Enzyme assays for confocal single molecule spectroscopy.
During the last years confocal techniques have become increasingly popular for probing biological enzymatic reactions. In this paper we will summarize some of these methods, mainly focusing on measurement techniques suitable for analysis of freely diffusing molecules, where either the substrates or the enzymes are fluorescently labeled. The different approaches are classified according to their basic principles and algorithms. Several examples of enzymatic studies involving correlation strategies for data processing, like auto- and cross correlation analysis, will be presented. In addition, other evaluation schemes like coincidence analysis and fluorescence intensity distribution analysis are introduced and discussed. With respect to assay development, the fluorescence energy transfer principle is addressed as far as it is has been applied for investigating biocatalysis in solution. Finally, one part of this review addresses the aspects of bioconjugation and the basic requirements for proper labeling dyes in order to be compatible with single molecule fluorescent spectroscopy.


HealthCare-Related Quality of Life and Lived Existential Experiences among Young Adults Diagnosed with Cancer: A Mixed-Method Study.
As cancer is a noncommunicable disease and it is a major global burden in terms of finances. It is also affecting quality of life of a person completely. The aim of the present study was to identify the effect of cancer on quality of life of an individual as a whole. The present study was triangulation study, and we examined 30 young adult cancer patients of age group 20-44 years who were admitted in different oncological units of our hospital in 2018. We included all their case datasheets for identifying clinical variables. Data collection tools used were the European organization for research and treatment for cancer quality of life questionnaire (version 3-Hindi). Qualitative data were collected using open-ended questionnaire regarding young adult cancer patient's experiences, feelings, and difficulties faced during cancer diagnosis and treatment. Results concluded that young adult cancer patient's global health status score were average. Their physical function as well as social function score depicted that both were affected significantly, whereas cognitive functions were not affected anymore. Most commonly symptoms faced by young adult's cancer patients were pain, insomnia, fatigue, nausea, vomiting, and appetite loss. Financial burden was major burden faced by patient as well as caregiver during the diagnosis and treatment of cancer. From qualitative data of the study, it was concluded that when patient were first told about cancer diagnosis first, they feel sad. Their primary relatives were first informed about their diagnosis. Most of patient's cancer were diagnosed in first stage. Cancer had affected patient's personal as well as social life completely. Nobody helps them during the diagnosis and treatment of their disease. Majority of cancer treatment options were chemotherapy, radiation therapy, and surgery and majority of them were getting chemotherapy from AIIMS, Rishikesh. The most common difficulty the patient's faced during the diagnosis of cancer was financial. Patient's opinion for cancer and its treatment were that everybody who had any symptoms of cancer they should immediately come to hospital for treatment. When we asked them about effect of cancer as a whole their responses were disturbed family role, disturbed attachment with family and friends, disturbed social role, financial burden as well as disturbed education, respectively. From this study, we concluded that quality of life of young adult cancer patients were affected badly in terms of physical, social, symptomatically, and financially. It may also help to plan ahead by patients as well as health professionals to improve the patient's quality of life.


Portrait: coincidences, convergences and opportunities.
Born in 1944, I grew up in a world in which polio was both a gripping fear and real threat. Then in a matter of a few years-polio was eradicated by a vaccine developed by Jonas Salk. Later I learned that Salk's efforts were built on pioneering work of many others, including John Enders, Thomas Weller and Frederick Robbins (Nobelists, 1954), and David Bodian, who pioneered studies of polio pathogenesis and immunity. Bodian became my teacher in medical school, and Robbins became a colleague. Later, Salk, Robbins and I shared a platform at an infectious diseases symposium, and I was privileged to speak at Robbins' retirement. But that gets ahead of my story. In January 1956, at age 12 y, I received my first of dose of the "Salk" vaccine. Other kids had pictures of athletes in their rooms; I had a picture of Jonas Salk.


Casual blood pressures and their possible relation to age, body weight, Quetelet's index, serum cholesterol, percentage of body fat and mid-arm muscle circumference in three groups of northern Nigerian residents.
Blood pressures were determined for rural outpatients, soldiers and university students. There was no consistent change of systolic blood pressure with age until the sixth decade but even here, the rise could be due to the inclusion of a relatively high number of hypertensive subjects in the sample mean. Diastolic blood pressures show a steady rise with age consistent with the decreased elasticity of arteries with age. Diastolic pressures are remarkably low and probably reflect a general vasodilation necessitated by the hot day-time temperatures of this environment to facilitate heat loss and maintain body temperature. Dietary and psychological influences may also be involved. Pulse pressures are predictably high and decrease with age. Hypertension was observed in many groups although totally absent in some. Body weight significantly correlates with systolic and diastolic pressures in 13-19-year old adolescents probably because during this period of rapid growth blood pressure changes parallel changes in body build. In most other groups blood pressures show no consistent relationship with either body weight, Quetelet's index, mid-arm muscle circumference, serum cholesterol or percentage of body fat.


Treatment of Castleman's disease.
Castleman's disease (CD) was first described in 1954 and further defined in 1956 by Castleman. Since then much has been learned about the heterogeneity of this condition. Subsequently, three pathologic classifications have been developed (hyaline vascular variant, plasma cell variant, and mixed variant) and two clinical classifications (unicentric [unifocal or localized] and multicentric [multifocal or generalized]). The pathology found with the unicentric presentation is most commonly that of the HV variant. It responds well to surgical resection and is associated with a benign course. The multicentric presentation is rarely composed of lymph nodes with HV pathology, but rather with the plasma cell or mixed pathology. This presentation requires systemic therapy and prognosis is guarded. Associated systemic symptoms are common. There is an increased incidence of CD in patients with HIV. The human herpes virus-8 is associated with nearly all of the HIV-associated CD cases and nearly 50% of non-HIV cases. Interleukin (IL)-6 has also been shown to play a significant role in the pathogenesis of the disease. Paraneoplastic and autoimmune entities are not uncommon in the disorder. Variable benefit has been achieved with single agent chemotherapy, combination chemotherapy, interferon (IFN)-alpha, rituximab, anti-IL-6 receptor antibodies, and thalidomide. Patients with CD are at increased risk for developing frank malignant lymphoma.


Scaling and mechanics of carnivoran footpads reveal the principles of footpad design.
In most mammals, footpads are what first strike ground with each stride. Their mechanical properties therefore inevitably affect functioning of the legs; yet interspecific studies of the scaling of locomotor mechanics have all but neglected the feet and their soft tissues. Here we determine how contact area and stiffness of footpads in digitigrade carnivorans scale with body mass in order to show how footpads' mechanical properties and size covary to maintain their functional integrity. As body mass increases across several orders of magnitude, we find the following: (i) foot contact area does not keep pace with increasing body mass; therefore pressure increases, placing footpad tissue of larger animals potentially at greater risk of damage; (ii) but stiffness of the pads also increases, so the tissues of larger animals must experience less strain; and (iii) total energy stored in hindpads increases slightly more than that in the forepads, allowing additional elastic energy to be returned for greater propulsive efficiency. Moreover, pad stiffness appears to be tuned across the size range to maintain loading regimes in the limbs that are favourable for long-bone remodelling. Thus, the structural properties of footpads, unlike other biological support-structures, scale interspecifically through changes in both geometry and material properties, rather than geometric proportions alone, and do so with consequences for both maintenance and operation of other components of the locomotor system.


Microsurgical Breast Reconstruction: Maximizing Success.
Breast reconstruction is becoming increasingly recognized as a fundamental component in comprehensive breast cancer treatment. The primary goal for any reconstruction is to safely restore a natural appearing breast. When it comes to achieving the elements of size, shape, symmetry, and softness, the use of autologous tissue has many advantages. The approach to autologous breast reconstruction has changed substantially over the years as microsurgical free tissue transplants become more routine and accessible. While a variety of flap donor sites exist, careful flap selection based on surgical history and the availability of donor tissue is critical in achieving reliable results. This article reviews the clinical considerations in patient evaluation, donor site selection, and surgical approach taken at the Buncke Clinic.


Study on the Development of a New Device with Dual Cameras for Evaluating Expiratory Nasal Flow.
Use of the Glatzel mirror for measuring expiratory nasal flow in preschool children has the disadvantage of vagueness, and the mirror may induce fear and inhibition of interest in those children. In response to these limitations, we developed a new device with dual cameras for measuring expiratory nasal flow in 2 to 6 year old children. The aim of this study is to compare the Glatzel mirror and the new device, in terms of accurate assessment of expiratory nasal flow, children's feelings, and correlation to each child's profile. This study evaluated 20 cleft lip and palate patients and 21 healthy children aged between 2 and 6 (under 7) years. After consent was granted, a 4-week screening period was undertaken followed by inspection at weeks 8, 16, 24, and 32. Each inspection was conducted while the children were asked to pronounce various sounds and comprised three stages: i) use of the Glatzel mirror, ii) subjective visual assessment using the new device, and iii) image recording by dual cameras of the new device. Questionnaires for the new device were administered at the initial and final inspections. To contrast the results between the Glatzel mirror and the new device, the numbers that indicated values of subjective visual assessment and camera assessment greater than the assessment values of the Glatzel mirror were compared. For measuring the children's responses to the new device compared with those to the Glatzel mirror, the answers to the questionnaires were compared. For the comparison of the children's profiles (age and sex) and feelings, the numbers of subjects who could use the new device were measured. The camera assessment of the new device indicated significantly greater values than that of the Glatzel mirror (P < 0.05). The feelings of the subjects to the new device mostly improved as the study progressed. Subjects aged 3 years and older were generally able to use the new device from the initial inspection. For both sexes, as the inspection progressed, the number occasions of successful use increased. This study demonstrated the superiority of the new device with dual cameras to the Glatzel mirror in terms of functionality and attitude of children.


The "forgotten" modified lipoprotein subspecies.
Insights from preclinical and clinical studies have attempted to highlight the importance of modified lipoprotein particles in the pathogenesis of cardiovascular diseases (CVD). However, evidence is not conclusive. Since there is a relative dearth of clinical research in collecting useful information from traditional advanced lipoproteins testing, this present editorial introduces the aim of a special issue on modified lipoproteins as potential biomarkers for CVD. This issue aims at gathering a selection of insightful articles that address major challenges related to potential clinical use of modified lipoproteins as new CVD biomarkers. The editors seek to promote better mobilization of lipoproteins measurement for the pursuit of sustainable CVD clinical outcome and development of potential biomarkers. Knowledge and progress in this particular field will certainly help answering questions about clinical relevance of circulating modified lipoprotein subspecies and their potential use for better patient care and disease prevention. We hope that, when taken together, the focus on modified lipoproteins will stimulate new vision and reveal study key aspects for better clinical data outcome and more effective therapeutic strategies.


