. Moreover, reduced expiratory flow rates and forced expiratory volumes, as well as increased functional residual capacity after rHuKGF but not vehicle, suggest obstructive lung function changes. In conclusion, the induction of alveolar and bronchiolar epithelial cell proliferation by KGF is paralleled by moderate functional consequences that should be taken into account when the therapeutic potential of KGF is tested.


Ester hydrolysis by a cyclodextrin dimer catalyst with a metallophenanthroline linking group.
A novel beta-cyclodextrin dimer, 1,10-phenanthroline-2,9-dimethyl-bridged-bis(6-monoammonio-beta-cyclodextrin) (phenBisCD, L), was synthesized. Its zinc complex (ZnL) has been prepared, characterized, and applied as a new catalyst for diester hydrolysis. The formation constant (logK(ML)=9.56+/-0.01) of the complex and deprotonation constant (pK(a)=8.18+/-0.04) of the coordinated water molecule were determined by a potentiometric pH titration at (298+/-0.1) K. Hydrolytic kinetics of carboxylic acid esters were performed with bis(4-nitrophenyl) carbonate (BNPC) and 4-nitrophenyl acetate (NA) as substrates. The obtained hydrolysis rate constants showed that ZnL has a very high rate of catalysis for BNPC hydrolysis, giving a 3.89x10(4)-fold rate enhancement over uncatalyzed hydrolysis at pH 7.01, relative to only a 42-fold rate enhancement for NA hydrolysis. Moreover, the hydrolysis second-order rate constants of both BNPC and NA greatly increases with pH. Hydrolytic kinetics of a phosphate diester catalyzed by ZnL was also investigated by using bis(4-nitrophenyl) phosphate (BNPP) as the substrate. The pH dependence of the BNPP cleavage in aqueous buffer shows a sigmoidal curve with an inflection point around pH 8.11, which was nearly identical to the pK(a) value from the potentiometric titration. The k(cat) of BNPP hydrolysis promoted by ZnL was found to be 9.9x10(-4) M(-1) s(-1), which is comparatively higher than most other reported Zn(II)-based systems. The possible intermediate for the hydrolysis of BNPP, BNPC, and NA catalyzed by ZnL is proposed on the basis of kinetic and thermodynamic analysis.


Discovery and optimization of benzotriazine di-N-oxides targeting replicating and nonreplicating Mycobacterium tuberculosis.
Compounds bactericidal against both replicating and nonreplicating Mtb may shorten the length of TB treatment regimens by eliminating infections more rapidly. Screening of a panel of antimicrobial and anticancer drug classes that are bioreduced into cytotoxic species revealed that 1,2,4-benzotriazine di-N-oxides (BTOs) are potently bactericidal against replicating and nonreplicating Mtb. Medicinal chemistry optimization, guided by semiempirical molecular orbital calculations, identified a new lead compound (20q) from this series with an MIC of 0.31 μg/mL against H37Rv and a cytotoxicity (CC(50)) against Vero cells of 25 μg/mL. 20q also had equivalent potency against a panel of single-drug resistant strains of Mtb and remarkably selective activity for Mtb over a panel of other pathogenic bacterial strains. 20q was also negative in a L5178Y MOLY assay, indicating low potential for genetic toxicity. These data along with measurements of the physiochemical properties and pharmacokinetic profile demonstrate that BTOs have the potential to be developed into a new class of antitubercular drugs.


Establishment of embryonic cultures and somatic embryogenesis in callus culture of guggul-Commiphora wightii (Arnott.) Bhandari.
Somatic embryogenesis in callus cultures of Commiphora wightii (Arnott.) Bhandari was achieved. Though the frequency of explants producing embryonic culture was low, immature zygotic embryos were the only suitable explants to produce embryonic callus after reciprocal transfers on media containing 2,4,5-trichlorophenoxy acetic acid (0.1 mgl(-1)) and kinetin (0.1 mgl(-1)) or devoid of growth regulators. All other media failed to produce embryonic callus. Embryonic cells were small, densely filled with cytoplasm and isodiametric as compared to non-embryonic cells, which were large, elongated and vacuolated. Maximum growth of embryonic callus was recorded on modified MS medium (MS-2 medium) supplemented with BA (0.25 mgl(-1)) and IBA (0.1 mgl(-1)). MS-2 salts supported higher growth of callus as compared to tissues grown on B5 medium containing same concentrations of plant growth regulators. Exogenous medium nutrients had no effect on somatic embryo development whereas plant growth regulators had little effect. Asynchronously growing embryos formed plantlets regularly which were successfully transferred to the field conditions.


Low-Terahertz Transparent Graphene-Based Absorber.
A new, transparent, metal-free absorber, based on the use of multilayer graphene/dielectric laminates (GLs), is proposed for applications in the low-terahertz frequency range. The designed absorber has a total thickness of around 70 µm and consists of a front matching dielectric layer followed by a GL, a dielectric spacer and a back GL. The laminates are periodic structures constituted of graphene sheets separated by 50-nm-thick polyethylene terephthalate (PET) interlayers, while the matching layer and the spacer are one-quarter-wavelength thick and made of PET. The GLs are modeled as homogeneous-equivalent single layers (ESLs) characterized by their sheet resistances Rs. An innovative analytical method is proposed in order to select Rs values optimizing the electromagnetic wave absorption either in low-gigahertz or low-terahertz frequency range. The frequency spectra of the absorption, reflection and transmission coefficients are computed in the range up to 4 THz by using different values of Rs. Then, realistic Rs values of chemically doped graphene monolayers over PET substrates are considered. The designed absorbers are characterized by an absorption coefficient with a peak value of about 0.8 at the first resonant frequency of 1.1 THz, and a 1.4 THz bandwidth centered at 1.5 THz with reflection coefficient below - 10 dB. Moreover, the optical transmittance of the proposed absorbers are computed by means of the optical matrix theory and it is found to be greater than 86% in all the visible ranges.


Large-scale quantum-emitter arrays in atomically thin semiconductors.
Quantum light emitters have been observed in atomically thin layers of transition metal dichalcogenides. However, they are found at random locations within the host material and usually in low densities, hindering experiments aiming to investigate this new class of emitters. Here, we create deterministic arrays of hundreds of quantum emitters in tungsten diselenide and tungsten disulphide monolayers, emitting across a range of wavelengths in the visible spectrum (610-680 nm and 740-820 nm), with a greater spectral stability than their randomly occurring counterparts. This is achieved by depositing monolayers onto silica substrates nanopatterned with arrays of 150-nm-diameter pillars ranging from 60 to 190 nm in height. The nanopillars create localized deformations in the material resulting in the quantum confinement of excitons. Our method may enable the placement of emitters in photonic structures such as optical waveguides in a scalable way, where precise and accurate positioning is paramount.


Effects of ethane-1-hydroxy-1, 1 diphosphonate on Dunn osteosarcoma cells.
We investigated the effects of ethane-1-hydroxy-1, 1 diphosphonate (EHDP) on Dunn osteosarcoma cells in vivo and in vitro. In in vivo study, an increase of tumor volume was significantly suppressed in the EHDP administered groups compared with the control group. Histologically, Dunn osteosarcoma cells' viability was maintained after EHDP administration. However, fatty degeneration of tumor tissue was suspected in two of eight mice in the 5.0 mg/kg EHDP administered group. In vitro study, EHDP inhibited DNA synthesis and induced morphological changes, such as pycnotic cells. These findings show that the growth of Dunn osteosarcoma cells is inhibited by EHDP.


Effects of Electron Microscope Parameters and Sample Thickness on High Angle Annular Dark Field Imaging.
Scanning transmission electron microscopy (STEM) developed into a very important characterization tool for atomic analysis of crystalline specimens. High-angle annular dark field (HAADF) scanning transmission electron microscopy (STEM) has become one of the most powerful tools to visualize material structures at atomic resolution. However, the parameter of electron microscope and sample thickness is the important influence factors on HAADF-STEM imaging. The effect of convergence angle, spherical aberration, and defocus to HAADF imaging process has been analyzed through simulation. The applicability of two HAADF simulation software has been compared, and suggestions for their usage have been given.


Toward mechanistic elucidation of iron acquisition in barley: efficient synthesis of mugineic acids and their transport activities.
Iron acquisition of graminaceous plants is characterized by the synthesis and secretion of iron-chelating compounds, mugineic acids (MAs), and by a specific uptake system for MAs-iron(III) complexes. We identified a transporter, HvYS1 (Hordeum vulgare L. yellow stripe 1), that is highly specific for MAs-iron(III) in barley roots. In this article we outline the characterization of HvYS1, and our recent work on the practical syntheses of MAs and investigations into the molecular basis of the specific transport of their iron(III) complexes by HvYS1. 2'-Deoxymugineic acid (DMA) was synthesized in a good overall yield from commercially available Boc-l-allylglycine using a minimal number of short simple operations with minimal protecting groups and work-up/purification procedures. The same strategy was also successfully applied to beta-hydroxy-l-allylglycine, which was obtained by an allylic oxidation of l-allylglycine derivatives, to give MA and 2'-epi-MA efficiently. HvYS1 transported the iron(III) complexes of all three synthetic specimens with efficiency similar to that of a natural mugineic acid complex. With sufficient quantities of MAs in hand, we analyzed the function of HvYS1 and revealed by preparing chimeric transporters that the sixth outer membrane loop of the transporter plays a vital role in substrate specificity.


