Inpatient Hospital Charge Variability of U.S. Hospitals.
The range of hospital charges for similar diagnoses show tremendous variability across U.S. hospitals. This charge variability remains unexplained. We aimed to describe hospital charge variability in the U.S. and examine its relationship to local health factors. This was a descriptive study of the 2011 Medicare Inpatient Charge data summarizing inpatient hospital charges billed to Medicare. This data was evaluated using 29 county-level measures of health status, health behavior, clinical access and quality, built environment, and socioeconomic status in a clustered, multivariate linear regression. 2871 U.S. hospitals registered with Medicare and with at least ten discharges for diagnosis-related groups (DRGs) of six common inpatient conditions. Inpatient hospital charges were assessed. No community health measures were associated with hospital charges. The one notable exception associated with higher charges was higher rates of uninsured status ($344.84 higher charges for every one-percentage point increase in prevalence (p < 0.001)). One variable was associated with lower hospital charges: the percentage of children living in poverty [$309.30 lower charges for every one-percentage point increase in prevalence (p < 0.001)]. Overall, hospital charges lacked an association with population health measures, and their variability remains largely unexplained. However, the association of higher charges with uninsured status raises concerns about hospitals' price-setting strategies, such as price discrimination and cost-shifting strategies that expose vulnerable populations to great financial risks.


One-year follow-up of pharmacotherapy-resistant patients with panic disorder treated with cognitive-behavior therapy: Outcome and predictors of remission.
Non-response to pharmacotherapy for panic disorder (PD) is a well-documented problem. However, little information exists to guide next-step strategies for these non-responders. In addition to pharmacologic augmentation strategies, several studies support the efficacy of cognitive-behavior therapy (CBT) for these patients, although data on long-term outcomes has been lacking. In this study, we provide one-year outcomes on a sample of 63 patients who completed group CBT for PD after failing to respond adequately to previous pharmacotherapy. Sustained significant benefit was found for all dimensional outcome scores, and nearly two-thirds of the sample met remission criteria. This occurred with reductions in medication use over the follow-up period. Negative predictors of remission status included comorbid dysthymia, social phobia, and generalized anxiety disorder. These results provide additional evidence for the efficacy of CBT for medication non-responders with PD.


Loudness dependence of auditory evoked potentials in patients with borderline personality disorder--impact of psychopathology.
Alterations of the central serotonergic system are considered to be involved in the pathophysiology of borderline personality disorder (BPD). The loudness dependence of the N1/P2 component of auditory evoked potentials (LD) has been shown to indirectly reflect central serotonergic activity. The aim of this study was to investigate LD in patients with BPD compared to healthy controls, and to evaluate the association between LD and psychopathology such as anxiety, anger or impulsiveness. Female patients with BPD were included and compared to age- and sex-matched healthy subjects. Self-rating instruments, such as the State-Trait Anxiety Inventory (STAI), State-Trait Anger Expression Inventory (STAXI), and the Barratt Impulsiveness Scale (BIS) were used to assess clinical scores of anxiety, anger, and impulsiveness. Evoked potentials were recorded following the application of acoustic stimuli with increasing intensities; the LD was analysed using dipole source analysis. The mean LD was significantly higher in patients with BPD compared to controls. In the entire sample there were significant positive correlations of LD with state anxiety scores and STAXI subscores. The data contribute to the knowledge of neurophysiological alterations in patients with BPD, supporting the hypothesis of serotonergic dysregulation in the pathophysiology of the disorder. The significant clinical correlations suggest monoaminergic modulations of psychopathology on the symptom level.


Wilms' tumor--model of a curable pediatric malignant solid tumor.
Wilms' tumor is the model of the treatment of a pediatric solid tumor. Initially it appeared that multi-modality therapy, consisting of transabodominal nephrectomy, post-operative radiation therapy to the tumor bed and adjuvant, single agent chemotherapy provided the highest likelihood of disease-free survival. The identification of important prognostic factors, such as histology, tumor weight, lymph node involvement and age at diagnosis has led to a re-examination of the treatment of Wilms' tumor. Future therapeutic developments will include the administration of less therapy to some well defined groups of patients, and the exploration of new programs for patients who have been demonstrated to have a poor prognosis using currently accepted treatment techniques.


[Active forms of oxygen, oxidative stress and its pathologic significance].
Chemically hyperactive forms of oxygen can induce a variety of functional and morphologic alterations in aerobic organisms. Defensive mechanisms against oxidative damage may be involved in the etiology of pathologic processes induced by oxidative stress. Different antioxidant substances are used in treatment of these conditions.


Effects of ambient oxygen concentration on the growth and antioxidant defenses of of human cell cultures established from fetal and postnatal skin.
Oxygen toxicity is believed to arise from changes in the rates at which cells generate reactive oxygen species (ROS). Sensitivity to hyperoxia has been postulated to depend on levels of antioxidant defense. Human cells obtained from fetal tissues have lower antioxidant defenses than those obtained from adult tissue. The present study was performed to determine whether the differences in fetal and adult antioxidant defense levels modulated their responses to changes in the ambient oxygen concentration. Our results demonstrate that oxygen modulates the proliferation of human fetal and adult skin fibroblasts in a similar fashion. In general, skin fibroblasts grew better at approximately 31 mm Hg, regardless of donor age. Manganese superoxide dismutase, catalase, and glutathione peroxidase activities were lower in fetal cells than in adult fibroblasts. Copper/zinc superoxide dismutase and glucose-6-phosphate dehydrogenase were similar in fetal and postnatal tissues and were unaltered appreciably by hyperoxic exposure. Glutathione concentration increased at higher oxygen tensions; however, the increase was much greater in fetal cells than in cultures derived from adult skin. These observations demonstrate that the capacity of fetal and adult cells to cope with oxidative stress, while similar, result from distinct mechanisms.


Conditioned fear is modulated by CRF mechanisms in the periaqueductal gray columns.
The periaqueductal gray (PAG) columns have been implicated in controlling stress responses through corticotropin-releasing factor (CRF), which is a neuropeptide with a prominent role in the etiology of fear- and anxiety-related psychopathologies. Several studies have investigated the involvement of dorsal PAG (dPAG) CRF mechanisms in models of unconditioned fear. However, less is known about the role of this neurotransmission in the expression of conditioned fear memories in the dPAG and ventrolateral PAG (vlPAG) columns. We assessed the effects of ovine CRF (oCRF 0.25 and 1.0 μg/0.2 μL) locally administered into the dPAG and vlPAG on behavioral (fear-potentiated startle and freezing) and autonomic (arterial pressure and heart rate) responses in rats subjected to contextual fear conditioning. The lower dose injected into the columns promoted proaversive effects, enhanced contextual freezing, increased the blood pressure and heart rate and decreased tail temperature. The lower dose of oCRF into the vlPAG, but not into the dPAG, produced a pronounced enhancement of the fear-potentiated startle response. The results imply that the PAG is a heterogeneous structure that is involved in the coordination of distinct behaviors and autonomic control, suggest PAG involvement in the expression of contextual fear memory as well as implicate the CRF as an important modulator of the neural substrates of fear in the PAG.


[Cisterna chyli ablation in three cats with idiopathic chylothorax].
Presentation of three cats with chronic, idiopathic chylothorax treated with ablation of the cisterna chyli as an additional or a sole surgical treatment. Results of clinical and diagnostic examination, therapy and course of disease in three cats as well as the surgical technique of ablation of the cisterna chyli in cats are described. There were no intraoperative or postoperative complications regarding cisterna chyli ablation. Intraoperative visualization of the cisterna chyli is easily achieved by administering a small portion of a fatty aliment preoperatively or by injection of diluted methylene blue into the lymphatic system intraoperatively. Ablation of the cisterna chyli was performed following an unsuccessful ligation of the thoracic duct, in combination with the ligation of the thoracic duct and subtotal pericardectomy or as a single surgical treatment. Cisterna chyli ablation can be performed without complications in cats. This technique should be considered in cases of previously failed surgical therapy or as an adjunct therapy used with other surgical options to decrease the risk of recurrence.


Resveratrol protects bone marrow mesenchymal stem cell derived chondrocytes cultured on chitosan-gelatin scaffolds from the inhibitory effect of interleukin-1beta.
To investigate the effects of resveratrol on interleukin-1beta (IL-1beta) induced catabolism in bone marrow mesenchymal stem cell (MSC) derived chondrocytes cultured on chitosan-gelatin scaffolds (CGS). The chondrogenesis of alginate-encapsulated MSCs was evaluated by toluidine blue staining, RT-PCR, and immunostaing. MSC-derived chondrocyte morphology cultured on CGS was evaluated by a scanning electron microscope (SEM) and a laser confocal microscope (LCM). When these cells on CGS were pre-stimulated with IL-1beta or co-treated with IL-1beta and resveratrol in the absence and presence of the specific beta1-integrin blocking antibody, collagen type II, aggrecan, matrix metalloproteinase-13 (MMP-13) expression, and the translocation of nuclear factor kappaB (NF-kappaB) were analyzed by Western blot analysis. Transforming growth factor beta 3 (TGF-beta3) combined with insulin-like growth factor I (IGF-I) induced the cartilage-specific collagen type II, aggrecan expression and extracellular matrix (ECM) accumulation at the end of a 3-week culture. CGS supported those differentiated chondrocytes'attachment, proliferation, migration, and ECM formation. When those cells cultured on CGS were stimulated with IL-beta1 alone, collagen type II and aggrecan expression was inhibited. However, MMP-13 expression increased. Resveratrol reversed the catabolic effects by reducing the translocation of NF-kappaB. A specific beta1-integrin blocking antibody abrogated the effects of resveratrol on IL-1beta stimulated MSC-derived chondrocytes. These results indicated that resveratrol acts as a NF-kappaB inhibitor to protect MSC-derived chondrocytes on the CGS from the IL-1beta catabolism and these effects are mediated by beta1-integrin.


