Clinical bleeding events and laboratory coagulation profiles in acute promyelocytic leukemia.
Bleeding is the leading cause of death for patients with acute promyelocytic leukemia (APL). Blood component transfusion to correct coagulopathy is the keystone in reducing bleeding. The benefit of fresh frozen plasma transfusion is unproven. Using laboratory profiles to predict bleeding is important guidance for the determination of transfusion policies in the treatment of APL. For 116 patients of APL, bleeding events were collected and correlated with various hematologic and coagulation parameters, including leukemic cell percentages, white blood cell (WBC) and platelet counts, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen levels, and disseminated intravascular coagulation (DIC) scores. Overt DIC occurred in 77.6% of patients. Severity of DIC was associated with bone marrow leukemic cell percentages but unrelated to bleeding. Patients with bleeding had significantly higher WBC counts (26.73 ± 6.18 vs. 13.03 ± 3.03 per μL, P = 0.026) and more prolonged PT (4.85 ± 0.70 vs. 2.59 ± 0.28 s, P = 0.002) and APTT (3.98 ± 1.68 vs. 0.96 ± 0.93 s, P = 0.017). Fibrinogen levels, platelet counts, and leukemia cell percentages were not significantly different between bleeding and non-bleeding patients. PT is valuable in prediction of bleeding. Patients with PT ≧ 5 s had a relative risk of 6.14 for bleeding. Seven patients had severe bleeding before initiation of all-trans retinoic acid (ATRA). Patients with APL are susceptible to DIC and subsequent bleeding events. Prompt ATRA administration is crucial in preventing hemorrhagic events. High WBC counts, prolonged PT, and APTT are associated with clinical bleeding in our series. PT is the most accurate parameter in predicting bleeding. Based on these findings, supportive care should be directed toward correction of coagulopathy to prevent bleeding complications and fresh frozen plasma appears to be indicated for coagulopathy associated with APL.


Exendin-4 Inhibits the Expression of SEPP1 and Fetuin-A via Improvement of Palmitic Acid-Induced Endoplasmic Reticulum Stress by AMPK.
Selenoprotein P (SEPP1) and fetuin-A, both circulating liver-derived glycoproteins, are novel biomarkers for insulin resistance and nonalcoholic fatty liver disease. However, the effect of exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, on the expression of hepatokines, SEPP1, and fetuin-A, is unknown. The human hepatoma cell line HepG2 was treated with palmitic acid (PA; 0.4 mM) and tunicamycin (tuni; 2ug/ml) with or without exendin-4 (100 nM) for 24 hours. The change in expression of PA-induced SEPP1, fetuin-A, and endoplasmic reticulum (ER) stress markers by exendin-4 treatment were evaluated using quantitative real-time reverse transcription polymerase chain reaction and Western blotting. Transfection of cells with AMP-activated protein kinase (AMPK) small interfering RNA (siRNA) was performed to establish the effect of exendin-4-mediated AMPK in the regulation of SEPP1 and fetuin-A expression. Exendin-4 reduced the expression of SEPP1, fetuin-A, and ER stress markers including PKR-like ER kinase, inositol-requiring kinase 1α, activating transcription factor 6, and C/EBP homologous protein in HepG2 cells. Exendin-4 also reduced the expression of SEPP1 and fetuin-A in cells treated with tunicamycin, an ER stress inducer. In cells treated with the AMPK activator 5-aminoidazole-4-carboxamide ribonucleotide (AICAR), the expression of hepatic SEPP1 and fetuin-A were negatively related by AMPK, which is the target of exendin-4. In addition, exendin-4 treatment did not decrease SEPP1 and fetuin-A expression in cells transfected with AMPK siRNA. These data suggest that exendin-4 can attenuate the expression of hepatic SEPP1 and fetuin-A via improvement of PA-induced ER stress by AMPK.


Studying autism in rodent models: reconciling endophenotypes with comorbidities.
Autism spectrum disorder (ASD) patients commonly exhibit a variety of comorbid traits including seizures, anxiety, aggressive behavior, gastrointestinal problems, motor deficits, abnormal sensory processing, and sleep disturbances for which the cause is unknown. These features impact negatively on daily life and can exaggerate the effects of the core diagnostic traits (social communication deficits and repetitive behaviors). Studying endophenotypes relevant to both core and comorbid features of ASD in rodent models can provide insight into biological mechanisms underlying these disorders. Here we review the characterization of endophenotypes in a selection of environmental, genetic, and behavioral rodent models of ASD. In addition to exhibiting core ASD-like behaviors, each of these animal models display one or more endophenotypes relevant to comorbid features including altered sensory processing, seizure susceptibility, anxiety-like behavior, and disturbed motor functions, suggesting that these traits are indicators of altered biological pathways in ASD. However, the study of behaviors paralleling comorbid traits in animal models of ASD is an emerging field and further research is needed to assess altered gastrointestinal function, aggression, and disorders of sleep onset across models. Future studies should include investigation of these endophenotypes in order to advance our understanding of the etiology of this complex disorder.


Emerging viral infections in neonatal intensive care unit.
Nosocomial infections are the most important cause of morbidity and mortality among neonates and mostly in infants admitted to neonatal intensive care units (NICU). The total number of neonates who develop nosocomial infections per admission varies from 6.2 to 30%. The role of nosocomial virus infections is generally neglected in the actual epidemiologic scenario mostly due to the lack of data in the medical literature. Based on a worldwide database of health care-associated outbreaks (http://www.outbreak-database.com) we performed an analysis of the incidence, type of pathogens and clinical features of neonatal viral outbreaks especially those reported in NICUs. We also describe, as an example of emerging virus in NICU, a Norovirus outbreak along with clinical presentation that varies from mild to moderate clinical symptoms like vomiting, gastric remainder, diarrhoea, abdominal distension or severe presentation like necrotizing enterocolitis. and measures implemented for terminating the outbreak. In conclusion, our study analyses the viral origins of nosocomial infections in NICU and underline that the role of viral agents in neonatal nosocomial infections needs to be further investigated even in diseases traditionally considered of bacterial origin like necrotizing enterocolitis.


