Can we change the natural course of inflammatory bowel disease?
Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are lifelong diseases characterized by chronic inflammation of the gastrointestinal tract leading to its progressive and irreversible destruction. Whether early initiation of IBD-specific therapy impacts the long-term course of the disease remains unclear and has to be further explored in prospective disease-modification trials. Historically, surgery and hospitalization rates have been the surrogate markers to measure disease progression in IBD, providing an overview of the effectiveness of medical therapies. However, neither surgery nor hospitalization necessarily reflects a fail in therapeutic medical management, and many confounding factors make them biased outcomes. The Selecting Endpoints for Disease-Modification Trials consensus has defined the disease-modification endpoints required for these trials, including the impact of the disease on patient's life (health-related quality of life, disability, and fecal incontinence), the mid-term disease complications (bowel damage in CD, IBD-related surgery and hospitalizations, disease extension in UC, extra-intestinal manifestations, permanent stoma, short bowel syndrome), and the development of dysplasia/cancer and mortality in the long term. Most available data in the literature regarding the impact of current therapies on disease progression focused on anti-tumor necrosis factor agents and are based on retrospective or post-hoc studies. Thus, prospective disease-modification trials are pressingly required to explore the effectiveness of early intensified treatment in patients with severe disease or at risk for disease progression.


Effect of late-gestation heat stress in nulliparous heifers on postnatal growth, passive transfer of immunoglobulin G, and thermoregulation of their calves.
Youngstock such as nulliparous pregnant dairy heifers are not typically considered for active cooling, as they are thought to be more heat tolerant than mature cows. Recently, the benefits of heat stress abatement in pregnant heifers were studied, but the effect of in utero hyperthermia on the calf is still unknown. Herein, we aimed to investigate the effects of late-gestation heat stress in nulliparous heifers on the growth, immune, and thermoregulatory responses of their calves. Pregnant nulliparous dams were randomly selected for either active cooling (CL; fans and soakers; n = 15) or heat stress (HT; n = 16) 60 d before expected calving. After birth, respiration rate, rectal temperature, skin temperature, and sweating rate were obtained from their heifer calves at 24 h and on d 14, 28, 42, and 56. Blood samples and body weights were both collected for measurement of total protein and hematocrit and calculation of average daily gains, respectively. Gestation length was shorter in HT heifers (272 vs. 276 ± 1.28 d) relative to CL heifers. Birth weights, weaning weights, body weights up to d 56, and average daily gain from birth to weaning were not different between in utero HT (IUHT; n = 13) and in utero CL (IUCL; n = 12) calves. Apparent efficiency of absorption of immunoglobulin G tended to be lower in IUHT calves (26.3 vs. 42.7 ± 9.0%), and serum IgG concentrations from birth to d 56 were significantly lower in IUHT calves relative to IUCL calves (22.0 vs. 32.4 ± 4.47 g/L). Postnatal respiration rate, rectal temperature, sweating rate, total protein, and hematocrit were not different between in utero treatments. There was a tendency for IUHT calves to have lower skin temperature at 24 h (34.9 vs. 36.9 ± 1.05°C), and skin temperature tended to be elevated in IUHT calves at d 56 (29.6 vs. 27.9 ± 1.05°C). In summary, the lack of heat stress abatement during late gestation reduces gestation length of nulliparous heifers. Additionally, providing active cooling to nulliparous heifers during the prepartum period confers immune benefits to their offspring, although it does not translate to growth improvements.


Onsager-Casimir reciprocity relation for the gyrothermal effect with polyatomic gases.
On the basis of the linearized Boltzmann equation and the boundary condition for the distribution function, the Onsager-Casimir reciprocity relation is derived for polyatomic gases confined between two cylinders in the presence of a magnetic field. The cross effect, namely, the heat flux caused by the rotation of the inner cylinder is predicted. Because of the heat flux the cylinder can be heated or cooled depending on the direction of the magnetic field. This effect is coupled with the gyrothermal effect by the reciprocity relation.


Characterization of presumptive histone messenger RNA from a cell line of Aedes aegypti.
Four presumptive histone messenger RNAs were characterized from a cell line of Aedes aegypti, and their molecular weights were determined by electrophoresis. They were shown to be associated with polysomes during the peak of DNA synthesis, but not when DNA synthesis was inhibited by cytosine arabinoside or when DNA was not being synthesized. These mRNAs are associated with polysomes containing less than 8 ribosomes and having a high ratio of incorporation of lysine to tryptophan into their nascent peptides. The mRNAs released from these polysomes were translated in vitro and histone products were synthesized. Histones were not synthesized when the mRNAs were obtained from large polysomes or from small polysomes during the non-DNA synthetic period.


Precise mid-trimester placenta localisation: does it predict adverse outcomes?
A low-lying placenta detected at the mid-pregnancy ultrasound is commonly reported to warn against potential morbidity associated with placenta praevia. There is no information on what distance away from the internal cervical os is safe. We examined whether a low-lying placenta not overlapping the cervical os in the second trimester increases the risk of obstetric complications and whether there is a cut-off point at which that increase occurs. Adverse perinatal outcomes were examined prospectively in a cohort of women with a placenta 0-30 mm from the internal cervical os ('low-lying') at the routine mid-trimester ultrasound and compared to those with a placenta further away. Two composite outcomes of 'major' and 'minor' adverse events were predefined as primary outcome measures, requiring a sample size of 480 women with a low-lying placenta. Chi-square and Fisher's exact tests were used for statistical analysis. In 1662 pregnancies ('low-lying': n = 484; 'normal': n = 1178), there was no increase in composite adverse outcomes with a low-lying placenta and no cut-off distance within 30 mm from the cervical os at which risks increased. Postpartum haemorrhage ≥ 1000 mL was more frequent with a low-lying placenta (7.6% vs 4.7%, P < 0.05). Women with a low-lying placenta, not overlapping the cervical os, in mid-pregnancy are at no higher risk of adverse outcomes than those with a normally located placenta, except postpartum haemorrhage. This suggests that the high-risk label can be removed from pregnancies with a low-lying placenta not overlapping the cervical os in mid-pregnancy, reducing anxiety and resource utilisation.


Management of giant cell tumors of the distal radius.
The distal radius is the most common location for giant cell tumors (GCT) in the upper extremity. Treatment should balance the goals of maximizing function and minimizing recurrence and other complications. Given the complexity in surgical treatment, various techniques have been described without clear standards of treatment. The purpose of this review is to provide an overview of evaluation of patients presenting with GCT of the distal radius, discuss management, and provide an updated summary on outcomes of treatment options. Surgical treatment should consider tumor Grade, involvement of the articular surface, and patient-specific factors. Options include intralesional curettage and en bloc resection with reconstruction. Within reconstruction techniques, radiocarpal joint preserving and sparing procedures can be considered. Campanacci Grade 1 tumors can be successfully treated with joint preserving procedures, whereas for Campanacci Grade 3 tumors consideration should be given to joint resection to prevent recurrence. Treatment of Campanacci Grade 2 tumors is debated in the literature. Intralesional curettage and adjuvants can successfully treat cases where the articular surface can be preserved, while en-bloc resection should be used in cases where the articular surface cannot undergo aggressive curettage. A variety of reconstructive techniques are used for cases needing resection, with no clear gold standard. Joint sparing procedures preserve motion at the wrist joint, whereas joint sacrificing procedures preserve grip strength. Choice of reconstructive procedure should be made based on patient-specific factors, considering relative functional outcomes, complications, and recurrence rates.


[Chromatographic separation of racemic thalidomide and teratogenic activity of its enantiomers (author's transl)].
Racemic thalidomide is chromatographically separated on optically active polyamide giving both enantiomers. After i.p. administration only the S-(-)-enantiomer is teratogenic on SWS mice and Natal rats.


Correlation of Acetabular Anteversion and Thoracic Kyphosis Postoperatively with Proximal Junctional Failure in Adult Spinal Deformity Fused to Pelvis.
To investigate whether the immediate thoracic kyphosis (TK) and acetabular anteversion (AA) postoperatively are correlated with proximal junctional failure (PJF) in adult spinal deformity (ASD) patients underwent surgical treatment. This is a retrospective study. Following institutional ethics approval, a total of 57 patients (49 Female, eight Male) with ASD underwent surgery fused to sacroiliac bone (S1, S2, or ilium) from March 2014 to January 2019 were included. All of those patients were followed up for at least 2 years. Demographic, radiographic and surgical data were recorded. The maximum range of flexion motion (F-ROM) and extension motion (E-ROM) actively of hip joints was measured and recorded at pre- and postoperation. The sum of F-ROM and E-ROM was defined as the range of hip motion (H-ROM). Receiver operating characteristic (ROC) curve analysis was used to obtain the cut off value of parameters for PJF. A Kaplan-Meier curve and log-rank test were used to analyze the differences in PJF-free survival. In all, 14 patients developed PJF during follow-up. Comparisons between patients with and without PJF showed significant differences in immediate TK (P < 0.001) and AA (P = 0.027) postoperatively. ROC curve analysis determined an optimal threshold of 13° for immediate AA postoperatively (sensitivity = 74.3%, specificity = 85.7%, area under the ROC curve [AUC] = 0.806, 95% CI [0.686-0.926]). Nineteen patients with post-AA ≤13° were assigned into the observational group, and 38 patients with post-AA >13° were being as the control group. Patients in the observational group had smaller H-ROM (P = 0.016) and F-ROM (P < 0.001), but much larger E-ROM (P < 0.001). There were 10 patients showing PJF in the observational group and four in the control group (10/9 vs 4/34, P < 0.001). PJF-free survival time significantly decreased in the observational group (P = 0.001, log-rank test). Furthermore, patients in the observational group had much larger TK (post-TK, P = 0.015). The optimal threshold for post-TK (sensitivity = 85.7%, specificity = 76.7%; AUC = 0.823, 95% CI [0.672-0.974]) was 28.1° after the ROC curve was analyzed. In the observational group, those patients with post-TK ≥28.1° had significantly higher incidence of PJF (9/2 vs 1/7, P < 0.001) than those with post-TK < 28.1°. Moreover, PJF-free survival time in those patients significantly decreased (P = 0.001, log-rank test). ASD patients with acetabular anteversion of ≤13° at early postoperation may suffer significantly restricted hip motion and much higher incidence of PJF during follow-up, moreover, in those patients, postoperative TK ≥28.1° would be a significant risk factor for PJF developing.


