Leptin, ghrelin, and adiponectin in the metabolic adjustment to burn injury in children.
Leptin, adiponectin, and ghrelin have diverse roles in the control of inflammation and metabolism in a normal state as well as in a chronic disease state. The aim of this study was to evaluate their role in the extreme metabolic and proinflammatory state after burn injury and during the initial weeks of recovery. A prospective descriptive study in a tertiary care center was undertaken. Patients were comprised of 5 children aged 20-108 months with severe burn injury; burn size ranged from 15%-36% of total body surface area. Early enteral feeding, according to estimated energy expenditure, was initiated as 150% of the recommended dietary allowance and in accordance with the patients' nitrogen balance. Seven blood samples were collected sequentially, approximately 5 days apart, during the first 65 days after the burn injury. Samples were tested for leptin, ghrelin, and adiponectin. Leptin, ghrelin, and adiponectin had a similar trajectory of concentration over time: low levels at the beginning, increasing until 2-3 weeks post-burn, where they reached a plateau at 5 weeks post-injury. The typical inverse correlations of ghrelin and adiponectin with leptin were absent. Interleukin-6 was negatively associated with ghrelin and adiponectin and was not associated with leptin. Insulin-like growth factor-1 (IGF-1) had a positive association with the 3 hormones; however, their profiles differ in their relationship to the expected concentration based on a literature review. Ghrelin and adiponectin were higher, leptin and IGF-1 were lower than expected. In the early weeks after burn injury, the hypermetabolic state and inflammation have a major effect on leptin, ghrelin, and adiponectin. The concurrent and similar change of the 3 hormones serves the parallel anabolic and catabolic processes during the recovery from burn injury. .


Characterization of a cationic phosphonium surfactant for micellar electrokinetic chromatography: using the linear solvation energy relationships model.
A phosphonium surfactant is introduced as a pseudostationary phase for MEKC and its performance and selectivity are compared to that of an analogous ammonium surfactant. The linear solvation energy relationship model has been applied to the two cationic surfactants, allowing the contributions of five chemical factors to the interactions between solutes and the micelles to be evaluated. Differences in the pseudophases cohesivity and acid/base interactions were observed. Despite the significant differences observed in the solvation parameter results the two phases have remarkably similar electrophoretic properties, with the anodic EOF produced by the dynamic coating and the electrophoretic mobility of the two surfactants being statistically equal.


Predominance of a proinflammatory phenotype in monocyte-derived macrophages from subjects with low plasma HDL-cholesterol.
Reduced plasma concentrations of high-density lipoprotein-cholesterol (HDL-C) are a significant risk factor for cardiovascular disease. Mechanisms that regulate HDL-C concentrations represent an important area of investigation. Comparative transcriptome analyses of monocyte-derived macrophages (MDM) from a large population of low HDL-C subjects and age- and sex-matched controls revealed a cluster of inflammatory genes highly expressed in low HDL-C subjects. The expression levels of peroxisome proliferator activated receptor (PPAR) gamma and several antioxidant metallothionein genes were decreased in MDM from all low HDL-C groups compared with controls, as was the expression of other genes regulated by PPARgamma, including CD36, adipocyte fatty acid binding protein (FABP4), and adipophilin (ADFP). In contrast, PPARdelta expression was increased in MDM from low HDL-C groups. Quantitative RT-PCR corroborated all major findings from the microarray analysis in two separate patient cohorts. Expression of several inflammatory cytokine genes including interleukin 1beta, interleukin 8, and tumor necrosis factor alpha were highly increased in low HDL-C subjects. The activated proinflammatory state of monocytes and MDM in low HDL-C subjects constitutes a novel parameter of risk associated with HDL deficiency, related to altered expression of metallothionein genes and the reciprocal regulation of PPARgamma and PPARdelta.


Cervical spondylotic myelopathy: a case report.
A case of cervical spondylotic myelopathy is presented, and the literature reviewing its etiology is discussed. Computed tomography is believed to be the most accurate method to use in order to confirm a diagnosis of cervical spondylotic myelopathy. Manipulation of the cervical spine is contraindicated for this condition.


Cerebral microvascular complications of type 2 diabetes: stroke, cognitive dysfunction, and depression.
Adults with type 2 diabetes are at an increased risk of developing certain brain or mental disorders, including stroke, dementia, and depression. Although these disorders are not usually considered classic microvascular complications of diabetes, evidence is growing that microvascular dysfunction is one of the key underlying mechanisms. Microvascular dysfunction is a widespread phenomenon in people with diabetes, including effects on the brain. Cerebral microvascular dysfunction is also apparent in adults with prediabetes, suggesting that cerebral microvascular disease processes start before the onset of diabetes. The microvasculature is involved in the regulation of many cerebral processes that when impaired predispose to lacunar and haemorrhagic stroke, cognitive dysfunction, and depression. Main drivers of diabetes-related cerebral microvascular dysfunction are hyperglycaemia, obesity and insulin resistance, and hypertension. Increasing amounts of data from observational studies suggest that diabetes-related microvascular dysfunction is associated with a higher risk of stroke, cognitive dysfunction, and depression. Cerebral outcomes in diabetes might be improved following treatments targeting the pathways through which diabetes damages the microcirculation. These treatments might include drugs that reduce dicarbonyl compounds, augment cerebral insulin signalling, or improve blood-brain barrier permeability and cerebral vasoreactivity.


Antibiotic susceptibility of black-pigmented Bacteroides isolates from the human oral cavity.
The minimal inhibitory concentrations of penicillin and six other antibiotics were determined for 66 oral black-pigmented Bacteroides isolates by using the National Committee for Clinical Laboratory Standards proposed standard agar dilution technique. These results plus iodometric determination of beta-lactamase activity showed that oral isolates of black-pigmented Bacteroides are remaining relatively susceptible to commonly used antibiotics.


Antagonistic actions of retinoic acid and dexamethasone on anchorage-independent growth and epidermal growth factor binding of normal rat kidney cells.
Type beta transforming growth factor (TGF-beta), in combination with epidermal growth factor (EGF) can induce nonneoplastic normal rat kidney cells to express a transformed phenotype and to form colonies in soft agar. Retinoic acid by itself has no effect on colony formation; but at concentrations of 10(-9) M or greater, it can greatly enhance the response of the cells to EGF and TGF-beta, as measured by colony growth in soft agar and expression of a transformed morphology in monolayer culture. Dexamethasone, at concentrations above 10(-9) M, has an opposite effect, inhibiting the TGF-beta-dependent formation of colonies in soft agar and restoring a more normal morphology to the cells. Added simultaneously, these two modulators act antagonistically; at equimolar concentrations, their opposite effects on colony formation are canceled. Retinoic acid and dexamethasone also have opposite and antagonistic effects on the binding of 125I-labeled EGF to normal rat kidney cells. Retinoic acid enhances the binding of EGF up to 6-fold, while dexamethasone reduces the binding to 50 to 60% of control levels. These effects on EGF binding show a dose dependence similar to the effects on colony formation in soft agar and on morphology in monolayer culture. Optimal effects on binding are observed 40 to 60 hr after treatment of the cells. It can be concluded that the abilities of retinoic acid and dexamethasone to alter expression of the transformed phenotype induced by treatment of normal rat kidney cells with TGF-beta and EGF are mediated at least in part through their effects on the EGF receptor.


Bacterial infection in exacerbated COPD with changes in sputum characteristics.
We examined the risk factors for bacterial exacerbation, defined as the presence of pathogenic bacteria in sputum, in 90 chronic obstructive pulmonary disease (COPD) patients with an exacerbation and changes in sputum characteristics. Smoking, alcohol, lung function, body mass index, medical visits and treatments were the independent variables assessed using multivariable logistic regression modelling (OR, 95% CI). A bacterial exacerbation was diagnosed in 39 (43.3%) of 90 patients. Bacterial exacerbations were more prevalent among current smokers (OR 3.77, 95% CI 1.17-12.12), in patients with poor compliance with inhalation therapy (OR 3.25, 95% CI 1.18-8.93) and with severe lung function impairment (FEV1 OR 0.96, 95% CI 0.93-1.00). Prior use of antibiotics was a risk factor for Pseudomonas aeruginosa infection (OR 6.06, 95% CI 1.29-28.44) and influenza vaccination appeared to have a protective effect against this infection (OR 0.15, 95% CI 0.03-0.67). We conclude that severe impairment of lung function, smoking and poor compliance with therapy are risk factors for bacterial infection in COPD, and P. aeruginosa should be suspected in patients who have been treated with antibiotics and in those not vaccinated against influenza.


Gallstones and Concomitant Gastric Helicobacter pylori Infection.
Background. The association of gallstones with Helicobacter pylori has been investigated but not clearly demonstrated. In this study, the presence of H. pylori in the gallbladder mucosa of patients with symptomatic gallstones was investigated. Method. Ninety-four consecutive patients with symptomatic gallstone disease were enrolled for the study. Gastroscopy and gastric H. pylori urease test were done before cholecystectomy to all patients who accepted. After cholecystectomy, the gallbladder tissue was investigated in terms of H. pylori by urease test, Giemsa, and immunohistochemical stain. Results. Overall 35 patients (37%) gallbladder mucosa tested positive for H. pylori with any of the three tests. Correlation of the three tests Giemsa, IHC, and rapid urease test was significant (r s : 0590, P > 0.001). Rapid urease test was positive in the gastric mucosa in 47 (58.7%) patients, and it was positive in the gallbladder mucosa in 21 patients (22%). In 15 patients both gastric and gallbladder tested positive with the urease test. There was significant correlation of rapid urease test in both of gallbladder and gastric mucosa (P = 0.0001). Conclusion. Study demonstrates the presence of H. pylori in the gallbladders of 37% of patients with symptomatic gallstones.


[Morbidity among the workers of the hydrolysis yeast production].
Influence of protein-containing dust on the workers results in respiratory diseases. Individuals working in the shops with high level of protein-containing dust in the air of workplace more frequently demonstrate chronic bronchitis and exogenous allergic alveolitis, workers of the shops with low level of the dust in the air of workplace more commonly suffer from bronchial asthma. The authors necessitate adaptation of engineering, technical and medical prophylactic means to lower the morbidity level.