[Radionuclide scrotal imaging: an effective method for detecting varicocele].
To evaluate radionuclide scrotal imaging (RSI) in the diagnosis of varicocele. We performed physical examination (PE) and RSI for 126 patients with infertility for at least 12 months and seminal abnormality, obtained the scrotal blood-pool index (SBPI), observed the reflux in the spermatic vein during RSI, typed and graded varicocele by color Doppler flow imaging (CDFI) and compared the results of PE and RSI with those of CDFI. The rates of sensitivity and specificity of RSI in the diagnosis of varicocele (96.5% and 97.1%) were both higher than those of PE (71.7% and 69.1%). Simple, accurate and noninvasive, RSI is an effective method for the diagnosis of clinical and subclinical varicocele.


Percutaneous transcatheter therapy of aorto-ostial stenoses.
The treatment of native coronary and saphenous vein graft aorto-ostial stenoses with balloon angioplasty (PTCA) has been associated with lower procedural success rates, more frequent in-hospital complications and a greater likelihood of late restenosis when compared with PTCA of non-ostial stenoses. The advent of ablative technologies and intracoronary stents have significantly altered both early and late outcomes of percutaneous intervention for aorto-ostial disease. The optimal approach to this complex lesion subset often involves decalcification or tissue ablation followed by stent deployment. Improvements in currently available stent technology including enhanced radial force and visibility, reduced thrombogenicity, and the availability of shorter stent lengths, may also facilitate stent deployment and further improve outcomes following percutaneous transcatheter therapy for aorto-ostial stenoses.


ADAM8 is a negative regulator of retinal neovascularization and of the growth of heterotopically injected tumor cells in mice.
ADAM8 is a member of the "a disintegrin and metalloproteinase" (ADAM) family of membrane-anchored metalloproteinases. ADAM8-deficient mice have no evident spontaneous developmental or pathological defects, and little is currently known about the role of ADAM8 in disease. Here, we investigated the contribution of ADAM8 to pathological neovascularization in mice using an oxygen-induced retinopathy (OIR) model and heterotopical injection of tumor cells. We found an increase in retinal re-vascularization but fewer neovascular tufts in the OIR model and increased growth of heterotopically injected tumor cells in Adam8-/- mice compared with wild-type controls. These results suggest that ADAM8 functions to limit both of these processes in wild-type mice. In cell-based assays, overexpression of ADAM8 increased the ectodomain shedding of several co-expressed membrane proteins with roles in angiogenesis (CD31, Tie-2, Flk-1, Flt-1, EphrinB2, EphB4, VE-cadherin, KL-1, E-selectin, and neuregulin-1beta2). Thus, dysregulated expression of ADAM8 in endothelial cells in vivo could potentially increase the processing of these and other substrate proteins. Taken together, our findings suggest that inhibiting ADAM8 could be useful for promoting re-vascularization and thereby preventing formation of neovascular tufts in proliferative retinopathies. On the other hand, blocking ADAM8 could be detrimental in the context of rapidly growing tumors.


[Measurement of nonuniform temperature and concentration distribution by absorption spectroscopy based on least-square fitting].
The measurement of nonuniform temperature and concentration distributions was investigated based on tunable diode laser absorption spectroscopy technology. Through direct scanning multiple absorption lines of H2O, two zones for temperature and concentration distribution were achieved by solving nonlinear equations by least-square fitting from numerical and experimental studies. The numerical results show that the calculated temperature and concentration have relative errors of 8.3% and 7.6% compared to the model, respectively. The calculating accuracy can be improved by increasing the number of absorption lines and reduction in unknown numbers. Compared with the thermocouple readings, the high and low temperatures have relative errors of 13.8% and 3.5% respectively. The numerical results are in agreement with the experimental results.


Nanotechnological strategies for systemic microbial infections treatment: A review.
Systemic infections is one of the major causes of mortality worldwide, and a shortage of drug approaches applied for the rapid and necessary treatment contribute to increase the levels of death in affected patients. Several drug delivery systems based in nanotechnology such as metallic nanoparticles, liposomes, nanoemulsion, microemulsion, polymeric nanoparticles, solid lipid nanoparticles, dendrimers, hydrogels and liquid crystals can contribute in the biological performance of active substances for the treatment of microbial diseases triggered by fungi, bacteria, virus and parasites. In the presentation of these statements, this review article present and demonstrate the effectiveness of these drug delivery systems for the treatment of systemic diseases caused by several microorganisms, through a review of studies on scientific literature worldwide that contributes to better information for the most diverse professionals from the areas of health sciences. The studies demonstrated that the drug delivery systems described can contribute to the therapeutic scenario of these diseases, being classified as safe, active platforms and with therapeutic versatility.