HLA-C KIR-Ligands Determine the Impact of Anti-Thymocyte Globulin (ATG) on Graft versus Host and Graft versus Leukemia Effects Following Hematopoietic Stem Cell Transplantation.
Rabbit anti-thymocyte globulins (ATGs) are widely used for the prevention of acute and chronic graft versus host disease (aGVHD, cGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). However, most prospective and retrospective studies did not reveal an overall survival (OS) benefit associated with ATG. Homozygosity for human leukocyte antigen (HLA)-C group 1 killer-cell immunoglobulin-like receptor ligands (KIR-L), i.e. C1/1 KIR-L status, was recently shown to be a risk factor for severe aGVHD. Congruously, we have previously reported favorable outcomes in C1/1 recipients after ATG-based transplants in a monocentric analysis. Here, within an extended cohort, we test the hypothesis that incorporation of ATG for GVHD prophylaxis may improve survival particularly in HSCT recipients with at least one C1 KIR-ligand. Retrospectively, 775 consecutive allogeneic (excluding haploidentical) HSCTs were analyzed, including peripheral blood and bone marrow grafts for adults with hematological diseases at two Austrian HSCT centers. ATG-Fresenius/Grafalon, Thymoglobuline, and alemtuzumab were applied in 256, 87, and 7 transplants, respectively (subsequently summarized as "ATG"), while 425 HSCT were performed without ATG. Median follow-up of surviving patients is 48 months. Adjusted for age, disease-risk, HLA-match, donor and graft type, sex match, cytomegalovirus serostatus, conditioning intensity, and type of post-grafting GVHD prophylaxis, Cox regression analysis of the entire cohort (n = 775) revealed a significant association of ATG with decreased non-relapse mortality (NRM) (risk ratio (RR), 0.57; p = 0.001), and overall mortality (RR, 0.71; p = 0.014). Upon stratification for HLA-C KIR-L, the greatest benefit for ATG emerged in C1/1 recipients (n = 291), by reduction of non-relapse (RR, 0.34; p = 0.0002) and overall mortality (RR, 0.50; p = 0.003). Less pronounced, ATG decreased NRM (RR, 0.60; p = 0.036) in HLA-C group 1/2 recipients (n = 364), without significantly influencing overall mortality (RR, 0.70; p = 0.065). After exclusion of higher-dose ATG-based transplants, serotherapy significantly improved both NRM (RR, 0.54; p = 0.019; n = 322) and overall mortality (RR, 0.60; p = 0.018) in C1/2 recipients as well. In both, C1/1 (RR, 1.70; p = 0.10) and particularly in C1/2 recipients (RR, 0.94; p = 0.81), there was no statistically significant impact of ATG on relapse incidence. By contrast, in C2/2 recipients (n = 121), ATG neither reduced NRM (RR, 1.10; p = 0.82) nor overall mortality (RR, 1.50; p = 0.17), but increased the risk for relapse (RR, 4.38; p = 0.02). These retrospective findings suggest ATG may provide a survival benefit in recipients with at least one C1 group KIR-L, by reducing NRM without significantly increasing the relapse risk.


Diabetes mellitus is not a contra-indication for peripheral vascular intervention in patients with leg ischemia.
The effect of diabetes mellitus on the patency of peripheral vascular interventions was investigated in patients with arterial insufficiency of the leg in a retrospective follow-up study performed between 1993 and 1995. In 65 patients without and 36 with diabetes 124 vascular reconstructions were performed because of rest pain and/or ulceration. In diabetic patients ulcers were found more frequently and more distal bypasses were performed. No significant differences were observed between diabetics and non-diabetics as to bypass patency, number of re-interventions and amputations. Smoking and age were significant factors influencing bypass patency. Diabetes mellitus in patients with critical leg ischaemia appears to be no reason to refrain from vascular surgery.


Akap1 genetic deletion increases the severity of hyperoxia-induced acute lung injury in mice.
Critically ill patients are commonly treated with high levels of oxygen, hyperoxia, for prolonged periods of time. Unfortunately, extended exposure to hyperoxia can exacerbate respiratory failure and lead to a high mortality rate. Mitochondrial A-kinase anchoring protein (Akap) has been shown to regulate mitochondrial function. It has been reported that, under hypoxic conditions, Akap121 undergoes proteolytic degradation and promotes cardiac injury. However, the role of Akap1 in hyperoxia-induced acute lung injury (ALI) is largely unknown. To address this gap in our understanding of Akap1, we exposed wild-type ( wt) and Akap1-/- mice to 100% oxygen for 48 h, a time point associated with lung damage in the murine model of ALI. We found that under hyperoxia, Akap1-/- mice display increased levels of proinflammatory cytokines, immune cell infiltration, and protein leakage in lungs, as well as increased alveolar capillary permeability compared with wt controls. Further analysis revealed that Akap1 deletion enhances lung NF-κB p65 activity as assessed by immunoblotting and DNA-binding assay and mitochondrial autophagy-related markers, PINK1 and Parkin. Ultrastructural analysis using electron microscopy revealed that Akap1 deletion was associated with remarkably aberrant mitochondria and lamellar bodies in type II alveolar epithelial cells. Taken together, these results demonstrate that Akap1 genetic deletion increases the severity of hyperoxia-induced acute lung injury in mice.


What insights have new imaging techniques given into aggressive forms of MS--different forms of MS or different from MS?
"Aggressive" multiple sclerosis (MS) is still a challenging diagnosis, in spite of the relevant progresses concerning the comprehension of the disease mechanisms, especially through pathology studies and the advent of conventional magnetic resonance imaging (MRI). Some reviews have been already published on their clinical and therapeutical aspects, but no systematic review is available in literature about the neuroradiological features, using both conventional and advanced techniques. In particular, advanced MRI techniques, namely diffusion-weighted and tensor imaging, magnetization transfer imaging, and proton magnetic resonance spectroscopy, are giving new insights to find specific and appropriate radiological parameters that can help in targeting the diagnosis. We report a review of literature on the neuroradiological findings of aggressive forms of MS, focusing specifically on the role of advanced MRI techniques in the diagnostic phase and during follow-up.


Effects of pancreatectomy, tolbutamide and insulin on glucose fluxes in chickens.
The effects of pancreatectomy and of injection of insulin or Tolbutamide on glucose fluxes in chickens were examined. This was prompted by earlier observations that Tolbutamide seems not to require the presence of pancreatic insulin for its acute hypoglycaemic action in this species. Rates of appearance (Ra) and disappearance (Rd) of glucose were estimated by isotope dilution using [14C]glucose in single-injection experiments and [14C]glucose and [6-3H]glucose in priming-injection + constant-infusion experiments. Six hours after sub-total pancreatectomy (splenic lobe remained in situ), chickens were hyperglycaemic (16.7 v. 10-4 mmol glucose/1 in controls), had a larger sampled glucose pool (4.41 v. 3.10 mmol) and a higher average rate of glucose utilization (41.7 v. 33.3 micron mol/kg per min) than sham-operated controls as estimated in single-injection experiments. Tolbutamide (50 mg/kg injected i.v.) reduced Ra in intact chickens from 33.9 to 1.1 micro mol/kg per min and reduced Ra in pancreatectomized chickens from 42.2 to 10.2 micro mol/kg per min. in priming-injection + constant-infusion experiments tolbutamide again reduced Ra significantly. In all case Rd tended to fall, apparently as a result of the developing hypoglycaemia. tolbutamide did not affect the volume of extracellular fluid (sucrose space). In single-injection experiments , insulin (1 unit/kg injected i.v.) reduced Ra by 56% and transiently increased Rd by 39%. It was concluded that pancreatectomy and injection of insulin or tolbutamide produce responses in glucose movements in chickens that are qualitatively similar to those in mammals. In chickens the hypoglcaemic action of tolbutamide, which persists in the absence of the pancreas, depends on an inhibition of glucose release by the liver.


The precursor molecule of a V lambda II-immunoglobulin light chain-derived amyloid fibril protein circulates precleaved.
The putative precursor molecule of a human AL type amyloid fibril protein was isolated from an ultrafiltrate after hemofiltration. Subsequent separation of this protein was achieved by high performance liquid chromatography (HPLC) after reduction and carboxymethylation of the disulfide bonds. The protein was separated into several fractions which were further analyzed by automatic amino acid sequence determination. It was deduced from the sequence data that the precursor molecule is an immunoglobulin L-chain of the lambda-type. The V-region of this protein is most closely related to the proteins of subgroup II. Internal splits occurred in the molecule after lysine residues in positions 110, 129 and 179. The predominant fragment commences with either serine or alanine in position 9 and extends to a serine in position 65 of the V-region. Tryptic peptides generated from the fragments cover nearly the entire V- and C-region of the L-chain, with the exception of positions 1-8, from which no peptide has been isolated.


