Successful treatment of prolonged cholestasis following hepatitis A infection in a child with oral steroid therapy.
Hepatitis A is a common cause of acute infectious hepatitis in children, transmitted through the faeco-oral route. Although mostly self-limiting, cholestasis is a rare but known complication of acute hepatitis A in children. This report presents an adolescent girl who developed cholestatic features following hepatitis A infection and successful treatment with oral steroid therapy. Prolonged cholestasis jaundice (PCJ) is a known manifestation of hepatitis A infection, characterised by prolonged fever, pruritus and jaundice. While the exact mechanisms causing PCJ are not fully understood, immunological-mediated responses could play a role. Treatment options for PCJ are limited, and there is no currently accepted standard of care. Steroids have shown promise in treating PCJ, as observed in this case and a few other reported cases. When other therapies fail to alleviate symptoms, corticosteroids should be considered as a potential treatment option. However, further studies are required to conclusively establish their efficacy.


Intradermal HIV-1 DNA Immunization Using Needle-Free Zetajet Injection Followed by HIV-Modified Vaccinia Virus Ankara Vaccination Is Safe and Immunogenic in Mozambican Young Adults: A Phase I Randomized Controlled Trial.
We assessed the safety and immunogenicity of HIV-DNA priming using Zetajet™, a needle-free device intradermally followed by intramuscular HIV-MVA boosts, in 24 healthy Mozambicans. Volunteers were randomized to receive three immunizations of 600 μg (n = 10; 2 × 0.1 ml) or 1,200 μg (n = 10; 2 × 0.2 ml) of HIV-DNA (3 mg/ml), followed by two boosts of 108 pfu HIV-MVA. Four subjects received placebo saline injections. Vaccines and injections were safe and well tolerated with no difference between the two priming groups. After three HIV-DNA immunizations, IFN-γ ELISpot responses to Gag were detected in 9/17 (53%) vaccinees, while none responded to Envelope (Env). After the first HIV-MVA, the overall response rate to Gag and/or Env increased to 14/15 (93%); 14/15 (93%) to Gag and 13/15 (87%) to Env. There were no significant differences between the immunization groups in frequency of response to Gag and Env or magnitude of Gag responses. Env responses were significantly higher in the higher dose group (median 420 vs. 157.5 SFC/million peripheral blood mononuclear cell, p = .014). HIV-specific antibodies to subtype C gp140 and subtype B gp160 were elicited in all vaccinees after the second HIV-MVA, without differences in titers between the groups. Neutralizing antibody responses were not detected. Two (13%) of 16 vaccinees, one in each of the priming groups, exhibited antibodies mediating antibody-dependent cellular cytotoxicity to CRF01_AE. In conclusion, HIV-DNA vaccine delivered intradermally in volumes of 0.1-0.2 ml using Zetajet was safe and well tolerated. Priming with the 1,200 μg dose of HIV-DNA generated higher magnitudes of ELISpot responses to Env.


Dietary treatment of diabetic nephropathy with chronic renal failure.
Thirty-two patients with diabetes mellitus (22 IDDM and 10 NIDDM, 21 males and 11 females, age 44+/-11.8 years) were followed for 5.2+/-3.8 years after the onset of chronic renal failure, with the aim of evaluating the effect of low protein diets on the rate of decline of the residual renal function. During the 1.8+/-1.6 year follow-up period on free or uncontrolled low protein diet the mean rate of decline of creatinine clearance was 0.9+/-0.6 ml/min/month, significantly greater than that observed during 3.7+/-3.1 years on low or very low protein diets. The reduction of protein intake was followed by a significant decrease in daily urinary protein loss. A better glycaemic control was obtained on the low protein diet, and the daily insulin requirement decreased. The anthropometry, as well as the serum concentrations of rapid turnover proteins, did not change, in spite of the low or very low protein dietary supply for a long duration. The values of mean arterial pressure were quite similar during the follow-up period on free or uncontrolled low protein diet and during the study period on the low protein diet. A good compliance with reduced dietary intake (as demonstrated by the measurement of the daily urea excretion) was obtained in a large number of patients. In conclusion, our study confirms the protective effect on the residual renal function of low protein diets in IDDM and NIDDM patients with chronic renal failure due to diabetic nephropathy, in the absence of any sign of protein malnutrition.


Characterization of palmprints by wavelet signatures via directional context modeling.
The palmprint is one of the most reliable physiological characteristics that can be used to distinguish between individuals. Current palmprint-based systems are more user friendly, more cost effective, and require fewer data signatures than traditional fingerprint-based identification systems. The principal lines and wrinkles captured in a low-resolution palmprint image provide more than enough information to uniquely identify an individual. This paper presents a palmprint identification scheme that characterizes a palmprint using a set of statistical signatures. The palmprint is first transformed into the wavelet domain, and the directional context of each wavelet subband is defined and computed in order to collect the predominant coefficients of its principal lines and wrinkles. A set of statistical signatures, which includes gravity center, density, spatial dispersivity and energy, is then defined to characterize the palmprint with the selected directional context values. A classification and identification scheme based on these signatures is subsequently developed. This scheme exploits the features of principal lines and prominent wrinkles sufficiently and achieves satisfactory results. Compared with the line-segments-matching or interesting-points-matching based palmprint verification schemes, the proposed scheme uses a much smaller amount of data signatures. It also provides a convenient classification strategy and more accurate identification.


The current state of sleep medicine education in US neurology residency training programs: where do we go from here?
To evaluate the current state of sleep medicine educational resources and training offered by US neurology residency programs. In 2010, a 20-item peer reviewed Sleep Education Survey (SES) was sent to neurology residency program directors surveying them about sleep medicine educational resources used in teaching residents. Pearson product momentum correlation was used to determine correlation of program attributes with resident interest in pursuing a career in sleep medicine. Of the programs completing the survey, 81% listed a formal sleep rotation and 24% included a forum for sleep research. A variety of innovative approaches for teaching sleep medicine were noted. Program directors noted that 5.7% residents entered sleep medicine fellowship training programs in the preceding 5 years. Programs that had a more substantial investment in sleep medicine teaching resources were more likely to report residents entering a sleep medicine training program. This is the first report providing an analysis of the current state of sleep medicine training in US Neurology Residency Programs. Our data provide evidence that investment by the residency program in sleep education may enhance the ultimate decision by the neurology trainee to pursue a career in sleep medicine.


Factors associated with overall and attributable mortality in invasive aspergillosis.
Invasive aspergillosis is associated with high death rates. Factors associated with increased mortality have not yet been identified in a large population of patients with various underlying conditions. We retrospectively reviewed 385 cases of suspected or documented aspergillosis that occurred during a 9-year period. We identified 289 episodes that fulfilled the criteria for possible, probable, or proven invasive aspergillosis according to the international definition criteria and that was treated with an anti-Aspergillus active antifungal drug. Clinical and microbiological variables were analyzed for their effects on overall and attributable mortality. Significant variables in univariate analysis were introduced into a multivariate Cox model. Twelve-week overall and disease-specific survival rates were 52.2% (95% confidence interval, 46.5%-57.9%) and 59.8% (95% confidence interval, 54.0%-65.4%), respectively. Receipt of allogeneic hematopoietic stem cell or solid-organ transplant, progression of underlying malignancy, prior respiratory disease, receipt of corticosteroid therapy, renal impairment, low monocyte counts, disseminated aspergillosis, diffuse pulmonary lesions, pleural effusion, and proven or probable (as opposed to possible) aspergillosis are predictors of increased overall mortality. Similar factors are also predictors of increased attributable mortality, with the following exceptions: pleural effusion and low monocyte counts have no impact, whereas neutropenia is associated with a higher attributable mortality. Identification of predictors of death helps in the identification of patients who could benefit from more-aggressive therapeutic strategies. Initiation of therapy at the stage of possible infection improves outcome, and this finding calls for the development of efficient preemptive strategies to fill the gap between empirical and directed therapy.


Impact of Cumulative Inflammation, Cardiac Risk Factors, and Medication Exposure on Coronary Atherosclerosis Progression in Rheumatoid Arthritis.
To explore incidence and progression of coronary atherosclerosis and identify determinants in patients with rheumatoid arthritis (RA). We specifically evaluated the impact of inflammation, cardiac risk factors, duration of medication exposure, and their interactions on coronary plaque progression. One hundred one participants with baseline coronary computed tomography angiography findings underwent follow-up assessment a mean ± SD of 83 ± 3.6 months after baseline. Plaque burden was reported as the segment involvement score (describing the number of coronary segments with plaque) and the segment stenosis score (characterizing the cumulative plaque stenosis over all evaluable segments). Plaque composition was classified as noncalcified, mixed, or calcified. Coronary artery calcium (CAC) was quantified using the Agatston method. Total plaque increased in 48% of patients, and progression was predicted by older age, higher cumulative inflammation, and total prednisone dose (P < 0.05). CAC progressors were older, more obese, hypertensive, and had higher cumulative inflammation compared to nonprogressors (P < 0.05). Longer exposure to biologics was associated with lower likelihood of noncalcified plaque progression, lesion remodeling, and constrained CAC change in patients without baseline calcification, independent of inflammation, prednisone dose, or statin exposure (all P < 0.05). Longer statin treatment further restricted noncalcified plaque progression and attenuated the effect of inflammation on increased plaque and CAC (P < 0.05). Stringent systolic blood pressure (BP) control further weakened the effect of inflammation on total plaque progression. Inflammation was a consistent and independent predictor of coronary atherosclerosis progression in RA. It should therefore be specifically targeted toward mitigating cardiovascular risk. Biologic disease-modifying antirheumatic drugs, statins, and BP control may further constrain plaque progression directly or indirectly.


Short posterior ciliary artery anatomy in normal and acutely glaucomatous dogs.
To quantify the total number and luminal areas of the short posterior ciliary arteries (SPCA) surrounding the canine optic nerve at the level of the sclera/lamina cribrosa in normal dogs and compare this data to dogs with a history of acute (≤7 days) glaucoma. Twelve normal globes were obtained through Harlan Laboratories, the UW-Madison School of Veterinary Medicine necropsy service and via enucleation submissions to the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW). Ten globes with a history of acute glaucoma were obtained from submissions to the COPLOW. Optic nerves were cross-sectioned in 20 micron steps, and five distinct levels were identified: the retinal nerve fiber layer; the retinal pigmented epithelium and neural canal opening; the choroid/pre-lamina; the sclera/lamina cribrosa; and the retro-lamina. At the level of the sclera/lamina cribrosa, SPCA profiles were counted and the luminal area was measured using Cell Sens software. Normal and glaucomatous globes were compared using ANOVA. Statistically significant smaller luminal areas and fewer numbers of arteries were recorded between normal and glaucomatous globes. The glaucomatous eyes in this study have SPCA with decreased lumina, suggestive of a vascular pathology present at the early stages of clinical glaucoma. Smaller lumina may be a contributing factor to the ischemia, necrosis, and the eventual full-thickness retinal atrophy often seen in glaucomatous dogs.


