Surgical treatment of stoma-related hernias: retrospective cohort study of damage claims to the Swedish National Patient Insurance Company 2010-2016.
Parastomal hernia and stoma-site hernia are common stoma complications. Parastomal hernia repair is associated with high complication and recurrence rates. Insurance data can provide novel information on the consequences of perioperative complications from the patient's point of view. The aim was to investigate what types of complications associated with stoma-related hernia surgery that cause patients to apply for economic compensation through the patient insurance system and to investigate demographic and clinical differences among cases based on gender and type of center at which the surgery was performed. A national patient damage claim database was searched for ICD-10 codes related to parastomal and stoma-site hernia surgery over a seven-year period. Medical records were screened for claims associated with parastomal hernia repair, relocation or reversal due to parastomal hernia, or stoma-site hernia repair. Claims were classified according to one of four primary complaints: surgical, anesthetic, medical or other. Clinical and demographic differences between genders and hospital types were investigated. Reasons for non-compensation were analyzed. Thirty claims met the inclusion criteria. Eighteen were related to parastomal hernia repair, seven to stoma-site hernia repair, three to stoma reversal and two to relocation due to parastomal hernia. Twenty-five claims were primarily surgical, two related to anesthesia and three classified as other. Seven claims were granted compensation. No demographic or clinical differences were found apart from female gender being associated with previous parastomal hernia repair [6 women and 0 men (p = 0.02)]. Surgical complaints predominated. Few claims were compensated, reflecting the complexity and unsatisfactory outcomes of these procedures. Many claims were identified in relation to the incidence of stoma-related hernia surgery. Due to its retrospective and descriptive nature, the study was not registered in any registry.


Genetic mapping of the novel Turnip mosaic virus resistance gene TuRB03 in Brassica napus.
A new source of resistance to the pathotype 4 isolate of Turnip mosaic virus (TuMV) CDN 1 has been identified in Brassica napus (oilseed rape). Analysis of segregation of resistance to TuMV isolate CDN 1 in a backcross generation following a cross between a resistant and a susceptible B. napus line showed that the resistance was dominant and monogenic. Molecular markers linked to this dominant resistance were identified using amplified fragment length polymorphism (AFLP) and microsatellite bulk segregant analysis. Bulks consisted of individuals from a BC(1) population with the resistant or the susceptible phenotype following challenge with CDN 1. One AFLP and six microsatellite markers were associated with the resistance locus, named TuRB03, and these mapped to the same region on chromosome N6 as a previously mapped TuMV resistance gene TuRB01. Further testing of TuRB03 with other TuMV isolates showed that it was not effective against all pathotype 4 isolates. It was effective against some, but not all pathotype 3 isolates tested. It provided further resolution of TuMV pathotypes by sub-dividing pathotypes 3 and 4. TuRB03 also provides a new source of resistance for combining with other resistances in our attempts to generate durable resistance to this virus.


Let-7 miRNA's Expression Profile and Its Potential Prognostic Role in Uterine Leiomyosarcoma.
The lethal-7 (let-7) family is an important microRNA (miRNA) group that usually exerts functions as a tumor suppressor. We aimed to evaluate the expression profile of let-7a, let-7b, let-7c, let-7d, let-7e, let-7f, let-7g, and let-7i and to assess their value as prognostic markers in uterine leiomyosarcoma (LMS) patients. The miRNAs expression profile was assessed in 34 LMS and 13 normal myometrium (MM) paraffin-embedded samples. All let-7 family members showed downregulation in LMS. Our findings showed that patients with let-7e downregulation had worse overall survival (OS) and is an independent prognostic factor (hazard ratio [HR] = 2.24). In addition, almost half the patients had distant metastasis. LMS patients with downregulated let-7b and let-7d had worse disease-free survival (DFS); they are not independent prognostic factors (HR = 2.65). Patients' ages were associated with let-7d, let-7e and let-7f (p = 0.0160) downregulation. In conclusion, all the let-7 family members were downregulated in LMS patients, and the greater the loss of expression of these molecules, the greater their relationship with worse prognosis of patients. Let-7e expression might influence the OS, while let-7b and le-7d might influence the DFS. The lowest expression levels of let-7d, let-7e, and let-7f were associated with the oldest patients. Our findings indicate strong evidence of let-7's role as a potential prognostic biomarker in LMS.


Modulation of colony stimulating factor release and apoptosis in human colon cancer cells by anticancer drugs.
Modulation of the immune response against tumour cells is emerging as a valuable approach for cancer treatment. Some experimental studies have shown that secretion of colony stimulating factors by cancer cells reduces their tumorigenicity and increases their immunogenicity probably by promoting the cytolitic and antigen presenting activities of leukocytes. We have observed that human colon cancer cells (HT-29) are able to secrete granulocyte-macrophage-colony stimulating factor, granulocyte-colony stimulating factor and macrophage-colony stimulating factor when stimulated with cytokines (IL-1beta and TNF-alpha). In this study we assessed, for the first time, the effects of several anticancer drugs on colony stimulating factor release or apoptosis in HT-29 cells. Cytokine-induced release of granulocyte-macrophage-colony stimulating factor, granulocyte-colony stimulating factor and macrophage-colony stimulating factor was significantly increased by cisplatin and 6-mercaptopurine. Taxol only increased macrophage-colony stimulating factor release while reduced that of granulocyte-colony stimulating factor. No changes in colony stimulating factor secretion were observed after treatment with methotrexate. Only cisplatin and taxol induced apoptosis in these cells. Secretion of colony stimulating factors by colon cancer cells may contribute to the immune host response against them. Anticancer drugs such as cisplatin and 6-mercaptopurine increase colony stimulating factor secretion by cytokine stimulated cancer cells probably through mechanisms different to those leading to cell apoptosis, an effect that may contribute to their anti-neoplasic action.


Adherence Measures for Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone Acetate plus Prednisone: Results of a Prospective, Cluster-Randomized Trial.
Residual androgen production causes tumor progression in metastatic, castration-resistant prostate cancer (mCRPC) patients. Abiraterone acetate (AA), a prodrug of abiraterone, is an oral CYP-17 inhibitor that blocks androgen production. It was hypothesized that adherence-enhancing measures (AEM) might be beneficial for mCRPC patients receiving abiraterone acetate plus prednisone (AA + P). This multicenter, prospective, 2-arm trial allocated mCRPC patients who were progressive after docetaxel-based chemotherapy or asymptomatic/mildly symptomatic after failure of an androgen deprivation therapy to Arm A (with AEM) or Arm B (without AEM) by center-based cluster-randomization. The primary objective was to assess the influence of AEM on discontinuation rates and medication adherence in mCRPC patients treated with AA + P. A total of 360 patients were allocated to Arm A, and 315 patients to Arm B. At month 3, the rate of treatment discontinuation, not due to disease progression or the start of new cancer therapy, was low in both arms (A: 9.0% vs. B: 7.3%, OR = 1.230). Few patients had a medium/low Morisky Medication Adherence Scale (MMAS-4) score (A: 6.4% vs. B: 9.1%, OR = 0.685). The results obtained did not suggest any clear adherence difference between Arm A and Arm B. In patients with mCRPC taking AA + P medication, adherence seemed to be generally high.


Analysis of clinically relevant variants from ancestrally diverse Asian genomes.
Asian populations are under-represented in human genomics research. Here, we characterize clinically significant genetic variation in 9051 genomes representing East Asian, South Asian, and severely under-represented Austronesian-speaking Southeast Asian ancestries. We observe disparate genetic risk burden attributable to ancestry-specific recurrent variants and identify individuals with variants specific to ancestries discordant to their self-reported ethnicity, mostly due to cryptic admixture. About 27% of severe recessive disorder genes with appreciable carrier frequencies in Asians are missed by carrier screening panels, and we estimate 0.5% Asian couples at-risk of having an affected child. Prevalence of medically-actionable variant carriers is 3.4% and a further 1.6% harbour variants with potential for pathogenic classification upon additional clinical/experimental evidence. We profile 23 pharmacogenes with high-confidence gene-drug associations and find 22.4% of Asians at-risk of Centers for Disease Control and Prevention Tier 1 genetic conditions concurrently harbour pharmacogenetic variants with actionable phenotypes, highlighting the benefits of pre-emptive pharmacogenomics. Our findings illuminate the diversity in genetic disease epidemiology and opportunities for precision medicine for a large, diverse Asian population.


Differential dependence on protein kinase C of arachidonic acid metabolism stimulated by hydrogen peroxide and by zymosan in the alveolar macrophage.
The dependence on protein kinase C (PKC) of arachidonic acid (AA) metabolism stimulated by the biologically important oxidant H2O2, as compared to zymosan particles, was investigated in the rat alveolar macrophage. The PKC inhibitor staurosporine markedly reduced AA release and eicosanoid synthesis stimulated by zymosan, but only slightly inhibited AA release and metabolism induced by H2O2. Furthermore, in macrophages depleted of PKC by extended exposure to phorbol 12-myristate 13-acetate, AA release in response to zymosan was greatly inhibited, whereas that stimulated by H2O2 was attenuated to a significantly lesser degree. Thus, zymosan-stimulated AA metabolism requires active PKC, whereas H2O2-induced metabolism is largely PKC-independent. This provides direct evidence for the existence of two pathways of agonist-stimulated AA metabolism, which differ in their dependence on PKC, in the alveolar macrophage.


Projection screen or video goggles as stimulus modality in functional magnetic resonance imaging.
The purpose of this study was to investigate the reliability of functional magnetic resonance imaging (fMRI) by using either a projection screen or video goggles as stimulus modality. A sequence of visual stimuli were presented to the same subject at different occasions. The sequence was optimized with a genetic algorithm. In five sessions the stimuli were presented using a projection screen viewed through a mirror in the head coil and in five sessions using video goggles. Failure to detect visual activation in the medial left hemisphere was observed in sessions using the projection screen as stimulus modality. Decreased thresholds for P values and cluster size resulted in activation outside the occipital lobe and did not significantly increase activated areas in this region. Results in this study indicate that presentation of fMRI tasks with visual routes is more reliable with direct input through video goggles than with the conventional use of projection screens. Failure to detect crucial visual areas has severe consequences for tumor surgery in the visual cortex. Inferior visual impression might also have negative consequences for cognitive tests with high demand on attention and perception.


