[Interaction of reticular structures in the brain of the cat].
In acute and chronic experiments on 35 cats an inhibitory influence was found of the caudal reticular nucleus of pons Varolii on unit activity of the sensorimotor cortex and dorsal part of the midbrain reticular formation. The influence of this structure on unit activity of the ventral part of the midbrain reticular formation was mainly of a facilitatory character. Activation of the ventral part inhibited the unit activity of the dorsal part of the same structure. Consequently, the caudal reticular nucleus of pons Varolii elicits inhibition at the level not only of the cerebral cortex but also of the midbrain reticular formation (of its dorsal part). The character of these influences coincides with that of unit activity changes of these two areas of the midbrain reticular formation during the development of the paradoxical phase of sleep. The obtained facts must underlie the stopping of convulsive activity in this phase of sleep.


Somatosensory demands modulate muscular Beta oscillations, independent of motor demands.
Neural oscillations in the beta band (15-30 Hz) occur coherently throughout the primate somatomotor network, comprising somatomotor cortices, basal ganglia, thalamus, cerebellum, and spinal cord, with the latter resulting in beta oscillations in muscular activity. In accordance with the anatomy of this network, these oscillations have traditionally been associated strictly with motor function. Here we show in humans that somatosensory demands, both in anticipation and during the processing of tactile stimuli, also modulate beta oscillations throughout this network. Specifically, somatosensory demands suppress the degree to which not only cortical activity but also muscular activity oscillates in the beta band. This suppression of muscular beta oscillations by perceptual demands is specific to demands in the somatosensory modality and occurs independent of movement preparation and execution: it occurs even when no movement is required at all. This places touch perception as an important computation within this widely distributed somatomotor beta network and suggests that, at least in healthy subjects, somatosensation and action should not be considered as separable processes, not even at the level of the muscles.


Historical review of clinical vaccine studies at Oswaldo Cruz Institute and Oswaldo Cruz Foundation--technological development issues.
This paper presents, from the perspective of technological development and production, the results of an investigation examining 61 clinical studies with vaccines conducted in Brazil between 1938-2013, with the participation of the Oswaldo Cruz Institute (IOC) and the Oswaldo Cruz Foundation (Fiocruz). These studies have been identified and reviewed according to criteria, such as the kind of vaccine (viral, bacterial, parasitic), their rationale, design and methodological strategies. The results indicate that IOC and Fiocruz have accumulated along this time significant knowledge and experience for the performance of studies in all clinical phases and are prepared for the development of new vaccines products and processes. We recommend national policy strategies to overcome existing regulatory and financing constraints.


Idiopathic granulomatous mastitis associated with corynebacterium sp. Infection.
Idiopathic granulomatous mastitis (IGM) is a rare inflammatory condition of the breast. The etiology and treatments options of IGM remain controversial. Previous case reports have suggested that Corynebacterium sp., a gram-positive bacillus endogenous to the skin, may be associated with IGM. In the present report, we describe the first case of IGM with a positive culture for Corynebacterium sp. reported in the United States.


Understanding the agency of home-based care volunteers: establishing identity and negotiating space in AIDS-home-based care in rural KwaZulu-Natal, South Africa.
In traditional Zulu communities, caregiving is rooted in compassionate and hardworking personal identity precepts and the traditional identity expectations of women. Home-based-care volunteerism in the community represents the performance of this identity. Data from a series of interviews with 15 home-based care volunteers (HBCVs), in a rural community in KwaZulu-Natal Province, South Africa, is used to illustrate how HBCVs promote the notion of women as paid home-based caregivers, with a recognised space in the care and support system regarding HIV and AIDS. Home-based-care volunteering also represents the attempt by women to be seen, heard and recognised in the hope that it will lead to self-improvement and the improvement of their families. Volunteer motivations vary from altruism, to volunteering as a means to be recognised and increasing the chances of self-improvement. We propose that home-based-care volunteering may be viewed as a form of agency in response to a lack of recognition, support and acknowledgement for AIDS caregivers and their patients. The continued lack of support for HBCVs over a long period undermines the work and the basis of the HBCVs' identity or the aspects of identity on which the motivation for the work is based.


Cardiac risk in the treatment of breast cancer: assessment and management.
As the number of long-term breast cancer survivors has increased, the side effects of adjuvant cancer therapy, such as cardiac toxicity, remain clinically important. Although the cardiac toxicity due to anthracyclines, radiotherapy, or trastuzumab is well-documented, several issues need to be clarified and are the subjects of extensive ongoing clinical research. This review summarizes the incidence of cardiac toxicity due to breast cancer adjuvant therapy and highlights the current trends in early detection and management of cardiac toxicities.


Anterior lumbar interbody fusion using recombinant human bone morphogenetic protein-2: a prospective study of complications.
The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in anterior lumbar interbody fusion (ALIF) is controversial regarding the reported complication rates and cost. The authors aimed to assess the complication rates of performing ALIF using rhBMP-2. This is a prospective study of consecutive patients who underwent ALIF performed by a single spine surgeon and a single vascular surgeon between 2009 and 2012. All patients underwent placement of a polyetheretherketone (PEEK) cage filled with rhBMP-2 and a separate anterior titanium plate. Preoperative clinical data, operative details, postoperative complications, and clinical and radiographic outcomes were recorded for all patients. Clinical outcome measures included back and leg pain visual analog scale scores, Oswestry Disability Index (ODI), and SF-36 Physical and Mental Component Summary (PCS and MCS) scores. Radiographic assessment of fusion was performed using high-definition CT scanning. Male patients were screened pre- and postoperatively regarding sexual dysfunction, specifically retrograde ejaculation (RE). The study comprised 131 patients with a mean age of 45.3 years. There were 67 men (51.1%) and 64 women (48.9%). Of the 131 patients, 117 (89.3%) underwent ALIF at L5-S1, 9 (6.9%) at L4-5, and 5 (3.8%) at both L4-5 and L5-S1. The overall complication rate was 19.1% (25 of 131), with 17 patients (13.0%) experiencing minor complications and 8 (6.1%) experiencing major complications. The mean estimated blood loss per ALIF level was 115 ml. There was 1 incidence (1.5%) of RE. No significant vascular injuries occurred. No prosthesis failure occurred with the PEEK cage and separate anterior screw-plate. Back and leg pain improved 57.2% and 61.8%, respectively. The ODI improved 54.3%, with PCS and MCS scores improving 41.7% and 21.3%, respectively. Solid interbody fusion was observed in 96.9% of patients at 12 months. Anterior lumbar interbody fusion with a vascular access surgeon and spine surgeon, using a separate cage and anterior screw-plate, provides a very robust and reliable construct with low complication rates, high fusion rates, and positive clinical outcomes, and it is cost-effective. The authors did not experience the high rates of RE reported by other authors using rhBMP-2.


Sialic acids in bone demineralised in organic solvents.
The sialic acid content of bovine shin bone, demineralised by a new process in ethanol-trimetrylammonium EDTA, was measured and compared with that of the original whole bone. New variants of the direct Ehrlich procedure, as well as the periodate-thiobarbituric acid assay, were employed. About 75% of the sialic acid remains in the bone matrix from ethanolic demineralisation, and the PAS reaction is correspondingly much more intense, compared with matrix from aqueous EDTA demineralisation.


Salmonella Oranienburg haemorrhagic cystitis in an immunocompetent young male.
Introduction. Non-typhoidal salmonella (NTS) bacteriuria is extremely rare. Haemorrhagic cystitis is defined by urinary symptoms including haematuria, frequency, urgency and dysuria. Reports of haemorrhagic cystitis caused by NTS are exceptionally uncommon, especially in immunocompetent, young, male patients. Case presentation. A 27-year-old male with no past medical history presented to the Emergency Department with a 24 h history of visible haematuria having returned five days earlier from a five month trip across South America. He also reported one week of suprapubic pain with associated dysuria, frequency, difficulty voiding and fevers. A non-contrast abdominal and pelvic CT scan showed a grossly thick-walled bladder with marked peri-vesical stranding, strongly suggestive of cystitis, with an unremarkable appearance of the remainder of the urinary tract. Urine culture at presentation subsequently grew Salmonella Oranienburg. The patient reported total symptomatic relief following just one week of oral antibiotics with no recurrence to date. Conclusion. NTS urinary tract infection (UTI), especially in healthy young people, is very rare. In such cases, the existence of underlying diseases must be considered, especially diabetes mellitus, urological abnormalities and immunosuppression. However, a diagnosis of NTS UTI should also be among the differentials in those presenting with acute urinary symptoms preceded by gastrointestinal upset, especially following travel in underdeveloped countries. Antibiotic therapy is invariably indicated and close follow-up is warranted due to the risk of several potentially serious complications.


Radiological Features of Brain Metastases from Non-small Cell Lung Cancer Harboring EGFR Mutation.
To investigate the radiological features on computed tomography (CT) of brain metastasis (BM) from epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). Thirty-four patients with NSCLC with BMs who underwent surgical resection of the BMs at the Department of Neurosurgery, Kyushu University from 2005 to 2016 were enrolled in the study. The EGFR statuses of the 34 BMs were investigated. Radiological features, including the number, size, and location of the tumor, were delineated by CT. Patients with EGFR-mutated BMs had significantly higher frequencies of multiple metastases than those with the non-EGFR-mutated type (p=0.042). BMs harboring mutations in EGFR were more frequently observed in the central area of the brain compared to those without mutations in EGFR (p=0.037). Careful follow-up of patients with EGFR-mutated NSCLC may be necessary given the high frequencies of multiple BMs and their location in the central area of the brain.


He use of the antibodies in the diagnosis of leukemia and lymphoma by flow cytometry.
Flow cytometry is an automated analysis of cells passing in the fluid suspension through a laser light beam, which react with monoclonal antibodies specific for a variety of cell surface antigens. A specimen of peripheral blood, bone marrow, or other cell suspension is incubated with fluorescent-labeled antibodies, which bind to target antigens on cell surfaces or--following cell permeabilization--to cytoplasmic and nuclear antigens. The analysis of surface antigens is performed on cells selected (gated) based on light-scatter properties. The expression of specific marker or confirmation of markers defines a specific cell population or the original of these cells. This in turn helps in diagnosis and classification of various hematological diseases and leads to choosing a specific therapy. Here, we describe a methodology for using flow cytometry with six colors for the analysis of various tissues for hematological diseases.


