Transvaginal sigmoid cancer resection: first case with 12 months of follow-up--technique description.
Several minimally invasive techniques using natural orifices as an entrance site to the peritoneal cavity have been described recently. Pure natural orifice translumenal endoscopic surgery (NOTES) techniques have been mainly implemented to perform cholecystectomies and appendectomies, while more complex operations like colon resections have been described in a hybrid setting and with the use of the transumbilical approach. Here we describe the technique of transvaginal sigmoid colon resection for cancer with standard laparoscopy equipment. After developing the transvaginal technique of sigmoid colon resection in an experimental sheep model, we have performed this operation in a human patient for cancer. Twelve months of follow-up is reported. A totally transvaginal R0 resection of the sigmoid colon for adenocarcinoma has been successfully performed in a female patient with laparoscopy equipment. The specimen included 13 lymph nodes, all of which were free of metastasis. Twelve months after surgery the patient is alive with no evidence of disease. A pure transvaginal NOTES approach to sigmoid colon cancer is feasible in human patients.


Scaling of form and function in the xenarthran femur: a 100-fold increase in body mass is mitigated by repositioning of the third trochanter.
How animals cope with increases in body size is a key issue in biology. Here, we consider scaling of xenarthrans, particularly how femoral form and function varies to accommodate the size range between the 3 kg armadillo and its giant relative the 300 kg glyptodont. It has already been noted that femoral morphology differs between these animals and suggested that this reflects a novel adaptation to size increase in glyptodont. We test this idea by applying a finite element analysis of coronal plane forces to femoral models of these animals, simulating the stance phase in the hind limb; where the femur is subject to bending owing to longitudinal compressive as well as abduction loads on the greater trochanter. We use these models to examine the hypothesis that muscles attaching on the third trochanter (T3) can reduce this bending in the loaded femur and that the T3 forces are more effective at reducing bending in glyptodont where the T3 is situated at the level of the knee. The analysis uses traditional finite element methods to produce strain maps and examine strains at 200 points on the femur. The coordinates of these points before and after loading are also used to carry out geometric morphometric (GM) analyses of the gross deformation of the model in different loading scenarios. The results show that longitudinal compressive and abductor muscle loading increases bending in the coronal plane, and that loads applied to the T3 reduce that bending. In the glyptodont model, the T3 loads are more effective and can more readily compensate for the bending owing to longitudinal and abductor loads. This study also demonstrates the usefulness of GM methods in interpreting the results of finite element analyses.


[Subperiosteal pisiform excision in misaligned fractures of the triquetrum].
Isolated fractures of the os triquetrum are a very rare condition, since they are usually combined with other fractures of the carpus. An undetected isolated fracture of the os triquetrum in a 28-year-old pieceworker revealed an osseous consolidation with a misalignment of the joint surface on presentation 6 months after his primary injury. During the whole time he was unable to work due to the severely painful restricted range of movement of his wrist. There are no general guidelines for treatment. Instead of correction of the anatomy of the os triquetrum, we decided to perform a subperiosteal pisiform excision according to Palmieri. As early as 6 weeks later, the patient was able to go back to work and demonstrated a pain-free full range of movement of his wrist. We encourage this procedure not only for degenerated joint disease but also for posttraumatic lesions in the early onset of painful blocking of the joint between the os triquetrum and os pisiforme.


Plasma metabolomics supports non-fasted sampling for metabolic profiling across a spectrum of glucose tolerance in the Nile rat model for type 2 diabetes.
Type 2 diabetes is a challenge in modern healthcare, and animal models are necessary to identify underlying mechanisms. The Nile rat (Arvicanthis niloticus) develops diet-induced diabetes rapidly on a conventional rodent chow diet without genetic or chemical manipulation. Unlike common laboratory models, the outbred Nile rat model is diurnal and has a wide range of overt diabetes onset and diabetes progression patterns in both sexes, better mimicking the heterogeneous diabetic phenotype in humans. While fasted blood glucose has historically been used to monitor diabetic progression, postprandial blood glucose is more sensitive to the initial stages of diabetes. However, there is a long-held assumption that ad libitum feeding in rodent models leads to increased variance, thus masking diabetes-related metabolic changes in the plasma. Here we compared repeatability within triplicates of non-fasted or fasted plasma samples and assessed metabolic changes relevant to glucose tolerance in fasted and non-fasted plasma of 8-10-week-old male Nile rats. We used liquid chromatography-mass spectrometry lipidomics and polar metabolomics to measure relative metabolite abundances in the plasma samples. We found that, compared to fasted metabolites, non-fasted plasma metabolites are not only more strongly associated with glucose tolerance on the basis of unsupervised clustering and elastic net regression model, but also have a lower replicate variance. Between the two sampling groups, we detected 66 non-fasted metabolites and 32 fasted metabolites that were associated with glucose tolerance using a combined approach with multivariable elastic net and individual metabolite linear models. Further, to test if metabolite replicate variance is affected by age and sex, we measured non-fasted replicate variance in a cohort of mature 30-week-old male and female Nile rats. Our results support using non-fasted plasma metabolomics to study glucose tolerance in Nile rats across the progression of diabetes.


Predictors of Instrumental Activities of Daily Living Performance in Patients with Stroke.
Instrumental activities of daily livings are important for independent living and active participation in the community. The present study is aimed at determining factors predicting instrumental activities of daily living performance in patients with stroke. In this cross-sectional study, a convenient sample of 90 patients with stroke entered from five occupational therapy centers, which were selected based on the cluster randomization method. Lawton IADL scale, Barthel Index, Trail Making Test (A and B), Digit span subtest of Wechsler memory scale, Motorcity index, and Beck Depression Inventory-II were used to investigate the study's aim. Statistical analyses were performed using independent sample t-test, one-way ANOVA, Pearson correlation, and multiple linear regression analysis. Age (r = -0.384, p < 0.001), memory (r = 0.565, p < 0.001), basic activities of daily living (r = 0.818, p < 0.001), depression (r = -0.758, p < 0.001), Trial Making Test (B-A) (r = -0.614, p < 0.001), and motoricity index (r = 0.670, p < 0.001) were significantly associated with instrumental activities of daily living performance. Basic activities of daily living were the strongest predictor of IADL's performance. Age, TMT (B-A), and depression were orderly the next strongest predictors. Stroke patients with more dependency in basic activities of daily living, older age, cognitive impairment, and depression are more opted to be dependent in instrumental activities of daily living and as a result, less participation in home and community affairs.


Mechanics of breathing, gas distribution and functional residual capacity at different frequencies of respiration during spontaneous and artificial ventilation.
Nine healthy volunteers were investigated, both while awake and breathing spontaneously, and while anaesthetized with IPPV, in all cases at rates of both 12 and 24 b.p.m. Gas flow and volume were measured with a pneumotachography. The transpulmonary pressure (the pressure difference between the trachea or the buccal cavity and the oesophagus) was also recorded. The distribution of gas was analysed by means of nitrogen washout curves, which also permitted the determination of functional residual capacity (FRC). Lung compliance during IPPV was approximately half that during spontaneous breathing. During IPPV the compliance was dependent on the frequency of ventilation, being lower with the greater frequency. Pulmonary resistance was approximately twice as great with artificial ventilation, but no significant relationship to frequency was demonstrated. Gas distribution was within normal limits and in this respect there was no difference between low and high rates of spontaneous breathing. With IPPV at the higher rate, gas distribution was significantly less even, but still within normal limits. Dfferences in FRC under the different conditions during the experiments were not significant, but the values obtained were lower with artificial ventilation. Neither the reduction in dynamic lung compliance induced by anaesthesia and artificial ventilation, nor its dependence on the frequency of such ventilation, can be explained with certainty by changes in gas distribution.


Stigma towards dependent drinking and its role on caregiving burden: A qualitative study from Goa, India.
Stigma towards alcohol use disorders is prevalent in India and can lead to social exclusion and hamper treatment access and outcomes. Family members of individuals with dependent drinking are often their primary caregivers and play a key role in decisions around help-seeking, treatment and recovery. The nature and role of stigma in caregiving, and the consequent burden on family caregivers of those with dependent drinking, has not been qualitatively studied in India. We conducted in-depth interviews with: (i) men with probable alcohol dependence (n = 11); (ii) family caregivers (n = 12); and (iii) doctors with experience of treating alcohol dependence (n = 13) in community settings in Goa. Data were analysed using inductive thematic analysis. Two primary themes were identified from the data: (i) stigma in the form of ignorance, prejudice and discrimination; and (ii) the impact of this stigma on caregiving decisions and the mental health of caregivers. We found that stigma functioned as a barrier to a proper course of treatment and care, as well as a detrimental factor for caregiver's mental health and caregiving decision-making. Stigma towards dependent drinking in the forms of ignorance, prejudice and discrimination is prevalent within homes, workplaces and health systems and might exacerbate the caregiving burden among female family caregivers. Policies, educational programs and campaigns aimed at preventing stigma in these forms would likely enable access to more inclusive and appropriate health services, benefit the health of family caregivers and improve the treatment outcomes of drinkers.


Postcontraction insulin sensitivity: relationship with contraction protocol, glycogen concentration, and 5' AMP-activated protein kinase phosphorylation.
Exercise enhances insulin-stimulated glucose transport (GT) in skeletal muscle. Evidence suggests that 5' AMP-activated protein kinase (AMPK) and glycogen may be important for enhanced insulin sensitivity. Our goals were to investigate the effect of various in situ muscle contraction protocols on insulin-stimulated GT and assess the relationship of contraction-induced changes in AMPK and glycogen with postcontraction improvement in insulin-stimulated GT. Rats were anesthetized, both ulnar nerves were exposed, and one nerve was electrically stimulated to contract forelimb muscles. We performed a series of five experiments, sequentially varying only one contraction parameter (train duration, train rate, pulse frequency, number of 5-min bouts, or pulse duration) while holding the others constant. Both epitrochlearis muscles were dissected out and incubated for 3.5 h before measurement of GT. For each contraction parameter studied, we identified an apparent threshold value that did not induce a significant increase in insulin-stimulated GT and an apparent peak value, above which there was a plateau or decline in insulin-stimulated GT. Using other rats, we evaluated muscle AMPK phosphorylation and glycogen concentration immediately postcontraction. AMPK phosphorylation and reduction in glycogen were increased compared with resting controls in each protocol, which had previously been shown to increase insulin-stimulated GT, as well as in several protocols that did not significantly increase insulin-stimulated GT. These data suggest that contraction-induced AMPK phosphorylation and decrease in glycogen may be necessary but are not sufficient for the postcontraction increase in insulin-stimulated GT in rat skeletal muscle.


