Crosstalk between high-molecular-weight adiponectin and T-cadherin during liver fibrosis development in rats.
Adiponectin, a circulating adipocyte-derived secretory protein, reportedly plays an important role in liver fibrosis development, although the biological role of adiponectin in liver fibrogenesis is still controversial. Adiponectin is present in the serum as three oligometric complexes; namely, high-, middle-, and low-molecular weight (HMW, MMW, and LMW, respectively). Adiponectin exerts different biological activities in an oligomerization-dependent manner. The aim of our current study was to examine the alteration of each isoform of adiponectin and its receptors (AdipoR1, AdipoR2, and T-cadherin) during the choline-deficient L-amino acid-defined (CDAA) diet-induced rat liver fibrosis development. We also elucidated the methylation status of all receptors. The serum level of total adiponectin significantly increased during the liver fibrosis development. Among the three isoforms, only HMW adiponectin was significantly up-regulated whereas MMW and LMW were not. The expression of T-cadherin, which exclusively binds with HMW adiponectin, was significantly augmented as well. The AdipoR2 expression was markedly decreased and showed no marked difference from that of AdipoR1. No obvious methylation change was observed in all three receptors, suggesting that another mechanism is involved in the alteration of receptor gene expression. Collectively, since the specific ligand and receptor were augmented together, crosstalk between HMW adiponectin and T-cadherin may play an important role during liver fibrosis development in rats.


CCR2 is localized in microglia and neurons, as well as infiltrating monocytes, in the lumbar spinal cord of ALS mice.
It remains controversial whether circulating monocytes expressing CCR2 infiltrate the central nervous system (CNS) and contribute to pathogenicity of amyotrophic lateral sclerosis (ALS). A previous report used conventional immunohistochemistry to show that CCR2 is exclusively expressed by astrocytes, but not infiltrating monocytes/microglia or neurons, in the spinal cords of ALS model mice. In this study, we assessed the cellular distribution of CCR2 in the CNS of ALS mice using CCR2-reporter mice (Ccr2rfp/+-Cx3cr1gfp/+-SOD1G93A Tg mice), a more sophisticated method for directly detecting the distribution of CCR2 protein. We found that infiltration of CCR2+ monocytes in the lumbar spinal cord increased over the course of disease progression. Moreover, from the middle stage of disease, CCR2 was partially distributed in microglia and neurons, but not astrocytes, in striking contrast to the previous findings. These novel observations suggested that CCR2+ monocyte infiltration leads to CNS environmental deterioration due to toxic conversion of microglia and neurons, creating a vicious cycle of neuroinflammation and leading to acceleration of ALS pathology. Our findings also show that this reporter mouse is a useful and powerful tool for obtaining new insights into the pathomechanisms of ALS.


Adhesive systems used for sealing contaminated surfaces: a microleakage evaluation.
The aim of this study was to compare two adhesive systems (OptiBond FL and OptiBond SOLO) used as a sole material for sealing pit and fissures on contaminated surfaces with respect to microleakage. After acid etching, 56 sound teeth were contaminated with 1microl of plasma and randomly divided into 8 groups (n = 7). The adhesives were light activated under two conditions (Optilux VCL-403 and VCL-500) for 30 s. Each specimen was exposed to one of the following aging treatments: thermal (4,000 X at 5-55 degrees C for 60 s) plus load cycling (225,000 X with 83.3 N) or thermal plus load and pH cycling (mineralizing/demineralizing solutions). Then, they were immersed in a 50% AgNO3 aqueous solution, sectioned twice and had dye penetration measured through digitized images. ANOVA methods were used to assess the main effects of the factors as well as their interactions. The results indicated a significant difference between the adhesive systems (p < 0.05), suggesting that OptiBond FL has a better performance with respect to microleakage and could be used as a sealing material in accidentally moist or contaminated surfaces.


Platelet and leukocyte activation, atherosclerosis and inflammation in European and South Asian men.
Increased platelet activation occurs in ischemic heart disease (IHD), but increased platelet activation is also seen in cerebrovascular atherosclerosis and peripheral artery disease. It is not clear therefore whether platelet activation is an indicator of IHD or a marker of generalized atherosclerosis and inflammation. South Asian subjects are at high risk of IHD, but little is known regarding differences in platelet and leukocyte function between European and South Asian subjects. Fifty-four male subjects (age 49-79 years) had coronary artery calcification measured by multislice computed tomography (CT), aortic atherosclerosis assessed by measurement of carotid-femoral pulse wave velocity (aortic PWV), and femoral and carotid atherosclerosis measured by B-mode ultrasound. Platelet and leukocyte activation was assessed by flow cytometry of platelet-monocyte complexes (PMC), platelet expression of PAC-1 binding site and CD62P, and expression of L-selectin on leukocytes. Elevated circulating PMC correlated significantly with elevated aortic PWV and PMC were higher in subjects with femoral plaques. In contrast PMC did not differ by increasing coronary artery calcification category or presence of carotid plaques. Higher numbers of PMC were independently related to elevated levels of C-reactive protein (CRP), higher aortic PWV, hypertension and smoking in a multivariate model. Markers of platelet and leukocyte activation did not differ significantly by ethnicity. Increased PMC are related to the extent of aortic and femoral atherosclerosis rather than coronary or carotid atherosclerosis. The association between elevated CRP and increased PMC suggests that inflammation in relation to generalized atherosclerosis may play an important role in PMC activation.


Using virtual reality to target positive autobiographical memory in individuals with moderate-to-moderately severe depressive symptoms: A single case experimental design.
So far, several aspects of autobiographical memory (AM) have been found to be impaired in depression. Among others, depressed patients show the tendency to recall more negative than positive events (i.e., negative bias) and usually retrieve memories that lack of specificity and details (i.e., overgeneral memories). Based on this, we designed an AM task enhanced by the use of virtual reality (VR) to specifically train the recall of positive memories. Using a single-case, multiple baseline experimental design, we explored the effects of a brief intervention consisting of two sessions of this training in a sample of 18 individuals with moderate-to-moderately severe depressive symptoms. According to the results, changes occurred at the short term only. In particular, almost all participants reported a significant improvement in at least one outcome measure 0-3 days after the intervention. However, these clinical gains were not maintained in the mid-term (from day 4 to 10). The present findings do not support the efficacy of our VR-based AM recall treatment as a standalone intervention. Nevertheless, it might represent a suitable procedure to obtain immediate and/or short-term improvements. It might also serve as a valid component to be integrated in broader protocols for patients with moderate-to-moderately severe depressive symptoms.


Amniotic fluid norepinephrine concentration as an indicator of fetal sympathetic nervous activity. Effect of pregnancy complications.
The concentrations of norepinephrine in amniotic fluid and maternal plasma were measured in 71 third trimester pregnancies, 31 of which were uncomplicated and 40 complicated. The amniotic fluid norepinephrine concentration (mean +/- SD) in cases of hypertension treated with clonidine (0.4 +/- 0.1 ng/ml, n = 12) and in insulin-dependent diabetes (0.5 +/- 0.2 ng/ml, n = 7) was lower, and in renal insufficiency (1.7 +/- 0.8 ng/ml, n = 8) higher than in control subjects (0.7 +/- 0.4 ng/ml, n = 31). In fetal-growth retardation (0.6 +/- 0.2 ng/ml, n = 8) and in latent diabetes (0.7 +/- 0.2 ng/ml, n = 5) the values were similar to those in the control subjects. There was a significant positive correlation between mature lecithin-sphingomyelin (L/S) ratio and norepinephrine concentration. Clonidine-treated hypertension was associated with decreased (0.2 +/- 0.1 ng/ml) and renal insufficiency with increased (0.9 +/- 0.7 ng/ml) maternal plasma norepinephrine concentrations (control group, 0.3 +/- 0.1 ng/ml). The present results indicate that measurement of catecholamines in amniotic fluid can be useful in the evaluation of fetal sympathoadrenal function.


Synthesis of novel estrogen receptor antagonists using metal-catalyzed coupling reactions and characterization of their biological activity.
Estrogen receptor (ER) antagonists are valuable in the treatment of ER-positive human breast cancer. In this study, we designed and synthesized nine new derivatives of 17β-estradiol (E2) with a bulky side chain attached to its C-7α position, and determined their ER antagonistic activity using in vitro bioassays. Four of the derivatives showed a strong inhibition of ERα transactivation activity in a luciferase reporter assay and blocked ERα interactions with coactivators. Similarly, these derivatives also strongly inhibited the growth of the ERα-positive human breast cancer cells. Computational docking analysis was conducted to model the interaction of these antagonists with the human ERα and showed that they could tightly bind to the ERα in a manner similar to that of ICI-182,780, a pure ER antagonist. These results provide an example that attachment of a bulky side chain to the C-7α position of E2 can produce ER antagonists with ER affinity comparable to that of ICI-182,780.


Plasma-Induced Surface Modification of Sapphire and Its Influence on Graphene Grown by Plasma-Enhanced Chemical Vapour Deposition.
In this work, we study the influence of the different surface terminations of c-plane sapphire substrates on the synthesis of graphene via plasma-enhanced chemical vapor deposition. The different terminations of the sapphire surface are controlled by a plasma process. A design of experiments procedure was carried out to evaluate the major effects governing the plasma process of four different parameters: i.e., discharge power, time, pressure and gas employed. In the characterization of the substrate, two sapphire surface terminations were identified and characterized by means of contact angle measurements, being a hydrophilic (hydrophobic) surface and the fingerprint of an Al- (OH-) terminated surface, respectively. The defects within the synthesized graphene were analyzed by Raman spectroscopy. Notably, we found that the ID/IG ratio decreases for graphene grown on OH-terminated surfaces. Furthermore, two different regimes related to the nature of graphene defects were identified and, depending on the sapphire terminated surface, are bound either to vacancy or boundary-like defects. Finally, studying the density of defects and the crystallite area, as well as their relationship with the sapphire surface termination, paves the way for increasing the crystallinity of the synthesized graphene.


