Processing Natural Wood into an Efficient and Durable Solar Steam Generation Device.
Harvesting solar energy for water desalination is one of the most promising ways to produce clean water. Because of the absorber detachment and base material degradation, the solar steam generator still suffers from drastic energy loss even when using absorber materials with high photothermal conversion efficiency. We herein propose a practical desalination design that can maintain both the working efficiency and operating life. This device is made from the Paulownia wood covalently bonded with MXene on the top. Paulownia wood, as a natural heat insulator, servers as an excellent transport and customized evaporator. This heat absorber-Paulownia wood system achieved an evaporation rate of 1.465 kg m-2 h-1 at 1 sun irradiation, corresponding to 96% solar conversion efficiency. This method is proved to be universal, and the other two implemented materials, graphene oxide and the active carbon, on Paulownia wood were also demonstrated. The theoretical model based on two-phase flow in porous media further suggests this design can accelerate the distillate rate. In this article, the covalently bonded device shows a high solar-thermal conversion efficiency, excellent evaporation rate, and long-time durability, making it a superior candidate for water desalination.


Electron injection and scaffold effects in perovskite solar cells.
In spite of the impressive efficiencies reported for perovskite solar cells (PSCs), key aspects of their working principles, such as electron injection at the contacts or the suitability of the utilization of a specific scaffold layer, are not yet fully understood. Increasingly complex scaffolds attained by the sequential deposition of TiO2 and SiO2 mesoporous layers onto transparent conducting substrates are used to perform a systematic characterization of both the injection process at the electron selective contact and the scaffold effect in PSCs. By forcing multiple electron injection processes at a controlled sequence of perovskite-TiO2 interfaces before extraction, interfacial injection effects are magnified and hence characterized in detail. An anomalous injection behavior is observed, the fingerprint of which is the presence of significant inductive loops in the impedance spectra with a magnitude that correlates with the number of interfaces in the scaffold. Analysis of the resistive and capacitive behavior of the impedance spectra indicates that the scaffolds could hinder ion migration, with positive consequences such as lowering the recombination rate and implications for the current-potential curve hysteresis. Our results suggest that an appropriate balance between these advantageous effects and the unavoidable charge transport resistive losses introduced by the scaffolds will help in the optimization of PSC performance.


Olanzapine pamoate for the treatment of schizophrenia--a safety evaluation.
Non-adherence to long-term treatment is a major issue for patients with schizophrenia and is associated with an increased risk of relapse. Long-acting injectable (LAI) antipsychotics can offer a useful option to improve adherence. Due to the type of sustained-release mechanism, olanzapine pamoate (OLAI) can differ in safety as compared with oral olanzapine. Recent safety data concerning olanzapine pamoate required an update of previous systematic reviews. Safety data were found in US and EU clinical trial registries, and a literature search was undertaken using the databases PubMed and EMBASE to find all relevant published studies. Where appropriate, the number needed to harm and 95% confidence interval for categorical safety outcomes were calculated. The safety profile of OLAI was similar to the well-known safety profile of oral olanzapine, except for the risk of occurrence of post-injection delirium/sedation syndrome (PDSS). Olanzapine pamoate can be a choice for schizophrenic patients with a history of response to and acceptable tolerance of oral olanzapine, who have easy access to mental healthcare settings with emergency services for the treatment of PDSS. Long-term, prospective studies assessing the efficacy and safety of OLAI and head-to-head comparisons with other LAI and oral antipsychotics are needed.


Impaction grafting in revision total elbow arthroplasty.
Revision total elbow arthroplasty is often undertaken in patients who have severe osteolysis of both the distal part of the humerus and the proximal part of the ulna. To deal with such bone loss, we have adopted the practice of impaction grafting, which has become a well-established technique in the proximal part of the femur. We retrospectively reviewed the results of twelve patients who had undergone revision total elbow arthroplasty with impaction grafting between 1993 and 1997. There were eight women and four men with a mean age of fifty-seven years. All patients were followed for at least two years (range, twenty-five to 113 months), with an average duration of follow-up of seventy-two months. Seven of the patients had an initial diagnosis of rheumatoid arthritis, and five had posttraumatic arthritis. Impaction grafting was undertaken during the initial revision in three of the patients, whereas the remaining nine patients had undergone at least one prior revision without impaction grafting. Four patients had impaction grafting on the ulnar side alone, six had it on the humeral side alone, and two underwent impaction grafting of both the humerus and the ulna. Six allograft struts were placed to span structural defects in five patients. At the time of the latest follow-up, eight of the elbow prostheses were intact after the index impaction grafting procedure. Two elbows had been revised because of loosening, and another had been revised because of a fracture of the ulnar component. A fourth patient had undergone a resection arthroplasty because of infection. The eight remaining patients demonstrated marked radiographic improvement in bone quality in the region of the impaction graft without clinical symptoms of loosening. At the time of the last follow-up, after an additional revision in three elbows, there were five excellent, four good, and three fair results. Impaction grafting is a reliable technique for treating osteolysis in patients undergoing revision total elbow arthroplasty; however, complications can occur, and a high percentage of patients need additional surgery.


Selective laser trabeculoplasty: Does energy dosage predict response?
Selective laser trabeculoplasty (SLT) is a widely used treatment for open angle glaucoma, producing sustained reductions of intraocular pressure (IOP). The aim of this study was to evaluate the long-term relationship between SLT energy dosage and IOP reduction. A retrospective review was performed for patients receiving primary SLT therapy, with inclusion of subjects treated with 360° of SLT. Energy settings were collected upon treatment and IOP was collected at baseline up to 36 months. Pearson's correlation coefficient was used to determine whether there was a significant correlation between SLT energy and IOP reduction at all time points. Kaplan-Meier analysis with log-rank test was performed to determine the differences in IOP reduction ≥20% from baseline among those treated with low (<85 mJ), medium (85-105 mJ), and high (>105 mJ) energy SLT. A total of 104 eyes (75 patients) were included. The mean total SLT energy was 93.73 mJ (standard deviation (SD) = 21.83 mJ, range: 34.4-122 mJ). A significant positive correlation (P ≤ 0.05) between the amount of energy delivered and IOP reduction was found at all time points. Log-rank test showed a significant difference in IOP reduction ≥20% from baseline between the three energy groups, with low energy patients experiencing failure at an earlier time (P = 0.05). Within the range of total energy examined, there is a positive correlation between total energy used and amount of pressure reduction achieved at up to 3 years of follow-up. This may be useful in determining the optimal energy dosage for maximum effect for patients receiving SLT.


Identification of a Novel Retrieval-dependent Memory Process in the Crab Neohelice granulata.
Fully consolidated associative memories may be altered by alternative retrieval dependent memory processes. While a brief exposure to the conditioned stimulus (CS) can trigger reconsolidation of the original memory, a prolonged CS exposure will trigger memory extinction. The conditioned response is maintained after reconsolidation, but is inhibited after extinction, presumably by the formation of a new inhibitory memory trace. In rats and humans, it has been shown that CS exposure of intermediate duration leave the memory in an insensitive or limbo state. Limbo is characterised by the absence of reconsolidation or extinction. Here we investigated the evolutionary conserved nature of limbo using a contextual Pavlovian conditioning (CPC) memory paradigm in the crab Neohelice granulata. In animals with fully consolidated CPC memory, systemic administration of the protein synthesis inhibitor cycloheximide after 1 CS presentation disrupted the memory, presumably by interfering with memory reconsolidation. The same intervention given after 320 CSs prevented CPC memory extinction. Cycloheximide had no behavioural effect when administered after 80 CS presentations, a protocol that failed to extinguish CPC memory. Also, we observed that a stronger CPC memory engaged reconsolidation after 80 CS instead of limbo, indicating that memory strength affects the parametrical conditions to engage either reconsolidation or limbo. Altogether, these results indicate that limbo is an evolutionary conserved memory process segregating reconsolidation from extinction in the number of CSs space. Limbo appears as an intrinsic component of retrieval dependent memory processing, with a key function in the transition from memory maintenance to inhibition.


The neurotopography of written word production: an fMRI investigation of the distribution of sensitivity to length and frequency.
This research is directed at charting the neurotopography of the component processes of the spelling system by using fMRI to identify the neural substrates that are sensitive to the factors of lexical frequency and word length. In spelling, word frequency effects index orthographic long-term memory whereas length effects, as measured by the number of letters, index orthographic working memory (grapheme buffering). Using the task of spelling to dictation in the scanner, we found a highly differentiated neural distribution of sensitivity to the factors of length and lexical frequency, with areas exhibiting sensitivity to length but not frequency and vice versa. In addition, a direct comparison with the results of a previous study [Rapp, B., & Lipka, K. The literate brain: The relationship between spelling and reading. Journal of Cognitive Neuroscience, 23, 1180-1197, 2011] that used a very different spelling task yielded a converging pattern of findings regarding the neural substrates of the central components of spelling. Also, with regard to relationship between reading and spelling, we replicated previous functional neuroimaging studies that have shown overlapping regions of activation in the left posterior inferior frontal gyrus and midfusiform gyrus for word reading and spelling.


Kosakonia quasisacchari sp. nov. recovered from human wound secretion in China.
A novel Kosakonia strain WCHEs120001T was recovered from the wound secretion of a patient at West China Hospital, Chengdu, PR China, in 2017. The strain was Gram-stain-negative, facultatively anaerobic, motile, and non-spore-forming. A preliminary analysis based on the 16S rRNA gene sequence revealed that this strain was closely related to members of the genus Kosakonia. The strain was subjected to whole genome sequencing. Phylogenetic analysis based on core gene sequences of type strains of all Enterobacteriaceae species revealed that this strain belonged to the genus Kosakonia but were distinct from any previously known Kosakonia species. Both average nucleotide identity (ANI) and in silico DNA-DNA hybridisation (isDDH) values between strain WCHEs120001T and type strains of all known Kosakonia species were 82.02 to 92.37% and 25.6 to 50.9 %, respectively, which are lower than the 95 % (ANI) and 70 % (isDDH) cutoff for species delineation. The major fatty acids of the strain WCHEs120001T are C16 : 0, sum of C16:1ω7c/C16:1ω6c and C18:1ω7c, which are similar to other Kosakonia species. Genomic DNA G+C content of strain WCHEs120001T was 53.33 mol%. Strain WCHEs120001T is positive for methyl-d-glucopyranoside but does not ferment adonitol, d-arabitol, dulcitol and melibiose, which distinguishes it from all other Kosakonia species. Genotypic and phenotypic characteristics indicate that strain WCHEs120001T represents a novel species of the genus Kosakonia, for which the name Kosakonia quasisacchari sp. nov. is proposed. The type strain of K. quasisacchari sp. nov. is WCHEs120001T (=GDMCC1.1570T=NCTC 14272T).


