Perioperative management of two cases of hemophilia with spontaneous intracerebral hemorrhage undergoing emergency craniotomy in resource constrained setup of Nepal.
Patients with hemophilia are prone to develop spontaneous intracranial hemorrhage. It carries a significant risk of morbidity and mortality. In this case series, we report two cases of hemophilia who suffered spontaneous intracerebral hemorrhage with features of raised intracranial pressure and were successfully managed perioperatively. The patients were managed with early intensive care unit management, measures to reduce intracranial pressure, perioperative clotting factor administration, airway management and surgery to decrease the raised intracranial pressure. Both patients improved following surgery and were discharged home. Perioperative multidisciplinary management of hemophilia is discussed in this series.


Effect of dose and frequency of exposure to infectious stages on trematode infection intensity and success in mussels.
Marine parasites such as trematodes often compromise the fitness of their hosts. Such effects are generally considered to be density-dependent, i.e. the greater the infection intensity in the host, the greater the detrimental impact on host fitness. However, the mechanisms determining infection in marine hosts are still poorly understood. Here, we investigated the effect of cercarial dose and exposure frequency (single vs. trickle infections) of a marine trematode parasite, Himasthla elongata (Trematoda: Echinostomatidae), on infection intensity and success in its second intermediate host, the blue mussel Mytilus edulis, an abundant and widely distributed bivalve in European coastal waters. In our laboratory experiment, we tested 4 levels of parasite doses and showed that mussels faced higher parasite infection intensity at higher doses of cercarial exposure and that they acquired more infections when repeatedly exposed to smaller doses compared to a single high dose. However, the infection success of cercariae did not differ among 4 dose levels but was only significantly different between trickle and single exposures. This indicates that cercariae were not subjected to a dose-dependent regulation of their infectivity, suggesting that infection intensity in mussels is largely driven by factors mediating the abundance of infective stages. With the combined investigation of the effect of cercarial dose and exposure frequency at realistic dose levels, our study contributes to our currently very limited understanding of the determinants of infection intensity in marine hosts and highlights the usefulness of experimental studies in advancing our knowledge in this field.


Simultaneous RNA-DNA FISH.
A highly useful tool for studying lncRNAs is simultaneous RNA-DNA FISH, which reveals the localization and quantitative information of RNA and DNA in cellular contexts. However, a simple combination of RNA FISH and DNA FISH often generates disappointing results because the fragile RNA signals are often damaged by the harsh conditions used in DNA FISH for denaturing the DNA. Here, we describe a robust and simple RNA-DNA FISH protocol, in which amino-labeled nucleic acid probes are used for RNA FISH . The method is suitable to detect single RNA molecules simultaneously with DNA.


Respiratory syncytial virus infection: clinical features, management, and prophylaxis.
Respiratory syncytial virus (RSV) infects almost all children by two years of age, resulting in a large number of hospital admissions in infants. Reactive airway disease is more common after RSV infection, even in previously healthy children. Management of the acute infection is supportive, but preliminary evidence suggests surfactant administration to ventilated infants may be of benefit. Whether ribavirin or corticosteroids reduce respiratory morbidity after RSV infection remains controversial. Immunoprophylaxis reduces RSV admissions, Palivizumab, a humanized monoclonal antibody, is a more cost-effective prophylaxis than RSV immune globulin. Nevertheless, the cost of prophylaxis, unless only given to very high-risk infants, exceeds savings made in reducing admissions.


An older adult man who is unable to sleep: advocating self-care in home healthcare.
Six weeks after a transurethral resection of the prostate, a home care patient experiences urinary urgency and frequency that wakes him up during the night and continues throughout the day. He is exhausted, depressed, and unwilling to interact with healthcare professionals. The home health nurse enables self-care with a medication regimen, resulting in rapid improvement.


Mechanisms of gas transport during ventilation by high-frequency oscillation.
Ventilation by high-frequency oscillation (HFO) presents some difficulties in understanding exactly how gas is transported in the lung. However, at a qualitative level, five modes of transport may be identified: 1) direct alveolar ventilation in the lung units situated near the airway opening; 2) bulk convective mixing in the conducting airways as a result of recirculation of air among units of inhomogeneous time constants; 3) convective transport of gases as a result of the asymmetry between inspiratory and expiratory velocity profiles; 4) longitudinal dispersion caused by the interaction between axial velocities and radial transports due to turbulent eddies and/or secondary swirling motions; and 5) molecular diffusion near the alveolocapillary membrane. These modes of transport are not mutually exclusive and certainly interact. It is therefore difficult to make quantitative predictions about the overall rate of transport. Qualitatively, it may now be stated with confidence that convective transport in the tracheobronchial tree is very important during HFO as in normal breathing and that increasing tidal volume is more effective than increasing frequency in improving gas exchange during HFO. To optimize the gas transport efficiency of HFO, future research should focus on identifying the rate-limiting mode of transport for a given set of geometric and dynamic conditions.


[Epigenetic Alterations in Gastrointestinal Cancers: Diagnostic and Therapeutic Applications].
Epigenetic alterations, represented byaberrant DNA methylation, are present in gastrointestinal cancers. Detection of cancer- specific DNA methylation can be used to detect cancer, and detection of colon cancer-specific aberrant DNA methylation is alreadyapproved byFDA. Aberrant DNA methylation is potentlyinduced bychronic inflammation, and also is accumulated in normal tissues before a cancer develops. In gastric cancer, potential of cancer risk diagnosis bymeasurement of aberrant DNA methylation in normal gastric mucosae has been clinically demonstrated. Therapeutically, DNA demethylating agents have been alreadyapproved for hematological tumors byFDA, and promising results in clinical trials against gastrointestinal cancers have been reported. Also, histone deacetylase inhibitors have been already approved for hematological tumors, and clinical trials against gastrointestinal cancers have been reported. Selection of right dose, schedule, combination, and patients is the keyto future success.


Slow cortical potential neurofeedback and self-management training in outpatient care for children with ADHD: study protocol and first preliminary results of a randomized controlled trial.
Treatment for children with attention deficit/hyperactivity disorder (ADHD) today is predominantly pharmacological. While it is the most common treatment, it might not always be the most appropriate one. Moreover, long term effects remain unclear. Behavior therapy (BT) and non-pharmacological treatments such as neurofeedback (NF) are promising alternatives, though there are no routine outpatient care/effectiveness studies yet that have included children with medication or changes in medication. This paper presents the protocol of a randomized controlled trial to compare the effectiveness of a Slow Cortical Potential (SCP) NF protocol with self-management (SM) in a high frequent outpatient care setting. Both groups (NF/SM) receive a total of 30 high frequent therapy sessions. Additionally, 6 sessions are reserved for comorbid problems. The primary outcome measure is the reduction of ADHD core symptoms according to parent and teacher ratings. Untill now 58 children were included in the study (48 males), with a mean age of 8.42 (1.34) years, and a mean IQ of 110 (13.37). Conners-3 parent and teacher ratings were used to estimate core symptom change. Since the study is still ongoing, and children are in different study stages, pre-post and follow-up results are not yet available for all children included. Preliminary results suggest overall good pre-post effects, though. For parent and teacher ratings an ANOVA with repeated measures yielded overall satisfying pre-post effects (η (2) 0.175-0.513). Differences between groups (NF vs. SM) could not yet be established (p = 0.81). This is the first randomized controlled trial to test the effectiveness of a NF protocol in a high frequent outpatient care setting that does not exclude children on or with changes in medication. First preliminary results show positive effects. The rationale for the trial, the design, and the strengths and limitations of the study are discussed. This trial is registered in www.clinicaltrials.gov as NCT01879644.


Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells.
Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancers but is responsible for a disproportionate number of deaths. We investigated the relevance, in TNBC, of nano-sized exosomes expelled from cells. Specifically, we compared effects of exosomes derived from the claudin-low TNBC cell line Hs578T and its more invasive Hs578Ts(i)8 variant, as well as exosomes from TNBC patient sera compared to normal sera. Exosomes were isolated from conditioned media (CM) of Hs578T and Hs578Ts(i)8 cells and from sera by filtration and ultracentrifugation. Successful isolation was confirmed by transmission electron microscopy and immunoblotting. Subsequent analysis, of secondary/recipient cells in response to exosomes, included proliferation; motility/migration; invasion; anoikis assays and endothelial tubule formation assays. Hs578Ts(i)8-exosomes versus Hs578T-exosomes significantly increased the proliferation, migration and invasion capacity of all three recipient cell lines evaluated i.e. SKBR3, MDA-MB-231 and HCC1954. Exosomes from Hs578Ts(i)8 cells also conferred increased invasiveness to parent Hs578T cells. Hs578Ts(i)8-exosomes increased sensitivity of SKBR3, MDA-MB-231 and HCC1954 to anoikis when compared to the effects of Hs578T-exosomes reflecting the fact that Hs578Ts(i)8 cells are themselves innately more sensitive to anoikis. In relation to vasculogenesis and subsequent angiogenesis, Hs578Ts(i)8-exosomes versus Hs578T-exosomes stimulated significantly more endothelial tubules formation. Finally, our pilot translational study showed that exosomes from TNBC patients' sera significantly increased recipient cells' invasion when compared to those derived from age- and gender-matched healthy control sera. This study supports the hypothesis that TNBC exosomes may be involved in cancer cell-to-cell communication, conferring phenotypic traits to secondary cells that reflect those of their cells of origin.


Dietary therapy in NIDDM.
Clearly the dietary treatment of the NIDDM patient remains an act of faith bearing in mind the poor compliance of the patient to dietary advice, and the lack of long-term studies confirming the efficacy of diets (old or new) in the prevention of diabetic vascular complications. Few of the newer recommended diets seem to have been tested in the hurly-burly of the busy, understaffed diabetic clinic. Perhaps another major hurdle has been the attitude of patients and doctors in failing to regard diet therapy as a form of treatment, akin to tablets. The phrase 'I eat my diet, doctor, then I have my usual meal' sums up the problem. There needs to be a change in attitude to diet by both doctors and patients so that the dietary changes suggested should be eating habits which would become second nature to patients--the so called 'healthy eating'--more fibre, less refined carbohydrate, less total and saturated fat and more polyunsaturated fats. It seems difficult for a majority of NIDDM patients to add onto 'healthy eating' calorie restriction to achieve weight loss. This difficulty also applies to non-diabetic obese subjects with similar poor results. One cannot help but feel that NIDDM patients should benefit from the general change in attitude of the general population towards nutrition, but reinforced education concerning diet goals for NIDDM patients is an urgent requirement and needs closer examination by the diabetic health care team as to how it may be delivered to the individual NIDDM patients. Perhaps dietitians in particular should become more critical in their approach to diet strategies and should investigate and report on the results of this treatment.