Bronchopulmonary dysplasia and early prophylactic inhaled nitric oxide in preterm infants: current concepts and future research strategies in animal models.
We reviewed the literature on the use of inhaled nitric oxide and the influence of supplemental oxygen on bronchopulmonary dysplasia (BPD), and the role of endogenous nitric oxide-synthase, vascular endothelial growth factor, the interplay of nitric oxide and superoxide, protein nitration and the nuclear factor kappa B-pathway. BPD is a major cause of neonatal mortality and morbidity leading to arrested lung development in newborns. Several studies indicate that inhaled nitric oxide (iNO) improves pulmonary angiogenesis, lung alveolarization, distal lung growth and pulmonary function in preterm infants. Given the inconclusive results of clinical studies, however, it is unclear which subpopulations of infants might benefit. Moreover, data on iNO are conflicting whether exogenous nitric oxide is protective or damaging in the presence of hyperoxia. The toxicology of iNO is poorly understood and its potential interaction with oxygen has to be considered given that infants treated with iNO are also supplemented with oxygen. The underlying mechanisms of the effects of iNO in the newborn lung need further analysis. New data clarifying the role of endogenous nitric oxide-synthases, vascular endothelial growth factor (VEGF), the interplay of nitric oxide and superoxide, and protein nitration with concurrent iNO-therapy might answer some of these questions.


[Lymphedema and function of the arm after mastectomy for breast cancer].
We made an investigation of lymphedema and function of the arm in 1,115 patients after mastectomy. Slight edema was observed in 26.7 per cent, moderate edema in 3.9 per cent and severe in 0.9 per cent. Lymphedema is dependent upon the extensiveness of surgical operation. The incidence of moderate and severe edema is 2.5 per cent for 637 patients with modified radical mastectomy, 7.7 per cent for 440 patients with standard radical mastectomy and 10.5 per cent for 38 patients with extended radical mastectomy. The development of edema is more frequent in irradiated patients than in those without irradiation. No difference of the incidence of arm movement limitation is observed between modified radical mastectomy and standard radical mastectomy. Modified radical mastectomy, especially Auchincloss operation, offers a much cosmetic appearance.


Contemporary psychopharmacotherapy in the context of brave new psychiatry, well-being therapy and life coaching.
Despite modern advances in clinical psychopharmacology, mental disorders are still the leading cause of disability all over the world. Drug treatment of mental disorders is unfortunately too often associated with partial remissions, frequent relapse or recurrence as well as with persistent residual symptoms, distress and low levels of well-being, life-satisfaction and quality of life. The practical failure of psychopharmacotherapy to improve life-satisfaction and well-being is related to treatment focus on psychopathology and decrease of illness and not on the development of wellness, purpose of life and creativity. NLP, life coaching and well-being therapy may significantly increase effectiveness of psychopharmacotherapy shaping an efficient and meaningful treatment context for achieving a full recovery.


Overexpression of the Wilms' tumor gene WT1 in pancreatic ductal adenocarcinoma.
The expression of the Wilms' tumor gene WT1 was examined by immunohistochemistry in 40 cases of pancreatic ductal adenocarcinoma. WT1 protein was expressed in 30 (75%) of the 40 pancreatic ductal adenocarcinomas, but not in the remaining 10 (25%). In normal pancreatic ductal cells, WT1 protein was undetectable. No correlations between WT1 expression and clinicopathological parameters such as age, sex, T or N stage, tumor location, and tumor differentiation were observed. Treatment with WT1 antisense oligomers significantly inhibited the growth of five human pancreatic cancer cell lines, PSN1, MiaPaCa2, ASPC1, BxPC3, and PCI6, expressing the WT1 gene. These results indicate an important role of the WT1 gene in the tumorigenesis of pancreatic ductal adenocarcinoma expressing WT1 and provide a rationale for new treatment strategies to treat pancreatic ductal adenocarcinoma by targeting the WT1 gene and its product.


Diffuse sclerosing variant of papillary thyroid carcinoma: case report and review of the literature.
To describe a patient with a diffuse sclerosing variant of papillary (DSVP) thyroid cancer and to summarize the reported clinical manifestations and treatment of other patients with this malignant tumor. We reviewed the pathologic findings in a 14-year-old girl, who had survived for 19 years after treatment of a presumed undifferentiated thyroid cancer. When reassessment revealed histologic features of DSVP cancer, we reviewed the case reports of this type of malignant lesion identified from a MEDLINE search of articles published between 1985 and 1995. Review of the pathologic features showed a diffuse tumor in the thyroid gland without an identifiable mass and extensive bilateral lymph node metastatic lesions. Histologic examination disclosed pronounced fibrosis, numerous psammoma bodies, primarily a solid growth pattern, lymphocytic infiltration, and extensive invasion of lymphatic spaces. The nuclear features were characteristic of papillary carcinoma. Review of 63 cases of DSVP cancer indicated that this variant accounted for 0.2 to 5.7% of papillary cancer, affected primarily young women, and usually manifested with diffuse involvement of one or both thyroid lobes. Thyroid antibodies were frequently detected in the serum. Cervical lymph node metastatic lesions, local invasion, and distant metastatic involvement were described in 75, 35, and 16% of patients, respectively. Although the cancer recurred in 37% of patients, only two died of this malignant tumor. DSVP cancer can be confused with nontoxic goiter, chronic thyroiditis, nonthyroidal malignant tumors, or undifferentiated thyroid cancer. We suggest that the same therapy used for young patients with conventional papillary thyroid cancer is also appropriate for most patients with the diffuse sclerosing variant.


Two- and three-dimensional networks of gadolinium(III) with dicarboxylate ligands: synthesis, crystal structure, and magnetic properties.
Four gadolinium(III) complexes with dicarboxylate ligands of formulas [Gd2(mal)3(H2O)5]n.2nH2O (1), [Gd2(mal)3(H2O)6]n (2), [NaGd(mal)(ox)(H2O)3]n (3), and [Gd2(ox)3(H2O)6]n.2.5nH2O (4) (mal = malonate; ox = oxalate) have been prepared, and their magnetic properties have been investigated as a function of the temperature. The structures of 1-3 have been determined by X-ray diffraction methods. The crystal structure of 4 was already known, and it is made of hexagonal layers of Gd atoms that are bridged by bis-bidentate oxalate. Compound 1 is isostructural with the europium(III) malonate complex [Eu2(mal)3(H2O)5]n.2nH2O,1 whose structure was reported elsewhere. The Gd atoms in 1 define a two-dimensional network where a terminal bidentate and bridging bidentate/bis-monodentate and tris-bidentate coordination modes of malonate occur. Compound 2 has a three-dimensional structure with a structural phase transition at 226 K, which involves a change of the space group from I2/a to Ia. Although its structure at room temperature was already known, that below 226 K was not. Pairs of Gd atoms with a double oxo-carboxylate bridge occur in both phases, and the main differences between both structures deal with the Gd environment and the H-bond pattern. 3 is also a three-dimensional compound, and it was obtained by reacting Gd(III) ions with malonic acid in a silica gel medium. Oxalic acid results as an oxidized product of the malonic acid, and single crystals of the heteroleptic complex were produced. The Gd atoms in 3 are connected through bis-bidentate oxalate and carboxylate-malonate bridges in the anti-anti and anti-syn coordination modes. Compounds 1 and 2 exhibit weak but significant ferromagnetic couplings between the Gd(III) ions through the single (1) and double (2) oxo-carboxylate bridges, whereas antiferromagnetic interactions across the bis-bidentate oxalate account for the overall antiferromagnetic behavior observed in 3 and 4.


The dependencies of phase velocity and dispersion on trabecular thickness and spacing in trabecular bone-mimicking phantoms.
Frequency-dependent phase velocity was measured in trabecular-bone-mimicking phantoms consisting of two-dimensional arrays of parallel nylon wires (simulating trabeculae) with thicknesses ranging from 152 to 305 microm and spacings ranging from 700 to 1000 microm. Phase velocity varied approximately linearly with frequency over the range from 400 to 750 kHz. Dispersion was characterized by the slope of a linear least-squares regression fit to phase velocity versus frequency data. The increase in phase velocity (compared with that in water) at 500 kHz was approximately proportional to the (1) square of trabecular thickness, (2) inverse square of trabecular spacing, and (3) volume fraction occupied by nylon wires. The first derivative of phase velocity with respect to frequency was negative and exhibited nonlinear, monotonically decreasing dependencies on trabecular thickness and volume fraction. The dependencies of phase velocity and its first derivative on volume fraction in the phantoms were consistent with those reported in trabecular bone.


Insertion of tantalum beads in RSA of the hip: variations in incidence of extra-osseous beads with insertion site.
Radiostereometric analysis (RSA) is a technique that can be used to measure the in-vivo micro-motion of the components of hip arthroplasty. It requires the insertion of tantalum beads into the bone permitting analysis of the radiographs. Extra-osseous beads reduce the usable bead pattern and previous studies have reported their incidence in the proximal femur as between 11% and 13% of all inserted beads. We reviewed the relative incidence of extra-osseous beads by examining 1038 radiographs of 97 patients who were part of an ongoing RSA hip study. Extra-osseous beads were seen in 44% of our patients with most having a single extra-osseous bead. The relative incidence of extra-osseous beads was 2% and 6% in the femur and pelvis, respectively. We observed a reduction in the incidence of the femoral beads with time, but not of the pelvis, which suggests that experience in the insertion technique improves the insertion rates at least of the femur. Our findings indicate that the incidence of extra-osseous beads is lower than previously reported. However, care should be taken in the design of studies to ensure that an adequate number of beads are placed in locations which are both surgically achievable and technically useful.


Extreme temperature stability of thermally insulating graphene-mesoporous-silicon nanocomposite.
We demonstrate the thermal stability and thermal insulation of graphene-mesoporous-silicon nanocomposites (GPSNC). By comparing the morphology of GPSNC carbonized at 650 °C as-formed to that after annealing, we show that this nanocomposite remains stable at temperatures as high as 1050 °C due to the presence of a few monolayers of graphene coating on the pore walls. This does not only make this material compatible with most thermal processes but also suggests applications in harsh high temperature environments. The thermal conductivity of GPSNCs carbonized at temperatures in the 500 °C-800 °C range is determined through Raman spectroscopy measurements. They indicate that the thermal conductivity of the composite is lower than that of silicon, with a value of 13 ± 1 W mK-1 at room temperature, and not affected by the thin graphene layer, suggesting a role of the high concentration of carbon related-defects as indicated by the high intensity of the D-band compared to G-band of the Raman spectra. This morphological stability at high temperature combined with a high thermal insulation make GPSNC a promising candidate for a broad range of applications including microelectromechanical systems and thermal effect microsystems such as flow sensors or IR detectors. Finally, at 120 °C, the thermal conductivity remains equal to that at room temperature, attesting to the potential of using our nanocomposite in devices that operate at high temperatures such as microreactors for distributed chemical conversion, solid oxide fuel cells, thermoelectric devices or thermal micromotors.


