Emerging zoonoses.
In the past few years, emergent disease episodes have increased; nearly all have involved zoonotic or species-jumping infectious agents. Because there is no way to predict when or where the next important new zoonotic pathogen will emerge or what its ultimate importance might be, investigation at the first sign of emergence of a new zoonotic disease is particularly important. Such investigation may be described in terms of a discovery-to-control continuum: from recognition of a new disease in a new setting to complex phases involving the hard science disciplines pertaining to discovery, the epidemiologic sciences pertaining to risk assessment, and activities pertaining to risk management. Today, many activities involving zoonotic disease control are at risk because of a failed investigative infrastructure or financial base. Because zoonotic diseases are distinct, their prevention and control will require unique strategies, based more on fundamental research than on traditional approaches. Such strategies require that we rebuild a cadre of career-committed professionals with a holistic appreciation of several medical and biologic sciences.


Natural and Synthetic Variants of the Tricarboxylic Acid Cycle in Cyanobacteria: Introduction of the GABA Shunt into Synechococcus sp. PCC 7002.
For nearly half a century, it was believed that cyanobacteria had an incomplete tricarboxylic acid (TCA) cycle, because 2-oxoglutarate dehydrogenase (2-OGDH) was missing. Recently, a bypass route via succinic semialdehyde (SSA), which utilizes 2-oxoglutarate decarboxylase (OgdA) and succinic semialdehyde dehydrogenase (SsaD) to convert 2-oxoglutarate (2-OG) into succinate, was identified, thus completing the TCA cycle in most cyanobacteria. In addition to the recently characterized glyoxylate shunt that occurs in a few of cyanobacteria, the existence of a third variant of the TCA cycle connecting these metabolites, the γ-aminobutyric acid (GABA) shunt, was considered to be ambiguous because the GABA aminotransferase is missing in many cyanobacteria. In this study we isolated and biochemically characterized the enzymes of the GABA shunt. We show that N-acetylornithine aminotransferase (ArgD) can function as a GABA aminotransferase and that, together with glutamate decarboxylase (GadA), it can complete a functional GABA shunt. To prove the connectivity between the OgdA/SsaD bypass and the GABA shunt, the gadA gene from Synechocystis sp. PCC 6803 was heterologously expressed in Synechococcus sp. PCC 7002, which naturally lacks this enzyme. Metabolite profiling of seven Synechococcus sp. PCC 7002 mutant strains related to these two routes to succinate were investigated and proved the functional connectivity. Metabolite profiling also indicated that, compared to the OgdA/SsaD shunt, the GABA shunt was less efficient in converting 2-OG to SSA in Synechococcus sp. PCC 7002. The metabolic profiling study of these two TCA cycle variants provides new insights into carbon metabolism as well as evolution of the TCA cycle in cyanobacteria.


Therapy-related myelodysplasia and acute myeloid leukemia after Ewing sarcoma and primitive neuroectodermal tumor of bone: A report from the Children's Oncology Group.
This study describes the magnitude of risk of therapy-related myelodysplasia and acute myeloid leukemia (t-MDS/AML) in 578 individuals diagnosed with Ewing sarcoma and enrolled on Children's Oncology Group therapeutic protocol, INT-0091. Between 1988 and 1992, patients with or without metastatic disease were randomized to receive doxorubicin, vincristine, cyclophosphamide, and dactinomycin (regimen A) or these 4 drugs alternating with etoposide and ifosfamide (regimen B). Between 1992 and 1994, patients with metastatic disease were nonrandomly assigned to receive high-intensity therapy (regimen C: regimen B therapy with higher doses of doxorubicin, cyclophosphamide, and ifosfamide). Median age at diagnosis of Ewing sarcoma was 12 years, and median length of follow-up, 8 years. Eleven patients developed t-MDS/AML, resulting in a cumulative incidence of 2% at 5 years. While patients treated on regimens A and B were at a low risk for development of t-MDS/AML (cumulative incidence: 0.4% and 0.9% at 5 years, respectively), patients treated on regimen C were at a 16-fold increased risk of developing t-MDS/AML (cumulative incidence: 11% at 5 years), when compared with those treated on regimen A. Increasing exposure to ifosfamide from 90 to 140 g/m2, cyclophosphamide from 9.6 to 17.6 g/m2, and doxorubicin from 375 to 450 mg/m2 increased the risk of t-MDS/AML significantly.


Proteomic approaches within the NCI early detection research network for the discovery and identification of cancer biomarkers.
In the postgenome era, proteomics provides a powerful approach for the analysis of normal and transformed cell functions, for the identification of disease-specific targets, and for uncovering novel endpoints for the evaluation of chemoprevention agents and drug toxicity. Unfortunately, the genomic information that has greatly expounded the genetic basis of cancer does not allow an accurate prediction of what is actually occurring at the protein level within a given cell type at any given time. The gene expression program of a given cell is affected by numerous factors in the in vivo environment resulting from tissue complexity and organ system orchestration, with cells acting in concert with each other and responding to changes in their microenvironment. Repositories of genomic information can be considered master "inventory lists" of genes and their maps, which need to be supplemented with protein-derived information. The National Cancer Institute's Early Detection Research Network is employing proteomics, or "protein walking", in the discovery and evaluation of biomarkers for cancer detection and for the identification of high-risk subjects. Armed with microdissection techniques, including the use of Laser Capture Microdissection (LCM) to procure pure populations of cells directly from human tissue, the Network is facilitating the development of technologies that can overcome the problem of tissue heterogeneity and address the need to identify markers in easily accessible biological fluids. Proteomic approaches complement plasma-based assays of circulating DNA for cancer detection and risk assessment. LCM, coupled with downstream proteomics applications, such as two-dimensional polyacrylamide gel electrophoresis and SELDI (surface enhanced laser desorption ionization) separation followed by mass spectrometry (MS) analysis, may greatly facilitate the characterization and identification of protein expression changes that track normal and disease phenotypes. We highlight recent work from Network investigators to demonstrate the potential of proteomics to identify proteins present in cancer tissues and body fluids that are relevant for cancer screening.


16S rRNA gene sequences of 'Candidatus Campylobacter hominis', a novel uncultivated species, are found in the gastrointestinal tract of healthy humans.
Although some Campylobacter species are agents of gastroenteritis and periodontal disease in humans, little is known of the variety of campylobacters in the gastrointestinal tract of healthy individuals. This paper provides evidence for the existence of a previously undescribed, uncultivated Campylobacter species that may be a commensal in the healthy human gut. Saliva and faeces from 20 healthy individuals were examined by PCR assays specific for nine species of campylobacter (C. sputorum, C. concisus, C. upsaliensis, C. helveticus, C. lari, C. fetus, C. hyointestinalis, C. jejuni and C. coli) and for the genus as a whole. Genus-specific amplicons were produced from 19 of 20 saliva samples and from 18 of 20 faecal samples. C. concisus species-specific amplicons were produced from 19 of 20 saliva samples and 3 of 20 faecal samples. The faecal samples were all PCR-negative for other Campylobacter species. Three unidentified 16S rRNA Campylobacter genus-specific amplicons of faecal origin were sequenced. Phylogenetic analysis showed that these sequences were 99% similar, and clustered within the genus as a novel group which was termed HS (HS = healthy subject). A PCR primer pair specific for the HS group was designed from the sequence data and used to reexamine the original samples. Although it was not possible to culture the organism from faeces, specific PCR assay detected it in 10 of the 20 faecal samples, but not in any corresponding saliva samples. The authors propose that the source of the amplicons is a previously undescribed and so far uncultivated species, which they term 'Candidatus Campylobacter hominis'.


Digital all-sky polarization imaging of partly cloudy skies.
Clouds reduce the degree of linear polarization (DOLP) of skylight relative to that of a clear sky. Even thin subvisual clouds in the "twilight zone" between clouds and aerosols produce a drop in skylight DOLP long before clouds become visible in the sky. In contrast, the angle of polarization (AOP) of light scattered by a cloud in a partly cloudy sky remains the same as in the clear sky for most cases. In unique instances, though, select clouds display AOP signatures that are oriented 90 degrees from the clear-sky AOP. For these clouds, scattered light oriented parallel to the scattering plane dominates the perpendicularly polarized Rayleigh-scattered light between the instrument and the cloud. For liquid clouds, this effect may assist cloud particle size identification because it occurs only over a relatively limited range of particle radii that will scatter parallel polarized light. Images are shown from a digital all-sky-polarization imager to illustrate these effects. Images are also shown that provide validation of previously published theories for weak (approximately 2%) polarization parallel to the scattering plane for a 22 degrees halo.


Can we predict immediate outcome after laparoscopic rectal surgery? Multivariate analysis of clinical, anatomic, and pathologic features after 3-dimensional reconstruction of the pelvic anatomy.
The laparoscopic approach for colon resection is widely accepted but its definitive role in rectal tumors is controversial due to the technical difficulties associated with this procedure. Tumor size and volume, and pelvic dimensions may influence intraoperative and/or immediate outcome. This study aimed to evaluate the predictive value of anatomic and pathologic features on immediate outcome after laparoscopic rectal resection. The study included a prospective series of 60 patients submitted to laparoscopic resection for rectal tumors. A preoperative computed tomography was performed in all patients. Three-dimension reconstruction of the pelvis, rectal tumor, and prostate was computed. Tumor and prostate volume and diameters were calculated, as were main pelvic diameters (subsacrum-retropubic, coccyx pubis, and promontorium coccyx), and lateral diameters, at the tumor level (3D Doctor Software package). Age, sex, body mass index (BMI), tumor height, previous radiotherapy treatment, and type of procedure (anterior resection, low anterior resection, and abdominoperineal resection) were recorded. Immediate outcome (morbidity, mortality, and stay) was also collected. Dependent variables were operative time, intraoperative difficulty, conversion, and postoperative morbidity. Univariate and multivariate analyses were performed (SPSS package). The series included 36 men and 24 women, with a mean age of 72 years (range, 38-87). Surgical procedures were 10 anterior resections, 31 low anterior resections, and 19 abdominoperineal resections. Conversion rate was 9 of 60 (15%), operative time: 172 minutes (range, 90-360), morbidity: 31% and stay: 9 days (range, 6-43). Multivariate analysis showed tumor craniocaudal length was an independent predictive factor for conversion (P < 0.04, odds ratio [OR]: 1.5, confidence interval [CI]95%: 1-2.2). Pubic coccyx axis (P < 0.005) and sex (P < 0.009) showed independent values for operative time, and BMI (P < 0.02, OR: 1.2, CI 95%:1-1.5) was related to postoperative morbidity. When a subanalysis was performed in relation to sex, independent factors differed between males and females, with a predominance of anatomic and tumor measures in men. Local anatomy and pathologic features directly affect surgical outcome in the laparoscopic approach to the rectum. Sex, BMI, lower pelvis diameter, and tumor size are independent predictors for conversion, operative time, and morbidity. These data should be taken into account when planning this kind of procedure.


