Temperature and hydrostatic pressure-dependent pathways of low-density lipoprotein transport across microvascular barrier.
To further investigate the chemical and physical nature of low-density lipoprotein (LDL) transport pathways across intact microvessels, the effect of changes in temperature and microvessel hydrostatic pressure were measured in individually perfused postcapillary vessels within frog mesenteric vascular beds. LDL microvessel transport was measured at two microvessel temperature ranges (18-21 degrees C and 4-6 degrees C) and compared with transport of fluorescein, a small solute. Also, LDL transport was measured at a series of hydrostatic pressures (3-20 cmH2O) at microvessel temperatures of 18-21 degrees C and 4-6 degrees C to determine whether LDL transport was coupled to water flow, which would be evidence for hydraulic pathways of solute transport across the microvascular barrier. Quantitative fluorescence microscopy was employed to determine apparent solute permeability coefficients (Ps) under the various temperature and hydrostatic pressure conditions studied. The ratio of Ps fluorescein 18-21 degrees C/4-6 degrees C [1.6 +/- 0.3 (SD)] indicated that fluorescein was freely diffusible across the microvascular barrier through water-filled pathways as transport was inversely proportional to temperature-dependent changes in viscosity. The larger ratio for LDL (Ps LDL 18-21/4-6 degrees C = 9.5 +/- 8.1) than for fluorescein cannot be explained by LDL transport through fixed hydraulic pathways alone and suggests additional or alternate LDL transport mechanisms. In addition, Ps LDL increased as microvessel hydrostatic pressure increased at microvessel temperatures of 18-21 degrees C but not at 4-6 degrees C. Coupling of LDL transport to water flow at the high microvessel temperature range, but not at the low range, indicated the presence of a hydraulic transport pathway that was effectively absent when the microvessel was cooled. These results demonstrated a highly temperature and hydrostatic pressure-dependent LDL pathway that is consistent with a dynamic porous extracellular or transcellular mechanism of LDL transport.


[Long-term good results of surgical treatment for spontaneous epi- and subdural hematoma in a female patient on maintenance hemodialysis].
Spontaneous intracranial hematoma is not rare, but with bad prognosis, complication in patients on maintenance hemodialysis (HD). Diagnostic difficulties result from a fact that symptoms of acute hematoma such as headaches,, nausea, vomitis, apathy, sleepiness, parestesia and seizures may also suggest dysequilibrium syndrome, dialytic dementia as well as hypertensive encephalopathy. We describe a case of female patient with 20-year interview data of hypertension on HD since 1981 because of end-stage renal failure in a course of chronic glomerulonephritis, who developed spontaneous epi- and subdural hematoma four year ago in 47 age of life. Performed CT examination confirmed diagnosis and on the same day the patient underwent right frontoparietotemporal craniotomy and the hematoma was removed. During postoperative period, HD sessions were performed without heparin. After surgery the patient developed transcient hypertonia, epileptic sizures and left-sided paresis. Currently, 48 months after craniotomy the patient is fully rehabilitated, with normal blood pressure, without epileptic sizures or palsy. Gradually we discontinued anticonvulsans and antihypertensives.


[Analysis of causes for falls in people with Parkinson's disease].
Falls in Parkinson's disease may pose a significant threat for patients. This is not only a clinical problem, but also an economic one. The effects of falls may cause deterioration of the quality of life for both patients and their caretakers. The causes of falls are not clinically uniform: the falls are caused by various factors and require a differential diagnosis. The purpose of this paper is to analyse the above mentioned causes, as well as to draw clinicians' attention to the possibility of effective therapy for certain disorders that cause such falls in patients with Parkinson's disease. 51 patients with recognized Parkinson's disease were examined, including 25 persons who reported falls that had occurred within the past 6 months and 26 persons who had no falls. In both groups there were patients with different types of the disease (tremulous, akinetic-hipertonic and mixed). The clinical status of the patients was assessed using the Hoehn and Yahr scale. In each patient Schellong test and EEG examinations were performed. It has been established that the occurrence of falls is related to the duration of the disease (on average 9.6 years in the group with falls versus 6.2 years in the group without falls) and the daily levodopa dosage (on average 806.0 mg in the group with falls versus 499.0 mg in the group without falls). The proportion of patients with abnormalities in the EEG (revealed mainly as slowing of EEG background activity) was notably higher in the group with falls. The comparison of such groups from the point of view of sex, age, stage of the disease and the occurrence of asymptomatic orthostatic hypotension did not reveal any statistically significant differences. The analysis of the causes of falls in the examined patients revealed that in 8 cases they fell due to unstable posture, 4--due to freezing or festination, 1--due to symptomatic orthostatic hypotension, 1--due to co-existing neurological disorders, 2--due to the heart arrhythmia (requiring implantation of pacemaker), in 8 persons--due to toppling falls and in 1 patients the falls could not be classified.


Myocardial fibrosis blunts nitric oxide synthase-related preload reserve in human dilated cardiomyopathy.
The purpose of the study was to investigate interactions between myocardial nitric oxide synthase (NOS) and myocardial fibrosis, both of which determine left ventricular (LV) preload reserve in patients with nonischemic dilated cardiomyopathy (DCM). In previous animal experiments, chronic inhibition of NOS induced myocardial fibrosis and limited LV preload reserve. Twenty-eight DCM patients underwent LV catheterization, balloon caval occlusions (BCO; n = 8), intracoronary substance P infusion (n = 8), and procurement of LV endomyocardial biopsies for determinations of collagen volume fraction (CVF), of gene expression of NOS2, NOS3, heme oxygenase (HO)-1, and TNF-alpha, and of NOS2 protein. CVF was unrelated to the intensity of NOS2, NOS3, HO-1, or TNF-alpha gene expression or of NOS2 protein expression. Preload recruitable LV stroke work (PR-LVSW) correlated directly with NOS2 gene expression (P = 0.001) and inversely with CVF (P = 0.04). High CVF (>10%) reduced baseline LVSW and PR-LVSW at each level of NOS2 gene expression. In DCM, myocardial fibrosis is unrelated to the intensity of myocardial gene expression of NOS, antioxidative enzymes (HO-1), or cytokines (TNF-alpha) and blunts NOS2-related recruitment of LV preload reserve.


[Multilayer analysis of signal transduction and cell cycle control in GIST. Identifying new interaction partners with differential regulation].
To identify new interactions as well as diagnostically, prognostically and therapeutically relevant differences in the regulation of gene expression in gastrointestinal stromal tumors (GISTs), we analyzed the methylation status, mRNA expression, microRNA expression, protein expression and protein phosphorylation in parallel in identical tumor tissue samples. The data were analyzed in a multilayer approach and were correlated to each other and to clinico-pathological parameters. Differentially regulated genes were mapped to signal transduction pathways which are already known to play a major role in GISTs. A functionally orientated overview of the different data layers was constructed, which enabled new insights into gene regulation in GISTs.


Tessier 30 Median Mandibular Hard and Soft Tissue Cleft, One-Stage Reconstruction Using a Template-Guided Resorbable "U"-Shaped Plate.
Midline clefts of the lower lip, tongue, and mandible are a rare type of facial cleft classified as "Tessier 30." We present the case of a female patient with an isolated Tessier 30 facial cleft affecting the tongue, lower lip, and mandibular symphysis with ankyloglossia. This was reconstructed with a template-guided resorbable "U"-shaped plate at 10 months of age. The procedure was carried out in one stage, which avoided the need for a repeat general anesthetic for the patient. We had a successful outcome with normal dental eruption and we believe such an approach could be considered as a relevant treatment modality for future cases.


A glycoprotein subunit vaccine elicits a strong Rift Valley fever virus neutralizing antibody response in sheep.
Rift Valley fever virus (RVFV), a member of the Bunyaviridae family, is a mosquito-borne zoonotic pathogen that causes serious morbidity and mortality in livestock and humans. The recent spread of the virus beyond its traditional endemic boundaries in Africa to the Arabian Peninsula coupled with the presence of susceptible vectors in nonendemic countries has created increased interest in RVF vaccines. Subunit vaccines composed of specific virus proteins expressed in eukaryotic or prokaryotic expression systems are shown to elicit neutralizing antibodies in susceptible hosts. RVFV structural proteins, amino-terminus glycoprotein (Gn), and carboxyl-terminus glycoprotein (Gc), were expressed using a recombinant baculovirus expression system. The recombinant proteins were reconstituted as a GnGc subunit vaccine formulation and evaluated for immunogenicity in a target species, sheep. Six sheep were each immunized with a primary dose of 50 μg of each vaccine immunogen with the adjuvant montanide ISA25; at day 21, postvaccination, each animal received a second dose of the same vaccine. The vaccine induced a strong antibody response in all animals as determined by indirect enzyme-linked immunosorbent assay (ELISA). A plaque reduction neutralization test (PRNT80) showed the primary dose of the vaccine was sufficient to elicit potentially protective virus neutralizing antibody titers ranging from 40 to 160, and the second vaccine dose boosted the titer to more than 1280. Furthermore, all animals tested positive for neutralizing antibodies at day 328 postvaccination. ELISA analysis using the recombinant nucleocapsid protein as a negative marker antigen indicated that the vaccine candidate is DIVA (differentiating infected from vaccinated animals) compatible and represents a promising vaccine platform for RVFV infection in susceptible species.


Inhibition of aromatic L-amino acid decarboxylase and tyrosine aminotransferase by the monoamine oxidase inhibitor phenelzine.
The concentration of p-tyramine in the rat striatum was increased significantly by intraperitoneal injection of phenelzine (5 or 100 mg/kg). Unlike other monoamine oxidase (MAO) inhibitors, phenelzine had no effect on p-tyramine levels in the first 1-2 h following injection. The high dose of phenelzine increased the p-tyramine levels much more than the low dose. In addition, the high dose of phenelzine increased striatal p-tyrosine levels significantly 12 h after injection. Further studies showed that phenelzine inhibited the tyrosine aminotransferase activity of rat liver homogenates; the IC50 was 50 microM. Phenelzine also inhibited the aromatic L-amino acid decarboxylase activity of rat brain homogenate with an IC50 of 25 microM. Following intraperitoneal injection of 100 mg/kg phenelzine, the initial concentration of phenelzine in the striatum appears to be high enough to inhibit aromatic L-amino acid decarboxylase. It is suggested that the multiple enzyme inhibition caused by administration of high doses of phenelzine accounts for its unusual effects on striatal p-tyramine levels compared with other MAO inhibitors, i.e., its initial lack of effect on p-tyramine levels followed later by very large increases in p-tyramine levels.