Prevalence and significance of early repolarisation in a black African population: data of 246 individuals with cardiovascular morbidity.
Early repolarisation (ER) is commonly seen on electrocardiograms (ECG). Recent reports have described the relationship between ER and sudden cardiac death (SCD). The prevalence and significance of ER have not been studied in black Africans. We matched clinical and ECG records of subjects over 18 years of age who consulted a cardiac unit in two medical centres of Douala, Cameroon. A questionnaire focusing on past history of syncope or family history of sudden unexplained death (SUD) was filled in by each subject. A 12-lead ECG was recorded by a trained nurse and analysed by two independent physicians. Of the 752 ECGs recorded, we studied 246 index cases. The mean age of subjects was 45 ± 16 years and 53% were female. Almost 57% had hypertension, 41% had palpitations and 18% reported a history of syncope. ER pattern was found in 20% [slurring in three (3%), notching in 13% and both in three (7%)]. ER subjects were younger than those without (41 ± 16 vs 49 ± 16 years, p = 0.0048). Lead localisation was predominantly the laterals for the slurring pattern, whereas the inferior and lateral leads were equally involved for the notching pattern. Negative T waves in the infero-lateral leads were associated with ER (p = 0.00025). Among the subjects with syncope, 41% displayed ER and 13% did not have ER (p = 0.00014). The notching pattern seemed to be associated with syncope (p = 0.00011). Early repolarisation is frequent in black Africans, especially in the setting of cardiovascular morbidity. Early repolarisation may be associated with a past history of syncope, especially the notched pattern.


Geographic disparities in access to glioblastoma treatment based on Hispanic ethnicity in the United States: Insights from a national database.
Access to treatment for glioblastoma (GBM) can be impacted by multiple demographic parameters. Barriers specific to the Hispanic population of the United States (US) are not fully understood. Therefore, the aim of this study was to elucidate geographic disparities for access to GBM treatment in the US Hispanic population. All GBM patients with known Hispanic ethnicity status (and Caucasian race) in the US National Cancer Database (NCDB) between the years 2005-2016 were retrospectively reviewed. Treatment statuses of surgical resection, chemotherapy, radiation therapy and triple therapy (resection, chemotherapy and radiation) were summarized, and analyzed by comparison and regression analyses over US Census regions. A total cohort size of 40,232 Caucasian GBM patients were included, with 3,111 (8%) identifying as Hispanic. The odds of treatment by chemotherapy (OR 0.78, P < 0.01), radiation therapy (OR 0.82, P < 0.01) and triple therapy (OR 0.84, P < 0.01) were all significantly lower in the Hispanic group versus non-Hispanic group. The odds of being treated in the Hispanic group were significantly lower in multiple Census regions with respect to surgical resection (New England, OR 0.51; Mountain, OR 0.68), chemotherapy (East North Central, OR 0.77; Middle Atlantic, OR 0.71; Pacific, OR 0.77), radiation therapy (Middle Atlantic, OR 0.77) and triple therapy (New England, OR 0.49; Middle Atlantic, OR 0.87; Pacific, OR 0.84). Significant barriers to triple therapy in the Hispanic group within these regions were older age (OR 0.97; P < 0.01), treatment in a community facility (OR 0.85, P = 0.03), lack of insurance (OR 0.71, P = 0.03), yearly income < $40,227 (OR 0.69, P < 0.01), low education levels (OR 0.75, P = 0.03) and presence of co-morbidity (OR 0.82; P < 0.01). Currently in the US, there exists heterogenous geographic disparities for Hispanic GBM patients to access different treatments compared to non-Hispanic patients. Multiple circumstances can influence access to treatment within the Hispanic community of these regions, and greater investigation with more granularity required to reveal mechanisms in which these disparities may be addressed in the future.


Risk of major cardiovascular events among incident dialysis patients: A Korean national population-based study.
Dialysis patients are at high risk for cardiovascular diseases, but until now there have been no detailed analyses of the incidences among Asian patients initiating dialysis. The aims of this study were to determine the incidence rates of major adverse cardiac and cerebrovascular events (MACCE) and to compare them between incident HD patients and PD patients. We included all patients who had started dialysis between January 1, 2005 and December 31, 2008 in Korea, and analyzed 30,279 eligible patients [22,892 hemodialysis (HD) patients and 7387 peritoneal dialysis (PD) patients] by intention-to-treat. Median follow-up was 21.5 months. The crude incidence rates were as follows: MACCE, 182 per 1000 patient-years (PY); major adverse cardiac events (MACE), 138/1000 PY; all-cause mortality, 116/1000 PY; non-fatal acute myocardial infarction (AMI), 18/1000 PY; target vessel revascularization (TVR), 17/1000 PY; and non-fatal stroke, 60/1000 PY. When comparing all baseline covariate-adjusted relative risks between HD and PD patients, HD is overall superior to PD in terms of MACCE. Further examined by each endpoint, all-cause mortality, non-fatal AMI, and TVR occurred significantly more frequently in patients on PD than in those on HD, whereas non-fatal hemorrhagic stroke occurred significantly more frequently in patients on HD than in those on PD. The incidence of MACCE may be different from Western dialysis patients. HD is overall superior to PD in terms of MACCE as an initial dialysis modality. Underlying mechanisms differentially affecting cardiovascular outcomes by dialysis modality remain to be further elucidated.


A phase I trial of palbociclib plus bortezomib in previously treated mantle cell lymphoma.
In mantle cell lymphoma (MCL), cyclin D1 combines with CDK4/6 to phosphorylate Rb, releasing a break on the G1 to S phase cell cycle. Palbociclib is a specific, potent, oral inhibitor of CDK4/6 capable of inducing a complete, prolonged G1 cell cycle arrest (pG1) in Rb+ MCL cells. The proteasome inhibitor bortezomib is approved by the US Food and Drug Administration for treatment of mantle cell lymphoma. Palbociclib-induced pG1 appears to sensitize MCL cells to killing by low-dose bortezomib, potentially improving its activity and tolerability. We conducted a phase 1 trial of palbociclib plus bortezomib in patients with previously treated MCL (NCT01111188). Patients received palbociclib at 75 mg (dose level 1), 100 mg (dose level 2), or 125 mg (dose levels 3 and 4) on days 1-12 of each 21-day cycle in addition to intravenous bortezomib 1.0 mg/m2 (dose levels 1, 2, 3) or 1.3 mg/m2 (dose level 4) on days 8, 11, 15 and 18. A total of 19 patients with a median age of 64 and an average of 2 prior therapies were enrolled. Two subjects experienced dose limiting toxicity (DLT): thrombocytopenia (dose level 1) and neutropenia (dose level 3). Although no DLTs were seen at dose level 4, all patients required dose delays during cycle 2 due to cytopenias, and the study team decided to stop the trial. Four of 19 patients achieved a clinical response, including one patient with a complete response. Three patients received treatment for more than one year, including one patient receiving single-agent palbociclib for more than 6 years. The combination of palbociclib 125 mg on days 1-12 plus bortezomib 1.0 mg/m2 on days 8, 11, 15, and 18 of a 21-day cycle is feasible and active in previously treated MCL, with the primary toxicity being myelosuppression. The regimen may be worthy of further evaluation in patients with non-blastoid MCL following failure of other newer agents.


The utility of endobronchial ultrasound-guided transbronchial needle aspiration in mediastinal or hilar lymph node evaluation in extrathoracic malignancy: Benign or malignant?
Newly arising enlarged or hypermetabolic mediastinal/hilar lymph nodes (LNs) in patients with previously diagnosed extrathoracic malignancies raise suspicion of metastasis. Relatively high proportion of these LNs is due to a benign condition. We aimed to determine frequency of malignant LNs and role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for clarification of the origin of suspicious LNs in these patients. Consecutive patients with a known extrathoracic malignancy and suspected hilar/mediastinal LN were included in this prospective study. Computed tomography (CT) of thorax and positron emission tomography-CT of all patients were taken. LNs with short axis >1 cm at CT of thorax and SUV ≥ 2.5 were accepted suspicious for malignancy. All patients underwent EBUS-TBNA for pathological verification of LNs. Patients with benign diagnosis either underwent invasive procedures or were followed up. The results were evaluated for frequency of malignant hilar/mediastinal LNs and sensitivity, specificity, and diagnostic values of EBUS-TBNA. A total of 48 cases with a mean age of 57.4±11.6 were included. All cases had the diagnosis of an extrathoracic malignancy. 78 LNs were aspirated with EBUS-TBNA in 48 cases (1.62 LNs/patient). The mean short axis of aspirated LNs was 1.51±0.63. Results of EBUS-TBNA revealed malignancy in 15 cases (31.2%), tuberculosis in six cases (12.5%), sarcoidosis in four cases (8.3%), and reactive adenitis in 23 cases (48%). The sensitivity, specificity, and negative predictive value of EBUS-TBNA for malignancy were 83.3%, 100%, and 90.9%, respectively. When both benign and malignant diseases were considered, sensitivity, specificity, negative predictive value, and diagnostic accuracy of EBUS-TBNA were 89.2%, 100%, 86.9%, and 93.7%, respectively. The ratio of benign LNs in patients with extrathoracic malignancies is relatively high. EBUS-TBNA is a safe, minimally invasive, and effective method for clarification of intrathoracic LNs.


Cloning of the IL-1β3 gene and IL-1β4 pseudogene in salmonids uncovers a second type of IL-1β gene in teleost fish.
To date two closely related interleukin-1β genes (IL-1β1 and IL-β2) have been found in salmonids. The cloning of trout and salmon IL-1β3, and a salmon IL-1β4 pseudogene reveals that two types of IL-1β genes exist in teleost species. Type I teleost IL-1β genes, including salmonid IL-1β3, share a similar 6 coding exon structure as in tetrapods. Type II teleost IL-1β genes, e.g. salmonid IL-1β1-2, lack one or two coding exons at their 5'-end, and share higher identities within this subgroup than within the type I subgroup. Both types of IL-1β genes have been found in species of Salmoniformes, Perciformes and Beloniformes, suggesting the divergence occurred early in teleost evolution. Trout IL-1β3 is highly expressed in ovary suggesting a role in reproduction. A relatively high constitutive expression in gills, spleen and kidney and the up-regulation by PAMPs, proinflammatory cytokines and viral infection suggests IL-1β3 also has a role in inflammation and host defence.