Establishment of a human 3D lung cancer model based on a biological tissue matrix combined with a Boolean in silico model.
For the development of new treatment strategies against cancer, understanding signaling networks and their changes upon drug response is a promising approach to identify new drug targets and biomarker profiles. Pre-requisites are tumor models with multiple read-out options that accurately reflect the clinical situation. Tissue engineering technologies offer the integration of components of the tumor microenvironment which are known to impair drug response of cancer cells. We established three-dimensional (3D) lung carcinoma models on a decellularized tissue matrix, providing a complex microenvironment for cell growth. For model generation, we used two cell lines with (HCC827) or without (A549) an activating mutation of the epidermal growth factor receptor (EGFR), exhibiting different sensitivities to the EGFR inhibitor gefitinib. EGFR activation in HCC827 was inhibited by gefitinib, resulting in a significant reduction of proliferation (Ki-67 proliferation index) and in the induction of apoptosis (TUNEL staining, M30-ELISA). No significant effect was observed in conventional cell culture. Results from the 3D model correlated with the results of an in silico model that integrates the EGFR signaling network according to clinical data. The application of TGFβ1 induced tumor cell invasion, accompanied by epithelial-mesenchymal transition (EMT) both in vitro and in silico. This was confirmed in the 3D model by acquisition of mesenchymal cell morphology and modified expression of fibronectin, E-cadherin, β-catenin and mucin-1. Quantitative read-outs for proliferation, apoptosis and invasion were established in the complex 3D tumor model. The combined in vitro and in silico model represents a powerful tool for systems analysis.


Serological level of ICAM and ELAM adhesion molecules in allergic vascularitis.
A 24-patient lot with hypersensitivity vasculitis was investigated for serological determinations of ICAM and ELAM adhesion molecules. Determinations were made in attack and in remission. Over two thirds of the cases presented elevated serological levels of ICAM and ELAM in attack, with twofold higher values than normal. In remission, in the absence of clinical signs, ICAM and ELAM values were normal in 19 cases (ICAM) and 22 cases (ELAM). Serological level of ICAM and ELAM was concordant with serological level of IL-2, IL-6, circulating immune complexes and clinical status. The increased values of ICAM and ELAM are due to the expression of these molecules both on the surface of endothelial cells and on immune cells. The adherence of leukocytes on the endothelial cells, by adhesion molecules involvement, followed by their extravasation represents an important event in the vascular lesion pathogeny of the hypersensitivity vasculitis.


Cardiovascular lesion of carcinoid syndrome. An autopsy case of bronchial carcinoid.
An autopsy case of a 67-year-old Japanese male is presented. He had been suffering from carcinoid syndrome for 5 years and showed a typical picture of carcinoid heart disease. In Japan, carcinoid heart disease is rare and we can find only four reported cases (33% of reported carcinoid syndrome). The patient had high urinary secretion of 5-HIAA and high serum serotonin, and finally he died of heart failure and bronchopneumonia. The primary site of this carcinoid tumor was of the bronchus of the right B10c , and it had large hepatic metastases. Electronmicroscopically, the tumor cells had secretory granules measuring 1500-3500 A in diameter. Immunohistochemically, the tumor cells were markedly positive for human chorionic gonadotropin (hCG) and antidiuretic hormone (ADH) and positive for serotonin, in both the primary site and hepatic metastases. Characteristic fibrous plaques were detected in the right atrium, tricuspid valve, right ventricle, and left atrium. Electron-microscopically, the fibrous plaques consisted of smooth muscle cells and myofibroblasts surrounded by basement membrane-like material. The abundant matrix of the fibrous plaques contained acid mucopolysaccharide, microfibrils and collagen fibers. The same fibrous plaques were also found in hepatic veins. Furthermore, retroperitoneal fibrosis was present, which showed proliferation of myofibroblasts, fibroblasts and immature mesenchymal cells.


Pain Prevalence, Management and Interference Among University Students in South Korea: An Exploratory Cross-Sectional Study.
Pain is a global health issue with a significant impact on young adults. Adverse effects caused by inappropriate pain management among university students are related to poor mental/physical health. This study aimed to explore pain prevalence, management, and interference among university students in South Korea. Pain intensity, painful body areas, pain management, and pain interference were measured in a convenience sample of 404 students. Descriptive statistics are reported, and a multivariable binomial logistic regression was conducted to reveal factors associated with pain interference. The prevalence of acute and chronic pain was 73.5%, while 7.8% reported chronic pain (≥ 3 months). Half of university students who experienced pain reported at least four painful body areas. The average pain intensity during the past 6 months was 4.8/10. About 56% of university students who experienced pain used over-the-counter pain pills for pain management. Rest and massage were the most used non-pharmacological pain management strategies. Mood was the most reported pain interference complaint amongst university students. Greater pain interference was associated with longer pain duration, more painful body areas, and greater pain intensity. Pain is highly prevalent among South Korean university students. Pain management programs, including education about appropriate methods of pain relief, should be developed for university students. Attention should be given to university students with widespread acute and chronic pain of high intensity to mitigate the negative impacts caused by pain interference.


Antisocial rewarding in structured populations.
Cooperation in collective action dilemmas usually breaks down in the absence of additional incentive mechanisms. This tragedy can be escaped if cooperators have the possibility to invest in reward funds that are shared exclusively among cooperators (prosocial rewarding). Yet, the presence of defectors who do not contribute to the public good but do reward themselves (antisocial rewarding) deters cooperation in the absence of additional countermeasures. A recent simulation study suggests that spatial structure is sufficient to prevent antisocial rewarding from deterring cooperation. Here we reinvestigate this issue assuming mixed strategies and weak selection on a game-theoretic model of social interactions, which we also validate using individual-based simulations. We show that increasing reward funds facilitates the maintenance of prosocial rewarding but prevents its invasion, and that spatial structure can sometimes select against the evolution of prosocial rewarding. Our results suggest that, even in spatially structured populations, additional mechanisms are required to prevent antisocial rewarding from deterring cooperation in public goods dilemmas.


Human macrophage colony stimulating factor (M-CSF): alternate RNA splicing generates three different proteins that are expressed on the cell surface and secreted.
Human macrophage colony stimulating factor (M-CSF) cDNA clones were isolated from a pancreatic carcinoma cell line. Three different classes of M-CSF precursor protein (256, 554 and 438 amino acids in length) were predicted to be encoded by these cDNAs. Two of these, that we designate M-CSF alpha and M-CSF beta have already been described. The third, M-CSF gamma represents a novel class of M-CSF cDNA. All three precursors share a 32 amino acid signal sequence and the first 149 amino acids of the mature protein. At this position, M-CSF beta and gamma have insertions of 298 and 182 amino acids relative to M-CSF alpha. The first 182 amino acids of these insertions are shared between M-CSF beta and gamma. All three precursors share the C-terminal 75 amino acids that encode the transmembrane and cytoplasmic domains. Expression of all three cDNAs in COS-7 monkey kidney cells gave rise to soluble M-CSF activity, associated with proteins of subunit molecular weight 44 Kda (beta and gamma) or 28 Kda (alpha). In addition, M-CSF proteins could be detected on the surface of the transfected cells by indirect immunofluorescence. When the transmembrane and cytoplasmic domains of M-CSF alpha were removed by introducing a stop codon after amino acid 190, no membrane-bound M-CSF could be detected, but the truncated protein was secreted efficiently and was biologically active. This suggests that all three forms of M-CSF can exist as cell surface proteins, anchored by their hydrophobic transmembrane domains, and can be processed to soluble forms by proteolytic digestion. Although all soluble forms of M-CSF were biologically active in murine bone marrow colony and proliferation assays, they showed greatly reduced or no activity in similar assays using human bone marrow.


How accurate is dobutamine stress electrocardiography for detection of coronary artery disease? Comparison with two-dimensional echocardiography and technetium-99m methoxyl isobutyl isonitrile (mibi) perfusion scintigraphy.
This study was designed to establish the appropriate diagnostic criteria for positive dobutamine electrocardiographic (ECG) stress test results and to compare their accuracy with those of dobutamine two-dimensional echocardiography and perfusion scintigraphy. Conventional criteria for positive findings on ECG exercise testing may not be appropriate for use with dobutamine ECG stress testing. One hundred twenty-nine consecutive patients with an interpretable ECG and without previous myocardial infarction were prospectively studied at the time of coronary arteriography. All completed a standard dobutamine protocol (5 to 40 micrograms/kg body weight per min in 3-min dose increments) without side effects. Significant coronary artery disease, defined as > 50% lumen diameter stenosis of a major epicardial coronary artery on coronary angiography, was present in 83 patients. Empiric receiver operating curves were generated for various ECG criteria derived from computer-averaged signals. The best ECG criterion, with a sensitivity of 42% and a specificity of 83%, was an ST segment shift, relative to baseline, of 0.5 mm 80 ms after the J point. The sensitivity of this criterion was greater than that of the conventional criterion of 1-mm ST segment depression 60 (23%) or 80 (18%) ms after the J point, was comparable to that of chest pain occurring during the test (44%, p = NS) but remained inferior to the sensitivities of technetium-99m methoxyl isobutyl isonitrile (mibi) perfusion (76%) or stress echocardiography (76%, p < 0.001, for both). The specificity of this criterion was not significantly different from that of technetium-99m mibi perfusion tomography (65%) or stress echocardiography (89%) but was superior to that of chest pain (59%, p < 0.025). We conclude that this new criterion for dobutamine electrocardiography is specific but that an imaging technique is still required to accurately predict coronary artery disease.