Observer agreement in evaluating coronary angiograms.
The reliability of interpretation of coronary arteriography as a diagnostic tool was investigated in a sub-study of the VA Cooperative Study of Surgical Treatment for Coronary Arterial Occlusive Disease. Twenty-two physicians with varying levels of experience read 13 cine angiograms -- blind -- on two different occasions. Analysis of inter- and intraobserver variability showed that angiographic items about which observers were most inconsistent from one reading to the other had the largest interobserver disagreement as well. They were the distal portions of the left anterior descending and left circumflex arteries. Among the items on which there was most consistent agreement -- namely, the right main coronary artery and presence of ventricular aneurysm -- there was most often agreement between observers as well. When individual readers were evaluated, some observers were far more consistent in their own readings of all the angiographic items than others. This intraobserver agreement in turn correlated fairly well with how often they agreed with the other observers and with how much experience they reported having in reading coronary cineangiograms.


Efficacy and toxicity profiles of two chemoradiotherapies for stage II laryngeal cancer - a comparison between late course accelerated hyperfractionation (LCAHF) and conventional fractionation (CF).
To evaluate the treatment results of late course accelerated hyperfractionation (LCAHF) compared with conventional fractionation (CF) for stage II laryngeal cancer. Fifty-nine consecutive patients treated for stage II laryngeal cancer were retrospectively reviewed. Thirty-two patients underwent LCAHF, twice-daily fractions during the latter half with a total dose of 69 Gy. Twenty-seven patients received CF of 70 Gy. The local control rates (LCRs), overall survival (OS), and disease-specific survival (DSS) at 5 years were 80.6%, 74.0%, and 90.4%, respectively, after LCAHF and 64.7%, 68.2%, and 90.5%, respectively, after CF. There were no significant differences in LCR, OS, and DSS (p = .11, 0.68, and 0.69, respectively). In a small number of patients with supraglottic cancer, LCAHF was associated with a significantly higher LCR at 5 years compared with CF (100% vs. 41.7%; p = .02). This is the first report that compared the results of LCAHF and CF for stage II laryngeal cancer. We could not find significant differences in LCR, DSS, and OS rates between LCAHF and CF groups. Although in a small number of patients with supraglottic cancer, LCAHF may improve the LCR compared with CF.


Resveratrol and curcumin suppress immune response through CD28/CTLA-4 and CD80 co-stimulatory pathway.
The role of resveratrol and curcumin is well documented in cancer, inflammation, diabetes and various other diseases. However, their immunosuppressive action on T cells, B cells and macrophages is not well documented. In the present study, we have ascertained the effect of resveratrol and curcumin on T and B cells and macrophages. The most striking findings were that both resveratrol and curcumin suppressed the activity of T and B cells and macrophages, as evidenced by significant inhibition in proliferation, antibody production and lymphokine secretion. Interestingly, curcumin imparted immunosuppression by mainly down-regulating the expression of CD28 and CD80 and up-regulating CTLA-4. Resveratrol also functioned by decreasing the expression of CD28 and CD80, as well as by augmenting the production of interleukin (IL)-10.


Reduced kidney function in acute coronary syndrome patients with undiagnosed diabetes or pre-diabetes.
Chronic kidney disease is highly prevalent in the diabetic population and it is also associated with adverse outcomes in patients with acute coronary syndrome (ACS). However, the risk of reduced kidney function (RKF) in ACS patients with undiagnosed diabetes or pre-diabetes is yet to be clear. Herein, the present study attempts to investigate the risk for RKF in ACS patients with special reference to undiagnosed diabetes and pre-diabetes, generating possible recommendations for early intervention and management in ACS patients. A cross-sectional design was performed to evaluate the risk for RKF in 2232 ACS patients according to glycaemic status from the China Heart Survey between June 2005 and August 2005 by using multivariate logistic regression. The prevalence of RKF in ACS patients with normal glucose metabolism, pre-diabetes, undiagnosed diabetes and diagnosed diabetes was 11.6%, 17.7%, 16.7% and 28.8%, respectively. In multivariate analysis, apart from ACS patients with diagnosed diabetes, those with pre-diabetes (odds ratio = 1.58, 95%:1.08-2.31) and undiagnosed diabetes (odds ratio = 1.51, 95%:1.01-2.26) also suffered from an increased risk for RKF, compared with those with normal glucose metabolism. Stratified by ACS subtypes, the associations of RKF with ACS subtypes remained statistically significant. The increased risk of RKF was significantly associated with undiagnosed diabetes and pre-diabetes, relative to normal glucose metabolism. Screenings for RKF among ACS patients with pre-diabetes or newly diagnosed diabetes would be highly recommended.


Gene Set-Based Functionome Analysis of Pathogenesis in Epithelial Ovarian Serous Carcinoma and the Molecular Features in Different FIGO Stages.
Serous carcinoma (SC) is the most common subtype of epithelial ovarian carcinoma and is divided into four stages by the Federation of Gynecologists and Obstetrics (FIGO) staging system. Currently, the molecular functions and biological processes of SC at different FIGO stages have not been quantified. Here, we conducted a whole-genome integrative analysis to investigate the functions of SC at different stages. The function, as defined by the GO term or canonical pathway gene set, was quantified by measuring the changes in the gene expressional order between cancerous and normal control states. The quantified function, i.e., the gene set regularity (GSR) index, was utilized to investigate the pathogenesis and functional regulation of SC at different FIGO stages. We showed that the informativeness of the GSR indices was sufficient for accurate pattern recognition and classification for machine learning. The function regularity presented by the GSR indices showed stepwise deterioration during SC progression from FIGO stage I to stage IV. The pathogenesis of SC was centered on cell cycle deregulation and accompanied with multiple functional aberrations as well as their interactions.


A phase II study of carboplatin in nasopharyngeal carcinoma.
This is a phase II study to evaluate the efficacy and toxicity of short-course carboplatin in advanced-stage nasopharyngeal carcinoma (NPC). Thirty-three previously untreated stage III-IV NPC patients were studied. Carboplatin was given as a rapid intravenous injection every 3 weeks. The dose of carboplatin was calculated according to the individual patient's creatinine clearance and desired platelet nadir of 75,000/microliter according to the Egorin formula. Response and toxicity were evaluated. Thirty-two patients were evaluated for response. The median age was 54 years, range 30-70 years. Twenty-four patients had local regional disease and 8 patients had metastatic disease. The median dose of carboplatin given was 415 mg/m2 (range 91-791 mg/m2). Fourteen (44%) patients had a partial response with a 95% confidence interval of 26-62%. Fifteen (47%) patients had stable disease and 3 (9%) progressive disease. The overall median survival rate was not reached at 43 months. Overall toxicity was tolerable. Grade III-IV myelosuppression occurred in 4 (12%) patients. There were no other major toxicity- or treatment-related deaths. We conclude that carboplatin has a significant anticancer effect in advanced NPC. Thus carboplatin combination chemotherapy for the treatment of NPC is worthy of future clinical investigations.


Exome sequencing reveals novel IRXI mutation in congenital heart disease.
Genetic variation in specific transcription factors during heart formation may lead to congenital heart disease (CHD) or even miscarriage. The aim of the present study was to identify CHD‑associated genes using next generation sequencing (NGS). The whole exome DNA sequence was obtained from a stillborn fetus diagnosed with tricuspid atresia and complete transposition of the great arteries using high‑throughput sequencing methods. Subsequently, genetic variants of CHD‑associated genes were selected and verified in 215 non‑syndromic CHD patients and 249 healthy control subjects using polymerase chain reaction combined with Sanger sequencing. Genetic variants of previously reported CHD‑inducing genes, such as cysteine rich with EGF like domains 1 and cbp/p300‑interacting transactivator with Glu/Asp rich carboxy‑terminal domain 2, were discovered through the NGS analysis. In addition, a novel non‑synonymous mutation of the iroquois homeobox 1 (IRX1) gene (p.Gln240Glu) was identified. A total of three non‑synonymous mutations (p.Gln240Glu, p.Ser298Asn and p.Ala381Glu) of the IRX1 gene were verified in 215 non‑syndromic CHD patients, but not in 249 healthy volunteers. The results demonstrated that NGS is a powerful tool to study the etiology of CHD. In addition, the results suggest that genetic variants of the IRX1 gene may contribute to the pathogenesis of CHD.


Enhancement of HIV-1-induced syncytium formation in T cells by the tyrosyl kinase p56lck.
The CD4 glycoprotein is the primary cellular receptor for human immunodeficiency virus type 1 (HIV-1) and has also been reported to be physically associated with p56lck, a tyrosyl protein kinase p56lck is a member of the src family of nonreceptor protein-tyrosine kinases and is expressed predominantly in T lymphocytes. Our objective was to study the effect of p56lck on the biology of HIV-1. For this purpose, we have stably transfected two human p56lck negative T cell lines (C8166-45 and MT-2) with plasmids encoding for this cellular protein. Following coculture with HIV-1-infected cells or infection with cell-free virus, p56lck-expressing cell lines showed a greater propensity for virus-mediated syncytium formation than parental p56lck-negative cells. The enhancement of HIV-1-induced syncytium formation was not associated with the kinase activity of p56lck, as demonstrated by experiments using a kinase-deficient mutant. However, the physical interaction between CD4 and p56lck was shown to be necessary to obtain the enhancement of syncytium formation since a mutated version of p56lck, which is deficient in its capacity to associate with CD4, did not lead to an increase in virus-mediated cell-to-cell fusion events. Finally, we determined that cells transfected with wild-type and kinase-negative mutant p56lck showed a reduced rate of CD4 endocytosis compared to parental p56lck-negative cells. Together, these results suggest that p56lck can be seen as an accessory molecule facilitating HIV-1-mediated syncytium formation in T cells by a mechanism involving the stabilization of the CD4 molecule at the cell surface.


[Hemiplegic forms of human African trypanosomiasis].
Hemiplegic forms of human African trypanosomiasis are unusual. From 1963 to 1987, 14 cases have been reported in the literature. One may be mistakenly led to look for a space-occupying lesion when clinical features include hemiplegia, vascular shift from median line during arteriography, focal EEG anomalies and intracranial hypertension. The discussion on diagnosis also covers subacute or chronic meningo encephalitis (tuberculosis syphilis or fungal infection). CT scanner findings suggest the association of a massive demyelination of centrum semiovale, with cerebral oedema.


