Growth failure, risk of hospitalization and death for children with end-stage renal disease.
Growth failure remains a significant problem for children with chronic renal insufficiency and end-stage renal disease (ESRD). We examined whether growth failure is associated with more-frequent hospitalizations or higher mortality in children with kidney disease. We studied data on prevalent United States pediatric patients with ESRD in 1990 who were followed through 1995. Patients were categorized according to the standard deviation score (SDS) of their incremental growth during 1990: severe (<-3 SDS), moderate growth failure (>-3 and <-2 SDS), and normal growth (>-2 SDS). Among 1,112 prevalent pediatric dialysis and transplant patients (<17 years, Tanner I-IV), those with severe and moderate growth failure had higher hospitalization rates [relative risk (RR) 1.14 [95% confidence interval (CI) 1.1, 1.2] and 1.24 [95% CI 1.2, 1.3]] respectively than those with normal growth after adjustment for age, gender, race, cause and duration of ESRD, and treatment modality (dialysis or transplant) in 1990. Kaplan-Meier survival analysis showed 5-year survival of 85% and 90% for patients with severe and moderate growth failure, respectively, compared with 96% for patients with normal growth ( P<0.001, log-rank). Cox proportional hazards analysis revealed that those with severe (RR 2.9, 95% CI 1.6, 5.3) and moderate growth failure (RR 2.01, 95% CI 1.1, 3.6) had an increased risk of death compared with youths with normal growth, after adjustment. A higher proportion of deaths in the severe and moderate growth failure groups were attributed to infectious causes (22% and 18.7%, respectively) than in the normal growth group (15.6%). We conclude that growth failure is associated with a more-complicated clinical course and increased risk of death for children with kidney failure.


Development of synaptic currents in immobilized muscle of Xenopus laevis.
The effect of chronic immobilization on the development of synaptic currents was studied in myotomal muscle of Xenopus laevis. Embryos and tadpoles were immobilized by rearing them in the presence of tetrodotoxin (TTX) after removal of the egg membranes. Immobilization did not affect the developmental change in duration of miniature end-plate currents (m.e.p.c.s). Rise times decreased from about 3 to 0.6 ms in both immobilized and control muscle, and decay constants decreased from about 7 to 1 - 2 ms in both conditions. M.e.p.c.s with double exponential decays were recorded in both immobilized and control muscle at intermediate and late developmental stages. The fast and slow decay constants were 0.7 ms and slightly less than 3 ms in older muscle of both groups. These values are comparable to the apparent open times of fast and slow ACh receptors present on Xenopus muscle. Application of an anticholinesterase (methanesulphonyl fluoride) lengthened the duration of m.e.p.c.s comparably in immobilized and control muscle. These data indicate that the deposition of junctional acetylcholinesterase and the reduction in open time of acetylcholine receptor channels in developing Xenopus myotomal muscle are independent of contractile activity of muscle and TTX-blockable action potentials in muscle or motoneurones.


Teaching medication compliance to psychiatric residents: placing an orphan topic into a training curriculum.
Medication compliance is an orphan topic. Training in the understanding and management of noncompliance does not neatly fall within the domain of psychopharmacology, nor does it clearly fit into other core curricula areas, such as clinical interviewing or psychotherapy training. The objective of this article is to increase awareness about this vagueness among academic psychiatrists and to offer a suggested curriculum to facilitate implementation. The authors present a curriculum covering major aspects of the theory and practice of compliance. The proposed curriculum is divided into five core components that can be used together or separately. These components are: 1) definition of compliance and noncompliance; 2) understanding how compliance depends on efficacy; 3) assessment of compliance and noncompliance; 4) the importance of the therapeutic alliance; and 5) pharmacological and psychosocial strategies to improve compliance. These five sections can be modified into specific lectures that are added to ongoing psychopharmacology, psychiatric interviewing, or psychotherapy courses. A careful review of the American Board of Psychiatry and Neurology (ABPN) core curriculum found no mention of medication compliance/adherence as a specific training goal, and our residency program, like many others, did not have a specific course that focused on this issue. To address this omission, the authors designed and taught a five-session course for PGY-III and PGY-IV psychiatry residents that specifically addressed assessment and management of noncompliance. It was piloted in the 2003-2004 academic year. The course was very well received and formed the basis of this material presented in this review and discussion. The principles of understanding, assessing, and managing medication compliance should be a part of the core curriculum for every psychiatric residency training program.


The representational status of pretence: evidence from typical development and autism.
The question of whether understanding pretend play requires meta-representational skill was examined among typically developing children and individuals with autism. Participants were presented with closely equated true and false pretence trials in which they had to judge a protagonist's pretend reading of a situation, which either matched or differed from their own. Results showed that individuals' theory of mind abilities determined their performance on false, but not true, pretence trials. These findings imply that meta-representation is involved when an individual has to make sense of a pretend state of mind that differs from their own, but, crucially, they also show that pretend play can often be understood without meta-representational competence.


Phosphorylation of CRMP2 is involved in proper bifurcation of the apical dendrite of hippocampal CA1 pyramidal neurons.
The neural circuit in the hippocampus is important for higher brain functions. Dendrites of CA1 pyramidal neurons mainly receive input from the axons of CA3 pyramidal neurons in this neural circuit. A CA1 pyramidal neuron has a single apical dendrite and multiple basal dendrites. In wild-type mice, most of CA1 pyramidal neurons extend a single trunk, or alternatively, the apical dendrite bifurcates into two daughter trunks at the stratum radiatum layer. We previously reported the proximal bifurcation phenotype in Sema3A-/-, p35-/-, and CRMP4-/- mice. Cdk5/p35 phosphorylates CRMP2 at Ser522, and inhibition of this phosphorylation suppressed Sema3A-induced growth cone collapse. In this study, we analyzed the bifurcation points of the apical dendrites of hippocampal CA1 pyramidal neurons in CRMP2KI/KI mice in which the Cdk5/p35-phosphorylation site Ser522 was mutated into an Ala residue. The proximal bifurcation phenotype was not observed in CRMP2KI/KI mice; however, severe proximal bifurcation of apical dendrites was found in CRMP2KI/KI;CRMP4-/- mice. Cultured hippocampal neurons from CRMP2KI/KI and CRMP2KI/KI;CRMP4-/- embryos showed an increased number of dendritic branching points compared to those from wild-type embryos. Sema3A increased the number of branching points and the total length of dendrites in wild-type hippocampal neurons, but these effects of Sema3A for dendrites were not observed in CRMP2KI/KI and CRMP2KI/KI;CRMP4-/-hippocampal neurons. Binding of CRMP2 to tubulin increased in both CRMP2KI/KI and CRMP2KI/KI:CRMP4-/- brain lysates. These results suggest that CRMP2 and CRMP4 synergistically regulate dendritic development, and CRMP2 phosphorylation is critical for proper bifurcation of apical dendrite of CA1 pyramidal neurons.


The membrane-topogenic vectorial behaviour of Nrf1 controls its post-translational modification and transactivation activity.
The integral membrane-bound Nrf1 transcription factor fulfils important functions in maintaining cellular homeostasis and organ integrity, but how it is controlled vectorially is unknown. Herein, creative use of Gal4-based reporter assays with protease protection assays (GRAPPA), and double fluorescence protease protection (dFPP), reveals that the membrane-topogenic vectorial behaviour of Nrf1 dictates its post-translational modification and transactivation activity. Nrf1 is integrated within endoplasmic reticulum (ER) membranes through its NHB1-associated TM1 in cooperation with other semihydrophobic amphipathic regions. The transactivation domains (TADs) of Nrf1, including its Asn/Ser/Thr-rich (NST) glycodomain, are transiently translocated into the ER lumen, where it is glycosylated in the presence of glucose to become a 120-kDa isoform. Thereafter, the NST-adjoining TADs are partially repartitioned out of membranes into the cyto/nucleoplasmic side, where Nrf1 is subject to deglycosylation and/or proteolysis to generate 95-kDa and 85-kDa isoforms. Therefore, the vectorial process of Nrf1 controls its target gene expression.


Toward Biomimetic Scaffolds for Tissue Engineering: 3D Printing Techniques in Regenerative Medicine.
Three-dimensional (3D) printing technology allows fabricating complex and precise structures by stacking materials layer by layer. The fabrication method has a strong potential in the regenerative medicine field to produce customizable and defect-fillable scaffolds for tissue regeneration. Plus, biocompatible materials, bioactive molecules, and cells can be printed together or separately to enhance scaffolds, which can save patients who suffer from shortage of transplantable organs. There are various 3D printing techniques that depend on the types of materials, or inks, used. Here, different types of organs (bone, cartilage, heart valve, liver, and skin) that are aided by 3D printed scaffolds and printing methods that are applied in the biomedical fields are reviewed.


Estimates of first-generation women and girls with female genital mutilation in the European Union, Norway and Switzerland.
Female genital mutilation (FGM) is the practice of partial or total removal of female genitalia for non-medical reasons. The procedure has no known health benefits but can cause serious immediate and long-term obstetric, gynaecological and sexual health problems. Health workers in Europe are often unaware of the consequences of FGM and lack the knowledge to treat women adequately. Our goal was to estimate the number of first-generation girls and women in the European Union, Norway and Switzerland who have undergone FGM. Before migration from FGM-practicing countries began, FGM was an unknown phenomenon in Europe. Secondary analysis of data from the 2011 EU census and extrapolation from age-specific FGM prevalence rates in the immigrants' home countries to these data were used to provide our estimates. Estimates based on census and other demographic data were compared to our results for Belgium. In 2011 over half a million first-generation women and girls in the EU, Norway and Switzerland had undergone FGM before immigration. One in two was living in the UK or France, one in two was born in East-Africa. For the first time, scientific evidence gives a reliable estimate of the number of first-generation women and girls in Europe coming from countries where FGM is practiced. The use of census data proves reliable for policy makers to guide their actions, e.g., regarding training needs for health workers who might be confronted with women who have undergone FGM, or the need for reconstructive surgery.


Covariate adjustment using propensity scores for dependent censoring problems in the accelerated failure time model.
In many medical studies, estimation of the association between treatment and outcome of interest is often of primary scientific interest. Standard methods for its evaluation in survival analysis typically require the assumption of independent censoring. This assumption might be invalid in many medical studies, where the presence of dependent censoring leads to difficulties in analyzing covariate effects on disease outcomes. This data structure is called "semicompeting risks data," for which many authors have proposed an artificial censoring technique. However, confounders with large variability may lead to excessive artificial censoring, which subsequently results in numerically unstable estimation. In this paper, we propose a strategy for weighted estimation of the associations in the accelerated failure time model. Weights are based on propensity score modeling of the treatment conditional on confounder variables. This novel application of propensity scores avoids excess artificial censoring caused by the confounders and simplifies computation. Monte Carlo simulation studies and application to AIDS and cancer research are used to illustrate the methodology.