Cognitive Ability as a Non-modifiable Risk Factor for Post-prostatectomy Urinary Incontinence: A Double-Blinded, Prospective, Single-Center Trial.
Introduction: Urinary incontinence (UI) is a wide-spread and feared side-effect of conventional or even robot-assisted laparoscopic prostatectomy (RALP) due to its high impact on patients' quality of life (QoL). Non-modifiable risk factors for UI have already been identified - on surgical and patient side. Yet, to our knowledge, focus thus far has not been placed on functional aspects regarding general cognitive ability. Materials and Methods: This is an observational single-center, prospective, double-blinded evaluation of 109 RALPs performed between 07/2020 and 03/2021. All patients underwent a Mini Mental State Examination (MMSE) prior to surgery to evaluate their cognitive ability. Early post-prostatectomy incontinence (PPI) was evaluated using a standardized 1 h pad test performed 24 h after removal of the urinary catheter. The association between MMSE results and PPI were evaluated using univariate and multivariate logistic regression models. Results: Multivariate logistic regression analyses identified MMSE results and nerve sparing (NS) as independent predictors for PPI in patients with an intermediate MMSE result (25-27 points) having a 3.17 times higher risk of PPI when compared to patients with a good MMSE result (≥28) (95% Confidence Interval (CI): 1.22-9.06, p = 0.023), while patients without NS had a 3.53 times higher risk of PPI when compared to patients with NS (95% CI: 1.54-11.09, p = 0.006). Conclusion: A lower cognitive ability should be treated as a non-modifiable risk-factor for early PPI. In the future it could find its place as a clinical screening tool to identify patients who require more attention especially in the pre-, but also in the postoperative phase.


A usage evaluation of total parenteral nutrition in pediatric patients.
Records of 20 consecutive pediatric patients receiving total parenteral nutrition over a 1-month period were reviewed for appropriateness of nutritional assessment and management. Each patient was monitored until total parenteral nutrition was discontinued or for a maximum of 2 weeks. A total of 124 therapy days were reviewed. Results demonstrated that only 35% of these patients had a nutritional assessment performed prior to initiation of therapy, and only 65% had nutritional goals determined. Nutritional goals were defined as patient-specific goals for fluid volume (FV), calories, protein, and fat emulsion. Analysis of data demonstrated that goals for FV were met on 62% of therapy days. Of the days on which FV goals were met, goals for calories, protein, and fat emulsion were met on 54%, 59%, and 51% of therapy days, respectively. Baseline serum triglyceride levels were measured in one of 20 patients. Serial laboratory monitoring was adequate, with the exception of hepatic enzymes and serum triglycerides, which were measured in 14 and 9 patients, respectively. Recommendations for pediatric parenteral nutrition therapy are discussed, as well as methods to implement these recommendations.


Activation of human neutrophils by the pollutant sodium sulfite: effect on cytokine production, chemotaxis, and cell surface expression of cell adhesion molecules.
We have previously demonstrated that the pollutant sodium sulfite (Na(2)SO(3)) possesses some proinflammatory properties. This study was conducted in order to elucidate how this environmentally significant chemical can alter human neutrophil cell physiology. Using sensitive ELISAs, we found that Na(2)SO(3) induces the total (intra- and extracellular fractions) production of interleukin-12 (IL-12) and IL-8 but not TNF-alpha, IL-1alpha, or IL-4. IL-8 levels were significantly increased in both fractions while the levels of IL-12 were significantly increased only in the extracellular milieu. In contrast, IL-1Ra levels were significantly decreased in both fractions when cells were treated at the highest Na(2)SO(3) concentration (10 mM). Despite the fact that Na(2)SO(3) was found to increase IL-8 production, it does not induce neutrophil chemotaxis in vitro. Cell surface expression of CD18, CD11a, CD11b, CD11c, CD50, and CD54 was not affected by Na(2)SO(3) treatment. We conclude that Na(2)SO(3) is a modulator of cytokine production but that it does not alter either chemotaxis or cell surface expression of the tested molecules. Our results attest to the importance of systematically monitoring cytokine production from both intracellular and extracellular fractions in pollutant-induced neutrophils, since this could lead to different interpretations.


A new interpretation of components in the ERG signals to sine wave luminance stimuli at different temporal frequencies and contrasts.
Full-field electroretinograms were recorded from five normal human subjects using white light (mean luminance: 250 cd/m2) sine wave stimuli at different frequencies and contrasts. In agreement with previous studies, we found that the amplitude of the fundamental component displayed a dip at about 12 Hz, coinciding with a maximum in the second harmonic component, indicating frequency doubling of the responses. By including measurements at different contrasts, we were able to recognize two (sine-like and transient) response components. We found that the waveform of the transient response was relatively frequency independent. An algorithm to separate the two components was developed. The interaction between these two components can explain the frequency-doubled responses around 12 Hz. The sine-like component is more linear and prominent in the low-frequency region, whereas the transient seems to be more nonlinear and prominent in the high-frequency region.


Public perceptions of cerebral palsy.
Neurologic disorders are often described in terms that relate to symptoms rather than specific etiologic factors. Such descriptive terms are confusing to healthcare professionals and to the parents of children in whom these disorders are diagnosed. Cerebral palsy is one example of a descriptive term that is applied to a disorder that is heterogeneous in its etiology, morbidity, and mortality. A random sampling of 100 adults selected from the waiting room of a suburban ambulatory pediatrics office associated with the University of Medicine and Dentistry of New Jersey-School of Osteopathic Medicine (Stratford, NJ) was surveyed with a 20-item questionnaire on their perceptions of the term cerebral palsy and its associated disability and prognosis. Subjects' responses suggest that a percentage of the general population holds several misconceptions about the disorder, including the belief that the disorder has a genetic etiology (40%) and that affected children cannot speak (20%), die earlier than unaffected children (57%), and cannot hold jobs as adults (20%) should they survive to adulthood. A small percentage of subjects believe that cerebral palsy is infectious (4%) and that parents should restrict their children from associating with those affected (3%). Our study population was somewhat homogenous in that most respondents were educated and most were middle to upper-middle class. Yet, even in this population, the term cerebral palsy is ambiguous to many and may have negative connotations. Further studies are needed to address whether a higher frequency of negative perceptions are present in more socioeconomically diverse populations.


