Eight Items to Check on a Temporal Bone CT-Scan.
Imaging data provided by computed tomography scans of the temporal bone are fundamental for both the diagnosis and treatment of diseases affecting this complex structure. Despite its importance, the expertise required to analyze this exam is seldom properly acquired as it is time-consuming and often neglected among young doctors and even otolaryngologists. Physicians may not even have a look at the scans but rely only on radiology reports. Radiologists, on the other hand, may not describe the individual scans the same way as clinicians. Lack of a standardized and didactic protocol for scrolling through the images obtained might also contribute to the difficulties reported by residents and physicians in daily practice. We present here a sequential checklist which could be employed in a systematic and organized manner, aiming to both develop and practice the know-how of this indispensable and challenging method of evaluation of the temporal bone.


Genotype and phenotype of N-acetyltransferase 2 (NAT2) polymorphism in patients with contact allergy.
We investigated whether patients with contact allergy differed from non-contact-allergic, non-atopic controls with regard to genotype and phenotype of the polymorphic enzyme N-acetyltransferase 2 (NAT2). 55 contact-allergic patients recruited from the Information Network of Departments of Dermatology (IVDK) were compared to 85 controls from among local health care personnel. NAT2 activity was calculated from HPLC analysis of the ratio of the caffeine metabolites 5-acetylamino-6-formylamino-3-methyluracil (AFMU) and 1-methylxanthine (1MX) in the urine. NAT2 genotype was determined by polymerase chain reaction (PCR). A statistically significantly increased proportion of rapid acetylators was found in contact-allergic patients. This may have 2 possible implications: acetylation may enhance contact sensitization; or NAT2 status may be a genetic marker for contact sensitizability.


Sparse Representation Based Multi-Instance Learning for Breast Ultrasound Image Classification.
We propose a novel method based on sparse representation for breast ultrasound image classification under the framework of multi-instance learning (MIL). After image enhancement and segmentation, concentric circle is used to extract the global and local features for improving the accuracy in diagnosis and prediction. The classification problem of ultrasound image is converted to sparse representation based MIL problem. Each instance of a bag is represented as a sparse linear combination of all basis vectors in the dictionary, and then the bag is represented by one feature vector which is obtained via sparse representations of all instances within the bag. The sparse and MIL problem is further converted to a conventional learning problem that is solved by relevance vector machine (RVM). Results of single classifiers are combined to be used for classification. Experimental results on the breast cancer datasets demonstrate the superiority of the proposed method in terms of classification accuracy as compared with state-of-the-art MIL methods.


Novel synthetic approach to 6,7-dihydro-5H-imidazo[1,5-a]-pyrazin-8-ones.
[reaction: see text] A novel route to highly substituted chiral 6,7-dihydro-5H-imidazo[1,5-a]pyrazine-8-ones starting from Meldrum's acid is disclosed. The key features of the methodology are the incorporation of amino esters as a chiral pool and facile mild intramolecular cyclization to form the pyrazine ring. Incorporation of various substituents at different stages of the synthesis from various building block sets makes this methodology readily amenable to parallel synthesis.


[A Case of Delayed-onset Multiple Metastatic Infection following Liver Abscess].
Klebsiella pneumoniae liver abscess has a tendency to spread to distant sites early in the course of disease and to involve multiple organs synchronously. A 59-year-old male was admitted because of liver abscess accompanied by fever and abdominal pain. The patient underwent percutaneous catheter drainage and received intravenous antibiotics. Symptom relief was achieved after the treatment as well as marked reduction in the size of the abscess. Despite proper treatment of the liver abscess, however, patient developed multiple metastatic infections in a non-concurrent manner: left and right endophthalmitis, psoas abscess, and infectious spondylitis at 5, 23, 30 and 65 days after initial manifestations of liver abscess, respectively. Each infectious episode followed one another after resolution of the former one. For each episode of metastatic infections, the patient promptly underwent treatment with systemic and local antibiotics, interventional abscess drainage, and surgical treatments as needed. The patient fully recovered without sequelae after the use of intravenous antibiotics for an extended period of time. Herein, we report a case of K. pneumoniae liver abscess complicated with delayed-onset multiple metastatic infections.


Copper-catalyzed oxidative homo- and cross-coupling of Grignard reagents using diaziridinone.
Transition-metal-catalyzed cross-coupling reactions are among the most powerful synthetic transformations. This paper describes an efficient copper-catalyzed homo- and cross-coupling of Grignard reagents with di-tert-butyldiaziridinone as oxidant under mild conditions, giving the coupling products in good to excellent yields. The reaction process has a broad substrate scope and is also effective for the C(sp)-C(sp(3)) coupling.


From contraceptive prevalence to family planning service users: implications for policy and programmes.
Contraceptive prevalence rate (CPR) is a widely accepted measure of maternal health and uptake of family planning (FP) services. However, the overall CPR obscures the actual utilization of FP services due to over-representation of long-term methods. This study used CPR from 2007 to arrive at and compare the number of actual number of women who availed different FP services in order to understand issues and gaps in FP services in Pakistan. This study used secondary data from the Pakistan Demographic and Health Survey 2006-7 estimate the CPR and modern method mix for 2007.These were then multiplied by the estimated number of married women of reproductive age (MWRA) to arrive at the actual numbers of women using specific FP methods and utilizing FP services in a given year. In 2007 the CPR was 30% overall and 22% for modern methods. However, the number of women availing FP services decreased to 12% when adjusted for FP users who had availed services in the past 12 months. Within this "service mix", self-procurement of FP commodities directly from stores without a advice from a health provider constitutes around 37% of all FP "services" and the public sector accounts for another 33%. Condoms are the commonest method served, accounting for over half of all "services". The bulk of FP is self-procured and the service mixed is skewed towards client controlled methods that do not require medical advice. Thus, lack of quality for contraceptive services that require some form of supportive healthcare services and counselling may be a bottleneck to improving CPR.


Clonal T-cell populations in angioimmunoblastic lymphadenopathy and angioimmunoblastic lymphadenopathy-like lymphoma.
Ten cases of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) and AILD-like lymphoma were studied by immunophenotypic and immunogenotypic analysis. All specimens were found to have a predominance of T cells by immunophenotypic analysis. DNA hybridization analyses showed three of five specimens of AILD and five of six specimens of AILD-like lymphoma to contain clonal rearrangements of the beta T-cell receptor gene. No rearrangements of the heavy or light chain immunoglobulin genes were seen in any case. A single case showed a progression of AILD with a germ-line pattern of beta T-cell receptor DNA to AILD-like lymphoma with detectable clonal rearrangements for beta T-cell receptor DNA. These results suggest that many, but not all, cases diagnosed histologically as AILD or AILD-like lymphoma contain a clonal proliferation of T-lymphocytes.


Sending The Wrong Price Signal: Why Do Some Brand-Name Drugs Cost Medicare Beneficiaries Less Than Generics?
The current Medicare Part D benefit may require greater out-of-pocket spending for beneficiaries filling prescriptions for higher-price generic drugs, compared to those filling brand-name counterparts. This can occur among patients who reach the catastrophic coverage phase under the Part D benefit, when differences between the prices for generic and brand-name drugs are not large. This scenario may be common with specialty drugs (typically high-price products used to treat rare or complex conditions), when the number of generic manufacturers or clinical alternatives are limited. In this study we demonstrated that patients would pay more out of pocket for generic medications than for brand-name drugs in these cases, driven by manufacturer discounts provided in the Medicare Part D coverage gap. Overpayments for specialty generic drugs relative to brand-name drugs ranged from $869 to $1,072 in 2019, despite lower point-of-sale prices for these drugs. Policy makers should consider modifying the Part D benefit to increase incentives for generic drug use.


[Effect of phosphodiestrase 4 inhibitor (rolipram) on experimental allergic asthma-guinea pig model].
Selective phosphodiesterases (PDE) inhibitors are the new group of antiasthmatic drugs, which integrate antiinflammatory activity with bronchoconstriction counteraction. Selective inhibitors of phosphodiesterase type 4 are used as alternative or assist drugs in treatment of respiratory system diseases. So far glucocorticosteroids remain the most efficient and widely used medicine in the treatment of asthma. However application of glucocorticosteroid is greatly limited because of numerous side effects, what induce to permanent search for new antiasthmatic drugs. Examination new substances are executed on animal models. Guinea pig model is widely used to research course of asthmatic reaction. This model is especially convenient on the ground of that: lung is major shock organ, airway respond to histamine, animals demonstrated early asthmatic reaction (EAR) and late asthmatic reaction (LAR), eosinophils flow in bronchoalveolar space during LAR. In ovalbumin (OA) sensitized guinea pigs hypersensitivity reaction breaks out as a result of OA provocation. Aims of our experiments, execute on guinea pig model were to determine the influence of rolipram (PDE 4 inhibitor) on modulation experimental asthmatic reaction and comparison activity of rolipram versus dexamethasone in attribution to chosen parameters of allergic reaction such as: lung resistance, influx of protein and inflammatory cells in airways, and mastocytes degranulation. Experiments were made on guinea pigs sensitized and provoked with ovalbumin The obtain data indicate that rolipram was effective in reduction the rise of lung resistance during EAR, restricted influx of eosinophils to bronchoalveolar space between 1,5 and 24 hours after provocation, and reduced increase of histamine concentration in bronchoalveolar lavage fluid (BALf). Rolipram had no influence on number of neutrophils present in BALf. Dexamethasone in double dose of 1,2mg/kg effectively bordered the growth of lung resistance during EAR, and broke influx of eosinophils and neutrophils to bronchoalveolar space.


Defining chronic conditions for primary care with ICPC-2.
With the increasing prevalence of chronic conditions, there is need for a standardized definition of chronicity for use in research, to evaluate the population prevalence and general practice management of chronic conditions. Our aims were to determine the characteristics required to define chronicity, apply them to a primary care classification and provide a defined codeset of chronic conditions. A literature review evaluated characteristics used to define chronic conditions. The final set of characteristics was applied to the International Classification of Primary Care-Version 2 (ICPC-2) through more specific terms available in ICPC-2 PLUS, an extended terminology classified to ICPC-2. A set of ICPC-2 rubrics was delineated as representing chronic conditions. Factors found to be relevant to a definition of chronic conditions for research were: duration; prognosis; pattern; and sequelae. Within ICPC-2, 129 rubrics were described as 'chronic', and another 20 rubrics had elements of chronicity. Duration was the criterion most frequently satisfied (98.4% of chronic rubrics), while 88.2% of rubrics met at least three of the four criteria. Monitoring the prevalence and management of chronic conditions is of increasing importance. This study provided evidence for multifaceted definitions of chronicity. While all characteristics examined could be used by those interested in chronicity, the list has been designed to identify chronic conditions managed in Australian general practice, and is therefore not a nomenclature of all chronic conditions. Subsequent analysis of chronic conditions using pre-existing data sets will provide a baseline measure of chronic condition prevalence and management in general practice.