Influence of component alignment on outcome for unicompartmental knee replacement.
This study's aim was to assess the effect of component mal-alignment on outcome of Oxford Unicompartmental Knee Replacement (UKR). Two hundred and eleven knees implanted with a medial UKR, using a minimally invasive approach, were followed up at a minimum of 4 years. Sagittal and frontal plane femoral and tibial component alignments were determined from antero-posterior and lateral radiographs. The cohort was divided into alignment groups which represented consecutive 2.5 degrees intervals over the range of measured values for femoral varus/valgus, femoral flexion/extension, tibial varus/valgus and tibial tilt. The Oxford Knee Score (OKS) and incidence of radiolucency (RL) were compared between alignment groups for each alignment parameter. In 98% of cases the femoral components were positioned between 10 degrees varus and 10 degrees valgus; all femoral components were within +/-10 degrees flexion. In 92% of cases the tibial components were positioned between +/-5 degrees varus/valgus and superior/inferior tilt (neutral tilt being 7 degrees). Within these ranges there were no significant differences in OKS or RL between the alignment groups; nor were there any differences between those at the extremes of component alignment compared to those in the inner ranges of alignment. We conclude that, because of the spherical femoral component, the Oxford UKR is tolerant to femoral mal-alignment of 10 degrees and tibial mal-alignment of 5 degrees.


miR-346 and miR-582-3p-regulated EG-VEGF expression and trophoblast invasion via matrix metalloproteinases 2 and 9.
Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an important regulator for embryo implantation and placental development, and is clinically associated with several obstetric disorders related to insufficient or inappropriate trophoblast invasion, such as recurrent abortion, preeclampsia, and intrauterine fetal growth restriction. This study was performed to identify the microRNAs targeting EG-VEGF, and evaluate the regulatory effect on trophoblast biology. miR-346 and miR-582-3p were initially identified via bioinformatic tools, and their specific binding sites on the EG-VEGF 3'UTR were further confirmed using dual luciferase and a co-transfection assays. miR-346 and miR-582-3p were demonstrated not only to suppress EG-VEGF expression, but also inhibit trophoblast invasion and migration in the JAR and HTR-8/SVneo cell lines. We further evaluated the effect of microRNAs in HTR-8/SVneo cells coexpressing EG-VEGF and miR-346 or miR-582-3p on matrix metalloproteinase (MMP 2 and MMP 9) and the tissue inhibitors of metalloproteinase (TIMP 1 and TIMP 2) using RT-PCR, western blotting and gelatin zymography. TIMP 1 and TIMP 2 were not affected by the two microRNAs, whereas the expressions and activities of MMP 2 and MMP 9 were significantly downregulated, which in turn inhibited the invasion ability of trophoblasts. In conclusion, miR-346 and miR-582-3p regulate EG-VEGF-induced trophoblast invasion through repressing MMP 2 and MMP 9, and may become novel diagnostic biomarkers or therapeutic targets for EG-VEGF-related obstetric disorders. © 2016 BioFactors, 43(2):210-219, 2017.


Medicaid Coverage of Methadone Maintenance and the Use of Opioid Agonist Therapy Among Pregnant Women in Specialty Treatment.
Opioid agonist therapy (OAT) is the standard of care for pregnant women with opioid use disorder (OUD). Medicaid coverage policies may strongly influence OAT use in this group. To examine the association between Medicaid coverage of methadone maintenance and planned use of OAT in the publicly funded treatment system. Retrospective cross-sectional analysis of treatment admissions in 30 states extracted from the Treatment Episode Data Set (2013 and 2014). Medicaid-insured pregnant women with OUD (n=3354 treatment admissions). The main outcome measure was planned use of OAT on admission. The main exposure was state Medicaid coverage of methadone maintenance. Using multivariable logistic regression models adjusting for sociodemographic, substance use, and treatment characteristics, we compared the probability of planned OAT use in states with Medicaid coverage of methadone maintenance versus states without coverage. A total of 71% of pregnant women admitted to OUD treatment were 18-29 years old, 85% were white non-Hispanic, and 56% used heroin. Overall, 74% of admissions occurred in the 18 states with Medicaid coverage of methadone maintenance and 53% of admissions involved planned use of OAT. Compared with states without Medicaid coverage of methadone maintenance, admissions in states with coverage were significantly more likely to involve planned OAT use (adjusted difference: 32.9 percentage points, 95% confidence interval, 19.2-46.7). Including methadone maintenance in the Medicaid benefit is essential to increasing OAT among pregnant women with OUD and should be considered a key policy strategy to enhance outcomes for mothers and newborns.


F-box proteins elongate translation during stress recovery.
Protein synthesis is energetically costly and is tightly regulated by evolutionarily conserved mechanisms. Under restrictive growth conditions and in response to various stresses, such as DNA damage, cells inhibit protein synthesis to redirect available adenosine triphosphate to more essential processes. Conversely, proliferating cells, such as cancer cells, increase protein synthetic rates to support growth-related anabolic processes. mRNA translation occurs in three separate phases, consisting of initiation, elongation, and termination. Although all three phases are highly regulated, most of the translational control occurs at the rate-limiting initiation step. New evidence has described a molecular mechanism involved in the regulation of translation elongation. DNA damage initially slowed down elongation rates by activating the eukaryotic elongation factor 2 kinase (eEF2K) through an adenosine monophosphate (AMP)-activated protein kinase (AMPK)-dependent mechanism. However, during checkpoint recovery, the SCF (Skp, Cullin, F-box-containing) βTrCP (β-transducin repeat-containing protein) E3 ubiquitin ligase promoted degradation of eEF2K, thereby allowing the restoration of peptide chain elongation. These findings establish an important link between DNA damage signaling and the regulation of translation elongation.


North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension.
Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world where TIPS creation is performed primarily by hepatologists. Thus, the successful use of TIPS in North America is dependent on a multidisciplinary approach and technical expertise, so as to optimize outcomes. Recently, new procedural techniques, TIPS stent technology, and indications for TIPS have emerged. As a result, practices and outcomes vary greatly across institutions and significant knowledge gaps exist. In this consensus statement, the Advancing Liver Therapeutic Approaches group critically reviews the application of TIPS in the management of portal hypertension. Advancing Liver Therapeutic Approaches convened a multidisciplinary group of North American experts from hepatology, interventional radiology, transplant surgery, nephrology, cardiology, pulmonology, and hematology to critically review existing literature and develop practice-based recommendations for the use of TIPS in patients with any cause of portal hypertension in terms of candidate selection, procedural best practices and, post-TIPS management; and to develop areas of consensus for TIPS indications and the prevention of complications. Finally, future research directions are identified related to TIPS for the management of portal hypertension.


Disease heterogeneity: does it impact our ability to detect dietary associations with breast cancer?
It is generally believed that breast cancer is a multistage process and that multiple and varying genetic events occur on the pathway to disease. We hypothesize that disease heterogeneity has an impact on our ability to identify risk factors. If a genetic alteration occurred in 50% of cases and a risk factor was associated only with that specific alteration, a risk estimate of 1.6 would be detected rather than the true risk estimate of 2.5 if analyses had been limited to those cases with the genetic alteration. Based on the literature we know that many genetic alterations occur in less than 50% of breast tumors. Thus, if environmental factors are related to some, but not all genetic alterations, we are decreasing our ability to identify potentially important risk factors. We therefore hypothesize that identification of dietary factors associated with breast cancer has been hampered by our inability to identify and capture the unique disease pathways which exist and contribute to the heterogeneity of common cancers such as breast cancer.


Molecular basis of the copulatory plug polymorphism in Caenorhabditis elegans.
Heritable variation is the raw material for evolutionary change, and understanding its genetic basis is one of the central problems in modern biology. We investigated the genetic basis of a classic phenotypic dimorphism in the nematode Caenorhabditis elegans. Males from many natural isolates deposit a copulatory plug after mating, whereas males from other natural isolates?including the standard wild-type strain (N2 Bristol) that is used in most research laboratories?do not deposit plugs. The copulatory plug is a gelatinous mass that covers the hermaphrodite vulva, and its deposition decreases the mating success of subsequent males. We show that the plugging polymorphism results from the insertion of a retrotransposon into an exon of a novel mucin-like gene, plg-1, whose product is a major structural component of the copulatory plug. The gene is expressed in a subset of secretory cells of the male somatic gonad, and its loss has no evident effects beyond the loss of male mate-guarding. Although C. elegans descends from an obligate-outcrossing, male?female ancestor, it occurs primarily as self-fertilizing hermaphrodites. The reduced selection on male?male competition associated with the origin of hermaphroditism may have permitted the global spread of a loss-of-function mutation with restricted pleiotropy.


JC virus T-antigen in colorectal cancer is associated with p53 expression and chromosomal instability, independent of CpG island methylator phenotype.
JC virus has a transforming gene encoding JC virus T-antigen (JCVT). JCVT may inactivate wild-type p53, cause chromosomal instability (CIN), and stabilize beta-catenin. A link between JCVT and CpG island methylator phenotype (CIMP) has been suggested. However, no large-scale study has examined the relations of JCVT with molecular alterations, clinical outcome, or prognosis in colon cancer. We detected JCVT expression (by immunohistochemistry) in 271 (35%) of 766 colorectal cancers. We quantified DNA methylation in eight CIMP-specific promoters (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1) and eight other loci (CHFR, HIC1, IGFBP3, MGMT, MINT1, MINT31, p14, WRN) by MethyLight. We examined loss of heterozygosity in 2p, 5q, 17q, and 18q. JCVT was significantly associated with p53 expression (P < .0001), p21 loss (P < .0001), CIN (>/=2 chromosomal segments with LOH; P < .0001), nuclear beta-catenin (P = .006), LINE-1 hypomethylation (P = .002), and inversely with CIMP-high (P = .0005) and microsatellite instability (MSI) (P < .0001), but not with PIK3CA mutation. In multivariate logistic regression analysis, the associations of JCVT with p53 [adjusted odds ratio (OR), 8.45; P < .0001], CIN (adjusted OR, 2.53; P = .003), cyclin D1 (adjusted OR, 1.57; P = .02), LINE-1 hypomethylation (adjusted OR, 1.97 for a 30% decline as a unit; P = .03), BRAF mutation (adjusted OR, 2.20; P = .04), and family history of colorectal cancer (adjusted OR, 0.64; P = .04) remained statistically significant. However, JCVT was no longer significantly associated with CIMP, MSI, beta-catenin, or cyclooxygenase-2 expression in multivariate analysis. JCVT was unrelated with patient survival. In conclusion, JCVT expression in colorectal cancer is independently associated with p53 expression and CIN, which may lead to uncontrolled cell proliferation.


