Missed Opportunities in Geriatric Oncology Research.
The field of geriatric oncology has made significant progress in recent decades, but there are still missed opportunities in important areas of research. One issue is the underrepresentation of older patients, especially those aged 75 years and older, in clinical trials. This has resulted in a lack of high-quality data for the care of this population, and the American Society of Clinical Oncology has called for an increase in the evidence base for older patients with cancer. The second missed opportunity is the chance to gather important knowledge from older patients participating in clinical trials, such as medications, social support, insurance, and financial information. These data can be easily collected and incorporated into the trial design to enhance the information available to researchers and clinicians. The third missed opportunity is the chance to robustly analyze and report clinical trial data for the benefit of geriatric oncology research. Many trials only report a median age and range, which is a disservice to both the participants and the patients who will be treated based on the study results. To advance geriatric oncology research, the necessary data need to be collected, analyzed, and reported through appropriate representation of older patients, collection of essential information, and thorough analysis and communication of results. Clinical trial design needs to include geriatric baseline parameters, and Cancer Therapy Evaluation Program (CTEP) has modified its template to include these parameters.


5,6-Dimethoxybenzofuran-3-one derivatives: a novel series of dual Acetylcholinesterase/Butyrylcholinesterase inhibitors bearing benzyl pyridinium moiety.
Several studies have been focused on design and synthesis of multi-target anti Alzheimer compounds. Utilizing of the dual Acetylcholinesterase/Butyrylcholinesterase inhibitors has gained more interest to treat the Alzheimer's disease. As a part of a research program to find a novel drug for treating Alzheimer disease, we have previously reported 6-alkoxybenzofuranone derivatives as potent acetylcholinesterase inhibitors. In continuation of our work, we would like to report the synthesis of 5,6-dimethoxy benzofuranone derivatives bearing a benzyl pyridinium moiety as dual Acetylcholinesterase/Butyrylcholinesterase inhibitors. The synthesis of target compounds was carried out using a conventional method. Bayer-Villiger oxidation of 3,4-dimethoxybenzaldehyde furnished 3,4-dimethoxyphenol. The reaction of 3,4-dimethoxyphenol with chloroacetonitrile followed by treatment with HCl solution and then ring closure yielded the 5,6-dimethoxy benzofuranone. Condensation of the later compound with pyridine-4-carboxaldehyde and subsequent reaction with different benzyl halides afforded target compounds. The biological activity was measured using standard Ellman's method. Docking studies were performed to get better insight into interaction of compounds with receptor. The in vitro anti acetylcholinesterase/butyrylcholinesterase activity of compounds revealed that, all of the target compounds have good inhibitory activity against both Acetylcholinesterase/Butyrylcholinesterase enzymes in which compound 5b (IC50 = 52 ± 6.38nM) was the most active compound against acetylcholinesterase. The same binding mode and interactions were observed for the reference drug donepezil and compound 5b in docking study. In this study, we presented a new series of benzofuranone-based derivatives having pyridinium moiety as potent dual acting Acetylcholinesterase/Butyrylcholinesterase inhibitors.


Effects of chewing menthol gum on the alertness of healthy volunteers and those with an upper respiratory tract illness.
Recent research has shown that chewing gum increases subjective alertness. Upper respiratory tract illnesses (URTIs) lead to reduced alertness, and it has been shown that stimulants such as caffeine can reverse this effect. It is now important to determine whether menthol chewing gum can produce a similar effect. Young adults with an URTI (N = 16) and a healthy control group (N = 12) rated their mood and symptoms on two occasions (the first when those with a URTI were ill and the second when both groups were healthy). During each session, volunteers provided a rating while chewing gum and when they were not chewing. Those with a URTI reported reduced alertness, which persisted into convalescence. Chewing gum was associated with greater alertness in both those with URTIs and the healthy group. Chewing gum reduced the severity of nasal symptoms in those with a cold. The effects of the URTI and menthol gum may reflect changes in trigeminal stimulation.


Incidence of Cardiometabolic Diseases in People With and Without Human Immunodeficiency Virus in the United Kingdom: A Population-Based Matched Cohort Study.
Evidence on the risk of cardiovascular disease (CVD) and CVD risk factors in people with human immunodeficiency virus (PWH) is limited. We aimed to identify the risk of composite CVD, individual CVD events, and common risk factors. This was a nationwide, population-based, cohort study comparing adult (≥18 years old) PWH with people without human immunodeficiency virus (HIV) matched on age, sex, ethnicity, and location. The primary outcome was composite CVD comprising stroke, myocardial infarction, peripheral vascular disease, ischemic heart disease, and heart failure. The secondary outcomes were individual CVD events, hypertension, diabetes, chronic kidney disease (CKD), and all-cause mortality. Cox proportional hazard regression models were used to examine the risk of each outcome. We identified 9233 PWH and matched them with 35 721 HIV-negative individuals. An increased risk was found for composite CVD (adjusted hazard ratio [aHR], 1.50; 95% confidence interval [CI], 1.28-1.77), stroke (aHR, 1.42; 95% CI, 1.08-1.86), ischemic heart disease (aHR, 1.55; 95% CI, 1.24-1.94), hypertension (aHR, 1.37; 95% CI, 1.23-1.53), type 2 diabetes (aHR, 1.28; 95% CI, 1.09-1.50), CKD (aHR, 2.42; 95% CI, 1.98-2.94), and all-cause mortality (aHR, 2.84; 95% CI, 2.48-3.25). PWH have a heightened risk for CVD and common CVD risk factors, reinforcing the importance for regular screening for such conditions.


Solution structure of an intramolecular DNA triplex linked by hexakis(ethylene glycol) units: d(AGAGAGAA-(EG)6-TTCTCTCT-(EG)6-TCTCTCTT).
A DNA molecule was designed and synthesized with three octanucleotide stretches linked by two hexakis(ethylene glycol) chains to form an intramolecular triplex in solution. The structural data obtained from a series of NMR NOESY spectra yielded interproton distances, and COSY experiments provided dihedral angle information for analysis of deoxyribose ring pucker. Using distance geometry followed by simulated annealing with restrained molecular dynamics and relaxation matrix refinement, a well-refined ensemble of conformations was calculated. Although some NOE cross-peaks involving protons of the hexakis(ethylene glycol) linker could be identified, most could not be assigned and the conformations of the linkers were not determined. The deoxyribose conformations are predominantly of the S type, except for the protonated cytosine residues in the third strand which show hybrid N and S character. Overall, the duplex part of the molecule resembles a B-DNA double helix with the third strand bound in its major groove by Hoogsteen hydrogen bonds. This structure provides a basis for comparison with triplexes containing noncanonical or nonnatural nucleotides.


Extreme Neonatal Hypernatremia and Acute Kidney Injury Associated with Failure of Lactation.
Hypoalimentation is an important cause of hypernatremic dehydration in neonates; however, extreme values of plasma sodium make it necessary to investigate the differential diagnosis. We report the case of a 20-day-old newborn who was admitted with severe hypernatremic dehydration, with plasma sodium of 213 mEq/L and oliguric acute renal failure. The patient was treated with intravenous fluids for correction of dehydration and peritoneal dialysis for adequate sodium correction. During the etiological study, a 10-fold increase in the concentration of sodium in breast milk was detected. Peritoneal dialysis was an effective therapy in the management of the extreme hypernatremia with sodium correction within the recommended rate. At the 1-year follow-up appointment, the child had normal renal function, normal for age psychomotor development, and neurological physical was unremarkable. In conclusion, we report a case of an unusual extreme hypernatremia with discussion of the underlying pathophysiology and, more importantly, the effective treatment with a mixed approach with intravenous fluids and peritoneal dialysis.


Benzylation of nitroalkanes using copper-catalyzed thermal redox catalysis: toward the facile C-alkylation of nitroalkanes.
The C-alkylation of nitroalkanes under mild conditions has been a significant challenge in organic synthesis for more than a century. Herein we report a simple Cu(I) catalyst, generated in situ, that is highly effective for C-benzylation of nitroalkanes using abundant benzyl bromides and related heteroaromatic compounds. This process, which we believe proceeds via a thermal redox mechanism, allows access to a variety of complex nitroalkanes under mild reaction conditions and represents the first step toward the development of a general catalytic system for the alkylation of nitroalkanes.


[Not Available].
Pain, and toothache in particular, belongs to the most basic human experiences. This paper describes how the experience of pain is shaped and modified by individual human minds and by specific medical cultures. It explores what social historians of medicine call the historical, social, cultural, and psychological construction of pain. The story of how people reconstruct the experience of pain in past and present demands that we look beyond the medical gaze. The voices most often neglected in medical history belong of course to patients. However, their testimony is difficult to recover, except for more recent times. We have to look therefore for their hidden voices in diaries, memoirs, essays, poems, novels and other literary genres. These scattered records and fragmentary episodes of bouts of illness suggest that the history of toothache cannot be reduced to a parable about biomedical progress, but stands at the crossroad of bodies, minds, and cultures.


The effects of postseason break on knee biomechanics and lower extremity EMG in a stop-jump task: implications for ACL injury.
The effects of training on biomechanical risk factors for anterior cruciate ligament (ACL) injuries have been investigated, but the effects of detraining have received little attention. The purpose of this study was to evaluate the effects of a one-month postseason break on knee biomechanics and lower extremity electromyography (EMG) during a stop-jump task. A postseason break is the phase between two seasons when no regular training routines are performed. Twelve NCAA female volleyball players participated in two stop-jump tests before and after the postseason break. Knee kinematics, kinetics, quadriceps EMG, and hamstring EMG were assessed. After one month of postseason break, the players demonstrated significantly decreased jump height, decreased initial knee flexion angle, decreased knee flexion angle at peak anterior tibial resultant force, decreased prelanding vastus lateralis EMG, and decreased prelanding biceps femoris EMG as compared with prebreak. No significant differences were observed for frontal plane biomechanics and quadriceps and hamstring landing EMG between prebreak and postbreak. Although it is still unknown whether internal ACL loading changes after a postseason break, the more extended knee movement pattern may present an increased risk factor for ACL injuries.


Countercurrent chromatography separation of vitamin E isomers in a co-current mode.
Vitamin E represents a group of lipophilic phenolic compounds, including α-tocopherol, β-tocopherol, γ-tocopherol, and δ-tocopherol, and α-tocotrienol, β-tocotrienol, γ-tocotrienol, and δ-tocotrienol isomers. Different forms of vitamin E have been proven to exhibit varying biological activities. However, due to their structural similarities, the separation of vitamin E isomers is a challenging task. Therefore, it is crucial to establish an efficient method for isolating individual isomers. In this study, co-current countercurrent chromatography was employed to isolate vitamin E isomers from commercial capsules using a n-heptane-methanol-water (10:9.5:0.5, v/v) solvent system. The partition coefficients of the main constituents in the capsules ranged from 0.94 to 6.23, requiring over 450 min for a complete separation. To improve separation efficiency, a co-current elution mode was implemented and the flow rates of the two liquid phases as well as sample amount were examined. The results suggested that increasing the flow rate of the stationary phase and sample size could result in more effective separation, shorter separation time, and higher yield. It proved that co-current countercurrent chromatography was an effective method for the separation of vitamin E isomers.