Characteristics of high alpha-linolenic acid accumulation in seed oils.
Modern diets are often deficient in omega-3 fatty acids and additional dietary sources of omega-3 fatty acids are useful. In order to investigate the molecular basis of the high accumulation of the omega-3 fatty acid, alpha-linolenic acid (18:3), in three different plants, flax (Linum usitatissimum), Dracocephalum moldavica, and Perilla frutescens omega-3 desaturase activity, transcript levels, and 18:3 in-vivo synthesis were examined. The 18:3 content was found to be higher at the later developmental stage of D. moldavica (68%) compared with P. frutescens (59%) and flax (45%) cotyledons. The 18:3 and 18:2 contents in both PC and TAG were determined during various stages of seed development for all three plants in addition to soybean (Glycine max). Northern blot analysis data of three different stages of D. moldavica, flax, and P. frutescens compared with moderately low 18:3 producers, soybean (Glycine max), and Arabidopsis thaliana and Brassica napus, (8-10% 18:3) at a stage of zygotic embryo development of high triglyceride synthesis showed that omega-3 desaturase mRNA levels were higher in all three high 18:3 producers, flax, D. moldavica and P. frutescens. This indicates that the high level of alpha-linolenic acid in TAG may be largely controlled by the level of omega-3 desaturase gene expression. However, the PC versus TAG fatty acid composition data suggested that along with omega-3 desaturase other enzymes also play a role in 18:3 accumulation in TAG, and the high accumulators have a selective transfer of alpha-linolenic acid into TAG.


Stumped by the Mystery: A Case Report of Progressive Shortening of Bone Following an Above-Knee Amputation.
Several studies have investigated the anatomical adaptations in amputation stumps. In this study, we present a case report of a patient who underwent an above-the-knee amputation and, over the course of time, the length of the residual bone spontaneously shortened. The patient had undergone a total hip replacement in the same leg, and the cement mantle of the hip replacement, which could be seen within the medullary canal in the early postoperative X-rays, protruded due to bone resorption one year after the amputation. Although changes in bone microarchitecture in amputation stumps are well established, this is the first report of macroscopic changes in its actual length.


Chemotherapy by M-VAC protocol in progressive bladder carcinoma treatment.
Treatment of invasive bladder carcinoma is complex therapy procedure which means surgical and non-surgical treatment appliance. In spite of radical surgical treatment conduction, the gold standard in invasive bladder tumor therapy, about 30-40% patients spread metastasis in further disease course. The system chemotherapy in invasive bladder tumors treatments is marked with accent. Its fundamental aim is to correct results of surgical treatment. This therapy option very often means the only modality in bladder carcinoma treatment, for instance, in the diseminal disease faze. The adjuvant chemotherapy imposes a task to correct surgical treatments results in case where the high risk of recidive breaking out exists. As risks for recidive breaking out cite are: a) lymphatic and vascular invasion into the primary tumor; b) extravezical tumor extension-T3b; c) tumor invasion neighboring structures-T4; d) positive lgl findings-N+. After radical cystectomy caused by high level malignancy tumors - T3b,T4, is founded frequency of positive IgI of about 40-60%. Patients with positive lgl have badly prognosis. Only 17% they survive longer than two years, and 7% have surviving of five years.


Nanoparticle-based drug delivery systems targeting cancer cell surfaces.
Traditional cancer chemotherapy easily produces serious toxic and side effects due to the lack of specific selection of tumor cells, which restricts its curative effect. Targeted delivery can increase the concentration of drugs in the target site and reduce their toxic and side effects on normal tissues and cells. Biocompatible and surface-modifiable nanocarriers are novel drug delivery systems, which are used to specifically target tumor sites in a controllable way. One of the effective ways to design effective targeting nanocarriers is to decorate with functional ligands, which can bind to specific receptors overexpressed on the surfaces of cancer cells. Various functional ligands, including transferrin, folic acid, polypeptide and hyaluronic acid, have been widely explored to develop tumor-selective drug delivery systems. This review focuses on the research progress of various receptors overexpressed on the surfaces of cancer cells and different nano-delivery systems of anticancer drugs targeted on the surfaces of cancer cells. We believe that through continuous research and development, actively targeted cancer nano-drugs will make a breakthrough and become an indispensable platform for accurate cancer treatment.


Accuracy of administrative claims data for cerebral palsy diagnosis: a retrospective cohort study.
Cerebral palsy is the most common cause of childhood physical disability, with multiple associated comorbidities. Administrative claims data provide population-level prevalence estimates for cerebral palsy surveillance; however, their diagnostic accuracy has never been validated in Quebec. This study aimed to assess the accuracy of administrative claims data for the diagnosis of cerebral palsy. We conducted a retrospective cohort study of children with cerebral palsy born between 1999 and 2002 within 6 health administrative regions of Quebec. Provincial cerebral palsy registry data (reference standard) and administrative physician claims were linked. We explored differences between true-positive and false-negative cases using subgroup sensitivity analysis. A total of 301 children were identified with confirmed cerebral palsy from the provincial registry, for an estimated prevalence of 1.8 (95% confidence interval [CI] 1.6-2.1) per 1000 children 5 years of age. The sensitivity and specificity of administrative claims data for cerebral palsy were 65.5% (95% CI 59.8%-70.8%) and 99.9% (95% CI 99.9%-99.9%), respectively, yielding a prevalence of 2.0 (95% CI 1.9-2.3) per 1000 children 5 years of age. The positive and negative predictive values were 58.8% (95% CI 53.3%-64.1%) and 99.9% (95% CI 99.9%-99.9%), respectively. The κ value was 0.62 (95% CI 0.57-0.67). Administrative claims data were more sensitive for children from rural regions, born preterm, with spastic quadriparesis and with higher levels of motor impairment. Administrative claims data do not capture the full spectrum of children with cerebral palsy. This suggests the need for a more sensitive case definition and caution when using such data without validation.


[A case of argyrophilic grain dementia with emotional disorder].
Autopsy of a patient with mild dementia associated with an emotional disorder characterized by paroxysmal rage and excitement during the clinical course revealed massive argyrophilic grains in the subicular, entorhinal and amygdaloid regions, and to a lesser extent in other limbic areas as well. A few argyrophilic coiled bodies were also found in the subcortical white matter in the same area as the cortical argyrophilic grains. These pathological findings are consistent with a type of cytoskeletal abnormality referred to as 'argyrophilic grain dementia', which some authors describe as a new type of progressive dementia. Immunohistochemically, the grains reacted with anti-human-tau, and in part with anti-ubiquitin antibodies. Immunoelectron microscopic examination revealed the grains to consist of tubulo-vesicular structures within processes, but it was impossible to identify their origin. The neuropathologic substrate of this peculiar case of dementia was thought to be the grains in the limbic area. The detailed clinical picture and distribution of the grains are described to contribute to further discussion.


Preparation and characterization of microcapsules of water-soluble pesticide monocrotophos using polyurethane as carrier material.
Microencapsulation of the water soluble pesticide monocrotophos (MCR), using polyurethane (PU) as the carrier polymer, has been developed using two types of steric stabilizers, namely PLMA macrodiol and PLMA-g-PEO graft copolymer. The microencapsulation process is carried out in non-aqueous medium and at a moderate temperature to avoid any chemical degradation of monocrotophos during the encapsulation process. Microcapsules were characterized by optical microscopy and SEM for particle size and morphology, respectively. The effects of loading of MCR, crosslinking density of PU, and nature of steric stabilizer on the release of MCR from PU microcapsules have been studied.


pH-Independence of trialanine and the effects of termini blocking in short peptides: a combined vibrational, NMR, UVCD, and molecular dynamics study.
Several lines of evidence now well establish that unfolded peptides in general, and alanine in specific, have an intrinsic preference for the polyproline II (pPII) conformation. Investigation of local order in the unfolded state is, however, complicated by experimental limitations and the inherent dynamics of the system, which has in some cases yielded inconsistent results from different types of experiments. One method of studying these systems is the use of short model peptides, and specifically short alanine peptides, known for predominantly sampling pPII structure in aqueous solution. Recently, He et al. ( J. Am. Chem. Soc. 2012 , 134 , 1571 - 1576 ) proposed that unblocked tripeptides may not be suitable models for studying conformational propensities in unfolded peptides due to the presence of end effect, that is, electrostatic interactions between investigated amino acid residues and terminal charges. To determine whether changing the protonation states of the N- and C-termini influence the conformational manifold of the central amino acid residue in tripeptides, we have examined the pH-dependence of unblocked trialanine and the conformational preferences of alanine in the alanine dipeptide. To this end, we measured and globally analyzed amide I' band profiles and NMR J-coupling constants. We described conformational distributions as the superposition of two-dimensional Gaussian distributions assignable to specific subspaces of the Ramachandran plot. Results show that the conformational ensemble of trialanine as a whole, and the pPII content (χpPII = 0.84) in particular, remains practically unaffected by changing the protonation state. We found that compared to trialanine, the alanine dipeptide has slightly lower pPII content (χpPII = 0.74) and an ensemble more reminiscent of the unblocked Gly-Ala-Gly model peptide. In addition, a two-state thermodynamic analysis of the conformational sensitive Δε(T) and (3)J(H(N)H(α))(T) data obtained from electronic circular dichroism and H NMR spectra indicate that the free energy landscape of trialanine is similar in all protonation states. MD simulations for the investigated peptides corroborate this notion and show further that the hydration shell around unblocked trialanine is unaffected by the protonation/deprotonation of the C-terminal group. In contrast, the alanine dipeptide shows a reduced water density around the central residue as well as a less ordered hydration shell, which decreases the pPII propensity and reduces the lifetime of sampled conformations.


Comparative stability of dimeric and monomeric pigments extracted from sea urchin Strongylocentrotus droebachiensis.
Ultraviolet-visible spectroscopy and UPLC-DAD-MS were used for analysis of stability of ethanol solutions of ethylidene-6,6'-bis(2,3,7-trihydroxynaphthazarin) (ENZ), spinochrome dimer (SDM) and spinochrome D (SD) that were isolated from Strongylocentrotus droebachiensis. In the freshly prepared solution, the concentration of ENZ at pH 6.0 was at 6 fold less comparing to pH 1.6. The increase of pH up to 4.0 resulted to increase of SD concentration and to decrease of SDM concentration. After 48 h storage, both dimers showed the highest stability at pH 1.6, while the elevation of the pH solution up to 6.0 activates degradation of SDM and ENZ at 1.3 and 3.6 fold correspondingly. The concentration of SD after 48 h storage at the pH 1.6 was at two-fold less comparing to the initial concentration, and at the pH 6.0 - at 4 fold less. This study contributes to increasing the knowledge on the stability of the spinochrome pigments.