Iron modified bentonite: Enhanced adsorption performance for organic pollutant and its regeneration by heterogeneous visible light photo-Fenton process at circumneutral pH.
Iron modified bentonite (FeMB) was prepared and used as an inexpensive adsorbent to rapidly remove organic pollutant (Rhodamine B, RhB) from aqueous solution. The iron modification significantly improved the adsorption performance of FeMB for RhB and permitted an easy separation of FeMB from the treated effluent. The equilibrium adsorption studies indicated that the dye molecules obeyed Langmuir type of adsorption with the calculated maximum adsorption capacity of 168.13 mg g(-1) for FeMB. The heterogeneous photo-Fenton process operated at circumneutral pH in the presence of visible light irradiation was found to be effective for the regeneration of the spent FeMB. Furthermore, the regeneration efficiency of as high as 79% was still achieved after 5 consecutive adsorption-regeneration cycles. Considering that, the visible light photo-Fenton approach could be applied as an excellent alternative for regenerating clay-based adsorbents by avoiding the use of dissolved iron salts.


Adenosine deaminase inhibitors enhance cerebral anoxic hyperemia in the rat.
Cerebral blood flow in the rat was monitored by a venous outflow technique with an extracorporeal circulation, which allows for the continuous recording of flow over periods of several hours. The adenosine deaminase inhibitors erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) (1.0-100 micrograms/kg) and deoxycoformycin (0.1-1 micrograms/kg) potentiated the reactive hyperemia elicited by a brief (24-s) anoxic challenge. Basal flow rate was unaltered by EHNA administration and slightly enhanced by deoxycoformycin. The results are consistent with the hypothesis that adenosine plays a significant role in cerebral vascular regulation and suggest that low doses of these deaminase inhibitors may be useful in the treatment of cerebral vascular insufficiency.


Ultrastructure of Saccharomyces cerevisiae cells accumulating Golgi organelles.
Restrictive phenotype of sec 7 mutant of Saccharomyces cerevisiae was examined by freezefracture electron microscopy. In accordance with previous findings (NOVICK et al. 1981) dictyosomes and middle-size (200-600 nm) vesicles (Berkeley bodies) were found to accumulate. Dictyosomes are formed by aggregated flattened or dilated cisternae without associated secretory vesicles. After transfer to permissive conditions the dictyosomes disappear and are not detectable, just like in the wild type or in the permissive phenotype. Associated with the restrictive phenotype is an extended plasma membrane and tonoplasts with particle-free impressions.


The Effect of Prednisolone on miR 15a and miR16-1 Expression Levels and Apoptosis in Acute Lymphoblastic Leukemia Cell Line: CCRF-CEM.
Glucocorticoids are probably the most important drugs in the treatment of childhood acute lymphoblastic leukemia (ALL). Prednisolone exerts its effect by induce apoptosis in lymphoid lineage cells. Micro RNAs are 18-24 nucleotides RNA implicated in the control of essential biological functions, including apoptosis. In the following study, the effect of prednisolone on the expression of miR 15a & miR16-1 and apoptosis in the CCRF-CEM cell line is investigated. The cell line of CCRF-CEM was cultured in standard conditions. The changes in the miR 15a and miR 16-1 expression levels were determined by Real Time-PCR technique. Also, the apoptosis is evaluated by flow cytometry using Annexin V and PI staining. This study revealed that, the prednisolone induced apoptosis in a time dependent manner. Prednisolone in concentration of 700 µM was significantly increased the expression of miR 16-1 and miR 15a after 24 h and 48 h treatment (p<0.05). prednisolone-induced apoptosis might be mediated by up-regulation of these 2 miRNAs in CCRF-CEM cells.


The polymorphism -2548G/A in leptin and severity of chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by airway obstruction that is not fully reversible, and there is evidence of a hereditary component in COPD. We aimed to determine whether the polymorphisms -2548G/A of leptin (LEP) gene were associated with COPD and its severity in Chinese. A total of 456 subjects with COPD and 422 healthy controls from West China Hospital were enrolled in this study. COPD patients had been undergone a spirometry and a physical examination to refer the GOLD I-IV stages. The polymorphisms in the leptin promoter region at position -2548G/A were detected by Polymerase chain reaction-restriction fragment length polymorphism analysis. The genotypes and alleles were scored, and the frequencies of the alleles and genotypes in patients and controls were compared. A significantly higher risk for COPD was observed for carriers of the LEP -2548AA genotype [odds ratio (OR)=7.87, 95% confidence interval (CI) 4.19-14.77, P<0.001] and carriers of the LEP -2548GA genotype (OR=2.98, 95% CI 1.57-5.66, P=0.001). The LEP -2548A allele: frequency was significantly higher in the patient group compared with the control group (OR=2.75, 95% CI: 2.20-3.44, P<0.001). We also found a significant relationship between leptin gene polymorphism and the severity of COPD. In the present case-control study, we found an association between the -2548G/A variant of the leptin gene and pathogenesis, severity of COPD in the Chinese population. It suggests that leptin -2548G/A should be used as a genetic marker of COPD severity.


Cross-education in people with Parkinson's disease, a short-term randomized controlled trial.
People with Parkinson's disease usually have a major impairment on one side of the body. It is hypothesized that unilateral resistance training may improve strength on the most affected limb when compared to bilateral resistance training. 1) To confirm that short-term unilateral resistance training improves strength on the most affected limb in people with PD. 2) To investigate if short-term unilateral resistance training reduces asymmetry. Seventeen individuals with Parkinson's disease were randomly assigned to unilateral resistance group (UTG, n = 9) and bilateral resistance group (BTG, n = 8). Twenty-four sessions of resistance training were performed. The nine-hole peg and box and blocks tests were performed to assess motor control of the upper limbs. The handgrip strength and isokinetic dynamometry were performed to assess the upper and lower limbs strength, respectively. All tests were assessed unilaterally at baseline (T0), during (T12), and at the end of the intervention (T24). Friedman's ANOVA was used to determine within group differences across the three time-points. In the event of significance, post-hoc analyses were performed using the Wilcoxon signed rank test. The U Mann-Whitney was used to determine between group differences at a specific time point. The BTG was significantly better than the UTG group at T24 compared to T12 with respect to peak torque at 60°/s and 180°/s (p < 0.05). Short-term bilateral resistance training is better than unilateral resistance training to improve strength for lower limbs most affected in people with Parkinson's disease.


Provision and Characterization of a Corpus for Pharmaceutical, Biomedical Named Entity Recognition for Pharmacovigilance: Evaluation of Language Registers and Training Data Sufficiency.
Machine learning (ML) systems are widely used for automatic entity recognition in pharmacovigilance. Publicly available datasets do not allow the use of annotated entities independently, focusing on small entity subsets or on single language registers (informal or scientific language). The objective of the current study was to create a dataset that enables independent usage of entities, explores the performance of predictive ML models on different registers, and introduces a method to investigate entity cut-off performance. A dataset has been created combining different registers with 18 different entities. We applied this dataset to compare the performance of integrated models with models created with single language registers only. We introduced fractional stratified k-fold cross-validation to determine model performance on entity level by using training dataset fractions. We investigated the course of entity performance with fractions of training datasets and evaluated entity peak and cut-off performance. The dataset combines 1400 records (scientific language: 790; informal language: 610) with 2622 sentences and 9989 entity occurrences and combines data from external (801 records) and internal sources (599 records). We demonstrated that single language register models underperform compared to integrated models trained with multiple language registers. A manually annotated dataset with a variety of different pharmaceutical and biomedical entities was created and is made available to the research community. Our results show that models that combine different registers provide better maintainability, have higher robustness, and have similar or higher performance. Fractional stratified k-fold cross-validation allows the evaluation of training data sufficiency on the entity level.


Ligand density characterization of peptide-modified biomaterials.
A simple fluorescence based characterization method was developed to assess ligand density on peptide-modified biomaterials. The method exploits the exquisite sensitivity of proteolysis for the purpose of liberating a fluorescently labeled probe fragment from an immobilized peptide. The released fragment can then be detected in solution using high-throughput fluorometry. In silico screening tools identified the enzyme chymotrypsin as a promising candidate for releasing a detectable probe fragment from the fluorescently labeled peptide, Ac-CGGNGEPRGDTYRAYK(FITC)GG-NH(2). After chymotrypsin digestion of the peptide in solution was first characterized using mass spectrometry and HPLC, a basic enzyme mediated release protocol was developed and implemented to generate peptide-binding isotherms on various peptide-modified biomaterials. The new method is sensitive, has good signal-to-noise ratio (S/N), and is easily standardized. Furthermore, the technique can be applied independent of material chemistry and geometry, making it a suitable alternative to radiolabeling for a wide range of biomaterial applications.


Diagnostic value of disease history, clinical presentation, and inflammatory parameters of appendicitis.
The clinical diagnosis of appendicitis needs to be improved, as up to 40% of explorations for suspected appendicitis are unnecessary. The use of body temperature and laboratory examinations as diagnostic aids in the management of these patients is controversial. The diagnostic power of these variables compared to that of the disease history and clinical findings is not well studied. In this study we prospectively assessed and compared the diagnostic value of 21 elements of the history, clinical findings, body temperature, and laboratory examinations in 496 patients with suspected appendicitis. The diagnostic value of each variable was compared from the area under the receiver operating characteristic (ROC) curve and the likelihood ratios (LR). Logistic regression was used to analyze the diagnostic value of a combination of variables and to analyze independent relations. No single variable had sufficiently high discriminating or predicting power to be used as a true diagnostic test. The inflammatory variables (temperature, leukocyte and differential white blood cell (WBC) counts, C-reactive protein) had discriminating and predicting powers similar to those of the clinical findings (direct and rebound abdominal tenderness and guarding). Anorexia, nausea, and right-sided rectal tenderness had no diagnostic value. The leukocyte and differential WBC counts, C-reactive protein, rebound tenderness, guarding, and gender were independent predictors of appendicitis with a combined ROC area of 0. 93 for appendicitis. This showed that inflammatory variables contain important diagnostic information, especially with advanced appendicitis. They should therefore always be included in the diagnostic workup in patients with suspected appendicitis.


Peroperative detection with a gamma probe of pelvic metastasis after differentiated thyroid carcinoma in female patients: about two cases and management reflections.
Distant metastases of differentiated thyroid cancers are exceptionally localized in the soft tissues and the pelvic cavity. This last event complicates diagnosis, especially in female patients because of false positive nuclear imaging and unrelated iodine uptakes. False positive due to body secretions, urinary and fecal iodine retention and iodine uptake by non-thyroid tissues or ectopic thyroid tissue and bone metastasis of differentiated thyroid carcinoma. We present two cases of metastasectomy, guided by a peroperative gamma probe and intraoperative frozen sections of the specimens. In females patients because of potentially false positive nuclear imaging and iodine uptakes unrelated to pathology, it is very difficult to identify a pelvic metastasis. Our experience of two cases underlines these pitfalls and the possibilities to avoid them: the use of 131 Iodine SPECT/CT whole body scan, peroperative gamma probe and intraoperative frozen sections of specimen. Preoperative localization needs a precise 3D imaging and the surgical treatment must be guided by a peroperative gamma probe and frozen sections.