Peripheral neuropathy in the hands of diabetic patients with lower extremity amputations.
One hundred unilateral ambulatory lower extremity amputees underwent sensibility testing of their remaining foot and right hands to determine if the magnitude of peripheral neuropathy present in the feet of patients with diabetes was of greater magnitude than that in their hands. Testing was performed with a series of Semmes-Weinstein monofilaments. Ninety-one of the subjects were male, and 9 were female. Sixty-five were diabetic, 40 required insulin. The magnitude of peripheral neuropathy was compared between the hands and feet of patients with and without diabetes, and between insulin-dependent and non-insulin-dependent diabetics. There was a slight trend to a more severe degree of insensitivity in the feet as compared with the hands in each of the individual groups. There was no statistically significant difference when comparing hand and foot sensibility in any of the comparison groupings. The quantitative amount of peripheral neuropathy appears to affect the hands and feet of diabetics in a similar "stocking-glove" fashion. The results of this screening gives further support to the concept of prophylactic foot care programs in diabetics with peripheral neuropathy to decrease the risk for the development of foot ulcers, which are often the precursor of eventual lower extremity amputation.


[Direct and prolonged effect of thyroliberin in ultra small doses on contractility of the white rat mesentery lymphatic vessels].
The prolonged effect of thyroliberin in ULD after single intramuscular injection on contractility of lymphatic vessels directly was investigated. The controlled group of animals received injection of 0.2 ml of physiological solution. The experimental group was injected by 0.2 ml of thyroliberin in concentrations of 10(-10) or 10(-16) mol/l (1 x 10(-4) and 1 x 10(-10) micrograms/kg of the body weight respectively). During the experiment the animals were grouped in the following way: 1) directly after the injection; 2) 3 hours later; 3) on the 1st day and then every day during 2 weeks. Lymphatic vessels reactivity of the experimental animals as well as controlled was studied by application of thyroliberin and noradrenalin (in concentrations of 1 x 10(-16) and 1 x 10(-6) mol/l respectively) directly on mesentery lymphatic vessels. The lymphatic vessels reaction in control group of animals on the noradrenalin and thyroliberin was the same during the period of observation. Thyroliberin stimulated contractility at concentration of 1 x 10(-16) mol/l. The reaction of experimental group was dramatically decreased to 10(-4) mol/l on the 1st and the 3rd day (in the case i.m. injected concentration 1 x 10(-10) mol/l) and to 10(-10) mol/l (in the case of i.m. injected concentration 10(-16) mol/l). The lymphatic vessels reactivity to exogenous thyroliberin gradually established at the 6-7th days till 12th day from the moment of thyroliberin injection. The mechanisms of the action of thyroliberin in ULD are discussed.


Hydrolysis of organic sulfates in periportal and pericentral regions of the liver lobule: studies with 4-methylumbelliferyl sulfate in the perfused rat liver.
The hydrolysis of 4-methylumbelliferyl sulfate by liver sulfatases to free fluorescent 4-methylumbelliferone and the subsequent formation of the glucuronide conjugate were studied in the isolated perfused rat liver. In livers from fed, phenobarbital-treated rats, 4-methylumbelliferyl sulfate (0.25-1.5 mM) was hydrolyzed rapidly to free 4-methylumbelliferone at maximal rates of about 5 mumol/g/hr. A major fraction of the free 4-methylumbelliferone formed was converted to the glucuronide at maximal rates around 20 mumol/g/hr. Similar rates of hydrolysis were observed in livers from fasted, phenobarbital-treated or normal rats, although the ratio of glucuronide to free product was decreased markedly by fasting. In liver homogenates, however, rates of organic sulfate hydrolysis exceeded those observed in the perfused liver by at least 2-fold, suggesting that 4-methylumbelliferyl sulfate content is an important determinant of rates of hydrolysis in the perfused liver. There was a good correlation (r = 0.91) between rates of product formation and fluorescence of 4-methylumbelliferone detected from the liver surface with fiber optic light guides. Fluorescence of 4-methylumbelliferone produced from hydrolysis of 4-methylumbelliferyl sulfate was also monitored with micro-light guides placed on periportal and pericentral areas of the liver lobule for the estimation of local rates of product formation. When perfusions were in the anterograde direction, desulfation of 4-methylumbelliferyl sulfate was about 50% higher in pericentral (28.8 +/- 9.3 mumol/g/hr) than in periportal (18.2 +/- 2.7 mumol/g/hr) areas. Furthermore, 4-methylumbelliferyl sulfate content determined in microdissected samples was 1.5- to 2-fold higher in pericentral than in periportal regions of the liver lobule but the activity of 4-methylumbelliferyl sulfate sulfatase was identical in both zones of the liver lobule. We conclude, therefore, that the local substrate content is an important determinant of rates of 4-methylumbelliferyl sulfate hydrolysis in sublobular zones of the liver.


Normal changes in orbital volume during childhood.
The aim of this study was to construct a model of changes in orbital volume that occur throughout childhood from the age of 1 month to 15 years, which could be used for comparative studies of disease states affecting orbital growth. Using the procedure of segmentation on magnetic resonance images obtained in 67 healthy children, orbital volume was measured and plotted against age. During the first few months of life left orbital volume is on average 15 cm3 in male and 13 cm3 in female infants; these volumes increase to 26 cm3 and 24 cm3, respectively, by the time the child reaches 15 years of age. During the first few months of life right orbital volume is on average 16 cm3 in male and 13 cm3 in female infants; these volumes increase to 27 cm3 and 25 cm3, respectively, by the time the child is 15 years old. This represents an overall increase in orbital volume by a factor of 1.7 in boys and 1.8 in girls. By the time the child has reached 5 years of age, the orbital volume for both right and left sides has reached on average 77% of the volume seen at 15 years in both sexes. The differences between the two sides are not statistically significant for either sex. The change in orbital volume that is associated with age in general displays a linear pattern. Throughout childhood, orbital volumes are larger in boys than in girls, but share a similar growth pattern. The difference between the two sexes tends toward statistical significance during the first 5 years of life (left orbit p = 0.1, right orbit p = 0.04). During early childhood, orbital volume increases in a linear fashion, achieving a significant proportion of its final growth by the time the child is 5 years old.


Suppressive properties of human CD4+CD25+ regulatory T cells are dependent on CTLA-4 expression.
It has been demonstrated that T cells with regulatory properties are present within the peripheral blood CD4(+)CD25(+) T cell compartment. Here, we describe an original method to purify human CD4(+)CD25(+)CD152(+) T lymphocytes as living cells by forcing the exportation of CTLA-4 molecules stored in intracellular vesicules at the cell surface. By doing so, we demonstrate that CD4(+)CD25(+) T cells contain a smaller and more homogeneous population enriched in cells with in vitro regulatory activity. Moreover, we show that this enrichment in regulatory T cells is associated with an increased expression of Foxp3 and that CD4(+)CD25(+)CD152(+) T lymphocytes display a much stronger suppressive activity in controlling in vitro proliferation of alloantigen-specific T cells than CD4(+)CD25(+)CD152(-) T lymphocytes purified in parallel. Lastly, by purifying such cells expressing CTLA-4, we demonstrate that indeed CTLA-4 is involved in CD4(+)CD25(+)CD152(+) T cell regulatory activity, while suppressive cytokines are not.


Serum concentrations and allotypes of immunoglobulins in two lines of mice genetically selected for "high" or "low" antibody synthesis.
Random-bred Swiss mice were selectively bred for 16 generations; selection was based on their agglutinin response to sheep and pigeon erythrocytes to produce a high and a low responder line. The serum levels of individual immunoglobulins differed significantly in these two lines before immunization. The differences in the levels of immunoglobulins were much more marked after immunization with pigeon or sheep erythrocytes. Greater differences between the two lines were noted in IgM and IgG levels than in IgA. Another remarkable finding was the presence of different immunoglobulin phenotypes in the two lines. The high responders were homozygous or heterozygous for heavy-chain linkage groups found separately in the prototype BALB/c and C57BL inbred strains. The low responders were homozygous for a heavy-chain linkage group not present in bred mice in the United States, but observed as a recombinant type among wild mice probably representing a crossover between the heavy-chain linkage groups of the prototype DBA/2 and NH inbred mice.


Tailoring cognitive behavioural therapy to subtypes of voice-hearing using a novel tabletised manual: a feasibility study.
Cognitive behavioural therapy for psychosis (CBTp) is a recommended treatment for psychotic experiences, but its effectiveness has been questioned. One way of addressing this may be to tailor therapy materials to the phenomenology of specific psychotic experiences. In this study, we investigated the acceptability of a novel treatment manual for subtypes of 'voice-hearing' experiences (i.e. auditory verbal hallucinations). An uncontrolled, single-arm design was used to assess feasibility and acceptability of using the manual in routine care for people with frequent voice-hearing experiences. The manual was delivered on a smart tablet and incorporated recent research evidence and theory into its psychoeducation materials. In total, 24 participants completed a baseline assessment; 19 started treatment, 15 completed treatment and 12 participants completed a follow-up assessment (after 10 sessions of using the manual). Satisfaction with therapy scores and acceptability ratings were high, while completion rates suggested that the manual may be more appropriate for help with participants from Early Intervention in Psychosis services rather than Community Mental Health Teams. Within-group changes in symptom scores suggested that overall symptom severity of hallucinations - but not other psychosis features, or beliefs about voices - are likely to be the most appropriate primary outcome for further evaluation in a full randomised controlled trial.


The tight junction-associated protein occludin is required for a postbinding step in hepatitis C virus entry and infection.
The precise mechanisms regulating hepatitis C virus (HCV) entry into hepatic cells remain unknown. However, several cell surface proteins have been identified as entry factors for this virus. Of these molecules, claudin-1, a tight junction (TJ) component, is considered a coreceptor required for HCV entry. Recently, we have demonstrated that HCV envelope glycoproteins (HCVgp) promote structural and functional TJ alterations. Additionally, we have shown that the intracellular interaction between viral E2 glycoprotein and occludin, another TJ-associated protein, could be the cause of the mislocalization of TJ proteins. Herein we demonstrated, by using cell culture-derived HCV particles (HCVcc), that interference of occludin expression markedly reduced HCV infection. Furthermore, our results with HCV pseudotyped particles indicated that occludin, but not other TJ-associated proteins, such as junctional adhesion molecule A or zonula occludens protein 1, was required for HCV entry. Using HCVcc, we demonstrated that occludin did not play an essential role in the initial attachment of HCV to target cells. Surface protein labeling experiments showed that both expression levels and cell surface localization of HCV (co)receptors CD81, scavenger receptor class B type I, and claudin-1 were not affected upon occludin knockdown. In addition, immunofluorescence confocal analysis showed that occludin interference did not affect subcellular distribution of the HCV (co)receptors analyzed. However, HCVgp fusion-associated events were altered after occludin silencing. In summary, we propose that occludin plays an essential role in HCV infection and probably affects late entry events. This observation may provide new insights into HCV infection and related pathogenesis.