Preliminary study of ectoparasites of horses in the western highlands of Cameroon.
To evaluate the prevalence of infestation of ectoparasites of horses, a total of 894 horses (367 males and 527 females), aged 1-7 years old were examined. Horses were groomed for collection of ectoparasites. Out of the horses examined, 164 came from Fundong, 80 from Acha, 30 from Fongo-Tongo, 30 from Fokoue and 17 from Dschang, all of which were infested with ectoparasites. Five hundred and seventy-three (573) horses came from Banso and 99.48% were infested by ectoparasites. From the results obtained, three species of hard ticks (Boophilus decoloratus, Amblyomma hebraeum and Hyalomma rufipes) and one species of biting lice (Bovicola equi) were identified. Boophilus decoloratus (66%) had the highest prevalence per locality, followed by A. hebraeum (18%), H. rufipes (11%) and B. equi (5%). Boophilus decoloratus infested horses of all ages, sex or colour. Meanwhile, A. hebraeum and H. rufipes had a higher prevalence in adult male horses. Mono-parasitic infestation (69%) was more common than poly-parasitic infestation (31%). Only three horses were free from infestation with ectoparasites. Understanding the biology, epidemiology and economic impact on the equine industry is important for public health and disease prevention programmes.


The conversion of redox status of peritoneal macrophages during pathological progression of spontaneous inflammatory bowel disease in Janus family tyrosine kinase 3(-/-) and IL-2 receptor gamma(-/-) mice.
The distinct thiol redox status in macrophages, either elevated or reduced intracellular content of glutathione (GSH), was confirmed during aging in IL-2 receptor (IL-2R)gamma and Janus family tyrosine kinase (JAK)3 gene-disrupted mice. Oxidative macrophages (OMp) with reduced GSH dominated initially at a younger age in both mice. OMp-dominated JAK3 or IL-2R gamma chain-deficient mice showed shortened life longevity compared with wild-type littermates. These mice elicited spontaneous onsets of inflammatory bowel disease (IBD)-like symptoms accompanied with the conversion of the redox status of macrophages to reductive phenotypes with elevated intracellular GSH. Conversion of OMp to the reductive phenotype by GSH monoethyl ester or by a beta-(1-3)-glucan accelerated the disease onset, concomitant with the skewing from T(h)2 to T(h)1 responses. On the contrary, N,N'-diacetyl cystine dimethylester, which is capable of inducing OMp, delayed the incidence of IBD-like symptoms and improved the survival rate. This implies that the conversion of OMp/T(h)2 to reductive macrophages/T(h)1 may be critical for the disease progression. The study of these mice may provide insight into the mechanisms underlying Crohn's disease and ulcerative colitis.


Distinguishing left ventricular aneurysm from pseudoaneurysm. A review of the literature.
A postmyocardial infarction left ventricular pseudoaneurysm occurs when a rupture of the ventricular free wall is contained by overlying, adherent pericardium. A postinfarction aneurysm, in contrast, is caused by scar formation resulting in thinning of the myocardium. Although the usual treatment for patients with pseudoaneurysm is urgent surgical repair, the imaging characteristics of pseudoaneurysm and aneurysm, for which treatment is more conservative, are quite similar. The literature on the natural history and imaging characteristics of the two entities is reviewed, and an approach to distinguishing between the two entities is proposed.


Management of postpartum hemorrhage in a rural hospital in Kenya: a best practice implementation project.
Postpartum hemorrhage accounts for 34% of maternal deaths in Kenya. The World Health Organization guidelines on postpartum hemorrhage are not always followed despite being prominently promoted in hospitals. The objectives of this study were to assess the current practice of health workers in the prevention and management of postpartum hemorrhage and to implement strategies to promote best practice. A baseline audit with five evidence-based audit criteria was conducted using the Joanna Briggs Institute Practical Application of Clinical Evidence System. Strategies to improve compliance were implemented and a follow-up audit was carried out using the same data collection methods. Results of both audits were compared. The baseline audit showed that 90% of health workers were aware of the existence and location of the national guidelines. Almost two thirds (65%) of staff had received education on postpartum hemorrhage within the last two years. Only 30% had received specific training on the use of the guidelines and compliance with the guidelines was 0%. At the follow-up audit, the proportion of health workers who had received recent education on postpartum hemorrhage and specific training on the use of a protocol increased to 90%. The use and documentation of a protocol for postpartum hemorrhage increased to 100%. Compliance in prenatal risk assessment for postpartum hemorrhage decreased from 65% to 35%. Knowledge of the guidelines did not translate into their use during management of patients with postpartum hemorrhage. The introduction of a tool and staff education and training improved compliance.


Multiplex Assay for Protein Profiling and Potency Measurement of German Cockroach Allergen Extracts.
German cockroach (GCr) allergens induce IgE responses and may cause asthma. Commercial GCr allergen extracts are variable and existing assays may not be appropriate for determining extract composition and potency. Our aim was to develop a multiplex antibody/bead-based assay for assessment of GCr allergen extracts. Single chain fragment variable (scFv) antibodies against GCr were obtained by screening libraries derived from naïve human lymphocytes and hyperimmunized chicken splenocytes and bone marrow. Selected clones were sequenced and characterized by immunoblotting. Eighteen scFv antibodies (17 chicken, 1 human) coupled to polystyrene beads were used in this suspension assay; binding of targeted GCr allergens to antibody-coated beads was detected using rabbit antisera against GCr, and against specific allergens rBla g 1, rBla g 2, and rBla g 4. The assay was tested for specificity, accuracy, and precision. Extracts were also compared by IgE competition ELISA. Chicken scFv's generated eight different binding patterns to GCr proteins from 14 to 150 kDa molecular weight. Human scFv's recognized a 100 kDa GCr protein. The multiplex assay was found to be specific and reproducible with intra-assay coefficient of variation (CV) of 2.64% and inter-assay CV of 10.0%. Overall potencies of various GCr extracts were calculated using mean logEC50s for eight selected scFvs. Overall potency measures were also analyzed by assessing the contributions to potency of each target. An scFv antibody-based multiplex assay has been developed capable of simultaneously measuring different proteins in a complex mixture, and to determine the potencies and compositions of allergen extracts.


Down-regulation of Skp2 is correlated with p27-associated cell cycle arrest induced by phenylacetate in human prostate cancer cells.
We have demonstrated that phenylacetate (PA)induced cell cycle arrest in human prostate cancer is mediated by increase of p27. In this study, we further investigated the mechanism of PA-induced p27 expression in prostate cancer cells (LNCaP, androgen-independent LNCaP [AIDL] and PC-3). A striking decrease in Skp2 mRNA and protein expression and reciprocal increase in p27 protein level were observed in three PA-treated prostate cancer cells. Interestingly, reduction of phospho-Akt and up-regulation of p27 mRNA levels were observed only in PC-3 cells. No significant differences were found in phospho-Akt and p27 mRNA levels in LNCaP and AIDL. In vitro ubiquitination assay showed a decreased p27 ubquitination in PA-treated prostate cancer cells. Our results suggest that PA attenuated Skp2 expression, thereby inhibiting ubiquitination and promoting p27 accumulation in all three prostate cancer cell lines. Therapeutic strategies designed to reduce Skp2 may clinically play an important role in the treatment of both androgen-sensitive and hormone-refractory prostate cancer.


Empathy by default: Correlates in the brain at rest.
Empathy, defined as the ability to access and respond to the inner world of another person, is a multidimensional construct involving cognitive, emotional and self-regulatory mechanisms. Neuroimaging studies report that empathy recruits brain regions which are part of the social cognition network. Among the different resting state networks, the Default Mode Network (DMN) may be of particular interest for the study of empathy since it has been implicated in social cognition tasks. The current study compared the cognitive and emotional empathy scores, as measured by the Interpersonal Reactivity Index, with the patterns of activation within the DMN, through the neuroimaging methodology of resting-state functional magnetic resonance. Results suggest a significant positive correlation between cognitive empathy and activation of the bilateral superior medial frontal cortex nodes of the DMN. Contrastingly, a negative correlation was found between emotional empathy and the same brain region. Overall, this data highlights a critical role of the medial cortical regions of the DMN, specifically its anterior node, for both cognitive and emotional domains of the empathic process.


Radioimmunoassay of 5-hydroxyindole acetic acid using an iodinated derivative.
A radioimmunoassay for the main catabolite of serotonin, 5-hydroxyindole acetic acid (5-HIAA), was developed by using specific antibodies and iodinated derivative. The synthesis of a 125I-iodinated analog was performed by coupling 5-HIAA to [125I-]glycyl-tyrosine without any contact between 5-HIAA and iodine or chloramine T. It was purified on a G25 Sephadex column and diluted in citrate buffer up to 2.5 X 10(5) cpm/ml. Antibodies were obtained by coupling 5-HIAA to human serum albumin with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and tested by equilibrium dialysis. After the third immunogen injection, the four rabbits gave antisera capable of binding 50% of iodinated 5-HIIA-glycyl-tyrosine at 1/2000 final dilution. A chemical conversion of the biological samples gives to the antigen molecules a better resemblance to the immunogen, thus conferring a 100-fold gain in specificity and sensitivity. This assay allows 5-HIAA to be determined in small amounts of tissue, blood, cerebrospinal fluid or perfusate without purification with a sensitivity threshold below 0.1 ng. Some applications in cat and rat are presented.


Development of a Competitive Enzyme-Linked Immunosorbent Assay Based on Purified Recombinant Viral Protein 7 for Serological Diagnosis of Epizootic Haemorrhagic Disease in Camels.
Epizootic haemorrhagic disease virus (EHDV) is a member of the Orbivirus genus in the Reoviridae family, and it is the etiological agent of an arthropod-transmitted disease that affects domestic and wild ruminants. Due to its significant economic impact, many attempts have been done in order to develop diagnostic immunoassays mainly based on the use of the viral protein 7 (VP7), that is, the immunodominant serogroup-specific antigen. In this work, a recombinant VP7 (recVP7) of EHDV serotype 2 was produced in a baculovirus system, and after purification using ion metal affinity chromatography, we obtained a high yield of recombinant protein characterized by a high degree of purity. We used the purified recVP7 as reagent to develop a competitive enzyme-linked immunoassay (c-ELISA), and we tested the presence of EHDV antibodies in 185 dromedary camel serum samples. The c-ELISA showed good performance parameters in recognising positive sera of naturally EHDV-infected dromedary camels; in particular, our developed test reached 85.7% of sensitivity, 98.1% of specificity, 93% of accuracy, and a high agreement value with results obtained by the commercial ELISA kit (Cohen's kappa value of 0.85) that we adopted as the reference method. This c-ELISA could be a useful screening test to monitor the virus spread in camels that are sentinel animals for endemic areas of disease.