Renal aspects of calcium and phosphorus metabolism in preterm infants.
The aim of this study is to emphasize renal aspects of calcium and phosphorus metabolism from our data of more than 200 metabolic balance studies carried out in preterm infants. Renal production of 1,25-dihydroxyvitamin D increased rapidly after birth provided the concentration of the substrate, 25-hydroxyvitamin D, is adequate. The gut of preterm infants is able to respond to the active metabolite of vitamin D. Mean plasma phosphate threshold for tubular reabsorption of phosphate is high, about 2.1 mmol/l or 6.5 mg/dl. The low fractional excretion of phosphate cannot be explained by immature parathyroid function nor by renal unresponsiveness to parathormone, at least after the first days of life. It is probably due to regulating factors related to the high rate of growth. Because of reduced glomerular filtration rate, a too high phosphorus intake may result in hyperphosphatemia. Conversely, a too low phosphorus intake will lead to a phosphate depletion syndrome characterized by marked increase in urinary calcium excretion, no urinary phosphate, and hypophosphatemia. Preterm infants with chronic metabolic acidosis are able to acidify urine so that titratable acid is directly related to urinary excretion of phosphate. Clinical implications are that calcium:phosphorus ratio in milk must be adapted according to net bone and soft tissue retention.


Clostridium septicum infection in a young pregnant patient.
This report describes a young pregnant woman who presented to a rural emergency department with vaginal bleeding at 7 weeks of gestation. Initially, the patient was stable; however, within 8 h the patient deteriorated into fulminant septic shock. She required aggressive resuscitation and surgical management of a septic abortion. The patient's condition improved rapidly following surgical evacuation of the uterus with dilatation and curettage. She has had no long-term sequelae. Blood and tissue cultures returned positive for Clostridium septicum. To the best of our knowledge, this is the only reported case of survival from C septicum infection in a pregnant woman and highlights the importance of improved awareness and management of such infections by the medical community so that future cases can achieve similarly successful outcomes.


Therapeutic inhibition of hepatitis B virus surface antigen expression by RNA interference.
RNA interference (RNAi) mediated inhibition of virus-specific genes has emerged as a potential therapeutic strategy against virus induced diseases. Human hepatitis B virus (HBV) surface antigen (HBsAg) has proven to be a significant risk factor in HBV induced liver diseases, and an increasing number of mutations in HBsAg are known to enhance the difficulty in therapeutic interventions. The key challenge for achieving effective gene silencing in particular for the purpose of the therapeutics is primarily based on the effectiveness and specificity of the RNAi targeting sequence. To explore the therapeutic potential of RNAi on HBV induced diseases in particular resulted from aberrant or persistent expression of HBsAg, we have especially screened and identified the most potent and specific RNAi targeting sequence that directly mediated inhibition of the HBsAg expression. Using an effective DNA vector-based shRNA expression system, we have screened 10 RNAi targeting sequences (HBsAg-1 to 10) that were chosen from HBsAg coding region, in particular the major S region, and have identified four targeting sequences that could mediate sequence specific inhibition of the HBsAg expression. Among these four shRNAs, an extremely potent and highly sequence specific HBsAg-3 shRNA was found to inhibit HBsAg expression in mouse HBV model. The inhibition was not only preventive in cotransfection experiments, but also had therapeutic effect as assessed by post-treatment protocols. Moreover, this HBsAg-3 shRNA also exhibited a great potency of inhibition in transgenic mice that constitutively expressed HBsAg. These results indicate that HBsAg-3 shRNA can be considered as a powerful therapeutic agent on HBsAg induced diseases.


Characteristics of Sputtered ZnO Thin Films for an Inverted Organic Solar Cell.
Several research groups have claimed high energy conversion efficiency in organic solar cells. However, it still has low efficiency and is unstable, because organic materials are easily oxidized by atmospheric humidity and UV light. In this work, ZnO thin film as the blocking layer attributed to the interference of the injection of the hole from the P3HT and no charge carrier recombination. We obtained the maximum power conversion efficiency of 1.9% under AM 1.5 G spectral illumination of 100 MWcm(-2), when we used a ZnO film of 60 nm and the optimized P3HT:PCBM, and Au as the back electrode to solve the reaction problem of Al electrode and to control the work function between the HOMO level of P3HT and the energy level of the metal electrode. Power conversion efficiency of inverted organic solar cell (IOSC) is significantly dependent on the thickness of the ZnO thin film deposited by unbalanced magnetron sputtering method. Also, the stability of IOSC is measured under ambient conditions.


The effect of parental social support and acculturation on childhood asthma control.
There exists large ethnic disparities in asthma among Latino children; Puerto Ricans (PRs) are disproportionately affected, while Mexicans have the lowest prevalence and morbidity. Disparities are poorly understood, however, acculturation and social support are suggested to influence asthma control among children. This study investigated the relationship between acculturation, social support and asthma control among PR and Mexican children and their caregivers. Primary caregiver-child dyads (n = 267) of PR (n = 79) and Mexican (n = 188) descent were recruited from clinics at two inner-city hospitals in Bronx, NY and three clinics in Phoenix, AZ. Children were 5-12 years of age and had a confirmed asthma diagnosis. Dyads completed measures of social support, acculturation and asthma control; logistic regression was used for analysis. Mexican children had better asthma control than PR children (p < 0.001). PR caregivers were more acculturated than Mexican caregivers (p < 0.05); however, acculturation did not predict control. Across Latino subgroups caregivers' total level of social support predicted better asthma control among children (p < 0.05), and support received from family and friends each independently predicted better control (p < 0.05). Results suggest that social support reduces some of the burden associated with asthma management enabling caretakers to better control their children's asthma.


The acute toxicity of selected alkylphenols to young and adult Daphnia magna.
Differences in sensitivity toward toxicants between young and adult individuals in a population are assumed to be primarily associated with their difference in body size. This assumption plays a key role in the modeling of effects of variable concentrations of toxicants on nonhomogeneous populations. The hazard-based no-effect-concentrations (NECs), killing rates, and elimination rates, estimated from the survival data of a series of acute toxicity tests with young and adults of Daphnia magna and six alkylphenols, were used to evaluated this assumption. The results lead to the conclusion that young and adult D. magna were equally sensitive in terms of NEC and killing rate and that the observed differences in elimination rates could be explained on the basis of a difference in body size. Furthermore, it was found that elimination rates estimated on the basis of the survival data were consistently smaller than those expected on the basis of a QSAR for Daphnia pulex, a comparable species. This discrepancy was likely due to a decreased uptake and elimination during a period of immobilization prior to death. Since it is unknown to what extent immobilized individuals are able to recover from short-term exposures, the observed deviation clearly identifies a complicating factor in the modeling of effects of variable concentrations of toxicants.


Effects of exercise on glomerular passage of macromolecules in patients with diabetic nephropathy and in healthy subjects.
The effects of exercise on glomerular permeability were investigated in 12 proteinuric insulin-dependent diabetic patients and in 12 healthy controls by measuring the fractional protein and dextran clearances at rest and after exercise. Exercise significantly reduced the glomerular filtration rate (GFR) and the renal plasma flow (RPF) and markedly increased the filtration fraction (FF) in both diabetics and controls. The fractional clearances of albumin and IgG increased significantly during exercise in diabetics. Exercise also significantly increased the fractional clearance of albumin in healthy controls. The changes in the fractional protein clearances correlated significantly with the changes in the FF. In diabetics the fractional dextran clearances of molecules with a radius greater than or equal to 4.8 nm were significantly elevated after exercise. This was not found in healthy controls. It is concluded that exercise increases glomerular permeability by influencing the renal haemodynamics. Probably partial depletion of negative charges on the glomerular capillary wall plays a role in exercise-induced proteinuria in both healthy and diabetic subjects. In addition, the altered glomerular permeability during exercise is associated with increased size of the filtering pores in diabetic nephropathy.


Radiographic features of an aneurysmal bone cyst of the orbit.
Aneurysmal bone cyst is an unusual benign solitary lesion of bone occurring rarely in the orbit. In this report, we present computed tomography and magnetic resonance images of an orbital aneurysmal bone cyst involving the frontal bone in a 16-month-old boy. The aneurysmal bone cyst exhibited bone destruction, new bone formation of the orbital roof and fluid-fluid levels in the lesion following hemorrhage. These radiographic features may be useful for diagnosing orbital aneurysmal bone cysts.


Studies on bi-layer osmotic pump tablets of water-insoluble allopurinol with large dose: in vitro and in vivo.
Controlled release bi-layer osmotic pump tablets (BOPT) of water-insoluble allopurinol with large dose (150 mg/BOPT) were successfully prepared merely with sodium chloride as osmotic promoting agent and polyethylene oxide (PEO) as suspending agent. Formulations of the two kinds of agents were investigated in order to discuss their effects on the release behavior of BOPT, and then the optimal formulation was evaluated. The pharmacokinetics studies of allopurinol and its active metabolite oxypurinol in two-preparation and two-period crossover design relative to the equivalent dose of commercially common allopurinol tablets were evaluated in six Beagle dogs. And the pharmacokinetics results showed that allopurinol BOPT were able to provide a slow release of allopurinol, and oxypurinol were bioequivalent between allopurinol BOPT and common allopurinol tablets. A good in vitro-in vivo correlation of allopurinol was also proved. In conclusion, water-insoluble drugs with large dose can be designed to BOPT for efficacy and safety use.


Inherited Disorders of Thyroid Hormone Metabolism Defect Caused by the Dysregulation of Selenoprotein Expression.
Consistent activation and functioning of thyroid hormones are essential to the human body as a whole, especially in controlling the metabolic rate of all organs and systems. Impaired sensitivity to thyroid hormones describes any process that interferes with the effectiveness of thyroid hormones. The genetic origin of inherited thyroid hormone defects and the investigation of genetic defects upon the processing of thyroid hormones are of utmost importance. Impaired sensitivity to thyroid hormone can be categorized into three conditions: thyroid hormone cell membrane transport defect (THCMTD), thyroid hormone metabolism defect (THMD), and thyroid hormone action defect (THAD). THMD is caused by defects in the synthesis and processing of deiodinases that convert the prohormone thyroxine (T4) to the active hormone triiodothyronine (T3). Deiodinase, a selenoprotein, requires unique translation machinery that is collectively composed of the selenocysteine (Sec) insertion sequence (SECIS) elements, Sec-insertion sequence-binding protein 2 (SECISBP2), Sec-specific eukaryotic elongation factor (EEFSEC), and Sec-specific tRNA (TRU-TCA1-1), which leads to the recognition of the UGA codon as a Sec codon for translation into the growing polypeptide. In addition, THMD could be expanded to the defects of enzymes that are involved in thyroid hormone conjugation, such as glucuronidation and sulphation. Paucity of inherited disorders in this category leaves them beyond the scope of this review. This review attempts to specifically explore the genomic causes and effects that result in a significant deficiency of T3 hormones due to inadequate function of deiodinases. Moreover, along with SECISBP2, TRU-TCA1-1, and deiodinase type-1 (DIO1) mutations, this review describes the variants in DIO2 single nucleotide polymorphism (SNP) and thyroid stimulating hormone receptor (TSHR) that result in the reduced activity of DIO2 and subsequent abnormal conversion of T3 from T4. Finally, this review provides additional insight into the general functionality of selenium supplementation and T3/T4 combination treatment in patients with hypothyroidism, suggesting the steps that need to be taken in the future.