[Membrane antigens of transformed and tumor cells of hamsters].
Normal membrane antigens to tumour and in vitro transformed tissue cultures of Syrian hamster cells were comparatively studied in cross-adsorption experiments. It was found that each cell strain has an individual profile of normal membrane antigens with characteristic quantitative and qualitative features seen on antigen expression. The absence of at least one of the antigens which the cells of other strains possessed was demonstrated with reference to the cells of each line tested. All 5 tumor cell lines were bearing antigen or a group of antigens absent on normal embryonic hamster cells (HE) and 5-strains of in vitro transformed HE cells.


Trephine bone biopsy by radiologists: results of 73 procedures.
Trephine bone biopsies were performed in 67 patients. Routine radiography, laminagraphy, and radioisotopic techniques were employed to determine areas of involvement and exact sites for biopsy. Sites were selected on the basis of accessibility, possible complications, and chances of recovering diagnostic material. The biopsy material was informative in 81% of patients. One controllable hemorrhage, one temporary sinus tract, a small pneumothorax requiring no therapy, and two benign vasovagal responses were the only complications. Widespread malignant disease and osteomyelitis, particularly disk-space infection, are the most suitable lesions for trephine biopsy.


Adsorption microcalorimetry: recent advances in instrumentation and application.
Adsorption microcalorimetry measures the energetics of adsorbate-surface interactions and can be performed by use of several different techniques. This review focuses on three methods: single-crystal adsorption calorimetry (SCAC), isothermal titration calorimetry (ITC), and electrochemical adsorption calorimetry. SCAC is a uniquely powerful technique that has been applied to a variety of atoms and molecules that represent a large variety of well-defined adsorbate species on a wide range of single-crystal surfaces. ITC and electrochemical microcalorimetry are useful for studying adsorption energies in liquid solutions (on surfaces of suspended powders) and at the electrode-electrolyte interface, respectively. Knowledge of the energetics of adsorbate formation is valuable to ongoing research in many fields, including catalysis, fuel cells, and solar power. In addition, calorimetric measurements serve as benchmarks for the improvement of computational approaches to understanding surface chemistry. We review instrumentation and applications, emphasizing our own work.


Freshwater systems and ecosystem services: Challenges and chances for cross-fertilization of disciplines.
Freshwater ecosystems are among the most threatened in the world, while providing numerous essential ecosystem services (ES) to humans. Despite their importance, research on freshwater ecosystem services is limited. Here, we examine how freshwater studies could help to advance ES research and vice versa. We summarize major knowledge gaps and suggest solutions focusing on science and policy in Europe. We found several features that are unique to freshwater ecosystems, but often disregarded in ES assessments. Insufficient transfer of knowledge towards stakeholders is also problematic. Knowledge transfer and implementation seems to be less effective towards South-east Europe. Focusing on the strengths of freshwater research regarding connectivity, across borders, involving multiple actors can help to improve ES research towards a more dynamic, landscape-level approach, which we believe can boost the implementation of the ES concept in freshwater policies. Bridging these gaps can contribute to achieve the ambitious targets of the EU's Green Deal.


Factor V Leiden prevalence in venous thromboembolism patients.
Recent findings have demonstrated a high frequency of activated protein C resistance in patients suffering from deep venous thrombosis (DVT). This abnormality has been related to a mutation in the factor V gene (at nucleotide position 1,691, guanine to adenine [G-->A] substitution). To assess the frequency of the mutation in unselected inpatients with a proved DVT. To study the clinical characteristics of such patients. All consecutive patients admitted to the hospital because of a clinical suspicion of DVT were eligible. Diagnosis of DVT with the help of venous ultrasound imaging or venography. Ventilation and perfusion lung scan was performed in all patients, and interpreted according to the Prospective Investigation of Pulmonary Embolism Diagnosis criteria; in patients with a low- or intermediate-probability lung scan, pulmonary angiography was requested. Polymerase chain reaction amplification was performed in patients with a proved DVT. A control group consisted of bone marrow volunteer donors. From July 1994 to November 1995, 165 patients were included. Thrombosis was considered as distal in 77 and proximal in 88; an associated pulmonary embolism (PE) was found in 75 patients. Of 165 patients, 24 (14.5%) showed the factor V gene mutation (95% confidence interval, 9.4 to 19.8); the mutation was present in 3.5% of 200 bone marrow volunteer donors; odds ratio for having DVT in the presence of the mutation was 4.1. No difference in the level of DVT, or the presence of an associated PE was observed according to the presence of the mutation. Patients with the mutation have a significantly more frequent history of DVT (p=0.04) and more previous reported episodes (1.1 vs 0.6; p=0.04). The factor V mutation is frequent in unselected DVT patients. No difference in the severity of the thrombosis episode was observed in these patients.


High Resolution Melt analysis for mutation screening in PKD1 and PKD2.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder. It is characterized by focal development and progressive enlargement of renal cysts leading to end-stage renal disease. PKD1 and PKD2 have been implicated in ADPKD pathogenesis but genetic features and the size of PKD1 make genetic diagnosis tedious. We aim to prove that high resolution melt analysis (HRM), a recent technique in molecular biology, can facilitate molecular diagnosis of ADPKD. We screened for mutations in PKD1 and PKD2 with HRM in 37 unrelated patients with ADPKD. We identified 440 sequence variants in the 37 patients. One hundred and thirty eight were different. We found 28 pathogenic mutations (25 in PKD1 and 3 in PKD2 ) within 28 different patients, which is a diagnosis rate of 75% consistent with literature mean direct sequencing diagnosis rate. We describe 52 new sequence variants in PKD1 and two in PKD2. HRM analysis is a sensitive and specific method for molecular diagnosis of ADPKD. HRM analysis is also costless and time sparing. Thus, this method is efficient and might be used for mutation pre-screening in ADPKD genes.


Thermal windows on the trunk of hauled-out seals: hot spots for thermoregulatory evaporation?
Seals have adapted to the high heat transfer coefficient in the aquatic environment by effective thermal insulation of the body core. While swimming and diving, excess metabolic heat is supposed to be dissipated mainly over the sparsely insulated body appendages, whereas the location of main heat sinks in hauled-out seals remains unclear. Here, we demonstrate thermal windows on the trunk of harbour seals, harp seals and a grey seal examined under various ambient temperatures using infrared thermography. Thermograms were analysed for location, size and development of thermal windows. Thermal windows were observed in all experimental sessions, shared some common characteristics in all seals and tended to reappear in similar body sites of individual seals. Nevertheless, the observed variations in order and location of appearance, number, size and shape of thermal windows would imply no special anatomical site for this avenue of heat loss. Based on our findings, we suggest that, in hauled-out seals, heat may be transported by blood flow to a small area of the wet body surface where the elevation of temperature facilitates evaporation of water trapped within the seals' pelages due to increased saturation vapour pressure. The comparatively large latent heat necessary for evaporation creates a temporary hot spot for heat dissipation.


Molecular dissection of transcriptional control elements within the long terminal repeat of the retrovirus.
The retroviral long terminal repeat (LTR) contains transcriptional control elements that affect viral gene expression. By deletion mutagenesis of the genome of the cloned Abelson murine leukemia virus, regulatory signals could be mapped to at least three domains within the LTR. A defective 5' LTR that did not sustain transforming gene function was complemented by an intact LTR positioned at the 3' end of the genome. This versatility of the retroviral genome with respect to its transcriptional control elements appears to provide a strong selective advantage for viral gene expression.


Gradients in compositions in the starchy endosperm of wheat have implications for milling and processing.
Wheat is the major food grain consumed in temperate countries. Most wheat is consumed after milling to produce white flour, which corresponds to the endosperm storage tissue of the grain. Because the starchy endosperm accounts for about 80% of the grain dry weight, the miller aims to achieve flour yields approaching this value. Bioimaging can be combined with biochemical analysis of fractions produced by sequential pearling of whole grains to determine the distributions of components within the endosperm tissue. This reveals that endosperm is not homogeneous, but exhibits gradients in composition from the outer to the inner part. These include gradients in both amount and composition. For example, the content of gluten proteins decreases but the proportion of glutenin polymers increases from the outside to the centre of the tissue. However, the content of starch increases with changes in the granule size distribution, the proportions of amylose and amylopectin, and their thermal properties. Hence these parts of the endosperm differ in the functional properties for food processing. Gradients also exist in minor components which may affect health and processing, such as dietary fibre and lipids. The gradients in grain composition are reflected in differences in the compositions of the mill streams which are combined to give white flour (which may number over 20). These differences could therefore be exploited by millers and food processors to develop flours with compositions and properties for specific end uses.


Motion Analysis in Lumbar Spinal Stenosis With Degenerative Spondylolisthesis: A Feasibility Study of the 3DCT Technique Comparing Laminectomy Versus Bilateral Laminotomy.
This was a randomized radiologic biomechanical pilot study in vivo. The objectives of this study was to evaluate if 3-dimensional computed tomography is a feasible tool in motion analyses of the lumbar spine and to study if preservation of segmental midline structures offers less postoperative instability compared with central decompression in patients with lumbar spinal stenosis with degenerative spondylolisthesis. The role of segmental instability after decompression is controversial. Validated techniques for biomechanical evaluation of segmental motion in human live subjects are lacking. In total, 23 patients (mean age, 68 y) with typical symptoms and magnetic resonance imaging findings of spinal stenosis with degenerative spondylolisthesis (>3 mm) in 1 or 2 adjacent lumbar levels from L3 to L5 were included. They were randomized to either laminectomy (LE) or bilateral laminotomy (LT) (preservation of the midline structures). Documentation of segmental motion was made preoperatively and 6 months postoperatively with CT in provoked flexion and extension. Analyses of movements were performed with validated software. The accuracy for this method is 0.6 mm in translation and 1 degree in rotation. Patient-reported outcome measures were collected from the Swespine register preoperatively and 2-year postoperatively. The mean preoperative values for 3D rotation and translation were 6.2 degrees and 1.8 mm. The mean increase in 3D rotation 6 months after surgery was 0.25 degrees after LT and 0.7 degrees after LE (P=0.79) while the mean increase in 3D translation was 0.15 mm after LT and 1.1 mm after LE (P=0.42). Both surgeries demonstrated significant improvement in patient-reported outcome measures 2 years postoperatively. The 3D computed tomography technique proved to be a feasible tool in the evaluation of segmental motion in this group of older patients. There was negligible increase in segmental motion after decompressive surgery. LE with removal of the midline structures did not create a greater instability compared with when these structures were preserved.