Microstructural characterization of gold nanoparticles synthesized by solution plasma processing.
Microstructural characteristics of gold nanoparticles (Au NPs) fabricated by solution plasma processing (SPP) in reverse micelle solutions have been studied by high-resolution transmission electron microscopy (HRTEM). The synthesized Au NPs, with an average size of 6.3 ± 1.4 nm, have different crystal characteristics; fcc single-crystalline particles, multiply twinned particles (MTPs), and incomplete MTPs (single-nanotwinned fcc configuration). The crystal structure characteristics of the Au NPs synthesized by the SPP method were analyzed and compared with similar-size Au NPs obtained by the conventional chemical reduction synthesis (CRS) method. The TEM analysis results show that the Au NPs synthesized by the CRS method have shapes and crystal structures similar to those nanoparticles obtained by the SPP method. However, from the detailed HRTEM analysis, the relative number of the Au MTPs and incomplete MTPs to the total number of the Au NPs synthesized by the SPP method was observed to be around 94%, whereas the relative number of these kinds of crystal structures fabricated by the CRS method was about 63%. It is most likely that the enhanced formation of the Au MTPs is due to the fact that the SPP method generates highly reaction-activated species under low environmental temperature conditions.


Alterations in the extracellular domain of M13 procoat protein make its membrane insertion dependent on secA and secY.
The products of genes secA and secY (SecA and SecY) are putative components of a bacterial protein export machinery and are required for the export of many periplasmic and membrane proteins. Only a few proteins, among them the M13 procoat protein, insert independently of SecA and SecY. To investigate the reason why the procoat protein inserts independently of sec functions, various hybrid proteins were constructed. By in-frame gene fusions the central procoat region, which translocates across the membrane, was extended in size. Fragments of the ompA gene ranging from 522-294 bp were ligated with the procoat gene. The hybrid proteins were inserted into the membrane and processed normally, but only in the presence of functional SecA and SecY.


[Sebaceous hyperplasia of the lower eyelid].
A 61-year-old man was evaluated for a yellow tumor located at the lid margin of his lower eyelid, which had recurred for the second time after surgical excision. The patient's ocular examination was otherwise unremarkable as was the general examination with the exception of the presence of a polyp in the colon and a family history of multiple colorectal carcinomas. The eyelid tumor was excised and histologic examination showed a sebaceous hyperplasia. When one encounters a sebaceous tumor involving the eyelid the possibility of Muir-Torre syndrome should be considered. Muir-Torre syndrome is an autosomal dominant genodermatosis characterized by at least a single sebaceous gland tumor (either a hyperplasia, an adenoma, an epithelioma, or a carcinoma) and a minimum of one internal malignancy.


Unfavorable effect of type 1 and type 2 diabetes on maternal and fetal essential fatty acid status: a potential marker of fetal insulin resistance.
Pregestational maternal diabetes increases obesity and diabetes risks in the offspring. Both conditions are characterized by insulin resistance, and diabetes is associated with low membrane arachidonic (AA) and docosahexaenoic (DHA) acids. We investigated whether type 1 and type 2 diabetes in pregnancy compromise maternal and fetal membrane essential fatty acids (FAs). We studied 39 nondiabetic (control subjects), 32 type 1 diabetic, and 17 type 2 diabetic pregnant women and the infants they delivered. Maternal and cord blood samples were obtained at midgestation and at delivery, respectively. Plasma triacylglycerols and choline phosphoglycerides and red blood cell (RBC) choline and ethanolamine phosphoglyceride FAs were assessed. The difference in maternal plasma triacylglycerol FAs between groups was not significant. However, the type 1 diabetes group had lower plasma choline phosphoglyceride DHA (3.7 +/- 0.9%; P < 0.01) than did the control group (5.2 +/- 1.6%). Likewise, RBC DHA was lower in the type 1 [choline: 3.4 +/- 1.5% (P < 0.01); ethanolamine: 5.9 +/- 2.5% (P < 0.05)] and type 2 [choline: 3.5 +/- 1.6% (P < 0.05)] diabetes groups than in the control group (choline: 5.5 +/- 2.2%; ethanolamine: 7.5 +/- 2.5%). Cord AA and DHA were lower in the plasma (type 1: P < 0.01) and RBC (type 2: P < 0.05) choline phosphoglycerides of the diabetics than of the control subjects, and cord RBC ethanolamine phosphoglycerides were lower in DHA (P < 0.05) in both diabetes groups than in the control group. Diabetes (either type) compromises maternal RBC DHA and cord plasma and RBC AA and DHA. The association of these 2 FAs with insulin sensitivity may mean that the current finding explains the higher incidence of insulin resistance and diabetes in the offspring of diabetic women.


Evaluation of liver fatty acid oxidation in the leptin-deficient obese mouse.
We hypothesized that liver fatty acid oxidation (FAO) is compromised in the leptin-deficient obese (Lep(ob)/Lep(ob)) mouse model, and that this would be further challenged when these mice were fed a high-fat diet. Obese mice had a 3.8-fold increased body fat content and a 9-fold increased liver fat content as compared to control mice when both groups were fed a low-fat diet. The expression of liver FAO enzymes, carnitine palmitoyltransferase-1a, long-chain acyl-CoA dehydrogenase, medium-chain acyl-CoA dehydrogenase, and short-chain acyl-CoA dehydrogenase, was not affected in obese mice as compared to controls on either a low-fat or a high-fat diet. The expression of very-long-chain acyl-CoA dehydrogenase was elevated in obese mice on the control diet, as compared to control mice. For all measures evaluated, increasing the level of fat in the diet had a smaller effect than leptin deficiency. In summary, despite obese mice having an excess of fat available for mitochondrial beta-oxidation in liver, overall energy balance appeared to dictate that the net liver FAO remained at control levels.


Specificity of soluble phospholipid binding sites on human factor Xa.
We explore here the specificities of lipid regulatory sites on factor X(a) that affect the rate of factor X(a)-catalyzed prothrombin activation. We examined a series of 11 phosphatidylserine (PS) analogues in order to map the structural features of a lipid molecule that are needed to elicit both the structural response and the full increase in activity that can be obtained with the PS molecule. Our observations are interpreted in terms of a model in which factor X(a) is regulated by sequential occupancy of a pair of linked lipid binding sites, each of which have different minimum ligand structural requirements to induce structural changes. The first site is apparently of higher affinity and recognizes diacylglycerol (DAG) as a minimal binding structure. The second site is occupied with an affinity slightly less than the first site only when the first is occupied, but binds PS with very low affinity otherwise. It recognizes glycerophosphorylserine (GPS) as the minimal ligand. To test this interpretation, experiments were performed in which more than one lipid species was present. It was necessary to invoke the existence of factor X(a) species containing different lipids at each site, each having different structural and functional responses. For optimal activity enhancement, both binding sites must be occupied, the first by PS, although the second can be occupied with other lipids.


Inducing and Manipulating Heteroelectronic States in a Single MoS_{2} Thin Flake.
By dual gating a few-layer MoS_{2} flake, we induce spatially separated electronic states showing superconductivity and Shubnikov-de Haas (SdH) oscillations. While the highly confined superconductivity forms at the K/K^{'} valleys of the topmost layer, the SdH oscillations are contributed by the electrons residing in the Q/Q^{'} valleys of the rest of the bottom layers, which is confirmed by the extracted Landau level degeneracy of 3, electron effective mass of 0.6m_{e}, and carrier density of 5×10^{12} cm^{-2}. Mimicking conventional heterostructures, the interaction between the heteroelectronic states can be electrically manipulated, which enables "bipolarlike" superconducting transistor operation. The off-on-off switching pattern can be continuously accessed at low temperatures by a field effect depletion of carriers with a negative back gate bias and the proximity effect between the top superconducting layer and the bottom metallic layers that quenches the superconductivity at a positive back gate bias.


ATM gene expression is associated with differentiation and angiogenesis in infiltrating breast carcinomas.
The product of the ATM gene, mutated in the human genetic disorder ataxia-telangiectasia (A-T) plays a key role in the detection and repair of DNA double-strand breaks. A-T is defined by progressive cerebellar ataxia, telangiectasia, sensitivity to ionising radiation and genomic instability with cancer predisposition. On the other hand, increased angiogenesis is essential for tumor growth and metastasis. The aim of this study was to investigate ATM expression in breast carcinomas and its relationship to neoangiogenesis. Fifty-two breast tumors from 51 patients, 38 of them with concomitant in situ component (CIS), were analyzed by immunohistochemistry for the expression of ATM. CD34 expression was used for the morphometric evaluation of vasculature. ATM was positive in 1 to 10% of normal epithelial cells. ATM expression was reduced in 55.8% of infiltrating carcinomas, non-reduced in 34.6%, and increased in 9.6%. Expression of ATM in CIS was similar to the infiltrating component in 71% of cases and reduced in 23.7% of them. High-grade ductal infiltrating carcinomas showed lower ATM expression than low-grade ones. Reduced ATM expression also correlated with increased microvascular area. Reduced ATM expression in breast carcinomas correlated with tumor differentiation and increased microvascular parameters, supporting its role in neoangiogenesis and tumor progression in breast carcinogenesis.


Life histories of hosts and pathogens predict patterns in tropical fungal plant diseases.
Plant pathogens affect the fitness of their hosts and maintain biodiversity. However, we lack theories to predict the type and intensity of infections in wild plants. Here we demonstrate using fungal pathogens of tropical plants that an examination of the life histories of hosts and pathogens can reveal general patterns in their interactions. Fungal infections were more commonly reported for light-demanding than for shade-tolerant species and for evergreen rather than for deciduous hosts. Both patterns are consistent with classical defence theory, which predicts lower resistance in fast-growing species and suggests that the deciduous habit can reduce enemy populations. In our literature survey, necrotrophs were found mainly to infect shade-tolerant woody species whereas biotrophs dominated in light-demanding herbaceous hosts. Far-red signalling and its inhibitory effects on jasmonic acid signalling are likely to explain this phenomenon. Multiple changes between the necrotrophic and the symptomless endophytic lifestyle at the ecological and evolutionary scale indicate that endophytes should be considered when trying to understand large-scale patterns in the fungal infections of plants. Combining knowledge about the molecular mechanisms of pathogen resistance with classical defence theory enables the formulation of testable predictions concerning general patterns in the infections of wild plants by fungal pathogens.