Design, Synthesis, and Bioactivity of Aldisine Derivatives Containing Oxime and Hydrazine Moieties Based on Hydrogen Bonds.
Marine natural products have attracted more and more attention in drug research and development due to their unique structure, diverse biological activities, and novel mode of action. Using antiviral alkaloid aldisine as the lead compound and drawing on the hydrogen bond effect widely used in drug design, derivatives containing oxime and hydrazone moieties were designed and synthesized by introducing functional groups with hydrogen-bond receptors or donors into molecules. The configuration of derivatives was systematically studied through nuclear Overhauser effect (NOE) spectroscopy and single crystal analysis. The antiviral activity test result showed that most derivatives had antiviral activity against tobacco mosaic virus (TMV), and some compounds had better activity than the commercial antiviral drug ribavirin, especially compounds 2 and 24, which had comparable activity to the most effective commercial antiviral drug ningnanmycin. Preliminary mode of action studies showed that compound 2 could affect the assembly of rod-shaped TMVs by promoting the aggregation and fragmentation of TMV coat proteins. Molecular docking experiments demonstrated that the introduction of oxime and hydrazone moieties could indeed increase the hydrogen bond between molecules and target proteins. In addition, we conducted fungicidal and larvicidal activities study of these derivatives. Most of these derivatives had good larvicidal activities against Mythimna separata and Plutella xylostella and showed broad-spectrum fungicidal activities.


Structural colour QR codes for multichannel information storage with enhanced optical security and life expectancy.
Current schemes for encoding and decoding anticounterfeiting optical quick response (QR) codes involve miscellaneous challenges. The need for using multiple light sources to read out the wavelength-multiplexed data from optically encoded organic dyes, photoblinking from quantum dots, and autofluorescence from carbon dots are some typical examples. In order to address these restrictions, we exploited our previously devised nanoimprinting-exposure-thermal-treatment (NETT) data storage approach to present a new structural-colour-based regime for optical encoding of high-security QR codes. The angle-dependent readability of our diffraction-based nanostructures poses an enhanced optical security feature that can substitute the existing inefficient encoding strategies by eliminating the constraints associated with them. Additionally, in comparison with conventional optical encoding media, using the long-lasting photocrosslinked SU-8 in the NETT method considerably enhances the life expectancy of the proposed QR codes. Also, considering the rapid NETT-based Ni stamp origination method, which was previously introduced by our group, mass-generation of the proposed codes is feasible. Owing to the special optically variable effects provided by the nanostructures, duplication of our QR codes is very difficult. The colour code design, which embeds 766 characters in 2907 modules in red, green and blue channels, was generated and fabricated onto generic nanostructure arrays using the NETT process. The encoded information was successfully read out from the pattern using a broadband light source and a digital camera. Higher capacities are also deemed to be reachable by implementing image processing and machine learning algorithms to overcome in-channel module recognition and cross-channel interferences.


[Delayed-type subacute measles encephalitis].
We analyze the clinical, neurological, EEG, neuroradiological features and evolution of two patients with subacute measles encephalitis. The patients, aged five years and eleven months respectively showed an acute, progressive neurological compromise and deterioration of consciousness, epilepsia partialis continua and progressive damage on neuroimaging, with a history of measles in the first case and exposure to the virus in the second. The first patient had Hodgkin's disease and the other had a familial C4 deficit disorder. Fundoscopic examination showed lesions on the retina. The EEG showed unilateral slow waves and spikes. Brain CT and MRI revealed progressive cerebral atrophy and a unilateral corticosubcortical lesion. Measles antibodies in CSF were found in the first child and oligoclonal bands in the second. Our first patient died after three months and the second has a severe neurological damage. In immunocompromised patients with the exposure to a history of measles, acute neurological compromised and deterioration of consciousness, epilepsia partialis continua and progressive damage on neuroimaging, subacute measles encephalitis should be considered.


Assessment of the genetic and clinical determinants of hip fracture risk: Genome-wide association and Mendelian randomization study.
Hip fracture is the clinically most important fracture, but the genetic architecture of hip fracture is unclear. Here, we perform a large-scale hip fracture genome-wide association study meta-analysis and Mendelian randomization study using five cohorts from European biobanks. The results show that five genetic signals associate with hip fractures. Among these, one signal associates with falls, but not with bone mineral density (BMD), while four signals are in loci known to be involved in bone biology. Mendelian randomization analyses demonstrate a strong causal effect of decreased femoral neck BMD and moderate causal effects of Alzheimer's disease and having ever smoked regularly on risk of hip fractures. The substantial causal effect of decreased femoral neck BMD on hip fractures in both young and old subjects and in both men and women supports the use of change in femoral neck BMD as a surrogate outcome for hip fractures in clinical trials.


Separation of six bovine complement components and one inactivator (1, 2).
Six components (C1, C5, C6, C7, C8 and C9) of bovine complement and one inactivator (C3 in) could be separated from bovine serum. Bovine C1 was separated by precipitation at low molarity (0.03 M of relative salt concentration) other components by DEAE-cellulose chromatography using 0.005 M sodium phosphate buffer, pH 7.5, as a base for solvents having the relative salt concentration adjusted by addition of NaCl from 0.03 to 0.3 M. The separated bovine complement components could be tested using intermediates formed from sheep erythrocytes, rabbit hemolysin, guinea pig C1 and remaining human complement components. C2, C3 and C4 of bovine origin remained undetected either because of incompatibility with the intermediates used or interference of inhibitors or inactivators.


A critical appraisal of the prognostic value of the VE/VCO2 slope in chronic heart failure.
Increased ventilatory drive, reflected by the slope of increase of ventilation relative to carbon dioxide production (VE/VCO2 slope), has been shown to have a high prognostic value in patients with chronic heart failure (CHF). However, there is no consensus on how to calculate it, as the relation between VE and VCO2 becomes nonlinear near the end of exercise, when ventilation is driven both by CO2 output and by decrease in plasma pH. This may influence the results. Ninety-seven CHF patients with ejection fraction <45% (mean 27 +/- 9%), in NYHA class II-IV underwent a cardiopulmonary exercise test. VE/VCO2 slope was assessed by linear regression using all the data points (Sl), using only points before (Sli), or after (Slf) the non-linear part of the curve, and using only the first 3-min data (Sl3 min). Peak oxygen uptake (VO2), and circulatory power (VO2 x systolic arterial pressure) were also assessed. Death and transplantation were the end-points considered (mean follow-up 22 months). Mean value of VE/VCO2 overall slope was 39.3 +/- 11.6 (22-78). In 64% of the patients, two distinct slopes could be found: an initial, linear slope (31.8 +/- 7.5, 18-62) and a final, steeper slope (48.6 +/- 15.7, 24-101). Patients in whom no rupture of slope was observed were sicker. There was a relation between initial and overall VE/VCO2 slopes (r=0.915, P<10(-4)) and between overall and 3-min VE/VCO2 slopes (r=0.808, P<10(-4)). VE/VCO2 slope correlated with peak VO2 (r=-0.55, P<10(-4)) and peak circulatory power (r=-0.49, P<10(-4)). Univariate analysis showed that the prognostic value of overall VE/VCO2 slope (chi2 25.4, P<10(-4)) was greater than initial (chi2 22.8, P<10(-4)), 3-min (chi2 14.6, P<10(-4)) or final VE/VCO2 slopes (chi2 6.7, P=0.09). By multivariate analysis, the prognostic value of the peak circulatory power was similar to that of the VE/VCO2 overall slope. The VE/VCO2 slope should be computed from all the data points to have its highest prognostic value. Peak circulatory power also has similar prognostic value.


Synthesis of Fucosyl-Oligosaccharides Using α-l-Fucosidase from Lactobacillus rhamnosus GG.
Fucosyl-oligosaccharides are natural prebiotics that promote the growth of probiotics in human gut and stimulate the innate immune system. In this work, the release of α-lfucosidase by Lactobacillus rhamnosus GG, and the use of this enzyme for the synthesis of fucosyl-oligosaccharides were investigated. Since α-lfucosidase is a membrane-bound enzyme, its release from the cells was induced by addition of 4-nitrophenyl-α-l-fucopyranoside (pNP-Fuc). Enzyme activity associated with the cell was recovered at 78% of its total activity. Fucosyl-oligosaccharides where synthesized using α-l-fucosidase extract and pNP-Fuc as donor substrate, and D-lactose or D-lactulose as acceptor substrates, reaching a yield up to 25%. Fucosyllactose was obtained as a reaction product with D-lactose, and its composition was confirmed by mass spectrometry (MALDI-TOF MS). It is possible that the fucosyl-oligosaccharide synthesized in this study has biological functions similar to human milk oligosaccharides.


Porphyromonas gingivalis infection-associated periodontal bone resorption is dependent on receptor activator of NF-κB ligand.
Porphyromonas gingivalis is one of the oral microorganisms associated with human chronic periodontitis. The purpose of this study is to determine the role of the receptor activator of nuclear factor-κB ligand (RANKL) in P. gingivalis infection-associated periodontal bone resorption. Inbred female Rowett rats were infected orally on four consecutive days (days 0 to 3) with 1 × 10(9) P. gingivalis bacteria (strain ATCC 33277). Separate groups of rats also received an injection of anti-RANKL antibody, osteoprotegerin fusion protein (OPG-Fc), or a control fusion protein (L6-Fc) into gingival papillae in addition to P. gingivalis infection. Robust serum IgG and salivary IgA antibody (P < 0.01) and T cell proliferation (P < 0.05) responses to P. gingivalis were detected at day 7 and peaked at day 28 in P. gingivalis-infected rats. Both the concentration of soluble RANKL (sRANKL) in rat gingival tissues (P < 0.01) and periodontal bone resorption (P < 0.05) were significantly elevated at day 28 in the P. gingivalis-infected group compared to levels in the uninfected group. Correspondingly, RANKL-expressing T and B cells in rat gingival tissues were significantly increased at day 28 in the P. gingivalis-infected group compared to the levels in the uninfected group (P < 0.01). Injection of anti-RANKL antibody (P < 0.05) or OPG-Fc (P < 0.01), but not L6-Fc, into rat gingival papillae after P. gingivalis infection resulted in significantly reduced periodontal bone resorption. This study suggests that P. gingivalis infection-associated periodontal bone resorption is RANKL dependent and is accompanied by increased local infiltration of RANKL-expressing T and B cells.