Linking Macroinvertebrates and Physicochemical Parameters for Water Quality Assessment in the Lower Basin of the Volta River in Ghana.
The health of the lower basin of the Volta River in Ghana was evaluated in January-February and May-June 2016 using physicochemical parameters and benthic macroinvertebrates sampled at 10 locations. Selected environmental variables were compared to accepted environmental water quality standard values where applicable. Principal component analysis (PCA) and redundancy analysis (RDA) were used to analyse the association between the benthic macroinvertebrates distribution and physicochemical variables. Pesticide concentrations were generally below the limit of detection 0.01 and 0.005 µg/L for organophosphate/synthetic pyrethroid and organochlorines respectively. Nutrient levels were also generally low; however, significant differences existed between the values of physicochemical parameters at the different sampling sites and seasons (Monte Carlo permutation test; p = 0.002), as well as between the abundance of macroinvertebrates at the different sites and seasons (p = 0.002). The environmental variables dissolved oxygen (DO), phosphate, pH, substratum (p < 0.05), turbidity, conductivity, total dissolved solids, total solids and nitrate (0.05 < p < 0.10) significantly explained the variation in macroinvertebrate composition between sampling stations in the Volta River. Polypedilum fuscipenne, was positively correlated with turbidity and DO concentrations; Physa sp., Centroptilum sp., Centroptiloides sp., Phaon iridipennis and juvenile fish were positively correlated with nitrate concentration and pH and negatively correlated with turbidity and DO. Polluted sites were dominated by the snail Lymnaea glabra. This demonstrates that physicochemical parameters and macroinvertebrates could be applied to describe the water quality and improve the biomonitoring for water resources management and the environmental protection in the Lower Volta River.


The potential role of gene duplications in the evolution of imprinting mechanisms.
Using the completed genomic sequences of mouse and human we performed a comparative analyses of imprinted genes and gene clusters. For many imprinted genes we could detect imprinted as well as non-imprinted paralogues. The inter- and intrachromosomal similarities between paralogues and their linkage to imprinting clusters suggests that imprinted genes were dispersed throughout the genome by gene duplications as well as translocation and transposition events. Our findings indicate that imprinting clusters may have been linked together on one (or a few) ancestral pre-imprinted chromosome(s), arguing for a common mechanistic origin of imprinting control. Imprinting may originally have evolved on a simple basis of dosage compensation required for some duplicated genes (chromosomes) followed by selection of sex-biased expression control.


Computational study of optical force between two nanodistant plasmonic submicrowires.
In this paper, the optical force between two circular plasmonic wires of submicrometer diameter (0.3 μm) with nanometer surface-to-surface distances (3-30 nm) interacting with radiation of a complex point source (λ≈0.2 μm) is numerically studied. Calculations (which are based on the Müller integral equations and the Maxwell stress tensor) show that an attractive optical force with a number of distinct peaks is created in distances 3-10 nm. However, for plasmonic-dielectric and plasmonic-reflector double-wires, the optical force has no such peaks. Comparisons reveal that the peaks are originated from the excitation of coupled surface plasmon polaritons in the gap region between the plasmonic wires.


Force Plate with Simple Mechanical Springs and Separated Noncontact Sensor Elements.
This paper reports on a force plate (FP) using mechanical springs and noncontact distance sensors. The ground reaction force (GRF) is one of the factors for clarify biomechanics, and FPs are widely used to measure it. The sensor elements of conventional FPs are mainly strain gauges. Thus, the mechanical properties of FP depend on the sensor element performance. If the FP performance must change, we must redesign the FP, including changing the sensor elements. Here, we proposed an FP that uses a measuring principle based on simple springs and noncontact sensors. The shape and performance of the proposed FP are expected to change easily. As a prototype device, we designed and fabricated an FP installed with 12 springs and four sensors for human walking. A planar coil and magnet were used as the sensor elements, and the sensor output was proportional to the vertical and horizontal displacements. The FP resonance frequency was 123 Hz, which was larger than the required specification. The calibration experiments showed that vertical and horizontal forces and moments could be measured independently. The FP's resolutions were 1.9 N and 1.4 N in the anterior-posterior and vertical directions, respectively. Furthermore, the fabricated FP measured GRF similarly to the commercial FP when a human walked on the plate. These results suggest that the proposed method will be helpful for FPs with custom-made requirements.


Agenesis of the internal carotid artery: a family pathology?
The internal carotid artery agenesis is a rare malformation disorder. We report the case of a 12-year-old boy suffering migraine, who had presented an episode featuring amaurosis fugax, spontaneously regressed. CT angiography images show hypoplasia of the left common carotid artery with loss of opacification of the left internal carotid artery consistent to agenesis. Moreover CT scans through the skull base demonstrate absence of left petrous carotid canal and an hypertrophic left middle cerebral artery originating from an aberrant artery arising from the right cavernous carotid. All diagnostic examinations confirmed the presence of the internal carotid artery agenesis, as Lie's type IV. We started an annual follow up that over the next 7 years did not reveal any change in magnetic resonance angiography images.


Ligand-gated ion channel interactions with cytoskeletal and signaling proteins.
In recent years, it has become apparent that ligand-gated ion channels (ionotropic receptors) in the neuronal plasma membrane interact via their cytoplasmic domains with a multitude of intracellular proteins. Different classes of ligand-gated channels associate with distinct sets of intracellular proteins, often through specialized scaffold proteins containing PDZ domains. These specific interactions link the receptor channel to the cortical cytoskeleton and to appropriate signal transduction pathways in the cell. Thus ionotropic receptors are components of extensive protein complexes that are likely involved in the subcellular targeting, cytoskeletal anchoring, and localized clustering of the receptors at specific sites on the neuronal surface. In addition to structural functions, receptor-associated proteins can play important roles as activity modulators or downstream effectors of ligand-gated channels.


Schisandrin B prevents doxorubicin induced cardiac dysfunction by modulation of DNA damage, oxidative stress and inflammation through inhibition of MAPK/p53 signaling.
Doxorubicin (Dox) is a highly effective antineoplastic drug. However, Dox-induced apoptosis in cardiomyocytes leads to irreversible degenerative cardiomyopathy, which limits Dox clinical application. Schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, has been shown to protect against oxidative damage in liver, heart and brain tissues in rodents. In current study, we investigated possible protective effects of Sch B against Dox-induced cardiomyopathy in mice. Mice received a single injection of Dox (20 mg/kg IP). Five days after Dox administration, left ventricular (LV) performance was significantly depressed and was improved by Sch B treatment. Sch B prevented the Dox-induced increase in lipid peroxidation, nitrotyrosine formation, and metalloproteinase activation in the heart. In addition, the increased expression of phospho-p38 MAPK and phospho-MAPK activated mitogen kinase 2 levels by Dox were significantly suppressed by Sch B treatment. Sch B also attenuated Dox-induced higher expression of LV proinflammatory cytokines, cardiomyocyte DNA damage, myocardial apoptosis, caspase-3 positive cells and phopho-p53 levels in mice. Moreover, LV expression of NADPH oxidase subunits and reactive oxygen species were significantly less in Sch B treatment mice after Dox injection. These findings suggest that Sch B attenuates Dox-induced cardiotoxicity via antioxidative and anti-inflammatory effects.


Vocational support approaches in autism spectrum disorder: a synthesis review of the literature.
This synthesis-based analysis identifies and reviews studies evaluating vocational resources for adults with autism spectrum disorder. It is based on a larger systematic review of intervention studies in autism spectrum disorder, from which a critical interpretive synthesis was conducted on studies related to vocation and autism spectrum disorder. In total, 10 studies were found that examine employment support for youth and adults with autism spectrum disorder. Two domains of vocational intervention in the literature were found: supported employment including community placement and job coaching and media and technology-based augmentative tools. The literature is limited in volume and quality of methodology, yet emerging constructs are promising in introducing the utility of vocational resources, in particular, supported employment in community settings. These vocational approaches are examined, along with representative studies. Recommendations for advancing practice, community capacity, and research are offered.


Measuring change in surgical practice.
We reviewed the work of a single general surgical firm over six years--about 11,500 patient episodes. Although the workload remained approximately constant, a severe reduction in the number of available beds was accompanied by a marked change towards shorter duration of stay. This affected particularly the elective cases. Previous authors, when trying to predict requirement of hospital beds, have accepted that duration of stay and number of beds available are independent variables; this was not what we observed.


Evidence that part of a centromeric DNA region induces pseudohyphal growth in a dimorphic yeast, Candida maltosa.
We observed that a YCp-type vector having the centromeric DNA (CEN) sequence previously isolated from the genome, but not a YRp-type vector lacking the CEN sequence, induced pseudohyphal growth in a dimorphic fungi, Candida maltosa, which had been shown to be closely related to Candida albicans by phylogenetic analysis. Deletion analysis of the CEN sequence revealed that the intact CEN sequence was not required for the induction, but part of it, having partial centromeric activity, was enough for the induction. By screening the gene library of this yeast for the sequences which induced pseudohyphal growth, we isolated three different DNA fragments which also had part of the centromere-like sequence. Partial centromeric activity of these fragments was confirmed by three criteria: low copy number and high stability of the plasmids carrying these fragments and rearrangement at high frequency of the plasmid DNA with one of these fragments plus the CEN sequence. Furthermore, when the GGTAGCG sequence commonly found in one copy in each of these four sequences was mutated in the CEN sequence by site-directed mutagenesis, both partial centromeric activity and pseudohyphal growth-inducing activity of the CEN sequence were lost. These results indicated that part of CEN region with partial centromeric activity induces pseudohyphal growth in C. maltosa. It is suggested that some cellular components which interact with the sequence containing GGTAGCG required for centromeric activity are involved in the regulation of the transition between yeast forms and pseudohyphal forms of the cells.


