It can be safe to discontinue oral anticoagulants after successful atrial fibrillation ablation: A systematic review and meta-analysis of cohort studies.
Current guidelines recommended that oral anticoagulants (OACs) should last for a minimum first 2 months after atrial fibrillation (AF) ablation and the long-term decision of anticoagulation after AF ablation should be based on the individual patient's risk of stroke rather than the rhythm status. There is controversy about the safety of discontinuing OACs in patients with atrial fibrillation after the blanking period due to the divergences between consensus recommendations and clinical practice. Electronic bibliographic sources (PubMed, Embase, and Web of Science) were searched until August 2023 to identify cohort studies about the safety of discontinuing OACs in patients with AF after the blanking period. The primary outcome was thromboembolism (TE). The secondary outcome was major bleeding events (MBEs). Two authors extracted articles independently using predefined data fields. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated based on a random-effects model. A total of 16 studies (11 prospective cohorts and 5 retrospective cohorts) enrolling 23,942 patients (14,382 OFF-OAC and 9560 ON-OAC) were included in our analysis. No significant difference emerged in the risk of TE between OFF-OAC and ON-OAC patients following AF ablation after the banking period (OR = 0.66; 95%CI, 0.43-1.01). Similar results emerged in the patients with a high risk of TE after stratification by the risk level of TE (OR = 0.72; 95%CI, 0.25-2.08). A significant reduction in incidences of major bleeding was found in the OFF-OAC patients compared with the ON-OAC patients (OR = 0.23; 95%CI, 0.12-0.42). Subgroup analyses for TE found a reduction of incidences in the subgroups who switched to antiplatelet drugs and with a follow-up duration <3 years. Subgroup analyses for MBEs found a significant reduction of incidences in all subgroups. Our study suggests it can be safe to discontinue OACs after successful AF ablation. Discontinuation of OACs may reduce the risk of MBEs while not increasing the risk of TE.


Sulodexide improves endothelial dysfunction in streptozotocin-induced diabetes in rats.
Diabetes mellitus is associated with many complications including retinopathy, nephropathy, neuropathy and angiopathy. Increased cardiovascular risk is accompanied with diabetes-induced endothelial dysfunction. Pharmacological agents with endothelium-protective effects may decrease cardiovascular complications. In present study sulodexide (glycosaminoglycans composed from heparin-like and dermatan fractions) was chosen to evaluate its protective properties on endothelial dysfunction in diabetes. Effect of sulodexide treatment (SLX, 100 UI/kg/day, i.p.) in 5 and 10 weeks lasting streptozotocin-induced diabetes (30 mg/kg/day, i.p. administered for three consecutive days) was investigated. Animals were divided into four groups: control (injected with saline solution), control-treated with sulodexide (SLX), diabetic (DM) and diabetic-treated with sulodexide (DM+SLX). The pre-prandial and postprandial plasma glucose levels, number of circulating endothelial cells (EC) and acetylcholine-induced relaxation of isolated aorta and mesenteric artery were evaluated. Streptozotocin elicited hyperglycemia irrespective of SLX treatment. Streptozotocin-induced diabetes enhanced the number of circulating endothelial cells compared to controls. SLX treatment decreased the number of EC in 10-week diabetes. Acetylcholine-induced relaxation of mesenteric arteries was significantly impaired in 5 and 10-week diabetes. SLX administration improved relaxation to acetylcholine in 5 and 10-week diabetes. Diabetes impaired acetylcholine-induced relaxation of rat aorta irrespective of SLX treatment. Our results demonstrate that SLX treatment lowers the number of circulating endothelial cells and improves endothelium-dependent relaxation in small arteries. These findings suggest endothelium-protective effect of sulodexide in streptozotocin-induced diabetes.


Ig gene rearrangement steps are initiated in early human precursor B cell subsets and correlate with specific transcription factor expression.
The role of specific transcription factors in the initiation and regulation of Ig gene rearrangements has been studied extensively in mouse models, but data on normal human precursor B cell differentiation are limited. We purified five human precursor B cell subsets, and assessed and quantified their IGH, IGK, and IGL gene rearrangement patterns and gene expression profiles. Pro-B cells already massively initiate D(H)-J(H) rearrangements, which are completed with V(H)-DJ(H) rearrangements in pre-B-I cells. Large cycling pre-B-II cells are selected for in-frame IGH gene rearrangements. The first IGK/IGL gene rearrangements were initiated in pre-B-I cells, but their frequency increased enormously in small pre-B-II cells, and in-frame selection was found in immature B cells. Transcripts of the RAG1 and RAG2 genes and earlier defined transcription factors, such as E2A, early B cell factor, E2-2, PAX5, and IRF4, were specifically up-regulated at stages undergoing Ig gene rearrangements. Based on the combined Ig gene rearrangement status and gene expression profiles of consecutive precursor B cell subsets, we identified 16 candidate genes involved in initiation and/or regulation of Ig gene rearrangements. These analyses provide new insights into early human precursor B cell differentiation steps and represent an excellent template for studies on oncogenic transformation in precursor B acute lymphoblastic leukemia and B cell differentiation blocks in primary Ab deficiencies.


The correlation of neurophysiological findings with clinical and functional status in patients following traumatic nerve injury.
In this study, we aimed to determine whether there is a correlation between the electrodiagnostic findings and the functional status, muscle strength and sensibility in patients with traumatic nerve injury to the wrists. We assessed 50 patients at a mean of 11.6 months (SD 5.85) (range 6-25) after nerve injury. Sensibility was assessed by monofilament testing. Motor function was evaluated by assessing the manual muscle grade of the abductor pollicis brevis and abductor digiti minimi muscles. Function was evaluated by the Sollerman Hand Function Test. The amplitudes of the compound muscle action potential and the sensory nerve action potential were determined by electroneuromyography. While the compound muscle action potential and sensory nerve action potential amplitudes had significant correlation with muscle grade and Semmes Weinstein Monofilament tests, there was no correlation with the functional scores.


Virtual screening, docking, and dynamics of potential new inhibitors of dihydrofolate reductase from Yersinia pestis.
In the present work, we propose to design drugs that target the enzyme dihydrofolate redutase (DHFR) as a means of a novel drug therapy against plague. Potential inhibitors of DHFR from Yersinia pestis (YpDHFR) were selected by virtual screening and subjected to docking, molecular dynamics (MD) simulations, and Poisson-Boltzmann surface area method, in order to evaluate their interactions in the active sites of YpDHFR and human DHFR (HssDHFR). The results suggested selectivity for three compounds that were further used to propose the structures of six new potential selective inhibitors for YpDHFR.


Four-square. Practice profitability stands on four foundations.
A medical practice's profitability stands on four legs: physician productivity, accounts receivable, overhead costs and ancillary revenue. The author describes where weakness can occur in each of these foundations and how to remedy such structural defects.


"Keep Me Doing What I Love": A Photovoice Evaluation of the Missouri AgrAbility Project.
The Missouri AgrAbility program links the Cooperative Extension Service at a land-grant university with a nonprofit disability organization to provide practical education and assistance that promotes rural independence. This project utilized Photovoice to describe how Missouri AgrAbility clients perceived how the program impacts their lives. This article relates clients' perceptions of the impact of the AgrAbility program on their lives to the socio-ecologic model framework. Although the primary focus of AgrAbility is to help individuals who have disabilities maintain their independence, all levels of the socio-ecological model are integral in meeting the needs of program participants.


A critique of Rasch residual fit statistics.
In test analysis involving the Rasch model, a large degree of importance is placed on the "objective" measurement of individual abilities and item difficulties. The degree to which the objectivity properties are attained, of course, depends on the degree to which the data fit the Rasch model. It is therefore important to utilize fit statistics that accurately and reliably detect the person-item response inconsistencies that threaten the measurement objectivity of persons and items. Given this argument, it is somewhat surprising that there is far more emphasis placed in the objective measurement of person and items than there is in the measurement quality of Rasch fit statistics. This paper provides a critical analysis of the residual fit statistics of the Rasch model, arguably the most often used fit statistics, in an effort to illustrate that the task of Rasch fit analysis is not as simple and straightforward as it appears to be. The faulty statistical properties of the residual fit statistics do not allow either a convenient or a straightforward approach to Rasch fit analysis. For instance, given a residual fit statistic, the use of a single minimum critical value for misfit diagnosis across different testing situations, where the situations vary in sample and test properties, leads to both the overdetection and underdetection of misfit. To improve this situation, it is argued that psychometricians need to implement residual-free Rasch fit statistics that are based on the number of Guttman response errors, or use indices that are statistically optimal in detecting measurement disturbances.


Night eating syndrome: implications for severe obesity.
Night eating syndrome (NES) was first identified in 1955 by Stunkard, a psychiatrist specialising in eating disorders (ED). Over the last 20 years considerable progress has been made in defining NES as a significant clinical entity in its own right and it has now been accepted for inclusion in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) due for publication in 2013. NES is considered a dysfunction of circadian rhythm with a disassociation between eating and sleeping. Core criteria include a daily pattern of eating with a significantly increased intake in the evening and/or night time, as manifested by one or both of the following: at least 25% of food intake is consumed after the evening meal or at least two episodes of nocturnal eating per week. An important recent addition to core criteria includes the presence of significant distress and/or impairment in functioning. Stunkard's team recommend further investigation on the pathogenesis of NES, in particular its relationship with traumatic life events, psychiatric comorbidity, the age of onset of NES and course of NES over time. The relationship between NES and other ED also requires further clarification as night-eaters exhibit some features of other ED; previous guidance to separate NES from other ED may have hindered earlier characterisation of NES. Evidence from European and American studies suggests NES features strongly in populations with severe obesity. The complex interplay between depression, impaired sleep and obesity-related comorbidity in severely obese individuals makes understanding NES in this context even more difficult. This review examines evidence to date on the characterisation of NES and concludes by examining the applicability of current NES criteria to individuals with severe obesity.