Single-isomer trisubstituted olefins from a novel reaction of (E)-beta-chloro-alpha-iodo-alpha,beta-unsaturated esters and amides.
(E)-beta-chloro-alpha-iodo-alpha,beta-unsaturated esters are converted to single isomer trisubstituted olefins bearing three different carbon substituents by cross-coupling under reflux. Mechanistic investigations suggest that this process transfers a hydrogen from the boronic acid to the alpha-position of the substrate and then introduces an aryl group to the beta-position of the intermediate template while replacing chloride. The reaction is highly stereoselective, showing preference for the E-isomer. The process proceeds through (E)-beta-chloro-alpha-aryl-alpha,beta-unsaturated esters that are transformed efficiently into the corresponding E-products through stereoselective Suzuki-type reactions giving single isomers. The observed stereochemistry is apparently enabled by the intermediacy of a palladium allenoate. The reaction involves a catalytic cycle in which Pd(II) is reduced to Pd(0) through the formation of biaryl-coupled products.


Outcome of surgery in patients with painful dorsal wrist ganglia and arthroscopic confirmed ligament injury: a five-year follow-up.
We report the outcome of a five-year follow-up after wrist arthroscopy and excision of painful dorsal wrist ganglia. The findings at the time of surgery have previously been published. Patients responded to a validated postal questionnaire regarding ganglion recurrence, wrist pain and function. None of the responding patients had recurrence of the ganglia since surgery but only one patient had remained pain free with normal function following surgery. Three of the remaining patients reported moderate to severe problems with work and four reported minimal work problems. Our findings suggest patients with arthroscopic confirmed ligament injuries leading to joint instability or localised osteoarthritis may develop functional disability but less severe injuries are unlikely to cause persistent problems in the short- to medium-term. Surgical excision of the ganglion can give lasting satisfactory cosmetic outcome despite persisting underlying ligament pathology.


Design, Preparation, and Evaluation of Enteric Coating Formulation of HPMC and Eudragit L100 on Carboxylated Agarose Hydrogel by Using Drug Tartrazine.
Enteric-coated application on drug is used to prevent the drug from inactivation which are degraded by gastric enzyme. The present study is aimed at achieving controlled drug delivery in acidic medium of gastrointestinal tract (GIT) by enteric coating of hydroxy propyl methylcellulose (HPMC) and Eudragit L100 on carboxylated agarose hydrogel, creating a pH-dependent delivery system. Fourier-transformed infrared spectroscopy (FTIR) was for the detection of carboxylic group on agarose hydrogel, and scanning electron microscope (SEM) was used for the determination surface of prepared formulation. To check the pH sensitivity of enteric-coated formulation, different pH solution was used. It was found that the formulation was not dissolved in 1.2 but dissolve in pH 6.8 similarly; hydrogels lacking coating showed that tartrazine was more dissolved in pH 1.2, and less dissolved at pH 6.8. The release of tartrazine from the hydrogels was measured by using spectrophotometer and using a scanning electron microscope to examine the morphology and surface appearance of hydrogel capsules. This study revealed cracks on coated samples, while noncoated samples showed clear appearance with no cracks. Our findings revealed that this method could be useful for the development of an enteric coating drug delivery system.


Medical humanities at New York University School of Medicine: an array of rich programs in diverse settings.
The New York University School of Medicine has a rich tradition of cultivating programs in medical humanities and professionalism. They are drawn from the departments, centers, students, and faculty in the School of Medicine, have linkages throughout the university, and are interwoven into the fabric and culture of the institution. Some are centrally based in the School of Medicine's deans' office, and others are located in individual departments and receive support from the dean's office. This article describes representative programs for medical students and faculty. Curricular initiatives, the fundamental components of medical students' learning, include a course entitled "The Physician, Patient, and Society," a clerkship essay in the Medicine Clerkship, an opportunity for reflection during the medicine clerkship, and a medical humanities elective. In 2002, the Professionalism Initiative was launched to enhance and reflect the values of the medical profession. Its curriculum consists of a series of events that coordinate, particularly, with existing elements of the first-year curriculum (e.g., orientation week, a session during anatomy, a self-assessment workshop, and a peer-assessment workshop). The Master Scholars Program is a group of five, theme-based master societies consisting of faculty and students who share common interests around the society's themes. Programs developed for the societies include colloquia, faculty-led seminars, a mandatory student-mentoring program, and visiting scholars. Finally, the authors describe three high-quality literary publications created at New York University School of Medicine. Each of the initiatives undergoes regular critical examination and reflection that drive future planning.


Multi-band optical resonance of all-dielectric metasurfaces toward high-performance ultraviolet sensing.
All-dielectric sensors featuring low-loss resonances have been proposed instead of plasmonic-based sensors. However, reported dielectric-based sensors generally work in the visible and near-infrared regions and detect the intensity variation of resonant modes because the electromagnetic energy is mainly confined inside dielectric nanoparticles. It is a challenge to adjust the hotspots from the inside to the surface of the all-dielectric metasurface. In this study, highly uniform Si3N4 all-dielectric metasurfaces have been successfully fabricated as sensing platforms by utilizing nanosphere self-assembly and plasma enhanced chemical vapor deposition techniques. Experimental and simulated results demonstrate that proposed Si3N4 all-dielectric metasurfaces exhibit multiple optical resonant modes in the ultraviolet and visible wavelength and present distinct field-confinement in the gaps of nanoparticles. The hotspots have been successfully adjusted to the surface of Si3N4 nanoparticles. Delightedly, Si3N4 all-dielectric metasurfaces show characteristic wavelength shifts with variation of the refractive index, and the sensitivity can reach 707 nm per RIU for trace detection as sensing substrates. Proposed Si3N4 all-dielectric metasurfaces are promising to act as high-sensitive sensing substrates in the ultraviolet and visible wavelength with the ease of high-throughput fabrication.


Treatment of metastatic non-small cell lung cancer: 2018 guidelines of the Italian Association of Medical Oncology (AIOM).
The treatment landscape of metastatic non-small cell lung cancer (NSCLC) has dramatically evolved in recent years, since the recognition of several clinical-biological entities requiring personalized treatment approaches, leading to significant improvements in patients' survival outcomes. In particular, targeted therapies acting against EGFR, ALK, and ROS1, and immunotherapeutic agents modulating the PD-1/PD-L1 axis, represent new milestones in the treatment of advanced disease, supporting a chemotherapy backbone within a multidisciplinary model. The Italian Association of Medical Oncology (AIOM) has developed evidence-based guidelines for the management of lung tumors. Given the epidemiologic relevance, this report is dedicated to the treatment of advanced/metastatic NSCLC. These guidelines serve as a practical tool for oncologists, physicians, and other healthcare professionals to easily embrace the updated key points of NSCLC treatment strategies. Considering the upcoming introduction of potential new standards of care in several disease settings, these guidelines represent a benchmark from which to move forward.


Investigations of a combination of atopic status and age of asthma onset identify asthma subphenotypes.
Subphenotypes of asthma may be determined by age onset and atopic status. We sought to characterize early or late onset atopic asthma with fungal or non-fungal sensitization (AAFS or AANFS) and non-atopic asthma (NAA) in children and adults in the Severe Asthma Research Program (SARP). SARP is an ongoing project involving well-phenotyped patients with mild to severe asthma. Phenotypic comparisons were performed using Kruskal-Wallis or chi-square test. Genetic association analyses were performed using logistic or linear regression. Airway hyper-responsiveness, total serum IgE levels, and T2 biomarkers showed an increasing trend from NAA to AANFS and then to AAFS. Children and adults with early onset asthma had greater % of AAFS than adults with late onset asthma (46% and 40% vs. 32%; P < 0.00001). In children, AAFS and AANFS had lower % predicted FEV1 (86% and 91% vs. 97%) and greater % of patients with severe asthma than NAA (61% and 59% vs. 43%). In adults with early or late onset asthma, NAA had greater % of patients with severe asthma than AANFS and AAFS (61% vs. 40% and 37% or 56% vs. 44% and 49%). The G allele of rs2872507 in GSDMB had higher frequency in AAFS than AANFS and NAA (0.63 vs. 0.55 and 0.55), and associated with earlier age onset and asthma severity. Early or late onset AAFS, AANFS, and NAA have shared and distinct phenotypic characteristics in children and adults. AAFS is a complex disorder involving genetic susceptibility and environmental factors.


Biophysical considerations concerning gravity receptors and effectors including experimental studies on Phycomyces blakesleeanus.
Part I. Migration and Diffusion of Graviceptors: The physical action of gravitational and inertial forces on graviceptors is considered. The motion of graviceptors as influenced by physical dimensions, density, electric charge, composition of the suspending medium and flow variables is demonstrated. Part II. Observations on Geotropism in Phycomyces blakesleeanus: Mutants of Phycomyces blakesleeanus exhibit strikingly different rates of geotropic response. It is shown that Phycomyces grown in the dark lack normal geotropic responses: pre-exposure to light is necessary for the synthesis of structures responsible for geotropism. A physical model is presented that may account for some of the geotropic phenomena observed in Phycomyces.


Methionine-Containing Rhabdopeptide/Xenortide-like Peptides from Heterologous Expression of the Biosynthetic Gene Cluster kj12ABC in Escherichia coli.
Seven new methionine-containing rhabdopeptide/xenortide-like peptides (1-7) were identified from Escherichia coli expressing the rhabdopeptide/xenortide-like peptide biosynthetic gene cluster kj12ABC from Xenorhabdus KJ12.1. Their structures were elucidated by detailed HPLC-HR-MS/MS analysis and confirmed by chemical synthesis. Bioactivity tests of these first rhabdopeptide/xenortide-like peptide derivatives (2-7) showing methionine building blocks compared to the usually found derivatives containing exclusively hydrophobic amino acids such as valine, leucine, or phenylalanine revealed good activities of 2-7 against protozoan parasites and no cytotoxicity against mammalian L6 cells.