Interferon production in leukaemia.
Leucocyte interferon production in vitro and circulating interferon levels were studied in healthy subjects and in 80 patients with acute or chronic leukaemia. Circulating interferon was not found in either group. Interferon synthesis in response to a virus was normal in patients with acute leukaemia and appeared to be enhanced in some. In chronic leukaemia reduced levels were common particularly in CLL, in which condition normal results were rarely found; lymphocyte transformation to PHA was also depressed in this group. No clinical or haematological correlation with the interferon levels was found and no consistent effect of treatment was shown. The possible factors which could account for these findings and their significance in relation to pathogenesis and treatment of leukaemia are discussed.


Febrile temperatures induce cytoadherence of ring-stage Plasmodium falciparum-infected erythrocytes.
In falciparum malaria, the malaria parasite induces changes at the infected red blood cell surface that lead to adherence to vascular endothelium and other red blood cells. As a result, the more mature stages of Plasmodium falciparum are sequestered in the microvasculature and cause vital organ dysfunction, whereas the ring stages circulate in the blood stream. Malaria is characterized by fever. We have studied the effect of febrile temperatures on the cytoadherence in vitro of P. falciparum-infected erythrocytes. Freshly obtained ring-stage-infected red blood cells from 10 patients with acute falciparum malaria did not adhere to the principle vascular adherence receptors CD36 or intercellular adhesion molecule-1 (ICAM-1). However, after a brief period of heating to 40 degrees C, all ring-infected red blood cells adhered to CD36, and some isolates adhered to ICAM-1, whereas controls incubated at 37 degrees C did not. Heating to 40 degrees C accelerated cytoadherence and doubled the maximum cytoadherence observed (P < 0.01). Erythrocytes infected by ring-stages of the ICAM-1 binding clone A4var also did not cytoadhere at 37 degrees C, but after heating to febrile temperatures bound to both CD36 and ICAM-1. Adherence of red blood cells infected with trophozoites was also increased considerably by brief heating. The factor responsible for heat induced adherence was shown to be the parasite derived variant surface protein PfEMP-1. RNA analysis showed that levels of var mRNA did not differ between heated and unheated ring-stage parasites. Thus fever-induced adherence appeared to involve increased trafficking of PfEMP-1 to the erythrocyte membrane. Fever induced cytoadherence is likely to have important pathological consequences and may explain both clinical deterioration with fever in severe malaria and the effects of antipyretics on parasite clearance.


Variability in digestive and respiratory tract Ace2 expression is associated with the microbiome.
COVID-19 (coronavirus disease 2019) patients exhibiting gastrointestinal symptoms are reported to have worse prognosis. Ace2 (angiotensin-converting enzyme 2), the gene encoding the host protein to which SARS-CoV-2 spike proteins bind, is expressed in the gut and therefore may be a target for preventing or reducing severity of COVID-19. Here we test the hypothesis that Ace2 expression in the gastrointestinal and respiratory tracts is modulated by the microbiome. We used quantitative PCR to profile Ace2 expression in germ-free mice, conventional raised specific pathogen-free mice, and gnotobiotic mice colonized with different microbiota. Intestinal Ace2 expression levels were significantly higher in germ-free mice compared to conventional mice. A similar trend was observed in the respiratory tract. Intriguingly, microbiota depletion via antibiotics partially recapitulated the germ-free phenotype, suggesting potential for microbiome-mediated regulation of Ace2 expression. Variability in intestinal Ace2 expression was observed in gnotobiotic mice colonized with different microbiota, partially attributable to differences in microbiome-encoded proteases and peptidases. Together, these data suggest that the microbiome may be one modifiable factor determining COVID-19 infection risk and disease severity.


Neofusicoccum parvum Colonization of the Grapevine Woody Stem Triggers Asynchronous Host Responses at the Site of Infection and in the Leaves.
Grapevine trunk diseases cause important economic losses in vineyards worldwide. Neofusicoccum parvum, one of the most aggressive causal agents of the trunk disease Botryosphaeria dieback, colonizes cells and tissues of the grapevine wood, leading to the formation of an internal canker. Symptoms then extend to distal shoots, with wilting of leaves and bud mortality. Our aim was to characterize the transcriptional dynamics of grapevine genes in the woody stem and in the leaves during Neofusicoccum parvum colonization. Genome-wide transcriptional profiling at seven distinct time points (0, 3, and 24 hours; 2, 6, 8, and 12 weeks) showed that both stems and leaves undergo extensive transcriptomic reprogramming in response to infection of the stem. While most intense transcriptional responses were detected in the stems at 24 hours, strong responses were not detected in the leaves until the next sampling point at 2 weeks post-inoculation. Network co-expression analysis identified modules of co-expressed genes common to both organs and showed most of these genes were asynchronously modulated. The temporal shift between stem vs. leaf responses affected transcriptional modulation of genes involved in both signal perception and transduction, as well as downstream biological processes, including oxidative stress, cell wall rearrangement and cell death. Promoter analysis of the genes asynchronously modulated in stem and leaves during N. parvum colonization suggests that the temporal shift of transcriptional reprogramming between the two organs might be due to asynchronous co-regulation by common transcriptional regulators. Topology analysis of stem and leaf co-expression networks pointed to specific transcription factor-encoding genes, including WRKY and MYB, which may be associated with the observed transcriptional responses in the two organs.


The role of chromodomain helicase DNA binding protein 1 (CHD1) in promoting an invasive prostate cancer phenotype.
Prostate cancer (PCa) phenotypes vary from indolent to aggressive. Molecular subtyping may be useful in predicting aggressive cancers and directing therapy. One such subtype involving deletions of chromodomain helicase DNA binding protein 1 (CHD1), a tumor suppressor gene, are found in 10-26% of PCa tumors. In this study, we evaluate the functional cellular effects that follow CHD1 deletion. CHD1 was knocked out (KO) in the non-tumorigenic, human papillomavirus 16 (HPV16)-immortalized prostate epithelial cell line, RWPE-1, using CRISPR/Cas9. In vitro assays such as T7 endonuclease assay, western blot, and sequencing were undertaken to characterize the CHD1 KO clones. Morphologic and functional assays for cell adhesion and viability were performed. To study expression of extracellular matrix (ECM) and adhesion molecules, a real-time (RT) profiler assay was performed using RWPE-1 parental, non-target cells (NT2) and CHD1 KO cells. Compared to parental RWPE-1 and non-target cells (NT2), the CHD1 KO cells had a smaller, rounder morphology and were less adherent under routine culture conditions. Compared to parental cells, CHD1 KO cells showed a reduction in ECM and adhesion molecules as well as a greater proportion of viable suspension cells when cultured on standard tissue culture plates and on plates coated with laminin, fibronectin or collagen I. CHD1 KO cells showed a decrease in the expression of secreted protein acidic and rich in cysteine (SPARC), matrix metalloproteinase 2 (MMP2), integrin subunit alpha 2 (ITGA2), integrin subunit alpha 5 (ITGA5), integrin subunit alpha 6 (ITGA6), fibronectin (FN1), laminin subunit beta-3 precursor (LAMB3), collagen, tenascin and vitronectin as compared to parental and NT2 cells. These data suggest that in erythroblast transformation specific (ETS) fusion-negative, phosphatase and tensin homolog (PTEN) wildtype PCa, deletion of CHD1 alters cell-cell and cell-matrix adhesion dynamics, suggesting an important role for CHD1 in the development and progression of PCa.


Spontaneous Vertebral Artery Dissection in a Healthy 26 Year Old Female Patient: A Case Study.
Spontaneous vertebral artery dissection (SVAD) is an extremely rare, yet life-threatening, event that can potentially result in ischemic stroke or subarachnoid hemorrhage, depending on the origin and extension of the dissection. Vertebral artery dissection is more commonly associated with traumatic injury to the neck, resulting in compromised structural integrity of the vertebral artery wall. This case study discusses the clinical presentation, physical examination, diagnosis, clinical course, and outcome for a young, otherwise healthy, female patient who presented to the emergency department with a SVAD.


Candida auris Invasive Infection after Kidney Transplantation.
C. auris has been associated not only with a variety of invasive fungal infections, including candidemia, sometimes related to central venous catheter, but also with pericarditis and respiratory tract and urinary tract infections. We describe the case of a patient with persistent fever despite antibiotics, who presented with Candida isolation in blood cultures, typified as Candida auris species. A 57-year-old male receiving peritoneal dialysis underwent kidney transplantation which was complicated by primary nonfunction due to arterial thrombosis necessitating graft nephrectomy. During the postoperative period, he presented with Pseudomonas aeruginosa pneumonia that was treated with levofloxacin and catheter-related Enterococcus faecalis bacteremia treated with linezolid. After hospital discharge, he then presented with herpes zoster infection treated with valacyclovir. Ten days later, he developed peritonitis and exit site infection with multidrug-resistant Pseudomonas aeruginosa treated with intraperitoneal aztreonam and peritoneal dialysis catheter removal. Despite broad-spectrum antibiotic therapy, the patient remained febrile. All microbiology laboratory tests were negative, so it was decided to stop antibiotic therapy for 48 hours and repeat cultures in order to avoid possible false negatives. In new blood cultures performed after suspension of antibiotic therapy, candidemia was observed, later typified as Candida auris species. After completing antifungal treatment (three weeks with intravenous amphotericin B 100 mg qd and two weeks of intravenous anidulafungin 100 mg qd), microbiological cultures remained negative and the patient made uneventful recovery. Candida auris invasive infection has been mainly described in patients with severe underlying comorbidities and immunocompromise. Multidrug-resistant clusters of Candida auris are increasingly emerging.