T cell activation in the presence of cyclosporine in three in vivo allograft models.
The effect of cyclosporine on a systemic graft-versus-host reaction, cardiac allograft rejection, and a local host-versus-graft reaction in the rat were examined in detail. Therapeutic levels of CsA did not inhibit the early stages of lymphocyte activation but did prevent maturation of the immune response to full effector function--viz., graft rejection or clinical GVH disease. In all three models the phenotype changes in T cells associated with the early stages of activation--i.e., induction of receptors for interleukin 2 (IL-R), induction of MHC class II expression, and coexpression of CD4 and CD8 glycoproteins--were not inhibited by CsA. In the GVH and HVG reactions lymphocyte activation proceeded as far as DNA synthesis. In the systemic GVH model animals showed no sign of GVHD for as long as CsA was administered, but withdrawal of the drug resulted in accelerated lethal GVHD.


Initial treatment patterns in younger adult patients with differentiated thyroid cancer in California.
Differentiated thyroid cancer (DTC) is among the most common malignancies in the adolescent and young adult (age 15-39 years) population, and its incidence is rising. Younger age (<45 years) is an important prognostic indicator and is incorporated into the TNM classification system. This study hypothesized that this would result in distinct treatment patterns for younger and older patients. Using the California Cancer Registry, 24,362 patients with DTC from 2004 to 2011 were identified, and they were divided into younger (<45 years) and older (≥45 years) cohorts. Demographic and clinical variables were tabulated and then compared using chi-square tests. Treatment variables included total or near total thyroidectomy, other types of thyroid surgery, and the administration of radioiodine as part of the initial treatment. Multivariable logistic regression was used to identify independent predictors of treatment administered. Younger patients were more likely to be Hispanic (32.5% vs. 21.2%) and female (82.7% vs. 74.7%), and to have papillary carcinoma (92.9% vs. 90.9%) and lymph node involvement (32.8% vs. 19.7%; p<0.0001). On multivariable analysis, younger patients (OR 1.20 [CI 1.11-1.30]), higher T-stage tumors, higher socioeconomic status (SES), and papillary carcinoma were predictors of undergoing total thyroidectomy versus less than total thyroid surgery. After adjustment, predictors of radioiodine administration included younger age (OR 1.12 [CI 1.05-1.18]), higher SES, total thyroidectomy, higher T stage, and lymph node positivity. Younger patients with DTC in California are more likely to be female and Hispanic with papillary histology. After adjustment for disease and demographic characteristics, younger patients are more likely to undergo total thyroidectomy as their initial surgery and are more likely to receive radioiodine. Given their excellent prognosis and the potential for adverse sequelae from initial treatment for DTC, these findings warrant consideration when managing younger patients with DTC.


Assembly in vitro of a spanning membrane protein of the endoplasmic reticulum: the E1 glycoprotein of coronavirus mouse hepatitis virus A59.
The E1 glycoprotein of coronavirus mouse hepatitis virus A59 was synthesized in vitro by translation of viral mRNA in the presence of dog pancreatic microsomes. Its disposition in the membrane was investigated by digestion with proteases and by selective NH2-terminal labeling. The protein spans the membrane, but only small portions from the NH2 and COOH terminus are exposed respectively in the lumenal and cytoplasmic domains; the bulk of the molecule is apparently buried in the membrane. The protein lacks a cleavable leader sequence and does not acquire its characteristic O-linked oligosaccharides in rough microsomes. It may enter the membrane at any stage during synthesis of the first 150 amino acid residues. These unusual features of the protein might help to explain why it is not transported to the cell surface in vivo but remains in intracellular membranes, causing the virus to bud there.


[Organization and the Role of Nutirition Support Team].
With the development of specialized nutrition therapy and the need for interdisciplinary approach, nutrition support teams (NSTs) were created to optimize effectiveness and safety of nutritional therapy. NSTs are interdisciplinary support teams with specialty training in nutrition that are typically comprised of physicians, dietitians, nurses, pharmacists, and others. Their role includes nutrition screening, assessment, determination of nutrition needs, recommendations for appropriate nutrition therapy, management of nutrition support therapy, and monitoring. Studies have demonstrated significant improvements in patient nutrition status and improved clinical outcomes as well as reductions in costs when patients were appropriately managed by NSTs. Organization and the role of NSTs are discussed in this review.


The Lived Experience of Providing Care and Support Services for Holocaust Survivors in Australia.
Lack of awareness among paid carers of the possible late-life consequences of early-life periods of extreme and prolonged traumatization may have negative impacts on the experiences of trauma survivors in receiving care. An interpretive phenomenological approach was used to investigate the lived experience of paid carers in providing care for Jewish Holocaust survivors. In total, 70 carers participated in 10 focus group discussions. Credibility of the findings was ensured by methodological triangulation and peer debriefing. Three major themes emerged: (a) knowing about survivors' past helps me make sense of who they are, (b) the trauma adds an extra dimension to caregiving, and (c) caring for survivors has an emotional impact. Specific knowledge, attitudes, and skills for building positive care relationships with Holocaust survivors were identified. The findings offer a starting point for advancing knowledge about the care of older survivors from other refugee backgrounds.


Psychological safety and self-regulated learning through near-peer learning for the sustainability of rural community-based medical education: grounded theory approach.
Difficulties in improving psychological safety in medical education can be attributed to the hierarchy among medical professionals. Near-peer learning (NPL) can increase learning between students and residents, and improve psychological safety. Rural community-based medical education (CBME) can use an NPL framework to improve psychological safety and compensate for the lack of resources, leading to sustainability. This qualitative study aimed to clarify the effects of NPL on the psychological safety and learning of medical trainees in rural CBME. This study used a grounded theory approach. Thirty-eight medical students, 12 second-year residents, and eight family medicine residents participated in this study. Purposive sampling was used to address the research objectives, followed by ethnographic and semi-structured interviews. Three themes were identified: facilitating learning, change in perception, and change in learning. Rural NPL-based CBME drove learners' engagement in clinical practice through constant participation and reflection. Respecting and supporting learners' motivation and participation and effectively accepting them increased their sense of ownership and psychological safety. Furthermore, NPL supported participants in becoming self-regulated learners. Rural CBMEs lack healthcare and educational resources, but implementing NPL could make rural medical education sustainable, increasing the motivation of healthcare students and the number of medical staff working in rural contexts.


[Problems in the demonstration of Toxoplasma gondii in muscle tissue of sheep].
It is a known fact that sheep usually show a high level of infection with the parasite Toxoplasma gondii. Samples of five grams of muscular tissue taken from the diaphragms of forty sheep were digested with trypsin. The digested material was microscopically examined for bradyzoites of Toxoplasma using the Giemsa-staining method and a Toxoplasma-specific immunofluorescence test. In spite of the fact that antibodies were detected with the ELISA in sixty-five percent of the sheep, Toxoplasma could not be identified in any of the samples of muscular tissue.


The treatment of gustilo grade IIIB tibia fractures with application of antibiotic spacer, flap, and sequential distraction osteogenesis.
Gustilo grade III (GIII) B-C open tibia shaft fractures have a wide spectrum of injury to the bone and soft tissues. At the severe end of the spectrum are GIII B tibia fractures that combine segmental bone loss with soft tissue injuries which require flap reconstruction. These complex injuries can be treated combining circular tensioned wire fixation and distraction histiogenesis with flap reconstruction. GIII B tibia shaft fractures were retrospectively reviewed at an urban Level One Trauma Center from 1992 to 2008 which were treated with the Ilizarov method. Seventy-six patients with 78 fractures were treated. Thirty-eight fractures were treated with flaps. Out of this cohort, a subset of 19 fractures were treated using the protocol of initial multiple debridements, half pin resuscitation external fixation, soft tissue reconstruction over antibiotic spacers and delayed Ilizarov reconstruction after stabilization of the soft tissue envelope. The fractures had multiple aggressive debridements removing nonviable bone. Thirteen free flaps and 6 rotation flaps were applied. Flaps were applied a mean time of 34 days (12-77) after initial injury. Two free flaps failed and had a second successful application. Flap survival was 17 of 19 (89%). There was one partial necrosis and one flap hematoma. There was no flap complication from delayed elevation and spacer removal. Mean tibial bone defect was 9.4 cm (5-17). Reconstruction time was 26.5 months (12-73). Eighteen of 19 fractures were reconstructed with union and no deep infection or osteomyelitis. One fracture had a hypertrophic nonunion in a noncompliant patient. The use of antibiotic spacers and flaps to construct a soft tissue tunnel combined with distraction histiogenesis is an effective technique to salvage complex GIII B tibia fractures with segmental bone loss.


Transient Heat Stress During Early Seed Development Primes Germination and Seedling Establishment in Rice.
Rice yield is highly sensitive to increased temperature. Given the trend of increasing global temperatures, this sensitivity to higher temperatures poses a challenge for achieving global food security. Early seed development in rice is highly sensitive to unfavorable environmental conditions. Heat stress (HS) during this stage decreases seed size and fertility, thus reducing yield. Here, we explore the transgenerational phenotypic consequences of HS during early seed development on seed viability, germination, and establishment. To elucidate the impact of HS on the developmental events in post-zygotic rice seeds, we imposed moderate (35°C) and severe (39°C) HS treatments initiated 1 day after fertilization and maintained for 24, 48, or 72 h. The transient HS treatments altered the initiation of endosperm (ED) cellularization, seed size and/or the duration of spikelet ripening. Notably, seeds exposed to 24 and 48 h moderate HS exhibited higher germination rate compared to seeds derived from plants grown under control or severe HS. A short-term HS resulted in altered expression of Gibberellin (GA) and ABA biosynthesis genes during early seed development, and GA and ABA levels and starch content at maturity. The increased germination rate after 24 of moderate HS could be due to altered ABA sensitivity and/or increased starch level. Our findings on the impact of transient HS on hormone homeostasis provide an experimental framework to elucidate the underlying molecular and metabolic pathways.