Medication problems among outpatients. A study with emphasis on the elderly.
When patients ascribe adverse symptoms to their medications, the medical care process can be affected. To investigate how often medical outpatients link various adverse symptoms with their medications and to learn what actions they take in response, 299 randomly selected medical outpatients were interviewed. Thirty percent of the subjects identified at least one medication as causing an undesirable symptom. Subjects 65 years or older attributed a lower mean number of adverse symptoms to their medications than did younger subjects. Subjects rarely reported modifying their medication regimens due to adverse symptoms, a finding supported by multiple regression analysis. Approximately one in four subjects did not discuss their symptoms with their providers. These results have important implications for medical care in general, and for the elderly in particular.


Insights into the structure and function of HV1 from a meta-analysis of mutation studies.
The voltage-gated proton channel (HV1) is a widely distributed, proton-specific ion channel with unique properties. Since 2006, when genes for HV1 were identified, a vast array of mutations have been generated and characterized. Accessing this potentially useful resource is hindered, however, by the sheer number of mutations and interspecies differences in amino acid numbering. This review organizes all existing information in a logical manner to allow swift identification of studies that have characterized any particular mutation. Although much can be gained from this meta-analysis, important questions about the inner workings of HV1 await future revelation.


Effects of taping therapy for carpal space expansion on electrophysiological change in patients with carpal tunnel syndrome.
Taping therapy is one of the most conservative treatments for carpal tunnel syndrome (CTS). Preceding research studied on pain control, grip strength, and wrist function but no studies have been reported on electrophysiolgical changes after taping therapy. The aim of this study is to evaluate the effects of taping therapy for carpal space expansion on electrophysiological in 20 female patients aged from 40s to 60s with CTS. Experimental group applied taping therapy for carpal space expansion twice a week for 4 weeks and control group did not. There were significant differences between distal motor latency (DML) and sensory nerve conduction velocity (SNCV), but no difference between compound muscle action potential and sensory nerve action potential (SNAP) after 4 weeks taping treatment. Also, there was a significant difference in DML, SNCV, and SNAP in between groups. In conclusion, taping therapy for carpal space expansion can help to reduce the pressure of the carpal tunnel in CTS patients with mild symptoms.


Predominance of community-associated, methicillin-susceptible Staphylococcus aureus infections among hospitalized children and adolescents.
Introduction. Staphylococcus aureus infections cause significant morbidity and mortality in children and adolescents.Gap Statement. There is limited data on the characteristics of S. aureus infections requiring hospitalization in childhood.Aim.To investigate the molecular epidemiology and antibiotic resistance of S. aureus clinical isolates from children and adolescents.Methodology.All S. aureus isolates recovered from patients aged <18 years, admitted to a referral hospital, with culture-proven invasive or non-invasive infections during the 4 year period 2015 to 2018 were analysed for antimicrobial resistance, virulence genes, PFGE and multilocus sequence typing (MLST). Cases were assigned to community-associated, community-onset healthcare-associated or hospital-associated infections based on epidemiological case definitions.Results.Among 139 S. aureus infections, 88.5 % (123/139) were caused by methicillin-susceptible isolates (MSSA) and 73.4 % (102/139) were classified as community-associated infections. tst and lukS/lukF-PV genes were more common among MRSA as compared to MSSA isolates (tst, p 0.04; lukS/lukF-PV, p 0.007). Invasive disease was noted in 22/139 patients (15.8 %). Staphylococcal scalded skin syndrome caused by fusidic-resistant MSSA increased over time (22.8 % in 2017-2018 vs 8.3 % in 2015-2016, OR 3.24; 95 % CI 1.10-8.36; P 0.03). By PFGE genotyping, 22 pulsotypes were identified. A total of five sequence types (STs) were identified among 58 isolates analysed by MLST. More than one third of MSSA isolates (40/123, 32.5 %) and 13/23 (56.5 %) of SSSS isolates belonged to pulsotype 1, classified as sequence type 121 (ST121). MRSA isolates were equally distributed to pulsotypes A (ST30), B (ST239), C (ST80), H (ST225). ST121 isolates carried fnbA (40/40), eta/etb genes (29/40), exhibited high resistance to fusidic acid and were increasingly resistant to mupirocin.Conclusion.In our population, community-associated MSSA was the predominant cause of S. aureus infections characterized by polyclonality, increasing resistance to fusidic acid and mupirocin. PFGE type 1 ST121 clone, harboured exfoliative toxin genes and was associated with rising trends of SSSS.


[Prenatally detected aortic arch anomalies and their consequences after birth].
Aortic arch anomalies are frequently associated with cardiac or extracardiac malformations, chromosomal aberrations and postpartum esophagus/trachea compression. We aimed to establish the prevalence of associated cardiac and extracardiac malformations, the frequency of chromosomal aberrations in fetuses with the diagnosis of aortic arch anomalies and to assess the pregnancy and the postnatal outcome. Retrospective cohort study of all fetuses with aortic arch anomalies and genetic diagnosis in a tertiary referral obstetric and fetal cardiology centre between 2016 and 2020. Postpartum data were collected within 24 months after birth. In a cohort of 11.380 pregnant women, the prevalence of aortic arch anomalies was 0.25%. Among 28 cases of right aortic arch anomalies, in 27 fetuses prenatal genetic diagnosis was available. We diagnosed 4 fetuses with mirror-image branching (right sided V-sign) and 23 fetuses with U-sign (4 fetuses with complete double aortic arch). 18 cases (66%) were isolated. Associated anomalies were cardiac in 3 cases and extracardiac in 7 cases (33%). The most frequent cardiac anomaly was tetralogy of Fallot (2/27), the extracardiac anomalies were thymus hypoplasia, single umbilical artery and subclavian artery malformations. In 1 case (3.7%), fluorescent in situ hybridization diagnosed 22q11.2 microdeletion. 75% of fetuses with right sided V-sign were associated with conotruncal malformations. Pregnancy and postpartum outcome were known in 24 pregnancies. Postnatal diagnosis was different from prenatal in 2 cases, the concordance rate was 93%. Isolated cases resulted in live birth in 17/18 pregnancies (93%). The frequency of postpartum trachea/esophagus compression was 42,9% (9 cases) due to vascular ring, in 6 children (28,6%) operation was necessary. Fetal aortic arch anomalies are multidisciplinary diseases to be diagnosed by proper prenatal ultrasound examination. Associated fetal anomalies necessitate extended obstetric and cardiac sonography, invasive prenatal testing should be offered, and thorough postnatal long-term follow-up is recommended. Orv Hetil. 2023; 164(28): 1111-1120.


Australian species of Ommatius Wiedemann (Diptera: Asilidae) with an anepimeral bristle.
The presence of an anepimeral bristle in Australian Ommatius Wiedemann species is newly recorded and descriptions of seven new species possessing this character are presented: O. aquilonaris sp. nov., O. burwelli sp. nov., O. imaginis sp. nov., O. limbatus sp. nov., O. melasmus sp. nov., O. musselbrookensis sp. nov. and O. radamnis sp. nov. All species occur in Queensland but O. melasmus sp. nov. also occurs in New South Wales and O. musselbrookensis sp. nov. also occurs in the Northern Territory. A key to separate the species is presented.


Tissue-specific expression of murine keratin K13 in internal stratified squamous epithelia and its aberrant expression during two-stage mouse skin carcinogenesis is associated with the methylation state of a distinct CpG site in the remote 5'-flanking region of the gene.
Under normal conditions, the expression of the murine type-I keratin K13 is restricted to the suprabasal, differentiating cell layers of internal stratified squamous epithelia that line the oral cavity and the upper digestive tract. It is, however, also expressed aberrantly but constitutively in only the differentiating parts of 7,12-dimethylbenz[alpha]anthracene/12.0-tetradecanoyl-phorbol-13-acetate (DMBA/TPA) induced malignant epidermal tumors of the back skin of mice, whereas its likewise suprabasal expression in papillomas is highly variable [27]. In an approach to unravel regulatory DNA sequence elements involved in the tissue-specific and aberrant K13 expression, the 5'-flanking region of the gene was analyzed with regard to potential methylation sites and DNase hypersensitive regions. We report on the identification of a CpG dinucleotide (designated M1; located about 2.3 kb upstream of the transcriptional start site), whose methylation state correlates with the differential gene activity in various epithelia and tumors. We show that in K13-nonexpressing integumental epidermis the M1 site is methylated in both suprabasal and basal cells. In contrast, internal stratified squamous epithelia (i.e. tongue, esophagus, forestomach) exhibit an unmethylated M1 site not only in their suprabasal. K13-expressing cells, but also in basal cells--in which, however, the keratin is not yet synthesized. The identical situation is encountered in DMBA TPA-induced moderately differentiating epidermal squamous cell carcinomas with compartmentalized K13 expression. In papillomas we observed a striking correlation between the extent of both suprabasally expressed K13 protein and demonstrable DNA copies carrying an unmethylated M1 site. Moreover we found that the sequence region around the M1 site was DNAseI hypersensitive in K13-expressing malignant tumors, but DNaseI insensitive in K13-nonexpressing epithelia and cells. DNAseI hypersensitivity in K13-expressing tissues was, however, independent of an active transcription of the gene in differentiating cells or transcriptional inertia in basal cells. These results strongly suggest that the sequence element around the demethylated M1 site is involved in a multi-level control mechanism mediating the selective expression of the K13 gene in internal squamous epithelia and in DMBA/TPA-induced epidermal tumors.


[Subcutaneous microdialysis: a simple technique for monitoring the extracellular biochemical environment. Combination with capillary electrophoresis and laser-induced fluorescence detection].
Microdialysis is a simple technique that allows monitoring endogenous or exogenous substances in any extracellular compartment. It has many useful experimental and clinical applications. The sampling of the extracellular fluid of the subcutaneous compartment is especially useful for metabolic evaluation in critically ill patients, pharmacokinetic studies and blood glucose monitoring. We built a subcutaneous microdialysis probe, with a cellulose hollow fiber (13,000 molecular weight cut off, 200 microns outside diameter) glued to stainless steel tubing (26 ga. outside diameter). It was implanted in the subcutaneous tissue of a critically ill child or anesthetized mice to obtain amino acids patterns by means of capillary electrophoresis with laser induced fluorescence detection (CE-LIFD). The probe was also implanted in ambulatory volunteers to monitor glucose. The results confirmed that subcutaneous microdialysis is a very simple, inexpensive and not aggressive method with advantages over repeated venipuncture sampling and endovenous microdialysis sampling. The present report shows that subcutaneous microdialysis with the proper analytical technique can be used to monitor the chemical composition of the interstitial compartment in very different preclinical or clinical conditions.