In situ fabrication of a temperature- and ethanol-responsive smart membrane in a microchip.
Here we report a simple and versatile strategy for the in situ fabrication of nanogel-containing smart membranes in microchannels of microchips. The fabrication approach is demonstrated by the in situ formation of a chitosan membrane containing poly(N-isopropylacrylamide) (PNIPAM) nanogels in a microchannel of a microchip. The PNIPAM nanogels, that allow temperature- and ethanol-responsive swelling-shrinking volume transitions, serve as smart nanovalves for controlling the diffusional permeability of solutes across the membrane. Such self-regulation of the membrane permeability is investigated by using fluorescein isothiocyanate (FITC) as a tracer molecule. This approach provides a promising strategy for the in situ fabrication of versatile nanogel-containing smart membranes within microchips via simply changing the functional nanogels for developing micro-scale detectors, sensors, separators and controlled release systems.


Synthesis of Ni3 B/Ni via Vacuum-Induced for Ultrahigh Stable and Efficient Methanol Oxidation.
Designing efficient catalysts to promote the electrochemical oxidation of anodes is the core of the development of electrochemical synthesis technologies, such as HER and CO2 RR. Here, a novel vacuum induction strategy is used to synthesize nickel boride/nickel (Ni3 B/Ni) heterostructure catalyst for electrochemical oxidation of methanol into formic acid. The catalyst has extremely high reactivity (only 146.9 mV overpotential at 10 mA cm-2 , the maximum current density reaches 555.70 mA mg-1 and 443.87 mA cm-2 ), ultra-high selectivity (Faraday efficiency of methanol conversion to formic acid is close to 100%), and ultra-long life (over 50 h at 100 mA cm-2 ). In-suit electrochemical impedance spectroscopy proved that MeOH is oxidized first and inhibits the phase transition of the electrocatalyst to the high-valent electrooxidation products, which not only enables the high selectivity of MeOH oxidation but also ensures high stability of the catalyst. The mechanism studies by density functional theory calculations show that the potential determining step, the formation of *CH2 O, occurs most favorably in the Ni3 B/Ni heterostructure. These results provide references for the development of MeOH oxidation catalysts with high activity, high stability, high selectivity, and low cost.


Vaso-dilating drugs and the large arteries in essential hypertension.
Vasodilating drugs are commonly used in the treatment of hypertension. These antihypertensive agents are considered as acting on small arteries which are preferentially damaged in the hypertensive vascular disease. Recent studies have emphasized that the hemodynamic abnormalities in hypertension were not restricted to arterioles but involved also large arteries, resulting in a decrease in arterial compliance. This finding is potentially important since cardio-vascular morbidity and mortality in patients treated for hypertension is related to ischemic accidents related to alterations of large vessels, as observed in the coronary and the carotid-cerebral circulation. From this observation, it ensues that the study of the effects of vasodilating drugs on the large arteries of hypertensive patients should be extremely relevant to improve cardiovascular morbidity and mortality. On the basis of experimental studies, several cases of pharmacological dissociation in the dilatation of small and large arteries have been observed in animals, mainly in the coronary circulation. However, little research has been done on the effect of antihypertensive drugs on large arteries in men with essential hypertension. In the present review, the hemodynamic concepts and the methodologic basis for the study of large arteries in man are presented. Thereafter, the different aspect of the dilatation of small and large arteries in hypertension are analyzed, with the study of consequences on the conduit and the buffering functions of large arteries and on the development of cardiac hypertrophy. Finally, large arteries have also an important baroreflex function involved in the neuro-humoral consequences of vasodilatation. This point will be particularly described and interpreted.


The activating p.Ser466Arg change in STAT1 causes a peculiar phenotype with features of interferonopathies.
Signal Transducer and Activator of Transcription 1 (STAT1) is a DNA-binding signal transducer that regulates transcription of specific genes in response to IFNγ and IFNα/β stimulation. Loss-of-function mutations impairing STAT1 activity are known to confer susceptibility to intracellular bacterial and viral diseases. Conversely, the few known activating mutations of STAT1 allow predisposition to chronic mucocutaneous candidiasis disease, and occur in patients with combined immunodeficiency and defective Th1 and Th17 responses. Here, we report on a de novo gain-of-function (GoF) STAT1 mutation (c.1398C>G, p.Ser466Arg) identified by exome sequencing in an individual with brain calcification, arthritis, recurrent pericarditis, leukopenia, thrombocytopenia and low C3 levels, a phenotype resembling an interferonopathy. The Ser466Arg change affects a highly conserved residue located in the DNA binding domain of the protein and the amino acid substitution was documented to have an activating role both in vitro and in vivo. Altogether, clinical features and functional studies are compatible with hyperactivation of the Interferon pathways, highlighting a role of STAT1 GoF mutation in clinical phenotypes fitting interferonopathies.


Gene Expression Profile of Human Cytokines in Response to Burkholderia pseudomallei Infection.
Melioidosis is an underreported infectious disease, caused by the Gram-negative bacterium Burkholderia pseudomallei. Understanding the disease susceptibility and pathogenesis is crucial for developing newer diagnostic and therapeutic strategies for this life-threatening infection. In this study, we aimed to analyze the gene expression levels of important cytokines in melioidosis patients and establish useful correlates with disease biomarkers compared to cases of sepsis infection caused by other pathogens and healthy individuals. A Qiagen common human cytokines array profiling the gene expression of 84 important cytokines by real-time quantitative PCR (RT-qPCR) was used. We analyzed 26 melioidosis cases, 5 healthy controls, and 10 cases of sepsis infection caused by other pathogens. Our results showed consistently upregulated expression of interleukins (IL) interleukin-4 (IL-4), interleukin-17 alpha (IL-17A), IL-23A, and IL-24, interferons (IFN) interferon alpha 1 (IFNA1) and interferon beta 1 (IFNB1), tumor necrosis factor (TNF) superfamily 4 (TNFSF4), transforming growth factor (TGF) superfamily, bone morphogenetic proteins 3 and 6 (BMP3 and BMP6), transforming growth factor beta 1 (TGFB1), and other growth factors, including macrophage colony-stimulating factor (M-CSF), C-fos-induced growth factor (FIGF), and platelet-derived growth factor alpha (PDGFA) polypeptide, in melioidosis patients compared to their expression in other sepsis cases, irrespective of comorbidities, duration of fever/clinical symptoms, and antibiotic treatment. Our findings indicate a dominant Th2- and Th17-type-cytokine response, suggesting that their dysregulation at initial stages of infection may play an important role in disease pathogenesis. IL-1A, interleukin-1 beta (IL-1B), and IL-8 were significantly downregulated in septicemic melioidosis patients compared to their expression in other sepsis cases. These differentially expressed genes may serve as biomarkers for melioidosis diagnosis and targets for therapeutic intervention and may help us understand immune response mechanisms. IMPORTANCE Melioidosis is a life-threatening infectious disease caused by a soil-associated Gram-negative bacterium, B. pseudomallei. Melioidosis is endemic in Southeast Asia and northern Australia; however, the global distribution of B. pseudomallei and the disease burden of melioidosisis are still poorly understood. Melioidosis is difficult to treat, as B. pseudomallei is intrinsically resistant to many antibiotics and requires a long course of antibiotic treatment. The mortality rates remain high in areas of endemicity, with reoccurrence being common. Therefore, it is imperative to diagnose the disease at an early stage and provide vital clinical care to reduce the mortality rate. With limitations in treatment and lack of a vaccine, it is crucial to study the immune response mechanisms to this infection to get a better understanding of disease susceptibility and pathogenesis. Therefore, this study aimed to analyze the gene expression levels of important cytokines to establish useful correlations for diagnostic and therapeutic purposes.


Identifying patients with ischemic heart disease in an electronic medical record.
Increasing utilization of electronic medical records (EMRs) presents an opportunity to efficiently measure quality indicators in primary care. Achieving this goal requires the development of accurate patient-disease registries. This study aimed to develop and validate an algorithm for identifying patients with ischemic heart disease (IHD) within the EMR. An algorithm was developed to search the unstructured text within the medical history fields in the EMR for IHD-related terminology. This algorithm was applied to a 5% random sample of adult patient charts (n = 969) drawn from a convenience sample of 17 Ontario family physicians. The accuracy of the algorithm for identifying patients with IHD was compared to the results of 3 trained chart abstractors. The manual chart abstraction identified 87 patients with IHD in the random sample (prevalence = 8.98%). The accuracy of the algorithm for identifying patients with IHD was as follows: sensitivity = 72.4% (95% confidence interval [CI]: 61.8-81.5); specificity = 99.3% (95% CI: 98.5-99.8); positive predictive value = 91.3% (95% CI: 82.0-96.7); negative predictive value = 97.3 (95% CI: 96.1-98.3); and kappa = 0.79 (95% CI: 0.72-0.86). Patients with IHD can be accurately identified by applying a search algorithm for the medical history fields in the EMR of primary care providers who were not using standardized approaches to code diagnoses. The accuracy compares favorably to other methods for identifying patients with IHD. The results of this study may aid policy makers, researchers, and clinicians to develop registries and to examine quality indicators for IHD in primary care.