SIRIM Berhad: The Frontier in Medical and Health Technology.
With the world recovering from a public health disaster in the form of the COVID-19 pandemic and with political and social upheaval in the forms of wars such as in Ukraine and Sudan, localised fighting in various hotspots, the medical field faces huge challenges in addressing the needs of the various stakeholders. Still, these disasters represent opportunities to advance the new discoveries without compromising on the safety of the patients or general population. The COVID-19 vaccines were pushed through with great urgency driving on new discoveries of the genomic research, i.e. RNA based vaccines. This is complemented by the use of big data to monitor the disbursement of the vaccine to the general public. Unmistakably these new developments in tackling serious health disasters will lead to improvements on how the world tackle future crisis. Recent advances in artificial intelligence (AI), genomics discoveries and cell biology are driving research and fueling hope for the future. Amid this scenario of great upheavals and significant advances in technologies or emerging technologies for the health sector, SIRIM Berhad is increasing its preparedness in terms of development of new facilities and new competencies as well as building the platform for the communication of conventional health or medical technologies with other technologies particularly digital technologies to unlock the potential of emerging technologies in both medical and digital to develop novel solutions to future problems or challenges.


Histological Confirmation of Myelinated Neural Filaments Within the Tip of the Neurotrophic Electrode After a Decade of Neural Recordings.
Electrodes that provide brain to machine or computer interfacing must survive the lifetime of the person to be considered an acceptable prosthetic. The electrodes may be external such as with electroencephalographic (EEG), internal extracortical such as electrocorticographic (ECoG) or intracortical. Most intracortical electrodes are placed close to the neuropil being recorded and do not survive years of recording. However, the Neurotrophic Electrode is placed within the cortex and the neuropil grows inside and through the hollow tip of the electrode and is thus trapped inside. Highly flexible coiled lead wires minimize the strain on the electrode tip. Histological analysis includes immunohistochemical detection of neurofilaments and the absence of gliosis. This configuration led to a decade long recording in this locked-in person. At year nine, the neural activity underwent conditioning experiments indicating that the neural activity was functional and not noise. This paper presents data on the histological analysis of the tissue inside the electrode tip after 13 years of implantation. This paper is a singular example of histological analysis after a decade of recording. The histological analysis laid out herein is strong evidence that the brain can grow neurites into the electrode tip and record for a decade. This is profoundly important in the field of brain to machine or computer interfacing by implying that long term electrodes should incorporate some means of growing the neuropil into the electrode rather than placing the electrode into the neuropil.


[Evaluation of 105 cases with tuberculous pleurisy].
Tuberculous pleurisy has still importance in the group of exudative pleurisy. In this study we aimed to evaluate clinical, radiological, biochemical, bacteriological and histopathological findings of 105 cases with tuberculous pleurisy retrospectively, between January 1999 and December 2002. Female/male ratio was approximately 1/9 and mean age was 32.6 (range: 15-68). The common symptoms were chest pain (75.2%), cough (54.3%) and dyspnea (47.6%). In 17% cases parenchymal lesions were seen in the chest radiography while parenchymal lesions were found 52% of patients by computed tomography. Adenosine deaminase levels in pleural fluid were high in 80% of cases. PPD reactions was found positive in 84.7% of case. Sputum was studied in 52 cases. In 6 (11.5%) patients both ARB and culture were positive but in 4 (7.7%) patients was only culture positive. Pleural fluid ARB examination of all patients was negative whereas culture was positive only in 5 (5%) of patients. In two patients pleural biopsy material culture was positive for ARB. Cytological examination of pleural fluid revealed lymphocyte predominance in 81 (81%) of cases. Eighty one patients had pleural biopsy and pathologic evaluation revealed tuberculosis in 59 (73%) of them. At the end of the treatment 24 (23%) patients had pleural thickening. Pleural fluid LDH level of the patients with pleural thickening was higher than the other patients significantly (p=0.024). It is concluded that, pleural biopsy is the most effective diagnostic method for the tuberculous pleurisy and in the patient with elevated pleural LDH level, pleural thickening seems more.


Conserved CPEs in the p53 3' untranslated region influence mRNA stability and protein synthesis.
The 3' untranslated region (UTR) of p53 mRNA contains two conserved U-rich sequences resembling cytoplasmic polyadenylation elements (CPE). It is not known if these sequences regulate p53 expression by post-transcriptional mechanisms. Stable p53 3'UTR reporter HaCaT skin and MCF-7 breast cancer cell lines were established. Quantitative PCR and an enzymatic assay were used to quantify the reporter mRNA and protein levels, respectively. Proteins binding to the CPEs were identified by RNA-immunoprecipitation (IP) and quantitative mass spectroscopy. The wild-type p53 3'UTR reduced mRNA steady state levels of the reporter gene and point mutations in the CPEs rescued the mRNA steady state levels in the MCF-7 cells, but not in the HaCaT cells. In both cell lines, the CPEs had a significant effect on translation of the reporter and influenced the effect of UV irradiation. Several proteins (including GAPDH, heterogeneous nuclear ribonucleoprotein (hnRNP) D and A/B) were identified from the MCF-7 cytoplasmic extracts that bound specifically to the CPEs. Two conserved CPEs in the p53 3'UTR regulate stability and translation of a reporter mRNA in non-irradiated as well as irradiated cells. GAPDH, hnRNP D and hnRNP A/B bind specifically to the p53 CPEs and could potentially be involved in the post-transcriptional regulation of p53.


Effect of dietary n-3 polyunsaturated fatty acids on brain lipid fatty acid composition, learning ability, and memory of senescence-accelerated mouse.
Animal studies have shown that a deficiency in brain of the n-3 polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) is associated with memory loss and diminished cognitive function. The senescence-accelerated prone 8 (SAMP8) mouse develops impairments in learning and memory at 8-12 months of age. The effect of diet supplemented with n-3 PUFA on brain phospholipid DHA status, learning, and memory ability in aged SAMP8 mice was investigated. At the age of 10 months, SAMP8 mice were fed either a low-DHA or a high-DHA diet for 8 weeks. In comparison to SAMP8 mice fed the low-DHA diet, those fed a high-DHA diet had improved acquisition and retention in a T-maze foot shock avoidance test and a higher proportion of DHA in hippocampal and amygdala phospholipids. This study demonstrates that, in mature animals, DHA is incorporated into brain phospholipids and that dietary n-3 PUFA is associated with delay in cognitive decline.


Sclerosing Muc-4-positive sarcoma with glandular differentiation resembling sclerosing epithelioid fibrosarcoma.
Sclerosing epithelioid fibrosarcoma is a rare soft tissue tumor that is composed of epithelioid fibroblasts embedded in an abundant extracellular collagenous matrix. They have been shown to be weakly epithelial membrane antigen (EMA) positive by immunohistochemistry and may contain intercellular junctions ultrastructurally. We present a case of a 52-year-old female who presented with a sclerosing Muc-4-positive sarcoma with glandular differentiation of the sciatic nerve, resembling sclerosing epithelioid fibrosarcoma. The glandular component showed strong expression of keratin and EMA and ultrastructurally showed numerous intercellular junctions and intraluminal microvilli, supportive of true glandular differentiation. The patient received preoperative radiotherapy (50 Gray) and subsequent resection of the mass with negative margins. She is currently disease free at 20-month follow-up. This case report describes an unusual sclerosing Muc-4-positive sarcoma with glandular differentiation, distinctive expression of epithelial immunohistochemical markers, and glandular differentiation by electron microscopy.


Self-reported COVID-19 symptoms on Twitter: an analysis and a research resource.
To mine Twitter and quantitatively analyze COVID-19 symptoms self-reported by users, compare symptom distributions across studies, and create a symptom lexicon for future research. We retrieved tweets using COVID-19-related keywords, and performed semiautomatic filtering to curate self-reports of positive-tested users. We extracted COVID-19-related symptoms mentioned by the users, mapped them to standard concept IDs in the Unified Medical Language System, and compared the distributions to those reported in early studies from clinical settings. We identified 203 positive-tested users who reported 1002 symptoms using 668 unique expressions. The most frequently-reported symptoms were fever/pyrexia (66.1%), cough (57.9%), body ache/pain (42.7%), fatigue (42.1%), headache (37.4%), and dyspnea (36.3%) amongst users who reported at least 1 symptom. Mild symptoms, such as anosmia (28.7%) and ageusia (28.1%), were frequently reported on Twitter, but not in clinical studies. The spectrum of COVID-19 symptoms identified from Twitter may complement those identified in clinical settings.


Methods to study adult hippocampal neurogenesis in humans and across the phylogeny.
The hippocampus hosts the continuous addition of new neurons throughout life-a phenomenon named adult hippocampal neurogenesis (AHN). Here we revisit the occurrence of AHN in more than 110 mammalian species, including humans, and discuss the further validation of these data by single-cell RNAseq and other alternative techniques. In this regard, our recent studies have addressed the long-standing controversy in the field, namely whether cells positive for AHN markers are present in the adult human dentate gyrus (DG). Here we review how we developed a tightly controlled methodology, based on the use of high-quality brain samples (characterized by short postmortem delays and ≤24 h of fixation in freshly prepared 4% paraformaldehyde), to address human AHN. We review that the detection of AHN markers in samples fixed for 24 h required mild antigen retrieval and chemical elimination of autofluorescence. However, these steps were not necessary for samples subjected to shorter fixation periods. Moreover, the detection of labile epitopes (such as Nestin) in the human hippocampus required the use of mild detergents. The application of this strictly controlled methodology allowed reconstruction of the entire AHN process, thus revealing the presence of neural stem cells, proliferative progenitors, neuroblasts, and immature neurons at distinct stages of differentiation in the human DG. The data reviewed here demonstrate that methodology is of utmost importance when studying AHN by means of distinct techniques across the phylogenetic scale. In this regard, we summarize the major findings made by our group that emphasize that overlooking fundamental technical principles might have consequences for any given research field.