Sulfonyliminoimidazolidines, a new class of oral hypoglycemic agents. 3. Hypoglycemic activity and mode of action of 1-[p-[2-(crotonylamino)-ethyl]-phenylsulfonyl]-3-cyclohexyl-2-imino- imidazolidine (CGP 11 112).
1-[p-[2-(Crotonylamino)-ethyl]-phenylsulfonyl]-3-cyclohexyl-2-imino- imidazolidine (CGP 11 112) is a representative of a new class of oral hypoglycemic agents. It lowers blood glucose in normal animals and in streptozocin (streptozotocin)-diabetic rats. In normal mice, rats and dogs the hypoglycemic effect is more potent (range 3-30 times) and has a shorter duration than that of tolbutamide. CGP 11 112 increases plasma insulin after oral administration in normal animals and stimulates release of insulin in perifused rat islets in vitro (sulfonylurea-like effect). In streptozocin-diabetic rats CGP 11 112 decreases blood glucose with a potency comparable to that of phenformin. In contrast to phenformin, CGP 11 112 does not increase blood lactate in diabetic rats or inhibit intestinal absorption of glucose. An effect of CGP 11 112 on gluconeogenesis and glycogenolysis could not be demonstrated. It is suggested that the hypoglycemic activity in streptozocin-diabetic rats may be due to stimulation of glucose efflux from the circulation. In vitro, CGP 11 112 inhibits glucose oxidation and lipolysis in isolated rat fat cells.


Correlation between the consumption of meropenem or doripenem and meropenem susceptibility of Pseudomonas aeruginosa in a university hospital in Japan.
The appropriate use of carbapenems is essential in order to prevent resistance in Pseudomonas aeruginosa. We investigated the correlation between the consumption of meropenem or doripenem and the susceptibility of P. aeruginosa to meropenem in a Japanese university hospital from 2004 to 2009. The susceptibility data of P. aeruginosa and the annual consumption of meropenem or doripenem were analyzed. The consumption of meropenem or doripenem was calculated using the Anatomic Therapeutic Chemical classification and defined daily doses methodology. Meropenem consumption decreased and doripenem consumption increased and throughout the entire investigation period, total consumption of meropenem plus doripenem was stable. Although the annual number of isolated P. aeruginosa has not changed, the annual number of isolated multidrug resistant P. aeruginosa decreased by measures against nosocomial infection. The rate of meropenem resistant P. aeruginosa decreased in a time-dependent manner. Meropenem consumption was positively correlated with the meropenem resistance rate among P. aeruginosa (r = 0.9455, p<0.01). The total consumption of meropenem and doripenem was not correlated with the meropenem resistance rate (r = -0.6601, p>0.1). These results suggested that even if the total consumption of meropenem plus doripenem was not changed, meropenem susceptibility among P. aeruginosa improved by the decrease of meropenem consumption. Although meropenem and doripenem have been suggested to show cross-resistance with each other, the reduction of meropenem consumption might be effective for preventing an increase of meropenem-resistant P. aeruginosa.


Walnut extract exhibits anti-fatigue action via improvement of exercise tolerance in mice.
This study was conducted to investigate the anti-fatigue effect of walnut extract (WE) on forced swimming capacity in mice. Twenty-eight male ICR mice were randomly divided into four groups, a vehicle control (VC) or one of three WE administered groups (300, 600 and 900 mg/kg/day). WE was orally administered to mice once a day for 4 weeks, during which time a forced swimming test was conducted once a week. The vehicle control group was given a corresponding volume of sterile distilled water. After 4 weeks, the forced swimming capacity and levels of blood lactate, glucose, glutamine, ammonia and triacylglycerol, and liver glycogen were measured. In the WE administration group (600 and 900 mg/kg) the maximum swimming time increased significantly when compared with the vehicle control group. WE (600 and 900 mg/kg) significantly decreased the levels of lactate andammonia and increased the blood glutamine levels and liver glycogen content after forced swimming relative to the vehicle control group. The results of this study demonstrated the anti-fatigue effects of WE in a dose-dependent manner. The effects of WE at 600 and 900 mg/kg were similar. Overall, these results suggest that walnut has anti-fatigue activity and could elevate exercise tolerance.


Immunological evaluation of minimal residual disease (MRD) in acute myeloid leukaemia (AML).
Immunophenotypic analysis of leukaemic cells using multiparametric flow cytometry has proved to be an attractive approach for MRD investigation in acute lymphoblastic leukaemia (ALL); by contrast, information on acute myeloid leukaemia (AML) is still scanty. Here, we first review the methodological strategies for these studies. Triple or quadruple antigenic combinations, analysed by multiparametric flow cytometry, have shown that in 80% of AML patients it is possible to identify aberrant or uncommon phenotypic profiles on blast cells, thereby allowing their distinction from normal cells and their use as leukaemia-associated phenotypes (LAP). We also focus on technical aspects that are important in the definition of LAP. We then review pitfalls that could potentially affect results using this approach. Finally, we review available information concerning the clinical value of these studies. Although reported data in the literature are still scanty, several authors have shown that this technique could be used for the prognostic evaluation of AML patients, when immunophenotypic evaluation is applied after induction therapy.


Serum levels of IgE anti-BP180 and anti-BP230 autoantibodies in patients with bullous pemphigoid.
Bullous pemphigoid (BP) is a subepidermal blistering disease characterized by autoantibodies against the hemidesmosomal proteins, BP180 and BP230. NC16A, a non-collagenous stretch of the BP180 ectodomain is the primary target of pathogenic IgG antibodies. Whereas IgG anti-BP180 autoantibodies play a primary role in the pathogenesis, there is a growing number of data regarding the potential pathogenic roles of IgE class autoantibodies in BP. To examine the levels of IgG and IgE autoantibodies against BP180 and BP230, and to investigate mutual association and clinical relevance. Sera obtained from 67BP patients and 36 healthy donors were subjected to ELISA assays to measure serum IgG and IgE levels of anti-BP180 and anti-BP230 antibodies. IgG anti-BP180 antibodies were positive in 63 (94%) of 67BP patients. IgG anti-BP230, IgE anti-BP180, and IgE anti-BP230 antibodies were found in 48 (72%), 20 (30%) and 45 (67%), respectively. IgG anti-BP180 levels were correlated with the affected areas. IgG anti-BP230 antibodies tended to increase in proportion to elongation of disease duration. IgE anti-BP230 levels showed a strong association with local eosinophil accumulation, while the levels were reversely related with the affected areas in BP. IgE autoantibodies to BP180 and BP230 are detected at high frequencies in BP. IgE anti-BP230 antibodies may have a role in attracting eosinophils to the skin lesions.


Diagnosing Periprosthetic Joint Infection: a Scoping Review.
The goal of this review is to provide an up to date understanding of the utility and limitations of the current tests utilized in the diagnosis of periprosthetic joint infection (PJI) in total knee and hip arthroplasty. Despite the growth in literature surrounding PJI diagnosis, there remains challenges in establishing a diagnosis of PJI. A combination of clinical, serum, and synovial tests and microbiologic and histologic examinations can yield a diagnosis in the majority of cases. Novel molecular and imaging studies may be beneficial for indeterminant cases. A number of emerging diagnostic tests have been proposed and may be incorporated into diagnostic algorithms in the future. Recently proposed stepwise diagnostic algorithms have shown high sensitivity and specificity. The diagnosis of PJI remains challenging due to a lack of tests that can definitively rule out infection. Diagnosis and investigations should occur in a stepwise fashion. There has been a plethora of new diagnostic tests introduced in attempts to improve the accuracy of diagnostic algorithms. The definition and algorithms for the diagnoses of PJI will continue to evolve as new techniques and tests are introduced.


Comparison of haemodynamic effects of rocuronium bromide with those of vecuronium in patients undergoing CABG surgery.
In a double-blind study, cardiovascular parameters (cardiac output, heart rate, systolic and diastolic arterial pressure, pulmonary and systemic vascular resistances) were measured invasively in two groups of patients receiving 3 x ED90 of rocuronium or vecuronium. Measurements were made at 2, 5 and 7 min after administration and 10 and 15 min after subsequent intubation. Systemic vascular resistance mostly increased, sometimes quite markedly, although, because of the variability, rarely statistically significantly. However, heart rate, arterial pressure and cardiac output were not altered to a clinically relevant degree.


Specificity in transition state binding: the Pauling model revisited.
Linus Pauling proposed that the large rate accelerations for enzymes are caused by the high specificity of the protein catalyst for binding the reaction transition state. The observation that stable analogues of the transition states for enzymatic reactions often act as tight-binding inhibitors provided early support for this simple and elegant proposal. We review experimental results that support the proposal that Pauling's model provides a satisfactory explanation for the rate accelerations for many heterolytic enzymatic reactions through high-energy reaction intermediates, such as proton transfer and decarboxylation. Specificity in transition state binding is obtained when the total intrinsic binding energy of the substrate is significantly larger than the binding energy observed at the Michaelis complex. The results of recent studies that aimed to characterize the specificity in binding of the enolate oxygen at the transition state for the 1,3-isomerization reaction catalyzed by ketosteroid isomerase are reviewed. Interactions between pig heart succinyl-coenzyme A:3-oxoacid coenzyme A transferase (SCOT) and the nonreacting portions of coenzyme A (CoA) are responsible for a rate increase of 3 × 10(12)-fold, which is close to the estimated total 5 × 10(13)-fold enzymatic rate acceleration. Studies that partition the interactions between SCOT and CoA into their contributing parts are reviewed. Interactions of the protein with the substrate phosphodianion group provide an ~12 kcal/mol stabilization of the transition state for the reactions catalyzed by triosephosphate isomerase, orotidine 5'-monophosphate decarboxylase, and α-glycerol phosphate dehydrogenase. The interactions of these enzymes with the substrate piece phosphite dianion provide a 6-8 kcal/mol stabilization of the transition state for reaction of the appropriate truncated substrate. Enzyme activation by phosphite dianion reflects the higher dianion affinity for binding to the enzyme-transition state complex compared with that of the free enzyme. Evidence is presented that supports a model in which the binding energy of the phosphite dianion piece, or the phosphodianion group of the whole substrate, is utilized to drive an enzyme conformational change from an inactive open form E(O) to an active closed form E(C), by closure of a phosphodianion gripper loop. Members of the enolase and haloalkanoic acid dehalogenase superfamilies use variable capping domains to interact with nonreacting portions of the substrate and sequester the substrate from interaction with bulk solvent. Interactions of this capping domain with the phenyl group of mandelate have been shown to activate mandelate racemase for catalysis of deprotonation of α-carbonyl carbon. We propose that an important function of these capping domains is to utilize the binding interactions with nonreacting portions of the substrate to activate the enzyme for catalysis.