Efficient stabilisation of a dihydrogenphosphate tetramer and a dihydrogenpyrophosphate dimer by a cyclic pseudopeptide containing 1,4-disubstituted 1,2,3-triazole moieties.
A cyclic pseudooctapeptide 2 is described containing 1,4-disubstituted 1,2,3-triazole moieties. This compound features eight converging hydrogen bond donors along the ring, namely four amide NH and four triazole CH groups, which enable 2 to engage in interactions with anions. While fully deprotonated sulfate anions exhibit only moderate affinity for 2, protonated anions such as dihydrogenpyrophosphate and dihydrogenphosphate anions are strongly bound. Complexation of the phosphate-derived anions involves sandwiching of a dihydrogenpyrophosphate dimer or a dihydrogenphosphate tetramer between two pseudopeptide rings. X-ray crystallography provided structural information, while 1H NMR spectroscopy, mass spectrometry, and isothermal titration calorimetry demonstrated that these complexes are stable in solution (2.5 vol% water/DMSO) and can even be transferred without decomposition into the gas phase. The observed high thermodynamic stabilities are attributed to the mutual reinforcement of the interactions between the individual complex components, namely, hydrogen-bonding between the anions, multiple hydrogen bonding interactions between the anion aggregates and the triazole CH and NH hydrogen bond donors of 2, and potential dispersive interactions between the closely arranged pseudopeptide rings. Pseudopeptide 2 thus represents a promising lead for the construction of phosphate receptors, whose binding selectivity makes use of the unique ability of certain anions to assemble into higher aggregates.


Tandem transplantation in multiple myeloma.
The use of high-dose chemotherapy and autologous stem cell support in the past decade has changed the outlook for patients with multiple myeloma. In newly diagnosed patients, complete remission rates of 25% to 50% can be achieved, with median disease-free and overall survivals exceeding 3 and 5 years, respectively. Despite these results, autologous transplantation has not changed the ultimately fatal outcome of the disease, as there is no substantial evidence of "cure" in most published studies. An additional high-dose chemotherapy course (with tandem transplants) appears to improve progression-free survival, although the effect is not discernible until 3 to 5 years posttransplant. The recent reports of tandem autologous transplant for maximum cytoreduction followed by nonmyeloablative allogeneic transplant for eradication of minimal residual disease appears promising and deserve further investigation. A central issue of tandem transplants, whether they involve autologous or allogeneic transplants, revolves around defining the subsets of patients who will benefit from the procedure. Good-risk patients (defined by normal cytogenetics and low beta-2-microglobulin levels), especially those who achieve a complete or near-complete response after the first transplant, appear to benefit the most from a second cycle. High-risk patients (defined by chromosomal abnormalities usually involving chromosomes 11 and 13 and high beta-2--microglobulin levels) whose median survival after tandem transplant is less than 2 years should be offered novel therapeutic interventions such as tandem "auto/allo" transplants. Until the efficacy and safety of this procedure is fully established, it should be limited to high-risk patients.


Medium-sized FLT3 internal tandem duplications confer worse prognosis than short and long duplications in a non-elderly acute myeloid leukemia cohort.
Internal tandem duplications (ITDs) of the fms-like tyrosine kinase 3 (FLT3) gene occur in about 25% of patients with adult acute myeloid leukemia (AML). The aim of our study was to investigate the frequency of FLT3-ITD mutations followed by a detailed analysis of the mutational load and size of ITD insertions in a cohort consisting of 324 patients younger than 60 years old and treated with curative intention. FLT3-ITD alone did not influence overall survival (OS) or disease-free survival (DFS). We observed worse OS and DFS for patients with high mutational load indicative for loss of the FLT3 wild type allele (p = 0.010, p = 0.038, respectively). In multivariate analyses, patients with FLT3-ITD(48-60bp) showed worse OS and DFS compared to other groups (FLT3-ITD(neg), FLT3-ITD (< 48b), FLT3-ITD (> 60bp); p = 0.014, p = 0.019, respectively). Our novel observation suggested that not only high FLT3-ITD load, but also medium-sized ITD insertions (48-60 bp) represented an adverse prognostic subgroup of patients with AML.


Expression of Epstein-Barr virus in children with sacrococcygeal pilonidal sinus determined by immunohistochemical methods.
In this study, we probed whether chronic infections of skin such as pilonidal sinus could be a potential site of Epstein-Barr virus (EBV) replication. Pilonidal sinus is associated with a high recurrence rate. Therefore, we decided to determine the role of EBV's presence to explain whether it is correlated with the recurrence of pilonidal sinuses. This study was conducted on 36 patient samples with sacrococcygeal pilonidal sinus. Samples were immunohistochemically stained for EBV, CD3 and CD20 expression. Thirty-six adolescents with pilonidal disease were evaluated. EBV-positive cells were located in dermis with high inflammatory activity. EBV-positive cells stained positive for the B-cell antigen CD20 and were detected in 10 of 36 (27%) pilonidal sinus specimens. Among those who had experienced a relapse, three were positive for EBV expression. In addition, EBV expression was detected in eight cases with severe inflammation, and in two with minimal or moderate inflammation. Our study advances the field by demonstrating that similar to gastrointestinal mucosa, skin could be a reservoir for EBV. EBV was found to be restricted to B cells in skin lesions, and it was found that skin lesions with severe inflammation showed higher frequency of EBV expression in comparison to minimal or moderately inflammed skin lesions. Additionally, recurrence was more frequently observed among EBV-positive cases. These findings point out for a role of EBV infection in the recurrence of pilonidal sinuses.


Aminooxy acetic acid suppresses Th17-mediated psoriasis-like skin inflammation by inhibiting serine metabolism.
Background: Psoriasis is a common chronic inflammatory skin disease characterized by an external red rash that is caused by abnormal proliferation and differentiation of keratinocytes and immune T cells. This study aimed to elucidate the role of aminooxy acetic acid (AOA) in alleviating psoriasis from the perspective of immunology and metabolomics. Therefore, contributing to the development of new drugs as candidates for psoriasis treatment. Methods: To investigate the symptom-alleviating effects and the related mechanisms of AOA on the treatment of psoriasis, we used a 12-O-tetradecanoylphorbol-13-acetate-induced psoriasis-like skin mouse model and interleukin (IL)-17-stimulated human keratinocytes. Results: The results showed that AOA ameliorated psoriasis-related symptoms and decreased inflammation-associated antimicrobial peptides and T-helper 17 (Th17)-associated cytokines in a mouse model of psoriasis. Furthermore, AOA inhibited the activation of mechanistic target of rapamycin (mTOR) by suppressing serine metabolism-related genes. Importantly, mTOR inhibition ameliorated psoriatic disease by affecting the differentiation of various T cells and normalizing the Th17/regulatory T (Treg) cell balance. In addition, IL-17-stimulated human keratinocytes showed the same results as in the in vivo experiments. Conclusion: Taken together, these results suggest that targeting the serine metabolism pathway in the treatment of psoriasis is a novel strategy, and that AOA could be utilized as a novel biologic to treat psoriasis.


BI-FedGNN: Federated graph neural networks framework based on Bayesian inference.
The development of the Industrial Internet of Things (IIoT) in recent years has resulted in an increase in the amount of data generated by connected devices, creating new opportunities to enhance the quality of service for machine learning in the IIoT through data sharing. Graph neural networks (GNNs) are the most popular technique in machine learning at the moment because they can learn extremely precise node representations from graph-structured data. Due to privacy issues and legal restrictions of clients in industrial IoT, it is not permissible to directly concentrate vast real-world graph-structured datasets for training on GNNs. To resolve the aforementioned difficulties, this paper proposes a federal graph learning framework based on Bayesian inference (BI-FedGNN) that performs effectively in the presence of noisy graph structure information or missing strong relational edges. BI-FedGNN extends Bayesian Inference (BI) to the process of Federal Graph Learning (FGL), adding random samples with weights and biases to the client-side local model training process, improving the accuracy and generalization ability of FGL in the training process by rendering the graph structure data involved in GNNs training more similar to the graph structure data existing in the real world. Through extensive experimental tests, the results show that BI-FedGNN has about 0.5%-5.0% accuracy improvement over other baselines of federal graph learning. In order to expand the applicability of BI-FedGNN, experiments are carried out on heterogeneous graph datasets, and the results indicate that BI-FedGNN can also have at least 1.4% improvement in classification accuracy.


Heart rate variability and the influence of craniosacral therapy on autonomous nervous system regulation in persons with subjective discomforts: a pilot study.
Subjective discomforts in a preclinical range are often due to imbalanced autonomic nervous system activity, which is a focus of craniosacral therapy. The aim of this work was to determine any changes in heart rate variability (HRV) in a study on craniosacral therapy. This is a quasi-experimental (controlled) study with cross-over design. In a private practice, measurements were performed on 31 patients with subjective discomforts before and after a control and an intervention period. HRV was determined using a device that requires a measuring time of 140 s and electrode contact only with the fingertips. Main HRV change under the influence of a defined one-time intervention (test intervention) with craniosacral therapy versus control (defined rest period). Standard deviation of all RR-intervals (ms) and total power of RR-interval variability in the frequency range (ms(2)) were together interpreted as an indicator of test subjects' autonomic nervous activity and as a measure of their ability to cope with demands on their health. Neither of these parameters increased during the control period (P>0.05), whereas during the test intervention period there was an increase in both (P<0.05, P<0.01). Nevertheless, interactions between treatment and the increase were statistically not significant (P>0.05). No changes were observed in the low frequency/high frequency ratio (sympathetic-vagal balance) in the course of the control or the test intervention period (P>0.05). Craniosacral treatment had a favourable effect on autonomic nervous activity. This in itself is an interesting result, but further research will be needed to distinguish specific effects of craniosacral therapy technique from less specific therapist-client interaction effects.


"Intrinsic" immunological tolerance in allophenic mice.
Mice experimentally derived from pairs of conjoined, undifferentiated, cleavage-stage embryos of different histocompatibility genotypes can retain cells of each strain, which still produce their characteristic antigenic products. The animals are permanently tolerant of cells of both original types, remain free of runt disease, and display a normal and specific immune response to introduction of a foreign antigen. Absence of autoimmunity in development of ordinary animals is explainable by the "intrinsic" kind of tolerance found here.