Primary tumor types and origins in positive abdominopelvic washing cytology, a single institution experience.
Abdominopelvic washing cytology is a common specimen evaluated for ovarian, fallopian tubal, and peritoneal cancer staging or other nongynecologic malignancies presented as metastases. We reviewed our experience in diagnosing abdominopelvic washing specimens and assessing the primary tumor types and origins of the positive abdominopelvic washings. A pathology archive database search was performed for abdominopelvic washing specimens from 2007 to 2018. The corresponding cytologic diagnoses, results of ancillary studies, clinical histories, and surgical follow-up were reviewed. The primary sites were determined based on the synoptic reports, when available. A total of 5.8% (350 of 6023) of cases were positive for malignancy or neoplasm. Additionally, 1.3% (78 of 6023) were diagnosed as atypical cells. Of the 350 positive cases, 93.4% were müllerian tumors. The frequency of primary sites for müllerian tumors in descending order were: ovary, uterus, fallopian tube, peritoneum, and uncertain müllerian sites. The common ovarian tumors identified in pelvic washing in descending order were: high-grade serous carcinoma, serous borderline tumor, clear cell carcinoma, low-grade serous carcinoma, and endometrioid carcinoma. Gastrointestinal, breast, bladder, and lymphoma primaries were the 23 nongynecologic tumors identified in pelvic washings. Positive findings in abdominopelvic washing cytology is rare. The majority of the positive cases were from müllerian origins, with ovary and uterus as the most common sites. Endometrial adenocarcinoma, endometrioid type and ovarian high-grade serous carcinoma were the most common tumor types. Knowing prior history of malignancy, morphologic comparison with concurrent surgical cases, and performing ancillary studies are keys to improve diagnostic accuracy of abdominopelvic washings.


MEK inhibitors in non-V600 BRAF mutations and fusions.
Mutations in BRAF at the 600th codon have proven sensitive to combination BRAF and MEK inhibition. Mutations outside this codon, however, are approximately as common but do not have approved targeted therapy approaches. Herein, we discuss targeting these non-V600 mutation and fusions in BRAF with MEK inhibitors.


Improvement of heat transfer by means of ultrasound: Application to a double-tube heat exchanger.
A new kind of ultrasonically-assisted heat exchanger has been designed, built and studied. It can be seen as a vibrating heat exchanger. A comprehensive description of the overall experimental set-up is provided, i.e. of the test rig and the acquisition system. Data acquisition and processing are explained step-by-step with a detailed example of graph obtained and how, from these experimental data, energy balance is calculated on the heat exchanger. It is demonstrated that ultrasound can be used efficiently as a heat transfer enhancement technique, even in such complex systems as heat exchangers.


[Role of surgical interventions in the treatment of patients with trophoblastic tumor resistant to chemotherapy].
A retrospective evaluation of 85 case histories of chemotherapy-resistant trophoblastic disease treated at the Center's clinic (1975-1996) was carried out. Both therapy efficacy and survival rates were lower in patients operated on prior to chemotherapy and during medication. However, excision of resistant foci of trophoblastic tumor contributed to the effectiveness of chemotherapy.


In vitro selection and analysis of RNA aptamer recognize arginine-rich motif (ARM) model peptide on a QCM.
To study RNA-peptide interactions, we performed an in vitro selection of RNA on a 27 MHz quartz-crystal microbalance (QCM) on which a simple R5 helix peptide was immobilized as a model of N peptide from bacteriophade lambda. The consensus sequences including a GNRA tetraloop were obtained from a random RNA pool after the 7th cycle selection.


Pathological studies and pathological principles on the management of extension injuries of the cervical spine.
Extension injury to the arthritic spine of elderly individuals involves rupture of the anterior longitudinal ligaments and disks at several levels, but no bony injury can be observed on X-ray. There are many small focal haemorrhages in the central portion of the spinal cord and the injury is often accompanied by incomplete paresis. As the injury is a stable injury with the posterior ligament complex being intact, it is only necessary to immobilise the cervical spine conservatively. Laminectomy is not indicated. In hyperextension injury of the rigid cervical spine and in momentary posterior dislocation observed in middle aged individuals, rupture of the anterior longitudinal ligament and disk is observed at a single site, but being spontaneously reduced, traumatic findings cannot be observed on X-ray. The spinal cord is crushed at the site of injury to bring about severe neural damage. When this type of injury is diagnosed or suspected, further damage may be inflicted on the spinal cord if skull traction is made with calipers in the extended position and the condition at the time of injury is reproduced. Therefore, the patient should be nursed in a shell or between sandbags in a neutral position or even in a position of slight flexion. In extension fracture dislocation with compression which resembles on X-ray a flexion injury, all of the three columns of the spine are destroyed to bring about an extremely unstable condition. As the spinal cord is extensively injured to involve several segments, decompression surgery for relief of neuroparalysis should not be performed when complete paralysis develops simultaneously with fracture dislocation. Therefore, it should be first treated conservatively with skull traction, and in cases where stability cannot be restored, surgical fixation of the spine should be performed.


Cogan syndrome: Descriptive analysis and clinical experience of 7 cases diagnosed and treated in two third level hospitals.
Cogan's syndrome (CS) is an inflammatory disease classified as variable vessel vasculitis. It is a rare disease with few published series, and therefore we reviewed our experience in the last ten years in two centres. Description of 7 diagnosed cases of CS, according to the classification criteria (typical or atypical), their clinical manifestations, treatments used and their complications. A comparative analysis was performed with the series and cases described in the literature. Seven cases were included, three men and four women, with a mean age at diagnosis of 43 years, and an average disease duration of 47 months. Five patients met the typical characteristics according to the 1980 classical criteria, the rest being atypical cases, one due to the absence of interstitial keratitis and another due to a period between the onset of ocular and auditory-vestibular clinical symptoms greater than two years. All received immunosuppressants, methotrexate being the most commonly used, followed by azathioprine. In 5 cases, biological drugs were used, infliximab in 4 times and 2 tocilizumab. One patient died from bacterial endocarditis and septic shock. The characteristics of the series presented are like those published to date, with clinical differences mainly in the involvement of large vessels. Given the low frequency, it seems necessary to create multicentre records to improve the evidence regarding the management of patients with CS.


Mucinous sweat gland adenocarcinoma of eyelid: a clinicopathologic study of 21 cases with histochemical and electron microscopic observations.
This is a clinicopathologic study of 21 cases of mucinous sweat gland adenocarcinoma involving the eyelid. The tumor occurred in middle-aged adults (median age 60 years) and has a predilection for males. In this series eight patients (40%) had one or more local recurrences, one of whom died with extensive local invasion of the face after multiple recurrences in a 15-year interval. Only one patient had metastasis to the submandibular lymph nodes, which was treated by radical neck dissection. Involvement of the head, especially the face and scalp, was observed in 78% of the cases from the literature. Combining our cases with those previously reported, we found that the eyelid was involved in almost half of the cases (21 out of 45 lesions). We believe that the identification by light microscopy of a mixed population of light and dark secretory cells within the tumor lobules, the histochemical findings (presence of sialomucin and absence of iron as well as periodic acid-Schiff positive, diastase-resistant granules), and the results of ultrastructural studies support the histogenetic postulate that this mucinous adenocarcinoma is probably derived from the secretory cells of the eccrine coil. Our interpretation concurs with Headington's view of origin from the eccrine glands.


A comparison of the stability of proplast-coated and cemented Thompson prostheses in the treatment of subcapital femoral fractures.
Twenty randomly selected patients with displaced subcapital fractures of the femur, were treated with prosthetic replacement of the femoral head using a Thompson prosthesis of which the intramedullary portion was coated with Proplast. The results were compared with a control group of 20 similar patients in whom the standard Thompson prosthesis was used with acrylic cement. At follow-up, which ranged from 3 to 17 months, there was substantial X-ray evidence of prosthetic loosening in the Proplast series.


Free radicals in Alzheimer's dementia: currently available therapeutic strategies.
Substantial evidence now exists that oxidative stress may play an important role in the etiopathogenesis of DAT. The different sources of oxidative stress in DAT are suggesting several pharmacological opportunities for influencing the disease. It is possible to distinguish 2 major types of possible therapeutic agents according to their pharmacological point of attack. 1. Radical scavengers, agents directly interacting with free radicals. Candidates of this type are gingko biloba, vitamins A, C, E and estrogen. 2. Antioxidants, which are able to prevent or decrease the production of free radicals by use of specific neuropharmacological properties. Candidates are selegiline, a MAO-B inhibitor well established in the therapy of Parkinson's disease, and tenilsetam, which is believed to be an AGE-inhibitor. Recent in vitro studies have demonstrated the efficacy of both types of therapeutic agents by preventing or delaying oxidative neural damage. Some clinical data exist regarding the antidementive properties particularly in terms of gingko biloba, selegiline and vitamin E. The efficacy studies about these compounds seem to indicate a promising future strategy in the therapy of DAT. But it is too early to draw definite conclusions since it is well known that all of our candidate substances do not act specifically as radical scavengers or antioxidants.


Negative exploration for lumbar disc prolapse--findings and possible causes.
32 cases of negative exploration in a joint follow-up series of 3,032 lumbar disc operations are described. Data from 15 hospitals were analyzed by means of questionnaires and computer-aided analysis. Detailed information is given about pre- as well as intraoperative findings. The causes of negative lumbar disc exploration can be divided into two groups. 1. Genuine misdiagnosis where other causes are responsible for the symptoms, and 2. poor technique where despite genuine disc prolapse no evidence was found at operation. The most important causes in the first group were osteochondrotic compression, distended epidural veins, and root tension. The results are less favourable in these patients than in the overall series but, compared to the other complicated courses, the results were markedly better. A review of the literature is given, the possible causes for negative explorations are discussed, and a directive is established for the surgical procedure in cases where an expected prolapse is not found at operation.


Comparison of bone mineral content between Japan-born and US-born Japanese subjects in Hawaii.
The bone mineral content (BMC) of the calcaneus, and distal and proximal radius was measured by the single photon absorptiometric technique for 2307 US-born and 172 Japan-born subjects of Japanese ancestry living in Hawaii. The bone mineral content of the US-born subjects was greater than that of their Japan-born counterparts, on the average, by 8.8% at the calcaneus, 3.5% at the distal radius and 4.5% at the proximal radius. Differences between the two groups in height, weight, thiazide use, exercise (in men), estrogen therapy (in women), and calcium and vitamin D intake accounted for much of the difference in BMC between the US-born and Japan-born women, but less so for the men. Additional studies of BMC in migrant populations are needed to characterize further the environmental factors affecting bone mineral content.