Comparative morphological and biochemical analysis of hypertrophic, non-hypertrophic and 1,25(OH)2D3 treated non-hypertrophic chondrocytes.
A comparative study of Type X collagen expression, chondrocyte morphology, and the expression of two genes controlling chondrocyte morphology (beta-actin and fibronectin) was carried out on chondrocytes derived from a tissue that remains as permanent hyaline cartilage in vivo (embryonic chicken caudal sterna), from a tissue that undergoes endochondral replacement (embryonic chicken ventral vertebrae) and caudal sternal chondrocytes treated with 1,25(OH)2D3. Under identical in vitro growth conditions and times, sternal chondrocytes grew as rounded non-adherent cells, and vertebral chondrocytes grew as adherent polygonal cells. Upon treatment with 10(-8) M 1,25(OH)2D3 over a twelve day period the sternal chondrocytes showed complete adherence and took on an identical appearance as the vertebral chondrocytes. Cellular adherence of both vertebral and 1,25(OH)2D3 treated sternal chondrocytes was associated with 10 X increased beta-actin, fibronectin and their corresponding mRNA's. Changes in connective tissue expression were observed with altered cellular morphology. Total collagen synthesis was 35-50% lower in both hormone treated and vertebral chondrocytes. Type II collagen was the major collagen type produced by all chondrocyte cultures; however, in both vertebral and 1,25(OH)2D3 treated sternal chondrocytes, a 60 kD collagenous protein was identified. This short chain collagen was determined to be Type X collagen based on its molecular weight and its CNBr peptide maps. Analysis of Type X mRNA levels using a 33 base pair anti sense oligonucleotide sequence to Type X, demonstrated that vertebral cells showed six to seven times more mRNA than sternal chondrocytes. However, the low mRNA levels of type X mRNA in sternal chondrocytes were increased two to three times by 1,25(OH)2D3 treatment. These studies demonstrate that the steroid hormone 1,25(OH)2 vitamin D3 induced morphological, biochemical and molecular changes indicative of chondrocyte maturation from a hyaline to a more hypertrophic phenotype.


Hyperthermia Using Antibody-Conjugated Magnetic Nanoparticles and Its Enhanced Effect with Cryptotanshinone.
Heat dissipation by magnetic nanoparticles (MNPs) under an alternating magnetic field can be used to selectively treat cancer tissues. Antibodies conjugated to MNPs can enhance the therapeutic effects of hyperthermia by altering antibody-antigen interactions. Fe₃O₄ nanoparticles (primary diameter, 20-30 nm) coated with polyethylenimine (PEI) were prepared and conjugated with CH11, an anti-Fas monoclonal antibody. HeLa cell growth was then evaluated as a function of antibody and MNP/antibody complex doses. HeLa cell growth decreased with increased doses of the antibody and complexes. However, MNPs alone did not affect cell growth; thus, only the antibody affected cell growth. In hyperthermia experiments conducted using an alternating magnetic field frequency of 210 kHz, cell viability varied with the intensity of the applied alternating magnetic field, because the temperature increase of the culture medium with added complexes was dependent on magnetic field intensity. The HeLa cell death rate with added complexes was significantly greater as compared with that with MNPs alone. Cryptotanshinone, an anti-apoptotic factor blocker, was also added to cell cultures, which provided an additional anti-cancer cell effect. Thus, an anti-cancer cell effect using a combination of magnetic hyperthermia, an anti-Fas antibody and cryptotanshinone was established.


Rapid Stereocomplexation between Enantiomeric Comb-Shaped Cellulose-g-poly(L-lactide) Nanohybrids and Poly(D-lactide) from the Melt.
In this work we report the in situ preparation of fully biobased stereocomplex poly(lactide) (SC-PLA) nanocomposites grafted onto nanocrystalline cellulose (NCC). The stereocomplexation rate by compounding high-molar-mass poly(D-lactide) (PDLA) with comb-like NCC grafted poly(L-lactide) is rather high in comparison with mixtures of PDLA and PLLA. The rapid stereocomplexation was evidenced by a high stereocomplexation temperature (Tc-sc = 145 °C) and a high SC crystallinity (Xc-sc = 38%) upon fast cooling (50 °C/min) from the melt (250 °C for 2 min), which are higher than currently reported values. Moreover, the half-life crystallization time (175-190 °C) of the SC-PLA was shortened by 84-92% in comparison with the PDLA/PLLA blends. The high(er) stereocomplexation rate and the melt stability of the SC in the nanocomposites were ascribed to the nucleation effect of the chemically bonded NCC and the "memory effect" of molecular pairs in the stereocomplex melt because of the confined freedom of the grafted PLLA chains.


The long-acting vasoactive intestinal polypeptide agonist RO 25-1553 is highly selective of the VIP2 receptor subclass.
RO 25-1553 is a synthetic VIP analogue that induced a long-lasting relaxation of tracheal and bronchial smooth muscles as well as a reduction of edema and eosinophilic mobilization during pulmonary anaphylaxis. In the present study, we tested in vitro the capacity of RO 25-1553 to occupy the different VIP/PACAP receptor subclasses and to stimulate adenylate cyclase activity. The cellular models tested expressed one single receptor subtype: Chinese hamster ovary (CHO) cells transfected with the rat recombinant PACAP I, rat VIP1, and human VIP2 receptors; SUP T1 cells expressing the human VIP2 and HCT 15 and LoVo cells expressing the human VIP1 receptor. RO 25-1553 was threefold more potent than VIP on the human VIP2 receptor, 100- and 600-fold less potent than VIP on the rat and human VIP1 receptors, respectively, and 10-fold less potent than VIP and 3000-fold less potent than PACAP on the PACAP I receptor. RO 25-1553 was a full agonist on the VIP2, the PACAP I, and the rat recombinant VIP1 receptor but a partial agonist only on the human VIP1 receptor. Thus, RO 25-1553 is a highly selective agonist ligand for the VIP2 receptor subclass.


Identification of Pulmonary Nodules by Sweeping the Surface of the Lung with an Electrical Bioimpedance Probe: A Feasibility Study.
Purpose: Identifying and localizing the invisible and nonpalpable pulmonary nodules are among the main challenges surgeons face during open and thoracoscopic surgeries. This in vitro study explores the feasibility of utilizing a simple and safe electrical bioimpedance probe in locating the pulmonary nodules by sweeping the surface of the lung tissue. Methods: A probe was designed with four spherical electrodes that were used for recording the bioimpedance spectrum of the lung tissue in a frequency range of 50 kHz to 5 MHz. In each of the 10 resected surgical specimens, the bioimpedance of normal lung tissue as well as the tumoral lung tissue were recorded and compared with each other. Results: By drawing the Nyquist curves, it was determined that the amplitude of the electrical impedance measured by moving the probe from the healthy point to the region of the pulmonary nodule decreases and the frequency characteristics of the bioimpedance spectrum increases. Conclusion: This method could be potentially beneficial in the localization of invisible and even nonpalpable in-depth pulmonary nodules in thoracic surgeries.


Prevention of accidents by transportation shiftworkers.
For commercial transportation operations, around-the-clock operations are not a recent development. Despite the tenure of these practices, many accidents related to hours worked continue to be a problem. Although efforts by shiftwork experts to solve these problems are often mode specific, the transportation field does suggest several alternative approaches, which may be relevant to general shiftwork problems outside the transportation area. Four contemporary approaches to transportation shiftwork are discussed: environmental design, equipment design, organizational design, and information access systems. Examples are presented within each of these approaches.


The anomaly of oxygen diffusion in aqueous xanthan solutions.
A membrane-covered polarographic oxygen electrode was used to measure oxygen diffusion coefficients in aqueous polyelectrolyte solutions of xanthan gum, sodium alginate, and sodium carboxymethylcellulose (CMC). In sodium alginate solutions, dilute xanthan solutions, and solutions containing more than 0.3 wt % CMC, oxygen diffusion coefficients decrease with increasing polymer concentrations. Interestingly, in dilute CMC solutions and concentrate xanthan solutions containing more than 0.5 wt % xanthan gum, oxygen diffusion coefficients increase with increasing polymer concentrations, and values exceeding that in pure water are generally observed.


Comparative Proteomic Analysis of Hymenolepis diminuta Cysticercoid and Adult Stages.
Cestodiases are common parasitic diseases of animals and humans. As cestodes have complex lifecycles, hexacanth larvae, metacestodes (including cysticercoids), and adults produce proteins allowing them to establish invasion and to survive in the hostile environment of the host. Hymenolepis diminuta is the most commonly used model cestode in experimental parasitology. The aims of the present study were to perform a comparative proteomic analysis of two consecutive developmental stages of H. diminuta (cysticercoid and adult) and to distinguish proteins which might be characteristic for each of the stages from those shared by both stages. Somatic proteins of H. diminuta were isolated from 6-week-old cysticercoids and adult tapeworms. Cysticercoids were obtained from experimentally infected beetles, Tenebrio molitor, whereas adult worms were collected from experimentally infected rats. Proteins were separated by GeLC-MS/MS (one dimensional gel electrophoresis coupled with liquid chromatography and tandem mass spectrometry). Additionally protein samples were digested in-liquid and identified by LC-MS/MS. The identified proteins were classified according to molecular function, cellular components and biological processes. Our study showed a number of differences and similarities in the protein profiles of cysticercoids and adults; 233 cysticercoid and 182 adult proteins were identified. From these proteins, 131 were present only in the cysticercoid and 80 only in the adult stage samples. Both developmental stages shared 102 proteins; among which six represented immunomodulators and one is a potential drug target. In-liquid digestion and LC-MS/MS complemented and confirmed some of the GeLC-MS/MS identifications. Possible roles and functions of proteins identified with both proteomic approaches are discussed.


CD4 counts in laboratory monitoring of HIV disease--experience from western India.
CD4 counts vary in different populations. The present study was conducted to determine CD4 counts in different World Health Organization (WHO) clinical stages in antiretroviral therapy naive individuals and to find out optimum CD4 cutoffs. Data of adult HIV seropositive patients who underwent CD4 count and total lymphocyte count (TLC) testing were included for analysis. The severity of immunosuppression was graded based on WHO criteria. To establish optimum CD4 cutoff values, receiver-operator characteristics (ROC) curves were generated. Of 754 patients, 52.2% had CD4 counts <200 cells/mm3, but only 2.3% belonged to WHO stage IV. Newer CD4 cutoffs generated were 280, 120-280, <120 cells/mm3. Spearman rank correlation between CD4 counts and TLC was found to be weak (r = .32). The cutoff values of CD4 counts for HIV disease may need to be revised for India. Regular CD4 count estimation is a must for monitoring disease progression in people living with HIV/AIDS.


Steroid-resistant nephrotic syndrome: long-term evolution after sequential therapy.
We present a retrospective study of 30 children of mean age 3.02 +/- 1.81 years with steroid-resistant nephrotic syndrome (SRNS) treated with intravenous injection of methylprednisolone plus orally administered prednisone; 24 children also received cyclophosphamide (CP). Sixteen were resistant to steroids from the beginning, and 14 after a mean of 11.26 +/- 16.61 months. The initial histological diagnosis was: 18 minimal change disease (MCD), 11 focal segmental glomerulosclerosis (FSGS) and one diffuse mesangial proliferative glomerulonephritis (DMPG). Total remission was achieved in 22 patients (73.3%), partial response in three (10%) and no response in five (16.6%), two of whom were brothers carrying an NPHS2 gene double mutation. There was no difference in response between the MCD and FSGS patients; the only patient with DMPG did not respond. Only initial resistance was a sign of bad prognosis. At follow-up (6.4 +/- 3.6 years from last pulse), 21/22 were still in remission, 14/21 were without treatment. Six patients required cyclosporine or mycophenolate mofetil because of steroid dependence. Two non-responders developed end-stage renal failure (ESRF); the remaining patients maintained normal glomerular filtration. The treatment was well tolerated. In conclusion, most of the patients treated with sequential therapy consisting of methylprednisolone (MP) (100%) and CP (80%) showed remission and preserved renal function, but 20% developed steroid dependence.