Susceptibility to human papillomavirus-associated cervical intra-epithelial neoplasia is determined by specific HLA DR-DQ alleles.
Human papillomaviruses (HPV) play a causative role in the aetiology of cervical intra-epithelial neoplasia (CIN) and cervical cancer. Human leukocyte antigens (HLA) are important in the regulation of immune response to foreign antigens. The role of genetic variation at the HLA class II loci (DR and DQ) in CIN (HPV 16, 18, 31 and 33 typed) was investigated by PCR DNA amplification and oligonucleotide probe typing of cervical smears from British Caucasian patients (n = 176) and controls (n = 416). The alleles of the DQB1*03, DRB1*04 and DRB1*11 loci were strongly associated with susceptibility to CIN. Specifically, the haplotypes DRB1*0401-DQB1*0301 and DRB1*1101-DQB1*0301 were significant and indicated susceptibility. The DQB1*03 locus was more contributory to this association than the DRB1 loci. A weak protective effect was shown for the haplotype DRB1*0101-DQB1*0501. Positive correlation was also observed for HPV-positive CIN, suggesting that specific HLA class II alleles may be important in determining the immune response to HPV antigens and the risk for CIN after HPV infection. Our results should help in the rational design of vaccines against HPV.


Prevalence and Correlates of Self-Rated Successful Aging Among Older Women Living With HIV.
Despite marked gains in longevity attributable to antiretroviral therapy (ART), older women living with HIV (OWLH) experience substantial health challenges, and few studies addressed whether they can achieve successful aging (SA). This is among the first studies examining prevalence and psychosocial correlates of self-rated SA (SRSA) among OWLH and women at risk of HIV. The sample included 386 OWLH and 137 HIV-seronegative women enrolled in the Women's Interagency HIV Study (WIHS) who were aged 50 years and older and participated in the "From Surviving to Thriving" (FROST) substudy. The FROST survey included measures of SRSA and positive psychosocial constructs. Participants were on average 57 years (SD = 5.3), 74% African American and 30% unemployed. Among OWLH, 94% were on ART and 73% were virally suppressed. Compared with OWLH, a higher proportion of HIV-seronegative women had an annual income ≤ $6000, no health insurance, and reported lower optimism and health-related quality of life. We found no differences in SRSA prevalence by HIV status: 84% of OWLH and 83% of HIV-seronegative women reported SRSA ≥7 (range = 2-10, higher scores signify better SRSA). Having SRSA ≥7 was associated with higher levels of positive psychosocial characteristics (eg, resilience and optimism) among both OWLH and HIV-seronegative women. SRSA is achievable among older women with and at risk of HIV despite health complications. Among disadvantaged women, factors other than HIV may be primary drivers of SRSA. Future research is needed to examine determinants of SRSA and to design public health interventions enhancing SA within this population.


Beta-2 microglobulin levels in hemodialysis patients.
The objective of the study was to determine the level of beta2-microglobulin (beta2-m) in hemodialysis (HD) patients and the factors affecting it. This cross sectional, hospital based study was conducted between September and December 2008 at the Hemodialysis unit of Shalamar Hospital, Lahore. All patients with end-stage renal disease (ESRD) who were on maintenance HD for more than three months were included in the study. Patients with acute renal failure and on dialysis for less than three months were excluded. Demographic data were collected and details of dialysis (type of dialyzers, dialysate bath, membrane used) were recorded. Blood samples of the patients were drawn for hematological (hemoglobin, hematocrit), biochemical (urea, creatinine, uric acid, albumin) and beta2-m level measurement. The total number of patients studied was 50. The major causes of ESRD included diabetes mellitus and hypertension seen in 37 (74%) and 10 patients (20%), respectively. The beta2-m levels were significantly elevated in the study patients; 92.6 +/- 17.1 mg/L with a range of 54 to 130 mg/L as compared to 2.0 +/- 1.29 mg/L in the control group. The patients' age had a statistically significant relationship with the beta2-m level. The major reason for increased beta2-m level was use of low-flux dialyzers. Synthetic polysulphone membrane, bicarbonate, ultra pure dialysate and duration on HD were not asso-ciated with high beta2-m levels. Also, we found an inverse relationship between beta2-m levels and serum albumin of the study patients. Our study suggests that the beta2-m levels are significantly high in dialysis patients. Use of low-flux dialyzer seems to be the major reason for the high beta2-m levels. Age and albumin have statistically significant relationship with beta2-m levels.


The impact of injecting networks on hepatitis C transmission and treatment in people who inject drugs.
With the development of new highly efficacious direct-acting antiviral (DAA) treatments for hepatitis C virus (HCV), the concept of treatment as prevention is gaining credence. To date, the majority of mathematical models assume perfect mixing, with injectors having equal contact with all other injectors. This article explores how using a networks-based approach to treat people who inject drugs (PWID) with DAAs affects HCV prevalence. Using observational data, we parameterized an exponential random graph model containing 524 nodes. We simulated transmission of HCV through this network using a discrete time, stochastic transmission model. The effect of five treatment strategies on the prevalence of HCV was investigated; two of these strategies were (1) treat randomly selected nodes and (2) "treat your friends," where an individual is chosen at random for treatment and all their infected neighbors are treated. As treatment coverage increases, HCV prevalence at 10 years reduces for both the high- and low-efficacy treatment. Within each set of parameters, the treat your friends strategy performed better than the random strategy being most marked for higher-efficacy treatment. For example, over 10 years of treating 25 per 1,000 PWID, the prevalence drops from 50% to 40% for the random strategy and to 33% for the treat your friends strategy (6.5% difference; 95% confidence interval: 5.1-8.1). Treat your friends is a feasible means of utilizing network strategies to improve treatment efficiency. In an era of highly efficacious and highly tolerable treatment, such an approach will benefit not just the individual, but also the community more broadly by reducing the prevalence of HCV among PWID.


An association between L-arginine/asymmetric dimethyl arginine balance, obesity, and the age of asthma onset phenotype.
Increasing body mass index (BMI) has been associated with less fractional exhaled nitric oxide (Fe(NO)). This may be explained by an increase in the concentration of asymmetric dimethyl arginine (ADMA) relative to L-arginine, which can lead to greater nitric oxide synthase uncoupling. To compare this mechanism across age of asthma onset groups and determine its association with asthma morbidity and lung function. Cross-sectional study of participants from the Severe Asthma Research Program, across early- (<12 yr) and late- (>12 yr) onset asthma phenotypes. Subjects with late-onset asthma had a higher median plasma ADMA level (0.48 μM, [interquartile range (IQR), 0.35-0.7] compared with early onset, 0.37 μM [IQR, 0.29-0.59], P = 0.01) and lower median plasma l-arginine (late onset, 52.3 [IQR, 43-61] compared with early onset, 51 μM [IQR 39-66]; P = 0.02). The log of plasma L-arginine/ADMA was inversely correlated with BMI in the late- (r = -0.4, P = 0.0006) in contrast to the early-onset phenotype (r = -0.2, P = 0.07). Although Fe(NO) was inversely associated with BMI in the late-onset phenotype (P = 0.02), the relationship was lost after adjusting for L-arginine/ADMA. Also in this phenotype, a reduced L-arginine/ADMA was associated with less IgE, increased respiratory symptoms, lower lung volumes, and worse asthma quality of life. In late-onset asthma phenotype, plasma ratios of L-arginine to ADMA may explain the inverse relationship of BMI to Fe(NO). In addition, these lower L-arginine/ADMA ratios are associated with reduced lung function and increased respiratory symptom frequency, suggesting a role in the pathobiology of the late-onset phenotype.


A high-quality genome assembly from a single, field-collected spotted lanternfly (Lycorma delicatula) using the PacBio Sequel II system.
A high-quality reference genome is an essential tool for applied and basic research on arthropods. Long-read sequencing technologies may be used to generate more complete and contiguous genome assemblies than alternate technologies; however, long-read methods have historically had greater input DNA requirements and higher costs than next-generation sequencing, which are barriers to their use on many samples. Here, we present a 2.3 Gb de novo genome assembly of a field-collected adult female spotted lanternfly (Lycorma delicatula) using a single Pacific Biosciences SMRT Cell. The spotted lanternfly is an invasive species recently discovered in the northeastern United States that threatens to damage economically important crop plants in the region. The DNA from 1 individual was used to make 1 standard, size-selected library with an average DNA fragment size of ∼20 kb. The library was run on 1 Sequel II SMRT Cell 8M, generating a total of 132 Gb of long-read sequences, of which 82 Gb were from unique library molecules, representing ∼36× coverage of the genome. The assembly had high contiguity (contig N50 length = 1.5 Mb), completeness, and sequence level accuracy as estimated by conserved gene set analysis (96.8% of conserved genes both complete and without frame shift errors). Furthermore, it was possible to segregate more than half of the diploid genome into the 2 separate haplotypes. The assembly also recovered 2 microbial symbiont genomes known to be associated with L. delicatula, each microbial genome being assembled into a single contig. We demonstrate that field-collected arthropods can be used for the rapid generation of high-quality genome assemblies, an attractive approach for projects on emerging invasive species, disease vectors, or conservation efforts of endangered species.


Screening of Korean medicinal plants for possible osteoclastogenesis effects in vitro.
Bone undergoes continuous remodeling through bone formation and resorption, and maintaining the balance for skeletal rigidity. Bone resorption and loss are generally attributed to osteoclasts. Differentiation of osteoclasts is regulated by receptor activator of nuclear factor NF-kB ligand (RANKL), a member of tumor necrosis factor family. When the balance is disturbed, pathological bone abnormality ensues. Through the screening of traditional Korean medicinal plants, the effective molecules for inhibition and stimulation of RANKL-induced osteoclast differentiation in mouse bone marrow macrophages were identified. Among 222 methanol extracts, of medicinal plants, 10 samples exhibited ability to induce osteoclast differentiation. These include Dryobalanops aromatica, Euphoria longana, Lithospermum erythrorhizon, Prunus mume, Prunus nakaii, and Polygonatum odoratum. In contrast, Ailanthus altissima, Curcuma longa, Solanum nigrum, Taraxacum platycarpa, Trichosanthes kirilowii, and Daphne genkwa showed inhibitory effects in RANKL-induced osteoclast differentiation.


