Czech multicenter research database of severe COPD.
Chronic obstructive pulmonary disease (COPD) has been recognized as a heterogeneous, multiple organ system-affecting disorder. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) places emphasis on symptom and exacerbation management. The aim of this study is examine the course of COPD and its impact on morbidity and all-cause mortality of patients, with respect to individual phenotypes and GOLD categories. This study will also evaluate COPD real-life patient care in the Czech Republic. The Czech Multicentre Research Database of COPD is projected to last for 5 years, with the aim of enrolling 1,000 patients. This is a multicenter, observational, and prospective study of patients with severe COPD (post-bronchodilator forced expiratory volume in 1 second ≤ 60%). Every consecutive patient, who fulfils the inclusion criteria, is asked to participate in the study. Patient recruitment is done on the basis of signed informed consent. The study was approved by the Multicentre Ethical Committee in Brno, Czech Republic. The objective of this paper was to outline the methodology of this study. The establishment of the database is a useful step in improving care for COPD subjects. Additionally, it will serve as a source of data elucidating the natural course of COPD, comorbidities, and overall impact on the patients. Moreover, it will provide information on the diverse course of the COPD syndrome in the Czech Republic.


Management of Acute Pancreatitis in the Early Stage.
Acute pancreatitis (AP) is a potential fatal disease with an overall mortality around 5%. The current treatment for AP relies on supportive medical therapy, sometimes associated with endoscopic procedures and/or surgical interventions. In this review we discuss the recent concepts regarding the fluid therapy, pain management, antibiotic prophylaxis, apheresis for hypertriglyceridemia-induced AP, timing and indications for ERCP and cholecystectomy in biliary AP. For each component, the importance and the impact of early phase treatment is presented in terms of benefits and risks.


Contrast-Enhanced Imaging in the Management of Intrahepatic Cholangiocarcinoma: State of Art and Future Perspectives.
Intrahepatic cholangiocarcinoma (iCCA) represents the second most common liver cancer after hepatocellular carcinoma, accounting for 15% of primary liver neoplasms. Its incidence and mortality rate have been rising during the last years, and total new cases are expected to increase up to 10-fold during the next two or three decades. Considering iCCA's poor prognosis and rapid spread, early diagnosis is still a crucial issue and can be very challenging due to the heterogeneity of tumor presentation at imaging exams and the need to assess a correct differential diagnosis with other liver lesions. Abdominal contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) plays an irreplaceable role in the evaluation of liver masses. iCCA's most typical imaging patterns are well-described, but atypical features are not uncommon at both CT and MRI; on the other hand, contrast-enhanced ultrasound (CEUS) has shown a great diagnostic value, with the interesting advantage of lower costs and no renal toxicity, but there is still no agreement regarding the most accurate contrastographic patterns for iCCA detection. Besides diagnostic accuracy, all these imaging techniques play a pivotal role in the choice of the therapeutic approach and eligibility for surgery, and there is an increasing interest in the specific imaging features which can predict tumor behavior or histologic subtypes. Further prognostic information may also be provided by the extraction of quantitative data through radiomic analysis, creating prognostic multi-parametric models, including clinical and serological parameters. In this review, we aim to summarize the role of contrast-enhanced imaging in the diagnosis and management of iCCA, from the actual issues in the differential diagnosis of liver masses to the newest prognostic implications.


The TAR model: use of therapeutic state transitions for quality assurance reporting in chronic disease management.
Chronic disease management represents one of the challenges for health informatics and demands the appropriate application of information technology for improved patient care. This paper presents an approach to quality assurance reporting wherein the recommendations of evidence-based clinical practice guidelines are considered in the context of empirical therapeutic state-transitions (in terms of changes in individual patient prescriptions over time). We apply a Transition-based Audit Report (TAR) model to antihypertensive prescribing and related data as stored in a New Zealand General Practice Management System database. The results provide a set of quality indicators and specific patient cohorts for potential practice quality improvement with strong linkage to the selected guidelines and observed practice patterns. We see the TAR model primarily as a tool to enable internal quality improvement efforts, but also to be of relevance for focusing pay-for-performance programs.


Time trend in annual kidney graft survival.
First cadaver, unrelated kidney graft survival at one year from 50 Eurotransplant centers was analyzed and found to show marked changes in survival rates over the 20-year period from 1967 to 1986 inclusive. Full information on HLA-A, -B, and -DR matching and use of cyclosporine therapy was only available for the period 1981 to 1986. When these factors were allowed for, the number (and type) of HLA mismatches was shown to have a significant and independent effect on differences in survival rates whereas the effect of cyclosporine differed over the different years.


Comparison of modified Ashworth scale and Hoffmann reflex in study of spasticity.
Spasticity is one of the common complications in upper motor neuron lesions and without appropriate treatment it causes disturbances in movement pattern. Assessments of patients are effective in patient's management. Modified Ashworth scale (MAS) is one of the criteria in qualitative assessment of spasticity, and there are lots of controversies about its validity. The purpose of this study is to compare MAS with electrophysiological indices of spasticity. The spasticity of upper limb muscles in patients with hemiplegic cerebral palsy are measured and recorded by MAS. Then electrophysiological indices of Hoffmann reflex (H reflex) and ratio of maximum range of action potential of combined movement of flexor carpi radialis (FCR) for upper limb and soleus for lower limb were estimated. Data of 11 patients with age range 4 to 6 were analyzed. There is no significant correlation between degree of spasticity and electrophysiological indices.


Mean-field theory of a plastic network of integrate-and-fire neurons.
We consider a noise-driven network of integrate-and-fire neurons. The network evolves as result of the activities of the neurons following spike-timing-dependent plasticity rules. We apply a self-consistent mean-field theory to the system to obtain the mean activity level for the system as a function of the mean synaptic weight, which predicts a first-order transition and hysteresis between a noise-dominated regime and a regime of persistent neural activity. Assuming Poisson firing statistics for the neurons, the plasticity dynamics of a synapse under the influence of the mean-field environment can be mapped to the dynamics of an asymmetric random walk in synaptic-weight space. Using a master equation for small steps, we predict a narrow distribution of synaptic weights that scales with the square root of the plasticity rate for the stationary state of the system given plausible physiological parameter values describing neural transmission and plasticity. The dependence of the distribution on the synaptic weight of the mean-field environment allows us to determine the mean synaptic weight self-consistently. The effect of fluctuations in the total synaptic conductance and plasticity step sizes are also considered. Such fluctuations result in a smoothing of the first-order transition for low number of afferent synapses per neuron and a broadening of the synaptic-weight distribution, respectively.


Sulphur compounds used in medicine.
Native sulphur has had limited success as a medicinal agent. There is, however, hardly a class of drugs which does not contain compounds having sulphur in their structure. Sulphur-containing dyes have given rise to many clinically useful substances, others, such as the -lactam antibiotics, have been developed from naturally occurring molecules and yet others have been designed on the basis of a detailed understanding of physiological mechanisms. Sulphur occurs in drug molecules in all its oxidative states and in all its forms of organic combination. Organo-sulphur compounds, unquestionably form a major therapeutic resource and their potential remains to be further exploited.


[New potentials for monitoring the temperature and the relative and absolute humidity of the air-oxygen mixture during the prolonged artificial ventilation of newborn infants].
A new HTM-902 monitor (UCCP, Germany/Serviceinstrument, Russia) was used for continuous measurements of the temperature and relative and absolute humidity of inspired gas during prolonged mechanical ventilation in 86 neonates with respiratory failure caused by the respiratory distress syndrome (n = 42), meconium aspiration syndrome (n = 28), and congenital pneumonia (n = 16). All measurements were performed with a special probe connected to the inspiratory contour through a standard adapter close to the patient's T-piece. The monitor helped maintain the optimal values of the inspired gas conditioning during assisted ventilation of the neonates. The optimal relationships between gas temperature and humidity can be attained only with humidifiers with a servocontrol of temperature and heated wire inside the inspiratory circle tube. For maintaining adequate humidity of inspired gas after any changes in the ventilator flow rate or in the temperature inside the incubator, the heating power of the humidifier had to be corrected. However, even with servocontrolled humidifiers and humidity regulation, an increase of temperature inside the incubator over 35 degrees C made impossible the maintenance of the inspired gas humidity at the level of 96-100% with its temperature at the level of the patient's T-piece no higher than 37 degrees C.


Analogues of Cis- and Transplatin with a Rich Solution Chemistry: cis-[PtCl2 (NH3 )(1-MeC-N3)] and trans-[PtI2 (NH3 )(1-MeC-N3)].
Mono(nucleobase) complexes of the general composition cis-[PtCl2 (NH3 )L] with L=1-methylcytosine, 1-MeC (1 a) and L=1-ethyl-5-methylcytosine, as well as trans-[PtX2 (NH3 )(1-MeC)] with X=I (5 a) and X=Br (5 b) have been isolated and were characterized by X-ray crystallography. The Pt coordination occurs through the N3 atom of the cytosine in all cases. The diaqua complexes of compounds 1 a and 5 a, cis-[Pt(H2 O)2 (NH3 )(1-MeC)](2+) and trans-[Pt(H2 O)2 (NH3 )(1-MeC)](2+) , display a rich chemistry in aqueous solution, which is dominated by extensive condensation reactions leading to μ-OH- and μ-(1-MeC(-) -N3,N4)-bridged species and ready oxidation of Pt to mixed-valence state complexes as well as diplatinum(III) compounds, one of which was characterized by X-ray crystallography: h,t-[{Pt(NH3 )2 (OH)(1-MeC(-) -N3,N4)}2 ](NO3 )2 ⋅2 [NH4 ](NO3 )⋅2 H2 O. A combination of (1) H NMR spectroscopy and ESI mass spectrometry was applied to identify some of the various species present in solution and the gas phase, respectively. As it turned out, mass spectrometry did not permit an unambiguous assignment of the structures of +1 cations due to the possibilities of realizing multiple bridging patterns in isomeric species, the occurrence of different tautomers, and uncertainties regarding the Pt oxidation states. Additionally, compound 1 a was found to have selective and moderate antiproliferative activity for a human cervix cancer line (SISO) compared to six other human cancer cell lines.