Current trends in guideline development: a cause for concern.
Although the development and use of practice-related guidelines as educational aids has a long history in the health professions, scientific assessment indicates that they have had limited success in changing practice patterns. This is principally due to the exclusion of practitioners from the development process, and the lack of a credible scientific basis for many guidelines. Past failures have led to new methods of guideline development based on a critical analysis of scientific data. These methods, which involve legitimate professional organizations at all stages of the development process, are clearly a step in the right direction. Unfortunately, there are signs that current guideline developers still fail to recognize the critical nature of the new methods or the need for an open and inclusive development process. It is even more disquieting that the objective of some guideline developers, such as licensing bodies, is the formulation of standards or review criteria, particularly when there are very few therapeutic practices with a sufficient scientific basis to justify such a designation. National and provincial societies, as well as dental educators, need to assume a leadership role to ensure that if guidelines are required, they will be developed as credible aids for the improvement of patient care. In this paper, the authors recount why the "traditional process" of guideline development resulted in guidelines that were mistrusted by the profession and, as a result, ineffective. They also outline the widely-documented current methodology, which should be followed if guidelines are to be accepted by the profession. Finally, they discuss the critical issue of who should develop guidelines, and examine their role in dental practice and education.


Histone deacetylase 6 delays motor neuron degeneration by ameliorating the autophagic flux defect in a transgenic mouse model of amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons. Abnormal protein aggregation and impaired protein degradation are believed to contribute to the pathogenesis of this disease. Our previous studies showed that an autophagic flux defect is involved in motor neuron degeneration in the SOD1(G93A) mouse model of ALS. Histone deacetylase 6 (HDAC6) is a class II deacetylase that promotes autophagy by inducing the fusion of autophagosomes to lysosomes. In the present study, we showed that HDAC6 expression was decreased at the onset of disease and became extremely low at the late stage in ALS mice. Using lentivirus-HDAC6 gene injection, we found that HDAC6 overexpression prolonged the lifespan and delayed the motor neuron degeneration in ALS mice. Moreover, HDAC6 induced the formation of autolysosomes and accelerated the degradation of SOD1 protein aggregates in the motor neurons of ALS mice. Collectively, our results indicate that HDAC6 has neuroprotective effects in an animal model of ALS by improving the autophagic flux in motor neurons, and autophagosome-lysosome fusion might be a therapeutic target for ALS.


Quantifying and Reducing Uncertainties in Cancer Therapy.
There are two basic sources of uncertainty in cancer chemotherapy: how much of the therapeutic agent reaches the cancer cells, and how effective it is in reducing or controlling the tumor when it gets there. There is also a concern about adverse effects of the therapy drug. Similarly in external-beam radiation therapy or radionuclide therapy, there are two sources of uncertainty: delivery and efficacy of the radiation absorbed dose, and again there is a concern about radiation damage to normal tissues. The therapy operating characteristic (TOC) curve, developed in the context of radiation therapy, is a plot of the probability of tumor control vs. the probability of normal-tissue complications as the overall radiation dose level is varied, e.g. by varying the beam current in external-beam radiotherapy or the total injected activity in radionuclide therapy. The TOC can be applied to chemotherapy with the administered drug dosage as the variable. The area under a TOC curve (AUTOC) can be used as a figure of merit for therapeutic efficacy, analogous to the area under an ROC curve (AUROC), which is a figure of merit for diagnostic efficacy. In radiation therapy AUTOC can be computed for a single patient by using image data along with radiobiological models for tumor response and adverse side effects. In this paper we discuss the potential of using mathematical models of drug delivery and tumor response with imaging data to estimate AUTOC for chemotherapy, again for a single patient. This approach provides a basis for truly personalized therapy and for rigorously assessing and optimizing the therapy regimen for the particular patient. A key role is played by Emission Computed Tomography (PET or SPECT) of radiolabeled chemotherapy drugs.


Injuries among young soccer players.
We registered all new injuries among 496 male youth soccer players, aged 12 to 18 years, during the course of one year. The incidence of injury was 3.7 injuries per 1000 hours of soccer per player. The incidence increased with age, and at the higher ages within the youth players, approached the incidence rate of senior players (age greater than or equal to 18 years). Seventy percent of the injuries were located in the lower extremities, particularly the knee (26%) and ankle (23%). Back pain occurred in 14% of players. Fractures, which accounted for 4% of injuries, were most often in the upper extremities. We conclude that youth soccer is a relatively low-risk sport with an injury pattern that differs slightly from that of senior players.


A novel molecular solution for ultraviolet light detection in Caenorhabditis elegans.
For many organisms the ability to transduce light into cellular signals is crucial for survival. Light stimulates DNA repair and metabolism changes in bacteria, avoidance responses in single-cell organisms, attraction responses in plants, and both visual and nonvisual perception in animals. Despite these widely differing responses, in all of nature there are only six known families of proteins that can transduce light. Although the roundworm Caenorhabditis elegans has none of the known light transduction systems, we show here that C. elegans strongly accelerates its locomotion in response to blue or shorter wavelengths of light, with maximal responsiveness to ultraviolet light. Our data suggest that C. elegans uses this light response to escape the lethal doses of sunlight that permeate its habitat. Short-wavelength light drives locomotion by bypassing two critical signals, cyclic adenosine monophosphate (cAMP) and diacylglycerol (DAG), that neurons use to shape and control behaviors. C. elegans mutants lacking these signals are paralyzed and unresponsive to harsh physical stimuli in ambient light, but short-wavelength light rapidly rescues their paralysis and restores normal levels of coordinated locomotion. This light response is mediated by LITE-1, a novel ultraviolet light receptor that acts in neurons and is a member of the invertebrate Gustatory receptor (Gr) family. Heterologous expression of the receptor in muscle cells is sufficient to confer light responsiveness on cells that are normally unresponsive to light. Our results reveal a novel molecular solution for ultraviolet light detection and an unusual sensory modality in C. elegans that is unlike any previously described light response in any organism.


Inhibitors of glutamine synthetase and their potential application in medicine.
Glutamine synthetase (E.C. 18.104.22.168) - an enzyme catalyzing formation of glutamine from glutamate and ammonium ion, is one of the most important enzymes in nitrogen metabolism. Due to glutamine synthetase activity, inorganic nitrogen is incorporated in the cell metabolism and is further used in biosynthesis of several highly important metabolites. The first part of the review presents the long-dating research on inhibitors of glutamine synthetase which started with the discovery of methionine sulfoximine in 1949. Since that time several inhibitors of this enzyme, classified in the following groups: derivatives of methionine sulfoximine, phosphorus containing analogues of glutamic acid, bisphosphonates and miscellaneous inhibitors, have been developed and described. Analysis of their structure-activity relationships is presented in some detail. The second part of the paper is dedicated to potential medical application of glutamine synthetase inhibitors, which proved to act as effective anti-tuberculosis agents with high selectivity towards the pathogenic bacteria. Moreover, it was also shown that glutamine synthetase inhibitors could be successfully applied in cancer therapy.


Potassium channels keep mobile cells on the go.
Cell motility is a prerequisite for the creation of new life, and it is required for maintaining the integrity of an organism. Under pathological conditions, "too much" motility may cause premature death. Studies over the past few years have revealed that ion channels are essential for cell motility. This review highlights the importance of K+ channels in regulating cell motility.


Surface and chemical characteristics of platinum modified activated carbon electrodes and their electrochemical performance.
Platinum (Pt) loaded activated carbons (ACs) were synthesized by the thermal decomposition of platinum (II) acetylacetonate (Pt(acac)2) over chemically activated glucose-based biochar. The effect of Pt loading on surface area, pore characteristics, surface chemistry, chemical structure, and surface morphology were determined by various techniques. XPS studies proved the presence of metallic Pt0 on the AC surface. The graphitization degree of Pt loaded ACs were increased with the loaded Pt0 amount. The electrochemical performance of the Pt-loaded ACs (Pt@AC) was determined not only by the conventional three-electrode system but also by packaged supercapacitors in CR2032 casings. The capacitive performance of Pt@AC electrodes was investigated via cyclic voltammetry (CV), galvanostatic charge-discharge curves (GCD), and impedance spectroscopy (EIS). It was found that the Pt loading increased the specific capacitance from 51 F/g to 100 F/g. The ESR drop of the packaged cell decreased with the Pt loading due to the fast flow of charge through the conductive pathways. The results showed that the surface chemistry is more dominant than the surface area for determining the capacitive performance of Pt loaded AC-based packaged supercapacitors.


Atypical post-kala-azar dermal leishmaniasis resembling histoid leprosy.
An adult male with atypical lesions of post-kala-azar dermal leishmaniasis (PKDL) is described. He had extensive ulcerated noduloplaque lesions on his hands, feet and genitalia. He had been diagnosed and treated for leprosy in the past. He came from an area endemic for kala-azar and leprosy and had a previous history of kala-azar. There was an abundance of Leishman Donovan bodies in slitskin smears and in histopathology sections. There was a good therapeutic response to sodium stibogluconate. An ulcerative variant of PKDL has been described but is extremely rare. Extensive lesions with ulceration have not been described before to the best of our knowledge. The epidemiological significance of the case is discussed.


Transvaginal pelvic abscess drainage with US guidance.
Transvaginal catheter drainage of pelvic and intraabdominal abscesses with the use of real-time ultrasound guidance is described. The technique was successfully used in two patients to drain abscesses in the cul-de-sac. Transvaginal drainage is a safe, simple alternative to transabdominal, transgluteal, and transrectal drainage of these abscesses.


IL-4 inhibits growth factor-stimulated rheumatoid synoviocyte proliferation by blocking the early phases of the cell cycle.
A major feature of rheumatoid arthritis is an uncontrolled proliferation of synoviocytes. This is consistent with the active production of factors such as platelet-derived growth factor (PDGF) and IL-1 by the synovitis, which act in vivo as well as in vitro as potent synoviocyte growth factors. We have previously shown that IL-4 is able to inhibit growth factor production in an ex vivo model of synovitis. Herein, we show that IL-4 strongly inhibited PDGF and IL-1 beta stimulated rheumatoid arthritis synoviocyte proliferation in a dose-dependent manner and through its 130 kDa receptor. This antiproliferative effect of IL-4 directly correlated with a blockade of the synoviocyte cell cycle at the G0 + G1 phases. We also observed that IL-4 induced striking morphologic changes in IL-1 beta or PDGF-stimulated synoviocytes, including increased volume and granulosity. These changes led to major perturbations of the cell monolayer, associated with a marked decrease of synoviocyte viability. Taken together, these data indicate that IL-4 inhibits growth factor-induced proliferation of synoviocytes by interfering with the cell cycle, and by decreasing cell survival.