A comparative study of automatic image segmentation algorithms for target tracking in MR-IGRT.
On-board magnetic resonance (MR) image guidance during radiation therapy offers the potential for more accurate treatment delivery. To utilize the real-time image information, a crucial prerequisite is the ability to successfully segment and track regions of interest (ROI). The purpose of this work is to evaluate the performance of different segmentation algorithms using motion images (4 frames per second) acquired using a MR image-guided radiotherapy (MR-IGRT) system. Manual con-tours of the kidney, bladder, duodenum, and a liver tumor by an experienced radiation oncologist were used as the ground truth for performance evaluation. Besides the manual segmentation, images were automatically segmented using thresholding, fuzzy k-means (FKM), k-harmonic means (KHM), and reaction-diffusion level set evolution (RD-LSE) algorithms, as well as the tissue tracking algorithm provided by the ViewRay treatment planning and delivery system (VR-TPDS). The performance of the five algorithms was evaluated quantitatively by comparing with the manual segmentation using the Dice coefficient and target registration error (TRE) measured as the distance between the centroid of the manual ROI and the centroid of the automatically segmented ROI. All methods were able to successfully segment the bladder and the kidney, but only FKM, KHM, and VR-TPDS were able to segment the liver tumor and the duodenum. The performance of the thresholding, FKM, KHM, and RD-LSE algorithms degraded as the local image contrast decreased, whereas the performance of the VP-TPDS method was nearly independent of local image contrast due to the reference registration algorithm. For segmenting high-contrast images (i.e., kidney), the thresholding method provided the best speed (< 1 ms) with a satisfying accuracy (Dice = 0.95). When the image contrast was low, the VR-TPDS method had the best automatic contour. Results suggest an image quality determination procedure before segmentation and a combination of different methods for optimal segmentation with the on-board MR-IGRT system.


An Overview of Phytotherapeutic Approaches for the Treatment of Tuberculosis.
Tuberculosis (TB) is highly infectious disease causing morbidity and death. Its causative organism is a contagious bacterium, Mycobacterium tuberculosis. The incidence of tuberculosis is increasing worldwide due to the emergence of drug resistance bacteria. The resistance is being developed in Mycobacterium tuberculosis against both the first line as well as the second line drugs used for the treatment. The tuberculosis control programme is being complicated and failed to get the desired impact due to the development of multi-drug resistant (MDR) and extensively-drug resistant (XDR) strains of Mycobacterium tuberculosis. So, there is a critical requirement to discover and produce newer anti-TB drugs with unique drug targets. Medicinal plants have been used for curing the diseases from ancient time. Medicinal plants are the novel sources for the production of alternate medicines for the treatment of TB caused by MDR and XDR strains. Plants produce a number of different kinds of secondary metabolites such as Alkaloids, Coumarins, Flavonoids, Polyphenols, Terpenoids, Quinines, etc. which have antimicrobial activity; thus may be useful in control of tuberculosis. These compounds do not contribute directly in growth and development but used by the plants for their defense. On the basis of various sources in the literature, about 72 phytochemicals constituents responsible for anti tubercular activity isolated from different plants have been explained along with their structure. Most effective isolated compounds from plants are plumbagin, maritinone, 3, 3'-biplumbagin, aloe emodin, epigallocatechin and umckalin. These phytochemicals are helpful for the treatment of MDR, XDR type of tuberculosis. This review describes an overview of the current synthetic medicines used for treatment of TB and the work carried out on anti tubercular plants along with their phytochemicals.


Autophagic dysregulation in doxorubicin cardiomyopathy.
Doxorubicin (DOX)-induced cardiotoxicity has been a well-known phenomenon to clinicians and scientists for decades; however, molecular mechanisms underlying DOX cardiotoxicity are still being uncovered. Although the majority of prior research have implicated nuclear and mitochondrial events to be an important etiological aspects of DOX cardiomyopathy, recent discoveries in autophagy have highlighted the renewed interest in the role of lysosome in DOX cardiomyopathy. Indeed, dysregulation of lysosomal autophagy is observed in pre-clinical models of DOX cardiotoxicity. In this review, we provide a comprehensive overview on mechanisms describing regulation of the autophagy pathway by DOX and its influence on cardiotoxic outcomes. We have put specific emphasis on experimental models, dosing and treatment duration with DOX, and methods to monitor autophagy, all of which contribute to inconsistencies observed in the literature. We have clarified processes by which DOX dysregulates macroautophagy in the heart by primarily focusing on the contribution of LC3, p62, Beclin, mTOR and AMPK pathways. We have also highlighted the impact of DOX on mitochondrial reactive oxygen species (ROS) and its contribution to the process of mitophagy. We have presented mechanisms by which DOX compromises lysosomal acidification, integrity and chaperone-mediated autophagy through its effect on lysosome-associated and resident proteins such as LAMP, vATPase, Hsp90, Hsc70 and cathepsins. Furthermore, we have discussed novel pathways in DOX cardiotoxicity, the most prominent being DOX-induced loss of TFEB, a member of the MITF family of transcription factors, which governs lysosomal biogenesis and function. This review summarizes that in the myocardium, DOX dysregulates autophagy by impairing transcriptional factors regulating lysosomal function, thereby, precipitating proteotoxicity, mitochondrial dysfunction and cell death, thus rendering the heart susceptible to cardiomyopathic failure.


Recruitment and retention in a multicentre randomised controlled trial in Bell's palsy: a case study.
It is notoriously difficult to recruit patients to randomised controlled trials in primary care. This is particularly true when the disease process under investigation occurs relatively infrequently and must be investigated during a brief time window. Bell's palsy, an acute unilateral paralysis of the facial nerve is just such a relatively rare condition. In this case study we describe the organisational issues presented in setting up a large randomised controlled trial of the management of Bell's palsy across primary and secondary care in Scotland and how we managed to successfully recruit and retain patients presenting in the community. Where possible we used existing evidence on recruitment strategies to maximise recruitment and retention. We consider that the key issues in the success of this study were; the fact that the research was seen as clinically important by the clinicians who had initial responsibility for recruitment; employing an experienced trial co-ordinator and dedicated researchers willing to recruit participants seven days per week and to visit them at home at a time convenient to them, hence reducing missed patients and ensuring they were retained in the study; national visibility and repeated publicity at a local level delivered by locally based principal investigators well known to their primary care community; encouraging recruitment by payment to practices and reducing the workload of the referring doctors by providing immediate access to specialist care; good collaboration between primary and secondary care and basing local investigators in the otolarnygology trial centres Although the recruitment rate did not meet our initial expectations, enhanced retention meant that we exceeded our planned target of recruiting 550 patients within the planned time-scale. While difficult, recruitment to and retention within multi-centre trials from primary care can be successfully achieved through the application of the best available evidence, establishing good relationships with practices, minimising the workload of those involved in recruitment and offering enhanced care to all participants. Primary care trialists should describe their experiences of the methods used to persuade patients to participate in their trials when publishing their results.


Autogenous regulation of the regA gene of bacteriophage T4: derepression of translation.
The regA gene of phage T4 encodes a translational repressor that inhibits utilization of its own mRNA as well as the translation of a number of other phage-induced mRNAs. In recombinant plasmids, autogenous translational repression limits production of the RegA protein when the cloned structural gene is expressed under control of a strong, plasmid-borne promoter (lambda PL). We have found that a genetic fusion which places the regA ribosome binding domain in proximity to active translation leads to partial derepression of wild-type RegA protein synthesis. The derepression is not due to increased synthesis of regA RNA, suggesting that it occurs at the translational level. Derepressed clones of the wild-type regA gene were used to overproduce and purify the repressor. In an in vitro assay the wild-type target was sensitive and a mutant target was resistant to inhibition by the added protein. The results suggest that the sensitivity of a regA-regulated cistron to translational repression may depend on the competition between ribosomes and RegA protein for overlapping recognition sequences in the translation initiation domain of the mRNA.


Analysis of koi herpesvirus latency in wild common carp and ornamental koi in Oregon, USA.
Koi herpesvirus (KHV) infection is associated with high mortalities in both common carp (Cyprinus carpio carpio) and koi carp (Cyprinus carpio koi) worldwide. Although acute infection has been reported in both domestic and wild common carp, the status of KHV latent infection is largely unknown in wild common carp. To investigate whether KHV latency is present in wild common carp, the distribution of KHV latent infection was investigated in two geographically distinct populations of wild common carp in Oregon, as well as in koi from an Oregon-based commercial supplier. Latent KHV infection was demonstrated in white blood cells from each of these populations. Although KHV isolated from acute infections has two distinct genetic groups, Asian and European, KHV detected in wild carp has not been genetically characterized. DNA sequences from ORF 25 to 26 that are unique between Asian and European were investigated in this study. KHV from captive koi and some wild common carp were found to have ORF-25-26 sequences similar to KHV-J (Asian), while the majority of KHV DNA detected in wild common carp has similarity to KHV-U/-I (European). In addition, DNA sequences from IL-10, and TNFR were sequenced and compared with no differences found, which suggests immune suppressor genes of KHV are conserved between KHV in wild common carp and koi, and is consistent with KHV-U, -I, -J.


Modulation of the heme electronic structure and cystathionine beta-synthase activity by second coordination sphere ligands: The role of heme ligand switching in redox regulation.
In humans, cystathionine beta-synthase (CBS) is a hemeprotein, which catalyzes a pyridoxal phosphate (PLP)-dependent condensation reaction. Changes in the heme environment are communicated to the active site, which is approximately 20A away. In this study, we have examined the role of H67 and R266, which are in the second coordination sphere of the heme ligands, H65 and C52, respectively, in modulating the heme's electronic properties and in transmitting information between the heme and active sites. While the H67A mutation is comparable to wild-type CBS, interesting differences are revealed by mutations at the R266 site. The pathogenic mutant, R266K, is moderately PLP-responsive while the R266M mutation shows dramatic differences in the ferrous state. The electrostatic interaction between C52 and R266 is critical for stabilizing the ferrous heme and its disruption leads to the facile formation of a 424nm (C-424) absorbing ferrous species, which is inactive, compared to the active 449nm ferrous species for wild-type CBS. Resonance Raman studies on the R266M mutant reveal that the kinetics of C52 rebinding after Fe-CO photolysis are comparable to that of wild-type CBS. EXAFS studies on C-424 CBS are consistent with the presence of two axial N/O low Z scatters with only one being a rigid unit of a histidine residue while the other could be a solvent molecule, an oxygen atom from the peptide backbone or a side chain nitrogen. The redox potential for the heme in full-length CBS is -350+/-4mV and is substantially lower than the value of -287+/-2mV determined for truncated CBS. A redox-regulated ligand change has the potential to serve as an allosteric on/off switch in human CBS and the second sphere ligand, R266, plays an important role in this transition.