Expression of protein kinase regulator genes in human ear and cloning of a gamma subtype of the 14-3-3 family of proteins.
We have used oligonucleotides corresponding to conserved regions of protein kinase regulators of 14-3-3 gene family as primers to amplify these genes from cDNAs constructed from the human fetal inner ear. Sequence characterization of clones revealed that the 14-3-3 cDNA library from the fetal inner ear has high abundance of clones encoding a protein kinase regulator (theta subtype), a member of 14-3-3 gene family, and relatively lower abundance of clones for two other members of the gene family. One of these genes is identical to the eta subtype of human 14-3-3 genes; there is no cloned gene for the other subtype in the human 14-3-3 gene family in the nucleic acid data bases. A sequence homology search revealed that the latter shared significant homology with the gamma subtype of the rat 14-3-3 family. On the basis of the sequence data, it appears that this clone represents a human homolog of the rat gamma subtype. The results demonstrate the expression of 14-3-3 genes in the inner ear, characterize a human homolog of the rat gamma subtype of 14-3-3, implicate these proteins in ear development, and indicate the utility of gene family polymerase chain reaction (PCR) for investigating gene expression in specific tissues.


Endoscopic papillectomy for carcinoma of the ampulla of Vater: possible standardization based on endoscopy and immunohistochemistry.
Clinicopathological investigation of the indications for the use of endoscopic papillectomy as a treatment for carcinoma in situ of the ampulla of Vater (CAV). Of 97 patients diagnosed with CAV in our department over the last 15 years, the 5 patients who received a carcinoma in situ diagnosis and were included in this retrospective study. The lesions in the patients were classified as either the superficial or luminal type, based on endoscopic findings. Histological findings showed that the major duodenal papilla (Ad) was the main site of CAV in the superficial type and that the common duct into the duodenal lumen (Ac) was the primary site in the luminal type. Immunohistochemical staining showed that the superficial-type lesions were positive for cytokeratin 20, suggesting development of the cancer from the Ad. The luminal-type lesion was positive for cytokeratin 7 and negative for cytokeratin 20, suggesting an origin in the pancreatobiliary duct. Mucin-2 was expressed in the superficial type, and mucin-1 in the luminal type. Superficial-type lesions, which are principally located in the Ad, exhibit little tendency to invade surrounding tissues, whereas the luminal-type lesions, which are predominantly located in the Ac, may tend to be more invasive. Although endoscopic papillectomy might be indicated for the superficial-type lesions, caution is needed in the determination of the extent of luminal-type lesions.


Low pH suppresses synthesis of heat-shock proteins and thermotolerance.
Chinese hamster ovary (CHO) cells heated for 10 min at 45 degrees C became thermotolerant to a second heat exposure at either pH 7.3 or 6.6. However, low pH delayed the development of thermotolerance and suppressed the rate of synthesis of all proteins, including heat-shock proteins (HSPs). Low-pH-tolerant mutant CHO cells (PHV2) in pH 6.6 medium were also delayed in both the development of thermotolerance and protein synthesis, though less than CHO cells in pH 6.6 medium. The rate of synthesis of inducible HSP-70 under the three conditions paralleled the kinetics of the development of thermotolerance. The intracellular pH (pHi) of CHO cells in pH 6.6 medium, whether heated or not, was far lower than CHO cells in pH 7.3 medium, and the pHi of PHV2 cells in pH 6.6 medium was close to that of CHO cells in pH 7.3 medium after the initial heat shock. Amiloride enhanced the effect of low-pH medium on pHi HSP synthesis and development of thermotolerance. The concentration of HSP-70 was also measured by flow cytometry. The level of HSP-70 was not altered within the first 4 h after a 10-min 45.0 degrees C initial heat treatment during which the major portion of thermotolerance developed, though the level of HSP-70 increased rapidly after 4 h. Low pH caused a further delay in the increase in HSP-70. We conclude that low-pH medium may inhibit the synthesis of HSPs in part by lowering pHi, but the delay and suppression of development of thermotolerance is not primarily due to the inhibition of HSP synthesis.


Improved method for intra-abdominal drainage.
It has been shown that, by the addition of both suction and sump to straight drainage, the efficiency of the drain can be improved. A drain is described herein which uses these principles by combining a Jackson-Pratt drain, urethral catheter and Penrose drain. The combination drain has been used clinically and has proved to be both efficient and safe.


Solid-state NMR investigation of effect of fluorination and methylation on prednisolone conformation.
Prednisolone (Prd) is a polymorphous synthetic corticosteroid that has three crystalline forms mediated by different solvents. In this study, we have demonstrated that solid-state {(1)H}(13)C cross-polarization/magic angle spinning (CP/MAS) NMR spectroscopy is able to resolve the effects of methylation and fluorination on the conformation of the steroidal rings in Prd. Two compounds were chosen for the study, 6-α-methylprednisolone (Prd-6M) and 6-α-fluoroprednisolone (Prd-6F). The (13)C signals of Prd-6F showed primarily doublet patterns, with splittings of 40-380 Hz, indicating multiple ring conformations, whereas the (13)C signals of Prd and Prd-6M exhibited a singlet pattern, indicating a unique conformation. Using evidence from chemical shift deviation and anisotropy analysis, we have demonstrated by solid-state NMR that Prd-6F adopts two different steroidal ring conformations that are different from that of Prd-6M, and less similar to that of unsubstituted Prd.


Experiences with different computerprograms for the ECG-analysis.
As the use of computers for ECG-analysis has left the stage of laboratory investigation, and different systems are offered by industrial firms with high grade promises concerning their reliability, it seemed about time to perform an evaluation of the programs available. Each ECG of 252 adult patients was recorded in one session from adhesive electrodes within 10 minutes on the magnetic tapes of the data-acquisition-units of four different manufacturers. The computer-analysis of each of these ECGs was done by six programs of Pordy (Mt. Sinai-Hospital, New York), Caceres, Smith (Mayo Clinic, Rochester), Arvedson, Riedl with modified criteria of the USPHS and Riedl with criteria of the Minnesota-code. Besides this each ECG was also analysed in the conventional way by each of the three cardiologists involved in this study. The results of the computers' and the physicians' analysis concerning rhythm, extrasystoles, infarctions and ST-T-segment-variations are demonstrated and discussed.


Suspicious of Acute Kidney Graft Rejection: Tacrolimus Pharmacokinetics Under Methylprednisolone Therapy.
Acute rejection remains one of the main complications in the first months after transplantation and may influence long-term outcomes. Tacrolimus has proven its usefulness in solid organ transplants and its monitoring through the application of pharmacokinetic concepts to optimize individual drug therapy. This research proposes to evaluate the tacrolimus pharmacokinetic parameters in patients suspected of acute kidney graft rejection under methylprednisolone pulse therapy. Eleven adult tacrolimus-treated renal recipients were selected from a prospective, single-arm, single-center cohort study, with suspicion of acute rejection although in use of methylprednisolone pulses therapy. They were followed up for three months posttransplantation, being tacrolimus trough serum concentrations determined using a chemiluminescent magnetic immunoassay, and pharmacokinetic parameters were estimated by using a nonlinear mixed-effects model implemented by Monolix 2020R1. A tacrolimus trough serum concentration range of 8 to 12 ng.mL-1 was considered therapeutic. Six patients showed acute cellular rejection, and two of them in addition had an antibody- mediated rejection. Tacrolimus trough serum concentration was below the reference range in eight patients. Most patients showed a high tacrolimus concentration intrapatient and pharmacokinetic parameters variability. The obtained pharmacokinetics parameters helped in understanding the kidney recipient patients' tacrolimus behavior, assisting in the improvement of individual drug therapy and reducing the risk of acute rejection episodes.


Evaluation of TATI and CYFRA 21-1 in patients with head and neck squamous cell carcinoma.
This preliminary nonrandomized study was conducted to evaluate the clinical usefulness of TATI and CYFRA 21-1 as tumor markers in head and neck squamous cell carcinoma. Serum levels of these markers were measured from 122 subjects of a tertiary-care university hospital, divided into four groups: (1) normal individuals and patients with (2) inflammatory pathology, (3) benign tumors and (4) squamous cell carcinoma of the head and neck. Serum samples were collected before and after treatment, with a mean follow-up period of 12 months. The cutoff level, sensitivity, specificity and likelihood ratio of a positive and negative test were: 21 microg/l, 66.6%, 93.75%, 10.6 and 0.35 for TATI; 3.3 microg/l, 28.5%, 95%, 5.7 and 0.75 for CYFRA 21-1, respectively. Both markers presented elevated mean values and statistically significant differences in the cancer patient group compared with the other groups. Significant differences were also observed between the stage of disease and tumor differentiation. TATI levels seem to relate positively to the course of disease during the follow-up period. Although CYFRA 21-1 values presented significant differences, the majority of them were under the cutoff level. We conclude that TATI seems to play a role in the clinical evaluation of head and neck squamous cell carcinoma, while the usefulness of CYFRA 21-1 is limited.


Bi Nanosheets on Porous Carbon Cloth Composites for Ultrastable Flexible Nickel-Bismuth Batteries.
The use of bismuth (Bi) as an anode material in nickel-metal batteries has gained significant attention due to its highly reversible redox reaction and suitable operating conditions. However, the cycling stability and flexibility of nickel-bismuth (Ni//Bi) batteries need to be further improved. This paper employs a facile electrodeposition technique to prepare Bi nanosheets uniformly grown on a porous carbon cloth (PCC), denoted as Bi-PCC electrodes. The Bi-PCC electrode portrays a specific surface area and good wettability that enable fast charge transfer and ion transport channels. Consequently, the Bi-PCC electrode demonstrates a high specific capacity of up to 297.1 mAh g-1 at 2 A g-1, with a capacity retention of up to 71.5% at 2-40 A g-1 and an impressive capacity retention of 79.9% after 1000 cycles at 2-40 A g-1. More importantly, the flexible rechargeable Ni//Bi battery (denoted as Ni(OH)2-PCC//Bi-PCC) with Bi-PCC as the anode and Ni(OH)2-PCC as the cathode has excellent electrochemical performance. The Ni(OH)2-PCC//Bi-PCC battery boasts a remarkable capacity retention of 93.6% after 3000 cycles at 10 A g-1. Further, the cell presents a maximum energy density of 73.1 Wh kg-1 and an impressive power density of 11.9 kW kg-1.