Nutrition in reproductive health.
This article reviews nutrition-related issues affecting women and their reproductive health. Health care providers must be able to perform a basic nutritional assessment to identify risk factors and develop a plan of care to reduce those risk factors and improve health. Guidelines are provided to assist in performing a nutritional status assessment. Nutritional assessment of women of reproductive age should identify factors that may affect fertility, periconceptional health, and pregnancy outcome. Recommendations are provided to assist the health care provider in counseling women regarding the relationship of food choices and exercise to health, fitness, and optimal bodily function. Controversies surrounding the effect of micronutrient deficits and excesses on reproduction and correction for these imbalances are discussed. Women should be encouraged to initiate dietary and other lifestyle changes to allow for optimal reproductive outcomes.


Process development for production of recombinant human interferon-gamma expressed in Escherichia coli.
A simple fed-batch process was carried out using constant and variable specific growth rates for high-cell-density cultivation of Escherichia coli BL21 (DE3) expressing human interferon-gamma(hIFN-gamma). The feeding rate was adjusted to achieve an appropriate specific growth rate. The dissolved oxygen level was maintained at 20-30% of air saturation by control of airflow and stirrer speed and, where necessary, by enrichment of inlet air with pure oxygen. Glucose was the sole source of carbon and energy and was provided by following a simple exponential feeding rate. The final cell density in the fed-batch fermentation with constant and variable specific growth rate feeding strategies was ~100 g dry cell wt l(-1) after 36 and 20 h, respectively. The final specific yield and overall productivity of recombinant hIFN-gamma in the variable specific growth rate strategy were 0.35 g rHu-IFN-gamma g(-1) dry cell wt and 0.9 g rHu-IFN-gamma l(-1) h(-1), respectively. A new chromatographic purification procedure involving anion exchange and cation exchange chromatographies was developed for purification of rHu-IFN-gamma from inclusion bodies. The established purification process is reproducible and the total recovery of rHu-IFN-gamma was ~30% (100 mg rHu-IFN-gamma g(-1) dry cell wt). The purity of the rHu-IFN-gamma was determined using HPLC. Sterility, pyrogenicity, and DNA content tests were conducted to assure the absence of toxic materials and other components of E. coli in the final product. The final purified rHu-IFN-gamma has a specific antiviral activity of ~2 x 10(7) IU/mg protein, as determined by viral cytopathic effect assay. These results certify the product for clinical purposes.


In vitro toxicity screening of chemical mixtures using HepG2/C3A cells.
Traditional toxicological methods that utilize only single pure compounds may not accurately predict risks from substances with multiple chemical constituents. A complementary approach to conventional methodologies includes in vitro systems that assess toxicity of chemical mixtures and identify components that may adversely impact biological processes. Compared to animal models, in vitro assays are inexpensive, rapid, and reduce and refine related animal testing. We utilized HepG2/C3A cells as a hepatotoxicity screening model to evaluate the cytotoxic and metabolic effects of three commercially available oil dispersants, Corexit EC9500A and EC9527A and ZI-400. The surfactant DOSS, a primary active constituent of the Corexit dispersants, was also evaluated. Biologically relevant endpoints were measured including cell viability, oxidative stress, and mitochondrial activity. Significant increases in cytotoxicity were observed with Corexit dispersants (LC(50)∼250 ppm), whereas ZI-400 was moderately cytotoxic (LC(50) >>400 ppm). Each dispersant caused an accumulation of reactive oxygen species and altered mitochondrial activity and other cellular processes. Generally, DOSS made notable contributions to the effects of EC9500A and EC9527A, however, they were observed at concentrations higher than those used in most consumer products. Overall, this system may represent a valuable complementary tool for predicting the toxicity of complex mixtures.


Generalized inferences on the overall treatment effect in meta-analysis with normally distributed outcomes.
This paper focuses on inferences about the overall treatment effect in meta-analysis with normally distributed responses based on the concepts of generalized inference. A refined generalized pivotal quantity based on t distribution is presented and simulation study shows that it can provide confidence intervals with satisfactory coverage probabilities and perform hypothesis testing with satisfactory type-I error control at very small sample sizes.


Clinical response to long term enzyme replacement treatment in children, adolescent and adult patients with Hunter syndrome.
Since enzyme replacement treatment (ERT) with idursulfase is available for Hunter syndrome (HS; mucopolysaccharidosis type II), for the first time, disease progression can be limited and organ damage reduced or prevented. We described retrospectively the clinical evolution of eight HS males, treated with ERT and followed in routine clinical practice in Hospital Infantil La Fe (Valencia, Spain). We studied three children, three adolescents and two adults. Time from diagnosis to ERT ranged from 13.7 to 0.2 years, and duration of ERT ranged from 24 to 77.1 months. From the start of ERT, weight and height increased in children and adolescents and remained stable in adults. Glycosaminoglycans (GAG) decreased in all patients; in patient 5 (aged 23 years), we observed the highest reduction (86%) with recovery of carpal tunnel syndrome, splenomegaly and a decrease in nocturnal oxygen dependence. Our results show that ERT improve respiratory impairment and organomegalies and decrease GAGs levels in all patients including children, adolescent and adults. While cardiac manifestations and facial features stabilized, responses in other parameters were heterogeneous.


Priming of human neutrophil superoxide generation by tumour necrosis factor-alpha is signalled by enhanced phosphatidylinositol 3,4,5-trisphosphate but not inositol 1,4,5-trisphosphate accumulation.
In human neutrophils, significant agonist-stimulated superoxide anion (O2-) release is observed only after exposure to a priming agent such as TNFalpha. We have investigated the potential for TNFalpha to modulate N-formyl-Met-Leu-Phe (fMLP)-triggered Ins(1,4,5)P3 and PtdIns(3,4,5)P3 accumulation. TNFalpha pretreatment did not affect basal or stimulated Ins(1,4,5)P3 levels but greatly upregulated fMLP-stimulated PtdIns(3,4,5)P3 accumulation, in a manner that matched, both temporally and in magnitude, the increase in O2- generation implying a possible role for PtdIns(3,4,5)P3 in signalling primed O2- release.


Do lower third molars increase the risk of complications during mandibular sagittal split osteotomy? Systematic review and meta-analysis.
The aim of this systematic review was to investigate whether the presence of third molars (3Ms) during sagittal split osteotomy of the mandible increases the risk of complications. Searches were conducted using MEDLINE via PubMed, LILACS, Cochrane Central, Scopus, DOSS, and SIGLE via OpenGrey up to December 2020. Fifteen articles were included for evaluation and 14 in the meta-analysis, with a total of 3909 patients and 7651 sagittal split osteotomies (670 complications). Inferior alveolar nerve (IAN) exposure in the proximal segment was the most frequent complication (n = 409), followed by bad splits (n = 151). Meta-analysis revealed no significant increase in the incidence of 3M-related IAN exposure (P = 0.45), post-surgical infections (P = 0.15), osteosynthesis material removal (P = 0.37), or bad splits (P = 0.23). The presence of 3Ms was associated with a reduced risk of nerve disorder (P = 0.05) and favoured bad splits in the lingual plate (P = 0.005). The quality of evidence was very low, mainly due to non-randomized study designs, high risk of bias, inconsistency, and imprecision. This systematic review suggests that the removal of 3Ms before sagittal mandibular osteotomy does not reduce the incidence of complications. Thus, we recommend future better-designed studies with rigorous methodologies and adjustments for confounding factors.


Community-acquired methicillin-resistant Staphylococcus aureus provoked cytokine storm causing severe infection on BALB/c mice.
Methicillin-resistant Staphylococcus aureus (MRSA) has become the most important pathogen of hospital-acquired (HA) or community-acquired (CA) infections. However, it is unclear of the cytokines responsible for pathological hyper-inflammation in sepsis related cytokine storm for MRSA infection. In this study, we selected typical HA-MRSA strain (YNSA163: ST239-t030-SCCmecⅢ) and two CA-MRSA isolates (YNSA7: ST59-t439-SCCmecⅣa and YNSA53: ST59-t437-SCCmecⅤb) from our previous research, infected on BALB/c mice, and analyzed the cytokine storm patterns during infection process. The animal experiments revealed the most serious lethal effect on BALB/c mice caused by YNSA7 strain infection, followed by YNSA53, and no BALB/c mice died for YNSA163 infection. Histopathological analyses revealed that lung was the most seriously damaged organs, followed by spleen and kidney, especially for CA-MRSA infection. The severe inflammatory reactions, tissue destruction, and massive exudation of inflammatory mediators and cells could be identified in CA-MRSA strains infected mice. Interleukin-6 (IL-6) and IL-10 were both highly expressed in spleen and lung of YNSA7 and YNSA53 dead cases compared with YNSA53 survived and YNSA163 cases, which demonstrated cytokine storm pattern for CA-MRSA strains infection. The results of IL-6 intervention experiment verified that the enhanced IL-6 secretion was responsible for the host lethality of YNSA7 infection. RNA-sequencing results among three MRSA isolates indicated most of the differentially expressed genes referred to cellular process, metabolism and genetic information processing of bacteria. Specifically, clpP, chp chemotaxis inhibit, fnbB, pathogencity island protein and virulence associated protein E were highly expressed in YNSA7 strain. In general, CA-MRSA strains provoked cytokine storm on BALB/c mice led to severe infection and lethality, the up-regulated of some virulence genes might play important role in pathogenesis.