Mental status after transurethral resection of the prostate.
We examined cognitive functions by means of a standardized mini-mental status (MMS) test before and 2 and 24 h after surgery in 100 patients undergoing transurethral resection of the prostate (TURP). There was a strong correlation between the results of this test on all three occasions, but a transient deterioration in the MMS score occurred 2 h after TURP in two thirds of the patients. Fluid absorption was the factor most strongly associated with the change in MMS status during TURP, while the preoperative health status and the choice of anesthesia (general or spinal) had no influence.


A scalable serology solution for profiling humoral immune responses to SARS-CoV-2 infection and vaccination.
Antibody testing against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been instrumental in detecting previous exposures and analyzing vaccine-elicited immune responses. Here, we describe a scalable solution to detect and quantify SARS-CoV-2 antibodies, discriminate between natural infection- and vaccination-induced responses, and assess antibody-mediated inhibition of the spike-angiotensin converting enzyme 2 (ACE2) interaction. We developed methods and reagents to detect SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay (ELISA). The main assays focus on the parallel detection of immunoglobulin (Ig)Gs against the spike trimer, its receptor binding domain (RBD) and nucleocapsid (N). We automated a surrogate neutralisation (sn)ELISA that measures inhibition of ACE2-spike or -RBD interactions by antibodies. The assays were calibrated to a World Health Organization reference standard. Our single-point IgG-based ELISAs accurately distinguished non-infected and infected individuals. For seroprevalence assessment (in a non-vaccinated cohort), classifying a sample as positive if antibodies were detected for ≥ 2 of the 3 antigens provided the highest specificity. In vaccinated cohorts, increases in anti-spike and -RBD (but not -N) antibodies are observed. We present detailed protocols for serum/plasma or dried blood spots analysis performed manually and on automated platforms. The snELISA can be performed automatically at single points, increasing its scalability. Measuring antibodies to three viral antigens and identify neutralising antibodies capable of disrupting spike-ACE2 interactions in high-throughput enables large-scale analyses of humoral immune responses to SARS-CoV-2 infection and vaccination. The reagents are available to enable scaling up of standardised serological assays, permitting inter-laboratory data comparison and aggregation.


Streptozotocin-induced diabetes decreases placenta growth factor (PlGF) levels in rat placenta.
The placenta produces several growth factors, including placenta growth factor (PlGF), which are essential for placenta growth and fetal growth. Diabetic pregnancy induces the abnormal placental growth and fetal development. This study investigated whether diabetes in pregnant rats induces changes in PlGF expression in the placenta. Diabetes was induced by a single intravenous injection of streptozotocin (35 mg/kg body weight) on day 0 of pregnancy, blood and tissue samples were collected on day 20 of pregnancy. In the diabetic group, maternal body weight and fetal weight significantly decreased compared to controls. RT-PCR and Western blot analyses showed that expression of PlGF was significantly decreased in placenta by streptozotocin treatment. Immunohistochemical study showed that the positive signal of PlGF in trophoblast cells was decreased in the diabetic group compared to controls. These findings demonstrate the decline of PlGF in the placenta in diabetic pregnancy.


Messages of the Newly Proposed Malaysian Dietary Guidelines (MDG): Do Adults in Kuala Lumpur Understand Them?
The Malaysian Dietary Guidelines (MDG) with eight key messages were first published in 1999. An updated version consisting of 14 key messages is being developed. The objective of this study was to evaluate the understanding of five key messages of the updated MDG among adults aged 18-59 years in Kuala Lumpur. A total of 773 adults comprising 330 Malays, 364 Chinese and 79 Indians were included in the study. A self-administrated questionnaire was used to obtain demographic data and to determine the level of understanding of key words and messages to be included in the new MDG. The results showed that 63% of the subjects were not aware of the existence of the MDG published in 1999. Overall, the understanding of the five messages in the updated MDG was moderate with a mean score of 60.0 ± 16.5. Between 52% to 93% of the subjects did not understand such key words as serving size, sedentary habits, blended vegetable oil and shortenings. The mean scores of understanding were significantly higher (p< 0.05) among the Chinese subjects (61.3 ± 17.8) than Malays (58.6 ± 14.2) and Indians (60.0 ± 18.9). The younger subjects (61.2 + 16.0) scored significantly (p< 0.05) higher than the older (58.7 ± 17.0) counterparts. There was also a significant association between the level of understanding of MDG with education level (p< 0.001) and occupational status (p< 0.001), respectively. This study suggests that some key words and messages in the updated MDG should be simplified to ensure that they are understood by Malaysians.


Functional ecology of a blue light photoreceptor: effects of phototropin-1 on root growth enhance drought tolerance in Arabidopsis thaliana.
* The blue light photoreceptor phototropin-1 has been shown to enhance fitness in Arabidosis thaliana under field conditions. Here, we ask whether performance consequences of phototropin-1 reflect its impact on root growth and drought tolerance. * We used a PHOT1-GFP gene construct to test whether phototropin-1 abundance in roots is highest at shallow soil depths where light penetration is greatest. We then compared root growth efficiency and size at maturity between individuals with and without functional phototropin-1. Comparisons were made under wet and dry conditions to assess the impact of phototropin-1 on drought tolerance. * Phototropin-1 was most abundant in upper root regions and its impact on root growth efficiency decreased with soil depth. Roots of plants with functional phototropin-1 made fewer random turns and traveled further for a given length (higher efficiency) than roots of phot1 mutants. In dry (but not wet) soil, enhancement of root growth efficiency by phototropin-1 increased plant size at maturity. * Results indicate that phototropin-1 enhances performance under drought by mediating plastic increases in root growth efficiency near the soil surface.


Results after resection of postinfarction left ventricular aneurysms.
Although left ventricular aneurysmectomy (LVA) is a common surgical procedure, the late functional and hemodynamic results have not been well defined. This presentation describes our results with LVA in 135 patients operated between 1969 and 1979. Associated procedures were performed in 57 (42%) including coronary bypass grafting in 50, valve replacement in 5, closure of ventricular septal defect in 2, or combinations of these in 3 patients. One hundred four of the 122 hospital survivors were followed from 2 to 107 months (mean = 37 months). There were 13 hospital deaths (9.6%), 12 late deaths (9.8%) and an actuarial 5-year survival rate of 77%. Clinical improvement of preoperative heart failure occurred in 82%, and of angina in 70%. Only 33 patients (30%) returned to normal work. Bicycle exercise testing in 70 patients showed normal working capacity in 41 (59%). Recatheterization in 49 patients showed no significant changes in left ventricular end-diastolic pressure or cardiac index, and a borderline reduction of the total ejection fraction. Ventricular arrhythmias were detected by long-term ECG in 70% of all patients after surgery. Of those with preoperative life-threatening arrhythmias, rhythm improvement was noted in 50%, but only 2 of 13 patients were free of arrhythmias after operation. This study demonstrates a greater frequency of postoperative symptomatic and functional improvement as compared to hemodynamic and ECG improvement. Ventricular tachyarrhythmias originating from post-infarct scars increased intra- and postoperative risk and aneurysmectomy alone is considered insufficient for treatment of these disturbances. Further electrophysiologic investigations are needed and additional surgical measures may be necessary to improve the subset of patients with life-threatening arrhythmias.


SENP2-mediated SERCA2a deSUMOylation increases calcium overload in cardiomyocytes to aggravate myocardial ischemia/reperfusion injury.
Sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) is a key protein that maintains myocardial Ca 2+ homeostasis. The present study aimed to investigate the mechanism underlying the SERCA2a-SUMOylation (small ubiquitin-like modifier) process after ischemia/reperfusion injury (I/RI) in vitro and in vivo . Calcium transient and systolic/diastolic function of cardiomyocytes isolated from Serca2a knockout (KO) and wild-type mice with I/RI were compared. SUMO-relevant protein expression and localization were detected by quantitative real-time PCR (RT-qPCR), Western blotting, and immunofluorescence in vitro and in vivo . Serca2a-SUMOylation, infarct size, and cardiac function of Senp1 or Senp2 overexpressed/suppressed adenovirus infected cardiomyocytes, were detected by immunoprecipitation, triphenyltetrazolium chloride (TTC)-Evans blue staining, and echocardiography respectively. The results showed that the changes of Fura-2 fluorescence intensity and contraction amplitude of cardiomyocytes decreased in the I/RI groups and were further reduced in the Serca2a KO + I/RI groups. Senp1 and Senp2 messenger ribose nucleic acid (mRNA) and protein expression levels in vivo and in cardiomyocytes were highest at 6 h and declined at 12 h after I/RI. However, the highest levels in HL-1 cells were recorded at 12 h. Senp2 expression increased in the cytoplasm, unlike that of Senp1. Inhibition of Senp2 protein reversed the I/RI-induced Serca2a-SUMOylation decline, reduced the infarction area, and improved cardiac function, while inhibition of Senp1 protein could not restore the above indicators. I/RI activated Senp1 and Senp2 protein expression, which promoted Serca2a-deSUMOylation, while inhibition of Senp2 expression reversed Serca2a-SUMOylation and improved cardiac function.


Tumor-targeted dual-action NSAID-platinum(iv) anticancer prodrugs.
Platinum(iv) prodrugs are a promising class of anticancer agents designed to overcome the limitations of conventional platinum(ii) therapeutics. In this work, we present oxaliplatin(iv)-based complexes, which upon reduction, release acetylsalicylic acid (aspirin), known for its antitumor activity against colon cancer and currently investigated in combination with oxaliplatin in a phase III clinical study. Comparison with a recently reported cisplatin analog (asplatin) revealed a massive increase in reduction stability for the oxaliplatin complex in mouse serum. This was in line with the cell culture data indicating the desired prodrug properties for the newly synthesized complex. For in vivo studies, a new derivative containing an albumin-binding maleimide unit was synthesized. Indeed, distinctly longer plasma half-life as well as higher tumor accumulation in comparison to asplatin and oxaliplatin were observed, also leading to significantly higher antitumor activity and overall survival of CT26 tumor-bearing mice.