Electrically pumped 1.5 μm InP-based quantum dot microring lasers directly grown on (001) Si.
Directly grown quantum dot (QD) lasers on silicon are appealing for monolithic integration of photonic circuits from a technoeconomic perspective. In this Letter, we report miniaturization of these Si-based lasers employing high-quality whispering-gallery mode microresonators. Based on previously developed InAs/InAlGaAs QDs on the complementary metal-oxide-semiconductor-standard (001) Si platform and optimized device implementation techniques, on-chip electrically pumped InP-based QD microring lasers (MRLs) on Si are successfully realized for the first time. Room-temperature pulsed lasing in the 1.5 μm wavelength band, with a threshold of 50 mA, is measured for 50-μm-diameter MRLs. Lasing up to 70°C is achieved with a characteristic temperature of 51.5 K.


Acid-Sensing Ion Channels: Focus on Physiological and Some Pathological Roles in the Brain.
Acid-sensing ion channels (ASICs) are Na+-permeable ion channels activated by protons and predominantly expressed in the nervous system. ASICs act as pH sensors leading to neuronal excitation. At least eight different ASIC subunits (including ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, ASIC4, ASIC5) are encoded by five genes (ASIC1-ASIC5). Functional ASICs assembled in the plasma membrane are homo- or heteromeric trimers. ASIC1a-containing trimers are of particular interest as, in addition to sodium ions, they also conduct calcium ions and thus can trigger or regulate multiple cellular processes. ASICs are widely but differentially expressed in the central and peripheral nervous systems. In the mammalian brain, a majority of neurons express at least one ASIC subunit. Several recent reviews have summarized findings of the role of ASICs in the peripheral nervous system, particularly in nociception and proprioception, and the structure-function relationship of ASICs. However, there is little coverage on recent findings regarding the role of ASICs in the brain. Here we review and discuss evidence regarding the roles of ASICs: (i) as postsynaptic receptors activated by protons coreleased with glutamate at glutamatergic synapses; (ii) as modulators of synaptic transmission at glutamatergic synapses and GABAergic synapses; (iii) in synaptic plasticity, memory and learning; (iv) in some pathologies such as epilepsy, mood disorders and Alzheimer's disease.


On the Pro-Metastatic Stress Response to Cancer Therapies: Evidence for a Positive Co-Operation between TIMP-1, HIF-1α, and miR-210.
In contrast to expectations in the past that tumor starvation or unselective inhibition of proteolytic activity would cure cancer, there is accumulating evidence that microenvironmental stress, such as hypoxia or broad-spectrum inhibition of metalloproteinases can promote metastasis. In fact, malignant tumor cells, due to their genetic and epigenetic instability, are predisposed to react to stress by adaptation and, if the stress persists, by escape and formation of metastasis. Recent recognition of the concepts of dynamic evolution as well as population and systems biology is extremely helpful to understand the disappointments of clinical trials with new drugs and may lead to paradigm-shifts in therapy strategies. This must be complemented by an increased understanding of molecular mechanism involved in stress response. Here, we review new roles of Hypoxia-inducible factor-1 (HIF-1), one transcription factor regulating stress response-related gene expression: HIF-1 is crucial for invasion and metastasis, independent from its pro-survival function. In addition, HIF-1 mediates pro-metastatic microenvironmental changes of the proteolytic balance as triggered by high systemic levels of tissue inhibitor of metalloproteinases-1 (TIMP-1), typical for many aggressive cancers, and regulates the metabolic switch to glycolysis, notably via activation of the microRNA miR-210. There is preliminary evidence that TIMP-1 also induces miR-210. Such positive-regulatory co-operation of HIF-1α, miR-210, and TIMP-1, all described to correlate with bad prognosis of cancer patients, opens new perspectives of gaining insight into molecular mechanisms of metastasis-inducing evasion of tumor cells from stress.


Heterogeneous mutations in the human lipoprotein lipase gene in patients with familial lipoprotein lipase deficiency.
The DNA sequences were determined for the lipoprotein lipase (LPL) gene from five unrelated Japanese patients with familial LPL deficiency. The results demonstrated that all five patients are homozygotes for distinct point mutations dispersed throughout the LPL gene. Patient 1 has a G-to-A transition at the first nucleotide of intron 2, which abolishes normal splicing. Patient 2 has a nonsense mutation in exon 3 (Tyr61----Stop) and patient 3 in exon 8 (Trp382----Stop). The latter mutation emphasizes the importance of the carboxy-terminal portion of the enzyme in the expression of LPL activity. Missense mutations were identified in patient 4 (Asp204----Glu) and patient 5 (Arg243----His) in the strictly conserved amino acids. Expression study of both mutant genes in COS-1 cells produced inactive enzymes, establishing the functional significance of the two mis-sense mutations. In these patients, postheparin plasma LPL mass was either virtually absent (patients 1 and 2) or significantly decreased (patients 3-5). To detect these mutations more easily, we developed a rapid diagnostic test for each mutation. We also determined the DNA haplotypes for patients and confirmed the occurrence of multiple mutations on the chromosomes with an identical haplotype. These results demonstrate that familial LPL deficiency is a heterogeneous genetic disease caused by a wide variety of gene mutations.


Cytotoxic Flavonoid Glycosides from Rapistrum rugosum L.
Five flavonoid glycosides were isolated from the n-butanol soluble fraction of the ethanolic extract of Rapistrum rugosum and their structures were assigned from (1)H- and (13)C-NMR spectra (DEPT) with 2D NMR as quercetin-3-O-α-L-rhamnopyranoside (1), quercetin-3-O- β-D-xyloside (2), quercetin, 3-O-α-L-arabinopyranoside,7-O-α-L-rhamnopyranoside (3), kaempferol 3-O-α-L-arabinopyranoside, 7-O-α-L-rhamnopyranoside (4) and rutin (5). The SRB cytotoxic assay was used to investigate the antitumor activities of n-butanol extract, compound 3 and its hexaacetate 3a, for the first time. Compounds 3 and 3a showed cytotoxic activity against the human cancer cell line, namely, HepG2 (hepatocellular carcinoma cell line) with IC50 (concentration of compound required to reduce cell survival by 50%) 0.86 μg/mL and 3.50 μg/mL, respectively. These results proved that compound 3, the major flavonoid of the n-butanol soluble fraction, has significant cytotoxic activity compared with the standard antitumor drug doxorubicin (0.60 μg/mL).


Suprofen: its usefulness in the control of pain following surgical removal of impacted wisdom tooth.
The results of the present investigation have shown the usefulness of suprofen in the control of pain following surgical removal of impacted wisdom tooth. The regime of 200 mg. q.d.s. orally, was shown to be satisfactory in the control of postoperative pain. Pain was rapidly controlled by the 1st hour after ingestion and subsequently maintained at a low profile until is was completely abolished by the 8th hour of the postoperative period.


Eradicating Breast Cancer: Longevity Impact on Kuwaiti Women
Objective: To explore salient trends in incidence and mortality from breast cancer among Kuwaiti females and to quantify the number of years that could be saved if breast cancer deaths were eliminated. Methods: Appling life table technique, the paper constructs a bridged, multiple decrement and cancer-elimination life tables for Kuwaiti females. Data sources include Kuwait Cancer Control Center Registry along with vital statistics on mortality by age groups, nationality, and causes of death according to ICD-10 revision. Result: The study finds that, without interventions, nearly 2.5% of Kuwaiti female live births are expected to die from breast cancer. By contrast, if this disease were to be completely eradicated, Kuwaiti females are expected to gain half a year of life expectancy at birth. Likewise, a 10% reduction in deaths attributed to breast cancer would produce a gain of 11 days of life at age 30. The gain would augment to 51 days when death is reduced by 50%. Kuwaiti females aged 50 would add almost 5 months when breast cancer is eradicated, while a 20 percent reduction in breast cancer mortality would raise their life expectancy by 26 days. Conclusion: The results strongly support policy interventions of Kuwait's government by instituting a well-documented public health policy for chronic diseases and mitigating the increase of cancer prevalence.


Risk of unintentional injuries in children and adolescents with ADHD and the impact of ADHD medications: protocol for a systematic review and meta-analysis.
Attention-deficit hyperactivity disorder (ADHD) has been related to increased rates of unintentional injuries. However, the magnitude of the effect and to which extent variables such as sex, age or comorbidity can influence this relationship is unknown. Additionally, and importantly, it is unclear if, and to which degree, ADHD medications can decrease the number of unintentional injuries. Due to the amount of economic and social resources invested in the treatment of injuries, filling these gaps in the literature is highly relevant from a public health standpoint. Here, we present a protocol for a systematic review and meta-analysis to estimate the relationship between ADHD and unintentional injuries and assess the impact of pharmacological treatment for ADHD METHODS AND ANALYSIS: We will combine results from 114 bibliographic databases for studies relating ADHD and risk of injuries. Bibliographic searches and data extraction will be carried out independently by two researchers. The studies' risk of bias will be assessed using the Newcastle-Ottawa Scale. Articles reporting ORs or HRs of suffering an injury in ADHD compared with controls (or enough data to calculate them) will be combined using Robust Variance Estimation, a method that permits to include multiple non-independent outcomes in the analysis. All analyses will be carried out in Stata. Age, sex and comorbid conduct disorders will be considered as potential causes of variance and their effect analysed through meta-regression and subgroup analysis. Sensitivity analyses will exclude articles with longer follow-ups, non-stringent definitions of ADHD or controls and statistically uncontrolled/controlled outcomes. Studies implementing a self-controlled case series methodology to investigate if ADHD drugs reduce the risk of injuries will be combined with a generalised linear mixed model using the Poisson distribution and a log link function. PROSPERO-Prospective Register of Systematic Reviews (CRD42017064967).