Time Out of General Surgery Specialty Training in the UK: A National Database Study.
General surgery specialty training in the United Kingdom takes 6 years and allows trainees to take time out of training. Studies from the United States have highlighted an increasing trend for taking time out of surgical training for research. This study aimed to evaluate trends in time out of training and the impact on the duration of UK general surgical specialty training. A cohort study using routinely collected surgical training data from the Intercollegiate Surgical Curriculum Program database for General surgery trainees registered from August 1, 2007. Trainees were classified as Completed Training or In-Training. Out of training periods were identified and time in training calculated (both unadjusted and adjusted for out of training periods) with a predicted time in training for those In-Training. Of the trainees still In-Training (n = 994), a greater proportion had taken time out of training compared with those who had completed training (n = 360; 54.5% vs 45.9%, p < 0.01). A greater proportion of the In-Training group had undertaken a formal research period compared with the Completed Training group (35.1% vs 6.1%, p < 0.01). Total unadjusted training time in the Completed Training group was a median 6.0 (interquartile range 6.0-7.0) years compared with a predicted unadjusted training time in the In-Training group, with an out of training period recorded, of a median 8.0 (interquartile range 7.0-9.0) years. Trainees are increasingly taking time out of surgical training, particularly for research, with a subsequent increase in total time of training. This should be considered when redesigning surgical training programs and planning the future surgical workforce.


Viral gastro-enteritis in children in Malawi.
In a 2-month survey of 186 children with gastro-enteritis attending an out-patient clinic in Malawi, 42% were infected with rotavirus (HRV), 9% Cryptosporidium, 4.2% adenovirus, 1.2% Astrovirus and 0.6% Norwalk agent and small round featureless viruses. We believe this to be the first report of HRV in Malawi and the first of Astrovirus in Africa. Almost all the HRV infections were in children under 12 months old, 40% were in children under 6 months and 64% of children were being breastfed at presentation. Signs of respiratory tract infection were not unique to HRV gastro-enteritis. Polyacrylamide gel electrophoresis of HRV dsRNA from 25 of the faecal samples revealed that each had the same long electropherotype.


Porous SiO2 interferometric biosensor for quantitative determination of protein interactions: binding of protein A to immunoglobulins derived from different species.
Determination of kinetic and thermodynamic protein binding constants using interferometry from a porous Si Fabry-Perot layer is presented. A protein A capture probe is adsorbed within the pores of an oxidized porous Si matrix, and binding of immunoglobulin G (IgG) antibodies derived from different species is investigated. The relative protein A/IgG binding affinity is human > rabbit > goat, in agreement with literature values. The equilibrium binding constant (Ka) for human IgG binding to surface-immobilized protein A is determined to be (3.0 +/- 0.5) x 107 M-1 using an equilibrium Langmuir model. Kinetic rate constants are calculated to be kd = (2.1 +/- 0.2) x 10-4 s-1 and ka = (1.2 +/- 0.4) x 104 M-1 s-1 using nonlinear least-squares analysis, yielding an equilibrium binding constant of Ka = (5.5 +/- 1.5) x 107 M-1. Both steady-state and time-dependent measurements yield equilibrium binding constants that are consistent with literature values. Kinetic rate constants determined through nonlinear least-squares analysis are also in agreement with protein A/IgG binding on a surface. Dosing with a high concentration of analyte leads to deviations from ideal binding behavior, interpreted in terms of restricted analyte diffusion within the porous SiO2 matrix. It is shown that the diffusion limitations can be minimized if the kinetic measurements are performed at low analyte concentrations or under conditions in which the protein A capture probe is not saturated with analyte. Potential limitations of the use of porous SiO2 interferometers for quantitative determination of protein binding constants are discussed.


Anaesthetic Concerns of Surgical Emphysema Following Thyroidectomy.
Surgical emphysema secondary to tracheal tear is a rare but serious complication after thyroidectomy. It is usually resolved by conservative management; but in case of compromised airway, early airway control and surgical intervention is required. This is the case report of a 52-year woman diagnosed as thyroid carcinoma, who developed rapidly progressive surgical emphysema involving head and upper thorax, following total thyroidectomy, in post anesthesia care unit (PACU). The complication was related to tracheal tear occurring during excision of huge thyroid mass, encroaching trachea. But with timely assessment in PACU and prompt surgical intervention, we were able to save the patient. Vigilant observation in the early postoperative period is very important in patients undergoing thyroidectomy because early recognition is the key in saving patients with surgical emphysema, postoperatively.


Antibiotic-Containing Agarose Hydrogel for Wound and Burn Care.
Wound infections cause inflammation, tissue damage, and delayed healing that can lead to invasive infection and even death. The efficacy of systemic antibiotics is limited due to poor tissue penetration that is especially a problem in burn and blast wounds where the microcirculation is disrupted. Topical administration of antimicrobials is an attractive approach because it prevents infection and avoids systemic toxicity, while hydrogels are an appealing vehicle for topical drug delivery. They are easy to apply to the wound site by being injectable, the drug release properties can be controlled, and their many characteristics, such as biodegradation, mechanical strength, and chemical and biological response to stimuli can be tailored. Hydrogels also create a moist wound environment that is beneficial for healing. The purpose of this study was to formulate an agarose hydrogel that contains high concentrations of minocycline or gentamicin and study its characteristics. Subsequently, the minocycline agarose hydrogel was tested in a porcine burn model and its effect as a prophylactic treatment was studied. The results demonstrated that 0.5% agarose in water was the optimal concentration in terms of viscosity and pH. Bench testing at room temperature demonstrated that both antibiotics remained stable in the hydrogel for at least 7 days and both antibiotics demonstrated sustained release over the time of the experiment. The porcine burn experiment showed that prophylactic treatment with the agarose minocycline hydrogel decreased the burn depth and reduced the number of bacteria as efficiently as the commonly used silver sulfadiazine cream.


Automating quality measurement: a system for scalable, comprehensive, and routine care quality assessment.
Electronic medical records (EMRs) hold the promise of making routine comprehensive measurement of care quality a reality. However, there are many informatics challenges that stand in the way of this goal. Guidelines are rarely stated in precise enough language for automated measurement of clinical practices and the data necessary for that measurement often reside in the text notes of EMRs. We designed a technology platform for scalable and routine measurement of care quality using comprehensive EMR data, including providers' freetext notes documenting clinical encounters. We are in the process of implementing this system to assess the quality of ambulatory asthma care in two diverse healthcare systems: a mid-size HMO and a consortium of Federally Qualified Healthcare Center (FQHC) clinics on the west coast of the United States.


Reliability of cerebral oximeter in non-invasive diagnosis and follow-up of hypercapnia.
In this study, aimed to evaluate the sensitivity and specificity of cerebral oximetry and EtCO2 values in non-invasive diagnosis and monitoring of hypercapnia. This study enrolled pediatric patients admitted to and mechanically ventilated at the Pediatric Intensive Care Unit of Gaziantep University Faculty of Medicine Hospital between January 2014 and January 2015. Patients' age, gender, diagnosis, ventilatory parameters, a measured of the mean end-tidal carbon dioxide value stream method, and the simultaneously monitored arterial blood gas PaCO < sub > 2 < /sub > level and near infrared spectroscopy device (NIRS) measurements were recorded. The mean age of patients was 61 months (min 4-max 193), and there were 8 (53.4%) female and 7 (46.6%) male subjects. A significant correlation was found between PCO2 and NIRS, PCO < sub > 2 < /sub > and EtCO < sub > 2 < /sub > (r = 0.571, p < 0.001). There was a significant positive correlation between EtCO2 and NIRS (r = 0.479, p < 0.001). NIRS levels were significantly higher (p < 0.001) in the group with pCO < sub > 2 < /sub > > 45; EtCO < sub > 2 < /sub > > 40 and pH < 7.35, compared to the group with PCO < sub > 2 < /sub > < 45 EtCO < sub > 2 < /sub > < 40 and ph≥7.35 . The best cut-off point for NIRS to distinguish the groups with PCO < sub > 2 < /sub > > 45 with PCO < sub > 2 < /sub > < 45 was 80.5, with a sensitivity of 65.3%, specificity of 84.3%, and positive and negative predictive values of 81.9% and 69.1%, respectively. The best cut-off point for NIRS to distinguish the groups with EtCO < sub > 2 < /sub > > 40 and EtCO < sub > 2 < /sub > < 40 was 81, with a sensitivity of 62.2%, specificity 77.9%, and positive and negative predictive values of 61.2% and 72.3%, respectively. As for pH < 7.35 and PaCO < sub > 2 < /sub > > 45, while sensitivity of EtCO < sub > 2 < /sub > (at a cut-off point of 40) was 64.9%; the sensitivity of NIRS (at a cut-off point of 80.5) was 28.1%, with EtCO < sub > 2 < /sub > being significantly more sensitive than NIRS (p < 0.001). The results of the present study suggest that NIRS values of above 80 should alert clinicians for hypercapnia associated with increased cerebral blood flow.


Molecular Imaging in Cancer Drug Development.
Development of new oncology drugs has increased since the improved understanding of cancer's complex biology. The oncology field has become the top therapeutic research area for new drugs. However, only a limited number of drugs entering clinical trials will be approved for use as the standard of care for cancer patients. Molecular imaging is increasingly perceived as a tool to support go/no-go decisions early during drug development. It encompasses a wide range of techniques that include radiolabeling a compound of interest followed by visualization with SPECT or PET. Radiolabeling can be performed using a variety of radionuclides, which are preferably matched to the compound on the basis of size and half-life. Imaging can provide information on drug behavior in vivo, whole-body drug target visualization, and heterogeneity in drug target expression. This review focuses on current applications of molecular imaging in the development of small molecules, antibodies, and antihormonal anticancer drugs.


[Tumor of posterior mediastinum - rare case of extramedullar myelolipoma].
A 71-year-old male with acute exacerbation of chronic bronchitis was treated in summer of 2015. The CT scan has revealed a mass on the right side of 11th thoracic vertebra in the adipose tissue with a sharp edge towards the lung and containing a small amount of contrast agent. The radiologist recommended histological sampling of the mass. The tumor was removed by Video-Assisted Thoracic Surgery (VATS) in August of 2015. The patient was discharged on the fifth postoperative day without complication. Myelolipoma was diagnosed by histological examination. Recurrence was not detected during the one-year-follow-up period. Myelolipoma is a benign tumor consisting of mature lobulated adipose tissue and hemopoetic bone marrow. It arises mainly from the adrenal gland. Surgical resection is recommended due to the potential of progressive enlargement. Although the extraadrenal myelolipoma is an uncommon entity, in case of mediastinal, encapsulated, slow-growing tumor, myelolipoma should be considered as a differential diagnosis.