Improving the data reliability of phase modulated holographic storage using a reliable bit aware low-density parity-check code.
Phase modulated holographic storage offers superior storage capacity and a longer life span compared with other storage technologies. However, its application is limited by its high raw bit error rate. We aimed to introduce low-density parity-check (LDPC) codes for data protection in phase modulated holographic storage systems. However, traditional LDPC codes can not fully exploit data error characteristics, causing inaccurate initial log-likelihood ratio (LLR) information, which degrades decoding performance, thus limiting the improvement degree of data reliability in phase modulated holographic storage. Therefore, we propose a reliable bit aware LDPC optimization method (RaLDPC) that analyzes and employs phase demodulation characteristics to obtain reliable bits. More accurate initial LLR weights are assigned to these reliable bits. Hence, the optimized initial LLR can reflect the reliability of the demodulated data more accurately. Experimental results show that RaLDPC can reduce the bit error rate by an average of 38.89% compared with the traditional LDPC code, improving the data reliability of phase modulated holographic storage.


Characterization of Aging-Related Genes to Predict Prognosis and Evaluate the Tumor Immune Microenvironment in Malignant Melanoma.
Malignant melanoma (MM) is one of the most malignant types of skin cancer and its incidence and mortality rates are increasing worldwide. Aging is well recognized as a significant risk factor for cancer. However, few studies have analyzed in depth the association between aging-related genes (AGs) and malignant melanoma prognosis with tumor immune microenvironment. Here, we downloaded 471 MM patients from The Cancer Genome Atlas (TCGA) with RNA sequence and clinicopathological data. 58 AGs from the TCGA dataset were examined using Cox regression and the LASSO assay. As a result, a gene signature for aging-related genes was created. The time-dependent ROC curve and Kaplan-Meier analysis were calculated to determine its predictive capability. Moreover, we created a nomogram for the clinicopathologic variables and the AGs gene signature to determine overall survival (OS). We also explored the association between three immune checkpoints, immune cell infiltration, and the aging-related gene signature. We established an aging risk model to identify and predict the immune microenvironment in malignant melanoma. Then we developed and validated a prognosis risk model using three AGs (CSNK1E, C1QA, and SOD-2) in the GSE65904 dataset. The aging signature was positively associated with clinical and molecular characteristics and can be used as a prognostic factor for malignant melanoma. The low aging risk score was associated with a poor prognosis and indicated an immunosuppressive microenvironment. To summarize, we established and validated a model of aging risk based on three aging-related genes that acted as an independent prognostic predictor of overall survival. Besides, it also characterized the immune response in the malignant melanoma microenvironment and could provide a potential indicator of individualized immunotherapy in malignant melanoma.


[Subjective well-being and ability to work of hospital staff after SARS-CoV2 immunization with the mRNA vaccine BNT162b2].
Since December 27, 2020, employees of the health system in Germany have been vaccinated against the SARS coronavirus-2 with the vaccine BNT162B2. Initial observations show that especially among younger vaccinated people side effects are common. In this study, using the example of clinic employees, the self-perceived well-being after the first and second dose of the vaccine was examined. Anonymized online questionnaire to be filled out once by all employees after the second dose of BNT162B2 was offered. The severity of side effects was queried using an ordinal numerical rating scale with values between 0 and 10. Other key data points were age, gender, and occupational group. The ability to work in the days following the injections was recorded by self-reporting. Data from 555 respondents were evaluated. The mean age was 40.25 years (standard deviation 12.35). 56 % of the respondents were female, 44.3 % belonged to the medical service, 42.9 % to the nursing service and 12.8 % were assigned to other professional groups with COVID-19 patient contact. Around 2 % of all employees did not experience any side effects at all. The most common side effect was pain at the injection site. Fatigue, headaches and myalgia followed with decreasing frequency. After the first dose, ¾ of the respondents said they had tolerated the vaccination well overall, after the second dose it was only half. After the first dose, over 90 % of the respondents felt that they were able to work again on the following day, after the second dose one third stated that they were only able to work again on the second day. 2.2 % of all employees had to report that they were unable to work for at least one day after the first dose and 19.5 % after the second dose. Vaccination with BNT162B2 frequently leads to side effects, especially after the second dose. Perception of side effects resulted in 19 % of those questioned being sick after the second dose. Nevertheless, 95 % of all respondents would choose a coronavirus vaccination again.


Pediatric parotitis: a 5-year review at a tertiary care pediatric institution.
Parotitis is a well recognized entity in the adult population, however there are very few studies concerning the clinical presentation and management of this condition in children. To characterize pediatric parotitis in a tertiary care setting, with the goal of clarifying management recommendations and outcomes. The charts of all pediatric patients with a diagnosis of parotitis treated at a tertiary care academic institution from 1999 to 2004 were reviewed. The management of inpatients and outpatients were characterized to define differences in presentation and care. Twenty-one children (6 months-15 years) with a diagnosis of parotitis were identified. Thirteen (62%) children were treated as inpatients, of which seven (54%), had significant medical co-morbidities. The most common clinical presentations of the inpatient group included dehydration (46%), fever (38%) and leukocytosis (46%). Two inpatients (15%) required surgical drainage due to abscess formation. Eight children (38%) were treated as outpatients, none with associated co-morbidity, fever, leukocytosis, or complication due to infection. All outpatients were treated with oral antibiotics or conservative therapy with eventual resolution. Parotitis in the pediatric population is uncommon. The presence of a significant co-morbidity, fever, or leukocytosis may require inpatient therapy and imaging if patients fail to improve with medical therapy. Other than abscess drainage, surgery for parotitis in children is not routinely recommended.


Probable genetic linkage between a locus for human urinary pepsinogen and the HL-A loci.
The genetic basis of familial variation in the relative intensities of human urinary pepsinogen isozymes is not completely clear from family studies. An investigation of the linkage relationships of pepsinogen isozyme 5, considering only segregation for the presence or absence of Pg 5, yields a peak lod score of 4.1 at theta = .1 for linkage with HL-A1 or HL-A2. Added to data from segregation interpreted according to a scheme proposed for the inheritance of intensity differences in Pg 5, the peak lod score becomes 3.0 at theta = .2. Data derived from the segregation of pepsinogen isozyme 4, possibly determined by an allele to that controlling the presence or absence of Pg 5, further reduces the total lod score at theta = .2 to 2.9. The results indicate probable linkage between a locus for urinary pepsinogen and the HL-A loci, but are insufficient to permit any conclusion concerning possible heterogeneity in the linkage relationships of Pg 4 and Pg 5 to HL-A.


Anxiolytics may promote locomotor function recovery in spinal cord injury patients.
Recent findings in animal models of paraplegia suggest that specific nonbenzodiazepine anxiolytics may temporarily restore locomotor functions after spinal cord injury (SCI). Experiments using in vitro models have revealed, indeed, that selective serotonin receptor (5-HTR) ligands such as 5-HTR(1A) agonists, known as relatively safe anxiolytics, can acutely elicit episodes of rhythmic neuronal activity refered to as fictive locomotion in isolated spinal cord preparations. Along the same line, in vivo studies have recently shown that this subclass of anxiolytics can induce, shortly after systemic administration (eg, orally or subcutaneously), some locomotor-like hindlimb movements during 45-60 minutes in completely spinal cord-transected (Tx) rodents. Using 'knock-out' mice (eg, 5-HTR(7)-/-) and selective antagonists, it has been clearly established that both 5-HTR(1A) and 5-HTR(7) were critically involved in mediating the pro-locomotor effects induced by 8-OH-DPAT (typically referred to as a 5-HTR(1A) agonist) in Tx animals. Taken together, these in vitro and in vivo data strongly support the idea that 5-HTR(1A) agonists may eventually become constitutive elements of a novel first-in-class combinatorial treatment aimed at periodically inducing short episodes of treadmill stepping in SCI patients.


Plausibility or truth? An essay on medicine and world view.
This paper introduces the notion of plausibility as a decisive condition for the acceptance by groups in society of fundamental ideas concerning the nature of illness. Plausibility, it is argued, helps to explain both transition from one system of fundamental ideas to another in history, and coexistence of different such systems in a single civilization. Hence this paper challenges an interpretation of medicine prevalent, especially in medical anthropology, since the 1940s, when Erwin Ackerknecht introduced the idea of medicine as an integrated aspect of a society's or community's culture. Because early research focused on small-scale communities where a majority, if not all, of the members adhered to one world view and experienced one and the same existential environment, medicine came to be identified as a cultural system representative of entire communities and, later, societies. Hence we speak of Chinese medicine as if there were one system of therapeutic ideas and practices representative of China as a whole. The fact is that even though medicine is indeed a cultural system, it is representative only of the culture developed by people sharing identical environments and experiences. That is, if within one civilization different groups coexist in different existential realities entailing different notions of what causes crisis and how to maintain harmony, then these groups will believe in different systems of ideas concerning the generation, treatment, and prevention of illness. Such systems of ideas are therefore always metaphorical reflections of a real social environment or of one aspired to. It is not truth (Wahrheit) that leads to an acceptance of basic therapeutic ideas but plausibility (Wahrschein).