Rejection sensitivity polarizes striatal-medial prefrontal activity when anticipating social feedback.
As a social species, humans are acutely aware of cues that signal inclusionary status. This study characterizes behavioral and neural responses when individuals anticipate social feedback. Across two fMRI studies, participants (n = 42) made social judgments about supposed peers and then received feedback from those individuals. Of particular interest was the neural activity occurring when participants were awaiting social feedback. During this anticipatory period, increased neural activity was observed in the ventral striatum, a central component of the brain's reward circuitry, and dorsomedial pFC, a brain region implicated in mentalizing about others. Individuals high in rejection sensitivity exhibited greater responses in both the ventral striatum and dorsomedial pFC when anticipating positive feedback. These findings provide initial insight into the neural mechanisms involved in anticipating social evaluations as well as the cognitive processes that underlie rejection sensitivity.


Methodological issues in using drugs data in epidemiology.
Using drugs data in epidemiological studies is becoming fashionable with the large databases available today. We describe the philosophical basis and the main methodological issues. The process leading a patient affected by a disease to be treated with an appropriate drug appears to be complex, and influenced by external and internal many factors, described here. The disease-drug use relationship is disentangled describing its main characteristics. Drug use data means the information concerning the use of drugs, which encompasses any form of record, on paper or computerised, collected from patients, doctors prescribing the drug, pharmacists dispensing it, the drug company that produces it, or its distributor. The possible sources of drug use data are described, along with the possible strengths and weaknesses of each source. Various examples of uses of drug utilisation data as indicator in epidemiological researches are presented. Drug utilisation studies are a recent issue of public health research, merging knowledge of public health doctors, epidemiologists, pharmacologists and health economists. Automated databases demonstrate nowadays to be a valuable approach to drug utilisation investigation. In conclusion, the aim of any forward looking health care system should be to collect and freely circulate these detailed information, allowing not only useful health care planning but also indeep, population based, health research.


No obligation? How gender influences the relationship between perceived organizational support and organizational citizenship behavior.
Previous research indicates that perceived organizational support (POS) elicits felt obligation on the part of employees who, in turn, reciprocate by helping the organization through the performance of organizational citizenship behavior (OCB). However, because gender roles dictate that women should be more helpful than men, women may feel more obligated to engage in OCB even when they experience relatively low levels of POS, whereas men may perform OCB only when they experience relatively high levels of POS. In this article, we use social role theory to predict that the relationship between POS and 3 types of OCB will be stronger for men than for women. Our results, using 4 samples of employee-supervisor dyads, support this prediction. Further, in 2 of those samples, we also investigate the possibility that gender moderates the positive POS-felt obligation relationship and the indirect effect of POS on OCB via felt obligation. Taken together, we find evidence of first-stage moderated-mediation. Specifically, the relationship between POS and felt obligation is moderated by gender, such that this relationship is stronger for men than for women (who feel more obligation, even at relatively low levels of POS). Felt obligation mediated the POS-OCB relationship, but only for men. Our findings suggest that men are more likely than women to need POS to feel obligated to make reciprocal organizational exchanges. Implications and future research directions are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Organic amendment treatments for antimicrobial resistance and mobile element genes risk reduction in soil-crop systems.
Agricultural fertilization with organic amendments of animal origin often leads to antibiotic resistance dissemination. In this study, we evaluated the effect of different treatments (anaerobic digestion, biochar application, ozonation, zerovalent iron nanoparticle application, and spent mushroom substrate addition) on the resistome in dairy cow manure-derived amendments (slurry, manure, and compost). Anaerobic digestion and biochar application resulted in the highest reduction in antibiotic resistance gene (ARG) and mobile genetic element (MGE) gene abundance. These two treatments were applied to cow manure compost, which was then used to fertilize the soil for lettuce growth. After crop harvest, ARG and MGE gene absolute and relative abundances in the soil and lettuce samples were determined by droplet digital PCR and high-throughput qPCR, respectively. Prokaryotic diversity in cow manure-amended soils was determined using 16S rRNA metabarcoding. Compared to untreated compost, anaerobic digestion led to a 38% and 83% reduction in sul2 and intl1 absolute abundances in the soil, respectively, while biochar led to a 60% reduction in intl1 absolute abundance. No differences in lettuce gene abundances were observed among treatments. We conclude that amendment treatments can minimize the risk of antibiotic resistance in agroecosystems.


Atypical ductal hyperplasia diagnosis by directional vacuum-assisted stereotactic biopsy of breast microcalcifications. Considerations for surgical excision.
In 824 patients who underwent directional vacuum-assisted biopsies (DVABs) of breast microcalcifications, 61 (7.4%) showed atypical ductal hyperplasia (ADH). The 42 who subsequently underwent excision were the subjects of this study. Cases were evaluated for the mammographic characteristics of the lesion, the percentage of lesion removed according to mammography, and histologic findings (including number of large ducts and/or terminal duct-lobular units involved with ADH) in DVAB specimens. Pathologic findings in the surgical specimens in the area of the biopsy site also were recorded. In the DVAB specimens, ADH was confined to an average of 1.5 large ducts or lobular units and was associated with microcalcifications in all of the patients. Surgical specimens showed ADH in 15 cases, no residual lesion in 24 cases, and ductal carcinoma in situ in 3 cases. We found that microcalcifications that contain ADH in less than 3 lobules or ducts and/or that are removed completely by DVAB do not reveal higher-risk lesions on excision; thus, removal is unnecessary. When assessing microcalcifications with ADH, clinicians should consider the percentage of microcalcifications removed by DVAB and the extent of lobular involvement to better assess the need for excision.


Associations between age, social reward processing and social anxiety symptoms.
Reward processing undergoes marked changes in adolescence, with social interactions representing a powerful source of reward. Reward processing is also an important factor in the development of social anxiety disorder, a condition that most commonly first appears in adolescence. This study investigated the relationship between age, social reward processing and social anxiety in a cross-sectional sample of female participants (N = 80) aged 13-34. Participants performed two versions of a probabilistic reward anticipation task, in which a speeded response could result in different probabilities of receiving either social or monetary rewarding feedback. Participants also completed self-report assessments of social reward value, trait anxiety and social anxiety symptoms. At high reward probabilities, performance on both reward tasks showed a quadratic effect of age, with the fastest responses at around 22-24 years. A similar quadratic effect was found for subjective liking ratings of both reward stimuli, although these were not associated with performance. Social anxiety was not associated with a subjective liking of the rewards but did predict performance on both tasks at all reward probabilities. Age-related variation in reward processing was not accounted for by age-related variation in social anxiety symptoms, suggesting that, while both social anxiety and age were associated with variation in reward processing, their effects were largely independent. Together, these findings provide evidence that social reward processing continues to develop across adolescence and that individual differences in social anxiety should be considered when considering reward sensitivity during this period. The online version contains supplementary material available at 10.1007/s12144-023-04551-y.


The Effect of Enamel Sandblasting on Enhancing Bond Strength of Orthodontic Brackets: A Systematic Review and Meta-analysis.
To critically appraise the evidence regarding the effect of enamel sandblasting on the bond strength of orthodontic brackets on either the labial or lingual tooth surface. An electronic database search of published and unpublished literature was performed. Search terms included sandblasting, enamel abrasion, tooth surface, bond strength, bond failure, and adhesive remnant; data were extracted in standardized piloted forms. Risk of bias was assessed using the Cochrane risk of bias tool, adapted for in vitro studies where necessary. Of the 81 articles initially retrieved, 13 were eligible for inclusion in the systematic review. All of the latter were in vitro studies with unclear risk of bias primarily due to unclear reporting of blinding of outcome assessors. Eight studies assessed the combined effect of enamel sandblasting and etching, while only five evaluated the isolated effect of sandblasting on the buccal enamel surface. In view of the apparently heterogeneous study settings, intervention protocols, specimen preparation and storage sequences, only two studies were deemed eligible for quantitative synthesis. Random effects meta-analysis revealed no evidence to support sandblasting prior to etching over etching alone with regard to shear bond strength of orthodontic brackets bonded in vitro to lingual enamel surfaces of extracted premolars (standardized mean difference: 0.36; 95% CI: -0.21, 0.94; p = 0.22). The findings of the present study cannot support lingual enamel sandblasting prior to etching for augmentation of the bond strength of orthodontic brackets.


Reliability of three landmarking methods for dual inclinometry measurements of lumbar flexion and extension.
To examine the intra and inter-rater reliability of lumbar flexion and extension measurements attained using three landmarking methods for dual inclinometry. This was a repeated measures reliability study. Convenience sampling was used to obtain forty volunteer subjects. Two assessors measured a series of lumbar flexion and extension movements using the J-Tech™ dual inclinometer. Three different landmarking methods were used: 1) straight palpation of PSIS and L1, 2) palpation of PSIS and the site of the nearest 5 cm interval point closest to L1 and 3) location of PSIS and 15 cm cephalad. Upon landmarking, adhesive tape was used to mark landmarks and the inclinometer was placed on sites for three trials of flexion and extension. Tape was removed and landmarks were relocated by the same assessor (intra-rater) for an additional three trials; and this process was repeated by a second assessor (inter-rater). Reliability was determined using intra-class correlation coefficients. Reliability within a set of three repetitions was very high (ICCs > 0.90); intra-rater reliability after relocating landmarks was high (ICCs > 0.80); reliability between therapists was moderate to high (0.60 > ICCs < 0.76). Assessment of flexion and extension movements by straight palpation of bony landmarks as in the Straight palpation of PSIS and L1 method (ICC: Flexion 0.60; Extension 0.74) was found to be marginally less reliable than the other two landmarking measurement strategies (ICC: Flexion 0.66; Extension 0.76). All three methods of land marking are reliable. We recommend the use of the PSIS to 15 cm cephalad method as used in the modified-modified Schobers test as it is the simplest to perform and aligns with current clinical practice.