Subjective Responses to Alcohol in the Development and Maintenance of Alcohol Use Disorder.
Alcohol use disorder (AUD) remains an urgent public health problem. Longitudinal data are needed to clarify the role of acute subjective responses to alcohol in the development and maintenance of excessive drinking and AUD. The authors report on 10 years of repeated examination of acute alcohol responses in the Chicago Social Drinking Project. Young adult drinkers (N=190) participated in an initial alcohol challenge (0.8 g/kg of alcohol compared with placebo) that was repeated 5 and 10 years later. They were also assessed on drinking behavior and AUD symptoms at numerous intervals across the decade. Retention was high, as 184 of the 185 (99%) nondeceased active participants completed the 10-year follow-up, and 91% (163 of 179) of those eligible for alcohol consumption engaged in repeated laboratory testing during this interval. At the end of the decade, 21% of participants met criteria for past-year AUD. Individuals who reported the greatest alcohol stimulation, liking, and wanting at the initial alcohol challenge were most likely to have developed AUD 10 years later. Further, alcohol-induced stimulation and wanting increased in reexamination testing among those with the highest AUD symptoms as the decade progressed. Initial stimulant and rewarding effects of alcohol predicted heavy alcohol use, and the magnitude of these positive subjective effects increased over a 10-year period in those who developed AUD compared with those who did not develop the disorder. The findings demonstrate systematic changes in subjective responses to alcohol over time, providing an empirical basis for prevention, early intervention, and treatment strategies.


Integrating mental health into primary care within the Veterans Health Administration.
The Veterans Health Administration (VHA) has been undertaking a major transformational program of integrating collaborative mental health resources into primary care settings. Key components of the program include colocated collaborative care provided by mental health professionals; care management; and blended programs that combine elements of these two components, whose functions are highly complementary to each other. The program has grown since 2007 from an initiative implementing pilot programs at participating facilities, to a routine expectation of primary care within all VHA medical centers and large community-based outpatient clinics. The national program office supports this VHA initiative in multiple ways, including technical assistance to sites, program and policy development, dissemination of informational tools to facilitate continuous quality improvement, education and training, and partnerships with other existing and emerging VHA programs such as postdeployment health clinics and the patient-centered medical home.


Revealing the role of the product metal in DNA polymerase β catalysis.
DNA polymerases catalyze a metal-dependent nucleotidyl transferase reaction during extension of a DNA strand using the complementary strand as a template. The reaction has long been considered to require two magnesium ions. Recently, a third active site magnesium ion was identified in some DNA polymerase product crystallographic structures, but its role is not known. Using quantum mechanical/ molecular mechanical calculations of polymerase β, we find that a third magnesium ion positioned near the newly identified product metal site does not alter the activation barrier for the chemical reaction indicating that it does not have a role in the forward reaction. This is consistent with time-lapse crystallographic structures following insertion of Sp-dCTPαS. Although sulfur substitution deters product metal binding, this has only a minimal effect on the rate of the forward reaction. Surprisingly, monovalent sodium or ammonium ions, positioned in the product metal site, lowered the activation barrier. These calculations highlight the impact that an active site water network can have on the energetics of the forward reaction and how metals or enzyme side chains may interact with the network to modulate the reaction barrier. These results also are discussed in the context of earlier findings indicating that magnesium at the product metal position blocks the reverse pyrophosphorolysis reaction.


Changes in Direct Healthcare Costs before and after the Diagnosis of Inflammatory Bowel Disease: A Nationwide Population-Based Study.
Background/Aims: We aimed to investigate the differences in direct healthcare costs between patients with and without inflammatory bowel disease (IBD) and changes in direct healthcare costs before and after IBD diagnosis. Methods: This population-based study identified 34,167 patients with IBD (11,014 patients with Crohn's disease and 23,153 patients with ulcerative colitis) and 102,501 age-and sex-matched subjects without IBD (the control group) from the National Health Insurance database using the International Classification of Disease, 10th revision codes and the rare intractable disease registration program codes. The mean healthcare costs per patient were analyzed for 3 years before and after IBD diagnosis, with follow-up data available until 2015. Results: Total direct healthcare costs increased and peaked at $2,396 during the first year after IBD diagnosis, but subsequently dropped sharply to $1,478 during the second year after diagnosis. Total healthcare costs were higher for the IBD patients than for the control group, even in the third year before the diagnosis ($497 vs $402, p<0.001). The costs for biologics for the treatment of IBD increased steeply over time, rising from $720.8 in the first year after diagnosis to $1,249.6 in the third year after diagnosis (p<0.001). Conclusions: IBD patients incurred the highest direct healthcare costs during the first year after diagnosis. IBD patients had higher costs than the control group even before diagnosis. The cost of biologics increased steeply over time, and it can be assumed that biologics could be the main driver of costs during the early period after IBD diagnosis.


Rapid aggregation of biofuel-producing algae by the bacterium Bacillus sp. strain RP1137.
Algal biofuels represent one of the most promising means of sustainably replacing liquid fuels. However, significant challenges remain before alga-based fuels become competitive with fossil fuels. One of the largest challenges is the ability to harvest the algae in an economical and low-energy manner. In this article, we describe the isolation of a bacterial strain, Bacillus sp. strain RP1137, which can rapidly aggregate several algae that are candidates for biofuel production, including a Nannochloropsis sp. This bacterium aggregates algae in a pH-dependent and reversible manner and retains its aggregation ability after paraformaldehyde fixation, opening the possibility for reuse of the cells. The optimal ratio of bacteria to algae is described, as is the robustness of aggregation at different salinities and temperatures. Aggregation is dependent on the presence of calcium or magnesium ions. The efficiency of aggregation of Nannochloropsis oceanica IMET1 is between 70 and 95% and is comparable to that obtained by other means of harvest; however, the rate of harvest is fast, with aggregates forming in 30 s.


The E3 ubiquitin ligase Itch inhibits p38α signaling and skin inflammation through the ubiquitylation of Tab1.
Deficiency in the E3 ubiquitin ligase Itch causes a skin-scratching phenotype in mice. We found that there was increased phosphorylation and activation of the mitogen-activated protein kinase p38α in spontaneous and experimentally induced skin lesions of Itch-deficient (Itch-/-) mice. Itch bound directly to the TGF-β-activated kinase 1-binding protein 1 (Tab1) through a conserved PPXY motif and inhibited the activation of p38α. Knockdown of Tab1 by short hairpin RNA attenuated the prolonged p38α phosphorylation exhibited by Itch-/- cells. Similarly, reconstitution of Itch-/- cells with wild-type Itch, but not the ligase-deficient Itch-C830A mutant, inhibited the phosphorylation and activation of p38α. Compared to the skin of wild-type mice, the skin of Itch-/- mice contained increased amounts of the mRNAs of proinflammatory cytokines, including tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-1β, IL-11, and IL-19. Inhibition of p38 or blocking the interaction between p38α and Tab1 with a cell-permeable peptide substantially attenuated skin inflammation in Itch-/- mice. These findings provide insight into how Itch-mediated regulatory mechanisms prevent chronic skin inflammation, which could be exploited therapeutically.


Public recognition of mental disorders and beliefs about treatment: changes in Australia over 16 years.
A 1995 Australian national survey of mental health literacy showed poor recognition of disorders and beliefs about treatment that differed from those of health professionals. A similar survey carried out in 2003/4 showed some improvements over 8 years. To investigate whether recognition of mental disorders and beliefs about treatment have changed over a 16-year period. A national survey of 6019 adults was carried out in 2011 using the same questions as the 1995 and 2003/4 surveys. Results showed improved recognition of depression and more positive ratings for a range of interventions, including help from mental health professionals and antidepressants. Although beliefs about effective medications and interventions have moved closer to those of health professionals since the previous surveys, there is still potential for mental health literacy gains in the areas of recognition and treatment beliefs for mental disorders. This is particularly the case for schizophrenia.


A 12-week comparison regarding symptom improvement in an urban university-based outpatient child psychiatry clinic.
To compare the efficacy of pharmacotherapy versus combination pharmacotherapy and psychotherapy for externalizing, conduct, and aggressive behaviors in children aged 6 through 18 years in an urban academic outpatient facility. Data from a child psychiatry outpatient population whose scores were identified as "at risk" or "clinically significant" based on a validated and standardized assessment tool were assessed at baseline and 12 weeks or more after treatment. Conduct symptoms worsened with medication management alone but improved with combination treatment (P < 0.05). Females and older youth were more likely to have therapy included in their treatment. Conduct problems that can be seen in a variety of youth disorders, such as disruptive behaviors, mood, and anxiety disorders, have a better probability of improving with treatment that includes psychotherapy versus medication management alone.


Household energy efficiency and health: Area-level analysis of hospital admissions in England.
Fuel poverty affects up to 35% of European homes, which represents a significant burden on society and healthcare systems. Draught proofing homes to prevent heat loss, improved glazing, insulation and heating (energy efficiency measures) can make more homes more affordable to heat. This has prompted significant investment in energy efficiency upgrades for around 40% of UK households to reduce the impact of fuel poverty. Despite some inconsistent evidence, household energy efficiency interventions can improve cardiovascular and respiratory health outcomes. However, the health benefits of these interventions have not been fully explored; this is the focus of this study. In this cross sectional ecological study, we conducted two sets of analyses at different spatial resolution to explore population data on housing energy efficiency measures and hospital admissions at the area-level (counts grouped over a 3-year period). Housing data were obtained from three data sets covering housing across England (Household Energy Efficiency Database), Energy Performance Certificate (EPC) and, in the South West of England, the Devon Home Analytics Portal. These databases provided data aggregated to Lower Area Super Output Area and postcode level (Home Analytics Portal only). These datasets provided measures of both state (e.g. EPC ratings) and intervention (e.g. number of boiler replacements), aggregated spatially and temporally to enable cross-sectional analyses with health outcome data. Hospital admissions for adult (over 18 years) asthma, chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) were obtained from the Hospital Episode Statistics database for the national (1st April 2011 to 31st March 2014) and Devon, South West of England (1st April 2014 to 31st March 2017) analyses. Descriptive statistics and regression models were used to describe the associations between small area household energy efficiency measures and hospital admissions. Three main analyses were undertaken to investigate the relationships between; 1) household energy efficiency improvements (i.e. improved glazing, insulation and boiler upgrades); 2) higher levels of energy efficiency ratings (measured by Energy Performance Certificate ratings); 3) energy efficiency improvements and ratings (i.e. physical improvements and rating assessed by the Standard Assessment Procedure) and hospital admissions. In the national analyses, household energy performance certificate ratings ranged from 37 to 83 (mean 61.98; Standard Deviation 5.24). There were a total of 312,837 emergency admissions for asthma, 587,770 for COPD and 839,416 for CVD. While analyses for individual energy efficiency metrics (i.e. boiler upgrades, draught proofing, glazing, loft and wall insulation) were mixed; a unit increase in mean energy performance rating was associated with increases of around 0.5% in asthma and CVD admissions, and 1% higher COPD admission rates. Admission rates were also influenced by the type of dwelling, tenure status (e.g. home owner versus renting), living in a rural area, and minimum winter temperature. Despite a range of limitations and some mixed and contrasting findings across the national and local analyses, there was some evidence that areas with more energy efficiency improvements resulted in higher admission rates for respiratory and cardiovascular diseases. This builds on existing evidence highlighting the complex relationships between health and housing. While energy efficiency measures can improve health outcomes (especially when targeting those with chronic respiratory illness), reduced household ventilation rates can impact indoor air quality for example and increase the risk of diseases such as asthma. Alternatively, these findings could be due to the ecological study design, reverse causality, or the non-detection of more vulnerable subpopulations, as well as the targeting of areas with poor housing stock, low income households, and the lack of "whole house approaches" when retrofitting the existing housing stock. To be sustainable, household energy efficiency policies and resulting interventions must account for whole house approaches (i.e. consideration of the whole house and occupant lifestyles). These must consider more alternative 'greener' and more sustainable measures, which are capable of accounting for variable lifestyles, as well as the need for adequate heating and ventilation. Larger natural experiments and more complex modelling are needed to further investigate the impact of ongoing dramatic changes in the housing stock and health. This study supports the need for more holistic approaches to delivering healthier indoor environments, which must consider a dynamic and complex system with multiple interactions between a range of interrelated factors. These need to consider the drivers and pressures (e.g. quality of the built environment and resident behaviours) resulting in environmental exposures and adverse health outcomes.