A case of chronic pancreatitis successfully treated by endoscopic removal of protein plugs.
A 56 years old male with chronic pancreatitis complained of intractable abdominal pain, anorexia, emaciation and peripheral edema. Medical treatment initiated only partial improvement in the general condition and hypoproteinemia. Endoscopic retrograde cholangiopancreatography revealed multiple filling defects in the dilated main pancreatic duct. Endoscopic aspiration of pure pancreatic juice yielded numerous protein plugs. The endoscopic removal of protein plugs from the pancreatic duct resulted in remarkable improvement in symptoms, laboratory findings and ERCP findings. We consider this procedure to be an important new treatment of chronic pancreatitis.


[Analysis and test of piezoelectric micropump for drug delivery].
With a microsystem or micropump, the release rate of drug delivery is able to be controlled easily to maintain the therapeutic efficacy. A piezoelectric membrane-valve micropump for implantable and carryhome drug delivery system is developed and tested. The influence elements of dynamic performance of the PZT actuator and valve were analyzed, and the calculation method of resonant frequency of the membrane valve was provided. Study results showed that the output performance of the micropump depended on the coupling effect of the actuator and valve. For a given actuator, the output value and the optimal frequency of a micropump could be enhanced only by valve design. Two micropumps with different valve dimensions were fabricated for comparing examination. The smaller -valve micropump obtained higher output values (the maximum flow rate and backpressure being 3.5 ml/min and 27 KPa, respectively) and two optimal frequencies (800 Hz and 3 000 Hz). The larger -valve micropump achieved lower output values (the maximum flow rate and backpressure being 3.0 ml/min and 9 KPa, respectively) and one optimal frequency (about 200 Hz). The test results suggest that the output values and optimal frequency of micropump can be improved by changing the valve dimension, and the viewpoint that checkvalve micropump works only with low acting frequency is wrong.


The additional value of gadolinium-enhanced MRI to standard assessment for cardiac involvement in patients with pulmonary sarcoidosis.
To determine whether gadolinium-enhanced cardiac MRI (CMR) was of additional diagnostic value to standard assessment in patients with sarcoidosis who underwent evaluation for cardiac involvement. We reviewed the findings in patients with pulmonary sarcoidosis who had been assessed with ECG, Doppler echocardiography, 201Tl scintigraphy, and CMR from 2002 to 2004. Of the 55 evaluated patients, standard evaluation diagnosed cardiac involvement in 13 patients while CMR diagnosed myocardial scarring (mean +/- SD, 2.5 +/- 1.9 segments) [all 6 patients] and impaired systolic left ventricular function (1 patient) in an additional 6 patients. The extent of delayed enhancement correlated with disease duration (p < 0.05), ventricular dimensions and function (p < 0.001), severity of mitral regurgitation (p < 0.05), and the presence of ventricular tachycardias (p < 0.001). Patients in whom cardiac involvement was diagnosed only with CMR had less myocardial scarring and functional impairment (p < 0.05) compared to patients with a diagnosis made by standard assessment. CMR provides an accurate estimation of the extent of cardiac involvement and may reveal signs of early infiltration that are not detected by standard assessment. The extent of late enhancement with gadolinium relates to the severity of cardiac involvement and may therefore have prognostic implications.


Characterization of antibody charge heterogeneity resolved by preparative immobilized pH gradients.
A capillary isoelectric focusing (cIEF) method has been developed as an alternative to cation exchange chromatography to determine charge heterogeneity for a therapeutic antibody. Characterization of the cIEF profile is important to understand the charged isoform distribution. A variety of preparative IEF methods have been developed over the years but have had various limitations including high levels of contaminating ampholytes and complex fractionation and isolation procedures. More recently, an off-line method that uses pI-based separation on immobilized pH gradients was developed to preparatively isolate material with convenient liquid phase recovery. This method uses the Agilent OFFGEL 3100 Fractionator and was optimized to produce fractions of antibody charge isoforms differing by as little as 0.1 pI units. The isolation of highly resolved fractions then allowed for the identification of N- and C-terminal basic charge modifications including noncyclized glutamine, signal peptide extensions, and various levels of C-terminal lysine processing and high mannose structures. These species could then be correlated to specific peaks in the cIEF profile. This work shows that a preparative IEF method using immobilized pH gradients can be optimized to generate highly resolved, pI-based fractions in solution which can be used for successful cIEF profile characterization. Access to preparative amounts of discrete charged species allows for a better understanding of the underlying covalent modifications responsible for the charge differences and facilitates evaluation of the impact of these modifications on stability and potency of therapeutic antibodies.


Targeting subjective engagement in experimental therapeutics for digital mental health interventions.
Engagement is a multifaceted construct and a likely mechanism by which digital interventions achieve clinical improvements. To date, clinical research on digital mental health interventions (DMHIs) has overwhelmingly defined engagement and assessed its association with clinical outcomes through the objective/behavioral metrics of use of or interactions with a DMHI, such as number of log-ins or time spent using the technology. However, engagement also entails users' subjective experience. Research is largely lacking that tests the relationship between subjective metrics of engagement and clinical outcomes. The purpose of this study is to present a proof-of-concept exploratory evaluation of the association between subjective engagement measures of a mobile DMHI with changes in depression and anxiety. Adult primary care patients (N = 146) who screened positive for depression or anxiety were randomized to receive a DMHI, IntelliCare, immediately or following an 8-week waitlist. Subjective engagement was measured via the Usefulness, Satisfaction, and Ease of Use (USE) Questionnaire. Across both conditions, results showed that individuals who perceived a mobile intervention as more useful, easy to use and learn, and satisfying had greater improvements in depression and anxiety over eight weeks. Findings support our proposed experimental therapeutics framework that hypothesizes objective/behavioral and subjective engagement metrics as mechanisms that lead to changes in clinical outcomes, as well as support directing intervention design efforts for DMHIs to target the user experience.


[Lymphoma in childhood].
Manifestation of childhood Hodgkin's disease and Non-Hodgkin's lymphoma differ, especially in the latter, from those in adults. Extranodal involvement is seen even more frequently in childhood Non-Hodgkin's lymphomas than in adults. This article reviews the radiological findings in malignant lymphomas in children, explains the differences in the manifestation of Hodgkin's lymphomas, of different subtypes and of the malignant lymphomas in adults. The problems in diagnosis of organ manifestation and special problems of diagnostic imaging procedures in children are discussed.


Sleep-Disordered Breathing Is a Stronger Risk Factor for Proliferative Diabetic Retinopathy than Metabolic Syndrome and the Number of Its Individual Components.
To evaluate whether the features of sleep-disordered breathing (SDB) are stronger independent factors for proliferative diabetic retinopathy (PDR) compared to the incidence of metabolic syndrome (MetS) and the number of its individual components. We studied a cross-sectional total of 132 patients with type 2 diabetes. Thirty-nine patients had non-proliferative diabetic retinopathy (NPDR) and 93 patients had PDR. Pulse oximetry was conducted, and the patients' mean oxygen saturation (mean SpO2%) and 4% oxygen desaturation index (4% ODI times/hour) were evaluated. We compared the SDB and MetS variables between the NPDR and PDR patients. A logistic regression analysis was used to determine the independent factors for the diagnosis of PDR. The MetS diagnosis was made significantly more often in the PDR group (p = 0.04). The number of individual MetS components was significantly greater in the PDR group compared to the NPDR group (p = 0.01). The mean SpO2 of the NPDR group was not significantly different from that of the PDR group. The 4% ODI in the NPDR group was significantly lower than that in the PDR group (p = 0.01). The logistic regression analysis using the prevalence of MetS and the number of MetS components revealed that younger age and high 4%ODI value were independent factors contributing to the diagnosis of PDR. Our findings confirmed that compared to MetS and the number of its individual components, SDB may be a factor contributing to the progression to PDR. However, further careful longitudinal validation studies are needed.


Proliferative response of different exocrine pancreatic cell types to hormonal stimuli. I. Effects of long-term cerulein administration.
The trophic effect on the exocrine pancreas of the cholecystokinin analogue cerulein was studied in a long-term experiment (20 or 160 micrograms/kg/24 h for 14 days) in mice by measuring changes in pancreatic weight and protein, amylase, and DNA content. Further, the selective cell growth stimulation exerted by various doses of cerulein (4, 20, 54, 160 micrograms/kg/24 h) on different exocrine pancreatic cell types was studied by continuous administration of 3H-thymidine. In the first experiment animals given 20 micrograms/kg/24 h of cerulein had increased pancreatic weight and amylase and protein content, whereas the animals given the higher dose had unchanged weight and a less pronounced increase in amylase and protein content. The pancreatic DNA content was unaffected in the 20-micrograms group but was clearly decreased by the higher dose. In the second experiment a statistically significant increase over controls was found in the fraction of labeled ductal cells when 20, 54, and 160 micrograms of cerulein was administered. However, in the acinar cell population an increase was measured only in the 160-micrograms group. A tendency to nadir in cell labeling was observed in both acinar and ductal cell groups at less stimulation. Labeling of centroacinar cells increased in all cerulein-treated groups. The results show that all cell types of the exocrine pancreas can be forced into proliferation by the cholecystokinin analogue used and that there is preferential cell growth stimulation in the ductal and centroacinar cell populations.