[Treatment strategy for relapsed or refractory myeloma according to the new Guidelines].
The development of novel agents for treating multiple myeloma (MM) has markedly improved the treatment outcome and has caused a major paradigm shift in treatment strategies. In Japan, bortezomib and lenalidomide have been approved for the initial treatment; additionally, seven novel drugs, including next-generation proteasome inhibitors, immunomodulatory drugs, histone deacetylase inhibitors, and monoclonal antibodies, have been approved for relapsed and/or refractory MM treatment. Of these novel agents, daratumumab-containing regimens have been reported to induce a deep response, such as minimal residual disease-negative status, even in relapsed patients. Thus, compared with the initial therapy, many efficacious choices are available for treatment at the time of MM relapse; and salvage therapy is currently considered to be the most important treatment strategy for MM. In clinical practice, it is desirable to consider patient, disease, and therapeutic factors to make an optimal treatment decision for each patient.


Psychomotor depressive symptoms may differentially respond to venlafaxine.
Predicting differential antidepressant efficacy remains an elusive goal in major depressive disorder (MDD). The aims of this study were three-fold. Firstly, to examine if psychomotor retardation symptoms (item 8 on the 17-item Hamilton Depression Rating Scale) improve preferentially to venlafaxine (VEN) over escitalopram (ESC) treatment. Secondly, whether the 18 item CORE psychomotor signs scale predicted antidepressant remission. Finally, to investigate the role of two norepinephrine transporter gene (NET) polymorphisms (rs2242446 and rs5569) on antidepressant efficacy. Adults with Diagnostic and Statistical Manual of Mental Disorders, 4th ed. MDD (n=113) were treated with ESC or VEN prospectively for 8 weeks and rated serially with the Hamilton Depression Rating Scale. In a subsample (n=51) of patients from one of the three recruitment sites, the CORE psychomotor signs scale was also administered at baseline. Participants treated with VEN had significantly greater reduction in psychomotor retardation symptoms than those treated with ESC. The CORE scale did not predict antidepressant response or remission. Neither NET polymorphism moderated antidepressant efficacy. Findings suggest possible preferential utility of a selective serotonin and noradrenaline reuptake inhibitor in cases of MDD presenting with greater psychomotor retardation. The moderate to small sample size makes a type II error risk possible, and the negative findings need to be interpreted with caution. The positive finding of preferential efficacy of VEN for psychomotor retardation symptoms has potential translational utility.


Metabolic Effect of an Oriental Herbal Medicine on Obesity and Its Comorbidities with Transcriptional Responses in Diet-Induced Obese Mice.
Taeeumjowuitang (TJ) is an alternative herbal medicine that has been used to treat obesity in Korea. The molecular mechanisms involved in TJ-induced anti-obesity effects have not yet been determined. The aim of the current study was to elucidate the effects of TJ on obesity and metabolic syndrome, by analyzing the transcriptional and metabolic responses to TJ treatment. C57BL/6J mice were fed a high-fat or high-fat + 3% (w/w) TJ diet for 12 weeks. Their phenotypic characteristics were measured and the anti-obesity mechanism was elucidated, based on the RNA sequencing (RNA-seq) transcriptomic profiles in an animal model of obesity. TJ treatment ameliorated insulin resistance, dyslipidemia, and hepatic steatosis in high-fat diet-induced obese mice, with a simultaneous reduction in body weight gain by enhancing energy expenditure and suppressing adiposity. An analysis of the global transcriptional changes by RNA-seq revealed that TJ upregulated mitochondrial oxidative phosphorylation-associated genes in epididymal white adipose tissue (eWAT), suggesting an enhanced mitochondrial function after TJ treatment. Moreover, TJ effectively attenuated the high-fat diet-induced inflammatory response through transcriptional changes in eWAT. Our findings provide some mechanistic insights into the effects of TJ, an alternative oriental medicine, in the treatment of obesity and its comorbidities. They demonstrate that metabolic and transcriptional responses to diet-induced obesity with TJ treatment were desirable in adipose tissue metabolism.


Severe unsuspected maternal hypothyroidism discovered after the diagnosis of thyrotropin receptor-blocking antibody-induced congenital hypothyroidism in the neonate: failure to recognize and implications to the fetus.
Whereas most adequately treated children with congenital hypothyroidism (CH) do well neurodevelopmentally, when both the maternal and fetal thyroid glands are compromised, significant cognitive delay can occur despite early and aggressive postnatal therapy. Maternal thyrotropin-stimulating hormone receptor (TSHR)-blocking antibodies (Abs) can be transmitted to the fetus and cause combined maternal-fetal hypothyroidism. Current guidelines recommend their measurement only if mothers have known autoimmune thyroid disease, there is a history of a previously affected sibling, or when transient CH is suspected. We report 3 infants in whom the diagnosis of maternal hypothyroidism was not known and was identified only after CH was diagnosed in their babies. One of these infants had developmental delay despite rapid normalization of thyroid function postnatally. All 3 mothers had potent TSHR Abs in serum, but thyroid peroxidase Abs and thyroglobulin Abs were detectable in only 2 of them. TSHR-blocking Ab-induced CH should be suspected in any baby with CH irrespective of the known family history, especially if the hypothyroidism is severe and a eutopic thyroid gland is demonstrated on imaging. Measurement of TSHR Abs is necessary to establish the diagnosis; the presence of other thyroid Abs is insufficiently sensitive and may miss some cases.


Relationships between measures of boat acceleration and performance in rowing, with and without controlling for stroke rate and power output.
Boat acceleration profiles provide a valuable feedback tool by reflecting both rower technique and force application. Relationships between measures of boat acceleration and velocity to inform interpretation of boat acceleration profiles in rowing were investigated here. Thirteen male singles, nine female singles, eight male pairs, and seven female pairs participated (national and international level, age 18-27 y). Data from each stroke for 74 2000-m races were collected using Peach PowerLine and OptimEye S5 GPS units. General linear mixed modelling established modifying effects on velocity of two within-crew SD of boat acceleration variables for each boat class, without and with adjustment for stroke rate and power, to identify potential performance-enhancement strategies for a given stroke rate and power. Measures of acceleration magnitude at six peaks or dips, and six measures of the rate of change (jerk) between these peaks and dips were analyzed. Results were interpreted using rejection of non-substantial and substantial hypotheses with a smallest substantial change in velocity of 0.3%. Several boat acceleration measures had decisively substantial effects (-2.4-2.5%) before adjustment for stroke rate and power. Most effect magnitudes reduced after adjustment for stroke rate and power, although maximum negative drive acceleration, peak drive acceleration, jerk during the mid-drive phase, and jerk in the late recovery remained decisively substantial (-1.8-1.9%) in some boat classes. Greater absolute values of maximum negative drive acceleration and jerk in the late recovery are related to improved performance, likely reflecting delayed rower centre-of-mass negative acceleration in preparation for the catch. Greater absolute values of peak drive acceleration, first peak acceleration, and jerk in the early and mid-drive are also associated with improved performance, likely reflecting propulsive force during the drive. These proposed mechanisms provide potential strategies for performance enhancement additional to increases in stroke rate and power output.


[Meta analysis for interventional effect on unexpected injury among children and adolescents in China].
To comprehensively evaluate the interventional effect on unexpected injury among children and adolescents in China, and to provide scientific basis for the injury control strategy. Meta analysis was utilized to analyze the selected literatures. After heterogeneity test of the data, a relevant model was chosen to estimate the combined effect values relative risk (RR) and the corresponding 95% confidence interval (95% CI). Subgroup analysis were performed based on the intervention measures, objects and places. Sensitivity and publication bias were analyzed. A total of 18 papers were included in the Meta analysis with a sample size of 32 599. The combined RR value was 0.54 (95% CI 0.44 to 0.68). Subgroup analysis showed that the RR value of health education and comprehensive intervention were 0.59 and 0.50, respectively, with no significant difference between them (P>0.05). The RR values of the interventions in school alone, in school and community or in community alone were 0.51, 0.78 or 0.63. The RR values on children alone, children and parents or parents alone were 0.53, 0.65 or 0.35. The differences were significant when the interventions were performed among different places or objects (P<0.05). Sensitivity analysis revealed that meta-analysis results were relatively stable. The targeted interventions were significant in the prevention of unexpected injuries among children and adolescents. It is worth further promoting and spreading.


A Raman microspectroscopy study of water and trehalose in spin-dried cells.
Long-term storage of desiccated nucleated mammalian cells at ambient temperature may be accomplished in a stable glassy state, which can be achieved by removal of water from the biological sample in the presence of glass-forming agents including trehalose. The stability of the glass may be compromised due to a nonuniform distribution of residual water and trehalose within and around the desiccated cells. Thus, quantification of water and trehalose contents at the single-cell level is critical for predicting the glass formation and stability for dry storage. Using Raman microspectroscopy, we estimated the trehalose and residual water contents in the microenvironment of spin-dried cells. Individual cells with or without intracellular trehalose were embedded in a solid thin layer of extracellular trehalose after spin-drying. We found strong evidence suggesting that the residual water was bound at a 2:1 water/trehalose molar ratio in both the extracellular and intracellular milieus. Other than the water associated with trehalose, we did not find any more residual water in the spin-dried sample, intra- or extracellularly. The extracellular trehalose film exhibited characteristics of an amorphous state with a glass transition temperature of ?22°C. The intracellular milieu also dried to levels suitable for glass formation at room temperature. These findings demonstrate a method for quantification of water and trehalose in desiccated specimens using confocal Raman microspectroscopy. This approach has broad use in desiccation studies to carefully investigate the relationship of water and trehalose content and distribution with the tolerance to drying in mammalian cells.


Morphology of global cerebral ischemia.
The cerebral tissue responses to ischemia are modified by many factors, including the mechanism by which ischemia is induced, and the severity and duration. Children can withstand brain ischemic insults that are usually lethal to older patients. Other modifying factors of ischemia, such as barbiturates and serum glucose, remain poorly defined in humans. Once a cerebral ischemic event occurs, for example, after cardiac arrest and resuscitation, secondary events (such as alterations in the perfusability and reactivity of the microcirculation) may aggravate the original ischemic injury at discrete sites of the brain. A more exact definition of a) the limits of reversibility of ischemic injury, b) the histologic features of sublethally injured tissues, and c) the effects of various therapeutic interventions, awaits the development of relatively inexpensive and reproducible animal models of ischemia in which objective comparisons can be made between the nature of the local circulatory conditions and the accompanying histologic abnormalities.