The Interplay of Autophagy and Oxidative Stress in the Kidney: What Do We Know?
Autophagy, as an indispensable metabolism, plays pivotal roles in maintaining intracellular homeostasis. Nutritional stress, amino acid deficiency, oxidative stress, and hypoxia can trigger its initiation. Oxidative stress in the kidney activates essential signal molecules, like mammalian target of rapamycin (mTOR), adenosine monophosphate-activated protein kinase (AMPK), and silent mating-type information regulation 2 homolog-1 (SIRT1), to stimulate autophagy, ultimately leading to degradation of intracellular oxidative substances and damaged organelles. Growing evidence suggests that autophagy protects the kidney from oxidative stress during acute ischemic kidney injury, chronic kidney disease, and even aging. This review emphasizes the cross talk between reactive oxygen species (ROS) signaling pathways and autophagy during renal homeostasis and chronic kidney disease according to the current latest research and provides therapeutic targets during kidney disorders by adjusting autophagy and suppressing oxidative stress. ROS arise through an imbalance of oxidation and antioxidant defense mechanisms, leading to impaired cellular and organ function. Targeting the overproduction of ROS and reactive nitrogen species, reducing the antioxidant enzyme activity and the recovery of the prooxidative-antioxidative balance provide novel therapeutic regimens to contribute to recovery in acute and chronic renal failure. Although, in recent years, great progress has been made in understanding the molecular mechanisms of oxidative stress and autophagy in acute and chronic renal failure, the focus on clinical therapies is still in its infancy. The growing number of studies on the interactive mechanisms of oxidative stress-mediated autophagy will be of great importance for the future treatment and prevention of kidney diseases.


Elasticity of stiff polymer networks.
We study the elasticity of a two-dimensional random network of rigid rods ("Mikado model"). The essential features incorporated into the model are the anisotropic elasticity of the rods and the random geometry of the network. We show that there are three distinct scaling regimes, characterized by two distinct length scales on the elastic backbone. In addition to a critical rigidity percolation region and a homogeneously elastic regime we find a novel intermediate scaling regime, where the elasticity is dominated by bending deformations.


Leukocyte CD11b and CD18 expression are increased in blood salvaged for autotransfusion.
To investigate whether activated leukocytes are present in salvaged blood, we measured complete blood counts and quantified the surface expression of the leukocyte adhesion receptors CD11b and CD18 in salvaged blood and arterial blood from six male patients undergoing elective abdominal aortic aneurysm repair. Salvaged blood contained 5,450 +/- 1010 leukocytes/microL and 7600 +/- 6200 platelets/microL and had a hematocrit of 50.6 +/- 3.7%. CD 11b expression was 3.3 +/- 0.5 fold higher on neutrophils and 3.8 +/- 1.0 fold higher on monocytes from salvaged blood compared with arterial blood (P < 0.05 for both). CD18 expression was increased 3.2 +/- 0.2 fold on neutrophils and 2.5 +/- 0.4 fold on lymphocytes (P < 0.05) in salvaged compared to arterial blood (P < .05). Monocyte expression of CD18 was increased 4.50 +/- 1.1 fold in salvaged blood, but this difference was not statistically significant. We conclude that a substantial number of activated leukocytes are present in salvaged blood. Because activated leukocytes could potentially be detrimental to the recipient, our findings raise theoretical concerns about the use of salvaged blood and emphasize the need for further refinement of the procedure.


The Effect of Spring Water Geochemistry on Copper Proteins in Tengchong Hot Springs, China.
Copper (Cu) is an essential trace metal cofactor for a variety of proteins; however, excess Cu is toxic to most organisms. Cu homeostasis is maintained by a complex machinery of Cu binding proteins that control the uptake, transport, sequestration, and efflux of Cu ions. Despite the importance of Cu binding proteins in electron transfer, substrate oxidation, superoxide dismutation, and denitrification, little information exists about microbial Cu utilization in extreme environments, where the geochemical conditions may affect Cu bioavailability. Using metagenomic data from 9 hot springs in Tengchong, China, which range in temperature from 42°C to 96°C and in pH from 2.3 to 9, the effects of pH, temperature, and spring geochemistry on the distribution of Cu binding domains of proteins and oxidoreductases were studied. Dissolved Cu and Cu binding domains were detected across all temperature and pH gradients. Cu binding domains of cytochrome c oxidase subunits, heavy-metal-associated domains, and nitrous oxide reductase were detected at all sites. DoxB, a quinol oxidase, and other quinol oxidase subunits were the dominant Cu binding oxidoreductase subunits present at low-pH and high-temperature sites, whereas cbb3-type cytochrome c oxidase subunits were dominant at high-pH and high-temperature sites. Additionally, aa3-type cytochrome c oxidase was more prominent than cbb3-type cytochrome c oxidase under circumneutral-pH conditions. This suggests that the type of cytochrome c oxidase pathway and the Cu proteins employed by microbes to carry out important functions such as energy acquisition and efflux of excess Cu are affected by the physicochemical conditions of the springs.IMPORTANCE Copper is present in a variety of proteins and is required to carry out essential functions by all organisms. However, in hot spring environments, copper availability may be limited due to the high temperatures and the wide range in pH. The significance of our research is in relating the physicochemical environment to the distribution of copper proteins across hot spring environments, which provides increased understanding of primary functions and adaptions in these environments.


Different mechanism of vocal cord paralysis between spinocerebellar ataxia (SCA 1 and SCA 3) and multiple system atrophy.
While multiple system atrophy (MSA) is frequently associated with vocal cord paralysis (VCP) causing severe respiratory failure, it is still unknown whether hereditary types of spinocerebellar degeneration develop similar laryngeal paralysis. We analyzed the laryngeal function from the viewpoints of fiberoptic laryngoscopy and laryngeal myopathology and then attempted to clarify the difference of the mechanism of VCP among the patients with spinocerebellar ataxia type 1 (SCA 1), type 3 (SCA 3), and MSA. Seven patients with SCA 1, nineteen with SCA 3, and eleven with MSA were studied. Vocal cord movement was analyzed by fiberoptic laryngoscopy during wakefulness and diazepam-induced sleep (sleep load test). Paraffin-embedded sections or cryosections of the intrinsic laryngeal muscles from five autopsied cases (one with SCA 1 and four with SCA 3) were histologically examined. VCP was found in two of the seven SCA 1 patients (29%), three of the nineteen SCA 3 patients (16%), and in nine of the eleven MSA patients (82%). VCP observed in SCA 1 and SCA 3 was various in the severity and showed no exacerbation on sleep load test in all of the eight patients but one SCA 3 patient. In this patient, the findings of fiberoptic laryngoscopy were quite similar to those found in MSA. All the intrinsic laryngeal muscles including cricothyroid (CT), interarytenoid (IA), and posterior cricoarytenoid (PCA) muscles showed neurogenic atrophy in one autopsied SCA 1 and four SCA 3 patients. Our conclusion is that VCP in SCA 1 and SCA 3 contrasts with that in MSA in its occurrence, response to the sleep load test, and the distribution of the neurogenic abnormalities among the intrinsic laryngeal muscles.


Pro-psychotic effects of synthetic cannabinoids: interactions with central dopamine, serotonin, and glutamate systems.
An association between marijuana use and schizophrenia has been noted for decades, and the recent emergence of high-efficacy synthetic cannabinoids (SCBs) as drugs of abuse has lead to a growing number of clinical reports of persistent psychotic effects in users of these substances. The mechanisms underlying SCB-elicited pro-psychotic effects is unknown, but given the ubiquitous neuromodulatory functions of the endocannabinoid system, it seems likely that agonist actions at cannabinoid type-1 receptors (CB1Rs) might modulate the functions of other neurotransmitter systems known to be involved in schizophrenia. The present review surveys what is currently known about the interactions of CB1Rs with dopamine, serotonin, and glutamate systems, because all three of those neurotransmitters are well-established in the pathophysiology of schizophrenia and psychosis. Identification of molecular mechanisms underlying the pro-psychotic effects of SCB drugs of abuse may establish certain classes of these substances as particularly dangerous, guiding regulations to control availability of these drugs. Likewise, an understanding of the pharmacological interactions which lead to schizophrenia and psychosis subsequent to SCB exposure might guide the development of novel therapies to treat afflicted users.


Auxiliary versus orthotopic liver transplantation for acute liver failure. EURALT Study Group. European Auxiliary Liver Transplant Registry.
We report 1-year results after auxiliary liver transplantation for acute liver failure in a cohort of 47 patients transplanted in 12 European centers as compared with those of 384 consecutive patients undergoing orthotopic liver transplantation for acute liver failure in the Eurotransplant area. One-year patient survival resp. retransplant-free patient survival did not differ between orthotopic (61%, 232/384 resp. 52%, 200/384) and auxiliary liver transplantation (62%, 29/47 resp. 53%, 25/47). One-year patient survival resp. retransplant-free patient survival after auxiliary partial orthotopic liver transplantation was 71% (25/35) resp. 60% (21/35), not significantly different from orthotopic liver transplantation (61%, 232/384 resp. 52%, 200/384), while both transplantation techniques had better 1-year patient survival resp. retransplant-free patient survival than after heterotopic auxiliary liver transplantation (33%, 4/12) (p < 0.05). Primary nonfunction was more frequent after heterotopic auxiliary liver transplantation (3/12, 25%) than after orthotopic liver transplantation (21/384, 5.5%), while the incidence did not differ between orthotopic liver transplantation and auxiliary partial orthotopic liver transplantation (3/35, 8.5%). Portal vein thrombosis was more frequent after both heterotopic auxiliary liver transplantation (5/12, 42%) and auxiliary partial orthotopic liver transplantation (5/35, 14%) than after orthotopic liver transplantation (2/384, 0.5%) (p < 0.001). Of the patients, 65% (17/26) surviving auxiliary liver transplantation for 1 year without retransplantation by orthotopic liver transplantation were free of immunosuppression within 1 year, compared with none of the patients transplanted by orthotopic liver transplantation (p < 0.01). Auxiliary liver transplantation, especially auxiliary partial orthotopic liver transplantation, offers an advantage over orthotopic liver transplantation in acute liver failure in terms of a chance of a life free of immunosuppression, apparently without jeopardizing chances of survival. Reduction of the incidence of primary nonfunction and vascular complications should be a focus of research in auxiliary liver transplantation. These findings need to be confirmed in a prospective study.


A serum antibody in patients with rheumatoid arthritis stimulates cathepsin B activity in peritoneal mouse macrophages.
Mouse peritoneal macrophages were stimulated by sera from patients with active rheumatoid arthritis (RA) to increased intracellular cathepsin B activity. By gel filtration of three RA sera, the stimulatory activity was found in the IgG and to a lesser extent in the IgM containing fraction. The DEAE-cellulose purified IgG preparations of five additional RA patients stimulated intracellular cathepsin B activity significantly above IgG from healthy controls. IgG and IgM antibodies to macrophages were detected in sera from RA patients but not from controls by indirect immunofluorescence (IIF) technique. Pepsin F (ab')2 fragments of IgG from the RA patients also gave clearcut membrane fluorescent staining of the macrophages which demonstrated the antibody nature of the binding. A good correlation between the cathepsin B assay and the IIF was found when serial dilutions of serum were compared.