High frequency of microsatellite instability and loss of mismatch-repair protein expression in patients with double primary tumors of the endometrium and colorectum.
Patients with the familial syndrome hereditary nonpolyposis colorectal carcinoma (HNPCC) exhibit an increased risk for several tumor types, of which the greatest lifetime risk is for colorectal and endometrial carcinoma. HNPCC is caused by a germline mutation in one of several identified mismatch repair (MMR) genes and typically presents with microsatellite instability (MSI) and frequent loss of MMR protein expression in the tumor tissue. The objective of this study was to estimate the proportion of double primary tumors of the endometrium and colorectum that displays tumor characteristics suggestive of MMR deficiency. The authors used the southern Sweden regional population-based Cancer Registry to identify women who developed double primary tumors of the endometrium and colorectum. Of the 256 women who were diagnosed with carcinoma at both of these sites during the period 1958-1998, 39 women had developed their first tumor before age 50 years. The authors successfully retrieved 67 tumors from 36 of these patients and analyzed them for MSI and immunohistochemical expression of the MMR genes, MLH1, MSH2, and MSH6. The MSI status of the 67 tumors was high MSI in 37 tumors, low MSI in 13 tumors, and microsatellite stable (MSS) in 17 tumors. Immunohistochemical loss of MMR protein expression was correlated with MSI status and was demonstrated in 29 high MSI tumors, in 1 low MSI tumor, and in 1 MSS tumor. A concordant loss of the same MMR protein in both tumors was found in 12 of 27 patients. The authors demonstrated a high frequency of MSI (75%) in tumors from women with endometrial and colorectal carcinoma who had their first tumor diagnosed before age 50 years and observed concordant immunohistochemical loss of MMR protein expression, suggestive of a possible underlying germline mutation, in 12 of 27 patients (44%). They concluded that double primary malignancies of the colorectum and endometrium at a young age should make the clinician suspect HNPCC.


One Target, Two Mechanisms: The Impact of 'Candidatus Liberibacter asiaticus' and Its Vector, Diaphorina citri, on Citrus Leaf Pigments.
Huanglongbing (HLB) is currently the largest threat to global citrus production. We examined the effect of HLB pathogen 'Candidatus Liberibacter asiaticus' infection or infestation by its vector, Diaphorina citri, on 'Valencia' sweet orange leaf pigments using high-performance liquid chromatography, followed by gene expression analysis for 46 involved genes in carotenoid and chlorophyll biosynthesis pathways. Both 'Ca. L. asiaticus' and D. citri alter the total citrus leaf pigment balance with a greater impact by 'Ca. L. asiaticus'. Although zeaxanthin was accumulated in 'Ca. L. asiaticus'-infected leaves, chlorophyllide a was increased in D. citri-infested plants. Our findings support the idea that both 'Ca. L. asiaticus' and D. citri affect the citrus pigments and promote symptom development but using two different mechanisms. 'Ca. L. asiaticus' promotes chlorophyll degradation but accelerates the biosynthesis of carotenoid pigments, resulting in accumulation of abscisic acid and its precursor, zeaxanthin. Zeaxanthin also has a photoprotective role. By contrast, D. citri induced the degradation of most carotenoids and accelerated chlorophyll biosynthesis, leading to chlorophyllide a accumulation. Chlorophyllide a might have an antiherbivory role. Accordingly, we suggest that citrus plants try to defend themselves against 'Ca. L. asiaticus' or D. citri using multifaceted defense systems, based on the stressor type. These findings will help in better understanding the tritrophic interactions among plant, pathogen, and vector.


Expression of USP22 and the chromosomal passenger complex is an indicator of malignant progression in oral squamous cell carcinoma.
Oral cancer is a common cancer of the head and neck. Oral squamous cell carcinoma (OSCC) represents almost 90% of the total cases of head and neck cancer. Ubiquitin-specific protease 22 (USP22) is a deubiquitinating hydrolase, and it is highly expressed in various types of cancer, which also typically have a poor prognosis. Aurora-B and Survivin, which belong to the chromosomal passenger complex, are also highly expressed in a number of types of cancer. In the present study, USP22 expression and its associations with Aurora-B and Survivin, and the clinicopathological features in OSCC were explored. USP22 is highly expressed in OSCC. Overexpression of USP22 is associated with lymph node metastasis and histological grade (P<0.01). Additionally, the expression of USP22 was positively associated with Aurora-B (P<0.01), Survivin (P<0.01), and Ki-67 (P<0.01). Furthermore, USP22 small interfering RNA inhibited cell growth and reduced the expression levels of Aurora-B, Survivin and Cyclin B, together with the upregulation of cyclin-dependent kinase inhibitor 1A (p21). These data suggest that USP22, Aurora-B and Survivin promote the OSCC development and may represent novel targets for OSCC diagnosis and treatment in the future.


Decrease in work function of transparent conducting ZnO tin films by phosphorus ion implantation.
To confirm the possibility of engineering the work function of ZnO thin films, we have implanted phosphorus ions into ZnO thin films deposited by radio-frequency magnetron sputtering. The fabricated films show n-type characteristics. It is shown that the electrical and optical properties of those thin films vary depending sensitively on the ion dose and rapid thermal annealing time. Compared to as-deposited ZnO films, the work-function of phosphorus ion-implanted ZnO thin films is observed to be lower and decreases with increasing ion doses. It is likely that the zinc or oxygen vacancies are firstly filled with the implanted phosphorus ions. With further increased ions, free electrons are generated as Zn2+ sites are replaced by those ions or interstitial phosphorus ions increase at the lattice sites, the fermi level by which approaches the conduction band and thus the work function decreases. Those films exhibit the optical transmittance higher than 85% within the visible wavelength range (up to 800 nm).


Thick filament length and isoform composition determine self-organized contractile units in actomyosin bundles.
Diverse myosin II isoforms regulate contractility of actomyosin bundles in disparate physiological processes by variations in both motor mechanochemistry and the extent to which motors are clustered into thick filaments. Although the role of mechanochemistry is well appreciated, the extent to which thick filament length regulates actomyosin contractility is unknown. Here, we study the contractility of minimal actomyosin bundles formed in vitro by mixtures of F-actin and thick filaments of nonmuscle, smooth, and skeletal muscle myosin isoforms with varied length. Diverse myosin II isoforms guide the self-organization of distinct contractile units within in vitro bundles with shortening rates similar to those of in vivo myofibrils and stress fibers. The tendency to form contractile units increases with the thick filament length, resulting in a bundle shortening rate proportional to the length of constituent myosin thick filament. We develop a model that describes our data, providing a framework in which to understand how diverse myosin II isoforms regulate the contractile behaviors of disordered actomyosin bundles found in muscle and nonmuscle cells. These experiments provide insight into physiological processes that use dynamic regulation of thick filament length, such as smooth muscle contraction.


Self-supervised learning of accelerometer data provides new insights for sleep and its association with mortality.
Sleep is essential to life. Accurate measurement and classification of sleep/wake and sleep stages is important in clinical studies for sleep disorder diagnoses and in the interpretation of data from consumer devices for monitoring physical and mental well-being. Existing non-polysomnography sleep classification techniques mainly rely on heuristic methods developed in relatively small cohorts. Thus, we aimed to establish the accuracy of wrist-worn accelerometers for sleep stage classification and subsequently describe the association between sleep duration and efficiency (proportion of total time asleep when in bed) with mortality outcomes. We developed and validated a self-supervised deep neural network for sleep stage classification using concurrent laboratory-based polysomnography and accelerometry data from three countries (Australia, the UK, and the USA). The model was validated within-cohort using subject-wise five-fold cross-validation for sleep-wake classification and in a three-class setting for sleep stage classification wake, rapid-eye-movement sleep (REM), non-rapid-eye-movement sleep (NREM) and by external validation. We assessed the face validity of our model for population inference by applying the model to the UK Biobank with 100,000 participants, each of whom wore a wristband for up to seven days. The derived sleep parameters were used in a Cox regression model to study the association of sleep duration and sleep efficiency with all-cause mortality. After exclusion, 1,448 participant nights of data were used to train the sleep classifier. The difference between polysomnography and the model classifications on the external validation was 34.7 minutes (95% limits of agreement (LoA): -37.8 to 107.2 minutes) for total sleep duration, 2.6 minutes for REM duration (95% LoA: -68.4 to 73.4 minutes) and 32.1 minutes (95% LoA: -54.4 to 118.5 minutes) for NREM duration. The derived sleep architecture estimate in the UK Biobank sample showed good face validity. Among 66,214 UK Biobank participants, 1,642 mortality events were observed. Short sleepers (<6 hours) had a higher risk of mortality compared to participants with normal sleep duration (6 to 7.9 hours), regardless of whether they had low sleep efficiency (Hazard ratios (HRs): 1.69; 95% confidence intervals (CIs): 1.28 to 2.24 ) or high sleep efficiency (HRs: 1.42; 95% CIs: 1.14 to 1.77). Deep-learning-based sleep classification using accelerometers has a fair to moderate agreement with polysomnography. Our findings suggest that having short overnight sleep confers mortality risk irrespective of sleep continuity.


Patients' Use of Multiple Hospitals in a Major US City: Implications for Population Management.
Understanding how often patients seek care from multiple hospitals is important for care of individuals and populations, but it is not routinely measured because of lack of data. This study used data from a health information exchange (HIE) to measure the frequency with which patients seek care from multiple hospitals. This was a retrospective cohort study (2010-2011) of all patients who sought emergency department (ED) or inpatient care at 6 participating hospitals in Manhattan. The study found that all 6 hospitals shared patients with each of the other hospitals and that 10.0% of all ED visits and 9.1% of all admissions were for patients who had been seen in a different hospital in the past 12 months. Patients are frequently seen by multiple hospitals, which poses a challenge for clinical care and population management. By capturing which patients are seen where and when, HIEs are well suited for facilitating population management.


Chemotherapeutic Potential of Carthamus Oxycantha Root Extract as Antidiarrheal and In Vitro Antibacterial Activities.
Our research work was designed to investigate the curative and preventive effects of Carthamus oxycantha root extract against diarrhea and microorganisms. For the antibacterial experiment, the agar well diffusion method was used against standard bacteria Staphylococcus aureus, Escherichia coli, Pseudomonas aeroginosa, and Salmonella typhi, while for the assessment of antidiarrheal activity, castor oil and the magnesium sulfate-induced diarrhea method was used on albino, laboratory-bred (BALB/c) mice at a dose rate of 200 and 400 mg/kg (body weight, b.w) orally. The methanol extract of C. oxycantha significantly (p < 0.001) decreased the frequency of defecation, and wet stools in a dose depended on the manner of after receiving magnesium sulfate (2 g/kg (b.w)) and castor oil (1.0 mL/mice). Furthermore, the extract of C. oxycantha showed concentration-dependent antimicrobial properties against S. aureus followed by S. typhi, E. coli, and P. aeroginosa bacterial strains, with inhibitions ranging from 10.5-15 mm. These findings show significant results that C. oxycantha is effective as an antidiarrheal and antibacterial agent. However, further works are needed to establish its mode of action.