Expression of GLUT-1 in oral squamous cell carcinoma in tobacco and non-tobacco users.
GLUTs are a family of proteins that mediate glucose transport through the membrane, expressed in head and neck squamous cell carcinoma. GLUT-1 positivity in malignant cells indicates increased proliferative activity, energy requirements, aggressive behaviour and poor radiation response. To observe the expression of GLUT-1 protein in oral squamous cell carcinoma in tobacco and non-tobacco users and to correlate the expression with histopathological grading and pathological staging. 50 cases (25 tobacco and 25 non-tobacco) of oral squamous cell carcinoma, selected during period of August 2014 to July 2015. Histopathological grading, TNM and staging were done. Immunohistochemical staining was performed using standard protocol for paraffin embedded sections. Analysis was performed on SPSS software (Windows version 17.0). Significant association of GLUT-1 expression was found with history of tobacco (p < 0.001), Bryne's grade (p < 0.001), tumour size (p = 0.001), nodal metastasis (p = 0.022) and stage (p < 0.001). Higher GLUT-1 expression in stage II, stage III and stage IV was found as compared to stage I. GLUT-1 immunoexpression also shows progressive switch from membranous to cytoplasmic to combined location correlating with histopathologic grade and pTNM stage. GLUT-1 expression correlates significantly with histological grade and pTNM staging of oral squamous cell carcinoma. It also significantly correlates with tobacco addiction. Thus, GLUT-1 expression may serve as a biomarker for patients of oral squamous cell carcinoma.


Nerve monitoring decreases recurrent laryngeal nerve injury risk for neoplasm-related thyroidectomy.
Conflicting reports exist regarding the benefit of intraoperative neuromonitoring (INM) for patients undergoing thyroidectomy. We hypothesized that in a national sample, the risk of mild and severe RLNi is decreased for patients undergoing neoplasm-related disease (NRD) thyroidectomy with INM compared to patients without INM. The database was queried for patients that underwent total thyroidectomy for NRD with and without INM. A multivariable logistic regression model was used to determine the associated odds of RLNi. From 6942 patients, 4269 (61.5%) had INM during thyroidectomy. Patients with INM had a similar rate of overall RLNi compared to patients without INM (5.7% vs. 6.6%, p = 0.118). After adjusting for covariates, INM was associated with decreased odds of severe-RLNi (OR 0.23, p = 0.036) but not mild-RLNi (p = 0.16). INM is associated with a nearly 80% decreased associated odds of severe RLNi during thyroidectomy for NRD. Future prospective confirmation is needed, and if confirmed, patients undergoing thyroidectomy for NRD should have INM to reduce the risk of RLNi and its associated morbidity.


Actionable reporting versus unwanted advice in PET-CT reports.
To investigate the opinions of clinician referrers on the presence and type of management advice in reports of positron-emission tomography (PET)-computed tomography (CT) examinations. Eighteen clinicians were interviewed using a structured questionnaire about their opinions on further management advice in PET-CT reports. Opinions varied amongst clinicians, but some themes predominated: (1) advice on further imaging tests and areas outside the referrer's area of expertise are more welcome than other types of advice; (2) a differential diagnosis or clinical significance is of greater value than specific management advice; (3) some referrers do not want any further advice. Before advising on further management, reporters should consider clinicians' opinions regarding this. Seeking the opinion of clinicians in other hospitals may be necessary. A review of the Royal College of Radiologists Actionable Reports standard to ensure it is more in line with the opinions of clinicians may be useful.


Extracranial Schwannomas of the Head and Neck: A Literature Review and Audit of Diagnosed Cases Over a Period of Eight Years.
Schwannoma is a benign, slow growing, usually solitary and encapsulated tumor derived from Schwann cells of the nerve sheath. Schwannomas can be divided into central, or intraosseous, and peripheral lesions. The etiology is unknown, but it is postulated that lesions arise by the proliferation of Schwann cells at one point inside the perineurium. Schwannomas may mimic other diseases of the head and neck, such as infection, tumor or metastasis. Extracranial schwannomas are rare; in this study we review a series of 22 cases of schwannomas originating in the head and neck region over a period of eight years. All tumors were benign and well-encapsulated. Tumor size ranged from 0.5 to 9 cm. The age range of patients studied was 15-74 years with a mean age of 35 years and a male predilection (M:F, 2.6:1)was noted. Four cases of schwannomas occurred in the tongue (18.18%) and lower lip (18.18%), three in the nasal cavity (13.64%), two each (9.09%) in the buccal mucosa, parapharyngeal space (9.09%), and eyebrow (9.09%), and one each in the upper lip (4.55%), lateral canthus of the eye (4.55%), intraorbital region (4.55%), submandibular gland (4.55%), and ear (4.55%). Schwannomas can present in a wide variety of sites within the head and neck. The tumor is benign and tend to be asymptomatic for long periods of time. Histopathology is the gold standard for diagnosis. Our study describes the clinicopathologic features of extracranial head and neck schwannomas, highlights the histopathologic features, and discusses pertinent findings with correlation to the present literature. It is important that both clinicians and pathologists be familiar with the uncommon sites of occurrence and the potential pitfalls associated with the diagnosis and management of these tumors.


Genetic, immunofluorescence labeling, and in situ hybridization techniques in identification of stem cells in male and female germline niches.
Stem cells have an enormous capacity of self-renewal, as well as the ability to differentiate into specialized cell types. Proper control of these two properties of stem cells is crucial for animal development, growth control, and reproduction. Germline stem cells (GSCs) are a self-renewing population of germ cells, which generate haploid gametes (sperms or oocyte) that transmit genetic information from generation to generation. In Drosophila testis and ovary, GSCs are anchored around the niche cells. The cap cells cluster in females and hub cells in males act as a niche to control GSC behavior. With highly sophisticated genetic techniques in Drosophila, tremendous progress has been made in understanding the interactions between stem cells and niches at cellular and molecular levels. Here, we provide details of genetic, immunofluorescence labeling, and in situ hybridization techniques in identification and characterization of stem cells in Drosophila male and female germline niches.


Combination effects of amino acid transporter LAT1 inhibitor nanvuranlat and cytotoxic anticancer drug gemcitabine on pancreatic and biliary tract cancer cells.
Cytotoxic anticancer drugs widely used in cancer chemotherapy have some limitations, such as the development of side effects and drug resistance. Furthermore, monotherapy is often less effective against heterogeneous cancer tissues. Combination therapies of cytotoxic anticancer drugs with molecularly targeted drugs have been pursued to solve such fundamental problems. Nanvuranlat (JPH203 or KYT-0353), an inhibitor for L-type amino acid transporter 1 (LAT1; SLC7A5), has novel mechanisms of action to suppress the cancer cell proliferation and tumor growth by inhibiting the transport of large neutral amino acids into cancer cells. This study investigated the potential of the combined use of nanvuranlat and cytotoxic anticancer drugs. The combination effects of cytotoxic anticancer drugs and nanvuranlat on cell growth were examined by a water-soluble tetrazolium salt assay in two-dimensional cultures of pancreatic and biliary tract cancer cell lines. To elucidate the pharmacological mechanisms underlying the combination of gemcitabine and nanvuranlat, we investigated apoptotic cell death and cell cycle by flow cytometry. The phosphorylation levels of amino acid-related signaling pathways were analyzed by Western blot. Furthermore, growth inhibition was examined in cancer cell spheroids. All the tested seven types of cytotoxic anticancer drugs combined with nanvuranlat significantly inhibited the cell growth of pancreatic cancer MIA PaCa-2 cells compared to their single treatment. Among them, the combined effects of gemcitabine and nanvuranlat were relatively high and confirmed in multiple pancreatic and biliary tract cell lines in two-dimensional cultures. The growth inhibitory effects were suggested to be additive but not synergistic under the tested conditions. Gemcitabine generally induced cell cycle arrest at the S phase and apoptotic cell death, while nanvuranlat induced cell cycle arrest at the G0/G1 phase and affected amino acid-related mTORC1 and GAAC signaling pathways. In combination, each anticancer drug basically exerted its own pharmacological activities, although gemcitabine more strongly influenced the cell cycle than nanvuranlat. The combination effects of growth inhibition were also verified in cancer cell spheroids. Our study demonstrates the potential of first-in-class LAT1 inhibitor nanvuranlat as a concomitant drug with cytotoxic anticancer drugs, especially gemcitabine, on pancreatic and biliary tract cancers.


Unified Biomimetic Approach to (+)-Hippolachnin A: In-Depth Insights into Its Biosynthetic Origin.
A formal biomimetic synthesis of (+)-hippolachnin A has been achieved under the guidance of its plausible biosynthetic pathway. Pivotal transformations include an intriguing 1O2-mediated [4 + 2] cycloaddition and a tandem Kornblum-DeLaMare rearrangement/hemiketalization/dehydration reaction. The current work not only offers a unified approach to access skeletally diverse plakortin-type polyketides but also provides convincing evidence to elucidate their underlying biosynthetic network.


An entropy-based metric for assessing the purity of single cell populations.
Single-cell RNA sequencing (scRNA-seq) is a versatile tool for discovering and annotating cell types and states, but the determination and annotation of cell subtypes is often subjective and arbitrary. Often, it is not even clear whether a given cluster is uniform. Here we present an entropy-based statistic, ROGUE, to accurately quantify the purity of identified cell clusters. We demonstrate that our ROGUE metric is broadly applicable, and enables accurate, sensitive and robust assessment of cluster purity on a wide range of simulated and real datasets. Applying this metric to fibroblast, B cell and brain data, we identify additional subtypes and demonstrate the application of ROGUE-guided analyses to detect precise signals in specific subpopulations. ROGUE can be applied to all tested scRNA-seq datasets, and has important implications for evaluating the quality of putative clusters, discovering pure cell subtypes and constructing comprehensive, detailed and standardized single cell atlas.


Involvement of capsaicin-sensitive neurones in hyperalgesia and enhanced opioid antinociception in inflammation.
The effects of capsaicin pretreatment of adult rats was investigated on consequences of unilateral paw inflammation induced by inoculation with Freund's adjuvant. Decrease in mechanical nociceptive threshold in the inflamed paw, as measured by the paw pressure test, was dose-dependently inhibited by capsaicin (20-150 mg/kg s.c.). In control rats, the antinociceptive action of morphine (0.8-1.9 mg/kg s.c.) was greater in the inflamed than in the non-inflamed paw; this difference was absent in capsaicin-treated animals. Increased volume or skin temperature of the inflamed paw was not influenced by capsaicin. It is concluded that capsaicin-sensitive, presumably C-fibre neurones, but not an alteration of the inflammation itself by capsaicin, mediate hyperalgesia and increased morphine antinociception in the rat paw with adjuvant-induced inflammation.


Notes from the Field: Investigation of Hepatitis C Virus Transmission Associated with Injection Therapy for Chronic Pain - California, 2015.
On November 26, 2014, the California Department of Public Health (CDPH) contacted CDC concerning a report from the Santa Barbara County Public Health Department (SBPHD) regarding acute hepatitis C virus (HCV) infection in a repeat blood donor. The patient, who was asymptomatic, was first alerted of the infection by the blood bank and had no traditional risk factors for HCV infection. The donor had a negative HCV nucleic acid test (NAT) 56 days before the first positive NAT test, and an investigation into the donor's health care exposures and other potential risk factors, including injection drug use, incarceration, and long-term hemodialysis within this narrow exposure window, was conducted by SBPHD.