Conservation and immunogenicity of novel antigens in diverse isolates of enterotoxigenic Escherichia coli.
Enterotoxigenic Escherichia coli (ETEC) are common causes of diarrheal morbidity and mortality in developing countries for which there is currently no vaccine. Heterogeneity in classical ETEC antigens known as colonization factors (CFs) and poor efficacy of toxoid-based approaches to date have impeded development of a broadly protective ETEC vaccine, prompting searches for novel molecular targets. Using a variety of molecular methods, we examined a large collection of ETEC isolates for production of two secreted plasmid-encoded pathotype-specific antigens, the EtpA extracellular adhesin, and EatA, a mucin-degrading serine protease; and two chromosomally-encoded molecules, the YghJ metalloprotease and the EaeH adhesin, that are not specific to the ETEC pathovar, but which have been implicated in ETEC pathogenesis. ELISA assays were also performed on control and convalescent sera to characterize the immune response to these antigens. Finally, mice were immunized with recombinant EtpA (rEtpA), and a protease deficient version of the secreted EatA passenger domain (rEatApH134R) to examine the feasibility of combining these molecules in a subunit vaccine approach. EtpA and EatA were secreted by more than half of all ETEC, distributed over diverse phylogenetic lineages belonging to multiple CF groups, and exhibited surprisingly little sequence variation. Both chromosomally-encoded molecules were also identified in a wide variety of ETEC strains and YghJ was secreted by 89% of isolates. Antibodies against both the ETEC pathovar-specific and conserved E. coli antigens were present in significantly higher titers in convalescent samples from subjects with ETEC infection than controls suggesting that each of these antigens is produced and recognized during infection. Finally, co-immunization of mice with rEtpA and rEatApH134R offered significant protection against ETEC infection. Collectively, these data suggest that novel antigens could significantly complement current approaches and foster improved strategies for development of broadly protective ETEC vaccines.


Effect of Extra Virgin Olive Oil on Biomarkers of Inflammation in HIV-Infected Patients: A Randomized, Crossover, Controlled Clinical Trial.
Premature atherosclerosis in HIV-infected patients is associated with chronic infection by itself and adverse effects of antiretroviral treatment (ART). Extra virgin olive oil (EVOO) has a beneficial effect on the cardiovascular system because of its anti-inflammatory properties. The objective of this study was to determine whether the consumption of EVOO improves inflammation and atherosclerosis biomarkers in HIV-infected patients receiving ART. This randomized, crossover, controlled trial included 39 HIV-positive male participants who consumed 50 mL of EVOO or refined olive oil (ROO) daily. Four participants dropped out of the study. Leukocyte count, erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), interleukin-6, fibrinogen, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, malondialdehyde, glutathione-peroxidase, superoxide dismutase, oxidized LDL and von Willebrand factor were determined before the first and after each of the 2 intervention periods. Intervention and washout periods lasted for 20 and 14 days, respectively. In participants with >90% compliance (N=30), hsCRP concentrations were lower after EVOO intervention (geometric mean [GM], 1.70 mg/L; 95% confidence interval [CI], 1.15-2.52) compared to ROO administration (GM, 2.92 mg/L; 95% CI, 1.95-4.37) (p=0.035). In participants using lopinavir/ritonavir, ESR and hsCRP concentrations decreased 62% and 151%, respectively, after EVOO administration. In the whole study population (N=35) we found no difference in analyzed biomarkers after EVOO administration. Our exploratory study suggests that EVOO consumption could lower hsCRP in patients on ART.


The biology of obesity.
Obesity is a multidisciplinary area, the 'biology' of which encompasses: (1) the fundamental mechanisms of energy balance and its regulation; (2) the biological basis for the development of obesity; (3) adipose tissue function; (4) the biological description of the obese state; (5) the pathological consequences of obesity; (6) the physiological basis for treatment strategies. At a mechanistic level, important developments in recent years include the identification of novel neuroendocrine factors in the control of appetite (such as cocaine- and amphetamine-regulated transcript, the orexins, the endocannabinoids) and the discovery of new peripheral signals (such as leptin, ghrelin). Despite the identification of additional uncoupling proteins (UCP2, UCP3), mitochondrial uncoupling in brown adipose tissue through UCP1 remains the only major mechanism for adaptive thermogenesis. White adipose tissue (WAT) has now moved centre stage in energy balance and obesity research, and there are three main reasons: (1) it is the organ which defines obesity; (2) it is the source of a critical endocrine signal in the control of body weight; (3) it secretes a range of diverse protein factors, termed adipokines, some of which are directly implicated in the pathologies associated with obesity. WAT is now recognised as a key endocrine organ, communicating both with the brain and peripheral tissues through the adipokines. Obesity is characterised by mild inflammation, and WAT may be the main locus of the inflammatory state, producing cytokines, chemokines, acute-phase proteins and angiogenic factors. It has been suggested that inflammation in obesity is principally an adaptive response to hypoxia in clusters of adipocytes within the expanding adipose mass.


Spider mites escape bacterial infection by avoiding contaminated food.
To fight infection, arthropods rely on the deployment of an innate immune response but also upon physical/chemical barriers and avoidance behaviours. However, most studies focus on immunity, with other defensive mechanisms being relatively overlooked. We have previously shown that the spider mite Tetranychus urticae does not mount an induced immune response towards systemic bacterial infections, entailing very high mortality rates. Therefore, we hypothesized that other defence mechanisms may be operating to minimize infection risk. Here, we test (a) if spider mites are also highly susceptible to other infection routes-spraying and feeding-and (b) if they display avoidance behaviours towards infected food. Individuals sprayed with or fed on Escherichia coli or Pseudomonas putida survived less than the control, pointing to a deficient capacity of the gut epithelium, and possibly of the cuticle, to contain bacteria. Additionally, we found that spider mites prefer uninfected food to food contaminated with bacteria, a choice that probably does not rely on olfactory cues. Our results suggest that spider mites may rely mostly on avoidance behaviours to minimize bacterial infection and highlight the multi-layered nature of immune strategies present in arthropods.


Knowledge of heart disease risk in a multicultural community sample of people with diabetes.
Prevention of coronary heart disease (CHD) is a primary goal of diabetes management. Unfortunately, CHD risk knowledge is poor among people with diabetes. The objective is to determine predictors of CHD risk knowledge in a community sample of people with diabetes. A total of 678 people with diabetes completed the Heart Disease Facts Questionnaire (HDFQ), a valid and reliable measure of knowledge about the relationship between diabetes and heart disease. In regression analysis with demographics predicting HDFQ scores, sex, annual income, education, and health insurance status predicted HDFQ scores. In a separate regression analysis, having CHD risk factors did not predict HDFQ scores, however, taking medication for CHD risk factors did predict higher HDFQ scores. An analysis of variance showed significant differences between ethnic groups for HDFQ scores; Whites (M = 20.9) showed more CHD risk knowledge than African Americans (M = 19.6), who in turn showed more than Latinos (M = 18.2). Asians scored near Whites (M = 20.4) but did not differ significantly from any other group. Controlling for numerous demographic, socioeconomic, health care, diabetes, and cardiovascular health variables, the magnitude of ethnic differences was attenuated, but persisted. Education regarding modifiable risk factors must be delivered in a timely fashion so that lifestyle modification can be implemented and evaluated before pharmacotherapy is deemed necessary. African Americans and Latinos with diabetes are in the greatest need of education regarding CHD risk.


A Bayesian phylogenetic method to estimate unknown sequence ages.
Heterochronous data sets comprise molecular sequences sampled at different points in time. If the temporal range of the sampled sequences is large relative to the rate of mutation, the sampling times can directly calibrate evolutionary rates to calendar time. Here, we extend this calibration process to provide a full probabilistic method that utilizes temporal information in heterochronous data sets to estimate sampling times (leaf-ages) for sequenced for which this information unavailable. Our method is similar to relaxing the constraints of the molecular clock on specific lineages within a phylogenetic tree. Using a combination of synthetic and empirical data sets, we demonstrate that the method estimates leaf-ages reliably and accurately. Potential applications of our approach include incorporating samples of uncertain or radiocarbon-infinite age into ancient DNA analyses, evaluating the temporal signal in a particular sequence or data set, and exploring the reliability of sequence ages that are somehow contentious.


Treatment of hyperlipidemia in cardiac transplant recipients.
Of the 60,000 patients receiving heart transplants between 1982 and 2001, approximately 12,000 are currently alive. The high incidence of hyperlipidemia and coronary disease (also known as accelerated graft atherosclerosis, or AGA) in these patients warrants early prophylaxis soon after transplantation with 3-hydroxy-3-methylglutaryl (HMG) Co-A reductase inhibitors (statins). Immunosuppressive agents such as prednisone, cyclosporine, mycophenylate mofetil, and sirolimus are associated with hyperlipidemia. Statins, in addition to lowering cholesterol levels, also benefit cardiac transplant recipients via effects on the immune system and endothelial function. Recent data have demonstrated that statins decrease AGA and mortality rates. Furthermore, greater benefits are seen when statins are started early. The 2 statins shown to decrease mortality in patients after cardiac transplantation are pravastatin and simvastatin, which differ in their metabolism (pravastatin is the only statin with non-cytochrome metabolism) and lipophilicity (pravastatin is less lipophilic). Although the benefit of simvastatin has been shown to extend to 8 years after transplantation, increased adverse effects in other studies with higher doses of simvastatin have resulted in new prescribing recommendations, which state that the dose of simvastatin should probably not exceed 10 mg with cyclosporine or gemfibrozil and 20 mg with amiodarone or verapamil. The evidence for potential benefits, interactions, and adverse effects of other potential lipid-lowering drugs for this patient population, such as fibrates, niacin, fish oil, cholestyramine, and ezetimibe, are also discussed. A summary algorithm is proposed, including approaches to patients with statin-associated musculoskeletal symptoms and patients with inadequate results after initial statin therapy.


Reliance on prey-derived nitrogen by the carnivorous plant Drosera rotundifolia decreases with increasing nitrogen deposition.
• Carnivory in plants is presumed to be an adaptation to a low-nutrient environment. Nitrogen (N) from carnivory is expected to become a less important component of the N budget as root N availability increases. • Here, we investigated the uptake of N via roots versus prey of the carnivorous plant Drosera rotundifolia growing in ombrotrophic bogs along a latitudinal N deposition gradient through Sweden, using a natural abundance stable isotope mass balance technique. • Drosera rotundifolia plants receiving the lowest level of N deposition obtained a greater proportion of N from prey (57%) than did plants on bogs with higher N deposition (22% at intermediate and 33% at the highest deposition). When adjusted for differences in plant mass, this pattern was also present when considering total prey N uptake (66, 26 and 26 μg prey N per plant at the low, intermediate and high N deposition sites, respectively). The pattern of mass-adjusted root N uptake was opposite to this (47, 75 and 86 μg N per plant). • Drosera rotundifolia plants in this study switched from reliance on prey N to reliance on root-derived N as a result of increasing N availability from atmospheric N deposition.