Expedite recovery from esophagectomy and reconstruction for esophageal squamous cell carcinoma after perioperative management protocol reinvention.
Surgery for esophageal cancer is invasive and challenging, and always to be followed with arduous post-operative care and recovery. This study, maybe one of the first in Asian populations, is to determine whether a reinvented protocol for perioperative management for esophageal cancer surgery which is being implemented in our department, will lead to a faster convalescence and also significantly decrease financial burdens garnered by patients during hospitalization. Operated on by the same surgeon and team in the same hospital, consecutive patients who had received esophagectomy and reconstruction for esophageal squamous cell carcinoma were retrospectively reviewed. On the basis of two different treatment periods, patients were divided into two groups: A and B. Group A was patients who had received the new reinvented protocol between 2012 and 2016, while group B patients were those having received the previous protocol between 2008 and 2011. Their demographics, post-operative outcome, and hospital charges were collected and compared. There were 64 patients in group A, and 69 in group B. Ventilator days (P<0.001), ICU stay (P<0.001), and post-operative stay (P<0.001) were significantly shorter in group A patients. Complication rates were similar between the two groups. No hospital mortality was noted in either group. Hospital charges in group A were found to be perceptively lower, although not statistically significant (P value =0.078). The current protocol of perioperative care effectively ameliorated convalescence after esophagectomy and reconstruction for esophageal squamous cell carcinoma without increasing complication rate or mortality. It is also potentially more practical in future health care policies during this era of financial shortage.


Epidemiology of adult rheumatoid arthritis in northwest Greece 1987-1995.
Rheumatoid arthritis (RA) in Greece differs in its clinical, serological, and genetic aspects from that of Northern European countries. We investigated the incidence and prevalence of RA in the district of Ioannina in northwest Greece for the period 1987-1995. We investigated records of patients at rheumatology clinics of university and general hospitals and private clinics in Ioannnina. Diagnosis was by 1987 ACR criteria, and the population data were based on the 1991 national census. Crude and age specific rates were calculated as number of cases per 1000 inhabitants. Age adjusted rates were obtained by the direct method using the European standard population. A total of 428 cases of RA were identified during the study period. Total prevalence of RA was for men 2.05 and for women 4.78 cases/1000 inhabitants, and the total women/men ratio was 2.33. Annual incidence rates fluctuated between 0.15 and 0.36/1000 inhabitants. Our findings suggest a low prevalence and low incidence of RA in northwest Greece. Environmental and/or genetic factors may explain this low frequency of the disease in the population studied.


Rofecoxib impairs adipose tissue development in a murine model of nutritionally induced obesity.
The effect of rofecoxib (Vioxx), a cyclooxygenase (COX)-2 inhibitor, on adipose tissue development was studied in a murine model of diet-induced obesity. Oral administration of Vioxx for six weeks (34 mg/kg/day) to C57Bl/6 mice kept on high-fat diet (n = 19) resulted in a significant reduction in total body weight (p < 0.01) and of subcutaneous (p < 0.05) and gonadal (p < 0.01) adipose tissue mass, as compared to placebo-treated animals (n = 21). There was no significant difference in food intake between both groups (2.8 +/- 0.09 vs. 3.0 +/- 0.10 g/day; p = 0.20). Administration of Vioxx resulted in reduced total cholesterol and high-density lipoprotein (HDL) cholesterol levels (p < 0.0001) and in enhanced levels of liver enzymes, as compared to place-bo. In the gonadal but not in the subcutaneous adipose tissue, adipocytes were smaller after Vioxx treatment (p < 0.05). The macrophage content was significantly lower in gonadal adipose tissues of Vioxx-treated mice (p < 0.05), but not in the subcutaneous adipose tissues. This was, however, not associated with differences in adipose tissue levels of the pro-inflammatory tumor necrosis factor (TNF)-alpha. Blood vessel size or density in either fat pad were not affected by Vioxx treatment. Thus, in a nutritionally induced murine obesity model, oral administration of Vioxx, as compared to placebo, resulted in reduced adipose tissue development, associated with lower feeding efficiency and smaller adipocytes.


Retrotransfer in Escherichia coli conjugation: bidirectional exchange or de novo mating?
DNA can be transferred among eubacteria and to plants and fungi by related, plasmid-mediated processes collectively referred to as bacterial conjugation. Conjugation occurs between cells in contact with one another and results in the unidirectional delivery of DNA from a bacterial donor to a recipient. Recent experiments that have reexamined the directionality of DNA flow during conjugation have come to different conclusions, some suggesting that genetic material also flows from recipient cells into the donor and that this process, termed retrotransfer, is likewise directed by donor-encoded functions. Given that bacteria are perhaps united with all living creatures by conjugation, the possibility of gene flow into donor bacteria during conjugation raises interesting evolutionary and biocontainment issues. Here we report that plasmid transmission from bacterial recipients to donors is not a donor-mediated event. Movement of genetic material from recipients to donors was inhibited by streptomycin, which does not inhibit the conjugative donor, indicating that retrotransfer requires gene expression in recipients. Furthermore, retrotransfer was reduced in matings mediated by plasmids that encode strong entry exclusion, to a similar degree as matings between two donors. Therefore we suggest that retrotransfer is in fact newly initiated conjugation between transconjugants and donors.