Probes for protein adduction in cholesterol biosynthesis disorders: Alkynyl lanosterol as a viable sterol precursor.
The formation of lipid electrophile-protein adducts is associated with many disorders that involve perturbations of cellular redox status. The identities of adducted proteins and the effects of adduction on protein function are mostly unknown and an increased understanding of these factors may help to define the pathogenesis of various human disorders involving oxidative stress. 7-Dehydrocholesterol (7-DHC), the immediate biosynthetic precursor to cholesterol, is highly oxidizable and gives electrophilic oxysterols that adduct proteins readily, a sequence of events proposed to occur in Smith-Lemli-Opitz syndrome (SLOS), a human disorder resulting from an error in cholesterol biosynthesis. Alkynyl lanosterol (a-Lan) was synthesized and studied in Neuro2a cells, Dhcr7-deficient Neuro2a cells and human fibroblasts. When incubated in control Neuro2a cells and control human fibroblasts, a-Lan completed the sequence of steps involved in cholesterol biosynthesis and alkynyl-cholesterol (a-Chol) was the major product formed. In Dhcr7-deficient Neuro2a cells or fibroblasts from SLOS patients, the biosynthetic transformation was interrupted at the penultimate step and alkynyl-7-DHC (a-7-DHC) was the major product formed. When a-Lan was incubated in Dhcr7-deficient Neuro2a cells and the alkynyl tag was used to ligate a biotin group to alkyne-containing products, protein-sterol adducts were isolated and identified. In parallel experiments with a-Lan and a-7-DHC in Dhcr7-deficient Neuro2a cells, a-7-DHC was found to adduct to a larger set of proteins (799) than a-Lan (457) with most of the a-Lan protein adducts (423) being common to the larger a-7-DHC set. Of the 423 proteins found common to both experiments, those formed from a-7-DHC were more highly enriched compared to a DMSO control than were those derived from a-Lan. The 423 common proteins were ranked according to the enrichment determined for each protein in the a-Lan and a-7-DHC experiments and there was a very strong correlation of protein ranks for the adducts formed in the parallel experiments.


Cortical stimulation for chronic pain: from anecdote to evidence.
Epidural stimulation of the motor cortex (eMCS) was devised in the 1990's, and has now largely supplanted thalamic stimulation for neuropathic pain relief. Its mechanisms of action involve activation of multiple cortico-subcortical areas initiated in the thalamus, with involvement of endogenous opioids and descending inhibition toward the spinal cord. Evidence for clinical efficacy is now supported by at least seven RCTs; benefits may persist up to 10 years, and can be reasonably predicted by preoperative use of non-invasive repetitive magnetic stimulation (rTMS). rTMS first developed as a means of predicting the efficacy of epidural procedures, then as an analgesic method on its own right. Reasonable evidence from at least six well-conducted RCTs favors a significant analgesic effect of high-frequency rTMS of the motor cortex in neuropathic pain (NP), and less consistently in widespread/fibromyalgic pain. Stimulation of the dorsolateral frontal cortex (DLPFC) has not proven efficacious for pain, so far. The posterior operculo-insular cortex is a new and attractive target but evidence remains inconsistent. Transcranial direct current stimulation (tDCS) is applied upon similar targets as rTMS and eMCS; it does not elicit action potentials but modulates the neuronal resting membrane state. tDCS presents practical advantages including low cost, few safety issues, and possibility of home-based protocols; however, the limited quality of most published reports entails a low level of evidence. Patients responsive to tDCS may differ from those improved by rTMS, and in both cases repeated sessions over a long time may be required to achieve clinically significant relief. Both invasive and non-invasive procedures exert their effects through multiple distributed brain networks influencing the sensory, affective and cognitive aspects of chronic pain. Their effects are mainly exerted upon abnormally sensitized pathways, rather than on acute physiological pain. Extending the duration of long-term benefits remains a challenge, for which different strategies are discussed in this review.


[Mobilization of peripheral blood stem cells with mitoxantrone and high-dose cytarabine chemotherapy and rhG-CSF in patients with hematopoietic malignancies].
To evaluate the efficacy of mitoxantrone combined high dose of cytarabine and recombinant human granulocyte colony-stimulating factor (MAG) regimen for mobilizing autologous peripheral blood stem cells (APBSC) in patients with hematopoietic malignancies. From December 1995 to April 2003, 14 lymphoma and 29 acute leukemia patients were treated with high-dose cytarabine (2 g/m2 every 12 h, days 1 and 2) and mitoxantrone (10 mg/m2, days 2 and 3), followed by 300 microgram recombinant human granulocyte colony-stimulating factor per day (rhG-CSF 300 microg/d) i.e, the MAG regimen as mobilization regimen of peripheral blood stem cells. rhG-CSF was given subcutaneously when the white blood cell (WBC) count below 1.0 x 10(9)/L following the MA chemotherapy, APBSC were harvested when WBC count increased using Baxter CS3000plus or Cobe Spectra. Mobilization was successful in 13 of 14 lymphoma patients with MNC (3.91 +/- 2.70) x 10(8)/kg, CD34+ cells (17.79 +/- 12.90) x 10(6)/kg. Meanwhile, mobilization was successful in 24 of 29 acute leukemia patients with average of 2.13 times for apheresis. The median MNC and CD34+ cells yielded were 3.62 x 10(8)/kg and 7.37 x 10(6)/kg respectively, rhG-CSF was used for a median time of 7 days. Excepting for grade I-II gastrointestinal toxicity in 8 and infection in 14 cases, no major side effects were observed. There was no mobilization-related mortality. Minimal residual diseases became undetectable after mobilization in some patients. MAG is a safe and highly effective mobilization regimen in patients with lymphoma and acute leukemia.


Ichthyosis follicularis with atrichia and photophobia (IFAP) syndrome in two unrelated female patients.
The IFAP syndrome is characterized by the congenital onset of ichthyosis follicularis, absence of hair, and photophobia. A limited number of patients with the disorder have been described, and X-linked recessive inheritance has been proposed. Two unrelated female patients with a complete IFAP syndrome are reported. Both patients show a diffuse distribution of the disorder without linear arrangement. Because the suggested X-linked recessive pattern of inheritance is unlikely in these patients, a different way of transmission or, alternatively, genetic heterogeneity of the disorder has to be considered.


[The quadriga phenomenon of the extensor tendon system and the superficial transverse metacarpal ligament].
The aponeurosis of the common extensor tendons is connected by intertendinous connections proximal to the metacarpophalangeal joints. These fibers are responsible for tenodesis effects in case of maximal finger extension and flexion and by this means they diminish the function of the other metacarpophalangeal joints. This mechanism can be described as the Quadriga-Syndrome of the extensor apparatus. These connecting structures also help to stabilize the transverse metacarpophalangeal arch and the position of the extensor tendons over the metacarpal heads. Cadaver dissections as well as operative findings have shown that there exists a superficial transverse intermetacarpal ligament, which connects the metacarpal heads in the area of its neck.


CEACAM1 confers resistance toward oxygen-induced vessel damage in a mouse model of retinopathy of prematurity.
To determine a functional role for the carcinoembryonic antigen-related cell-adhesion molecule 1 (CEACAM1) in retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). In a 21/75/21% OIR mouse model, retinal neovascularization was compared in wild-type and CEACAM1-deficient mice. Animals were housed under normoxic conditions until postnatal day 7, followed by exposure to 75% oxygen for 5 days, and further housing under normoxic conditions. Retinal vascular anatomy, vaso-obliteration, neovascularization, and tuft formation were characterized and quantified in retinal flat-mounts from untreated mice and from experimental mice during and at different time points after exposure to high oxygen levels. The vascular network was stained with fluorescently labeled isolectin B4. Mice deficient in CEACAM1 did not present any apparent abnormalities in their postnatal retinal vascular development under normoxic housing conditions. However, after hyperoxia and under relative hypoxic conditions, retinal neovascularization and tuft formation were aggravated in the mutant. Congruently, revascularization and vessel maturation were delayed in CEACAM1-deficient mice whereas in wild-type mice, tuft regression and vascular remodeling occurred efficiently after exposure to high oxygen levels. Our report describes a functional role for CEACAM1 in retinal neovascularization in a mouse model of OIR. This is the first study demonstrating that CEACAM1 enhances vascular remodeling and tuft regression by increasing endothelial resistance to alterations in oxygen tension, thus accelerating vascular recovery after systemic hypoxia.


Clostridium difficile in the normal adult faecal flora.
One hundred and seventy-seven out of 324 routine non-diarrhoeal faecal specimens investigated for the presence of Clostridium difficile were culture-positive. Twelve of the faecal specimens obtained from thirty-six normal healthy volunteers yielded Cl. difficile prior to oral administration of clindamycin. Thereafter all the volunteers excreted the organism from the second day to the fifth day during clindamycin administration. Three months after stoppage of oral clindamycin sixteen of the thirty-six volunteers still excreted Cl. difficile. Peak or trough serum levels of clindamycin had no relationship with the density of growth. None of the volunteers developed any Cl. difficile associated diseases.


'If it helps my patient...' Perspectives on complementary medicine.
The argument 'if it helps my patient, I don't need science to prove that it works' is rife in complementary medicine. This article is an attempt to examine it from the perspective of the provider of complementary medicine, the clinical scientist and the politician. It is concluded that the dichotomy between experience and science is a regrettable misunderstanding. The revised argument should be 'if it helps my patient, I want research undertaken to find out whether more people could benefit from it'.


Dental health in a group of Swedish 8-year-olds followed since the age of 3.
A study was made of the dental health of a group of 8-year-old children studied earlier as 3-, 4- and 5-year-olds, including examination of caries, gingivitis and occlusion, as well as certain data on oral habits and fluoride prophylaxis. Caries was found in 92% of the children. The mean DMFS-value was 3.1 and the mean defs-value 8.8. A statistically significant correlation was demonstrated between caries indices at 3 and 8 years of age in the group as a whole. Children with a defs-value higher than the mean defs-value at the age of 3, had a higher mean DMFS-value at the age of 8 than the rest of the group. Sagittal relationships remained largely unchanged between 3 and 8 years of age, while the number of children with an anterior open bite decreased from 51% to 4% during the same time, probably due to a decrease in sucking habits.