Biochemical Responses to Chemically Distinct Chemoattractants During the Growth and Development of Dictyostelium.
Dictyostelium discoideum has proven an excellent model for the study of eukaryotic chemotaxis. During growth in its native environment, Dictyostelium phagocytose bacteria and fungi for primary nutrient capture. Growing Dictyostelium can detect these nutrient sources through chemotaxis toward the metabolic by-product folate. Although Dictyostelium grow as individual cells, nutrient depletion induces a multicellular development program and a separate chemotactic response pathway. During development, Dictyostelium synthesize and secrete cAMP, which serves as a chemoattractant to mobilize and coordinate cells for multicellular formation and development. Separate classes of GPCRs and Gα proteins mediate chemotactic signaling to the chemically distinct ligands. We discuss common and separate component responses of Dictyostelium to folate and cAMP during growth and development, and the advantages and disadvantages for each. As examples, we present biochemical assays to characterize the chemoattractant-induced kinase activations of mTORC2 and the ERKs.


EpiDope: a deep neural network for linear B-cell epitope prediction.
By binding to specific structures on antigenic proteins, the so-called epitopes, B-cell antibodies can neutralize pathogens. The identification of B-cell epitopes is of great value for the development of specific serodiagnostic assays and the optimization of medical therapy. However, identifying diagnostically or therapeutically relevant epitopes is a challenging task that usually involves extensive laboratory work. In this study, we show that the time, cost and labor-intensive process of epitope detection in the lab can be significantly reduced using in silico prediction. Here, we present EpiDope, a python tool which uses a deep neural network to detect linear B-cell epitope regions on individual protein sequences. With an area under the curve between 0.67 ± 0.07 in the receiver operating characteristic curve, EpiDope exceeds all other currently used linear B-cell epitope prediction tools. Our software is shown to reliably predict linear B-cell epitopes of a given protein sequence, thus contributing to a significant reduction of laboratory experiments and costs required for the conventional approach. EpiDope is available on GitHub (http://github.com/mcollatz/EpiDope). Supplementary data are available at Bioinformatics online.


Periodic expression of Sm proteins parallels formation of nuclear Cajal bodies and cytoplasmic snRNP-rich bodies.
Small nuclear ribonucleoproteins (snRNPs) play a fundamental role in pre-mRNA processing in the nucleus. The biogenesis of snRNPs involves a sequence of events that occurs in both the nucleus and cytoplasm. Despite the wealth of biochemical information about the cytoplasmic assembly of snRNPs, little is known about the spatial organization of snRNPs in the cytoplasm. In the cytoplasm of larch microsporocytes, a cyclic appearance of bodies containing small nuclear RNA (snRNA) and Sm proteins was observed during anther meiosis. We observed a correlation between the occurrence of cytoplasmic snRNP bodies, the levels of Sm proteins, and the dynamic formation of Cajal bodies. Larch microsporocytes were used for these studies. This model is characterized by natural fluctuations in the level of RNA metabolism, in which periods of high transcriptional activity are separated from periods of low transcriptional activity. In designing experiments, the authors considered the differences between the nuclear and cytoplasmic phases of snRNP maturation and generated a hypothesis about the direct participation of Sm proteins in a molecular switch triggering the formation of Cajal bodies.


Recurrence of glomerulonephritis after renal transplantation.
Recurrence of glomerulonephritis following renal transplantation is considered an important cause of allograft failure. The incidence of recurrence of glomerulonephritis varies widely depending on the definition of recurrence (pathologic recurrence or clinicopathologic recurrence) and the original glomerular disease. Moreover the impact of recurrence of glomerular disease on allograft outcome varies widely between different forms of glomerulonephritis. Whereas IgA nephritis recurs in up to one third of transplanted patients, this is not associated with adverse effects on graft survival. In contrast, recurrent focal segmental glomerulosclerosis and membranoproliferative glomerulopathy have an unfavorable prognosis. Overall, long-term graft survival in patients transplanted for glomerulonephritis is comparable to survival in patients with other causes of ESRD. In recent years, several mechanisms for recurrent disease after transplantation (e.g. PLA2R antibodies in membranous nephropathy and suPAR in FSGS) have been identified, and these findings have helped to elucidate the pathogenesis of glomerular diseases. Although renal transplantation is the treatment of choice for end-stage renal disease as a consequence of glomerulonephritis, further studies are required to develop optimal strategies to prevent, diagnose and treat recurrent glomerular diseases.


Alternating mealtimes during pregnancy and weaning triggers behavioral changes in adult offspring.
Mealtime changes in pregnant mice revealed impaired neurobehavioral development in mouse offspring. This study is the basis for investigating diseases associated with neurobehavioral development of adult offspring of pregnant shift-working women. Most organisms on Earth have a biological clock, and their physiological processes are regulated by a 1-day cycle. In modern society, several factors can disturb these biological clocks in humans; in particular, individuals working in shifts are exposed to stark environmental changes that interfere with their biological clock. They have a high risk of various diseases. However, there are scarce experimental approaches to address the reproductive and health consequences of shift work in the offspring of exposed individuals. In this study, considering the fact that shift workers usually have their meals during their adjusted working time, we aimed to examine the effects of a 12-h shift with usual mealtime as a plausible night work model on the neurobehavioral development of adult mouse offspring. In these offspring, early exposure to this mealtime shift differentially affected circadian rhythmic variables and total locomotor activity depending on the timing and duration of restrictive feeding. Moreover, neurobehavioral alterations such as declined short-term memory and depressive-like behavior were observed in adulthood. These results have implications for the health concerns of shift-working women and their children.


Determination of dopexamine hydrochloride in human blood by high-performance liquid chromatography with electrochemical detection.
A method is described for the determination of dopexamine hydrochloride at concentrations of 5 to 100 ng/ml in human blood using electrochemical detection. The method uses a Hypersil ODS column and a mobile phase containing heptane sulphonate, orthophosphoric acid, diisopropylamine and disodium EDTA. Blood samples are stabilised immediately after collection by the use of dipotassium EDTA and a high concentration of sodium metabisulphite. The sample preparation procedure consists of a simple de-proteinisation with perchloric acid. The method is accurate, with inter-assay accuracies ranging from 100 to 104%, and is free of interference by blood from different individuals. Known and potential metabolites of dopexamine hydrochloride and a wide range of drugs do not interfere with the method. The method is precise with inter-assay coefficients of variation of 10.6% at 5 ng/ml and of less than 4.2% at higher concentrations. Stabilised blood samples may be stored for over six months at -25 degrees C prior to analysis.


Effect of famotidine on cognitive and behavioral dysfunctions induced in post-COVID-19 infection: A randomized, double-blind, and placebo-controlled study.
This is an investigation of the efficacy and safety of famotidine, a selective histamine H2 receptor antagonist, on improvement of cognitive impairment, depression and anxiety symptoms developing post-COVID-19, in a 12-week, randomized controlled trial. A total of 50 patients with a confirmed diagnosis of COVID-19 and a score ≤ 23 on the Mini-Mental State Examination (MMSE) test or a score ≤ 22 on the Montreal Cognitive Assessment (MoCA) were randomly assigned to either the famotidine (40 mg twice daily) or the placebo group. Changes in MMSE scores at weeks 6 and 12 were the primary outcome, while changes in other scales were the secondary outcomes. Participants and evaluators were blinded. At weeks 6 and 12, patients in the famotidine group had significantly higher MMSE scores (p = 0.014, p < 0.001, respectively). Regarding the MoCA scale, the famotidine group had a significantly higher score at weeks 6 and 12 (p = 0.001, p < 0.001, respectively). Considering the HAM-D scale (Hamilton Depression Rating Scale), at weeks 6 and 12, the famotidine group experienced a larger reduction (p = 0.009, p = 0.02, respectively). Additionally, comparison of the HAM-A scale scores (Hamilton Anxiety Rating Scale) at weeks 6 and 12 showed a statistically significant larger reduction in the famotidine group (p = 0.04, p = 0.02, respectively). The two groups did not differ in the frequency of adverse effects. Our study supports safety and efficacy of famotidine in treating cognitive impairment, depression and anxiety symptoms induced by COVID-19. This trial was registered at the Iranian registry of clinical trials (IRCT: www.irct.ir; registration number: IRCT20090117001556N138).


Expression of c-Jun as a response to dorsal root and peripheral nerve section in damaged and adjacent intact primary sensory neurons in the rat.
It was previously shown that the immediate early gene, c-jun, was highly expressed over long periods, in both peripheral sensory and motor neurons following axon damage or block of axoplasmic transport. Here we have examined the question of whether the expression of c-Jun protein is related to axon injury per se or to the process of axon growth. We have examined dorsal root ganglion (DRG) cells subjected to different manipulations which are associated with varying degrees of regrowth, as follows: (i) after peripheral nerve section, where it appears that all damaged neurons make some regenerative effort. 1-24 days after sciatic nerve section and ligation most cells in L4/L5 DRG were c-Jun-positive; (ii) after section of the central processes of the DRG cells, which then showed a slow and limited regrowth of their axons towards, but not into, the spinal cord. This resulted in a variable, but significant, expression of c-Jun in a small number of DRG cells; (iii) in intact sensory neurons that were offered the opportunity to sprout into adjacent denervated peripheral tissue. The sciatic nerve was ligated and the response of cells in the L3 ganglia (many of which project to the saphenous nerve) was measured. A small but significant number of cells were c-Jun-positive; (iv) in intact sensory neurons that were offered the opportunity to sprout centrally into partialy denervated neuropil of the spinal cord. We examined neurons in the L3 DRG after rhizotomy of the adjacent L4/L5 dorsal roots. Previous work suggests that sensory neurons show at best a very limited growth under these conditions.(ABSTRACT TRUNCATED AT 250 WORDS)


Mineral characteristics of leaves of plants from different phylogeny grown in various soil types in the temperate region.
The objective of this research was to analyze selected minerals in leaves of plants, belonging to 166 species growing in alluvial, low pH, brown forest and serpentine soils. Mineral characteristics of the soils involved were also determined. For the macronutrients, in trees grown in alluvial soil, N, P, Ca, and Mg concentrations of leaves were higher in recently evolved plants than in plants with a longer period of evolution; K concentration remained constant regardless of evolution. In grasses grown in alluvial soil, it was difficult to detect the general tendency of mineral concentration. N, P, and K concentrations in alluvial soil were closely related to those in low pH and serpentine soils. Ca concentration in alluvial soil was lower than that in low pH and serpentine soils. Mg concentration in alluvial soils was higher than that in low pH soils, while lower than that in serpentine soil. Therefore, N, P, and K accumulated according to the plant characteristics for these elements, while Ca and Mg accumulation was strongly affected by the soil properties. For the micronutrients, in trees, Fe and Mn remained constant regardless of evolution; Zn concentration was lower in recently-evolved plants than in plants with a longer period of evolution. In grasses, Fe, Mn, and Zn concentrations in Caryophyllids were high. Except for Caryophyllids, Fe and Cu concentrations remained constant. Mn concentration decreased with evolution, Zn concentration was higher in recently-evolved plants than in plants with a longer period of evolution.