Secondary prevention after ischaemic stroke: the ASPIRE-S study.
Survivors of ischaemic stroke (IS) are at high-risk for future vascular events. Comprehensive information on the adequacy of secondary prevention after IS is lacking despite the knowledge that appropriate secondary prevention improves long-term patient outcomes. ASPIRE-S (Action on Secondary Prevention Interventions and Rehabilitation in Stroke) aimed to prospectively assess secondary prevention in patients 6 months following IS. Consenting patients admitted with IS to three Dublin hospitals were recruited over 1 year, from October 2011. At 6 months post IS a comprehensive assessment was completed, modelled on the EUROASPIRE protocol for evaluation of the adequacy of secondary prevention in post-discharge cardiac patients. This assessment included measurements of blood pressure, body mass index and fasting lipid and glucose profiles. Secondary preventive medications and smoking status were also documented. Three hundred two patients (58 % male) participated, of whom 256 (85 %) were followed-up at 6 months. Mean age was 69 years (range 22-95). At follow-up, 68 % of patients had a BMI >25 kg/m(2) and 16.4 % were still smoking. Almost two-thirds (63.4 %) had a blood pressure >140/90 and 23 % had low-density-lipoprotein >2.5 mmol/L. 28 % of diabetic patients had HbA1c ≥ 7 %. Ninety seven percent of patients were on anti-platelet and/or anticoagulant therapy. Of those with atrial fibrillation, 82 % were anti-coagulated (mean INR of 2.4). Ninety-five percent were on lipid-lowering therapy and three-quarters were on anti-hypertensive therapy. This prospective multi-centre survey of IS patients demonstrated a high prevalence of remaining modifiable risk factors at 6 months post stroke, despite the widespread prescription of secondary preventive medications. There is scope to improve preventive measures after IS (in particular blood pressure) by incorporating evidence-based guidelines into quality assurance cycles in stroke care.


Intranasal cocaine use does not appear to be an independent risk factor for HCV infection.
To determine the prevalence of HCV infection among intranasal cocaine users and evaluate underlying parental risk factors. A cross-sectional study evaluated prospectively 60 patients admitted to a chemical dependency unit. A standardized questionnaire was designed to obtain epidemiological data. Aminotransferases and anti-HCV antibodies were determined. Anti-HCV antibody positivity was confirmed by polymerase chain reaction (PCR). Fifteen (25%) patients of 60 tested intranasal cocaine users were anti-HCV positive. Ten (75%) of them had detectable HCV-RNA. Comparison between 15 anti-HCV positive and 45 anti-HCV negative patients showed significant differences in mean age (35 versus 27 years), estimated time of drug use (10 versus 4 years), rate of elevated ALT and/or AST (60% versus 16%) and presence of parenteral risk factors (100% versus 7%). Comparison between patients with and without elevated aminotransferases showed significant difference in mean duration of drug use (8 versus 5 years) and rate of anti-HCV positivity (56% versus 14%). Among 15 anti-HCV positive patients, HCV-RNA was detectable in all with elevated aminotransferases and only one of six with normal aminotransferases (100% versus 17%). While there was a high prevalence of anti-HCV antibodies in this sample of intranasal cocaine users, the infection was highly correlated with the presence of intravenous (i.v.) drug use and duration of drug use. In this sample, therefore, intranasal cocaine use alone was not an important risk factor for HCV infection.


Cost-effectiveness of lifestyle counselling as primary prevention of gestational diabetes mellitus: findings from a cluster-randomised trial.
The aim was to evaluate the cost-effectiveness of primary prevention of gestational diabetes mellitus (GDM) through intensified counselling on physical activity, diet, and appropriate weight gain among the risk group. The cost-effectiveness analysis was based on data from a cluster-randomised controlled GDM prevention trial carried out in primary health-care maternity clinics in Finland. Women (n = 399) with at least one risk factor for GDM were included. The incremental cost-effectiveness ratio (ICER) was calculated in terms of birth weight, 15D, and perceived health as measured with a visual analogue scale (VAS). A bootstrap technique for cluster-randomised samples was used to estimate uncertainty around a cost-effectiveness acceptability curve. The mean total cost in the intervention group was €7,763 (standard deviation (SD): €4,511) and in the usual-care group was €6,994 (SD: €4,326, p = 0.14). The mean intervention cost was €141. The difference for costs in the birth-weight group was €753 (95% CI: -250 to 1,818) and in effects for birth weight was 115 g (95% CI: 15 to 222). The ICER for birth weight was almost €7, with 86.7% of bootstrap pairs located in the north-east quadrant, indicating that the intervention was more effective and more expensive in birth weight terms than the usual care was. The data show an 86.7% probability that each gram of birth weight avoided requires an additional cost of €7. Intervention was effective for birth weight but was not cost-effective for birth weight, 15D, or VAS when compared to the usual care. ISRCTN 33885819.


The Frequency, Characteristics, and Outcomes Among Cancer Patients With Delirium Admitted to an Acute Palliative Care Unit.
Delirium is a common neuropsychiatric condition seen in patients with severe illness, such as advanced cancer. Few published studies are available of the frequency, course, and outcomes of standardized management of delirium in advanced cancer patients admitted to acute palliative care unit (APCU). In this study, we examined the frequency, characteristics, and outcomes of delirium in patients with advanced cancer admitted to an APCU. Medical records of 609 consecutive patients admitted to the APCU from January 2011 through December 2011 were reviewed. Data on patients' demographics; Memorial Delirium Assessment Scale (MDAS) score; palliative care specialist (PCS) diagnosis of delirium; delirium etiology, subtype, and reversibility; late development of delirium; and discharge outcome were collected. Delirium was diagnosed with MDAS score ≥7 and by a PCS using Diagnostic and Statistical Manual, 4th edition, Text Revision criteria. All patients admitted to the APCU received standardized assessments and management of delirium per best practice guidelines in delirium management. Of 556 patients in the APCU, 323 (58%) had a diagnosis of delirium. Of these, 229 (71%) had a delirium diagnosis on admission and 94 (29%) developed delirium after admission to the APCU. Delirium reversed in 85 of 323 episodes (26%). Half of patients with delirium (n = 162) died. Patients with the diagnosis of delirium had a lower median overall survival than those without delirium. Patients who developed delirium after admission to the APCU had poorer survival (p ≤ .0001) and a lower rate of delirium reversal (p = .03) compared with those admitted with delirium. More than half of the patients admitted to the APCU had delirium. Reversibility occurred in almost one-third of cases. Diagnosis of delirium was associated with poorer survival.


Static force and tipover stability analysis of an assistive device for paraplegics.
Stability plays a vital role in any robotic system. Its significance increases in systems related to health and medicine. For rehabilitation devices meant for Spinal Cord Injury (SCI) patients, stability is crucial and key element in ensuring patient safety and the usefulness of the devices. In this study, kinematics, force analysis, and the static tip-over stability of a device for rehabilitation of paraplegic patients is discussed. Kinematics modeling and static force analysis provide critical information about position and loading at different points on the device. Force-Angle Stability Criterion is used to find the static tip-over stability of the device while the patient is on board the device. The Criterion relies on the support boundary, tip-over mode axes, and the Center of Mass (COM) of the complete system. The Criterion is sensitive to the COM position and therefore is more suitable for the application. The linear actuator mounted on the device causes the end effector of the device to move. The patient, strapped with the end effector, in turn moves from sitting position to standing position. The study focuses on the analysis of stability based on changing COM during this motion. The results verify that although the system is well within the stability bounds, it is more stable as it moves from sitting position to standing position.


Heroism. A core value of the Army Nurse Corps.
Celebrating the 100th Anniversary of the Army Nurse Corps, this article describes the heroic acts of a number of Army nurses. Beginning with the Civil War and concluding with the Vietnam War, examples are given of nurses who were not afraid to take risks to serve the United States of America and its soldiers. Examples portray the steadfast, bold, ethical, caring, and brave behaviors of these nurses as they took the lead on behalf of their patients and other nurses and soldiers.


Internal Medicine Residents' Perceptions of Nephrology as a Career: A Focus Group Study.
Interest in nephrology as a career has declined dramatically over the past several years. Only 62% of nephrology fellowship positions are filled for the upcoming 2020 appointment year. The purpose of this study was to identify perceptions, attitudes, motivators, and barriers to a career in nephrology among internal medicine residents. We recruited focus groups of internal medicine residents (N=25) from the University of Colorado, and asked questions aimed at exploring perceptions, attitudes, and barriers to a career in nephrology, and ways to increase interest in nephrology. All focus groups were conducted on the University of Colorado Denver Anschutz Medical Campus. Focus group sessions were recorded and transcribed. Thematic analysis was used to identify key concepts and themes. Residents described many barriers to a career in nephrology, including lack of exposure, lack of advances in the field, low monetary compensation, high complexity, lack of role models/mentors, and low-prestige/noncompetitive nature of the field. Most residents had no exposure to outpatient nephrology. Lack of new therapeutics was a significant deterrent to nephrology. Nephrology teaching in medical school was described as not clinically relevant and too complicated. Several residents felt they were not smart enough for nephrology. Only three residents had a role model within nephrology. Residents used the word "stigmatized" to describe nephrology, and discussed how low prestige decreased their interest in a field. Participants expressed suggestions to increase interest in nephrology through earlier and more outpatient nephrology exposure, enhanced interactions with nephrologists, and research and advancements in the field. Residents identified several modifiable barriers to a career in nephrology. Changing how nephrology is taught in medical school, enhancing interactions with nephrologists through increased exposure, and highlighting research and advancements in nephrology may change the perception of nephrology and increase the number of residents entering the field.