Sky coverage modeling for the whole sky for laser guide star multiconjugate adaptive optics.
The scientific productivity of laser guide star adaptive optics systems strongly depends on the sky coverage, which describes the probability of finding natural guide stars for the tip/tilt wavefront sensor(s) to achieve a certain performance. Knowledge of the sky coverage is also important for astronomers planning their observations. In this paper, we present an efficient method to compute the sky coverage for the laser guide star multiconjugate adaptive optics system, the Narrow Field Infrared Adaptive Optics System (NFIRAOS), being designed for the Thirty Meter Telescope project. We show that NFIRAOS can achieve more than 70% sky coverage over most of the accessible sky with the requirement of 191 nm total rms wavefront.


Immune response to postprimary tuberculosis in mice: Mycobacterium tuberculosis and Miycobacterium bovis bacille Calmette-Guérin induce equal protection.
We addressed the question of whether protective immunity induced by natural infection with Mycobacterium tuberculosis and that induced by vaccination with Mycobacterium bovis bacille Calmette-Guerin (BCG) differ in the murine model. We infected mice with M. tuberculosis Erdman, cured them by chemotherapy, and subsequently reinfected them with a low dose of M. tuberculosis H37Rv. The course of tuberculosis was compared with that in mice previously vaccinated with BCG Danish 1331. Protection against postprimary M. tuberculosis infection did not differ significantly between the 2 groups. After challenge infection, numbers of interferon- gamma -positive splenocytes did not differ between mice with primary infection and vaccinated mice. Splenocytes from primary M. tuberculosis-infected mice conferred marginally higher protection than did those from BCG-vaccinated mice. Serum transfer did not protect against reinfection in either group. Our data emphasize that natural infection with M. tuberculosis and vaccination with BCG do not differ in their capacity to induce protective immunity against tuberculosis and support the notions that reinfection contributes to the development of active disease and that any novel vaccine against tuberculosis has to perform better than both vaccination with BCG and immunity evoked by natural infection.


Function and Clinical Implications of Long Non-Coding RNAs in Melanoma.
Metastatic melanoma is the most deadly type of skin cancer. Despite the success of immunotherapy and targeted agents, the majority of patients experience disease recurrence upon treatment and die due to their disease. Long non-coding RNAs (lncRNAs) are a new subclass of non-protein coding RNAs involved in (epigenetic) regulation of cell growth, invasion, and other important cellular functions. Consequently, recent research activities focused on the discovery of these lncRNAs in a broad spectrum of human diseases, especially cancer. Additional efforts have been undertaken to dissect the underlying molecular mechanisms employed by lncRNAs. In this review, we will summarize the growing evidence of deregulated lncRNA expression in melanoma, which is linked to tumor growth and progression. Moreover, we will highlight specific molecular pathways and modes of action for some well-studied lncRNAs and discuss their potential clinical implications.


Postoperative analgesia after radical retropubic prostatectomy: a double-blind comparison between low thoracic epidural and patient-controlled intravenous analgesia.
Postoperative pain after radical retropubic prostatectomy can be severe unless adequately treated. Low thoracic epidural analgesia and patient-controlled intravenous analgesia were compared in this double-blind, randomized study. Sixty patients were randomly assigned to receive either low thoracic epidural analgesia (group E) or patient-controlled intravenous analgesia (group P) for postoperative pain relief. All patients had general anesthesia combined with thoracic epidural analgesia during the operation. Postoperatively, patients in group E received an infusion of 1 mg/ml ropivacaine, 2 microg/ml fentanyl, and 2 microg/ml adrenaline, 10 ml/h during 48 h epidurally, and a placebo patient-controlled intravenous analgesia pump intravenously. Patients in group P received a patient-controlled intravenous analgesia pump with morphine intravenously and 10 ml/h placebo epidurally. Pain, the primary outcome variable, was measured using the numeric rating scale at rest (incision pain and "deep" visceral pain) and on coughing. Secondary outcome variables included gastrointestinal function, respiratory function, mobilization, and full recovery. Health-related quality of life was measured using the Short Form-36 questionnaire, and plasma concentration of fentanyl was measured in five patients to exclude a systemic effect of fentanyl. Incisional pain and pain on coughing were lower in group E compared with group P at 2-24 h, as was deep pain between 3 and 24 h postoperatively (P < 0.05). Maximum expiratory pressure was greater in group E at 4 and 24 h (P < 0.05) compared with group P. No difference in time to home discharge was found between the groups. The mean plasma fentanyl concentration varied from 0.2 to 0.3 ng/ml during 0-48 h postoperatively. At 1 month, the scores on emotional role, physical functioning, and general health of the Short Form-36 were higher in group E compared with group P. However, no group x time interaction was found in the Short Form-36. The authors found evidence for better pain relief and improved expiratory muscle function in patients receiving low thoracic epidural analgesia compared with patient-controlled analgesia for radical retropubic prostatectomy. Low thoracic epidural analgesia can be recommended as a good method for postoperative analgesia after abdominal surgery.


Pure-tone threshold estimation from extrapolated distortion product otoacoustic emission I/O-functions in normal and cochlear hearing loss ears.
A new method for direct pure-tone threshold estimation from input/output functions of distortion product otoacoustic emissions (DPOAEs) in humans is presented. Previous methods use statistical models relating DPOAE level to hearing threshold including additional parameters e.g., age or slope of DPOAE I/O-function. Here we derive a DPOAE threshold from extrapolated DPOAE I/O-functions directly. Cubic 2 f1-f2 distortion products and pure-tone threshold at f2 were measured at 51 frequencies between f2=500 Hz and 8 kHz at up to ten primary tone levels between L2=65 and 20 dB SPL in 30 normally hearing and 119 sensorineural hearing loss ears. Using an optimized primary tone level setting (L1 = 0.4L2 + 39 dB) that accounts for the nonlinear interaction of the two primaries at the DPOAE generation site at f2, the pressure of the 2 f1-f2 distortion product pDP is a linear function of the primary tone level L2. Linear regression yields correlation coefficients higher than 0.8 in the majority of the DPOAE I/O-functions. The linear behavior is sufficiently fulfilled for all frequencies in normal and impaired hearing. This suggests that the observed linear functional dependency is quite general. Extrapolating towards pDP=0 yields the DPOAE threshold for L2. There is a significant correlation between DPOAE threshold and pure-tone threshold (r=0.65, p<0.001). Thus, the DPOAEs that reflect the functioning of an essential element of peripheral sound processing enable a reliable estimation of cochlear hearing threshold up to hearing losses of 50 dBHL without any statistical data.


Endothelial cell activation and glycocalyx shedding - potential as biomarkers in patients with lupus nephritis.
Lupus nephritis (LN) is a common and severe manifestation of systemic lupus erythematosus and an important cause of acute and chronic kidney injury. Early diagnosis of LN and preventing relapses are key to preserving renal reserve. However, due to the complexity and heterogeneity of the disease, clinical management remains challenging. Kidney biopsy remains the gold standard for confirming the diagnosis of LN and subsequent assessment of kidney histopathology, but it is invasive and cannot be repeated frequently. Current clinical indicators of kidney function such as proteinuria and serum creatinine level are non-specific and do not accurately reflect histopathological changes, while anti-dsDNA antibody and C3 levels reflect immunological status but not kidney injury. Identification of novel and specific biomarkers for LN is prerequisite to improve management. Renal function deterioration is associated with changes in the endothelial glycocalyx, a delicate gel-like layer located at the interface between the endothelium and bloodstream. Inflammation induces endothelial cell activation and shedding of glycocalyx constituents into the circulation. This review discusses the potential role of soluble glycocalyx components as biomarkers of active LN, especially in patients in whom conventional serological and biochemical markers do not appear helpful.


Organocatalyzed Trifluoromethylation of Ketones and Sulfonyl Fluorides by Fluoroform under a Superbase System.
Fluoroform (HCF3, HFC-23) is a side product in the manufacture of polytetrafluoroethylene (Teflon). Despite its attractive properties, taming HCF3 for trifluoromethylation is quite problematic owing to its low acidity and the lability of the naked trifluoromethyl carbanion generated from HCF3. Herein we report the organic-superbase-catalyzed trifluoromethylation of ketones and arylsulfonyl fluorides by HCF3. The reactions were carried out by using a newly developed "superbase organocatalyst system" consisting of catalytic amounts of P4-tBu and N(SiMe3)3. A series of aryl and alkyl ketones were converted into the corresponding α-trifluoromethyl carbinols in good yields under the organocatalysis conditions in THF. The superbase organocatalytic system can also be applied to the trifluoromethylation of arylsulfonyl fluorides for biologically important aryl triflones in THF or DMF in good yields. Protonated P4-tBu, H[P4-tBu](+), is suggested to be crucial for the catalytic process. This new catalytic methodology using HCF3 is expected to expand the range of synthetic applications of trifluoromethylation.


Risk factors for dogs becoming rectal carriers of multidrug-resistant Escherichia coli during hospitalization.
This study aimed to identify risk factors for dogs becoming rectal carriers of multidrug-resistant (MDR) Escherichia coli while hospitalized in a veterinary teaching hospital. Exposures to potential risk factors, including treatments, hospitalization, and interventions during a 42-day pre-admission period and hospitalization variables, were assessed for 90 cases and 93 controls in a retrospective, risk-based, case-control study. On multivariable analyses, hospitalization for >6 days [odds ratio (OR) 2·91-8·00], treatment with cephalosporins prior to admission (OR 5·04, 95% CI 1·25-20·27), treatment with cephalosporins for >1 day (OR 5·18, 95% CI 1·86-14·41), and treatment with metronidazole (OR 7·17, 95% CI 1·01-50·79) while hospitalized were associated with increased risk of rectal carriage of MDR E. coli during hospitalization. The majority of rectal isolates obtained during the study period conformed to MDR E. coli clonal groups previously obtained from extraintestinal infections. These results can assist the development of improved infection control guidelines for the management of dogs in veterinary hospitals to prevent the occurrence of nosocomial clinical infections.