Thygeson lecture. Amniotic membrane transplantation: why is it effective?
To review the uses and previously proposed mechanisms of action of amniotic membrane transplantation (AMT) and to suggest a new mechanism of action for the effectiveness of AMT in resolving a persistent epithelial defect (PED). Significant clinical and experimental publications are reviewed. Evidence from the scientific literature suggests a new hypothesis for the effectiveness of AMT in the reepithelialization of a PED and the reduction of corneal stromal inflammation and continued fibrosis. It is suggested that reepithelialization of a PED, and hence the reduction of stromal inflammation and continued fibrosis following reepithelialization, is aided by the combination of oxygenation, moisture and protection of the fragile epithelium by the amniotic membrane.


Neuroendocrine (Merkel cell) carcinoma of the vulva.
The clinical, histopathologic, and ultrastructural features of a primary cutaneous vulvar neuroendocrine neoplasm (Merkel cell carcinoma) are presented. This recently described tumor arises in the dermis and is often aggressive with metastasis to regional lymph nodes. Ultrastructural study of this case reveals morphologic similarities to normal cutaneous Merkel cells, including peripherally located dense-core neurosecondary-like granules, and immunohistochemical studies revealed ACTH within neoplastic cells. By light microscopy this tumor is readily confused with other primary or metastatic cutaneous neoplasms; therefore, the importance of electron microscopic examination is emphasized for definitive diagnosis of this unusual tumor.


A comprehensive review on glucokinase activators: Promising agents for the treatment of Type 2 diabetes.
Glucokinase is a key enzyme which converts glucose into glucose-6-phosphate in the liver and pancreatic cells of the human. In the liver, glucokinase promotes the synthesis of glycogen, and in the pancreas, it helps in glucose-sensitive insulin release. It serves as a "glucose sensor" and thereby plays an important role in the regulation of glucose homeostasis. Due to this activity, glucokinase is considered as an attractive drug target for type 2 diabetes. It created a lot of interest among the researchers, and several small molecules were discovered. The research work was initiated in 1990. However, the hypoglycemic effect, increased liver burden, and loss of efficacy over time were faced during clinical development. Dorzagliatin, a novel glucokinase activator that acts on both the liver and pancreas, is in the late-stage clinical development. TTP399, a promising hepatoselective GK activator, showed a clinically significant and sustained reduction in glycated hemoglobin with a low risk of adverse effects. The successful findings generated immense interest to continue further research in finding small molecule GK activators for the treatment of type 2 diabetes. The article covers different series of GK activators reported over the past decade and the structural insights into the GK-GK activator binding which, we believe will stimulate the discovery of novel GK activators to treat type 2 diabetes.


Do more intelligent brains retain heightened plasticity for longer in development? A computational investigation.
Twin studies indicate that the heritability of general cognitive ability - the genetic contribution to individual differences - increases with age. Brant et al. (2013) reported that this increase in heritability occurs earlier in development for low ability children than high ability children. Allied with structural brain imaging results that indicate faster thickening and thinning of cortex for high ability children (Shaw et al., 2006), Brant and colleagues argued higher cognitive ability represents an extended sensitive period for brain development. However, they admitted no coherent mechanistic account can currently reconcile the key empirical data. Here, computational methods are employed to demonstrate the empirical data can be reconciled without recourse to variations in sensitive periods. These methods utilized population-based artificial neural network models of cognitive development. In the model, ability-related variations stemmed from the timing of the increases in the non-linearity of computational processes, causing dizygotic twins to diverge in their behavior. These occurred in a population where: (a) ability was determined by the combined small contributions of many neurocomputational factors, and (b) individual differences in ability were largely genetically constrained. The model's explanation of developmental increases in heritability contrasts with proposals that these increases represent emerging gene-environment correlations (Haworth et al., 2010). The article advocates simulating inherited individual differences within an explicitly developmental framework.


The efficacy and safety of vonoprazan-amoxicillin dual therapy in eradicating Helicobacter pylori: a systematic review and meta-analysis.
To evaluate the efficacy and safety of vonoprazan-amoxicillin (VA) dual therapy for radically eradicating Helicobacter pylori (H. pylori). The PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang databases were searched up to July 7, 2022, to identify clinical trials comparing the efficacy of VA dual therapy and triple therapy for H. pylori eradication. After evaluating the quality of the included studies, random effects models were conducted, and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated to estimate the efficacy and safety of each approach. Six publications (including four randomized controlled trials) involving 2019 patients were included in this meta-analysis. Overall, the eradication rate for VA dual therapy was 89.9%, while it was 85.2% for triple therapy based on other acid inhibitors. The eradication rate of H. pylori in the VA dual regimen group was higher than that in the PPI-based (omeprazole or lansoprazole) triple therapy group (RR = 1.15, 95% CI 1.07-1.23, p < 0.0001). However, the efficacy of VA dual therapy was comparable with VA-Clarithromycin (VAC) triple therapy (RR = 0.97, 95% CI 0.93-1.02). Besides, the incidence of adverse reactions in VA dual therapy was also lower than that in triple therapy (RR = 0.80, 95% CI 0.70-0.91, p = 0.0009). Compared with PPI-based triple therapy, VA dual therapy showed a better therapeutic effect, safety and patient compliance rate for eradicating H. pylori, which should be used as a novel curative strategy in the future.


[The judgement of collagen metabolism by hydroxyproline in plasma and urine and plasma collagenic peptidase under different diet (author's transl)].
In 34 subjects--coal workers with pneumoconiosis, patients with collagenic diseases and healthy subjects--the daily urinary excretion of hydroxyproline (HP) and the plasma concentrations of HP and of collagenic peptidase have been measured during one week under HP-free and HP-enriched diet. It is shown that a 24-hour period of HP-free diet is necessary and sufficient before collecting urine or plasma for diet independent measurements of total or non-protein bound HP. Concentrations in plasma correlate well with the amounts excreted in urine. Collagenic peptidase is independent from the diet and well suited for assessment of the activity of the metabolism of collagene. There are no differences between healthy subjects and coal workers with pneumoconiosis.


Combined measurement of perfusion, venous oxygen saturation, and skeletal muscle T2* during reactive hyperemia in the leg.
The function of the peripheral microvascular may be interrogated by measuring perfusion, tissue oxygen concentration, or venous oxygen saturation (SvO2) recovery dynamics following induced ischemia. The purpose of this work is to develop and evaluate a magnetic resonance (MR) technique for simultaneous measurement of perfusion, SvO2, and skeletal muscle T2*. Perfusion, Intravascular Venous Oxygen saturation, and T2* (PIVOT) is comprised of interleaved pulsed arterial spin labeling (PASL) and multi-echo gradient-recalled echo (GRE) sequences. During the PASL post-labeling delay, images are acquired with a multi-echo GRE to quantify SvO2 and T2* at a downstream slice location. Thus time-courses of perfusion, SvO2, and T2* are quantified simultaneously within a single scan. The new sequence was compared to separately measured PASL or multi-echo GRE data during reactive hyperemia in five young healthy subjects. To explore the impairment present in peripheral artery disease patients, five patients were evaluated with PIVOT. Comparison of PIVOT-derived data to the standard techniques shows that there was no significant bias in any of the time-course-derived metrics. Preliminary data show that PAD patients exhibited alterations in perfusion, SvO2, and T2* time-courses compared to young healthy subjects. Simultaneous quantification of perfusion, SvO2, and T2* is possible with PIVOT. Kinetics of perfusion, SvO2, and T2* during reactive hyperemia may help to provide insight into the function of the peripheral microvasculature in patients with PAD.


Adolescent weight status and self-reported school performance in South Korea.
Using a nationally representative sample of 142 783 middle school (13-15 years old) and high school (16-18 years old) students in South Korea, this study examined whether (1) overweight and obesity are more likely to be associated with lower self-reported school performance; (2) overweight and obese students are more likely to enrol in a vocational high school as opposed to a general high school; (3) the association between obesity and poorer self-reported school performance is mediated through body image stress and health status. We found that excess weight was negatively associated with self-reported school performance among middle and general high school students, and that obese students had a higher probability of being enrolled in a vocational over a general high school. We did not find strong evidence on the mediating role of body image stress and health status.


Outcome of the first 220 cases of endometrial balloon ablation using Cavaterm plus.
The objective of this prospective study was to evaluate the effectiveness of day-case Cavaterm plus thermal balloon endometrial ablation in the treatment of therapy-resistant menorrhagia. The study included 220 patients with a mean age of 41 years, mean parity of 2.1 and mean duration of menorrhagia of 3.2 years. A 6-mm diameter Cavaterm plus catheter with a silicone balloon at its tip was used. The ablation time was 10 minutes at a temperature of 78 degrees C. No procedure-related operative or immediate postoperative complications were encountered. The mean follow-up period was 19 months (range 6-24 months). The amenorrhoea-hypomenorrhoea rates at the various follow-up periods ranged between 74% and 83%. At the end of follow-up, 83% of patients were satisfied with the procedure. We conclude that Cavaterm plus is a safe and effective treatment for menorrhagia and has good patient acceptability.