Invasive versus medically managed acute coronary syndromes with prior bypass (CABG-ACS): insights into the registry versus randomised trial populations.
Coronary artery bypass graft (CABG) patients are under-represented in acute coronary syndrome (ACS) trials. We compared characteristics and outcomes for patients who did and did not participate in a randomised trial of invasive versus non-invasive management (CABG-ACS). ACS patients with prior CABG in four hospitals were randomised to invasive or non-invasive management. Non-randomised patients entered a registry. Primary efficacy (composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction (MI), heart failure) and safety outcomes (composite of bleeding, stroke, procedure-related MI, worsening renal function) were independently adjudicated. Of 217 patients screened, 84 (39%) screenfailed, of whom 24 (29%) did not consent and 60 (71%) were ineligible. Of 133 (61%) eligible, 60 (mean±SD age, 71±9 years, 72% male) entered the trial and 73 (age, 72±10 years, 73% male) entered a registry (preferences: physician (79%), patient (38%), both (21%)).Compared with trial participants, registry patients had more valve disease, lower haemoglobin, worse New York Heart Association class and higher frailty.At baseline, invasive management was performed in 52% and 49% trial and registry patients, respectively, of whom 32% and 36% had percutaneous coronary intervention at baseline, respectively (p=0.800). After 2 years follow-up (694 (median, IQR 558-841) days), primary efficacy (43% trial vs 49% registry (HR 1.14, 95% CI 0.69 to 1.89)) and safety outcomes (28% trial vs 22% registry (HR 0.74, 95% CI 0.37 to 1.46)) were similar. EuroQol was lower in registry patients at 1 year. Compared with trial participants, registry participants had excess morbidity, but longer-term outcomes were similar. NCT01895751.


The Malnutrition Awareness Scale for community-dwelling older adults: Development and psychometric properties.
Qualitative studies suggest that malnutrition awareness is poor in older adults. The aim of this study was to develop a questionnaire to quantitatively assess malnutrition awareness in community-dwelling older adults aged 60+ years. The Malnutrition Awareness Scale (MAS) was developed based on the awareness phase of the Integrated-Change model, and included four domains: knowledge, perceived cues, risk perceptions, and cognizance. Twenty-six scale items were developed using results from mainly qualitative research and the expertise of the authors. Items were piloted in 10 Dutch older adults using the Thinking Aloud method to optimize wording. In a feasibility study, annoyance, difficulty and time to complete the MAS and its comprehensibility were tested. After final revisions, the MAS was applied to a large sample to test its psychometric properties (i.e., inter-item correlations, Cronbach's alpha, score distribution) and relevance of the items was rated on a 5-point scale by 12 experts to determine content validity. The feasibility study (n = 42, 55 % women, 19 % 80+ y) showed that the MAS took 12 ± 6 min to complete. Most participants found it not (at all) annoying (81 %) and not (at all) difficult (79 %) to complete the MAS, and found it (very) comprehensible (83 %). Psychometric analyses (n = 216, 63 % women, 28 % 80+ y) showed no redundant items, but two items correlated negatively with other items, and one correlated very low. After removal, the final MAS consists of 23 items with a min-max scoring range from 0 to 22 (with higher scores indicating higher awareness) and an overall Cronbach's alpha of 0.67. The mean MAS score in our sample (n = 216) was 14.8 ± 3.2. The lowest obtained score was 6 (n = 3) and the highest 22 (n = 1), indicating no floor or ceiling effects. Based on the relevance rating, the overall median across all 22 items was 4.0 with IQR 4.0-5.0. The Malnutrition Awareness Scale is a novel, feasible and reliable tool with good content validity to quantitively assess malnutrition awareness in community-dwelling older adults. The scale is now ready to identify groups with poor malnutrition awareness, as a basis to start interventions to increase malnutrition knowledge and awareness.


Seasonal trophic ecology of the dominant Antarctic coral Malacobelemnon daytoni (Octocorallia, Pennatulacea, Kophobelemnidae).
Antarctic ecosystems present highly marked seasonal patterns in energy input, which in turn determines the biology and ecology of marine invertebrate species. This relationship is stronger at lower levels of the food web, while upper levels may be less dependent on primary production pulses. The pennatulid Malacobelemnon daytoni, is one of the most abundant species in Potter Cove, Antarctica. In order to assess its trophic ecology and energetic strategies, its biochemical (carbohydrates, proteins and lipids), Fatty Acid (FA) and Stable Isotope (SI) (δ15N and δ13C) compositions were studied over a year-round period. The FA and SI profiles suggest an omnivorous diet and opportunistic feeding strategy for the species. These results, together with biochemical analysis (higher lipid and carbohydrate concentration observed in July and October 2009), support the hypothesis that resuspension events may be an important source of energy, reducing the seasonality of food depletion periods in winter. The evidence presented here gives us a better insight into the success that this species has in Potter Cove and under the current environmental changes experienced by the Antarctic Peninsula.


Identification of a Genotype IX Newcastle Disease Virus in a Guangxi White Duck.
We report the complete genomic sequence of a novel Newcastle disease virus (NDV) strain, duck/China/Guangxi19/2011, isolated from a white duck in Guangxi Province, southern China. Phylogenetic analysis based on a fusion gene comparison with different NDV strains revealed that duck/China/Guangxi19/2011 is phylogenetically close to genotype IX NDV, and the deduced amino acid sequence of the fusion protein cleavage site was 112R-R-Q-R-R-F117. The whole nucleotide sequence had the highest homology (99.7%) to the sequence of strain F48E8 (GenBank accession number FJ436302). This study will help us understand the epidemiology and molecular characteristics of genotype IX Newcastle disease virus in ducks.


Illumination and errors in dispensing.
The relationship between the level of illumination and the prescription-dispensing error rate in a high-volume Army outpatient pharmacy was investigated. The prescription error rate was determined by direct, undisguised observation and retrospective prescription review under three levels of illumination (45, 102, and 146 foot-candles) during 21 consecutive weekdays. Illumination was controlled in the prescription-checking area of the pharmacy by using additional fluorescent lamps and filters. The three levels of illumination were randomly assigned to the 21 days to provide a total of 7 days of observations per level. The final sample consisted of 10,888 prescriptions dispensed by five pharmacists. The overall prescription error rate (including both content and labeling errors) was 3.39% (369 prescriptions). An illumination level of 146 foot-candles was associated with a significantly lower error rate (2.6%) than the baseline level of 45 foot-candles (3.8%). There was a linear relationship between each pharmacist's error rate and that pharmacist's corresponding daily prescription workload for all three illumination levels. The effect of the observer was minimal. The rate of prescription-dispensing errors was associated with the level of illumination. Ergonomics can affect the performance of professional tasks.


Combining left and right palmprint images for more accurate personal identification.
Multibiometrics can provide higher identification accuracy than single biometrics, so it is more suitable for some real-world personal identification applications that need high-standard security. Among various biometrics technologies, palmprint identification has received much attention because of its good performance. Combining the left and right palmprint images to perform multibiometrics is easy to implement and can obtain better results. However, previous studies did not explore this issue in depth. In this paper, we proposed a novel framework to perform multibiometrics by comprehensively combining the left and right palmprint images. This framework integrated three kinds of scores generated from the left and right palmprint images to perform matching score-level fusion. The first two kinds of scores were, respectively, generated from the left and right palmprint images and can be obtained by any palmprint identification method, whereas the third kind of score was obtained using a specialized algorithm proposed in this paper. As the proposed algorithm carefully takes the nature of the left and right palmprint images into account, it can properly exploit the similarity of the left and right palmprints of the same subject. Moreover, the proposed weighted fusion scheme allowed perfect identification performance to be obtained in comparison with previous palmprint identification methods.


Viability-reducing activity of Coryllus avellana L. extracts against human cancer cell lines.
The increasing rate of cancer incidence has encouraged the search for novel natural sources of anticancer compounds. The presence of small quantities of taxol and taxanes in Corylus avellana L. has impelled new potential applications for this plant in the field of biomedicine. In the present work, the cell viability-reducing activity of stems and leaves from three different hazel trees was studiedagainst three human-derived cancer cell lines (HeLa, HepG2 and MCF-7). Both leaf and stem extracts significantly reduced viability of the three cell lines either after maceration with methanol or using taxane extraction methods. Since maceration reduced cell viability to a greater extent than taxane extraction methods, we scaled up the maceration extraction process using a method for solid/liquid extraction (Zippertex technology). Methanol leaf extracts promoted a higher reduction in viability of all cell lines assayed than stem extracts. Fractionation of methanol leaf extracts using silica gel chormatography led to the purification and identification of two compounds by HPLC-MS and NMR: (3R,5R)-3,5-dihydroxy-1,7-bis(4-hydroxyphenyl) heptane 3-O-β-d-glucopyranoside and quercetin-3-O-rhamnoside. The isolated compounds decreased viability of HeLa and HepG2 cells to a greater extent than MCF-7 cells. Our results suggest a potential use of C. avellana extracts in the pharmacotherapy of cervical cancer and hepatocarcinoma and, to a lesser extent, breast cancer.


Beliefs and attitudes toward Buruli ulcer in Ghana.
Buruli ulcer is a devastating emerging disease in tropical countries. Quantitative and qualitative data were obtained by interviewing patients with this disease and control subjects in Ghana. Common perceived causes were witchcraft and curses. Other reported causes were personal hygiene, environment, and close contact with a patient with this disease. Financial difficulties, fear of the mutilating aspects of treatment, and social stigma were the main reasons found for delay in obtaining treatment. Patients are reluctant to seek treatment outside their own community. Patients often expected medical treatment instead of surgery, and underestimated the duration of hospital admission. The stigma of the disease is huge, and is strongly associated with the mysterious nature of the condition, the lack of knowledge about its mode of transmission, and the lack of proper treatment. Stigma scores were higher in unaffected respondents and in a less endemic location. Education on the disease, usually propagated for early case detection, might be useful in reducing stigma.