Immunochemical methods for rapid mycotoxin detection: evolution from single to multiple analyte screening: a review.
This review focuses on recent developments in immunochemical methods for detection of mycotoxins, with a particular emphasis on simultaneous multiple analyte determination. This includes high-throughput instrumental analysis for the laboratory environment (microtitre plate enzyme-linked immunoabsorbant assay (ELISA), different kinds of immunosensors, fluorescence polarization immunoassay, and capillary electrophoretic immunoassay), as well as rapid visual tests for on-site testing (lateral-flow, dipstick, flow-through and column tests). For each type of immunoassay, perspectives for multiple analyte application are discussed and examples cited.


Disease-modifying anti-rheumatic drugs associated with different diabetes risks in patients with rheumatoid arthritis.
Patients with rheumatoid arthritis are prone to developing diabetes, which may lead to various sequelae and even cardiovascular diseases, the most common cause of death in such patients. Previous research has shown that some rheumatoid arthritis treatments may help prevent the development of diabetes. This study aimed to investigate whether patients using disease-modifying anti-rheumatic drugs (DMARDs) may have different levels of risk for diabetes and to analyse other risk factors for diabetes. This cohort study used data from the Chang Gung Research Database. 5530 adults with rheumatoid arthritis but without diabetes were eligible for the analysis. The endpoint of this study was new-onset diabetes, defined as an HbA1c value ≥7% during follow-up. The entire follow-up period was divided into monthly subunits. These 1-month units were then divided into methotrexate (MTX) monotherapy, any biological DMARDs (bDMARDs), MTX combination, other conventional DMARDs (cDMARDs) and non-DMARDs. A total of 546 participants (9.87%) developed diabetes between 2001 and 2018. The risk of diabetes was significantly lower in the bDMARD periods (HR 0.51; 95% CI 0.32 to 0.83), MTX combination periods (HR 0.50; 95% CI 0.32 to 0.78) and other cDMARD periods (HR 0.56; 95% CI 0.37 to 0.84) than in the MTX monotherapy periods. Individual drug analysis showed that hydroxychloroquine (HR 0.52; 95% CI 0.42 to 0.65) reduced the risk of diabetes. Tumour necrosis factor-α inhibitors (HR 0.69; 95% CI 0.46 to 1.03) tended to be protective. Patients with rheumatoid arthritis may have different levels of risk of diabetes depending on the treatment options.


A persistent influence of supernovae on biodiversity over the Phanerozoic.
It is an open question what has constrained macroevolutionary changes in marine animal diversity on the time scale of the Phanerozoic. Here, we will show that supernovae appear to have significantly influenced the biodiversity of life. After normalizing diversity curves of major animal marine genera by the changes in the area of shallow marine margins, a close correlation between supernovae frequency and biodiversity is obtained. The interpretation is that supernovae influence Earth's climate, which controls the ocean and atmospheric circulation of nutrients. With this, supernovae influence ocean bioproductivity and are speculated to affect genera-level diversity. The implication is a surprisingly influential role of stellar processes on evolution.


Salvage cryotherapy: is there a role for focal therapy?
Prostate cancer treatment has undergone vast development over the last few decades, but the most notable changes have included nerve-sparing open radical prostatectomy, laparoscopic radical prostatectomy, including robot-assisted and, more recently, cryotherapy and high-intensity focused ultrasound (HIFU). While radical surgery is the current gold standard, the less invasive therapeutic options of cryotherapy and HIFU are regarded as largely experimental by governing bodies. In the case of cryotherapy, a wealth of experience has been accumulated demonstrating its efficacy. Initially used as a salvage treatment for radiation-failed prostate cancer, cryotherapy has been widely used as a primary treatment for localized and locally advanced prostate cancer. More recently, there has been interest expressed in the concept of focal therapy in prostate cancer. This has been evaluated as a primary treatment for prostate cancer, but little information is available regarding the potential use as a salvage treatment. In this article, we evaluate the potential for focal treatment in the salvage setting.


Evidence of restoration cost in the annual gynodioecious Phacelia dubia.
A negative pleiotropic effect on fitness of nuclear sex-determining genes (cost of restoration) could explain nuclear-cytoplasmic gynodioecy but rarely has been demonstrated empirically. In a gynodioecious Phacelia dubia population, maternal lineages produce only hermaphroditic progenies irrespective of the pollen parent (N) or can segregate females (S). Natural progenies of N maternal plants had lower seed viability than that of S. Full-sib progenies of unrelated hermaphrodites from all possible matings between N and S lineages had similar pollen filling but differed in sporophyte performance, mainly at seed germination stage. A discrete multivariate analysis reveals that the performance of N(female symbol) x S(male symbol) progeny at early stages of development was significantly lower than that of the other three types of mating in agreement with the silent-cost-of-restoration hypothesis, affecting the sporophyte. The restoration cost and male sterility appear to be dominant and consequence of nuclear-cytoplasmic incompatibilities that may maintain nuclear-cytoplasmic polymorphism by frequency-dependent selection.


21st-century health care: the effect of computer use by physicians on patient satisfaction at a family medicine clinic.
Trust and satisfaction in the physician-patient relationship is the cornerstone of family medicine. Today, computers are playing an increasingly prominent role in the delivery of health care, yet recent data detailing their effect on the physician-patient relationship are limited. For physicians to "first do no harm," it is critical to determine that computers used at the point of care do not decrease patient satisfaction, because this is a good proxy for the physician-patient relationship. This study assessed patients' views of computer use and its effect on patient satisfaction in a family medicine clinic before and after implementation of an electronic environment developed by our institution. A survey was mailed to patients who had been evaluated at a family medicine clinic for hypertension, high blood pressure without hypertension, or hyperlipidemia. These diseases were selected because they are common and require strong physician-patient relationships for successful treatment. The survey assessed patients' overall satisfaction with health care received at the clinic and their opinions about how their physician's computer use affected their visit. This survey was compared with a survey done in 1995 at the same clinic, before adoption of the electronic environment. A total of 478 patients were enrolled in the study; 304 (63.6%) of these returned surveys. A majority of the patients (74.6%) thought that the computer had an overall positive impact on the quality of care provided. There was a positive association between a physician's computer skills, as rated by patients, and the patients' satisfaction with the computer's effect on the visit. There were no differences in overall satisfaction between the 1995 survey and the current survey. This study shows that physician competence with computers plays an important role in patient satisfaction and that computers can be integrated into the office visit without a detrimental effect on patient satisfaction. Surprisingly, patient familiarity with computers was shown to have a slight negative correlation with patient satisfaction. These findings are significant in view of research indicating that compliance, health outcomes, perception of physician competence, and malpractice suits are all related to physicians' interpersonal skills and patient satisfaction.


Gastrointestinal manifestations of pelvic floor disorders in adolescents: a diagnostic framework for the general practitioner.
Pelvic floor disorders (PFDs) can present with gastrointestinal complaints in the adolescent patient, and identification of PFDs is aided by clues in the history and physical examination apparent to the knowledgeable clinician. The aim of this article is to provide a framework for the diagnostic evaluation of the adolescent patient with a PFD and introduce management strategies. Patients with PFDs can present with gastrointestinal symptoms, including abdominal pain, constipation, incomplete evacuation, and fecal incontinence or nongastrointestinal complaints around genitourinary symptoms or sexual health. Although such symptoms can be attributed to a variety of diagnoses, PFDs should be considered in the adolescent patient based on history and physical examination findings, including a careful digital rectal examination. Adolescent patients in high-risk groups may be especially susceptible to PFDs. Such groups include postpartum women, victims of sexual abuse, those with congenital anorectal malformations, or acquired spinal cord or pelvic floor injuries. Biofeedback can be beneficial in patients with PFDs. PFDs may present with a spectrum of symptoms, but a familiarity with the clinical characteristics and understanding of the digital rectal examination may guide the skillful clinician in diagnosis, initial management, and subspecialist referral if needed.


General screening for celiac disease is advisable in children with type 1 diabetes.
The association between celiac disease (CD) and diabetes mellitus type 1 is well known. Only about one-third of all patients with CD are diagnosed in childhood as a result of typical gastrointestinal symptoms or growth retardation. To evaluate the feasibility of CD screening in diabetic children, we tested autoantibodies to tissue transglutaminase (tTGA) in all children with type 1 diabetes from our pediatric department during a 12-month period. In antibody-positive cases, we analyzed the clinical presentation and offered a duodenal biopsy to confirm the diagnosis and grade the severity of the inflammatory process. Of 205 children, 13 (6.3 %) were tTGA-positive. In seven of eight children who agreed to perform a biopsy, CD typical histological signs were detected (Marsh 1: n = 1, Marsh 3: n = 6). In three patients with confirmed disease, symptoms (iron deficiency, recurrent abdominal pain) remained undiscovered up to time of screening (latent form); in four, the disease was asymptomatic (silent form). Since clinical symptoms are mostly mild or absent in spite of severe signs of duodenal inflammation, we recommend tTGA screening in all diabetic children. This strategy may allow the identification of patients in an early stage in respect of prevention of long-term complications.