Association between increased inflammatory cytokine expression in the lateral habenular nucleus and depressive-like behavior induced by unpredictable chronic stress in rats.
Depression induced by unpredictable chronic stress (UCS) has been widely studied using animal models. However, its underlying pathological mechanisms remain unclear. Increased inflammatory cytokines (ICs) in the central nervous system (CNS) are closely related to depressive disorder. UCS was used as an animal model in this study to investigate how UCS-induced changes in cytokine signaling lead to depression. We found that UCS could increase ICs in the CNS, especially in the habenular nucleus (Hb). UCS resulted in decreased expression of Menin in Hb and increased the activation of the NF-κB signaling pathway. Local administration of tumor necrosis factor-α in the lateral Hb (LHb) could induce depressive-like behavior in rats. The anti-inflammatory drug aspirin and the NF-κB inhibitor pyrrolidine dithiocarbamate could alleviate depressive-like behavior. This phenomenon was not observed for local administration in the dorsal raphe nucleus and paraventricular nucleus. These results indicate that LHb is the main central target for ICs to regulate depressive-like behaviors. We also found that LHb lesions could improve the inflammatory response in the hippocampus, reduce the activation of the NF-κB signaling pathway and the expression of ICs, and increase the expression of brain-derived neurotrophic factor and its receptor tropomyosin receptor kinase B, collectively improving the neuroinflammation caused by UCS. Moreover, LHb lesions improve not only hippocampal neurogenesis damage caused by UCS by activating the PI3K/mTOR signaling pathway but also hippocampal function by reducing the expression of apoptosis-related proteins, including phosphorylated p53, Bax, Bcl2, and cleaved-caspase3. In conclusion, our study sheds light on the pathogenesis of ICs-induced depression. Anti-inflammation in the CNS could be a new strategy in the treatment of depression.


How much does the typical ecological meta-analysis overestimate the true mean effect size?
Many primary research studies in ecology are underpowered, providing very imprecise estimates of effect size. Meta-analyses partially mitigate this imprecision by combining data from different studies. But meta-analytic estimates of mean effect size may still remain imprecise, particularly if the meta-analysis includes a small number of studies. Imprecise, large-magnitude estimates of mean effect size from small meta-analyses likely would shrink if additional studies were conducted (regression towards the mean). Here, I propose a way to estimate and correct this regression to the mean, using meta-meta-analysis (meta-analysis of meta-analyses). Hierarchical random effects meta-meta-analysis shrinks estimated mean effect sizes from different meta-analyses towards the grand mean, bringing those estimated means closer on average to their unknown true values. The intuition is that, if a meta-analysis reports a mean effect size much larger in magnitude than that reported by other meta-analyses, that large mean effect size likely is an overestimate. This intuition holds even if different meta-analyses of different topics have different true mean effect sizes. Drawing on a compilation of data from hundreds of ecological meta-analyses, I find that the typical (median) ecological meta-analysis overestimates the absolute magnitude of the true mean effect size by ~10%. Some small ecological meta-analyses overestimate the magnitude of the true mean effect size by >50%. Meta-meta-analysis is a promising tool for improving the accuracy of meta-analytic estimates of mean effect size, particularly estimates based on just a few studies.


Risk of Tics with Psychostimulants for ADHD.
Investigators at Yale University, New Haven, CT, conducted a meta-analysis to examine the risk of new onset or worsening of tics caused by psychostimulants used in the treatment of children with ADHD.


Ejaculatory ducts opening into accessory urethral channel with hypospadias and absent verumontanum: a rare association.
Ejaculatory ducts draining into accessory urethral channel opening into perineum is rare. This is a case report of a 27-year-old male who had hypospadias surgery at 3 years of age, presenting with discharge of semen through the perineal opening from adolescence. Cystoscopy and dye study showed that it was a short channel communicating with both ejaculatory ducts. Cystoscopy of the native urethra revealed that the vermontanum had not developed. The mucous lined accessory urethra was anastomosed to the bulbar urethra. Urethrogram done after one year showed that the accessory urethra was draining well into the bulbar urethra. Such type of accessory urethral channel communicating with ejaculatory ducts and associated with hypospadias and absent vermontanum has not been reported so far.


Self-assembling nanomaterials: monitoring the formation of amyloid fibrils, with a focus on small-angle X-ray scattering.
Amyloid fibrils are attractive targets for applications in biotechnology. These thin, nanoscale protein fibers are highly ordered structures that self-assemble from their component proteins or peptides. This chapter describes the use of several biophysical techniques to monitor the formation of amyloid fibrils including a common dye-binding assay, turbidity assay, and small-angle X-ray scattering. These techniques provide information about the assembly mechanism, the rate and reproducibility of assembly, as well as the size of species along the assembly pathway.


A synthetic peptide vector system for optimal gene delivery to corneal endothelium.
Efficient and non-toxic gene delivery, preferably with non-viral DNA vectors readily transferable to clinical practice, is generally regarded as a major limitation for gene therapy. A 31 amino acid, integrin-targeted bifunctional synthetic peptide (polylysine-molossin), and two (Lys)(16)-containing control peptides, were assessed for ex vivo gene delivery to the rabbit cornea. Critical physical properties of polylysine-molossin/DNA complexes were evaluated and both chloroquine and a 20 amino acid fusogenic peptide were used to promote endocytic exit. Polylysine-molossin/DNA complexes and (Lys)(16)/DNA complexes at 10 microg/ml of DNA were much smaller and much more positively charged in non-ionic isotonic medium (5% dextrose or 5% dextrose buffered to pH 7.4 in 10 mM Tris) when compared with culture medium or phosphate-buffered saline (PBS). Addition of the fusogenic peptide (net charge -5) reversed the positive charge of complexes in PBS, and reduced the strong positive charge of polylysine-molossin/DNA complexes in dextrose. Polylysine-molossin/DNA complexes in 5% dextrose were much more effective for gene delivery to the cornea when compared with complexes in culture medium, and the fusogenic peptide was much more effective than chloroquine for promoting gene delivery. The optimal DNA/polylysine-molossin/fusogenic peptide w/w ratio was 1 : 3 : 2 at 10 microg/ml of DNA. Essentially 100% of corneal endothelial cells were transfected under these optimal conditions, without any evidence of toxicity. Integrin-targeting did not contribute significantly to gene delivery in this system. This DNA vector system, consisting entirely of synthetic peptides, is ideally suited for clinical applications of gene therapy of the corneal endothelium.


International assessment of inter- and intrarater reliability of the International Frontal Sinus Anatomy Classification system.
Inconsistencies in the nomenclature of structures of the frontal sinus have impeded the development of a validated "reference standard" classification system that surgeons can reliably agree upon. The International Frontal Sinus Anatomy Classification (IFAC) system was developed as a consensus document, based on expert opinion, attempting to address this issue. The purposes of this study are to: establish the reliability of the IFAC as a tool for classifying cells in the frontal recess among an international group of rhinologists; and improve communication and teaching of frontal endoscopic sinus surgery (ESS). Forty-two computed tomography (CT) scans, each with a marked frontal cell, were reviewed by 15 international fellowship-trained rhinologists. Each marked cell was classified into 1 of 7 categories described in the IFAC, on 2 occasions separated by 2 weeks. Inter- and intrarater reliability were evaluated using Light's kappa (κ), the interclass correlation coefficient (ICC), and simple proportion of agreement. Interrater reliability showed pairwise κ values ranging from 0.7248 to 1.0, with a mean of 0.9162 (SD, 0.0537). The ICC was 0.98. Intrarater reliability showed κ values ranging from 0.8613 to 1.0, with a mean of 0.9407 (SD, 0.0376). The within-rater ICC was 0.98. Among a diverse sample of rhinologists (raters), there was substantial to almost perfect agreement between raters, and among individual raters at different timepoints. The IFAC is a reliable tool for classification of cells in the frontal sinus. Further outcome studies are still needed to determine the validity of the IFAC.


Acute toxicity of hydrogen cyanide to freshwater fishes.
Acute toxicity of hydrogen cyanide was determined at various temperatures from 4 degrees to 30 degrees C and oxygen concentrations of 3.36 to 9.26 mg/L on different life history stages of five species of fish: fathead minnow, Pimephales promelas Refinesque; bluegill, Lepomis macrochirus Rafinesque; yellow perch, Perca flavescens (Mitchill); brook trout, Salvelinus fontinalis (Mitchill); and rainbow trout, Salmo gairdneri Richardson. Median lethal threshold concentrations and 96-hr LC50's were established by flow-through type biassays. Acute toxicity varied from 57 microgram/L for juvenile rainbow trout to 191 microgram/L for field stocks of juvenile fathead minnows. Juvenile fish were more sensitive at lower temperatures and at oxygen levels below 5 mg/L. For most species juveniles were most sensitive and eggs more resistant.


Umbilical cord blood mesenchymal stem cells application in hematopoietic stem cells expansion on nanofiber three-dimensional scaffold.
Umbilical cord blood (UCB) hematopoietic stem cells (HSCs) transplantation (HSCTs) is considered as a therapeutic strategy for malignant and nonmalignant hematologic disorders. Nevertheless, the low number of HSCs obtained from each unit of UCB can be a major challenge for using these cells in adults. In addition, UCB is a rich source of mesenchymal stem cells (MSCs) creating hopes for nonaggressive and painless treatment in tissue engineering compared with bone marrow MSCs. This study was designed to evaluate the effects of UCB-MSCs application in UCB-HSCs expansion on the nanoscaffold that mimics the cell's natural niche. To achieve this goal, after flow cytometry confirmation of isolated HSCs from UCB, they were expanded on three-dimensional (3D) poly-l-lactic acid (PLLA) scaffolds fabricated by electrospinning and two-dimensional (2D)-culture systems, such as (1) HSCs-MSCs culturing on the scaffold, (2) HSCs culturing on the scaffold, (3) HSCs-MSCs culturing on 2D, and (4) HSCs culturing on 2D. After 7 days, real-time polymerase chain reaction (PCR) was performed to evaluate the CXCR4 gene expression in the mentioned groups. Moreover, for the next validation, the number of total HSCs, 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide assay, scanning electron microscopy imaging, and colony-forming unit assay were evaluated as well. The results of the study indicated that UCB-MSCs interaction with HSCs in 3D-culture systems led to the highest expansion of UCB-HSCs on day 7. Flow cytometry results showed the highest purity of HSCs cocultured with MSCs. Real-time PCR showed a significant increase in gene expression of CXCR4 in the mentioned group. The highest viability and clonogenicity were detected in the mentioned group too. Considered together, our results suggest that UCB-HSCs and MSCs coculturing on PLLA scaffold could provide a proper microenvironment that efficiently promotes UCB-HSCs expansion and UCB-MSCs can also be considered as a promising candidate for UCB-HSCTs.