Mitochondrial coenzyme Q10 determination by isotope-dilution liquid chromatography-tandem mass spectrometry.
Coenzyme Q10 (CoQ10) is an essential part of the mitochondrial respiratory chain. Unlike most other respiratory chain disorders, CoQ10 deficiency is potentially treatable. We aimed to develop and validate an accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of mitochondrial CoQ10 in clinical samples. We used mitochondria isolated from muscle biopsies of patients (n = 166) suspected to have oxidative phosphorylation deficiency. We also used fibroblast mitochondria from 1 patient with CoQ10 deficiency and 3 healthy individuals. Samples were spiked with nonphysiologic CoQ10-[(2)H6] internal standard, extracted with 1-propanol and with ethanol and hexane (2 mL/5 mL), and CoQ10 quantified by LC-MS/MS. The method and sample stability were validated. A reference interval was established from the patient data. The method had a limit of quantification of 0.5 nmol/L. The assay range was 0.5-1000 nmol/L and the CVs were 7.5%-8.2%. CoQ10 was stable in concentrated mitochondrial suspensions. In isolated mitochondria, the mean ratio of CoQ10 to citrate synthase (CS) activity (CoQ10/CS) was 1.7 nmol/U (95% CI, 1.6-1.7 nmol/U). We suggest a CoQ10/CS reference interval of 1.1-2.8 nmol/U for both sexes and all ages. The CoQ10/CS ratio was 5-fold decreased in fibroblast mitochondria from a patient with known CoQ10 deficiency due to recessive prenyl (decaprenyl) diphosphate synthase, subunit 2 (PDSS2) mutations. Normalization of mitochondrial CoQ10 concentration against citrate synthase activity is likely to reflect most accurately the CoQ10 content available for the respiratory chain. Our assay and the established reference range should facilitate the diagnosis of respiratory chain disorders and treatment of patients with CoQ10 deficiency.


Expression of the neuronal cyclin-dependent kinase 5 activator p35Nck5a in human monocytic cells is associated with differentiation.
Although cyclin-dependent kinase 5 (Cdk5) is widely expressed in human tissues, its activator p35Nck5a is generally considered to be neuron specific. In addition to neuronal cells, active Cdk5 complexes have been reported in developing tissues, such as the embryonic muscle and ocular lens, and in human leukemia HL60 cells induced to differentiate by an exposure to 1,25-dihydroxyvitamin D(3); however, its activator in these cells has not been demonstrated. The results of this study indicate that p35Nck5a is associated with Cdk5 in monocytic differentiation of hematopoietic cells. Specifically, p35Nck5a is expressed in normal human monocytes and in leukemic cells induced to differentiate toward the monocytic lineage, but not in lymphocytes or cells induced to granulocytic differentiation by retinoic acid. It is present in a complex with Cdk5 that has protein kinase activity, and when ectopically expressed together with Cdk5 in undifferentiated HL60 cells, it induces the expression of CD14 and "nonspecific" esterase, markers of monocytic phenotype. These observations not only indicate a functional relationship between Cdk5 and p35Nck5a, but also support a role for this complex in monocytic differentiation. (Blood. 2001;97:3763-3767)


Bilateral maxillary sinus cholesterol granuloma: a rare entity.
Cholesterol granuloma in the paranasal sinuses is rare. It is more common in the mastoid antrum and temporal bone air cells in chronic middle ear disease. A case of bilateral maxillary sinus cholesterol granuloma that mimics chronic maxillary sinusitis is reported. This is the first reported case of cholesterol granuloma of the maxillary sinus in the Malaysian Literature.


Pronounced cell death in the absence of NMDA receptors in the developing somatosensory thalamus.
Genetic deletion of NMDA glutamate receptors disrupts development of whisker-related neuronal patterns in the somatosensory system. Independent studies have shown that NMDA receptor antagonists increase cell death among developing neurons. Here, we report that a dramatic feature of the developing somatosensory system in newborn NMDA receptor 1 (NMDAR1) knock-out mice is increased cell death in the ventrobasal nucleus (VB) of the thalamus. Sections were subject to terminal deoxynucleotidyl transferase dUTP nick end labeling staining for apoptotic DNA fragmentation, thionine staining for pyknotic nuclei, silver staining for degenerating cells, and immunostaining for caspase-3. All four methods demonstrated that deletion of NMDAR1 causes a large (on the order of threefold to fivefold) increase in cell death in the VB. The NMDA receptor antagonists dizocilpine maleate (MK-801) and phencyclidine also increase cell death in this structure. The onset of increased cell death in the VB in the absence of NMDA receptor function is approximately the time of birth, overlaps with naturally occurring cell death and synaptogenesis, and displays some anatomical specificity. For example, there was no increase in cell death in the hippocampus or neocortex of NMDAR1 knock-out mice at any of the time points examined: embryonic day 15.5 (E15.5), E17.5, and postnatal day 0. We also report a significant reduction in the size of the VB that is evident starting at E17.5. The results indicate that NMDA receptors play a major role in cell survival during naturally occurring cell death in the VB and demonstrate that cell death is a consideration in NMDA receptor knock-out studies.