High-Density Linkage Map Construction and QTL Identification in a Diploid Blueberry Mapping Population.
Genotyping by sequencing approaches have been widely applied in major crops and are now being used in horticultural crops like berries and fruit trees. As the original and largest producer of cultivated blueberry, the United States maintains the most diverse blueberry germplasm resources comprised of many species of different ploidy levels. We previously constructed an interspecific mapping population of diploid blueberry by crossing the parent F1#10 (Vaccinium darrowii Fla4B × diploid V. corymbosum W85-20) with the parent W85-23 (diploid V. corymbosum). Employing the Capture-Seq technology developed by RAPiD Genomics, with an emphasis on probes designed in predicted gene regions, 117 F1 progeny, the two parents, and two grandparents of this population were sequenced, yielding 131.7 Gbp clean sequenced reads. A total of 160,535 single nucleotide polymorphisms (SNPs), referenced to 4,522 blueberry genome sequence scaffolds, were identified and subjected to a parent-dependent sliding window approach to further genotype the population. Recombination breakpoints were determined and marker bins were deduced to construct a high density linkage map. Twelve blueberry linkage groups (LGs) consisting of 17,486 SNP markers were obtained, spanning a total genetic distance of 1,539.4 cM. Among 18 horticultural traits phenotyped in this population, quantitative trait loci (QTLs) that were significant over at least 2 years were identified for chilling requirement, cold hardiness, and fruit quality traits of color, scar size, and firmness. Interestingly, in 1 year, a QTL associated with timing of early bloom, full bloom, petal fall, and early green fruit was identified in the same region harboring the major QTL for chilling requirement. In summary, we report here the first high density bin map of a diploid blueberry mapping population and the identification of several horticulturally important QTLs.


Right ventricular global longitudinal strain is an independent predictor of right ventricular function: a multimodality study of cardiac magnetic resonance imaging, real time three-dimensional echocardiography and speckle tracking echocardiography.
Accurate assessment of right ventricular (RV) systolic function is important, as it is an established predictor of mortality in cardiac and respiratory diseases. We aimed to compare speckle tracking-derived longitudinal deformation measurements with traditional two-dimensional (2D) echocardiographic parameters, as well as real time three-dimensional echocardiography (RT3DE) and cardiac magnetic resonance imaging (CMR)-derived RV volumes and ejection fraction (EF). Subjects referred for CMR also underwent echocardiography. On both RT3DE and CMR, we measured RV volumes and EF. On 2D echocardiography, we analyzed RV fractional area change, RV internal diastolic diameter, tricuspid annular plane systolic excursion, tricuspid annular tissue Doppler-derived velocity, myocardial performance index, and RV global longitudinal strain (RV GLS). Sixty subjects were recruited (mean age = 45 ± 10 years; 60% male). RV GLS (R = -0.69, P < 0.001) and RT3DE RVEF (R = 0.56, P < 0.001) correlated well with CMR RVEF. RT3DE RV end-diastolic (RVEDV) and end-systolic (RVESV) volumes also correlated with CMR RV volumes: RVEDV, R = 0.74, P < 0.001 and RVESV, R = 0.84, P < 0.001. In addition, RV GLS best predicted the presence of RV dysfunction, defined as RVEF <48% on CMR (hazard ratio = 7.0 [1.5-31.7], P < 0.01). On receiver operator characteristic analysis, a RV GLS of -20% was the most sensitive and specific predictor of RV dysfunction (AUC 0.8 [0.57-1.0], P < 0.02). RVEF and volumes estimated on RT3DE were closely correlated with CMR measurements. When compared to more traditional markers of RV systolic function and RT3DE, RVGLS produced the highest correlation with CMR RVEF and was a good predictor of RV dysfunction. RV GLS should be considered a complementary modality to RT3DE and CMR in the assessment of RV systolic function.


Two new molecular bases for the Dombrock null phenotype.
Red blood cells (RBCs) with the Do(null) phenotype lack all antigens in the Dombrock blood group system, i.e. Do(a), Do(b), Gy(a), Hy and Jo(a). Sequence analysis of DNA from one proband with the Do(null) phenotype revealed a single nucleotide mutation of t to c in the donor splice site of DO (IVS1 + 2t > c), with outsplicing of exon 2. Analysis of a second proband revealed a homozygous nonsense mutation 442 C > T in exon 2 predicting a premature stop codon (Gln148 Stop). The molecular bases described in these two probands provide an explanation for the lack of Do glycoprotein on their RBCs.


Disorder-Enriched Magnetic Excitations in a Heisenberg-Kitaev Quantum Magnet Na_{2}Co_{2}TeO_{6}.
Using optical magnetospectroscopy, we investigate the magnetic excitations of Na_{2}Co_{2}TeO_{6} in a broad magnetic field range (0 T≤B≤17.5 T) at low temperature. Our measurements reveal rich spectra of in-plane magnetic excitations with a surprisingly large number of modes, even in the high-field spin-polarized state. Theoretical calculations find that the Na-occupation disorder in Na_{2}Co_{2}TeO_{6} plays a crucial role in generating these modes. Our Letter demonstrates the necessity to consider disorder in the spin environment in the search for Kitaev quantum spin liquid states in practicable materials.


An inducible RNA interference system for the functional dissection of mouse embryogenesis.
Functional analysis of multiple genes is key to understanding gene regulatory networks controlling embryonic development. We have developed an integrated vector system for inducible gene silencing by shRNAmir-mediated RNA interference in mouse embryos, as a fast method for dissecting mammalian gene function. For validation of the vector system, we generated mutant phenotypes for Brachyury, Foxa2 and Noto, transcription factors which play pivotal roles in embryonic development. Using a series of Brachyury shRNAmir vectors of various strengths we generated hypomorphic and loss of function phenotypes allowing the identification of Brachyury target genes involved in trunk development. We also demonstrate temporal control of gene silencing, thus bypassing early embryonic lethality. Importantly, off-target effects of shRNAmir expression were not detectable. Taken together, the system allows the dissection of gene function at unprecedented detail and speed, and provides tight control of the genetic background minimizing intrinsic variation.


Open and Closed Endotracheal Suctioning and Arterial Blood Gas Values: A Single-Blind Crossover Randomized Clinical Trial.
Aim. This study was aimed at comparing the effects of the open and closed suctioning techniques on the arterial blood gas values in patients undergoing open-heart surgery. Methods. In a clinical trial, we recruited 42 patients after open-heart surgery in an educational hospital. Each patient randomly underwent both open and closed suctioning. ABGs, PaO2, SaO2, PaCO2, were analyzed before and one, five, and fifteen minutes after each suctioning episode. Results. At first the pressure of oxygen in arterial blood increased; however, this increase in the open technique was greater than that of the closed system (P < 0.001). The pressure of oxygen decreased five and fifteen minutes after both suctioning techniques (P < 0.05). The trends of carbon dioxide variations after the open and closed techniques were upward and downward, respectively. Moreover, the decrease in the level of oxygen saturation five and fifteen minutes after the open suctioning was greater than that of the closed suctioning technique (P < 0.05). Conclusion. Arterial blood gas disturbances in the closed suctioning technique were less than those of the open technique. Therefore, to eliminate the unwanted effects of endotracheal suctioning on the arterial blood gases, the closed suctioning technique is recommended.


[A multicenter, randomized controlled trial of wheat cellulose particles in the treatment of internal hemorrhoids].
To evaluate the efficacy and safety of wheat cellulose particles (testa triticum tricum purify, Fiberform) in the treatment of internal hemorrhoid. A multicenter randomized controlled clinical trial was adopted. From October 2015 to July 2016, 60 patients with internal hemorrhoid were enrolled from three medical centers, including Department of Anorectum, Shuguang Hospital of Shanghai University of Traditional Chinese Medicine, Department of Anorectum, The Third Affiliated Hospital of Nanjing University of Chinese Medicine, Department of Anorectum, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine. Enrollment criteria: Patients aging from 18 to 65 years old; being diagnosed with the second or third grade internal hemorrhoid; having good communication skills and being able to complete the records and follow-ups according to the research program requirements. Patients combined with other anal diseases, or whose anus tube or rectum suffering occupying lesions; patients currently using other methods and defecation drugs in the treatment of their hemorrhoids; patients in pregnancy or with diseases of heart, liver, kidney or metabolic disorders; patients suffering from constipation due to other diseases and drugs, and long-term laxatives abusers. According to the random number table method, 60 patients were randomly divided into the combined treatment group [30 cases, wheat cellulose particles 1 bag each time, 2 times per day; Diosmin tablet 2 pills, 2 times per day] and the single treatment group [30 cases, Diosmin tablet 2 pills, 2 times per day]. The treatment courses for both groups were 7 days. According to the four-grade scoring method, the efficacy evaluation would be made on six indicators, which were the degree of hematochezia or bleeding, the degree of pain, hemorrhoid prolapse, the shapes and properties of stool, the defecation frequency and the defecation duration. The higher the score a participant got, the more severe the symptom was. The effectiveness was evaluated by the scoring reduction rate, and marked effectiveness and effectiveness were both found to be effective. Incidence of adverse events was compared between two groups before the treatment, and on postoperative 3-day and 7-day respectively. There were no significant differences between two groups in gender, age, internal hemorrhoids gradings, disease course, and onset time as well as the baseline data, such as the degree of hematochezia or bleeding before the treatment, the degree of pain, hemorrhoid prolapse, the shapes and properties of stool, the defecation frequency and the defecation duration (all P>0.05). After the seven-day treatment, there was significant difference in effective rate between combination group and single group [96.7%(29/30) vs. 66.7%(20/30), Z=-4.376, P=0.000]. Meanwhile, the scores of combined group and single group in hematochezia or bleeding were 0(0, 1) and 0(0, 2) (Z=9.241, P=0.002); in shapes and properties of stool were 0(0, 1) and 0(0, 1) (Z=5.364, P=0.021); in defecation frequency were 0(0, 1) and 0(0, 2) (Z=7.552, P=0.006); and in defecation duration were 0(0, 1) and 0(0, 2) (Z=4.425, P=0.035), whose differences were all significant. The scores of pain degree and hemorrhoid prolapse of two groups also decreased, but the difference was not statistically significant (P>0.05). During the treatment, abdominal pain, diarrhea and other adverse reactions were not observed in participants of two groups. Combination therapy of wheat cellulose particles (testa triticum tricum purify, Fiberform) can significantly improve the efficacy of internal hemorrhoid with safety and tolerance.