Carbon budgets for catchments across a managed landscape mosaic in southeast Sweden: contributing to the safety assessment of a nuclear waste repository.
Ecosystem budgets of matter contribute to the assessment of transport and accumulation of bioavailable contaminants in a landscape, since flows of matter and energy ultimately determine the rates at which contaminants will be partitioned in the environment. This study compares ecosystem properties, such as net primary production (NPP), sequestration of matter and fluxes to food sources for humans, which are of potential interest to describe fluxes and accumulation of bioavailable radionuclides in 14 catchments within a larger catchment area in southeast Sweden. The carbon budgets, used as a proxy for organic matter, are mainly based on local estimates of pools and fluxes, which have been distributed across a landscape mosaic of different vegetation types and management regimes using a geographical information system (GIS). NPP varied by a factor close to two (432 - 709 g x Cx m(-2)x y(-1)), while net ecosystem production ranged between -124 and 159 gx C x m(-2) x y (-1) for the different catchments. Carbon sequestration mainly occurred in the vegetation while the soil organic carbon pool was mainly a source of carbon. Large herbivores consumed on average 4.5 % of the above-ground green tissue production. When arable land was present in the catchment, the flux of carbon to humans was highest from crops and, in decreasing order, milk and beef, followed by the flux from hunting and berry/fungus picking. The results can be used to estimate the potential assimilation of radionuclides in vegetation and the potential exposure to humans of bioavailable radionuclides.


Depression of the fast IPSP underlies paired-pulse facilitation in area CA1 of the rat hippocampus.
1. Intracellular recordings from CA1 pyramidal neurons in the rat hippocampal slice have been used to study synaptic transmission after maximal orthodromic stimulation of the Schaffer collateral-commissural fibers. Paired-pulse stimulation was used to investigate how the first (conditioning) stimulation influenced the response to the second (test) stimulation. 2. When the test stimulation was delivered up to approximately 4 s after the conditioning stimulation, the late phase of the excitatory postsynaptic synaptic potential (EPSP) was increased ("late-phase facilitation") whereas the fast (f-) and the slow (s-) inhibitory postsynaptic potentials (IPSPs) were depressed. 3. In terms of appearance and time course, facilitation of the intracellularly recorded EPSP was similar to that of the extracellularly recorded field EPSP in stratum radiatum. 4. The s-IPSP is not involved in facilitation of the EPSP. To show this, we counteracted the s-IPSP either by repolarizing the membrane potential to the resting level or by intracellularly injecting the quaternary lignocaine derivative QX 314. Facilitation of the late phase of the EPSP was unaffected by either procedure. 5. The conditioned response was modified in two ways when the stimulation was delivered at the equilibrium potential for the f-IPSP (Ef-IPSP) and the s-IPSP had been blocked by intracellular injection of QX 314. The amplitude of the EPSP was increased, and the repolarizing phase was delayed with an apparent depolarizing shift of Ef-IPSP. This effect was present at pulse intervals greater than 20 ms and was maximal after 150 ms. Facilitation could be detected at interpulse intervals of up to 4 s. 6. The gamma-aminobutyric acid-B (GABAB) agonist baclofen (1 microM) reduced late-phase facilitation by preferentially increasing the unconditioned response, such that this came to resemble a conditioned response in control medium. 7. The f-IPSP was isolated pharmacologically to investigate its role in the facilitation of the EPSP. This was done by blocking the s-IPSP with QX314 and the EPSP with a mixture of the N-methyl-D-aspartate (NMDA) receptor blocker, 2-amino-5-phosphonovaleric acid (APV, 50 microM), and the non-NMDA receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM). An f-IPSP was then evoked by stimulating the interneurons directly. This potential could be blocked by the GABAA receptor antagonist bicuculline (20 microM), thereby confirming the successful isolation of GABAAergic transmission. 8. With paired-pulse stimulation, the amplitude of the conditioned f-IPSP was depressed.(ABSTRACT TRUNCATED AT 400 WORDS)


Diabetic ketoacidosis: predictors of outcome in a pediatric intensive care unit of a developing country.
To study the outcome and predictors of mortality in children with diabetic ketoacidosis. Retrospective case series. Pediatric intensive care unit of an urban multiple-specialty teaching and referral hospital in north India. Sixty-eight patients with diabetic ketoacidosis treated between 1993 and 2000. Data were retrieved from case records with respect to patients' age; clinical features; osmolality at admission; blood glucose, serum potassium, and arterial pH at admission, 6 hrs, and 24 hrs; complications during the course of hospital stay; treatment; and outcome in terms of survival or death. Survivors and nonsurvivors were compared to determine the predictors of mortality. The mean (sd) age of the study population was 6.9 (3.5) yrs (range, 0.5-12 yrs). Impaired consciousness (n = 45; 66%), rapid breathing (n = 41; 60%), and vomiting (n = 35; 51.4%) were common presenting symptoms. Thirty-two (50%) patients had clinically evident dehydration. Precipitating events identified were new-onset diabetes with sepsis (37%), new-onset diabetes alone (31%), insulin omission (15%), and infection with insulin omission (7%). The mean (sd) blood glucose, osmolality, and pH at admission were 473 (sd 184) mg/dL, 305 (sd 24) mOsm/L, and 7.08 (sd 0.1), respectively. Complications noted during treatment were hypokalemia (n = 28; 41%), hypoglycemia (n = 10; 15%), cerebral edema (n = 9; 13.2%), and pulmonary edema (n = 2; 3%). Nine (13.2%) patient died, with the causes of death being septic shock (n = 4), cerebral edema (n = 2), cerebral edema with pulmonary edema (n = 2), and hypokalemia with ventricular tachycardia (n = 1). Those who died were older, had higher osmolality and severe acidosis at admission, and had persistent hyperglycemia and acidosis at 6-12 hrs. On multiple logistic regression analysis, osmolality at admission was the most significant predictor of death. Two thirds of children with diabetic ketoacidosis in our series had new-onset diabetes, and 13.2% died. Serum osmolality at admission was the most important predictor of death.


Molecular orbital theory study on surface complex structures of glyphosate on goethite: calculation of vibrational frequencies.
Six possible complexes of glyphosate (O-PO(OH)-CH2NH2+CH2CO2H) with an Fe-hydroxide dimer were modeled with hybrid molecular orbital/density functional theory calculations to establish the nature of the bonds of glyphosate on goethite (alpha-FeOOH). Monodentate and bidentate coordination of the phosphonate moiety were considered, using three forms of the glyphosate molecule appropriate for different pH ranges: glyphosate with both phosphonate and amino moieties protonated, glyphosate with unprotonated phosphonates, and glyphosate with both unprotonated phosphonates and no hydrogen ion on the amino group. The calculated infrared vibrational modes were compared to experimental values, finding particularly good agreements with the monodentate complexes in all the pH ranges.


[Mineralogy Characteristics and Heavy Metal Distribution of MSWI Fly Ash].
Fly ash from municipal solid waste incineration (MSWI) plants can be categorized as a highly toxic mineral material due to the potential for leaching heavy metals. The mineralogical properties of MSWI fly ash visually reflect the heavy metals distribution in the ash, and are closely related to the release and migration behaviors of heavy metals in fly ash disposal or utilization scenarios. In order to understand the distribution of heavy metals in MSWI fly ash and provide support for heavy metals control technology, comprehensive tests on the macroscopic and microscopic mineralogical characteristics of the fly ash were conducted using X-ray diffraction (XRD), scanning electron microscope, a mineral liberation analysis system, and other methods. The results showed that MSWI fly ash was a heterogeneous material of closely combined mineral and non-mineral phases. The main mineral phases identified by XRD included chlorides and calcium-bearing minerals, mainly calcite and portlandite. The element distribution analysis, conducted with a mineral liberation analyzer, revealed that heavy metals of MSWI fly ash were mainly present in three forms:uniform distribution in the non-mineral amorphous phase, isomorphism in calcite and other minerals, and adsorption on the surfaces of quartz and hematite. Most content of Cu and Cr were distributed in the non-mineral phase due to their lower volatility, while most of semi-volatile heavy metals (43.92% of Zn and 60.61% of Cd) were present in mineral phases. In particular, Cd, Cr and Zn were mainly present in calcite, hematite and silicates respectively.


Effects of high-frequency, low-magnitude mechanical stimulus on bone healing.
Recent studies have shown osteogenic effects of high-frequency mechanical stimuli. The purpose of this study was whether externally applied, high-frequency, low-magnitude interfragmentary movements affect the process of bone healing. In 12 sheep, a transverse osteotomy with a 3 mm gap was created in the right metatarsus and externally stabilized by a rigid circular fixator. External stimulation was performed in six sheep with the use of ground-based vibration. The sheep were standing with their hind limbs on a platform that produced vertical movements resulting in interfragmentary movements of approximately 0.02 mm magnitude at 20 Hz frequency. The other six sheep remained rigidly stabilized by external fixation during the 8-week study and served as a control group. Healing was assessed postmortem by densitometric and mechanical examinations. No significant differences were found between the two groups, although callus formation was slightly enhanced (11%) in the stimulated group compared with the control group. Mechanical stimuli attributable to weightbearing in the control group were sufficient enough to initiate callus formation even under rigid, external fixation. Thus, external mechanical stimulation with the stimulation design described in the current study might not be indicated for improvement of bone healing.


Spontaneous Formation of an Ideal-Like Field-Effect Channel for Decay-Free Polymeric Thin-Film Transistors by Multiple-Scale Phase Separation.
We demonstrate semiconducting polymer-based thin-film transistors (PTFTs) with fast switching performance and an uncommon nondecaying feature. These PTFTs based on widely studied poly(3-hexylthiophene) are developed by incorporating the insulating polymer into the active channel and subjecting the compound to specific, spontaneous multiple-scale phase separation (MSPS). An in-depth study is conducted on the interfacial and phase-separated microstructure of the semiconducting/insulating blending active layer and its effect on the electrical characteristics of PTFTs. The polyblends exhibit a confined crystallization behavior with continuously semiconducting crystalline domains between scattered insulator-rich domains. The insulator-rich domains can block leakage current and strengthen the gate control of the channel. A small amount of the insulating polymer penetrates the bottom of the active channel, resulting in effective interface modification. We show specific MSPS morphology of the present blending films to reduce charge trapping effects, enhance charge accumulation, and create a high-seed switching channel. The findings enable us to develop the required morphological conceptual model of the ideal-like field-effect-modulated polymer-based active channel. The polyblend-based PTFTs with MSPS morphology also have promising sensing functions. This study offers an effective approach for overcoming the major drawbacks (instability and poor switching) of PTFTs, thus allowing such transistors to have potential applications.