What are the limits of accuracy in fetal weight estimation with conventional biometry in two-dimensional ultrasound? A novel postpartum study.
Commonly used formulae for fetal weight estimation, including combinations of several biometric parameters, lack accuracy despite efforts to improve them. This study aimed to investigate the limits of fetal weight estimation based on conventional biometric parameters on two-dimensional (2D) ultrasound by developing and evaluating new weight equations using postpartum biometric parameters. This was a prospective multicenter study including 628 singleton pregnancies at term. Inclusion criteria were healthy newborns with no physical or chromosomal malformations. Postpartum measurement of head circumference, abdominal circumference and thigh length was performed. Six 'best-fit' formulae were derived using forward regression analysis in a formula-finding group (n = 419), and their accuracy was compared with birth weight in an evaluation group (n = 209) using percentage error, absolute percentage error, limits of agreement and the proportion of weight estimations falling within a discrepancy level of ± 10%. The new formulae showed no systematic error, with SD for the percentage error between 7.42 and 8.77 and no significant differences between median absolute percentage errors (4.84-5.71). They included 74.6-81.3% of neonates within a discrepancy level of 10%. With regard to the 95% limits of agreement, weight estimates were within a range of about ± 500 g. These results show that a good sonographic weight formula has the following features: no systematic error, an SD of about 7% and inclusion of 80% of cases within a discrepancy level of 10%. The study indicates that the current accuracy of fetal weight estimation with conventional biometric parameters by 2D ultrasound has reached its limits. Further improvement will probably only be achieved through new approaches in ultrasonography.


[Management in preretinal macular hemorrhage. Case report].
The report presents a method of management in case of clotted premacular haemorrhage in a 46 year-old woman. The used method of treatment proceeded in 2 stages: 1) pars plana, intravitreal injection of 50 mg tissue plasminogen activator (tPA-Actilise), 2) after 24 hours intravitreal 0.5 cc SF6 with air mixture (1:5). Fibrinolytic tPA action and mechanic action of expanding gas caused after argon laser puncture intravitreal haemorrhage dislocation and following its resorption. The almost full visual acuity persisted for over 2 years.


Possible involvement of silent mutations in cancer pathogenesis and evolution.
Recent studies have shown that some silent mutations can be harmful to various processes. In this study, we performed a comprehensive in silico analysis to elucidate the effects of silent mutations on cancer pathogenesis using exome sequencing data derived from the Cancer Genome Atlas. We focused on the codon optimality scores of silent mutations, which were defined as the difference between the optimality of synonymous codons, calculated using the codon usage table. The relationship between cancer evolution and silent mutations showed that the codon optimality score of the mutations that occurred later in carcinogenesis was significantly higher than of those that occurred earlier. In addition, mutations with higher scores were enriched in genes involved in the cell cycle and cell division, while those with lower scores were enriched in genes involved in apoptosis and cellular senescence. Our results demonstrate that some silent mutations can be involved in cancer pathogenesis.


Post-stEnting assessment of Re-endothelialization with optical Frequency domain imaging aftEr Chronic Total Occlusion procedure: The PERFE-CTO Study Design and Rationale.
The treatment of chronic total occlusion of coronary arteries by percutaneous coronary intervention (CTO PCI) is one of the most representative technical advances in ischemic cardiomyopathy of last decade. However, how the complex histopathological remodeling and the new techniques affect healing processes after stent implantation remains unknown. The objective of the PERFE-CTO study is to analyze stent coverage, malapposition and other mechanical abnormalities 3 months after CTO recanalization using intravascular imaging. In a French prospective interventional multicenter study, stent strut coverage, acquired malapposition and neointimal hyperplasia (NIH) proliferation will be systematically assessed with 3 months angiogram control and intracoronary optical frequency domain imaging (OFDI) after successful CTO PCI of >20 mm in length. The impact of routine systematical intracoronary imaging after these complex procedures will also be evaluated by measuring the rate of significant mechanical abnormalities (strut malapposition, edge dissection, thrombus) that was undetected by fluoroscopy alone and by complementary PCI when needed. Secondarily, these data will be compared according to clinical characteristics, antiplatelet therapy use or desobstruction technique (antegrade vs. retrograde, true lumen vs. subintima). Each patient will undergo a one-year clinical follow-up. A total of 150 analyzed CTO lesions is expected. The PERFE-CTO study will provide essential understanding of the early history after CTO recanalization and the identification of inadequate evolution (stent thrombosis, restenosis or late delayed stent endothelization and cardiovascular outcomes) using intravascular imaging to improve long-term CTO results.


A new triterpenoid saponin from Gleditisia sinensis and structure-activity relationships of inhibitory effects on lipopolysaccharide-induced nitric oxide production.
A phytochemical investigation of the anomalous fruits of Gleditisia sinensis led to one new oleanane-type triterpenoid saponin acylated with one monoterpenic acid, 3-O-beta-D-glucopyranosyl oleanolic acid 28-O-beta-D-xylopyranosyl-(1 --> 3)-beta-D-xylopyranosyl-(1 --> 4)-alpha-L-rhamnopyranosyl-(1 --> 2)-[(6S,2E)-6-hydroxy-2,6-dimethyl-2,7-octadienoyl-(1 --> 6)]-beta-D-glucopyranosyl ester, named gleditsioside Z (1), together with nine known ones (2-10). Their structural details were mainly established on the basis of 1D, 2D NMR and HR-MS analysis as well as some chemical methods. Structure-activity relationships of the isolated saponins that affected nitric oxide production from cultured mouse macrophages (RAW 264.7 cell lines) induced by lipopolysaccharide were discussed.


Diuretic dose trajectories in dilated cardiomyopathy: prognostic implications.
For patients with heart failure, prescription of loop diuretics (LD) and of higher doses are associated with an adverse prognosis. We investigated LD dose trajectories and their associations with outcomes in patients with dilated cardiomyopathy (DCM). Associations between outcomes and both furosemide-equivalent dose (FED) at enrolment and change in FED in the subsequent 24 months were evaluated. According to FED trajectory, patients were classified as (i) dose↑ (FED increase by ≥ 50% or newly initiated); (ii) dose↓ (FED decrease by ≥ 50%); (iii) stable dose (change in FED by < 50%); and (iv) never-users. The primary outcome was all-cause-death/heart transplantation/ventricular-assist-device/heart failure hospitalization. The secondary outcome was all-cause-death/heart transplantation/ventricular-assist-device. Of 1,131 patients enrolled, 738 (65%) were prescribed LD at baseline. Baseline FED was independently associated with outcome (HR per 20 mg increase: 1.12 [95% CI 1.04-1.22], p = 0.003). Of the 908 with information on FED within 24 months from enrolment, 31% were never-users; 29% were dose↓; 26% were stable dose and 14% were dose↑. In adjusted models, compared to never-users, stable dose had a higher risk of the primary outcome (HR 2.42 [95% CI 1.19-4.93], p = 0.015), while dose↑ had the worst prognosis (HR 2.76 [95% CI 1.27-6.03], p = 0.011). Results were similar for the secondary outcome. Compared to patients who remained on LD, discontinuation of LD (143, 24%) was associated with an improved outcome (HR 0.43 [95% CI 0.28-0.65], p < 0.001). In patients with DCM, LD use and increasing FED are powerful markers of adverse outcomes. Patients who never receive LD have an excellent prognosis. Among 1131 DCM patients 65% received loop diuretics at enrolment (upper left side). The bar chart on the upper right side shows the categorization in never-users/ dose↓/stable dose/ dose↑ over 24 months of follow-up. At the bottom is reported on the left side of each panel (observation period) the trajectory of LD dose in the four groups (left panel) and in patients who have their LD suspended vs those who continue LD (right panel) in the first two years. On the right side of each panel is shown the incidence of primary outcomes during the subsequent follow-up in the subgroups (outcome assessment).


Expression and immunolocalisation of the endocytic receptors megalin and cubilin in the human yolk sac and placenta across gestation.
Megalin and cubilin are multifunctional endocytic receptors associated with many transporting epithelia. They play an essential role in transport of nutrients through the visceral yolk sac of rodents during embryogenesis. Here, we immunolocalise them to the endodermal layer of the human yolk sac, and to the syncytiotrophoblast and cytotrophoblast cells of placental villi. In villi, the protein level of both receptors increased with gestation. The mRNA for megalin remained constant, while that encoding cubilin increased with gestation. These results suggest megalin and cubilin may be important in human maternal-fetal transfer, and that they increase across gestation to facilitate this function.


Characteristic patterns of maternal and fetal arterial construction in the rabbit placenta.
We studied vascular structure of the rabbit placenta, especially on three-dimensional morphological patterns and developmental process. Basic structure of maternal arterial system was re-constructed during day 13-18 of pregnancy, forming main routes for blood supply through the arterial sinuses and radial arteries. Intra-villous spaces were drastically developed showing as branches from the terminal radial arteries. Fetal arterial system was generated accompanied with maternal vascular development, showing characteristic features such as the perforating linear artery, hairpin flexion, and circular anastomoses in the capillaries. From the correlation of maternal and fetal blood currents, gas-exchange style in the rabbit placenta was considered as counter-current and pool mixed patterns. These data demonstrated an original feature for the placental arterial systems in rabbits, which differed from other animals having a property for discoid placenta.


A 1H-NMR study of the solution conformation of Icaria chemotactic peptide and its [Lys7] analog: effects on the physiological activity of a substitution of proline to lysine at position 7.
Solution conformations of Icaria chemotactic peptide isolated from the Ropalidian wasp venom and its [Lys7] analog have been analyzed by the use of two-dimensional proton nuclear resonance spectroscopy. It has been shown that Icaria chemotactic peptide takes alpha helical conformation in the C-terminal 8-13 segment with the N-terminal 1-7 segment disordered. By contrast, the [Lys7] analog takes alpha helical conformation over a wider range from residues 3 to 13. The present results indicate that the substitution of proline to lysine at position 7 results in a drastic change in solution conformation, providing the Icaria chemotactic peptide with new physiological functions.


[A new method for haemostasis by tonsillectomy by use of infrared radiation (author's transl)].
Using infrared radiation tisssue is coagulated by infrared radiation and not by electrical current. Main purpose for this procedure is to apply mechanical pressure and radiation. No crust will stick to the artificial tip of the infrared apparatus to open up wounds once more. Infrared radiation for coagulation has been used in the clinic for 2 1/2 years, mainly in parenchymatous haemostasis during tonsillectomy. The method seems to be very effective and should enlargen the different means of dealing with haemorrhage.