BNP: pathophysiological and potential therapeutic roles in acute congestive heart failure.
Controversy persists regarding the acute responsiveness of atrial (ANP) and brain (BNP) natriuretic peptides in pathophysiological conditions such as acute heart failure (AHF). This study was designed to test the hypothesis that AHF is characterized by selective activation of ANP, but not BNP. We also hypothesized that BNP replacement in AHF would reduce cardiac filling pressures, increase sodium excretion, and inhibit circulating renin. Two groups of anesthetized dogs underwent rapid left ventricular pacing to induce AHF. Group 1 (n = 7) served as control and group 2 (n = 7) received canine BNP (10 ng x kg(-1) x min(-1)). Cardiorenal parameters, circulating natriuretic peptides, 3',5'-cyclic guanosine monophosphate (cGMP), and plasma renin activity (PRA) were determined at baseline and during AHF in both groups. AHF was characterized by reductions in cardiac output (2.3 +/- 0.2 vs. 3.7 +/- 0.3 l/min, P < 0.05), pulmonary capillary wedge pressure (PCWP; 11.7 +/- 0.8 vs. 5.1 +/- 0.3 mmHg, P < 0.05), and selective activation of ANP (250 +/- 51 vs. 39 +/- 13 pg/ml, P < 0.05), with no increase in circulating BNP (49 +/- 15 vs. 60 +/- 16 pg/ml, P = not significant). Compared with control, exogenous supplemental BNP in AHF resulted in marked increases in circulating cGMP (65 +/- 6 vs. 18 +/- 5 pg/ml, P < 0.05), with reductions in PCWP (9.1 +/- 0.9 vs. 12.9 +/- 1.1 mmHg, P < 0.05) and increased urinary sodium excretion (120 +/- 36.8 vs. 24 +/- 6.3 microeq/min, P < 0.05) via reductions in distal tubular sodium reabsorption (94.3 +/- 1.8 vs. 98.0 +/- 0.4%, P < 0.05). Exogenous BNP prevented the increase in PRA that occurred in the control group. We conclude that AHF is characterized by a failure to increase circulating BNP underscoring differential physiological and pathophysiological roles for ANP and BNP in states of immediate cardiac overload. These studies also support a potential role for BNP in the therapeutics of AHF.


Molecular Theory of Hydration at Different Temperatures.
Solvation plays an important role in diverse chemical processes ranging from reaction kinetics to molecular recognition, solubility, and phase separations. Despite a long-history of theoretical exploration, quantitative prediction of solvation remains a theoretical challenge without relying on the macroscopic properties of the solvent as an input. Here we present a molecular density functional theory that provides a self-consistent description of the solvation structure and thermodynamic properties of small organic molecules in liquid water at different temperatures. Based on the solute configuration and force-field parameters generated from first-principles calculations, the theoretical predictions are found in good agreement with experimental data for the hydration free energies of 197 organic molecules in a temperature range from 0 to 40 °C. In addition to calibration with experimental results, the theoretical predictions are compared with recent molecular dynamics simulations for the hydration of five highly explosive nitrotoluenes. This work demonstrates the potential of the classical density functional theory for high-throughput prediction of solvation properties over a broad range of temperatures.


BC200 RNA in invasive and preinvasive breast cancer.
BC200 RNA, a small functional RNA that operates as a translational modulator, has been implicated in the regulation of local synaptodendritic protein synthesis in neurons. Cell type-specific expression of BC200 RNA is tightly controlled such that the RNA is not normally detected in somatic cells other than neurons. However, the neuron-specific control of BC200 expression is deregulated in a number of tumors. We here report that BC200 RNA is expressed at high levels in invasive carcinomas of the breast. In normal breast tissue or in benign tumors such as fibroadenomas, in contrast, we found that the RNA is not detectable at significant levels. The difference in expression levels between invasive carcinomas and normal/benign tissue was statistically highly significant. Receiver Operating Characteristics analysis of sensitivity and specificity confirmed the diagnostic power of BC200 RNA as a molecular marker of invasive breast cancer. In ductal carcinomas in situ, furthermore, significant BC200 expression was associated with high nuclear grade, suggesting that the presence of BC200 RNA in such tumors may be used as a prognostic indicator of tumor progression. The combined results demonstrate the potential of BC200 expression to serve as a molecular tool in the diagnosis and/or prognosis of breast cancer.


Evaluation of the metabolic rate based on the recording of the heart rate.
The assessment of harsh working conditions requires a correct evaluation of the metabolic rate. This paper revises the basis described in the ISO 8996 standard for the evaluation of the metabolic rate at a work station from the recording of the heart rate of a worker during a representative period of time. From a review of the literature, formulas different from those given in the standard are proposed to estimate the maximum working capacity, the maximum heart rate, the heart rate and the metabolic rate at rest and the relation (HR vs. M) at the basis of the estimation of the equivalent metabolic rate, as a function of the age, height and weight of the person. A Monte Carlo simulation is used to determine, from the approximations of these parameters and formulas, the imprecision of the estimated equivalent metabolic rate. The results show that the standard deviation of this estimate varies from 10 to 15%.


Before itard: intellectual disability and the enlightened voice of Daniel Defoe.
Although positive regard for the needs of people with disabilities was apparently uncommon by many accounts prior to the 20(th) century, this may be a misconception of history. There were likely many people who responded to the needs of their family members and others in need of assistance because of their disablities, and their physical and emotional proximity. This, however, if so, is not easily discernable in historical records. Few and rare voices raised that endeavored to inform and inspire others toward humane treatment and educational interventions for people with disabilities have been documented. This rarity was particulary true for those considered to have an intellectual disability. Evidence of advocacy in disbility history are difficult to find. When found they have been embraced as critical to understanding the development of the field of developmental disabilities. A famous example is the work of Jean Itard. The proposals of the well-known author, Daniel Defoe, however, are also notable for his forward-thinking writing as it related to how society should respond to the needs of people with disabilities. A review of his work provides important examples of a philosophy of advocacy and education that preceded the work of Itard by approximately 75 years but that has rarely been acknowledged. This manuscript highlights and discusses several of these important works and provides a context for Defoe's contributions.


Composite tissue transplantation: a rapidly advancing field.
Composite tissue allotransplantation (CTA) is emerging as a potential treatment for complex tissue defects. It is currently being performed with increasing frequency in the clinic. The feasibility of the procedure has been confirmed through 30 hand transplantation, 3 facial reconstructions, and vascularized knee, esophageal, and tracheal allografts. A major drawback for CTA is the requirement for lifelong immunosuppression. The toxicity of these agents has limited the widespread application of CTA. Methods to reduce or eliminate the requirement for immunosuppression and promote CTA acceptance would represent a significant step forward in the field. Multiple studies suggest that mixed chimerism established by bone marrow transplantation promotes tolerance resulting in allograft acceptance. This overview focuses on the history and the exponentially expanding applications of the new frontier in CTA transplantation: immunology associated with CTA; preclinical animal models of CTA; clinical experience with CTA; and advances in mixed chimerism-induced tolerance in CTA. Additionally, some important hurdles that must be overcome in using bone marrow chimerism to induce tolerance to CTA are also discussed.


A simple assay for agonist-regulated Cl and K conductances in salt-secreting epithelial cells.
We developed a convenient flux assay that permits simultaneous measurement of Cl and K conductance pathways in Cl-secreting epithelial cells. Monolayers of the colonic tumor cell line T84 were preloaded with 125I and 86Rb, and isotope effluxes were monitored by a sample-replace procedure. The adenosine 3',5'-cyclic monophosphate (cAMP)-mediated agonists forskolin and prostaglandin E2 increased I efflux with little effect on Rb efflux, whereas the Ca-mediated agonists ionomycin, A23187, and carbachol increased both I and Rb effluxes. Simultaneous determinations of I and Cl or Rb and K effluxes indicated that I and Rb provide good measures of the effluxes of Cl and K, respectively. Forskolin- and ionomycin-stimulated I effluxes were inhibited by the Cl-channel blockers diphenylamine-2-dicarboxylate (DPC), 5-nitro-2-(3-phenylpropyl-amino)benzoic acid (NPPB), and 2-[cyclopentyl-6,7-dichloro-2,3-dihydro-2-methyl-1-oxo-1H- inden-5-yl)oxy]acetic acid (IAA-94) and by high external K. The Rb efflux evoked by ionomycin was inhibited by the K-channel blockers Ba and charybdotoxin. These findings suggest that I and Rb effluxes provide qualitative estimates of agonist-stimulated Cl and K conductance pathways. Thus this method can provide a simple and relatively inexpensive screening assay for Cl and K conductances in cultured cells to assess the effects of agonist, blockers, or genetic manipulations.


Transcriptional patterns associated with BDCA3 expression on BDCA1+ myeloid dendritic cells.
Myeloid dendritic cells, including BDCA3hi DCs and BDCA1+ DCs (hereafter dubbed DC1 and DC2 for clarity), play a pivotal role in the induction and regulation of immune responses. Interestingly, a fraction of DC2 also express low to intermediate levels of BDCA3. It is unknown whether BDCA3+ DC2 also share other traits with DC1 that are absent in BDCA3- DC2 and/or whether BDCA3 expression renders DC2 functionally distinct from their BDCA3-lacking counterparts. Here, we used expression analysis on a predefined set of immunology-related genes to determine divergence between BDCA3-positive and BDCA3-negative DC2 and their relation to bona fide BDCA3hi DC1. Results showed that mRNA fingerprints of BDCA3+ DC2 and BDCA3- DC2 are very similar, and clearly distinct from that of DC1. Differences in mRNA expression, however, were observed between BDCA3+ DC2 and BDCA3- DC2 that pointed toward a more activated status of BDCA3+ DC2. In line with this, higher steady state maturation marker expression and TLR-induced maturation marker expression and inflammatory cytokine production by BDCA3+ DC2 were observed. This dataset provides insight into the relationship between myeloid DC populations and contributes to further understanding of DC immunobiology.


Osteoporosis: non-hormonal treatment.
Significant progress has been achieved in osteoporosis treatment, in terms of agents with novel mechanisms of action, of new schedules of administration, and of long-term treatment safety demonstration. Alendronate, ibandronate, intranasal calcitonin, parathyroid hormones, raloxifene, risedronate, hormone replacement therapy, strontium ranelate and zoledronate decrease the risk of vertebral fracture. Alendronate, risedronate, strontium ranelate and zoledronate reduce the risk of hip fracture in women with osteoporosis, hormone replacement therapy in postmenopausal women, and calcium and vitamin D in institutionalized patients. In two meta-analyses, the combination of calcium and vitamin D was able to reduce the risk of falling, and hip fracture risk was decreased (>700 IU/day). Two subsequently published large trials were unable to detect any antifracture effect. PTH(1-84) reduces the risk of new vertebral fracture. There is no indication that combining PTH with a bone resorption inhibitor has any additional benefit to either drug alone. Strontium ranelate is a new agent for the treatment of osteoporosis, with antifracture efficacy whatever the severity of osteoporosis. An extension of the phase 3 trials up to 5 years has shown sustained antifracture efficacy. The humanized monoclonal antibody to the receptor activator of nuclear factor-kappaB ligand (RANKL) denosumab causes a rapid, high-magnitude, dose-dependent inhibition of bone resorption. Spine, hip and forearm bone mineral density increased, to an extent slightly higher than with the weekly administration of 70 mg alendronate.