Fitness, fatness, and estimated coronary heart disease risk: the HERITAGE Family Study.
To determine the contributions of fatness and fitness to the estimated risk of future coronary heart disease (CHD). The sample consisted of 212 black and 411 white adult sedentary participants. Percent body fat (%BF) was measured using densitometry, whereas maximal oxygen uptake (VO(2max)) was measured on a cycle ergometer. Risk of future CHD was estimated using the revised Framingham Heart Study algorithm. For fatness, the odds ratios for risk of future CHD were 1.83 and 1.70 for the moderate and high tertiles, respectively, compared with the low tertile. Similarly, the odds ratios for VO(2max) were 1.29 (NS) and 1.62, for the moderate and low tertiles, respectively. Removing VO(2max) from the full model had no effect; however, removing %BF resulted in a significantly weaker model (chi(2) = 10.38, P < 0.01). Both fatness and fitness are important predictors of risk of future CHD, based on the Framingham index.


Distinct expression of gelatinase A [matrix metalloproteinase (MMP)-2], collagenase-3 (MMP-13), membrane type MMP 1 (MMP-14), and tissue inhibitor of MMPs type 1 mediated by physiological signals during formation and regression of the rat corpus luteum.
The corpus luteum (CL) is a transient endocrine organ that secretes progesterone to support pregnancy. The CL is formed from an ovulated follicle in a process that involves extensive angiogenesis and tissue remodeling. If fertilization does not occur or implantation is unsuccessful, the CL will undergo regression, which involves extensive tissue degradation. Extracellular proteases, such as serine proteases and matrix metalloproteinases (MMPs), are thought to play important roles in both the formation and regression of the CL. In this study, we have examined the physiological regulation pattern and cellular distribution of messenger RNAs coding for gelatinase A (MMP-2), collagenase-3 (MMP-13), membrane type MMP 1 (MT1-MMP, MMP-14), and the major MMP inhibitor, tissue inhibitor of MMPs type 1 (TIMP-1) in the CL of adult pseudopregnant (psp) rat. Northern blot and in situ hybridization analyses revealed that gelatinase A messenger RNA was mainly expressed during luteal development, indicating that gelatinase A may be associated with the neovascularization and tissue remodeling that takes place during CL formation. Collagenase-3 had a separate expression pattern and was only expressed in the regressing CL, suggesting that this MMP may be related with luteal regression. MT1-MMP that in vitro can activate progelatinase A and procollagenase-3 was constitutively expressed during the formation, function, and regression of the CL and may therefore be involved in the activation of these MMPs. TIMP-1 was induced during both the formation and regression of the CL, suggesting that this inhibitor modulates MMP activity during these processes. To test whether the induction of collagenase-3 and TIMP-1 is coupled with luteal regression, we prolonged the luteal phase by performing hysterectomies, and induced premature luteal regression by treating the pseudopregnant rats with a PGF2alpha analog, cloprostenol. In both treatments, collagenase-3 and TIMP-1 were induced only after the serum level of progesterone had decreased, suggesting that collagenase-3 and TIMP-1 are induced by physiological signals, which initiate functional luteolysis to play a role in tissue degradation during structural luteolysis. In conclusion, our data suggest that gelatinase A, collagenase-3, and MT1-MMP may have separate functions during the CL life span: gelatinase A mainly takes part in CL formation, whereas collagenase-3 mainly takes part in luteal regression; MT1-MMP is constitutively expressed during the CL life span and may therefore serve as an in vivo activator of both gelatinase A and collagenase-3. TIMP-1 is up-regulated both during the formation and regression of the CL and may therefore regulate MMP activity during both processes.


Early clinical experience of dolutegravir in an HIV cohort in a larger teaching hospital.
Dolutegravir (DTG) is the third HIV integrase inhibitor (INI) available for prescription in Belfast since July 2014. It has shown high virological efficacy in both treatment-naïve and -experienced patients. We carried out a retrospective case chart analysis of HIV-1-positive adults commenced on DTG between July 2014 and September 2015. Patients were identified from records as either treatment-naïve or antiretroviral therapy (ART) experienced. Outcomes included: (1) virological response (HIV-1 RNA viral load at 0, 4, 8 and 12 weeks), (2) immunological response (CD4+ cell count at 0, 4, 8 and 12 weeks) and (3) tolerability (side effects and discontinuation). The main exclusion criteria were patients transferring care already established on DTG from other treatment centres or inadequate follow-up information (defined as attendance at <50% of clinical and serological follow-up visits). One hundred and fifty-seven commenced DTG out of 823 patients on ART; 106 (68%) were switched to DTG from another regimen, and 51 (32%) were ART-naïve. One naïve and 14 treatment-experienced patients were excluded from the analysis due to failure to attend clinical follow-up. Analysis of HIV-1 RNA viral load (HIV-1 VL) was divided into three groups: 50 new starters, 68 suppressed at switch and 24 not suppressed at switch. New starters: Baseline median HIV-1 RNA VL 71,259 copies/mL (19,536Q25-196,413Q75); 73% were virally undetectable (HIV-1 RNA VL <70 copies/mL) by week 4. Switching patients: Of those with an HIV-1 RNA undetectable viral load prior to switching, two were detectable with a mean viral load of 443,730 copies/mL after four weeks. Of the 24 patients detectable at switch (median HIV-1 VL 2212 [311Q25-43,467Q75]), 10 were detectable after four weeks. For those with a recordable viraemia, the median HIV-1 VL reduced to 376 (220Q25-1181Q75). At week 12, four patients were detectable with a median VL of 12,390 (567Q25-52,285Q75). Overall, 56 (35%) reported side effects; 40 (25%) reported either difficulty with low mood, anxiety or sleep disturbance. Sixteen (10%) discontinued DTG, with 13 (8%) due to intolerable side effects. DTG is a useful drug in naïve or switch patients. It has the potential to effectively suppress the viral load within the first four weeks of treatment and thus reduces infectiousness. Within the cohort, DTG was generally well tolerated but side effects such as low mood, anxiety and sleep disturbance were high, with 8% of patients discontinuing treatment.


EGF-mediated induction of Mcl-1 at the switch to lactation is essential for alveolar cell survival.
Expansion and remodelling of the mammary epithelium requires a tight balance between cellular proliferation, differentiation and death. To explore cell survival versus cell death decisions in this organ, we deleted the pro-survival gene Mcl-1 in the mammary epithelium. Mcl-1 was found to be essential at multiple developmental stages including morphogenesis in puberty and alveologenesis in pregnancy. Moreover, Mcl-1-deficient basal cells were virtually devoid of repopulating activity, suggesting that this gene is required for stem cell function. Profound upregulation of the Mcl-1 protein was evident in alveolar cells at the switch to lactation, and Mcl-1 deficiency impaired lactation. Interestingly, EGF was identified as one of the most highly upregulated genes on lactogenesis and inhibition of EGF or mTOR signalling markedly impaired lactation, with concomitant decreases in Mcl-1 and phosphorylated ribosomal protein S6. These data demonstrate that Mcl-1 is essential for mammopoiesis and identify EGF as a critical trigger of Mcl-1 translation to ensure survival of milk-producing alveolar cells.


Saikosaponin a Ameliorates LPS-Induced Acute Lung Injury in Mice.
The purpose of this study was to investigate the protective effects of Saikosaponin a (SSa), a triterpene saponin derived from Radix bupleuri, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) using a murine model. The mice were given SSa 1 h after intranasal instillation of LPS. Then, lung histopathological examination, the wet/dry (W/D) ratio, myeloperoxidase (MPO), and inflammatory cytokines in bronchoalveolar lavage fluid (BALF) were detected in this study. The results showed that SSa reduced lung pathological injury induced by LPS. Furthermore, LPS-induced lung W/D ratio, MPO activity, and inflammatory cytokines TNF-α and IL-1β in BALF were significantly inhibited by SSa. In addition, SSa suppressed LPS-induced NF-κB activation and NLRP3 inflammasome expression. In conclusion, we found that SSa played a critical anti-inflammatory effect through inhibition of NF-κB and NLRP3 signaling pathways and protected against LPS-induced ALI.