Engineering of CYP82Y1, a cytochrome P450 monooxygenase: a key enzyme in noscapine biosynthesis in opium poppy.
Protein engineering provides a powerful base for the circumvention of challenges tied with characteristics accountable for enzyme functions. CYP82Y1 introduces a hydroxyl group (-OH) into C1 of N-methylcanadine as the substrate to yield 1-hydroxy-N-methylcanadine. This chemical process has been found to be the gateway to noscapine biosynthesis. Owning to the importance of CYP82Y1 in this biosynthetic pathway, it has been selected as a target for enzyme engineering. The insertion of tags to the N- and C-terminal of CYP82Y1 was assessed for their efficiencies for improvement of the physiological performances of CYP82Y1. Although these attempts achieved some positive results, further strategies are required to dramatically enhance the CYP82Y1 activity. Here methods that have been adopted to achieve a functionally improved CYP82Y1 will be reviewed. In addition, the possibility of recruitment of other techniques having not yet been implemented in CYP82Y1 engineering, including the substitution of the residues located in the substrate recognition site, formation of the synthetic fusion proteins, and construction of the artificial lipid-based scaffold will be discussed. Given the fact that the pace of noscapine synthesis is constrained by the CYP82Y1-catalyzing step, the methods proposed here are capable of accelerating the rate of reaction performed by CYP82Y1 through improving its properties, resulting in the enhancement of noscapine accumulation.


Isolation of a third bovine neurophysin.
1. A third native hormone-binding protein, neurophysin-C, has been isolated from acetone-desiccated bovine pituitary posterior lobes. 2. This protein was detected in lysates of neurosecretory granules isolated from bovine pituitary posterior lobes. 3. The molecular weight appears to be close to 10000. 4. Neurophysin-C is similar in amino acid composition to neurophysin-I and -II; it contains a single residue of tyrosine and of methionine. The N-terminal amino acid in all three neurophysins is alanine. 5. Neurophysin-C accounts for approximately 15% of the total hormone-binding protein present in the pituitary posterior lobes. 6. The new neurophysin forms complexes with oxytocin as well as with [8-arginine]-vasopressin. The complex with vasopressin has been crystallized. 7. Bioassay of the pressor and oxytocic activities of the protein-hormone complexes shows that neurophysin-C binds one molecule of either vasopressin or oxytocin.


Intraocular medulloepithelioma: an unusual and challenging entity in paediatric population.
Intraocular medulloepithelioma is a rare, congenital tumour of the non-pigmented ciliary epithelium. It most frequently arises from the ciliary body but can also have its origin from the retina, iris and optic nerve. The age when lesion first appears is typically around 2-10 years. Nearly 50-60% of patients having this lesion may also have secondary features such as cataract and neovascular glaucoma. Those with extrascleral medulloepithelioma are at risk for metastasis. Systemic correlation of the tumour with pleuropulmonary blastoma/DICER1 gene is reported in the literature. Here, we report a case of a 15 years old boy with one year history of right eye proptosis and painful red right eye along with decreased vision for one week. He was assessed and operated for cataract elsewhere three years back. The ophthalmology team managed him for endophthalmitis with intravenous antibiotics, followed by 2 sessions of cryotherapy and finally an enucleation of right eye was performed due to severe pain and no vision in the involved eye. His left eye, general physical examination and systemic evaluation were normal. Histopathology revealed the diagnosis of 'malignant teratoid medulloepithelioma'. Therefore, evaluation of systemic associations for DICER1 gene mutations was performed by the oncology team. For high risk feature of scleral invasion on histopathology, he was treated with chemotherapy. Since the tumour is of rare occurrence; an international expert team with vast research experience in PPB/DICER1 associated tumours was also contacted. He was registered in International PPB/DICER1 registry where a detailed central radiology and pathology review was performed. Genetic counseling and surveillance plan was also suggested by the international registry.


[The olfactory sense].
In mammals, olfactory stimuli influence various aspects of life including feeding, social behaviour, and reproduction. We review the progress in olfactory research in the last decade. In this era of gene-based techniques, a breakthrough in our knowledge on odorant and pheromone detection has occurred. Most importantly, a large gene family of odorant receptors expressed in the olfactory epithelium has been discovered. Subsets of receptor cells express one and only one receptor type and send their axons to a corresponding glomerulus in the olfactory bulb, giving rise to an odor-specific map in this structure. Two gene families of pheromone receptors expressed in the vomeronasal organ have also been discovered, and a role of pheromones in mammalian reproduction has been established. Although the crucial steps in odorant binding and transduction to nerve signals have been revealed, the central processing of this sensory information is basically unknown. Moreover, whether pheromones serve a significant role in human behaviour is still an open question.


Nutrition transition, overweight and obesity among rural-to-urban migrant women in Kenya.
To assess the effect of rural-to-urban migration on nutrition transition and overweight/obesity risk among women in Kenya. Secondary analysis of data from nationally representative cross-sectional samples. Outcome variables were women's BMI and nutrition transition. Nutrition transition was based on fifteen different household food groups and was adjusted for socio-economic and demographic characteristics. Stepwise backward multiple ordinal regression analysis was applied. Kenya Demographic and Health Survey 2014. Rural non-migrant, rural-to-urban migrant and urban non-migrant women aged 15-49 years (n 6171). Crude data analysis showed rural-to-urban migration to be associated with overweight/obesity risk and nutrition transition. After adjustment for household wealth, no significant differences between rural non-migrants and rural-to-urban migrants for overweight/obesity risk and household consumption of several food groups characteristic of nutrition transition (animal-source, fats and sweets) were observed. Regardless of wealth, migrants were less likely to consume main staples and legumes, and more likely to consume fruits and vegetables. Identified predictive factors of overweight/obesity among migrant women were age, duration of residence in urban area, marital status and household wealth. Our analysis showed that nutrition transition and overweight/obesity risk among rural-to-urban migrants is apparent with increasing wealth in urban areas. Several predictive factors were identified characterising migrant women being at risk for overweight/obesity. Future research is needed which investigates in depth the association between rural-to-urban migration and wealth to address inequalities in diet and overweight/obesity in Kenya.


Building a Lego wall: Sequential action selection.
The present study draws together two distinct lines of enquiry into the selection and control of sequential action: motor sequence production and action selection in everyday tasks. Participants were asked to build 2 different Lego walls. The walls were designed to have hierarchical structures with shared and dissociated colors and spatial components. Participants built 1 wall at a time, under low and high load cognitive states. Selection times for correctly completed trials were measured using 3-dimensional motion tracking. The paradigm enabled precise measurement of the timing of actions, while using real objects to create an end product. The experiment demonstrated that action selection was slowed at decision boundary points, relative to boundaries where no between-wall decision was required. Decision points also affected selection time prior to the actual selection window. Dual-task conditions increased selection errors. Errors mostly occurred at boundaries between chunks and especially when these required decisions. The data support hierarchical control of sequenced behavior. (PsycINFO Database Record


A Generalized Line and Junction Labeling Scheme with Application to scene Analysis.
A line and junction labeling scheme is introduced that is valid for both planar and curved-surface bodies. Seven generalized junction types are defined and shown to cover all valid projections for a wide class of planar and curved-surface bodies. It is further shown that there are limitations on the permissible junction types as one moves from one end of a line segment to the other. The valid junction transitions provide 1) a new set of edge semantics for line labeling and 2) an ability to verify whether a given sequence of junctions forms a realizable configuration.


Body mass index and pancreatic adenocarcinoma: A nationwide registry-based cohort study.
An association between body mass index (BMI) and pancreatic cancer is suggested in observational studies. However, further studies are required to substantiate available evidence. The aim of this study was to explore the association between BMI and pancreatic ductal adenocarcinoma (PDAC) risk, treatment, and mortality. A registry-based cohort study was performed by combining data from four registries in Norway. Baseline data were collected between 1963 and 1975 with follow-up data collected until 2018. Kaplan-Meier curves and multivariable Cox regressions were estimated. Chi-square tests were used to analyze differences between groups. The study cohort consisted of 1,723,692 individuals. A total of 8973 PDAC cases were identified during 55,744,749 person-years of follow-up. A 5 kg/m2 increase in BMI was associated with an increased risk of PDAC if high BMI at young age (16-29 years) (hazard ratio (HR): 1.21, 95% confidence interval (CI): 1.13-1.31), both for men (HR: 1.30, 95% CI: 1.15-1.46) and women (HR: 1.16, 95% CI: 1.05-1.28). In men, there was a 52% increase in risk of early-onset PDAC (<age 50) (HR: 1.52, 95% CI: 1.13-2.03) with 5 kg/m2 increase in BMI. A total of 2645 individuals were diagnosed with stage 1-3 disease, of whom 1131 underwent curative surgery. In all, 49% of normal weight, 38% overweight, and 30% obese individuals with stage 1-3 PDAC underwent surgery with curative intent (p < 0.001). Cancer survival was lower in overweight and obese individuals for both sexes. Analysis adjusted for sex, age, and period of diagnosis confirmed increased risk of cancer death in obese individuals. This study suggests that increased BMI in young adults may increase the risk of PDAC, and higher BMI in men is associated with an increased risk of early onset PDAC (<age 50). Overweight and obese individuals were less likely to undergo curative surgery and obese individuals had a higher risk of cancer-related death.


Effective genetic vaccination with a widely shared endogenous retroviral tumor antigen requires CD40 stimulation during tumor rejection phase.
Endogenous retrovirus (ERV) products are recognized by T lymphocytes in mice and humans. As these Ags are preferentially expressed by neoplastic tissues, they might represent an ideal target for active immunization by genetic vaccination. However, i.m. inoculation of plasmid DNA encoding mouse gp70 or p15E, two products of the env gene of an endogenous murine leukemia virus, elicited a weak Ag-specific T lymphocyte response and resulted in partial protection from challenge with mouse tumors possessing these Ags. Depletion experiments showed that CD8(+), but not CD4(+), T lymphocytes were crucial for the antitumor activity of the vaccines. Systemic administration of agonistic anti-CD40 mAb increased the therapeutic potential of genetic vaccination, but only when given during the tumor rejection phase and not at the time of immunization. This effect correlated with a dramatic increase in the number of ERV-specific CD8(+) T lymphocytes. Adjuvant activity of CD40 agonists thus seems to be relevant to enhance the CD8(+) T cell-dependent response in tumor-bearing hosts, suggesting that sustaining tumor-specific T lymphocyte survival in subjects undergoing vaccination might be a key event in the successful vaccination with weak tumor Ags.