Identification of a Novel Genetic Marker for Risk of Degenerative Rotator Cuff Disease Surgery in the UK Biobank.
While evidence indicates that familial predisposition influences the risk of developing degenerative rotator cuff disease (RCD), knowledge of specific genetic markers is limited. We conducted a genome-wide association study of RCD surgery using the UK Biobank, a prospective cohort of 500,000 people (40 to 69 years of age at enrollment) with genotype data. Cases with surgery for degenerative RCD were identified using linked hospital records. The cases were defined as an International Classification of Diseases, Tenth Revision (ICD-10) code of M75.1 determined by a trauma/orthopaedic specialist and surgery consistent with RCD treatment. Cases were excluded if a diagnosis of traumatic injury had been made during the same hospital visit. For each case, up to 5 controls matched by age, sex, and follow-up time were chosen from the UK Biobank. Analyses were limited to European-ancestry individuals who were not third-degree or closer relations. We used logistic regression to test for genetic association of 674,405 typed and >10 million imputed markers, after adjusting for age, sex, population principal components, and follow-up. We identified 2,917 RCD surgery cases and 14,158 matched controls. We observed 1 genome-wide significant signal (p < 5 × 10-8) for a novel locus tagged by rs2237352 in the CREB5 gene on chromosome 7 (odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.11 to 1.24). The single-nucleotide polymorphism (SNP) rs2237352 was imputed with a high degree of confidence (info score = 0.9847) and is common, with a minor allele frequency of 47%. After expanding the control sample to include additional unmatched non-cases, rs2237352 and another SNP in the CREB5 gene, rs12700903, were genome-wide significant. We did not detect genome-wide significant signals at loci associated with RCD in previous studies. We identified a novel association between a variant in the CREB5 gene and RCD surgery. Validation of this finding in studies with imaging data to confirm diagnoses will be an important next step. Identification of genetic RCD susceptibility markers can guide understanding of biological processes in rotator cuff degeneration and help inform disease risk in the clinical setting. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Pterygium: nonsurgical treatment using topical dipyridamole - a case report.
We report a case of a symptomatic, inflamed pterygium treated nonsurgically with topical dipyridamole and followed for 12 months. A 35-year-old woman presented with a stage II to III, V3, C3, K2, P1 (using Johnston, Williams & Sheppard's classification) pterygium in her right eye. She complained of a foreign body sensation, dryness, burning, and persistent uncontrolled blinking. A raised lesion was observed on the nasal conjunctiva that was 1.5 mm in size. It extended slightly onto the nasal cornea. There was moderate vascularity of the lesion that obscured the underlying scleral vessels. Moderate conjunctival hyperemia was detected at and medial to the pterygium. The cornea, anterior chamber, and external anatomy were otherwise unremarkable. The eye was initially treated twice daily with a topical application of dipyridamole in a normal saline solution, which was later reduced to once daily. There was a marked improvement in both the pterygium and the patient's symptoms. The tissue regressed from the limbal region of the cornea, had decreased in length from 1.5 to 1.0 mm, and decreased in height from approximately 1.0 to approximately 0.3 mm. Conjunctival hyperemia and vascularization resolved completely, and the underlying scleral vessels could once again be visualized. At 12 months, the pterygium was graded as stage 0 to I, V0, C2, K0, P0. To our knowledge, this is the first case of successful management of a pterygium and associated symptoms using topical dipyridamole. Further investigation is required to clarify the potential role of dipyridamole in the treatment of pterygia and pingueculae.


Hepatitis E infection in HIV-infected liver and kidney transplant candidates.
Hepatitis E virus (HEV) has been reported to cause acute and chronic hepatitis in those with HIV infection and among solid organ transplant recipients in Europe. Limited data indicate that HEV is endemic in the United States, but the prevalence and significance of HEV infection among those with HIV and awaiting solid organ transplantation is unknown. We evaluated anti-HEV IgM and IgG antibodies and HEV RNA in 166 HIV-infected solid organ transplant candidates enrolled in the NIH HIV-Transplant Cohort. Overall prevalence of anti-HEV IgG approached 20% in both liver and renal transplant candidates. Evidence of recent infection was present in approximately 2% of liver transplant candidates and none of the kidney transplant candidates. HEV RNA was not detected in any patient. We conclude that markers of HEV infection are frequent among candidates for transplantation, but active, ongoing viremia is not seen. Evidence of recent infection (acute on chronic) liver disease was present in liver but not kidney recipients.


Substrate ambiguity and crystal structure of Pyrococcus furiosus 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase: an ancestral 3-deoxyald-2-ulosonate-phosphate synthase?
3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAH7PS) catalyzes the condensation reaction between phosphoenolpyruvate (PEP) and the four-carbon monosaccharide D-erythrose 4-phosphate (E4P). DAH7PS from the hyperthermophile Pyrococcus furiosus is a member of the DAH7PS Ibeta subfamily, which also includes the KDO8PS enzymes. KDO8PS (3-deoxy-D-manno-octulosonate-8-phosphate synthase) catalyzes a closely related reaction of PEP with the five-carbon monosaccharide D-arabinose 5-phosphate (A5P). DAH7PS from P. furiosus requires a metal ion for activity and, unlike other characterized DAH7PS enzymes, is not inhibited by aromatic amino acids. Purified P. furiosus DAH7PS is able to utilize not only the four-carbon phosphorylated monosaccharides E4P and 2-deoxy-D-erythrose 4-phosphate but also the five-carbon phosphorylated monosaccharides A5P, D-ribose 5-phosphate, and 2-deoxy-D-ribose 5-phosphate with similar kcat but much increased KM values. DL-glyceraldehyde 3-phosphate and D-glucose 6-phosphate are not substrates. The structure of recombinant P. furiosus DAH7PS in complex with PEP was determined to 2.25 A resolution. The asymmetric unit consists of a dimer of (beta/alpha)8-barrel subunits. Analysis of the buried surfaces formed by dimerization and tetramerization, as observed in the crystal structure, provides insight into both the oligomeric status in solution and the substrate ambiguity of P. furiosus DAH7PS. P. furiosus DAH7PS is both the first archaeal and the first "naked" DAH7PS (without N-terminal extensions) to be fully characterized functionally and structurally. The broad substrate specificity of this DAH7PS, the lack of allosteric inhibition, and various structural features indicate that, of the enzymes characterized to date, P. furiosus DAH7PS may be the contemporary protein closest to the ancestral type I enzyme.


Molecular identification of Cryptococcus gattii from cerebrospinal fluid using single-cell sequencing: A case study.
A 31-year-old man presented with cryptococcal meningitis (CM) without typical clinical characteristics, but with abnormal walking, difficult leg lifting and frequent falling. He was admitted to Peking Union Medical College Hospital. After multiple tests failed to identify the pathogen, single-cell sequencing (scS) was used to test the cerebrospinal fluid (CSF). Comparing the sequence obtained from single-cell sequencing with the reference database, it was found that the infection was caused by Cryptococcus gattii sensu stricto (AFLP4/VGI genotype). Cryptococcus is difficult to cultivate from complex body fluids. The etiological agent of this patient was identified and the patient was treated. This is the first case in which scS was used to detect and identify fungal pathogen after conventional testing failed to identify the cause of the disease. This report demonstrates that the scS approach can be used to generate fungal genome sequences directly from the CSF of a CM patient. The scS technology could become a powerful tool to precise detect microscopically visible but uncultured pathogens in clinical samples.


Cutaneous and post kala-azar dermal leishmaniasis caused by Leishmania infantum in endemic areas of visceral leishmaniasis, northwestern Iran 2002-2011: a case series.
Visceral leishmaniasis (VL) is endemic in Northwest and southern Iran. Reports of cutaneous leishmaniasis (CL) in Northwest areas are rare, and its etiological agents are unknown. In the current study, we report six CL and two post kala-azar dermal leishmaniasis (PKDL) cases caused by Leishmania infantum from endemic areas of VL in the Northwest. Smears were made from skin lesions of 30 suspected patients in 2002-2011, and CL was determined by microscopy or culture. Leishmania spp. were identified by nested-PCR assay. The disease was confirmed in 20 out of 30 (66%) suspected patients by parasitological examinations. L. infantum was identified in eight and Leishmania major in 12 CL cases by nested-PCR. Cutaneous leishmaniasis patients infected with L. major had the history of travel to CL endemic areas. L. infantum antibodies were detected by direct agglutination test (DAT) at titers of 1:3200 in two cases with history of VL. Results of this study indicated that L. infantum is a causative agent of CL as well as PKDL in the VL endemic areas.


Safety and Efficacy Outcomes Following Spinal Endoscopic Procedures for Thoracic Ligamentous Ossification: A Systematic Review and Meta-Analysis.
Systematic review and meta-analysis. This study systematically reviewed and evaluated the safety and efficacy of spinal endoscopic techniques as a treatment for thoracic ligamentum flavum ossification (TOLF). The use of spinal endoscopic techniques for the treatment of TOLF has increased in recent years. The present study is the first comprehensive systematic review and meta-analysis focused on the use of spinal endoscopic techniques for TOLF. The Cochrane Central, PubMed, Web of Science, and Embase databases were systematically searched for studies focused on patients undergoing spinal endoscopic techniques to treat symptomatic TOLF. This meta-analysis included 23 studies. We included 323 patients (177 males, 146 females) with a mean age of 58.40±10.06 years, with 304 total recorded lesion locations of which 245 were located in the lower thoracic spine. Complications affected 35/323 patients, and the mean operative duration for 305 patients was 108.15±47.34 minutes. For 187 patients, the mean operative bleeding was 25.13±12.54 mL, while for 87 patients the mean duration of hospitalization was 4.59±1.93 days. At last follow-up,functional assessment was performed for 260 patients, of whom 200 were in excellent condition, visual analog scale (VAS) scores were assessed for 160 patients, with a mean improvement of 4.40 (3.95,4.86) Japanese Orthopedic Association (JOA) scores were recorded for 115 patients, with a mean improvement of 2.99 (2.77,3.22) , and modified Japanese Orthopedic Association (mJOA) scores were recorded for 208 patients, with a mean improvement of 3.41 (3.17,3.64) . These results support several advantages of spinal endoscopic techniques for the treatment of symptomatic TOLF. These include low complication rates, rapid postoperative recovery, and good functional recovery when used for single-segment, non-nodular ossification and no combined dural ossification.


[Argon laser treatment of the iris: an experimental study (author's transl)].
Description of various affections of the iris which may be treated with argon-laser. The problem of the laser iridectomy in the treatment of glaucoma is illustrated by a histologic study of the evolution of the lesions up to four months after coagulation of rabbit's iris.