Retrospective evidence for clinical validity of expanded genetic model in warfarin dose optimization in a South Indian population.
To optimize warfarin dose in patients at risk for thrombotic events, we have recently developed a pharmacogenomic algorithm, which explained 44.9% of the variability in warfarin dose requirements using age, gender, BMI, vitamin K intake, CYP2C9 (*2 and *3) and VKORC1 (*3, *4 and -1639 G>A) as predictors. The aim of the current study is to develop an expanded genetic model that can explain greater percentage of warfarin variability and that has clinical validity. CYP2C9*8, CYP4F2 V433M, GGCX G8016A and thyroid status were added to an expanded genetic model (n = 243). The expanded genetic model explained 61% of the variability in warfarin dose requirements, has a prediction accuracy of ±11 mg/week and can differentiate warfarin sensitive and warfarin resistant groups efficiently (areas under receiver operating characteristic curves: 0.93 and 0.998, respectively; p < 0.0001). Higher percentage of International Normalized Ratios in therapeutic range (52.68 ± 4.21 vs 43.80 ± 2.27; p = 0.04) and prolonged time in therapeutic range (61.74 ± 3.18 vs 47.75 ± 5.77; p = 0.03) were observed in subjects with a prediction accuracy of <1 mg/day compared with subjects with prediction accuracy >1 mg/day. In the warfarin-resistant group, primary hypothyroidism was found to induce more resistance while in the warfarin-sensitive group, hyperthyroidism was found to increase sensitivity. The expanded genetic model explains greater variability in warfarin dose requirements and it prolongs time in therapeutic range and minimizes out-of-range International Normalized Ratios. Thyroid status also influences warfarin dose adjustments.


Laying down one's life for oneself.
Roman Catholicism has long opposed suicide. Although Scripture neither condones nor condemns suicide explicitly, cases in the Bible that are purported to be suicides fall into several different categories, and the Roman Catholic tradition can show why some of these should be considered morally wrong and some should not. While Christian martyrdom is praised, it is not correct to argue that this Christian outlook invites suicide, or that it recommends physician-assisted suicide for altruistic motives. Church Tradition, from its earliest days, has clearly distinguished martyrdom from suicide. The principles of double effect and cooperation, mainstays in Roman Catholic moral theology, enable one to see the moral difference between martyrdom and suicide, and to appreciate why physician-assisted suicide is wrong for both patient and physician.


Effect of 5-Aminolevulinic Acid Photodynamic Therapy on Aspergillus fumigatus Biofilms in Vitro.
Aspergillus fumigatus biofilm development results in enhanced pathogenicity and treatment resistance. Most contemporary antibiotics, however, are unable to eliminate biofilms. In recent years, with the application of new photosensitizers and the development of treatment, ALA-PDT (5-aminolevulinic acid photodynamic treatment) has achieved remarkable curative effect in the treatment of fungal infectious diseases; however, no research has been conducted on ALA-PDT against A. fumigatus. This study investigated the inhibitory effect of ALA-PDT at various 5-aminolevulinic acid concentrations and light doses on A. fumigatus planktonic and biofilms in vitro. We found that ALA-PDT may successfully inhibit the development of A. fumigatus biofilm and disintegrate mature biofilm. After ALA-PDT treatment, the adherence rate and vitality dramatically decreased, and the biofilm's structure was severely compromised. Our findings show for the first time that ALA-PDT may be used to prevent the formation of A. fumigatus biofilm and disturb the structure of mature biofilm, and that it could be employed as a therapeutic therapy for A. fumigatus superficial infection.


Population genomic analysis of model and nonmodel organisms using sequenced RAD tags.
The evolutionary processes of mutation, migration, genetic drift, and natural selection shape patterns of genetic variation among individuals, populations, and species, and they can do so differentially across genomes. The field of population genomics provides a comprehensive genome-scale view of these processes, even beyond traditional model organisms. Until recently, genome-wide studies of genetic variation have been prohibitively expensive. However, next-generation sequencing (NGS) technologies are revolutionizing the field of population genomics, allowing for genetic analysis at scales not previously possible even in organisms for which few genomic resources presently exist. To speed this revolution in evolutionary genetics, we and colleagues developed Restriction site Associated DNA (RAD) sequencing, a method that uses Illumina NGS to simultaneously type and score tens to hundreds of thousands of single nucleotide polymorphism (SNP) markers in hundreds of individuals for minimal investment of resources. The core molecular protocol is described elsewhere in this volume, which can be modified to suit a diversity of evolutionary genetic questions. In this chapter, we outline the conceptual framework of population genomics, relate genomic patterns of variation to evolutionary processes, and discuss how RAD sequencing can be used to study population genomics. In addition, we discuss bioinformatic considerations that arise from unique aspects of NGS data as compared to traditional marker based approaches, and we outline some general analytical approaches for RAD-seq and similar data, including a computational pipeline that we developed called Stacks. This software can be used for the analysis of RAD-seq data in organisms with and without a reference genome. Nonetheless, the development of analytical tools remains in its infancy, and further work is needed to fully quantify sampling variance and biases in these data types. As data-gathering technology continues to advance, our ability to understand genomic evolution in natural populations will be limited more by conceptual and analytical weaknesses than by the amount of molecular data.


Multitask learning of signaling and regulatory networks with application to studying human response to flu.
Reconstructing regulatory and signaling response networks is one of the major goals of systems biology. While several successful methods have been suggested for this task, some integrating large and diverse datasets, these methods have so far been applied to reconstruct a single response network at a time, even when studying and modeling related conditions. To improve network reconstruction we developed MT-SDREM, a multi-task learning method which jointly models networks for several related conditions. In MT-SDREM, parameters are jointly constrained across the networks while still allowing for condition-specific pathways and regulation. We formulate the multi-task learning problem and discuss methods for optimizing the joint target function. We applied MT-SDREM to reconstruct dynamic human response networks for three flu strains: H1N1, H5N1 and H3N2. Our multi-task learning method was able to identify known and novel factors and genes, improving upon prior methods that model each condition independently. The MT-SDREM networks were also better at identifying proteins whose removal affects viral load indicating that joint learning can still lead to accurate, condition-specific, networks. Supporting website with MT-SDREM implementation: http://sb.cs.cmu.edu/mtsdrem.


Cross talk between adipose tissue cells: impact on pathophysiology.
The metabolic functionality of adipose tissue is intimately dependent on local communication between various cell types. It influences not only the equilibrium between lipogenesis and lipolysis but also between hypertrophic and hyperplastic growth, thereby determining the role adipose tissue plays in the insulin resistance syndrome.


Burkitt's tumors contain particles encapsulating RNA-instructed DNA polymerase and high molecular weight virus-related RNA.
Burkitt's lymphomas, linked by previous studies with the DNA-containing Epstein-Barr virus, contain an RNA related in sequence to that of Rauscher leukemia virus. The present study establishes that the viral-related RNA found in Burkitt's tumors is a 70S component encapsulated with RNA-instructed DNA polymerase in a particle possessing a density characteristic of RNA tumor viruses. Further, the DNA synthesized by the Burkitt particles hybridizes specifically to the RNA of Rauscher leukemia virus. Thus, four features characteristic of a known oncogenic RNA agent are also exhibited by particles found with a high (87%) frequency in Burkitt's tumors. The relation between the RNA particle and the Epstein-Barr virus and their etiological roles remains to be elucidated. However, relevant to these issues is the finding reported here that the presence of Epstein-Barr virus information in nonneoplastic cells does not lead to the production of the RNA particles that have been detected now in three different human neoplasias, including leukemias, breast cancer, and Burkitt's disease.


Crohn's disease of the esophagus.
Crohn's disease of the esophagus is rare but is being detected more frequently because of the use of upper endoscopy. Clinicopathologic correlation is required to establish the correct diagnosis. We present a case of esophageal Crohn's disease and review the literature to demonstrate that esophageal involvement is usually associated with disease elsewhere in the gut.


Recruiting community health centers into pragmatic research: Findings from STOP CRC.
Challenges of recruiting participants into pragmatic trials, particularly at the level of the health system, remain largely unexplored. As part of Strategies and Opportunities to STOP Colon Cancer in Priority Populations (STOP CRC), we recruited eight separate community health centers (consisting of 26 individual safety net clinics) into a large comparative effectiveness pragmatic study to evaluate methods of raising the rates of colorectal cancer screening. In partnership with STOP CRC's advisory board, we defined criteria to identify eligible health centers and applied these criteria to a list of health centers in Washington, Oregon, and California affiliated with Oregon Community Health Information Network, a 16-state practice-based research network of federally sponsored health centers. Project staff contacted centers that met eligibility criteria and arranged in-person meetings of key study investigators with health center leadership teams. We used the Consolidated Framework for Implementation Research to thematically analyze the content of discussions during these meetings to identify major facilitators of and barriers to health center participation. From an initial list of 41 health centers, 11 met the initial inclusion criteria. Of these, leaders at three centers declined and at eight centers (26 clinic sites) agreed to participate (73%). Participating and nonparticipating health centers were similar with respect to clinic size, percent Hispanic patients, and percent uninsured patients. Participating health centers had higher proportions of Medicaid patients and higher baseline colorectal cancer screening rates. Common facilitators of participation were perception by center leadership that the project was an opportunity to increase colorectal cancer screening rates and to use electronic health record tools for population management. Barriers to participation were concerns of center leaders about ability to provide fecal testing to and assure follow-up of uninsured patients, limited clinic capacity to prepare mailings required by the study protocol, discomfort with randomization, and concerns about delaying program implementation at some clinics due to the research requirements. Our findings address an important research gap and may inform future efforts to recruit community health centers into pragmatic research.


Comprehensive analysis of long non-coding RNA expression profiles in hepatitis B virus-related hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common kinds of malignancies and is closely correlated with hepatitis B virus (HBV) infection. Recent evidence has proved that long non-coding RNAs (lncRNAs) are implicated in development and progression of cancer. However, the contributions of lncRNAs to HBV-related HCC remain largely unknown. Here, we comprehensively investigated lncRNA expression profiles in HBV-related HCC by annotating and analyzing microarray datasets. By analyzing 42 HCC tissue samples with different etiology (HBV-related, alcohol-related, and primary HCC) and 15 normal liver tissues, we identified 182 lncRNAs that were specifically differentially expressed in HBV-related HCC, namely HBV-related HCC specific lncRNAs(HH-lncRNAs). Using an online function annotation tool, we found these HH-lncRNAs were associated many oncogenes and immunity related biological processes. 6 candidate HH-lncRNAs were selected and further validated by quantitative real-time PCR analysis in a cohort of HCC tissue samples. Function of a candidate HH-lncRNAs, BAIAP2-AS1, was further predicted by co-expression network and gene set enrichment analysis. These findings provide insights into HH-lncRNAs and offer resource for further search of biomarkers and therapeutic targets of HBV-related HCC.