Cryo-EM structure of the Hedgehog release protein Dispatched.
The Hedgehog (Hh) signaling pathway controls embryonic development and adult tissue homeostasis in multicellular organisms. In Drosophila melanogaster, the pathway is primed by secretion of a dually lipid-modified morphogen, Hh, a process dependent on a membrane-integral protein Dispatched. Although Dispatched is a critical component of the pathway, the structural basis of its activity has, so far, not been described. Here, we describe a cryo-electron microscopy structure of the D. melanogaster Dispatched at 3.2-Å resolution. The ectodomains of Dispatched adopt an open conformation suggestive of a receptor-chaperone role. A three-dimensional reconstruction of Dispatched bound to Hh confirms the ability of Dispatched to bind Hh but using a unique mode distinct from those previously observed in structures of Hh complexes. The structure may represent the state of the complex that precedes shedding of Hh from the surface of the morphogen-releasing cell.


Inhibitory effects of Akacid (plus) on growth and aflatoxin production by Aspergillus parasiticus.
The effects of Akacid plus, a novel guanidine-based polymer first introduced as a biocidal and disinfectant agent were studied on Aspergillus parasiticus growth and its aflatoxin (AF) productivity. The fungus was cultured on yeast extract-sucrose (YES) broth in presence of various twofold serial dilutions of 25% Akacid plus (1.5-96 microL/50 mL medium) and then incubated in shaking condition with 150 rev./min at 28 degrees C for 96 h. Based on obtained results, Akacid plus was found to significantly inhibit both growth and aflatoxin B1 (AFB1) synthesis in very low concentrations in a dose-dependent manner. Fungal growth inhibition was determined in the range of 9.6-99.6% in mycelia exposed to the total concentration range of 1.5-48 microL. A final concentration of 96 microL was necessary to completely inhibit the growth of fungus. Under similar conditions, AFB1 synthesis was found to be strongly inhibited by 8.1-98.0% in presence of 1.5-24 microL Akacid plus with a maximum of 100% by 48 microL concentration. With respect to the unique physico-chemical properties of Akacid plus, its marked inhibitory effects on A. parasiticus growth and its AFB1 synthesis shown for the first time in this study make it a promising candidate for application in prevention programmes of AF contamination of susceptible crops.


Myelofibrosis presenting as chronic cholecystitis.
A 61 year old man presented with abdominal pain typical of chronic cholecystitis of one month's duration. Pallor was noted on examination and investigation uncovered myelofibrosis and a small gallstone. Cholecystectomy relieved the pain and pathological examination of the gall bladder showed widespread myeloid metaplasia. This is the first reported case of myelofibrosis presenting as chronic cholecystitis.


Visuospatial Working Memory Capacity in the Brain After Working Memory Training in College Students With ADHD: A Randomized Controlled Trial.
Objective: ADHD has been associated with persistent problems of working memory. This study investigated the efficacy of an intensive and adaptive computerized working memory treatment (CWMT) at behavioral and neural levels. Method: College students (n = 89; 40 females) with ADHD were randomized into a standard-length CWMT (45 min/session, 25 sessions, n = 29), shortened-length CWMT (15 min/session, 25 sessions, n = 32), and a waitlist group (n = 28). Both CWMT groups received treatment for 5 days a week for 5 weeks. Lab sessions before and after CWMT assessed electroencephalography (EEG) indicators of working memory, behavioral indicators of working memory performance, and ADHD symptomatology. Results: No evidence was found for neural or any other behavioral transfer effects of improvement for the CWMT treatment groups over the active control or waitlist group. Conclusion: Our study does not provide evidence for the benefits of CWMT at neural or behavioral levels.


Synthesis and biological activity of some new 5-hydrothiazolo[4,3-b]-1,3,4-oxa(thia)diazoles and 5-hydrothiazolo[3,4-b]-1,2,4-triazoles containing 1,2,3-selena(thia)diazole moiety.
p-Acetylphenyl thiosemicarbazide (I) was reacted with different aldehydes yielding the corresponding semicarbazones II. Addition condensation of thioglycolic acid with compounds II gave 4-thiazolidinones III. Reaction of compounds III with conc. H2SO4, KI/I2-NaOH and NaOH afforded the cyclized products (IV-VI). Compounds (IV-VI) reacted with semicarbazide to give the corresponding semicarbazones (VII-IX) which either were oxidized with selenium dioxide or thionyl chloride to give 1,2,3-selenadiazoles (X-XII) and 1,2,3-thiadiazoles (XIII-XV) respectively. Some of the prepared compounds were tested against some strains of bacteria.


Studies on the kinetics of melatonin and N-acetylserotonin in the rat at mid-light and mid-dark.
The distribution and disappearance of melatonin and N-acetylserotonin after intravenous injection were studied at mid-light and mid-dark. Male rats were adapted under a photoperiod of 12 h light and 12 h dark cycle for a minimum of 1 week. After the intravenous injection of melatonin (10 micrograms), N-acetylserotonin (10 micrograms), or 3H-melatonin (76 ng), blood samples were collected at 1, 3, 5, 10, 20, 30, 45, 60, 75, 90, and 120 min. The concentrations of indoles in the plasma samples were determined by radioimmunoassay, while the radioactivity of 3H-melatonin was determined by scintillation counting. The distribution of melatonin and N-acetylserotonin followed a two-compartment model, showing an initial distribution phase followed by an elimination phase. The biological half-life of melatonin at mid-light and mid-dark were similar but the volume of distribution (V beta and Vc) and metabolic clearance rate (C1s) were greater at mid-dark than at mid-light. The estimated melatonin secretory rate at mid-dark was fivefold greater than that at mid-light. When 3H-melatonin was used, the half-life was significantly longer. A diurnal difference in the distribution was also evident in the N-acetylserotonin studies. The volume of distribution (V beta and Vc) was greater at mid-dark while the C1s was not significantly faster at mid-dark compared with that at mid-light. However, the estimated N-acetylserotonin secretory rate at mid-dark was eightfold greater than at mid-light.


Conductive black silicon surface made by silver nanonetwork assisted etching.
Conductive black silicon surfaces (CBSSs) are fabricated by Ag network-assisted catalytic etching, with the Ag network buried in silicon for low reflectance. The CBSSs present a high light absorbance of 97% and good electrical conductivity of less than 10 Ω/□. The CBSSs might be used as anti-reflection-coating free light-harvesting devices.


Relationship between motor FIM and muscle strength in lower cervical-level spinal cord injuries.
Retrospective analysis. The objectives of this research were to, in subjects with lower cervical spinal cord injury (SCI), examine the relationship between strength of muscle groups as measured by the manual muscle test (MMT) and function (reflected as burden of care) as measured by individual functional independence measure (FIM) motor tasks, and investigate the extent to which MMT scores explain the variance of the motor FIM scores. Acute rehabilitation hospitals, Boston, MA, USA. Retrospective pilot study of 20 in-patients, age 18-62 years, with an SCI between C5 and C7. Discharge demographic variables, MMT and motor FIM scores were analyzed. Descriptive statistics, Spearman's rank correlation coefficients, stepwise regressions were performed. MMT scores for elbow flexion followed by shoulder flexion and wrist extension correlated with the greatest number of FIM tasks. MMT scores explained some part of the variance in the eight of 12 motor FIM tasks. In six of eight tasks, one key muscle explained a large portion of the variance. Key muscles relative to FIM tasks can be identified. These findings may help focus therapeutic interventions aimed at achievement in these tasks.


Extrusion Cooking Effect on Carbohydrate Fraction in Novel Gluten-Free Flours Based on Chickpea and Rice.
Extrusion cooking allows the development of value-added products from pulses, such as gluten-free snacks with added functional properties. The main objective of this study was to evaluate the changes induced by the extrusion process on the carbohydrate fraction (total carbohydrates, soluble sugars and oligosaccharides, dietary fiber, and arabinoxylans) of novel flour formulations based on chickpeas and rice enriched with different dietary fiber sources. Moreover, the influence of the addition of fiber-rich ingredients, such as Fibersol® and passion fruit, on the analyzed compounds was also evaluated. Sucrose was the main soluble sugar found in analyzed formulations, and raffinose was the prevalent oligosaccharide, followed by stachyose. The content of total α-galactosides tended to be higher after extrusion cooking. As a consequence of the extrusion treatment, the content of total and soluble dietary fiber was statistically increased in most of the analyzed samples. In general, no significant changes were observed in total arabinoxylan content as a consequence of the extrusion process, while the content of water-soluble arabinoxylans was significantly increased in extruded formulations. It was observed that the content of total available carbohydrates, stachyose, and water-soluble arabinoxylans were significantly influenced by the addition of passion fruit, Fibersol®, and both. The incorporation of these ingredients in gluten-free formulations based on chickpeas and rice allows one to obtain suitable functional formulations for the development of innovative, gluten-free, extruded snack-type products, which could be an interesting alternative for people with celiac disease.


[Microsomal monooxygenases of the liver in mice with transplanted tumors].
Hepatoma 22a and Ehrlich's tumor growth were shown to be accompanied by decrease in cytochrome P-450 level in liver of noninbred and C3HA mice, these changes being more pronounced as compared to solid neoplasms. Benzo(a)pyrene-hydroxylase and amidopyrine-N-demethylase activity varied with tumor pattern. It was not changed in cases of hepatoma 22a but decreased in mice bearing Ehrlich's tumor, particularly, in those with the ascitic form. The inhibition analysis using metyrapone and 7,8-benzoflavone identified phenobarbital and methylcholanthrene forms of benzo(a)pyrene-hydroxylase in murine liver; isoform profile was not significantly affected by tumor. Liver microsomal monooxygenases of tumor-bearing mice retained inducibility by 3-methylcholanthrene.


Measurement of the steady-state shear characteristics of filamentous suspensions using turbine, vane, and helical impellers.
The impeller viscometer technique is frequently used to characterize the rheology of filamentous suspensions in order to avoid difficulties encountered with conventional instruments. This work presents the results of experiments conducted with vane, turbine, and helical impellers. The validity of the assumptions made in the determination of the torque and shear-rate constants were assessed for each impeller type. For the turbine and vane impellers, an increase in the apparent torque constant c was observed with increasing Reynolds number even when measurements were confined to the viscous regime. The shear-rate constants determined for the vane and turbine impellers varied for different calibration fluids, which contradicts the assumptions usually invoked in the analysis of data for this technique. When the helical impeller was calibrated, consistent values for the torque and shear-rate constants were obtained. The three impeller types were also used to characterize the rheology of cellulose fiber suspensions and the results compared for consistency and reproducibility. The results have application in design of rheometers for use in process control and product quality assessment in the fermentation and pulp and paper industries.