HJC0416 Attenuates Fibrogenesis in Activated Hepatic Stellate Cells via STAT3 and NF-κB Pathways.
Hepatic fibrosis is wound-healing response that is the result of hepatic stellate cell (HSC) activation and subsequent excess extracellular matrix deposition. HSCs can be activated by a variety of inflammatory stimuli as well as through the signal transducer and activator of transcription 3 (STAT3) pathway. HJC0416 is a novel, orally bioavailable small-molecule inhibitor of STAT3 that was developed by our team using a fragment-based drug design approach. Previously, our team has shown that HJC0416 has antifibrogenic effects in activated HSCs. Recently, increasing evidence suggests that nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) plays an important role in the activation of HSCs. In the present study, we examined the role of NF-κB inhibition of HSC activation by HJC0416. LX-2 (human) and HSC-T6 (rat) cell lines were used. Expression levels of extracellular proteins, NF-κB and STAT3 expression and DNA binding, and inflammatory cytokine levels were determined using western blot, ELISA, and immunofluorescence assay. HJC0416 decreased cell viability in a dose-dependent manner in both cell lines and arrested the cell cycle at the S phase. Increased apoptosis was seen in LX-2 cells through Yo-Pro-1 and propidium iodide immunofluorescent stating. HJC0416 significantly decreased expression of fibronectin and collagen I as well as markedly decreased α-SMA and laminin. HJC0416 inhibited the STAT3 pathway by decreasing phosphorylation of STAT3, as well as signal transduction pathway activation. Notably, HJC0416 also inhibited the classic and alternative pathways of NF-κB activation. HJC0416 inhibited LPS-induced p65 nuclear translocation and DNA binding, as well as prevented phosphorylation and degradation of inhibitory protein IκBα. HJC0416 also prevented phosphorylation of serine residue 536 on p65. HJC0416, an inhibitor of STAT3, was found to have antifibrogenic properties in activated hepatic stellate cell lines. In addition, HJC0416 was found to inhibit the NF-κB pathway. Owing to this double effect, HJC0416 demonstrates promise for in vivo experimentation as an antifibrosis treatment.


[Effects of essential oil on lipid peroxidation and lipid metabolism in patients with chronic bronchitis].
Natural concentrations of some essential oils were examined for effects on the system lipid peroxidation-antioxidant defense and lipid metabolism in 150 patients with chronic bronchitis. Lowering of plasm levels of dienic conjugates and ketons, activation of catalase in red cells characteristic of antioxidant effect were observed in exposure to essential oils of rosemary, basil, fir, eucalyptus. Lavender essential oil promotes normalization of the level of total lipids, ratio of total cholesterol to its alpha-fraction.


The role of pyrimidine dimers as premutagenic lesions: a study of targeted vs. untargeted mutagenesis in the lacI gene of Escherichia coli.
We have employed conjugal transfer of an F' lac episome to examine targeted and untargeted mutagenesis in the lacI gene of Escherichia coli and to determine the relative importance of pyrimidine dimers as premutational UV lesions compared to (6-4) photoproducts that also may have a mutational role. This conjugal system allowed us to assess the premutagenic role of UV lesions independently from any role as inducers of SOS functions. F' DNA was transferred to an SOS-induced recipient strain from: unirradiated donor cells, UV-treated donor cells or donor cells that were irradiated and then exposed to photoreactivating light. The results indicate that SOS-related, untargeted events may account for as much as one-third of the nonsense mutations (i.e., base substitutions) recovered after undamaged F' DNA is transferred to UV-irradiated recipients. When the donor strain also is irradiated, in excess of 90% of the mutations detected following conjugation appear to be targeted. Photoreactivation of the UV-treated donors cells, prior to F' transfer to the SOS-induced recipient strain, demonstrated that in this experimental system virtually all recovered UV-induced mutations are targeted by photoreactivable lesions. We presume that these lesions are pyrimidine dimers because (6-4) photoproducts are not photoreactivable.


Acute rheumatic fever: a chink in the chain that links the heart to the throat?
Acute rheumatic fever (ARF) remains a major problem in tropical regions, resource-poor countries, and minority indigenous communities. It has long been thought that group A streptococcal (GAS) pharyngitis alone was responsible for acute rheumatic fever; this belief has been supported by laboratory and epidemiological evidence gathered over more than 60 years, mainly in temperate climates where GAS skin infection is uncommon. GAS strains have been characterised as either rheumatogenic or nephritogenic based on phenotypic and genotypic properties. Primary prevention strategies and vaccine development have long been based on these concepts. The epidemiology of ARF in Aboriginal communities of central and northern Australia challenges this view with reported rates of ARF and rheumatic heart disease (RHD) that are among the highest in the world. GAS throat colonisation is uncommon, however, and symptomatic GAS pharyngitis is rare; pyoderma is the major manifestation of GAS infection. Typical rheumatogenic strains do not occur. Moreover, group C and G streptococci have been shown to exchange key virulence determinants with GAS and are more commonly isolated from the throats of Aboriginal children. We suggest that GAS pyoderma and/or non-GAS infections are driving forces behind ARF in these communities and other high-incidence settings. The question needs to be resolved as a matter of urgency because current approaches to controlling ARF/RHD in Aboriginal communities have clearly been ineffective. New understanding of the pathogenesis of ARF would have an immediate effect on primary prevention strategies and vaccine development.


Stimulation of ammonia oxidizer and denitrifier abundances by nitrogen loading: Poor predictability for increased soil N2 O emission.
Unprecedented nitrogen (N) inputs into terrestrial ecosystems have profoundly altered soil N cycling. Ammonia oxidizers and denitrifiers are the main producers of nitrous oxide (N2 O), but it remains unclear how ammonia oxidizer and denitrifier abundances will respond to N loading and whether their responses can predict N-induced changes in soil N2 O emission. By synthesizing 101 field studies worldwide, we showed that N loading significantly increased ammonia oxidizer abundance by 107% and denitrifier abundance by 45%. The increases in both ammonia oxidizer and denitrifier abundances were primarily explained by N loading form, and more specifically, organic N loading had stronger effects on their abundances than mineral N loading. Nitrogen loading increased soil N2 O emission by 261%, whereas there was no clear relationship between changes in soil N2 O emission and shifts in ammonia oxidizer and denitrifier abundances. Our field-based results challenge the laboratory-based hypothesis that increased ammonia oxidizer and denitrifier abundances by N loading would directly cause higher soil N2 O emission. Instead, key abiotic factors (mean annual precipitation, soil pH, soil C:N ratio, and ecosystem type) explained N-induced changes in soil N2 O emission. Altogether, these findings highlight the need for considering the roles of key abiotic factors in regulating soil N transformations under N loading to better understand the microbially mediated soil N2 O emission.


Enzymatic extraction of activated sludge extracellular polymers and implications on bioflocculation.
This study examines enzyme hydrolysis, a mild, effective, but a rarely used method of extracellular polymer extraction, in removing polymers from mixed culture activated sludge flocs. Two carbohydrate specific enzymes (alpha-amylase and cellulase) and a protein specific enzyme (proteinase) are used during the study. First, the kinetic aspect is investigated, then enzyme dose optimization is carried out on laboratory grown activated sludge samples cultured at solids retention times (SRT) of 4 and 20 days. A more commonly used cation exchange resin (CER) extraction technique is also employed for comparison purposes. Results indicate that the extraction of extracellular polymers by enzymes is a rather quick process reaching equilibrium within only a few hours. As the doses of enzymes are increased, the extracted polymer quantities increase up to a certain dose, beyond which not much extraction is observed. The method does not cause any significant cell lysis as measured by the viable cell counts. Carbohydrate-hydrolyzing enzymes extract small amount of proteins along with the carbohydrates and protein-hydrolyzing enzyme extracts some carbohydrates together with the proteins, indicating that proteins and carbohydrates exist bound to each other in the extracellular polymer network of sludge. Enzyme extraction generally gives a lower estimate of polymers compared to the CER method, but correctly detects the trends in the polymer quantity.


Fungal brain infections.
Fungal infections of the central nervous system, once a relatively rare occurrence, are increasingly common due to the expansion of immunocompromised populations at risk, and therefore are important to recognize early and manage appropriately. The specific infectious risk posed by novel immune-modifying therapies can, in most cases, be predicted on the basis of the immune target and medication timing. In addition, major advances in noninvasive diagnostic tests (e.g. serum beta glucan and galactomannan assays), and the recent introduction of more effective antifungal therapies, have led to a dramatic improvement in clinical outcomes. The current review provides approaches to patients with suspected central nervous system fungal infections based on host-risk factors, clinical syndromes and specific pathogens.


Investigating oral health among US adults with sleep disorder: a cross-sectional study.
This study aims to investigate the relationship between sleep disorders and oral health outcomes among a representative sample of the United States population. The study sample comprised 6,161 participants who participated in the NHANES 2017-2018, representing a population of 255,939,599. Oral health outcomes were assessed using the Oral Health Questionnaire (OHQ), covering dental pain, periodontal disease, bone loss, emotional perceptions of oral health, and impact on daily life. Sleep disorders were evaluated using questions related to sleep trouble and daytime sleepiness. Analysis of the NHANES 2017-2018 dataset, revealed notable associations between sleep disorders and oral health outcomes. Individuals with sleep disorders were more likely to report dental pain (19.79% vs. 11.8%), periodontal issues (19.5% vs. 12.25%), and feeling bad or embarrassed about their oral health (21% vs. 12%), compared to those without sleep disorders. Difficulty due to oral health issues was also more prevalent among participants with sleep disorders (32.6% vs. 12.9%). Adjusted models demonstrated that individuals with sleep disorders had a significantly higher likelihood of experiencing oral aches [adjusted odds ratio (aOR) = 1.58 (1.22-2.22)], reporting negative emotions about oral health [aOR = 1.59 (1.06-2.37)], and encountering challenges in school or job performance [aOR = 2.27 (1.47-3.51)], compared to individuals without sleep disorders (refer to Table 3). Other significant covariates affecting oral health outcomes included smoking, income, and education level. This study reveals a compelling association between sleep disorders and adverse oral health outcomes in the U.S.


Prediction of fetal lung maturity by use of the Lumadex-FSI test.
We analyzed amniotic fluid from 91 pregnancies (estimated gestational age range 31 to 41 weeks), using the Lumadex-FSI Fetal Lung Maturity test (Beckman Instruments), and also determining phosphatidylglycerol content, the lecithin/sphingomyelin ratio, and foam stability index by the "shake test," and compared results with newborn outcome. Five of 64 babies born within 72 h of testing developed hyaline membrane disease. Except for the lecithin/sphingomyelin ratio, the predictive value of a negative test was 100% but that of a positive test was less than 50%. Use of all four tests did not offer diagnostic advantage over the use of Lumadex-FSI alone. For the laboratory that infrequently assesses fetal lung maturity, we believe the sealed cassette format of the Lumadex-FSI will permit better quality assurance than the shake test. The Lumadex-FSI test is intended to provide a graded estimate of positive risk for hyaline membrane disease, but more data from different centers and patient populations are needed to establish reliable predictive values.