Structure of poliovirus replicative intermediate RNA. Electron microscope analysis of RNA cross-linked in vivo with psoralen derivative.
The structure of the poliovirus replicative intermediate RNA was examined by electron microscopy after cross-linking in vivo with 4'-aminomethyl-4,5',8-trimethylpsoralen. After purification from infected cells, undenatured RI appeared as a double-stranded backbone of genome length, with an average of three (and occasionally up to eight) nascent, single-stranded tails. After denaturation, however, only single strands of heterogeneous length were visualized, indicating that the RI in the cell contains little or no duplex structure, and thus nascent chains are only transiently hydrogen-bonded to their template over short regions. The double-stranded backbone of undenatured RI, observed previously by others and in these experiments, is due to collapse of complementary chains during the deproteinization and purification procedures. The effectiveness of the in vivo cross-linking procedure was demonstrated by the complete inhibition of viral RNA synthesis in treated cells and by direct binding of [3H]AMT to RI molecules in vivo. Mature polio virions are impermeable to AMT; however, growth of virus in cells incubated with AMT in the dark resulted in normal yields of virus particles containing RNA genomes, whose infectivity could be subsequently photo-inactivated. The frequency of AMT-induced cross-linking was determined by analyses of double-stranded poliovirus RNA (RF). Cross-linking in vitro followed by spreading for electron microscopy under denaturing conditions yielded bubbled duplex structures with a minimum of one interstrand cross-link per 80 base-pairs. RF cross-linked in vivo also showed extensive cross-linking, decreased about fivefold from the in vitro cross-linked value. Thus, the failure to detect cross-linked RI under these conditions indicates that extensive base-pairing does not exist in vivo.


[Preparation of oral sustained-action preparations with a base of biologically degradable polymers. 2. Preparation of matrix tablets with a base of polylactic acid].
It is reported on the preparation and investigation of matrix tablets on the basis of the polylactic acid. Caffeine and phenazone served as model drugs. The release values obtained were analyzed by the equations of Noyes-Whitney and of Higuchi. It was demonstrated, that the solubility and the grain size of the drugs, their content in the tablets and an addition of Heweten 12 have an influence of the release of the drugs. In in vitro-investigations can be shown a hydrolytic degradation of the polymer, but not an enzymatic degradation.


Body dysmorphic disorder: implications for its validity as a DSM-III-R clinical syndrome.
A sample of 258 college students responded to three items in Likert-format designed by the authors to elicit information relating directly to the three criteria for body-dysmorphic disorder described in DSM-III-R (1987). 70% of the participants endorsed some agreement with an item regarding dissatisfaction with some aspect(s) of their bodies. 46% indicated some preoccupation with this aspect of their appearance, and 48% indicated some exaggeration of their perceived body image. Sex differences were significant on all three items. 28% of the sample endorsed all three of the items taken together. These results raise questions about the utility of a diagnosis which, as it is currently defined, could conceivably apply to a large percentage of the population and which disproportionately targets women.


Salmonella delivered Lawsonia intracellularis novel epitope-fusion vaccines enhance immunogenicity and confers protection against Lawsonia intracellularis in mice.
Attenuated Salmonella-mediated vaccine constructs were designed by employing selected discontinuous immunodominant epitopes of LatA, FliC, and PAL antigens of Lawsonia intracellularis to create vaccines against porcine proliferative enteropathy (PPE). Whole protein sequences were subjected to in silico prediction of dominant epitopes, the stability of fusions, and hydropathicity and to ensure that the fused epitopes were feasible for expression in a Salmonella system. Two fusion constructs, one comprising LatA epitopes and the other FliC-PAL-FliC epitopes, were built into a prokaryotic constitutive expression system and transformed into the auxotrophic Salmonella host strain JOL1800. Epitope selection eliminated the majority of less immunodominant regions of target proteins and resulted in an efficient secretion platform that induced significant protective responses. Overall, our results demonstrated that the Salmonella-mediated LI- multi-epitope vaccines elicited significant humoral and cellular immune responses. Additionally, the challenge study suggested that the vaccinated mice were protected against experimental Lawsonia intracellularis infection. Based on the outcomes of the study, Salmonella-mediated LI- multi-epitope vaccines have the potential to prevent PPE.


Positron emission tomography quantification of [11C]-harmine binding to monoamine oxidase-A in the human brain.
This article describes the kinetic modeling of [(11)C]-harmine binding to monoamine oxidase A (MAO-A) binding sites in the human brain using positron emission tomography (PET). Positron emission tomography studies were performed in healthy volunteers at placebo conditions and after treatment with clinical doses of moclobemide. In either condition, a two-tissue compartment model (2CM) provided better fits to the data than a one-tissue model. Estimates of k(3)/k(4) values from an unconstrained 2CM were highly variable. In contrast, estimates of the specifically bound radioligand distribution volume (DV(B)) from an unconstrained 2CM were exceptionally stable, correlated well with the known distribution of MAO-A in the brain (cerebellum <frontal cortex approximately putamen <temporal cortex approximately cingulate <thalamus) and thus provided reliable indices of MAO-A density. Total distribution volume (DV) values were also highly stable and not different from those estimated with the Logan approach. Fixing the DV of free and nonspecifically bound radiotracer (DV(F + NS)) or coupling DV(F + NS) between brain regions enabled more stable estimates of k(3)/k(4) as compared with an unconstrained 2CM. Moclobemide treatment leads to a 64% to 79% MAO-A blockade across brain regions, a result that supports the specificity of [(11)C]-harmine binding to MAO-A. The stability and reliability of DV(B) values obtained from an unconstrained 2CM, together with the computational simplicity associated with this method, support the use of DV(B) as an appropriate outcome measure for [(11)C]-harmine. These results indicate the suitability of using [(11)C]-harmine for quantitative evaluation of MAO-A densities using PET and should enable further studies of potential MAO-A dysregulation in several psychiatric and neurologic illnesses.


The role of platelets in diabetes-related vascular complications.
The contribution of platelets to the pathogenesis and progression of vascular complications in diabetes is supported by several studies. In general, platelets obtained from diabetic subjects show increased adhesiveness and an exaggerated aggregation, both spontaneous and in response to stimulating agents. The causes for this activation are multifold: altered exposure and/or abundance of glycoprotein receptors for agonists and adhesive proteins on the platelet surface, increased binding of fibrinogen, decreased membrane fluidity, altered platelet metabolism and changes in intraplatelet signalling pathways. The altered biophysical state of platelet membrane components in diabetes mellitus may be one of the major determinants of platelet hypersensitivity and hyperfunction and may contribute to impairments in various metabolic pathways, like intensified calcium mobilisation and accentuated thromboxane synthesis and release. Activated platelets interact with other cells, such as endothelial cells and leukocytes as well with the coagulation system in the process of atherosclerosis. Some studies indicated that platelet dysfunction was especially apparent in diabetic subjects with macro- or microangiopathy, while others showed that it may be related to the presence of diabetes mellitus per se. Several pharmaceutical compounds have been developed for the inhibition of platelet activation. However, aspirin treatment is cheap and effective, and aspirin remains to be the drug of choice for diabetic patients. It should be prescribed widely for patients who are at high risk of cardiovascular events.


Evaluating carotid artery disease. The concordance between pulsed Doppler/spectrum analysis and angiography.
The results of ultrasonic pulsed Doppler duplex scanning with spectral analysis and computer pattern recognition are compared with the results of contrast arteriography in patients screened for extracranial carotid artery disease. The intraangiographer variability (one radiologist reading the same films twice) and the interangiographer variability (two radiologists reading the same film independently) were also studied. To calculate degrees of agreement corrected for chance, the Kappa statistic was computed for all the evaluation methods employed. At the present time, the concordance between spectral analysis and cerebral contrast angiography reaches a Kappa value of 0.682 +/- 0.064. This level of agreement compares favorably with the interangiographer agreement level (K = 0.568 +/- 0.058) and the intraangiographer agreement (K = 0.711 +/- 0.054). The computer pattern recognition program predicted the degree of stenosis by angiography with an agreement of K = 0.721 +/- 0.059. This concordance compares favorably to that observed when the radiologists are compared with themselves and is greater than that reached by two different radiologists. The continuous improvement in precision and accuracy of duplex scanning offers the promise of its usefulness in clinical and epidemiological studies.


Lesbian landscape.
In this article about first love, the author discusses her coming of age as a lesbian who is also tribally affiliated.


C6 Glioma-Secreted NGF and FGF2 Regulate Neuronal APP Processing Through Up-Regulation of ADAM10 and Down-Regulation of BACE1, Respectively.
Excessive accumulation of amyloid-β (Aβ) caused by cleavage of amyloid precursor protein (APP) is thought to be the primary cause of Alzheimer's disease (AD). Two key enzymes ADAM10 and BACE1 are involved in the initial cleavage of APP, resulting in the onset of two pathways, the amyloidogenic pathway and the non-amyloidogenic pathway, respectively. Altering APP metabolism towards the non-amyloidogenic pathway is thought to reduce Aβ production. It has been reported that, in vivo, exogenous neurotrophic factors make APP apt to entering the non-amyloidogenic pathway. Since astrocytes secrete a battery of neurotrophic factors, we investigated the role of astrocyte-derived factors in the dynamics of Aβ generation in neural cells. Results show that C6 glioma cell-conditioned medium (GCM), obtained from cultured astrocyte-derived C6 glioma cells, inhibit Aβ1-42 production and shift APP processing towards the non-amyloidogenic pathway in APPswe-HEK293 cells. Such effect is attributed to two key APP cleavage enzymes, ADAM10 and BACE1. Two neurotrophic factors in the GCM, nerve growth factor and fibroblast growth factor 2, are responsible for the up-regulation of ADAM10 and down-regulation of BACE1, respectively. Our findings enhance our understanding of the relationship between astrocytes and Aβ generation, indicating that stimulation of astrocytic neurotrophic factors could slow AD progression.


Reaction of the trichloromethyl and halothane-derived peroxy radicals with unsaturated fatty acids: a pulse radiolysis study.
The absolute rates of reaction of the trichloromethylperoxy radical, CCl3OO., derived from carbon tetrachloride and the halothane peroxy radical, CF3CHClOO., with oleic, linoleic, linolenic and arachidonic acids have been determined using the fast reaction technique of pulse radiolysis. In general, the rates of reaction of the radical derived from carbon tetrachloride are approximately five times greater than those for the halothane related radical. In both cases the rate constant increases with increasing unsaturation of the fatty acid in agreement with the known greater susceptibility of polyunsaturated fatty acids to peroxidative decomposition.