Neurourologic dysfunction: evaluation, surveillance and therapy.
Neurogenic bladder dysfunction results from a variety of neurologic pathologies and can lead to significant patient morbidity and mortality. This article reviews the evaluation, surveillance and management of patients with spinal cord injury, multiple sclerosis, spina bifida and Parkinson's disease. Recent studies of patients with neurogenic bladder have highlighted their risk for potentially preventable urologic complications ranging from renal failure to urinary tract infections. However, these same studies bring attention to the lack of compliance and consensus regarding the recommended evaluation of these high-risk patients. Patients with neurovesical dysfunction must be followed at regular intervals to preserve upper tract function, maintain safe bladder pressures, prevent urinary tract infections and address continence. Future studies and guidelines are needed to direct the management of these complicated patients.


Functional variation among frugivorous birds: implications for rainforest seed dispersal in a fragmented subtropical landscape.
Seed dispersal plays a critical role in rainforest regeneration patterns, hence loss of avian seed dispersers in fragmented landscapes may disrupt forest regeneration dynamics. To predict whether or not a plant will be dispersed in fragmented forests, it is necessary to have information about frugivorous bird distribution and dietary composition. However, specific dietary information for frugivorous birds is often limited. In such cases, information on the seed-crushing behaviour, gape width and relative dietary dominance by fruit may be used to describe functional groups of bird species with respect to their potential to disperse similar seeds. We used this information to assess differences in the seed dispersal potential of frugivorous bird assemblages in a fragmented rainforest landscape of southeast Queensland, Australia. The relative abundance of frugivorous birds was surveyed in extensive, remnant and regrowth rainforest sites (16 replicates of each). Large-gaped birds with mixed diets and medium-gaped birds with fruit-dominated diets were usually less abundant in remnants and regrowth than in continuous forest. Small-gaped birds with mixed diets and birds with fruit as a minor dietary component were most abundant in regrowth. We recorded a similar number of seed-crushing birds and large-gaped birds with fruit-dominated diets across site types. Bird species that may have the greatest potential to disperse a large volume and wide variety of plants, including large-seeded plants, tended to be less abundant outside of extensive forests, although one species, the figbird Sphecotheres viridis, was much more abundant in these areas. The results suggest that the dispersal of certain plant taxa would be limited in this fragmented landscape, although the potential for the dispersal of large-seeded plants may remain, despite the loss of several large-gaped disperser species.


Current perspectives for treating children with diabetic ketoacidosis.
To review current concepts of physiopathology, diagnosis and treatment of diabetic ketoacidosis (DKA) in childhood, as well as preventive measures to avoid cerebral edema. The authors selected articles from MEDLINE with the keywords diabetes, ketoacidosis, hyperglycemia and cerebral edema, and priority was given to studies including children and that contained complete texts published in English, Portuguese or Spanish. Chapters of books published in Brazil describing the treatment of DKA in pediatric intensive care unit were also reviewed. Based on the reviewed literature and on the author's experience, the most efficient and recommended measures for DKA management are presented. Normal saline solution (NaCl 0.9%) has been increasingly used for fast replacement and hydration, as a substitute to diluted (hypotonic) solutions, as well as contraindication of sodium bicarbonate to repair metabolic acidosis in DKA. Regular insulin should be used as continuous infusion (0.1 IU/kg/h) without the need of a loading dose. For fast corrections of glucose oscillations, a practical scheme using two bags of electrolytic solutions is presented. Cerebral edema, its physiopathological mechanism and current treatment are reviewed. Use of continuous infusion of regular insulin associated with adequate water and electrolyte replacement using isotonic solutions, besides being an effective treatment for DKA, preserves plasma osmolarity and prevents cerebral edema.


Addressing Stigma in Medication Treatment of Adolescents With Opioid Use Disorder.
: In September 2016, the American Academic of Pediatrics released a policy statement that adolescents with opioid use disorder should be offered pharmacotherapy with buprenorphine/naloxone, methadone, or naltrexone. In our clinical practice, however, we have encountered the perception among patients, families, and clinicians alike that medications should be used as a last resort. That we should wait until things get worse is a discarded approach. As addiction specialists, it is imperative that we prevent and identify risky use and use disorders, then intervene early and offer timely, evidence-based treatment. We suggest that adolescents deserve special attention and that specific efforts should be made to reduce the stigma associated with treating adolescents with opioid use disorder with medications to optimize those efforts.


Comparison of disseminated and nondisseminated strains of Borrelia burgdorferi sensu stricto in mice naturally infected by tick bite.
Clinical isolates of Borrelia burgdorferi sensu stricto have been categorized into disseminated and nondisseminated groups based on distinct ribosomal spacer restriction fragment length polymorphism genotypes (RSTs). In order to determine whether transmission by tick bite would alter the dissemination dynamics and disease produced by distinct genotypes, disseminated isolates (RST1), nondisseminated isolates (RST3), and a standard laboratory strain (B-31) were established in a murine cycle utilizing infections transmitted by ticks. B-31 spirochetes circulated in the blood of inbred C3H/HeJ mice longer than in the blood of outbred mice. The majority of C3H mice exposed to RST1-infected ticks contained cultivable spirochetes in their blood for up to 17 days; in contrast, mice exposed to RST3 isolates demonstrated a precipitous decline in infection after day 7 postexposure. A quantitative PCR (q-PCR) assay demonstrated that the densities of spirochetes in blood were similar for the RST1 and RST3 isolates, except during the 2nd week postexposure, when the RST1 isolates displayed a markedly higher density in blood. Spirochete load in the heart and bladder of infected mice was measured by q-PCR at 8 weeks postexposure; the numbers of spirochetes in these tissues were similar for mice infected with either disseminated or nondisseminated strains. Similarly, histopathology samples of heart, bladder, and joint tissue obtained at 8 weeks postexposure did not reveal greater pathology in mice infected with the disseminated isolates. We conclude that although the spirochetemia induced by tick-transmitted disseminated isolates was more intense and of longer duration than that induced by nondisseminated isolates, the resultant pathologies produced by these strains were ultimately similar.


Pertactin-negative Bordetella pertussis strains: evidence for a possible selective advantage.
A recent increase in Bordetella pertussis without the pertactin protein, an acellular vaccine immunogen, has been reported in the United States. Determining whether pertactin-deficient (PRN(-)) B. pertussis is evading vaccine-induced immunity or altering the severity of illness is needed. We retrospectively assessed for associations between pertactin production and both clinical presentation and vaccine history. Cases with isolates collected between May 2011 and February 2013 from 8 states were included. We calculated unadjusted and adjusted odds ratios (ORs) using multivariable logistic regression analysis. Among 753 isolates, 640 (85%) were PRN(-). The age distribution differed between cases caused by PRN(-) B. pertussis and cases caused by B. pertussis producing pertactin (PRN(+)) (P = .01). The proportion reporting individual pertussis symptoms was similar between the 2 groups, except a higher proportion of PRN(+) case-patients reported apnea (P = .005). Twenty-two case-patients were hospitalized; 6% in the PRN(+) group compared to 3% in the PRN(-) group (P = .11). Case-patients having received at least 1 pertussis vaccine dose had a higher odds of having PRN(-) B. pertussis compared with unvaccinated case-patients (adjusted OR = 2.2; 95% confidence interval [CI], 1.3-4.0). When restricted to case-patients at least 1 year of age and those age-appropriately vaccinated, the adjusted OR increased to 2.7 (95% CI, 1.2-6.1). The significant association between vaccination and isolate pertactin production suggests that the likelihood of having reported disease caused by PRN(-) compared with PRN(+) strains is greater in vaccinated persons. Additional studies are needed to assess whether vaccine effectiveness is diminished against PRN(-) strains.


Molecular genetics applied to clinical practice: the Cx26 hearing impairment.
Mutations in the Cx26/GJB2 gene account for a large proportion of pre-lingual hearing impairment with a prevalence up to 50% in autosomal recessive cases and a still undefined prevalence in sporadic cases. Ninety-four subjects affected by non-syndromal sensorineural hearing impairment (NSHI) were enrolled in the study. The patients had either a family history of childhood hearing deficit or represented sporadic cases. The risk of an acquired cause of the deficit has been carefully excluded. Audiological characteristics were investigated. Cx26 mutations were found in 50% of subjects. Seventy-three per cent of mutations in this gene were 35delG, with significant geographical variations. In 7% of the putative Cx26 alleles no mutations were detected either in the coding region or in the non-coding exon 1. Cx26 hearing impairment involves all frequencies, is of variable severity, and is very rarely progressive and most frequently symmetrical between the two ears. The high occurrence of this type of pre-lingual hearing impairment argues for modification of the protocols used to investigate the aetiology of childhood hearing impairment. Early screening for Cx26 mutations in all patients with non-syndromal familial and sporadic permanent childhood hearing impairment seems justified.


Inflammatory and Cholesterol Risk in the FOURIER Trial.
In the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk), the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor evolocumab reduced low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk. It is not known whether the efficacy of evolocumab is modified by baseline inflammatory risk. We explored the efficacy of evolocumab stratified by baseline high-sensitivity C-reactive protein (hsCRP). We also assessed the importance of inflammatory and residual cholesterol risk across the range of on-treatment LDL-C concentrations. Patients (n=27 564) with stable atherosclerotic cardiovascular disease and LDL-C ≥70 mg/dL on a statin were randomly assigned to evolocumab versus placebo and followed for a median of 2.2 years (1.8-2.5). The effects of evolocumab on the primary end point of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina or coronary revascularization, and the key secondary end point of cardiovascular death, myocardial infarction, or stroke were compared across strata of baseline hsCRP (<1, 1-3, and >3 mg/dL). Outcomes were also assessed across values for baseline hsCRP and 1-month LDL-C in the entire trial population. Multivariable models adjusted for variables associated with hsCRP and 1-month LDL-C were evaluated. A total of 7981 (29%) patients had a baseline hsCRP<1 mg/L, 11 177 (41%) had a hsCRP 1 to 3 mg/L, and 8337 (30%) had a hsCRP >3 mg/L. Median (interquartile range) baseline hsCRP was 1.8 (0.9-3.6) mg/L and levels were not altered by evolocumab (change at 48 weeks of -0.2 mg/dL [-1.0 to 0.4] in both treatment arms). In the placebo arm, patients in higher baseline hsCRP categories experienced significantly higher 3-year Kaplan-Meier rates of the primary and key secondary end points: 12.0%, 13.7%, and 18.1% for the primary end point (Ptrend<0.0001) and 7.4%, 9.1%, and 13.2% for the key secondary end point (Ptrend<0.0001) for categories of <1, 1 to 3, and >3 mg/dL, respectively. The relative risk reductions for the primary end point and key secondary end point with evolocumab were consistent across hsCRP strata (P-interactions>0.15 for both). In contrast, the absolute risk reductions with evolocumab tended to be greater in patients with higher hsCRP: 1.6%, 1.8%, and 2.6% and 0.8%, 2.0%, and 3.0%, respectively, for the primary and key secondary end points across hsCRP strata. In adjusted analyses of the association between LDL-C and hsCRP levels and cardiovascular risk, both LDL-C and hsCRP were independently associated with the primary outcome (P<0.0001 for each). LDL-C reduction with evolocumab reduces cardiovascular events across hsCRP strata with greater absolute risk reductions in patients with higher-baseline hsCRP. Event rates were lowest in patients with the lowest hsCRP and LDL-C. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01764633.