Phenylalkyl isothiocyanate-cysteine conjugates as glutathione S-transferase stimulating agents.
To develop analogues of phenylalkyl isothiocyanate with less toxicity and better biological activity, two water-soluble phenylalkyl isothiocyanate-cysteine conjugates, S-[N-benzyl(thiocarbamoyl)]-L-cysteine (1) and S-[N-(3-phenylpropyl)(thiocarbamoyl)]-L-cysteine (2), were synthesized. The induction of increased activity of the detoxifying enzyme glutathione S-transferase by the conjugates and their parent compounds was determined and compared in several tissues of A/J mice. The biological evaluation revealed that the conjugates as GST enzyme inducers appeared to be less toxic and even more potent than the parent compounds in the mouse bladder. Compounds 1 was much more active than 2 in all the tissues examined, while their parent compounds showed an inverse order of activity. Thus, an increase in the alkyl chain length of the parent isothiocyanates or a decrease in the alkyl length of the conjugates could result in higher enzyme-inducing activity in the same compound series. Since a number of nitrosamines have been identified as prime bladder carcinogens and phenylalkyl isothiocyanates have been reported to inhibit a wide range of carcinogenic nitrosamines, the corresponding conjugates may serve as prodrugs to protect against nitrosamine-induced urinary bladder carcinogenesis once they are delivered to the target organ.


Peripheral Arterial Stiffness Increases the Risk of Progression of Renal Disease in Type 2 Diabetic Patients.
Aims: Our aim was to investigate the effects of peripheral arterial stiffness on the risk of progression of renal disease in patients with type 2 diabetes (T2D). Methods: This was a single center, retrospective cohort study. Brachial-ankle pulse wave velocity (baPWV) tests were performed on T2D patients in 2015. Increased arterial stiffness was defined as baPWV of ≥ 1800 cm/s. We applied criteria for progression of renal disease according to EMPA-REG OUTCOME trial. Results: In total, 186 patients were enrolled in the final study. The mean age was 59.1 years and male:female ratio was 1.73:1. Thirteen (7%) patients progressed to renal disease during the average follow-up time of 35.3 months. In particular, the risk of progression to macroalbuminuria was significantly higher in the baPWV ≥ 1800 cm/s group (HR 6.216, p = 0.020). Individuals with a baPWV of ≥ 1800 cm/s (when comparisons were adjusted for age, sex, blood pressure, diabetes duration, eGFR, and use of renin-angiotensin system inhibitors) had a significantly higher risk of the progression of renal disease (HR = 8.480, p = 0.014). Conclusion: These results suggest that peripheral arterial stiffness (baPWV ≥ 1800 cm/s) may be a risk factor for the progression of renal disease in T2D patients.


Quality of life in diabetic patients registered with primary health care services in Sweden.
To evaluate the health-related quality of life in diabetic subjects in primary health care. A cross-sectional, questionnaire survey of diabetic patients registered with primary health services, compared with a standard population sample. Three community health centres in the Metropolitan Stockholm area. 341 diabetic individuals aged 21-84 years, with 229 respondents, i.e. 67%. Matched controls of the same age and sex from a standard population sample of 2366 individuals. Quality of life was assessed by the Swedish Health-Related Quality of Life Survey (SWEDQUAL), adopted from the Medical Outcomes Study and consisting of 61 items covering aspects of physical, mental, social, and general health. Medical data were extracted from the medical records. Diabetic patients had significantly lower scores on all scales (p < 0.001 for ten, and p < 0.01 for one), except for social health, when compared with the standard population sample. Outcomes were correlated with vascular and non-vascular comorbidity, age, and income, but not with level of metabolic control. Diabetic patients in primary health care have a markedly lower health-related quality of life, compared with a standard population.


Structural characterisation, stability and antibody recognition of chimeric NHBA-GNA1030: an investigational vaccine component against Neisseria meningitidis.
A new generation multi-component vaccine, principally directed against serogroup B Neisseria meningitidis (4CMenB), has recently been developed. One of its components, identified through reverse vaccinology, is the neisserial heparin-binding antigen (NHBA) which is included in the formulation as a novel NHBA-GNA1030 fusion protein (NHBA-FP). We describe here the biophysical characteristics of this vaccine antigen to understand better its structural properties in solution and concurrent immunogenicity prior to formulation. By deliberately stressing the protein to lose its immune responses, we were able to study the protein's structural changes at the molecular level. The unmodified NHBA-FP was found to be mainly monomeric with mass of 67kDa and secondary structure dominated by β-sheets and turns (57% average). The antigen was very stable in storage buffer. It could be forced to unfold in a low-salt buffer resulting in the exposure of one of its two tryptophan residues at 50°C. Long-term stress studies (10-15 days at 37°C) showed modification in the chromatographic and electrophoretic profiles with progressive degradation and aggregation. Since there was little change in secondary structure (as monitored by circular dichroism and tryptophan fluorescence spectroscopy), the loss of functional immunogenicity of the thermal stressed protein could be mainly attributed to the observed fragmentation and aggregation. We therefore conclude that the maintenance of the intact, non-fragmented state of the NHBA-FP is important to preserve its functional immunogenicity. This may thus be utilised as an assay for the control testing of the protein.


Stunting and associated factors among 6-23 month old children in drought vulnerable kebeles of Demba Gofa district, southern Ethiopia.
Stunting is impaired linear growth of children: they experience stunting in the first 1000 days after conception and is an indication of chronic malnutrition. Children under the age of two are regarded as the most vulnerable to malnutrition due to their rapid growth and greater exposure to infectious disease. To assess the magnitude and associated factors of stunting among 6 to 23-month-old children in drought-vulnerable kebeles of the Demba Gofa district, southern Ethiopia. A community-based cross-sectional study was conducted from February to March 2021. Systematic random sampling was used to select pairs of mothers/caregivers with children aged 6 to 23 months. A semistructured questionnaire and anthropometric measurement were used to collect the data. The data were checked coded and entered into Epi-data version 3.1 and exported to SPSS for Windows version 20.0 for analysis. Simple and multivariable linear regressions were conducted. The level of significance was declared at 95% CI and p-value < 0.05. The magnitude of stunting in the study area was 79(21.82%). Household dietary diversity [β = 0.217, 95% CI, 0.093-0.342], early initiation of complementary feeding [β = 0.444, 95% CI, 0.344-0.543], frequency of breastfeeding within 24 h [β = 0.217, 95% CI, 0.179-0.263] and child eating animal source food [β = 0.351, 95% CI, 0.196-0.506] were positively significant predictors of child height/length-for-age (HAZ). The extent of stunting in the study area is relatively lower than that in regional and national reports, but one out of five children were still stunted. Therefore, health education on infant and young child feeding practices should be provided to mothers to reduce the problem.


Obesity and survival in patients with heart failure and preserved systolic function: a U-shaped relationship.
Studies document better survival in heart failure patients with decreased left ventricular ejection fraction (EF) and higher body mass index (BMI; kg/m(2)) compared to those with a lower BMI. However, it is unknown if this "obesity paradox" applies to heart failure patients with preserved EF or if it extends to the very obese (BMI >35). We determined all-cause mortality for 1,236 consecutive patients with a prior diagnosis of heart failure and a preserved EF (> or =50%). Obesity (BMI>30) was noted in 542 patients (44%). The mean age was 71 +/- 12 years, but this varied depending on BMI. One-year all-cause mortality decreased with increasing BMI, except at BMI >45 where mortality began to increase (55% if BMI <20, 38% if BMI 20-25, 26% if BMI 26-30, 25% if BMI 31-35, 17% if BMI 36-40, 18% if BMI 41-45, and 25% if BMI>45, P < .001). After adjustment for patient age, history, medications, and laboratory and echocardiographic parameters, the hazard ratios for total mortality (relative to BMI 26-30) were 1.68 (95% CI, 1.04-2.69) for BMI <20, 1.25 (95% CI, 0.92-1.68) for BMI 20 to 25, 0.99 (95% CI, 0.71-1.36) for BMI 31-35, 0.58 (95% CI, 0.35-0.97) for BMI 36 to 40, 0.79 (95% CI, 0.44-1.4) for BMI 41 to 45, and 1.38 (95% CI 0.74-2.6) for BMI >45 (P < .0001). Low BMI is associated with increased mortality in patients with heart failure and preserved systolic function. However, with a BMI of >45, mortality increased, raising the possibility of a U-shaped relationship between BMI and survival.


In vitro biological and mechanical evaluation of various scaffold materials for myocardial tissue engineering.
A cardiac patch is a construct devised in regenerative medicine to replace necrotic heart tissue after myocardial infarctions. The cardiac patch consists of a scaffold seeded with stem cells. To identify the best scaffold for cardiac patch construction we compared polyurethane, Collagen Cell Carriers, ePTFE, and ePTFE SSP1-RGD regarding their receptiveness to seeding with mesenchymal stem cells isolated from umbilical cord tissue. Seeding was tested at an array of cell seeding densities. The bioartificial patches were cultured for up to 35 days and evaluated by scanning electron microscopy, microscopy of histological stains, fluorescence microscopy, and mitochondrial assays. Polyurethane was the only biomaterial which resulted in an organized multilayer (seeding density: 0.750 × 10(6) cells/cm(2)). Cultured over 35 days at this seeding density the mitochondrial activity of the cells on polyurethane patches continually increased. There was no decrease in the E Modulus of polyurethane once seeded with cells. Seeding of CCC could only be realized at a low seeding density and both ePTFE and ePTFE SSP1-RGD were found to be unreceptive to seeding. Of the tested scaffolds polyurethane thus crystallized as the most appropriate for seeding with mesenchymal stem cells in the framework of myocardial tissue engineering.