Polymerase chain reaction assay for verifying the labeling of meat and commercial meat products from game birds targeting specific sequences from the mitochondrial D-loop region.
A PCR assay was developed for the identification of meats and commercial meat products from quail (Coturnix coturnix), pheasant (Phasianus colchicus), partridge (Alectoris spp.), guinea fowl (Numida meleagris), pigeon (Columba spp.), Eurasian woodcock (Scolopax rusticola), and song thrush (Turdus philomelos) based on oligonucleotide primers targeting specific sequences from the mitochondrial D-loop region. The primers designed generated specific fragments of 96, 100, 104, 106, 147, 127, and 154 bp in length for quail, pheasant, partridge, guinea fowl, pigeon, Eurasian woodcock, and song thrush tissues, respectively. The specificity of each primer pair was tested against DNA from various game and domestic species. In this work, satisfactory amplification was accomplished in the analysis of experimentally pasteurized (72 degrees C for 30 min) and sterilized (121 degrees C for 20 min) meats, as well as in commercial meat products from the target species. The technique was also applied to raw and sterilized muscular binary mixtures, with a detection limit of 0.1% (wt/wt) for each of the targeted species. The proposed PCR assay represents a rapid and straightforward method for the detection of possible mislabeling in game bird meat products.


Proton nuclear magnetic resonance and Raman spectroscopic studies of Japanese sake, an alcoholic beverage.
The hydrogen-bonding property of water--ethanol in Japanese sake, a kind of brewage, was examined on the basis of both (1)H NMR chemical shifts of the OH of water--ethanol and the Raman OH stretching spectra. In 20% (v/v) EtOH-H(2)O solution, amino acids as well as organic acids caused low-field chemical shifts, i.e., the development of a hydrogen-bonding structure. Additional functional groups, apart from the essential amino- and carboxyl groups, in amino acids caused differences in their effects. The low-field chemical shifts caused by solutes were demonstrated under constant pH conditions maintained by sodium hydrogen citrate. Using both the measurement of (1)H NMR chemical shifts and Raman OH stretching spectra, the strength of the hydrogen bond of water--ethanol in Japanese sake products was found to be correlated with the total concentration of organic acids and amino acids. Glucose or saccharides should not have a strengthening effect on the hydrogen bond of water--ethanol. The effects of the main inorganic ions and amines were also discussed. It was concluded that chemical components originating from the starting material, rice, or products produced by microorganisms during the ethanol fermentation affect the hydrogen-bonding structure in Japanese sake.


Aquaporin-4 Is Downregulated in the Basolateral Membrane of Ileum Epithelial Cells during Enterotoxigenic Escherichia coli-Induced Diarrhea in Mice.
Enterotoxigenic Escherichia coli (ETEC) are opportunistic pathogens that colonize the small intestine, produce enterotoxins and induce diarrhea. Some aquaporins (AQPs), such as AQP3 and AQP8, have been reported to participate in diarrhea by decreasing cellular influx in the gastrointestinal (GI) tract. AQP4 is another important water channel in the GI tract, but its role in ETEC-induced diarrhea has not been reported. Here, we demonstrated the potential roles of AQP4 in ETEC-induced diarrhea. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting showed that AQP4 was expressed in the mouse ileum, but not in the duodenum or jejunum while immunohistochemical staining showed that AQP4 localized to the basolateral membrane of ileum epithelial cells. Using an ETEC-induced mice diarrhea model, we demonstrated that both AQP4 mRNA level and the AQP4 protein level in the ileum decreased gradually over a time course of 7 days. These results suggest that AQP4 plays a role in the pathogenesis of ETEC-induced diarrhea by mediating water transport.


Tight linkage of the human c-erbA beta gene with the syndrome of generalized thyroid hormone resistance is present in multiple kindreds.
Generalized thyroid hormone resistance recently was reported to map in a single kindred to the same chromosomal region as the c-erbA beta gene, which codes for a putative thyroid hormone receptor. Restriction fragment length polymorphisms (RFLPs) of c-erbA beta were linked with GTHR in three kindreds with variable neuropsychologic dysfunction; two unrelated kindreds have been reported to possess different single base mutations in the T3 binding domain of c-erbA beta. In order to ascertain if tight linkage with c-erbA beta could be generalized to other families with this syndrome, we performed RFLP analysis in a separate laboratory on an unrelated family with GTHR which lacks the neuropsychologic defects or short stature often associated with GTHR (Kindred WR). RFLPs were identified after Bam Hl and Eco RV digestion of DNA from leukocytes from 14 family members. The Bam Hl RFLPs were 2.8 and 5.3 kb bands, and the Eco RV RFLPs were 1.6 and 3.3 kb bands. These RFLPs cosegregated with the GTHR phenotype and 11 family members were informative when both RFLPs were employed. The logarithm of the odds ratio between GTHR and c-erbA beta was 3.67, and therefore GTHR mapped to the c-erbA beta locus in this kindred. Allelic-specific hybridization with a probe constructed to identify the C to A mutation at nucleotide position 1643 (previously identified in one other kindred) suggested that our family has a different c-erbA beta abnormality. Although GTHR appears to be commonly associated with alterations in the human c-erbA beta gene, different kindreds may inherit different genetic defects.


What's the good of education on our overall quality of life? A simultaneous equation model of education and life satisfaction for Australia.
Many economists and educators favour public support for education on the premise that education improves the overall quality of life of citizens. However, little is known about the different pathways through which education shapes people's satisfaction with life overall. One reason for this is because previous studies have traditionally analysed the effect of education on life satisfaction using single-equation models that ignore interrelationships between different theoretical explanatory variables. In order to advance our understanding of how education may be related to overall quality of life, the current study estimates a structural equation model using nationally representative data for Australia to obtain the direct and indirect associations between education and life satisfaction through five different adult outcomes: income, employment, marriage, children, and health. Although we find the estimated direct (or net) effect of education on life satisfaction to be negative and statistically significant in Australia, the total indirect effect is positive, sizeable and statistically significant for both men and women. This implies that misleading conclusions regarding the influence of education on life satisfaction might be obtained if only single-equation models were used in the analysis.


Complex anemia in tuberculosis: the need to consider causes and timing when designing interventions.
Anemia is common in tuberculosis, and multiple etiologies necessitate targeted interventions. The proportion of iron-responsive anemia due to iron deficiency compared with iron-unresponsive anemia due to impaired iron absorption/redistribution from tuberculosis-associated immune activation or inflammation is unknown. This impedes selection of safe and effective treatment and appropriate intervention timing. Baseline hemoglobin, ferritin, hepcidin, soluble transferrin receptor (sTfR), and transferrin were measured in 45 patients with confirmed pulmonary tuberculosis (cases), 47 tuberculin skin test (TST)-positive controls, and 39 TST-negative controls in The Gambia. Tuberculosis cases were additionally followed 2 and 6 months after tuberculosis treatment initiation. Mutually exclusive anemia categories based on iron biomarker concentrations were iron deficiency anemia (IDA), anemia of inflammation (AI), and multifactorial anemia (IDA+AI). Anemia was more frequent in tuberculosis cases (67%) than in TST-positive (36%) or TST-negative (21%) controls. AI was the predominant anemia at tuberculosis diagnosis, declining from 36% to 8% after 6 months of treatment; however, a corresponding reduction was not evident for anemia with iron-responsive components (IDA, IDA+AI). Iron biomarkers discriminated between active tuberculosis and TST-positive or TST-negative controls, as well as between active untreated and treated tuberculosis. This was most noticeable for hepcidin, which decreased from a median of 84.0 ng/mL at diagnosis to 9.7 ng/mL after 2 months (P < .001). Tuberculosis chemotherapy is associated with significant reductions in AI, but IDA and IDA+AI remain unresolved. Iron-based interventions are needed for IDA and IDA+AI, and monitoring of iron biomarkers reveals a window for intervention opening as early as 2 months into tuberculosis treatment.


Accuracy of contrast-enhanced MR angiography in predicting angiographic stenosis of the internal carotid artery: linear regression analysis.
We sought to assess whether contrast-enhanced MR angiography is able to predict the degree of angiographic stenosis of the internal carotid artery within a clinically acceptable margin of error, thereby decreasing the need for angiography. In addition, we sought to assess whether adding ultrasound peak systolic velocity (PSV) as an additional regressor improves the accuracy of prediction. A retrospective review of our institution's records for a 4-year period was conducted to identify all patients who had undergone evaluation of their carotid arteries using digital subtraction angiography, contrast-enhanced MR angiography, and ultrasonography. All internal carotid artery stenoses ranging from 10% to 90% at carotid angiography were selected (n = 22). Measurements were then obtained based on the North American Symptomatic Carotid Endarterectomy Trial style by using the digital subtraction angiograms and contrast-enhanced MR angiograms in a blinded fashion. The correlation between digital subtraction angiography data and contrast-enhanced MR angiography data was assessed by conducting linear regression analysis. Multiple regression analysis was then conducted to determine whether the inclusion of ultrasound PSV as an additional regressor increased the accuracy of prediction. The correlation between the degree of stenosis measured by digital subtraction angiography and that measured by contrast-enhanced MR angiography was r = 0.967. The 95% confidence interval for the line of means showed low errors bounds, ranging as low as +/-2.8%. The 95% confidence interval for individual prediction of angiographic stenosis based on a given contrast-enhanced MR angiographic measurement, however, was significantly larger, being no less than +/-13.6%. With the inclusion of PSV, the adjusted correlation was r = 0.965. A clear linear relationship exists between digital subtraction angiographic and contrast-enhanced MR angiographic measurements of carotid stenosis. Increasing severity of stenosis as measured by contrast-enhanced MR angiography corresponds to increasing severity at angiography. Although the predictive value of contrast-enhanced MR angiography is excellent in the mean, it is less reliable for predicting the degree of angiographic stenosis in the individual patient, showing rather wide confidence intervals. Furthermore, the inclusion of PSV as an additional regressor does not improve the predictive accuracy beyond that of contrast-enhanced MR angiography alone.