[Simultaneous Fluorescent Imaging of Mg2+ and Ca2+].
Simultaneous fluorescent imaging technique with several indicators is a powerful bio-imaging tool for a comprehensive survey about molecular functions in living cells. There are several interactions between Mg(2+) and Ca(2+) such as a counter transport or a competition at binding sites of divalent cation. To measure Mg-Ca images simultaneously, indicators with high selectivity to each divalent cation and multi-color fluorescent imaging system are essential. Here we introduce a setup for Mg-Ca fluorescent imaging we construct, and some reports about Mg-Ca imaging.


Bilayer tension-induced clustering of the UPR sensor IRE1.
The endoplasmic reticulum acts as a protein quality control center where a range of chaperones and foldases facilitates protein folding. IRE1 is a sensory transmembrane protein that transduces signals of proteotoxic stress by forming clusters and activating a cellular program called the unfolded protein response (UPR). Recently, membrane thickness variation due to membrane compositional changes have been shown to drive IRE1 cluster formation, activating the UPR even in the absence of proteotoxic stress. Here, we demonstrate a direct relationship between bilayer tension and UPR activation based on IRE1 dimer stability. The stability of the IRE1 dimer in a (50%DOPC-50%POPC) membrane at different applied bilayer tensions was analyzed via molecular dynamics simulations. The potential of mean force for IRE1 dimerization predicts a higher concentration of IRE1 dimers for both tensed and compressed ER membranes. This study shows that IRE1 may be a mechanosensitive membrane protein and establishes a direct biophysical relationship between bilayer tension and UPR activation.


Evaluation of total aflatoxin, nitrate and nitrite levels in layer feed samples of companies producing their own feed in Edincik and Bandırma province of Turkey.
Feed contamination by fungi can lead to nutrient losses and detrimental effects on animal health and production. The presence of nitrates and nitrites in food can be harmful to both people and animals. The aim of this study was to determine total aflatoxin, nitrate and nitrite levels in layer feed samples from companies producing their own feed in Edincik and Bandırma provinces in Turkey and to discuss the potential risk to animal health. The results of the analyses indicated that mean total aflatoxin (AFT) ranged from 0.4 to 36.8 µg kg(-1) and from 0.45 to 47.0 µg kg(-1) in the year 2007 and the year 2008 samples, respectively. It was determined that nitrate levels were 2.4-10 and 1.7-13 µg kg(-1) and that nitrite levels were 0-2.4 µg kg(-1) and 0-2.6 µg kg(-1) in these years, respectively. The levels of total aflatoxin, nitrate and nitrite in the layer samples could not be considered a risk to poultry health and productivity.


An Unexpectedly Broad Thermal and Salinity-Tolerant Estuarine Methanogen Community.
Moderately thermophilic (Tmax, ~55 °C) methanogens are identified after extended enrichments from temperate, tropical and low-temperature environments. However, thermophilic methanogens with higher growth temperatures (Topt ≥ 60 °C) are only reported from high-temperature environments. A microcosm-based approach was used to measure the rate of methane production and methanogen community structure over a range of temperatures and salinities in sediment from a temperate estuary. We report short-term incubations (<48 h) revealing methanogens with optimal activity reaching 70 °C in a temperate estuary sediment (in situ temperature 4-5 °C). While 30 °C enrichments amended with acetate, H2 or methanol selected for corresponding mesophilic trophic groups, at 60 °C, only hydrogenotrophs (genus Methanothermobacter) were observed. Since these methanogens are not known to be active under in situ temperatures, we conclude constant dispersal from high temperature habitats. The likely provenance of the thermophilic methanogens was studied by enrichments covering a range of temperatures and salinities. These enrichments indicated that the estuarine sediment hosted methanogens encompassing the global activity envelope of most cultured species. We suggest that estuaries are fascinating sink and source environments for microbial function study.


[Leukocytic and thrombocytic generation of nitric oxide in patients with bronchial asthma].
Leukocytic and thrombocytic nitric oxide generation was studied in 23 healthy individuals and 17 patients with bronchial asthma. Differential centrifugation was used to isolate leukocytes and platelets from blood. The suspensions of leukocytes (5.10(6)) and platelets (0.5.10(8)) were incubated in 0.5 ml of the medium RPMI 1640 at 37 degrees C for 15 hours. The concentration of the stable metabolite of NO nitrite was estimated by the Griss test. The relative leukocytic NO production was 0.75 +/- 0.06 and 1.32 +/- 0.06 mumole/l in healthy individuals and patients, respectively (p < 0.001). The relative thrombocytic NO production was 2.15 +/- 0.14 and 2.26 +/- 0.07 mumole/l in healthy individuals and patients, respectively. The absolute leukocytic NO production was 0.47 +/- 0.05 and 0.65 +/- 0.05 mumol/l in healthy individuals and patients, respectively (p < 0.01). The absolute thrombocytic NO production was 7.70 +/- 0.55 and 5.32 +/- 0.27 mumole/l in healthy individuals and patients, respectively (p < 0.001). Therefore, the absolute production of NO by platelets is 16 times higher than that by leukocytes. In the patients, the relative and absolute leukocytic NO productions increased and the absolute thrombocytic NO production significantly decreased.


Prophylactic antibiotics in vaginal and abdominal hysterectomy.
A double-blind, prospective study over a 12-month period evaluated the effectiveness of cefazolin and cephalexin in reducing infection and morbidity in private patients undergoing vaginal and abdominal hysterectomy. Prophylactic antibiotics reduced febrile morbidity from 74.4% to 20.8% in the vaginal group and from 46.2% to 24.0% in the abdominal group. Serious postoperative infections such as pelvic abscess, pelvic cellulitis and abdominal wound infection were reduced from 11.5% to 0% in the abdominal group and from 32.6% to 2.1% in the vaginal group. The use of prophylactic antibiotics was of benefit in the perimenopausal and postmenopausal patient, as well as in the premenopausal patient, although, in some categories, the numbers were too small to be statistically significant.


Improvements in oocyte competence in superovulated mice following treatment with cilostazol: Ovulation of immature oocytes with high developmental rates.
Exogenous administration of superovulatory hormones negatively affects oocyte competence in mammals. Phosphodiesterase 3A inhibitors were found to improve competence of oocytes matured in vitro in several species, including humans. This study was therefore designed to define oocyte maturation synchronization and competence, in vivo, using superovulated mice treated with cilostazol, a selective phosphodiesterase 3A inhibitor. Swiss Webster mice were superovulated and treated orally with 7.5mg cilostazol once or twice to result in ovulation of immature oocytes at the metaphase I (MI) or germinal vesicle (GV) stage, respectively. Control immature oocytes were recovered from preovulatory follicles of superovulated mice not treated with cilostazol. Treated GV oocytes had significantly higher rates of synchronized and advanced chromatin configuration and cortical granule distribution than did control GV oocytes. Treated GV oocytes had a moderate increase in cAMP levels and consequently higher rates of meiotic maturation, IVF, and blastocyst formation than did control GV oocytes (P<0.0001). Treated MI oocytes had higher rates of normal spindles and chromosomes aligned at the metaphase plate than did control MI oocytes (P<0.003). Treated mice ovulating MI oocytes produced litter sizes larger than those observed in control mice ovulating mature oocytes (P<0.002). This study reveals that synchronization of oocyte maturation in superovulated mice improves oocyte development and competence. The capability of cilostazol, a clinically approved medication, to improve mouse oocyte competence suggests the potential benefit of including this compound in ovarian hyperstimulation programs to improve in vitro fertilization outcomes in infertile women.


Validation and uses of a Y-chromosome STR 10-plex for forensic and paternity laboratories.
Y-chromosome short tandem repeats (Y-STRs) provide valuable information in cases of rape and questioned paternity, and they allow for the genetic identification of male lineages. The present study validated a Y-STR 10-plex on the ABI PRISM 3100 Genetic Analyzer for use in forensic and paternity laboratories at Orchid Cellmark. Following optimization of the polymerase chain reaction, father-son pairs were analyzed to ensure that each pair generated identical haplotypes. This study demonstrated that the 10-plex is sensitive to 0.125 ng of input DNA and that female samples mixed with male samples did not interfere with Y-STR haplotyping. In a sample of 525 males, there were three instances of locus multiplication, two at DYS19 and one at DYS435. Overall, haplotype diversity was 0.996, suggesting that the 10-plex can effectively distinguish among male lineages.


Intra-urban variability of long-term exposure to PM2.5 and NO2 in five cities in Colombia.
Rapidly urbanizing cities in Latin America experience high levels of air pollution which are known risk factors for population health. However, the estimates of long-term exposure to air pollution are scarce in the region. We developed intraurban land use regression (LUR) models to map long-term exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) in the five largest cities in Colombia. We conducted air pollution measurement campaigns using gravimetric PM2.5 and passive NO2 sensors for 2 weeks during both the dry and rainy seasons in 2021 in the cities of Barranquilla, Bucaramanga, Bogotá, Cali, and Medellín, and combined these data with geospatial and meteorological variables. Annual models were developed using multivariable spatial regression models. The city annual PM2.5 mean concentrations measured ranged between 12.32 and 15.99 µg/m3 while NO2 concentrations ranged between 24.92 and 49.15 µg/m3. The PM2.5 annual models explained 82% of the variance (R2) in Medellín, 77% in Bucaramanga, 73% in Barranquilla, 70% in Cali, and 44% in Bogotá. The NO2 models explained 65% of the variance in Bucaramanga, 57% in Medellín, 44% in Cali, 40% in Bogotá, and 30% in Barranquilla. Most of the predictor variables included in the models were a combination of specific land use characteristics and roadway variables. Cross-validation suggests that PM2.5 outperformed NO2 models. The developed models can be used as exposure estimate in epidemiological studies, as input in hybrid models to improve personal exposure assessment, and for policy evaluation.


The uniqueness of hair transplantation in black patients.
The author presents his own observations on hair transplant procedures in black patients. With slight modifications in the manner of obtaining donor autografts, the integrity of the hair shafts and papillae are maintained. Genrally, the aesthetic results are comparable to those obtained in white patients and often are achieved with considerably fewer autografts.