Catabolism of glucose and lactose in Bifidobacterium animalis subsp. lactis, studied by 13C Nuclear Magnetic Resonance.
Bifidobacteria are widely used as probiotics in several commercial products; however, to date there is little knowledge about their carbohydrate metabolic pathways. In this work, we studied the metabolism of glucose and lactose in the widely used probiotic strain Bifidobacterium animalis subsp. lactis BB-12 by in vivo (13)C nuclear magnetic resonance (NMR) spectroscopy. The metabolism of [1-(13)C]glucose was characterized in cells grown in glucose as the sole carbon source. Moreover, the metabolism of lactose specifically labeled with (13)C on carbon 1 of the glucose or the galactose moiety was determined in suspensions of cells grown in lactose. These experiments allowed the quantification of some intermediate and end products of the metabolic pathways, as well as determination of the consumption rate of carbon sources. Additionally, the labeling patterns in metabolites derived from the metabolism of glucose specifically labeled with (13)C on carbon 1, 2, or 3 in cells grown in glucose or lactose specifically labeled in carbon 1 of the glucose moiety ([1-(13)Cglucose]lactose), lactose specifically labeled in carbon 1 of the galactose moiety ([1-(13)Cgalactose]lactose), and [1-(13)C]glucose in lactose-grown cells were determined in cell extracts by (13)C NMR. The NMR analysis showed that the recovery of carbon was fully compatible with the fructose 6-phosphate, or bifid, shunt. The activity of lactate dehydrogenase, acetate kinase, fructose 6-phosphate phosphoketolase, and pyruvate formate lyase differed significantly between glucose and lactose cultures. The transcriptional analysis of several putative glucose and lactose transporters showed a significant induction of Balat_0475 in the presence of lactose, suggesting a role for this protein as a lactose permease. This report provides the first in vivo experimental evidence of the metabolic flux distribution in the catabolic pathway of glucose and lactose in bifidobacteria and shows that the bifid shunt is the only pathway involved in energy recruitment from these two sugars. On the basis of our experimental results, a model of sugar metabolism in B. animalis subsp. lactis is proposed.


An MCASE approach to the search of a cure for Parkinson's Disease.
Parkinson's disease is caused by a dopamine deficiency state in the fore brain area. Dopamine receptor agonists, MAO-B inhibitors, and N-Methyl-D-Aspartate (NMDA) receptor antagonists are known to have antiparkinson effect. Levodopa, a dopamine structural analog, is the best currently available medication for the treatment of Parkinsons disease. Unfortunately, it also induces side effects upon long administration time. Thus, multidrug therapy is often used, in which various adjuvants alleviate side effects of levodopa and enhance its antiparkinsonian action. Computer models have been created for three known antiparkinson mechanisms using the MCASE methodology. New drugs for Parkinsons disease can be designed on the basis of these models. We also speculate that the presence of biophores belonging to different groups can be beneficial and designed some potential drugs along this line. The proposed compounds bear pharmacophores of MAO-B inhibitors, dopamine agonists and NMDA antagonists, which could synergistically enhance their antiparkinson effect. The methodology could readily be expanded to other endpoints where drugs with multiple activity mechanisms would be desirable.


Comparison of RAW264.7, human whole blood and PBMC assays to screen for immunomodulators.
The RAW264.7 mouse macrophage cell line is used extensively to carry out in vitro screens for immunomodulators. Compounds that are effective at reducing the expression of pro-inflammatory cytokines or nitric oxide (NO) from lipopolysaccharide (LPS)-stimulated RAW264.7 cells are often considered candidate anti-inflammatory agents for humans. There is, however, very little data on the reliability of this screen to identify bona fide human immunomodulators. We compared the efficacy of 37 purported immunomodulators to modulate LPS or E. coli-induced inflammatory responses in RAW264.7 cell, whole human blood and human peripheral blood mononuclear cell (PBMC) assays. Interestingly, there was no significant correlation (R=0.315) between the responses obtained with RAW264.7 cells and the whole blood assay (WBA), suggesting that compounds demonstrating efficacy in RAW264.7 cells may be ineffective in humans, and, more importantly, compounds that are effective in humans may be missed with a RAW264.7 screen. Interestingly, there was also no significant correlation between the WBA and human PBMCs when the latter were cultured with 10% FCS, but a moderate correlation was seen when the PBMCs were cultured with 25% autologous plasma. The presence of plasma thus contributes to the overall inflammatory response observed in the WBA. We then asked if RAW264.7 cells, given that they are mouse macrophage-like cells, respond in a manner similar to primary murine derived macrophages. Intriguingly, there was no significant correlation (R=0.012) with the 37 putative immunomodulators, pointing to distinct inflammatory response mechanisms in the two model systems. We conclude that the use of a WBA to confirm potential immunomodulators obtained from high throughput screening with RAW264.7 cells is advisable and that future screens be carried out using a WBA.


Endogenous lipoid pneumonia associated with undifferentiated connective tissue disease (UCTD).
Lipoid pneumonia is a rare pulmonary disease, a form of pneumonia that has no classical radiological appearance, thus it can imitate other lung diseases. Lipoid pneumonia is usually classified into two major groups, depending on whether the source of oil/fat in the respiratory tract is from an exogenous or endogenous source. Undifferentiated connective tissue disease is a term used by rheumatologists to define a group of diffuse connective tissue disorders that lack definitive characteristics of any particular well-defined disorder. A case study is reported of concomitant undifferentiated connective tissue disease and endogenous lipoid pneumonia. Histologically the macrophages appeared filled with lipid and were similar to atherosclerotic foam cell macrophages. Antibiotic and antimycotic treatments were ineffective. However, with concomitant steroid treatment, the patient exhibited absence of lung infiltration as well as other symptoms and was discharged. Therefore it is concluded that the lipoid pneumonia was steroid dependent. Since the patient's condition responded to steroid treatment, and it is clear that steroids inhibit phospholipase activity, the authors speculate that the subsequent decreased endoperoxide production may diminish lipid uptake by macrophages via decreasing modification of LDL or other lipid sources.


Language-based embedded performance validity measures in traumatic brain injury.
No studies to date have investigated the Boston Naming Test (BNT) as an embedded performance validity test (PVT). This study investigated the classification accuracy of the Boston Naming Test (BNT) and the Verbal Fluency Test (FAS and Animal Fluency), as embedded PVTs in a compensation-seeking mild traumatic brain injury (MTBI) sample (N = 57) compared to a non-compensation-seeking moderate-to-severe TBI (STBI) sample (N = 61). Participants in the MTBI sample who failed two or more PVTs were included, as were STBI participants who passed all PVTs. The classification accuracy of the individual tests and a logistically derived combined (LANGPVT) measure were studied. Results showed significant group differences (p < .05) on BNT, Animal Fluency, and LANGPVT between the MTBI and STBI groups. However, receiver operating characteristic (ROC) analyses indicated that only LANGPVT had acceptable classification accuracy (area under the curve > .70). Setting specificity at approximately .90, the recommended LANGPVT cutoff scores had sensitivity of .26. Results indicated that, similar to other embedded PVTs, these measures had low sensitivity when adequate specificity levels were maintained. However, extremely low scores on these measures are unlikely to occur in non-compensation-seeking, non-language-impaired, STBI cases.


Evidence for historical introgression along a contact zone between two species of char (Pisces: Salmonidae) in northwestern North America.
Phylogeographic analyses can yield valuable insights into the geographic and historical contexts of contact and hybridization between taxa. Two species of char (Salmonidae), Dolly Varden (Salvelinus malma) and bull trout (S. confluentus) have largely parapatric distributions in watersheds of northwestern North America. They are, however, sympatric in several localities and hybridization and some introgression occurs across a broad area of contact. We conducted a comparative phylogenetic analysis of Dolly Varden and bull trout to gain a historical perspective of hybridization between these species and to test for footprints of historical introgression. We resolved two major Dolly Varden mitochondrial DNA (mtDNA) clades (with 1.4-2.2% sequence divergence between haplotypes) that had different geographical distributions. Clade N is distributed across most of the range of Dolly Varden, from southern British Columbia through to the Kuril Islands in Asia. Clade S had a much more limited distribution, from Washington state, at the southern limit of the Dolly Varden range, to the middle of Vancouver Island. The distribution and inferred ages of the mtDNA clades suggested that Dolly Varden survived the Wisconsinan glaciation in a previously unsuspected refuge south of the ice sheet, and that Dolly Varden and bull trout were probably in continuous contact over most of the last 100,000 years. When bull trout were included in the phylogenetic analysis, however, the mtDNA of neither species was monophyletic: Clade S Dolly Varden clustered within the bull trout mtDNA clade. This pattern was discordant with two nuclear phylogenies produced (growth hormone 2 and rRNA internal transcribed sequence 1), in which Dolly Varden and bull trout were reciprocally monophyletic. This discordance between mtDNA- and nDNA-based phylogenies indicates that historical introgression of bull trout mtDNA into Dolly Varden occurred. Percent sequence divergence within these introgressed Dolly Varden (clade S) was 0.2-0.6%, implying that the introgression occurred prior to the most recent glaciation. Our analysis and other evidence of contact between divergent lineages in northwestern North America strongly suggests that the area may be the site of previously unsuspected suture zones of aquatic biotas.


Diagnosis and general practice.
This discussion paper presents the case for a rigorous diagnostic research agenda within primary care. In view of unique aspects of primary care medicine and the relatively unselected nature of the populations encountered by general practitioners, it is clear that diagnostic research undertaken in other settings may be inapplicable. Most diagnostic studies adopt designs that seek to compare items, or clusters of items, of clinical information against a gold standard. In order to enhance the feasibility and rigour of such research within primary care, suggestions are made about priorities and specific key methodological issues. It is essential that the information generated by primary care diagnostic research should be reliable, valid, useful, and useable within general practice. The ultimate objective must be the identification of specific items, or small clusters of items, of clinical information of high discriminant ability among the groups of patients encountered in general practice.


Induction of Rhizobium meliloti nodC expression by plant exudate requires nodD.
The soil bacterium Rhizobium meliloti invades and establishes a symbiosis with host plants such as alfalfa. Bacterial nodulation (nod) genes are required for this invasion, but their mechanism of action and the timing of their expression are not known. We have used translational lacZ fusions to monitor expression of nodD and nodC, which are located in the cluster of four nod genes on the R. meliloti megaplasmid (pSym). nodD is expressed at comparable levels by broth-grown bacterial cells and by cells exposed to exudates from aseptically grown plants. Activity of the nodC-lacZ protein fusion in broth-grown bacterial cells is very low. nodC-lacZ activity is increased approximately equal to 30-fold by plant exudate when nodD is expressed at a high level but not when nodD expression is low. Both fusions show differences in expression when borne on inc-P vectors as compared to when located on the pSym megaplasmid. nodD expression from vector-borne copies of the nod segment and response of nodC to plant exudate appear to require additional loci on the megaplasmid. Our results suggest that regulation of bacterial nod gene expression is an important control mechanism early in the symbiosis, and that the biochemical nature of some nod gene products may be cryptic except in cells grown in the presence of plant exudate.