Extracorporeal shock wave lithotripsy in pediatric patients using a late generation portable lithotriptor: experience at Children's Hospital Boston.
Kidney stones in children are increasing in incidence. The continued evolution of stone treatment modalities, including shock wave lithotripsy, makes the assessment of continuous outcomes essential. We describe contemporary shock wave lithotripsy outcomes in pediatric patients. A medical record review was performed of all patients younger than 20 years who underwent shock wave lithotripsy in 1998 to 2007. Patients were treated using a Dornier Compact Delta lithotriptor with ultrasound and fluoroscopic imaging. Subjects were defined as stone-free if imaging within 12 months showed no evidence of stones with no additional treatment. Patient and treatment factors associated with successful outcomes were analyzed. In 101 children a total of 114 treatment sequences were performed at a total of 150 shock wave lithotripsy sessions. Mean patient age was 10.5 years and 53% of the patients were girls. Mean stone diameter was 8 mm. Treatment was done for a solitary stone in 76% of cases, for 2 stones in 17% and for 3 or more in 7% with a mean shock count of 2,247. One, 2 and 3 or more treatment sessions were done in 78%, 16% and 6% of patients, respectively. The overall stone-free rate was 58.6%. However, the stone-free rate was only 12.5% after treatment sequences in 20 children with a history of anatomical urological conditions or surgery, while the stone-free rate in children without urological conditions was 67% (p <0.0001). Another factor associated with a decreased stone-free rate was stone size greater than 10 mm (25% vs 63%, p = 0.01). Complications included requiring acute reevaluation or treatment after 7% of shock wave lithotripsy sessions and 3.4% of patients required readmission. Extracorporeal shock wave lithotripsy is effective in many children with urolithiasis and it is well tolerated. However, in some children, particularly those with a history of urological surgery or congenital genitourinary conditions, success rates are low. These children may be best treated with other modalities.


Landscape of the Plasmodium Interactome Reveals Both Conserved and Species-Specific Functionality.
Malaria represents a major global health issue, and the identification of new intervention targets remains an urgent priority. This search is hampered by more than one-third of the genes of malaria-causing Plasmodium parasites being uncharacterized. We report a large-scale protein interaction network in Plasmodium schizonts, generated by combining blue native-polyacrylamide electrophoresis with quantitative mass spectrometry and machine learning. This integrative approach, spanning 3 species, identifies >20,000 putative protein interactions, organized into 600 protein clusters. We validate selected interactions, assigning functions in chromatin regulation to previously unannotated proteins and suggesting a role for an EELM2 domain-containing protein and a putative microrchidia protein as mechanistic links between AP2-domain transcription factors and epigenetic regulation. Our interactome represents a high-confidence map of the native organization of core cellular processes in Plasmodium parasites. The network reveals putative functions for uncharacterized proteins, provides mechanistic and structural insight, and uncovers potential alternative therapeutic targets.


Isolation and reconstitution of the heme-thiolate protein obtusifoliol 14alpha-demethylase from Sorghum bicolor (L.) Moench.
The heme-thiolate (cytochrome P450) enzyme which catalyzes the 14alpha-demethylation of obtusifoliol has been isolated from microsomes prepared from etiolated seedlings of Sorghum bicolor (L.) Moench. The obtusifoliol 14alpha-demethylase is a key enzyme in plant sterol biosynthesis and a target for the design of phyla-specific sterol 14alpha-demethylase inhibitors. Microsomal cytochrome P450s were solubilized by using the detergents Renex 690 and reduced Triton X-100, and the obtusifoliol 14alpha-demethylase was isolated by DEAE ion exchange and dye affinity column chromatography. The isolated enzyme has an absorption spectrum characteristic for low spin cytochrome P450s and produces a Type I binding spectrum with obtusifoliol as substrate. Binding spectra were not obtained with lanosterol, campesterol, sitosterol, or stigmasterol. Obtusifoliol 14alpha-demethylase has an apparent molecular mass of 53 kDa and is estimated to constitute approximately 20% of the total cytochrome P450 content of the microsomal membranes and about 0.2% of the total microsomal protein. Gas chromatography-mass spectrometry analysis of reconstitution experiments with dilauroylphosphatidylcholine micelles containing isolated obtusifoliol 14alpha-demethylase and sorghum NADPHcytochrome P450 oxidoreductase demonstrated the conversion of obtusifoliol (4alpha,14alpha-dimethyl-5alpha-ergosta-8, 24(28)-dien-3beta-ol) to 4alpha-methyl-5alpha-ergosta-8,14, 24(28)-trien3beta-ol, the 14alpha-demethylated product of obtusifoliol with a double bond introduced at the Delta14 position. The N-terminal amino acid sequence of the protein is MDLADIPQ/KQQRLMAGXALVV. Five internal sequences were obtained after endoproteinase Lys-C and Glu-C digestion. The fragment AAGAFSYISFGGGRH aligns with the unique heme binding domain of mammalian and yeast sterol 14alpha-demethylases which belong to the CYP51 family. Therefore it is conceivable that the obtusifoliol 14alpha-demethylase from plants also belongs to the CYP51 family, the only P450 family so far known to be conserved across the phyla.


Phenylethanolamine N-methyltransferase gene polymorphisms associate with crisis pain in sickle cell disease patients.
Aim: Phenylethanolamine N-methyltransferase (PNMT) catalyzes the conversion of sympathetic neurotransmitter norepinephrine to epinephrine. We examined the association of PNMT polymorphisms with acute and chronic pain in sickle cell disease (SCD). Methods: Utilization of emergency care owing to painful crisis was used as a marker for acute pain in 131 patients with SCD. Results: rs876493 A allele, rs2934965 T allele and rs2941523 G allele were significantly associated with decreased utilization (p ≤ 0.05). rs876493 A allele showed association with utilization in females (p = 0.003), not males (p = 0.803). rs2934965 T allele and rs2941523 G allele were predicted to cause loss of putative transcription factor binding sites. This is the first report of the association of PNMT polymorphisms with acute crisis pain in SCD. Together with our previous findings in catechol-o-methyltransferase, polymorphisms in catecholamine metabolizing enzymes appear to primarily influence acute pain in SCD.


The orthogeriatric unit for acute patients: a new model of care that improves efficiency in the management of patients with hip fracture.
We performed a prospective, quasi-experimental, randomised, interventional study comparing two models of care for patients admitted with osteoporotic hip fractures between February and August 2007 in a tertiary university hospital. The usual model of care was treatment of patients admitted to the orthopaedics ward, with consultation by the geriatrician (CG model). The study model involved admission to an acute orthogeriatric unit (OGU model), with joint care provided by geriatricians and orthopaedic surgeons which included immediate geriatric assessment, coordinated daily clinical care, weekly combined ward rounds, and joint planning of the surgical schedule, initial mobilisation, discharge date and destination. No differences were found between CG patients (123) and OGU patients (101) in terms of previous characteristics, number of patients surgically treated, functional level obtained, or discharge destination. OGU patients had earlier geriatric assessment (median 1 day, P25-P75: 1-2) than CG patients (median 4 days, P25-P75: 3-8), earlier surgery (median 5 days from admission to OGU, P25-P75: 3-6, versus 6 days in the CG group, P25-P75: 5-9), and had a shorter acute hospital stay (33% reduction, median 12 days in OGU, P25-P75: 9-14, versus 18 days, P25-P75: 13-23 in the CG group) and total (acute and subacute) hospital stay (30% reduction, median 14 days in OGU, P25-P75: 10-31, versus 20 days, P25-P75: 14-30 in the CG group). All these comparisons were statistically significant (p<0.01). The organization of an OGU in a tertiary hospital allowed hip fracture patients to receive earlier geriatric assessment and surgical treatment. Acute hospital stay was reduced by 33%, and total hospital stay was reduced by 30% with no differences at discharge in clinical and functional outcomes.


Synthesis and secretion of a cobalamin-binding protein by HT 29 cell line.
An HT 29 cell line derived from human colonic carcinoma was shown to synthesize and release a cobalamin-binding protein. The cobalamin-binding protein was classified as transcobalamin (TC). By gel filtration on Sephacryl S200 HR, we observed that the secreted protein bound to cobalamin had the same size as plasma transcobalamin. Like transcobalamin, the cobalamin-binding protein bound cobalamin but not cobinamide. Purification of the cobalamin-binding protein was performed by heparin-Sepharose affinity chromatography and by Sephacryl S200 gel filtration. The molecular mass of the purified protein was estimated at 44 kDa by SDS/PAGE. The isoelectric point was determined to be 6.4. The purified cobalamin-binding protein reacted with an antiserum produced against human transcobalamin. A 44 kDa band was also identified by SDS/PAGE of an immunoprecipitated homogenate from HT 29 cells labelled with [35S]methionine and in a Western blot of cell homogenates. The secretion of the cobalamin-binding protein was maximal between 10 and 12 days of cell culture and was inhibited by cycloheximide.


Foraging patterns in online searches.
Nowadays online searches are undeniably the most common form of information gathering, as witnessed by billions of clicks generated each day on search engines. In this work we describe online searches as foraging processes that take place on the semi-infinite line. Using a variety of quantities like probability distributions and complementary cumulative distribution functions of step length and waiting time as well as mean square displacements and entropies, we analyze three different click-through logs that contain the detailed information of millions of queries submitted to search engines. Notable differences between the different logs reveal an increased efficiency of the search engines. In the language of foraging, the newer logs indicate that online searches overwhelmingly yield local searches (i.e., on one page of links provided by the search engines), whereas for the older logs the foraging processes are a combination of local searches and relocation phases that are power law distributed. Our investigation of click logs of search engines therefore highlights the presence of intermittent search processes (where phases of local explorations are separated by power law distributed relocation jumps) in online searches. It follows that good search engines enable the users to find the information they are looking for through a local exploration of a single page with search results, whereas for poor search engine users are often forced to do a broader exploration of different pages.


Issues in the selection of an antiarrhythmic agent.
The approach to patients with cardiac arrhythmias involves four steps: diagnosis, determination of whether therapy is needed, choice of appropriate treatment, and evaluation of efficacy of therapy. Factors affecting the decision to treat a patient include the presence and type of symptoms associated with the tachyarrhythmia, as well as the frequency with which the arrhythmia occurs. Antiarrhythmic drugs are usually recommended as first-line therapy although nonpharmacologic approaches are preferable in certain specific situations. There are minimal data for most arrhythmias that aid the physician in the selection of a specific drug for a given patient, and many agents will often be equally effective. Most often drugs are selected that have the least potential to produce harmful side effects to the patient; thus, choice of therapy must be individualized. Newer agents are effective but their antiarrhythmic and side effect profiles will not be understood fully until they have been used widely in diverse patient populations. Regardless of which drug is prescribed, invasive or noninvasive methods should be employed to evaluate therapeutic efficacy.