Genome-Wide Identification and Characterization of the Potato bHLH Transcription Factor Family.
Plant basic/helix-loop-helix (bHLH) transcription factors participate in a number of biological processes, such as growth, development and abiotic stress responses. The bHLH family has been identified in many plants, and several bHLH transcription factors have been functionally characterized in Arabidopsis. However, no systematic identification of bHLH family members has been reported in potato (Solanum tuberosum). Here, 124 StbHLH genes were identified and named according to their chromosomal locations. The intron numbers varied from zero to seven. Most StbHLH proteins had the highly conserved intron phase 0, which accounted for 86.2% of the introns. According to the Neighbor-joining phylogenetic tree, 259 bHLH proteins acquired from Arabidopsis and potato were divided into 15 groups. All of the StbHLH genes were randomly distributed on 12 chromosomes, and 20 tandem duplicated genes and four pairs of duplicated gene segments were detected in the StbHLH family. The gene ontology (GO) analysis revealed that StbHLH mainly function in protein and DNA binding. Through the RNA-seq and quantitative real time PCR (qRT-PCR) analyses, StbHLH were found to be expressed in various tissues and to respond to abiotic stresses, including salt, drought and heat. StbHLH1, 41 and 60 were highly expressed in flower tissues, and were predicted to be involved in flower development by GO annotation. StbHLH45 was highly expressed in salt, drought and heat stress, which suggested its important role in abiotic stress response. The results provide comprehensive information for further analyses of the molecular functions of the StbHLH gene family.


Fatty change in the brain in perinatal and unexpected death.
The presence of fat-laden cells in the cerebrospinal fluid is usually associated with a fatty change found particularly in the area of the tapetum in the postnatal infant. In a series of 307 child deaths the presence of fatty change in this area of the brain was age-related, decreased with age, and was rarely present over the age of 4 years. It was particularly common in stillborns and in children dying with respiratory distress, but was rare in children dying from acute surgical conditions or from acute infections. It was found in one-half of a series of 41 infants found unexpectedly dead and in whom no adequate cause of death was found. The most likely cause of this fatty change is thought to be chronic hypoxia.


Intrauterine devices.
The aim of this chapter is to review the worldwide use of intrauterine devices (IUDs) for contraception and the long-term contraceptive efficacy and safety of copper-bearing IUDs. The TCu380A and Multiload Cu375 have a very low failure rate (0.2-0.5%) over 10 years. The main concerns of the use of IUDs are risk of pelvic inflammatory diseases and increased menstrual blood loss and irregular bleeding. Factors associated with an increase in risk of pelvic inflammatory diseases are discussed. Preventive measures can be taken with careful screening of eligible IUD users, technical training and adequate service facilities for provision of IUDs. Levonorgestrel-releasing IUDs have the benefit of reducing menstrual blood loss in addition to high contraceptive efficacy. The copper IUD is the most effective method for emergency contraception. It can prevent over 95% of unwanted pregnancies within 5 days of unprotected intercourse.


The role of the carrier in the formulation of pharmaceutical solid dispersions. Part II: amorphous carriers.
Amorphous solid dispersions are considered as one of the most powerful strategies to formulate poorly soluble drugs. They are made up of an active pharmaceutical ingredient (API) dispersed at the molecular level in an amorphous polymeric carrier. As the latter component constitutes the largest part of the formulation, its characteristics will contribute to a large extent to the properties and behavior of the solid dispersion. Areas covered: Amorphous polymers are most often used in modern solid dispersion formulations. This review discusses carrier properties like molecular weight, conformation, hygroscopicity, their stabilization effects, issues related to solid dispersion manufacturing technology, response to downstream processing, and potential to generate supersaturation, next to criteria to select a carrier to formulate stable amorphous solid dispersions. Expert opinion: Different amorphous carriers lead to solid dispersions with various properties in terms of physical stability, phase behavior and drug release rate and extent. Despite more than 50 years of intensive research in this field it remains difficult to predict what carrier is best suited for a given API, pointing to the complex nature of this formulation strategy. Sustained efforts to understand the link and complex interplay between material properties, processing parameters, physical stability and dissolution behavior are required from pharmaceutical scientists with a strong physicochemical background to shift the development from trial and error to science driven.


[The composition of the gastrointestinal bacterial flora of mouse embryos and the placenta tissue bacterial flora].
Objective: To explore the composition of the gastrointestinal bacterial flora of mouse embryos and the placenta tissue bacterial flora. Method: Twenty-four specimens were collected from pregnant Kunming mouse including 8 mice of early embryonic (12-13 days) gastrointestinal tissues, 8 cases of late embryonic (19-20 days)gastrointestinal tissues, 8 of late pregnancy placental tissues.The 24 samples were extracted by DNeasy Blood & Tissue kit for high-throughput DNA sequencing. Result: The level of Proteobacteria, Bacteroidetes, Actino-bacteria and Firmicutes were predominantin all specimens.The relative content of predominant bacterial phyla in each group: Proteobacteria (95.00%, 88.14%, 87.26%), Bacteroidetes(1.71%, 2.15%, 2.63%), Actino-Bacteria(1.16%, 4.10%, 3.38%), Firmicutes(0.75%, 2.62%, 2.01%). At the level of family, there were nine predominant bacterial families in which Enterobacteriaeae, Shewanel laceae and Moraxellaceae were dominant.The relative content of dominant bacterial family in eachgroup: Enterobacteriaeae (46.99%, 44.34%, 41.08%), Shewanellaceae (21.99%, 21.10%, 19.05%), Moraxellaceae(9.18%, 7.09%, 5.64%). From the species of flora, the flora from fetal gastrointestinal in early pregnancy and late pregnancy (65.44% and 62.73%) were the same as that from placenta tissue in the late pregnancy.From the abundance of bacteria, at the level of family, the same content of bacteria in three groups accounted for 78.16%, 72.53% and 65.78% respectively. Conclusion: It was proved that the gastrointestinal bacterial flora of mouse embryos and the placenta tissue bacterial flora were colonized. At the same time the bacteria are classified.


Tumoral cubilin is a predictive marker for treatment of renal cancer patients with sunitinib and sorafenib.
Tyrosine kinase inhibitors like sunitinib and sorafenib are commonly used to treat metastatic renal cell cancer patients. Cubilin is a membrane protein expressed in the proximal renal tubule. Cubilin and megalin function together as endocytic receptors mediating uptake of many proteins. There is no established predictive marker for metastatic renal cell cancer patients and the purpose of the present study was to assess if cubilin can predict response to treatment with tyrosine kinase inhibitors. Cubilin protein expression was analyzsed in tumor tissue from a cohort of patients with metastatic renal cell cancer (n = 139) using immunohistochemistry. One hundred and thirty six of the patients were treated with sunitinib or sorafenib in the first- or second-line setting. Thirty of these were censored because of toxicity leading to the termination of treatment and the remaining (n = 106) were selected for the current study. Fifty-three (50%) of the tumors expressed cubilin in the membrane. The median progression-free survival was 8 months in patients with cubilin expressing tumors and 4 months in the cubilin negative group. In addition, the overall survival was better for patients with cubilin positive tumors. We also found that the fraction of cubilin negative patients was significantly higher in the non-responding group (PFS ≤3 months) compared to responding patients (PFS >3 months). We show for the first time that tumoral expression of cubilin is a positive predictive marker for treatment of metastatic renal cell cancer patients with sunitinib and sorafenib.


Perioperative Outcome Comparisons Between Open and Laparoscopic Nephroureterectomy Among a Population-Based Cohort from 2010 to 2012.
To compare the perioperative outcomes and costs between open and laparoscopic nephroureterectomy for malignant diseases on a contemporary population-based level. Based on the Japanese Diagnosis Procedure Combination database for 2010 to 2012, we compared six end points of in-hospital mortality, intraoperative and postoperative complications, transfusion, anesthesia time, postoperative length of stay, and costs between open and laparoscopic nephroureterectomy under one-to-one matching based on the propensity scores. Multivariate analyses included sex, age, Charlson comorbidity index, body mass index, oncologic stage, hospital volume, and hospital academic status. Missing values were filled in by five-copy multiple imputations. Among 3595 open and 3349 laparoscopic nephroureterectomies, an average of 2902 matched pairs were generated by the imputation and matching process. The outcomes showing significantly favorable association with the laparoscopic approach over the open approach were in-hospital mortality (0.3% vs 0.7%; odds ratio [OR], 0.41 [95% confidence interval, CI, 0.17 to 0.99]), postoperative complications (9.4% vs 12.6%; OR, 0.73 [0.58 to 0.91]), transfusion (12.9% vs 20.6%; OR, 0.54 [0.46 to 0.64]), postoperative length of stay (median, 11 vs 12 days; Beta, -0.041 [-0.059 to -0.023]), and costs without the operating room (median, $6607 vs $7077; Beta, -0.030 [-0.048 to -0.013]), while significantly longer anesthesia time (median, 278 vs 245 min; Beta, 0.057 [0.041 to 0.074]) and higher total costs (median, $15691 vs $12846; Beta, 0.078 [0.068 to 0.088]) for laparoscopic than for open nephroureterectomies were noted. There was no difference in intraoperative complications (P=0.774). Several favorable perioperative outcomes including low mortality were observed in laparoscopic nephroureterectomy compared with open nephroureterectomy.


Systematic Reviews Published in the October 2016 Issue of the Cochrane Library.
The Cochrane Library of Systematic Reviews has been published quarterly as a DVD and monthly online ( http://www.thecochranelibrary.com ). The final October 2016 issue (4th DVD for 2016) contains 7068 complete reviews and 2467 protocols for reviews in production. In addition, there are citations of 973,000 randomized controlled trials, and 15,700 cited papers in the Cochrane Methodology Register. The Health Technology Assessment database contains some 16,000 citations. One hundred and seventeen new reviews have been published in the previous 3 months, of which three have potential relevance for practitioners in pain and palliative medicine. The impact factor of the Cochrane Library stands at 6.1. Readers are encouraged to access the full report for any articles of interest, as only a brief commentary is provided. The CD version of the Cochrane Library will be discontinued and the Library will only available online in the future.