The association between conventional ultrasound and contrast-enhanced ultrasound appearances and pathological features in small breast cancer.
To investigate the association between ultrasound appearances and pathological features in small breast cancer. A total of 186 small breast cancers in 186 patients were analyzed in this retrospective study from January 2015 to December 2019 according to pathological results. Forty-seven cases of axillary lymph node metastasis were found. All patients underwent radical axillary surgery following conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) examinations. The association between ultrasound appearances and pathological features was analyzed using univariate distributions and multivariate analysis. Then, a logistic regression model was established using the pathological diagnosis of lymph node metastasis and biochemical indicators as the dependent variable and the ultrasound appearances as independent variables. In small breast cancer, risk factors of axillary lymph node metastasis were crab claw-like enhancement on CEUS and abnormal axillary lymph nodes on US. The logistic regression model was established as follows: (axillary lymph node metastasis) = 1.100×(crab claw-like enhancement of CEUS) + 2.749×(abnormal axillary lymph nodes of US) -5.790. In addition, irregular shape on CEUS and posterior echo attenuation on US were risk factors for both positive estrogen receptor and progesterone receptor expression, whereas calcification on US was a risk factor for positive Her-2 expression. A specific relationship could be found using the following logistic models: (positive ER expression) = 1.367×(irregular shape of CEUS) + 1.441×(posterior echo attenuation of US) -5.668; (positive PR expression) = 1.265×(irregular shape of CEUS) + 1.136×(posterior echo attenuation of US) -4.320; (positive Her-2 expression) = 1.658×(calcification of US) -0.896. Logistic models were established to provide significant value for the prediction of pre-operative lymph node metastasis and positive biochemical indicators, which may guide clinical treatment.


Recurrent MALAT1-GLI1 oncogenic fusion and GLI1 up-regulation define a subset of plexiform fibromyxoma.
Plexiform fibromyxomas are rare neoplasms, being officially recognized as a distinct entity among benign mesenchymal gastric tumours in the 2010 WHO Classification of Tumours of the Digestive System. Characteristically, these tumours have a multinodular/plexiform growth pattern, and histologically contain variably cellular areas of bland myofibroblastic-type spindle cells embedded in an abundant myxoid matrix, rich in capillary-type vessels. As yet, the molecular and/or genetic features of these tumours are unknown. Here we describe a recurrent translocation, t(11;12)(q11;q13), involving the long non-coding gene metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and the gene glioma-associated oncogene homologue 1 (GLI1) in a subgroup of these tumours. The presence of the fusion transcript in our index case was confirmed using polymerase chain reaction (PCR) on genomic DNA, followed by Sanger sequencing. We showed that the truncated GLI1 protein is overexpressed and retains its capacity to transcriptionally activate its target genes. A specific FISH assay was developed to detect the novel MALAT1-GLI1 translocation in formalin-fixed, paraffin-embedded (FFPE) material. This resulted in the identification of two additional cases with this fusion and two cases with polysomy of the GLI1 gene. Finally, immunohistochemistry revealed that the GLI1 protein is exclusively overexpressed in those cases that harbour GLI1/12q13 genomic alterations. In conclusion, overexpression of GLI1 through a recurrent MALAT1-GLI1 translocation or GLI1 up-regulation delineates a pathogenically distinct subgroup of plexiform fibromyxomas with activation of the Sonic Hedgehog signalling pathway. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Circulating Plasma Biomarkers for TSU-68, an Oral Antiangiogenic Agent, in Patients with Metastatic Breast Cancer.
This study analyzed the role of plasma biomarkers for TSU-68 in a previous phase II trial comparing TSU-68 plus docetaxel and docetaxel alone in patients with metastatic breast cancer. A total of 77 patients were eligible for this study (38 in the TSU-68 plus docetaxel arm and 39 in the docetaxel alone arm). Blood samples were collected prior to the start of each cycle, and vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)-AA, -AB, -BB, fibroblast growth factor, M30, C-reactive protein (CRP), and interleukin 6 (IL-6) levels were measured using enzyme linked immunosorbent assay. The primary endpoint was progression-free survival (PFS). In patients with baseline PDGF-AA ≥ median, median PFS was significantly worse in the TSU-68 plus docetaxel group than in the docetaxel alone group (5.4 months vs. 13.7 months, p=0.049), while a trend toward a PFS benefit was observed in those with baseline PDGF-AA < median (9.7 months vs. 4.0 months, p=0.18; p for interaction=0.03). In the TSU-68 plus docetaxel group, PFS showed significant association with fold changes in CRP (p=0.001), IL-6 (p < .001), PDGF-BB (p=0.02), and VEGF (p=0.047) following the first treatment cycle. Baseline PDGF-AA levels and dynamics of VEGF, PDGF-BB, CRP, and IL-6 levels were predictive for the efficacy of TSU-68.


[Characteristic of ocular safety profile of triamcinolone made in China].
To characterize the safety profile of triamcinolone acetonide made in China (Transton) and triamcinolone acetonide acetate (Tongyong) for their ocular application. Experimental study. In vitro cell viability assay was performed on 3 types of human ocular cells to evaluate the cytotoxicity of the simulated vitreal concentrations (from a 1:15 dilution as if injected into 1.5 ml of rabbit vitreous to 1:50 dilution as if injected into 5 ml of human vitreous) of Transton and Tongyong using MTT method.In vivo 28 guinea pigs, randomly divided into four groups, were used for evaluating either intravitreal 6 µl of the two types of triamcinolone suspension or 18 µl of their supernatant. Following the injections, the eyes were monitored by biomicroscopy, ophthalmoscopy, tonometry, electroretinography, and histology. The Dunnett's test was used to analyze in vitro cell viability. Paired sample t-test and Generalized Estimating Equations (GEE) were respectively used to compare electroretinography data and intraocular pressure between experimental eyes and the control eyes. The undiluted supernatant of Transton and Tongyong was toxic to human scleral fibroblasts when compared with their control groups (MTT values = 0.046 ± 0.036 and 0.044 ± 0.05 versus 0.367 ± 0.106 and 0.413 ± 0.128) (P < 0.01) or with the BSS group (0.368 ± 0.106 and 0.441 ± 0.137) (P < 0.01). 1:15 or greater dilution of supernatant of Transton and Tongyong did not show cytotoxicity on cultured human retinal pigment epithelium cells or Müller cell (P > 0.05), but 1:15 dilution of Tongyong supernatant showed cytotoxicity on the Müller cells (MTT value = 0.366 ± 0.062 versus 0.417 ± 0.042 for BSS) (P = 0.03). In vivo, neither intravitreal 6 µl (0.25 mg, equivalent to 4 mg in 0.1 ml for human eyes) of the suspension nor 18 µl (equivalent resultant preservative concentration to intravitreal 4 mg in 0.1 ml for rabbit eyes) of the supernatant of Transton and Tongyong showed ocular toxicity. The equivalent dose (6 µl) to 4 mg in 0.1 ml intravitreal suspension for human eye or equivalent resultant preservative concentration to 0.1 ml intravitreal suspension for rabbit eye is found safe in guinea pig eyes.