Do Concepts of Depression Predict Treatment Pathways? A Closer Look at Explanatory Models Among Clinical and Nonclinical Samples in Uganda.
Explanatory models (EMs) are a collection of beliefs about a disorder that can help us understand help-seeking and treatment pathways in diverse contexts. In 2 related studies, we explore EMs about depression held among both clinical and nonclinical samples in Uganda. To explore the potential of EMs to predict help seeking, we assessed the relationship between 2 main aspects of the EM: problem conceptualization and treatment. In Study 1, we interviewed and assessed EMs of depression for 135 lay community members and 111 professional practitioners using a vignette. In Study 2, we assessed actual EMs among 33 clinically depressed adults. We transcribed all interviews and analyzed and coded the content. In Study 1, we used logistic regression to examine the relationship of problem conceptualization and stigma to treatment choice; in Study 2, we used Fisher's exact tests to examine the relationship between conceptualization and treatment. Sociodemographics such as age, income, and language were also examined. Interviews elicited a diverse range of beliefs about the nature of depression and the types of treatment needed. However, problem conceptualization did not predict treatment in either group. Instead, education and interview language predicted treatment in clinical and nonclinical samples. Although EMs can be useful for both exploring mental health and treatment-related beliefs in clinical settings and developing mental health services, contextual factors may be more significant predictors of help seeking.


Modulation of cisPlatin cytotoxicity by interleukin-1 alpha and resident tumor macrophages.
The modulation of cisPlatin cytotoxicity by interleukin-1 (IL-1 alpha) was studied in cultures of SCC-7 tumor cells with and without tumor macrophages to examine potential mechanisms for the synergistic antitumor activity of cisPlatin and IL-1 alpha in SCC-7 solid tumors. Neither IL-1 alpha nor tumor macrophages affected the survival of clonogenic tumor cells and IL-1 alpha had no direct effect on tumor cell growth in vitro. Macrophages had no direct effect on cisPlatin sensitivity (IC90 = 6.0 microM), but, the addition of IL-1 alpha (500-2000U/ml) to co-cultures of cisPlatin pretreated tumor cells and resident tumor macrophages increased cell killing (IC90 = 3.1 microM). Similar responses were seen in primary cultures treated with cisPlatin before IL-1 alpha. The modulation of cisPlatin cytotoxicity by IL-1 alpha exhibited a biphasic dose response that paralleled the IL-1 alpha dose dependent release of H2O2 by resident tumor macrophages. Further, IL-1 alpha modification of cisPlatin cytotoxicity was prompt and inhibited by catalase. CisPlatin and exogenous H2O2 (50 microM) produced more than additive SCC-7 clonogenic cell kill and hydroxyl radicals played an important role in the response. Interleukin-1 modulation of cisPlatin cytotoxicity was schedule dependent. IL-1 alpha treatment for 24 hrs, before cisPlatin, produced drug resistance (IC90 = 11.1 microM). Our study shows that IL-1 alpha can stimulate tumor macrophages to release pro-oxidants that modify cellular chemosensitivity in a schedule and dose dependent fashion. Our findings may also provide a mechanistic explantation for the synergistic antitumor activity of cisPlatin and IL-1 alpha in vivo.


CLE6 expression recovers gibberellin deficiency to promote shoot growth in Arabidopsis.
Small peptides act as local signals during plant development, but few studies have examined their interaction with phytohormone signaling. Here, we show that application of gibberellin (GA) to Arabidopsis shoots induces substantial accumulation of transcripts encoded by CLE6, a member of the CLAVATA/ESR-RELATED (CLE) gene family, in the root stele, followed by promotion of organ growth by CLE6 in GA-deficient plants. The long-distance effect of GA4 was demonstrated by the observation that its application to the shoot apex of the GA-deficient mutant ga3ox1/ga3ox2 rescued the short-root phenotype. Microarray analysis was used to identify root-expressed genes that respond to systemic application of GA, and CLE6 was selected for further analysis. CLE6 was highly expressed in roots at the young seedling stage, and CLE6 promoter activity was strong in hypocotyls and roots, especially in root stele cells at branch points. Application of CLE6 peptide had no obvious effect on the growth and development of GA-deficient mutant plants. Nonetheless, the fact that ectopic over-expression of CLE6 in the GA-deficient mutant promoted root growth and branching, petiole elongation, bolting rate and stem length showed that CLE6 expression partially compensates for the GA deficiency. Reciprocal grafting of GA-deficient mutant plants to 35S::CLE6 transformants complemented the shoot phenotype associated with GA deficiency, demonstrating the systemic effect of CLE6 from root to shoot. These data suggest that root-expressed CLE6 is systemically involved in shoot growth under GA action in Arabidopsis.


Synthesis of Aggregation-Induced Emission-Active Conjugated Polymers Composed of Group 13 Diiminate Complexes with Tunable Energy Levels via Alteration of Central Element.
Conjugated polymers containing boron and gallium diiminate complexes were prepared with various electron-donating comonomers via pre- and post-complexation methods, respectively. From a comparison of emission quantum yields between solution and film states, it was seen that all polymers containing group 13 elements possessed an aggregation-induced emission property. Additionally, the frontier orbital energies and the optical and electrochemical properties of the polymers can be tuned by altering a central element at the complex moieties as well as by changing a comonomer unit. In particular, it was demonstrated that the gallium atom can contribute to stabilizing the energy levels of the lowest unoccupied molecular orbitals, resulting in narrow band gaps of the conjugated polymers. This study presents the potential of gallium not only for preparing solid-state emissive conjugated polymers but also for fabricating low-band gap materials by employing the conjugated ligand.


Gabor-GLCM-Based Texture Feature Extraction Using Flame Image to Predict the O2 Content and NO x.
Flame image feature extraction is the basis for boiler combustion monitoring and control. The flame video images of recent research are mainly derived from experimental burners in the laboratory, and few pay attention to the flame images in industrial boilers. The actual industrial boiler flame images differ significantly from the laboratory flame images. Additionally, certain flame image features cannot be captured in the laboratory owing to the limitations of the camera installations. Therefore, a flame image texture feature extraction algorithm based on an industrial boiler is proposed in this paper. The texture features were enhanced using a Gabor filter for the RGB channels of the flame images, and then, the statistics of the texture features were scalarized by a gray-level co-occurrence matrix (GLCM). The data were filtered and downscaled by a data compressor consisting of Gaussian-weighted mean and principal component analysis (PCA) to obtain eight key variables. The extracted eight variables were verified to be effective in characterizing the O2 and NO x contents of flue gas using the mutual information method. The combustion process regression model was constructed using a gated recurrent unit (GRU) on the 8 h combustion data of the boiler, and the predicted mean absolute percentage error (MAPE) for O2 and NO x content in the test set reached 7.5 and 10.2%, respectively. Compared to the conventional methods of direct PCA on images and GLCM plus PCA on images, the MAPE for O2 content prediction was reduced by 12.3 and 7.3%, and the MAPE for NO x content prediction was reduced by 10.5 and 6.1%, respectively. The advantage of the new flame feature based on Gabor-GLCM is suitable for the subsequent analysis and control of an industrial combustion system.


[Transgenerational transmission of bovine satellite DNA in transgenic mice].
Genetical, cytogenetical and molecular analysis was made for 5 generations of mice transgenic for bovine satellite DNA (Sat). In all cases transgenic mice were generated by crosses of transgenic males and females with normal (CBA x C57B1) mice. No abnormalities in the founder development were noticed. A normal (near 50 %) ratio of transgenic and nontransgenic offsprings was observed in blastocysts. However, profound differences occurred in the rate of transgene bearing offsprings, depending on the sex of grandparents rather than of parents. The grandfather Sat transmission resulted in the appearance of 0-52.4 % transgenic grandchildren, whereas the grandmother transmission ended in the theoretically expected rate. This means that stabilization of transsatellite took place upon the female germ line transmission (a positive grandmother effect). It is essential that in hemizygous transsatellite mice Sat integration led to the occurrence of mammary tumors, inflammation of uterine horns, and infringement of mother care of transgenic females. Simultaneous FISH and G-banding showed Sat to be localized in the internal region of chromosome 12 near Pax 9 and Brms 11 genes. Commonly, these genes are implicated in tumorigenesis as their expression decreases. Thus, a kind of silencing effect of these genes' expression may be supposed.


Mitochondrial mutations in cancer.
The metabolism of solid tumors is associated with high lactate production while growing in oxygen (aerobic glycolysis) suggesting that tumors may have defects in mitochondrial function. The mitochondria produce cellular energy by oxidative phosphorylation (OXPHOS), generate reactive oxygen species (ROS) as a by-product, and regulate apoptosis via the mitochondrial permeability transition pore (mtPTP). The mitochondria are assembled from both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) genes. The mtDNA codes for 37 genes essential of OXPHOS, is present in thousands of copies per cell, and has a very high mutations rate. In humans, severe mtDNA mutations result in multisystem disease, while some functional population-specific polymorphisms appear to have permitted humans to adapt to new environments. Mutations in the nDNA-encoded mitochondrial genes for fumarate hydratase and succinate dehydrogenase have been linked to uterine leiomyomas and paragangliomas, and cancer cells have been shown to induce hexokinase II which harnesses OXPHOS adenosine triphosphate (ATP) production to drive glycolysis. Germline mtDNA mutations at nucleotides 10398 and 16189 have been associated with breast cancer and endometrial cancer. Tumor mtDNA somatic mutations range from severe insertion-deletion and chain termination mutations to mild missense mutations. Surprisingly, of the 190 tumor-specific somatic mtDNA mutations reported, 72% are also mtDNA sequence variants found in the general population. These include 52% of the tumor somatic mRNA missense mutations, 83% of the tRNA mutations, 38% of the rRNA mutations, and 85% of the control region mutations. Some associations might reflect mtDNA sequencing errors, but analysis of several of the tumor-specific somatic missense mutations with population counterparts appear legitimate. Therefore, mtDNA mutations in tumors may fall into two main classes: (1) severe mutations that inhibit OXPHOS, increase ROS production and promote tumor cell proliferation and (2) milder mutations that may permit tumors to adapt to new environments. The former may be lost during subsequent tumor oxygenation while the latter may become fixed. Hence, mitochondrial dysfunction does appear to be a factor in cancer etiology, an insight that may suggest new approaches for diagnosis and treatment.


Development of an Asia-Pacific regional network for public health.
As public health by its very nature is multi-disciplinary, it may benefit individual programs to formulate a regional network, joining researchers and academics across programs. This approach may afford extended benefits, such as the establishment of regional health surveillance systems and collaborative funding initiatives. To explore this potential, member institutions comprising the Asia-Pacific Academic Consortium for Public Health provided data to form an aggregate profile of cross-institutional expertise and resources, which was presented to Health Specialists at the Asian Development Bank. The study provided a foundation for a planned regional network. A four-pronged approach was proffered detailing concurrent aspects of development: 1) network formation and expansion, 2) research coordination, 3) cross-institutional communication and instruction, and 4) promotion of self-sufficiency. The proposed plan affords the groundwork for an improved approach to public health research and practice that builds upon the established Consortium, and encourages new horizons. Regionalization is an increasing phenomenon world wide, and should be furthered as a concept for improved public health intervention and control.