Novel autologous cell therapy in ischemic limb disease through growth factor secretion by cultured adipose tissue-derived stromal cells.
The delivery of autologous progenitor cells into ischemic tissue of patients is emerging as a novel therapeutic option. Here, we report the potential impact of cultured adipose tissue-derived cells (ADSC) on angiogenic cell therapy. ADSC were isolated from C57Bl/6 mouse inguinal adipose tissue and showed high expression of ScaI and CD44, but not c-kit, Lin, CD34, CD45, CD11b, and CD31, compatible with that of mesenchymal stem cells from bone marrow. In coculture conditions with ADSC and human aortic endothelial cells (ECs) under treatment with growth factors, ADSC significantly increased EC viability, migration and tube formation mainly through secretion of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). At 4 weeks after transplantation of ADSC into the ischemic mouse hindlimb, the angiogenic scores were improved in the ADSC-treated group, which were evaluated with blood flow by laser Doppler imaging (LDI) and capillary density by immunostaining with anti-CD31 antibody. However, injected ADSC did not correspond to CD31, von Willebrand factor, and alpha-smooth muscle actin-positive cells in ischemic tissue. These adipose tissue-derived cells demonstrated potential as angiogenic cell therapy for ischemic disease, which appears to be mainly achieved by their ability to secrete angiogenic growth factors.


An electrochemical study of microporous track-etched membrane permeability and the effect of surface protein layers.
Microporous track-etched membranes serve as important permeable growth surfaces for cell culture where diffusive solute transport is needed across two growth compartments. This study has established effective solute diffusion coefficients for four probe micro-solutes: hydrogen peroxide, pyrocatechol, acetaminophen and ascorbic acid across three track-etched membranes formulated, respectively, from polycarbonate and polyethylene terephthalate. Chronoamperometry and cyclic voltammetry were used for the diffusion measurements. These showed substantially reduced intra-pore diffusion in relation to available pore area. Diffusion coefficients ranging from 1.43×10-10 to 3.17×10-7cm2s-1 were demonstrated. This strongly suggests that water organisation in micro-pores is not equivalent to that of bulk water. Superimposed protein layers of Type I and IV collagen, Type I collagen-fibronectin, Type I collagen-heparin, and Type I collagen-chondroitin sulphate increased diffusional resistance, but with disproportional retardation of ascorbate diffusion due to charge repulsion at collagen-heparin and collagen-chondroitin sulphate combinations. Diffusive resistance at natural tendon and cartilage was considerably smaller; diffusion coefficients ranged from 8.33×10-6 to 1.09×10-8cm2s-1.


The organization of hospital infection control committees and their importance in Brazil.
The importance of Hospital Infection Control Committees (HICC) increases every year due to the emergence of multiresistant bacterial strains, hospital outbreaks, and other factors that cause HI. This demonstrates the fragility of the quality of hospital and medical care. Having a well-organized HICC benefits hospitals by improving quality, lowering costs and, most important, reducing patient morbidity and mortality. This review records the history of the development of HICCs, their present organizational structure, and offers recommendations for hte best methods of infection surveillance.


Two new tocopherol polymers from the seeds of Euryale ferox.
Two new tocopherol polymers, chroman-type dimer named ferotocodimer A (1) and spiro-type trimer named ferotocotrimer E (2), were isolated from the seeds of Euryale ferox. Their structures were elucidated on the basis of spectroscopic methods including HR-ESI-MS and 1D and 2D NMR. The absolute configurations of 1 and 2 were determined by CD and ROESY experiments.


What Influences Children's Physical Activity? Investigating the Effects of Physical Self-Concept, Physical Self-Guides, Self-Efficacy, and Motivation.
Physical fitness self-concept (PFSC) is an important predictor of motivation and physical activity in children. Recent studies revealed that not only PFSC but also its interplay with perceptions of one's ideal and ought physical fitness self are related to motivation and physical activity. As the meaning of ideal and ought selves in children is yet unclear, this study aimed to investigate how PFSC, ideal physical fitness self, and ought physical fitness self are related to children's motivation and physical activity. Six hundred forty-five children (Mage = 8.87 years) filled out questionnaires twice with an interval of approximately 8 months. Polynomial regression with response surface analyses and mediation analyses was conducted. Results showed that PFSC, rather than ideal and ought self-perceptions, is associated with autonomous motivation, self-efficacy, and physical activity. The relationship between PFSC and physical activity was mediated by self-efficacy. Findings indicate that physical activity promotion programs should include PFSC and self-efficacy enhancement in childhood.


Identifying carotenoids and phenolic compounds in naranjilla (Solanum quitoense Lam. var. Puyo hybrid), an Andean fruit.
The naranjilla or lulo (Solanum quitoense Lam.) is a little known fruit that originated in the Andes. Commonly consumed as a fresh drink, it is particularly appreciated for its aroma. Besides its organoleptic qualities, the naranjilla also seems to have good antioxidant properties. We therefore studied the physicochemical characteristics of variety "Puyo hybrid"; determined its juice composition; identified its carotenoids and phenolic compounds, using HPLC-DAD and HPLC/ESI-MS, respectively, in each fruit part; and measured the antioxidant capacities of each part, using the ORAC and DPPH methods. We found the following bioactive compounds: all-trans-beta-carotene, 13-cis-beta-carotene, and 9-cis-beta-carotene and the lutein (carotenoids); chlorogenic acids and their hexosides in the flesh and placental tissues, and flavonol glycosides in the skin (phenolic compounds); and many dihydrocaffeoyl spermidines in all three parts of the fruit. The naranjilla appeared to be a fruit with good nutritional potential that can provide the basis for a new fruit-drink flavor or other fruit derived-products.


Quantum chemical studies of redox-active enzymes.
In applications on mechanisms for metalloenzymes, the hybrid density functional method B3LYP has been used in most cases. The present knowledge about the accuracy of this method on transition metal complexes is described. In comparison to ab initio methods like CASPT2 and CCSD(T), B3LYP has generally been shown to perform quite well. However, there is one exception and this is for the type of copper dimer which is found in enzymes like hemocyanin, catechol oxidase and tyrosinase. Large deviations have been found between CASPT2 and B3LYP and also between B3LYP and experiments on model complexes. This situation is carefully investigated. The accuracy of B3LYP for the activation of O2 in enzymes is also analyzed by comparisons to experiments. For the barrier of O-O bond cleavage B3LYP appears to behave quite satisfactorily, while for the binding of O2 to the metal there are deviations compared to experiment. The question whether this is due to the B3LYP method or to the chemical models used is addressed.


[Brief intervention in psychiatric consultation].
This essay presents a perspective on intervention in psychiatric consultation based on the patient's subjective experience as supported by Kendler in 2005 in the American Journal of Psychiatry in his position against biological reductionism in psychiatry, distinguishing the psychic approach from the biological. The paper presents aspects of the setting and major features of the assessment in the consultation process, then proceeds to discussing principles of intervention as to specify dimensions of the psychiatric intervention in this particular context.


Serotonin Transporter Gene Polymorphisms and Early Parent-Infant Interactions Are Related to Adult Male Heart Rate Response to Female Crying.
Adults' adaptive interactions with intimate partners enhance well-being. Here we hypothesized that adult males' physiological responses to opposite-sex conspecifics' distress result from an interaction between an environmental factor (early social interaction with caregivers) and a genetic factor (a polymorphism within the promoter region of the serotonin transporter gene, 5-HTTLPR). We assessed heart rate changes in 42 non-married male adults to distress vocalizations (female, infant, and bonobo cries). Males' early interaction with parents was assessed using the Parental Bonding Instrument. Buccal mucosa cell samples were collected to assess their 5-HTTLPR genotype. A significant interaction emerged between early experience and genetic predisposition. Males with a genetic predisposition for higher sensitivity to environmental factors showed atypical physiological responses to adult female cries according to their experienced early maternal parenting. Environmental experiences and genetic characteristics are associated with adult males' physiological responses to socially meaningfully stimuli. Understanding the mechanisms that modulate responses to opposite-sex conspecifics may improve personal well-being and social adaptiveness.


Change in drinking behaviors with retirement: findings from the normative aging study.
This study examines changes in drinking behaviors over an approximately 2-year span in two groups of community-dwelling men: 100 men who retired between baseline (T1) and follow-up (T2) and 316 men who remained employed. Measures were obtained from two drinking surveys conducted as part of a panel study of aging. Results indicate that the event of retirement was not a significant predictor of changes in average alcohol consumption, although retirees showed more variability between T1 and T2. Considering other binary drinking behavior variables, continuing workers and eventual retirees did not differ in the proportions moving into or out of the nondrinker status, or the situation of consuming an average of 3+ drinks/day. However, retirees by T2 were more likely to report the onset of periodic heavier drinking and problems with drinking. Evidence from this study indicates that retirement generally heralds no great shift in alcohol consumption or drinking behaviors.