A pragmatic contouring guideline for salivary gland structures in head and neck radiation oncology: the MOIST target.
One of the main normal tissue toxicities in head and neck radiation oncology is xerostomia. In several studies, reduced radiation dose to the salivary glands has been shown to diminish the effects of gland dysfunction. However, no clear guidelines exist to define the anatomic location of the involved glands on cross-sectional imaging in a pragmatic manner. This study presents an anatomic, computed tomography (CT)-based definition of the major and minor salivary glands. On the basis of information from normal structure anatomy, the location of major and minor salivary glands was identified and translated into a cross-sectional CT-based description of the salivary glands. The major salivary glands include the parotids and submandibular glands. The minor salivary glands are presented as a part of a surrogate structure (the Minor Oral Including Sublingual Salivary Tissue target), including the minor glands located in the oral mucosa of the tongue, hard and soft palate, buccal mucosa, and inner surface of the lips. Clinical implementation of CT-based delineations of the salivary glands according to the proposed guideline should reduce interobserver variability. This may lead to an improved understanding of the relationship between radiation dose and volume and effects on salivary function.


Chemoimmunotherapy of metastatic malignant melanoma. The Salpétrière Hospital (SOMPS) experience.
Optimistic results were obtained in the treatment of 39 patients with surgically incurable metastatic malignant melanoma using a regimen including 2 to 3 monthly induction cycles of cis-diamminedichloroplatinum (CDDP), recombinant interleukin-2 (rIL-2) and interferon alpha-2a (IFN alpha-2a). 33 of 39 patients were pretreated with chemotherapy (dacarbazine and/or fotemustine:31, CDDP:6) and 17 of 39 with IFN alpha-2a. Overall response rate was 54% with 13% achieving a complete response for up to 59+ weeks. Moderate to severe side-effects were reversible on rIL-2 cessation and toxicity was manageable in a routine inpatient setting. These results are especially encouraging as they were seen in previously treated patients, classically low responders, including 3 who were resistant to cisplatin or other platinum complexes. The question remains if this regimen bypasses traditional mechanisms of drug resistance.


Unfolding of nucleosome core induced by phosphatidylserine.
The main experimental findings on the actual presence of lipids among the minor chromatin components are revised and discussed especially in the light of the reported effects that exogenous lipids induce in DNA and RNA synthesis by using purified templates. Moreover, all the available evidence of the influence of phospholipid liposomes on the activities and structure of isolated nuclei are reported. In order to further clarify the possible mechanism by which phospholipids could affect gene expression, the modifications at the nucleosome core level have been investigated by means of IAF staining and electron microscopy. The results obtained indicate that the increased transcriptional activity induced by PS MLV in isolated nuclei requires both the removal of histone H1, which causes the unfolding of the solenoid into the nucleosome fiber configuration of the chromatin, and the subsequent splitting of the H3 dimer. This latter process, monitored by IAF accessibility to H3 in isolated nucleosomes incubated with PS, causes the transition from the nucleosome to the lexosome structure, which is the configuration favoring the activity of RNA polymerases.


Mercuric chloride-induced gastrin/cholecystokinin 8 immunoreactivity in the central nervous system of the terrestrial slug Semperula maculata: an immunohistochemical study.
We measured the immunoreactivity of the neuropeptide gastrin cholecystokinin 8 (gastrin/CCK 8) in neurons of the terrestrial slug Semperula maculata following acute treatment with mercuric chloride (HgCl2). The distribution of gastrin/CCK 8 was analyzed in neurons of different regions, specifically from cerebral ganglia (procerebrum (pro-c), mesocerebrum (meso-c) and metacerebrum (meta-c). In the control group, neurons of pedal, pleural, parietal and visceral ganglia showed positive immunoreactivity using vertebrate antiserum against gastrin/CCK 8. Gastrin/CCK 8 immunoreactivity was also seen in the fibers and neuropil region of all ganglia. In the cerebral ganglion, 10, 12 and 8 % of the neurons from pro-c, meso-c and meta-c, respectively, were stained with the antibody. The immunostaining was increased in neurons (giant, large, medium and small) after HgCl2 treatment. The treatment greatly increased the mucin content within the neurons. Exposure to HgCl2 enhanced gastrin immunoreactivity in the neurons and this increased with time. Results are discussed in the context of neuropathology in cerebral ganglia associated with the feeding behavior of Semperula maculata.


The best way of preventing device-device interactions may be avoiding implanting 2 devices in the first place.
Extensive testing during the second device implantation was required to best program the devices in order to decrease these negative interactions. Unfortunately, these programming changes were not always successful at preventing device-device interactions during clinical follow-up.


Long-term outcome of intravitreal ranibizumab treatment, compared with photodynamic therapy, in patients with polypoidal choroidal vasculopathy.
To evaluate the functional outcomes of patients with polypoidal choroidal vasculopathy (PCV) who underwent intravitreal ranibizumab (IVR) treatment, compared with photodynamic therapy (PDT), after at least 2 years. We retrospectively studied all the treatment-naïve patients with PCV who were scheduled to undergo IVR or PDT between August 2005 and June 2010. All the patients who had a 2-year or longer follow-up period were included in the study. The best-corrected visual acuity (BCVA) in the two groups was compared before treatment and at 3, 6, 12, 18 and 24 months after the initial treatment. The regression of the polyps was also assessed using indocyanine green angiography. A total of 77 patients were included in this study. Thirty-three eyes were treated with IVR, and 44 eyes were treated with PDT. Although no significant differences between the two groups were observed at baseline or at 3, 6, and 12 months after treatment, a significantly better BCVA was seen in the IVR group, compared with the PDT group, at 18 and 24 months after treatment (P=0.035 and P=0.021, respectively). No significant difference in the rate of polyp regression was observed between the two groups (P=0.092). IVR was well tolerated and maintained or improved the vision of patients with PCV, compared with PDT, as evaluated at 2-year follow-up examinations. PDT for the treatment of PCV might result in unfavorable outcomes, with no superiority to achieving the involution of polyps.


Classic and rare manifestations of multiple osteoma: A case report.
Osteoma is a benign tumor that can arise from compact or cancellous bone and is more commonly found in the face or skull. The incidence of osteoma believed to be underreported as most are asymptomatic. To date, the best modality to diagnose osteoma is CT scan. We report a unique case of osteoma presenting with cranial and extracranial manifestations and highlight the importance of bone survey in evaluating patients with osteoma. A 26-year-old female complained of bilateral pain in the jawbone and several areas of her head. On physical examination, there were several masses in the head with the largest on the left mandible measuring 5.6 × 6.0 × 4.5 cm from MSCT examination. Hemi-mandibulectomy, histopathological and cytopathology examination were performed on the tissue obtained from the left mandible which concluded osteoma. Post-operative bone survey was performed and found osteoma on left ulna and bilateral fibula. Suspected Gardner syndrome with multiple osteoma manifestation was excluded from normal results of colon in-loop examination. We conservatively monitored the patient and most recent 6-month follow-up found no complaint nor changes in the extracranial osteoma manifestation on left ulna and both fibulas. The benign tumor osteoma is incredibly uncommon to present both intra and extracranially. We suggest thorough skeletal studies such as bone survey to be performed as they are crucial in the full evaluation of patients with multiple osteomas. Osteoma treatment is based on the patient's symptoms, surgery for patients with symptoms and periodic monitoring for asymptomatic patients. It is necessary to consider radiological modality for diagnosing osteoma patients. The majority of osteomas are asymptomatic and the choice of radiological examination sometimes still misses the lesion. It is important to evaluate histologically if the lesion difficult to diagnose.


Western disturbances alter the trend of winter precipitation and its extremes over Northwest Himalayas: Kashmir Himalaya.
The perception of spatio-temporal variability of winter precipitation covering dominant water resources and environment over Kashmir Himalaya is a pre-eminent perspective under current social interests. The main objectives of the study are, firstly, to unriddle the whole (1980-2020) and post-2000 trend in the winter season precipitation (WP), frequency of low-pressure systems (Lp-S), and western disturbances (WDs) to understand the footprints of climate change over the region; secondly, to evaluate the spatio-temporal variability of winter precipitation under the dominance of global teleconnection indices, using both station and reanalysis datasets. Modified Mann-Kendell test and a linear regression model were utilized to extract the trend and significance in WP, Lp-S, and WDs. The results reveal that WP shows an insignificant decreasing trend (1980-2020), with an increasing trend post-2000, while a decreasing trend is seen during post-2000 in the frequency of Lp-S and WDs. The contribution of WP to annual precipitation shows decadal variability with a decreasing trend post-2000. The anatomy of winter extreme precipitation days has shown a decreasing trend (1980-2020), with a robust coupled increasing trend with WP post-2000. The dynamics of ten severe WD-based extreme precipitation events show that a cyclonic circulation and trough connects the Arabian Sea and the Himalayas, bringing additional moisture to the study region and resulting in extreme precipitation. The cogency of global teleconnections on the variability of WP shows that a pattern with positive phase of NAO, ENSO, and a negative phase in Siberian high intensifies the WD-based precipitation. The study discovers its applicability for the regional forecast system in predicting the winters.


Feedback circuits are numerous in embryonic gene regulatory networks and offer a stabilizing influence on evolution of those networks.
The developmental gene regulatory networks (dGRNs) of two sea urchin species, Lytechinus variegatus (Lv) and Strongylocentrotus purpuratus (Sp), have remained remarkably similar despite about 50 million years since a common ancestor. Hundreds of parallel experimental perturbations of transcription factors with similar outcomes support this conclusion. A recent scRNA-seq analysis suggested that the earliest expression of several genes within the dGRNs differs between Lv and Sp. Here, we present a careful reanalysis of the dGRNs in these two species, paying close attention to timing of first expression. We find that initial expression of genes critical for cell fate specification occurs during several compressed time periods in both species. Previously unrecognized feedback circuits are inferred from the temporally corrected dGRNs. Although many of these feedbacks differ in location within the respective GRNs, the overall number is similar between species. We identify several prominent differences in timing of first expression for key developmental regulatory genes; comparison with a third species indicates that these heterochronies likely originated in an unbiased manner with respect to embryonic cell lineage and evolutionary branch. Together, these results suggest that interactions can evolve even within highly conserved dGRNs and that feedback circuits may buffer the effects of heterochronies in the expression of key regulatory genes.


Dietary fiber polysaccharides of amaranth, buckwheat and quinoa grains: A review of chemical structure, biological functions and food uses.
Seeds of amaranth (Amaranthus spp.), buckwheat (Fagopyrum esculentum and F. tataricum) and quinoa (Chenopodium quinoa) become popular foods due to their attractive health effects. Cell wall polysaccharides are the major components of dietary fiber and significantly contribute to diverse health effects of the grains. This review summarizes chemical and physical structure, biological functions and food uses of the cell wall polysaccharides and fractions as fiber components from the 3 pseudocereals. The properties and uses of the polysaccharides and fractions are compared with those of fiber polysaccharides from common sources such as fruits and vegetables. Overall, the fiber polysaccharide composition of the pseudocereals is more similar to that of fruits and vegetables than to that of cereals. The fiber polysaccharides showed a range of biological functions such as antioxidation, anticancer and immunomodulation. The fiber polysaccharides of amaranth, buckwheat and quinoa have potential to be used in formulations of functional foods.