Decoding and Reconstructing the Focus of Spatial Attention from the Topography of Alpha-band Oscillations.
Many aspects of perception and cognition are supported by activity in neural populations that are tuned to different stimulus features (e.g., orientation, spatial location, color). Goal-directed behavior, such as sustained attention, requires a mechanism for the selective prioritization of contextually appropriate representations. A candidate mechanism of sustained spatial attention is neural activity in the alpha band (8-13 Hz), whose power in the human EEG covaries with the focus of covert attention. Here, we applied an inverted encoding model to assess whether spatially selective neural responses could be recovered from the topography of alpha-band oscillations during spatial attention. Participants were cued to covertly attend to one of six spatial locations arranged concentrically around fixation while EEG was recorded. A linear classifier applied to EEG data during sustained attention demonstrated successful classification of the attended location from the topography of alpha power, although not from other frequency bands. We next sought to reconstruct the focus of spatial attention over time by applying inverted encoding models to the topography of alpha power and phase. Alpha power, but not phase, allowed for robust reconstructions of the specific attended location beginning around 450 msec postcue, an onset earlier than previous reports. These results demonstrate that posterior alpha-band oscillations can be used to track activity in feature-selective neural populations with high temporal precision during the deployment of covert spatial attention.


New laboratory guidelines for serologic diagnosis of Lyme disease: evaluation of the two-test protocol.
Recent guidelines established by the Association of State and Territorial Public Health Laboratory Directors (ASTPHLD) and the U.S. Centers for Disease Control and Prevention (CDC) recommend the use of a two-test protocol for the serologic diagnosis of Lyme disease (LD). The two-test protocol relies on a sensitive screening test, which is followed by specific immunoglobulin M (IgM) and/or IgG immunoblotting (IB), depending on the date of disease onset, of all samples with equivocal and positive screening test results. We evaluated a commercially available IgM-IgG enzyme-linked immunosorbent assay (ELISA) and separate IB tests for IgM and IgG antibodies to Borrelia burgdorferi as candidate assays for the two-test protocol. Serum samples obtained from healthy controls (n = 29), from patients with diagnoses or laboratory findings associated with serologic cross-reactivity to LD (n = 24), and from patients with well-documented early- and late-stage LD provided by the CDC and the College of American Pathologists (n = 53) were examined to determine each assay's individual sensitivity and specificity. No false-positive results were detected among the healthy controls by either ELISA or IB, whereas four false-positive ELISA results were recorded within the cross-reactive group. None of these sera, however, were positive for either IgM or IgG reactivity according to IB band criteria. With regard to the patients with LD, we determined the sensitivity and specificity of the ELISA to be 96 and 100%, respectively, compared with the reference data provided for these specimens. When we compared our IB results with data from CDC, the assay sensitivity and specificity were 80 and 96.2%, respectively, for IgM and 81.8 and 95.8%, respectively, for IgG. Pursuant to this evaluation we assessed the suitability of the two-test protocol by performing a retrospective analysis using clinical history to define samples as positive or negative for LD. We determined clinical sensitivity and specificity for all study subjects (n = 112) to be 50 and 100%, respectively. A reduction in the clinical sensitivity of the two-test protocol was associated with a lack of antibody response or seroconversion in LD patients treated with antibiotics. We conclude that the CDC-ASTPHLD guidelines provide useful criteria for test performance and interpretation aimed at standardizing the serologic diagnosis of LD.


Anesthetic and operative management of potential upper airway obstruction.
Potential or actual supraglottic airway obstruction becomes critical when general anesthesia is begun. Four cases illustrated such obstruction, and the anesthetic and surgical management of each condition was critical. In carcinoma of the supraglottic larynx and in pharyngeal abscess, the unobstructed airway in the conscious patient became impossible to secure once general anesthesia was begun. Unappreciated pathological deformity prohibited endotracheal intubation, and anesthesia precipitated obstruction. In epiglottitis and peritonsillar abscess, the nature of the impending airway obstruction was appreciated, and the selection of a safe technique to secure the airway was made. Anesthetic and surgical management of potential supraglottic obstruction includes five options: (1) oral tracheal intubation by laryngoscopy while the patient is awake; (2) awake nasotracheal intubation; (3) inhalation induction by general anesthesia with intubation; (4) rapid induction with barbiturates and muscle relaxants with intubation; and (5) tracheostomy with local anesthesia.


Early vitrectomy for severe vitreous hemorrhage in diabetic retinopathy. Two-year results of a randomized trial. Diabetic Retinopathy Vitrectomy Study report 2. The Diabetic Retinopathy Vitrectomy Study Research Group.
Six hundred sixteen eyes with recent severe diabetic vitreous hemorrhage reducing visual acuity to 5/200 or less for at least one month were randomly assigned to either early vitrectomy or deferral of vitrectomy for one year. After two years of follow-up, 25% of the early vitrectomy group had visual acuity of 10/20 or better compared with 15% in the deferral group (P = .01). In patients with Type I diabetes, who were on the average younger and had more-severe proliferative retinopathy, there was a clear-cut advantage for early vitrectomy, as reflected in the percentage of eyes recovering visual acuity of 10/20 or better (36% vs 12% in the deferral group, P = .0001). No such advantage was found in the Type II diabetes group (16% in the early group vs 18% in the deferral group), but evidence that this advantage differed by diabetes type was of borderline significance.


Polymorphism of Myostatin Gene in Intron 1 and 2 and Exon 3, and Their Associations with Yearling Weight, Using PCR-RFLP and PCR-SSCP Techniques in Zel Sheep.
The aim of present study was to investigate myostatin gene polymorphism and its association with yearling weight records in Zel sheep using PCR-RFLP and PCR-SSCP methods. Blood samples were collected from 200 Zel sheep, randomly, and DNA was extracted using modified salting out method. Polymerase chain reaction was carried out to amplify 337, 222, and 311 bp fragments, respectively, comprising a part of exon 3, intron 1, and intron 2 of myostatin gene. In addition, exon 3 was digested by HaeIII enzyme under RFLP method, and introns 1 and 2 were studied using SSCP. Under RFLP method, all samples showed mm genotype. Under SSCP method, intron 1 was also monomorph but intron 2 was polymorph (AA, AB, and BB). The allelic frequencies for A and B were 75.5 and 24.5%, respectively. This locus was not in Hardy-Weinberg equilibrium (P < 0.05), and there was no significant effect of myostatin gene on yearling weights.


Marathon run: cardiovascular adaptation and cardiovascular risk.
The first marathon run as an athletic event took place in the context of the Olympic Games in 1896 in Athens, Greece. Today, participation in a 'marathon run' has become a global phenomenon attracting young professional athletes as well as millions of mainly middle-aged amateur athletes worldwide each year. One of the main motives for these amateur marathon runners is the expectation that endurance exercise (EE) delivers profound beneficial health effects. However, with respect to the cardiovascular system, a controversial debate has emerged whether the marathon run itself is healthy or potentially harmful to the cardiovascular system, especially in middle-aged non-elite male amateur runners. In this cohort, exercise-induced increases in cardiac biomarkers-troponin and brain natriuretic peptide-and acute functional cardiac alterations have been observed and interpreted as potential cardiac damage. Furthermore, in the cohort of 40- to 65-year-old males engaged in intensive EE, a significant risk for the development of atrial fibrillation has been identified. Fortunately, recent studies demonstrated a normalization of the cardiac biomarkers and the functional alterations within a short time frame. Therefore, these alterations may be perceived as physiological myocardial reactions to the strenuous exercise and the term 'cardiac fatigue' has been coined. This interpretation is supported by a recent analysis of 10.9 million marathon runners demonstrating that there was no significantly increased overall risk of cardiac arrest during long-distance running races. In conclusion, intensive and long-lasting EE, e.g. running a full-distance Marathon, results in high cardiovascular strain whose clinical relevance especially for middle-aged and older athletes is unclear and remains a matter of controversy. Furthermore, there is a need for evidence-based recommendations with respect to medical screening and training strategies especially in male amateur runners over the age of 35 years engaged in regular and intensive EE.


Pinnacle3 modeling and end-to-end dosimetric testing of a Versa HD linear accelerator with the Agility head and flattening filter-free modes.
The Elekta Versa HD incorporates a variety of upgrades to the line of Elekta linear accelerators, primarily including the Agility head and flattening filter-free (FFF) photon beam delivery. The completely distinct dosimetric output of the head from its predecessors, combined with the FFF beams, requires a new investigation of modeling in treatment planning systems. A model was created in Pinnacle3 v9.8 with the commissioned beam data. A phantom consisting of several plastic water and Styrofoam slabs was scanned and imported into Pinnacle3, where beams of different field sizes, source-to-surface distances (SSDs), wedges, and gantry angles were devised. Beams included all of the available photon energies (6, 10, 18, 6FFF, and 10 FFF MV), as well as the four electron energies commissioned for clinical use (6, 9, 12, and 15 MeV). The plans were verified at calculation points by measurement with a calibrated ionization chamber. Homogeneous and hetero-geneous point-dose measurements agreed within 2% relative to maximum dose for all photon and electron beams. AP photon open field measurements along the central axis at 100 cm SSD passed within 1%. In addition, IMRT testing was also performed with three standard plans (step and shoot IMRT, as well as a small- and large-field VMAT plan). The IMRT plans were delivered on the Delta4 IMRT QA phantom, for which a gamma passing rate was > 99.5% for all plans with a 3% dose deviation, 3 mm distance-to-agreement, and 10% dose threshold. The IMRT QA results for the first 23 patients yielded gamma passing rates of 97.4% ± 2.3%. Such testing ensures confidence in the ability of Pinnacle3 to model photon and electron beams with the Agility head.


Prodrug-inspired probes selective to cathepsin B over other cysteine cathepsins.
Cathepsin B (CTB) is a cysteine protease believed to be an important therapeutic target or biomarker for several diseases including aggressive cancer, arthritis, and parasitic infections. The development of probes capable of assessing CTB activity in cell lysates, living cells, and animal models of disease are needed to understand its role in disease progression. However, discovering probes selective to cathepsin B over other cysteine cathepsins is a significant challenge due to overlap of preferred substrates and binding site homology in this family of proteases. Herein we report the synthesis and detailed evaluation of two prodrug-inspired fluorogenic peptides designed to be efficient and selective substrate-based probes for CTB. Through cell lysate and cell assays, a promising lead candidate was identified that is efficiently processed and has high specificity for CTB over other cysteine cathepsins. This work represents a key step toward the design of rapid release prodrugs or substrate-based molecular imaging probes specific to CTB.