Conformational features of crystal-surface cellulose from higher plants.
Native cellulose in higher plants forms crystalline fibrils a few nm across, with a substantial fraction of their glucan chains at the surface. The accepted crystal structures feature a flat-ribbon 21 helical chain conformation with every glucose residue locked to the next by hydrogen bonds from O-3' to O-5 and from O-2 to O-6'. Using solid-state NMR spectroscopy we show that the surface chains have a different C-6 conformation so that O-6 is not in the correct position for the hydrogen bond from O-2. We also present evidence consistent with a model in which alternate glucosyl residues are transiently or permanently twisted away from the flat-ribbon conformation of the chain, weakening the O-3' - 0-5 hydrogen bond. Previous molecular modelling and the modelling studies reported here indicate that this 'translational' chain conformation is energetically feasible and does not preclude binding of the surface chains to the interior chains, because the surface chains share the axial repeat distance of the 21 helix. Reduced intramolecular hydrogen bonding allows the surface chains to form more hydrogen bonds to external molecules in textiles, wood, paper and the living plant.


Curcumin-Based Inhibitors of Thrombosis and Cancer Metastasis Promoting Factor CLEC 2 from Traditional Medicinal Species Curcuma longa.
The CLEC-2 receptor protein belongs to the C-type lectin superfamily of transmembrane receptors that have one or more C-type lectin-like domains. CLEC-2 is a physiological binding receptor of podoplanin (PDPN), which is expressed on specific tumour cell types and involved in tumour cell-induced platelet aggregation and tumour metastasis. CLEC-2 and podoplanin-expressing tumour cells interact to increase angiogenesis, tumour development, and metastasis. CLEC-2 is a hemi-immunoreceptor tyrosine-based activation motif (hemi-ITAM) receptor located on platelets and a subset of dendritic cells that are expressed constitutively. This molecule is secreted by activated platelets around tumours and has been shown to inhibit platelet aggregation and tumour metastasis in colon carcinoma by binding to the surface of tumour cells. Pharmacokinetic studies were carried using a DrugLiTo, and molecular docking was performed using AutoDock Tools 1.5.6 (ADT). Twenty-nine bioactive compounds were included in the study, and four of them, namely, piperine, dihydrocurcumin, bisdemethoxycurcumin, and demothoxycurcumin, showed potential antagonist properties against the target. The resultant best bioactive was compared with commercially available standard drugs. Further, validation of respective compounds with an intensive molecular dynamics simulation was performed using Schrödinger software. To the best of our knowledge, this is the first report on major bioactive found on clove as natural antagonists for CLEC-2 computationally. To further validate the bioactive and delimit the screening process of potential drugs against CLEC-2, in vitro and in vivo studies are needed to prove their efficacy.


A comparative evaluation of bone regeneration using mesenchymal stem cells versus blood coagulum in sinus augmentation procedures.
The present study evaluated the quality and quantity of new bone formation in the maxillary sinus lift procedures and stability of implants in posterior atrophic maxilla. This prospective randomized controlled split-mouth study included 20 patients (16 males and 4 females having a mean age of 36.7 years) having atrophic maxilla. They were divided randomly into two groups: Group A using mesenchymal stem cells and Group B into blood coagulum. They were radiographically evaluated using cone-beam computed tomography (CBCT) for residual bone height preoperatively and availability of new bone formation around implants, density, and stability of implants 6 months postoperatively. The placement of dental implants in posterior maxilla is challenging due to rapid resorption of alveolar bone after extraction of teeth due to pneumatization of maxillary sinuses. In both the groups, more pain and swelling were observed in the 2nd postoperative day which gradually decreased over a period of 7 days. Membrane perforation occurs in only four cases (20%). A significant gain in alveolar bone height was observed in Group A (7.69 mm ± 2.5 mm) and Group B (9.32 mm ± 2 mm) after 6 months. On comparing both the groups, there is a similar significant increase in bone density in Hounsfield units postoperatively at various levels buccally and palatally. Total 40 sinuses were lifted and 42 implants were placed, respectively. All implants showed primary stability. Such findings provide a significant contribution in future perspective studies that the use of stem cells had the same success rate as blood coagulum.


Biallelic variants in BRCA1 gene cause a recognisable phenotype within chromosomal instability syndromes reframed as BRCA1 deficiency.
Pathogenic variants in BRCA1 gene in heterozygous state are known to be associated with breast-ovarian cancer susceptibility; however, biallelic variants cause a phenotype recognised as Fanconi anaemia complementation group S. Due to its rarity, medical management and preventive screening measures are insufficiently understood. Here, we present nine individuals (one new and eight previously presented) with biallelic variants in BRCA1 gene, to delineate clinical features in comparison with other chromosome instability syndromes and understand the patients' health risk. Features seen in these 9 individuals (7 females/2 males) include prenatal and postnatal growth failure (9/9), microcephaly (9/9), hypo/hyperpigmented lesions (9/9), facial dysmorphism (9/9), mild developmental delay (8/9) and early-onset solid tumours (5/9). None presented bone marrow failure or immunodeficiency. Individuals with biallelic variants in BRCA1 also showed chromosomal instability by mitomycin and diepoxybutane test. The phenotype caused by biallelic BRCA1 variants is best framed between Fanconi anaemia and Nijmegen syndrome, yet distinct due to lack of bone marrow failure and immunodeficiency. We hypothesise that disease class should be reframed and medical management in people with biallelic variants in BRCA1 should emphasise on detection of solid tumour development and avoiding exposure to ionising radiation.


Potential diagnostic and prognostic value of the long non-coding RNA SNHG3 in human cancers: A systematic review and meta-analysis.
Small nucleolar RNA host gene 3 (SNHG3), as a novel long non-coding RNA (lncRNA) participates in the oncogenic processes of various cancers. We combined a systematic review and a meta-analysis to assess the potential role of SNHG3 as a pan-cancer marker for cancer diagnosis and prognosis. Our study comprehensively searched for SNHG3 expression profiling studies from PubMed, Web of Science, Excerpta Medica Database (EMBASE), Cochrane Library, Google Scholar, and The Cancer Genome Atlas (TCGA). The diagnostic capacity of SNHG3 for all cancers in TCGA database was evaluated from the perspective of pooled sensitivity, specificity, diagnostic odds ratio (DOR), area under the curve (AUC) of the summary receiver operating characteristic (sROC) curve. Also, this research studied the correlation of SNHG3 expression and the overall survival to access its prognostic value. A sum total of 11,888 cancer patients and 730 controls from 44 eligible studies were enrolled in this integrated analysis. In TCGA database, SNHG3 was significantly upregulated in most types of cancers (16/33, 48%). The pooled sensitivity, specificity, and DOR with 95% CIs was 0.72 (95% CI: 0.60-0.82), 0.87 (95% CI: 0.84-0.90), and 18 (95% CI: 11-30), respectively. Similarly, the AUC of the sROC curve was 0.89 (95% CI: 0.86-0.92), indicating SNHG3 was highly conserved as a diagnosis biomarker. Additionally, SNHG3 overexpression significantly deteriorated the overall survival of cancer patients (pooled HR = 1.28, 95% CI:1.11-1.48; P < 0.05). These findings suggest that the lncRNA SNHG3 could serve as a promising diagnostic and prognostic biomarker.


Modeling compositional heterogeneity.
Compositional heterogeneity among lineages can compromise phylogenetic analyses, because models in common use assume compositionally homogeneous data. Models that can accommodate compositional heterogeneity with few extra parameters are described here, and used in two examples where the true tree is known with confidence. It is shown using likelihood ratio tests that adequate modeling of compositional heterogeneity can be achieved with few composition parameters, that the data may not need to be modelled with separate composition parameters for each branch in the tree. Tree searching and placement of composition vectors on the tree are done in a Bayesian framework using Markov chain Monte Carlo (MCMC) methods. Assessment of fit of the model to the data is made in both maximum likelihood (ML) and Bayesian frameworks. In an ML framework, overall model fit is assessed using the Goldman-Cox test, and the fit of the composition implied by a (possibly heterogeneous) model to the composition of the data is assessed using a novel tree-and model-based composition fit test. In a Bayesian framework, overall model fit and composition fit are assessed using posterior predictive simulation. It is shown that when composition is not accommodated, then the model does not fit, and incorrect trees are found; but when composition is accommodated, the model then fits, and the known correct phylogenies are obtained.


Computer-Based Analysis of Hologram Imagery and Aberrations II: Aberrations Induced by a Wavelength Shift.
Numerical values are shown for the aberrations that are induced by a wavelength shift from construction to reconstruction. The holograms discussed in this paper may be constructed and reconstructed from a plane wave or point source. Four types of hologram geometries have been studied: in-line, off-axis, near-image plane, and lensless-fourier transform. The aberrations are first considered where the reconstruction beam geometry is the same as that needed to reconstruct an ideal image if no wavelength shift is present. The change in wavelength, however, causes aberrations and these are discussed as a function of the various hologram geometries and parameters. A considerable reduction in the aberrations can be realized in off-axis holograms by a technique of aberration balancing. In one example the total aberrations were reduced to approximately a Rayleigh limit of lambda/4 in a hologram that was recorded at 4880 A and reconstructed at 6328 A. The minimum aberrations possible using the balancing process are discussed with respect to various hologram parameters.


The effect of natalizumab on disability score and relapse rate of multiple sclerosis patients: a prospective cohort study.
Multiple sclerosis (MS) is a progressive immune-related disorder of the central nervous system leading to destruction of myelin sheaths. Natalizumab is a humanized monoclonal antibody against the cell adhesion molecule α4-integrin which has been approved for treatment of relapsing forms of MS. This study aims at determining the effect of natalizumab on expanded disability status scale (EDSS) score and relapse rate of MS patients. Fifty MS patients participated in the present prospective cohort study. Twenty patients (Mean age ± SD: 33 ± 6.03) received natalizumab and 30 patients (Mean age ± SD: 36.83 ± 7.24) were under treatment with IFN-β (control group). Patients were followed-up during a 12-month period. EDSS score and clinical signs were assessed monthly. Significant decreases were detected in EDSS score in natalizumab treated patients compared with the controls in months 10, 11 and 12. EDSS score showed a significant decrease in 80% of natalizumab treated patients. Number of relapses was significantly lower in natalizumab treated patients compared with control group. Natalizumab is effective in improvement of disability and reduction of relapse rate in MS patients.