Relationships between the nigrotectal pathway and the cells of origin of the predorsal bundle.
The goal of this study was to define the anatomical relationships between the terminal field of the nigrotectal pathway and the tectal neurons which project to contralateral brainstem gaze centers by way of the predorsal bundle. The distribution and morphology of the cells of origin for the predorsal bundle were determined by using a modification of the retrograde horseradish peroxidase technique which homogeneously filled their somas and dendrites. The terminal distribution of the nigrotectal tract was determined using both anterograde horseradish peroxidase and autoradiographic procedures. The results indicate that, in the grey squirrel (Sciurus carolinensis), the predorsal bundle cells are a heterogeneous population whose dendritic fields form a well-defined band confined to the inner half of stratum griseum intermediate. This inner sublamina also can be identified in Nissl and myelin stains. The same sublamina is the major target of the nigrotectal tract. The striking anatomical correspondence between the distribution of nigrotectal terminals and the cells projecting in the predorsal bundle supports a proposal, based on recent physiological investigations, that the nigrotectal tract plays an important role in the initiation of the saccade-related activity of the deep tectal cells (Chevalier et al., '81; Hikosaka and Wurtz, '83a-d).


Mineralocorticoid receptor antagonist initiation during admission is associated with improved outcomes irrespective of ejection fraction in patients with acute heart failure.
Heart failure (HF) guidelines recommend initiation and optimization of guideline-directed medical therapy, including mineralocorticoid receptor antagonists (MRAs), before hospital discharge. However, scientific evidence for this recommendation is lacking. Our objective was to determine whether initiation of MRA prior to hospital discharge is associated with improved outcomes. We performed a secondary analysis of 6197 patients enrolled in the RELAX-AHF-2 study. Patients were divided into four groups according to MRA therapy at baseline and discharge. At baseline 30% of patients received MRA therapy, which increased to 50% of patients at discharge. In-hospital initiation of an MRA was observed in 1690 (27%) patients, 1438 (23%) patients remained on MRA therapy, 418 (7%) patients discontinued MRA treatment, and 2651 (43%) patients did not receive an MRA during hospital stay. Compared with patients who did not receive MRA therapy, in-hospital initiation of an MRA was independently associated with lower risks of mortality (multivariable hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.60-0.96; p = 0.02), cardiovascular death (HR 0.77, 95% CI 0.59-1.01; p = 0.06), hospitalization for HF or renal failure (HR 0.72, 95% CI 0.60-0.86; p = 0.0003) and the composite endpoint of cardiovascular death and/or rehospitalization for HF or renal failure (HR 0.71, 95% CI 0.61-0.83; p < 0.0001) at 180 days. These results were independent of baseline left ventricular ejection fraction. In patients hospitalized for acute HF, in-hospital initiation of an MRA was associated with improved post-discharge outcomes, independent of left ventricular ejection fraction and other potential confounders.


Influence of electrochemical polishing on the mechanical properties of K3 nickel-titanium rotary instruments.
Instrument fracture is a serious concern in endodontic treatment. Several studies have evaluated the influence of various factors on the fracture of nickel-titanium endodontic rotary instruments. The present study analyzes the influence of electrochemical polishing on flexural fatigue and torsional properties of K3 nickel-titanium endodontic rotary instruments. New files and polished files were tested for flexural fatigue and for resistance to fracture by twisting. The t test was used to compare the groups for number of cycles, angle of rotation, and maximum torque necessary to fracture. No statistical difference existed between these groups. Scanning electron microscopy analysis showed no significant differences caused by electrochemical polishing between these groups. These results suggest that electrochemical polishing has no influence on resistance to fracture of K3 rotary instruments.


[Comparative effectiveness of complex physiotherapeutic treatment of patients in the early stages of avascular necrosis of the femoral head].
In the late stages of avascular necrosis of the femoral head (ANFH), total hip arthroplasty (THA) is a non-alternative treatment method. In the early stages, methods of conservative treatment show some effectiveness. Among them, most often there is evidence of the effectiveness of physiotherapy options. Of this study is the development and study of a method of complex non-surgical treatment of ANFH based on a combination of physiotherapy and phytotherapy methods. We examined 60 patients with early stages of ANFH, who underwent courses of complex treatment. Patients of the primary group received a complex, including: exposure to acupuncture points in the area of hip joint (HJ) with low-frequency currents using the Osteon-1 apparatus in combination with phytoapplications, HJ massage, special physiotherapy exercises. Unloading the HJ (walking on crutches) was mandatory component. Patients in the control group were treated using a complex including: manual massage of HJ, the use of sinusoidally modulated currents and ultraphonophoresis of hydrocortisone on the affected joint. In order to assess the dynamics of the clinical and functional state of HJ before and after the treatment, Harris questionnaire, radiography, ultrasound densitometry, and laser Doppler imaging were used. Quality of life was assessed using the SF36 questionnaire. The full course of treatment was 1 month. Long-term results were studied after 1 year by the questionnaire method. In patients of both groups, a positive dynamics of the clinical and functional state of the joints was registered, but higher statistically significant indicators were obtained in the primary group. Moreover, in a significant number of patients (in 95% of cases), positive clinical results persisted throughout the year. The use of a complex of treatment based on physiotherapy and a combination of physiotherapy and phytotherapy makes it possible for us to obtain positive clinical and functional dynamics of the state of the joints and an increase in the quality of life in patients with ANFH.


Blood Platelet Volume Represents a Novel Prognostic Factor in Patients with Nonmetastatic Renal Cell Carcinoma and Improves the Predictive Ability of Established Prognostic Scores.
The average size of blood platelets determined by mean platelet volume might represent a biologically meaningful parameter in carcinogenesis and potentially serve as a novel prognostic biomarker in renal cell carcinoma. In this retrospective analysis of the records of 652 patients we evaluated the potential prognostic value of mean platelet volume and its ability to improve existing risk assessment tools used in adjuvant clinical trials in nonmetastatic renal cell carcinoma cases. Associations of mean platelet volume with baseline covariates and clinical outcomes (recurrence, and death from renal cell carcinoma and other causes) were assessed with the competing risk estimators of Kaplan-Meier, and Marubini and Valsecchi, respectively. Univariable and multivariable Cox proportional hazard models were constructed. The Harrell c-index was applied to test improvements in the predictive accuracy of the established Leibovich prognosis score. Small platelet volume was associated with large tumors (p = 0.043), high Fuhrman grade (p = 0.001), sarcomatoid components (p <0.0001), histological tumor necrosis (p = 0.044) and vascular invasion (p = 0.022). On univariable and multivariable analyses small platelet volume accurately predicted recurrent renal cell carcinoma (continuously and binary coded) and cancer specific survival. Adding mean platelet volume to the Leibovich prognosis score improved its discriminative performance (c-index = 0.83, p = 0.004). Mean platelet volume represented a highly significant predictor of recurrence and cancer specific death in patients with renal cell carcinoma. This parameter improved the accuracy of the Leibovich prognosis score to better predict long-term outcomes in localized renal cell carcinoma cases after curative surgical resection.


P056 Real life experience with the use of tofacitinib in ulcerative colitis in Colombia: case series.
Tofacitinib is a molecule that inhibits Janus kinases, enzymes involved ulcerative colitis (UC) pathogenesis. This drug has recently been approved by INVIMA (abbreviation in Spanish of National Institute of Food and Drug Surveillance) in Colombia. to describe real-life experience in Colombian patients with a diagnosis of UC treated with tofacitinib since its approval. Case series of 6 patients diagnosed with UC with moderate-severe activity defined by the American College of Gastroenterology Ulcerative Colitis Activity Index (ACG score) treated with tofacitinib 10 mg every 12 hours (BID) in the induction and maintenance phase. The decision to use tofacitinib was based on clinical judgment and patient preference. Response to treatment was evaluated in terms of endoscopic (Mayo score), paraclinical (CRP, ESR, fecal Calprotectin, Hemoglobin) and clinical response (absence of abdominal pain, diarrhea, and rectal bleeding). Additionally, adverse events, steroid use and response to extraintestinal manifestations (EIM) were evaluated. Four men and two women with an average age of 35.6 years were included. All 6 patients had moderate to severe UC; 5 patients with pancolitis and 1 with left-colitis. The average time of diagnosis was 4.08 years. Four patients had previously failed TNF-inhibitors (3 Adalimumab, 2 Infliximab, 1 Golimumab), and 2 patients had previously failed integrin alpha-4beta7-inhibitor (Vedolizumab). Two patients were naïve to biological therapy. Three patients were at risk of colectomy due to severe disease activity. Three patients presented EIM. During the induction phase, 1 maintained disease activity without response, 5 presented clinical and paraclinical remission, 20% remained in moderate-severe activity, 20% mild activity and 60% in remission, the 3 patients who were at risk of colectomy were ruled out from surgery due to symptom improvement. At the endoscopic level, 3 endoscopic studies were obtained in the end of induction, of which 1 presented a Mayo score 3, and 2 patients with Mayo score 1. For naïve patients to biological therapy, one achieved clinical and paraclinical remission upon induction, the endoscopic response still has not been measured, in the second naive patient, tofacitinib was used in-hospital since he didn't respond to intravenous steroids for 72 hours and there was no availability of infliximab, ruling out other predisposing factors to exacerbation, achieving the discharge with adequate symptoms control and paraclinical findings. Three patients discontinued corticosteroids, and three patients achieved dose reduction. One patient reported and adverse event, none had drug-associated leukopenia, and 3 of them without lipid alteration after induction. All patients resolved their EIM during induction. Only one patient has completed follow-up during maintenance for 26 weeks, which is in clinical, paraclinical and endoscopic remission with a dose of 10 mg BID, 1 patient at 16 weeks decided to suspend the medication due to lack of response and the other 4 patients are in clinical and paraclinical remission but have not completed the 26 weeks of maintenance and have a follow-up appointment pending. The results of this case report suggest that tofacitinib may be an effective therapeutic alternative in patients with moderate to severe UC and associated extraintestinal manifestations, with a good safety profile.


Response inhibition is more effortful than response activation: behavioral and electrophysiological evidence.
The present study aimed to measure the response inhibition by embedding a secondary probe task within a Go/NoGo paradigm. The response time for the probe and the time course of the discrimination process for the probe shown by event-related potentials were measured to investigate the effect of response inhibition. The results showed that the probe response time were longer for the NoGo-probes versus Go-probes, indicating a more cognitively demanding process in processing NoGo stimuli. The event-related potential results showed that the NoGo stimuli evoked a more positive frontal P3 component relative to the Go stimuli. Compared with the NoGo-probes, the Go-probes evoked enhanced N1, but decreased P2 and P3 components over frontocentral scalps, indicating increased orienting process, but decreased selective attention process for the Go-probes. These results indicated that response inhibition (NoGo) was more cognitively demanding than the response activation (Go).