Long non-coding RNAs MALAT1, MIAT and ANRIL gene expression profiles in beta-thalassemia patients: a cross-sectional analysis.
Beta-thalassemia (β-thal) is one of the most common genetic disorders worldwide. Multiple genetic and epigenetic mechanisms could be implicated in the pathogenesis and/or phenotype variations. We sought to explore the serum expression profile of three disease-related long non-coding RNAs (lncRNAs) in a sample of Egyptian β-thal patients with correlation to the patients' clinicolaboratory data. Fifty consecutive β-thal patients and 50 unrelated controls were enrolled in the study. Quantification of circulating lncRNAs; MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), MIAT (myocardial infarction associated transcript), and ANRIL (antisense non-coding RNA in the INK4 locus) was done by Real-time qRT-PCR. Significant higher expression levels of the studied lncRNAs in β-thal patients compared to the controls (all P values < 0.001) were identified. There was no significant difference between β-thal-major and intermedia patients at the level of any of the studied lncRNAs. Higher MALAT1 expression profile was associated with early age at onset, early age at first blood transfusion, and a higher frequency of splenomegaly. Whereas, up-regulated MIAT levels were associated with early age at first blood transfusion. Taken together, the studied lncRNAs MALAT1, MIAT, and ANRIL might be implicated in β-thal pathogenesis and could provide new molecular biomarkers for β-thalassemia after validation in large-scale future studies.


mRNA-based SARS-CoV-2 Comirnaty vaccine elicits weak and short specific memory B cell response in individuals with no previous infection.
The dynamics of the memory B cell (MBC) repertoire after SARS-CoV-2 vaccination is crucial for assessing long-term immunity. We compare spike-specific MBC responses between SARS-CoV-2 unexposed and recovered individuals, and their impact on breakthrough infections during follow-up. Spike-specific MBC and T cells were quantified at inclusion and after two doses of mRNA vaccine in a longitudinal cohort of 85 naïve and 64 recovered participants (47 with positive serology and 17 with negative serology after infection). At inclusion, there was minimal spike-specific MBC in naïve SARS-CoV-2 individuals. After the second vaccine dose, MBCs were significantly boosted in naïve individuals, but reached a significantly lower level than that observed even in unvaccinated SARS-CoV-2 convalescents (p<0.001). Furthermore, while the secondary memory B cell (MBC) population consisted of 100%, 33%, and 76% IgG+, IgM+, and IgA+ expressing cells, respectively, in the unexposed group, the MBC response showed a significant decrease across all isotypes. Similarly, although secondary specific IgG+, IgM+, and IgA+-MBC isotypes were found in 100%, 39%, and 76% of the unexposed participants, respectively, the magnitude of the MBC levels was significantly lower for all the isotypes compared to convalescents. Interestingly, convalescents without an initial serological response had a lower MBC response, like what found in unexposed subjects. There was an inverse correlation between specific MBCs (r=-0.307; p=0.027), especially for isotype IgA+ (r=-0.279, p=0.045), and the time since the second vaccination dose. Furthermore, during a median follow-up of 434 days (IQR, 339-495), 49 out of 149 individuals (33%) became infected, 29 in naïve and 20 in convalescent individuals, showing a significant correlation between spike-specific MBC magnitude after vaccination and the time for SARS-CoV-2 infection, especially for IgA+/IgG+ MBC isotypes. MBCs were primed by mRNA-based vaccination in most cases, but SARS-CoV-2 naïve individuals had a blunted specific MBC response, and this was associated with a shorter time to breakthrough SARS-CoV-2 infection.


Hyperbaric oxygen therapy for severe acute pancreatitis.
Despite improvements in the supportive management of severe acute pancreatitis over the last decade, the morbidity and mortality rate remains high. The main feature of this condition is pancreatic necrosis leading to sepsis, with both localized and systemic inflammatory response syndromes. Early pathophysiological changes of the pancreas include alterations in microcirculation, ischemia reperfusion injury, and leukocyte and cytokine activation. The efficacy of hyperbaric oxygen (HBO) therapy in improving these pathophysiological disturbances is documented for various conditions. However, its effect in the treatment of severe acute pancreatitis is undetermined. This report documents the case of a 56-year-old woman presenting with severe acute pancreatitis treated by HBO therapy. The severity of disease was based on an Acute Physiology and Chronic Health Evaluation (APACHE II) illness grading score of 11 and a Baltazar based computed tomography severity index (CTSI) score of 9. Administration of 100% oxygen was commenced within 72 h of presentation at a pressure of 2.5 atmospheres for 90 min and given twice daily for a total of 5 days. Therapy was well tolerated with improvements in APACHE II and CTSI grading scores. HBO therapy for severe acute pancreatitis appeared to be safe and may have a role in improving treatment outcomes. Further study is required.


[Effect of HIF-1α Gene Silence on Biological Characteristics of Human Colon Cancer Cells SW480].
To investigate changes in proliferation and apoptosis of human colon cancer SW480 cells after silencing hypoxia inducible factor-lα (HIF-1α) expression. siRNA interference technology was performed to silence the expression of HIF-1α using lipofectamine mediation to transfect siRNA into human colon cancer SW480 cells. The siRNA interfered SW480 cells were compared with a negative control group, an empty vector group, and a blank control group. Real-time PCR and Western blot were used to measure the expressions of HIF-lα protein and mRNA. MTT and flow cytometry (FCM) were used to evaluate the apoptosis and proliferation of SW480 cells. The interfered SW480 cells had a higher level of silence of HIF-lα mRNA (> 80%) compared with those of in the three control groups (P < 0.05). Higher levels of apoptosis and lower levels of proliferation were detected in the interfered cells compared with those in the control groups (P < 0.01). HIF-lα silencing promotes apoptosis and inhibits the proliferation of SW480 cells in vitro.


Responsibility amid the social determinants of health.
It is natural to think that there is a tight connection between whether someone is responsible for some outcome and whether it is appropriate to hold her accountable for that outcome. And this natural thought naturally extends to health: if someone is responsible for her health, then, all else being equal, she is accountable for it. Given this, some have thought that responsibility for health has an important role to play in distributing the benefits and burdens of healthcare. But there is a reason for caution. That health is influenced by social, economic, and environmental factors is a matter of consensus. And some have argued that in light of these social determinants of health, individuals are not typically responsible for their health, rendering inappropriate policies that employ a responsibility-for-health criterion. This debate implicates a number of overlapping concepts and questions that are often difficult to pull apart. And I worry that those who maintain that social determinants undermine responsibility for health have latched on to the wrong target. The social determinants of health are relevant to such policies, but, I argue, not by globally undermining responsibility. Rather, social determinants are sometimes responsibility-undermining, sometimes responsibility-preserving, and often relevant to whether we should hold individuals accountable for their health regardless of their responsibility. This calls for a more nuanced appraisal of the ways in which the social determinants of health are relevant to such policies. And here I attempt to provide one.


Task-Shifting: An Approach to Decentralized Hepatitis C Treatment in Medically Underserved Areas.
Despite the availability of safe and effective direct-acting antiviral drugs (DAAs), the vast majority of patients with chronic hepatitis C (HCV) in the USA remain untreated, in part due to lack of access to specialist providers. To determine the effectiveness of DAA-based treatment in medically underserved areas in California, in a healthcare model dependent on task-shifting--wherein a visiting hepatologist assesses patients for treatment eligibility, but subsequent routine follow-up evaluation of patients prescribed treatment is devolved to a part-time licensed vocational nurse under remote supervision of the hepatologist. We retrospectively determined rates of sustained virologic response 12 weeks after treatment completion (SVR-12), adverse events, and treatment discontinuations in patients who received sofosbuvir-based DAA regimens between December 2013 and November 2014. Despite limited specialist provider involvement in medically underserved areas, all but two of 58 patients completed treatment, and 88 % of patients achieved the curative endpoint of undetectable HCV RNA 12 weeks after completing treatment (sustained virologic response, SVR-12). Almost 80 % of patients with cirrhosis and 85 % of patients with prior treatment experience achieved SVR-12. Treatment effectiveness with sofosbuvir-based regimens in medically underserved areas utilizing task-shifting from a specialist to a mid-level provider is comparable to those achieved in pivotal clinical trials for these regimens, and to "real-world" experiences of tertiary care centers in the USA.


Gastrointestinal distress to serotonergic challenge: a risk marker for emotional disorder?
Serotonin is an important mediator of gut sensation and motility. The authors' aim was to determine whether inadvertent gastrointestinal (GI) distress to serotonergic challenge predicted future major depressive and/or anxiety disorders in exposed children. l-5-hydroxytryptophan was administered to 119 prepubertal children free of psychiatric disorder as part of a psychobiological cohort study initially designed to examine familial loading for mood disorder as the exposure of interest. Subjects were followed longitudinally with standardized psychiatric interviews to identify new-onset mood and anxiety disorders over 90.3 +/- 29.2 months, with the average assessment interval being 16.6 +/- 6.2 months. Reports of GI distress in a subgroup during serotonergic challenge led the authors to examine GI distress to infusion as an exposure post hoc and to perform survival analysis using major depressive and/or anxiety disorders as the outcomes of interest. GI distress to serotonergic challenge was experienced by 23 subjects, with 7 (30.4%) developing an emotional disorder during follow-up in comparison to 12 (10.4%) of 96 nondistressed subjects. The distressed group was at significantly greater risk of subsequent major depression and/or anxiety (p =.026), even after controlling for family history of psychiatric disorder. GI distress to serotonergic challenge in childhood is associated with heightened risk for subsequent major depressive and/or anxiety disorders. Studies of serotonergic neurotransmission may aid our understanding of nonrandom associations between functional GI symptoms and emotional symptoms and disorders.


Oxime Coupling of Active Site Inhibited Factor Seven with a Nonvolatile, Water-Soluble Fluorine-18 Labeled Aldehyde.
A nonvolatile fluorine-18 aldehyde prosthetic group was developed from [18F]SFB, and used for site-specific labeling of active site inhibited factor VII (FVIIai). FVIIai has a high affinity for tissue factor (TF), a transmembrane protein involved in angiogenesis, proliferation, cell migration, and survival of cancer cells. A hydroxylamine N-glycan modified FVIIai (FVIIai-ONH2) was used for oxime coupling with the aldehyde [18F]2 under mild and optimized conditions in an isolated RCY of 4.7 ± 0.9%, and a synthesis time of 267 ± 5 min (from EOB). Retained binding and specificity of the resulting [18F]FVIIai to TF was shown in vitro. TF-expression imaging capability was evaluated by in vivo PET/CT imaging in a pancreatic human xenograft cancer mouse model. The conjugate showed exceptional stability in plasma (>95% at 4 h) and a binding fraction of 90%. In vivo PET/CT imaging showed a mean tumor uptake of 3.8 ± 0.2% ID/g at 4 h post-injection, a comparable uptake in liver and kidneys, and low uptake in normal tissues. In conclusion, FVIIai was labeled with fluorine-18 at the N-glycan chain without affecting TF binding. In vitro specificity and a good in vivo imaging contrast at 4 h postinjection was demonstrated.


Recombinant human beta-galactoside binding lectin suppresses clinical and histological signs of experimental autoimmune encephalomyelitis.
Human placental tissue contains regulatory molecules that may prevent allo-sensitization. Recently, a 14 kDa beta-galactoside binding protein with demonstrated immunoregulatory properties has been cloned using cDNA from human placenta and expressed in Escherichia coli. The present study assesses the ability of this recombinant immunomodulatory lectin (rIML-1), to prevent experimental autoimmune encephalomyelitis (EAE), a paralytic T cell-mediated disease directed against myelin basic protein (BP). Injection of rIML-1 into Lewis rats inhibited the induction of both clinical and histological signs of EAE, apparently by blocking sensitization of encephalitogenic BP-specific T cells and inducing BP-dependent suppressor cells. Because it is neither immunogenic nor toxic, rIML-1 may have application in humans, and would have distinct advantages over unselective cytotoxic immunosuppressive agents used currently in the treatment of autoimmune diseases and transplantation.