Comparison of eating attitudes among university students from the five Brazilian regions.
Eating attitudes can be defined as beliefs, thoughts, feelings, behavior and relationship with food. They can influence people's food choices and health status. The scope of this paper is to compare eating attitudes of university students from different regions of Brazil and investigate possible associations and correlations with nutritional status, age, individual income and parental education. 2489 female university students in the area of health answered the Eating Attitude Scale--evaluated by total score and 5 sub-scores. The eating attitudes were compared by means of an analysis of covariance. A logistic regression was conducted to evaluate which variables were associated to the scale score. The Northeast presented more restrictive and compensatory practices and the North and Northeast presented less positive feelings about food and worse ideas about normal eating. The score on the scale did not present strong correlation with any of the variables studied, but nutritional status and age were associated with the total score. The profile of university students was similar among regions with the worst response in the North and Northeast regions. It is believed that these data could help to elucidate dietary patterns and nutritional differences among groups.


Ionotropic glutamate receptor subunit expression in the rat hippocampus: lack of an effect of a long-term ethanol exposure paradigm.
Studies have shown that acute ethanol exposure inhibits ionotropic glutamate receptor function and that long-term ethanol exposure results in maladaptive increases in the expression of some of these receptors in neurons. It has been postulated that these changes, when unopposed by ethanol, contribute, in part, to the hyperexcitability associated with ethanol withdrawal. In this study, we compared the effect of long-term ethanol exposure on the hippocampal expression levels of subunits belonging to the three families of ionotropic glutamate receptors. Adult male Sprague-Dawley rats were fed an ethanol-containing diet for 16 days. This diet contained 0% ethanol on days 1 and 2, 3% on days 3 and 4, 5% on days 5 to 7, and 6.7% on days 8 to 16. Control rats received an equivalent amount of an isocaloric diet without ethanol. Rats were killed on day 16 at the peak of ethanol consumption. Hippocampal homogenates were prepared by sonication and analyzed by Western immunoblotting techniques. On a separate group of rats, we measured withdrawal scores and audiogenic seizures on day 17. Ethanol-exposed rats had significantly higher withdrawal scores, and a significantly higher percentage of them developed audiogenic seizures; this indicates that the 16-day ethanol diet induces ethanol dependence. Unexpectedly, we found that expression of NR1 (including the expression of NR1 subunits containing the N1, C1, and C2 inserts), NR2A, NR2B, NR2C, GluR1, GluR2/3, GluR5, GluR6/7, and KA2 subunits was not altered in hippocampal homogenates from ethanol-exposed rats. These results indicate that maladaptive changes in the hippocampal expression levels of ionotropic glutamate receptor subunits do not always occur in ethanol-dependent rats. Consequently, other mechanisms must mediate the hyperexcitability state associated with ethanol withdrawal in these animals.


Perceptual organization of sequential stimuli in cochlear implant listeners: A temporal processing approach.
Cochlear Implant (CI) users often suffer difficulties in perceiving speech in noisy environments that could be attributed to reduced Auditory Stream Segregation (ASS) ability. ASS is the process used to separate a complex sound into different perceptual streams. The evidence that CI listeners routinely experience stream segregation skill is limited and equivocal. The present study was aimed to investigate the effects of temporal cues on ASS performance in postlingually deaf listeners with CI. Nineteen (age range: 28-64 years old) monaurally cochlear implanted listener participated in this study. They were presented with 30-s sequences of alternating stimuli in a repeating A-B-A-A-B-A…sequence, where "tone A" corresponds to a stimulus applied to electrode 11, and "tone B" to a stimulus on one of the other electrode. To investigate the effect of temporal cues on ASS, four different tone repetition times (TRTs) were utilized: 50, 100, 150, and 200 ms. Speech discrimination scores in noise were also recorded for every CI recipients. Only 6 (32%) CI users demonstrated ASS pattern similar to the normal hearing subjects, while the majority of the users (n=13) possessed poorer ASS skills. An analysis of variance showed a significant effect of electrode separation (p<0.001) and TRT (p=0.041), but there was no significant interaction between electrode separation and TRT variables. The best ASS performance was obtained when TRT was 200 ms, and there was no significant effect for other TRT conditions. Moderate, significant correlations between streaming and speech discrimination measurement in noise was also observed (r=0.62), with better stream segregation associated with better understanding of speech in noise. ASS is a contributing factor in the ability to perceive speech in background noise. The inability of some CI recipients to perform stream segregation may therefore contribute to their difficulties in noisy backgrounds. Furthermore, stream segregation ability is related to the tone repetition time between the sounds.


The tobacco genome sequence and its comparison with those of tomato and potato.
The allotetraploid plant Nicotiana tabacum (common tobacco) is a major crop species and a model organism, for which only very fragmented genomic sequences are currently available. Here we report high-quality draft genomes for three main tobacco varieties. These genomes show both the low divergence of tobacco from its ancestors and microsynteny with other Solanaceae species. We identify over 90,000 gene models and determine the ancestral origin of tobacco mosaic virus and potyvirus disease resistance in tobacco. We anticipate that the draft genomes will strengthen the use of N. tabacum as a versatile model organism for functional genomics and biotechnology applications.


Use of compounded dispersing media for extemporaneous pediatric syrups with candesartan cilexetil and valsartan.
Available tablets or capsules for adults are often used to prepare extemporaneously formulated medicines appropriate for children. The most acceptable drug forms in pediatric population are oral liquids and pharmacists use commercial dispersing media to compound syrups from an active substance or from tablets available on the market. In many countries ready-to-use dispersing media are not available or refunded, but pharmacists can use other compounded media, providing their compatibility and stability are proven. The aim of this study was to formulate and evaluate the stability of syrups with candesartan cilexetil (1 mg mL-1) and valsartan (4 mg mL-1) extemporaneously prepared using commercial tablets (Diovan® and Atacand®). The following three different suspending media, which could be easily made in a pharmacy, were investigated: V1 - with xanthan gum (0.5 %), V2 - the USP/NF vehicle for oral solution and V3 - the medium based on a simple sucrose syrup. The stability of preparations was studied during 35 days of storage in a dark place at controlled temperature of 25 and 4 °C. During the study, microscopic observation was carried out and pH, viscosity, and concentration of candesartan cilexetil and valsartan were analyzed. Syrups with valsartan prepared with V2 and V3 media were stable for 3 or 4 weeks when stored at 25 °C, while syrups with candesartan were stable for as long as 35 days. For syrups prepared using V1 medium, the 14-day expiry date was not achieved because of microbial deterioration.


Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats.
The administration of insulin-like growth factor-I (IGF-I) via subcutaneously implanted osmotic pumps partially reversed a catabolic state produced by the co-administration of 20 micrograms of dexamethasone/day to 150 g male rats. Marked dose-dependent effects on body weight and nitrogen retention were produced, with the highest IGF-I dose, 695 micrograms/day, giving a 6 g increase in body weight over 7 days, compared with a 19 g loss in the dexamethasone-only group and an 18 g gain in pair-fed controls. Two IGF-I analogues that bind poorly to IGF-binding proteins, the truncated form, des(1-3)IGF-I, and a variant with an N-terminal extension as well as arginine at residue 3, LR3IGF-I, were approx. 2.5-fold more potent than IGF-I. The response with LR3IGF-I was particularly striking because this peptide binds 3-fold less well than IGF-I to the type 1 IGF receptor. The increased potencies of the IGF-I variants may relate to the substantially increased plasma levels of IGF-binding proteins, particularly IGFBP-3, produced by the combined treatment of dexamethasone with IGF-I or the variants. These binding proteins would be expected to decrease the transfer of IGF-I, but not that of the variants, from blood to tissue sites of action. Measurements of muscle protein synthesis at the end of the treatment period and muscle protein breakdown by 3-methylhistidine (3MH) excretion throughout the experiment indicated coordinate anabolic effects of the IGF peptides on both processes. Thus 3MH excretion was decreased at the highest IGF-I dose from 83.5 +/- 4.2 (S.E.M.) mumol/kg per 7 days to 65.1 +/- 2.2, compared with 54.9 +/- 1.2 in the pair-fed controls. Part of this response in 3MH excretion may have reflected a decrease in gut protein breakdown, because IGF-I and especially the IGF analogues increased the gut weight by up to 45%. Notwithstanding the effects on protein synthesis and breakdown, the fractional carcass weights remained low in the IGF-treated groups, although the increase in total carcass weight reflected nitrogen rather than fat gain. The dexamethasone-induced changes in liver, spleen and heart weight were restored towards normal by the IGF treatment. The experiment demonstrates the potential of IGF-I treatment of catabolic states and especially the value of modified forms of growth factors that bind weakly to IGF-binding proteins.


SimTB, a simulation toolbox for fMRI data under a model of spatiotemporal separability.
We introduce SimTB, a MATLAB toolbox designed to simulate functional magnetic resonance imaging (fMRI) datasets under a model of spatiotemporal separability. The toolbox meets the increasing need of the fMRI community to more comprehensively understand the effects of complex processing strategies by providing a ground truth that estimation methods may be compared against. SimTB captures the fundamental structure of real data, but data generation is fully parameterized and fully controlled by the user, allowing for accurate and precise comparisons. The toolbox offers a wealth of options regarding the number and configuration of spatial sources, implementation of experimental paradigms, inclusion of tissue-specific properties, addition of noise and head movement, and much more. A straightforward data generation method and short computation time (3-10 seconds for each dataset) allow a practitioner to simulate and analyze many datasets to potentially understand a problem from many angles. Beginning MATLAB users can use the SimTB graphical user interface (GUI) to design and execute simulations while experienced users can write batch scripts to automate and customize this process. The toolbox is freely available at http://mialab.mrn.org/software together with sample scripts and tutorials.