Reciprocal relationship between multifidus and psoas at L4-L5 level in women with low back pain.
Background Low back pain (LBP) may originate from different sources such as intervertebral disc degeneration (IVDD), end-plate and paraspinal muscle changes. Our aim is to explore the relevance of paraspinal muscles' fat-infiltration in women with LBP and its association with IVDD and Modic changes.Methods Consecutive female patients presenting with chronic LBP to the outpatient clinics were included. Patients were evaluated in terms of IVDD, vertebral end-plate changes, and fatty infiltration in the paraspinal muscles at all lumbar levels on lumbar spine magnetic resonance imaging (MRI). Visual Analogue Scale (VAS) scores were recorded using our prospectively collected database.Results Patients with higher VAS scores were significantly more likely to have more fatty infiltration in the multifidus and less fatty infiltration in the psoas at L4-L5 level when compared to those with lower VAS scores (69.1 vs. 31.8%, p = 0.003). To predict LBP, fatty infiltration in the multifidus and psoas had odds ratio (OR) of 4 (p = 0.010), and 0.3 (p = 0.013), respectively; whereas disc degeneration had an OR of 0.5 (p = 0.028).Conclusion This is the first clinical cross-sectional study suggested that women with chronic low back pain could have less fat-infiltrated psoas to compensate more fat-infiltrated multifidus at L4-L5 disc level.


Low production "efficiency" of homoeotherm populations: a misunderstanding.
The production/respiration (P/R) ratios of homoeotherm populations are about one order of magnitude lower than those of poikilotherm populations. This has suggested to ecologists that homoeotherms are much less efficient converters of food energy into growth and reproduction than poikilotherms, the reason being the high cost of thermal homoeostasis. That this conclusion is wrong can be demonstrated by plotting three measures of production: individual growth rate; maximum rate of population increase; and natural rate of population increase, against rate of basal netabolism. It follows that to call the P/R ratio of communities a measure of production "efficiency" leads to confusion. If the P/R ratios of homoeotherm poulations are lower than those of poikilotherm populations it is not because their individual members are less "efficient" but because the low rate of natural increase happens to have been the most stable evolutionary solution for the organization of life cycle schedules in these animals.


[Effects of lipopolysaccharides from various Porphyromonas on the expression of CD14 and TLRs in mouse osteoblast].
To observe the effect of lipopolysaccharides(LPS) extracted from Porphyromonas endodontalis(P.e) and Porphyromonas gingivals(P.g) on the expression of CD14 and TLRs in osteoblast. MC3T3-E1 cells were stimulated with 10μg/mL P.e-LPS and P.g-LPS. The change of CD14,TLR2 and TLR4 mRNA was observed at different time point (0,1,3,6,12,24h) using RT-PCR,and the expression of CD14,TLR2 and TLR4 protein was measured by flow cytometry at 24-hour. Statistical analysis was performed using one-way ANOVA and Dunnett t test with SPSS11.0 software package. MC3T3-E1 cells were stimulated with 10μg/mL P.e-LPS for 1h,the expression of CD14 and TLR4 mRNA increased significantly. There was no increase of TLR2 mRNA with stimulation of P.e-LPS. The CD14,TLR2 and TLR4 mRNA expression increased significantly after stimulation with 10μg/mL P.g-LPS. Flow cytometry showed that CD14 and TLR4 protein increased significantly after stimulation with 10μg/mL P.e-LPS. CD14,TLR2 and TLR4 protein increased significantly after treatment with 10μg/mL P.g-LPS. CD14,TLR4 receptors are involved in P.e-LPS effect and CD14,TLR2 and TLR4 receptors are involved in P.g-LPS effect in mouse osteoblast.


Evaluation of cell recycling in continuous fermentation of enzymatic hydrolysates of spruce with Saccharomyces cerevisiae and on-line monitoring of glucose and ethanol.
The maximum growth rate of Saccharomyces cerevisiae ATCC 96581, adapted to fermentation of spent sulphite liquor (SSL), was 7 times higher in SSL of hardwood than the maximum growth rate of bakers' yeast. ATCC 96581 was studied in the continuous fermentation of spruce hydrolysate without and with cell recycling. Ethanol productivity by ATCC 96581 in continuous fermentation of an enzymatic hydrolysate of spruce was increased 4.6 times by employing cell recycling. On-line analysis of CO2, glucose and ethanol (using a microdialysis probe) was used to investigate the effect of fermentation pH on cell growth and ethanol production, and to set the dilution rate. Cell growth in the spruce hydrolysates was strongly influenced by fermentation pH. The fermentation was operated in continuous mode for 210 h and a theoretical ethanol yield on fermentable sugars was obtained.


Activation of serotonin 5-HT(2C) receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice.
Abuse and dependence to heroin has evolved into a global epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to heroin can induce long-lasting behavioral sensitization and withdrawal. Pharmacological activation of 5-HT2C receptors (5-HT2CRs) suppresses psychostimulant-induced drug-seeking and behavioral sensitization. The present study examined the effect of a selective 5-HT2CR agonist lorcaserin on behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. Male mice received heroin (1.0 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of heroin (1.0 mg/kg) was administered to examine the expression of behavioral sensitization. Lorcaserin administered during the development, withdrawal or expression stage suppressed heroin-induced behavioral sensitization on day 9. Another cohort of mice received increasing doses of heroin over a 4.5-day period. Lorcaserin, or the positive control clonidine (an α2-adrenoceptor agonist) suppressed naloxone-precipitated withdrawal symptoms in heroin-treated mice. These findings suggest that activation of 5-HT2CRs suppresses behavioral sensitization and withdrawal in heroin-treated mice. Thus, pharmacological activation of 5-HT2CRs may represent a new avenue for the treatment of heroin addiction.


Factors controlling the in vitro and in vivo oxygen affinity of the hemocyanin in the crab Carcinus maenas (L.).
The oxygen affinity of the hemocyanin of the crab Carcinus maenas was studied in vitro by measuring the O2 partial pressure at 50% saturation, P50, at various conditions of pH, temperature and salt concentration. At alkaline pH, the hemocyanin exhibits a normal Bohr effect, inverted below pH=pH0=6.9 at 15 degrees C. A rise of temperature provokes an increase of both P50 and pH0. Within the physiological range, only Ca++ and Mg++ ions influence the oxygen affinity. Both ions decrease P50, and Mg++ increases the Bohr factor, deltalogP50/deltapH. The variations of P50 due to changes of pH, temperature (degrees C) and Ca++ and Mg++ concentrations (mEq-L-1) are satisfactorily described by the empirical quantitative expressions: see article. Long-term temperature adaptation of the animals results in changes of the parameter k' which appears to be dependent on the concentration of an unidentified dialysable substance in blood. As temperature rises, this phenomenon limits the in vivo increase of P50 induced by both the intrinsic temperature effect and the decrease of in vivo blood pH. When external salinity decreases, lower blood Ca++ and Mg++ concentrations entail an increase of P50, but without changes of k', an effect compensated for in vivo by an increase of the blood pH. The observations suggest that the functional oxygen affinity of the pigment is physiologically regulated to ensure an adequate oxygen transport by the blood in quite varied conditions of temperature and salinity.


Protection against suture insufficiency in ante-thoracic esophagogastrostomy.
In attempts to decrease suture insufficiency in case of ante-thoracic esophagogastrostomy, a gastric tube was so specially prepared that the short gastric vessels as well as the splenic vessels were severed very adjacent to the spleen. The anastomosis of the gastric tube thus prepared to the cervical esophagus was made using EEA-autosuture instruments. The suture insufficiency rate was thus markedly improved, with a value of approximately 10 per cent. Even cases of suture insufficiency with minor leakage, control was complete with simple pressure with gauze.


The mannose transporter of Escherichia coli. Structure and function of the IIABMan subunit.
The mannose transporter of the bacterial phosphotransferase system consists of two transmembrane subunits (IICMan and IIDMan) and a hydrophilic subunit (IIABMan). IIABMan has two flexibly linked domains containing one phosphorylation site each and occurs as a dimer. Substrate transport is coupled to phosphorylation. The phosphoryl group is transferred from a phosphoryl carrier protein to His10 on IIA, hence to His175 on IIB and finally to the substrate. IIABMan mutants were analyzed in vitro for complementation, negative dominance, cysteine cross-linking and reactivity. (i) His10, Trp12, Lys48, and Ser72 form a functional unit (phosphorylation site 1); (ii) His86 on the IIA domain and His175 on the IIB domain of the same subunit form a functional unit (phosphorylation site 2); (iii) phosphoryl transfer can occur between His10 and His175 of the same as well as of different subunits and His86 is necessary for this transfer; (iv) the subunits in the dimer are interdependent; (v) The phosphorylation site mutant H175C is highly reactive toward thiol reagents and it forms extensive homo- and heterocross-links with other surface-exposed cysteines. The phosphorylation site mutant H10C is 1000-fold less reactive. The two residues might be in complementary locations, His10 buried in a concave, His175 exposed on a convex surface.


Psychosocial interventions and support programs for fathers of NICU infants - A comprehensive review.
The experience of having a child in the neonatal intensive care unit (NICU) is often unexpected, traumatic, and presents numerous stressors for new fathers. Past research has shown that parents of all genders with children in the NICU experience clinically significant psychological symptoms, yet the bulk of research and intervention efforts to date have focused on the needs of mothers. This paper will provide a review of the literature, outline current knowledge about the specific needs of men with children in the NICU, and recommend areas of focus for future research. The paper will also highlight the need to tailored interventions that specifically address the unique needs of fathers.


A novel role of fatty acid-binding protein as a vehicle of retinoids.
Intracellular transport and storage of retinoids were shown to be conducted by fatty acid-binding protein (FABP). When rat liver cytosol was gel filtrated, retinyl palmitate-binding activity was mainly eluted in the fraction with a Mr. of around 14,000, in which both FABP and cellular retinol-binding protein (CRBP) co-existed. From the binding analysis of purified FABP and CRBP to retinyl palmitate, FABP was found to have a relatively high affinity (Kd = 1.4 X 10(-6) M) to retinyl palmitate, while binding of retinyl palmitate to CRBP was scarcely detectable. By using anti-FABP serum, it was shown that FABP was distributed in organs relating to absorption and storage of retinoids, such as jejunum, ileum, and liver. In liver, the protein was localized in the parenchymal cells and with particularly high concentration in the perisinusoidal cells, probably fat-storing cells.