Active smoking and survival following breast cancer among African American and non-African American women in the Carolina Breast Cancer Study.
To examine racial differences in smoking rates at the time of breast cancer diagnosis and subsequent survival among African American and non-African American women in the Carolina Breast Cancer Study (Phases I/II), a large population-based North Carolina study. We interviewed 788 African American and 1,020 Caucasian/non-African American women diagnosed with invasive breast cancer from 1993 to 2000, to assess smoking history. After a median follow-up of 13.56 years, we identified 717 deaths using the National Death Index; 427 were breast cancer-related. We used Cox regression to examine associations between self-reported measures of smoking and breast cancer-specific survival within 5 years and up to 18 years after diagnosis conditional on 5-year survival. We examined race and estrogen receptor status as potential modifiers. Current (vs never) smoking was not associated with 5-year survival; however, risk of 13 year conditional breast cancer-specific mortality was elevated among women who were current smokers at diagnosis (HR 1.54, 95% CI 1.06-2.25), compared to never smokers. Although smoking rates were similar among African American (22.0%) and non-African American (22.1%) women, risk of breast cancer-specific mortality was elevated among African American (HR 1.69, 95% CI 1.00-2.85), but only weakly elevated among non-African American (HR 1.22, 95% CI 0.70-2.14) current (vs. never) smokers (P Interaction = 0.30). Risk of breast cancer-specific mortality was also elevated among current (vs never) smokers diagnosed with ER- (HR 2.58, 95% CI 1.35-4.93), but not ER+ (HR 1.11, 95% CI 0.69-1.78) tumors (P Interaction = 0.17). Smoking may negatively impact long-term survival following breast cancer. Racial differences in long-term survival, as related to smoking, may be driven by ER status, rather than by differences in smoking patterns.


Bilateral primary brucellar psoas abscess.
Skeletal involvement is a relatively common complication of human brucellosis. Muscle infection and particularly psoas abcess is rarely reported and always secondary to spondylitis. We report here a case of brucellar abscesses in both psoas and right gluteal and posterior thigh muscles occurring without any skeletal, renal or bowel lesion.


ATP-Dependent human erythrocyte glutathione-conjugate transporter. I. Purification, photoaffinity labeling, and kinetic characteristics of ATPase activity.
Dinitrophenyl S-glutathione (DNP-SG) ATPase is a 38 kDa membrane protein expressed in erythrocytes and other tissues. Although stimulation of ATP hydrolysis catalyzed by DNP-SG ATPase has been demonstrated in the presence of several structurally unrelated amphiphilic ions, structural and functional properties of this protein have not been well-defined. In the present study, we have developed an improved protocol for the purification of DNP-SG ATPase and investigated its kinetic and substrate-binding properties. The purification procedure was based on highly specific elution of the 38 kDa protein from DNP-SG affinity resin in the presence of ATP. The protein could not be eluted using either ADP or adenosine-5'-[beta,gamma-methylene]triphosphate (methylene-ATP), a nonhydrolyzable analogue of ATP. Doxorubicin (DOX), a weakly basic anthracycline chemotherapy agent, was found to be the preferred activator for stimulation of ATP hydrolysis by the enzyme. ATP binding to the enzyme was demonstrated using 8-azido-ATP photoaffinity labeling and binding of trinitrophenyl (TNP)-ATP, a fluorescent analogue of ATP. The photoaffinity labeling of DNP-SG ATPase (38 kDa) was saturable with respect to 8-azido ATP (Kd = 2 microM), indicating that the enzyme was capable of specific and saturable binding to ATP. DNP-SG binding was evident from the purification procedure itself and was also demonstrable by quenching of tryptophan fluorescence. Results of quenching of tryptophan fluorescence as well as radioactive isotope-binding studies indicated that DOX was bound to the purified protein as well.


Nosocomial pneumonia in 27 ICUs in Europe: perspectives from the EU-VAP/CAP study.
We report on intensive care nosocomial pneumonia (NP) in Europe through a review of EU-VAP/CAP manuscripts: a prospective observational study, enrolling patients from 27 ICUs in nine European countries. From 2,436 eligible ICU patients, 827 cases presented NP, with 18.3 episodes of VAP per 1000 ventilator-days. Most common findings were worsening oxygenation, purulent respiratory secretions and temperature increase. At least three criteria from Clinical Pulmonary Infection score (CPIS) were present in 77.9 % of episodes, but only 0.2 % met six CPIS criteria. Diagnosis was confirmed mainly noninvasively (74.8 %), with half qualitative and quantitative cultures. The dominant isolate was S. aureus in Spain, France, Belgium and Ireland, P. aeruginosa in Italy and Portugal, Acinetobacter in Greece and Turkey, but Escherichia coli in Germany. NP resulted in 6 % higher mortality, longer ICU stay and duration of mechanical ventilation (12 and 10 days). COPD and age ≥45 years were not associated with higher VAP incidence but did correlate with increased mortality. Trauma had higher VAP incidence but lower mortality. Bacteremia (led by MRSA and Acinetobacter baumannii) was documented in 14.6 %, being associated with extra ICU stay and mortality. Vasopressors and ICUs with above 25 % prevalence of Potential Resistant Organisms (PRM) were independently associated with PRM, being documented in 50.7 % of patients with early-onset VAP without known risk factors. Most patients initially received combination therapy. Delay in appropriate antimicrobial choice significantly increased mortality, and LOS in survivors was six days longer (p < 0.05). In conclusion, NP management in Europe presents local differences and major shifts when compared to reports from North America, outcomes of randomized trials and general guidelines.


[Fatal skiing accidents: a forensic analysis taking the example of Salzburg].
The rising popularity of Alpine skiing in recent years has led to an increase of skiing accidents, some with fatal outcome. In this paper, all fatal skiing accidents from the autopsy material of the Institute of Forensic Medicine of the Paris Lodron University Salzburg were evaluated and compared with statistical data of the Alpine Police. In the wintertime of 2005/2006 until 2013/2014, 22 deadly skiing accidents were autopsied. The age of the male and female victims ranged between 12 and 71 years. The main cause of death was craniocerebral and chest trauma. A relevant blood alcohol concentration was detected in only one case. Together with trauma-biomechanical and technical experts, forensic medicine serves as a necessary clarification interface between the investigating authorities and the judiciary. Determining the cause and manner of death as well as reconstructing the accident is the main task of the forensic pathologist. The present study shows that in the county of Salzburg, only a small percentage of fatal skiing accidents is evaluated from a forensic and trauma-biomechanical point of view. Thus the possibilities of an interdisciplinary accident analysis are not always fully utilized.


Mechanisms Linking Ethical Leadership to Ethical Sales Behavior.
This study investigated the relationship between ethical leadership and ethical sales behavior. A total of 248 matched surveys with participant responses from insurance agents and their customers were collected. The insurance agents were asked to rate the ethical leadership of their leaders, the ethical climate in their organization, and their individual moral identity. Customers were asked to rate the perceived ethical sales behavior of the insurance agents. This empirical study utilized moderated mediation techniques to analyze the data. Results indicated that ethical climate mediated the relationship between ethical leadership and ethical sales behavior when moral identity was high, however, did not when moral identity was low. The research framework including contextual effects (i.e., ethical climate) and individual differences in moral judgment (i.e., moral identity) can provide a comprehensive picture of how ethical leadership influences ethical sales behavior. Theoretical and practical implications of these findings are also discussed.


Solution-phase parallel synthesis of a 1,2,7-trialkyl-1H-imidazo[4,5-g]quinoxalin-6-ol library scaffold.
This paper describes solution-phase parallel synthesis of a library with a novel 1,2,7-trialky-1H-imidazo[4,5-g]quinoxalin-6-ol scaffold and three points of diversity. The library is prepared using 1,5-difluoro-2,4-dinitrobenzene as the starting material and commercially available chemicals as the building blocks. A new, inexpensive, and practical apparatus for parallel filtration is also described.


Assessment of bone marrow involvement by magnetic resonance imaging in small cell lung cancer. No significant change of staging.
This prospective study was performed in an attempt to evaluate (1) the rate of magnetic resonance imaging (MRI) demonstrating bone marrow (BM) abnormalities, (2) the correlation of these abnormalities with a pathologic malignant BM involvement, and (3) the possible modification of patients' usual disease staging in the light of these abnormalities. After extensive staging investigations, patients' diseases were classified as limited or extensive. Dorsal and lumbar spine MRI was performed for second staging. Thirty-two patients were eligible for this study. In ten patients (31.2 percent), MRI showed abnormalities; in four of them, the BM sample from the posterior iliac crest was free from malignancy. Three of these four patients had extensive disease. The last patient, because he had limited disease, had biopsy at the site of MRI abnormalities; the biopsy specimen revealed a malignant involvement and therefore this patient, initially classified as having limited disease, was classified in the extensive disease group. In only 1 of 32 patients, BM-MRI data modified initial staging. The metastases disclosure yield of the MRI in the detection of medullar involvement is higher than BM biopsy but especially in patients with extensive disease. Therefore, MRI should not be considered in routine practice, in particular in patients with extensive disease.


Adaptive Memory of a Neuromorphic Transistor with Multi-Sensory Signal Fusion.
One of the ultimate goals of artificial intelligence is to achieve the capability of memory evolution and adaptability to changing environments, which is termed adaptive memory. To realize adaptive memory in artificial neuromorphic devices, artificial synapses with multi-sensing capability are required to collect and analyze various sensory cues from the external changing environments. However, due to the lack of platforms for mediating multiple sensory signals, most artificial synapses have been mainly limited to unimodal or bimodal sensory devices. Herein, we present a multi-modal artificial sensory synapse (MASS) based on an organic synapse to realize sensory fusion and adaptive memory. The MASS receives optical, electrical, and pressure information and in turn generates typical synaptic behaviors, mimicking the multi-sensory neurons in the brain. Sophisticated synaptic behaviors, such as Pavlovian dogs, writing/erasing, signal accumulation, and offset, were emulated to demonstrate the joint efforts of bimodal sensory cues. Moreover, associative memory can be formed in the device and be subsequently reshaped by signals from a third perception, mimicking modification of the memory and cognition when encountering a new environment. Our MASS provides a step toward next-generation artificial neural networks with an adaptive memory capability.