Unique Physicochemical Patterns of Residues in Protein-Protein Interfaces.
Protein-protein interactions can be characterized by high-resolution structures of complexes, from which diverse features of the interfaces can be derived. For the majority of protein-protein interactions identified, however, there is no information on the structure of the complex or the interface involved in the interaction. Understanding what surface properties drive certain interactions is crucial in the functional evaluation of protein complexes. Here we show that the local patterning of the physicochemical properties of amino acids within surface patches is characteristic of interfaces. To describe this feature in a quantitative manner, we have defined a statistical potential, iPat, as a measure of surface patterning. iPat, which does not take evolutionary conservation or knowledge of the interaction partner into consideration, represents a function principally different from algorithms that consider intermolecular contacts. We assess its suitability for characterizing protein and peptide interfaces, and we demonstrate that iPat is uniquely descriptive for interfaces of proteins that undergo large conformational changes or that are involved in the binding of intrinsically disordered protein (IDP) partners. We suggest that as a stand-alone propensity or in combination with other features, iPat represents a new feature in analyzing the functional binding specificity of protein-protein interactions that has better predictive potential than other simple 1D features, such as hydrophobicity or stickiness.


The histomorphological spectrum of restrictive chronic lung allograft dysfunction and implications for prognosis.
Chronic lung allograft dysfunction continues to be the main contributor to poor long-term allograft survival after lung transplantation. The restrictive phenotype of chronic lung allograft dysfunction carries a particularly poor prognosis. Little is known about the pathogenetic mechanisms involved in restrictive chronic lung allograft dysfunction. In this study, we performed histomorphological and immunohistochemical analysis of restrictive chronic lung allograft dysfunction lungs. Explant lung tissue from 21 restrictive chronic lung allograft dysfunction patients was collected and histopathologic patterns of rejection, fibrosis and vascular changes were scored after routine histochemical stains and additional immunohistochemistry for endothelial markers and C4d. In all, 75% of cases showed evidence of acute cellular rejection; lymphocytic bronchiolitis was absent in most lungs, whereas in 55% there was obliterative bronchiolitis. Almost half of the cases showed a pattern consistent with pleuroparenchymal fibro-elastosis (n=10), and a subset showed nonspecific interstitial pneumonia (n=5) or irregular emphysema (n=5). Fibrinous alveolar exudates were frequently seen in association with fibrosis (n=6), but no diffuse alveolar damage was found. Evidence of microvascular damage was present in most cases. An emphysematous pattern of fibrosis was associated with a better survival (P=0.0030), whereas fibrinous exudates were associated with a worse survival (P=0.0007). In addition to the previously described nonspecific interstitial pneumonia and pleuroparenchymal fibro-elastosis patterns in restrictive chronic lung allograft dysfunction, we are the first to describe a pattern of fibrosis-induced subpleural/paraseptal emphysema. This pattern confers a better survival, whereas fibrinous exudates are associated with a worse survival. We believe that our findings offer a pathogenetic theory for pleuroparenchymal fibro-elastosis in restrictive chronic lung allograft dysfunction, and show that restrictive chronic lung allograft dysfunction is an increasingly heterogeneous disease with presumably different mechanisms of subpattern formation.


The GPR120 agonist TUG-891 promotes metabolic health by stimulating mitochondrial respiration in brown fat.
Brown adipose tissue (BAT) activation stimulates energy expenditure in human adults, which makes it an attractive target to combat obesity and related disorders. Recent studies demonstrated a role for G protein-coupled receptor 120 (GPR120) in BAT thermogenesis. Here, we investigated the therapeutic potential of GPR120 agonism and addressed GPR120-mediated signaling in BAT We found that activation of GPR120 by the selective agonist TUG-891 acutely increases fat oxidation and reduces body weight and fat mass in C57Bl/6J mice. These effects coincided with decreased brown adipocyte lipid content and increased nutrient uptake by BAT, confirming increased BAT activity. Consistent with these observations, GPR120 deficiency reduced expression of genes involved in nutrient handling in BAT Stimulation of brown adipocytes in vitro with TUG-891 acutely induced O2 consumption, through GPR120-dependent and GPR120-independent mechanisms. TUG-891 not only stimulated GPR120 signaling resulting in intracellular calcium release, mitochondrial depolarization, and mitochondrial fission, but also activated UCP1. Collectively, these data suggest that activation of brown adipocytes with the GPR120 agonist TUG-891 is a promising strategy to increase lipid combustion and reduce obesity.


Macrophage infiltration of electrospun polyester fibers.
Electrospun fibrous polylactide (PLA) membranes have been widely used for peritendinous anti-adhesion, but their degradation may lead to granuloma formation triggered by macrophages as the result of a foreign body reaction. To understand and solve this problem in peritendinous anti-adhesion, the effects of electrospun fibrous PLA membranes (PLA-M) and the mechanism by which macrophages elicit a foreign body reaction should be elaborated. Thus, the purpose of this study was to evaluate the ability of PLA-M and ibuprofen (IBU)-loaded fibrous PLA membranes (IBU/PLA-M) to prevent adhesion/granuloma formation around the tendon, and to understand the mechanism of macrophage infiltration. The results showed that PLA-M and IBU/PLA-M were porous and that IBU could be sustainably released from IBU/PLA-M. The adhesion and proliferation of RAW264.7 macrophages were worse on the surface of IBU/PLA-M than on PLA-M. After implantation around the tendon, IBU/PLA-M had higher anti-adhesion and tendon healing scores than PLA-M. Furthermore, PLA-M was able to promote macrophage infiltration, neovascularization, TNF-α expression and collagen III deposition to a greater extent than IBU/PLA-M. Consequently, these results show that macrophages can be triggered by PLA-M which subsequently leads to inflammation and granuloma formation, while IBU/PLA-M results in enhanced anti-inflammation and anti-adhesion effects when compared to PLA-M, by reducing macrophage infiltration.


Toward a global understanding of students who participate in rural primary care longitudinal integrated clerkships: considering personality across 2 continents.
Medical schools worldwide have developed rural primary care immersive experiences to nurture students' interest in future rural careers and address workforce shortages. Few studies have looked at the students who participate in these programs. This study explores personality traits in US and Australian students who undertake rural-focused medical training. A cross-sectional cohort design used the Temperament and Character Inventory to identify levels of the 7 basic dimensions of personality. Data were collected in successive cohorts over 2007-2011. Multivariate analysis compared trait levels between groups and by demographic variables. The majority of the 302 students (US-167; Australia-135) were female, aged 20-29 years and single. A greater proportion of US students reported being partnered, living longest in a small rural/remote community and having a rural background. Significant differences between groups were detected in several traits but effect sizes were small. The personality pattern of the combined sample indicates students with a mature and stable personality high in Self-Directedness, Persistence, and Cooperativeness. Rural background and marital status enhanced this pattern. Despite coming from different educational and societal backgrounds, similar personality patterns are evident in US and Australian students who pursue rural medical education. Data provide support for a pattern of traits associated with a rural background and its predictive influence on interest in rural practice. Considering the international expansion of rural longitudinal integrated clerkships, understanding student attributes may assist in identifying strategies to enhance the rural workforce that are relevant across cultures and continents.


Thermal mixing of two miscible fluids in a T-shaped microchannel.
In this paper, thermal mixing characteristics of two miscible fluids in a T-shaped microchannel are investigated theoretically, experimentally, and numerically. Thermal mixing processes in a T-shaped microchannel are divided into two zones, consisting of a T-junction and a mixing channel. An analytical two-dimensional model was first built to describe the heat transfer processes in the mixing channel. In the experiments, de-ionized water was employed as the working fluid. Laser induced fluorescence method was used to measure the fluid temperature field in the microchannel. Different combinations of flow rate ratios were studied to investigate the thermal mixing characteristics in the microchannel. At the T-junction, thermal diffusion is found to be dominant in this area due to the striation in the temperature contours. In the mixing channel, heat transfer processes are found to be controlled by thermal diffusion and convection. Measured temperature profiles at the T-junction and mixing channel are compared with analytical model and numerical simulation, respectively.


Adalimumab Induced or Provoked MS in Patient with Autoimmune Uveitis: A Case Report and Review of the Literature.
Anti-tumor necrosis factor α (anti-TNF-α) agents have been widely used in the field of autoimmune diseases and have proved decisive efficacy and relative safety. Data concerning their adverse effects has been lately describing central nervous system (CNS) demyelination process at escalating basis. Case Presentation. A 23-year-old male with autoimmune uveitis and a family history of multiple sclerosis (MS) developed two neurological attacks, after Adalimumab infusion, simultaneously with several cerebral lesions on magnetic resonance imaging (MRI). Hence the diagnosis of Adalimumab induced MS was suspected. Conclusion. This case is reported to tell physicians to be cautious when using anti-TNF-α in patients with family history of MS and to reconsider the risk of MS in patients with autoimmune diseases.


Fabrication and Validation of an Organ-on-chip System with Integrated Electrodes to Directly Quantify Transendothelial Electrical Resistance.
Organs-on-chips, in vitro models involving the culture of (human) tissues inside microfluidic devices, are rapidly emerging and promise to provide useful research tools for studying human health and disease. To characterize the barrier function of cell layers cultured inside organ-on-chip devices, often transendothelial or transepithelial electrical resistance (TEER) is measured. To this end, electrodes are usually integrated into the chip by micromachining methods to provide more stable measurements than is achieved with manual insertion of electrodes into the inlets of the chip. However, these electrodes frequently hamper visual inspection of the studied cell layer or require expensive cleanroom processes for fabrication. To overcome these limitations, the device described here contains four easily integrated electrodes that are placed and fixed outside of the culture area, making visual inspection possible. Using these four electrodes the resistance of six measurement paths can be quantified, from which the TEER can be directly isolated, independent of the resistance of culture medium-filled microchannels. The blood-brain barrier was replicated in this device and its TEER was monitored to show the device applicability. This chip, the integrated electrodes and the TEER determination method are generally applicable in organs-on-chips, both to mimic other organs or to be incorporated into existing organ-on-chip systems.