Safety and efficacy of central cannulation through ascending aorta for type A aortic dissection.
The femoral and axillary arteries are common arterial cannulation sites for repair of type A dissection. However, these peripheral approaches involve certain problems. From January 2002 to August 2009, a total of 77 patients underwent emergency surgery for acute type A dissection. Central cannulation was applied in 26 patients and peripheral cannulation in 51. The arterial cannulation site was decided according to preoperative computed tomography findings, the patient's condition, and intraoperative epiaortic ultrasonography findings. Central cannulation was avoided in cases of cardiac tamponade with shock. A cannula was inserted under ultrasound guidance using the Seldinger technique. Preoperative patient comorbidities and dissection-related complications were equally distributed between the two groups. Central cannulation was successfully performed in all 26 cases without incident. Operation time, cardiopulmonary bypass time, mean intubation time and mean intensive care unit stay duration were significant shorter in the central group. One patient (4%) died in the central group compared with four patients (8%) in the peripheral group (P=0.45). Direct central cannulation was successful for repair of type A dissection in selected patients and produced equal or superior surgical data to peripheral cannulation, thus providing one option in the approach to this condition.


Trends of Various Techniques of Tubectomy: A Five Year Study in a Tertiary Institute.
Female sterilization is one of the best and effective methods of contraception for women who have completed their family. Tubectomy during caesarean operation and minilaparotomy are popular methods in developing countries whereas laparoscopic sterilization and hysteroscopic tubal occlusion are the preferred methods in developed countries. To know the trends, incidence and immediate complications of methods of female sterilizations performed at our institute. This is a retrospective analytical study conducted at our tertiary care centre from January 2010 to December 2014 in Karnataka Institute of Medical Sciences, Hubli, Karnataka. The case files of all the patients who underwent sterilization were taken from the medical records section and reviewed in detail. The cases were grouped as caesarean tubectomy, minilaparotomy and laparoscopic sterilization, based on the abdominal entry. For minilaparotomy and during caesarean tubectomy, modified pomeroy's technique was used. For laparoscopic sterilization, falope rings were used. Data was analysed by Karl Pearson's correlation co-efficient method and Chi-Square test. The p-value < 0.05 was considered significant. Out of 5442 cases of female sterilization, 2872 underwent caesarean tubectomy, remaining half underwent minilaparotomy (1306) and laparoscopic sterilization (1264). Sterilizations were significantly more during puerperal period (caesarean tubectomy + post abortal + postpartum) compared to interval period. There was an increasing trend in caesarean tubectomy and laparoscopic sterilization. There were 11 procedure related complications in the laparoscopic sterilization, one in caesarean tubectomy and none in minilaparotomy. Two deaths were reported in minilaparotomy, one in laparoscopic sterilization and four in the caesarean tubectomy, which were due to septicaemia. An increasing trend in caesarean tubectomy and laparoscopic sterilization is seen in this study. Female sterilization should be individualized based on the timing, place and surgeons experience. Sepsis is a major cause of death and asepsis could be compromised when female sterilization is done in large numbers in camps. Hence target related approach towards female sterilization should be avoided. Laparoscopic sterilization has more procedure related complications, which can be better handled in tertiary care centres.


Compression of femtosecond light pulses by one-dimensional photonic crystals with two-component relaxing nonlinearity
The compression of ultrashort light pulses in a one-dimensional nonlinear photonic crystal is investigated for light frequencies lying outside the forbidden gap of a periodic structure taking into account the delayed nonlinear response of a medium. It is shown that the relatively slow-responding defocusing nonlinearity can suppress the distortion of Bragg solitons caused by the relaxation of the fast self-focusing component and improve the compression efficiency. Stable optical quasisoliton propagation of light pulses and their compression are numerically confirmed for both band gap composite materials and photonic crystals with alternating layers of different types of nonlinearity.


Identification of genes subject to positive selection in uropathogenic strains of Escherichia coli: a comparative genomics approach.
Escherichia coli is a model laboratory bacterium, a species that is widely distributed in the environment, as well as a mutualist and pathogen in its human hosts. As such, E. coli represents an attractive organism to study how environment impacts microbial genome structure and function. Uropathogenic E. coli (UPEC) must adapt to life in several microbial communities in the human body, and has a complex life cycle in the bladder when it causes acute or recurrent urinary tract infection (UTI). Several studies designed to identify virulence factors have focused on genes that are uniquely represented in UPEC strains, whereas the role of genes that are common to all E. coli has received much less attention. Here we describe the complete 5,065,741-bp genome sequence of a UPEC strain recovered from a patient with an acute bladder infection and compare it with six other finished E. coli genome sequences. We searched 3,470 ortholog sets for genes that are under positive selection only in UPEC strains. Our maximum likelihood-based analysis yielded 29 genes involved in various aspects of cell surface structure, DNA metabolism, nutrient acquisition, and UTI. These results were validated by resequencing a subset of the 29 genes in a panel of 50 urinary, periurethral, and rectal E. coli isolates from patients with UTI. These studies outline a computational approach that may be broadly applicable for studying strain-specific adaptation and pathogenesis in other bacteria.


Subpectoral biceps tenodesis for the treatment of type II and IV superior labral anterior and posterior lesions.
Surgical repair remains the gold standard for most type II and type IV superior labral anterior and posterior (SLAP) lesions that fail nonoperative management. However, most recently, there have been data demonstrating unacceptably high failure rates with primary repair of type II SLAP lesions. Biceps tenodesis may offer an acceptable, if not better, alternative to primary repair of SLAP lesions. Subpectoral biceps tenodesis provides satisfactory, reproducible outcomes for the treatment of type II and type IV SLAP lesions. Case series; Level of evidence, 4. Patients who underwent subpectoral biceps tenodesis and labral debridement for type II and type IV SLAP lesions by a single board-certified shoulder surgeon from 2006 to 2012 were evaluated. Exclusion criteria included those patients who underwent biceps tenodesis with an associated rotator cuff repair, anterior labral repair, or posterior labral repair. Outcome measures included the visual analog scale (VAS) for pain, the American Shoulder and Elbow Surgeons (ASES) score, and demographic data. Between 2006 and 2012, a total of 36 subpectoral biceps tenodesis procedures were performed in 33 patients for type II or IV SLAP lesions. Twenty-six patients with 29 shoulder surgeries were available for follow-up. The average age was 46.7 years, with 16 male and 10 female patients participating in the study. The average follow-up was 40.17 months. There was a significant improvement in ASES and VAS scores: 48.1 and 6.4 preoperatively compared with 87.5 and 1.5 postoperatively, respectively (P < .001). There was no significant difference based on SLAP lesion type, patient age, or patient sex. Of 29 shoulders, 26 (89.66%) were able to return to the previous level of activity. This study adds to the evolving literature supporting biceps tenodesis as a viable treatment for type II and IV SLAP lesions. Patient age had no effect on the outcomes. Based on these results, biceps tenodesis is a safe, effective, and technically straightforward alternative to primary SLAP repair in patients with type II and IV SLAP tears.


New screening system for selection of anticancer drugs for treatment of human colorectal cancer.
We report an evaluation of a new radiometric technique (BACTEC assay) as a potential screening system for cytotoxic compounds with activity against cancer of the large bowel. Exponentially growing cells of nine different human colorectal cancer cell lines were exposed to a variety of standard anticancer agents with or without documented clinical activity. Each drug was tested in a series of 1-h and continuous exposure studies utilizing three different concentrations. Antineoplastic effects were analyzed as a function of in vivo achievable serum concentrations, namely by a ratio of the concentration required to decrease cell growth to 10% of control to one-tenth of the peak plasma concentration in humans. Our results suggest that COLO 320DM, OM-1, and Ht-29 cells manifest responsiveness to anticancer drugs consistent with that noted in clinical studies with most agents tested. The radiometric technique provides several advantages for a screening system, including reproducibility, a good agreement with the cloning assay, speed, and low costs. The combined use of the BACTEC technique and the three colon cancer cell lines could prove useful as a screen for new anticancer compounds with activity in colorectal cancer.


Hypoxia enhances the phosphorylation and cytotoxicity of ganciclovir and zidovudine in Kaposi's sarcoma-associated herpesvirus infected cells.
Primary effusion lymphoma (PEL) is a rare B-cell lymphoma caused by Kaposi's sarcoma-associated herpesvirus (KSHV). PEL is poorly responsive to standard cytotoxic chemotherapy and portends a poor survival. Consequently, new effective treatment options are urgently needed. It is known that KSHV encodes two lytic genes, ORF36 (phosphotransferase) and KSHV ORF21 (thymidine kinase), which can phosphorylate ganciclovir and azidothymidine, respectively. Here, we have explored whether these genes can be used as therapeutic targets for PEL. PEL arises in pleural spaces and other effusions that provide a hypoxic environment. Based on Northern blot analysis, exposure of PEL cells to hypoxia up-regulated the expression of both ORF36 and ORF21. Using a newly developed nonradioactive reverse-phase high-performance liquid chromatography/mass spectrometry method to separate and quantify the phosphorylated forms of ganciclovir and azidothymidine, we found that PEL cells exposed to hypoxia produced increased amounts of the toxic triphosphates of these drugs. Moreover, we found that hypoxia increased the cell toxicity of ganciclovir and azidothymidine in PEL cells but had no significant effect on the herpesvirus-negative cell line CA46. These findings may have clinical applicability in the development of effective therapies for PEL or other KSHV-related malignancies.