Human papillomavirus type 16 in bowenoid papulosis, intraoral papillomas, and squamous cell carcinoma of the tongue.
A 33-year-old immunosuppressed man developed bowenoid papulosis on his genitalia, velvety papules and plaques in his mouth, and invasive squamous cell carcinoma of his tongue. All three lesions were positive for human papillomavirus type 16 (HPV-16). The case provides further circumstantial evidence for a role of HPV-16 in epithelial neoplasia. The possible roles of a second HPV infection and of immunosuppression are also discussed.


Anticholinergic Exposure During Rehabilitation: Cognitive and Physical Function Outcomes in Patients with Delirium Superimposed on Dementia.
We examined the association between anticholinergic medication exposure and subsequent cognitive and physical function in patients with delirium superimposed on dementia during rehabilitation. We also examined length of stay and discharge disposition by anticholinergic medication exposure. In this secondary analysis we used control group data from an ongoing randomized clinical trial. Participants with delirium and dementia were enrolled at admission to post-acute care. These 99 participants had a mean age of 86.11 (±6.83) years; 67.6% were women; 98% were Caucasian; and 33% were positive for at least one APOE e4 allele. We obtained daily measures of cognitive and physical function using: Digit Span; memory, orientation and attention items from the Montreal Cognitive Assessment; CLOX; the Confusion Assessment Method; and the Barthel Index. Anticholinergic medication exposure was measured weekly using the Anticholinergic Cognitive Burden Scale. Using multilevel models for time we found that greater use of clinically relevant anticholinergic medications in the previous week reduced cognitive and physical function, as measured by Digit Span Backwards and the Barthel index, in the current week. There was no effect of anticholinergic medication use on delirium severity, and APOE status did not moderate any outcomes. Greater use of clinically relevant anticholinergic medications was related to longer length of stay but not discharge disposition. For vulnerable older adults, anticholinergic exposure represents a potentially modifiable risk factor for poor attention, working memory, physical function, and greater length of stay during rehabilitation.


Mechanisms of the modulation of pacemaker activity by GnRH peptides in the terminal nerve-GnRH neurons.
According to our working hypothesis, the terminal nerve (TN)-gonadotropin releasing hormone (GnRH) system functions as a neuromodulatory system that regulates many long-lasting changes in animal behaviors. We have already shown by using in vitro whole brain preparations of a small fish (dwarf gourami) that the pacemaker activities of TN-GnRH neurons are modulated biphasically by salmon GnRH, which is the same molecular species of GnRH produced by TN-GnRH neurons themselves; the modulation consists of initial transient decrease and late increase of firing frequency. In the present study, we investigated the possible involvement of Ca2+ release from intracellular store and voltage dependent Ca2+ currents in the modulation of pacemaker activities. Pharmacological blockade of Ca2+ release from intracellular stores or apamin-sensitive Ca(2+)-activated K+ current inhibited the initial transient decrease of firing frequency by sGnRH. On the other hand, bath application of Ca2+ channel blockers Ni2+ or La3+ slowed down the pacemaker frequency and attenuated the rate of the late increase of pacemaker frequency by GnRH. Furthermore, voltage-clamp experiments suggested that low-voltage-activated (LVA) Ca2+ current and hihg-voltage-activated (HVA) Ca2+ current were present in the TN-GnRH neurons, and bath application of GnRH shifted the activation threshold of HVA Ca2+ current to more negative potentials. These results suggest that (1) sGnRH induces Ca2+ release from intracellular stores and activates apaminsensitive Ca(2+)-activated K+ current so that it decreases the frequency of pacemaker activity in the initial phase, (2) some kinds of Ca2+ currents contribute to the generation and modulation of pacemaker activities, and (3) HVA Ca2+ current is facilitated by sGnRH so that it increases the frequency of pacemaker activity in the late phase.


Synergistic coactivator function by coactivator-associated arginine methyltransferase (CARM) 1 and beta-catenin with two different classes of DNA-binding transcriptional activators.
The androgen receptor (AR) binds to and activates transcription of specific genes in response to its cognate steroid hormone, dihydrotestosterone. Transcriptional activation by the DNA-bound AR is accomplished with the help of a variety of coactivator proteins. For example, the p160 coactivators bind directly to AR and recruit additional coactivators such as the histone acetyltransferase p300 and the histone methyltransferase CARM1. The current study tested whether CARM1 can cooperate with other types of coactivator proteins. Recently it was shown that beta-catenin can also bind directly to and serve as a coactivator for AR. Here it is shown that CARM1 binds to beta-catenin and can function in synergy with beta-catenin and p300 as coactivators for AR. The methyltransferase activity of CARM1 is important for its synergistic coactivator function with beta-catenin. The synergistic coactivator function of beta-catenin and CARM1 is not restricted to steroid receptors because these two coactivators can also act synergistically with another type of DNA binding transcriptional activator, LEF-1/TCF-4.


The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia.
Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML.


High-efficiency cascaded Raman fiber laser with random distributed feedback.
Cascaded lasing provided by Raman gain (at 1115-nm pumping) and random distributed feedback (via Rayleigh backscattering) in a 1.65-km phosphosilicate fiber is studied. Output power for the second Stokes component (1398 nm) exceeds 5 W at pump power of 11 W. In contrast to conventional cascaded Raman laser with high-Q cavity for the intermediate first Stokes component, there is no cavity here and no cavity losses, correspondingly. Longitudinal power distribution is shown to be quite different also. As a result, the efficiency of pump to 2nd Stokes wave conversion is not influenced by the intermediate stage and depends only on the integral attenuation in the fiber. Herewith, the number of generated 2nd Stokes photons at the output may even exceed the absorbed pump photons due to the lower attenuation of Stokes waves.


Solute Stabilization Effects of Nanoparticles Containing Boronic Acids in the Absence of Binding Pairs.
Boronic acids are widely used in materials science because of their ability to reversibly bind with diol and catechol moieties through dynamic covalent interactions in a pH- and oxidative-dependent manner. Considerably fewer studies focus on property modulation of boronic acid-based materials in the absence of a biding pair. Herein, we discuss the effects of the boronic acid-containing polymer block length on solute release kinetics from nanoparticles in a stimuli-responsive manner for on-demand delivery. In this study, ABC-type linear amphiphiles of poly(d,l-lactide) and poly(2-methacryloyloxyethyl phosphorylcholine) containing a middle block functionalized with 3-aminophenylboronic acid were synthesized by a combination of ring-opening and controlled free radical polymerizations. Nile red-loaded nanoparticles were self-assembled using a multi-inlet vortex mixer in a well-controlled manner. Release was evaluated at pH above and below the pKa of the boronic acid and in the presence of hydrogen peroxide. Our results show that release kinetics from nanoparticles incorporating a boronic acid-functionalized interlayer were slower than those without it, and the rate could be modulated according to pH and oxidative conditions. These effects can be attributed to several factors, including the hydrophobicity of the boronic acid block as well as hydrogen bonding interactions existing between locally confined boronic acids. While boronic acids are generally utilized as boronic/boronate esters, their stabilizing effects in the absence of appropriate binding pairs are relevant and should be considered in the design of boronic acid-based technologies.


[ENT news 2018].
The articles have been again selected among more than 15 000 abstracts and the review aims to be generalist. Interest of honey in head and neck pathologies, apnea syndrome, tonsillectomy and immunotherapy. In otology, middle ear infections and mastoiditis, cochlear implant in the elderly, deafness in children, auto-evaluation of audition and new perspectives regarding ciliar cell cultures. In rhinology the interest of different treatments including Xylitol, new technologies and nasal bleeding. In laryngology and thyroid surgery, guidelines for dysphonia, the interest of ultrasound in vocal cord evaluation and relation between thyroid surgery outcomes and training. HPV will be largely discussed as well as immunotherapy, interest of cannabis in cancer patients. Regarding salivary glands sialendoscopy, rerouting of salivary ducts and multiple detection of diseases in saliva.


Exploring polymorphism of benzene and naphthalene with free energy based enhanced molecular dynamics.
Prediction and exploration of possible polymorphism in organic crystal compounds are of great importance for industries ranging from organic electronics to pharmaceuticals to high-energy materials. Here we apply our crystal structure prediction procedure and the enhanced molecular dynamics based sampling approach called the Crystal-Adiabatic Free Energy Dynamics (Crystal-AFED) method to benzene and naphthalene. Crystal-AFED allows the free energy landscape of structures to be explored efficiently at any desired temperature and pressure. For each system, we successfully predict the most stable crystal structures at atmospheric pressure and explore the relative Gibbs free energies of predicted polymorphs at high pressures. Using Crystal-AFED sampling, we find that mixed structures, which typically cannot be discovered by standard crystal structure prediction methods, are prevalent in the solid forms of these compounds at high pressure.


Value of Duke treadmill score in predicting coronary artery lesion and the need for revascularisation.
Exercise electrocardiography is a long-standing method for the evaluation of coronary artery disease (CAD), and it remains the initial test for most patients who can exercise adequately with a baseline interpretable electrocardiogram. However, there is little information about the relationship between Duke treadmill test score (DTS) and severity of coronary artery lesion, as well as estimating the need for revascularisation. The aim of the study was to ascertain whether the DTS could be an efficient parameter in choosing coronary revascularisation in different DTS groups. Two hundred and fifty-eight (n = 258) patients had positive exercise testing for CAD and underwent coronary angiography. The patients were divided into three groups according to the DTS: low-risk (with a score of ≥ +5), moderate-risk (with scores ranging from -10 to +4), and high-risk (with a score of ≤ -11). Coronary angiography was done by the Judkins technique. A coronary lesion was considered significant when stenosis of the coronary artery was ≥ 70% and stenosis of the trunk was ≥ 50%. The SYNTAX score was determined. The study group included 258 patients with mean age 62.66 ± 9.6 years, and most of them were men (72.8%). Patients with high- and intermediate-risk DTS had the same SYNTAX score (16.35 ± 7.3, 15.09 ± 10.08 and 11.80 ± 9.88, respectively; p = 0.064) compared to low-risk DTS. A negative correlation between DTS and significant coronary artery stenosis (r = -0.181; p = 0.005), SYNTAX score (r = -0.173; p = 0.007), and cardiac revascularisations (r = -0.213; p = 0.001) were found. In multiple linear regressions to predict coronary revascularisation the SYNTAX score (B = 0.018; p = 0.0001), DTS (B = -0.014, p = 0.008) and previous myocardial infarction (B = -0.143; p = 0.047) were significant predictors. The DTS alone is a useful tool in suspecting a significant coronary artery stenosis, but it is not accurate enough for revascularisation. Thus, by adding clinical information, its value may be maximised.