Long-term HbA1c variability and the development and progression of diabetic retinopathy in subjects with type 2 diabetes.
This study aimed to investigate whether long-term HbA1c variability is associated with the development and progression of diabetic retinopathy (DR) in subjects with type 2 diabetes. We retrospectively reviewed 434 type 2 diabetes subjects without DR who underwent regular DR screening. We reviewed fundus findings, collected HbA1c levels, and calculated the coefficient of variation (CV) and average real variability (ARV) of each subject's HbA1c level. DR was developed in 55 subjects and progressed to moderate nonproliferative DR or worse DR in 23 subjects. On Cox proportional hazards regression analysis, HbA1c ARV, but not HbA1c CV, was significantly associated with DR development. However, the association between HbA1c variability and the DR progression rate to moderate nonproliferative DR or worse DR was not significant. The inter-visit HbA1c difference value on consecutive examination predicted DR development well and more careful screening for DR is needed for those with an absolute value change of 2.05%, an absolute increase of 1.75%, and an absolute decrease of 1.45% in HbA1c levels on consecutive examination. These results indicate that long-term glucose variability measured by HbA1c ARV might be an independent risk factor for DR development in addition to the mean HbA1c level in early diabetic subjects.


Swiss cheese interventricular septum presenting with catastrophic stroke: the potential role of ECG-gated CTA.
Ventricular septal defect is a common congenital cardiac condition that presents in a variety of morphologies. Less commonly, when an individual patient is found to have multiple ventricular septal defects, the term "Swiss cheese ventricular septal defect" is applied. Although not routinely utilized in clinical practice, electrocardiogram (ECG)-gated computed tomographic angiography (CTA) has been shown to provide utility in detecting intracardiac shunts, demonstrating promise in preventing acute strokes secondary to a paradoxical embolus from occurring; this is especially important when atypical cardiac septa are suspected. This case seeks to illustrate how usage of ECG-gated CTA can assist in early detection and prevention of adverse outcomes resulting from an atypical presentation of a ventricular septal defect.


Hand preferences in sign-learning students with autistic disorder.
The purpose of the study was fourfold: (a) to document the hand preferences of nonspeaking individuals with autism as they produced signs and nonsign actions; (b) to find out if sign-language proficiency in such individuals is associated with directionality or consistency of signing hand preference; (c) to explore the link between hand preference for signing and standardised measures of cognitive and motor development; (d) to compare the hand preferences (sign and nonsign actions) of such individuals to sign-learning children with normal cognitive functioning. In this study, the hand preferences of 14 nonspeaking students with autistic disorder were determined from videotape records of their sign production and nonsign actions. In their sign production, four students strongly favoured their right hands, four had a distinct left-hand preference, and six did not significantly favour either hand. There was little evidence linking sign-language proficiency, cognitive maturity, or motor development to strongly lateralised signing or handedness in general in these students. Compared with the hand preferences of the children in the two comparison groups, the autistic students were markedly less lateralised with respect to signing, but not nonsign actions.


Medication and programming in controlling the behavior of mentally retarded individuals in community settings.
Behavioral outcomes of a behavioral-chemical intervention procedure on stereotypic and non-compliant behavior were evaluated. One group (n = 22) of community-based mentally retarded clients was initially on psychotropic medication (major tranquilizers). Their dosage was either increased, decreased, or kept the same following behavioral intervention. A second group (n = 19) was placed on psychotropic medication following behavioral intervention. A nonequivalent between-groups design was employed that permitted 36 outcome combinations involving Conditions X Subject X Group. The effects of behavioral intervention, the validity of drug-intervention decision rules, drug-intervention effects, and the validity of the behavioral-chemical intervention model were evaluated. Results indicated that the behavioral-chemical intervention produced expected and desirable behavioral change as well as reduced levels of psychotropic drug usage.


Methodical approaches in the identification of areas with a potential risk of infection by bird schistosomes causing cercarial dermatitis.
Larval stages (cercariae) of schistosomatid flukes represent the causative agents of swimmer's itch (cercarial dermatitis), a waterborne allergic disease. Cercariae of bird schistosomes are the most frequently reported agent. Recent studies on parasite behaviour in mammals showed that infections by cercariae can be linked to more than skin syndromes. Despite the failure of complete development in mammals, bird schistosomes can escape from the skin and migrate transitorily in the hosts. These findings brought novel insights into the fate and potential pathogenic effect of the parasites in non-compatible hosts, including humans. Cercarial dermatitis occurs globally and recently is considered to be re-emerging; however, there are no data on the number of afflicted persons per year. This might be explained by a relatively low interest in human skin infections arising after bathing in fresh water. In addition, the real occurrence of bird schistosomes in the field is known only for a few areas. The paucity of epidemiological/biogeographical data is probably caused by difficulties associated with detection of the parasites in intermediate and definitive hosts. Therefore, based on personal experience and data available in the literature, we have summarized methodological approaches enabling the detection of bird schistosomes in various hosts and environments.


Lessons we have learned from our children: cancer risks from diagnostic radiology.
The A-bomb survivors represent the best source of data for risk estimates of radiation-induced cancer. It is clear that children are ten times more sensitive than adults to the induction of cancer. The introduction of helical CT has transformed diagnostic radiology, especially in pediatric patients. The undoubted benefits carry the price tag of much higher doses, and in children, even higher effective doses. The A-bomb data have "matured" and we now have cancer risk estimates for a dose range which coincides with the organ doses from pediatric CT. Individuals exposed 50 years ago to doses comparable to those associated with helical CT today, show a small but statistically significant excess incidence of cancer. There are no assumptions, and no extrapolations involved. An abdominal helical CT scan in a young girl results in a risk of fatal cancer later in life that amounts to about one in a thousand. The risk to the individual is small, and readily balanced by the medical benefits. The public health problem is, however, significant when the small individual risk is multiplied by the 2.7 million of such procedures performed annually. Every effort is needed to minimize doses by an appropriate choice of peak kilovoltage (kVp) and milliampere-seconds (mAs), and at the same time to urge a more selective use of pediatric CT.


Chemoproteomic discovery of cysteine-containing human short open reading frames.
The application of ribosome profiling and mass spectrometry technologies has recently revealed that the human proteome is larger than previously appreciated. Short open reading frames (sORFs), which are difficult to identify using traditional gene-finding algorithms, constitute a significant fraction of unknown protein-coding genes. Thus, experimental approaches to identify sORFs provide invaluable insight into the protein-coding potential of genomes. Here, we report an affinity-based approach to enrich and identify cysteine-containing human sORF-encoded polypeptides (ccSEPs) from cells. This approach revealed 16 novel ccSEPs, each derived from an uncharacterized sORF, demonstrating its potential for discovering new genes. We validated expression of a SEP from its endogenous RNA, and demonstrated the specificity of our labeling approach using synthetic SEP. The discovery of additional human SEPs and their conservation indicate the potential importance of these molecules in biology.


Promises and pitfalls of deep neural networks in neuroimaging-based psychiatric research.
By promising more accurate diagnostics and individual treatment recommendations, deep neural networks and in particular convolutional neural networks have advanced to a powerful tool in medical imaging. Here, we first give an introduction into methodological key concepts and resulting methodological promises including representation and transfer learning, as well as modelling domain-specific priors. After reviewing recent applications within neuroimaging-based psychiatric research, such as the diagnosis of psychiatric diseases, delineation of disease subtypes, normative modeling, and the development of neuroimaging biomarkers, we discuss current challenges. This includes for example the difficulty of training models on small, heterogeneous and biased data sets, the lack of validity of clinical labels, algorithmic bias, and the influence of confounding variables.


Critical Care Updates for the Nephrologist, 2016.
With improvements in supportive care, mortality from sepsis and the acute respiratory distress syndrome has declined over the past 20 years. However, mortality associated with these conditions is still high. We will review the latest clinical trial findings in these fields, along with implications for the nephrologist. Very recently, there have been significant changes with regard to the management of anterior ischemic strokes; given the high rate of cerebrovascular disease in patients with CKD or ESRD, we will review those studies here. Finally, we will comment on best care practices in the intensive care unit, which are relevant to the nephrologist.


Technique of using Cionni capsular tension ring in the management of of ectopia lentis cases.
Ectopia lentis is a condition that compromises vision in childhood by inducing either double vision or aphakic visual axis. Correction of lens status is of prime importance to prevent amblyopia or sensory strabismus. Placing an intraocular lens (IOL) in the bag in such cases will maintain aqueous vitreous barrier but it is a difficult task.This video demonstrates the method of placing modified Cionni capsular tension ring (CTR) and placement of IOL in children. This video shows the management of multiple cases of ectopia lentis with more than 180 degree subluxation. Making intact rhexis is crucial and technically difficult in such cases. The way of making a proper capsulorhexis is shown. After making capsulorhexis, all the cases were managed with single loop Cionni CTR. Cionni CTR has a loop with a anterior offset of 0.4 mm to override the anterior capsule. It has two designs - right and left design, based on the position of islet in the CTR. Since the offset of the hook is tiny, there are high chances to flip the Cionni CTR. If the Cionni CTR is placed in a flipped manner, it would not give effective pull of the bag, when fixated to sclera. And also, it could be traumatic to explant and place in correct manner. Hence it is vital to place the Cionni CTR in correct orientation, so that anterior offset will orient anteriorly. This video gives guidance to the viewers about the correct way of placing different designs of Cionni CTR in different types of subluxation.Timing of passing sutures through sclera may be done either before or after placing the Cionni CTR in the bag. Both the ways are demonstrated in different cases. Different technique of doing Cionni CTR fixation with IOL placement are demonstrated. Surgeons who wish to try this procedure can choose the option that they feel comfortable with. We conclude that choice of Cionni CTR design and technique of placement depends on surgeon's choice and not based on the type of subluxation. https://youtu.be/zbdpP0lhykw.


[Gender-specific aspects of physicians work].
The influences of physicians' and patients' gender on the prescription behaviour seems to be important in background of epidemiology, economy and medicine. Dataset of 24 physicians (general and internal medicine) and their 11 322 patients in 1995 and 1996 were examined focusing the prescription of psychopharmaceuticals, analgesics and hypnoticals. Distinct effects of physicians gender were shown: Male physicians prescribed more frequently drugs in all three groups (p < 0,001). In the prescription of analgesics, male physicians prescribed significantly more daily defined doses (DDD) (p = 0,001). Concerning the patients' gender it was shown, that female patients received psychopharmaceuticals significantly more frequently than male patients. The results point out that there are differences in the prescribing behaviour of psychopharmaceuticals, analgesics and hypnoticals. This surprising result should be taken into consideration in research and training of physicians.