Differential regulation of Kidins220 isoforms in Huntington's disease.
Huntington's disease (HD) is an inherited progressive neurodegenerative disease characterized by brain atrophy particularly in the striatum that produces motor impairment, and cognitive and psychiatric disturbances. Multiple pathogenic mechanisms have been proposed including dysfunctions in neurotrophic support and calpain-overactivation, among others. Kinase D-interacting substrate of 220 kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning (ARMS), is an essential mediator of neurotrophin signaling. In adult brain, Kidins220 presents two main isoforms that differ in their carboxy-terminal length and critical protein-protein interaction domains. These variants are generated through alternative terminal exon splicing of the conventional exon 32 (Kidins220-C32) and the recently identified exon 33 (Kidins220-C33). The lack of domains encoded by exon 32 involved in key neuronal functions, including those controlling neurotrophin pathways, pointed to Kidins220-C33 as a form detrimental for neurons. However, the functional role of Kidins220-C33 in neurodegeneration or other pathologies, including HD, has not been explored. In the present work, we discover an unexpected selective downregulation of Kidins220-C33, in the striatum of HD patients, as well as in the R6/1 HD mouse model starting at early symptomatic stages. These changes are C33-specific as Kidins220-C32 variant remains unchanged. We also find the early decrease in Kidins220-C33 levels takes place in neurons, suggesting an unanticipated neuroprotective role for this isoform. Finally, using ex vivo assays and primary neurons, we demonstrate that Kidins220-C33 is downregulated by mechanisms that depend on the activation of the protease calpain. Altogether, these results strongly suggest that calpain-mediated Kidins220-C33 proteolysis modulates onset and/or progression of HD.


[2 types of neuromuscular junction in the pharyngeal retractor muscle of snails].
The pharyngeal retractor muscle of Helix lucorum is innervated by two symmetrical nerves which contain axons of two types forming myoneural junctions with the muscle cells. Type I junctions correspond to thick axons. These axon terminals which contain a large number of spherical, clear vesicles (41 +/- 5 nm) and a smaller number of dense-cored vesicles (67 +/- 3 nm) make contacts mainly with noncontractile sarcoplasmic processes of muscle cells. Type II junctions correspond to thin axons containing many of granules. Their axon terminals contact with contractile parts of muscle cells and contain a heterogenous population of vesicles: small spherical clear vesicles (44 +/- 2 nm), dense-cored vesicles and numerous irregularly outlined granules with fine-granular content (135 +/- 5 nm). Space between muscle cell is usually wide (50 nm and more) with the exception of sarcoplasmic processes where the gap may be less than 10 nm.


Effect of dietary alpha-lipoic acid on growth, body composition, muscle pH, and AMP-activated protein kinase phosphorylation in mice.
The effects of alpha-lipoic acid (ALA) on the growth, body composition, postmortem AMP-activated protein kinase (AMPK) activation, and 24-h muscle pH were investigated. Thirty male C57BL/6J mice were fed diets containing 0, 0.5, or 1.0% ALA (DM basis). At the end of the 3-wk feeding trial, carcass weights decreased (P < 0.05) 14 and 30% for mice fed 0.5 and 1.0% ALA, respectively, compared with the 0% group, with decreases in BW as the levels of dietary ALA increased. This change in carcass weight occurred because carcass fat content for mice receiving 0.5 and 1.0% ALA was 7.32 and 8.09% lower (P < 0.05), respectively, than for the 0% ALA treatment, and because gonadal fat decreased (P < 0.05) 85% in mice fed 1.0% ALA compared with those fed 0% ALA. Dietary ALA caused a slight increase (P < 0.05) in carcass moisture content, with no (P = 0.07) effect on protein and ash content. Furthermore, ALA supplement decreased (P < 0.05) ADFI (DM basis) from 4.3 g/d for 0% ALA-fed mice to 3.4 g/d for 1.0% ALA-fed mice. At 20 min postmortem, pH was greater (P < 0.05) in muscle of mice fed 1.0% ALA than in muscle of mice fed 0% ALA. Ultimate (24-h) pH values differed (P < 0.05) among treatments, and mean values were 5.83, 6.08, and 6.29 for 0, 0.5, and 1.0% ALA, respectively. Phosphorylation of AMPK alpha subunit at Thr172, an indicator of AMPK activation, was decreased (P < 0.05) in muscle of ALA-treated mice at 20 min postmortem. Because AMPK has a crucial role in the control of glycolysis, the reduction in AMPK activation decreases glycolysis, and thereby increases the ultimate pH of postmortem muscle. In summary, dietary ALA supplement can decrease fat accumulation in mice, and because ALA increased muscle pH at 20 min and 24 h postmortem, these results suggest that dietary ALA supplementation might decrease carcass fatness and prevent the development of PSE pork and poultry. However, further research is required to test the effects of ALA in swine and poultry.


Neurological aspects of sinoatrial heart block.
The symptoms of 100 patients with chronic cardiac sinoatrial disorder were analysed. The most common presenting features were syncope in 34 cases and dizziness in 22 cases. Over three-quarters of the patients had cerebral ischaemic symptoms at some stage of the disease. Diagnostic difficulties are often encountered and are illustrated by two case histories. Although sinoatrial disorder has been described in association with neuromuscular diseases, only one such example was found in this series. The patient had a limb girdle dystrophy with cardiomyopathy and diffuse disease of the cardiac conducting system. Muscle biopsy samples taken from 11 patients with idiopathic sinoatrial disorder were normal showing no evidence of subclinical muscular disease.


Propagation of pseudorabies virus in the nervous system of the mouse after intranasal inoculation.
The propagation of pseudorabies virus (PrV) in the mouse nervous system was studied after intranasal inoculation of a PrV mutant expressing beta-galactosidase after insertion of the Escherichia coli Lac-Z gene into the gene encoding the nonstructural, nonessential glycoprotein gG. This allowed rapid detection of infected cells by a single step reaction with the substrate X-gal. The gG-beta-gal+ mutant behaved like the wild-type Kaplan strain of origin. The incubation period was very short and the animals did not survive more than 52 hr after inoculation. In the nasal cavity, the virus infected almost exclusively the respiratory epithelium. The virus propagated to the nervous system via three neuronal pathways: (i) the trigeminal route, with primary infection in the trigeminal ganglion followed by anterograde transneuronal transfer to the spinal trigeminal nucleus; (ii) the sympathetic route, with a first cycle of replication in the superior cervical ganglion and retrograde transneuronal transfer to sympathetic preganglionic neurons in the intermediolateral nucleus in the spinal cord; and (iii) the parasympathetic route, with primary infection in the pterygopalatine ganglion, followed by retrograde transneuronal transfer and replication in the superior salivatory nucleus. In contrast, the olfactory system was rarely found infected, probably because of the short survival of the animals.


Myocardial Infarction Presenting as Ear Fullness and Pain.
Acute coronary syndrome usually presents with retrosternal chest pain, nausea, vomiting, sweating, and jaw and arm pain. Some patients only present with neck, epigastric, or ear discomfort. A 47-year-old male with a history of hypertension and coronary artery disease presented to the emergency department complaining of bilateral otalgia. He never felt chest pain, jaw pain, nausea, diaphoresis, or shortness of breath. He had a history of 2 acute coronary events and had a stress test 2 months prior to admission, which was unremarkable. The initial electrocardiography was sinus rhythm with Q-waves in the inferior leads and nonspecific ST changes in the lateral leads. His troponin on admission was normal but subsequently elevated to 20.00 mg/mL after 24 hours. He underwent left heart catheterization, which found significant occlusive disease of the second and fourth obtuse marginal branches and 2 drug-eluting stents were placed. His ear pain resolved soon after cardiac catheterization. The pathophysiology of this referred pain is thought to be related to the neuroanatomy of the nerves innervating the heart and ear. The auricular nerve branch of the vagus nerve supplies the inner portion of the external ear. Only a few cases with the complaint of otalgia have been reported. Patients were older, more frequently women, and with diabetes or heart failure. Clinicians should be aware of the atypical presentation of angina that may be life-threatening cardiac ischemia. Ear pain and fullness could be the sole presenting symptom in a patient with acute coronary syndrome.


Image quality assessment for machine learning tasks using meta-reinforcement learning.
In this paper, we consider image quality assessment (IQA) as a measure of how images are amenable with respect to a given downstream task, or task amenability. When the task is performed using machine learning algorithms, such as a neural-network-based task predictor for image classification or segmentation, the performance of the task predictor provides an objective estimate of task amenability. In this work, we use an IQA controller to predict the task amenability which, itself being parameterised by neural networks, can be trained simultaneously with the task predictor. We further develop a meta-reinforcement learning framework to improve the adaptability for both IQA controllers and task predictors, such that they can be fine-tuned efficiently on new datasets or meta-tasks. We demonstrate the efficacy of the proposed task-specific, adaptable IQA approach, using two clinical applications for ultrasound-guided prostate intervention and pneumonia detection on X-ray images.


Autophagy in hypoxia-ischemia induced brain injury: evidence and speculations.
The interaction among autophagy, apoptosis and necrosis is complex and still a matter of debate. We have recently studied this interaction after neonatal hypoxia-ischemia (HI) in rats. We found that autophagic and apoptotic pathways were significantly increased at short times after HI in neuronal cells. 3-Methyladenine (3-MA) and wortmannin (WM), which inhibit autophagy, significantly reduced autophagic pathway activation and switched the mechanism of cell death from apoptotic to necrotic. Rapamycin, conversely, which increases autophagy, reduced necrotic cell death, and decreased brain injury. A prophylactic treatment with simvastatin or hypoxic preconditioning also caused upregulation of autophagic pathways. In this addendum, we summarize these findings and speculate on the possible physiological role of autophagy during hypoxia-ischemia induced neurodegeneration.