Canine systemic lupus erythematosus. Transmission of serologic abnormalities by cell-free filtrates.
The presence of viruses was sought in a colony of dogs bred from parents with systemic lupus crythematosus (SLE). Cell-free filtrates prepared from the spleens of these animals were injected into newborn dogs, mice, and rats. The canine recipients developed antinuclear antibody (ANA) and positive lupus erythematosus (LE) cell tests: ANA and, in some cases, antinative DNA antibodies were produced by the murine recipients: no abnormalities were detected in the rats. Serial passage of spleen cells or cell-free filtrates of spleen tissue in syngeneic mice reduced the time required for appearance of ANA from 9 to 4 mo. Some murine recipients of the canine filtrate developed malignant lymphomas. Murine leukemia viruses were identified in these tumors by electron microscopic, virologic, and serologic technics. These neoplasms, but not other tumors known to contain murine leukemia viruses, were associated with the production of ANA. Puppies inoculated with the canine filtrate-induced mouse lymphoma developed ANA and positive LE cell tests within 4 mo. THE RESULTS WERE INTERPRETED TO INDICATE THE PRESENCE IN CANINE SLE OF A VIRUS CAPABLE OF: (a) inducing the serologic abnormalities of SLE in normal dogs and mice: (b) activating latent murine leukemia viruses: and (c) spreading by both horizonal and vertical routes.


Low Antigen Dose in Adjuvant-Based Vaccination Selectively Induces CD4 T Cells with Enhanced Functional Avidity and Protective Efficacy.
T cells with high functional avidity can sense and respond to low levels of cognate Ag, a characteristic that is associated with more potent responses against tumors and many infections, including HIV. Although an important determinant of T cell efficacy, it has proven difficult to selectively induce T cells of high functional avidity through vaccination. Attempts to induce high-avidity T cells by low-dose in vivo vaccination failed because this strategy simply gave no response. Instead, selective induction of high-avidity T cells has required in vitro culturing of specific T cells with low Ag concentrations. In this study, we combined low vaccine Ag doses with a novel potent cationic liposomal adjuvant, cationic adjuvant formulation 09, consisting of dimethyldioctadecylammonium liposomes incorporating two immunomodulators (monomycolyl glycerol analog and polyinosinic-polycytidylic acid) that efficiently induces CD4 Th cells, as well as cross-primes CD8 CTL responses. We show that vaccination with low Ag dose selectively primes CD4 T cells of higher functional avidity, whereas CD8 T cell functional avidity was unrelated to vaccine dose in mice. Importantly, CD4 T cells of higher functional avidity induced by low-dose vaccinations showed higher cytokine release per cell and lower inhibitory receptor expression (PD-1, CTLA-4, and the apoptosis-inducing Fas death receptor) compared with their lower-avidity CD4 counterparts. Notably, increased functional CD4 T cell avidity improved antiviral efficacy of CD8 T cells. These data suggest that potent adjuvants, such as cationic adjuvant formulation 09, render low-dose vaccination a feasible and promising approach for generating high-avidity T cells through vaccination.


Hydrodynamics of driven granular gases.
Hydrodynamic equations for granular gases driven by the Fokker-Planck operator are derived. Transport coefficients appeared in Navier-Stokes order change from the values of a free-cooling state to those of a steady state. The mismatch between the granular temperature and the constant temperature of the heat bath produces a nontrivial steady state.


Further observations on the morphology and sensitive innervation of the retractor penis muscle in several species of ungulates.
The retractor penis muscle originates from the vertebrae in pigs, horses, cattle and goats; it arises from the rectum in sheep. In all the species considered, sensitive innervation was found. This was represented by encapsulated receptors. Nervous vegetative supply, made up of isolated or assembled ganglion cells, was also present. Among the numerous sensory nerve endings found in pigs, goats and sheep were Pacinian, Pacinian-like, Golgi-Mazzoni corpuscles and Krause's end bulbs (genital corpuscles). Few Pacinian and Pacinian-like corpuscles were found in cattle and horses. A hypothesis on the probable functional role of the observed receptorial apparatus was formulated.


Cardiac tamponade as an initial manifestation of systemic lupus erythematosus.
Clinical manifestations of pericardial disease may precede other signs and symptoms associated with systemic lupus erythematosus. Although pericardial effusion is one of the most common cardiac problems in patients with systemic lupus erythematosus, haemodynamically significant effusions manifesting as cardiac tamponade are rare and require prompt diagnosis and treatment.


Visible-light-sensitized near-infrared luminescence from rare-earth complexes of the 9-hydroxyphenalen-1-one ligand.
The unique absorption properties of the 9-hydroxyphenalen-1-one (HPHN) ligand have been exploited to obtain visible-light-sensitizable rare-earth complexes in 1:3 and 1:4 metal-to-ligand ratios. In both stoichiometries (1:3, tris, Ln(PHN)3; 1:4, tetrakis, A[Ln(PHN)4], with Ln being a trivalent rare-earth ion and A being a monovalent cation), the complexes of Nd(III), Er(III), and Yb(III) show typical near-infrared luminescence upon excitation with visible light with wavelengths up to 475 nm. The X-ray crystal structures of the tris complexes show solvent coordination to the central rare-earth ion, whereas in the tetrakis complexes, the four PHN- ligands form a protective shield around the central ion, preventing small solvent molecules from coordinating to the rare-earth ion, at least in the solid state.


Ceftazidime-Avibactam Is Superior to Other Treatment Regimens against Carbapenem-Resistant Klebsiella pneumoniae Bacteremia.
There are no data comparing outcomes of patients treated with ceftazidime-avibactam versus comparators for carbapenem-resistant Enterobacteriaceae infections. At our center, ceftazidime-avibactam treatment of carbapenem-resistant Klebsiella pneumoniae bacteremia was associated with higher rates of clinical success (P = 0.006) and survival (P = 0.01) than other regimens. Across treatment groups, there were no differences in underlying diseases, severity of illness, source of bacteremia, or strain characteristics (97% produced K. pneumoniae carbapenemase). Aminoglycoside- and colistin-containing regimens were associated with increased rates of nephrotoxicity (P = 0.002).


Spectrum of general surgery in rural America.
To define the types of surgery performed by rural surgeons, to compare their experience to that of graduating US surgical residents and to document rural surgical mortality. Prospective registry of consecutive cases recorded by 7 rural general surgeons working in one department of surgery from December 31, 1994, through March 30, 1996. Comparison with the 1995 Report C (Resident Operative Logs) of the Residency Review Committee. National survey of surgical residency programs regarding formal gynecology experience. Nine rural community hospitals in the Midwest. Patients undergoing surgery in 9 cities with populations of fewer than 10000. Type of surgery and postoperative (30-day) mortality. Two thousand four hundred twenty procedures were performed by 7 surgeons practicing in 9 cities with populations of 1500 to 8000. There were 6 (0.25%) postoperative deaths. Case types are as follows: endoscopy, 686 (28.3%); gynecology, 498 (20.6%); hernia, 241 (10%); colorectal, 194 (8%); biliary, 183 (7.6%); cesarean sections, 130 (5.4%); breast, 129 (5.3%); orthopedic, 115 (4.8%); carpal tunnel, 63 (2.6%); otolaryngology, 35 (1.4%); and endocrine, 1 (0.4%); for a total of 2420 (100%). Report C indicated 1995 graduating chief residents averaged 8 obstetric and and gynecologic and 5.3 orthopedic cases during their residency. Of 204 surgical residency programs surveyed, 106 (52%) offered no obstetrics and gynecology rotation. A large volume of surgery was performed with low mortality by 7 rural general surgeons. The operative experience of 1995 residency graduates differed from our rural surgeons. We recommend a rural surgical track in selected training programs to prepare graduates better for rural practice. Senior level rotations in endoscopic, gynecologic, obstetric, and orthopedic surgery and mentorship with rural surgeons would be optimal.


Toxic behavior of silver and zinc oxide nanoparticles on environmental microorganisms.
Silver and zinc oxide nanoparticles (Ag and ZnO NPs) are widely used as antimicrobial agents. However, their potential toxicological impact on environmental microorganisms is largely unexplored. The aim of this work was to investigate the sensitivity and adaptability of five bacterial species isolated from sewage towards Ag and ZnO NPs. The bacterial species were exposed to increasing concentration of nanoparticles and the growth inhibitory effect, exopolysaccharides (EPSs) and extracellular proteins (ECPs) productions were determined. The involvement of surface charge in nanoparticles toxicity was also determined. The bacterial species were constantly exposed to nanoparticles to determine the adaptation behavior toward nanoparticles. The nanoparticles exhibited remarkable growth inhibitory effect on tested bacterial species. The toxicity of nanoparticles was found to be strongly dependent on surface charge effects. Though, these organisms are highly sensitive to Ag and ZnO NPs, the continuous exposure to these nanoparticles leads to moderate adaptation of bacterial species and the adapted bacterial species convert the highly toxic nano form to less toxic microform. Finally we predict that the continuing applications of nanoparticles in consumer products may lead to the development of nanoparticles resistant bacterial strains in future.