[Splenectomy in haematologic diseases. Clinical indications and surgical technique].
After the introduction of corticosteroids fifty years ago the indications for splenectomy in benign haematological diseases became more controversial, also due to the morbidity and mortality associated at that time with open splenectomy. The advent of minimally invasive techniques has provided safe procedures for removal of the spleen in cases of benign as well as malignant haematological disease. Laparoscopic splenectomy has been performed for spleens of normal size or larger size or weight. In this study the indications in haematological diseases and the results after splenectomy are analysed. From June 1998 to December 2004 107 patients with benign or malignant haematological disease were referred to our unit for splenectomy. Splenomegaly was defined as a spleen diameter > 15 cm and weight > 400 g and was present in 53% of cases in this series. Open splenectomy was carried out in 30 cases and laparoscopic splenectomy in 77. Operating time, blood loss, conversion rate, need for transfusion, complications, length of hospital stay and operative morbidity were analysed for both open and laparoscopic procedures. In the laparoscopic splenectomy group the outcomes after removal of spleens < 15 cm and > 15 cm were compared. Clinical results after splenectomy in haemolytic anaemia and idiopathic thrombocytopenic purpura are reported. In the open splenectomy group the spleens were larger and heavier, hence the operating time was greater than in the laparoscopic splenectomy group. The mean age of patients in the open group was 65 years as against 43 years in the laparoscopic group. Morbidity was 23% in the open group and 10% in the laparoscopic group. Mortality was nil in both groups. The overall conversion rate in the laparoscopic group was 2.6% owing to extensive adhesions and bleeding in 2 large spleens measuring > 27 cm and weighing > 2 kg (conversion rate for larger spleens: 6.2%). Spleens > 15 cm were associated with greater blood loss (p < 0.01), longer operating times and a longer hospital stay. No cases of overwhelming post-splenectomy infection were registered in either group. The healing rate for idiopathic thrombocytopenic purpura after splenectomy was 87%, while for haemolytic anaemia it was 100%. In this study splenomegaly was associated with malignant haematological disease occurring in patients aged 65 on average in whom an open splenectomy was generally carried out. Benign diseases occurred in patients aged 43 on average in whom laparoscopic splenectomy was the preferred procedure. Conversion rate, morbidity and length of hospital stay were comparable with those of other series. Laparoscopic splenectomy can be considered the gold standard procedure for benign disease in young patients and also as a safe procedure in selected cases of malignant haematological disease.


Surgical management of familial adenomatous polyposis: pancreas-sparing duodenectomy or pancreaticoduodenectomy (Whipple procedure).
Duodenal cancer is the main cause of death for patients with FAP syndrome (familial adenomatous polyposis) treated with a colectomy. The disease follows the adenoma to carcinoma sequence and is diagnosed during follow-up in 7-36% of patients. Endoscopic treatment is used during the first treatment stage of the disease and surgery is an adequate therapeutic option when endoscopic control is insufficient.


Understanding how and why psychotherapy leads to change.
The rich research literature on psychotherapies for children, adolescents, and adults has identified several interventions that can ameliorate or effect significant change in psychiatric disorders and a variety of social, behavioral, and emotional problems and can enhance medical outcomes and recovery. After decades of psychotherapy research and thousands of studies, there is no evidence-based explanation of how or why even the most well-studied interventions produce change, that is, the mechanisms through which treatments operate. This article discusses central requirements for demonstrating mediators and mechanisms of change. Also presented are promising lines of work to identify mediators and mechanisms, ways of bringing to bear multiple types of evidence, recommendations to make progress in understanding how therapy works, and conceptual and research challenges in evaluating mediators and mechanisms.


Simultaneous SPECT studies of pre- and postsynaptic dopamine binding sites in baboons.
The central nervous system dopamine transporters (DATs) and dopamine D2/D3 receptors are implicated in a variety of neurological disorders. Both sites are also targets for drug treatment. With the successful development of [99mTc]TRODAT-1, single-isotope imaging studies using this ligand for DAT imaging can be complemented by additional use of 123I-labeled D2/D3 receptor ligand co-injected to assess both pre- and postsynaptic sites of the dopaminergic system simultaneously. Twelve SPECT scans of the brain were obtained in two baboons after intravenous administration of 740 MBq (20 mCi) [99mTc]-TRODAT-1 (technetium, [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl ](2-mercaptoethyl) amino]ethyl]-amino]ethanethiolato (3-)]- oxo-[1R-(exo-exo)]) and 185 MBq (5 mCi) [123I]iodobenzamide or [123I]iodobenzofuran. SPECT data were acquired by a triple-head gamma camera equipped with ultra-high-resolution fanbeam collimators (scan duration = 210 min). Two sets of SPECT data were obtained using energy windows of 15% centered on 140 keV for 99mTc and 10% asymmetric with a lower bound at 159 keV for 123I. After coregistration with MRI, region-of-interest analysis was performed using predefined templates from coregistered MRI. In blocking studies, baboons were pretreated with N-methyl-2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT, 14 mg) or raclopride (14 mg) to block DAT or D2/D3 binding site, respectively. Image quality of dual-isotope studies was similar to that obtained from single-isotope studies. When one site was blocked with CFT or raclopride, the binding of the respective ligand to the other site was not affected. This is the first example that clearly demonstrates the feasibility of simultaneous imaging of both pre- and postsynaptic sites of the dopaminergic system in baboons with dual-isotope SPECT studies. With or without corrections for cross-contamination of 123I into the 99mTc window, striatum-to-cerebellum ratios (target-to-nontarget) of dual-isotope experiments did not differ significantly from single-isotope experiments. This method may be a valuable and cost-effective tool for gaining comprehensive information about the dopaminergic system in one SPECT imaging session.


The Forensic Psychiatric Network of Observation and Documentation: At the Intersection of Review Board Hearings and Nursing Practice.
Forensic psychiatric nursing is a specialty at the junction of two well-researched intersecting systems with two mandates: criminal justice and health care. Nurses' involvement at one of the systems' points of juncture, review board (RB) hearings, has largely been left unexplored. At RB hearings, a panel of legal and healthcare professionals determines if persons unfit to stand trial (UST) or not criminally responsible on account of mental disorder (NCR) represent significant threats to the safety of the public and orders conditions aimed at keeping the community safe. The aim of this article is to present the results of a critical ethnography that explored how psychiatric and public safety discourses construct the identity of persons UST or NCR during RB hearings as well as nurses' contribution to such identity construction. The main finding is that the forensic psychiatric structure leverages nursing interventions and documentation as evidence of deviancy, so that persons UST or NCR can be objectified and produced as dangerous. Structures sustaining the forensic psychiatric system inscribe nursing care within a disciplinary scheme, rendering the care-and-custody dichotomy insufficient to explain the complex processes at play in forensic psychiatry. These findings have implications for the practice of nurses working in forensic psychiatric settings and for that of other nurses who practice on the medicolegal borderland.


Effects of long-term repeated topical fluoride applications and adhesion promoter on shear bond strengths of orthodontic brackets.
The purpose of this study was to assess the effects of long-term repeated topical application of fluoride before bonding and an adhesion promoter on the bond strength of orthodontic brackets. A total of 76 bovine incisors were collected and divided equally into four groups. In group 1, the brackets were bonded without topical fluoride application or adhesion promoter. In group 2, before bonding, the adhesion promoter was applied to nonfluoridated enamel. In group 3, the brackets were bonded without the application of the adhesion promoter to enamel, which had undergone long-term repeated topical fluoride treatments. Teeth in group 4 received the long-term repeated topical applications of fluoride, and the brackets were bonded using the adhesion promoter. All the brackets were bonded using BeautyOrtho Bond self-etching adhesive. The shear bond strength was measured and the bond failure modes were evaluated with the use of the adhesive remnant index (ARI) after debonding. The mean shear bond strength was significantly lower in group 3 than in groups 1, 2, and 4, and there were no significant differences between the groups except for group 3. There were significant differences in the distribution of ARI scores between groups 2 and 3, and between groups 3 and 4. The adhesion promoter can recover the bond strength reduced by the long-term repeated topical applications of fluoride to the prefluoridation level and had a significantly great amount of adhesives left on either fluoridated or nonfluoridated enamel.