Lightning safety awareness level in Malaysia.
Introduction: Malaysia is one of the countries with the highest lightning flash density globally. While sufficiency of lightning protection system is crucial to ensure human safety against lightning strikes, the public awareness towards lightning safety is also equally important in Malaysia. Hence, this study was conducted to understand the current lightning safety awareness level of the Malaysian population. Methods: An online questionnaire survey which consists of 22 scientific statements of lightning was first developed in Malay and English. The questionnaire allows the respondent to also check their own score upon completion of the questionnaire. It was then distributed to the public for data collection. The sample size comprised of both genders, all layers of society from various educational level and social background. Results: Overall, the awareness on lightning safety amongst Malaysian is at moderate level with an average score of slightly above 50%. Urbanites scored marginally better than their rural counterparts. One's education level does not dictate their awareness level of lightning safety. Discussion: In conclusion, the public in Malaysia needs to be better educated on lightning safety. Similar studies should be replicated in other countries experiencing similar levels of lightning activity to better understand the public's perception on lightning.


Prevalence and correlates of physical activity within on-reserve first nations youth.
Youth in Canada age 5-17 years require a minimum of 60 minutes of moderate to vigorous physical activity (PA) everyday. Regrettably, there are no published studies on levels of PA within on-reserve First Nations youth in Canada that use validated surveys. The objective was to determine what percentage of Saskatoon Tribal Council (STC) First Nations on-reserve youth met the Canadian Society for Exercise and Physiology's (CSEP) definition for being physically active, and what influences are associated with meeting this standard. Students in grades 5-8 within the STC were asked to complete a youth health survey. Only 7.4% of STC youth met CSEP's PA standard. Male youth (13.9%) were more likely to meet the PA standard than female youth (4.1%). Having parents who watch youth participate and who provide transportation to classes, having enough equipment at home, having friends bike or walk to school, participating in physical activity headed by a coach or instructor, and participating in structured classes are associated with meeting the standard. The prevalence of meeting the PA standard among on-reserve First Nations youth is very low. More research is needed to identify independent risk indicators of being physically inactive.


Level dominance in sound source identification.
Impact sounds were synthesized according to standard textbook equations given for the motion of simply supported, metal plates. In a two-interval, forced-choice procedure, highly practiced listeners identified from these sounds a predefined class of target plates based on their particular material and geometric properties. The effects of two factors on identification were examined: the relative level of partials comprising the sounds and the relative amount of information (given as the difference in d(')) each partial provided for identification. In different conditions one factor was fixed while the other either increased or decreased with frequency. The effect on listener identification in each case was determined from a logistic discriminant analysis of trial-by-trial responses, yielding a vector of listener decision weights on the frequency and decay of individual partials. The weights increased proportionally with relative level, but were largely uninfluenced by relative information content--a result exactly opposite to that expected from a maximum-likelihood observer. The dominant effect of relative level was replicated for other sound sources (clamped bars and stretched membranes) and was not diminished by randomizing the relative level of partials across trials. The results are taken to underscore the importance of relative level in the identification of rudimentary sound sources.


In vitro circadian rhythms of the mammalian suprachiasmatic nuclei: comparison of multi-unit and single-unit neuronal activity recordings.
The circadian clock in the mammalian suprachiasmatic nuclei (SCN) expresses 24-h rhythms when isolated in vitro. Numerous studies have demonstrated that recordings of SCN single-unit neuronal activity (SUA), when expressed as a population rhythm, can be used to reliably estimate SCN circadian clock phase in vitro. The main disadvantage of this technique is its laborious nature. Thus, the present experiments were designed to investigate whether in vitro multi-unit neuronal activity (MUA) recordings from the SCN could reliably substitute for SUA recordings. The results show that an MUA rhythm can be recorded from rat SCN for 3 days in vitro but that this rhythm is extremely variable; times of peak MUA in control experiments vary by 7 to 9 h each day. They also show that several serotonergic agents previously shown to consistently advance the SUA rhythm 2 to 3 h when applied during the day induce apparent advances in the MUA rhythm in some experiments; in other cases, however, there appears to be a delay or no change in the phase of the rhythm. Thus, the mean change in time of peak seen after these treatments was an advance of about 1 h. Finally, the results show that glutamate and optic chiasm stimulation applied during early subjective night can induce apparent delays in the MUA rhythm. The results of these experiments were less variable, so that the overall effect was a delay in peak MUA of 2.5 to 3.5 h. Nevertheless, these experiments still exhibited more variability than that generally seen in SUA experiments. Taken together, these results indicate that MUA recordings of the SCN exhibit significantly more variability than do SUA recordings. The extent of this variability leads to the conclusion that, using the techniques and equipment outlined here, MUA recordings are not an adequate substitute for SUA recordings when trying to estimate the phase of the SCN circadian clock.


Molecular weight analysis of antithrombin III-heparin and antithrombin III-thrombin-heparin complexes.
The molecular interactions between components of the heparin-catalyzed antithrombin III/thrombin reaction were investigated by light scattering. When heparin was added to antithrombin III, the molecular weight increased to a maximum and then decreased to that of a 1:1 (antithrombin III X heparin) complex. The initial molecular weights at low heparin to antithrombin III ratios were consistent with the formation of a 2:1 (antithrombin III X heparin) complex in which only one antithrombin III molecule had undergone the conformational change measured by protein fluorescence enhancement. The peak molecular weight never reached that of a complete 2:1 complex. This behavior was observed for bovine and human antithrombin III in the presence of both unfractionated heparin and high molecular weight-high affinity heparin. Pentosane polysulfate also caused some multiple associations. Bovine antithrombin III and thrombin formed a 1:1 complex that underwent further aggregation within minutes, while the human proteins did not aggregate on this time scale after forming the 1:1 complex. In the presence of stoichiometric amounts of heparin, the bovine proteins formed an initial complex of Mr = 230,000 (corresponding to a dimer of heparin-antithrombin III-thrombin) which underwent further aggregation. The human proteins, however, formed a 1:1 (antithrombin III X thrombin) initial complex in the presence of heparin, followed by aggregation. These interactions of thrombin and antithrombin with heparin suggest complex interactions that could relate to heparin function.


Preoperative localization of small peripheral pulmonary nodules by percutaneous marking under computed tomography guidance.
The outcome of computed tomography (CT)-guided percutaneous marking for the preoperative localization of small peripheral pulmonary nodules was analyzed retrospectively. This procedure, in which 21-gauge markers were placed near nodules under local anesthesia on the day of surgery, concerned the patients who received video-assisted thoracoscopic surgery as a primary operative technique. The study included all the 57 patients who underwent CT-guided percutaneous marking before pulmonary resection. The mean nodule size was 1.1 cm. Pneumothorax and pulmonary bleeding were observed in 28 and 17 patients, respectively. Other complications included pain (four), subcutaneous bleeding (two) and dislodgment of the marker (one). Wedge resection during thoracotomy was necessary in seven patients because of severe adhesions (four), multiple wedge resections (one), dislodgment of the marker (one) and difficulty in identifying a nodule (one). Pathological studies revealed 24 metastatic lung tumors, 19 bronchioloalveolar carcinomas (BACs), five adenocarcinomas with mixed subtypes, three granulomas, two atypical adenomatous hyperplasias and six miscellaneous others. Wedge resection for malignancy was performed in 39 patients with 41 lesions. The median follow-up period was 46 months. A positive surgical margin and recurrence at the surgical stump were observed in one case each. In conclusion, preoperative CT-guided marking was safe and effective, although marker dislodgment, positive surgical margin and recurrence at the surgical stump were observed infrequently.


Detection of 5-methylcytosine and 5-hydroxymethylcytosine in DNA via host-guest interactions inside α-hemolysin nanopores.
Cytosine methylation and hydroxymethylation are both important epigenetic modifications of DNA in mammalian cells. Therefore, profiling DNA (hydroxy)methylation across the genome is vital for understanding their roles in gene regulation. Here, we report a nanopore-based approach for quick and reliable detection of 5-methylcytosine and 5-hydroxymethylcytosine in DNA at the single-molecule level. The single-stranded DNA containing 5-methylcytosine or 5-hydroxymethylcytosine was first selectively modified on the epigenetic base to attach a host-guest complex. Threading of the modified DNA molecules through α-hemolysin nanopores causes unbinding of the host-guest complex and generates highly characteristic current signatures. Statistical analysis of the signature events affords quantitative information about 5-methylcytosine and 5-hydroxymethylcytosine in DNA. Our results suggest that other DNA modifications could also be detected with the developed method. Furthermore, we anticipate our nanopore sensing strategy to be generally useful in biochemical analysis and to find applications in the early diagnosis of diseases.


VEGF secretion by adipose tissue-derived regenerative cells is impaired under hyperglycemic conditions via glucose transporter activation and ROS increase.
Transplantation of cultured adipose-derived regenerative cells (ADRCs) into ischemic tissues promotes neovascularization and blood perfusion recovery. These effects are attenuated in diabetes patients. We examined the effects of hyperglycemia on the angiogenic capacity of ADRCs derived from Wistar rats both in vivo and in vitro. Cultured ADRCs were predominantly composed of CD90 positive cells; prevalence of CD90 positive cells was not affected by hyperglycemia. mRNA and protein levels of vascular endothelial growth factor (VEGF) were significantly decreased in ADRCs under hyperglycemic conditions independent of osmolarity, whereas mRNA levels of hepatocyte growth factor and fibroblast growth factor were unaffected. Since ADRCs express glucose transporter proteins GLUT1, 3 and 4, we examined the effects of the glucose transporter inhibitor phloretin on reactive oxygen species (ROS) and angiogenic factors. Phloretin decreased the glucose uptake rate, reduced ROS, and increased VEGF mRNA in ADRCs exposed to a hyperglycemic condition. In vivo transplantation of ADRCs cultured under hyperglycemic conditions into mouse ischemic limbs resulted in significantly decreased blood perfusion and capillary density in ischemic regions compared with transplantation of ADRCs cultured under normoglycemic conditions. These results suggest that hyperglycemia impaired VEGF production in ADRCs via an increase of ROS, impairing the angiogenic capacity of ADRCs transplanted into ischemic limbs.


Spatial analysis of determinants of choice of treatment provider for fever in under-five children in Iganga, Uganda.
Although health facilities and drug shops are the main alternatives to home management of fever in children in Uganda, the influence of distance on the choice of treatment provider by caretakers is still unclear. We examined the spatial distribution of choice of treatment provider for fever in under-five children and the influence of household and geographical factors. Spatial and regression analysis of choices of treatment provider was done using data from a 2-week recall survey conducted in the Iganga-Mayuge Health and Demographic Surveillance Site. Of 3483 households with febrile children, 45% of caretakers treated the child at home, 33% took the child to a health facility, and 22% obtained treatment at drug shops. The distance to access care outside the home was crucial as seen in the greater preference for treatment at home or at drug shops among caretakers living more than 3 km from health facilities. The influence of proximity to health facilities in the choice of treatment provider highlights the need for greater access to health care services. The current Uganda Ministry of Health threshold of 5 km for access to health facilities needs to be reviewed for rural areas.