Four types of vibration behaviors in a mole cricket.
Vibrational communication is known in some subterranean insects. Except for their use in sexual signaling, vibration behavior has rarely been reported. We report here four distinct types of substrate-based vibration behaviors in the mole cricket, Gryllotalpa orientalis, which are not associated with sexual signaling because of the occurrence of these behaviors in nymphs: (1) scraping with the forelegs; (2) foreleg taps (tapping with the forelegs); (3) palpal taps (tapping with the maxillary palpi); and (4) tremulation (back-and-forth movement of the whole body). Scraping is hypothesized to be used for the inspection of borrows. Foreleg taps are possibly informing nearby individuals of their presence, because it is never observed in solitary conditions. Palpal taps are rarely observed and its function is unknown. Tremulation is possibly related to avoidance of conspecific individual approaching and touching. The combination of the four vibration behaviors in the mole cricket may be unique among insects.


Substance Abuse in Pregnancy.
Addiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry. Like many other chronic diseases, addiction often involves cycles of relapse and remission. It is key that clinicians understand it as such and treat it appropriately with evidence-based interventions including medication-assisted treatment.


Acceleration of intensity-modulated radiotherapy dose calculation by importance sampling of the calculation matrices.
In inverse planning for intensity-modulated radiotherapy, the dose calculation is a crucial element limiting both the maximum achievable plan quality and the speed of the optimization process. One way to integrate accurate dose calculation algorithms into inverse planning is to precalculate the dose contribution of each beam element to each voxel for unit fluence. These precalculated values are stored in a big dose calculation matrix. Then the dose calculation during the iterative optimization process consists merely of matrix look-up and multiplication with the actual fluence values. However, because the dose calculation matrix can become very large, this ansatz requires a lot of computer memory and is still very time consuming, making it not practical for clinical routine without further modifications. In this work we present a new method to significantly reduce the number of entries in the dose calculation matrix. The method utilizes the fact that a photon pencil beam has a rapid radial dose falloff, and has very small dose values for the most part. In this low-dose part of the pencil beam, the dose contribution to a voxel is only integrated into the dose calculation matrix with a certain probability. Normalization with the reciprocal of this probability preserves the total energy, even though many matrix elements are omitted. Three probability distributions were tested to find the most accurate one for a given memory size. The sampling method is compared with the use of a fully filled matrix and with the well-known method of just cutting off the pencil beam at a certain lateral distance. A clinical example of a head and neck case is presented. It turns out that a sampled dose calculation matrix with only 1/3 of the entries of the fully filled matrix does not sacrifice the quality of the resulting plans, whereby the cutoff method results in a suboptimal treatment plan.


Why parents refuse immunization?
Rates of child immunization are falling in many countries, leading to the increase of morbidity and mortality from diseases controlled by vaccinations. The simplified model of the natural history of immunization follows a sequence of fear of the disease before vaccination, followed by acceptance of the vaccination until plateau, where the population forgets the morbidity and mortality of pre-immunization. Historical factors including withdrawals of vaccines, and publications regarding the true or falsified dangers of vaccines still resonate with parents. Building on these historical factors, unscientific sources such as naturopaths, homeopaths, chiropractors, celebrities and lay-people with anecdotal evidence and even scientific sources such as some universities and some medical doctors push their views on anti-vaccination, which proves to make the decision to vaccinate more difficult on parents. The main reason that parents refuse vaccination is a desire to protect their children. These parents believe that vaccination is harmful, or that not vaccinated children are healthier than vaccinated children. Scientific data often will lose with pseudoscientific, false or anecdotal data that have higher sensational and emotional impact on parents. With so many sources giving so many factors which sometimes contradict themselves, it is indeed difficult for a parent to make a clear decision for their child.


Pigmented iris angiography.
A small volume of concentrated fluorescein was used in a technique of fluorescein angiography in rabbits. The procedure is not accompanied by the usual risks of general anesthesia in rabbits. Angiographic findings demonstrated that the pigmented rabbit iris vessel pattern is similar to that found in albino rabbits.


Spectral and kinetic properties of radicals derived from oxidation of quinoxalin-2-one and its methyl derivative.
The kinetics and spectral characteristics of the transients formed in the reactions of •OH and •N3 with quinoxalin-2(1H)-one (Q), its methyl derivative, 3-methylquinoxalin-2(1H)-one (3-MeQ) and pyrazin-2-one (Pyr) were studied by pulse radiolysis in aqueous solutions at pH 7. The transient absorption spectra recorded in the reactions of •OH with Q and 3-MeQ consisted of an absorption band with λmax = 470 nm assigned to the OH-adducts on the benzene ring, and a second band with λmax = 390 nm (for Q) and 370 nm (for 3-MeQ) assigned, inter alia, to the N-centered radicals on a pyrazin-2-one ring. The rate constants of the reactions of •OH with Q and 3-MeQ were found to be in the interval (5.9-9.7) × 109 M-1·s-1 and were assigned to their addition to benzene and pyrazin-2-one rings and H-abstraction from the pyrazin-2-one nitrogen. In turn, the transient absorption spectrum observed in the reaction of •N3 exhibits an absorption band with λmax = 350 nm. This absorption was assigned to the N-centered radical on the Pyr ring formed after deprotonation of the respective radical cation resulting from one-electron oxidation of 3-MeQ. The rate constant of the reaction of •N3 with 3 MeQ was found to be (6.0 ± 0.5) × 109 M-1·s-1. Oxidation of 3-MeQ by •N3 and Pyr by •OH and •N3 confirms earlier spectral assignments. With the rate constant of the •OH radical with Pyr (k = 9.2 ± 0.2) × 109 M-1·s‒1, a primary distribution of the •OH attack was estimated nearly equal between benzene and pyrazin-2-one rings.


Left atrial remodelling, mid-regional pro-atrial natriuretic peptide, and prognosis across a range of ejection fractions in heart failure.
Measures of structural and functional remodelling of the left atrium (LA) are emerging as useful biomarkers in heart failure (HF). We hypothesized that LA volume and its contribution to stroke volume (SV) would predict a composite endpoint of HF hospitalization or death in patients with HF. We recruited 57 controls and 86 patients with HF, including preserved and reduced left ventricular ejection fraction (LVEF). Cardiac magnetic resonance imaging was used to evaluate LA volumes and contribution to LV SV. Plasma mid-region pro-atrial natriuretic peptide (MR-proANP) was evaluated. LA volume was negatively correlated with LVEF (P = 0.001) and positively correlated with LV mass in HFrEF (P < 0.001) but not in HFpEF. LA volume at end-diastole was associated with the composite endpoint in HFrEF (hazard ratio 1.26, 95% confidence interval 1.01-1.54; P = 0.044), but not HFpEF (1.06, 0.85-1.30; P = 0.612), per 10 mL/m increase. Active contribution to SV was negatively associated with the composite endpoint in HFpEF (0.32, 0.14-0.66; P = 0.001), but not HFrEF (0.91, 0.38-2.1; P = 0.828) per 10% increase. MR-proANP was associated with the composite endpoint in HFpEF (1.46, 1.03-1.94; P = 0.034), but not in HFrEF (1.14, 0.88-1.37; P = 0.278), per 100 pM increase. We found different relationships between LA remodelling and biomarkers in HFrEF and HFpEF. Our results support the hypothesis that the pathophysiologic underpinnings of HFpEF and HFrEF are different, and atrial remodelling encompasses distinct components for each HF subtype.


A positive psychological intervention using virtual reality for patients with advanced cancer in a hospital setting: a pilot study to assess feasibility.
This study presents data on the feasibility and possible benefits of a psychological intervention that uses virtual reality to induce positive emotions on adult hospitalized patients with metastatic cancer. The patient's satisfaction and perceived utility was also examined. The sample was composed of 19 patients (53 % men, aged from 29 to 85 years old; x = 60.9; standard deviation = 14.54). The intervention consisted of four 30-min sessions during 1 week in which patients navigated through virtual environments designed to induce joy or relaxation. Mood was assessed before and after each session using the Visual Analog Scale. Patient satisfaction was assessed after each session and at the end of the intervention. Qualitative data were also collected with open-ended questions. There were no major difficulties with the use of devices, and any difficulties that did arise were solved through practice. There were adequate levels of pleasantness and perceived utility of the proposed intervention. The main perceived benefits were distraction, entertainment, and promotion of relaxation states. Regarding mood changes, an increase in positive emotions and a decrease in negative emotions were also detected. The intervention was positively assessed and rated as minimally uncomfortable. Future actions are discussed as well as the need to implement brief interventions that take into account the patients' medical state and physical discomfort level, especially with those in the advanced stages of disease.


Two-stage amplification of an ultrasensitive MXene-based intelligent artificial eardrum.
We report an artificial eardrum using an acoustic sensor based on two-dimensional MXene (Ti3C2Tx), which mimics the function of a human eardrum for realizing voice detection and recognition. Using MXene with a large interlayer distance and micropyramid polydimethylsiloxane arrays can enable a two-stage amplification of pressure and acoustic sensing. The MXene artificial eardrum shows an extremely high sensitivity of 62 kPa-1 and a very low detection limit of 0.1 Pa. Notably, benefiting from the ultrasensitive MXene eardrum, the machine-learning algorithm for real-time voice classification can be realized with high accuracy. The 280 voice signals are successfully classified for seven categories, and a high accuracy of 96.4 and 95% can be achieved by the training dataset and the test dataset, respectively. The current results indicate that the MXene artificial intelligent eardrum shows great potential for applications in wearable acoustical health care devices.


The 100th: An appealing new species of Dendropsophus (Amphibia: Anura: Hylidae) from northeastern Brazil.
We describe a new species of the Dendropsophus leucophyllatus Group from the Atlantic Forest of the southern region of State of Bahia, Brazil. It can be distinguished from all species of the D. leucophyllatus Group on the basis of morphological characters (especially its unique dorsal pattern and snout in dorsal view), advertisement calls and divergence in mitochondrial DNA gene sequences. The inclusion of D. anceps on the group remains controversial but our phylogenetic analyses do not recover the new species as sister to syntopic species of the D. leucophyllatus Group (with or without D. anceps). These results also highlight the palimpsest that is past relation between the Atlantic and Amazon forests.


Clustered sites of DNA repair synthesis during early nucleotide excision repair in ultraviolet light-irradiated quiescent human fibroblasts.
The ubiquitous process of nucleotide excision repair includes an obligatory step of DNA repair synthesis (DRS) to fill the gapped heteroduplex following excision of a short (approximately 30-nucleotide) damaged single-strand fragment. Using 5-iododeoxyuridine to label repair patches during the first 10-60 min after UV irradiation of quiescent normal human fibroblasts we have visualized a limited number of discrete foci of DRS. These must reflect clusters of elementary DRS patches, since single patches would not be detected. The DRS foci are attenuated in normal cells treated with alpha-amanitin or in Cockayne syndrome (CS) cells, which are specifically deficient in the pathway of transcription-coupled repair (TCR). It is therefore likely that the clusters of DRS arise in chromatin domains within which RNA polymerase II transcription is compartmentalized. However, we also found significant suppression of DRS foci in xeroderma pigmentosum, complementation group C cells in which global genome repair (GGR) is defective, but TCR is normal. This suggests that the TCR is responsible for the DRS cluster formation in the absence of GGR. The residual foci detected in CS cells indicate that, even at early times following UV irradiation, GGR may open some chromatin domains for processive scanning and consequent DRS independent of transcription.