Compensated deleterious mutations in insect genomes.
Relatively little is known about the importance of amino acid interactions in protein and phenotypic evolution. Here we examine whether mutations that are pathogenic in Drosophila melanogaster become fixed via epistasis in other Dipteran genomes. Overall divergence at pathogenic amino acid sites is reduced. However, approximately 10% of the substitutions at these sites carry the exact same pathogenic amino acid found in D. melanogaster mutants. Hence compensatory mutation(s) must have evolved. Surprisingly, the fraction 10% is not affected by phylogenetic distance. These results support a selection-driven process that allows compensated amino acid substitutions to become rapidly fixed in taxa with large populations.


[Validity of indicators on physical activity and sedentary behavior from the Brazilian National School-Based Health Survey among adolescents in Rio de Janeiro, Brazil].
This study evaluated the relative validity of physical activity indicators from the questionnaire used in the Brazilian National School-Based Health Survey (PeNSE) in the city of Rio de Janeiro, Brazil, based on a sample of 174 students. The following indicators of weekly physical activity were evaluated: ACTIVE-300MIN (≥ 300 minutes/week); ACTIVE-150MIN (≥ 150 minutes), INACTIVE (no physical activity). Additionally, indicators of sedentary behavior were also assessed, as daily screen time (TV, videogames, and computer). The results from the questionnaire were compared with three 24-hour recalls. The results of ACTIVE-300MIN, ACTIVE-150MIN, and INACTIVE generated by PeNSE showed high accuracy. These indicators performed better than those of sedentary behavior in relation to frequency estimates as well as sensitivity, specificity, and correct classification rate. The indicators of physical activity from PeNSE showed satisfactory relative validity.


Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis.
The sustained antibody response to nuclear envelope gp210 antigen indicates a group of primary biliary cirrhosis (PBC) patients at high risk for the progression to end-stage hepatic failure. To address this issue, we immunohistochemically studied the expression of gp210 antigen in needle liver biopsy specimens from PBC patients using a monoclonal antibody specific for gp210 antigen. The specimens from autoimmune hepatitis (AIH), chronic viral hepatitis B (CHB) and C (CHC) patients served as disease controls. The expression of gp210 antigen was apparently increased on the nuclear envelope of biliary epithelial cells (BECs) of small bile ducts in almost all specimens from PBC. In contrast, the expression of gp210 antigen was negative in BECs of small bile ducts in normal liver, while relatively weak anti-gp210 immunostaining was observed in AIH, CHC and CHB. In addition, the degree of gp210 expression in BECs of small bile ducts was positively correlated to that of portal inflammation, interface hepatitis and lobular inflammation in PBC. These results indicate that the increased expression of gp210 in small bile ducts, which is probably associated with damage to BECs by inflammation, is possibly involved in autoimmune response to gp210 leading to the progression to end-stage hepatic failure in PBC.


Extrarolandic electroclinical findings in the evolution of adult-onset Rasmussen's encephalitis.
Rasmussen's encephalitis (RE) is a rare immunomediated disorder characterized by unilateral hemispheric atrophy, drug-resistant focal epilepsy, and progressive neurological deficits. Its onset typically occurs in childhood, though it has also been reported in adult age (A-RE) with atypical clinical features. The aim of this study was to describe the electroclinical features in a group of seven patients with A-RE. We retrospectively studied seven women aged 23-43years (mean: 32.1years) with a diagnosis of RE according to commonly accepted diagnostic criteria. All the patients were clinically evaluated and underwent prolonged video-EEG monitoring, laboratory investigations, and high-resolution MRI follow-up. All the patients displayed an ictal electroclinical pattern whose evolution varied. We identified an early phase characterized by polymorphic ictal electroclinical manifestations (temporal semiology in five cases, frontal in one, and parietal in the remaining case) and a late phase clinically characterized by viscerosensitive phenomena followed by somatosensitive signs, experiential symptoms, and motor signs in all the cases. In the late phase, the ictal EEG pattern was characterized by monomorphic, pseudorhythmic, repetitive slow-wave theta activity over the frontal and central regions, with ipsilateral propagation and/or secondary spreading to contralateral perisylvian structures. Patients were treated with a combination of AEDs and immunotherapy (steroids and IVIg); epilepsy surgery was performed in 3 cases. Our results show that A-RE is characterized by early and late clinical- and EEG-different features which may reflect a progressive involvement of a specific "extrarolandic" network in the advanced phase of the disease and may suggest that the electroclinical expression of RE varies according to the different stages of the pathological process.