Health promotion at local level: a case study of content, organization and development in four Swedish municipalities.
Several health determinants are related to local conditions and prerequisites at community level. For this reason, strengthening community action has been one of five strategies implemented in health promotion since the end of the 1980s. Such action includes setting priorities, making decisions, planning strategies, and implementing them to achieve better health. The aim of this paper is to obtain a deeper understanding of content, organization and processes in the development of local health promotion. A qualitative multiple case study of four Swedish municipalities. The cases were analyzed in accordance with the principles of cross-case study analysis, and a content analysis of documents and interviews was conducted in two steps. First, a manifest content analysis was performed to identify present and former actors and measures. Thereafter, a latent content analysis was performed to investigate structures and processes in local contexts. The results of the inductive content analysis showed development of local health promotion in three phases: initiation, action, and achievement. Strengthening factors were local actors, health statistics and events. Hindering factors were lack of resources and vague objectives. External factors, e.g. national policies, were not perceived as prominent influencing factors. Media reports were regarded as having had an influence, but only to some extent. The content of local health promotion has developed from ad-hoc lifestyle and behaviour-related actions into structural, intersectoral actions related to determinants of health. The municipalities have organized and developed their health promotion targets, actions and priorities on the basis of local needs and prerequisites. The three phases in the identified health promotion processes were experienced and documented as being subject to greater influence from internal rather than external strengthening and hindering factors in their local contexts.


Natural selection vs. random drift: evidence from temporal variation in allele frequencies in nature.
We have obtained monthly samples of two species, Drosophila pseudoobscura and Drosophila persimilis, in a natural population from Napa County, California. In each species, about 300 genes have been assayed by electrophoresis for each of seven enzyme loci in each monthly sample from March 1972 to June 1975. Using statistical methods developed for the purpose, we have examined whether the allele frequencies at different loci vary in a correlated fashion. The methods used do not detect natural selection when it is deterministic (e.g., overdominance or directional selection), but only when alleles at different loci vary simultaneously in response to the same environmental variations. Moreover, only relatively large fitness differences (of the order of 15%) are detectable. We have found strong evidence of correlated allele frequency variation in 13-20% of the cases examined. We interpret this as evidence that natural selection plays a major role in the evolution of protein polymorphisms in nature.


Celiac disease and the endocrinologist: a diagnostic opportunity.
To review the association of celiac disease and various endocrine disorders and present the related clinical experience of a 3-physician adult endocrinology practice. We provide an overview of the pertinent literature, discuss the clinical manifestations, genetics, and pathogenesis of celiac disease, and describe our clinical experience during a 5-year period. Celiac disease has been associated with numerous disorders, including several conditions treated by endocrinologists-type 1 diabetes mellitus, autoimmune thyroid disease, Addison disease, osteomalacia, secondary hyperparathyroidism, vitamin D or iron deficiency, fertility problems, hypogonadism in men, and autoimmune hypopituitarism. After our clinical awareness was raised about these potential comorbidities, 18 patients were newly diagnosed with celiac disease in our clinical practice during a 5-year interval. All patients had been referred for endocrine evaluation or were undergoing follow-up for ongoing management of endocrine disorders. When a "celiac-associated" endocrine disorder coexists with other factors associated with celiac disease, we recommend performance of IgA class antibody testing, and either antiendomysial or anti-tissue transglutaminase antibodies provide high specificity and sensitivity for the diagnosis of celiac disease. Endocrinologists have an opportunity to diagnose celiac disease, a relatively common disorder with profound clinical implications that can often be associated with various endocrinopathies.


Reinforcement Learning Control of Robotic Knee With Human-in-the-Loop by Flexible Policy Iteration.
We are motivated by the real challenges presented in a human-robot system to develop new designs that are efficient at data level and with performance guarantees, such as stability and optimality at system level. Existing approximate/adaptive dynamic programming (ADP) results that consider system performance theoretically are not readily providing practically useful learning control algorithms for this problem, and reinforcement learning (RL) algorithms that address the issue of data efficiency usually do not have performance guarantees for the controlled system. This study fills these important voids by introducing innovative features to the policy iteration algorithm. We introduce flexible policy iteration (FPI), which can flexibly and organically integrate experience replay and supplemental values from prior experience into the RL controller. We show system-level performances, including convergence of the approximate value function, (sub)optimality of the solution, and stability of the system. We demonstrate the effectiveness of the FPI via realistic simulations of the human-robot system. It is noted that the problem we face in this study may be difficult to address by design methods based on classical control theory as it is nearly impossible to obtain a customized mathematical model of a human-robot system either online or offline. The results we have obtained also indicate the great potential of RL control to solving realistic and challenging problems with high-dimensional control inputs.


Effect of processing methods on xylitol-starch base co-processed adjuvant for orally disintegrating tablet application.
Orally disintegrating tablet (ODT) is a friendly dosage form that requires no access to water and serves as a solution to non-compliance. There are many co-processed adjuvants available in the market. However, there is no single product possesses all the ideal characteristics such as good compressibility, fast disintegration and good palatability for ODT application. The aim of this research was to produce a xylitol-starch base co-processed adjuvant which is suitable for ODT application. Two processing methods namely wet granulation and freeze drying were used to compare the characteristics of co-processed adjuvant comprising of xylitol, starch and crospovidone XL-10 mixed at various ratios. The co-processed excipients were compressed into ODT and physically characterized for powder flow, particle size, hardness, thickness, weight, friability, in-vitro disintegration time and in-situ disintegration time, lubricant sensitivity, dilution potential, Fourier transform infrared spectroscopy, scanning electronic microscopy and x-ray diffraction analysis. Formulation F6 was selected as the optimum formulation due to the fastest in-vitro (135.33±11.52 s) and in-situ disintegration time (88.67±13.56s) among all the formulations (p<0.05). Increase in starch component decreases disintegration time of ODT. The powder flow fell under the category of fair flow. Generally, it was observed that freeze drying method produced smaller particle size granules compared to wet granulation method. ODT produced from freeze drying method had shorter disintegration time compared to ODT from wet granulation batch. In conclusion, a novel co-processed excipient comprised of xylitol, starch and crospovidone XL-10, produced using freeze drying method with fast disintegration time, good compressibility and palatability was developed and characterized. The co-processed excipient is suitable for ODT application.


Prey nutrient content creates omnivores out of predators.
The proximate forces that create omnivores out of herbivores and predators have long fascinated ecologists, but the causal reasons for a shift to omnivory are poorly understood. Determining what factors influence changes in trophic position are essential as omnivory plays a central role in theoretical and applied ecology. We used sevenspotted lady beetles (Coccinella septempunctata) to test how prey nutrient content affects beetles' propensity to engage in herbivory. We show that beetles consuming an all-prey diet demonstrate normal growth and development, but suffer a complete loss of fitness (spermatogenic failure) that is restored via herbivory and supplementation with phytosterols and cholesterol. Furthermore, we show that lady beetles possess a state-dependent sterol-specific appetite and redressed their sterol deficit by feeding on foliage. These results demonstrate that predators balance their nutrient intake via herbivory when prey quality is low, and reveal a selective force (sterol nutrition) that drives predatory taxa to omnivory.


Brief resolved unexplained event: New diagnosis in infants.
For many years, the term apparent life-threatening event (ALTE) was associated with sudden infant death syndrome, and parents who described an acute event in their infants were sent to the hospital for admission. I understand that for infants new terminology is recommended. What is the current approach to a near-death experience of an infant? A recent clinical practice guideline revised the name and definition of an ALTE to a brief resolved unexplained event (BRUE). The diagnosis of BRUE in infants younger than 1 year of age is made when infants experience 1 of the following BRUE symptoms: a brief episode (ie, less than 1 minute and usually less than 20 to 30 seconds) that is entirely resolved (infant is at baseline), which remains unexplained after the history and physical examination are completed, and includes an event characterized by cyanosis or pallor; absent, decreased, or irregular breathing; hypertonia or hypotonia; or altered responsiveness. Low-risk infants should not be admitted to the hospital and overtesting is discouraged.


[Adverse drug reactions in the Spanish medical bibliographic literature: a comparison of 3 periods].
A quantitative and qualitative assessment of reports on suspected adverse drug reactions (ARD) in Spanish medical literature was carried out. The periods analysed were 1972-1974, 1986-1988 and 1992-1994, and the medical journals were Anales de Medicina Interna, Medicina Clínica and Revista Clínica Española. We selected all articles including specific information on suspect ADR. The percentage of articles has increased considerably (1972-1974: 2.1%, 1986-1988: 5.7%, and 1992-1994: 8.2%). In spite of this growth, the qualitative data studied have not significantly improved. It is necessary to device some mechanism in order to improve ADR reporting.


Drug Insight: gastrointestinal stromal tumors (GIST)--the solid tumor model for cancer-specific treatment.
We are living in an exciting era in the treatment of cancer, using drugs that target specific proteins rather than agents that cause more general cytotoxic effects. The identification of proteins and signal transduction pathways that play crucial roles in the pathogenesis of cancer has allowed treatments to be designed that target these tumor-driven events. Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors and were among the first solid tumor types for which such a novel treatment (in this case imatinib) became available. The tyrosine kinase inhibitor imatinib targets the human KIT receptor and the platelet-derived growth factor receptor-alpha. This drug exhibits impressive antitumor effects against GIST and has become the first-line therapy for advanced disease. Major insights into the mechanism of action of this drug, drug resistance, and patient management issues have been gleaned. Additionally, new drugs developed for the treatment of GIST have been identified. As a consequence, lessons learned from GIST are widely applicable to other tumor entities, thereby rendering GIST the paradigm of solid tumors treated with tyrosine kinase inhibitors. This Review discusses the pathogenesis of GIST, treatment strategies, mechanisms accounting for drug resistance, and potential future perspectives.