Cross-talk among writers, readers, and erasers of m6A regulates cancer growth and progression.
The importance of RNA methylation in biological processes is an emerging focus of investigation. We report that altering m6A levels by silencing either N 6-adenosine methyltransferase METTL14 (methyltransferase-like 14) or demethylase ALKBH5 (ALKB homolog 5) inhibits cancer growth and invasion. METTL14/ALKBH5 mediate their protumorigenic function by regulating m6A levels of key epithelial-mesenchymal transition and angiogenesis-associated transcripts, including transforming growth factor-β signaling pathway genes. Using MeRIP-seq (methylated RNA immunoprecipitation sequencing) analysis and functional studies, we find that these target genes are particularly sensitive to changes in m6A modifications, as altered m6A status leads to aberrant expression of these genes, resulting in inappropriate cell cycle progression and evasion of apoptosis. Our results reveal that METTL14 and ALKBH5 determine the m6A status of target genes by controlling each other's expression and by inhibiting m6A reader YTHDF3 (YTH N 6-methyladenosine RNA binding protein 3), which blocks RNA demethylase activity. Furthermore, we show that ALKBH5/METTL14 constitute a positive feedback loop with RNA stability factor HuR to regulate the stability of target transcripts. We discover that hypoxia alters the level/activity of writers, erasers, and readers, leading to decreased m6A and consequently increased expression of target transcripts in cancer cells. This study unveils a previously undefined role for m6A in cancer and shows that the collaboration among writers-erasers-readers sets up the m6A threshold to ensure the stability of progrowth/proliferation-specific genes, and protumorigenic stimulus, such as hypoxia, perturbs that m6A threshold, leading to uncontrolled expression/activity of those genes, resulting in tumor growth, angiogenesis, and progression.


[Choleperitonitis after hepatoportocholecystostomy for atresia of the biliary tract].
The gallbladder, the cystic and the choledocal ducts are patent in one fifth of biliary atresia cases, and can be used for the corrective operation. The main interest of this hepatoportocholecystostomy (HPC) is to prevent the cholangitis episodes which are the most severe complication of successful hepatoportoenterostomies (HPE). However a singular complication of HPC has been noticed by previous authors: the choleperitonitis. We report a recent case in which this complication was diagnosed by a routine ultrasonography at the 3rd week of the uneventful postoperative course of a HPC performed in an 1 1/2 month old infant. An early reoperation (HPE) had a good result with restoration of a satisfactory bile flow. The child is anicteric with a follow-up of one year. In our experience with 208 corrective operations between 1969 and 1981, HPC was used in 38 cases, with restoration of bile flow in 17 cases. A choleperitonitis was noticed in 4 cases in this series, and in a 5th additional recent case. Three children were not suitable for reoperation because of very poor condition and died within 3 to 17 months after HPC. Two children were reoperated upon early with a good result. We advocate the HPC procedure despite the risk of choleperitonitis and emphasize the interest of early postoperative routine ultrasonography, especially when stools remain acholic at the 4th postoperative week.


Outcome of free digital artery perforator flap transfer for reconstruction of fingertip defects.
Fingertip defect can be treated with many flaps such as random pattern abdominal flap, retrograde digital artery island flap, V-Y advancement flap, etc. However, swelling in the fingertip, dysfunction of sensation, flexion and extension contracture or injury in the hemi-artery of the finger usually occurs during the recovery phase. Recently, digital artery perforator flaps have been used for fingertip reconstructions. With the development of super microsurgery techniques, free flaps can be more effective for sensory recovery and durability of the fingertip. Six cases (six fingers) of fingertip defects were treated with free digital artery perforator flaps of appropriate size and shape from the proximal phalanx. During surgery, the superficial veins at the edge of flap were used as reflux vessels and the branches of the intrinsic nerve and dorsal digital nerve toward the flap were used as sensory nerves. The proximal segment of the digital artery (cutaneous branches) towards the flap was cut off to form the pedicled free flap. The fingertips were reconstructed with the free flap by anastomosing the cutaneous branches of digital artery in the flap with the distal branch or trunk of the digital artery, the flap nerve with the nerve stump and the veins of the flap with the digital artery accompanying veins or the superficial veins in the recipient site. Six flaps survived with successful skin grafting. Patients were followed up for 6-9 months. The appearance and texture of the flaps was satisfactory. The feeling within the six fingers recovered to S4 level (BMRC scale) and the two point discrimination was 3-8 mm. Free digital artery perforator flap is suitable for repairing fingertip defect, with good texture, fine fingertip sensation and without sacrificing the branch of the digital artery or nerve.


Lanthanide(III) complexes with 4,5-bis(diphenylphosphinoyl)-1,2,3-triazolate and the use of 1,10-phenanthroline as auxiliary ligand.
New lanthanide complexes with 4,5-bis(diphenyl)phosphoranyl-1,2,3-triazolate (L(-)), LnL(3).nH(2)O (1-8) and LnL(3)(phen).nH(2)O (9-16) (Ln = La, Ce, Nd, Sm, Eu, Gd, Tb, Er), have been prepared and spectroscopically characterized. The structures of LnL(3).nH(2)O (Ln = La, Ce, Nd, Sm and Gd) were determined by X-ray crystallography. The metal centers exhibit a distorted trigonal dodecahedron coordination environment with two symmetrically O,O-bidentate ligands and one unsymmetrically O,N- ligand attached to the metal; two oxygen atoms from neighboring dimethyl sulfoxide (DMSO) molecules complete the coordination sphere. This unsymmetrical ligand coordination behavior was also identified in solution through (31)P{(1)H} NMR studies. Photoluminescence spectroscopy experiments in CH(2)Cl(2) for both types of complexes containing Eu(III) (6, 14) and Tb(III) (7, 15) exhibit strong characteristic red and green emission bands for Eu(III) and Tb(III), respectively. Furthermore, NdL(3) (phen).5H (2)O (11) displays emission in the near-infrared spectral region ((4)F(3/2) --> (4)F(9/2) at 872 nm and (4)F(3/2) --> (4)F(11/2) at 1073 nm). The complexes containing 1,10-phenantroline exhibit higher quantum yields upon excitation at 267 nm, indicating that this auxiliary ligand promotes the luminescence of the complexes; however, luminescence lifetimes (tau) in this case are shorter than those of the LnL(3).nH(2)O series.


Increased auditory cortical representation in musicians.
Acoustic stimuli are processed throughout the auditory projection pathway, including the neocortex, by neurons that are aggregated into 'tonotopic' maps according to their specific frequency tunings. Research on animals has shown that tonotopic representations are not statically fixed in the adult organism but can reorganize after damage to the cochlea or after training the intact subject to discriminate between auditory stimuli. Here we used functional magnetic source imaging (single dipole model) to measure cortical representations in highly skilled musicians. Dipole moments for piano tones, but not for pure tones of similar fundamental frequency (matched in loudness), were found to be enlarged by about 25% in musicians compared with control subjects who had never played an instrument. Enlargement was correlated with the age at which musicians began to practise and did not differ between musicians with absolute or relative pitch. These results, when interpreted with evidence for modified somatosensory representations of the fingering digits in skilled violinists, suggest that use-dependent functional reorganization extends across the sensory cortices to reflect the pattern of sensory input processed by the subject during development of musical skill.


The demographic impact of the First World War: an anthropometric perspective.
During the 1970s and 1980s Jay Winter published a series of highly influential articles on the demographic impact of the First World War, culminating in his study of The Great War and the British People in 1986. Winter argued that the war led to a dramatic improvement in average living standards, and that the survival chances of most sections of the civilian population improved more rapidly than they might have done if peace had been maintained. This paper seeks to test the strength of Winter's hypothesis in three main ways. Section I examines the arguments which Winter himself put forward to support his view that the war led to a systematic erosion of pre-war differentials in infant mortality. Section III utilizes evidence relating to children's heights to examine the extent to which the war led to improvements in children's 'nutritional status'. The paper's overall conclusion is that the war did not lead to any dramatic improvements in civilian health; the overall impression to be gained from an analysis of wartime health statistics is one of continuity rather than change.


Land use intensity determines soil properties and biomass recovery after abandonment of agricultural land in an Amazonian biodiversity hotspot.
There has been widespread clearance of tropical forests for agriculture, but in many cases the cultivation phase is only transient. The secondary forests recovering on these abandoned sites may contribute to mitigation of greenhouse gas emissions and protection of biodiversity, but the rates of recovery may be dependent on land-use intensity and changes in soil properties during cultivation. However fine-scale details on these changes are poorly known for many tropical forest locations. We quantified soil properties and recovery of woody biomass in 42 tropical forest fragments representing a chronosequence following two types of agricultural land-uses, and in 15 comparable reference old growth forests, between the Andes and the Amazon in Peru. Soil fertility, particularly base cation concentrations, responded negatively to increasing intensity of agricultural land-use, and either decreased or increased with time after abandonment dependent on prior land-use. The predicted mean recovery rate of woody biomass over the first 20 years following abandonment matched that predicted by a general model for the Neotropics, but recovery was three-fold higher on sites abandoned following traditional agriculture than on sites recovering from intensive agriculture. Estimated total biomass recovered to just above half that of reference old growth forests within 71 years. The inclusion of the biomass of lianas and smaller tree stems did not modify the apparent rate of ecosystem biomass recovery, however the proportion of the total biomass stored in small stems was greater following intensive than traditional agriculture, which suggests that patterns of stand structural development are sensitive to land-use history. We conclude that effects of historic land use on soil nutrient concentrations and their changes through time are required for a more complete interpretation of variation in biomass recovery rates at local scales. These results also highlight the critical importance of contemporary agricultural intensification for carbon storage in tropical forests.


[Role of vitamin D in HIV infection].
Besides its role in bone metabolism, vitamin D shows properties on autoimmune, oncological, cardiovascular, metabolic, or infectious diseases. In this article, we talk about interpellant relationships between vitamin D and HIV. This hormone plays an important role in HIV infection, as much at a skeletal level than in the course of the disease itself. First, we notice that a low vitamin D status is currently associated with HIV infection. Moreover, it is now known that low rate of 1,25-dihydroxyvitamin D in HIV patients is associated with advanced clinical HIV infection and increased mortality. Thus, vitamin D deficiency has to be considered as an important factor in HIV progression. Indeed, vitamin D increases macrophage activity, in some way through autophagy, and this process can inhibit HIV-1 infection. Then we consider the implications of antiretroviral therapies on vitamin D metabolism. We finally evaluate the benefits of a vitamin D supplementation in HIV + patients.


Biodegradable Poly(lactic acid) Stabilized Nanoemulsions for the Treatment of Multidrug-Resistant Bacterial Biofilms.
Biofilm infections caused by multidrug-resistant (MDR) bacteria are an urgent global health threat. Incorporation of natural essential oils into biodegradable oil-in-water cross-linked polymeric nanoemulsions (X-NEs) provides effective eradication of MDR bacterial biofilms. The X-NE platform combines the degradability of functionalized poly(lactic acid) polymers with the antimicrobial activity of carvacrol (from oregano oil). These X-NEs exhibited effective penetration and killing of biofilms formed by pathogenic bacteria. Biofilm-fibroblast coculture models demonstrate that X-NEs selectively eliminate bacteria without harming mammalian cells, making them promising candidates for antibiofilm therapeutics.