Alterations in sleep physiology in young children with insulin-dependent diabetes mellitus: relationship to nocturnal hypoglycemia.
To examine the effect of diabetes per se and nocturnal hypoglycemia on sleep in children with insulin-dependent diabetes mellitus (IDDM). Overnight polysomnography was performed on 3 occasions in 29 children with IDDM - twice during metabolic profiling. Sleep data were analyzed from 14 children (median [range], 8.7 [5.9 to 12.9] years) with a night of hypoglycemia and a nonhypoglycemic night. Seven children in the control group (9 [5.6 to 11.4] years) underwent 2 nights of polysomnography, once during metabolic profiling (to assess the effects of metabolic profiling), and 15 members of the control group had polysomnography only (to assess the effects of diabetes per se and to compare with the index group). Children with IDDM had disrupted sleep compared with the control group (short wakes, percentage of sleep time, 0.8 [0.5 to 1.9] vs 0.0 [0.0 to 0.3], median [interquartile range], IDDM vs control group, respectively, P =.001; long wakes, 1.2 [0.7 to 3. 0] vs 0.0 [0.0 to 0.0], P =.033; total number of wakes, 6 [3.5 to 11. 5] vs 1 [0 to 2], P =.002). Blood sampling disrupted sleep with increased long wakes as percentage of sleep time (0.3 [0.0 to 3.8] vs 4.3 [3.1 to 16.9], nonsampling vs sampling night, respectively, P =.003). Episodes of hypoglycemia were profound, with a glucose nadir of 2.0 [1.4 to 3.3] mmol/L (35.0 [24.5 to 57.8] mg/dL) and prolonged, 308 [30 to 630] minutes, with no effect on sleep. Children with diabetes had disrupted sleep compared with a control group, but there was no effect of profound nocturnal hypoglycemia on sleep quality. J Pediatr 2000;137:233-8)


[Reexpansion pulmonary edema after pneumothorax. Apropos of a case. Review of the literature].
Pulmonary edema after re-expansion of a pneumothorax occurs within a maximum of 3 days of the pneumothorax and manifests by intense clinical signs (cough, abundant foamy expectoration, major cyanosis), marked hypoxia and a "white lung" radiologic image. The outcome was rapidly favorable in the case reported, despite the severity of the initial symptomatology. Currently accepted physiopathologic mechanisms implicate numerous factors in the genesis of edema due to re-expansion. The lesional pulmonary edema can be explained by alteration in alveolar capillary permeability, by the atelectasis, hypoperfusion and stretching during revascularization, and possibly by the action of free radicals. A hemodynamic edema also exists as a consequence of the reduction in pulmonary interstitial pressure. Possible prophylactic measures are discussed, the most appropriate appearing to be very progressive evacuation of the pneumothorax.


The resting surface electrocardiogram as a predictor of future hypertension.
Resting supine and post-provocation (dynamic exercise, isometric exercise and cold pressor) levels of blood pressure were measured in 80 normotensive offspring of normotensive parents (control) and 55 normotensive offspring of parents with essential hypertension. The surface electrocardiogram (including conventional twelve leads, posterior chest leads, right-sided chest leads and bipolar precordial leads) was also recorded in all subjects. Twenty-eight offspring of parents with essential hypertension had their resting and/or post-provocation blood pressure above the upper limit of standard deviation in age- and sex-matched control group. Flat or upright T waves, with either S waves less than 0.2 mV, or S/R ratio less than 2, or T waves equal to or higher than the accompanying R waves in lead V4R, could identify these potential hypertensives with nearly 90% specificity and nearly 75% sensitivity. The criterion had been derived, however, by analysis of the data achieved retrospectively. Therefore, the exact discriminating value of this criterion can be assessed only by a long-term prospective study.


Characterization of the cytochrome P-450 monooxygenase system of hamster liver microsomes. Effects of prior treatment with ethanol and other xenobiotics.
The cytochrome P-450 monooxygenase system of hamster liver microsomes and its response to prior treatment with ethanol and other xenobiotics have been examined. Male Syrian golden hamsters were administered ethanol (ETOH), phenobarbital (PB), 5,6-benzoflavone (BF) or isoniazid (INH). Each treatment resulted in a moderate increase (20-60%) in the specific content of liver microsomal cytochrome P-450 along with a unique hemeprotein ferrous carbonyl Soret maximum. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of liver microsomes revealed distinctive changes in protein banding patterns in the cytochrome P-450 (45-60 kDa) region with each treatment. NADPH: cytochrome c reductase activity was increased by both PB and INH, whereas cytochrome b5 content was increased by INH only. Microsomal oxidation of ETOH and aniline p-hydroxylation (expressed per nmol cytochrome P-450) were enhanced dramatically by ETOH and INH, whereas PB and BF had no effect on these enzymatic activities. Both ETOH and INH also increased zoxazolamine 6-hydroxylation but, in contrast to other rodent species, this drug-metabolizing activity was decreased in hamster liver microsomes after treatment with either PB or BF. Microsomal benzphetamine N-demethylation was decreased by ETOH, INH and BF administration and was only modestly enhanced after treatment with PB. ETOH and INH had no effect on the O-deethylation of 7-ethoxycoumarin, and enzymatic activity increased by BF but decreased by PB. These results demonstrate that the cytochrome P-450-dependent monooxygenase system of hamster liver microsomes responds to treatment with ETOH and other xenobiotics in a manner that is quantitatively and, in certain respects, qualitatively different from that reported for the rat, rabbit, and mouse.


The sensitization of cells treated with O6-methylguanine to alkylation damage is affected by the number of O6-methylguanine-DNA methyltransferase molecules escaped from inactivation.
O6-Methylguanine (MeG) can bind to the active site of O6-methylguanine-DNA methyltransferase (MGMT) as a free base. The subsequent methyl transfer reaction inactivates the repair protein. Hence, MeG is used to deplete the active MGMT pools in Chinese hamster cell lines (CHO) transfected to express varying amounts of human MGMT. After treatment with the free base, a residual population of active protein molecules remains localized mostly in the cytoplasm. Depleted cells are then challenged with the alkylating drug mitozolomide. Genotoxicity of this agent varied among the cell lines, and the compound sensitivity seemed to be regulated by a steady state equilibrium of residual MGMT molecules between nucleus and cytoplasm.


[Renovascular hypertension: prediction of surgical treatment by angiotensin II blockade and saralasin (author's transl)].
The response of arterial pressure to an infusion of saralasin was compared to the effect of surgical correction of renal vascular lesions (3 to 6 months after surgery) in eleven patients whose hypertension was associated with uni or bilateral stenosis of renal artery. Saralasin was infused after four days of dietary sodium restriction (10--40 mEq/day). An excellent correlation (r = 0.83, p less than 0.005) between the effects of saralasin and surgery was obtained. There was no correlation between the response to saralasin or to surgery and the ratio of renal vein renin activities. It is suggested that saralasin may be a good tool for predicting the effect of surgery in renovascular hypertension, when infused in moderately sodium depleted patients.


Natural potent androgens: lessons from human genetic models.
Male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase-3 (17 beta-HSD-3) deficiency and 5 alpha-reductase-2 (5 alpha-RD-2) deficiency provides natural human genetic models to elucidate androgen actions. To date, five 17 beta-HSD isozymes have been cloned that catalyse the oxidoreduction of androstenedione and testosterone and dihydrotestosterone (DHT), oestrone and oestradiol. Mutations in the isozyme 17 beta-HSD-3 gene are responsible for male pseudohermaphroditism due to 17 beta-HSD deficiency. The type 3 isozyme preferentially catalyses the reduction of androstenedione to testosterone and is primarily expressed in the testes. Fourteen mutations in the 17 beta-HSD-3 gene have been identified from different ethnic groups. Affected males with the 17 beta-HSD-3 gene defect have normal wolffian structures but ambiguous external genitalia at birth. Many are raised as girls but virilize at the time of puberty and adopt a male gender role. Some develop gynaecomastia at puberty, which appears to be related to the testosterone/oestradiol ratio. Two 5 alpha-reductase (5 alpha-RD) isozymes, types 1 and 2, have been identified, which convert testosterone to the more potent androgen DHT. Mutations in the 5 alpha-RD-2 gene cause male pseudohermaphroditism, and 31 mutations in the 5 alpha-RD-2 gene have been reported from various ethnic groups. Such individuals also have normal wolffian structure but ambiguous external genitalia at birth and are raised as girls. Virilization occurs at puberty, often with a gender role change. The prostate remains infantile and facial hair is decreased. Balding has not been reported.


Transcriptomic comparison of bone marrow CD34 + cells and peripheral blood neutrophils from ET patients with JAK2 or CALR mutations.
Essential thrombocythemia (ET) is one of the most common types of Ph-negative myeloproliferative neoplasms, an infrequent group of blood cancers that arise from a CD34 + hematopoietic stem cell (HSC) in the bone marrow (BM) primarily due to driver mutations in JAK2, CALR or MPL. These aberrations result in an overproduction of mature myeloid cells in peripheral blood (PB). To date, no targeted therapies have been approved for ET patients, so the study of the molecular mechanisms behind the disease and the identification of new therapeutic targets may be of interest. For this reason, in this study, we have compared the transcriptomic profile of undifferentiated CD34 + cells and mature myeloid cells from ET patients (CALR and JAK2-mutated) and healthy donors deposited in publicly available databases. The study of the similarities and differences between these samples might help to better understand the molecular mechanisms behind the disease according to the degree of maturation of the malignant clone and the type of mutation and ultimately help identify new therapeutic targets for these patients. The results show that most of the altered hallmarks in neutrophils were also found in CD34 + cells. However, only a few genes showed a similar aberrant expression pattern in both types of cells. We have identified a signature of six genes common to patients with CALR and JAK2 mutations (BPI, CRISP3, LTF, MMP8, and PTGS1 upregulated, and PBXIP1 downregulated), a different signature of seven genes for patients with CALR mutations (BMP6, CEACAM8, ITK, LCN2, and PRG2 upregulated, and MAN1A1 and MME downregulated) and a signature of 13 genes for patients with JAK2 mutations (ARG1, CAST, CD177, CLEC5A, DAPP1, EPS15, IL18RAP, OLFM4, OLR1, RIOK3, SELP, and THBS1 upregulated, and IGHM downregulated). Our results highlight transcriptomic similarities and differences in ET patients according to the degree of maturation of the malignant clone and the type of mutation. The genes and processes altered in both CD34 + cells and mature neutrophils may reveal altered sustained processes that could be studied as future therapeutic targets for ET patients.