Cancer Risk Factors in Southern Brazil: Report of a Comprehensive, Matched Case-Control Study.
To evaluate cancer risk factors among cancer cases and controls from Southern Brazil, to analyze a multigene hereditary panel testing (MGPT, 26 genes) for breast cancer (BC) and colorectal cancer (CCR) cases diagnosed age younger than 50 years and to characterize them for hereditary cancer syndrome (HCS) phenotypes. A case-control (matched by age group and sex) study was conducted on regional cancer. Data on exposure factors and first-/second-degree family history of cancer (1/2FHC) were collected. The MGPT was performed using Illumina next-generation sequencing technology. A total of 1,007 cases and 1,007 controls were included. The most frequent cancers were BC (n = 311), CCR (n = 147), prostate (n = 132), and lung cancers (n = 89). It was independently associated with cancer, 1/2FHC, tobacco consumption (TC), pesticide exposure (PE), solvent/glue exposure, and BMI <24. BC was associated with 1/2FHC, TC, and hormone replacement therapy use; CCR with 1/2FHC, TC, and BMI <24; prostate cancer with 1/2FHC, TC, and alcohol consumption; and lung cancer with 1/2FHC, TC, PE, and BMI <24. MGPT identified pathogenic/likely pathogenic mutations in 24 (32%) women with BC and in three (18%) women and four (24%) men diagnosed with CCR at under 50 years. Among the tested patients under 50 years with diagnosed BC and CCR, 98.6% and 97% present criteria for HCS, respectively. This study confirmed the association of several factors associated with BC, CCR, prostate, and lung cancers and reinforced the importance of evaluating FHC and genetic testing, especially for patients under 50 years with diagnosed BC or CCR. A better understanding of population-specific cancer risk factors builds on sustainable data for developing prevention strategies. These efforts increase the commitment to early detection and surveillance.


The outer membrane protein Omp35 affects the reduction of Fe(III), nitrate, and fumarate by Shewanella oneidensis MR-1.
Shewanella oneidensis MR-1 uses several electron acceptors to support anaerobic respiration including insoluble species such as iron(III) and manganese(IV) oxides, and soluble species such as nitrate, fumarate, dimethylsulfoxide and many others. MR-1 has complex branched electron transport chains that include components in the cytoplasmic membrane, periplasm, and outer membrane (OM). Previous studies have implicated a role for anaerobically upregulated OM electron transport components in the use of insoluble electron acceptors, and have suggested that other OM components may also contribute to insoluble electron acceptor use. In this study, the role for an anaerobically upregulated 35-kDa OM protein (Omp35) in the use of anaerobic electron acceptors was explored. Omp35 was purified from the OM of anaerobically grown cells, the gene encoding Omp35 was identified, and an omp35 null mutant (OMP35-1) was isolated and characterized. Although OMP35-1 grew on all electron acceptors tested, a significant lag was seen when grown on fumarate, nitrate, and Fe(III). Complementation studies confirmed that the phenotype of OMP35-1 was due to the loss of Omp35. Despite its requirement for wild-type rates of electron acceptor use, analysis of Omp35 protein and predicted sequence did not identify any electron transport moieties or predicted motifs. OMP35-1 had normal levels and distribution of known electron transport components including quinones, cytochromes, and fumarate reductase. Omp35 is related to putative porins from MR-1 and S. frigidimarina as well as to the PorA porin from Neisseria meningitidis. Subcellular fraction analysis confirmed that Omp35 is an OM protein. The seven-fold anaerobic upregulation of Omp35 is mediated post-transcriptionally. Omp35 is a putative porin in the OM of MR-1 that is markedly upregulated anaerobically by a post-transcriptional mechanism. Omp35 is required for normal rates of growth on Fe(III), fumarate, and nitrate, but its absence has no effect on the use of other electron acceptors. Omp35 does not contain obvious electron transport moieties, and its absence does not alter the amounts or distribution of other known electron transport components including quinones and cytochromes. The effects of Omp35 on anaerobic electron acceptor use are therefore likely indirect. The results demonstrate the ability of non-electron transport proteins to influence anaerobic respiratory phenotypes.


Expression of T cell receptors by thymocytes: in situ staining and biochemical analysis.
We have examined the in situ expression of T cell receptor (TCR) V beta 8 protein in murine thymus during ontogeny using the monoclonal antibody F23.1. Positive cells were first detected at day 15 of gestation (0.6%). By day 16 the frequency of positive cells increased dramatically (4.18%). From day 16 to day 17 positive cells doubled (8.17%). The first clusters of F23.1 positive cells were seen at day 17. In the cortex, positive cells decreased from 14% in the newborn mice to 9.8% in 8-week-old mice, whereas in the medulla the frequency remained unchanged at 20%. The antibody F23.1, as well as an antiserum raised against the constant region of the beta chain, immunoprecipitated receptor dimers from highly purified Lyt2+, L3T4+ thymocytes and from two thymic lymphomas of cortical phenotype which express full size alpha and beta mRNA. The receptor dimer could not be precipitated from Lyt2-, L3T4- thymocytes. The results are discussed with regard to intrathymic T cell repertoire selection.


Polymorphisms in ER-alpha gene interact with estrogen receptor status in breast cancer survival.
The effects of estrogens are mediated primarily through estrogen receptor (ER) in breast tissue, and polymorphisms in the ER genes may alter the functions of these receptors. Polymorphisms in the ER-alpha gene have been reported to be associated with breast cancer risk. However, to our knowledge, no study has been published on the relation between ER-alpha gene polymorphisms and breast cancer survival. To determine whether three common polymorphisms in the ER-alpha gene, PvuII, XbaI, and GT dinucleotide repeats are associated with breast cancer survival, we evaluated data from a cohort of 1,069 breast cancer patients who participated in the Shanghai Breast Cancer Study between 1996 and 1998. The median follow-up time for this cohort of women was 5.2 years. No overall association was observed between ER gene polymorphisms and breast cancer survival. The genotype associations, however, were modified by ER status in breast cancer tissues. Comparing those with the PP genotype to the pp genotype of the PvuII polymorphism, the hazard ratios (HR) of dying were 3.30 [95% confidence interval (95% CI), 1.42-7.69] and 0.54 (95% CI, 0.24-1.23), respectively, for participants with ER-negative breast cancer and ER-positive breast cancer. Similarly, compared with those with no (GT)(23) alleles, carrying one or two (GT)(23) alleles of the GT repeat polymorphism was related to a HR of 1.48 (95% CI, 0.77-2.87) for ER-negative breast cancer and a HR of 0.25 (95% CI, 0.09-0.69) for ER-positive cancer. The effect of ER on breast cancer survival was also modified by genotypes of ER-alpha gene. Tests for multiplicative interaction were highly significant. These data suggest that the ER-alpha gene polymorphisms and ER status may have an interactive effect on breast cancer survival.


Ribozyme-mediated REV1 inhibition reduces the frequency of UV-induced mutations in the human HPRT gene.
In yeast, mutations induced by UV radiation are dependent on the function of the Rev1 gene product, a Y-family DNA polymerase that assists in translesion replication with potentially mutagenic consequences. Human REV1 has been cloned, but its role in mutagenesis and carcinogenesis remains obscure. To examine the role of REV1 in UV mutagenesis in human cells and to evaluate its potential as a therapeutic target to prevent such mutations, we developed a ribozyme that cleaves human REV1 mRNA in vitro. Stable expression of the ribozyme in human cells reduced the target REV1 mRNA up to 90%. We examined the cytotoxic and mutagenic response to UV of seven independent clones that had reduced levels of endogenous REV1 mRNA. In each case, the clonogenic survival after UV was not different from that of the parental cell strains. In contrast, the UV-induced mutant frequencies at the endogenous HPRT locus were reduced up to 75% in cells with reduced levels of REV1 mRNA. The data support the idea that targeting the mutagenic translesion DNA replication pathway can greatly reduce the frequency of induced mutations.


Macroscopic qualitative evaluation of solid pancreatic lesion specimens from endoscopic ultrasound-guided fine needle aspiration/biopsies.
To pathologically clarify the macroscopic features of endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNA/B) specimens in representative pancreatic diseases and establish tissue-handling standards based on the macroscopic findings. We gathered EUS-FNA/B specimens of cases at our institution with the final diagnoses of pancreatic ductal adenocarcinoma (PDAC, n = 172), neuroendocrine tumor (NET, n = 19), and chronic inflammatory lesion (CIL, n = 24) including autoimmune pancreatitis. We classified the specimens' macroscopic features in five categories (red strings, mixed-red-and-white strings, white cores, gray tissues, gelatinous tissues) and compared the specimens' features on cytological and histological slides. All five macroscopic categories were observed in variable combinations in the PDACs; red strings and white cores predominated in the NETs and CILs. White cores represented neoplastic (PDAC, NET) or lesion (CIL) tissues. Mixed-red-and-white strings were unique to PDACs and contained cancerous cells. Neoplastic cells were numerous in red strings in NETs but not the other groups. Gray and gelatinous tissues represented necrosis and mucin, respectively, and the former were almost exclusively observed in PDACs. Red strings, mixed-red-and-white strings, and white cores were suitable for histological examination, whereas gray and gelatinous tissues were suitable for cytological examination. The white cores, mixed-red-and-white strings, and gelatinous tissues may be composed of non-neoplastic tissues such as contaminated gastrointestinal epithelium. In seven PDACs, although white cores were obtained, a histological diagnosis was not established. Macroscopic evaluations of EUS-FNA/B can enable the identification of specimen components and a possible diagnosis. They also contribute to the selection of the optimal tissue-handling methods.


Accelerated evolution in the protein-coding region of galectin cDNAs, congerin I and congerin II, from skin mucus of conger eel (Conger myriaster).
Two cDNAs encoding galectins named congerins I and II from the skin mucus of conger eel (Conger myriaster) were isolated and sequenced. Comparison of the nucleotide sequences of congerins I and II showed that the sequence similarities of the 5' and 3' untranslated regions (86 and 88%, respectively) were much higher than those of the protein-coding region (73%). The numbers of nucleotide substitutions per site (KN) for the untranslated regions are smaller than the numbers of nucleotide substitutions per synonymous site (KS) for the protein coding region. Furthermore, nonsynonymous nucleotide substitutions have accelerated more frequently than synonymous nucleotide substitutions in the protein coding region (KA/KS = 2.57). These results suggest that accelerated substitutions have occurred in the protein-coding regions of galectin genes to generate diverse galectins with different molecular properties. Northern blot analysis showed that both congerins were expressed not only in the skin tissues but also in the stomach of conger eel.