Ward atmosphere changes during restructuring of an alcoholism treatment center. A quasi-experimental study.
At an Alcoholism Treatment Center which was under restructuring, the Ward Atmosphere Scale (WAS) was used to study the effect of changes on the climate of two wards. Before implementation, after the first phase of changes one year later, and after the second phase changes a year later, patients (n1 = 19, n2 = 16, n3 = 23) and staff members (n1 = 21, n2 = 24, n3 = 25) filled out WAS forms. The patients were divided into two groups according to a quasi-experimental design. In a Short-term intensive inpatient unit all of the restructuring was implemented, whereas only some were in a Half-way house. The Short-term intensive patients reported significant improvements between the second and the third assessment (p less than .05) and between the first and the third year (p less than .02), but not from the first to the second year. The Half-way house patients showed no significant improvements. The patients altogether reported significant improvements in six subvariables of the eight hypothesized. The total WAS score of the staff increased significantly each year (p less than .01), and there was a clear improvement between the first and third assessment (p less than .001). The staff reported significant improvements from the first to the third assessment in seven subvariables of the eight hypothesized.


Experimental and DFT Study on the Compounds [PdCl2L2] (L = 4-methylpyrazole, 4-iodopyrazole).
Theoretical molecular structures of the complexes [PdCl(2)(HmPz)(2)] (1) and [PdCl(2)(HIPz)(2)] (2) (HmPz = 4-methylpyrazole; HIPz = 4-iodopyrazole) were studied using B3LYP/DFT method. The new complex 2 and the complex 1 were synthesized and characterized by elemental analysis and IR spectroscopy. The calculated bond distances and angles showed that both compounds exhibited a slightly distorted square planar coordination environment around the palladium center. The theoretical IR spectra of C(s) symmetry (electronic state 1A') of the complexes agree well with the experimental data.


Surgical emphysema and upper airway obstruction complicating recovery from anaesthesia.
We describe a case of surgical emphysema and life-threatening airway obstruction resulting from a small pharyngeal perforation. The perforation apparently resulted from the use of a Yankauer-type sucker after uneventful anaesthesia for stapedectomy.


Effects of convolution filter with beam hardening correction on computed tomography image quality.
To quantify the effects of convolution filters (FC) with beam hardening correction (BHC) compared to FC without BHC on the computed tomography (CT) image quality. This study was conducted on a Canon® Aquilion Lightning scanner. The exposure protocol includes acquisitions at 120 and 100 kVp. Sixteen FCs (8 with and 8 without BHC) were investigated using a Catphan®504 phantom. Uniformity, slice thickness, spatial resolution, Hounsfield unit and noise were analysed using the SPICE-CT ImageJ plugin and the noise power spectrum was analysed using the Imquest software. It was observed that the BHC did not significantly influence the uniformity, slice thickness, noise and noise power spectrum. Comparisons of 10% MTF between FC01 and FC11 showed relative differences of -29% and -5% at 120 and 100 kVp, respectively, while those between FC09 and FC19 were -55% and -25%. The Hounsfield unit of the Catphan's region of highest electron density was reduced by -7.29% at 120 kVp for FC with BHC. In both cases (FC with and without BHC), the noise values agreed with CT operating manual. At 120 kVp, FC11 and FC09 presented the maximum and minimum noise values, respectively. In CT procedures that quantitatively evaluate the bone or calcium Hounsfield unit, FC with BHC should be avoided due to its effects on Hounsfield units, in special at higher voltage, such as 120 kVp.


Frequency and age-related course of mitral valve dysfunction in the Marfan syndrome.
Mitral valve (MV) prolapse (MVP) has a high prevalence of 2% to 3% in the general population and thus constitutes the most common cause of severe nonischemic MV regurgitation (MVR). MVP is also common in persons with the Marfan syndrome. However, to date, a large-scale population-based cohort study using modern echocardiographic techniques has not been performed, and the frequency of MVP and the relation of MV dysfunction and age have not been investigated. Therefore, we conducted a population-based cohort study of 204 patients (108 males and 96 females, aged 31.2 ± 16.4 years) with classic Marfan syndrome. We performed echocardiographic follow-up of 174 patients for a mean of 4.4 ± 4.3 years. On the initial or subsequent echocardiographic scan, MVP was present in 82 patients (40%), severe MVR in 25 (12%), and MV endocarditis in 5 patients (2.5%). At 30 years of age, the Weibull cumulative distribution was 42.6% (95% confidence interval [CI] 36% to 50%) for MVP, 56.5% (95% CI 49.3% to 64%) for MVR of any degree, 6.7% (95% CI 3.9% to 11.3%) for severe MVR, and 0.92% (95% CI 0.21% to 3.91%) for MV endocarditis. The cumulative hazard for severe MVR and MV endocarditis was estimated to increase with age. MVP was associated with dural ectasia (p = 0.01), ectopia lentis (p = 0.02), and skeletal involvement (p <0.001). Severe MVR was related to tricuspid valve prolapse (p = 0.002) and to the sporadic form of the Marfan syndrome (p = 0.006). In conclusion, MVP was comparatively frequent in patients with the Marfan syndrome and carries an increased risk of progression to severe MVR and endocarditis, especially in older adults.


Evolution of a genetic code simulated with the computer.
A simple selforganizing model system of molecules is considered and it is demonstrated by a computer simulation, that a genetic code of 16 elements (aminoacids) can gradually be formed by such a system in the course of many generations. By a number of rare chance events, each suppressing other events of equal a priori probability, a single code results out of an immense number of possible codes of the same a priori probability. The result is discussed in relation to the uniqueness of the genetic code in living systems. The computer simulation emphasizes a particular step in a model pathway discussed elsewhere consisting of many assumed physicochemical steps leading to a genetic apparatus.


Testicular metastasis from an extramedullary plasmacytoma.
Plasmacytoma is a blood disease featuring the proliferation of abnormal plasmacytes accompanied by the production of monoclonal immunoglobulins. It usually arises in the medulla; thus, extramedullary plasmacytoma is rare, and metastatic testicular tumors are also infrequent. In this report, we present a case of testicular metastasis from an extramedullary plasmacytoma involving the nasopharynx, with good control being achieved by surgery (left high inguinal orchiectomy) and vincristine, adriamycin, and dexamethasone (VAD) chemotherapy.


Unilateral versus bilateral percutaneous vertebroplasty for osteoporotic vertebral compression fractures in elderly patients: A meta-analysis.
To contrast the effects and complications in unilateral and bilateral percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fractures in elderly patients. Multiple databases were adopted to search relevant studies, and the articles eventually satisfied the criteria were included. All the meta-analyses were conducted with the Review Manager 5.2. To estimate the quality of each article, risk of bias table was performed. Finally, 627 patients were enrolled in 9 studies and ultimately met the eligibility criteria. The unilateral and bilateral surgical samples were 314 and 313, respectively. The meta-analysis showed no significant difference in Visual Analog Scale/Score (VAS) (MD = -0.05, 95% confidence interval [CI] [-0.24, 0.13], P = .57), Oswestry Disability Index (ODI) score (MD = 0.03, 95% CI [-0.57, 0.62], P = .93) and cement leakage (OR = 1.00, 95% CI [0.67, 1.50], P = 1.00) between unilateral group and bilateral group. The surgery time of unilateral PVP is much less than that of bilateral PVP (MD = -8.42, 95% CI [-13.17, -3.66], P = .0005). Patients with bilateral PVP surgery have been injected more cement than patients with a unilateral surgery (MD = -2.56, 95% CI [-2.79, -2.33], P <.00001). This study demonstrated unipedicular approach is the preferred surgical technique for treatment of osteoporotic vertebral fracture (OVF) compared with bilateral PVP since unipedicular approach injects less cement and cost less surgery time.


Brain metabolism during short-term starvation in humans.
During prolonged starvation, brain energy requirements are covered in part by the metabolism of ketone bodies. It is unknown whether short-term starvation of a few days' duration may lead to reduced brain glucose metabolism due to the change toward ketone body consumption. In the present study we measured the cerebral metabolism of glucose and ketone bodies in nine healthy volunteers before and after 3.5 days of starvation. Regional glucose metabolism was measured by dynamic positron emission tomography using [18F]2-fluoro-2-deoxy-D-glucose. The mean value of K1* in gray and white matter increased by 12% (p < 0.05), whereas k2* and k3* were unchanged compared with control values. Regional glucose metabolism in cortical gray matter was reduced by 26% from 0.294 +/- 0.054 to 0.217 +/- 0.040 mumol g-1 min-1 (p < 0.001). White matter glucose metabolism decreased by 27% (p < 0.02). The decrease was uniform in gray and white matter with regional decreases ranging from 24 to 30%. A determination using Fick's principle confirmed the reduction in glucose metabolism yielding a decrease of 24% from 0.307 +/- 0.050 to 0.233 +/- 0.073 mumol g-1 min-1 (p < 0.05), whereas CBF did not change (0.57 +/- 0.07 vs. 0.57 +/- 0.06 ml g-1 min-1). The global net uptake of beta-hydroxybutyrate increased 13-fold from 0.012 +/- 0.024 to 0.155 +/- 0.140 mumol g-1 min-1 (p < 0.05). Net uptake of acetoacetate and net efflux of lactate and pyruvate did not change significantly during starvation. The present study shows that the human brain adapts to the changes in energy supply as early as 3 days following initiation of starvation, at which time ketone bodies account for approximately one-fourth of the cerebral energy requirements.


When priming persists: long-lasting implicit memory for a single episode in amnesic patients.
This experiment investigated the durability of implicit memory for a single episode in normal and amnesic subjects. The target materials consisted of sentence puzzles that were difficult to comprehend in the absence of a key word or phrase. Sentences were re-presented at delays ranging from one minute to one week, and implicit memory was indicated by facilitation in solving previously incomprehensible sentences on subsequent exposures. Patients with severe memory impairments on tests of explicit recall and recognition showed substantial and robust facilitation, or priming, from a single prior presentation and there was no evidence of a systematic decay of facilitation over retention intervals up to one week. The long-lasting implicit memory observed in the sentence puzzle task contrasts with previous findings of rapid decay of priming effects in amnesic patients.