Contribution of in Vivo Experimental Challenges to Understanding Flat Oyster Ostrea edulis Resistance to Bonamia ostreae.
Bonamiosis due to the parasite Bonamia ostreae has been associated with massive mortality outbreaks in European flat oyster stocks in Europe. As eradication and treatment are not possible, the control of the disease mainly relies on transfer restriction. Moreover, selection has been applied to produce resistant flat oyster families, which present better survival and lower prevalence than non-selected oysters. In order to better understand the mechanisms involved in resistance to bonamiosis, cellular and molecular responses of 2 oyster groups (selected oysters and wild-type oysters) were analyzed in the context of experimental injection and cohabitation infections. Cellular responses including non-specific esterases detection, ROS production and phagocytosis activity were analyzed by flow cytometry. Four genes homologous to those shown to be involved in immunity were selected (Inhibitor of apotosis OeIAP, Fas ligand OeFas-ligand, Oe-SOD, and OeEc-SOD) and monitored by quantitative reverse-transcription PCR (qRT-PCR). Infected oysters showed higher phagocytosis activity than controls. Infected selected oyster show a lower phagocytosis activity which might be a protection against the parasite infection. The expression of OeIAP and OeFas-ligand gene was significantly increased in selected oysters at 5 days post-injection. OeIAP gene expression appeared to be significantly increased in wild-type oysters at 8 days post-injection. Our results suggest that resistance to bonamiosis partly relies on the ability of the oysters to modulate apoptosis.


Two-dimensional electrophoresis of human serum proteins modified by ampicillin during therapeutic treatment.
Two-dimensional electrophoretograms of serum proteins from ampicillin-treated patients were analyzed-by immunoblotting with an antiserum specific for penicilloyl groups. As expected, human serum albumin (HSA) was the main ampicilloylated serum component. Transferrin main form II was found to be the second most important component as regards immunoblotting intensity. Immunoreactive spots were present on the acidic side of the transferrin isoelectric series, suggesting a modification mechanism similar to that observed in HSA, i.e., acylation of basic amino acid residues. Several additional ampicilloylated spots were detected but could not be assigned. Their electrophoretic parameters were determined using internal standards. This is the first description of serum proteins other than HSA being modified by ampicillin in the course of routine therapeutic treatment.


Charles fabry.
The opening session of the 1968 International Ozone Symposium in Monaco was a centenary year ribute to Charles Fabry. This paper is a record of the three speeches made during the session.


Pharmacist assessment of drug allergies.
The impact of pharmacist-conducted drug allergy assessment on patient allergy labeling and subsequent drug therapy is reported. Pharmacists at an acute-care teaching hospital interviewed selected patients to verify their drug allergy status. If an interview resulted in the removal of an allergy label from the patient's allergy profile, the patient's medication profile was monitored daily to detect any subsequent use of the drug. If the targeted drug was prescribed, the patient's clinical status was assessed to determine the effect of the prescribed drug. A total of 606 drug allergy assessments were conducted in 358 patients. The allergy label was removed after 169 (28%) of the assessments; at least one label was removed for 121 (34%) of the patients. Fourteen patients (4%) received a targeted drug or drugs. Four of these patients had signs of clinical improvement. No adverse allergic reactions were observed in patients who received targeted agents. By interviewing patients, pharmacists identified and removed inappropriate drug allergy labels, enabling patients to receive medication that otherwise would have been withheld.


Continuous tonic spike activity in spider warm cells in the absence of sensory input.
The warm cells of the spider tarsal organ respond very sensitively to low-amplitude changes in temperature and discharge continuously as the rate of change in temperature reaches zero. To test whether the continuous tonic discharge remains without sensory input, we blocked the warm cell's receptive region by Epoxy glue. The activity continued in this situation, but its dependence on temperature changes was strongly reduced. We interpret this to mean that the warm cells exhibit specific intrinsic properties that underlie the generation of the tonic discharge. Experiments with electrical stimulation confirmed the observation that the warm cells persist in activity without an external drive. In warm cells with blocked receptive region, the response curves describing the relationship between the tonic discharge and the level of depolarization is the same for different temperatures. In warm cells with intact receptive region, the curves are shifted upward with rising temperature, as if the injected current is simply added to the receptor current. This indicates a modulating effect of the receptor current on the tonic discharge. Stimulation causes a change in the tonic discharge rate and thereby enables individual warm cells to signal the direction in addition to the magnitude of temperature changes.


A honey bee hexamerin, HEX 70a, is likely to play an intranuclear role in developing and mature ovarioles and testioles.
Insect hexamerins have long been known as storage proteins that are massively synthesized by the larval fat body and secreted into hemolymph. Following the larval-to-pupal molt, hexamerins are sequestered by the fat body via receptor-mediated endocytosis, broken up, and used as amino acid resources for metamorphosis. In the honey bee, the transcript and protein subunit of a hexamerin, HEX 70a, were also detected in ovaries and testes. Aiming to identify the subcellular localization of HEX 70a in the female and male gonads, we used a specific antibody in whole mount preparations of ovaries and testes for analysis by confocal laser-scanning microscopy. Intranuclear HEX 70a foci were evidenced in germ and somatic cells of ovarioles and testioles of pharate-adult workers and drones, suggesting a regulatory or structural role. Following injection of the thymidine analog EdU we observed co-labeling with HEX 70a in ovariole cell nuclei, inferring possible HEX 70a involvement in cell proliferation. Further support to this hypothesis came from an injection of anti-HEX 70a into newly ecdysed queen pupae where it had a negative effect on ovariole thickening. HEX 70a foci were also detected in ovarioles of egg laying queens, particularly in the nuclei of the highly polyploid nurse cells and in proliferating follicle cells. Additional roles for this storage protein are indicated by the detection of nuclear HEX 70a foci in post-meiotic spermatids and spermatozoa. Taken together, these results imply undescribed roles for HEX 70a in the developing gonads of the honey bee and raise the possibility that other hexamerins may also have tissue specific functions.


A multifunctional dual-shell magnetic nanocomposite with near-infrared light response for synergistic chemo-thermal tumor therapy.
The synergistic tumor therapy in single nanoplatform has always been the goal for high efficacy tumor treatment while still remains great challenge. This paper reports a versatile nanotheranostic platform enlisting magnetic iron oxide nanoparticles, polydopamine (PDA), gold nanocages (Au nanocage) and metal organic framework (MOF, MIL101-NH2 ) in order to achieve synergistic chemothermal tumor therapy both in vitro and in vivo. The prepared magnetic photothermal nanoparticles (MPNPs) exhibit high drug loading capacity (31.34 mg/g), superior photo-thermal capacity (11.5°C enhancement in 180 s), low bio-toxicity, good magnetic resonance with a low dosage of 22 μg/g, as well as high antitumor efficacy in vivo. Such a novel and multifunctional nanoplatform is expected to find promising applications in target tumor synergistic therapy.


Altered event processing in persons with Parkinson's disease.
Persons with Parkinson's disease (PD) often show particular problems in seemingly simple routines despite relatively preserved cognitive function. We therefore investigated the processing of everyday events on behavioral and neurophysiological levels in a PD and control group. The participants had to indicate via button press whether three sequentially presented sub-events described a previously defined event (e.g., going grocery shopping). Sub-event sequences were either correct or included an event that did not belong to the event (content violation), or events were chronologically wrong (temporal violation). During task execution event-related potentials (ERPs) were recorded. Generally, the PD group showed less accurate performance independently from task conditions, and reaction times to temporal violations were particularly slow compared to the control group. Regarding ERP results, the control group showed a right lateralized N400 effect in response to content violations, which was absent in the PD group indicating altered content event processing. Concerning the reanalysis of content event violations, the expression of late positive components (LPCs) was similar between both groups. Upon temporal violations, both groups also showed a LPC with a tendentially earlier onset in the PD group, resembling positive components indicative of novelty processing. Together, these findings suggest poor event prediction in PD, which may originate from weak event representation or retrieval and possibly relate to prevalent behavioral dysfunctions in everyday life in PD.


Growth of Spoilage Bacteria in Broth and Vacuum-Packed Bologna-Type Sausage at Fluctuating Temperatures and Low Temperature Storage.
The influence of fluctuating temperatures on some important spoilage bacteria, i.e., Brochothrix thermosphacta , Serratia liquefaciens and a Lactobacillus sp., as well as Vibrio sp. and Yersinia enterocolitica was determined in broth culture and in vacuum-packed Bologna-type sausage. Temperatures used were -2.0, 2.0 and 5.0°C. The influence of fluctuating temperatures varied considerably among the organisms studied. B. thermosphacta grew irrespective of temperature, numbers of S. liquefaciens decreased each time the product was stored at -2°C but grew at temperatures above 0°C. The effect on the Lactobacillus sp., depended on the initial storage temperature, whereas no significant difference in numbers of Y. enterocolitica were observed during fluctuating temperature storage. Generally the time-temperature combination was important and was the determining factor in the number of bacteria present after equivalent periods at the incubation temperatures above and below 0°C. The study indicated that with short periods of 2 to 3 d at each temperature, B. thermosphacta was favored. For long periods of 5 or 7 d at each temperature, lactics, S. liquefaciens and Vibrio sp. also increased to high numbers. B. thermosphacta , but neither S. liquefaciens nor Y. enterocolitica grew at a constant temperature of -2°C.


The Significance of Proteomic Biomarkers in Male Breast Cancer.
Breast cancer in men (MBC) is an uncommon malignancy and accounts for only 1% of all diagnosed breast cancers. By using genomic and transcriptomic approaches, researchers have been able to expand our insight into the genetic basis of breast cancer, by providing new biomarkers. We currently know that gene analysis by itself does not show the complete picture. Along with the genomic approach, proteomics are crucial for the improvement of breast cancer diagnosis, sub-classification, for predicting response to different treatment modalities and for predicting prognosis. There are great challenges in identifying discriminatory proteins and the use of specific techniques along with additional analytical tools is required. A number of techniques allow testing for proteins produced during specific diseases. In this review, an effort is made to summarize the studies and results linked to the implementation of proteomics in the field of MBC detection and diagnosis.