Enhanced anti-tumor efficacy of checkpoint inhibitors in combination with the histone deacetylase inhibitor Belinostat in a murine hepatocellular carcinoma model.
Immune checkpoint inhibitors are currently tested in different combinations in patients with advanced hepatocellular carcinoma (HCC). Nivolumab, an anti-PD-1 agent, has gained approval in the second-line setting in the USA. Epigenetic drugs have immune-mediated antitumor effects that may improve the activity of immunotherapy agents. Our aim was to study the therapeutic efficacy of checkpoint inhibitors (anti-CTLA-4 and anti-PD-1 antibodies) in combination with the histone deacetylase inhibitor (HDACi) Belinostat. In a subcutaneous Hepa129 murine HCC model, we demonstrated that Belinostat improves the antitumor activity of anti-CTLA-4 but not of anti-PD-1 therapy. This effect correlated with enhanced IFN-γ production by antitumor T-cells and a decrease in regulatory T-cells. Moreover, the combination induced early upregulation of PD-L1 on tumor antigen-presenting cells and late expression of PD-1 on tumor-infiltrating effector T-cells, suggesting the suitability of PD-1 blockade. Indeed, Belinostat combined with the simultaneous blockade of CTLA-4 and PD-1 led to complete tumor rejection. These results provide a rationale for testing Belinostat in combination with checkpoint inhibitors to enhance their therapeutic activity in patients with HCC.


Establishment of metanephros transplantation in mice highlights contributions by both nephrectomy and pregnancy to developmental progression.
It has been demonstrated that embryonic kidneys (metanephroi) xenotransplanted into the omentum of adult recipients continue to develop and display immune protection due to their more naïve immune presentation. To date, this has been achieved using rat, pig and human metanephroi, with unilateral nephrectomy (UNX) of recipient rats a requisite of renal development. The aim of this study was to adapt this approach for use in mice and examine the parameters affecting successful onward development in this species. Metanephroi at embryonic age (E) 13.5 were transplanted either onto the body wall, abdominal fat pads or omentum of recipient isogenic C57/Bl6 mice using either sutures or polyglycolic acid mesh. Having established greatest success with polyglycolic acid mesh on the body wall, E12.5 and 15.5 days metanephroi from C57/Bl6 mice were then transplanted onto the body wall of control (non-pregnant non-UNX), UNX or 12.5 days post-coitum pregnant isogenic recipients. After 7 days, implanted tissue was harvested and examined using histology and immunohistochemistry for markers of renal maturation. The mean number of S-shaped bodies and glomeruli per section were recorded and statistically analysed for significant differences between all recipient groups and untransplanted metanephroi. The degree of development was scored qualitatively. Transplanted E12.5 metanephroi developed S-shaped bodies and glomeruli in all recipient groups, although there were statistically higher numbers of S-shaped bodies in UNX (n = 2) and pregnant recipients (n = 9) than in control recipients (n = 4). Continued development, as indicated by mature vascularized glomeruli, was only observed in those E15.5 metanephroi transplanted into pregnant recipients (n = 11) with a 15.5-fold increase in S-shaped bodies and 4-fold increase in glomeruli compared with control transplants (n = 12). We have successfully established metanephros transplantation in mice and demonstrated enhancement of onward development of E12.5 metanephroi in response to both pregnancy and UNX. Using E15.5 metanephroi, continued development only occurred in pregnant recipients, implying pregnancy provides an environment conducive to continued organogenesis. This murine assay, when coupled with transgenically-tagged strains of mice, will allow the investigation of the relative contribution of donor and recipient cells to this process.


Hybrid sunlight/LED illumination and renewable solar energy saving concepts for indoor lighting.
A hybrid method for using sunlight and light-emitting diode (LED) illumination powered by renewable solar energy for indoor lighting is simulated and presented in this study. We can illuminate an indoor space and collect the solar energy using an optical switching system. When the system is turned off, the full spectrum of the sunlight is concentrated by a concentrator, to be absorbed by solar photovoltaic devices that provide the electricity to power the LEDs. When the system is turned on, the sunlight collected by the concentrator is split into visible and non-visible rays by a beam splitter. The visible rays pass through the light guide into a light box where it is mixed with LED light to ultimately provide uniform illumination by a diffuser. The non-visible rays are absorbed by the solar photovoltaic devices to provide electrical power for the LEDs. Simulation results show that the efficiency of the hybrid sunlight/LED illumination with the renewable solar energy saving design is better than that of LED and traditional lighting systems.


Employment-based health benefits: analysis of the April 1993 Current Population Survey.
The April 1993 CPS differs from the March 1993 CPS in a number of respects. The April 1993 CPS supplement surveys only workers, whereas the March CPS examines the noncash benefits received by all Americans. The April CPS asks workers about health coverage in the week in which the questions were fielded, whereas the March CPS asks about coverage in the preceding year. In April 1993, there were 112.5 million civilian American workers between the ages of 18 and 64 with jobs. Eighty-two million (73 percent) of them worked for an employer that sponsored a health insurance plan, and 65 million (58 percent of all workers) participated in their employer's health plan. About one-third of workers at firms with fewer than 10 employees had employers who offer health benefits; about one-quarter of all of the workers in these firms participated in their employer's plan. Conversely, 94 percent of workers at firms with more than 1,000 employees had an employer who sponsored health benefits, and over 77 percent of these workers participated in their employer's plan. There are 16.5 million American workers whose employers sponsored health benefits but who did not participate in these benefits. Over one-half of these workers (8.5 million) chose not to be covered. Another 36 percent of these workers (5.9 million) did not participate because they were ineligible or denied coverage. Over 66 percent of the ineligible workers did not participate because they were part-time, contract, or temporary workers. Another 26 percent had not yet completed a probationary period. Among the reasons that those who chose not to participate in their employer's coverage, the vast majority (75 percent) stated they were covered by another health care plan. Twenty-nine percent stated that they chose not to purchase coverage because it was too costly or that they did not need or want the coverage. In 1993, there were 16.7 million workers with no health insurance coverage. The vast majority of these workers (95 percent) were employed by private employers. Sixty-six percent of the workers with no health insurance coverage were self-employed or worked for firms with fewer than 100 employees.


Multi-stage generation of extreme ultraviolet dispersive waves by tapering gas-filled hollow-core anti-resonant fibers.
In this work, we numerically investigate an experimentally feasible design of a tapered Ne-filled hollow-core anti-resonant fiber and we report multi-stage generation of dispersive waves (DWs) in the range 90-120 nm, well into the extreme ultraviolet (UV) region. The simulations assume a 800 nm pump pulse with 30 fs 10 µJ pulse energy, launched into a 9 bar Ne-filled fiber with a 34 µm initial core diameter that is then tapered to a 10 µm core diameter. The simulations were performed using a new model that provides a realistic description of both loss and dispersion of the resonant and anti-resonant spectral bands of the fiber, and also importantly includes the material loss of silica in the UV. We show that by first generating solitons that emit DWs in the far-UV region in the pre-taper section, optimization of the following taper structure can allow re-collision with the solitons and further up-conversion of the far-UV DWs to the extreme-UV with energies up to 190 nJ in the 90-120 nm range. This process provides a new way to generate light in the extreme-UV spectral range using relatively low gas pressure.


Patient-directed titration for achieving glycaemic goals using a once-daily basal insulin analogue: an assessment of two different fasting plasma glucose targets - the TITRATE study.
To compare efficacy and safety of two fasting plasma glucose (FPG) titration targets [4.4-6.1 mmol/l (80-110 mg/dl) and 3.9-5.0 mmol/l (70-90 mg/dl)] using a patient-directed, treat-to-target algorithm for once-daily basal insulin in insulin-naïve subjects with type 2 diabetes suboptimally treated with oral antidiabetes drugs (OADs). In this 20-week, randomized, controlled, open-label, multicentre, treat-to-target study, 244 insulin-naïve subjects with type 2 diabetes, HbA(1c)>or=7.0 and <or=9.0% on OAD treatment, were randomized (1 : 1) to one of two treatment arms using 3.9-5.0 or 4.4-6.1 mmol/l FPG as titration targets. Once-daily insulin detemir doses were adjusted using algorithm-guided patient-directed titration to achieve target FPG values. Overall, the combined treatment groups achieved a mean HbA(1c) level of 6.9% at the end of the study. Substantial reductions in HbA(1c) were seen in both treatment groups, with the majority of subjects in both titration groups at the end of the study achieving the American Diabetes Association (ADA)-recommended HbA(1c) level of <7%. In the 3.9-5.0 mmol/l FPG target treatment group, HbA(1c) values decreased from a baseline mean of 8.0% to 6.8% at 20 weeks. In the 4.4-6.1 mmol/l FPG target group, HbA(1c) values decreased from 7.9% at baseline to 7.0% at 20 weeks (Intention to treat - last observation carried forward data set). These decreases were significantly different between the two treatment groups (Least squares mean difference = -0.271, 95% CI -0.441 to -0.101, p = 0.0019), favouring the FPG target of 3.9-5.0 mmol/l vs. the 4.4-6.1 mmol/l target. At the end of the study period, 64.3% of subjects in the 3.9-5.0 mmol/l treatment group achieved HbA(1c) levels <7% compared with 54.5% of subjects in the 4.4-6.1 mmol/l group (95% CI 1.03-3.37, odds ratio 1.86, p = 0.04). Insulin detemir dosing patterns were similar between treatment groups, with the 3.9-5.0 mmol/l group using slightly greater doses throughout the study period (0.57 U/kg vs. 0.51 U/kg at the end of the study). Overall rates of hypoglycaemia episodes were low and were comparable between treatment groups (7.73 and 5.27 events/subject/year for the 3.9-5.0 and 4.4-6.1 mmol/l groups, respectively). A single event of major hypoglycaemia was reported in the 3.9-5.0 mmol/l group. Mean weight changes from baseline to the end of the study were small and did not differ significantly between treatment groups. The 3.9-5.0 mmol/l FPG target showed superior efficacy compared with the 4.4-6.1 mmol/l target, although both FPG titration targets resulted in substantial reductions of HbA(1c) in patients with type 2 diabetes using a patient-directed insulin titration algorithm. A majority of subjects in both titration groups achieved the ADA-recommended guideline of <7% HbA(1c) at the end of the study with low rates of hypoglycaemia. These data indicate that lowering the fasting glucose target using a self-directed titration algorithm with once-daily detemir is safe and increases the likelihood of achieving the target level of HbA(1c). Indeed, using this approach, a majority of patients can achieve an HbA(1c) of <7%.