Dynamic response of RNA editing to temperature in grape by RNA deep sequencing.
RNA editing is a post-transcriptional process of modifying genetic information on RNA molecules, which provides cells an additional level of gene expression regulation. Unlike mammals, in land plants, RNA editing converts C-to-U residues in organelles. However, its potential roles in response to different stressors (heat, salt, and so on) remains unclear. Grape is one of the most popular and economically important fruits in the world, and its production, like other crops, must deal with abiotic and biotic stresses, which cause reductions in yield and fruit quality. In our study, we tested the influence of the environmental factor temperature on RNA editing process in the whole mRNA from grape organelle. In total, we identified 122 and 627 RNA editing sites in chloroplast and mitochondria respectively with the average editing efficiency nearly ~ 60%. The analyses revealed that number of non-synonymous editing sites were higher than that of synonymous editing sites, and the amino acid substitution type tends to be hydrophobic. Additionally, the overall editing level decreased with the temperature rises, especially for several gene transcripts in chloroplast and mitochondria (matK, ndhB, etc.). We also found that the expression level of most PPR genes decreased with the temperature rises, which may contribute to the decline of RNA editing efficiency at high temperature. Our findings suggested that the RNA editing events were very sensitive to heat stress; the changes of amino acid in RNA editing genes may contribute to the stress adaption for grape.


Cyclic fatigue testing of denture teeth for bulk fracture.
Clinical experience with implant-supported dentures indicates that fracture and chipping of teeth are becoming an issue. Tooth fracture and chipping rates of approximately 2.5% per year are being experienced at one university. There has been no standardized test developed for bulk fracture or chipping of denture teeth. Such a test would aid in the development of improved teeth and in their evaluation. Central incisor teeth were embedded in acrylic and loaded on incisal edges at 90° to their long axes. Teeth tested included ones commercially available and two sets made from improved materials designed to increase toughness. Cyclic loading was done at 5Hz from 20N to 135N, 150N, 175N and 200N. Data was analyzed using lifetime analysis software fit at each of the accelerated loads and then extrapolated to clinical use loads (Alta 7, Reliasoft Corp.) Clinical use loads were derived from extrapolation of probability of failure (Pf) data to 2.5% Pf. When carefully embedded, teeth could be reproducibly loaded to failure by bulk fracture involving a failure mode similar to that seen clinically. Clinical use loads were calculated to be in the range of 70N. Results from accelerated loading could be fit to similar probability of failure distributions allowing extrapolation to clinical use loads. This work was able to develop a clinically valid bulk fracture test for the fatigue failure of incisor denture teeth. It appears that teeth fabricated with improved materials will be expected to perform better clinically. Thus both the null hypotheses were rejected.


DSP30 enhances the immunosuppressive properties of mesenchymal stromal cells and protects their suppressive potential from lipopolysaccharide effects: A potential role of adenosine.
Multipotent mesenchymal stromal cells (MSC) are imbued with an immunosuppressive phenotype that extends to several immune system cells. In this study, we evaluated how distinct Toll-like receptor (TLR) agonists impact immunosuppressive properties of bone marrow (BM)-MSC and explored the potential mechanisms involved. We show that TLR4 stimulation by lipopolysaccharide (LPS) restricted the ability of MSC to suppress the proliferation of T lymphocytes, increasing the gene expression of interleukin (IL)-1β and IL-6. In contrast, stimulation of TLR9 by DSP30 induced proliferation and the suppressive potential of BM-MSC, coinciding with reducing tumor necrosis factor (TNF)-α expression, increased expression of transforming growth factor (TGF)-β1, increased percentages of BM-MSC double positive for the ectonucleotidases CD39+CD73+ and adenosine levels. Importantly, following simultaneous stimulation with LPS and DSP30, BM-MSC's ability to suppress T lymphocyte proliferation was comparable with that of non-stimulated BM-MSC levels. Moreover, stimulation of BM-MSC with LPS reduced significantly the gene expression levels, on co-cultured T lymphocyte, of IL-10 and interferon (IFN)γ, a cytokine with potential to enhance the immunosuppression mediated by MSC and ameliorate the clinical outcome of patients with graft-versus-host disease (GVHD). Altogether, our findings reiterate the harmful effects of LPS on MSC immunosuppression, besides indicating that DSP30 could provide a protective effect against LPS circulating in the blood of GVHD patients who receive BM-MSC infusions, ensuring a more predictable immunosuppressive effect. The novel effects and potential mechanisms following the stimulation of BM-MSC by DSP30 might impact their clinical use, by allowing the derivation of optimal "licensing" protocols for obtaining therapeutically efficient MSC.


Detection of pregnancy specific protein SP-1 by enzyme immunoassay in early pregnancy.
Levels of pregnancy specific beta 1-glycoprotein (SP-1) were measured serially in serum by using enzyme immunoassay in 10 women after ovulation detected by LH-surge. Serum SP-1 levels rose at 13 and 20 days after the LH-surge.


Extracellular diffusion in laminar brain structures exemplified by hippocampus.
Numerous brain structures are composed of distinct layers and such stratification has a profound effect on extracellular diffusion transport in these structures. We have derived a more general form of diffusion equation incorporating inhomogeneities in both the extracellular volume fraction (α) and diffusion permeability (θ). A numerical solution of this equation for a special case of layered environment was employed to analyze diffusion in the CA1 region of hippocampus where stratum pyramidale occupied by the bodies of principal neurons is flanked by stratum radiatum and stratum oriens. Extracellular diffusion in the CA1 region was measured in vitro by real-time iontophoretic and real-time pressure methods, and numerical analysis found that stratum pyramidale had a significantly smaller extracellular volume fraction (α=0.127) and lower diffusion permeability (θ=0.327) than the other two layers (α=0.218, θ=0.447). Stratum pyramidale thus functioned as a diffusion barrier for molecules attempting to cross it. We also demonstrate that unless the detailed properties of all layers are taken into account when diffusion experiments are interpreted, the extracted apparent parameters of the extracellular space lose their physical meaning and capacity to describe any individual layer. Such apparent parameters depend on diffusion distance and direction, giving a false impression of microscopic anisotropy and non-Gaussian behavior. This finding has implications for all diffusion mediated physiological processes as well as for other diffusion methods including integrative optical imaging and diffusion-weighted magnetic resonance imaging.


Increased cerebrospinal fluid concentrations of C- but not N-terminal cholecystokinin fragments in multiple sclerosis.
The sulfated N-terminus and the carboxyamidated C-terminus of cholecystokinin octapeptide (CCK-8) were radioimmunoassayed in cerebrospinal fluid from 19 patients with multiple sclerosis (MS) and 17 control subjects. While the N-terminal immunoreactivity was normal in all phases of MS, the concentration of C-terminal CCK immunoreactivity was significantly increased from 3.7 +/- 0.3 to 7.9 +/- 1.0 pmol/l (mean +/- S.E.M.) in both progressive and stable phases. The results indicate that C-terminal forms of CCK are released at an increased rate or that increased amounts of CCK-8 are released together with enhanced aminopeptidase activity in MS.


Parsimonious item response theory modeling with the negative log-log link: The role of inflection point shift.
In item response theory (IRT) modeling, the magnitude of the lower and upper asymptote parameters determines the degree to which the inflection point shifts above or below P = 0.50. The current study examines the one-parameter negative log-log model (NLLM), which is characterized by a downward shift in the inflection point, among other distinctive psychometric properties. After detailing the statistical foundations of the NLLM, we present a series of simulation studies to establish item and person parameter estimation accuracy and to demonstrate that this parsimonious model addresses the "slipping" effect (i.e., unexpectedly incorrect answers) via an inflection point < 0.50 rather than through computationally difficult estimation of the upper asymptote. We then provide further support for these simulation results through empirical data analysis. Finally, we discuss how the NLLM contributes to recent methodological literature on the utility of asymmetric IRT models.


Romanow, Kirby and Courchene: Canada's health system--a moral or a business enterprise?
This paper examines Thomas Courchene's argument that Senator Kirby was closer to the truth than Commissioner Romanow when Kirby argued that Canada's healthcare system is only sustainable though introducing more private investment. The paper finds that Romanow's position, and indeed the nature of Canada's healthcare system, have been misrepresented by those seeking a larger private market share. The paper concludes the balance of evidence supports Ramanow, not Kirby.


Association between body image dissatisfaction and poor quality of life and depression among patients with hematopoietic stem cell transplantation.
This study aims to evaluate the association between body image dissatisfaction and quality of life and depression among patients after hematopoietic stem cell transplantation (HSCT). We conducted a cross-sectional survey at three university-based HSCT outpatient clinics and the Korea Blood Cancer Association. We assessed the body image using the body image scale; quality of life and depression were measured using the World Health Organization Quality of Life-BREF and the Patient Health Questionnaire 9, respectively. Univariate and multivariate linear regression models were used to find an association between body image, quality of life, and depression. Among 163 study participants, 71.8% were male, and the mean age of the participants was 48.3 (SD = 11.2). Over 70% of the participants reported that they felt less physically and sexually attractive due to HSCT, and 39.3% of the patients were dissatisfied with their body image. In fully adjusted models, patients with dissatisfied body image had significantly poorer quality of life (- 13.68, 95% confidence interval [CI] = - 18.16, - 9.21). Moreover, patients with body image dissatisfaction were 8.59 times (95% CI = 3.79, 19.48) more likely to have depressive symptoms than patients without it. The majority of HSCT patients experienced body image dissatisfaction, which was significantly associated with poor quality of life and depression. It would be essential to evaluate body image after HSCT and provide appropriate interventions for preventing further psychological consequences.


Endophthalmitis secondary to corneal sutures: series of delayed-onset keratitis requiring intravitreal antibiotics.
To describe 5 cases of endophthalmitis secondary to corneal sutures. Department of Ophthalmology, University College Hospital, Galway, Ireland. A retrospective review was done of 5 patients who presented over a period of 19 months with suture-related bacterial keratitis that progressed to endophthalmitis. Intravitreal antibiotics were used to control the infection. Despite intensive topical broad-spectrum antibiotic treatment for suture-related infective keratitis, the infection progressed to endophthalmitis in all 5 patients. Intravitreal antibiotics resolved the infection. Corneal sutures are a risk factor for infective keratitis irrespective of their site. Suture-related keratitis may progress rapidly to endophthalmitis despite intensive topical antibiotics. Intravitreal antibiotics are indicated when endophthalmitis is present.


Annotation of the Effect of Chemogenomic Compounds on Cell Health Using High-Content Microscopy in Live-Cell Mode.
The characterization of chemogenomic libraries with respect to their general effect on cellular health represents essential data for the annotation of phenotypic responses. Here, we describe a multidimensional high-content live cell assay that allows to examine cell viability in different cell lines, based on their nuclear morphology as well as modulation of small molecules of tubulin structure, mitochondrial health, and membrane integrity. The protocol monitors cells during a time course of 48 h using osteosarcoma cells, human embryonic kidney cells, and untransformed human fibroblasts as an example. The described protocol can be easily established and it can be adapted to other cell lines or other parameters important for cellular health.


[Complex treatment of patients with non-healing stomach ulcers using hyperbaric oxygenation].
The possibilities of local therapy used together with hyperbaric oxygenation were studied in patients with persistent gastric ulcers. The most effective in combined therapy of these patients was local administration of granulocyte concentrate and the use of hyperbaric oxygenation because of the action on the basic pathogenetic links such as impairment of the local and systemic microcirculation and pathological microflora.