Voltage-dependent modulation of GABAA receptor channel desensitization in rat hippocampal neurons.
1. The mechanism of the time-dependent decline in gamma-amino-butyric acid (GABA)-induced chloride conductance, referred to as desensitization, was studied in dissociated rat hippocampal cell culture with the use of a whole-cell voltage-clamp recording. 2. In most cells the gradual decline of membrane conductance was dependent simultaneously on the agonist concentration and membrane voltage. Even in the continued presence of GABA, desensitization could be prevented by holding the membrane potential > 0 mV in a near symmetrical chloride gradient across the cell membrane. 3. The "recovery" from desensitization occurred after removal of the agonist with a time constant of approximately 35 s. The rate of recovery from desensitization was independent of membrane voltage. 4. When the membrane potential was jumped from a negative to a positive membrane potential during steady state of desensitization, the GABA-induced chloride conductance gradually "relaxed" to the undesensitized state. This phenomenon of gradual increase in chloride conductance or "reactivation" from desensitization was both voltage and agonist dependent. 5. The process of recovery of the GABA ionophore from the desensitized state is distinct from the process of reactivation, which is dependent both on the voltage and agonist. 6. These observations suggest that the ligand-bound GABA receptor has two alternate states, i.e., permissive (activated) and desensitized. The rates of transition between these two states are voltage dependent.


Traditional trapping methods outperform eDNA sampling for introduced semi-aquatic snakes.
Given limited resources for managing invasive species, traditional survey methods may not be feasible to implement at a regional scale. Environmental DNA (eDNA) sampling has proven to be an effective method for detecting some invasive species, but comparisons between the detection probability of eDNA and traditional survey methods using modern occupancy modeling methods are rare. We developed a qPCR assay to detect two species of watersnake (Nerodia fasciata and Nerodia sipedon) introduced to California, USA, and we compared the efficacy of eDNA and aquatic trapping. We tested 3-9 water samples each from 30 sites near the known range of N. fasciata, and 61 sites near the known range of N. sipedon. We also deployed aquatic funnel traps at a subset of sites for each species. We detected N. fasciata eDNA in three of nine water samples from just one site, but captured N. fasciata in traps at three of ten sites. We detected N. sipedon eDNA in five of six water samples from one site, which was also the only site of nine at which this species was captured in traps. Traditional trapping surveys had a higher probability of detecting watersnakes than eDNA surveys, and both survey methods had higher detection probability for N. sipedon than N. fasciata. Occupancy models that integrated both trapping and eDNA surveys estimated that 5 sites (95% Credible Interval: 4-10) of 91 were occupied by watersnakes (both species combined), although snakes were only detected at four sites (three for N. fasciata, one for N. sipedon). Our study shows that despite the many successes of eDNA surveys, traditional sampling methods can have higher detection probability for some species. We recommend those tasked with managing species invasions explicitly compare eDNA and traditional survey methods in an occupancy framework to inform their choice of the best method for detecting nascent populations.


Poplar MYB115 and MYB134 Transcription Factors Regulate Proanthocyanidin Synthesis and Structure.
The accumulation of proanthocyanidins is regulated by a complex of transcription factors composed of R2R3 MYB, basic helix-loop-helix, and WD40 proteins that activate the promoters of biosynthetic genes. In poplar (genus Populus), MYB134 is known to regulate proanthocyanidin biosynthesis by activating key flavonoid genes. Here, we characterize a second MYB regulator of proanthocyanidins, MYB115. Transgenic poplar overexpressing MYB115 showed a high-proanthocyanidin phenotype and reduced salicinoid accumulation, similar to the effects of MYB134 overexpression. Transcriptomic analysis of MYB115- and MYB134-overexpressing poplar plants identified a set of common up-regulated genes encoding proanthocyanidin biosynthetic enzymes and several novel uncharacterized MYB transcriptional repressors. Transient expression experiments demonstrated the capacity of both MYB134 and MYB115 to activate flavonoid promoters, but only in the presence of a basic helix-loop-helix cofactor. Yeast two-hybrid experiments confirmed the direct interaction of these transcription factors. The unexpected identification of dihydromyricetin in leaf extracts of both MYB115- and MYB134-overexpressing poplar led to the discovery of enhanced flavonoid B-ring hydroxylation and an increased proportion of prodelphinidins in proanthocyanidin of the transgenics. The dramatic hydroxylation phenotype of MYB115 overexpressors is likely due to the up-regulation of both flavonoid 3',5'-hydroxylases and cytochrome b5 Overall, this work provides new insight into the complexity of the gene regulatory network for proanthocyanidin synthesis in poplar.


Obsessive-compulsive symptoms associated with clozapine and risperidone treatment: three case reports and review of the literature.
Treatment-emergent obsessive-compulsive symptoms (OCSs) have raised concern since the widespread introduction of serotonin-dopamine antagonists (SDAs) for the treatment of schizophrenia. Further investigations of SDA-emergent OCSs and their response to anti-obsessional agents will be beneficial for clinicians in helping patients who suffer from this problem. We present three cases of schizophrenia in which distressing OCSs occurred during clozapine or risperidone treatment. OCSs were assessed consecutively using the Yale-Brown Obsessive-Compulsive Scale. The OCSs of these three patients were responsive to anti-obsessional agents, including fluvoxamine, clomipramine, and paroxetine. We also review the current literature and discuss the possible pathophysiology and psychopathology of SDA-emergent OCSs.


Oral Postbiotics as a Therapeutic Strategy for Atopic Dermatitis: A Systematic Review of Randomized Controlled Trials.
Atopic dermatitis (AD) is a prevalent chronic skin disease affecting all age groups. The connection with the gut microbiome led to oral probiotics as a therapeutic strategy. However, being viable microorganisms, probiotics might present risks. Thus, non-viable postbiotics have been considered as an alternative. We aimed to evaluate the efficacy of oral Lactobacillus postbiotics for managing symptoms of AD in pediatric and adult patients. A systematic review was conducted following PRISMA guidelines. Nine randomized controlled trials assessing the effects of non-viable Lactobacillus spp. administered orally to patients diagnosed with AD were included in the review, in which 512 subjects were evaluated after the intervention. Most studies allowed the concomitant usage of corticosteroids. Three studies focused on adults and indicated symptom improvement. In contrast, three out of six trials evaluating pediatric patients did not report postbiotics-favoring results. The dosage seems to be relevant for outcome determination. Two trials compared postbiotics with their viable analogs, and only one reported positive results in both groups. Postbiotics-associated shifts in gut microbial communities were reported in one trial. Mild adverse effects were detected by a single study. The overall results suggested that Lactobacillus postbiotics might be successfully used as adjuvant AD therapy in adults. Thus far, data do not indicate efficacy in pediatric patients. Standardizing nomenclatures and experimental procedures, as well as expanding the studies to more geographic locations and assessing comprehensively the effects on the gut microbiome would provide better perspectives of postbiotics as a therapeutic option for AD.


MCPIP1 is a positive regulator of type I interferons antiviral activity.
Type-I interferons (IFN-I) are widely used for antiviral immunotherapy in clinic. Therefore, identification of the regulators of IFN-I antiviral activity is important for developing novel targets for IFN-based antiviral therapy. Monocyte chemoattractant protein 1-induced protein 1 (MCPIP1) is critical for cellular inflammatory responses. However, the roles of MCPIP1 in interferons (IFNs)-mediated antiviral immunity are unexplored. In this study, we demonstrate for the first time that MCPIP1 is an important positive regulator of IFNs antiviral activity. We found that MCPIP1 can promote innate antiviral immunity independently of both its RNase and deubiquitinase activity. Furthermore, we reveal that MCPIP1 is an IFN-induced positive feedback signal molecule which promotes IFN-I-mediated antiviral efficacy. Mechanistically, MCPIP1 does not affect the activation of JAK/STAT upstream of IFN-I signaling, but significantly promotes IFN-I signaling by enhancing ISRE promoter activity and expression of interferon-stimulated genes (ISGs). And MCPIP1-mediated activation of IFN-I signaling is independently of its RNase and deubiquitinase activity. These findings uncover a novel innate antiviral mechanism mediated by the IFN-MCPIP1 axis, and may provide potential targets for enhancing IFNs antiviral therapy.


Evaluation of a new serotyping kit for Streptococcus pneumoniae.
A new serotyping test kit (Streptococcus pneumoniae antisera "Seiken" set; Denka kit) was evaluated for 285 strains of Streptococcus pneumoniae in comparison with the standard capsular reaction (Quellung test). This new kit is based on the slide-agglutination method and is composed of eight pool sera, 40 group or type sera and 41 specific type sera. All serotyping results by using the Denka kit were completely identical to those obtained by using the conventional Quellung test. For types and groups, sensitivity and specificity were 100 and 100 %, respectively. For specific types, sensitivity and specificity were 100 and 100 %, respectively. The Denka kit is relatively rapid (mean test time, 5 min, versus 15 min by Quellung test), cheap (0.5 US$ per test, versus 1.4 US$ per Quellung test), easy to perform and does not require special equipment. The Denka kit may be useful for fieldworkers in developing countries involved in epidemiological surveys and vaccine development.


Disparities in radiation therapy utilization for cancer patients in Victoria.
To evaluate the proportion of cancer patients who received radiation therapy (RT) within 12 months of cancer diagnosis (RTU12) and identify factors associated with RTU12. This is a population-based cohort of individuals with incident cancer, diagnosed between 2013 and 2017 in Victoria. Data linkages were performed between the Victorian Cancer Registry and Victorian Radiotherapy Minimum Dataset. The primary outcome was the proportion of patients who had RTU12. For the three most common cancers (i.e., prostate, breast and lung cancer), the time trend in RTU12 and factors associated with RTU12 were evaluated. The overall RTU12 in our study cohort was 26-20% radical RT and 6% palliative RT. Of the 21,735 men with prostate cancer, RTU12 was 17%, with no significant change over time (P-trend = 0.53). In multivariate analyses, increasing age and lower socioeconomic status were independently associated with higher RTU12 for prostate cancer. Of the 20,883 women with breast cancer, RTU12 was 64%, which increased from 62% in 2013 to 65% in 2017 (P-trend < 0.05). In multivariate analyses, age, socioeconomic status and area of residency were independently associated with RTU12 for breast cancer. Of the 13,093 patients with lung cancer, RTU12 was 42%, with no significant change over time (P-trend = 0.16). In multivariate analyses, younger age, male and lower socioeconomic status were independently associated with higher RTU12. In this large population-based state-wide cohort of cancer patients, only 1 in 4 had RT within 12 months of diagnosis. There were marked sociodemographic disparities in RTU12 for prostate, breast and lung cancer patients.