Heterogeneity of hepatitis C virus genotypes in hemophilia: relationship with chronic liver disease.
In this study we have determined the hepatitis C virus (HCV) serotype and genotype in a cohort of 96 HCV-infected hemophiliacs and have examined the relationship between HCV genotype and severity of chronic liver disease as determined by liver biopsy. HCV serotype was determined by specific enzyme-linked immunosorbent assays (ELISAs) and genotype by restriction fragment length polymorphism (RFLP) and HCV viral sequencing. The pattern of genotype distribution was quite unlike that of HCV-infected United Kingdom (UK) blood donors in that five of the six known HCV genotypes were represented, 50% were type 1, 13% type 2, and 18% type 3. An unexpected observation was the presence of HCV genotype 4 in four patients and type 5 in two patients. An additional feature was the presence of mixed infection, detected in 14% and 7% by serotype and genotype analysis, respectively. Liver biopsies were available from 51 patients. Cirrhosis was present in five of 27 (19%) of individuals with type 1, in 2 of 9 (22%) with type 2, and 5 of 8 (63%) of those with type 3. The heterogeneous pattern of HCV genotype distribution in this cohort of patients and the observed relationship between the severity of the related liver disease and specific HCV genotype may have important implications with respect to the natural history and treatment of HCV-related chronic liver disease in infected hemophiliacs worldwide.


Human DNA helicase V, a novel DNA unwinding enzyme from HeLa cells.
Using a strand-displacement assay with 32P labeled oligonucleotide annealed to M13 ssDNA we have purified to apparent homogeneity and characterized a novel DNA unwinding enzyme from HeLa cell nuclei, human DNA helicase V (HDH V). This is present in extremely low abundance in the cells and has the highest turnover rate among other human helicases. From 300 grams of cultured cells only 0.012 mg of pure protein was isolated which was free of DNA topoisomerase, ligase, nicking and nuclease activities. The enzyme also shows ATPase activity dependent on single-stranded DNA and has an apparent molecular weight of 92 kDa by SDS-polyacrylamide gel electrophoresis. Only ATP or dATP hydrolysis supports the unwinding activity. The helicase requires a divalent cation (Mg2+ > Mn2+) at an optimum concentration of 1.0 mM for activity; it unwinds DNA duplexes less than 25 bp long and having a ssDNA stretch as short as 49 nucleotides. A replication fork-like structure is not required to perform DNA unwinding. HDH V cannot unwind either blunt-ended duplex DNA or DNA-RNA hybrids; it unwinds DNA unidirectionally by moving in the 3' to 5' direction along the bound strand, a polarity similar to the previously described human DNA helicases I and III (Tuteja et al. Nucleic Acids Res. 18, 6785-6792, 1990; Tuteja et al. Nucleic Acid Res. 20, 5329-5337, 1992) and opposite to that of human DNA helicase IV (Tuteja et al. Nucleic Acid Res. 19, 3613-3618, 1991).


Role of testosterone in mediating prenatal ethanol effects on hypothalamic-pituitary-adrenal activity in male rats.
Prenatal ethanol (E) exposure programs the fetal hypothalamic-pituitary-adrenal (HPA) and -gonadal (HPG) axes such that E rats show HPA hyperresponsiveness to stressors and altered HPG and reproductive function in adulthood. Importantly, prenatal ethanol may differentially alter stress responsiveness in adult male and female offspring compared to their control counterparts. To test the hypothesis that alterations in HPA activity in E males are mediated, at least in part, by ethanol-induced changes in the capacity of testosterone to regulate HPA activity, we explored dose-related effects of testosterone on HPA and HPG function in adult male offspring from prenatal E, pair-fed (PF) and ad libitum-fed control (C) dams. Our data suggest that E males show changes in both HPA and HPG regulation, as well as altered sensitivity to the inhibitory effects of testosterone. While gonadectomy (GDX) reduced weight gain in all animals, low testosterone replacement restored body weights in PF and C but not E males. Further, sensitivity of the thymus and adrenal to circulating testosterone was reduced in E rats. In addition, stress-induced corticosterone (CORT) levels were increased in PF and C but not E males following GDX, and while low dose testosterone replacement restored CORT levels for PF and C, high testosterone levels were needed to normalize CORT levels for E males. A negative correlation between pre-stress testosterone and post-stress CORT levels in C but not in E and PF males further supports the finding of reduced sensitivity to testosterone. Importantly, testosterone appeared to have reduced effects on central corticotrophin releasing hormone (CRH) pathways in E, but greater effects on central arginine vasopressin (AVP) pathways in E and/or PF compared to C males. Testosterone also had less of an inhibitory effect on stress-induced luteinizing hormone increases in E than in PF and C males following GDX. In addition, androgen receptor mRNA levels in the medial preoptic nucleus and the principal nucleus of posterior bed nucleus of the stria terminalis were lower in E and PF compared to C males under intact conditions. Together, these data support our previous work suggesting altered sensitivity to testosterone in E males. Furthermore, differential effects of testosterone on the complex balance between central CRH and central AVP pathways may play a role in the HPA alterations observed. That some findings were similar in E and PF males suggest that nutritional effects of diet may have played a role in mediating at least some of the changes seen in E animals.


An alternative method of transperitoneal graft introduction in aortobifemoral bypass surgery.
Intestinal injury and bleeding, which usually occurs while taking the graft through the transperitoneal tunnel, is one of the most important complications of aortobifemoral bypass surgery. In this study, case reports were examined where, for some reason, the tunneller instrument could not be used to create the transperitoneal tunnel and the tunnelling forceps was used. In some of these cases, the grafts were taken through conventionally and in others an alternative method was used. Between 2002 and 2013, the records of 81 patients treated surgically by aortobifemoral bypass for peripheral arterial disease, were investigated retrospectively. In the conventional method, after creating a tunnel with tunnelling forceps, the forceps was re-introduced into the tunnel and the graft was clasped and brought through the tunnel. In the alternative method, a nylon tape was left as a guide in the tunnel while creating the tunnel, and the forceps was not introduced again. The graft was taken through the tunnel with the help of the nylon tape. Patients treated with the conventional method were included in group 1 (n = 49) and patients in which the graft was guided with nylon tape were included in group 2 (n = 32). The groups were compared peri-operatively. There were no significant differences between the groups in terms of co-morbidity factors. Extubation time, intensive care length of stay, revision for bleeding, other postoperative complications, and infection and late-term infection rates were similar in the two groups (p > 0.05). Hospital length of stay and blood usage were significantly higher in group 1 (p < 0.05). Drainage amounts were higher in group 1 but not statistically significant. Using nylon tape to introduce the graft into the femoral area during aortobifemoral bypass operations was found to be more effective than using the tunnelling forceps.


Comparison of the accuracy of digital face scans obtained by two different scanners.
To compare the degree of accuracy of the Face Hunter facial scanner and the Dental Pro application for facial scanning, with respect to both manual measurements and each other. Twenty-five patients were measured manually and scanned using each device. Six reference markers were placed on each subject's face at the cephalometric points Tr, Na', Prn, Pog', and L-R Zyg. Digital measurement software was used to calculate the distances between the cephalometric reference points on each of the scans. Geomagic X Control was used to superimpose the scans, automatically determining the best-fit alignment and calculating the percentage of overlapping surfaces within the tolerance ranges. Individual comparisons of the four distances measured anthropometrically and on the scans yielded an intraclass correlation coefficient index greater than .9. The t-test for matched samples yielded a P value below the significance threshold. Right and left cheeks reached around 60% of the surface, with a margin of error between 0.5 mm and -0.5 mm. The forehead was the only area in which most of the surface fell within the poorly reproducible range, presenting values out of tolerance of more than 20%. Three-dimensional scans of the facial surface provide an excellent analytical tool for clinical evaluation; it does not appear that one or the other of the measuring tools is systematically more accurate, and the cheeks are the area with the highest average percentage of surface in the highly reproducible range.


Mineral-Based Amendments for Remediation.
Amending soils with mineral-based materials to immobilize contaminants is both old and new. Although mineral amendments have been used for decades in agriculture, new applications with a variety of natural and reprocessed materials are emerging. By sequestering contaminants in or on solid phases and reducing their ability to partition into water or air, amendments can reduce the risk of exposure to humans or biota. A variety of mineral types are commonly used to amend contaminated soils, with different modes of molecular-scale sequestration. Regulatory, social, and economic factors also influence decisions to employ mineral amendments as a treatment technology.


Aquatic Biodiversity in the Amazon: Habitat Specialization and Geographic Isolation Promote Species Richness.
The Neotropical freshwater ichthyofauna has among the highest species richness and density of any vertebrate fauna on Earth, with more than 5,600 species compressed into less than 12% of the world's land surface area, and less than 0.002% of the world's total liquid water supply. How have so many species come to co-exist in such a small amount of total habitat space? Here we report results of an aquatic faunal survey of the Fitzcarrald region in southeastern Peru, an area of low-elevation upland (200-500 m above sea level) rainforest in the Western Amazon, that straddles the headwaters of four large Amazonian tributaries; the Juruá (Yurúa), Ucayali, Purús, and Madre de Dios rivers. All measures of fish species diversity in this region are high; there is high alpha diversity with many species coexisting in the same locality, high beta diversity with high turnover between habitats, and high gamma diversity with high turnover between adjacent tributary basins. Current data show little species endemism, and no known examples of sympatric sister species, within the Fitzcarrald region, suggesting a lack of localized or recent adaptive divergences. These results support the hypothesis that the fish species of the Fitzcarrald region are relatively ancient, predating the Late Miocene-Pliocene (c. 4 Ma) uplift that isolated its several headwater basins. The results also suggest that habitat specialization (phylogenetic niche conservatism) and geographic isolation (dispersal limitation) have contributed to the maintenance of high species richness in this region of the Amazon Basin.


Sampling of the native conformational ensemble of myoglobin via structures in different crystalline environments.
Proteins sample multiple conformational substates in their native environment, but the process of crystallization selects the conformers that allow for close packing. The population of conformers can be shifted by varying the environment through a range of crystallization conditions, often resulting in different space groups and changes in the packing arrangements. Three high resolution structures of myoglobin (Mb) in different crystal space groups are presented, including one in a new space group P6(1)22 and two structures in space groups P2(1)2(1)2(1) and P6. We compare coordinates and anisotropic displacement parameters (ADPs) from these three structures plus an existing structure in space group P2(1). While the overall changes are small, there is substantial variation in several external regions with varying patterns of crystal contacts across the space group packing arrangements. The structural ensemble containing four different crystal forms displays greater conformational variance (Calpha rmsd of 0.54-0.79 A) in comparison to a collection of four Mb structures with different ligands and mutations in the same crystal form (Calpha rmsd values of 0.28-0.37 A). The high resolution of the data enables comparison of both the magnitudes and directions of ADPs, which are found to be suppressed by crystal contacts. A composite dynamic profile of Mb structural variation from the four structures was compared with an independent structural ensemble developed from NMR refinement. Despite the limitations and biases of each method, the ADPs of the crystallographic ensemble closely match the positional variance from the solution NMR ensemble with linear correlation of 0.8. This suggests that crystal packing selects conformers representative of the solution ensemble, and several different crystal forms give a more complete view of the plasticity of a protein structure.