Pharmacodynamics and drug therapy.
Medical pharmacology is the study of chemicals or drugs that interact with the human body. Knowledge of the molecular biology of drug action can enhance nursing practice and the provision of holistic patient care.


[Practical implications of the results of recent Soviet research concerning the prevention of cardiovascular diseases].
Data of two Soviet preventive studies, "Multifactorial prevention of coronary heart disease" and "Control of arterial hypertension in industrial workers", reported in 1985, are reviewed. There are data indicative of the role of arterial hypertension, smoking and hypercholesterolemia as coronary risk factors. The two preventive studies demonstrated a 20% and 21% decrease in total mortality, a 38% decrease in the incidence of myocardial infarction and a 70% decrease in the incidence of cerebral apoplexy. The success of the two programs is chiefly attributed to the control of arterial hypertension that has high prevalence among the population. Antismoking campaign can make an additional significant, even if moderate, contribution to the prevention of coronary disease within a multifactorial preventive effort.


Electrical lumped model for arterial vessel beds.
Numerous electrical analog models of the circulatory system have been proposed. However, conventional models are either too simple, focusing exclusively on heart function, or overly complex, characterizing arteries in excessive detail. The vessel beds, which comprise arteries, capillaries and veins, are well known to be responsible for most of the pressure drop in blood pressure and to dominate the draining of blood flow. Consequently, electrical analog models of the circulatory system should pay more attention to the vessel beds. This investigation divided the arterial system into several aortic segments with vessel beds, and proposed a model that used electrical lumped elements to represent the vessel beds. The model was adopted to simulate blood pressure propagation by considering each vessel bed as an isolated subsystem. The transfer function between the terminals of isolated subsystems was used to identify the electrical components of the lumped elements that characterized the vessel beds. Simulation results reveal that the compliance and impedance of the vessel beds are larger than in previous models that focused on the aorta or arteries. The proposed electrical lumped model could deal with much more information than the simple models due to the lumped element structure. Furthermore, its isolated subsystem approach also makes the proposed model significantly easier to use than the complex models.


Dissociable influences of reward and punishment on adaptive cognitive control.
To invest effort into any cognitive task, people must be sufficiently motivated. Whereas prior research has focused primarily on how the cognitive control required to complete these tasks is motivated by the potential rewards for success, it is also known that control investment can be equally motivated by the potential negative consequence for failure. Previous theoretical and experimental work has yet to examine how positive and negative incentives differentially influence the manner and intensity with which people allocate control. Here, we develop and test a normative model of control allocation under conditions of varying positive and negative performance incentives. Our model predicts, and our empirical findings confirm, that rewards for success and punishment for failure should differentially influence adjustments to the evidence accumulation rate versus response threshold, respectively. This dissociation further enabled us to infer how motivated a given person was by the consequences of success versus failure.


Bridged Analogues for p53-Dependent Cancer Therapy Obtained by S-Alkylation.
A small library of anticancer, cell-permeating, stapled peptides based on potent dual-specific antagonist of p53-MDM2/MDMX interactions, PMI-N8A, was synthesized, characterized and screened for anticancer activity against human colorectal cancer cell line, HCT-116. Employed synthetic modifications included: S-alkylation-based stapling, point mutations increasing hydrophobicity in key residues as well as improvement of cell-permeability by introduction of polycationic sequence(s) that were woven into the sequence of parental peptide. Selected analogue, ArB14Co, was also tested in vivo and exhibited potent anticancer bioactivity at the low dose (3.0 mg/kg). Collectively, our findings suggest that application of stapling in combination with rational design of polycationic short analogues may be a suitable approach in the development of physiologically active p53-MDM2/MDMX peptide inhibitors.


Toys in the upper aerodigestive tract: new evidence on their risk as emerging from the Susy Safe Study.
Foreign body (FB) inhalation, aspiration or ingestion are relatively common events in children. Despite many efforts made in several countries to achieve acceptable safety levels for consumer products devoted to children, small toys or toy parts are still frequently mentioned among risky foreign bodies. The aim of the present study is to characterize the risk of complications and prolonged hospitalization due to toys inhalation, aspiration or ingestion according to age and gender of patients, FB characteristics, circumstances of the accident, as emerging from the Susy Safe Registry. The Susy Safe Registry started in the 2005 to collect data to serve as a basis for a knowledge-based consumer protection activity. It is actually one of the wider databases collecting foreign body injuries in the upper aero-digestive tract in pediatric patients. It is distinguished by a deep characterization of objects which caused the injuries and a multi-step quality control procedure which assures its reliability. Preventive strategies imposing a regulation of industrial production, even if fundamental, are not sufficient and need to be integrated along with other intervention addressed to make aware caregivers toward a proper surveillance of children.


Phospholipid source and molecular species composition of 1,2-diacylglycerol in agonist-stimulated rat cardiomyocytes.
The aim was to investigate the consequences of simultaneous stimulation of phospholipase C and D by agonists for the molecular species composition of 1,2-diacylglycerol and phospholipids in cardiomyocytes. Serum-free cultured neonatal rat cardiomyocytes were stimulated by endothelin-1, phenylephrine or phorbolester. The molecular species of 1,2-diacylglycerol (in mol%) and those derived from phosphatidylcholine and phosphatidylinositol were analyzed by high-performance liquid chromatography and their absolute total concentration (nmol per dish) by gas-liquid chromatography. Phospholipids were labelled with [14C]glycerol or double-labelled with [14C]16:0 and [3H]20:4n6 for measurements of respectively, the amount of or relative rate of label incorporation into 1,2-diacylglycerol. The major molecular species of 1,2-diacylglycerol in unstimulated cells was found to be 18:0/20:4 (57 mol%). The same species was observed predominantly in phosphatidylinositol (73 mol% compared to 11 mol% in phosphatidylcholine). A significant decrease (about 10 mol%) was found for the 18:0/20:4 species of 1,2-diacylglycerol during stimulation (10-40 min) with endothelin-1 or phorbolester, but not phenylephrine. The results of the double-labelling experiments were consistent with the latter finding: the ratio [3H]20:4 over [14C]16:0 in 1,2-diacylglycerol decreased from 1.70 in the control to 1.40 during 10-min endothelin-1 or phorbolester stimulation, but not during phenylephrine stimulation. The [14C]glycerol incorporation into 1,2-diacylglycerol remained relatively constant under agonist-stimulated conditions as did the total concentration of 1,2-diacylglycerol. 1,2-Diacylglycerol present in unstimulated cardiomyocytes is likely derived from phosphatidylinositol. During stimulation with endothelin-1 and phorbolester, but not phenylephrine, phosphatidylcholine becomes an increasingly important source for 1,2-diacylglycerol due to sustained activation of phospholipase D. The 1,2-diacylglycerol level remains relatively constant during agonist stimulation which strongly indicates that particular molecular species of 1,2-diacylglycerol more than its total concentration determine the activation of protein kinase C isoenzymes.


Serodiagnosis of Lyme borreliosis infection using surface plasmon resonance.
Label-free biosensors are ideally suited for the direct monitoring of binding events without the need for additional labeling substances; however, their application in the field of serodiagnosis is not trivial. The major problem is the unspecific adsorption of blood serum components to the sensor surface. A surface plasmon resonance (SPR) sensor has been used for the direct detection of Lyme borreliosis specific antibodies in blood serum. The combination of an optimal dilution factor with the addition of suitable detergents minimizes the unspecific adsorption. Serum samples from healthy donors and infected patients have been analyzed and the results were compared with a certified immunoassay and a western blot. A serum dilution of 1:20 in HBS-buffer with 0.05% Tween20 and 1 mg/mL carboxymethyl dextran reduces unspecific adsorption significantly and enables the identification of antibodies against the OspC/pepC10 antigen pair with a sensitivity of 92% and that against the VlsE/C6 pair with 81% sensitivity; the specificities are 82% and 86% respectively. Positive hits in the western blot could also be determined in the SPR-assay with a correlation of 96.5%. The presented optical label-free technique has the potential for a precise and fast identification of pathogen-specific antibodies without the need for a secondary labeling antibody.


Optical Absorption of Atomically-Precise Sn14 Nanoclusters: The Antagonistic Interplay of Ligand Stabilization, Molecular Symmetry, and Solvatochromism.
The synthesis of atomically precise clusters is nowadays well established. The study of isolated clusters in the gas phase has also become an approved field of research. Although both approaches examine the same research objects, namely nanoclusters, little is known about to what extent results from gas phase studies can be transferred to colloidal systems and vice versa. In particular, it is not yet sufficiently understood how ligands influence the geometric and electronic structure of clusters from an experimental point of view. By comparing a ligand-stabilized tin nanocluster in solution with an isolated species in the gas phase and considering different geometric arrangements with the same number of tin atoms, the impacts of ligand stabilization, molecular symmetry, and solvatochromism on the optical behavior are thoroughly worked out for the first time.


Sensitivity of the association between increased lung cancer risk and bitumen fume exposure to the assumptions in the assessment of exposure.
A multi-centre IARC-coordinated European cohort study provided evidence of an association between lung cancer risk and bitumen fume exposure. Sensitivity analyses were conducted to assess whether these associations were robust to assumptions in the exposure assessment for which support could not be obtained due to lack of either measurements or direct observations. New exposure estimates were generated by changing assumptions on exposure levels, specific tasks, lags, and coal tar use. Subsequently, Poisson regression models estimated relative risks (RRs); change in fit of models was evaluated. The influence of these assumptions was minimal, with log-likelihood deviations between -5.0 and 4.7% and similar patterns in dose-dependent increases of lung cancer risk. In the highest exposure categories, point estimates of RRs ranged 2.07-2.83 for average, and 1.22-2.23 for cumulative exposure. The small increase in lung cancer risk associated with bitumen fume exposure depends only to a limited extent on the subjective judgments made in the exposure assessment for this cohort.


Carbon ion radiotherapy boosts anti-tumour immune responses by inhibiting myeloid-derived suppressor cells in melanoma-bearing mice.
Numerous studies have shown that carbon ion radiotherapy (CIRT) induces anti-cancer immune responses in melanoma patients, yet the mechanism remains elusive. The abundance of myeloid-derived suppressor cells (MDSC) in the tumour microenvironment is associated with therapeutic efficacy and disease outcome. This study analysed the changes in the immune contexture in response to the carbon ion treatment. The murine melanoma B16, MelanA, and S91 tumour models were established in syngeneic immunocompetent mice. Then, the tumours were irradiated with carbon ion beams, and flow cytometry was utilised to observe the immune contexture changes in the bone marrow, peripheral blood, spleen, and tumours. The immune infiltrates in the tumour tissues were further assessed using haematoxylin/eosin staining and immunohistochemistry. The immunoblot detected the expression of proteins associated with the JAK/STAT signalling pathway. The secretion of immune-related cytokines was examined using ELISA. Compared to conventional radiotherapy, particle beams have distinct advantages in cancer therapy. Here, the use of carbon ion beams (5 GyE) for melanoma-bearing mice was found to reduce the population of MDSC in the bone marrow, peripheral blood, and spleen of the animals via a JAK2/STAT3-dependent mechanism. The percentage of CD3+, CD4+, CD8+ T cells, macrophages, and natural killer cells increased after radiation, resulting in reduced tumour growth and prolonged overall survival in the three different mouse models of melanoma. This study, therefore, substantiated that CIRT boosts anti-tumour immune responses via the inhibition of MDSC.