Pulmonary Lymphoepithelioma-like Carcinoma.
Pulmonary lymphoepithelioma-like carcinoma is a rare type of non-small cell lung cancer. The tumor is usually discovered in young, nonsmoking Asian populations. The patients are diagnosed at an earlier stage and have a better prognosis than those with other non-small cell lung cancers. Histologically, the tumor morphology is indistinguishable from undifferentiated carcinoma of the nasopharynx. It is characterized by nests or diffuse sheets of syncytial tumor cells, which show round to oval vesicular nuclei with prominent nucleoli, along with an admixed heavy lymphocytic and plasma cell infiltrate. The presence of Epstein-Barr virus in the tumor cells is crucial for the diagnosis. The differential diagnoses include lymphoepithelioma-like carcinoma from other sites and pulmonary involvement of lymphoma. EGFR mutations and ALK rearrangements are not commonly found in lymphoepithelioma-like carcinoma, in contrast to programmed death ligand-1 expression, which is shown in a majority of cases.


Inhibition of tyrosine aminotransferase by beta-N-oxalyl-L-alpha,beta-diaminopropionic acid, the Lathyrus sativus neurotoxin.
Species differences in susceptibility are a unique feature associated with the neurotoxicity of beta-N-oxalyl-L-alpha,beta-diaminopropionic acid (L-ODAP), the Lathyrus sativus neurotoxin, and the excitotoxic mechanism proposed for its mechanism of toxicity does not account for this feature. The present study examines whether neurotoxicity of L-ODAP is the result of an interference in the metabolism of any amino acid and if it could form the basis to explain the species differences in susceptibility. Thus, Wistar rats and BALB/c (white) mice, which are normally resistant to L-ODAP, became susceptible to it following pretreatment with tyrosine (or phenylalanine), exhibiting typical neurotoxic symptoms. C57BL/6J (black) mice were, however, normally susceptible to L-ODAP without any pretreatment with tyrosine. Among the various enzymes associated with tyrosine metabolism examined, the activity of only tyrosine aminotransferase (TAT) was inhibited specifically by L-ODAP. The inhibition was noncompetitive with respect to tyrosine (Ki = 2.0 +/- 0.1 mM) and uncompetitive with respect to alpha-ketoglutarate (Ki = 8.4 +/- 1.5 mM). The inhibition of TAT was also reflected in a marked decrease in the rate of oxidation of tyrosine by liver slices, an increase in tyrosine levels of liver, and also a twofold increase in the dopa and dopamine contents of brain in L-ODAP-injected black mice. The dopa and dopamine contents in the brain of only L-ODAP-injected white mice did not show any change, whereas levels of these compounds were much higher in tyrosine-pretreated animals. Also, the radioactivity associated with tyrosine, dopa, and dopamine arising from [14C]tyrosine was twofold higher in both liver and brain of L-ODAP-treated black mice. Thus, a transient increase in tyrosine levels following the inhibition of hepatic TAT by L-ODAP and its increased availability for the enhanced synthesis of dopa and dopamine and other likely metabolites (toxic?) resulting therefrom could be the mechanism of neurotoxicity and may even underlie the species differences in susceptibility to this neurotoxin.


Endoscopic techniques for myotomy of the lower esophageal sphincter and pylorus.
Peroral endoscopic myotomy (POEM) and gastric peroral endoscopic myotomy (G-POEM) are minimally invasive endoscopic procedures for the treatment of esophageal motility disorders and refractory gastroparesis, respectively. In this review, we highlight the most recent publications on the technical aspects of POEM and G-POEM. POEM has evolved into a standard therapeutic option in patients with all achalasia subtypes with excellent durability and safety profile. G-POEM is a novel endoscopic procedure with promising results in terms of efficacy, safety, and symptom improvement in patients with refractory gastroparesis. POEM and G-POEM are novel endoscopic procedures. Practice patterns vary among endoscopists and procedure techniques continue to evolve. Comparative studies examining outcomes of different techniques are needed.


[Bacterial synthesis of immunogenic epitopes of foot-and-mouth disease virus fused either to human necrosis factor or to hepatitis B core antigen].
Using recombinant DNA technology, construction and bacterial expression of genes was carried out which code for hybrid proteins, human tumor necrosis factor and hepatitis B core protein fused to immunogenic epitopes of foot-and-mouth disease virus, strains A22 and O1-194. Hybrids of tumor necrosis factor with foot-and-mouth disease antigenic determinants protected laboratory animals against the experimental challenge with a homologous strain of foot-and-mouth disease virus. Hybrid protein that contained immunogenic regions of two strains, A22 and O1-194, protected animals against infection with both A and O serotypes. Hybrid proteins based on hepatitis B virus core antigen retained the ability to assemble into core-like particles.


Photochemical air pollution in the northeast United States.
Statistical analyses of meteorological and contaminant data and chemical kinetic modeling demonstrate that (i) the concentrations of ozone in the New Jersey-New York City metropolitan area are regional in character; (ii) ozone concentrations in Connecticut are increased by approximately 20 percent as a consequence of primary emissions in the New Jersey-New York City metropolitan region and subsequent transport; and (iii) the concentrations of a variety of products of smog chemistry in the New Jersey area are markedly increased by an increase in NO emissions, but are minimally affected by a change in hydrocarbon emissions.


The episodic resurgence of highly pathogenic avian influenza H5 virus.
Highly pathogenic avian influenza (HPAI) H5N1 activity has intensified globally since 2021, increasingly causing mass mortality in wild birds and poultry and incidental infections in mammals1-3. However, the ecological and virological properties that underscore future mitigation strategies still remain unclear. Using epidemiological, spatial and genomic approaches, we demonstrate changes in the origins of resurgent HPAI H5 and reveal significant shifts in virus ecology and evolution. Outbreak data show key resurgent events in 2016-2017 and 2020-2021, contributing to the emergence and panzootic spread of H5N1 in 2021-2022. Genomic analysis reveals that the 2016-2017 epizootics originated in Asia, where HPAI H5 reservoirs are endemic. In 2020-2021, 18.104.22.168b H5N8 viruses emerged in African poultry, featuring mutations altering HA structure and receptor binding. In 2021-2022, a new H5N1 virus evolved through reassortment in wild birds in Europe, undergoing further reassortment with low-pathogenic avian influenza in wild and domestic birds during global dissemination. These results highlight a shift in the HPAI H5 epicentre beyond Asia and indicate that increasing persistence of HPAI H5 in wild birds is facilitating geographic and host range expansion, accelerating dispersion velocity and increasing reassortment potential. As earlier outbreaks of H5N1 and H5N8 were caused by more stable genomic constellations, these recent changes reflect adaptation across the domestic-bird-wild-bird interface. Elimination strategies in domestic birds therefore remain a high priority to limit future epizootics.


Structural Characterization and Immunobiological Activity of Polysaccharides from Astragalus Oyster Mushroom.
When added to mushroom growing substrates, edible and medicinal herbs affect the mushrooms' nutritional and medicinal value. In this study, polysaccharides (P0OP-I and P15OP-I) were extracted and purified from oyster mushrooms grown on substrates supplemented with 0% and 15% Astragalus roots (P0 and P15), respectively, and their chemical structure and immunobiological activities were compared. P15OP-I and P0OP-I were extracted using ultrasound-assisted hot water and deproteinized with the Sevage method, depigmented with 30% H2O2, desalted with dialysis, and purified using DEAE-52 cellulose and Sephadex G-100 dextran column chromatography. The molecular weight of P0OP-I and P15OP-I was 21,706.96 and 20,172.65 Da, respectively. Both were composed of monosaccharides D-mannose, galacturonic acid, D-glucose, D-galactose, and L-arabinose but in different molar ratios, and both were connected by a pyranoside linkage. P15OP-I consisted of higher contents of mannose, glucose, galactose and arabinose and lower content of galacturonic acid as compared to P0OP-I. Both P0OP-I and P15OP-I induced NO and TNF-α production but did not show cytotoxic effect or induce ROS generation in RAW264.7 cells. P15OP-I showed a stronger ability to promote NO and TNF-α production relative to P0OP-I. In vitro experiments showed that the immunomodulatory activity of P0OP-I and P15OP-I in RAW264.7 macrophages were mediated by the JNK/MAPK, Erk/MAPK, and NF-κB signaling pathways. The results would be helpful for elucidation of the health promoting mechanism of Astragalus oyster mushrooms as a source of neutraceuticals.


Diagnostic decision. The measurement of anticonvulsant agent levels.
Monitoring levels of antiepileptic drugs is useful in formulating a therapeutic plan but not in making a diagnosis. Differences in assay methods are not important. Differences in therapeutic ranges do not reflect procedural differences but merely the source that is quoted. Therapeutic ranges are not absolute criteria for therapy, but guides to a clinical balance between dose and side effects. Because therapeutic ranges reflect trough (early morning) serum levels, clinical determinations should be done at this time. Serum drug determinations should be used to establish the successful drug level for a patient; assess compliance; identify the relative contributions of each drug to efficacy and to side effects in complex programs; identify bioavailability problems; and characterize idiosyncrasies in the rate of drug metabolism.


Overhydrated stomatocytosis associated with a complex RHAG genotype including a novel de novo mutation.
Overhydrated stomatocytosis is a rare autosomal dominant disorder known to cause variably severe haemolytic anaemia due to heterozygous mutations in the RHAG gene. We report a 26-year-old man with recurring jaundice, splenohepatomegaly and mild chronic haemolytic anaemia with significant stomatocytosis. Extensive haemolytic work-up including flow cytometry for eosin-5'-maleimide and CD47 expression levels was carried out. Targeted resequencing revealed two probably causative heterozygous mutations in RHAG (Leu336Ser and Ile149Met) and one heterozygous mutation in ANK1 (Glu1046Lys). RHAG involvement was confirmed by decreased RhAG macrocomplex component indicated by the reduced CD47 expression on erythrocytes. In silico analysis concordantly flagged RHAG:Leu336Ser and ANK1:Glu1046Lys as likely deleterious mutation, whereas RHAG:Ile149Met was reported as likely neutral by PROVEAN. Family screening by Sanger sequencing revealed RHAG:Leu336Ser in a mother and ANK1:Glu1046Lys in a father who were both asymptomatic, excluding them as causative dominant events, thus establishing RHAG:Ile149Met, novel de novo mutation as probably causative. This case illustrates the importance of family screening in interpreting next-generation sequencing (NGS) data, as in silico analysis alone can be misleading. Erudite generation of diagnostic possibilities based on a thorough baseline clinical and laboratory work-up remains as important as ever, even as NGS brings about a paradigm shift in the diagnostic work-up of rare haemolytic anaemias.