Association of protein tyrosine phosphatases (PTPs)-1B with c-Met receptor and modulation of corneal epithelial wound healing.
The purpose of this study was to investigate the expression and activity of protein tyrosine phosphatases (PTPs) in epithelium during corneal wound healing and to investigate how PTPs regulate activation of the c-Met receptor and the receptor's proximal signaling. Rabbit corneas were injured by gentle scraping of the surface, leaving the limbal epithelium intact, and epithelium was collected at 1, 2, 3, and 7 days after injury. In organ culture models, epithelium was removed and corneas were incubated with hepatocyte growth factor (HGF), with or without the PTP inhibitor bpV(phen), and the PI-3K inhibitors wortmannin and LY294002. Human corneal epithelial (HCE) cells were stimulated with HGF with or without bpV(phen). Total cell lysates and cytosolic and membrane fractions were analyzed by Western blot. PTP activities were measured with specific substrates. PTP1B and SHP-2 genes were knocked down by interference RNA (siRNA). PTP activity and expression increased during wound healing. The most abundant were SHP-2, PTP1B, and PTEN. HGF activated the c-Met receptor in HCE cells up to 30 minutes and was downregulated by 2 hours. Inhibition of PTPs increased HGF-promoted wound healing, HGF-activated phosphorylation of c-Met, and its downstream signal PI-3K/Akt, but not ERK1/2 or p70S6K. PTP1B and SHP-2 were bound to the c-Met. Part of the c-Met was colocalized in the endoplasmic reticulum with PTP1B. PTP1B phosphorylation increased when the c-Met receptor was deactivated, and gene knockdown of PTP1B increased c-Met activation. SHP-2 phosphorylation and binding to c-Met was higher during receptor activation, and SHP-2 gene silencing decreased receptor phosphorylation. Inhibition of PTP activity mimics the effect of HGF by activating the PI-3K/Akt signal involved in wound healing. PTP1B and SHP-2 are bound to the c-Met receptor to control its activity. Although the binding of PTP1B increases when there is a decrease in c-Met activation and acts as a negative regulator of the receptor, the increased binding and phosphorylation of SHP-2 coincide with maximal stimulation of c-Met, acting as a positive regulator.


Structure of bistramide A-actin complex at a 1.35 angstroms resolution.
Bistramide A is a highly potent antiproliferative marine natural product from Lissoclinum bistratum. We have previously established actin as the primary cellular receptor of bistramide A. We report herein the X-ray structure of bistramide A bound to monomeric actin at a resolution of 1.35 A. The most notable aspect of the bistramide A-actin structure is an extensive hydrogen-bonding network established upon a deep penetration of the central segment of bistramide A into the actin-binding cleft between subdomains 1 and 3. The structure presents the first insight into the observed ability of bistramide A to modulate G-actin polymerization. The structural information combined with our ability to chemically modify the bistramide framework provides the basis for rational development of a series of new synthetic analogues as useful probes for studying actin cytoskeleton and as potential therapeutic leads.


Accurate hematopoietic stem cell frequency estimates by fitting multicell Poisson models substituting to the single-hit Poisson model in limiting dilution transplantation assays.
Limiting dilution transplantation assay (LDTA) is considered as the gold standard method to assess hematopoietic stem cell (HSC) content. Traditionally, HSC frequency estimates are based on the single-hit Poisson model (SHPM), which posits that one donor HSC is sufficient to generate a progeny of detectable differentiated cells above a threshold value in hosts. However, there is no clear support for this statement, and it is receivable that more than one donor HSC may be necessary to provide detectable reconstitution in hosts above the threshold level for detection, usually 0.5% to 1% of donor-derived cells. To address this hypothesis, we evaluated the ability of a class of multiCell Poisson models (C(≥1)PMs) to fit to LDTAs. In 7 of the 8 reanalyzed LDTAs, C(≥1)PMs plausibly compete with the traditional SHPM. Model averaging across the set of plausible models gives 1.32- to 5.88-fold increases in HSC frequencies compared with the SHPM.


Estimate of the pollution removed by leaching of standard domestic waste: mass assessments carried out in batches and columns.
Batch and column tests allowed estimation of the mobilization of pollution of standard domestic waste in leachate and biogas. Three laboratory tests (biochemical methane potential (BMP), tank leaching test (TLT), and column tests) have been applied to evaluate the emission of pollutants in liquid and/or gas phase from reconstituted municipal solid waste (MSW) on the basis of French waste. In the case of the batch tests (BMP and TLT), BMP tests indicated a maximum organic carbon share produced by waste (biogas potential) equal to 59% of the initial carbon. The maximum quantity of carbon likely to be leached by the waste (TLT) corresponded to 6% of the carbon contained in the waste. On the other hand, during column tests, 3.3% of carbon was leached and 8% of carbon was evacuated in biogas at the end of a 440-day follow-up. It thus appears that the test conditions have a great influence on the remobilization of pollution. In particular it has been proven than the greater the optimization of the liquid/solid ratio, the agitation, the sowing, and the temperature, the greater the pollutant is leached. This study highlights the possible use of batch and column tests to evaluate the pollution risk of a landfill.


Orbital diffuse large B-cell lymphoma with combined variable immunodeficiency.
Common variable immunodeficiency (CVID) is a primary immunodeficiency manifesting as a reduction in the level of total immunoglobulin (Ig) G, a reduction in the level of either IgA or IgM, poor response to polysaccharide vaccine, and usually frequent infections. The association of CVID with an increased risk of malignancy, specifically lymphoma, is well known. A 63-year-old female with a past medical history significant for CVID presented with a 1-month history of dull, left eye pain with proptosis, hypoglobus, and left upper lid fullness without a discrete palpable mass. Magnetic resonance imaging (MRI) of the orbits revealed a diffuse infiltrating orbital mass superonasally with extension into the superior rectus muscle, medial rectus muscle, and optic nerve up to the orbital apex and ethmoid sinus. A superonasal orbital biopsy with a caruncular approach was performed and demonstrated a sparse lymphoid infiltrate that was suggestive for a large B-cell neoplasm. Positron emission tomography (PET) scan demonstrated a hypermetabolic right lymph node, anterior to the right submandibular gland, which was biopsied and histopathology confirmed diffuse large B-cell lymphoma (DLBCL). Our patient achieved a very good response to chemotherapy with minimal residual disease on PET scan at the end of treatment. She attained a complete remission after radiation therapy. In conclusion, patients with new orbital and adnexa masses in the setting of a primary immunodeficiency can have an aggressive malignancy such as DLBCL and early diagnosis and systemic treatment carries a good prognosis.


Identification of essential β-oxidation genes and corresponding metabolites for oestrogen degradation by actinobacteria.
Steroidal oestrogens (C18 ) are contaminants receiving increasing attention due to their endocrine-disrupting activities at sub-nanomolar concentrations. Although oestrogens can be eliminated through photodegradation, microbial function is critical for removing oestrogens from ecosystems devoid of sunlight exposure including activated sludge, soils and aquatic sediments. Actinobacteria were found to be key oestrogen degraders in manure-contaminated soils and estuarine sediments. Previously, we used the actinobacterium Rhodococcus sp. strain B50 as a model microorganism to identify two oxygenase genes, aedA and aedB, involved in the activation and subsequent cleavage of the estrogenic A-ring respectively. However, genes responsible for the downstream degradation of oestrogen A/B-rings remained completely unknown. In this study, we employed tiered comparative transcriptomics, gene disruption experiments and mass spectrometry-based metabolite profile analysis to identify oestrogen catabolic genes. We observed the up-regulation of thiolase-encoding aedF and aedK in the transcriptome of strain B50 grown with oestrone. Consistently, two downstream oestrogenic metabolites, 5-oxo-4-norestrogenic acid (C17 ) and 2,3,4-trinorestrogenic acid (C15 ), were accumulated in aedF- and aedK-disrupted strain B50 cultures. Disruption of fadD3 [3aα-H-4α(3'-propanoate)-7aβ-methylhexahydro-1,5-indanedione (HIP)-coenzyme A-ligase gene] in strain B50 resulted in apparent HIP accumulation in oestrone-fed cultures, indicating the essential role of fadD3 in actinobacterial oestrogen degradation. In addition, we detected a unique meta-cleavage product, 4,5-seco-estrogenic acid (C18 ), during actinobacterial oestrogen degradation. Differentiating the oestrogenic metabolite profile and degradation genes of actinobacteria and proteobacteria enables the cost-effective and time-saving identification of potential oestrogen degraders in various ecosystems through liquid chromatography-mass spectrometry analysis and polymerase chain reaction-based functional assays.


[Socioeconomic inequalities in oral health: factors associated with tooth brushing frequency among Nicaraguan schoolchildren].
To identify the association between tooth brushing frequency and variables of socioeconomic position in Nicaraguan schoolchildren. A cross sectional study was undertaken in 1353 schoolchildren ages 6 to 12 randomly selected from 25 elementary schools in Leon, Nicaragua. Using a questionnaire addressed to mothers, sociodemographic, socioeconomic and behavioral variables were collected. The dependent variable was tooth brushing frequency, which was dichotomized in 0 "at least one 7 times/week" and 1 "7 or more times/week". A multivariate analysis was carried out with logistic regression in STATA 9. The average age of child participants was 8.99 +/- 2.00 years and 49.7% were women. In the final model, older age (OR = 2.04), female sex (OR = 1.39) and having a mother with positive attitudes toward oral health (OR = 2.5) were positively associated with the tooth brushing frequency (p < 0.05). Larger family size (OR = 0.89) and having low socioeconomic status (1st quartile; OR = 0.54, 2nd quartile; OR = 0.62, 3rd quartile; OR = 0.67) showed a negative relationship with the tooth brushing frequency. To have had at least one preventive dental visit in the previous year was positively associated (p < 0.10) with tooth brushing frequency. This study suggested that existence of indicators of socioeconomic inequalities exist even within less developed countries, and thus emphasize the need to target health promotion programs to vulnerable socioeconomic groups.