Identification of novel inhibitors of angiotensin-converting enzyme 2 (ACE-2) receptor from Urtica dioica to combat coronavirus disease 2019 (COVID-19).
The pandemic outbreak of coronavirus (SARS-CoV-2) is rapidly spreading across the globe, so the development of anti-SARS-CoV-2 agents is urgently needed. Angiotensin-converting enzyme 2 (ACE-2), a human receptor that facilitates entry of SARS-CoV-2, serves as a prominent target for drug discovery. In the present study, we have applied the bioinformatics approach for screening of a series of bioactive chemical compounds from Himalayan stinging nettle (Urtica dioica) as potent inhibitors of ACE-2 receptor (PDB ID: 1R4L). The molecular docking was applied to dock a set of representative compounds within the active site region of target receptor protein using 0.8 version of the PyRx virtual screen tool and analyzed by using discovery studio visualizer. Based on the highest binding affinity, 23 compounds were shortlisted as a lead molecule using molecular docking analysis. Among them, β-sitosterol was found with the highest binding affinity - 12.2 kcal/mol and stable interactions with the amino acid residues present on the active site of the ACE-2 receptor. Similarly, luteoxanthin and violaxanthin followed by rutin also displayed stronger binding efficiency. We propose these compounds as potential lead candidates for the development of target-specific therapeutic drugs against COVID-19.


Formation and repair of DNA interstrand cross-links in relation to cytotoxicity and unscheduled DNA synthesis induced in control and mutant human cells treated with cis-diamminedichloroplatinum(II).
A comparative study was performed with a variety of human cell lines on the effects of treatments with cis-diamminedichloroplatinum(II) (cisplatin) on cell survival and the induction of unscheduled DNA synthesis. In addition to control fibroblasts (Han, MB), cell lines defective in DNA repair were used [xeroderma pigmentosum, XP(A) and XP(F), and Fanconi's anemia (FA)], as well as cells deficient in arylsulfatase A (mucolipidosis II, ML1 and ML2). Ultraviolet light and mitomycin C were included in this study as model DNA-damaging agents. Furthermore, induction of DNA interstrand cross-links by cisplatin and their repair were studied. As for survival, only XP cells were abnormally sensitive to ultraviolet light, and only FA cells were abnormally sensitive to mitomycin C. To cisplatin, however, all mutants tested were more sensitive (2 to 5 times) than were normal cells. Unscheduled DNA synthesis induction by ultraviolet light was strong in all but the XP cells; the other two agents did not induce unscheduled DNA synthesis. Induction of DNA interstrand cross-links by cisplatin was linear with dose. Formation continued for up to 18 to 24 h after treatment. During this period, all cells but the ML mutants responded similarly. In ML cells, much fewer cross-links were induced, which were repaired rapidly. In FA cells, accumulation continued for at least 96 h; in the other cells, most of the cross-links had been removed after that period. In the discussion, the cisplatin-induced DNA interstrand cross-links are proposed as an important potentially lethal lesion, in view of their persistence in the highly sensitive FA cells. Furthermore, the possible involvement of certain steps of the long-patch excision repair pathway in the removal of this lesion is considered. The sensitivity of ML cells to cisplatin is attributed to cytoplasmic effects, rather than to chromosomal damage.


Factors Predicting Treatment of World Trade Center-Related Lung Injury: A Longitudinal Cohort Study.
The factors that predict treatment of lung injury in occupational cohorts are poorly defined. We aimed to identify patient characteristics associated with initiation of treatment with inhaled corticosteroid/long-acting beta-agonist (ICS/LABA) >2 years among World Trade Center (WTC)-exposed firefighters. The study population included 8530 WTC-exposed firefighters. Multivariable logistic regression assessed the association of patient characteristics with ICS/LABA treatment for >2 years over two-year intervals from 11 September 2001-10 September 2017. Cox proportional hazards models measured the association of high probability of ICS/LABA initiation with actual ICS/LABA initiation in subsequent intervals. Between 11 September 2001-1 July 2018, 1629/8530 (19.1%) firefighters initiated ICS/LABA treatment for >2 years. Forced Expiratory Volume in 1 s (FEV1), wheeze, and dyspnea were consistently and independently associated with ICS/LABA treatment. High-intensity WTC exposure was associated with ICS/LABA between 11 September 2001-10 September 2003. The 10th percentile of risk for ICS/LABA between 11 September 2005-10 Septmeber 2007 was associated with a 3.32-fold increased hazard of actual ICS/LABA initiation in the subsequent 4 years. In firefighters with WTC exposure, FEV1, wheeze, and dyspnea were independently associated with prolonged ICS/LABA treatment. A high risk for treatment was identifiable from routine monitoring exam results years before treatment initiation.


Comparative charge analysis of one- and two-level lumbar total disc arthroplasty versus circumferential lumbar fusion.
This is a retrospective, independent study comparing 2 groups of patients treated surgically for discogenic low back pain associated with degenerative disc disease (DDD) in the lumbosacral spine. To compare the surgical and hospitalization charges associated with 1- and 2-level lumbar total disc replacement and circumferential lumbar fusion. Reported series of lumbar total disc replacement have been favorable. However, economic aspects of lumbar total disc replacement (TDR) have not been published or studied. This information is important considering the recent widespread utilization of new technologies. Recent studies have demonstrated comparable short-term clinical results between TDR and lumbar fusion recipients. Relative charges may be another important indicator of the most appropriate procedure. We report a hospital charge-analysis comparing ProDisc lumbar disc replacement with circumferential fusion for discogenic low back pain. In a cohort of 53 prospectively selected patients with severe, disabling back pain and lumbar disc degeneration, 36 received Synthes ProDisc TDR and 17 underwent circumferential fusion for 1- and 2-level degenerative disc disease between L3 and S1. Randomization was performed using a 2-to-1 ratio of ProDisc recipients to control spinal fusion recipients. Charge comparisons, including operating room charges, inpatient hospital charges, and implant charges, were made from hospital records using inflation-corrected 2006 U.S. dollars. Operating room times, estimated blood loss, and length of stay were obtained from hospital records as well. Surgeon and anesthesiologist fees were, for the purposes of comparison, based on Medicare reimbursement rates. Statistical analysis was performed using a 2-tailed Student t test. For patients with 1-level disease, significant differences were noted between the TDR and fusion control group. The mean total charge for the TDR group was $35,592 versus $46,280 for the fusion group (P = 0.0018). Operating room charges were $12,000 and $18,950, respectively, for the TDR and fusion groups (P < 0.05). Implant charges averaged $13,990 for the fusion group, which is slightly higher than the $13,800 for the ProDisc (P = 0.9). Estimated blood loss averaged 794 mL in the fusion group versus 412 mL in the TDR group (P = 0.0058). Mean OR minutes averaged 344 minutes for the fusion group and 185 minutes for the TDR (P < 0.05) Mean length of stay was 4.78 days for fusion versus 4.32 days for TDR (P = 0.394). For patients with 2-level disease, charges were similar between the TDR and fusion groups. The mean total charge for the 2-level TDR group was $55,524 versus $56,823 for the fusion group (P = 0.55). Operating room charges were $15,340 and $20,560, respectively, for the TDR and fusion groups (P = 0.0003). Surgeon fees and anesthesiologist charges based on Medicare reimbursement rates were $5857 and $525 for the fusion group, respectively, versus $2826 and $331 for the TDR group (P < 0.05 for each). Implant charges were significantly lower for the fusion group (mean, $18,460) than those for 2-level Synthes ProDisc ($27,600) (P < 0.05). Operative time averaged 387 minutes for fusion versus 242 minutes for TDR (P < 0.0001). EBL and length of stay were similar. Patients undergoing 1- and 2-level ProDisc total disc replacement spent significantly less time in the OR and had less EBL than controls. Charges were significantly lower for TDR compared with circumferential fusions in the 1-level patient group, while charges were similar in the 2-level group.


The role of angiography in the congruence of cardiovascular measurements between autopsy and postmortem imaging.
Postmortem CT angiography is the method of choice for the postmortem imaging investigations of the cardiovascular (CV) system. However, autopsy still remains the gold standard for CV measurement. Nevertheless, there are not any studies on CV measurements on the multi-phase postmortem angiography (MPMCTA) which includes comparisons with autopsy. Therefore, the aim of this study is to compare CV measurements between the native CT scan and the three phases of the MPMCTA to find out which of these modalities correlate the best with autopsy measurements. For this study, we selected retrospectively 50 postmortem cases that underwent both MPMCTA and autopsy. A comparison was carried out between the CV measurements obtained with imaging (aorta; heart cavities and cardiac wall thicknesses; maximum cardiac diameter and cardiothoracic ratio) and at the autopsy (aorta; cardiac valves, ventricular thicknesses, and weight). Our results show that the dynamic phase displays an advantage for the measurement of the aortas. However, the MPMCTA is not accurate to measure the cardiac wall thicknesses. The measurements of the heart cavities show no correlation with the heart valves. The cardiothoracic ratio measured by the MPMCTA shows no correlation with the heart weight. Nevertheless, the maximum cardiac diameter exhibits a correlation with the latter on the venous and dynamic phase. These results show that only few CV parameters measured with imaging correlate with measurement obtained at the autopsy. These results indicate that in order to better estimate values obtained at the autopsy, we need to define new reference values for the CV measurement on MPMCTA.


Rescue of the orphan enzyme isoguanine deaminase.
Cytosine deaminase (CDA) from Escherichia coli was shown to catalyze the deamination of isoguanine (2-oxoadenine) to xanthine. Isoguanine is an oxidation product of adenine in DNA that is mutagenic to the cell. The isoguanine deaminase activity in E. coli was partially purified by ammonium sulfate fractionation, gel filtration, and anion exchange chromatography. The active protein was identified by peptide mass fingerprint analysis as cytosine deaminase. The kinetic constants for the deamination of isoguanine at pH 7.7 are as follows: k(cat) = 49 s(-1), K(m) = 72 μM, and k(cat)/K(m) = 6.7 × 10(5) M(-1) s(-1). The kinetic constants for the deamination of cytosine are as follows: k(cat) = 45 s(-1), K(m) = 302 μM, and k(cat)/K(m) = 1.5 × 10(5) M(-1) s(-1). Under these reaction conditions, isoguanine is the better substrate for cytosine deaminase. The three-dimensional structure of CDA was determined with isoguanine in the active site.