Expression of Biliverdin Reductase A in peripheral blood leukocytes is associated with treatment response in HCV-infected patients.
Hepatitis C virus (HCV) infection is associated with systemic oxidative stress. Since the heme catabolic pathway plays an important role in antioxidant protection, we attempted to assess the gene expression of key enzymes of heme catabolism, heme oxygenase 1 (HMOX1), heme oxygenase 2 (HMOX2), and biliverdin reductase A (BLVRA) in the liver and peripheral blood leukocytes (PBL) of patients chronically infected with HCV. Gene expressions (HMOX1, HMOX2, BLVRA) and HCV RNA were analyzed in PBL of HCV treatment naïve patients (n = 58) and controls (n = 55), with a subset of HCV patients having data on hepatic gene expression (n = 35). Based upon the therapeutic outcome, HCV patients were classified as either responders (n = 38) or treatment-failure patients (n = 20). Blood samples in HCV patients were collected at day 0, and week 12, 24, 36, and 48 after the initiation of standard antiviral therapy. Compared to the controls, substantially increased BLVRA expression was detected in PBL (p<0.001) of therapeutically naïve HCV patients. mRNA levels of BLVRA in PBL closely correlated with those in liver tissue (r2 = 0.347,p = 0.03). A marked difference in BLVRA expression in PBL between the sustained responders and patients with treatment failure was detected at week 0 and during the follow-up (p<0.001). Multivariate analysis revealed that BLVRA basal expression in PBL was an independent predictor for sustained virological response (OR 15; 95% CI 1.05-214.2; P = 0.046). HMOX1/2 expression did not have any effect on the treatment outcome. Our results suggest that patients with chronic HCV infection significantly upregulate BLVRA expression in PBL. The lack of BLVRA overexpression is associated with non-responsiveness to standard antiviral therapy; whereas, HMOX1/2 does not seem to have any predictive potential.


Ancient mitochondrial diversity reveals population homogeneity in Neolithic Greece and identifies population dynamics along the Danubian expansion axis.
The aim of the study is to investigate mitochondrial diversity in Neolithic Greece and its relation to hunter-gatherers and farmers who populated the Danubian Neolithic expansion axis. We sequenced 42 mitochondrial palaeogenomes from Greece and analysed them together with European set of 328 mtDNA sequences dating from the Early to the Final Neolithic and 319 modern sequences. To test for population continuity through time in Greece, we use an original structured population continuity test that simulates DNA from different periods by explicitly considering the spatial and temporal dynamics of populations. We explore specific scenarios of the mode and tempo of the European Neolithic expansion along the Danubian axis applying spatially explicit simulations coupled with Approximate Bayesian Computation. We observe a striking genetic homogeneity for the maternal line throughout the Neolithic in Greece whereas population continuity is rejected between the Neolithic and present-day Greeks. Along the Danubian expansion axis, our best-fitting scenario supports a substantial decrease in mobility and an increasing local hunter-gatherer contribution to the gene-pool of farmers following the initial rapid Neolithic expansion. Οur original simulation approach models key demographic parameters rather than inferring them from fragmentary data leading to a better understanding of this important process in European prehistory.


Catalytic mechanisms and specificities of glutathione peroxidases: variations of a basic scheme.
Kinetics and molecular mechanisms of GPx-type enzymes are reviewed with emphasis on structural features relevant to efficiency and specificity. In Sec-GPxs the reaction takes place at a single redox centre with selenocysteine as redox-active residue (peroxidatic Sec, U(P)). In contrast, most of the non-vertebrate GPx have the U(P) replaced by a cysteine (peroxidatic Cys, C(P)) and work with a second redox centre that contains a resolving cysteine (C(R)). While the former type of enzymes is more or less specific for GSH, the latter are reduced by "redoxins". The common denominator of the GPx family is the first redox centre comprising the (seleno)cysteine, tryptophan, asparagine and glutamine. In this architectural context the rate of hydroperoxide reduction by U(P) or C(P), respectively, is enhanced by several orders of magnitude compared to that of free selenolate or thiolate. Mammalian GPx-1 dominates H(2)O(2) metabolism, whereas the domain of GPx-4 is the reduction of lipid hydroperoxides with important consequences such as counteracting 12/15-lipoxygenase-induced apoptosis and regulation of inflammatory responses. Beyond, the degenerate GSH specificity of GPx-4 allows selenylation and oxidation to disulfides of protein thiols. Heterodimer formation of yeast GPx with a transcription factor is discussed as paradigm of a redox sensing that might also be valid in vertebrates.


Current Surveys of the Seroprevalence of Borrelia burgdorferi, Ehrlichia canis, Anaplasma phagocytophilum, Leishmania infantum, Babesia canis, Angiostrongylus vasorum and Dirofilaria immitis in Dogs in Bulgaria.
Canine vector-borne diseases (CVBDs) have increasingly become a focus of interest in recent years. Some of the CVBDs are zoonotic and may therefore also represent a risk for the human population. Different factors are in discussion to explain the expansion of vectors and pathogens into formerly unaffected areas. Knowledge of the prevalence and distribution of CVBDs in Bulgaria is scant overall and most data rely on single case descriptions. The aim of the present study was to determine the seroprevalence of important CVBDs in 167 dogs from central-southern Bulgaria (Stara Zagora), with special emphasis on hitherto uninvestigated babesiosis and angiostrongylosis, on poorly investigated Lyme borreliosis and canine granulocytic anaplasmosis, and on the potentially zoonotic dirofilariosis and leishmaniosis. Relatively high prevalence rates were documented for anti-Babesia canis antibodies, Dirofilaria immitis antigen (16.2 %; 27/167 each), anti-Ehrlichia canis (21 %; 35/167) and anti-Anaplasma phagocytophilum antibodies (30.5 - 46.1 %; 51 - 77/167), while Borrelia burgdorferi seroprevalence was low (2.4 %; 4/167). All samples were negative for Leishmania infantum antibodies and Angiostrongylus vasorum antigen and antibodies. In total, 64.7 % (108/167) of the samples indicated infection or exposure to at least one agent and a high proportion of dual infections (39.8 %; 43/108) was demonstrated. Multiple infections with up to four different organisms were also detected. Our data underline the importance of CVBDs and especially of co-infections which could influence the clinical outcome in dogs.


Preparation and layer-by-layer solution deposition of Cu(In,Ga)O2 nanoparticles with conversion to Cu(In,Ga)S2 films.
We present a method of Cu(In,Ga)S2 (CIGS) thin film formation via conversion of layer-by-layer (LbL) assembled Cu-In-Ga oxide (CIGO) nanoparticles and polyelectrolytes. CIGO nanoparticles were created via a novel flame-spray pyrolysis method using metal nitrate precursors, subsequently coated with polyallylamine (PAH), and dispersed in aqueous solution. Multilayer films were assembled by alternately dipping quartz, Si, and/or Mo substrates into a solution of either polydopamine (PDA) or polystyrenesulfonate (PSS) and then in the CIGO-PAH dispersion to fabricate films as thick as 1-2 microns. PSS/CIGO-PAH films were found to be inadequate due to weak adhesion to the Si and Mo substrates, excessive particle diffusion during sulfurization, and mechanical softness ill-suited to further processing. PDA/CIGO-PAH films, in contrast, were more mechanically robust and more tolerant of high temperature processing. After LbL deposition, films were oxidized to remove polymer and sulfurized at high temperature under flowing hydrogen sulfide to convert CIGO to CIGS. Complete film conversion from the oxide to the sulfide is confirmed by X-ray diffraction characterization.


Combined analytical FEM approach for efficient simulation of Lamb wave damage detection.
Lamb waves have been widely explored as a promising inspection tool for non-destructive evaluation (NDE) and structural health monitoring (SHM). This article presents a combined analytical finite element model (FEM) approach (CAFA) for the accurate, efficient, and versatile simulation of 2-D Lamb wave propagation and interaction with damage. CAFA used a global analytical solution to model wave generation, propagation, scattering, mode conversion, and detection, while the wave-damage interaction coefficients (WDICs) were extracted from harmonic analysis of local FEM with non-reflective boundaries (NRB). The analytical procedure was coded using MATLAB, and a predictive simulation tool called WaveFormRevealer 2-D was developed. The methodology of obtaining WDICs from local FEM was presented. Case studies were carried out for Lamb wave propagation in a pristine plate and a damaged plate. CAFA predictions compared well with full scale multi-physics FEM simulations and experiments with scanning laser Doppler vibrometry (SLDV), while achieving remarkable performance in computational efficiency and computer resource saving compared with conventional FEM.


How goats learn to distinguish between novel foods that differ in postingestive consequences.
To better understand some of the mechanisms that control selection of novel foods differing in postingestive consequences, we offered goats current season's (CSG) and older (OG) growth twigs from the shrub blackbrush (Coleogyne ramosissima). CSG is higher than OG in nitrogen (1.04% v. 0.74%) and it is more digestible in vitro in goat rumen fluid (48% v. 38%). Nevertheless, goats acquire a preference for OG because CSG contains much higher levels of a condensed tannin that causes a learned food aversion. When CSG and OG were offered to goat naive to blackbrush, the goats did not choose either OG or CSG exclusively, but when they finally (1) ate more CSG than OG within a meal (averages of 44 g and 16 g, respectively) and (2) ate enough CSG within the meal to acquire an aversion (average of 44 g), they ingested less CSG than OG from then onward. Accordingly, the change in food selection resulting from postingestive feedback was influenced by the amount of each food ingested within a meal. This was further shown when we varied the amounts of CSG and OG that goats ingested within a meal, and then gave them by gavage the toxin lithium chloride (LiCl). They subsequently ate less of the food eaten in the greatest amount, regardless of whether it was CSG or OG. The salience of the flavor (i.e., taste and odor) of CSG and OG also played a role in the acquired aversion to CSG. Salience evidently was due to a flavor common to both OG and CSG that was more concentrated in CSG. We conclude that the relative amounts of different foods ingested within a meal, and the salience of the flavors of those foods, are both important variables that cause goats to distinguish between novel foods that differ in postingestive consequences.