Improving Si solar cell performance using Mn:ZnSe quantum dot-doped PLMA thin film.
Poly(lauryl methacrylate) (PLMA) thin film doped with Mn:ZnSe quantum dots (QDs) was spin-deposited on the front surface of Si solar cell for enhancing the solar cell efficiency via photoluminescence (PL) conversion. Significant solar cell efficiency enhancements (approximately 5% to 10%) under all-solar-spectrum (AM0) condition were observed after QD-doped PLMA coatings. Furthermore, the real contribution of the PL conversion was precisely assessed by investigating the photovoltaic responses of the QD-doped PLMA to monochromatic and AM0 light sources as functions of QD concentration, combined with reflectance and external quantum efficiency measurements. At a QD concentration of 1.6 mg/ml for example, among the efficiency enhancement of 5.96%, about 1.04% was due to the PL conversion, and the rest came from antireflection. Our work indicates that for the practical use of PL conversion in solar cell performance improvement, cautions are to be taken, as the achieved efficiency enhancement might not be wholly due to the PL conversion.


Train duration effects on perception: sensory deficit, neglect, and cerebral lateralization.
The mechanisms of conscious perception are uncertain. In a preliminary study, dramatic effects of train duration on perception in a patient with right brain stroke were noted. In this study, the mechanisms of train duration on perception of peripheral somatosensory stimuli are examined. Subjects included healthy adults and patients with right brain infarctions. Train duration effects on perception were examined in relation to cerebral infarction, handedness, age, elevated peripheral threshold via bupivacaine, and impaired attention via diazepam or scopolamine. Perceptual thresholds to electrical pulses on the hand decreased as train duration increased, but only over the first several hundred milliseconds. Compared to controls, right brain stroke patients showed much greater lowering of threshold in the affected hand as train duration was extended. Age and bupivacaine elevated thresholds, but had little or no influence on train duration effects. Diazepam and scopolamine had no effect on thresholds. Thresholds were lower in the left than right hand of healthy dextral subjects, irrespective of age. Sinistral subjects had less left/right asymmetry. Increased train duration effect in patients is not explained by a primary elevation in threshold or by impaired vigilance. Lower perceptual thresholds in the left hand of healthy dextral subjects is consistent with right cerebral dominance for externally directed attention.


Hyaluronidase inhibitors from Takuran, Lycopus lucidus.
Takuran is a traditional herbal medicine that is produced from the herbal plant Lycopus lucidas TURCZ. (Lamiaceae). Takuran is used as a treatment for diseases in women. From Takuran, four new phenylpropanoids along with 18 known compounds were isolated, and their structures were elucidated by spectroscopic analyses. Five phenylpropanoids isolated from the plant showed hyaluronidase inhibitory activity comparable to that of rosmarinic acid.


Use of influenza C virus for detection of 9-O-acetylated sialic acids on immobilized glycoconjugates by esterase activity.
An overlay and a solid-phase assay are presented which allow the specific detection of 9-O-acetylated sialic acids on sialoglycoconjugates immobilized on microtiter plates, nitrocellulose or separated on thin-layer chromatograms. The assay takes advantage of two different biological properties of influenza C virus, its high-affinity binding to 9-O-acetylated sialic acids and its sialate 9-O-acetylesterase that is used for detection of bound virus with fluorogenic or chromogenic substrates. Though simple and rapid, the assay is highly sensitive with a detection limit of 65 fmol 9-O-acetylated sialic acid in 9-O-acetylated ganglioside GD1a. Influenza C virus is able to bind to a wide spectrum of sialoglycoconjugates like mucins, serum glycoproteins or gangliosides containing naturally or synthetically O-acetylated sialic acids. 9-O-Acetyl-N-glycoloylneuraminic acid can also function as a high-affinity receptor determinant for influenza C virus. While the acetyl ester at the 9 position is essential for virus binding in all cases, a 4-O-acetyl group is not recognized. In addition to alpha(2.3) or alpha(2.6) bonds, 9-O-acetyl-N-acetylneuraminic acid in alpha(2.8) linkage to N-acetylneuraminic acid is also functionally active.


Effects of Natural Habitat and Season on Cursorial Spider Assemblages in Mediterranean Vineyards.
Natural habitats adjacent to vineyards are presumed to have a positive effect on the diversity of natural enemies within the vineyards. However, these habitats differ in vegetation structure and seasonal phenology and in turn could affect the species composition of natural enemies. Here, we compared the species richness and diversity and the composition of spider assemblages in several locations within three commercial vineyards and the nearby natural habitats in a Mediterranean landscape in northern Israel. We sampled spiders by means of pitfall traps in early and in late summer. Both the time in the season and the habitat (natural versus vineyard) affected spider species richness and diversity. More species were found in early summer (47) than in late summer (33), and more occurred in the natural habitat (34 species) than in the vineyards (27-31 species). Fifteen species were found exclusively in the natural habitat, and only 11 species were shared by the vineyards and natural habitat, four of which were the most abundant and geographically widely distributed species in the samples. In late summer, spider diversity in the natural habitat was higher than within the vineyards: the spider assemblages in the vineyards became dominated by a few species late in the crop season, while those of the natural habitat remained stable. Overall, the natural habitat differed in assemblage composition from all within-vineyard locations, while the three locations within the vineyard did not differ significantly in assemblage composition. Season (early vs. late summer), however, significantly affected the spider assemblage composition. This study documents the large diversity of spiders in a local Mediterranean vineyard agroecosystem. Over 60% of the known spider families in the region occurred in our samples, highlighting the importance of this agroecosystem for spider diversity and the potential for conservation biocontrol, where natural habitats may be a source of natural enemies for nearby vineyards.


Evaluation of the early response in fMRI in individual subjects using short stimulus duration.
Optical imaging studies have provided evidence of an initial increase in deoxyhemoglobin following the onset of neuronal stimulation/activation and demonstrated that this initial increase could be spatially more specific to the site of neuronal activity. These studies also raised the possibility of improving the specificity of fMRI by selective mapping of this early response. Previous MR studies reported the observation of this early response but were limited in scope and not in full agreement. This paper presents a more extensive study that (a) demonstrates the initial signal decrease in individual subjects and (b) examines its dependence on stimulus duration and subject. Binocular visual stimulation experiments were performed on 14 subjects using echo-planar imaging (EPI) with high temporal resolution. An initial signal decrease was consistently observed in regions that were more localized than those displaying the delayed positive response. In agreement with previous fMRI and optical imaging findings, the maximum signal decrease was 1-2% and occurred at approximately 2 s after the onset of the stimulus, depending on the subject. For stimulus longer then 3.0 s, the temporal dynamics and the amount of signal change of the early response was essentially independent of the stimulus duration, while the delayed response and the post-stimulus undershoot increased both in terms of magnitude and rise time as the duration of the stimulus increased; this observation is concordant with the recent optical imaging study.


COVID-19-related worries, social disruptions, and depressive symptoms among community-dwelling older adults with disabilities: What makes the difference?
This study explores how home- and community-based services use, COVID-19-related worries and social disruptions are related to the depressive symptoms of community-dwelling older adults with disabilities, and whether the associations differ by month of interview. Data on a sample of 593 older individuals in Taiwan were collected between April and July 2020. Multiple regression analyses were performed to test the hypothesized relationships. As the number of confirmed cases of COVID-19 in Taiwan continuously declined from April 2020, participants who were interviewed in May, June and July experienced significantly fewer COVID-19-related worries and social disruptions than those interviewed in April. The month interviewed, representing the pandemic development phase of COVID-19, moderated the relationships between home-based service (HBS) use and COVID-19 worries. Month interviewed also moderated the association between COVID-19-related social disruptions and depressive symptoms. Differences in the level of COVID-19-related worries between HBS users and non-users were greatest in April, followed by May, and least in June and July, suggesting that the disparities between HBS users and non-users attenuated over time. Perceived high COVID-19-related social disruptions was weakly and negatively correlated with depressive symptoms in April, but the relationship became moderately positive in May, and strongly positive in June and July. These results supported the claim that the associations between COVID-19-related social disruptions and depressive symptoms can vary over time. Professionals who serve disabled older individuals in communities should be aware of their unstated needs and adopt strategies that are appropriate for the current stage of the COVID-19 pandemic to respond better to their needs and emotional state.


Racial/ethnic patterns of uptake of colorectal screening, National Health Interview Survey 2000-2008.
Lower access and/or utilization of colorectal screening are thought to be major contributors to the higher proportion of cancers among African Americans and Hispanics that are diagnosed at advanced stages of disease and the poorer outcomes observed among Hispanics and African Americans compared with non-Hispanic whites. We examine rates of initiation, utilization of specific screening modalities, adherence tocolorectal screening guidelines, and rate of uptake of colonoscopy among age-eligible African Americans, Hispanics and non-Hispanic whites. Data on 46145 African American, Hispanic, and non-Hispanic white survey respondents to the 2000 and 2005 Cancer Control Modules and the 2003 and 2008 Sample Adult Cores of the National Health Interview Surveys are examined in these analyses. There was a modest increase in the initiation of colorectal screening among non-Hispanic whites, only and racial/ethnic disparities colorectal screening utilization persisted. The proportion of respondents for whom colonoscopy was the most complete guideline consistent exam received increased over time, while use of other modalities decreased among all racial/ethnic groups. More effort must be made to increase colorectal screening among the U.S. population in general but particularly among racial/ethnic minority populations. With the increased attention on prevention, there is also a need to increase knowledge of the strengths and limitations of specific screening modalities and the need to receive screening exams within recommended time intervals among both patients and providers making screening recommendations.


Pharmacotherapy for older veterans diagnosed with posttraumatic stress disorder in Veterans Administration.
Despite increasing numbers of older veterans diagnosed with posttraumatic stress disorder (PTSD) in veterans administration (VA), limited research has focused on pharmacotherapy of PTSD among the elderly. The authors examined pharmacotherapy provided to patients carrying a clinical diagnosis of PTSD in VA. Data on outpatients treated at VA nationally were utilized. Patients were veterans over 45 years of age diagnosed with PTSD in FY 2004 (N = 244,947) grouped into five age cohorts with patients 45-55 as the reference group. Psychotropic prescriptions were examined. Descriptive statistics and multivariable logistic regression adjusting for confounding characteristics, including receipt of VA service connected disability benefits which may create incentives to artificially maintain historical diagnoses, were used to identify the relationship of age to receipt of psychotropic medications net of these factors. All analyses were repeated using data only from nonservice connected veterans. Most older veterans received psychotropic medication and among these, 88.3% were prescribed antidepressants, 61.2% anxiolytics/sedative hypnotics, and 32.9% antipsychotics. A pronounced monotonic trend showed decrease use of any psychotropic medication and of each subclass with age. Medication use was higher among those treated in specialty mental health clinics than among those treated exclusively in primary care or medical clinics and interaction analysis of age by clinic type showed significantly more steeply declining use of medications with age among patients treated in specialty mental health clinics. Data from nonservice connected veterans revealed the same patterns. Diverse psychotropic medication classes are used to treat veterans diagnosed with PTSD in VA with declining use among older veterans. Medication utilization is greater in mental health clinics but declined more steeply with age, perhaps reflecting the greater sensitivity of specialists to the risks of elderly veterans. Older veterans diagnosed with PTSD appear to receive conservative, cautious treatment although observed patterns of care may reflect some degree of undertreatment.