Analysis of spatial and temporal dynamics of xylem refilling in Acer rubrum L. using magnetic resonance imaging.
We report results of an analysis of embolism formation and subsequent refilling observed in stems of Acer rubrum L. using magnetic resonance imaging (MRI). MRI is one of the very few techniques that can provide direct non-destructive observations of the water content within opaque biological materials at a micrometer resolution. Thus, it has been used to determine temporal dynamics and water distributions within xylem tissue. In this study, we found good agreement between MRI measures of pixel brightness to assess xylem liquid water content and the percent loss in hydraulic conductivity (PLC) in response to water stress (P50 values of 2.51 and 2.70 for MRI and PLC, respectively). These data provide strong support that pixel brightness is well correlated to PLC and can be used as a proxy of PLC even when single vessels cannot be resolved on the image. Pressure induced embolism in moderately stressed plants resulted in initial drop of pixel brightness. This drop was followed by brightness gain over 100 min following pressure application suggesting that plants can restore water content in stem after induced embolism. This recovery was limited only to current-year wood ring; older wood did not show signs of recovery within the length of experiment (16 h). In vivo MRI observations of the xylem of moderately stressed (~-0.5 MPa) A. rubrum stems revealed evidence of a spontaneous embolism formation followed by rapid refilling (~30 min). Spontaneous (not induced) embolism formation was observed only once, despite over 60 h of continuous MRI observations made on several plants. Thus this observation provide evidence for the presence of naturally occurring embolism-refilling cycle in A. rubrum, but it is impossible to infer any conclusions in relation to its frequency in nature.


Triiodothyronine radioimmunoassay and its application to thyroid disorders.
An accurate, highly sensitive triiodothyrone (T3) radioimmunoassay system is described. Direct measurement in serum is made possible by the use of T3-free serum for standards, and blocking of T3 binding to thyroxine (T4)-binding globulin with salicylate. T4 cross reactivity was less than 0.3%. Mean T3 levels in 55 euthyroid, 32 hyperthyroid and 19 primary hypothyroid patients were 1.46 +/- 0.17, 5.34 +/- 1.86 and 0.49 +/- 0.34 (SD) ng/ml, respectively. T3 was found to be a more sensitive index than T4 in hyperthyroidism; in hypothyroidism it overlapped with euthyroidism. The presence of goiter had no effect on T3 concentrations in euthyroid patients. Among the patients studied, eight were found to have T3 toxicosis, including two patients with recurrent thyrotoxicosis. A significant T3 elevation was also found in euthyroid patients after thyroidectomy whereas T4 remained normal. The extent of T4 and T3 elevation was similar during the initial phase of subacute thyroiditis. There were significantly lower T3 values and higher thyroid-stimulating hormone values in umbilical cord blood than in maternal blood. In two euthyroid subjects, thyrotropin-releasing hormone stimulation caused a 50% rise in T3 levels and no change in T4 levels over a 2-h period.


Gracilis muscle interposition for the treatment of rectourethral, rectovaginal, and pouch-vaginal fistulas: results in 53 patients.
The aim of this study was to review our experience with gracilis muscle interposition for complex perineal fistulas. A retrospective review of all patients who underwent repair of perineal fistula using the gracilis muscle between 1995 and 2007 was undertaken. Patients were divided into 2 groups according to the fistula type by gender: females (rectovaginal and pouch-vaginal) and males (rectourethral). Gracilis interposition was performed in 53 patients. Seventeen women underwent 19 gracilis interpositions for 15 rectovaginal and 2 pouch-vaginal fistulas; 76% had a mean of (1-4) (mean of 2) prior failed attempt at repair. Eight patients experienced at least one postoperative complication. Two women required a second gracilis interposition. Thirty-three percent of the Crohn's disease-associated fistulas successfully healed; 75% without Crohn's successfully healed.Thirty-six males underwent gracilis interposition for rectourethral fistulas, mainly due to prostate cancer treatment; 13 (36%) had a mean of 1.5 (range 1-3) failed prior repairs. Seventeen patients experienced postoperative complications. The initial success rate in men with rectourethral fistulas was 78%. After successful second procedures in 8 patients, the overall clinical healing rate was 97%. The gracilis muscle transposition is a safe and effective method of treating complex perianal fistulas.


Progressive myelopathy due to idiopathic intraspinal tumoral calcinosis of the cervical spine. Case report.
Tumoral calcinosis is a rare disorder that most often occurs in periarticular regions of the extremities. Here, the authors report on an extremely rare case of idiopathic intraspinal tumoral calcinosis of the cervical spine. This 54-year-old man presented with a 2-week history of progressive cervical myelopathy. Results of magnetic resonance imaging and computed tomography myelography of the cervical spine revealed an intraspinal calcified mass lesion posterior to the spinal cord at the C3-4 level, resulting in marked spinal cord compression. Spinal cord decompression and en bloc resection of the mass lesion were performed via a C-2 laminoplasty and C3-4 laminectomy. The mass was localized in the dura mater. Histologically, the lesion consisted of numerous nodules with amorphous calcified materials and a florid proliferation of multinucleated giant cells; that is, its histological characteristics were identical to those of tumoral calcinosis. The symptoms disappeared completely after surgery. In all previously reported cases of cervical tumoral calcinosis, the lesion was located in the paraspinal soft tissue, with bone and facet joint involvement. The present case is the first reported instance of cervical tumoral calcinosis localized only in the spinal canal.


Believing and perceiving: authorship belief modulates sensory attenuation.
Sensory attenuation refers to the observation that self-generated stimuli are attenuated, both in terms of their phenomenology and their cortical response compared to the same stimuli when generated externally. Accordingly, it has been assumed that sensory attenuation might help individuals to determine whether a sensory event was caused by themselves or not. In the present study, we investigated whether this dependency is reciprocal, namely whether sensory attenuation is modulated by prior beliefs of authorship. Participants had to judge the loudness of auditory effects that they believed were either self-generated or triggered by another person. However, in reality, the sounds were always triggered by the participants' actions. Participants perceived the tones' loudness attenuated when they believed that the sounds were self-generated compared to when they believed that they were generated by another person. Sensory attenuation is considered to contribute to the emergence of people's belief of authorship. Our results suggest that sensory attenuation is also a consequence of prior belief about the causal link between an action and a sensory change in the environment.


Preservation of the superficial lobe for deep-lobe parotid tumors: a better aesthetic outcome.
Deep-lobe parotid tumors are relatively uncommon. Most of these tumors present as external masses. They can also present in the oral cavity or oropharynx. Magnetic resonance imaging and ultrasound-guided fine-needle aspiration for biopsy and cytology have made it possible to establish a definitive diagnosis and identify the exact location of the tumor in almost all cases before surgery. Traditionally, deep-lobe tumors have been managed by a formal superficial parotidectomy and identification and preservation of the facial nerve, followed by removal of the deep lobe that contains the tumor Superficialparotidectomy is associated in most cases with periauricular depression secondary to a loss of volume, leading to variable aesthetic deformities. A complete parotidectomy is more likely to be associated with a larger aesthetic deficit secondary to a greater loss of tissue volume. The incidence of gustatory sweating is high after superficial parotidectomy, particularly in the early postoperative period. We hypothesize that if the superficial lobe is preserved, there is less likelihood of gustatory sweating because of the interposition of tissue between the skin and the cut ends of the secretomotor fibers. Approximately 80% of parotid tissue volume is made up of the superficial lobe, and therefore preservation of the superficial lobe should be associated with less postparotidectomy depression. Therefore, we decided to preserve the superficial lobe of the gland for deep-lobe tumors. Nine patients underwent deep-lobe parotidectomy with preservation of the superficial lobe over a 6-year period. Patients were studied prospectively with regard to technical difficulty, complications, and cosmetic outcome. Follow-up ranged from 12 months to 6 years. We did not experience any undue technical difficulty, and there were no cases of facial weakness. One patient developed gustatory sweating, which almost completely resolved over a 2-year period. There were no cases of post parotidectomy depression, and both patients and surgeons were satisfied with the cosmetic appearance. We present our technique and experience.


Diastereoselective C-alkylation of aldimines, derived from chiral α-carbon heteroatom-substituted aldehydes, with triethylborane. Application to the synthesis of benzylisoquinolines.
The one-pot reaction of a chiral aldehyde, p-methoxyaniline or p-fluoroaniline, and triethylborane produces the corresponding alkylated chiral amine with high yields and diastereoisomeric ratios. Stereocontrol is induced by the presence of a heteroatom in the α-position to the aldehyde. In the case of alkylation of imines derived from chiral aliphatic amines, good yields and moderate to high diastereoselectivity are obtained: yields are significantly better when the preformed imine is used in the reaction with triethyl borane, and diastereoselectivity of the reactions largely depends on the structure of the chiral aliphatic amine. The methodology is successfully applied to the synthesis of romneine, a natural benzylisoquinoline.


Paediatric admissions at a tertiary hospital in Kuala Lumpur--a case for a short-stay ward.
The profile of admissions staying less than 24 hours admitted to the paediatric wards of University Malaya Medical Center, Kuala Lumpur, over a period of six weeks was reviewed to ascertain the need of a short-stay ward. Ninety-three (22%) of the 428 admissions admitted during the study period were discharged within 24 hours, 56 (60%) were discharged within 12 hours. Major categories of admissions were: elective investigative procedures (43%), and emergency admissions (44%). Reasons for emergency admissions: infections 42%, minor trauma/cerebral concussion 25% and febrile/afebrile seizures 11%. Only 20% required percutaneous oximetry monitoring and 2% required observations more frequently than 2 hourly. There may be a case for a short stay ward in a big paediatric unit in Malaysia.