The role of pattern recognition in creative problem solving: a case study in search of new mathematics for biology.
Rosen classified sciences into two categories: formalizable and unformalizable. Whereas formalizable sciences expressed in terms of mathematical theories were highly valued by Rutherford, Hutchins pointed out that unformalizable parts of soft sciences are of genuine interest and importance. Attempts to build mathematical theories for biology in the past century was met with modest and sporadic successes, and only in simple systems. In this article, a qualitative model of humans' high creativity is presented as a starting point to consider whether the gap between soft and hard sciences is bridgeable. Simonton's chance-configuration theory, which mimics the process of evolution, was modified and improved. By treating problem solving as a process of pattern recognition, the known dichotomy of visual thinking vs. verbal thinking can be recast in terms of analog pattern recognition (non-algorithmic process) and digital pattern recognition (algorithmic process), respectively. Additional concepts commonly encountered in computer science, operations research and artificial intelligence were also invoked: heuristic searching, parallel and sequential processing. The refurbished chance-configuration model is now capable of explaining several long-standing puzzles in human cognition: a) why novel discoveries often came without prior warning, b) why some creators had no ideas about the source of inspiration even after the fact, c) why some creators were consistently luckier than others, and, last but not least, d) why it was so difficult to explain what intuition, inspiration, insight, hunch, serendipity, etc. are all about. The predictive power of the present model was tested by means of resolving Zeno's paradox of Achilles and the Tortoise after one deliberately invoked visual thinking. Additional evidence of its predictive power must await future large-scale field studies. The analysis was further generalized to constructions of scientific theories in general. This approach is in line with Campbell's evolutionary epistemology. Instead of treating science as immutable Natural Laws, which already existed and which were just waiting to be discovered, scientific theories are regarded as humans' mental constructs, which must be invented to reconcile with observed natural phenomena. In this way, the pursuit of science is shifted from diligent and systematic (or random) searching for existing Natural Laws to firing up humans' imagination to comprehend Nature's behavioral pattern. The insights gained in understanding human creativity indicated that new mathematics that is capable of handling effectively parallel processing and human subjectivity is sorely needed. The past classification of formalizability vs. non-formalizability was made in reference to contemporary mathematics. Rosen's conclusion did not preclude future inventions of new biology-friendly mathematics.


Josephson coupled Ising pairing induced in suspended MoS2 bilayers by double-side ionic gating.
Superconductivity in monolayer transition metal dichalcogenides is characterized by Ising-type pairing induced via a strong Zeeman-type spin-orbit coupling. When two transition metal dichalcogenides layers are coupled, more exotic superconducting phases emerge, which depend on the ratio of Ising-type protection and interlayer coupling strength. Here, we induce superconductivity in suspended MoS2 bilayers and unveil a coupled superconducting state with strong Ising-type spin-orbit coupling. Gating the bilayer symmetrically from both sides by ionic liquid gating varies the interlayer interaction and accesses electronic states with broken local inversion symmetry while maintaining the global inversion symmetry. We observe a strong suppression of the Ising protection that evidences a coupled superconducting state. The symmetric gating scheme not only induces superconductivity in both atomic sheets but also controls the Josephson coupling between the layers, which gives rise to a dimensional crossover in the bilayer.


Influence of atropine and N-methyl atropine pretreatments on behavioral and physiological effects of the irreversible muscarinic agonist, BM123.
The irreversible muscarinic agonist, BM123 (63 mu moles kg-1, IV), was shown to produce central and peripheral physiological signs characteristic of cholinergic agonists. It also induced hypothermia, elevated nociceptive thresholds, reduced locomotor activity and disrupted spontaneous alternation performance in rats. The centrally acting muscarinic antagonist, atropine (50 mu mole kg-1) prevented or reduced all the above effects of BM123 when given SC 40 min prior to the BM123 injection. In contrast, the peripherally acting muscarinic antagonist, N-methyl atropine, prevented only the peripheral effects and the elevated nociceptive thresholds. Habituation of activity during a 20 min session was observed in all groups despite different levels of general activity. These findings are consistent with a model in which atropine and N-methyl atropine compete with BM123 for reversible association with the muscarinic receptor. In the case of BM123 administered alone, the association results, first, in agonist effects and proceeds to form an irreversible complex. Our present results show that by competing with BM123 for mAChR sites during the initial, reversible state of the interaction, atropine blocks the cholinomimetic effects of the agonist during both this state and its otherwise subsequent irreversible state.


Past and familial depression predict current symptoms of professional burnout.
Despite a substantial association between professional burnout and depression, the exact nature of the relationship is unclear. It is hypothesized that an underlying susceptibility for depression is associated with an enhanced risk for professional burnout. In the present study, the relationship was examined between indices of personal and familial history of depression and current symptoms of burnout. Respondents were 3385 employees of different work settings (61% female, age 18-65 years), who completed questionnaires regarding demographic variables, working hours, personal and familial history of depression, current depressive symptomatology, and current symptoms of professional burnout. After controlling for background variables, the strongest predictor of all three burnout facets was current depressive symptomatology. Independent of the effects of background variables and current depressive symptoms, having ever experienced a depressive episode further predicted current symptoms of two burnout facets: emotional exhaustion (OR=1.82, 95% CI=1.38-2.40, P<0.001) and cynicism (OR=1.51, 95% CI=1.16-1.98, P=0.002). In addition, a history of depression in close family members independently predicted current symptoms of emotional exhaustion (OR=1.63, 95% CI=1.27-2.10, P<0.001), while a trend appeared for a similar effect on cynicism (OR=1.23, 95% CI=0.96-1.58, P=0.095). The study is based on a cross-sectional retrospective design. A predisposition for depression, as reflected by a personal and familial history of depression, may enhance the risk for burnout.


Novel Cu@SiO2/bacterial cellulose nanofibers: Preparation and excellent performance in antibacterial activity.
The antibacterial composite based on bacterial cellulose (BC) was successfully prepared by in-situ synthesis of SiO2 coated Cu nanoparticles (Cu@SiO2/BC) and its properties were characterized. Its chemical structures and morphologies were evaluated by Fourier transformation infrared spectrum (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The results demonstrated that the SiO2 coated Cu particles were well homogeneously precipitated on the surface of BC. The Cu@SiO2/BC was more resistant to oxidation than the Cu nanoparticles impregnated into BC (Cu/BC) and then Cu@SiO2/BC could prolong the antimicrobial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli).


Derivative electrophoretograms and their applications.
A differentiator was constructed to produce the first and second derivative curves of routine cellulose acetate membrane electrophoretograms of human serum protein. The derivative curves could reveal the presence of multicomponent in each globulin fraction. The "M" components could be detected easily and semiquantitatively, when the cellulose acetate membrane electrophoretic pattern was evaluated by the derivative curves. Utilization of the derivative curves could be a useful adjunct to the detection of an "M" component since the presence of a narrow band produces a sharper peak on the second derivative curve and more indentation on the first derivative curve.


Physicochemical studies on the antigen-antibody complexes of two monoclonal antibodies against rabbit thymocytes.
We have characterized two monoclonal antibodies directed against rabbit thymocyte antigens. Using internally labelled MD3 cells (a transformed T-cell line), ART-F immunoprecipitated a membrane glycoprotein of 95,000 mol. wt, while ART-A immunoprecipitated two major glycoproteins, one of 95,000 mol. wt, the other of 105,000 mol. wt as analysed on reduced SDS-PAGE. ART-A recognizes 650,000 sites both on rabbit thymocytes and MD3 cells with an association constant of 1.5 X 10(5)/M. ART-F shows a biphasic binding curve with a high affinity constant of 3.3 and 0.6 X 10(8)/M and a low affinity constant of 2.2 and 6.9 X 10(5)/M for thymocytes and MD3 cells respectively. The numbers of high affinity and low affinity antigens are 200,000 for the former and 800,000 for the latter. On the basis of the kinetic data, the difference between low and high affinity is attributed to the difference in association-rate constants. The affinity constants calculated from the reaction-rate constants are in good agreement with those obtained from equilibrium measurements. While ART-F prevents the binding of ART-A, ART-A does not inhibit the affinity binding of ART-F. The analysis of the equilibrium, inhibition and kinetic data allow us to present a model for the structural relation of the epitopes recognized on the T-cells by the two monoclonal antibodies.


Actinobacteria associated with Glycyrrhiza inflata Bat. are diverse and have plant growth promoting and antimicrobial activity.
Many of the plant associated microbes may directly and indirectly contribute to plant growth and stress resistance. Our aim was to assess the plant growth-promoting and antimicrobial activities of actinobacteria isolated from Glycyrrhiza inflata Bat. plants to find strains that could be applied in agricultural industry, for example in reclaiming saline soils. We isolated 36 and 52 strains that showed morphological characteristics of actinobacteria from one year old and three year old G. inflata plants, respectively. Based on 16S rRNA gene sequence analysis, the strains represented ten actinobacterial genera. Most of the strains had plant growth promoting characteristics in vitro, tolerated 200 mM NaCl and inhibited the growth of at least one indicator organism. The eight selected Streptomyces strains increased the germination rate of G. inflata seeds under salt stress. In addition, the four best seed germination promoters promoted the growth of G. inflata in vivo. The best promoters of G. inflata growth, strains SCAU5283 and SCAU5215, inhibited a wide range of indicator organisms, and may thus be considered as promising candidates to be applied in inoculating G. inflata.