Effect of different irrigation solutions and calcium hydroxide on bacterial LPS.
To evaluate the effect of biomechanical preparation with different irrigating solutions and calcium hydroxide dressing in dog root canals containing bacterial endotoxin (lipopolysaccharides; LPS). One hundred and forty premolar roots from seven dogs were filled with Escherichia coli LPS for 10 days (three roots were lost during histological processing). The following irrigating solutions were used for biomechanical preparation: 1% (group I, n = 20), 2.5% (group II, n = 19) and 5% sodium hypochlorite (group III, n = 19), 2% chlorhexidine digluconate (group IV, n = 20) and physiological saline solution (group V, n = 19). In group VI (n = 20), the LPS solution was maintained in the root canal during the entire experiment and in group VII (n = 20), after biomechanical preparation with saline solution, the root canals were filled with a calcium hydroxide dressing (Calen; control). After 60 days, the animals were sacrificed and the following parameters of periapical disease were evaluated: (a) inflammatory infiltrate, (b) periodontal ligament thickness, (c) cementum resorption and (d) bone resorption. Scores were given and data were analysed statistically with the Kruskal-Wallis and Dunn tests (P < 0.05). Histopathological evaluation showed that groups I-VI had more inflammatory infiltrate, greater periodontal ligament thickening and greater cementum and bone resorption (P < 0.05) compared to group VII, which received the calcium hydroxide intracanal dressing. Biomechanical preparation with the irrigating solutions did not inactivate the effects of the endotoxin but the calcium hydroxide intracanal dressing did appear to inactivate the effects induced by the endotoxin in vivo.


Interference-based multiple-image encryption with silhouette removal by position multiplexing.
An approach for multiple-image encryption based on interference and position multiplexing is proposed. In the encryption process, multiple images are analytically hidden into three phase-only masks (POMs). The encryption algorithm for this method is quite simple and does not need iterative encoding. For decryption, both the digital method and optical method could be employed. Also, we analyze the multiplexing capacity through the correlation coefficient. In addition, the silhouette problem that exists in previous interference-based encryption methods with two POMs can be eliminated during the generation procedure of POMs based on the interference principle. Simulation results are presented to verify the validity of the proposed approach.


A gain-of-function mutation in a plant disease resistance gene leads to constitutive activation of downstream signal transduction pathways in suppressor of npr1-1, constitutive 1.
Plants have evolved sophisticated defense mechanisms against pathogen infections, during which resistance (R) genes play central roles in recognizing pathogens and initiating defense cascades. Most of the cloned R genes share two common domains: the central domain, which encodes a nucleotide binding adaptor shared by APAF-1, certain R proteins, and CED-4 (NB-ARC), plus a C-terminal region that encodes Leu-rich repeats (LRR). In Arabidopsis, a dominant mutant, suppressor of npr1-1, constitutive 1 (snc1), was identified previously that constitutively expresses pathogenesis-related (PR) genes and resistance against both Pseudomonas syringae pv maculicola ES4326 and Peronospora parasitica Noco2. The snc1 mutation was mapped to the RPP4 cluster. In snc1, one of the TIR-NB-LRR-type R genes contains a point mutation that results in a single amino acid change from Glu to Lys in the region between NB-ARC and LRR. Deletions of this R gene in snc1 reverted the plants to wild-type morphology and completely abolished constitutive PR gene expression and disease resistance. The constitutive activation of the defense responses was not the result of the overexpression of the R gene, because its expression level was not altered in snc1. Our data suggest that the point mutation in snc1 renders the R gene constitutively active without interaction with pathogens. To analyze signal transduction pathways downstream of snc1, epistasis analyses between snc1 and pad4-1 or eds5-3 were performed. Although the resistance signaling in snc1 was fully dependent on PAD4, it was only partially affected by blocking salicylic acid (SA) synthesis, suggesting that snc1 activates both SA-dependent and SA-independent resistance pathways.


Bone marrow examination in cases of pancytopenia.
This study was carried to identify the causes of pancytopenia and to find out the bone marrow morphology in cases of pancytopenia. It was a cross sectional study conducted over a period of two years in the Department of Pathology, Tribhuvan University Teaching Hospital. Bone marrow aspiration smears of patients fulfilling the criteria of pancytopenia were examined. The data obtained were analyzed using measures of central tendency. One hundred and forty eight cases underwent bone marrow aspiration and it constituted 15.74% of total cases. Mean age was 30 years (range, 1-79 years). 42 cases were children (28.37%). Male: female ratio was 1.5:1. The commonest cause was hypoplastic bone marrow seen in 43 cases (29%) followed by megaloblastic anemia in 35 cases (23.64%), and hematological malignancy in 32 cases (21.62%). Erythroid hyperplasia was seen in 29 cases (19.6%) and normal bone marrow was seen in 5 cases (3.38%). There was one case each of Niemann-Pick disease and metastatic neuroblastoma in children and chronic pure red cell aplasia and leishmaniasis in adults. Acute leukemia was the commonest hematological malignancy. In children, commonest finding was hypoplastic bone marrow (38.1%) while in adults megaloblastic anemia (30.18%) was commonest finding followed by hypoplastic anemia (25.47%). In present study bone marrow examination was able to establish diagnosis in 77% of cases. Hypoplastic marrow was the commonest diagnosis, followed by megaloblastic anemia, and hematological malignancies.


Fatty acid and triacylglycerol utilisation by perfused rat spleen: differential metabolic fate and the effect of endotoxin.
The spleen uses significant amounts of non-esterified fatty acid (NEFA) and chylomicron (CM)-derived triacylglycerol (TAG); however, its utilisation of very-low-density lipoprotein triacylglycerol (VLDL-TAG), and the effect of endotoxin on lipid assimilation and fate are unknown. This study aims to define spleen utilisation of esterified and non-esterified fatty acid in quiescent and endotoxin-stimulated states. Rat spleens were perfused for 2h with glucose (11mM) and either NEFA (oleate; 0.4mM fatty acid), rat CM (0.4mM TAG), or rat VLDL (0.4mM TAG). Lipid oxidation and tissue lipid deposition were measured. Total utilisation of oleate and VLDL-TAG were not significantly different. Utilisation of CM was 2-3 fold greater; however oxidation of CM-TAG (5.5nmols FA/min/gram spleen) was not significantly different from either NEFA or VLDL-TAG. More TAG (CM and VLDL) was deposited as tissue lipid compared to oxidation than NEFA; the pattern of intracellular lipid accumulation of TAG and NEFA also differed. Endotoxin (LPS) did not affect the proportion of lipid oxidised and accumulated or on TAG tissue lipid distribution but it increased the proportion of oleate recovered as tissue TAG and cholesterol ester. Perfusion with CM-TAG significantly decreased heparin-releasable lipoprotein lipase (LPL) activity compared with oleate or VLDL-perfused spleens. LPS increased LPL activity 5-fold in oleate-perfused spleens, but had no effect on VLDL-perfused spleens. VLDL-TAG is utilised by spleen to a similar extent as NEFA, but its pattern of metabolic fate resembles that of CM-TAG. Endotoxin affects the pattern of NEFA deposition in tissue lipids but has no significant effect on VLDL utilisation by the spleen.


The relationship between mitochondrial DNA copy number and stallion sperm function.
Mitochondrial DNA (mtDNA) copy number has been utilized as a measure of sperm quality in several species including mice, dogs, and humans, and has been suggested as a potential biomarker of fertility in stallion sperm. The results of the present study extend this recent discovery using sperm samples from American Quarter Horse stallions of varying age. By determining copy number of three mitochondrial genes, cytochrome b (CYTB), NADH dehydrogenase 1 (ND1) and NADH dehydrogenase 4 (ND4), instead of a single gene, we demonstrate an improved understanding of mtDNA fate in stallion sperm mitochondria following spermatogenesis. Sperm samples from 37 stallions ranging from 3 to 24 years old were collected at four breeding ranches in north and central Texas during the 2015 breeding season. Samples were analyzed for sperm motion characteristics, nuclear DNA denaturability and mtDNA copy number. Mitochondrial DNA content in individual sperm was determined by real-time qPCR and normalized with a single copy nuclear gene, Beta actin. Exploratory correlation analysis revealed that total motility was negatively correlated with CYTB copy number and sperm chromatin structure. Stallion age did not have a significant effect on copy number for any of the genes. Copy number differences existed between the three genes with CYTB having the greatest number of copies (20.6 ± 1.2 copies, range: 6.0 to 41.1) followed by ND4 (15.5 ± 0.8 copies, range: 6.7 to 27.8) and finally ND1 (12.0 ± 1.0 copies, range: 0.4 to 26.6) (P < 0.05). Varying copy number across mitochondrial genes is likely to be a result of mtDNA fragmentation and degradation since downregulation of sperm mtDNA occurs during spermatogenesis and may be important for normal sperm function. Beta regression analysis suggested that for every unit increase in mtDNA copy number of CYTB, there was a 4% decrease in the odds of sperm movement (P = 0.001). Influential analysis suggested that results are robust and not highly influenced by data from individual stallions despite the low number of stallions sampled with low sperm motility. Further genome sequencing is necessary to investigate if mutations or deletions are the underlying causes of inconsistent copy numbers across mitochondrial genes. In conclusion, we show, for the first time, that increased mtDNA copy number is associated with decreased total sperm motility in stallions. We therefore suggest that mtDNA copy number may be an indicator of defective spermatogenesis in stallions.