Influence of cultivar and culture system on nutritional and organoleptic quality of strawberry.
Strawberries are widely appreciated and consumed as a pleasant-tasting fruit either in fresh form or as processed product. Of the many factors which can affect the quality of fruit (sensorial and nutritional), the cultivar is especially important, but it is also affected by crop conditions. The main characteristics related to the fruit quality and nutritional attributes were assessed in several varieties of strawberry grown in soilless and soil culture. The effect of different cultivars and cropping systems on selected quality parameters, were assessed by applying multivariate statistical methods, such as principal component analysis and partial least square discriminant analysis (PLS-DA). Differences among cultivars were observed based on the mineral composition and glucose and fructose concentrations in both cultivation systems. However, no significant differences between cultivars were detected in sourness. Tamar and Camarosa were the sweetest cultivars among those grown in soilless and soil system, respectively. Both varieties also had the highest total sugars/total acids ratio. The comparison between strawberries cultivated in soil and soilless systems also revealed significant differences in the mineral composition, content of sugars and related parameters. Good discrimination was observed between cultivars of conventional crops, whereas no clear separation between cultivars grown in the soilless system was achieved by PLS-DA. PLS-DA also allowed differentiation of samples by type of crop (soilless vs. conventional crop). This information could be useful for selection of growing conditions and high-quality cultivars.


Exosomal microRNAs and long noncoding RNAs: Novel mediators of drug resistance in lung cancer.
Lung cancer therapeutic resistance, especially chemoresistance, is a key issue in the management of this malignancy. Despite the development of novel molecularly targeted drugs to promote therapeutic efficacy, 5-year survival of lung cancer patients is still dismal. Molecular studies through the recent years have fortunately presented multiple genes and signaling pathways, which contribute to lung cancer chemoresistance, providing a better perception of the biology of tumor cells, as well as the molecular mechanisms involved in their resistance to chemotherapeutic agents. Among those mechanisms, transfer of extracellular vesicles, such as exosomes, between cancer cells and the surrounding noncancerous ones is considered as an emerging route. Exosomes can desirably function as signaling vesicles to transmit multiple molecules from normal cells to cancer cells and their microenvironment, or vice versa. Using this ability, exosomes may affect the cancer cells' chemoresistance/chemosensitivity. Recently, noncoding RNAs (esp. microRNAs and long noncoding RNAs), as key molecules transferred by exosomes, have been reported to play a substantial role in the process of drug resistance, through modulation of various proteins and their corresponding genes. Accordingly, the current review principally aims to highlight exosomal micro- and long noncoding RNAs involved in lung cancer chemoresistance. Moreover, major molecular mechanisms, which connect corresponding RNA molecules to drug resistance, will briefly be addressed, for better clarifying of possible roles of exosomal noncoding RNAs in promoting the effectiveness of lung cancer therapy.


Compensatory follicular hypertrophy during the ovarian cycle of the house gecko, Hemidactylus frenatus.
The house gecko ( Hemidactylus frenatus ) exhibits an ovarian cycle that can be divided into early follicular, vitellogenic, and luteal phases. Serial sections through the right ovary of animals in the three phases allowed us to quantify follicular size, condition, and number, as well as germinal bed activity. There are six to eight healthy, growing follicles in each ovary, arranged in a stepwise size hierarchy. This number does not vary among the three phases, even though one follicle becomes atretic and one ovulates during each cycle. Therefore, compensatory follicular hypertrophy occurs, leading to replacement of lost follicles and maintenance of the follicular size hierarchy.


[Evaluation of gastric emptying and gastrointestinal symptoms in dyspeptic patients before and after hydropinic therapy].
Dispepsy is one of the most diffuse syndromes in general population. The high number of subjects affected from this pathology and the very annoying symptomatology does so as that the pharmaceutical costs of antacids and of prokinetics are very high. Aim of the study is to assess if a hydropinic therapy is able to facilitate digestive processes of the dispeptic patients accelerating gastric emptying. The 30 recruited subjects, 20 patients and 10 healthy volunteers, have answered to test about their symptoms and have executed a 13C octanoic acid breath test in order to estimate the gastric emptying to a basal time, and 30 days after supplementation of mineral water, 1.5 liters/day, for 21 days. At the end of the study, both the time of gastric emptying and the gastrointestinal symptoms improved after the hydropinic therapy, demonstrating that a supplementazione with mineral water can induce a benefit in the dispeptics subjects.


Observational learning of instrumental discriminations in the rat: the role of demonstrator type.
In two experiments, observer rats saw a pretrained demonstrator rat of either the same or a different strain engaging in a discrimination task in which the presentation of a discriminative stimulus indicated whether performing a particular response (pulling a chain) would be reinforced. In both experiments an effect of demonstrator familiarity was found: Observers of a demonstrator from a different strain behaved in a manner that was consistent with the demonstrator whereas observers of a demonstrator from the same strain did not. These results suggest that an effect akin to latent inhibition operates in the social domain: Familiarity with the demonstrator retards the readiness with which observational learning proceeds.


Analytic optimization of Plasmodium falciparum marker gene haplotype recovery from amplicon deep sequencing of complex mixtures.
Molecular epidemiologic studies of malaria parasites commonly employ amplicon deep sequencing (AmpSeq) of marker genes derived from dried blood spots (DBS) to answer public health questions related to topics such as transmission and drug resistance. As these methods are increasingly employed to inform direct public health action, it is important to rigorously evaluate the risk of false positive and false negative haplotypes derived from clinically-relevant sample types. We performed a control experiment evaluating haplotype recovery from AmpSeq of 5 marker genes (ama1, csp, msp7, sera2, and trap) from DBS containing mixtures of DNA from 1 to 10 known P. falciparum reference strains across 3 parasite densities in triplicate (n=270 samples). While false positive haplotypes were present across all parasite densities and mixtures, we optimized censoring criteria to remove 83% (148/179) of false positives while removing only 8% (67/859) of true positives. Post-censoring, the median pairwise Jaccard distance between replicates was 0.83. We failed to recover 35% (477/1365) of haplotypes expected to be present in the sample. Haplotypes were more likely to be missed in low-density samples with <1.5 genomes/μL (OR: 3.88, CI: 1.82-8.27, vs. high-density samples with ≥75 genomes/μL) and in samples with lower read depth (OR per 10,000 reads: 0.61, CI: 0.54-0.69). Furthermore, minority haplotypes within a sample were more likely to be missed than dominant haplotypes (OR per 0.01 increase in proportion: 0.96, CI: 0.96-0.97). Finally, in clinical samples the percent concordance across markers for multiplicity of infection ranged from 40%-80%. Taken together, our observations indicate that, with sufficient read depth, haplotypes can be successfully recovered from DBS while limiting the false positive rate.


[Breast tuberculosis: case report and literature review].
The authors present a case of tuberculosis of the breast as the AIDS--defining illness in a male adult patient, with CD4 counts still moderately low (475 cells/mm3) and without evidence of tuberculosis in any other organ. Literature review emphasizes the rarity of the isolated infection of the breast, especially in males, with no increase in the number of cases of this infection site even in patients with AIDS.


General practitioners' perceived barriers to smoking cessation-results from four Nordic countries.
Studies indicate that doctors may be reluctant to discuss smoking with their patients. Knowledge about how this problem might be solved is limited. The aim of this study was to identify barriers for engaging in tobacco prevention in general practice. An anonymous questionnaire was mailed to 3,167 randomly selected general practitioners (GPs) in Sweden Norway, Finland, and Iceland. The questionnaire identified practice and barriers for the discussion of smoking and smoking cessation with patients and the GPs' own smoking behaviour. The overall response rate was 67%. A large majority of the GPs perceived the discussion of patients' smoking habits as part of their job. However, most GPs did not enquire about smoking unless the patient had smoking-related symptoms and few engaged in smoking cessation support. Many GPs felt that smoking cessation support was too time consuming and that the time spent was not effective because few patients quit. Shortage of smoking cessation experts to whom patients could be referred was the most common barrier for systematic involvement in smoking cessation support. On average, GPs had spent approximately one hour during the previous month on smoking cessation support. The main barriers identified in this study indicate that smoking cessation expertise needs to be more accessible. One alternative is to establish telephone help-lines (Quit-lines) that are easily available for all and could serve as a back-up for the GPs. Another more costly approach is to develop smoking cessation expertise at major clinics. A combination of both is probably the best solution.


Clinical benefits of an immune-enhancing diet for early postinjury enteral feeding.
In this multicenter prospective controlled trial, 98 evaluable patients sustaining major torso trauma were randomized to receive early enteral nutrition with a new "immune-enhancing" diet (study: n = 51) or a standard stress enteral formula (control: n = 47). At baseline, both groups had comparable demographics and Injury Severity Scores. After 7 days of feeding, the groups had equivalent increases in serum total protein, albumin, and transferrin concentrations. Patients receiving the "immune-enhancing" diet, however, experienced significantly greater increases in total lymphocyte (p = 0.014), T lymphocyte (p = 0.04), and T-helper (p = 0.004) cell numbers. Additionally, these patients had significantly fewer intraabdominal abscesses (study, 0% vs. control, 11%; p = 0.023) and significantly less multiple organ failure (study, 0% vs. control, 11%; p = 0.023). In conclusion, this multicenter trial suggests this "immune-enhancing" enteral diet offers clinical benefits in stressed surgical patients.


Targeted vertebral fracture assessment for optimizing fracture prevention in Canada.
Vertebral fracture assessment (VFA) provides incremental information in identifying women and men aged 70 years and older qualifying for anti-osteoporosis treatment compared with FRAX® major osteoporotic fracture (MOF) probability computed with bone mineral density (BMD). This analysis was performed to inform appropriate use of VFA testing as part of Osteoporosis Canada's Guidelines Update, assuming vertebral fracture is an indication for pharmacotherapy in women and men. Women and men aged 70 years and older without previous high-risk fracture (i.e., hip, spine, or multiple fractures) were identified in a BMD registry for the province of Manitoba, Canada. MOF probability with BMD was computed using the Canadian FRAX® tool. VFA was performed in those with a minimum BMD T-score of -1.5 or lower. The study population consisted of 7289 women (mean age 76.7 ± 5.6 years) and 1323 men (77.9 ± 5.8 years). More women than men qualified for VFA testing (48.7% vs 25.4%, respectively, p < 0.001). Among those undergoing VFA, a vertebral fracture was more commonly detected among men than women (22.9% vs 13.3%, p < 0.001), and vertebral fracture prevalence increased with lower BMD T-score (both p trend <0.001). The number needed to screen with VFA to detect a vertebral fracture was 8 for women and 4 for men. MOF probability was substantially lower in men than in women, and fewer men than women (3.3% vs 20.2%, p < 0.001) met a treatment threshold of MOF 20% or greater. In those with MOF probability <20%, VFA identified an incremental 5.4% of men and 3.4% of women for treatment based upon vertebral fracture. The number needed to screen to identify a previously unappreciated vertebral fracture is low and further improves with lower BMD T-score. VFA identified more men as qualifying for treatment than MOF probability. In women, treatment qualification was predominantly from MOF probability.