Automating a new host-protein assay for differentiating bacterial from viral infection to reduce operator hands-on time.
Distinguishing bacterial from viral infections is often challenging, leading to antibiotic misuse, and detrimental ramifications for the patient, the healthcare system and society. A novel ELISA-based assay that integrates the circulating levels of three host-response proteins (TRAIL, IP-10 and CRP) was developed to assist in differentiation between bacterial and viral etiologies. We developed a new protocol for measuring the host-based assay biomarkers using an automated ELISA workstation. The automated protocol was validated and was able to reduce technician hands-on time by 76%, while maintaining high analytical performance. Following automation, the assay has been incorporated into the routine workflow at a pediatric department, and is performed daily on admitted and emergency department patients. The automation protocol reduces the overall burden on the hospital laboratory performing the assay. This benefit has potential to promote adoption of the host-based assay, facilitating timely triage of febrile patients and prudent use of antibiotics.


Evaluation of bacterial contamination and control methods in soluble metalworking fluids.
In the United States, 1.2 million workers are exposed to metalworking fluids. During operations, aerosols are produced and airborne contaminants can be inhaled. Although biocides are used to control the bacterial content of metalworking fluids, they can create health-related problems, and their efficiency remains to be proved. The objectives of this project were (1) to verify whether rigorous cleaning according to a standard protocol could reduce microbial contamination and (2) whether the use of biocides with different spectra could reduce the bacterial population. Four similar machines producing similar components were evaluated; a specific treatment was applied to each machine. The machine used as a control (1) was thoroughly cleaned prior to sampling, (2) did not undergo any major cleaning afterward, and (3) was operated without the use of any biocide. A major cleaning is a protocol described and recommended by the fluid manufacturer and was performed on the three other machines, two of which were subsequently treated with biocides weekly. Fluid samples from the four lathes were collected weekly during a 6-month period, and total bacterial and cultivable Gram-negative bacteria were analyzed for each sample. Major cleaning of the machines (120-4) did not significantly reduce the concentration of bacteria in the cutting fluids when compared with the control machine (120-3), which had not undergone major cleaning. The concentrations of total bacteria were in the 10(6) CFU/mL range for these two lathes; however, a reduction in the total number of fluid changes was observed for this machine. Bacterial flora in the cutting fluids was significantly controlled with the use of biocides. Bacteria concentrations were in the 10(3)-10(5) CFU/mL range for the lathes with the use of biocides. Since thorough cleaning is insufficient and biocides are recognized as being responsible for some worker health problems, other avenues for controlling bacterial flora in cutting fluids should be evaluated to reduce worker exposure to their bacterial contaminants.


Effects of arginine-vasopressin and ACTH 4-10 on acquisition of active avoidance response in rats with alcohol pretreatment in prenatal and adult age.
Alcohol administration in drinking water to mother rats during gestation resulted in a permanent learning deficit of the offspring when behavioural reactions were tested in active avoidance conditioned reflex situation in adult age. A similar deficit of learning capacity was observed in adult rats following alcohol administration for two weeks; the acquisition of active avoidance response was tested later. Administration of arginine-vasopressin and ACTH 4-10 during behavioural test led to a significant improvement of learning ability of the animals pretreated with alcohol. The observations indicate that the ethanol-induced deficit of learning capacity involves peptidergic mechanisms and the behavioural manifestations following chronic alcohol treatment are not irreversible processes.


Tactical maneuvering and calculated risks: independent child migrants and the complex terrain of flight.
Similar to refugees in general, independent child migrants are frequently constructed in academic and popular discourse as passive and powerless or as untrustworthy and potentially threatening. Such portrayals fail to capture how these youth actively navigate the complex experiences of forced migration. Drawing on interviews with independent child migrants who arrived in Canada and on the conceptual framework of social navigation, we argue that contrary to being powerless, and despite significant structural barriers, these youth deliberately and thoughtfully navigate flight by making strategic decisions and taking calculated risks thereby ensuring their survival and well-being.


Targeting the hepatocyte growth factor/c-Met signaling pathway in renal cell carcinoma.
The product of a proto-oncogene, the c-Met protein is a transmembrane receptor tyrosine kinase. Its only known ligand, hepatocyte growth factor/scatter factor, regulates cell growth, motility, migration, invasion, proliferation, and angiogenesis. Dysregulation of c-Met and hepatocyte growth factor have been observed in both clear cell and non-clear cell renal cell carcinomas (RCCs), although only papillary RCCs harbor activating mutations in the MET gene. In clear cell RCC, there is evidence of a direct link between loss of von Hippel-Lindau and up-regulation of c-Met. As in other cancers, high expression of c-Met correlates with worse outcomes in RCC. In vitro and in vivo preclinical RCC models demonstrate cancer control with small molecule and antibodies against c-Met. Given these findings, the c-Met pathway is a logical therapeutic target in RCC, and several agents are in clinical testing with early signs of efficacy.


Hyper-invasive mutants define a novel Pho-regulated invasion pathway in Escherichia coli.
We have isolated two transposon insertion mutations of the pst-phoU operon which result in the constitutive expression of the phoA gene product, alkaline phosphatase. The two mutations also render Escherichia coli invasive towards cultured HEp-2 cells and define a novel Pho-regulated invasion pathway. The presence of the large 'invasion' plasmid derived from an entero-invasive E. coli (EIEC) clinical isolate in these mutants leads to enhanced invasiveness toward cultured HEp-2 cells, a phenomenon referred to as the 'hyper-invasive' phenotype. Transduction of a pst-phoU insertion mutation into clinical isolates of EIEC and Shigella flexneri results in constitutive PhoA expression and coupled hyper-invasiveness in the former but not the latter. We speculate that the Pho-regulated invasion pathway described here, while silent in bacteria grown in standard laboratory rich media, may become functional in the host when invasive bacteria encounter nutrient starvation and/or other related stress conditions.


COLONY SEX RATIOS, CONFLICT BETWEEN QUEENS AND WORKERS, AND APPARENT QUEEN CONTROL IN THE ANT PHEIDOLE DESERTORUM.
Sex-ratio conflict between queens and workers was explored in a study of colony sex ratios, relatedness, and population investment in the ant Pheidole desertorum. Colony reproductive broods consist of only females, only males, or have a sex ratio that is extremely male biased. Colonies producing females (female specialists) and colonies producing males (male specialists) occur at near equal frequency in the population. Most colonies apparently specialize in producing one reproductive sex throughout their life. Allozyme analyses show that relatedness does not differ within male-specialist and female-specialist colonies and they do not appear to differ in available resources. In the population, workers are nearly three times more closely related to females than males; however, the investment sex ratio is near equal (1.01, female/male), which is consistent with queen control. Selection should be strong on workers to increase investment in reproductive females, so why do workers in male-specialist colonies produce only (or nearly only) males? One hypothesis is that queens in male-specialist colonies prevent the occurrence of reproductive females, perhaps by producing worker-biased female eggs. An earlier simulation study of genetic evolution of sex ratios in social Hymenoptera (Pamilo 1982b) predicts that such mechanisms can result in the evolution of bimodal colony sex ratios and queen control. Results on P. desertorum are generally consistent with that study; however, information is not currently available to test some of the model's predictions and assumptions.


Perspectives in carotid body research.
This review deals with some basic mechanisms that are operative in carotid body chemoreception. It describes the evolution of concepts and different hypotheses or theories developed to explain possible mechanisms responsible for the onset of sensory discharges in the carotid nerve. Unfortunately, no single hypothesis has been proved beyond doubt, and this may explain their variety. At present, we do not know why this task has been so difficult, although one may think of several possibilities. 1) Carotid body chemoreceptors are anatomically complex being formed by glomus (type I) and sustentacular (type II) cells. Branches of the carotid (sinus) nerve innervate the glomus cells forming sensory synapses oriented in either or both directions and the junction is enveloped by processes of the sustentacular cells. 2) Chemoreceptors are polymodal, since they respond to a variety of natural and chemical stimuli. 3) It is possible that various stimuli may act on different elements of the receptor complex. 4) It is also possible that stimuli may act using different mechanisms. In addition, the multitude of biochemical and biophysical processes (some of them still unknown) operating at different receptor levels has made it very difficult to propose a unified mechanism of action.


[Use of botulinum neurotoxin therapy].
Botulinum neurotoxins (BoNTs), produced by the gram-positive anaerobic bacterium Clostridium botulinum, act on motor nerve endings and induce muscle relaxation. BoNT type A and B are used as therapeutic agents. Several preparations of BoNT type A are commercially available; Botox®, Dysport®, and Xeomin® are popular. They differ in the manufacturing method used, for example, BoNT consists of neurotoxin and a complex protein, Botox® and Dysport® contain a complex protein, whereas Xeomin® is free from the protein. However, when applied clinically, there is no significant difference in the efficacy and adverse effects between these BoNT products. Intramuscular BoNT injection is widely recognized as a safe and effective treatment for blepharospasm, hemifacial spasm, cervical dystonia, spasticity, squint, migraine, hyperhidrosis, wrinkles (cosmetic purpose), achalasia, hyperactive bladder, etc. BoNT preparations are used in more than 70 countries. In Japan, BoNT is used to treat blepharospasm, hemifacial spasm, cervical dystonia, and spasticity in addition to being used to treat wrinkles. However, its use is not yet widespread in Japan. This article reviews the structure and characteristics of BoNT, and throws light upon the technique of injecting BoNT.


[Cigarette manufacturers and their corrective statement].
Half a century of lying, an eighteen-year litigation, and an eleven-year disagreement with few words - to sum up a media campaign forced on cigarette manufacturers in the US at the turn of 2017/2018. In the given media, in the given extent and at the given frequency, they are forced to publish an apology for public lying with an impact on human health and lives.


Electrical properties in magnetic field of macroscopic carbon nanotube objects.
The electrical properties including zero-field resistivity, magnetoresistance and current-voltage (I-V) curves of macroscopic carbon nanotube (CNT) objects (yarns, bundles, films, and networks) have been measured. The macroscopic CNT objects exhibit semiconductor-like behaviors. Under the magnetic field applied perpendicular to the plane or axis of the Macroscopic CNT objects, a pronounced negative magnetoresistance have been observed. Due to the aligned, close-packed structure of MWNT yarn, its MR reach as high as -17% at 9 T. The I-V curves of the MWNT network exhibit a linear relationship even at low temperature, but the other samples exhibit a nonlinear relationship, indicating the effect of morphology and defects of CNTs in macroscopic CNT objects.