Effect of sleep deprivation on the performance of simulated laparoscopic surgical skill.
Resident work hours may impact patient care. We hypothesized that "call-associated" acute sleep deprivation has no effect on technical dexterity as measured on a minimally invasive surgery trainer, virtual reality (MIST VR) surgical simulator. Thirty-five surgical residents were prospectively evaluated pre-call (rested), on-call (rested), and post-call (acutely sleep deprived). Participants completed questionnaires regarding sleep hours and level of fatigue. Technical skill was assessed using the MIST VR. Speed, errors, and economy of motion were automatically recorded by the MIST VR computer simulator. Data were analyzed by paired Student t test and analysis of variance. Estimated hours of sleep and subjective indicators of fatigue were different between rested and sleep-deprived residents. The number of errors and time to complete all tasks increased at the post-call assessment. Resident work schedules lead to sleep deprivation and fatigue. Call-associated sleep deprivation and fatigue are associated with increased technical errors in the performance of simulated laparoscopic surgical skills.


Pseudohermaphroditism in Ilyanassa obsoleta (Mollusca: Neogastropoda).
Field studies, a rearing and maintenance program, and a transfer experiment have shown that anomalous male traits found in some female Ilyanassa obsoleta are an expression of environmentally controlled psuedohermaphroditism. The particular pattern of pseudohermaphroditism discovered in this species has not been reported previously from any other group, but may be characteristic of the Neogastropoda.


Dimethyl 3,3'-[(4-nitro-phen-yl)methyl-ene]bis-(1H-indole-2-carboxyl-ate) ethanol hemisolvate.
There are two main molecules in asymmetric unit of the title compound, C27H21N3O6·0.5C2H5OH. In both, the indole ring systems are approximately perpendicular to each other, at dihedral angles of 69.3 (5) and 82.8(4)°. In the crystal, mol-ecules are linked by N-H⋯O and O-H⋯O hydrogen bonds into a three-dimensional supra-molecular architecture. The solvent ethanol mol-ecule acts as a donor, forming an O-H⋯O hydrogen bond, reinforcing the structure.


Composition and key-influencing factors of bacterial communities active in sulfur cycling of soda lake sediments.
Bacteria are important participants in sulfur cycle of the extremely haloalkaline environment, e.g. soda lake. The effects of physicochemical factors on the composition of sulfide-oxidizing bacteria (SOB) and sulfate-reducing bacteria (SRB) in soda lake have remained elusive. Here, we surveyed the community structure of total bacteria, SOB and SRB based on 16S rRNA, soxB and dsrB gene sequencing, respectively, in five soda lakes with different physicochemical factors. The results showed that the dominant bacteria belonged to the phyla Proteobacteria, Bacteroidetes, Halanaerobiaeota, Firmicutes and Actinobacteria. SOB and SRB were widely distributed in lakes with different physicochemical characteristics, and the community composition were different. In general, salinity and inorganic nitrogen sources (NH4+-N, NO3--N) were the most significant factors. Specifically, the communities of SOB, mainly including Thioalkalivibrio, Burkholderia, Paracoccus, Bradyrhizobium, and Hydrogenophaga genera, were remarkably influenced by the levels of NH4+-N and salinity. Yet, for SRB communities, including Desulfurivibrio, Candidatus Electrothrix, Desulfonatronospira, Desulfonatronum, Desulfonatronovibrio, Desulfonatronobacter and so on, the most significant determinants were salinity and NO3--N. Besides, Rhodoplanes played a significant role in the interaction between SOB and SRB. From our results, the knowledge regarding the community structures of SOB and SRB in extremely haloalkaline environment was extended.


Estimations of dietary vitamin D requirements in black and white children.
The Institute of Medicine (IOM) dietary guidelines for vitamin D are based on limited pediatric data. Our objective was to estimate the dietary vitamin D requirements for maintaining serum 25-hydroxyvitamin D [25(OH)D] concentrations at the various IOM-considered thresholds of vitamin D status (12, 16, and 20 ng/ml) during fall and winter in children. Ninety-six healthy 8- to 14-y-old Pittsburgh-area black and white children enrolled in a randomized, placebo-controlled trial of vitamin D3 1,000 IU daily for 6 mo with baseline and 2-mo follow-up assessments completed during October through April were studied. Vitamin D intake from diet and study supplement adjusted for adherence and serum 25(OH)D were measured. The vitamin D intakes needed to maintain serum 25(OH)D concentrations at 12, 16, and 20 ng/ml in 90% of the children were 581, 1,062, and 1543 IU/day, respectively. The estimated vitamin D intakes needed to maintain serum 25(OH)D concentrations at 20 ng/ml in 97.5% of the children was 2,098 IU/day. Our data suggest that the current vitamin D recommended dietary allowance (RDA) (600 IU/day) is insufficient to cover the skeletal health needs of at least 50% of black and white children.


GABA modulates the release of dopamine and acetylcholine from rat caudate nucleus slices.
The effects of GABA on depolarization-induced (26 mM K+) release of radiolabeled dopamine (DA) and acetylcholine (ACh) from slices of rat caudate nucleus were examined with a superfusion method. GABA, in concentrations of 10(-5)--10(-3) M, dose-dependently enhanced the release of DA, either accumulated by high-affinity uptake or synthesized from 14-C-tyrosine. In contrast, the release of ACh was reduced by GABA. This reduction appeared to be caused by the increase in DA-release. These effects of GABA decreased from the caudal to rostral part within the caudate nucleus, an order which parallels the distribution of endogenous GABA and glutamic acid decarboxylase. However, GABA had little, if any, effect in the nucleus accumbens. Since it was difficult to antagonize the effects of GABA on DA and ACh release with bicuculline or picrotoxin, it remains uncertain whether these effects were mediated via GABA receptors. In view of the high endogenous GABA level in the caudate nucleus it is concluded that GABA may be one of the local factors involved in the control of the amount of transmitter that will be released from dopaminergic varicosities upon depolarization.


New species and records of Otiothopinae from the Southern Atlantic Rainforest, with notes on the claw tufts in Fernandezina Birabén (Araneae: Palpimanidae).
Two new species of Otiothops MacLeay, 1839 (O. atalaia sp. n. and O. goytacaz sp. n.), a new species of Fernandezina Birabén, 1951 (F. jurubatiba sp. n.) as well as the female of F. tijuca Ramírez & Grismado, 1996 are described from the Atlantic Rainforest of southeastern Brazil, in the state of Rio de Janeiro. Scanning electron microscope images of the tarsi of F. jurubatiba sp. n. and F. dasilvai Platnick, Grismado & Ramírez, 1999 show that this genus has claw tufts on the posterior legs, composed of setae of variable structure.


Increasing saltiness of salts (NaCl) using mid-infrared radiation to reduce the health hazards.
Table salt, rock salt, and iodized salts (composed principally of NaCl) are commonly used in many areas, such as medicine, cooking, industry, or personal care. Common fried, salty, and spicy foods contain an excess of added salt, which has detrimental health effects, especially on the kidneys. Our research aims to enhance the inherent saltiness of these three salts, which would reduce intake and thereby minimize salt's health hazards. We invented a water-based 2-6 μm of Mid-Infrared Generating Atomizer (MIRGA), which, when applied to salts, caused changes in the salts' chemistry and enhanced saltiness, thus allowing the reduction of salt intake by 25%-30%. This easy-to-use technology did not show any side effects. MIRGA was found to have enhanced the saltiness, thus allowing the reduction of salt intake by 25%-30%. MIRGA is safe, portable, highly economical, unique in the mid-IR laser technology, and possesses vast research scope in other areas of food science.


Demonstration of specific antibodies in the central nervous system of horses naturally infected with Borna disease virus.
From 18 horses with clinical symptoms of an affection of the central nervous system and with histopathologic alterations in the brain, four were demonstrated to have Bornavirus-specific antibodies. The antibodies are monospecific, recognizing identical antigens from infected brains of different animal species as well as from persistently infected tissue culture cells. Discrete immunoglobulin species (oligoclonal IgG) can be demonstrated in concentrated horse cerebrospinal fluid; they carry Bornavirus antibody specificity. Their presence, together with the higher antibody titers in the cerebrospinal fluid as compared to those in the serum, indicate that in these natural Bornavirus infections local antibody production occurred in the central nervous system.


Ibuprofen, zomepirac, aspirin, and placebo in the relief of postepisiotomy pain.
Our purpose was to compare the analgesic efficacy of single oral doses of ibuprofen, zomepirac, aspirin, and placebo in severe postepisiotomy pain. One hundred twenty subjects participated in a double-blind, single-dose, parallel-group, 4-hr trial comparing 400 mg ibuprofen, 100 mg zomepirac sodium, 600 mg aspirin, and placebo. For most parameters, including the sum of the pain intensity differences (SPID) and the sum of the hourly pain relief values (TOTAL), which are summary variables, each of the drugs was more effective than placebo. Ibuprofen was more effective than aspirin and zomepirac. Zomepirac and aspirin were equally effective for most of the analgesic variables. There were no adverse effects. Ibuprofen, 400 mg, is an effective oral analgesic and is more effective than 100 mg zomepirac and 600 mg aspirin in most parameters of pain.