Myofibroblasts in the cirrhotic rat liver reflect hepatic remodeling and correlate with fibrosis and sinusoidal capillarization.
Myofibroblasts are essential in fibrogenesis during development of cirrhosis. In the present study we stereologically quantitated MFB's and correlated them with fibrosis and sinusoidal capillarization. Male SD rats were rendered cirrhotic by chronic exposure to phenobarbital/CCl4, (CIR; n = 16); untreated littermates served as controls (CTR; n = 10). Sinusoidal capillarization was assessed by a multiple indicator dilution technique as previously described. The volume fractions of myofibroblasts and other liver components were estimated by morphometry. Myofibroblasts averaged 15.7 +/- SD 0.7% in CIR as compared to 6.7% +/- SD 0.4% in CTR (p < 0.01). An extra-littoral compartment of myofibroblasts was found in portal tracts and within fibrous septa. In CIR, hepatocytes showed a bimodal distribution of volume fractions, and hepatocyte volume distribution disclosed a mirror image of that of myofibroblasts. Connective tissue was markedly increased in CIR, averaging 13.2 +/- 1.2% in CIR vs. 1.2 +/- 0.3% in CTR (p < 0.0001). Extravascular albumin space--a measure of sinusoidal capillarization--was reduced by 44% in CIR (0.028 +/- 0.017 vs. 0.050 +/- 0.010 ml/g; p < 0.001). The volume fraction of myofibroblasts correlated best with extravascular albumin space (r = -0.84, p < 0.001). Multiple regression analysis selected only extravascular albumin space and connective tissue to be determined by the volume fraction of myofibroblasts (r = 0.923; p < 0.001). We conclude that increased myofibroblasts reflect the degree of hepatic remodeling rather than cirrhosis inasmuch as myofibroblast volume fraction inversely reflects that of hepatocyte bimodality. Myofibroblasts form an extra-littoral compartment in this model of CIR and correlate with hepatic fibrosis and sinusoidal capillarization.


Responding to the Needs of People with Disabilities in the COVID-19 Pandemic: Community Perspectives from Centers for Independent Living.
Centers for Independent Living (CILs) are federally funded, community-based organizations designed and operated by people with disabilities that provide individual and systems advocacy, peer support, information and referral, independent living skills training, and transition services throughout the U.S. and its territories. Centers for Independent Living therefore offer a rich and detailed perspective on the needs of people with disabilities during the COVID-19 pandemic. In this brief report, we summarize COVID-19-related issues raised by 144 CIL administrators and staff in a national survey conducted in April and May 2020 and discuss their research and policy implications. Respondents voiced concerns about health and safety, long-term supportive services, social isolation, and economic insecurity. In the words of one center director, "The pandemic has pulled back the curtain on the depth of need in our local disability community."


In ovo administration of copper nanoparticles and copper sulfate positively influences chicken performance.
Copper (Cu) is a key trace mineral involved in a variety of physiological processes, and is commonly used in poultry production. However, regardless of the inclusion level the majority of Cu is excreted with poultry faeces. We hypothesise that in ovo administration will allow for better utilisation of Cu during embryo development than when supplied post-natally with feed to growing chickens. Thus, the objective of this study was to evaluate effects of in ovo administration of NanoCu and copper sulfate (CuSO4 ) on broiler chicken performance. The study showed the positive influences of Cu nanoparticles and CuSO4 on broiler chickens performance. Body weight, at the end of the rearing period (day 42) was significantly higher in NanoCu (2206 g) and CuSO4 (2402 g) groups compared to the control group (2000 g). Both treatment groups had significantly lower feed conversion rate and mortality, and higher percentage of breast and leg muscles in the carcass versus control. The in ovo application of Cu colloids may ensure an efficient penetration of Cu into the embryonic tissue with long lasting effects on postnatal growth. The method may provide a successful alternative to using Cu as a feed additive. © 2015 Society of Chemical Industry.


New stability and stabilization conditions for nonlinear systems with time-varying delay based on delay-partitioning approach.
This paper focuses on stability analysis and stabilization of nonlinear systems with interval time-varying delay, modeled by Takagi-Sugeno (T-S) fuzzy approach. To achieve more relaxation in the feasibility region, delay-partitioning approach is used for all integral terms in the Lyapunov-Krasovskii functional (LKF). A fuzzy Lyapunov function is proposed instead of non-integral term in LKF, and moreover, some slack matrices variables are offered to enlarge the design space. By doing this, new delay-dependent stability criteria are obtained. During the derivation of stability conditions, Jensen's integral inequality is applied to deal with integral terms. Furthermore, in this paper the problem of controller design via the parallel distributed compensation (PDC) scheme is studied. Stability and stabilization conditions with less conservative are achieved in terms of linear matrix inequality (LMI). Finally, two numerical examples are presented to show the effectiveness of the proposed results.


Helical CT: clinical performance and imaging strategies.
For nonelectron beam systems, scan speed and image quality have reached a relative plateau of performance. Helical CT makes rapid coverage of the z axis possible, allowing scanning to occur during the optimal phase of vascular and organ enhancement. With the split breath-hold variable-mode approach, extended helical coverage across multiple anatomic regions is possible. The technique adds flexibility in choice of collimation, milliamperage, and breath-hold interval. It is easily tolerated by patients and reproducible, and the intersegment delays produce less heat loading on the x-ray tube.


Glutaminolysis: A Hallmark of Cancer Metabolism.
Glutamine is the most abundant circulating amino acid in blood and muscle and is critical for many fundamental cell functions in cancer cells, including synthesis of metabolites that maintain mitochondrial metabolism; generation of antioxidants to remove reactive oxygen species; synthesis of nonessential amino acids (NEAAs), purines, pyrimidines, and fatty acids for cellular replication; and activation of cell signaling. In light of the pleiotropic role of glutamine in cancer cells, a comprehensive understanding of glutamine metabolism is essential for the development of metabolic therapeutic strategies for targeting cancer cells. In this article, we review oncogene-, tumor suppressor-, and tumor microenvironment-mediated regulation of glutamine metabolism in cancer cells. We describe the mechanism of glutamine's regulation of tumor proliferation, metastasis, and global methylation. Furthermore, we highlight the therapeutic potential of glutamine metabolism and emphasize that clinical application of in vivo assessment of glutamine metabolism is critical for identifying new ways to treat patients through glutamine-based metabolic therapy.


24 h rhythm of blood pressure and forearm peripheral resistance in normotensive and hypertensive subjects confined to bed.
To define whether a diurnal rhythm of peripheral resistance exists in normotensive and hypertensive subjects, has any relationship with that of blood pressure and differs in dipper and non-dipper hypertensives. Forty-three subjects (13 normotensives and 30 mild-to-moderate essential hypertensives) confined for 24 h to bed were included. Blood pressure was recorded for 22 h at 15 min intervals, plethysmographic forearm flow was simultaneously measured and forearm resistance calculated. The analysis was performed for the whole 22 h period and for three 4 h truncated periods, two of certain wakefulness and one of certain sleep. A circadian rhythm of forearm resistance was shown in the normotensives, paralleling that of blood pressure. All the normotensives were dippers, with a nocturnal blood pressure dip (systolic/diastolic) of -4.5/-6.0%. In the hypertensives, the day/night blood pressure trends were not homogeneous: 21 showed higher blood pressure values during waking time, with a trend quite similar to that of the normotensives, whereas the other nine were non-dippers. Resistance was lower during sleep than during waking both in the normotensives and in the dipper hypertensives, whereas in the non-dippers it was higher during sleep. A sleep/waking rhythm of peripheral resistance with the highest values during daytime and the lowest during night-time does exist in normotensive as well as in the majority of hypertensive subjects resting continuously in bed, and therefore is largely independent of physical activity. Only in a minority of hypertensive patients are higher values of peripheral resistance present during sleep.


Regulation of the Ras signalling network.
The mitogenic action of cytokines such as epidermal growth factor (EGF) or platelet derived growth factor (PDGF) involves the stimulation of a signal cascade controlled by a small G protein called Ras. Mutations of Ras can cause its constitutive activation and, as a consequence, bypass the regulation of cell growth by cytokines. Both growth factor-induced and oncogenic activation of Ras involve the conversion of Ras from the GDP-bound (D-Ras) to the GTP-bound (T-Ras) forms. T-Ras activates a network of protein kinases including c-Mos, c-Raf-1 and MAP kinase. Eventually the activation of MAP kinase leads to the activation of the elongation factor 4E and several transcription factors such as c-Jun, c-Myc and c-Fos. There are several modulators of Ras activity, such as the GTPase activating proteins (GAP1 and NF1), which stimulate the conversion of T-Ras to D-Ras. A series of small NF1 fragments, which bind T-Ras, as well as truncated forms of derivatives of c-Raf-1, c-Jun and c-Myc, are capable of blocking the T-Ras-activated mitogenesis in a competitive manner. These agents offer a unique opportunity to control the proliferation of T-Ras-associated tumors, which represent more than 30% of total human carcinomas.


Mechano-Nanoarchitectonics: Design and Function.
Mechanical stimuli have rather ambiguous and less-specific features among various physical stimuli, but most materials exhibit a certain level of responses upon mechanical inputs. Unexplored sciences remain in mechanical responding systems as one of the frontiers of materials science. Nanoarchitectonics approaches for mechanically responding materials are discussed as mechano-nanoarchitectonics in this review article. Recent approaches on molecular and materials systems with mechanical response capabilities are first exemplified with two viewpoints: i) mechanical control of supramolecular assemblies and materials and ii) mechanical control and evaluation of atom/molecular level structures. In the following sections, special attentions on interfacial environments for mechano-nanoarchitectonics are emphasized. The section entitled iii) Mechanical Control of Molecular System at Dynamic Interface describes coupling of macroscopic mechanical forces and molecular-level phenomena. Delicate mechanical forces can be applied to functional molecules embedded at the air-water interface where operation of molecular machines and tuning of molecular receptors upon macroscopic mechanical actions are discussed. Finally, the important role of the interfacial media are further extended to the control of living cells as described in the section entitled iv) Mechanical Control of Biosystems. Pioneering approaches on cell fate regulations at liquid-liquid interfaces are discussed in addition to well-known mechanobiology.


Co-localization of particulate methane monooxygenase and cd1 nitrite reductase in the denitrifying methanotroph 'Candidatus Methylomirabilis oxyfera'.
'Candidatus Methylomirabilis oxyfera'; is a polygon-shaped bacterium that was shown to have the unique ability to couple anaerobic methane oxidation to denitrification, through a newly discovered intra-aerobic pathway. Recently, the complete genome of Methylomirabilis oxyfera was assembled into a 2.7-Mb circular single chromosome by metagenomic sequencing. The genome of M. oxyfera revealed the full potential to perform both methane oxidation and the conversion of nitrite via nitric oxide into oxygen and dinitrogen gas. In this study, we show by immunogold localization that key enzymes from both methane- and nitrite-converting pathways are indeed present in single M. oxyfera cells. Antisera targeting the particulate methane monooxygenase (pMMO) and the cd(1) nitrite reductase (NirS) were raised and used for immunogold localization in both single- and double-labelling experiments. Our previous studies have shown that M. oxyfera does not develop pMMO-containing intracytoplasmic membranes as is observed in classical proteobacterial methanotrophs. Our results suggest that in M. oxyfera, the pMMO and NirS enzymes localized to the cytoplasmic membrane and periplasm, respectively. Further, double-labelling showed co-occurrence of pMMO and NirS in single M. oxyfera cells.