Immunologic observations in canine interstitial nephritis.
Immunofluorescence studies in cases of chronic interstitial nephritis (CIN) in the dog demonstrated deposition of canine IgC and C'3 in the thickened capillary walls of the glomeruli and in the mesangium. Eluates obtained from the nephritic kidneys contained antibodies of IgG type and reacted with autologous or homologous nephritic kidneys but not with normal kidneys or with any normal canine tissue. The staining pattern of fluorescein-conjugated eluates was similar to that obtained with anti-canine IgG or anti-canine C'3. The eluates did not contain leptospiral antibodies. The findings indicate that complement-fixing immune complexes are deposited in the damaged glomeruli in CIN. The nature of the antigen involved in these complexes is unknown, but it does not seem to be a component of normal canine tissue and could thus be viral or bacterial.


Comparison of the Measurement of Long-Term Care Costs between China and Other Countries: A Systematic Review of the Last Decade.
The rapid aging of populations in some countries has led to a growing number of the disabled elderly, creating a huge need for Long-Term Care (LTC) and meeting its costs, which is a heavy economic burden on the families of the disabled elderly and governments. Therefore, the measurement of Long-Term Care (LTC) costs has become an important basis for the government to formulate Long-Term Care (LTC) policies, and academic research on Long-Term Care (LTC) costs is also in the process of continuous development and deepening. This is a systematic review that aims to examine the evidence published in the last decade (2010-2019) regarding the comparison of the measurement of Long-Term Care (LTC) costs between China and other countries. Eighteen Chinese studies and 17 other countries' studies were included in this review. Most Chinese scholars estimated long-term care costs based on the degree of disability among the disabled elderly. However, the studies of European and American countries are more and more in-depth and comprehensive, and more detailed regarding the post-care cost of specific diseases, such as Parkinson's disease, Alzheimer's disease, and epilepsy. In future academic research, we should fully consider the human value of long-term care providers and further study the differences in the long-term care costs of different chronic diseases. In China's future policymaking, according to the experience of Germany, Sweden, and other countries, it may be an effective way to develop private long-term care insurance and realize the effective complementarity between private long-term care insurance and public long-term care insurance (LTCI).


Enhancement of Solar Fuel Production Schemes by Using a Ru,Rh,Ru Supramolecular Photocatalyst Containing Hydroxide Labile Ligands.
Polyazine-bridged Ru(II)Rh(III)Ru(II) complexes with two halide ligands, Cl(-) or Br(-), bound to the catalytically active Rh center are efficient single-component photocatalysts for H2O reduction to H2 fuel, with the coordination environment on Rh impacting photocatalysis. Herein reported is a new, halide-free Ru(II)Rh(III)Ru(II) photocatalyst with OH(-) ligands bound to Rh, further enhancing the photocatalytic reactivity of the structural motif. H2 production experiments using the photocatalyst bearing OH(-) ligands at Rh relative to the analogues bearing halides at Rh in solvents of varying polarity (DMF, CH3CN, and H2O) suggest that ion pairing with halides deactivates photocatalyst function, representing an exciting phenomenon to exploit in the development of catalysts for solar H2 production schemes.


Three New Abietane-Type Diterpenoids from Callicarpa macrophylla Vahl.
Three new abietane-type diterpenoids, named callicapoic acid M3 (1), callicapoic acid M4 (2) and callicapoic acid M5 (3), were isolated from the Callicarpa macrophylla Vahl. Their structures were established by spectroscopic techniques (IR, UV, MS, 1D and 2D NMR). All the isolated three compounds were evaluated for inhibitory activity on NO production in LPS-activated RAW 264.7 macrophage cells by using MTT assays. Compounds 1, 2 and 3 showed potent inhibitory activity, with inhibition rates of 34.47-40.13%.


Causal Relationship Between Inflammation and Preeclampsia: Genetic Evidence from a Mendelian Randomization Study.
Preeclampsia (PE) is a hypertensive disorder of pregnancy. PE patients were reported to have higher serum levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) than those in healthy controls. However, whether the expressions of these inflammation biomarkers have a causal relationship with PE is unspecified. We applied the Mendelian randomization method to infer the causal relationship between inflammation biomarkers (e.g., CRP, IL-6, interleukin 1 receptor antagonist [IL-1ra] and TNF-α) and PE. Single nucleotide polymorphisms (SNPs) strongly related to inflammation biomarkers were used as instrumental variables. CRP, IL-1ra and IL-6 levels showed no significant effect on PE progression, while the genetic predicted higher level of TNF-α significantly increased the risk of PE (OR per 1-SD increase in TNF-α: 4.33; 95% CI [1.99, 9.39]; p = .00021). The findings suggest that pro-inflammatory activity of TNF-α could be a determinant for PE progression. More antenatal care should be given to those pregnant women with higher level of inflammation biomarkers, especially TNF-α.


Comparative biomechanical testing of customized three-dimensional printing acetabular-wing plates for complex acetabular fractures.
Three-dimensional (3D) printing of an acetabular wing-plate is a new minimally invasive surgical technique for complex acetabular fractures. To investigate the biomechanical stability of 3D printing acetabular wing-plates. The results were compared with 2 conventional fixation systems. Eighteen fresh frozen cadaveric pelvises with both column fractures were randomly divided to 3 groups: A - iliosciatic plates fixation system; B - 3D printing plates; C - 2 parallel reconstruction plates fixation system. These constructions were loaded onto a biomechanical testing machine. Longitudinal displacement and stiffness values of the constructs were measured to estimate their stability. When the load force reached 700 N, Group A was superior to Group B in the longitudinal displacement of point 1 (p > 0.05). The longitudinal displacement of point 2 showed no significant differences among Groups A, B and C, and the displacement of the fracture line over point 3 showed no significant differences between Groups A and B (p > 0.05). The axial stiffness of Groups A, B and C were 122.4800 ±8.8480 N/mm, 168.4830 ±14.8091 N/mm and 83.1300 ±3.8091 N/mm, respectively. Group B was significantly stiffer than A and C (p < 0.05). Loads at failure of internal fixation were 1378.83 ±34.383 N, 1516.83 ±30.896 N and 1351.00 ±26.046 N for Groups A, B and C, respectively. Group B was significantly superior to Groups A and C (p > 0.05). Customized 3D printing acetabular-wing plates provide stability for acetabular fractures compared to intraspecific buttressing fixation.


The H2O2-regulated Ep5C gene encodes a peroxidase required for bacterial speck susceptibility in tomato.
Bacterial speck caused by the pathogen Pseudomonas syringae pv. tomato (P. s. tomato) is a devastating disease of tomato plants. Here we show that inhibition of Ep5C gene expression, which encodes a secreted cationic peroxidase, is sufficient to confer resistance against P. s. tomato. The inhibition of Ep5C protein accumulation in antisense tomato plants established resistance that was not accompanied by the pre-activation of known defense pathways. Therefore, Ep5C inhibition represents a novel form of disease resistance based on a loss-of-gene function in the plant required for successful infection by a compatible bacterial pathogen. Ep5C expression is rapidly induced by H2O2, a reactive oxygen intermediate normally generated during the course of a plant-pathogen interaction. This was corroborated by monitoring the expression of an Ep5C-GUS gene in transgenic Arabidopsis plants. Collectively, these results identify a signaling pathway that uses early signals generated during the oxidative burst, such as H2O2, for the selective activation of host factors required for mounting a compatible interaction. Thus, Ep5C provides a new resource for developing bacterial speck disease-resistant varieties.


Access to novel graphene-like sheet of hydroboron: first-principles investigation.
We designed a cyclic borane (B6 H12 ) molecule with a benzene-like structure, in which the six B atoms are located in the same plane. Three methods of B3LYP, MP2, and CCSD with the 6-311++G** basis were used to investigate its structure, electronic property, and stability. Next, we calculated the stability and electronic property of three hydroboron derivatives with fused rings of B10 H18 , B14 H24 , and B16 H26 . Finally, we investigated three types of novel two-dimensional infinite hydroboron sheets with diborane as a building block. The results of the phonon spectra ensure the dynamic stability of these predicted structures. Furthermore, the three types of hydroboron sheets are shown to have different band gap energies of less than 3.0 eV. Some investigations on the optical properties have also been performed. The predicted sheets are candidates for semiconductors, whose band gap energy can be tuned by the positions of the bridge hydrogen atoms in the sheets.


[Radiotherapy of inflammatory diseases -- indicated still today? (author's transl)].
The good response of inflammatory diseases to a low dose radiotherapy is well known. Mainly, this fact is based on experiences made in the time before antibacterial chemotherapy area. In this study our results are presented which were obtained by treating 90 patients with radiotherapy in the last years, exlusively. With respect to the end of the treatment a success rate of more than 90% was achieved. This result was compared with literature and with own findings from radiotherapy of patients with degenerative joint diseases. From the viewpoint of radio-protection the radiotherapy should be initiated as early as possible because in these cases better results could be attained at low doses. Especially, the radiotherapy of the following diseases seems to be favourable: parotitis, mastitis, abscess, furuncle, paronychia and panaritium. Besides the complications and risks of the chemotherapy the somatic and genetic radiation injuries are discussed. When radiation therapy is applied skilfully the side effects of a locally and regionally limited therapy may be neglected. It is recommended to extend the indication for radiotherapy of inflammatory diseases.


The change in position of the axillary nerve with rotation of the arm.
The axillary nerve is the most commonly injured nerve around the arm. In the deltopectoral approach, classical teaching states that lateral rotation of the humerus increases the distance between the subscapularis and the axillary nerve. This is the first anatomical study to quantify the distance change between the axillary nerve and subscapularis produced by arm rotation. Eight arms were placed in the supine position and a classical deltopectoral approach was performed. With digital calipers, measurements were made from the closest identifiable margin of the nerve to the inferior extent of the tenotomy. All measurements were made with the arm in 0° abduction and elbow in 90° of flexion, and repeated with the arm in 45° of medial rotation, 0° lateral rotation and 45° of lateral rotation. The mean d Axillary Nerve to subscapularis was recorded as 30.9 mm (95% CI:25.3-36.3), 39.4 mm(95% CI:34.1-44.8), and 46.1 mm (95% CI:41.1-51.2) for 45° MR, 0°, and 45° LR, respectively. Using paired-samples T-testing, the mean change in distance when moving from 45° MR to 0° was +8.5 mm (P < 0.0001), and from 0° to LR 45°, +6.7 mm (P < 0.0001). There is a significant difference in the distance between the subscapularis tenotomy and the axillary nerve with medial and lateral rotation. Laterally rotating the arm increased the distance by 6.7 mm, reaffirming that positioning the glenohumeral joint in a position of LR during subscapular tenotomy is protective against iatrogenic injury of the axillary nerve. Clin. Anat. 32:268-271, 2019. © 2018 Wiley Periodicals, Inc.