Breast cancer risk in older women: results from the NIH-AARP Diet and Health Study.
Divergent risk factors exist for premenopausal and postmenopausal breast cancers, but it is unclear whether differences by age exist among postmenopausal women. We examined relationships among 190,872 postmenopausal women, ages 50-71 years recruited during 1995-1996 for the NIH-AARP Diet and Health Study, in whom 7,384 incident invasive breast carcinomas were identified through 2006. Multivariable Cox regression hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for breast cancer risk factors by age (50-59, 60-69, ≥70 years). The only factor showing significant statistical heterogeneity by age (p(het) = 0.001) was menopausal hormone therapy duration, but trends were apparent across all ages and the strongest association prevailed among women 60-69 years. Although other risk factors did not show statistically significant heterogeneity by age, we did observe attenuated relations for parity and late age at first birth among older women [e.g., HR for age at first birth ≥30 vs. 20-24 = 1.62 (95% CI 1.23-2.14) for women 50-59 years vs. 1.12 (0.96-1.31) for ≥70 years]. In contrast, risk estimates associated with alcohol consumption and BMI tended to be slightly stronger among the oldest subjects [e.g., HR for BMI ≥35 vs. 18.5-24.9 = 1.24 (95% CI 0.97-1.58) for 50-59 years vs. 1.46 (1.26-1.70) for ≥70 years]. These differences were somewhat more pronounced for estrogen receptor positive and ductal cancers, tumors predominating among older women. Breast cancer family history, physical activity, and previous breast biopsies did not show divergent associations by age. Although breast cancer risk factor differences among older women were not large, they may merit further consideration with respect to individualized risk prediction.


Human SNORA31 variations impair cortical neuron-intrinsic immunity to HSV-1 and underlie herpes simplex encephalitis.
Herpes simplex virus-1 (HSV-1) encephalitis (HSE) is typically sporadic. Inborn errors of TLR3- and DBR1-mediated central nervous system cell-intrinsic immunity can account for forebrain and brainstem HSE, respectively. We report five unrelated patients with forebrain HSE, each heterozygous for one of four rare variants of SNORA31, encoding a small nucleolar RNA of the H/ACA class that are predicted to direct the isomerization of uridine residues to pseudouridine in small nuclear RNA and ribosomal RNA. We show that CRISPR/Cas9-introduced bi- and monoallelic SNORA31 deletions render human pluripotent stem cell (hPSC)-derived cortical neurons susceptible to HSV-1. Accordingly, SNORA31-mutated patient hPSC-derived cortical neurons are susceptible to HSV-1, like those from TLR3- or STAT1-deficient patients. Exogenous interferon (IFN)-β renders SNORA31- and TLR3- but not STAT1-mutated neurons resistant to HSV-1. Finally, transcriptome analysis of SNORA31-mutated neurons revealed normal responses to TLR3 and IFN-α/β stimulation but abnormal responses to HSV-1. Human SNORA31 thus controls central nervous system neuron-intrinsic immunity to HSV-1 by a distinctive mechanism.


Relation of lipid content and exotoxin production to virulence of Corynebacterium pseudotuberculosis in mice.
Twenty-five isolates of Corynebacterium pseudotuberculosis from lesions of caseous lymphadenitis in goats were examined for cell wall lipid content, exotoxin production, and virulence in mice. The mean percentage of lipid content was 6.52% and significant (P less than 0.005) differences were demonstrated between some isolates. Exotoxin in broth culture filtrates of the 25 isolates was measured by the staphylococcal beta-hemolysin inhibition (BHI) test and a radioassay for phospholipase D. All isolates were positive for exotoxin in both tests and 1 isolate had higher activity than the others. Because the correlation between the BHI test and radioassay was poor, it may be that the radioassay detects only enzymatically active exotoxin, whereas the BHI test detects active and inactive exotoxin. All isolates were virulent in mice at 2 dosage levels used to produce subacute-chronic and acute disease. Differences in virulence among isolates were detected only at the lower dosage level. There was a direct relationship between percentage of lipid and induction of chronic abscessation in mice, but not between lipid content and mortality. Although exotoxin production in vitro could not be related quantitatively to virulence, the results of inoculating mice with bacterial cells and broth culture supernatant were consistent with a role for exotoxin in disease.


Notch signaling is required for exocrine regeneration after acute pancreatitis.
The mechanisms for tissue regeneration and renewal after acute pancreatitis are not well understood but may involve activation of Notch signaling. To study the effect of Notch signaling ablation during acute experimental pancreatitis, we used a chemical and genetic approach to ablate Notch signaling in cerulein-induced pancreatitis in mice. Acute pancreatitis was induced by cerulein treatment in mice treated with the gamma-secretase inhibitor dibenzazepine or in conditional Notch1 knockout mice. Mice were characterized using immunohistologic, biochemical, and molecular methods. To investigate Notch and beta-catenin interaction, acinar 266-6 cells were analyzed using transfection and biochemical assays. Loss of Notch signaling results in impaired regeneration after acute pancreatitis with fewer mature acinar cells in dibenzazepine-treated and Notch1-deficient mice in the regenerative phase 3 days after induction. beta-catenin expression was increased and prolonged during exocrine regeneration. Crosstalk between Notch and beta-catenin-mediated signaling was identified, with Notch1-IC inhibiting beta-catenin-mediated transcriptional activity. This inhibition was dependent on a functional RAM domain. Inhibition of Notch signaling in vivo leads to impaired regeneration of the exocrine pancreas after acute pancreatitis. Our results suggest an interaction of Notch and Wnt signaling in pancreatic acinar cells, providing evidence for a role of these pathways in the regulation of the maturation process of acinar cells.


Impact of the new kidney allocation system A2/A2B → B policy on access to transplantation among minority candidates.
Blood group B candidates, many of whom represent ethnic minorities, have historically had diminished access to deceased donor kidney transplantation (DDKT). The new national kidney allocation system (KAS) preferentially allocates blood group A2/A2B deceased donor kidneys to B recipients to address this ethnic and blood group disparity. No study has yet examined the impact of KAS on A2 incompatible (A2i) DDKT for blood group B recipients overall or among minorities. A case-control study of adult blood group B DDKT recipients from 2013 to 2017 was performed, as reported to the Scientific Registry of Transplant Recipients. Cases were defined as recipients of A2/A2B kidneys, whereas controls were all remaining recipients of non-A2/A2B kidneys. A2i DDKT trends were compared from the pre-KAS (1/1/2013-12/3/2014) to the post-KAS period (12/4/2014-2/28/2017) using multivariable logistic regression. Post-KAS, there was a 4.9-fold increase in the likelihood of A2i DDKT, compared to the pre-KAS period (odds ratio [OR] 4.92, 95% confidence interval [CI] 3.67-6.60). However, compared to whites, there was no difference in the likelihood of A2i DDKT among minorities post-KAS. Although KAS resulted in increasing A2/A2B→B DDKT, the likelihood of A2i DDKT among minorities, relative to whites, was not improved. Further discussion regarding A2/A2B→B policy revisions aiming to improve DDKT access for minorities is warranted.


Renal tubular ACE-mediated tubular injury is the major contributor to microalbuminuria in early diabetic nephropathy.
Diabetic nephropathy is a major cause of end-stage renal disease in developed countries. While angiotensin-converting enzyme (ACE) inhibitors are used to treat diabetic nephropathy, how intrarenal ACE contributes to diabetic renal injury is uncertain. Here, two mouse models with different patterns of renal ACE expression were studied to determine the specific contribution of tubular vs. glomerular ACE to early diabetic nephropathy: it-ACE mice, which make endothelial ACE but lack ACE expression by renal tubular epithelium, and ACE 3/9 mice, which lack endothelial ACE and only express renal ACE in tubular epithelial cells. The absence of endothelial ACE normalized the glomerular filtration rate and endothelial injury in diabetic ACE 3/9 mice. However, these mice developed tubular injury and albuminuria and displayed low renal levels of megalin that were similar to those observed in diabetic wild-type mice. In diabetic it-ACE mice, despite hyperfiltration, the absence of renal tubular ACE greatly reduced tubulointerstitial injury and albuminuria and increased renal megalin expression compared with diabetic wild-type and diabetic ACE 3/9 mice. These findings demonstrate that endothelial ACE is a central regulator of the glomerular filtration rate while tubular ACE is a key player in the development of tubular injury and albuminuria. These data suggest that tubular injury, rather than hyperfiltration, is the main cause of microalbuminuria in early diabetic nephropathy.


Effectiveness of bariatric surgery in reducing weight and body mass index among Hispanic adolescents.
Ethnic minority adolescents, Hispanics in particular, are disproportionately affected by extreme obesity and its associated co-morbidities. Bariatric surgery is one of the few effective treatments for morbid obesity, yet little information about weight outcomes after surgery in this demographic are available. We determined the effectiveness of bariatric surgery in reducing weight and body mass index (BMI) in adolescents, a majority of whom were non-Mexican American Hispanic and originated from Central and/or South America and the Caribbean Basin region. Adolescents (16-to-19 years old) who had undergone gastric bypass or adjustable gastric band surgery between 2001 and 2010 and who had complete follow-up data available (91 %) were included in the analysis. Mean weight and BMI before and 1-year after surgery were compared. Among 71 adolescents (80 % Hispanic, 77 % female), mean BMI and weight, and z-scores and percentile transformations were all significantly lower after surgery for the entire sample (P < 0.001). Gastric bypass surgery showed significantly better weight loss outcomes for all anthropometric measures versus adjustable gastric band surgery (P < 0.05). Weight loss was similar among Hispanics and non-Hispanics. No peri-operative complications were reported. Three patients who stopped taking supplements as prescribed experienced iron deficiency anemia within the year following surgery. Our results show that bariatric surgery, gastric bypass procedure in particular, can markedly reduce weight among a predominantly Hispanic adolescent patient sample. These findings indicate that bariatric surgery has the potential to be safe and effective in substantially reducing weight in a group of adolescents who are at a particularly high risk for obesity-related health consequences.