Malnutrition, Airflow Limitation and Severe Emphysema are Risks for Exacerbation of Chronic Obstructive Pulmonary Disease in Japanese Subjects: A Retrospective Single-Center Study.
Different characteristics of patients with chronic obstructive pulmonary disease (COPD) between Western and Japanese populations have been reported. Risk factors for COPD exacerbation have been reported in Western countries but have not been studied in Japan. We retrospectively examined risk factors for COPD exacerbation. A total of 156 Japanese patients were enrolled, and the records of 136 patients were analyzed. In the exacerbation group (n=60), body mass index, forced vital capacity (FVC), forced expiratory volume in one second (FEV1), the FEV1/FVC ratio (FEV1/FVC), the percent predicted values of FEV1 (%FEV1), and serum total protein (TP) and albumin concentrations were lower, and age, mortality rate, frequency of common cold and pneumonia, COPD severity rankings, modified Medical Research Council (mMRC) dyspnea score, and proportions of patients with severe emphysema (>50% of low attenuation area) and receiving long-term oxygen therapy were higher than those in the nonexacerbation group (n=76). However, the proportion of patients with a greater number of eosinophils (≥200/μL and/or ≥2%) and the exhaled nitric oxide concentration did not differ between the two groups. In the univariate analysis, the risk factors for exacerbation were age; long-term oxygen therapy; low FVC, FEV1, FEV1/FVC and %FEV1; high COPD severity ranking and mMRC score; severe emphysema; hypoproteinemia (<6.5 g/dL); hypoalbuminemia (<3.5 g/dL); leukocytosis; lymphocytopenia; and anemia. In the multivariate analysis, the risk factors were hypoalbuminemia, hypoproteinemia and low FEV1. Additionally, in patients in the exacerbation-induced mortality subgroup, age, exacerbation frequency, mMRC score and the proportion of patients with lymphocytopenia were higher, and FVC, %FVC, FEV1, serum TP concentration and the lymphocyte number were lower than those in the exacerbation survival subgroup. Malnutrition, airflow limitation and severe emphysema were risks for exacerbation and mortality associated with infection in Japanese patients with COPD.


Histochemical localization of renal trehalase: demonstration of a tubular site.
Trehalase activity has been localized histochemically within the cortical tubules of the human, rabbit, and mouse kidneys. The specific localization of the enzyme supports the hypothesis that trehalase, in concert with a series of other enzymes which synthesize trehalose from glucose, functions in a mechanism for the reabsorption of glucose from the glomerular filtrate.


The social anxiety disorder spectrum.
Current diagnostic classifications emphasize the categorical nature of disorders such as social anxiety disorder. Nevertheless, phenomenological and psychobiological data have led to the hypothesis that social anxiety symptoms and disorders lie on various dimensions. A MEDLINE search (1966-2003) for relevant articles on the social anxiety disorder spectrum was undertaken using the terms shyness, behavioral inhibition, social phobia, social anxiety disorder, avoidant personality, dimension, and spectrum to aim at objective coverage, but references for this article were chosen more subjectively to illustrate data and themes in description, pathogenesis, pharmacotherapy, and psychotherapy of the social anxiety disorder spectrum. Several different approaches to delineating a social anxiety disorder spectrum of conditions have been described. These include (1) a spectrum of social fear and avoidance, (2) a spectrum of body-focused concerns, (3) a spectrum of anxiety disorders and affective dysfunction, and (4) a spectrum of social deficits. Social anxiety symptoms and disorders do appear to lie on a number of different dimensions. Nevertheless, additional research is necessary to determine the clinical utility of assessing these different dimensions and to investigate their underlying psychobiology.


Analysis of physiological data from long- term physical exercise: A basis for improving the health of rural residents of Korea.
Analysis of the change pattern of a user's physiological signals collected over a long time and user health information prediction technology based on personal history data can provide the user with accurate health information. In this study, we analyzed the change pattern of health information that was altered by performing personal training (PT) at the beginning of the study and subsequently quitting exercise and only performing activities of daily living (ADL). The subject performed PT for 75 days, and then consistently performed relatively simple ADL, such as standing, sitting, and walking, for 325 days that followed. After 400 days, the health information was analyzed through the change patterns of various physiological signals. Personal exercise information and heart rate data were collected through a smart watch (Apple watch Nike+, Apple Inc.) and the obesity parameters (i.e. information on the weight, body fat fate, and body muscle rate) were measured using a smart scale (PICOOC S1 Pro, EasySolar). We found that the weight and body fat rate linearly decreased and the body muscle rate increased for the first 75 days when hard training was performed whereas they repeatedly increased or decreased when only ADL were performed. As the daily exercise distance increased, weight and body fat rate tended to decrease while body muscle rate tended to increase. There was no significant change in the weight, body fat rate, and body muscle rate while daily activities were performed, but continuous exercise is expected to improve cardiac function by increasing the cardiac output of the heart. We expected that the simple physiological data measured with smart watches and smart scales can be used for the health management of the elderly living in rural areas in the future.


Toxicity and effects of mosquito larvicides methoprene and surface film (Agnique® MMF) on the development and fecundity of the tadpole shrimp Triops newberryi (Packard) (Notostraca: Triopsidae).
We investigated the interactions of tadpole shrimp, a mosquito biological control agent, with the juvenile hormone analog methoprene and a monomolecular surface film. In laboratory assays, the tadpole shrimp (TPS) Triops newberryi (Packard) was able to tolerate high concentrations of methoprene without negative impacts on its growth, longevity, and fecundity when exposed to 1 to 10 mg/liter, or 90-900 fold, of the IE(90) levels against a laboratory colony of Culex quinquefasciatus Say. The same held true in field trials when the habitats were treated with Altosid(®) Liquid Larvicide (Altosid(®) LL, 5% methoprene) at 0.3-1.2 liters/ha. or 1-4 fold of the label rates for mosquito control. However, some significant impacts on the TPS occurred when they were exposed to Agnique(®) Monomolecular Film (Agnique(®) MMF) at the label rates for mosquito control ranging from 1.89-9.45 liters/ha. under laboratory and field conditions. To avoid the negative impact of Agnique MMF on tadpole shrimp, it appears that 1.89 liters/ha. would be the maximum rate when Agnique MMF is used to control mosquitoes in the habitats where the TPS is employed as a biological control agent, or prevailing in the aquatic habitats with potential for suppressing mosquito larval populations.


Evaluating the impact of private land conservation with synthetic control design.
Programs to protect biodiversity on private land are increasingly being used worldwide. To understand the efficacy of such programs, it is important to determine their impact: the difference between the program's outcome and what would have happened without the program. Typically, these programs are evaluated by estimating the average program-level impact, which readily allows comparisons between programs or regions, but masks important heterogeneity in impact across the individual conservation interventions. We used synthetic control design, statistical matching, and time-series data to estimate the impact of individual protected areas over time and combined individual-level impacts to estimate program-level impact with a meta-analytic approach. We applied the method to private protected areas governed by conservation covenants (legally binding on-title agreements to protect biodiversity) in the Goldfields region of Victoria, Australia using woody vegetation cover as our outcome variable. We compared our results with traditional approaches to estimating program-level impact based on a subset of covenants that were the same age. Our results showed an overall program-level impact of a 0.3-0.8% increase in woody vegetation cover per year. However, there was significant heterogeneity in the temporal pattern of impact for individual covenants, ranging from -4 to +7% change in woody vegetation cover per year. Results of our approach were consistent with results based on traditional approaches to estimating program-level impact. Our study provides a transparent and robust workflow to estimate individual and program-level impacts of private protected areas.


Recombinant human erythropoietin in severe anaemia: issues of dosing and duration.
The majority of Jehovah's Witnesses refuse blood product transfusion, even when it can be lifesaving. Treatment with recombinant human erythropoietin (RHuEPO) is a valuable adjunct in Jehovah's Witness patients undergoing surgery. A number of additional strategies, including acute normovolaemic haemodilution, intra-operative blood salvage and reinfusion, iron and folate supplementation are also utilized to avoid blood transfusion. Critically ill patients have blunted erythropoietin production and decreased endogenous iron availability. This case report reviews the treatment of anaemia in critically ill Jehovah's Witness patients after surgery and discusses the potential need for higher RHuEPO dosing strategies and longer duration of therapy.


Evaluation of GLUT-1 in the granular cell tumour and congenital granular cell epulis.
The glucose transporter type 1 (GLUT-1) protein is a useful marker for perineurial cells. Because of the possible neuroectodermal histogenesis of the granular cell tumour and congenital granular cell epulis, the aim of this study was to assess the immunoexpression of GLUT-1 protein in granular cell tumour and congenital granular cell epulis to aid in clarifying their histogenesis. The protocol of this study was approved by the Committee of Bioethics in Research at Universidade Federal Minas Gerais. Six cases of granular cell tumour and three cases of congenital granular cell epulis were submitted to immunohistochemistry for GLUT-1 and S-100 using the streptavidin-biotin standard protocol. Five cases of granular cell tumour were located on the tongue and one case on the upper lip. All cases of congenital granular cell epulis were observed in the alveolar ridge of newborns. All lesions evaluated proved to be immunonegative for GLUT-1. S-100 was found to be positive in all granular cell tumours and negative in congenital granular cell epulis. Neither granular cell tumour nor congenital granular cell epulis is directly related to perineurial cells.


Ammonia formation by the reduction of nitrite/nitrate by FeS: ammonia formation under acidic conditions.
One issue for the origin of life under a non-reducing atmosphere is the availability of the reduced nitrogen necessary for amino acids, nucleic acids, etc. One possible source of this nitrogen is the formation of ammonia from the reduction of nitrates and nitrites produced by the shock heating of the atmosphere and subsequent chemistry. Ferrous ions will reduce these species to ammonium, but not under acidic conditions. We wish to report results on the reduction of nitrite and nitrate by another source of iron (II), ferrous sulfide, FeS. FeS reduces nitrite to ammonia at lower pHs than the corresponding reduction by aqueous Fe+ 2. The reduction follows a first order decay, in nitrite concentration, with a half-life of about 150 min (room temperature, CO2, pH 6.25). The highest product yield of ammonia measured was 53%. Under CO2, the product yield decreases from pH 5.0 to pH 6.9. The increasing concentration of bicarbonate, at higher pH, interferes with the reaction. Comparing experiments under N2 CO2 shows the interference of bicarbonate. The reaction proceeds well in the presence of such species as chloride, sulfate, and phosphate, though the yield drops significantly with phosphate. FeS also reduces nitrate and, unlike with Fe+ 2, the reduction shows more reproducibility. Again, the product yield decreases with increasing pH, from 7% at pH 4.7 to 0% at pH 6.9. It appears that nitrate is much more sensitive to the presence of added species, perhaps not competing as well for binding sites on the FeS surface. This may be the cause of the lack of reproducibility of nitrate reduction by Fe+ 2 (which also can be sensitive to binding by certain species).