[Anesthetics management in patients with epidermolysis bullosa].
The anesthetic management used in a 4-yr-old boy with dystrophic epidermolysis bullosa (DEB) submitted to long-lasting urological surgery is reported. Medical treatment of cutaneous bullae in various stages of healing was undertaken preoperatively. Other preoperative therapies were performed to treat sepsis and to improve poor nutritional state. Different measures were used during monitoring and inhalation induction and maintenance of anesthesia in order to prevent frictional trauma to the skin and oropharyngeal mucosa, leading to blistering. Anesthesia and surgery proceeded uneventfully, while surgical complications and sepsis occurred postoperatively. However the patient was discharged from intensive care unit to surgical ward on 35 postoperative days without evidence of oropharyngeal bullae and with a good improvement of his cutaneous condition. The conclusions are drawn that, even if the patient with DEB represents a challenge to the anesthesiologist, a long-lasting surgical intervention can be performed successfully. The main aspect in the anesthetic management of these patients is the detailed knowledge of all problems that anesthesiologist must face and solve to preserve skin and mucosa integrity, avoiding the risk of severe complications.


Prevalence of chronic pain, posttraumatic stress disorder, and persistent postconcussive symptoms in OIF/OEF veterans: polytrauma clinical triad.
This study examines the prevalence and coprevalence with which returning Operation Iraqi Freedom (OIF)/Operation Enduring Freedom (OEF) veterans were reporting symptoms consistent with chronic pain, posttraumatic stress disorder (PTSD), and persistent postconcussive symptoms (PPCS). The medical records of 340 OIF/OEF veterans seen at a Department of Veterans Affairs Polytrauma Network Site were comprehensively reviewed. Analyses indicated a high prevalence of all three conditions in this population, with chronic pain, PTSD, and PPCS present in 81.5%, 68.2%, and 66.8%, respectively. Only 12 of the veterans (3.5%) had no chronic pain, PTSD, or PPCS. The frequency at which these three conditions were present in isolation (10.3%, 2.9%, and 5.3%, respectively) was significantly lower than the frequency at which they were present in combination with one another, with 42.1% of the sample being diagnosed with all three conditions simultaneously. The most common chronic pain locations were the back (58%) and head (55%). These results underscore the complexity of the presenting complaints in OIF/OEF veterans and support the importance of a multidisciplinary team approach to assessment and treatment.


Specific T-type calcium channel isoforms are associated with distinct burst phenotypes in deep cerebellar nuclear neurons.
T-type calcium channels are thought to transform neuronal output to a burst mode by generating low voltage-activated (LVA) calcium currents and rebound burst discharge. In this study we assess the expression pattern of the three different T-type channel isoforms (Ca(v)3.1, Ca(v)3.2, and Ca(v)3.3) in cerebellar neurons and focus on their potential role in generating LVA spikes and rebound discharge in deep cerebellar nuclear (DCN) neurons. We detected expression of one or more Ca(v)3 channel isoforms in a wide range of cerebellar neurons and selective expression of different isoforms in DCN cells. We further identify two classes of large-diameter DCN neurons that exhibit either a strong or weak capability for rebound discharge, despite the ability to generate LVA spikes when calcium currents are pharmacologically isolated. By correlating the Ca(v)3 channel expression pattern with the electrophysiological profile of identified DCN cells, we show that Ca(v)3.1 channels are expressed in isolation in DCN-burst cells, whereas Ca(v)3.3 is expressed in DCN-weak burst cells. Ca(v)3.1-expressing DCN cells correspond to excitatory or GABAergic neurons, whereas Ca(v)3.3-expressing cells are non-GABAergic. The Ca(v)3 class of LVA calcium channels is thus expressed in specific combinations in a wide range of cerebellar neurons but contributes to rebound burst discharge in only a select number of cell classes.


HPV seroconversion following anal and penile HPV infection in HIV-negative and HIV-infected MSM.
We assessed human papillomavirus (HPV) seroconversion following anal and penile HPV infection in HIV-negative and HIV-infected men who have sex with men (MSM). MSM aged ≥18 years were recruited in Amsterdam, the Netherlands (2010-2011), and followed up semiannually. Antibodies against 7 high-risk HPV types in baseline and 12-month serum samples were tested using a multiplex immunoassay. Baseline, 6-, and 12-month anal and penile samples were tested for HPV DNA using the SPF10-PCR DEIA/LiPA25 system. Statistical analyses were performed using logistic regression with generalized estimating equations. Of 644 MSM included in the analysis, 245 (38%) were HIV-infected. Median age was 38 years for HIV-negative and 47 years for HIV-infected MSM (P < 0.001). Seroconversion against ≥1 of the 7 HPV types was observed in 74 of 396 (19%) HIV-negative and 52 of 223 (23%) HIV-infected MSM at risk (P = 0.2). Incident [adjusted OR (aOR) 2.0; 95% confidence interval (CI), 1.1-3.4] and persistent (aOR 3.7; 95% CI, 1.5-9.5) anal HPV infections were independently associated with type-specific seroconversion in HIV-negative MSM. In HIV-infected MSM, there was a nonsignificant positive association between penile HPV infection at any time point and seroconversion (aOR 1.7; 95% CI, 0.9-3.2). Incident or persistent anal HPV infection was an independent determinant of seroconversion in HIV-negative MSM. Our data support that seroresponse may vary per anatomic site and that persistent HPV infections are more likely to elicit a detectable humoral immune response.


A digitizer with exceptional accuracy for use in prosthetics research: a technical note.
A mechanical digitizer was developed for use in prosthetics research where measurements of small differences in shape are of interest. Root-mean-square error was 0.075 mm in the radial direction, 0.05 degrees in the tangential direction, and 0.1 mm in the vertical direction. The system has potential use for time-dependent assessment of changes in socket and residuum cast shape, assessment of socket fabrication systems, and development of accurate prosthetic finite element models.


Solution of Dirac's equation in Reissner-Nordström geometry.
The nature of the singularity at the origin of the solution of Dirac's equation in Reissner-Nordström geometry is different from that in flat space. Here, both independent solutions are regular at the origin, and both give a convergent normalization integral. The choice between the two solutions is made by requiring that the variational integral, from which the differential equation can be derived, be convergent. The gravitational shift of the ground state of hydrogen in Reissner-Nordström geometry is estimated to be only of order 10(-36) MH.


In situ evaluation of oxidative stress and immunological parameters as ecotoxicological biomarkers in a novel sentinel species (Mimachlamys varia).
Although the variegated scallop Mimachlamys varia seems to be a suitable sentinel species for contaminant monitoring, no study has identified biomarkers in this species. In order to fill this gap, this study conducted an in situ biomarker approach. M. varia were collected in contaminated and uncontaminated areas and responsiveness of oxidative stress and immunological biomarkers was evaluated in the digestive gland. In parallel, 14 trace element concentrations were evaluated in the same organ. Superoxide dismutase activity and malondialdehyde content responded efficiently to in situ contamination when a certain degree of contamination was reached. Laccase-type phenoloxidase showed a high sensitivity but saturation of the response was highlighted for the highest contaminations. Additionally, correlations were found between biomarkers and trace element concentrations. Taken together, results showed that biomarker approach conducted in the digestive gland of M. varia represents a sensitive analytical tool to highlight ecotoxicological issues in coastal marine ecosystems.


Public sources of information and information needs for pandemic influenza A(H1N1).
Providing health information during disease outbreaks is a fundamental component of outbreak control strategies. This study aimed to explore sources of influenza A(H1N1)-related information, specific information needs and preferences of the lay public during the peak of the outbreak. A cross-sectional, population-based, computer-assisted telephone interview of 1,050 respondents was conducted in Malaysia between July 11 and September 12, 2009. Newspaper, television and family were three main sources of information about A(H1N1). There were substantial ethnic differences; the Malays were significantly more likely to identify television as main source, while newspapers and family were identified as the main sources by the Chinese and Indians, respectively. Overall, the two main information needs identified were prevention and treatment. The Malays expressed lesser need for overall information than other ethnic groups. The three most preferred sources of information were television, newspapers and healthcare providers. There were significant positive correlations between amount of information received with knowledge (r = 0.149), perceived susceptibility to infection (r = 0.177), and other behavioral responses. Health information dissemination should be dedicated to meeting the information needs of diverse sociodemographic and ethnic groups. The findings highlight the importance of providing information that increases awareness and behavioral changes in disease prevention yet reduce fear.


Elderly ailing Highlanders of Papua New Guinea.
A retrospective case-control study of 100 elderly patients admitted to Goroka Hospital was undertaken. Chronic disease with cor pulmonale was the commonest condition diagnosed in this group (22%) and lobar pneumonia was the commonest infection (17%). Cancer occurred in only 5% of subjects, and in all of these patients, hepatocellular carcinoma was diagnosed. No cases of degenerative cardiovascular disease were observed. Mean hospital stay was 12.9 days.


IL-1 alpha beta blockade prevents cartilage and bone destruction in murine type II collagen-induced arthritis, whereas TNF-alpha blockade only ameliorates joint inflammation.
Anti-TNF-alpha treatment of rheumatoid arthritis patients markedly suppresses inflammatory disease activity, but so far no tissue-protective effects have been reported. In contrast, blockade of IL-1 in rheumatoid arthritis patients, by an IL-1 receptor antagonist, was only moderately effective in suppressing inflammatory symptoms but appeared to reduce the rate of progression of joint destruction. We therefore used an established collagen II murine arthritis model (collagen-induced arthritis(CIA)) to study effects on joint structures of neutralization of either TNF-alpha or IL-1. Both soluble TNF binding protein and anti-IL-1 treatment ameliorated disease activity when applied shortly after onset of CIA. Serum analysis revealed that early anti-TNF-alpha treatment of CIA did not decrease the process in the cartilage, as indicated by the elevated COMP levels. In contrast, anti-IL-1 treatment of established CIA normalized COMP levels, apparently alleviating the process in the tissue. Histology of knee and ankle joints corroborated the finding and showed that cartilage and joint destruction was significantly decreased after anti-IL-1 treatment but was hardly affected by anti-TNF-alpha treatment. Radiographic analysis of knee and ankle joints revealed that bone erosions were prevented by anti-IL-1 treatment, whereas the anti-TNF-alpha-treated animals exhibited changes comparable to the controls. In line with these findings, metalloproteinase activity, visualized by VDIPEN production, was almost absent throughout the cartilage layers in anti-IL-1-treated animals, whereas massive VDIPEN appearance was found in control and sTNFbp-treated mice. These results indicate that blocking of IL-1 is a cartilage- and bone-protective therapy in destructive arthritis, whereas the TNF-alpha antagonist has little effect on tissue destruction.