The relationship of white matter microstructure with psychomotor disturbance and relapse in remitted psychotic depression.
Psychomotor disturbance is common in psychotic depression and is associated with relapse. In this analysis, we examined whether white matter microstructure is associated with relapse probability in psychotic depression and, if so, whether white matter microstructure accounts for the association between psychomotor disturbance and relapse. We used tractography to characterize diffusion-weighted MRI data in 80 participants enrolled in a randomized clinical trial that compared efficacy and tolerability of sertraline plus olanzapine with sertraline plus placebo in the continuation treatment of remitted psychotic depression. Cox proportional hazard models tested the relationships between psychomotor disturbance (processing speed and CORE score) at baseline, white matter microstructure (fractional anisotropy [FA] and mean diffusivity [MD]) in 15 selected tracts at baseline, and relapse probability. CORE was significantly associated with relapse. Higher mean MD was significantly associated with relapse in the each of the following tracts: corpus callosum, left striato-frontal, left thalamo-frontal, and right thalamo-frontal. CORE and MD were each associated with relapse in the final models. As a secondary analysis with a small sample size, this study was not powered for its aims, and is vulnerable to types I and II statistical errors. Further, the sample size was not sufficient to test the interaction of the independent variables and randomized treatment group with relapse probability. While both psychomotor disturbance and MD were associated with psychotic depression relapse, MD did not account for the relationship between psychomotor disturbance and relapse. The mechanism by which of psychomotor disturbance increases the risk of relapse requires further investigation. Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II); NCT01427608. URL: https://clinicaltrials.gov/ct2/show/NCT01427608.


N-cadherin localization in early heart development and polar expression of Na+,K(+)-ATPase, and integrin during pericardial coelom formation and epithelialization of the differentiating myocardium.
N-cadherin, a Ca(2+)-dependent cell adhesion molecule, has been localized previously to the mesoderm during chick gastrulation and to adherens junctions in beating avian hearts. However, a systematic study of the dynamic nature of N-cadherin localization in the critical early stages of heart development is lacking. The presented work defines the changes in the spatial and temporal expression of N-cadherin during early stages of chick heart development, principally between Hamburger and Hamilton stages 5-8, 18-29 hr of development. During gastrulation N-cadherin appears evenly distributed in the heart forming region. As development proceeds to form the pericardial coelom (stages 6, 7, and 8, i.e., between 22 and 26 hr of development) N-cadherin localization becomes restricted to the more central areas of the mesoderm. The localization also shows a periodicity that correlates closely with the distance between foci of cavities that eventually coalesce to form the coelom. This distribution suggests that N-cadherin may have a function in the sorting out of somatic and splanchnic mesoderm cells to form the coelom. This separation of the mesoderm in the embryo for the first time physically delineates the precardiac mesoderm population. Concomitant with cell sorting during coelom formation, the precardiac cells change shape and show a distinct polarity as conveyed by (1) the apical expression of N-cadherin on precardiac cell surfaces lining the pericardial coelom, (2) the primarily lateral expression of Na+,K(+)-ATPase, and (3) an enrichment of integrin (beta 1 subunit) on basal cell surfaces. The somatic mesoderm cells apparently down-regulate N-cadherin expression. N-cadherin is also absent from the precardiac cells close to the endoderm. The latter cells eventually form the endocardium, i.e., the endothelial lining of the heart. By contrast, in the tubular, beating heart N-cadherin is found throughout the myocardium. In summary, immunolocalization patterns of N-cadherin during early cardiogenesis suggest that this cell adhesion molecule has a major role in the dynamics of pericardial coelom formation. Subsequently, its continued expression during cell differentiation of the cardiomyocyte to form the myocardium, but not endocardium, suggests N-cadherin is an essential morphoregulatory molecule in heart organogenesis.


Plasma-specific proteins: their response to surgical trauma and tumour load, and modification of this response by post-operative metabolic support.
Concentrations of plasma proteins with short half-life have been suggested as indicators of nutritional state in surgical patients. Trauma also affects the circulating concentrations of these proteins. Serum concentrations of retinol binding protein (RBP), pre-albumin and transferrin were determined pre- and post-operatively on different supporting regimens. The circulating concentration of these liver proteins displayed no differential effect of the supporting regimen during the first 5 post-operative days. None of the patients with tumour demonstrated any indication of hepatic metastases pre-operatively or at the time of laparotomy but, as a group, had lower pre-operative concentrations of RBP (p < 0.001) and pre-albumin (p < 0.01) than patients with no tumour load. In addition 55% of patients (15:27) with tumour had RBP concentrations <3.5 mg/dl; all of the non-tumour bearing patients (13/13) had RBP concentrations >3.5 mg/dl. RBP and pre-albumin appear to act as non-specific tumour markers, but not to serve a useful function as short-term nutritional markers of post-operative support.


Glandular Odontogenic Cyst-A Case Series.
The glandular odontogenic cyst (GOC) is an uncommon jawbone cyst with a challenging diagnosis because of the presence of several clinical and histopathologic overlaps with other odontogenic lesions and central mucoepidermoid carcinoma. To date, less than 200 cases of GOC have been published in the literature with reliable clinical and histopathologic information. Furthermore, the lack of a well-documented GOC case series impairs a more detailed understanding about the biological behavior and appropriate management of the lesion. Therefore, in this study, we report 3 well-documented cases of GOC in the literature. In one of the cases, the incisional biopsy was misdiagnosed as a dentigerous cyst, and the lesion recurred. Therefore, we also discuss key points regarding the diagnosis and treatment of GOC.


Long-term glucose homeostasis in patients on home parenteral nutrition.
Glycated haemoglobin (Hb A1c) was used as a marker of long-term hyperglycaemia in patients receiving high glucose loads for home parenteral nutrition (HPN). Thirty-six patients received a median weekly glucose delivery of 2000 g (800-4200) at a median infusion rate of 11.8 mg/kg/min (5.0-19.2). There was no correlation between Hb A1c (median- 3.1%, range 2.0-6.3%) and glucose infusion rate or weekly glucose load. It is concluded that significant prolonged hyperglycaemia does not appear to be a problem in patients on HPN managed by this unit.


Visual and refractive outcomes of small incision lenticule extraction for the correction of myopia: 1-year follow-up.
To assess the 1 year clinical outcomes of small incision lenticule extraction (SMILE) for the correction of myopia and myopic astigmatism using a 500 kHz femtosecond laser system. This prospective study evaluated 52 eyes of 39 consecutive patients (31.8±6.9 years, mean age±SD) with spherical equivalents of -4.11±1.73 D (range, -1.25 to -8.25 D) who underwent SMILE for myopia and myopic astigmatism. Preoperatively, 1 week, and 1, 3, 6 and 12 months postoperatively, we assessed the safety, efficacy, predictability, stability, corneal endothelial cell loss and the adverse events of the surgery. The logarithm of the minimal angle of resolution (logMAR) uncorrected distance visual acuity and LogMAR corrected distance visual acuity were -0.16±0.11 and -0.22±0.07, respectively, 1 year postoperatively. At 1 year, all eyes were within±0.5 D of the targeted correction. Manifest refraction changes of -0.05±0.32 D occurred from 1 week to 1 year postoperatively (p=0.20, Wilcoxon signed-rank test). The endothelial cell density was not significantly changed from 2804±267 cells/mm(2) preoperatively to 2743±308 cells/mm(2) 1 year postoperatively (p=0.12). No vision-threatening complications occurred during the observation period. SMILE performed well in the correction of myopia and myopic astigmatism, and no significant change in endothelial cell density or any other serious complications occurred throughout the 1-year follow-up period, suggesting its viability as a surgical option for the treatment of such eyes.


Gut Microbiota Might Act as a Potential Therapeutic Pathway in COVID-19.
It has been very recently suggested that individuals with chronic gut inflammation are highly susceptible to COVID-19. They constitute the serious cases of COVID-19, in which inflammatory cytokine storm is observed. On the contrary, the healthy gut microbiota is linked with low chronic gut and systemic inflammation. This raises the idea that maintenance of the healthy gut microbiota and prevention of gut microbial dysbiosis in COVID-19 patients might avoid the increased cytokine storm, which in turn might reduce the mortality rate. It has been shown that the modulation of the gut microbiota is an effective strategy to strengthen immunity and might be a possible treatment for individuals with viral infections. Currently, there is no clinical data considering the impact of the modulation of the gut microbiota on the treatment of COVID-19. We hypothesize that targeting the gut microbiota might be a novel therapeutic approach or at least a supportive therapy. In the present review article, we described the interaction between SARS-CoV-2 and gut microbiota dysbiosis through two possible mechanisms, including aberrant immune activation and aberrant mammalian target of rapamycin (mTOR) activation. Further, the disruption of the gastrointestinal reninangiotensin system (GI RAS), dysregulation of the coagulation and fibrinolytic systems, and the activity of human serine proteases in COVID-19 pathogenesis were addressed. We also provided possible strategies to restore all the discussed aspects via gut microbiota modulation.


Layered Low-Dimensional Ruddlesden-Popper and Dion-Jacobson Perovskites: From Material Properties to Photovoltaic Device Performance.
Layered low-dimensional halide perovskites (LDPs) with multiple quantum well structure have shown increasing research interest in photovoltaic solar cell applications owing to their intrinsic moisture stability and favorable photophysical properties in comparison with their three-dimensional (3D) counterparts. The most common LDPs are Ruddlesden-Popper (RP) phases and Dion-Jacobson (DJ) phases, both of which have made significant research advances in efficiency and stability. However, distinct interlayer cations between RP and DJ phase lead to disparate chemical bonds and different perovskite structures, which endow RP and DJ perovskite with distinctive chemical and physical properties. Plenty of reviews have reported the research progress of LDPs but no summary has elaborated from the perspective of the merits and drawbacks of the RP and DJ phases. Herein, in this review, we offer a comprehensive expound on the merits and promises of RP and DJ LDPs from their chemical structure, physicochemical properties, and photovoltaic performance research progress aiming to provide a new insight into the dominance of RP and DJ phases. Then, we reviewed the recent progress on the synthesis and implementation of RP and DJ LDPs thin films and devices, as well as their optoelectronic properties. Finally, we discussed the possible strategies to resolve existing toughs to realize the desired high-performance LDPs solar cells.


Canine prostatic fluid: techniques of collection, quantitative bacterial culture, and interpretation of results.
Specimens of prostatic fluid were collected by ejaculation from 104 dogs after collection of a specimen of urethral contents and after collection of a urine specimen by antepubic cystocentesis. For purposes of data analysis, results of bacterial culture of the specimens were grouped according to individual colony counts in each specimen group (ie, urine, urethra, prostatic fluid). For purposes of this study, prostatic infection was defined as greater than or equal to 2 log10 of one or more bacterial species in prostatic fluid over the number of colonies of the same species in the paired urethral specimens.