Physical environment may modify the association between depressive symptoms and change in waist circumference: the multi-ethnic study of atherosclerosis.
Although the bidirectional association between depressive symptoms and adiposity has been recognized, the contribution of neighborhood factors to this relationship has not been assessed. This study evaluates whether physical and social neighborhood environments modify the bidirectional relationship between depressive symptoms and adiposity (measured by waist circumference and body mass index). Using data on 5,122 men and women (ages 45 to 84 years) from the Multi-Ethnic Study of Atherosclerosis (MESA) we investigated whether neighborhood physical (i.e., walking environment and availability of healthy food) and social (i.e., safety, aesthetics, and social coherence) environments modified the association between the following: (1) baseline elevated depressive symptoms (Center for Epidemiologic Study Depression Scale score ≥ 16) and change in adiposity (as measured by waist circumference and body mass index) and (2) baseline overweight/obesity (waist circumference > 102 cm for men and >88 cm for women, or body mass index ≥ 25 kg/m(2)) and change in depressive symptoms using multilevel models. Neighborhood-level factors were obtained from the MESA Neighborhood Study. A greater increase in waist circumference in participants with vs without elevated depressive symptoms was observed in those living in poorly-rated physical environments but not in those living in better-rated environments (interaction p = 0.045). No associations were observed with body mass index. Baseline overweight/obesity was not associated with change in depressive symptoms and there was no modification by neighborhood-level factors. Elevated depressive symptoms were associated with greater increase in waist circumference among individuals living in poorly-rated physical environments than in those in better-rated physical environments. No association was found between overweight/obesity and change in depressive symptoms.


From rings to crescents: a novel fabrication technique uncovers the transition details.
A novel fabrication route is reported for the generation of substrate-supported symmetric and asymmetric metal nanostructures. We combine a colloidal template and angled evaporation to deposit in situ mask materials for subsequent lithographic pattern transfer. The technique is demonstrated for the fabrication of concentric and nonconcentric gold rings and crescents. Optical properties of localized plasmon resonances in such structures are studied by UV-vis-NIR spectroscopy and finite-difference time domain simulations during the transition from rings to crescents revealing the development of strong quadrupolar modes.


Chronic infections and atherosclerosis.
The established risk factors for atherosclerosis such as hypertension, smoking, diabetes mellitus, hyperlipidemia, and hyperhomocysteinemia do not explain clinical and epidemiological features of coronary heart disease (CHD). The role of infectious disease as a CHD risk factor may partly explain these features. Chronic infection with various microorganisms, particularly, Chlamydia pneumoniae, Cytomegalovirus (CMV) and Helicobacter pylori may play a role in etiological factors, linking inflammation and atherogenesis. Results from epidemiological studies, pathology of atherosclerotic plaques, animal studies, molecular biology and clinical antibiotic trials indicated a positive association between C. pneumoniae infection and CHD. Chronic infection might also influence preexisting plaque by enhancing T cell activation, which participate in destabilization of intimal cap. However, the exact nature of pathophysiological link between the organisms and CHD remains to be elucidated. Future antibiotic interventional studies may help to further clarify the role of chronic infection and inflammation in CHD.


Novel expansion techniques for skin grafts.
The quest for skin expansion is not restricted to cover a large area alone, but to produce acceptable uniform surfaces, robust engraftment to withstand mechanical shear and infection, with a minimal donor morbidity. Ease of the technique, shorter healing period and reproducible results are essential parameters to adopt novel techniques. Significant advances seen in four fronts of autologous grafting are: (1) Dermal-epidermal graft expansion techniques, (2) epidermal graft harvests technique, (3) melanocyte-rich basal cell therapy for vitiligo and (4) robust and faster autologous cell cultures. Meek's original concept that the sum of perimeter of smaller grafts is larger than the harvested graft, and smaller the graft size, the greater is the potential for regeneration is witnessed in newer modification. Further, as graft size becomes smaller or minced, these micrografts can survive on the wound bed exudate irrespective of their dermal orientation. Expansion produced by 4 mm × 4 mm sized Meek micrografts is 10-folds, similarly 0.8 mm × 0.8 mm size micrografts produce 100-fold expansion, which becomes 700-fold with pixel grafts of 0.3 mm × 0.3 mm size. Fractional skin harvest is another new technique with 700 μ size full thickness graft. These provide instant autologous non-cultured graft to cover extensive areas with similar quality of engraftment surface as split skin grafts. Newer tools for epidermal blister graft harvest quickly, with uniform size to produce 7-fold expansions with reproducible results. In addition, donor area heals faster with minimal scar. Melanocyte-rich cell suspension is utilised in vitiligo surgery tapping the potential of hair root melanocytes. Further advances in the cell culture to reduce the cultivation time and provide stronger epidermal sheets with dermal carrier are seen in trials.


[Specificity of hatchet flaps in the laterofacial region].
The hatchet flap, well known for the repair after skin resection of the nasal pyramid, is adapted, in a cutaneo-aponeurotic form, to the laterofacial region. The authors describe the principle of the technique which they illustrate by several clinical cases. Its simplicity, its harmonious adaptation and its reliability led them to consider that it has a place in the therapeutic arsenal for skin repair after resection of jugal and temporo-jugal lesions.


Antenatal ultrasound visualization of left testis that then vanished after birth.
A 10-month-old infant was referred for disappearance of the left testis, which had been confirmed as present on antenatal ultrasound at 38 weeks of gestation, as well as at the newborn physical exam and the 4 month exam. The right testis was enlarged, whereas the left testis was palpated as a nubbin. The right testis measured on ultrasound was 1.6 × 0.8 × 1.0 cm; the testicular volume was 0.67 cm(3). The left nubbin was hyperechoic, and accurate measurement of testicular components was difficult. At the age of 1 year 8 months, with the diagnosis of left vanishing testis, inguinal exploration was undertaken to rule out intra-abdominal cryptorchidism. A fibrous nodule that connected to the spermatic vessels and the vas deferens was resected. Histopathology indicated a testicular remnant containing seminiferous tubules, hemosiderin deposits, calcification and marked fibrosis of the stroma, suggesting hemorrhagic infarction in utero.


[Júlio Dantas and medical archaeology].
Júlio Dantas (1876-1962), was a doctor of very restricted practice. Literature was his great passion, and projected him to a place in the Academy and to an interesting diplomatic career. Dantas, an archaizing and baroque writer who lived in the first times of the modernistic trends, became the object of a vivid controversy. We must, however, recognize he was the most successful of the popular playwrights in Portugal, having sold over two hundred thousand copies of his most known play. In Dantas', somewhat irregular work there are very beautiful pages of prose. The retrospective study of the diseases that afflicted the Portuguese kings is the subject of a collectanea of papers, published by Júlio Dantas in 1909, under the title Medical inquiries to the portuguese royal genealogies-Avis and Bragança. The book is within the limits of the so-called medical archaeology, a mix of history and speculation. Dantas presents a generic thesis of degeneration of the royal dynasties of Portugal, explained as natural consequence of heredity and consanguinity. Between the 13th. century and the beginning of the 1800s, monarchs and princes are implacably flagelatted, because of their physical diseases or moral faults. Isabel of Aragon, the saint-queen; prince Henry the Navigator; even the national hero, the constable Nun'Alvares, as many others, do not escape the severity of an analysis which, in most cases, is not medically accurate.


[Not Available].
In general, the desinfection of surfaces is done through scrubbing and wiping using substances on the basis of aldehydes, oxidants and tensides. We propose a 4-stage procedure (see Table 1). The concentration of the agent and the duration of application depend on the circumstances, whether one is dealing with a prophylactic measure, a nosocomial infection or an infection which has to be reported. The epidemiologic relevance dictates the extent of desinfection.


New polymeric composites based on poly(-caprolactone) and layered double hydroxides containing antimicrobial species.
Benzoate (Bz), 2,4-dichlorobenzoate (BzDC), and p- and o-hydroxybenzoate (p- and o-BzOH) anions with antimicrobial activity have been intercalated into [Zn(0.65)Al(0.35)(OH)(2)](NO(3))(0.35).0.6H(2)O, layered double hydroxide (LDH), via anion-exchange reactions. The composition of the obtained intercalation compounds, determined by chemical, thermogravimetric, and ion chromatographic analyses, indicates that benzoate and benzoate derivative anions replace the nitrate counteranions, almost completely. Information on the interactions of the intercalated anions with the inorganic layer have been obtained from Fourier transform IR absorption spectroscopy and powder X-ray diffraction of the samples. It has been found that both the nature and the position of the aromatic ring substituents affect the value of the basal distance and the host-guest hydrogen bond network. Knowledge of the chemical composition, basal distance, and van der Waals dimensions of the guests has finally allowed the proposal of structural models of the intercalation compounds that have been used as fillers of poly(caprolactone), a biodegradable polymer. Films of polymeric composites were obtained by hot-pressing the powders of polymer and filler previously milled by a high-energy ball milling procedure. X-ray diffraction analysis and optical and scanning electron microscopy of the composites indicate that the LDH samples containing BzDC anions are delaminated into the polymeric matrix, whereas those containing p-BzOH anions maintain for the most part the crystal packing and give rise to microcomposites. Intermediate behavior was found for LDH modified with Bz and o-BzOH anions because exfoliated and partly intercalated composites were obtained. Preliminary antimicrobial tests indicate that the composites are able to inhibit the Saccharomyces cerevisiae growth of 40% in comparison with the growth in a pure culture medium. The composites can be studied as the model for "active packaging" systems because of the antimicrobial properties of the anions anchored to the LDH layer.


What are health disparities and health equity? We need to be clear.
"Health disparities" and "health equity" have become increasingly familiar terms in public health, but rarely are they defined explicitly. Ambiguity in the definitions of these terms could lead to misdirection of resources. This article discusses the need for greater clarity about the concepts of health disparities and health equity, proposes definitions, and explains the rationale based on principles from the fields of ethics and human rights.