Synergistic Effects of Heat-Treated Green Tea Extract and Enzymatically-Modified Isoquercitrin in Preventing Obesity.
Previous research has shown that both heat-treated green tea extract (HTGT) and enzymatically modified isoquercitrin (EMIQ) have anti-obesity effects. Given the absence of in vivo evidence demonstrating their synergistic effects, our study aimed to elucidate the combined obesity prevention potential of HTGT and EMIQ in mice. Mice were treated with these compounds for 8 weeks, while being fed a high-fat diet, to investigate their preventive anti-obesity effects. We demonstrated that the co-treatment of HTGT and EMIQ results in a synergistic anti-obesity effect, as determined by a Kruskal-Wallis test. Furthermore, the combined treatment of HTGT and EMIQ was more effective than orlistat in reducing body weight gain and adipocyte hypertrophy induced by high-fat diet. The co-treatment also significantly reduced total body fat mass and abdominal fat volume. Additionally, the group receiving the co-treatment exhibited increased energy expenditure and higher glucose intolerance. We observed a dose-dependent upregulation of genes associated with mitochondrial oxidative metabolism and PKA signaling, which is linked to lipolysis, in response to the co-treatment. The co-treatment group displayed elevated cAMP levels and AMPK activation in adipose tissue and increased excretion of fecal lipids. The results indicate that the co-treatment of HTGT and EMIQ holds the potential to be a promising combination therapy for combating obesity. To further validate the anti-obesity effect of the combined treatment of HTGT and EMIQ in human subjects, additional clinical studies are warranted.


[Laparoscopy in traumatic abdominal emergencies].
Over the past few years the laparoscopic technique has changed most of the concepts of traditional surgery and is today the standard approach in elective surgery for many pathologies requiring surgery. Unfortunately the same cannot be said for emergency surgery, though much progress has been made in this field, too. The Authors examine the most important abdominal diseases that can be diagnosed and, possibly, treated by the laparoscopic approach in the emergency setting, concluding that laparoscopic management of such conditions is a feasible proposition in many cases. Technological improvements and the development of new, more versatile surgical instruments will undoubtedly contribute to the increasingly widespread use of the laparoscopic approach also in emergency procedures.


Job satisfaction, stress, and burnout among Canadian gynecologic oncologists.
(1). To provide a job description of Canadian gynecologic oncologists. (2). To assess job satisfaction and job stress, and measure the prevalence of burnout and psychological morbidity. A cross-sectional survey was mailed to all Canadian gynecologic oncologists in September 2002. The job profile on Canadian gynecologic oncologists is predominantly clinical with a minor component of administration and to a less extent education or research. Clinically, 80% of the activity is focused on gynecologic cancer care. The majority of physicians (92%) are satisfied with their job, but there are clear concerns raised concerning systems issues in health care delivery. Approximately 26% of physicians are experiencing high stress, and this is strongly associated with emotional exhaustion and high depersonalization. Fourteen percent of Canadian gynecologic oncologists are actively looking for alternative jobs and 45% are trying to decrease the number of hours worked per week. When considering an alternate job, the most important factors are location, colleagues, and potential for personal growth. High stress and low personal accomplishment were seen in Canadian gynecologic oncologists. Organizations (i.e., hospitals) and health care funders have the opportunity to incorporate preventative strategies to keep this physician resource healthy.


Laryngeal mask airway.
The laryngeal mask airway (LMA) was first used in anaesthetic practice in the 1980s. It is now increasingly promoted as a first-line airway device during resuscitation, if a practitioner skilled in tracheal intubation is not available (Resuscitation Council (UK), 2002).


Polymerization of additional actin is not required for capping of surface antigens in B-lymphocytes.
CH12 is a murine B-cell lymphoma whose surface immunoglobulin (sIg) and concanavalin A (Con A) receptors patch and cap readily. Actin may be involved in CH12 patching and capping, since fodrin and F-actin collect under the cap, and cytochalasin D inhibits sIg capping. We have examined the state of the actin cytoskeleton during patching and capping. A wide range of concentrations of rabbit anti-mouse antibody (RAM) and Con A were used to patch or cap CH12 cells. G-actin was quantitated by DNase I inhibition, F-actin was quantitated by fluorescence-activated cell sorter analysis of fluorescent phalloidin staining, and actin nucleation sites were measured by pyrene actin polymerization. None of these methods detected any significant changes in actin when compared to control cells or untreated cells, leading us to conclude that increased actin polymerization is not necessary for capping to occur. The significance of these data to the membrane flow and cytoskeletal models of capping is discussed.


Effects of applying gamma-aminobutyric acid(B) drugs into the medial basal hypothalamus on basal luteinizing hormone concentrations and on luteinizing hormone surges in the female sheep.
Prior investigations have shown that localized infusion by microdialysis of gamma-aminobutyric acid(B) (GABA(B)) agonists into the medial basal hypothalamus of male sheep rapidly increases GnRH and LH pulse amplitude. The objectives of these studies were to determine if infusion of GABA(B) agonists SKF 97541 or baclofen into the medial basal hypothalamus of female sheep would affect basal LH secretion and if infusion of a potent antagonist would alter expression of LH surges induced by injection of estrogen. Infusion of either SKF 97541 (10 or 40 microM) or baclofen (1 mM) into estrogen-treated ovariectomized ewes did not alter basal LH secretory patterns, whereas both drugs significantly elevated mean LH and LH pulse amplitude in ovariectomized ewes during the nonbreeding season. Infusion of the antagonist CGP 52432 (250 or 500 microM) did not affect expression of estrogen-induced LH surges in ovariectomized ewes. These observations support the concept that GABA(B) receptors in the medial basal hypothalamus regulate basal LH secretion but do not regulate the surge mode of LH secretion in the female sheep.


Z-palatoplasty (ZPP): a technique for patients without tonsils.
Patients without tonsils and with Friedman tongue position (FTP) III and IV are poor candidates for uvulopalatopharyngoplasty (UP3). Even when combined with adjunctive hyopharyngeal techniques, results are poor. We assessed a modified uvulopalatoplasty based on a bilateral Z-plasty in treating patients without tonsils who have obstructive sleep apnea/hypopnea syndrome (OSAHS). 25 patients treated with a modified technique were matched with 25 patients previously treated with classic UP3. All patients in both groups also had radiofrequency tongue base reduction. Preoperative vs. postoperative measures of objective treatment success and subjective symptoms were compared for the 2 groups. Morbidity, including pain levels, narcotic use, and return to solid diet and normal activity, as well as complications were studied. Subjective improvement was good for both groups, but objective clinical improvement was significantly better for the experimental group. Morbidity and complications for the experimental group were comparable to the control group and to other published series on UP3. A modified technique for patients without tonsils who have OSAHS is presented. The new technique is more successful with acceptable morbidity for patients with OSAHS than classical techniques.


Decreasing Goal Oxygen Saturations in Bronchiolitis Is Associated With Decreased Length of Stay.
For patients hospitalized with bronchiolitis, many hospitals have implemented clinical practice guidelines to decrease variability in care. Our hospital updated its bronchiolitis clinical pathway by lowering goal oxygen saturation from 90% to 88%. We compared clinical outcomes before and after this change within the context of the pathway update. This was a retrospective analysis of patients <24 months old admitted to a pediatric tertiary care center from 2019 to 2021 with bronchiolitis. Patients with congenital heart disease, asthma, home oxygen, or admitted to an ICU were excluded. The data were stratified for patients admitted before and after the clinical pathway update. Statistical methods consisted of 2 group comparisons using the χ-square test for categorical variables, the Wilcoxon rank-sum test for continuous variables, and multiple regression analysis. A total of 1386 patients were included, 779 preupdate and 607 postupdate. There was no statistically significant difference in the admission rate of patients presenting to the emergency department with bronchiolitis between the 2 groups (P value .60). The median time to room air was 40.0 hours preupdate versus 30.0 hours postupdate (P value < .001). The median length of stay was 48.0 hours preupdate versus 41.0 hours postupdate (P value < .001). Readmission rate was 2.7% within 7 days of discharge preupdate, and 2.1% postupdate (P value .51). Decreasing goal oxygen saturation to 88% was associated with a statistically significant decrease in time spent on oxygen and length of stay for patients admitted with bronchiolitis with no increase in readmissions.


Gene set differential analysis of time course expression profiles via sparse estimation in functional logistic model with application to time-dependent biomarker detection.
High-throughput time course expression profiles have been available in the last decade due to developments in measurement techniques and devices. Functional data analysis, which treats smoothed curves instead of originally observed discrete data, is effective for the time course expression profiles in terms of dimension reduction, robustness, and applicability to data measured at small and irregularly spaced time points. However, the statistical method of differential analysis for time course expression profiles has not been well established. We propose a functional logistic model based on elastic net regularization (F-Logistic) in order to identify the genes with dynamic alterations in case/control study. We employ a mixed model as a smoothing method to obtain functional data; then F-Logistic is applied to time course profiles measured at small and irregularly spaced time points. We evaluate the performance of F-Logistic in comparison with another functional data approach, i.e. functional ANOVA test (F-ANOVA), by applying the methods to real and synthetic time course data sets. The real data sets consist of the time course gene expression profiles for long-term effects of recombinant interferon β on disease progression in multiple sclerosis. F-Logistic distinguishes dynamic alterations, which cannot be found by competitive approaches such as F-ANOVA, in case/control study based on time course expression profiles. F-Logistic is effective for time-dependent biomarker detection, diagnosis, and therapy.


[Management of dyspepsia, gastroduodenal ulcer and Helicobacter pylori infection in primary care].
To evaluate management of dyspepsia, gastroduodenal ulcer and Helicobacter pylori infection in the setting of family practice. An observational transversal study was performed. An anonymous questionnaire was send by mail between January and October 2000. Primary care. Physicians of 17 Primary Care centers. Sixty-four per cent of the physicians returned the answered questionnaire (107/165). Primary care doctors reported they had indicated eradication therapy at least once during last year in 94.3%; 89.7% usually indicate H. pylori eradication for duodenal ulcer and 70.1% for gastric ulcer. The main method for the study of dyspepsia was endoscopy associated with antral histology or rapid urease test for determination of H. pylori status. Omeprazole, clarithromycin and amoxicillin twice daily for seven days was the preferred eradication therapy (77.6%). Forty-five percent of physicians systematically tested patients to confirm cure of the infection; 36.4% tested patients only if symptoms relapsed. Breath test (72.7%) was the preferred method to confirm eradication. Physicians with postgraduate specialty in Family Care and Community Medicine (MFyC) demand less often gastroenterologist evaluation, indicate less frequently upper tract radiology, use more often C13 urea breath test for diagnosis and indicate more often eradication treatment for erosive duodenitis than unspecialised family doctors. Management of dyspepsia and H. pylori infection in Primary Care in our area is reasonably adapted to current consensus recommendations. Many differences in management were observed between MFyC and non-specialised primary care physicians.