Stent-Assisted Coiling of Unruptured Intracranial Aneurysms with Wide Neck.
Morbidity and mortality in patients experiencing the rupture of intracranial aneurysm ruptures are high. We conducted a systematic review and meta-analysis to investigate the role of stent-assisted coiling (SAC) for unruptured intracranial aneurysms (UIAs) with wide neck. The current meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled proportions with 95% confidence intervals (CIs) of ten outcomes of interest were calculated. We finally reviewed 13 studies, including 976 patients. The technical success of the method was 98.43% (95% CI: 95.62-99.95). Early outcomes included total periprocedural obliteration with a rate of 50.20% (95% CI: 36.09-64.30) and periprocedural rupture with zero rate. During the follow-up period, ranging from 6 months to 2 years, the total postprocedural obliteration rate was 63.83% (95% CI: 45.80-80.18) and the overall late rupture rate was 0.41% (95% CI: 0.00-2.38). The pooled in-stent stenosis rate was calculated at 1.24% (95% CI: 0.02-3.63). We also estimated a pooled rate of 0.02% (95% CI: 0.00-0.51) and 4.33% (95% CI: 2.03-7.23) for total mortality and overall neurological complications, respectively. A pooled rate of 3.94% (95% CI: 1.48-7.33) was found for stroke. Finally, the recanalization rate was recorded at 7.07% (95% CI: 4.35-10.26). SAC of UIAs with wide neck seems to be a safe and acceptable alternative to surgical clipping. Although early results concerning total periprocedural obliteration may be modest, follow-up outcomes may be indicative of adequate occlusion of treated UIAs.


Antitumor effects of WNT2B silencing in GLUT1 overexpressing cisplatin resistant head and neck squamous cell carcinoma.
The increased rate of glucose uptake necessary to support the growth of tumor cells is mediated by glucose transporters, and glucose transporter 1 (GLUT1) is overexpressed in several types of cancer in correlation with poor prognosis. And WNT2B overexpression is thought to be involved in tumor progression. Here, we investigated the effects of WNT2B in GLUT1 overexpressing cisplatin resistant head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo. We generated GLUT1 overexpressing cisplatin resistant CAL27 and SCC25 oral cancer cells. Lentiviral mediated knock-down of WNT2B was performed in CAL27 and SCC25. QRT-PCR and Western blot analysis were used to detect the mRNA and protein expression of GLUT1, WNT2B, Cyclin D1 and β-catenin. Cell viability was assessed by MTT analysis. Colony formation assay was performed by staining with 0.5% crystal violet. The role of WNT2B in HNSCC was examined in vivo through the generation of a CAL27 (or cisplatin resistant CAL27 or cisplatin resistant CAL27 with WNT2B knock-down) nude mice xenograft model of HNSCC. Knock-down of WNT2B in decreased cell viability and colony formation in cisplatin resistant CAL27 and SCC25 in association with the downregulation of GLUT1, cyclin D1 and β-catenin. In a cisplatin resistant CAL27 mouse xenograft model, shRNA mediated silencing of WNT2B increased survival and decreased tumor growth in correlation with the downregulation of GLUT1, cyclin D1 and β-catenin. WNT2B plays a role in tumorigenesis and chemotherapy resistance in oral cancer and provide a potential therapeutic target for the treatment of patients with HNSCC.


Efficient use of continuous, real-time prostate localization.
Recent technological advances make it possible to monitor prostate movement during radiation delivery. Using previously published data from 35 patients who underwent continuous localization during prostate cancer treatment, we simulated various interventions to identify the radiation-gating and patient-repositioning strategies that least prolonged the time to complete the daily treatment. Acceptable response protocols were those that resulted in at least 95% of patients' prostates remaining within the planning margins at least 95% of the time. Gating and repositioning were not necessary for margins of 7 or 10 mm because of the rarity of excursions at these margins. However, intervention was routinely necessary for margins of 3 and 5 mm. In simulated interventions for which the therapist could reposition the treatment couch without entering the room, the most time-efficient response protocol was to reposition the couch immediately after the prostate position was outside the treatment margins. In simulations in which the therapist had to enter the room to reposition the couch, overall treatment time could be reduced and accuracy could be increased by manually gating treatment for 11 and 21 s for 3- and 5-mm margins, respectively, before interrupting treatment to reposition the treatment couch.


The hippocampus: a special place for time.
Many findings have demonstrated that memories of past events are temporally organized. It is well known that the hippocampus is critical for such episodic memories, but, until recently, little was known about the temporal organization of mnemonic representations in the hippocampus. Recent developments in human and animal research have revealed important insights into the role of the hippocampus in learning and retrieving sequences of events. Here, we review these findings, including lesion and single-unit recording studies in rodents, functional magnetic resonance imaging studies in humans, and computational models that link findings from these studies to the anatomy of the hippocampal circuit. The findings converge toward the idea that the hippocampus is essential for learning sequences of events, allowing the brain to distinguish between memories for conceptually similar but temporally distinct episodes, and to associate representations of temporally contiguous, but otherwise unrelated experiences.


Can Coronavirus Disease 2019 Induce Sarcoidosis: A Case Report.
Since the emergence of coronavirus disease 2019, a large spectrum of clinical manifestations following this acute viral infection has been reported especially autoimmune manifestations and inflammatory disorders. However, a causal link has not yet been established. Herein, we reported a case of pulmonary mediastinal sarcoidosis following coronavirus disease 2019 infection. A 41-year-old woman with no clinical or radiographic symptoms or signs of sarcoidosis prior to coronavirus disease 2019 infection developed dyspnea, cough, and fatigue, a few months after discharge. A chest thoracic scan performed 3 months after hospital discharge showed regression of groundglass opacities with the appearance of pulmonary micronodules. Clinical examination and spirometry were normal. The evolution was marked by progressive worsening of dyspnea and significant weight loss. A chest thoracic scan performed 6 months after discharge showed bilateral and symmetrical hilar and mediastinal and paratracheal lymphadenopathy. Bronchoalveolar lavage with cell count showed a lymphocytosis of 19.5% and a CD4/CD8 T cell ratio of 2.2. Endobronchial lung biopsy revealed noncaseating epithelioid granulomas. Sputum culture excluded tuberculosis. The diagnosis of pulmonary-mediastinal sarcoidosis was made. She was treated with an oral corticosteroid. The patient showed significant improvement during the 3-month follow-up period. Post-coronavirus disease sarcoidosis is very rare. Complementary studies are needed to discern the link between these diseases.


Galangin (GLN) Suppresses Proliferation, Migration, and Invasion of Human Glioblastoma Cells by Targeting Skp2-Induced Epithelial-Mesenchymal Transition (EMT).
Galangin (GLN), a pure natural flavonoid compound found in plants, has been shown to exert anti-cancer effects against multiple cancer types, including glioma. However, its underlying molecular mechanism remains unclear. Epithelial-to-mesenchymal transition (EMT) performs an important function in the genesis and development of cancer. Skp2, a pivotal component of SCFSkp2 E3 ubiquitin ligase, has been shown to function as an oncogene in GBM invasion that contributes to the EMT process. Thus, we explored whether GLN inhibited Skp2-mediated EMT and the mechanism underlying the Skp2 degradation pathway. CCK-8 assay, wound healing assay and transwell assay were used to examine cell proliferation, migration, and invasion after treatment with or without GLN. RT-PCR and Western blotting analysis were performed to evaluate mRNA and protein expression, respectively. Co-immunoprecipitation was conducted to detect ubiquitinated Skp2 levels in vitro and in vivo after GLN treatment. Bioluminescence imaging was performed to examine the intracranial tumor size of U87 xenograft mice. Microscale thermophoresis (MST) experiment was used to detect interactions between Skp2 and GLN. GLN suppressed GBM cell growth, migration, and invasion, and also downregulated the expression of Skp2 and mesenchymal markers (Zeb1, N-cadherin, snail, vimentin) in vitro. Moreover, the overexpression of Skp2 in GBM cells decreased the effect of GLN on EMT. Furthermore, we demonstrated that GLN degraded skp2 protein through the ubiquitination proteasome pathway and directly interacted with skp2 protein, as shown through the MST assay. This study is the first to identify Skp2 as a novel target of GLN for the treatment of GBM and report of Skp2 protein degradation in a ubiquitination proteasome pathway. Results from our study indicated the potential of GLN for the treatment of GBM through ubiquitin-mediated degradation of Skp2.


On the mechanisms of the inhibition of calcium sequestering activity of liver microsomes in bromotrichloromethane intoxication.
The mechanisms by which the in vivo intoxication with BrCCl3 inhibits the calcium sequestration activity of liver microsomes were studied. The initial rate of Ca2+ transport is inhibited by nearly 50% in the intoxicated rats as compared to the controls; this indicates that the active transport of Ca2+ is markedly affected by the intoxication. The microsomal ATPase activities both in the presence and in the absence of Ca2+ were not decreased at all in the intoxicated animals. However, the Ca2+-dependent extra ATP-hydrolysis shows a different kinetics in the BrCCl3-poisoned rats with respect to the controls. The release of Ca2+ from Ca2+-loaded liver microsomes is higher in the intoxicated animals. It seems therefore that the increased permeability of the membrane to Ca2+ contributes to some extent to the haloalkane-induced inhibition of the calcium sequestration activity of liver microsomes.


Computed tomography measured epicardial adipose tissue and psoas muscle attenuation: new biomarkers to predict major adverse cardiac events and mortality in patients with heart disease and critically ill patients. Part II: Psoas muscle area and density.
Sarcopenia is a syndrome characterised by loss of skeletal muscle mass, loss of muscle quality, and reduced muscle strength, resulting in low performance. Sarcopenia has been associated with increased mortality and complications after medical interventions. In daily clinical practice, sarcopenia is assessed by clinical assessment of muscle strength and performance tests and muscle mass quantification by dual-energy X-ray absorptio-metry (DXA) or bioelectrical impedance analysis (BIA). Assessment of the skeletal muscle quantity and quality obtained by abdominal computed tomography (CT) has gained interest in the medical community, as abdominal CT is performed for various medical reasons, and quantification of the psoas and skeletal muscle can be performed without additional radiation load and dye administration. The definitions of CT-derived skeletal muscle mass quantification are briefly reviewed: psoas muscle area (PMA), skeletal muscle area (SMA), and transverse psoas muscle thickness (TPMT). We explain how CT attenuation coefficient filters are used to determine PMA and SMA, resulting in the psoas muscle index (PMI) and skeletal muscle index (SMI), respectively, after indexation to body habitus. Psoas muscle density (PMD), a biomarker for skeletal muscle quality, can be assessed by measuring the psoas muscle CT attenuation coefficient, expressed in Hounsfield units. The concept of low-density muscle (LDM) is explained. Finally, we review the medical literature on PMI and PMD as predictors of adverse outcomes in patients undergoing trauma or elective major surgery, transplantation, and in patients with cardiovascular and internal disease. PMI and PMD are promising new biomarkers predicting adverse outcomes after medical interventions.