Prophylactic Groin Wound Vacuum-assisted Therapy in Vascular Surgery Patients at Enhanced Risk for Postoperative Wound Infection.
Vascular groin wounds have higher than expected surgical site infection (SSI) rates and some patients are at enhanced risk. The Wiseman et al. paper suggests an objective scoring system that identifies patients at enhanced risk of postdischarge SSI. We hypothesize that prophylactic groin wound vacuum-assisted closure (VAC) therapy in enhanced risk patients will decrease SSI and readmission and the Wiseman model provides potential evidence that enhanced risk patients can be objectively identified. A single institution, retrospective analysis was conducted from January 2013 to September 2016 utilizing procedure codes to identify patients with wound VACs placed in the operating room. Two distinct groups were identified. The first was a wound complication patient group with 15 limbs (13 patients) with a groin wound VAC placed within 45 days postoperatively for groin wound complications. Eleven of these limbs had the VAC placed at readmission. The second group was a prophylactic patient group that included 8 limbs (7 patients) who received a VAC prophylactically placed in the enhanced risk wounds. These wounds were determined to be enhanced risk based on clinical criteria judged by the operating surgeon such as a large overhanging panniculus and/or one of several ongoing medical issues. We calculated a Wiseman score for all patients, determined total cost of the readmissions, and determined 30-day postsurgical SSI incidence for the prophylactic VAC group. Per the Wiseman scores, 9 limbs with postoperative complications were high risk and 3 limbs were moderate/high risk. Eleven limbs had a VAC placed at readmission with an average readmission cost of $8876.77. For the prophylactic group, 8 limbs were high risk with no observed postdischarge SSI in the first 30 days from surgery. The Wiseman scores showed close correlation between the retrospective high and moderate/high risk groups versus the prophylactic VAC group (31.5 ± 7.3 vs. 32 ± 5.5, P = 0.87). The Wiseman scores showed objective validation in the prognosis of anticipating groin wound breakdown. Our initial results suggest that prophylactic groin wound VAC placement for enhanced risk vascular surgery patients may proactively decrease wound morbidity, decrease readmission secondary to groin wound complications, and provide some cost benefit.


Speech audiometry and fitting of hearing aids in noise.
Conventional speech audiometry, performed in a noise-free testing room, often gives only little information on the patient's impairment of speech perception in daily life. A sensitized form of free-field speech audiometry is suggested which simulates everyday speech perception and, at the same time, supplies comparable and reproducible results. The test material consists of phonetically balanced sentences. From separate loudspeakers, a standardized environmental noise with a constant sound pressure level, 50 dB(A) is admixed. By this technique, certain handicaps in speech perception, undetected by conventional test procedures, can be revealed. Above all, the results are in good accordance with the subjective assessment of disability. A standardization of 'handicap speech audiometry' based on these principles is therefore suggested. The comparative hearing-aid fitting in noise improves the final selection with special regard to practical use.


Characterization of a line of pigs previously selected for increased litter size for RBP4 and follistatin.
The objective of this study was to determine if selection response for increased litter size in pigs could be partially attributed to three type 1 marker loci coding for genes known to affect litter size: oestrogen receptor (ESR), retinol-binding protein 4 (RBP4) and follistatin (FS). In the high litter size line (LS), pigs from the largest litters, based on number of pigs born alive (NBA), were retained to parent the next generation. A randomly selected control line (LC) was maintained. Gilts were reared in litters of 10 pigs or less to minimize maternal effects. Pigs were measured at generations 10-12. Additional traits scored were number of fully formed pigs (NFF) and number of mummified fetuses (MUM). Breeding values for NFF and NBA were greater (p < 0.05) in LS than LC in generations 11 and 12, but no significant line differences were found for MUM. The A allele of the ESR locus was fixed in both lines. After adjustment for effects of genetic drift, frequency of the two alleles segregating for the FS and RBP4 loci did not differ significantly between lines. No significant additive or dominance effects of the FS markers were detected for NFF, NBA and MUM in either LS or LC. Response to selection for increased litter size could not be attributed to effects at the ESR, RBP4 or FS loci.


Selective interaction of heparin with the variable region 3 within surface glycoprotein of laboratory-adapted feline immunodeficiency virus.
Heparan sulfate proteoglycans (HSPG) can act as binding receptors for certain laboratory-adapted (TCA) strains of feline immunodeficiency virus (FIV) and human immunodeficiency virus (HIV). Heparin, a soluble heparin sulfate (HS), can inhibit TCA HIV and FIV entry mediated by HSPG interaction in vitro. In the present study, we further determined the selective interaction of heparin with the V3 loop of TCA of FIV. Our current results indicate that heparin selectively inhibits infection by TCA strains, but not for field isolates (FS). Heparin also specifically interferes with TCA surface glycoprotein (SU) binding to CXCR4, by interactions with HSPG binding sites on the V3 loop of the FIV envelope protein. Peptides representing either the N- or C-terminal side of the V3 loop and containing HSPG binding sites were able to compete away the heparin block of TCA SU binding to CXCR4. Heparin does not interfere with the interaction of SU with anti-V3 antibodies that target the CXCR4 binding region or with the interaction between FS FIV and anti-V3 antibodies since FS SU has no HSPG binding sites within the HSPG binding region. Our data show that heparin blocks TCA FIV infection or entry not only through its competition of HSPG on the cell surface interaction with SU, but also by its interference with CXCR4 binding to SU. These studies aid in the design and development of heparin derivatives or analogues that can inhibit steps in virus infection and are informative regarding the HSPG/SU interaction.


Sensory attenuation of self-initiated sounds maps onto habitual associations between motor action and sound.
Sensory attenuation refers to reduced brain responses to self-initiated sensations relative to those produced by the external world, a distinction that is vital for dynamic motor control and our sense of agency. Typically, willed vocalizations elicit larger N1 reduction of the auditory evoked potential compared to indirectly evoked sounds, such as tones generated by button-presses, which is attributed to the prediction and cancellation of incoming signals enabled by speech motor commands. However, physical confounds exist, including different stimuli and the increased motor artefact associated with mouth vs. finger movements. The present study investigated N1 attenuation to physically identical sounds evoked by hand, eye, and mouth-initiated movements. Twenty-eight healthy participants had their electroencephalogram (EEG) recorded as they blew into a microphone, pressed a button, or moved their eye to generate a pure tone. We found that N1 and P2 response was most reduced in the blow initiation condition, and that both blow and button-press but not saccade initiated tones elicited significantly reduced N1 and P2 amplitude compared to external initiation. This indicates that the eliciting motor action markedly influences ERP response to auditory stimuli. Given that saccades are never associated with sounds, finger movements sometimes are, and mouth movements often are, the pattern of results suggests that N1 attenuation to self-initiated sounds may depend on existing associations between the initiating action and resultant sensation.


Improvement in human semen quality after oral supplementation of vitamin C.
This study was carried out to monitor the effect of oral supplementation of vitamin C on various semen parameters in oligospermic, infertile, otherwise healthy individuals. Various semen parameters, including sperm motility, sperm count, and sperm morphology, were studied before and after the vitamin C treatment. A total of 13 infertile patients were included. Their ages ranged between 25 and 35 years. They had no genital infection or varicocele. Physical examination and other routine laboratory investigations were normal. General semen analysis revealed oligozoospermia (mean sperm count was 14.3 +/- 7.38 x 10(6) sperms/mL, mean sperm with normal morphology was 43 +/- 7.87%, and mean sperm motility was 31.2 +/- 9.61%). Testicular biopsy was not done. These patients received in an open trial of 1,000 mg of vitamin C twice daily for a maximum of 2 months. Results showed that the mean sperm count was increased to 32.8 +/- 10.3 x 10(6) sperms/mL (P < .001) after 2 months of vitamin C intake. The mean sperm motility was increased significantly to 60.1 +/- 8.47% (P < .001), and mean sperms with normal morphology increased significantly to 66.7 +/- 4.77% (P < .001). This study showed that vitamin C supplementation in infertile men might improve sperm count, sperm motility, and sperm morphology and might have a place as an additional supplement to improve the semen quality towards conception.


[General Anesthesia for a Patient with Purulent Spondylitis with Retropharyngeal Abscess and Vocal Cord Dysfunction: A Case Report].
A 43-year-old man was admitted to our hospital for neck pain, and diagnosis was fixed as purulent spondylitis with retropharyngeal abscess and vocal cord dysfunction. Deteriorating paresthesia, paralysis and airway narrowing needed airway management emergency cervical laminoplasty and abscess drainage under general anesthesia. On standby of an otorhinolaryngologist for urgent tracheotomy, nasal tracheal intubation with bronchofiberscope was performed in the patient with semi-awake condition. Postoperative airway narrowing and vocal cord dysfunction improved, and the trachea was extubated on the third day after surgery.


Sesquiterpene Lactones from Artemisia Genus: Biological Activities and Methods of Analysis.
Sesquiterpene lactones are a large group of natural compounds, found primarily in plants of Asteraceae family, with over 5000 structures reported to date. Within this family, genus Artemisia is very well represented, having approximately 500 species characterized by the presence of eudesmanolides and guaianolides, especially highly oxygenated ones, and rarely of germacranolides. Sesquiterpene lactones exhibit a wide range of biological activities, such as antitumor, anti-inflammatory, analgesic, antiulcer, antibacterial, antifungal, antiviral, antiparasitic, and insect deterrent. Many of the biological activities are attributed to the α-methylene-γ-lactone group in their molecule which reacts through a Michael-addition with free sulfhydryl or amino groups in proteins and alkylates them. Due to the fact that most sesquiterpene lactones are thermolabile, less volatile compounds, they present no specific chromophores in the molecule and are sensitive to acidic and basic mediums, and their identification and quantification represent a difficult task for the analyst. Another problematic aspect is represented by the complexity of vegetal samples, which may contain compounds that can interfere with the analysis. Therefore, this paper proposes an overview of the methods used for the identification and quantification of sesquiterpene lactones found in Artemisia genus, as well as the optimal conditions for their extraction and separation.


Thermodynamic Bounds on Precision in Ballistic Multiterminal Transport.
For classical ballistic transport in a multiterminal geometry, we derive a universal trade-off relation between total dissipation and the precision, at which particles are extracted from individual reservoirs. Remarkably, this bound becomes significantly weaker in the presence of a magnetic field breaking time-reversal symmetry. By working out an explicit model for chiral transport enforced by a strong magnetic field, we show that our bounds are tight. Beyond the classical regime, we find that, in quantum systems far from equilibrium, the correlated exchange of particles makes it possible to exponentially reduce the thermodynamic cost of precision.