Preparing and Wear-Resisting Property of Al2O3/Cu Composite Material Enhanced Using Novel In Situ Generated Al2O3 Nanoparticles.
Al2O3/Cu composite material (ACCM) are highly suitable for various advanced applications owing to its excellent properties. In the present work, a combination of the solution combustion synthesis and hydrogen reduction method was first employed to prepare Al2O3/Cu composite powder (ACCP), and subsequently ACCM was prepared by employing spark plasma sintering (SPS) technique. The effect of Al2O3 contents and SPS temperatures on the properties (relative density, hardness, friction coefficient, and electrical conductivity, et al.) of ACCM were investigated in detail. The results indicated that ACCM was very dense, and microstructure was consisted of fine Al2O3 particles evenly distributed in the Cu matrix. With the increase of SPS temperature, the relative density and hardness of ACCM had first increased and then decreased. At 775 °C, the relative density and hardness had attained the maximum values of 98.19% and 121.4 HV, respectively. With the increase of Al2O3 content, although the relative density of ACCM had gradually decreased, nevertheless, its friction coefficient had increased. Moreover, with the increase of Al2O3 contents, the hardness of ACCM first increased and then decreased, and reached the maximum value (121.4 HV) with 3 wt.% addition. On the contrary, the wear rate of ACCM had first decreased and then increased with the increase of Al2O3 contents, and attained the minimum (2.32 × 10-5 mm3/(N.m)) with 3 wt.% addition.


Is Ki-67 of Diagnostic Value in Distinguishing Between Partial and Complete Hydatidiform Moles? A Systematic Review and Meta-analysis.
To demonstrate the value of Ki-67 in distinguishing between partial and complete hydatidiform moles. We searched electronic databases included Medline, WOK, Cochrane Library and CNKI, through January 24, 2015. Experts were consulted, and references from related articles were examined. The meta-analysis was conducted with RevMan5.3, according to the PRISMA guidelines. Mantel-Haenszel estimates were calculated and pooled under a random effect model, with data expressed as odds ratio (OR) and 95% confidence interval (CI). We analyzed eight trials with a total of 337 participants who underwent uterine curettage and met the inclusion criteria. A significantly higher expression of Ki-67 was observed in complete than in partial hydatidiform moles (OR=3.28; 95%CI=1.80-5.96; p<0.0001). The Ki-67 expression was higher in complete than in partial hydatidiform moles. Therefore, Ki-67 may be of diagnostic value in distinguishing between partial and complete hydatidiform moles. However, the present study had only a limited number of samples, so investigation of a greater number of cases is needed to confirm this conclusion.


Torin and cylindrin, two extrinsic proteins of the erythrocyte membrane: a review.
This review integrates the work of the author with that of others who have studied these proteins. the discovery, release, localization, and purification of cylindrin and torin are considered in depth and the available evidence for their biochemical characterization is presented. The electron microscopy of torin and cylindrin, which throughout their study has been of prime significance, is expanded in a section dealing with the interpretation of the negatively stained images and the production of paracrystalline arrays. The functional activity for torin and cylindrin is discussed and possible future lines of investigation are presented.


Modeling Human Myocardium Exposure to Doxorubicin Defines the Risk of Heart Failure from Low-Dose Doxorubicin.
The antitumor anthracycline, doxorubicin (DOX), can cause heart failure (HF) upon cumulative administration. Lowering the cumulative dose of DOX proved useful to minimize HF risk, and, yet, there is a growing concern that HF might occur after doses that were thought to be safe. Clinical trials that prospectively address such concerns are lacking. Because HF risk correlates with cardiac exposure to DOX, cumulative doses associated with HF risk were re-explored by modeling the accumulation of anthracycline pools in human myocardium. Ex vivo myocardial samples were used in vitro to simulate DOX rapid infusions. The accumulation of anthracycline pools was measured and incorporated into equations from which a risk versus dose curve was obtained. The experimental curve identified a 5% risk dose that was congruent with a previously reported clinical value (380 versus 400 mg/m2, respectively); however, 1-2% risk occurred after lower doses than reported. Simulations of gain-of-function polymorphism of carbonyl reductase 3, which converts DOX to its poorly diffusible alcohol metabolite, doxorubicinol (DOXOL), expanded anthracycline pools and caused 5% or 1-2% risk doses to decrease to 330 or 180-230 mg DOX/m2, respectively. These data show there is no safe dose of DOX. Diminishing cardiac exposure to circulating DOX may represent a cardioprotective strategy. We show that DOX slow infusions or liposomal DOX, which reduce cardiac exposure to DOX, caused formation of smaller anthracycline pools, did not generate DOXOL, increased the 5% risk dose to 750-800 mg/m2, and prevented HF risk aggravation by carbonyl reductase polymorphism.


[Herpes zoster and post-herpetic neuralgia in older adults].
Varicella-Zoster virus is responsible for chickenpox and, after reactivation, herpes zoster. Herpes zoster causes a vesicular dermatomal rash, traditionally metameric. Old adults can present severe pain during the acute phase, and late complications, such as post-herpetic neuralgia that can trying and crippling. Initiated within the first 72 hours of the rash, antivirals accelerate rash healing, reducing both rash and acute pain severity but incompletely the onset of other complications. Complementary therapeutic drug is often necessary. However, their application in old, frail, co-morbid and often poly-medicated patients have to be carefully considered as their use may be contraindicated. A specific vaccine is enable to reduce herpes zoster-related morbidity.


Prevalence and symptomatology of depression in older people living in institutions in England and Wales.
Epidemiological studies have shown that depression is common in institutional settings. However, the symptomatology of depression in this group has not been compared to those living in the community. To estimate the prevalence of depression and depressive symptomatology in participants living in institutions and compare these to people living in other settings. The Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) is a population-based cohort comprising 13,004 individuals aged 65 and above, from five sites across England and Wales. Following screening, a stratified random sub-sample of 2,640 participants received the Geriatric Mental State (GMS) examination of whom 340 resided in institutions. Diagnoses of depression were made using the Automated Geriatric Examination for Computer-assisted Taxonomy system (AGECAT). The prevalence of depression in those living in institutions was 27.1% (95% CI 17.8-36.3) compared to 9.3% (95% CI 7.8-10.9) in those living at home. Symptoms relating to depressed mood, severity of illness (e.g. wishing to be dead, future looking bleak) and some non-specific symptoms were more common in those living in residential homes. Depression was significantly associated with younger age (P = 0.002) and high functional disability (P = 0.009) in those living in institutions. Consistent with previous estimates, depression was highly prevalent in institutions, particularly in younger individuals with severe functional impairment. Those in institutions report considerably more symptoms of depression. Finding interventions which address these symptoms might improve quality of life for people in institutions, irrespective of formal diagnoses.


[Mucinous adenocarcinoma of the renal pelvis in the horseshoe kidney: a case report].
A 41-year-old man with macroscopic hematuria and abdominal fullness was referred to our hospital. Computed tomography (CT) revealed a left renal pelvic tumor in the horseshoe kidney. We performed left heminephrectomy and ureterectomy. The pathological diagnosis was the mucinous adenocarcinoma in the renal pelvis. He received postoperative adjuvant chemotherapy (CAP therapy). He died of retroperitoneal recurrence 8 months postoperatively. In the literature we found 95 cases of primary adenocarcinoma in the renal pelvis including our case.


Dynamic and Functional Profiling of Xylan-Degrading Enzymes in Aspergillus Secretomes Using Activity-Based Probes.
Plant polysaccharides represent a virtually unlimited feedstock for the generation of biofuels and other commodities. However, the extraordinary recalcitrance of plant polysaccharides toward breakdown necessitates a continued search for enzymes that degrade these materials efficiently under defined conditions. Activity-based protein profiling provides a route for the functional discovery of such enzymes in complex mixtures and under industrially relevant conditions. Here, we show the detection and identification of β-xylosidases and endo-β-1,4-xylanases in the secretomes of Aspergillus niger, by the use of chemical probes inspired by the β-glucosidase inhibitor cyclophellitol. Furthermore, we demonstrate the use of these activity-based probes (ABPs) to assess enzyme-substrate specificities, thermal stabilities, and other biotechnologically relevant parameters. Our experiments highlight the utility of ABPs as promising tools for the discovery of relevant enzymes useful for biomass breakdown.


Prevalence of Candida dubliniensis fungemia in Argentina: identification by a novel multiplex PCR and comparison of different phenotypic methods.
Candida dubliniensis is an emerging pathogen that can cause invasive disease in patients who have a variety of clinical conditions. C. dubliniensis is often misidentified as Candida albicans by clinical laboratories. In Argentina, incidence data are still scarce, and only one systemic infection has been reported. This study aims to determine the prevalence of C. dubliniensis in blood samples in Argentina, to evaluate a novel PCR multiplex as well as several phenotypic methods for the identification of this yeast, and to know the susceptibility profile of isolates against seven antifungal drugs. We have found that prevalence in Argentina appears to be lower than that reported in other countries, occurring only in 0.96% of the Candidemia cases recovered in 47 hospitals during a 1-year period. All C. dubliniensis clinical isolates included in this study were genetically identical when comparing ITS genes sequences. This is in agreement with the previous studies suggesting little genetic variation within this species. The novel multiplex PCR proved to be 100% sensitive and specific for the identification of C. dubliniensis. Therefore, we propose its use as a rapid and inexpensive method for laboratories having access to molecular techniques. Although no single phenotypic test has proved to be infallible, both colony morphology on tobacco agar, as well as abundant chlamydospore formation on both tobacco agar and on sunflower seed agar, may be used as a presumptive differentiation method in routine mycology laboratories. It has been suggested that C. dubliniensis may have higher propensity to develop azole antifungal drug resistance than C. albicans. In this study, one of the five clinical isolates of C. dubliniensis was resistant to fluconazole.


Advancements of the sFIDA method for oligomer-based diagnostics of neurodegenerative diseases.
Early diagnosis of Alzheimer's disease (AD) is of great importance for the development of therapeutics and their application in the clinical environment. Amyloid β (Aβ) oligomers are crucial for the onset and progression of AD and represent a popular drug target, being presumably the most direct biomarker. Efforts to measure Aβ oligomers in body fluids are hampered by the low analyte concentration and presence of Aβ monomers. The surface-based fluorescence intensity distribution analysis (sFIDA) features both highly specific and sensitive oligomer quantitation as well as total insensitivity towards monomers. In this Review, we highlight structural features of oligomeric and fibrillar Aβ. Recent advancements in sFIDA assay development have been the successful automation, adaption for additional biomarkers such as α-synuclein oligomers, and significant improvement of essential assay parameters.