Climate-driven uncertainties in modeling terrestrial gross primary production: a site level to global-scale analysis.
We used a land surface model to quantify the causes and extents of biases in terrestrial gross primary production (GPP) due to the use of meteorological reanalysis datasets. We first calibrated the model using meteorology and eddy covariance data from 25 flux tower sites ranging from the tropics to the northern high latitudes and subsequently repeated the site simulations using two reanalysis datasets: NCEP/NCAR and CRUNCEP. The results show that at most sites, the reanalysis-driven GPP bias was significantly positive with respect to the observed meteorology-driven simulations. Notably, the absolute GPP bias was highest at the tropical evergreen tree sites, averaging up to ca. 0.45 kg C m(-2) yr(-1) across sites (ca. 15% of site level GPP). At the northern mid-/high-latitude broadleaf deciduous and the needleleaf evergreen tree sites, the corresponding annual GPP biases were up to 20%. For the nontree sites, average annual biases of up to ca. 20-30% were simulated within savanna, grassland, and shrubland vegetation types. At the tree sites, the biases in short-wave radiation and humidity strongly influenced the GPP biases, while the nontree sites were more affected by biases in factors controlling water stress (precipitation, humidity, and air temperature). In this study, we also discuss the influence of seasonal patterns of meteorological biases on GPP. Finally, using model simulations for the global land surface, we discuss the potential impacts of site-level reanalysis-driven biases on the global estimates of GPP. In a broader context, our results can have important consequences on other terrestrial ecosystem fluxes (e.g., net primary production, net ecosystem production, energy/water fluxes) and reservoirs (e.g., soil carbon stocks). In a complementary study (Barman et al., ), we extend the present analysis for latent and sensible heat fluxes, thus consistently integrating the analysis of climate-driven uncertainties in carbon, energy, and water fluxes using a single modeling framework.


Diversity of Guilds of Amphibian Larvae in North-Western Africa.
The composition and diversity of biotic assemblages is regulated by a complex interplay of environmental features. We investigated the influence of climate and the aquatic habitat conditions on the larval traits and the structure of amphibian larval guilds in north-western Africa. We classified the species into morphological groups, based on external traits: body shape, size, and the relative positions of the eyes and oral apparatus. We characterized the guild diversity based on species richness and interspecific phylogenetic/functional relationships. The larvae of the urodeles were classified as typical of either the stream or pond type, and the anurans as typical of either the lentic-benthic or lentic-nektonic type. The variations in the body shapes of both urodeles and anurans were associated with the type of aquatic habitat (lentic vs lotic) and the types of predators present. Most of the urodele guilds (98.9%) contained a single species, whereas the anuran guilds were usually more diverse. Both the phylogenetic and functional diversity of the anuran guilds were positively influenced by the size of the aquatic habitat and negatively by aridity. In anurans, the benthic and nektonic morphological types frequently co-occurred, possibly influenced by their opportunistic breeding strategies.


Risk factors for overweight and overfatness in rural South African children and adolescents.
To determine risk factors for overweight/overfatness in children and adolescents from rural KwaZulu-Natal, South Africa. Anthropometric data were collected from a cross-sectional sample (n = 1519, ages 7, 11 and 15 years) and linked to demographic information (n = 1310 and n = 1317 in overweight and overfat analyses, respectively). Candidate risk factors for overweight/overfatness were identified and tested for associations with overweight (BMI-for-age >+1SD, WHO reference) and overfatness (>85th centile body fatness, McCarthy reference) as outcomes. Associations were examined using simple tests of proportions (χ(2)/Mann-Whitney U tests) and multivariable logistic regression. Sex was a consistent variable across both analyses; girls at significantly increased risk of overweight and overfatness (overweight: n = 180, 73.9 and 26.1% females and males, respectively (P < 0.0001); overfat: n = 187, 72.7 and 27.3% females and males, respectively (P < 0.0001)). In regression analyses, sex and age (defined by school grade) were consistent variables, with boys at lower risk of overweight (adjusted odds ratio (AOR) 0.40 (confidence interval (CI) -0.28-0.57)) and risk of overweight increasing with age (AOR 0.65 (CI- 0.44-0.96), 0.50 (CI-0.33-0.75) and 1.00 for school grades 1, 5 and 9, respectively). Results were similar for overfatness. This study suggests that pre-adolescent/adolescent females may be the most appropriate targets of future interventions aimed at preventing obesity in rural South Africa.


Sensitivity and specificity of the Rey Dot Counting Test in patients with suspect effort and various clinical samples.
The Rey Dot Counting Test was administered to 100 patients with suspect effort drawn from two separate settings (personal injury/disability, n=86; prison hospital, n=14) and to 251 subjects in nine clinical groups (head injury, learning disability, right and left cerebrovascular accident, schizophrenia, older normals, depressed elderly, and mild and moderate dementia). Sensitivity of cut-offs for individual test scores (mean grouped dot counting time, ratio of mean grouped to ungrouped dot counting time, and number of errors) differed markedly across the two suspect effort groups (e.g., 28-100%), indicating that noncredible patients drawn from different settings employ somewhat differing approaches in their fabrication of cognitive symptoms. Use of a cut-off of > or =17 applied to a combination score (mean ungrouped dot counting time+meangrouped dot counting time+number of errors) resulted in 100% sensitivity in the forensic suspect effort group and 75% sensitivity in the civil litigation/disability suspect effort group, while maintaining specificity of > or =90% for the clinical groups combined (excluding moderate dementia).


Pd-catalyzed α-arylation of trimethylsilyl enolates of α,α-difluoroacetamides.
We report the arylation and heteroarylation of α,α-difluoro-α-(trimethylsilyl)acetamides with aryl and heteroaryl bromides catalyzed by an air- and moisture-stable palladacyclic complex containing P(t-Bu)2Cy as ligand. A broad range of electronically varied aryl and heteroaryl bromides underwent this transformation to afford α-aryl-α,α-difluoroacetamides in high yields. Due to the electrophilicity of the fluorinated amide, this palladium-catalyzed cross-coupling reaction provides a versatile platform to generate a range of α,α-difluoro carbonyl compounds, such as α-aryl-α,α-difluoroketones, -acetaldehydes, -acetates, and acetic acids, and difluoroalkyl derivatives, such as 2-aryl-2,2-difluoroethanols and -ethylamines, under mild conditions.


[Tertiary syphilis of the pancreas and liver in 82-year-old patient: case study].
It has been described a clinical case of late diagnosis of syphilis of the pancreas and liver of elderly patients. Two years before that it was wrongly diagnosed with cancer of the pancreas with liver metastases, and the patient was operated on with the imposition of cholecystostomy. It was conducted appropriate therapy and reconstructive surgery after verification of the diagnosis of syphilis of the pancreas and liver.


The intussusception antireflux valve is ineffective in preventing cholangitis in biliary atresia.
Cholangitis is the most common complication after portoenterostomy for biliary atresia. The construction of an intussusception valve in the Roux-en-Y limb of the portoenterostomy has been advocated as a means to ameliorate this complication. The authors reviewed the records of children who underwent portoenterostomy to assess the incidence and severity of cholangitis, as well as outcome. The children were divided into two groups according to whether they did not have (group I) or did have (group II) an antireflux valve in the Roux limb of the bilioenteric conduit. There were 19 children in each group. There were no significant differences between the groups with respect to age at time of portoenterostomy or length of follow-up (Table 1). Nine group I patients are alive and well; five died and five have had or are awaiting transplantation. In group II, 10 patients are alive and well, eight have had transplantation, and one is awaiting transplantation. Outcome with respect to death or the need for liver transplantation because of progressive hepatic failure is not different between the groups (P = 1.0, Fisher's 2 x 2). The incidence of cholangitis was evaluated by comparing the average number of episodes of cholangitis during the follow-up period, the number of episodes per year, and the number of episodes in the first postoperative year (when this complication is most prevalent). Analysis of the data showed no difference in incidence between those with valved and nonvalved biliary conduits. The severity of cholangitis, judged by total length of antibiotic treatment, did not differ between the groups. It appears that the presence of an intussusception valve in the Roux-en-Y biliary conduit does not affect the incidence of cholangitis or the outcome after portoenterostomy, over short-term follow-up.


Species differences in the metabolism of suprofen in laboratory animals and man.
The metabolism of the oral anti-inflammatory agent suprofen (S), 2-4-(2-thienylcarbonyl)phenyl)propionic acid, has been studied in mice, rats, guinea pigs, dogs, monkeys, and human volunteers. The major metabolites of S in the serum, urine, and feces of these species were determined by GC/MS and HPLC techniques. The metabolic pathways of S in these species involved reduction of the ketone group to an alcohol (S-OH), hydroxylation of the thiophene ring (T-OH), elimination of the thiophene ring to a dicarboxylic acid (S-COOH), and conjugation with glucuronic acid or taurine. In 72-hr urine and feces of these species after po dosing of 1.6 to 2 mg/kg of S, S and these metabolites accounted for 46 to 92% of the dose and were mainly excreted in the urine. S was present as a major product (excreted mainly in conjugated form) in all species. S-OH was a major component in guinea pig and dog but a minor one in other species. T-OH was identified as a major metabolite in monkey, rat, mouse, and man, but a minor one in guinea pig, and it was absent in the dog. S-COOH was present as the minor metabolite in mouse and rat, and present at trace levels in dog, monkey, and man. Conjugation of the propionic acid functionality with taurine was observed only in the dog; in the other species, conjugation with glucuronic acid was extensive. Absorption parameters of S in the rat and monkey were similar to those in man; however, other species were very different from man.