The coronary risk of unsuspected renal artery stenosis.
This study was designed to determine the prevalence of unsuspected renal artery stenoses (RAS) in patients undergoing arteriography for evaluation of aneurysmal or occlusive vascular disease and whether symptomatic coronary artery disease (CAD) is more prevalent among patients with unsuspected RAS. We reviewed the arteriograms and medical records of 346 consecutive patients with aortic aneurysms or occlusive disease in whom RAS was unsuspected on clinical grounds. Aortography revealed unsuspected RAS (50% or greater diameter loss) in 98 patients (28%). Patients with RAS had a higher prevalence of mild, controlled hypertension (p < 0.001) and mild renal insufficiency (p < 0.001), but in no case was arteriography obtained to diagnose renovascular hypertension or ischemic nephropathy. Fifty-seven patients (58%) with unsuspected RAS had clinically overt CAD (documented myocardial infarction, positive coronary catheterization, previous coronary revascularization, ischemic electrocardiography changes, or angina pectoris), compared with 96 patients (39%) without RAS (p = 0.002). The correlation between the prevalence of CAD and RAS severity was highly significant (p < 0.001), and the relative odds ratio of CAD was highest for RAS measuring 75% or greater. Stepwise logistic regression analysis demonstrated three variables to be significantly and independently associated with CAD: 75% or greater RAS (p = 0.001), aortic aneurysm disease (p = 0.01), and hypertension (p = 0.001). RAS measuring 75% or greater diameter loss was associated with the highest estimated odds ratio: patients with this degree of RAS had a fourfold increase in the prevalence of clinically overt CAD. We also evaluated the relationship between RAS, mesenteric artery stenosis, and CAD; although RAS was more frequent among patients with mesenteric artery stenoses, mesenteric artery stenoses were not associated with CAD. Unsuspected RAS is common among patients with peripheral vascular disease and should be considered an independent marker for CAD.


Single-center retrospective analysis of 162 cases with thymoma complicating myasthenia gravis.
We conducted this study to retrospectively analyze the clinical effects of surgical resection for patients with myasthenia gravis (MG) complicated with thymoma. 162 patients with myasthenia gravis complicated with thymoma, that were admitted to our hospital and underwent surgical disease resection from Nov. 1993 to Nov. 2015, were selected for this study. Analyzed were the pathology (2004 WHO), Masaoka clinical stage, myasthenia gravis types (Osserman types), myasthenic crisis during the perioperative period, and the relationship between recurrence and survival rates during follow-up visits. Operational methods included thymusectomy by sternal incision or video-assisted thoracoscopic thymusectomy. There were significant differences regarding distribution of clinical stages among different types of pathology. The operation time, efficacy rate, 5 and 10-year survival rates and complication rates during the perioperative period of video-assisted thoracoscopy were compared to those of the conventional surgery group. Among these groups, hemorrhage during operation, postoperative drainage and recurrence rate were significantly lower in the thoracoscopy group than in those of the conventional surgery group (p<0.05). The pathology type and clinical stages of thymoma complicating myasthenia gravis are related to the types of myasthenia gravis and the myasthenic crisis during perioperative period. Therefore, our results indicate that the thoracoscope treatment is safe and effective.


Characterization of cAMP-phosphodiesterase activity in bovine seminal plasma.
The second messenger cyclic adenosine monophosphate (cAMP) has a central role in sperm physiology. Extracellular cAMP can be sequentially degraded into 5'AMP and adenosine by ecto-phosphodiesterases (ecto-PDE) and ecto-nucleotidases, a phenomenon called extracellular cAMP-adenosine pathway. As cAMP-adenosine pathway is involved in sperm capacitation, we hypothesize that extracellular PDEs are functionally present in seminal plasma. Exclusively measuring cAMP-PDE activity, total activity in bovine seminal plasma was 10.1 ± 1.5 fmoles/min/μg. Using different family-specific PDE inhibitors, we showed that in seminal plasma, the major cAMP-PDE activity was papaverine sensitive (47.5%). These data support the presence of PDE10 in bovine seminal plasma and was further confirmed by western blot. In epididymal fluid, total cAMP-PDE activity was 48.2 ± 14.8 fmoles/min/μg and we showed that the major cAMP-PDE activity was 3-isobutyl-methylxanthine insensitive and thus ascribed to PDE8 family. PDE10A mRNAs were found in the testis, epididymis, and seminal vesicles. cAMP-PDE activity is present in bovine seminal plasma and epididymal fluid. The results suggest a role for ecto-PDEs present in those fluids in the signaling pathways involved in sperm functions.


Seasonal and spatial patterns of metals at a restored copper mine site. I. Stream copper and zinc.
Seasonal and spatial variations in metal concentrations and pH were found in a stream at a restored copper mine site located near a massive sulfide deposit in the Foothill copper-zinc belt of the Sierra Nevada, California. At the mouth of the stream, copper concentrations increased and pH decreased with increased streamflow after the onset of winter rain and, unexpectedly, reached extreme values 1 or 2 months after peaks in the seasonal hydrographs. In contrast, aqueous zinc and sulfate concentrations were highest during low-flow periods. Spatial variation was assessed in 400 m of reach encompassing an acidic, metal-laden seep. At this seep, pH remained low (2-3) throughout the year, and copper concentrations were highest. In contrast, the zinc concentrations increased with downstream distance. These spatial patterns were caused by immobilization of copper by hydrous ferric oxides in benthic sediments, coupled with increasing downstream supply of zinc from groundwater seepage.


Effects of cannabidiol interactions with Wnt/β-catenin pathway and PPARγ on oxidative stress and neuroinflammation in Alzheimer's disease.
Alzheimer's disease (AD) is a neurodegenerative disease, in which the primary etiology remains unknown. AD presents amyloid beta (Aβ) protein aggregation and neurofibrillary plaque deposits. AD shows oxidative stress and chronic inflammation. In AD, canonical Wingless-Int (Wnt)/β-catenin pathway is downregulated, whereas peroxisome proliferator-activated receptor γ (PPARγ) is increased. Downregulation of Wnt/β-catenin, through activation of glycogen synthase kinase-3β (GSK-3β) by Aβ, and inactivation of phosphatidylinositol 3-kinase/Akt signaling involve oxidative stress in AD. Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid from Cannabis sativa plant. In PC12 cells, Aβ-induced tau protein hyperphosphorylation is inhibited by CBD. This inhibition is associated with a downregulation of p-GSK-3β, an inhibitor of Wnt pathway. CBD may also increase Wnt/β-catenin by stimulation of PPARγ, inhibition of Aβ and ubiquitination of amyloid precursor protein. CBD attenuates oxidative stress and diminishes mitochondrial dysfunction and reactive oxygen species generation. CBD suppresses, through activation of PPARγ, pro-inflammatory signaling and may be a potential new candidate for AD therapy.


Reactions of arynes promoted by silver ions.
Arynes are unique aromatic species that display versatile reactivity in a variety of transformations. It has been demonstrated that the reaction profiles of arynes can be altered by transition metal additives, and one of the earliest examples of the metal additive effect was observed with silver ions (Ag(+)). Especially, in the presence of Ag(+), benzyne showed distinctive reactivity and selectivity toward π-nucleophiles compared to the corresponding reaction in its absence. Although more experimental data need to be accumulated to accurately define the Ag(+) additive effect, based on its role displayed in various transformations, we can infer that Ag(+) interacts with arynes to form a reactive intermediate, which behaves like a silver-bound aryl cation or 1,2-carbene-silver carbenoid. In this tutorial review, various aryne-mediated reactions involving Ag(+) or other organosilver species are discussed, which show a bird's-eye view on the Ag(+) effect in aryne chemistry such that further explorations of the unique reactivity of arynes under the influence Ag(+) will be inspired.


Mediterranean diet and cognitive health: Initial results from the Hellenic Longitudinal Investigation of Ageing and Diet.
The Mediterranean dietary pattern has been associated with a decreased risk of many degenerative diseases and cognitive function in particular; however, relevant information from Mediterranean regions, where the prototype Mediterranean diet is typically adhered to, have been very limited. Additionally, predefined Mediterranean diet (MeDi) scores with use of a priori cut-offs have been used very rarely, limiting comparisons between different populations and thus external validity of the associations. Finally, associations between individual components of MeDi (i.e., food groups, macronutrients) and particular aspects of cognitive performance have rarely been explored. We evaluated the association of adherence to an a priori defined Mediterranean dietary pattern and its components with dementia and specific aspects of cognitive function in a representative population cohort in Greece. Participants from the Hellenic Longitudinal Investigation of Ageing and Diet (HELIAD), an on-going population-based study, exploring potential associations between diet and cognitive performance in a representative sample from Greek regions, were included in this analysis. Diagnosis of dementia was made by a full clinical and neuropsychological evaluation, while cognitive performance was assessed according to five cognitive domains (memory, language, attention-speed, executive functioning, visuospatial perception) and a composite cognitive score. Adherence to MeDi was evaluated by an a priori score (range 0-55), derived from a detailed food frequency questionnaire. Among 1,865 individuals (mean age 73±6 years, 41% male), 90 were diagnosed with dementia and 223 with mild cognitive impairment. Each unit increase in the Mediterranean dietary score (MedDietScore) was associated with a 10% decrease in the odds for dementia. Adherence to the MeDi was also associated with better performance in memory, language, visuospatial perception and the composite cognitive score; the associations were strongest for memory. Fish consumption was negatively associated with dementia and cognitive performance positively associated with non-refined cereal consumption. Our results suggest that adherence to the MeDi is associated with better cognitive performance and lower dementia rates in Greek elders. Thus, the MeDi in its a priori constructed prototype form may have cognitive benefits in traditional Mediterranean populations.


Immunological time scale for hominid evolution.
Several workers have observed that there is an extremely close immunological resemblance between the serum albumins of apes and man. Our studies with the quantitative micro-complement fixation method confirm this observation. To explain the closeness of the resemblance, previous workers suggested that there has been a slowing down of albumin evolution since the time of divergence of apes and man. Recent evidence, however, indicates that the albumin molecule has evolved at a steady rate. Hence, we suggest that apes and man have a more recent common ancestry than is usually supposed. Our calculations lead to the suggestion that, if man and Old World monkeys last shared a common ancestor 30 million years ago, then man and African apes shared a common ancestor 5 million years ago, that is, in the Pliocene era.