Pretreatment High MCV as Adverse Prognostic Marker in Nonanemic Patients with Head and Neck Cancer.
Mean corpuscular volume (MCV) has been shown in to be a reliable prognostic marker in other cancers; however, no evidence exists on its use in head and neck squamous cell carcinoma (HNSCC). This study aimed to investigate the association between MCV, hemoglobin, platelet count and albumin concentration, and survival in stage III/IVA-B HNSCC treated with concurrent chemoradiotherapy. Retrospective cohort study. In this multicenter retrospective study, we analyzed MCV, platelet count, hemoglobin concentration, and albumin concentration in peripheral blood samples from 260 patients with HNSCC undergoing organ preservation treatment with curative intent at the time of diagnosis. We then analyzed survival outcomes after accounting for confounders using multivariate analysis. After adjustment for potential confounders, patients with low hemoglobin had a 3.3-fold higher risk of death (95% confidence interval [CI]: 2.26-4.81) than those with normal hemoglobin. Patients with an elevated MCV had a 1.54-fold higher risk of death (95% CI: 1.06-2.24), independent of site, stage, and human papillomavirus status. Interestingly, the effect of MCV on overall and progression-free survival was limited to those with a normal pretreatment hemoglobin. We identified no associations between pretreatment platelet count or albumin concentration and survival. These findings suggest that pretreatment anemia and macrocytosis are independent predictors of lower overall and progression-free survival in HNSCC patients undergoing organ preservation treatment. III Laryngoscope, 131:E836-E843, 2021.


Molecular Characterization and Distribution of Two Strains of Dasheen mosaic virus on Taro in Hawaii.
Dasheen mosaic virus (DsMV) is one of the major viruses affecting taro (Colocasia esculenta) production worldwide. Whole genome sequences were determined for two DsMV strains, Hawaii Strain I (KY242358) and Hawaii Strain II (KY242359), from taro in Hawaii. They represent the first full-length coding sequences of DsMV reported from the United States. Hawaii Strains I and II were 77 and 85% identical, respectively, with other completely sequenced DsMV isolates. Hawaii Strain I was most closely related to vanilla mosaic virus (VanMV) (KX505964.1), a strain of DsMV infecting vanilla in the southern Pacific Islands. Hawaii Strain II was most closely related to a taro DsMV isolate CTCRI-II-14 (KT026108.1) from India. Phylogenetic analysis of all available DsMV isolates based on amino acid sequences of their coat protein showed some correlation between host plant and genetic diversity. Analyses of DsMV genome sequences detected three recombinants from China and India among the six isolates with known complete genome sequences. The DsMV strain NC003537.1 from China is a recombinant of KJ786965.1 from India and Hawaii Strain II. Another DsMV strain KT026108.1 is a recombinant of Hawaii Strain II and NC003537.1 from China. The third DsMV strain KJ786965.1 from India is a recombinant of Hawaii Strain II and NC003537.1 from China. To our knowledge, this is the first report of recombination events in DsMV. Both Hawaii Strains I and II of DsMV were found widespread throughout the Hawaiian islands.


The incidence of colorectal cancer during pregnancy in Japan: report of two cases and review of Japanese cases.
Colorectal cancer during pregnancy is very rare. We report two additional cases of rectal carcinoma. A 34-year-old woman with an obstructive adenocarcinoma of the rectal region was diagnosed at labor. A 35-year-old woman with an adenocarcinoma of the rectal region was diagnosed at 32 weeks of gestation and underwent a cesarean section and rectal resection at 35 weeks of gestation. A retrospective review of the Japanese literature was performed to identify patients who appeared to have primary colorectal cancer during pregnancy. Thirty-six patients with colon cancer (75.0%), 10 (20.8%) with rectal cancer, and two (4.2%) of unknown sites have been reported in Japanese series. The average age of the mother was 32.2 years. The calculated incidence of colorectal cancer among Japanese pregnant women was one case per 502,316 live births during the years between 1986 through 1995. Although the majority of colorectal cancers diagnosed during pregnancy are rectal carcinomas, the patients in Japan were predominantly complicated by colon cancer. The fetal risk seems small, because there were no cases of colorectal cancer metastatic to the products of conception.


Bioreactor cultivation enhances NTEB formation and differentiation of NTES cells into cardiomyocytes.
Autogenic embryonic stem cells established from somatic cell nuclear transfer (SCNT) embryos have been proposed as unlimited cell sources for cell transplantation-based treatment of many genetic and degenerative diseases, which can eliminate the immune rejection that occurs after transplantation. In the present study, pluripotent nuclear transfer ES (NTES) cell lines were successfully established from different strains of mice. One NTES cell line, NT1, with capacity of germline transmission, was used to investigate in vitro differentiation into cardiomyocytes. To optimize differentiation conditions for mass production of embryoid bodies (NTEBs) from NTES cells, a slow-turning lateral vessel (STLV) rotating bioreactor was used for culturing the NTES cells to produce NTEBs compared with a conventional static cultivation method. Our results demonstrated that the NTEBs formed in STLV bioreactor were more uniform in size, and no large necrotic centers with most of the cells in NTEBs were viable. Differentiation of the NTEBs formed in both the STLV bioreactor and static culture into cardiomyocytes was induced by ascorbic acid, and the results demonstrated that STLV-produced NTEBs differentiated into cardiomyocytes more efficiently. Taken together, our results suggested that STLV bioreactor provided a more ideal culture condition, which can facilitate the formation of better quality NTEBs and differentiation into cardiomyocytes more efficiently in vitro.


Role of residual potentials inside circumferential pulmonary veins ablation lines in the recurrence of paroxysmal atrial fibrillation.
Residual gaps due to incomplete ablation lines are known to be the most common cause of recurrent atrial fibrillation (AF) after catheter ablation. We hypothesized that any residual potentials at the junction of the left atrium and pulmonary vein (PV), inside the circumferential PV ablation (CPVA) lines, would contribute to the recurrence of AF or post-AF ablation atrial flutter (AFL); therefore, the elimination of these potentials increases AF-/AFL-free survival rates. One hundred and two patients with paroxysmal AF (PAF) were enrolled and prospectively randomized to a group with ablation of residual potentials as add-on therapy to CPVA + PV electrical isolation (PVI) (group 1, n = 49), or a group without ablation of the residual potentials (group 2, n = 53). Post-CPVA residual potentials, inside the ablation lines, were identified by contact bipolar electrode mapping catheter and a detailed 3-dimensional voltage map. Twenty-three patients in group 1 and 18 patients in group 2 had post-CPVA residual potentials (46.9% vs 34.0%, P = 0.182). The AF-/AFL-free survival rate during follow-up of 23.3 ± 7.9 months was not different in comparisons between the 2 groups (P = 0.818), and 79.6% and 81.1% of the patients in groups 1 and 2 maintained a sinus rhythm (P = 0.845), respectively. Residual potentials inside CPVA were commonly found in the patients with PAF after CPVA + PVI. Further ablation of residual potentials did not increase the efficacy of catheter ablation in patients with PAF.


Plasmacytoid monocytes (so-called plasmacytoid T-cells) in Kikuchi's lymphadenitis. An immunohistologic study.
Three cases of Kikuchi's lymphadenitis were studied immunohistochemically on paraffin-embedded material in order to compare the plasmacytoid monocyte aggregates occurring in this disorder with plasmacytoid monocyte clusters in nonspecific reactive lymphadenitis. One of the cases was also analyzed on frozen material. In Kikuchi's lymphadenitis, plasmacytoid monocytes expressed the CD38 and LN1 antigens in addition to their monocyte/macrophage antigens found in nonspecific reactive lymph nodes. These plasmacytoid monocyte aggregates contained large numbers of Mac387+ lysozyme+ macrophages, scattered HLADR+ dendritic cells, and high numbers of CD8+ T-lymphocytes. Collections of T-immunoblasts or areas of necrosis were observed within these aggregates. The authors speculate that the histologic feature of Kikuchi's lymphadenitis is the morphologic substrate of a T-cell-mediated cytotoxic immune reaction occurring in plasmacytoid monocyte aggregates and resulting in plasmacytoid monocyte damage and necrosis.


PCI-24781 can improve in vitro and in vivo developmental capacity of pig somatic cell nuclear transfer embryos.
To examine the effect of PCI-24781 (abexinostat) on the blastocyst formation rate in pig somatic cell nuclear transferred (SCNT) embryos and acetylation levels of the histone H3 lysine 9 and histone H4 lysine 12. Treatment with 0.5 nM PCI-24781 for 6 h significantly improved the development of cloned embryos, in comparison to the control group (25.3 vs. 10.5 %, P < 0.05). Furthermore, PCI-24781 treatment led to elevated acetylation of H3K9 and H4K12. TUNEL assay and Hoechst 33342 staining revealed that the percentage of apoptotic cells in blastocysts was significantly lower in PCI-24781-treated SCNT embryos than in untreated embryos. Also, PCI-24781-treated embryos were transferred into three surrogate sows, one of whom became pregnant and two fetuses developed. PCI-24781 improves nuclear reprogramming and the developmental potential of pig SCNT embryos.


Performance of preoperative breast MRI based on breast cancer molecular subtype.
To assess the performance of preoperative breast MRI biopsy recommendations based on breast cancer molecular subtype. All preoperative breast MRIs at a single academic medical center from May 2010 to March 2014 were identified. Reports were reviewed for biopsy recommendations. All pathology reports were reviewed to determine biopsy recommendation outcomes. Molecular subtypes were defined as Luminal A (ER/PR+ and HER2-), Luminal B (ER/PR+ and HER2+), HER2 (ER-, PR- and HER2+), and Basal (ER-, PR-, and HER2-). Logistic regression assessed the probability of true positive versus false positive biopsy and mastectomy versus lumpectomy. There were 383 patients included with a molecular subtype distribution of 253 Luminal A, 44 Luminal B, 20 HER2, and 66 Basal. Two hundred and thirteen (56%) patients and 319 sites were recommended for biopsy. Molecular subtype did not influence the recommendation for biopsy (p = 0.69) or the number of biopsy site recommendations (p = 0.30). The positive predictive value for a biopsy recommendation was 42% overall and 46% for Luminal A, 43% for Luminal B, 36% for HER2, and 29% for Basal subtype cancers. The multivariate logistic regression model showed no difference in true positive biopsy rate based on molecular subtype (p = 0.78). Fifty-one percent of patients underwent mastectomy and the multivariate model demonstrated that only a true positive biopsy (odds ratio: 5.3) was associated with higher mastectomy rates. Breast cancer molecular subtype did not influence biopsy recommendations, positive predictive values, or surgical approaches. Only true positive biopsies increased the mastectomy rate.