Vibrational Coherence Controls Molecular Fragmentation: Ultrafast Photodynamics of the [Ag2Cl]+ Scaffold.
The recently introduced pump-probe fragmentation action spectroscopy reveals a unique observation of excited state vibrational coherence (430-460 fs) in the isolated metal complex [Ag2(Cl)(dcpm)2)]+ (dcpm = bis(dicyclohexylphosphino)methane) containing the [Ag2Cl]+ scaffold. After photoexcitation by an 1XMCT transition (260 nm) in an ion trap, an unexpected correlation between specific fragment ions (loss of HCl/Cl- vs loss of dcpm) and the phase of the wave packet is probed (1150 nm). Based on ab initio calculations, we assign the primary electronically excited state and ascribe the observed coherences (72-78 cm-1) to contain predominantly Ag-Ag stretch character. We propose specific probe absorption and vibronic coupling at the classical turning points to switch remarkably early on between the different fragmentation pathways. The overall excited state dynamics are fitted to a multiexponential decay with time constants: 0.2-0.4/3-4/19-26/104-161 ps. These findings open new perspectives for further dynamics investigations and possible applications in photocatalysis.


[Herpes gestationis. Apropos of 2 cases].
Herpes gestationis is an autoimmune disorder specific of pregnancy. The authors report two cases of this condition with distinctive clinical and immunological features. Both the pathogenesis and the nosologic connections between Herpes gestationis and Bullous pemphigoid are reviewed and discussed.


4-Hydroxylation of debrisoquine by human CYP1A1 and its inhibition by quinidine and quinine.
A panel of 15 recombinant cytochromes P450 expressed in human B-lymphoblastoid cells was used to study debrisoquine 4-hydroxylation. Both CYP2D6 and CYP1A1 carried out the reaction. The apparent K(m) (micromolar) and V(max) (picomoles per minute per picomole of P450) for CYP2D6 were 12.1 and 18.2 and for CYP1A1 were 23.1 and 15.2, respectively. CYP1A1 debrisoquine 4-hydroxylase was inhibited by the CYP1A1 inhibitor alpha-naphthoflavone and the CYP1A1 substrate 7-ethoxyresorufin. Additionally and surprisingly, this reaction was also inhibited by quinidine and quinine, with respective IC(50) values of 1.38 +/- 0.10 and 3.31 +/- 0.14 microM, compared with those for CYP2D6 debrisoquine 4-hydroxylase of 0.018 +/- 0.05 and 3.75 +/- 2.07 microM, respectively. Anti-CYP1A1 monoclonal antibody (mAb) 1-7-1 abolished CYP1A1 debrisoquine hydroxylase and anti-CYP2D6 mAb 50-1-3 eradicated CYP2D6 debrisoquine 4-hydroxylase. Three further CYP2D6-specific reactions were tested: dextromethorphan O-demethylation, bufuralol 1'-hydroxylation, and sparteine dehydrogenation. The CYP2D6 specificity, judged by the CYP2D6/CYP1A1 activity ratios was 18.5, 7.0, 6.0, and 1.6 for dextromethorphan, bufuralol, sparteine, and debrisoquine, respectively. Thus, debrisoquine is not a specific CYP2D6 substrate and quinidine is not a specific CYP2D6 inhibitor. These findings have significant implications for the conduct of in vitro drug metabolism inhibition studies and underscore the fallacy of "specific chemical inhibitors" of a supergene family of enzymes that have overlapping substrate specificities. The use of highly specific mAbs in such studies is mandated. It is unclear as yet whether these findings have implications for the relationship between CYP2D6 genotype and in vivo debrisoquine 4-hydroxylase activity.


A review of self-rated generic quality of life instruments used among older patients receiving home care nursing.
In the last two decades, quality of life and health-related quality of life have become commonly used outcome measures in the large number of studies evaluating healthcare and home care nursing. The objective of this systematic search and review was to evaluate studies that include self-rated generic quality of life instrument used among elderly patients receiving home care nursing. Searches were conducted in Medline, Embase, PsycINFO and Cinahl for articles published between January 2005 and June 2016, with 17 studies in eight countries meeting the inclusion criteria and assessed for quality. Overall, the review shows great variations in the included studies regarding characteristics of the participants and place of origin, the generic quality of life instruments applied and their dimensions. In this review, we raise the question of whether the generic questionnaires used to measure quality of life do in fact measure what is essential for quality of life in elderly users of home care nursing. The psychological and physical dimensions of quality of life were assessed in almost all included studies, while older-specific dimensions like autonomy, control and sensation were less frequently assessed. There is reason to believe that generic quality of life instruments frequently do not capture the dimensions that are most important for elderly people with health problems in need of home care nursing.


Renal handling of beta-2-microglobulin in renal disorders: with special reference to hepatorenal syndrome.
A study of serum beta 2-microglobulin and urinary beta 2-microglobulin in patients with liver and/or kidney disease was done to determine if such information is of diagnostic help. Serum concentrations and beta 2M/Cr clearance ratios are higher in patients with primary tubular disorders than in those with glomerular diseases, a finding unaltered by hepatic disease. These data suggest either an increased production or decreased tubular degradation of beta 2M, independent of the glomerular filtration rate (GFR), in primary tubular disorders. The marked increase in urinary beta 2-microglobulin that followed insertion of the peritoneal-jugular shunt is evidence that this procedure resulted in improvement of the GFR, in previously underperfused nephrons.


Hybridization and range expansion in tamarisk beetles (Diorhabda spp.) introduced to North America for classical biological control.
With the global rise of human-mediated translocations and invasions, it is critical to understand the genomic consequences of hybridization and mechanisms of range expansion. Conventional wisdom is that high genetic drift and loss of genetic diversity due to repeated founder effects will constrain introduced species. However, reduced genetic variation can be countered by behavioral aspects and admixture with other distinct populations. As planned invasions, classical biological control (biocontrol) agents present important opportunities to understand the mechanisms of establishment and spread in a novel environment. The ability of biocontrol agents to spread and adapt, and their effects on local ecosystems, depends on genomic variation and the consequences of admixture in novel environments. Here, we use a biocontrol system to examine the genome-wide outcomes of introduction, spread, and hybridization in four cryptic species of a biocontrol agent, the tamarisk beetle (Diorhabda carinata, D. carinulata, D. elongata, and D. sublineata), introduced from six localities across Eurasia to control the invasive shrub tamarisk (Tamarix spp.) in western North America. We assembled a de novo draft reference genome and applied RADseq to over 500 individuals across laboratory cultures, the native ranges, and the introduced range. Despite evidence of a substantial genetic bottleneck among D. carinulata in N. America, populations continue to establish and spread, possibly due to aggregation behavior. We found that D. carinata, D. elongata, and D. sublineata hybridize in the field to varying extents, with D. carinata × D. sublineata hybrids being the most abundant. Genetic diversity was greater at sites with hybrids, highlighting potential for increased ability to adapt and expand. Our results demonstrate the complex patterns of genomic variation that can result from introduction of multiple ecotypes or species for biocontrol, and the importance of understanding them to predict and manage the effects of biocontrol agents in novel ecosystems.


Extension of the GROMOS 56a6CARBO/CARBO_R Force Field for Charged, Protonated, and Esterified Uronates.
An extension of the GROMOS 56a6CARBO/CARBO_R force field for hexopyranose-based carbohydrates is presented. The additional parameters describe the conformational properties of uronate residues. The three distinct chemical states of the carboxyl group are considered: deprotonated (negatively charged), protonated (neutral), and esterified (neutral). The parametrization procedure was based on quantum-chemical calculations, and the resulting parameters were tested in the context of (i) flexibility of the pyranose rings under different pH conditions, (ii) conformation of the glycosidic linkage of the (1 → 4)-type for uronates with different chemical states of carboxyl moieties, (iii) conformation of the exocyclic (i.e., carboxylate and lactol) moieties, and (iv) structure of the Ca2+-linked chain-chain complexes of uronates. The presently proposed parameters in combination with the 56a6CARBO/CARBO_R set can be used to describe the naturally occurring polyuronates, composed either of homogeneous (e.g., glucuronans) or heterogeneous (e.g., pectins, alginates) segments. The results of simulations relying on the new set of parameters indicate that the conformation of glycosidic linkage is nearly unaffected by the chemical state of the carboxyl group, in contrary to the ring conformational equilibria. The calculations for the poly(α-d-galacturonate)-Ca2+ and poly(α-l-guluronate)-Ca2+ complexes show that both parallel and anitiparallel arrangements of uronate chains are possible but differ in several structural aspects.


[Clinicopathologic features and treatment of primary splenic tumors].
To investigate the clinical pathological characteristics and treatment of primary splenic tumor. The clinical data of 43 patients with primary splenic rumors, 23 males and 20 females, aged 44.7 (19 - 66), treated in the Cancer Hospital, Chinese Academy of Medical Science from Feb 1972 through Mar 2006 were analyzed. Of the 43 cases, 21 cases (48.8%) were found in physical examination. 42 cases underwent splenectomy and 1 case underwent rumor biopsy. Sixteen cases were with benign splenic tumors, including 15 cases of hemangioma and 1 case of lymphangioma. Of the 24 malignant cases, 16 suffered from splenic lymphoma and 8 from angiosarcoma. Most lymphoma cases survived and the mean three year surviving rate was 88.7%. The mean surviving time of angiosarcoma was only 10.4 months. Primary splenic tumors lack specificity; B-ultrasonography and CT are primary examination methods. Surgery is an effective method in treatment of primary splenic tumors.


Getting it right? Lessons from the interwar years on pulmonary tuberculosis control in England and Wales.
This paper examines morbidity and mortality patterns in interwar England and Wales, using previously under-explored primary archival source materials. These materials help us understand not only what local authorities could and did do, but also the reasons for the marked variations in the ability of different authorities to manage the problem. We identify where and why there were problems and also how and why some authorities were more successful than others in dealing with the disease. Wealth was not an issue. We find a combination of pro-active preventative measures was significant.