Graft-versus-tumor effect according to type of graft-versus-host disease defined by National Institutes of Health consensus criteria and associated outcomes.
The impact of National Institutes of Health consensus criteria (NCC) graft-versus-host disease (GVHD) on survival has rarely been investigated in a large cohort of patients with GVHD presenting before and after day 100 posttransplantation. We retrospectively investigated 775 patients who underwent allogeneic stem cell transplantation and assessed the GVHD effects on survival by the time-dependent covariates in Cox proportional hazards regression models. Using the NCC, the patients were classified into 4 groups: (1) no GVHD (n = 251); (2) acute GVHD (aGVHD) only (n = 199), including 26 patients with late aGVHD; (3) classic chronic GVHD (cGVHD; n = 232); and (4) overlap syndrome (OS; n = 93). Multivariate analyses showed that classic cGVHD (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.27-0.77) and OS (HR, 0.52; 95% CI, 0.28-0.96) were associated with significantly decreased risk of relapse, whereas aGVHD only was not associated with relapse rate (HR, 1.11; 95% CI, 0.76-1.63). All aGVHD events, including the period of aGVHD in patients who developed cGVHD after aGVHD, also did not affect the risk of relapse (HR, 0.74; 95% CI, 0.49-1.12). All types of GVHD were significantly associated with higher nonrelapse mortality in common. Finally, patients with aGVHD only had significantly lower overall survival and disease-free survival compared with those without GVHD, in contrast to favorable survival outcomes in patients with cGVHD without previous aGVHD. This study demonstrates that NCC GVHD type is associated with different graft-versus-tumor effects. Further studies are needed to investigate risk factors, pathogenesis, and biomarkers for each type of NCC GVHD.


Pediatric residents' simulation-based training in patient safety during sedation.
In Israeli emergency departments, pediatric residents are allowed to independently perform procedural sedation after training. Preparing the residents to practice unsupervised sedations requires participation in a simulation-based training in patient safety during sedation (STPSDS). The study objective was to evaluate participants' perception of knowledge and confidence from the STPSDS. We performed a retrospective analysis of participants' self-reported perception of knowledge acquisition. At the end of each course, participants were requested to rate, anonymously and independently, the training contribution to their knowledge and confidence using a four-point Likert scale. Between January 2010 and December 2017, 321 pediatric residents participated in 67 STPSDS courses; 315 completed the self-assessments. Participants' median responses of the training contribution were 4 (IQR 3-4) for overall knowledge, 4 (IQR 4-4) for understanding potential complications during sedation, 3 (IQR 3-4) for knowledge in managing adverse events, and 3 (IQR 2-4) for knowledge in practicing safe sedation. Median response for contribution to participants' confidence in performing sedation was 3 (IQR 3-4).Conclusion: We found that the STPSDS improved perception of knowledge and confidence among pediatric residents. Our findings suggest that this training has a valuable role in preparing pediatric residents to practice unsupervised sedations in the ED. What is Known: • In Israel, sedation-trained pediatric residents performed sedations in the Emergency Department • Successful completion of a simulation-based training in patient safety during sedation (STPSDS) is a mandatory requirement to perform unsupervised sedation. What is New: • The STPSDS improved perception of knowledge and confidence among pediatric residents. • This training may be valuable in preparing pediatric residents to practice unsupervised sedations.


Obstetric emergency simulation training course: experience of a private-public partnership in Brazil.
Lack of skills on how to diagnose and manage obstetric emergencies contribute to substandard institutional care and preventable maternal deaths in Brazil. Simulation-based obstetric emergency team training can reduce adverse maternal outcomes. However, this type of training is expensive and not widely available, especially in low resource settings. We present the experience of a private-public partnership that offered a two-day obstetric emergency simulation-training course to hundreds of Brazilian professionals working in the public sector. We also present participants´ short-term learning outcomes (Kirkpatrick's level 2) and satisfaction (Kirkpatrick's level 1). This was a non-experimental before-and-after study. The free 16-h course was held over a 14 months period in a large private hospital's simulation center using multidisciplinary scenario and model-based training. The training sessions consisted of four (4-h) modules on pre-eclampsia/eclampsia, hemorrhage, sepsis and resuscitation. An anonymous questionnaire collected participants´ satisfaction at the end of each module. Learning outcomes were assessed by comparing differences in participants´ pre- versus immediate post-course test scores. Wilcoxon, Kruskal-Wallis and Friedman tests were used for statistical analyses. P < 0.05 was considered significant. 340 professionals (117 doctors, 179 registered nurses-RN and 44 licensed practical nurses-LPN) working in 33 public Brazilian hospitals were trained. There was a significant increase in post-course test scores in all four modules. On average, scores increased 55% in the hypertension and 65-69% in the hemorrhage, sepsis and resuscitation modules (p = 0.019). Knowledge acquisition of RN and LPN was similar in the hypertension, hemorrhage and sepsis modules and significantly higher than doctors´ (p < 0.05). On a 0 to 10 scale, mean overall satisfaction ranged from 9.6 (for the hypertension module) to 9.8 (for the resuscitation module). This successful experience of a private-public partnership to offer obstetric emergency simulation training required strategic organization and a strong commitment from both sides. This promising private-public partnership model could be replicated in similar settings. The training course obtained high satisfaction scores and significantly improved the knowledge of public-sector health professionals on how to manage the main causes of maternal mortality.


A preventive intervention program in adolescent schoolgirls: a longitudinal study.
To explore the impact of a prevention program on the eating and body attitudes of a sample of adolescent schoolgirls. The program involved lessons and group discussions of general adolescent problems and eating disorders. A total of 254 16-year-old schoolgirls were evaluated, of whom 154 participated in the program and a further 154 subjects formed the control group. Variations in weight, Eating Attitudes Test and Eating Disorders Inventory at a 1-year follow-up were compared for the two groups. Among high-risk subjects, no significant differences were found between the prevention and the control group. The preventive program appeared to reduce significantly body dissatisfaction and to decrease the risk of bulimic attitudes in low-risk subjects. Providing schoolgirls with the correct information about eating disorders did not encourage unhealthy attitudes to eating and weight regulation practices. However, for high-risk subjects more intensive and specific intervention may be required, for which further research is needed.


Parallel insertion endoscopic technique for precise catheter placement in cystic craniopharyngiomas.
Total removal of craniopharyngioma is the most acceptable therapeutic modality; however, there are cases in which radical excision is not possible. To reduce the cystic component volume, an Ommaya reservoir catheter can be placed endoscopically. However, there are certain complications and risks with this type of maneuver, such as misplacement of the catheter, which may result in leakage of cyst contents or installed fluids such as bleomycin. Thus, accurate placement of intracystic catheter is extremely important. The authors placed Ommaya reservoir catheters running over the outer surface of a transparent endoscopic sheath in three cases. This neuroendoscopic procedure permits easier manipulation of the catheter and precise placement of the catheter tip. This technique was useful for placement of Ommaya reservoir catheters. This new technique of catheter placement with neuroendoscopy is more accurate, safer, and less invasive.


Regulation of magnesium reabsorption in DCT.
The distal convoluted tubule (DCT) is the shortest segment of the nephron and consists of an early (DCT1) and late part (DCT2). Here, several transport proteins, like the thiazide-sensitive NaCl cotransporter (NCC) and the epithelial magnesium (Mg(2+)) channel (TRPM6), are exclusively expressed. This makes the DCT the major site of active transcellular Mg(2+) reabsorption determining the final excretion in the urine. Following the Mg(2+) influx via the apically localized TRPM6, intracellular Mg(2+) diffuses to the basolateral membrane where it is extruded to the blood compartment via still-unidentified Mg(2+) transporters. Recent years have witnessed multiple breakthroughs in the field of transcellular Mg(2+) reabsorption. Epidermal growth factor and estrogen were identified as magnesiotropic hormones by their effect on TRPM6 activity. Intracellularly, receptor of activated protein kinase C 1 and adenosine triphosphate were shown to inhibit TRPM6 activity through its alpha-kinase domain. Furthermore, dysregulation or malfunction of transcellular Mg(2+) reabsorption in DCT has been associated with renal Mg(2+) wasting. Mutations in TRPM6 are responsible for hypomagnesemia with secondary hypocalcemia. A defect in the gamma-subunit of the Na(+)/K(+)-adenosine triphosphatase causes isolated dominant hypomagnesemia resulting from renal Mg(2+) wasting. Moreover, in Gitelman's syndrome, mutations in NCC also result in impaired transcellular Mg(2+) reabsorption in DCT. This review highlights our recently obtained knowledge concerning the molecular regulation of transcellular Mg(2+) reabsorption.


Adenosine A1 and dopamine d1 receptor regulation of AMPA receptor phosphorylation and cocaine-seeking behavior.
AMPAR (α-amino-3-hydroxy-5-methylisoxazole-4-propionate glutamate receptor) stimulation in the nucleus accumbens (NAc) is critical in cocaine seeking. Here, we investigate the functional interaction between D1 dopamine receptors (D1DR) and AMPARs in the NAc, and explore how A1 adenosine receptor (A1AR) stimulation may reduce dopamine-induced facilitation of AMPARs and cocaine seeking. All animals were trained to self-administer cocaine and were tested for reinstatement of cocaine seeking following extinction procedures. The role of AMPARs in both AMPA- and D1DR-induced cocaine seeking was assessed using viral-mediated gene transfer to bi-directionally modulate AMPAR activity in the NAc core. The ability of pharmacological AMPAR blockade to modulate D1DR-induced cocaine seeking also was tested. Immunoblotting was used to determine whether stimulating D1DR altered synaptic AMPA GluA1 phosphorylation (pGluA1). Finally, the ability of an A1AR agonist to modulate D1DR-induced cocaine seeking and synaptic GluA1 receptor subunit phosphorylation was explored. Decreasing AMPAR function inhibited both AMPA- and D1DR-induced cocaine seeking. D1DR stimulation increased AMPA pGluA1(S845). Administration of the A1AR agonist alone decreased synaptic GluA1 expression, whereas coadministration of the A1AR agonist inhibited both cocaine- and D1DR-induced cocaine seeking and reversed D1DR-induced AMPA pGluA1(S845). These findings suggest that D1DR stimulation facilitates AMPAR function to initiate cocaine seeking in D1DR-containing direct pathway NAc neurons. A1AR stimulation inhibits both the facilitation of AMPAR function and subsequent cocaine seeking, suggesting that reducing AMPA glutamate neurotransmission in direct pathway neurons may restore inhibitory control and reduce cocaine relapse.


Focal nodular hyperplasia of the liver and oral contraceptives.
The increased incidence of liver tumors in women of childbearing age who have been using oral contraceptives for many years suggests an environmental causation. The causative agent may be the steroidal oral contraceptives. Two lesions are recognized: focal nodular hyperplasia and hepatic adenoma. This paper concentrates on focal nodular hyperplasia, with two cases added to the four previously described cases. It is postulated that the estrogen component causes vascular lesions characterized by myointimal hyperplasia and thrombosis, leading to infarct, necrosis, and subsequent nodular hepatic regeneration. The clinical feature highlighted is the long history of gastrointestinal disturbance associated with negative gastrointestinal investigation with the possible exception of cholelithiasis. It is suggested that gray-scale ultrasonography is an effective screening method that also aids in a definitive diagnosis. As these tumors are often incidental findings it is emphasized that the liver should always be inspected at laparoscopy. Ultimately, diagnosis by biopsy or excision is essential as it may well be possible to treat cases of focal nodular hyperplasia of the liver conservatively, once oral contraceptives have been discontinued.