Mesoporous silica nanotubes hybrid membranes for functional nanofiltration.
The development of nanofiltration systems would greatly assist in the production of well-defined particles and biomolecules with unique properties. We report a direct, simple synthesis of hexagonal silica nanotubes (NTs), which vertically aligned inside anodic alumina membranes (AAM) by means of a direct templating method of microemulsion phases with cationic surfactants. The direct approach was used as soft templates for predicting ordered assemblies of surfactant/silica composites through strong interactions within AAM pockets. Thus, densely packed NTs were successfully formed in the entirety of the AAM channels. These silica NTs were coated with layers of organic moieties to create a powerful technique for the ultrafine filtration. The resulting modified-silica NTs were chemically robust and showed affinity toward the transport of small molecular particles. The rigid silica NTs inside AAM channels had a pore diameter of <or= 4 nm and were used as ultrafine filtration systems for noble metal nanoparticles (NM NPs) and semiconductor nanocrystals (SC NCs) fabricated with a wide range of sizes (1.0-50 nm) and spherical/pyramidal morphologies. Moreover, the silica NTs hybrid membranes were also found to be suitable for separation of biomolecules such as cytochrome c (CytC). Importantly, this nanofilter design retains high nanofiltration efficiency of NM NPs, SC NCs and biomolecules after a number of reuse cycles. Such retention is crucial in industrial applications.


Disease-resistant genetically modified animals.
Infectious disease adversely affects livestock production and animal welfare, and has impacts upon both human health and public perception of livestock production. The authors argue that the combination of new methodology that enables the efficient production of genetically-modified (GM) animals with exciting new tools to alter gene activity makes the applications of transgenic animals for the benefit of animal (and human health) increasingly likely. This is illustrated through descriptions of specific examples. This technology is likely to have specific application where genetic variation does not exist in a given population or species and where novel genetic improvements can be engineered. These engineered animals would provide valuable models with which to investigate disease progression and evaluate this approach to controlling the disease. The authors propose that the use of GM animals will complement the more traditional tactics to combat disease, and will provide novel intervention strategies that are not possible through the established approaches.


Long-term surveillance and treatment outcomes of metachronous gastric cancer occurring after curative endoscopic submucosal dissection.
As more early gastric cancer (EGC) patients are being treated with endoscopic submucosal dissection (ESD), it is important to understand the outcomes of patients who develop metachronous gastric cancer (MGC). The aim of this study was to evaluate the long-term surveillance and treatment outcomes of MGC after curative gastric ESD. The study included 1526 consecutive patients who underwent curative ESD resection of EGC. They were generally followed by annual or biannual esophagogastroduodenoscopy. The risk factors and treatment outcomes for MGC were assessed along with the 5-year, 7-year, and 10-year cumulative incidence functions of MGC and disease-specific survival (DSS). During a median follow-up period of 82.2 months, 238 patients developed MGC post-ESD resection of EGC. The 5-year, 7-year, and 10-year cumulative incidence functions of MGC were 9.5%, 13.1% and 22.7%, respectively. Male sex and multiple initial EGCs were independent risk factors for MGC in the Cox proportional hazard model. Of the 238 patients with MGC, 215 were treated with endoscopic resection, of which 183 achieved curative resection, although one patient later died of his initial EGC. A further 14 patients were treated surgically, three had metastatic disease and received palliative chemotherapy, and the remaining six were observed without any intervention. A total of seven patients died of MGC, five at least 5 years after their index ESD. The 5-year, 7-year, and 10-year DSSs were 99.2%, 98.6%, and 92.5%, respectively. The incidence of MGC increases with time after curative gastric ESD, therefore surveillance endoscopy should be continued indefinitely.


Evolutionary changes in the notochord genetic toolkit: a comparative analysis of notochord genes in the ascidian Ciona and the larvacean Oikopleura.
The notochord is a defining feature of the chordate clade, and invertebrate chordates, such as tunicates, are uniquely suited for studies of this structure. Here we used a well-characterized set of 50 notochord genes known to be targets of the notochord-specific Brachyury transcription factor in one tunicate, Ciona intestinalis (Class Ascidiacea), to begin determining whether the same genetic toolkit is employed to build the notochord in another tunicate, Oikopleura dioica (Class Larvacea). We identified Oikopleura orthologs of the Ciona notochord genes, as well as lineage-specific duplicates for which we determined the phylogenetic relationships with related genes from other chordates, and we analyzed their expression patterns in Oikopleura embryos. Of the 50 Ciona notochord genes that were used as a reference, only 26 had clearly identifiable orthologs in Oikopleura. Two of these conserved genes appeared to have undergone Oikopleura- and/or tunicate-specific duplications, and one was present in three copies in Oikopleura, thus bringing the number of genes to test to 30. We were able to clone and test 28 of these genes. Thirteen of the 28 Oikopleura orthologs of Ciona notochord genes showed clear expression in all or in part of the Oikopleura notochord, seven were diffusely expressed throughout the tail, six were expressed in tissues other than the notochord, while two probes did not provide a detectable signal at any of the stages analyzed. One of the notochord genes identified, Oikopleura netrin, was found to be unevenly expressed in notochord cells, in a pattern reminiscent of that previously observed for one of the Oikopleura Hox genes. A surprisingly high number of Ciona notochord genes do not have apparent counterparts in Oikopleura, and only a fraction of the evolutionarily conserved genes show clear notochord expression. This suggests that Ciona and Oikopleura, despite the morphological similarities of their notochords, have developed rather divergent sets of notochord genes after their split from a common tunicate ancestor. This study demonstrates that comparisons between divergent tunicates can lead to insights into the basic complement of genes sufficient for notochord development, and elucidate the constraints that control its composition.


Heterotopic Intracranial Skin Presenting as Chronic Draining Sinus After Remote Craniotomy.
Craniotomies for trauma are associated with a significant risk of wound complications. We report a case in which a chronic nonhealing draining sinus was caused by an ectopic epidermal lining deep to the craniotomy bone flap, adherent to the underlying dura. A 61-year-old man was examined for a 3-year-old, nonhealing scalp wound resulting after a traumatic brain injury. His initial surgery consisted of an intracranial hematoma evacuation through a temporoparietal craniotomy; this was complicated by wound dehiscence and a chronic sinus draining clear fluid that did not resolve with antimicrobial therapy. Intraoperatively, a layer of hair-bearing skin adherent to the dura was found deep to the entirety of the previous bone flap. There was no dura tear or overt cerebrospinal fluid leak. This necessitated removal of the skin over the dura as well as the overlying bone flap. The resultant defect was reconstructed with a titanium mesh and hydroxyapatite cranioplasty, with a scalp rotation flap for coverage of the cutaneous defect. Pathology confirmed skin with intact adnexal structures. This case demonstrates that it is possible for hair-bearing skin to grow directly on dura, deep to an intact craniotomy bone flap. With a chronic draining sinus in the absence of computed tomography and magnetic resonance imaging findings, this should be part of the differential diagnosis.


Catharanthus mosaic virus: A potyvirus from a gymnosperm, Welwitschia mirabilis.
A virus from a symptomatic plant of the gymnosperm Welwitschia mirabilis Hook. growing as an ornamental plant in a domestic garden in Western Australia was inoculated to a plant of Nicotiana benthamiana where it established a systemic infection. The complete genome sequence of 9636 nucleotides was determined using high-throughput and Sanger sequencing technologies. The genome sequence shared greatest identity (83% nucleotides and 91% amino acids) with available partial sequences of catharanthus mosaic virus, indicating that the new isolate belonged to that taxon. Analysis of the phylogeny of the complete virus sequence placed it in a monotypic group in the genus Potyvirus. This is the first record of a virus from W. mirabilis, the first complete genome sequence of catharanthus mosaic virus determined, and the first record from Australia. This finding illustrates the risk to natural and managed systems posed by the international trade in live plants and propagules, which enables viruses to establish in new regions and infect new hosts.


Application of genotypic and phenotypic analyses to commercial probiotic strain identity and relatedness.
The objective of this study was to generate strain-specific genomic patterns of a bank of 67 commercial and reference probiotic strains, with a focus on probiotic lactobacilli. Pulsed-field gel electrophoresis (PFGE) was used as the primary method for strain differentiation. This method was compared with carbohydrate fermentation analysis. To supplement visual comparison, PFGE patterns were analysed quantitatively by cluster analysis using unweighted pair group method with arithmetic averages. SmaI, NotI and XbaI were found to effectively generate clear and easy-to-interpret PFGE patterns of a range of probiotic strains. Some probiotic strains from different sources shared highly similar PFGE patterns. Results document the value of genotypic strain identification methods, combined with phenotypic methods, for determining probiotic strain identity and relatedness. No correlation was found between relatedness determined by carbohydrate fermentation profiles alone compared with PFGE analysis alone. Some commercial strains are probably derived from similar sources. This approach is valuable to the probiotic industry to develop commercial strain identification patterns, to provide quality control of strain manufacturing production runs, to track use of protected strains and to determine the relatedness among different research and commercial probiotic strains.


Dual-mode spiral vortices.
We show that spiral vortices in oscillatory systems can lose stability to secondary modes to form dual-mode spiral vortices. The secondary modes grow at the vortex core where the oscillation amplitude vanishes but are nonlinearly damped by the oscillatory mode away from the core. Gradients of the oscillation phase, induced by the hosted secondary mode, can lead to additional hosting events that culminate in periodic core oscillations or in a novel form of spatiotemporal chaos. The results of this study apply to physical, chemical, and biological systems that go through cusp-Hopf, fold-Hopf, and Hopf-Turing bifurcations.


DNA promoter methylation in breast tumors: no association with genetic polymorphisms in MTHFR and MTR.
Aberrant promoter methylation is recognized as an important feature of breast carcinogenesis. We hypothesized that genetic variation of genes for methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR), two critical enzymes in the one-carbon metabolism, may alter DNA methylation levels and thus influence DNA methylation in breast cancer. We evaluated case-control association of MTHFR C677T, A1298C, and MTR A2756G polymorphisms for cases strata-defined by promoter methylation status for each of three genes, E-cadherin, p16, and RAR-beta2 in breast cancer; in addition, we evaluated case-case comparisons of the likelihood of promoter methylation in relation to genotypes using a population-based case-control study conducted in Western New York State. Methylation was evaluated with real-time methylation-specific PCRs for 803 paraffin-embedded breast tumor tissues from women with primary, incident breast cancer. We applied unordered polytomous regression and unconditional logistic regression to derive adjusted odds ratios and 95% confidence intervals. We did not find any association of MTHFR and MTR polymorphisms with breast cancer risk stratified by methylation status nor between polymorphisms and likelihood of promoter methylation of any of the genes. There was no evidence of difference within strata defined by menopausal status, estrogen receptor status, folate intake, and lifetime alcohol consumption. Overall, we found no evidence that these common polymorphisms of the MTHFR and MTR genes are associated with promoter methylation of E-cadherin, p16, and RAR-beta2 genes in breast cancer.