Camphene-Assisted Fabrication of Free-Standing Lithium-Ion Battery Electrode Composites.
Free-standing electrode (FSE) architectures hold the potential to dramatically increase the gravimetric and volumetric energy density of lithium-ion batteries (LIBs) by eliminating the parasitic dead weight and volume associated with traditional metal foil current collectors. However, current FSE fabrication methods suffer from insufficient mechanical stability, electrochemical performance, or industrial adoptability. Here, we demonstrate a scalable camphene-assisted fabrication method that allows simultaneous casting and templating of FSEs comprising common LIB materials with a performance superior to their foil-cast counterparts. These porous, lightweight, and robust electrodes simultaneously enable enhanced rate performance by improving the mass and ion transport within the percolating conductive carbon pore network and eliminating current collectors for efficient and stable Li+ storage (>1000 cycles in half-cells) at increased gravimetric and areal energy densities. Compared to conventional foil-cast counterparts, the camphene-derived electrodes exhibit ∼1.5× enhanced gravimetric energy density, increased rate capability, and improved capacity retention in coin-cell configurations. A full cell containing both a free-standing anode and cathode was cycled for over 250 cycles with greater than 80% capacity retention at an areal capacity of 0.73 mA h/cm2. This active-material-agnostic electrode fabrication method holds potential to tailor the morphology of flexible, current-collector-free electrodes, thus enabling LIBs to be optimized for high power or high energy density Li+ storage. Furthermore, this platform provides an electrode fabrication method that is applicable to other electrochemical technologies and advanced manufacturing methods.


Triplicate post-traumatic sciatic nerve palsy: evoked potentials in the diagnosis.
Three episodes of sciatic nerve palsy occurred after open reduction and internal fixation of a fracture-dislocation of the left hip and pelvis in a 20-year-old female injured in a motor cycle accident. There were also ipsilateral open fractures of the tibia and fibula and an open knee injury. When the palsy first developed the patient was in a hip spica plaster cast extending from the costal margin to encase the whole left lower limb. At the time of the second and third episodes of palsy she was in a left below-knee cast and it was not possible to fully assess the function of involved muscles clinically or electromyographically. Psychological factors due to prolonged disability and hospitalization were suspected as a possible cause of weakness. Therefore evoked potentials obtained by stimulation of the peroneal nerves were used to aid diagnosis. There was no response from lumbar and cerebral recording sites on stimulation of the peroneal nerve on the affected side. Diagnosis of a conduction block in the sciatic nerve was thus established. The patient recovered clinically and on repeated testing after motor recovery the cortical potential was attenuated and delayed by 15ms. Recurrent sciatic nerve palsy, occurring three times after hip trauma and with heterotopic bone formation and diagnostic application of evoked potential techniques, has not been previously reported.


Management of Differentiated Thyroid Cancer in Children: Focus on the American Thyroid Association Pediatric Guidelines.
First introduced in 1946, radioactive iodine (I-131) produces short-range beta radiation with a half-life of 8 days. The physical properties of I-131 combined with the high degree of uptake in the differentiated thyroid cancers (DTCs) led to the use of I-131 as a therapeutic agent for DTC in adults. There are two indications for the potential use of I-131 therapy in pediatric thyroid disorders: nonsurgical treatment of hyperthyroidism owing to Graves' disease and the treatment of children with intermediate- and high-risk DTC. However, children are not just miniature adults. Not only are children and the pediatric thyroid gland more sensitive to radiation than adults but also the biologic behavior of DTC differs between children and adults as well. As opposed to adults, children with DTC typically present with advanced disease at diagnosis; yet, they respond rapidly to therapy and have an excellent prognosis that is significantly better than that in adult counterparts with advanced disease. Unfortunately, there are also higher rates of local and distant disease recurrence in children with DTC compared with adults, mandating lifelong surveillance. Further, children have a longer life expectancy during which the adverse effects of I-131 therapy may become manifest. Recognizing the differences between adults and children with DTC, the American Thyroid Association commissioned a task force of experts who developed and recently published a guideline to address the unique issues related to the management of thyroid nodules and DTC in children. This article reviews the epidemiology, diagnosis, staging, treatment, therapy-related effects, and suggestions for surveillance in children with DTC, focusing not only on the differences between adults and children with this disease but also on the latest recommendations from the inaugural pediatric management guidelines of the American Thyroid Association.


Essential Mineral Intake During Pregnancy and Its Association With Maternal Health and Birth Outcomes in South East Queensland, Australia.
Micronutrient supplements are often recommended during pregnancy, yet their role and necessity remain poorly understood in the Australian population. This study aimed to determine the essential mineral intake of a population of pregnant women in South East Queensland and investigate the effects of supplements on their micronutrient status and birth outcomes. Women completing the Oral Glucose Tolerance Test at two South East Queensland hospitals between 180 and 210 days gestation provided fasting blood samples and dietary data using the Maternal Outcomes and Nutrition Tool (n = 127). Birth outcomes were sourced from medical records. Serum elemental profiles were determined by inductively coupled plasma mass spectrometry (ICP-MS) analysis. Intake of 8 essential minerals was compared with Australian dietary recommendations; matched serum mineral levels were compared with the current Queensland pregnancy reference ranges. Data were examined using cross-sectional cohort design and independent sample t-tests. Supplement use had no significant influence on serum values of trace elements or the incidence of hypertensive disorders, gestational diabetes, preterm birth or infant birthweight. Dietary selenium, zinc and iodine were significantly higher in women birthing beyond 41 completed weeks; selenium (P = .026) and zinc (P = .034) both made unique contributions to the regression models when controlling for confounders. Women exhibited adequate to excessive serum micronutrient levels compared with pregnancy reference ranges, a finding consistent with dietary intake calculations. Data suggest that excessive essential mineral intake contributed to prolonged pregnancy in this cohort, supporting previous studies in this population. Further research is required to determine individual needs and eliminate the potential for harm before recommending pregnancy supplements.


Characterization and identification of numerically abundant culturable bacteria from the anoxic bulk soil of rice paddy microcosms.
Most-probable-number (liquid serial dilution culture) counts were obtained for polysaccharolytic and saccharolytic fermenting bacteria in the anoxic bulk soil of flooded microcosms containing rice plants. The highest viable counts (up to 2.5 x 10(8) cells per g [dry weight] of soil) were obtained by using xylan, pectin, or a mixture of seven mono- and disaccharides as the growth substrate. The total cell count for the soil, as determined by using 4', 6-diamidino-2-phenylindole staining, was 4.8 x 10(8) cells per g (dry weight) of soil. The nine strains isolated from the terminal positive tubes in counting experiments which yielded culturable populations that were equivalent to about 5% or more of the total microscopic count population belonged to the division Verrucomicrobia, the Cytophaga-Flavobacterium-Bacteroides division, clostridial cluster XIVa, clostridial cluster IX, Bacillus spp., and the class Actinobacteria. Isolates originating from the terminal positive tubes of liquid dilution series can be expected to be representatives of species whose populations in the soil are large. None of the isolates had 16S rRNA gene sequences identical to 16S rRNA gene sequences of previously described species for which data are available. Eight of the nine strains isolated fermented sugars to acetate and propionate (and some also fermented sugars to succinate). The closest relatives of these strains (except for the two strains of actinobacteria) were as-yet-uncultivated bacteria detected in the same soil sample by cloning PCR-amplified 16S rRNA genes (U. Hengstmann, K.-J. Chin, P. H. Janssen, and W. Liesack, Appl. Environ. Microbiol. 65:5050-5058, 1999). Twelve other isolates, which originated from most-probable-number counting series indicating that the culturable populations were smaller, were less closely related to cloned 16S rRNA genes.


Experimental H1N1pdm09 infection in pigs mimics human seasonal influenza infections.
Pigs are anatomically, genetically and physiologically comparable to humans and represent a natural host for influenza A virus (IAV) infections. Thus, pigs may represent a relevant biomedical model for human IAV infections. We set out to investigate the systemic as well as the local immune response in pigs upon two subsequent intranasal infections with IAV H1N1pdm09. We detected decreasing numbers of peripheral blood lymphocytes after the first infection. The simultaneous increase in the frequencies of proliferating cells correlated with an increase in infiltrating leukocytes in the lung. Enhanced perforin expression in αβ and γδ T cells in the respiratory tract indicated a cytotoxic T cell response restricted to the route of virus entry such as the nose, the lung and the bronchoalveolar lavage. Simultaneously, increasing frequencies of CD8αα expressing αβ T cells were observed rapidly after the first infection, which may have inhibited uncontrolled inflammation in the respiratory tract. Taking together, the results of this study demonstrate that experimental IAV infection in pigs mimics major characteristics of human seasonal IAV infections.


CTX-M-27- and CTX-M-14-producing, ciprofloxacin-resistant Escherichia coli of the H30 subclonal group within ST131 drive a Japanese regional ESBL epidemic.
The global increase in ESBL-producing Escherichia coli is associated with the ST131 clonal group, especially its CTX-M-15-producing H30Rx subset. To understand the rapid spread of ESBL-producing E. coli in Japan, we investigated the molecular epidemiology and ESBL-associated genetic environments of Japanese ST131 isolates. Between 2001 and 2012, 1079 ESBL-producing E. coli isolates were collected at 10 Japanese acute-care hospitals. ESBL types, ST131 status, fimH allele, H30Rx-defining sequences and ESBL-associated genetic environments were defined using PCR and sequencing. Subclonal groups were defined based on fimH allele and H30Rx status. Overall, 461 (43%) of the 1079 ESBL-producing E. coli isolates represented ST131. According to fimH-based subclonal typing, the ST131 isolates included 398 fimH allele 30 (H30) isolates, 49 H41 isolates, 10 H22 isolates and 4 other fimH-type isolates. The 398 H30 isolates included 396 ciprofloxacin-resistant H30R isolates, of which 64 (16%) represented the H30Rx subset. Between 2001 and 2007, the CTX-M-14-producing H30R subgroup predominated, accounting for 46% of ST131 isolates, whereas the CTX-M-27-producing H30R and CTX-M-15-producing H30Rx subgroups were rarely detected. In contrast, from 2008 onward the latter two subgroups rose to dominance, accounting for 45% and 24% of ST131 isolates, respectively, versus only 15% for the (formerly dominant) CTX-M-14-producing H30R subgroup. The emergent CTX-M-27-H30R subgroup frequently had an IS26-ΔISEcp1-blaCTX-M-27-ΔIS903D-IS26-like structure, whereas the older CTX-M-14-H30R subgroup frequently had an ISEcp1-blaCTX-M-14-IS903D-like structure. This Japanese regional ESBL-producing E. coli epidemic is closely associated with newly identified CTX-M-27- and CTX-M-14-producing ST131 H30R subclonal groups and with mobile elements IS26, ISEcp1 and IS903D.