[Pediatric sepsis - new national recommendations for recognition and initial treatment].
A task force appointed by the Swedish Society of Pediatric Infectious Diseases developed national treatment recommendations for pediatric sepsis. It is limited to previously healthy children between 28 days (corrected) to 18 years of age and presented as a flow chart. Sepsis should be thought of as a life-threatening organ dysfunction caused by a dysregulated host response to infection. If the child is in shock, e.g. tachycardia with signs of decreased perfusion, sepsis treatment should be initiated immediately. If not in shock, but sepsis is very likely, sepsis treatment should be initiated as soon as possible. If the child is stable and sepsis is suspected, attempts should be made to revert symptoms not associated with the suspected primary infection and basic work-up performed. If no improvement is seen within three hours, sepsis treatment should be initiated. Sepsis treatment consists of fluids and antibiotics, sometimes with vasopressors, corticosteroids and/or immunomodulatory drugs.


Bioavailability Assessment of Copper, Iron, Manganese, Molybdenum, Selenium, and Zinc from Selenium-Enriched Lettuce.
Cu, Fe, Mn, Mo, Selenium (Se), and Zn bioavailability from selenate- and selenite-enriched lettuce plants was studied by in vitro gastrointestinal digestion followed by an assay with Caco-2 cells. The plants were cultivated in the absence and presence of two concentrations (25 and 40 µmol/L of Se). After 28 days of cultivation, the plants were harvested, dried, and evaluated regarding the total concentration, bioaccessibility, and bioavailability of the analytes. The results showed that biofortification with selenate leads to higher Se absorption by the plant than biofortification with selenite. For the other nutrients, Mo showed high accumulation in the plants of selenate assays, and the presence of any Se species led to a reduction of the plant uptake of Cu and Fe. The accumulation of Zn and Mn was not strongly influenced by the presence of any Se species. The bioaccessibility values were approximately 71%, 10%, 52%, 84%, 71%, and 86% for Cu, Fe, Mn, Mo, Se, and Zn, respectively, and the contribution of the biofortified lettuce to the ingestion of these minerals is very small (except for Se and Mo). Due to the low concentrations of elements from digested plants, it was not possible to estimate the bioavailability for some elements, and for Mo and Zn, the values are below 6.9% and 3.4% of the total concentration, respectively. For Se, the bioavailability was greater for selenite-enriched than selenate-enriched plants (22% and 6.0%, respectively), because selenite is biotransformed by the plant to organic forms that are better assimilated by the cells.


Effectiveness of a short-term steroid treatment on the reduction in goiter size in antithyroid drug-treated patients with Graves' disease.
Reduction of goiter size is one of the criteria necessary to determine clinical remission in antithyroid drug (ATD)-treated Graves' patients. To facilitate goiter reduction or to achieve quick remission, a short-term steroid treatment was administered to 5 Graves' patients. These patients had been treated with ATD for a considerable period of time, had maintained euthyroidism with negative or weak thyrotropin-binding inhibitor immunoglobulin (TBII), but still had an enlarged goiter and remained T3 unsuppressive. Betamethazone was initially given 1.5 mg daily and then gradually tapered to 0 mg for 3 months. Compared to the 6-month observation period or the pre-medication period, goiter reduction exceeding 0.7 cm was achieved in all 5 patients during the steroid treatment. These reductions partly reversed to an extent smaller than pre-treatment levels in 2 patients, but continuous goiter reductions were observed for at least 3 months after steroid cessation in 3 patients. In 2 of these reduced goiter patients, T3 suppressibility was confirmed, and they were diagnosed in remission. During steroid administration, serum T3 and TSH concentrations were lowered but reversed shortly, serum fT4 concentrations did not change, and TBII levels became negative in all patients including the 2 with weak positive values before the treatment. In conclusion, a short-term steroid treatment for goitrous ATD-treated Graves' patients appears promising in achieving goiter reduction or remission.


Crystal structure of the inhibitor-free form of the serine protease kallikrein-4.
Kallikrein 4 (KLK4) is a serine protease that is predominantly expressed in the prostate and is overexpressed in prostate cancer. As such, it has gained attention as an attractive target for prostate cancer therapeutics. Currently, only liganded structures of KLK4 exist in the Protein Data Bank. Until now, inferences about the subtle structural changes in KLK4 upon ligand binding have been made by comparison to other liganded forms, rather than to an apo form. In this study, an inhibitor-free form of KLK4 was crystallized. The crystals obtained belonged to space group P1, contained four molecules in the asymmetric unit and diffracted to 1.64 Å resolution. Interestingly, a nonstandard rotamer of the specificity-determining residue Asp189 was observed in all chains. This model will provide a useful unliganded structure for the future structure-guided design of KLK4 inhibitors.


Nucleotide sequence shows that Bean leafroll virus has a Luteovirus-like genome organization.
The complete nucleotide sequence of the Bean leafroll virus (BLRV) genomic RNA and the termini of its smallest subgenomic RNAs were determined to better understand its mechanisms of gene expression and replication and its phylogenetic position within the Luteoviridae: The number and placement of open reading frames (ORFs) within the BLRV genome was Luteovirus-like. The nucleotide and predicted amino acid sequences of BLRV were most similar to those of Soybean dwarf virus (SbDV). Phylogenetic analyses employing the neighbour-joining method and sister-scanning analysis indicated that the BLRV nonstructural proteins were closely related to those of Barley yellow dwarf virus-PAV (BYDV-PAV), a luteovirus: The region surrounding the frameshift at the junction between ORFs 1 and 2 also contained sequences very similar to those of BYDV-PAV and a Dianthovirus, Red clover necrotic mosaic virus. Similar analyses showed that the structural proteins were most similar to those of the Polerovirus genus. The 3'-noncoding regions downstream of ORF5 contained sequences similar to translational control elements identified in the BYDV-PAV genome. These data suggest that BLRV, like SbDV, is derived either through selection from a common ancestor with BYDV-PAV or that BLRV is the product of two recombination events between luteovirus-like and polerovirus-like ancestors where the 5' 2900 nt and 3' 700 nt of the BLRV genome are from a Luteovirus and the intervening sequences are derived from a Polerovirus:


Diaphragm function does not independently predict exercise intolerance in patients with precapillary pulmonary hypertension after adjustment for right ventricular function.
Background: Several determinants of exercise intolerance in patients with precapillary pulmonary hypertension (PH) due to pulmonary arterial hypertension and/or chronic thromboembolic PH (CTEPH) have been suggested, including diaphragm dysfunction. However, these have rarely been evaluated in a multimodal manner. Methods: Forty-three patients with PH (age 58 ± 17 years, 30% male) and 43 age- and gender-matched controls (age 54 ± 13 years, 30% male) underwent diaphragm function (excursion and thickening) assessment by ultrasound, standard spirometry, arterial blood gas analysis, echocardiographic assessment of pulmonary artery pressure (PAP), assay of amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and cardiac magnetic resonance (CMR) imaging to evaluate right ventricular systolic ejection fraction (RVEF). Exercise capacity was determined using the 6-min walk distance (6MWD). Results: Excursion velocity during a sniff maneuver (SniffV, 4.5 ± 1.7 vs. 6.8 ± 2.3 cm/s, P<0.01) and diaphragm thickening ratio (DTR, 1.7 ± 0.5 vs. 2.8 ± 0.8, P<0.01) were significantly lower in PH patients versus controls. PH patients with worse exercise tolerance (6MWD <377 vs. ≥377 m) were characterized by worse SniffV, worse DTR, and higher NT-pro-BNP levels as well as by lower arterial carbon dioxide levels and RVEF, which were all univariate predictors of exercise limitation. On multivariate analysis, the only independent predictors of exercise limitation were RVEF (r = 0.47, P=0.001) and NT-proBNP (r = -0.27, P=0.047). Conclusion: Patients with PH showed diaphragm dysfunction, especially as exercise intolerance progressed. However, diaphragm dysfunction does not independently contribute to exercise intolerance, beyond what can be explained from right heart failure.


Plasma cell granuloma of the lung with extrapulmonal extension. Immunohistochemical and electron microscopic studies.
A rare case of plasma cell granuloma of the lung in a 5-year-old girl showing extrapulmonal extension to the adjoining thoracic wall was reported. Intrapulmonal and thoracic wall granulomas revealed the same histopathologic features; proliferation of plasma cells and fibrous connective tissue. Although slightly atypical plasma cells were observed among many mature ones, immunohistochemical examination revealed polyclonal proliferation, confirming their inflammatory nature. Cellular components of fibrous connective tissue were identified as fibroblastic cells and myofibroblasts by electron microscopy. The present case and literature suggested the importance of the fact that "infiltrative" plasma cell granuloma had a tendency to occur in children.


How do the sleep features that characterise depression impact memory?
Depression is associated with general sleep disturbance and abnormalities in sleep physiology. For example, compared with control subjects, depressed patients exhibit lower sleep efficiency, longer rapid eye movement (REM) sleep duration, and diminished slow-wave activity during non-REM sleep. A separate literature indicates that depression is also associated with many distinguishing memory characteristics, including emotional memory bias, overgeneral autobiographical memory, and impaired memory suppression. The sleep and memory features that hallmark depression may both contribute to the onset and maintenance of the disorder. Despite our rapidly growing understanding of the intimate relationship between sleep and memory, our comprehension of how sleep and memory interact in the aetiology of depression remains poor. In this narrative review, we consider how the sleep signatures of depression could contribute to the accompanying memory characteristics.


Global synchronization of complex dynamical networks through digital communication with limited data rate.
This paper studies the global synchronization of complex dynamical network (CDN) under digital communication with limited bandwidth. To realize the digital communication, the so-called uniform-quantizer-sets are introduced to quantize the states of nodes, which are then encoded and decoded by newly designed encoders and decoders. To meet the requirement of the bandwidth constraint, a scaling function is utilized to guarantee the quantizers having bounded inputs and thus achieving bounded real-time quantization levels. Moreover, a new type of vector norm is introduced to simplify the expression of the bandwidth limit. Through mathematical induction, a sufficient condition is derived to ensure global synchronization of the CDNs. The lower bound on the sum of the real-time quantization levels is analyzed for different cases. Optimization method is employed to relax the requirements on the network topology and to determine the minimum of such lower bound for each case, respectively. Simulation examples are also presented to illustrate the established results.