Review: Using artificial insemination v. natural service in beef herds.
The aim of this review is to compare the performance of different reproductive programs using natural service, estrus synchronization treatment before natural service (timed natural breeding (TNB)), artificial insemination (AI) following estrus detection and timed artificial insemination (TAI) in beef herds. It is well known that after parturition the beef cow undergoes a period of anestrous, when they do not exhibit estrus, eliminating the opportunity to become pregnant in the early postpartum by natural mating or by AI after detection of estrus. Hormonal stimulation is already a consistent and well-proven strategy used to overcome postpartum anestrus in beef herds. Basically, hormones that normally are produced during the estrous cycle of the cow can be administered in physiological doses to induce cyclicity and to precisely synchronize follicular growth, estrus and ovulation. Furthermore, two options of mating may be used after hormonal stimulation: natural service (i.e. utilization of bull service after synchronization, referred to as TNB) and TAI. These strategies improve the reproductive efficiency of the herds compared with natural service without estrus induction or synchronization. After the first synchronized service, the most common strategy adopted to get non-pregnant cows pregnant soon is the introduction of clean-up bulls until the end of the breeding season. However, methods to resynchronize non-pregnant cows after the first service are already well established and offer a potential tool to reduce the time for subsequent inseminations. Thus, the use of these technologies enable to eliminate the use of bulls by using resynchronization programs (i.e. two, three or four sequential TAI procedures). The dissemination of efficient reproductive procedures, such as TNB, TAI and Resynch programs, either isolated or in combination, enables the production of a greater quantity (obtaining increased pregnancy rates early in the breeding season) and quality (maximization of the use of AI with superior genetic sires) of beef calves. These technologies can contribute to improve the production efficiency, and consequently, improve livestock profitability.


Analysis of MicroRNA-mRNA Interactions in Stem Cell-Enriched Fraction of Oral Squamous Cell Carcinoma.
This study is an integrated analysis of the transcriptome profile microRNA (miRNA) and its experimentally validated mRNA targets differentially expressed in the tumorigenic stem-like fraction of oral squamous cell carcinoma (OSCC). We had previously reported the coexistence of multiple drug-resistant tumorigenic fractions, termed side population (SP1, SP2, and MP2), and a nontumorigenic fraction, termed main population (MP1), in oral cancer. These fractions displayed a self-renewal, regenerative potential and expressed known stemness-related cell surface markers despite functional differences. Flow cytometrically sorted pure fractions of SP1 and MP1 cells were subjected to differential expression analysis of both mRNAs and miRNAs. A significant upregulation of genes associated with inflammation, cell survival, cell proliferation, drug transporters, and antiapoptotic pathways, in addition to enhanced transcriptome reprogramming mediated by DNA-histone binding proteins and pattern recognition receptor-mediated signaling, was found to play a crucial role in the transformation of the nontumorigenic MP1 fraction to the tumorigenic SP1 fraction. We also identified several differentially expressed miRNAs that specifically target genes distinctive of tumorigenic SP1 fraction. miRNA-mediated downregulation of stemness-associated markers CD44 and CD147 and upregulation of CD151 may also account for the emergence and persistence of multiple tumorigenic stem cell fractions with varying degrees of malignancy. The phenotypic switch of cancer cells to stem-like OSCC cells mediated by transcriptomal regulation is effectual in addressing biological tumor heterogeneity and subsequent therapeutic resistance leading to a minimal residual disease (MRD) condition in oral cancer. A detailed study of the interplay of miRNAs, mRNA, and the cellular phases involved in the gradual transition of nontumorigenic cancer cells to tumorigenic stem-like cells in solid tumors would enable detection and development of a treatment regimen that targets and successfully eliminates multiple, drug-resistant fractions of cancer cells.


Au Promoted Nickel-Iron Layered Double Hydroxide Nanoarrays: A Modular Catalyst Enabling High-Performance Oxygen Evolution.
Oxygen evolution reaction (OER) plays a key role in various energy conversion and storage technologies, such as water electrolysis, regenerative fuel cells, and rechargeable metal-air batteries. However, the slow kinetics of OER limit the performance and commercialization of such devices. Herein, we report on NiFe LDH@Au hybrid nanoarrays on Ni foam for much enhanced OER. By hybridization of electronegative Au and NiFe LDH with intrinsic remarkable OER catalytic activity, this modular electrode could drive an overall ultrahigh-performance and robust OER in base with the demand of overpotentials of only 221, 235, and 270 mV to afford 50, 100, and 500 mA cm-2, respectively. Also, it exhibits superior catalytic activity and durability toward OER in 30 wt % KOH.


Effect of dual tasking on a dynamic balance task in children with and without DCD.
The purpose of this study was to compare performance of children with Developmental Coordination Disorder (DCD) and typically developing (TD) children in a dual task paradigm with a dynamic balance task on the Wii Fit as primary task and a concurrent cognitive (counting) or a concurrent bimanual fine motor task as secondary tasks. Using a cross-sectional design, 25 children with DCD and 38 TD children were assessed with the Movement Assessment Battery for Children, 2nd edition (MABC-2) and Divided Attention (DA) task of the KiTAP. Next, the single- and dual-tasks were performed and the level of interference or facilitation of the dual tasks was calculated. Regression analysis determined the predictive value of the DA and MABC-2 component balance outcomes on the dual task performance. On the motor and attentional tasks, the group of children with DCD scored significantly below the level of the TD children. The dual task effect showed similar interference and facilitation of tasks in the different dual-task conditions in both groups. In the dual task-cognitive condition, the divided attention abilities and the MABC-2 balance score predicted 25% of the Wii Fit dynamic balance task performance, whereas in the dual task-motor condition this was higher (31.6%). In both conditions, DA was a stronger predictor than MABC balance score and appears to be an important factor to consider when developing motor task training for children with DCD.


Knockdown of Angiopoietin-Like Protein 2 Inhibits Proliferation and Invasion in Glioma Cells via Suppressing the ERK/MAPK Signaling Pathway.
Angiopoietin-like protein 2 (ANGPTL2), a member of the glycoprotein family, is mainly secreted by adipose tissues under normal conditions. Recently, ANGPTL2 has been found to be upregulated in some types of cancers and is considered to be a tumor promoter. However, the functional significance of ANGPTL2 in glioma has not yet been elucidated. In this study, we investigated the specific role of ANGPTL2 in glioma. The results showed that ANGPTL2 was highly expressed in glioma tissues and cell lines. Knockdown of ANGPTL2 reduced the proliferative and invasive abilities of glioma cells. Moreover, the tumorigenesis assay showed that ANGPTL2 knockdown inhibited glioma tumor growth in vivo. We also found that ANGPTL2 knockdown decreased the protein levels of p-ERK1/2 in glioma cells and thus blocked the activity of the ERK/MAPK signaling pathway. Taken together, our study provided the first evidence that ANGPTL2 played an oncogenic role in glioma development and might be considered as a new therapeutic target for glioma treatment.


Development of a harmonised method for the profiling of amphetamines VI: Evaluation of methods for comparison of amphetamine.
Amphetamine samples were analysed by gas chromatography-mass spectrometry (GC-MS), and the peak areas of 33 target compounds were transformed by applying various pretreatment techniques. The objective was to optimise the ability of a number of distance metrics to establish links between samples of amphetamine originating from the same batch (henceforth referred to as linked distances). Furthermore, partial least squares discriminant analysis (PLS-DA) was used to evaluate the effects of various pretreatment methods on separation of amphetamine batches synthesised by the Leuckart reaction, reductive amination of benzyl methyl ketone, and the nitrostyrene route. The most efficient way to pretreat GC-MS data varied for the different distance metrics, although best results were obtained when data were normalised to the sum of peak areas, and either the fourth root or a logarithm was applied to the normalised data. When pretreating normalised data by fourth root transformation, Pearson correlation was the distance metric that was most successful at finding linked samples. Normalisation and the use of fourth root also represented the best method of pretreating data when employing PLS-DA to separate samples synthesised by different routes. To achieve a faster and more user-friendly procedure for evaluating chromatograms, experiments were performed in which the number of target compounds used to compare samples was reduced. The effect of each compound that was removed was studied by applying PLS-DA and by using Pearson correlation to calculate linked distances as well as unlinked distances (between samples from different batches of amphetamine). Considering both links between samples from the same batch and separation of samples synthesised by different routes, the best results were obtained with the data set comprising 26 compounds. Finally, it was found that the profiling method developed in this work was superior to an existing technique with respect to separating linked and unlinked distances.


Keeping Children Safe at Home: Parent Perspectives to Firearms Safety Education Delivered by Pediatric Providers.
The aims of this study were to assess parent acceptance of firearms education delivered by clinical providers, determine whether parents engage in firearms safety dialog with their children, and evaluate reasons for ownership and storage behaviors. The parents of children ages 0 to 18 years completed surveys while in a pediatric inpatient setting in Texas. Demographics, acceptability, current behaviors, and storage practices were queried. Responses between firearms owners and nonowners were analyzed using the Fisher exact and χ2 tests. Of the 115 parents who completed surveys, 41% reported owning firearms. Most parents were likely or highly likely to follow their pediatrician's gun safety advice (67%), were accepting of safety videos in waiting rooms (59%), and accepted firearms locks distributed by clinical providers (69%). Nonowners were less likely than owners to have spoken to their children about gun safety (P = 0.004). Parents owned firearms for self-protection and recreation (50%), self-protection only (38%), or recreation only (12%). Owners stored them unloaded (75%), used safety devices (95%), and stored them in the closet of the master bedroom (54%). Talking about firearms safety in a healthcare setting was not a contentious issue in the majority of our sample. Parents were accepting of provider-led firearms guidance regardless of ownership status. This provides an opportunity for providers to focus on effective messaging and time-efficient delivery of firearms safety education.