Spinal Fusion in Parkinson's Disease Patients: A Propensity Score-Matched Analysis With Minimum 2-Year Surveillance.
Retrospective analysis. To compare outcomes and complication rates between patients with and without Parkinson's disease (PD) patients undergoing surgery for adult spinal deformity (ASD). There is limited literature evaluating the impact of PD on long-term outcomes after thoracolumbar fusion surgery for ASD. Patients admitted from 2009 to 2011 with diagnoses of ASD who underwent any thoracolumbar fusion procedure with a minimum 2-year follow-up surveillance were retrospectively reviewed using New York State's Statewide Planning and Research Cooperative System. A 1:1 propensity score-match by age, Deyo score, and number of fused vertebral levels was conducted before comparing surgical outcomes of patients with ASD with and without PD. Univariate analysis compared demographics, complications, and subsequent revision. Multivariate binary stepwise logistic regression models identified independent predictors of these outcomes (covariates: age, sex, Deyo Index score, and PD diagnosis). A total of 576 propensity score-matched patients were identified (PD: n = 288; no-PD: n = 288), with a mean age of 69.7 years (PD) and 70.2 years (no-PD). Each cohort had comparable distributions of age, sex, race, insurance provider, Deyo score, and number of levels fused (all P > 0.05). Patients with PD incurred higher total charges across ASD surgery-related visits ($187,807 vs. $126,610, P < 0.001), yet rates of medical complications (35.8% PD vs. 34.0% no-PD, P = 0.662) and revision surgery (12.2% vs. 10.8%, P > 0.05) were comparable. Postoperative mortality rates were comparable between PD and no-PD cohorts (2.8% vs. 1.4%, P = 0.243). Logistic regression identified nine-level or higher spinal fusion as a significant predictor for an increase in total complications (odds ratio = 5.64); PD was not associated with increased odds of any adverse outcomes. Aside from higher hospital charges incurred, patients with PD experienced comparable overall complication and revision rates to a propensity score-matched patient cohort without PD from the general population undergoing thoracolumbar fusion surgery. These results can support management of concerns and postoperative expectations in this patient cohort. 3.


Additive hypoglycemic effects of drugs that modify free-fatty acid metabolism by different mechanisms in rats with streptozocin-induced diabetes.
In this study the effect of two drugs [etomoxir and nicotinic acid (NA)] on plasma glucose, free-fatty acid (FFA), and triglyceride (TG) concentrations was determined in rats with streptozocin (STZ)-induced diabetes. The two compounds modify FFA metabolism by different mechanisms, etomoxir (ethyl-2-[6-(4-cholorophenoxyl)-hexyl]oxirane-2-carboxylate) by inhibiting hepatic fatty acid oxidation, and NA by inhibiting lipolysis in adipose tissue. Diabetes was induced in male Sprague-Dawley rats, weighing approximately 400 g, by STZ injection (30 mg/kg i.v.), and the metabolic effects of the two drugs were studied 7-10 days later. The acute administration of either etomoxir or NA lowered plasma glucose concentrations in diabetic rats by approximately 150 mg/dl (P less than .001) in 4 h. However, the two drugs differed dramatically in their effects on plasma FFA and TG concentrations. Specifically, etomoxir produced striking increases in plasma FFA and TG concentrations, whereas NA administration caused a marked decrease. However, when NA was given in conjunction with etomoxir, NA prevented the increase in plasma FFA and TG concentration seen with etomoxir; the combination of NA and etomoxir approximately doubled the decrease in plasma glucose concentration produced by NA or etomoxir when given alone. Because plasma insulin concentrations did not change in response to either drug, whether administered singly or in combination, these metabolic effects do not result from a change in insulin secretion. These results suggest that modulation of FFA metabolism at the level of the adipocyte or the liver can have dramatic effects on carbohydrate and lipid metabolism.


Social needs and health-related quality of life among African American cancer survivors: Results from the Detroit Research on Cancer Survivors study.
Social needs may affect cancer survivors' health-related quality of life (HRQOL) above and beyond sociodemographic and cancer-related factors. The purpose of this study was to estimate associations between social needs and HRQOL. Results included data from 1754 participants in the Detroit Research on Cancer Survivors cohort, a population-based study of African American survivors of breast, colorectal, lung, and prostate cancer. Social needs included items related to food insecurity, utility shutoffs, housing instability, not getting health care because of cost or a lack of transportation, and perceptions of neighborhood safety. HRQOL was measured with the validated Functional Assessment of Cancer Therapy-General (FACT-G). Linear regression models controlled for demographic, socioeconomic, and cancer-related factors. More than one-third of the survivors (36.3%) reported social needs including 17.1% of survivors reported 2 or more. The prevalence of social needs ranged from 14.8% for food insecurity to 8.9% for utility shutoffs. FACT-G score differences associated with social needs were -12.2 (95% confidence interval [CI] to -15.2 to -9.3) for not getting care because of a lack of transportation, -11.3 (95% CI, -14.2 to -8.4) for housing instability, -10.1 (95% CI, -12.7 to -7.4) for food insecurity, -9.8 (95% CI, -12.7 to -6.9) for feeling unsafe in the neighborhood, -8.6 (95% CI, -11.7 to -5.4) for utility shutoffs, and -6.7 (95% CI, -9.2 to -4.1) for not getting care because of cost. Social needs were common in this cohort of African American cancer survivors and were associated with clinically significant differences in HRQOL. Clinical oncology care and survivorship care planning may present opportunities to screen for and address social needs to mitigate their impact on survivors' HRQOL.


Factors affecting the outcome of foetal hydrocephaly.
In this study, the authors attempt to provide an account of the factors that affect the outcome of hydrocephaly in 26 foetuses. The hydrocephalus was related to a myelomeningocele in 35% of patients. Sixty-two percent of foetuses showed intra-uterine progression of their hydrocephalus and 50% were shunted postnatally. At a mean follow up of 2 years, the outcome was considered "fair" in 54% of patients. Our findings demonstrate that in foetal hydrocephaly a more favourable outcome is expected in patients with hydrocephalus which does not progress in utero, in whom the labour is not induced before 36 weeks of gestation, who are delivered vaginally weighing more than 2.5 kg and have a head circumference below the 95th centile and a CT cortical mantle thickness of 2 cm and more and who are treated by CSF shunting. The diagnosis of the foetal hydrocephaly at or before 28 weeks of gestation and the presence of a myelomeningocele did not affect the outcome significantly. Neurosurgeons are reminded to keep an open mind for infants with foetal hydrocephaly and to offer active treatment to patients with a potentially favourable outcome.


Selective inhibition of reproduction in aminopterin-treated nematodes.
Aminopterin was applied to the free-living nematode Caenorhabditis briggsae and subsequent growth was recorded. Nematode populations, containing all developmental stages and selected juvenile stages, were exposed to the drug in both growth-promoting and non-promoting media. It is suggested that aminopterin creates a specific requirement for thymine in thymine-free medium. In otherwise growth-promoting medium, aminopterin-induced thymine deficiency will lead to progressively unbalanced growth and maturation and hence to sterility even after removal of the drug. The omission of essential amino acids from the medium during thymine starvation prevents larval growth and results in better reproduction and faster proliferation in aminopterin-free medium. The 4 juvenile stages exhibit a different response to thymine starvation created by aminopterin.


Human papillomavirus DNA detection in women with primary abnormal cytology of the cervix: prevalence and distribution of HPV genotypes.
In this study, we focus on the prevalence and occurrence of different anogenital human papillomavirus (HPV) genotypes in a first abnormal cervical screening test, and correlate HPV genotyping with the cytological diagnosis on thin-layer liquid-based preparations in routine gynaecological screening. Out of 780 abnormal smears, 513 tested positive for HPV. All 25 different HPV types were identified by Line Probe Assay. The prevalence of high-risk HPV types increased from 72% in atypical squamous cell of undetermined significance to 94.5% in high-grade intra-epithelial lesion (HSIL). Co-infection with multiple HPV types was predominantly found in HSIL (35.8%). In the HSIL group the most common HPV types were 16, 52, 51 and 31; type 18 was rarely present. The role of types 31, 51 and 52 should be considered in future studies on vaccine development.


Effect of aging and obesity on esophageal mucosal integrity as measured by baseline impedance.
Low mean nocturnal baseline impedance (MNBI) values support gastroesophageal reflux disease (GERD) diagnosis. Recent data denote that age and obesity may affect MNBI. We aimed to evaluate diagnostic MNBI cutoffs as also the effect of aging and body mass index (BMI) on MNBI. In total 311 patients (M/F: 139/172, mean age: 47 ± 13) referred for typical GERD symptoms that have undertaken both high-resolution manometry (HRM) and pH-Impedance studies off PPI were evaluated. MNBI at 3, 5, and 17 cm over lower esophageal sphincter (LES) were evaluated. GERD was diagnosed if acid exposure time (AET) >6%. Mean BMI was 26.6 ± 5.9 kg/cm2 . GERD was diagnosed in 39.2% and 13.5% had inconclusive GERD. MNBI was correlated to patients' age, BMI, AET, and the length of LES-CD separation and at 3 cm also to the total number of reflux and LES hypotension. In the multivariate analysis MNBI at 3 and 5 cm was independently correlated only to age, BMI, and AET. Patients with definite GERD showed lower MNBI at 3 cm compared with inconclusive GERD though both showed lower values when compared with GERD absence. At 3 cm MNBI ability for diagnosing GERD was good (0.815, p < 0.001 95% CI: 0.766-0.863) with an optimal cutoff point of 1281 Ohm. According to our study findings age and BMI affect independently lower esophageal MNBI values in patients evaluated for GERD. MNBI significantly aids toward GERD diagnosis though in a real-life setting MNBI values much lower than the one previously proposed should be used.


Inorganic Bergman Cyclization: An Appeal From Theory.
The scope of Bergman cyclization is expanded computationally by exploring the cyclization in inorganic B, N substituted derivative. This substitution has introduced polarity into the transition state, which resulted in dramatic lowering of the activation barrier. Natural charge distribution throughout the reaction profile has ascertained this hypothesis. Single B and N atom substitution at 1 and 6 terminal positions lowers the activation barrier by almost half of the original value which becomes even lower in the complete B, N analogue. The parent Bergman and single B, N substituted products were characterized by significant biradical character while the complete B, N substituted analogue was characterized by significant zwitterionic character. Reduction in electron delocalization is also observed in the complete B, N substituted analogue.