Dispositional mindfulness attenuates the emotional attentional blink.
Emotional stimuli have been shown to automatically hijack attention, hindering the detection of forthcoming targets. Mindfulness is defined as a present moment non-judgemental attentional stance that can be cultivated by meditation practices, but that may present interindividual variability in the general population. The mechanisms underlying modification in emotional reactivity linked to mindfulness are still a matter of debate. In particular, it is not clear whether mindfulness is associated with a diminished emotional response, or with faster recovery. We presented participants with target pictures embedded in a rapid visual presentation stream. The targets could be preceded by negative, neutral or scrambled critical distractors. We showed that dispositional mindfulness, in particular the Non-reacting facet, was related to faster disengagement of attention from emotional stimuli. These results could have implications for mood disorders characterised by an exaggerated attentional bias toward emotional stimuli, such as anxiety and post-traumatic stress disorders.


Field research in humanitarian medical programmes. Treatment of neuropathic pain in Sierra Leone.
A pilot study was carried out among 223 war wounded and amputees in Sierra Leone in 2001 to investigate whether an intervention using proven medication for clinically diagnosed neuropathic pain would work in a developing country with limited health services. Compliance with medication was assessed in 79 patients and their pain and mood scores were assessed by questionnaire before medication and 6-10 months later. The pain and mood scores of 33 patients who stopped taking medication were compared for the initial and follow-up assessments indicating that, although the scores showed an improvement at follow-up, there was no significant improvement. Compliance was reasonable in 46 patients who continued with their medication, with 86.5% of possible doses collected although many had difficulty understanding how to take the drugs properly. Their pain and mood scores showed significant improvement at reassessment indicating that pain will be reduced with a longer duration of treatment. This study showed that it is possible to run an effective intervention for neuropathic pain in Sierra Leone with intermittent expert involvement and MSF have been able to develop a protocol for the assessment and treatment of neuropathic pain that may be useful in other difficult settings in which they work.


[Clinico-catamnestic study of the development of remissions in adolescents suffering recurrent schizophrenia].
The formation of remissions of recurrent schizophrenia was studied over time in 32 adolescents (12-17 years of age). Over the period of follow-up (4-8 years) the author analyzed 23 affective-oneiric and 50 affective-delirious attacks of schizophrenia and traced the history of patients at the age of 18-23 years. Following attacks of recurrent schizophrenia all patients presented a gradual formation of remissions. At the first stages continuous affective disturbances were well pronounced. In the course of their subsidence, 1.5-2 years after the end of attacks the patients were characterized by mild personality changes and a slight decrease in the energy potential as compared to its high premorbid level. A number of therapeutic-adaptational recommendations has been developed for the management of patients with recurrent schizophrenia in the period of remission formation.


Functional analysis of an individual IFT protein: IFT46 is required for transport of outer dynein arms into flagella.
Intraflagellar transport (IFT), which is the bidirectional movement of particles within flagella, is required for flagellar assembly. IFT particles are composed of approximately 16 proteins, which are organized into complexes A and B. We have cloned Chlamydomonas reinhardtii and mouse IFT46, and show that IFT46 is a highly conserved complex B protein in both organisms. A C. reinhardtii insertional mutant null for IFT46 has short, paralyzed flagella lacking dynein arms and with central pair defects. The mutant has greatly reduced levels of most complex B proteins, indicating that IFT46 is necessary for complex B stability. A partial suppressor mutation restores flagellar length to the ift46 mutant. IFT46 is still absent, but levels of the other IFT particle proteins are largely restored, indicating that complex B is stabilized in the suppressed strain. Axonemal ultrastructure is restored, except that the outer arms are still missing, although outer arm subunits are present in the cytoplasm. Thus, IFT46 is specifically required for transporting outer arms into the flagellum.


Effects of honey on inflammation and nitric oxide production in Wistar rats.
The aim of the study is to investigate the effects of honey on acute and chronic inflammations and nitric oxide production in rats. Carrageenan, cotton pellet and formaldehyde methods were used in quantifying the anti-inflammatory effect of honey while the effect of honey on nitric oxide (NO) production was investigated by administering NG-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg body weight, subcutaneously) and L-arginine (300 mg/kg body weight, intraperitoneally) to groups of rats. Animals were divided into five groups each comprising of five rats in each experiment; two groups were orally administered distilled water (control) and indomethacin (5 mg/kg body weight), respectively, while the remaining three groups were administered 2, 6 and 10 g/kg honey for anti-inflammatory studies. Honey significantly (P<0.05) reduced the paw size in the carrageenan model, while in the cotton pellet model, the granuloma weight was significantly (P<0.05) reduced. Honey also significantly (P<0.05) reduced the arthritis induced by formaldehyde injection from the second day of the study. In the investigation on NO involvement, L-NAME significantly inhibited paw oedema while the administration of L-arginine abolished the anti-inflammatory effect of honey and L-NAME. The results obtained from the study confirm that honey has an anti-inflammatory effect which may be due in part to inhibition of NO release. Therefore honey may be used to treat certain acute and chronic inflammatory conditions.


Ectoparasite fitness in auxiliary hosts: phylogenetic distance from a principal host matters.
We studied reproductive performance in two flea species (Parapulex chephrenis and Xenopsylla ramesis) exploiting either a principal or one of eight auxiliary host species. We predicted that fleas would produce more eggs and adult offspring when exploiting (i) a principal host than an auxiliary host and (ii) an auxiliary host phylogenetically close to a principal host than an auxiliary host phylogenetically distant from a principal host. In both flea species, egg production per female after one feeding and production of new imago after a timed period of an uninterrupted stay on a host differed significantly between host species. In general, egg and/or new imago production in fleas feeding on an auxiliary host was lower than in fleas feeding on the principal host, except for the auxiliary host that was the closest relative of the principal host. When all auxiliary host species were considered, we did not find any significant relationship between either egg or new imago production in fleas exploiting an auxiliary host and phylogenetic distance between this host and the principal host. However, when the analyses were restricted to auxiliary hosts belonging to the same family as the principal host (Muridae), new imago production (for P. chephrenis) or both egg and new imago production (for X. ramesis) in an auxiliary host decreased significantly with an increase in phylogenetic distance between the auxiliary and principal host. Our results demonstrated that a parasite achieves higher fitness in auxiliary hosts that are either the most closely related to or the most distant from its principal host. This may affect host associations of a parasite invading new areas.


Applying a COVID Virtual Ward model, assessing patient outcomes and staff workload.
A COVID virtual ward (CVW) is recommended by NHS England, but 'usual care' outcomes have not been reported. A retrospective study of all adults with COVID-19 attending Queen Elizabeth Hospital Birmingham between 01/06/2020-31/01/2021, assessed against CVW criteria and followed for 28 days. Of 2301 COVID-19 patients, 571(25%) would have met CVW criteria. Of these, 325(57%) were discharged after review and 246(43%) admitted. Of admitted patients who met CVW criteria, 81% required hospital-supported therapies; 11% died. Of the 325 discharged, 13% re-presented, 9% with COVID-related symptoms, 2% required intensive care admission, and one died (0.3%). In this comparison, discharging patients without a CVW did not lead to more re-presentations, re-admissions, ITU escalations or deaths compared to published outcomes for hospitals with a CVW.


Reduced constrictor reactivity balances impaired vasodilation in the mesenteric circulation of the obese Zucker rat.
Obesity causes whole body insulin resistance and impaired vasodilation to nitric oxide (NO). Because NO is a major contributor to the regulation of mesenteric blood flow, the mesenteric circulation of obese animals is faced with reduced capacity to increase flow and increased demand for flow associated with elevated consumption of food. This study hypothesized that insulin resistance impairs NO-mediated dilation but that constrictor reactivity would be reduced to compensate in obese animals. We further hypothesized that elevated superoxide levels caused impaired responses to NO in insulin resistance. Vasodilator reactivity and vasoconstrictor reactivity of mesenteric resistance arteries from lean (LZR) and obese (OZR) Zucker rats were examined in vitro using videomicroscopy. Insulin resistance independent of obesity was induced via fructose feeding in LZR (FF-LZR). Endothelium-dependent NO-mediated dilation was reduced in OZR and FF-LZR compared with LZR. Impairments in NO-mediated dilation were reversed with 1 mM tempol, a SOD mimetic. Constrictor reactivity to norepinephrine was reduced in OZR but not in FF-LZR relative to LZR. Basal mesenteric vascular resistance was similar in LZR and OZR despite impaired NO-dependent dilation in OZR. Mesenteric vascular resistance was increased in FF-LZR relative to LZR. These data indicate that there is reduced constrictor reactivity in OZR that may offset the impaired NO-mediated dilation and preserve mesenteric blood flow in hyperphagic, obese animals.


Oropharyngeal Contamination Predisposes to Complications after Neck Dissection: An Analysis of 9462 Patients.
While neck dissection is important in the treatment of head and neck cancer, there is a paucity of studies evaluating outcomes. We sought to compare preoperative variables and outcomes between clean and contaminated neck dissections, using the 2006-2011 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) data sets. Retrospective review of prospectively maintained database. Multicenter (university hospitals; tertiary referral centers). A retrospective review was performed of the NSQIP database to identify patients undergoing neck dissection in clean vs oropharyngeal contaminated cases. Clinical factors, comorbidities, epidemiologic factors, and procedural characteristics were analyzed to identify factors associated with 30-day postoperative adverse events, including medical and surgical complications, unplanned reoperation, and mortality. Bivariate and multivariable analyses were performed for the outcome of one or more adverse events. In total, 8890 patients had clean neck dissections, while 572 patients had neck wound contamination with oropharyngeal flora. On multivariable regression analysis, oropharyngeal contamination was a significant risk factor for surgical complications (odds ratio [OR], 3.42; 95% confidence interval [CI], 1.96-5.96; P < .001). However, medical complications and mortality were not significantly different between the 2 cohorts. This finding persisted after subgroup analysis, with removal of all thyroidectomy patients from analysis (OR, 2.33; 95% CI, 1.25-4.36; P = .008). Using the ACS-NSQIP data set, this study found an increased risk of surgical complications in the setting of contaminated neck dissections. These data should be used for patient risk stratification, informed consent, and to guide further research.