Desulfatiferula olefinivorans gen. nov., sp. nov., a long-chain n-alkene-degrading, sulfate-reducing bacterium.
A novel anaerobic, long-chain alkene-degrading, sulfate-reducing bacterium, strain LM2801T, was isolated from brackish sediment of a wastewater decantation facility of an oil refinery (Berre lagoon, France). Cells of strain LM2801T were Gram-negative, motile, slightly curved or vibrioid rods. Its optimum growth conditions were 30-36 degrees C, 6-10 g NaCl l(-1) and pH 7.5. Strain LM2801T incompletely oxidized long-chain alkenes (from C14 to C23) and fatty acids (C14 to C24). The DNA G+C content was 45.5 mol%. Sequence analyses of the 16S rRNA and dsrAB genes indicated that the strain was a member of the family Desulfobacteraceae within the Deltaproteobacteria. This novel isolate possesses phenotypic and phylogenetic traits that do not allow its classification as a member of any previously described genus. Therefore, strain LM2801T is described as a member of a new genus, Desulfatiferula gen. nov., of which Desulfatiferula olefinivorans sp. nov. is the type species. The type strain of Desulfatiferula olefinivorans is LM2801T (=DSM 18843T=JCM 14469T).


[Model studies of DNA-protein interaction. I. Effect of aminocarboxylic and amide groups of amino acids on DNA thermostability and conformation].
To elucidate interactions of amino-carboxylate dipole and amide group of amino acids with DNA, glycine and glutamine, concentration dependences of the melting curves and CD spectra of calf thymus DNA at low ionic strength (10(-4) M) Na-citrate have been studied. A considerable increase of the melting temperature delta t1/2 and a decrease of the temperature interval of melting delta t with the rise of glycine concentration were observed without changes in the CD spectrum. A comparison was made between the influence of dipolar glycine ion and isolated amino and carboxylate ions of ammonium acetate. The data obtained indicated the predominance of electrostatic interaction of glycine with DNA phosphates until the ligand concentration was approximately 0.6 M and, apparently, specific interactions of carboxylate ion with guanine at higher glycine concentrations. Destabilizing effect of glutamine on DNA at a concentration of 5.10(-3) M was observed, whereas at higher concentrations two-phase increase of delta t1/2 was shown. Small changes in DNA CD spectrum under the action of glutamine were registered. The comparison data for glutamine and acrylamide showed that DNA destabilizing effect was due to the amide group. The destabilizing effect of amide group can be explained by its interaction with the bases in single-stranded regions of DNA with the formation of two H-bonds. It is possible that the increase of DNA delta t1/2 is the result of the interaction of phosphates both with aminocarboxylate and amide groups of glutamine.


Microbial metabolism directly affects trace gases in (sub) polar snowpacks.
Concentrations of trace gases trapped in ice are considered to develop uniquely from direct snow/atmosphere interactions at the time of contact. This assumption relies upon limited or no biological, chemical or physical transformations occurring during transition from snow to firn to ice; a process that can take decades to complete. Here, we present the first evidence of environmental alteration due to in situ microbial metabolism of trace gases (methyl halides and dimethyl sulfide) in polar snow. We collected evidence for ongoing microbial metabolism from an Arctic and an Antarctic location during different years. Methyl iodide production in the snowpack decreased significantly after exposure to enhanced UV radiation. Our results also show large variations in the production and consumption of other methyl halides, including methyl bromide and methyl chloride, used in climate interpretations. These results suggest that this long-neglected microbial activity could constitute a potential source of error in climate history interpretations, by introducing a so far unappreciated source of bias in the quantification of atmospheric-derived trace gases trapped within the polar ice caps.


Atypical cutaneous lesions of Lyme disease.
In 30 patients with Lyme disease, the lesions of erythema chronicum migrans were absent or atypical. Thirty biopsy specimens were obtained from cutaneous lesions of these patients. The predominant histological finding was a superficial dermal and deep perivascular and interstitial infiltrate composed mostly of lymphocytes but containing a few eosinophils and plasma cells. In serial sections with a silver stain, a few Borrelia burgdorferi were found in the biopsy specimens from cutaneous lesions in five patients. Thus, there is evidence that the typical lesions of erythema chronicum migrans of the classical Lyme disease do not develop while Borrelia burgdorferi survive and persist in cutaneous lesions.


The relationship between insufficient sleep and self-rated health in a nationally representative sample.
Reduced sleep has been found to be associated with increased risk of diabetes mellitus, hypertension, cardiovascular disease (CVD), and mortality. Self-rated health (SRH) has been shown to be a predictor of CVD and mortality. However, study of the association between insufficient sleep and SRH is limited. We examined participants >18 years of age (n = 377, 160) from a representative, cross-sectional survey (2008 BRFSS). Self-reported insufficient sleep in the previous 30 days was categorized into six groups. The outcome was poor SRH. We calculated odds ratios ((OR) (95% confidence interval (CI)) of increasing categories of insufficient rest/sleep, taking zero days of insufficient sleep as the referent category. We found a positive association between increasing categories of insufficient sleep and poor SRH, independent of relevant covariates. In the multivariable-adjusted model, compared to 0 days insufficient sleep, the OR (95% CI) of poor SRH was 1.03 (0.97-1.10) for 1-6 days, 1.45 (1.34-1.57) for 7-13 days, 2.12 (1.97-2.27) for 14-20 days, 2.32 (2.09-2.58) for 21-29 days, and and 2.71 (2.53-2.90) for 30 days of insufficient sleep in the prior 30 days (P-trend <0.0001). In a nationally representative sample, increasing categories of insufficient sleep were associated with poor SRH.


Characterization of the DNA-binding domain of the avian Y-box protein, chkYB-2, and mutational analysis of its single-strand binding motif in the Rous sarcoma virus enhancer.
chkYB-2 is a sequence-specific, single-stranded DNA binding chicken Y-box protein that promotes Rous sarcoma virus long terminal repeat (RSV LTR)-driven transcription in avian fibroblasts. The DNA-binding domain of chkYB-2 has been mapped by characterizing the DNA binding properties of purified recombinant chkYB-2 mutant polypeptides. The data indicate that the invariant cold shock domain (CSD) is necessary but not sufficient for association with DNA and suggest that another conserved region, adjacent to the carboxyl boundary of the CSD, plays a role in high-affinity DNA binding. chkYB-2 binds to a tandem repeat of the 5'-GTACCACC-3' motif on the RSV LTR. Mutational analysis of this recognition sequence revealed the requirement of an essentially unaltered template for both high-affinity binding by chkYB-2 as well as maximal transcriptional activity of the RSV LTR in vivo. The single-stranded DNA binding activity of chkYB-2 is augmented by Mg2+. The possible significance of this finding for transactivation by a single-strand DNA binding protein is discussed.


Effect of deep brain simulation on arm, leg, and chin tremor in Parkinson disease.
The efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in the treatment of Parkinson disease (PD)-related tremor has been well established. However, the relative impact on arm, leg, and chin tremor has been less clearly elucidated. The authors evaluated the distribution of tremors in a PD cohort undergoing STN DBS and sought to evaluate the differential impact of DBS as a function of tremor location. A retrospective study of patients with PD with tremor who underwent DBS surgery between 2012 and 2016 was performed to evaluate the impact of STN stimulation on overall and regional tremor scores. Across 66 patients the authors found an average of 78% overall reduction in tremor after 6 months. In this cohort, the authors found that tremor reduction was somewhat better for arm than for leg tremors, especially in instances of higher preoperative tremor (84% vs 71% reduction, respectively, for initial tremor scores ≥ 2). No significant difference in response was found between patients with medication-responsive versus medication-nonresponsive tremors. The authors found that although DBS improved tremor in all regions, the improvement was not uniform between chin, arm, and leg-even within the same patient. The reasons behind these differing responses are speculative but suggest that STN DBS may more reliably reduce arm tremors than leg tremors.


'Carcinoma en cuirasse' in the neck: extremely unusual initial presentation of gastric cancer.
Cutaneous metastasis from visceral malignancy is a relatively rare phenomenon. It is even rarer to have cutaneous lesions as the first mode of clinical presentation in such malignancies. The lesions are usually nodular, although they can have varied appearances. Common sites of primaries include breast, lung, colorectum, kidney, ovary, and headandneck. We report an unusual form of cutaneous metastasis in the neck, known as 'carcinoma en cuirasse', in an elderly man that subsequently led to the diagnosis of an occult gastric cancer. Our case highlights the importance of recognising cutaneous metastatic lesions early, as they may herald the diagnosis of an occult internal malignancy.


Different molecular subtypes of breast invasive ductal carcinoma.
This study aims to analyze the clinical characteristics of breast invasive ductal carcinoma (BIDC) in patients with different molecular subtypes and identify possible correlation to prognosis. miR- 10b expression level was detected using real-time quantitative polymerase chain reaction (RT-PCR). Tissue sections were collected and stained using the immunohistochemical method. The samples were grouped into human epidermal growth factor receptor 2, (HER2) overexpression, Triple negative, Luminal A and Luminal B groups. Age, tumor size, breast cancer molecular subtype, clinical stage, miR-10b positive expression, positive expression of Ki-67 and survival rate of patients diagnosed with BIDC were analyzed. The expression of miR-10b was down-regulated in the breast carcinoma tissues. Age and clinical stage were distinctly different among patients with different molecular subtypes of BIDC (p less than 0.05). Tumor size was not remarkably different (p less than 0.05) among different subtypes. The positive expression rate of miR-10b was lowest in patients with Luminal B BIDC; the positive expression of Ki-67 was in different correlation with the expression of different receptors, and there was a remarkable difference (p less than 0.05); moreover, the survival rate of patients with Luminal A and B BIDC was significantly higher compared to patients with other molecular subtypes (p less than 0.05). Clinical characteristics and prognosis of BIDC vary among different molecular subtypes. This study provides valuable input on BIDC therapy.