A model of myosin crossbridge structure consistent with the low-angle x-ray diffraction pattern of vertebrate muscle.
Low-angle X-ray diffraction patterns have been taken of relaxed frog sartorius muscles stretched to destroy the lattice sampling in the pattern and the observed layer line pattern has been interpreted with model-building studies. The modelling calculations indicate that each crossbridge cannot be represented by a single cylindrical shape, but that the two S-1 heads of the crossbridge are tilted in opposite directions along the filament while twisted the same way round it so that the crossbridge lies wrapped round the filament backbone. The radial position derived for the crossbridge depends on how many strands the filament is assumed to have. If the filament is 2, 3 or 4 stranded then the centre of mass of the crossbridge lies at about 9.5, 12.5, or 15.5 nm respectively from the filament axis.


Strangulation deaths during 1993-2002 in East Delhi (India).
Strangulation is one of the common modes of violent asphyxias. Frequently, the deaths from strangulation are homicidal in nature. To study the pattern of the strangulation deaths in the capital city of Delhi, a retrospective analysis of 10 years records from the period 1993-2002 was undertaken in the department of Forensic Medicine and Toxicology at UCMS and GTB Hospital. During the above period, 8385 Forensic autopsies were conducted out of these 98 (1.17%) cases were found to be of strangulation. These 98 cases were analyzed in detail and showed that: (a) incidence of strangulation have increased many folds in comparison in 1970s; (b) maximum incidence of strangulation is amongst individuals in third decade of life; (c) male, female ratio was 3:2; (d) ligating material was found present in neck in 40% cases; (e) fractures of the neck bones/cartilage were observed in 80% cases; and (f) other associated injuries were seen in as high as approximately 90% of cases. The paper describes and discusses the findings in detail.


Differential induction of chitinase in Piper colubrinum in response to inoculation with Phytophthora capsici, the cause of foot rot in black pepper.
Plant chitinases have been of particular interest since they are known to be induced upon pathogen invasion. Inoculation of Piper colubrinum leaves with the foot rot fungus, Phytophthora capsici leads to increase in chitinase activity. A marked increase in chitinase activity in the inoculated leaves was observed, with the maximum activity after 60 h of inoculation and gradually decreased thereafter. Older leaves showed more chitinase activity than young leaves. The level of chitinase in black pepper (Piper nigrum L.) upon inoculation was found to be substantially high when compared to P. colubrinum. RT-PCR using chitinase specific primers revealed differential accumulation of mRNA in P. colubrinum leaves inoculated with P. capsici. However, hyphal extension assays revealed no obvious differences in the ability of the protein extracts to inhibit growth of P. capsici in vitro.


Temperature-dependent binding of monoclonal antibodies to C hordein.
The consensus octapeptide repeat motif of the barley seed storage protein C hordein, Pro-Gln-Gln-Pro-Phe-Pro-Gln-Gln, forms the epitope of two anti-prolamin monoclonal antibodies (Mabs), IFRN 0061 and 0614. The Mabs were found to exhibit unusual temperature-dependent binding characteristics, recognising C hordein and a peptide corresponding to the consensus repeat at 5 degrees C but not at 37 degrees C, as determined by enzyme-linked immunosorbent assay (ELISA). The K(d) of IFRN 0614 for the consensus peptide was found to be 1.2x10(12) mol(-1) at 12 degrees C, but no constant could be calculated at 37 degrees C due to a lack of binding. Similar ELISA binding characteristics were observed with an anti-C hordein polyclonal antiserum and a Mab raised to the consensus peptide. Circular dichroism (CD) and Fourier-transform infrared (FTIR) spectroscopy showed that the protein and the consensus peptide exist in a temperature-dependent equilibrium of poly-L-proline II type structures and beta-turn conformations. Whilst thermodynamic and kinetic effects may reduce antibody binding at higher temperatures, they cannot account for the complete loss of Mab recognition at higher temperatures. It seems likely that the Mabs preferentially recognise the Pro-Gln-Gln-Pro-Phe-Pro-Gln-Gln motif when presented in a conformation which may correspond to the poly-L-proline II type conformation which dominates the CD and FTIR spectra at 4-12 degrees C.


Prevalence of pathological duodenogastric reflux and the relationship between duodenogastric and duodenogastrooesophageal reflux in chronic gastrooesophageal reflux disease.
The role of duodenogastric reflux in gastrooesophageal reflux disease is still controversial. (i) To determine the prevalence of pathological duodenogastric reflux (DGR) in gastrooesophageal reflux disease patients and (ii) to define the relationship between DGR and duodenogastrooesophageal reflux. We evaluated 92 patients referred for investigation of recurrent reflux symptoms after proton pump inhibitors (PPI) therapy. All the patients filled out symptom questionnaires and underwent endoscopy, oesophageal manometry and combined oesophagogastric pH and bilirubin monitoring. Endoscopy divided the 92 patients into four groups (group I: 25 nonoesophagitis patients, group II: 26 patients with grade A-B oesophagitis, group III: 21 patients with grade C-D oesophagitis and group IV: 20 patients with Barrett's oesophagus. Twenty-four of the 92 patients (26%) showed pathological DGR. Abnormal oesophageal bilirubin exposure was observed in 62 of the 92 patients (67.4%). Of the 62 patients with abnormal oesophageal bilimetry, 15 (24.2%) patients simultaneously showed pathological DGR. The gastric bilirubin exposure in patients with abnormal oesophageal, Bilitec tests did not differ from that in patients with normal oesophageal bilimetry (P>0.05). A weak correlation between oesophageal and gastric bilirubin exposure, both expressed as a percentage of time, was found (r=0.28; P<0.01). Pathological DGR is present in a little more than a quarter of patients with recurrent reflux and dyspeptic symptoms after PPI therapy. Excessive DGR is not a prerequisite for pathological oesophageal exposure to duodenal contents. Gastric bilirubin monitoring may be useful to choose the best surgical treatment for patients with reflux and dyspeptic symptoms refractory to PPI.


A volume conductor study of compound action potentials of nerves in situ: the forward problem.
A computer model for the stimulation of compound nerve action potentials, based on superposition of volume conducted single nerve fibre potentials, is presented. The model assumes that the intracellular fibre potential, the fibre diameter distribution and the electrical conductivities of different tissues are known. Volume conductor fields are calculated in the spatial frequency domain. The influence of important parameters in the model is evaluated numerically. It is shown that it is necessary to give up the usual assumption of homogeneity and isotropy in the extracellular medium. In the present model parameters are introduced which allow an overall description of the complex morphological and physiological structure of the nerve trunk. Simulation results indicate that the model is a rather promising tool in studying the main properties of compound action potentials which up till now have not been sufficiently well understood.


Optimizing placement of constructed wetlands at landscape scale in order to reduce phosphorus losses.
Constructed wetlands (CWs) are one of the main countermeasures to reduce diffuse phosphorus (P) losses, but there is still a lack of systematic guidance accounting for spatially variable effects of hydraulic and P load on P retention. We present a three-step modelling approach for determining suitable placement of CWs in four different size groups (0.1-1.0 ha), based on incoming hydraulic and P load. The modelled hypothetical CW area was only 17% of that previously estimated and area of efficient CWs is even lower. The mean area-specific P retention increased with CW size. However, the spatial variation in retention was large for all size groups and largest (6-155 kg ha-1 year-1) for the smallest CWs due to highly variable incoming P loads, showing the possible benefits of targeted placement of CWs. The presented modelling approach has also flexibility to include and account for possible future changes in land cover and management.


Hemophilus parainfluenzae complicating total knee arthroplasty. A case report.
Infections are an unfortunate but well-known complication of prosthetic joint replacements. Prophylactic antibiotics have been prescribed to help combat infections in total joint arthroplasties. A 78-year-old woman with a cemented total knee replacement developed a Hemophilus parainfluenzae infection following routine root canal dental surgery. The infection was successfully treated with arthroscopic irrigation and antibiotic therapy.


Attraction effect of different colored cards on thrips Frankliniella intonsa in cowpea greenhouses in China.
The flower thrips Frankliniella intonsa (Trybom) is one of the most economically important pests in cowpea greenhouses in China. Widespread pesticide resistance of thrips and the negative environmental effects limit the application of pesticides for thrips control. Two commercial cowpea greenhouse experiments were designed to determine the color preference of F. intonsa to colored cards, including white, pink, pale green, light yellow, powder blue, crimson, yellow green, deep sky blue, dark slate blue, dark orange, medium orchid, gold, and black. Clear pieces of plastic were used as the control cards. Additionally, the effects of placement height and orientation (cardinal direction) of the cards were also studied. Both greenhouse trials showed that white cards were significantly more attractive to F. intonsa than the other 13 card colors, followed by deep sky blue cards. White or deep sky blue cards placed low to the ground were found to be most attractive to F. intonsa. Orientation of the colored cards also affected the attractiveness to F. intonsa. The results indicate that white sticky cards were significantly more attractive to F. intonsa than blue cards and therefore can be recommended to monitor F. intonsa population densities and to control them in cowpea greenhouses as part of integrated pest management programs.


Gene expression and localization of a β-1,3-glucanase of Lotus japonicus.
Phytohormone abscisic acid (ABA) inhibits root nodule formation of leguminous plants. LjGlu1, a β-1,3-glucanase gene of Lotus japonicus, has been identified as an ABA responsive gene. RNA interference of LjGlu1 increased nodule number. This suggests that LjGlu1 is involved in the regulation of nodule formation. Host legumes control nodule number by autoregulation of nodulation (AON), in which the presence of existing root nodules inhibits further nodulation. For further characterization of LjGlu1, we focused on the expression of LjGlu1 in relation to AON. In a split-root system, LjGlu1 expression peaked when AON was fully induced. Hairy roots transformed with LjCLE-RS1, a gene that induces AON, were generated. Expression of LjGlu1 was greater in the transgenic roots than in untransformed roots. LjGlu1 was not induced in a hypernodulating mutant inoculated with Mesorhizobium loti. These results suggest that the expression of LjGlu1 is involved in the system of AON. However, neither hypernodulation nor enlarged nodulation zone was observed on the transgenic hairy roots carrying LjGlu1-RNAi, suggesting that LjGlu1 is not a key player of AON. Recombinant LjGlu1 showed endo-β-1,3-glucanase activity. LjGlu1-mOrange fusion protein suggested that LjGlu1 associated with M. loti on the root hairs. Exogenous β-1,3-glucanase inhibited infection thread formation by both the wild type and the mutant, and nodule numbers were reduced. These results suggest that LjGlu1 is expressed in response to M. loti infection and functions outside root tissues, resulting in the inhibition of infection.