Temperature dependence of the concentration kinetics of absorption of phosphate and potassium in corn roots.
The effect of temperature on respiration and kinetics of H(2)PO(4) (-) and K(+) uptake in corn roots was determined in the range of 2 to 42 C. The response of uptake to temperature, determined from Q(10) and activation energy (Ea) data, for the anion and the cation differ significantly, especially in the range of uptake mechanism (Mech.) I. At 2.5 micromolar the Ea for K(+) uptake below the 13 C transition is 29.3 kilocalories per mole. As the K(+) concentration is increased, Ea declines and at 0.25 millimolar is 21.6 kilocalories per mole. Accompanying this change in Ea is a shifting of the apparent transition temperature from 13 to 17 C. Above the temperature transition the Ea's for K(+) uptake in the Mech. I range are quite low (3.0) and this value is unchanged by increases of K(+) concentration to 0.25 millimolar. In the range of Mech. II above 1 millimolar K(+) the temperature transitions are not seen and plots become linear. The Ea's show an increasing trend from 4.7 at 1 millimolar to 6.1 at 50 millimolar. The uptake of H(2)PO(4) (-) is much more temperature sensitive having a constant Ea at concentrations in the Mech. I range below the 13 C temperature transition. The Arrhenius plots reveal a second transition at 22 C and the Ea for this segment is 21.0. Above the second transition the Ea remains high (10.0) and is constant in the range of Mech. I. In the range of Mech. II there is a concentration dependent decline in Ea for H(2)PO(4) (-) uptake (22.7 at 1.0 millimolar to 1.0 at 50 millimolar). There is no definable low temperature transition at these concentrations. Ion uptake is found to be much more sensitive to low temperature than respiration in this chill-sensitive species. The data suggest that the low temperature reduction of ion transport is more closely related to restriction of function of active transport systems than to either respiration or membrane permeability.


The generation of memory B cells is maintained, but the antibody response is not, in the elderly after repeated influenza immunizations.
The success of a vaccine in inducing a protective antibody response depends on the longevity of both long-lived plasma cells (PC) and memory B cells. We have previously shown that the in vivo antibody response to a new influenza vaccine, the ex vivo plasmablast response, the in vitro B cell function, measured by AID (activation-induced cytidine deaminase), and the transcription factor E47, are significantly associated and decreased in elderly individuals. We hypothesized that because AID is decreased in the elderly, the ability to generate memory B cells would also be decreased, but our findings here show that memory B cells are maintained in the elderly probably due to further amplification in response to repeated vaccination. We recruited young and elderly individuals immunized in at least two consecutive influenza vaccine seasons in which the influenza A viral strains H1N1 and H3N2 in the vaccine were the same as in the previous year. PBMC were cultured with CpG/IL2 to measure the frequency of IgG vaccine-specific memory B cells. Serum antibody response was measured by hemagglutination inhibition assay. Blood plasmablasts were measured by flow cytometry. Surprisingly, the frequencies of influenza vaccine-specific memory B cells and plasmablasts were similar in young and elderly individuals, but the fold-increase in serum titers after vaccination was lower in the elderly although most of the elderly were seroprotected. We then measured the transcription factor Blimp-1, considered the master regulator of PC differentiation, and found it significantly reduced in cultures of B cells from elderly versus young individuals, as well as E47/AID and IgG secretion. Taken together, these results suggest an impaired memory B cell to PC differentiation in the elderly.


Spatial distribution and temporal trends of persistent organochlorine pollutants in sediments from Lake Maryut, Alexandria, Egypt.
Organochlorine compounds (OCs) in surface and core sediments collected from Lake Maryut, Egypt, were examined to elucidate their distribution, ecological risk and historical trend. To our knowledge, this is the first study on residue levels of OCs in sediments from Lake Maryut. Concentrations of PCBs and DDTs were higher than other OCs, ranging from 3.06 to 388 and from 0.07 to 106 ng/g dry wt., respectively. The highest concentrations of OCs were found at stations near the discharge point of sewage and close to industrial areas. The distribution of DDT and its metabolites suggest no recent inputs into the lake environment. Contamination levels of sedimentary PCBs and DDTs, can be categorized moderate to high compared to other urbanized regions worldwide. Temporal trends in OCs levels were influenced by input pathways at two sites. Evaluation of ecotoxicological risks suggests that adverse biological effects are expected mainly in the main basin area.


The diverse cellular responses of the choroid plexus during infection of the central nervous system.
The choroid plexus (CP) is responsible for the production of a large amount of the cerebrospinal fluid (CSF). As a highly vascularized structure, the CP also presents a significant frontier between the blood and the central nervous system (CNS). To seal this border, the epithelium of the CP forms the blood-CSF barrier, one of the most important barriers separating the CNS from the blood. During the course of infectious disease, cells of the CP can experience interactions with intruding pathogens, especially when the CP is used as gateway for entry into the CNS. In return, the CP answers to these encounters with diverse measures. Here, we will review the distinct responses of the CP during infection of the CNS, which include engaging of signal transduction pathways, the regulation of gene expression in the host cells, inflammatory cell response, alterations of the barrier, and, under certain circumstances, cell death. Many of these actions may contribute to stage an immunological response against the pathogen and subsequently help in the clearance of the infection.


Adjustable suture technique for levator recession.
To determine whether an adjustable suture technique is clinically useful in levator recession surgery. Consecutive clinical series. Inpatient hospital and ambulatory surgical center. Ten patients who were undergoing levator recession surgical procedures for correction of eyelid retraction constituted the group of subjects of this study. Outcome measures included margin-reflex distance and palpebral fissure measurements. Postoperative margin-reflex distance and palpebral fissure measurements were within 0.5 mm of the desired eyelid position in 10 or 14 procedures and within 1 mm of the desired position in 12 of 14 procedures. Adjustable sutures may be a useful adjunct in levator recession surgery.


Ultrasound findings in pure invasive lobular carcinoma of the breast: comparison with matched cases of invasive ductal carcinoma of the breast.
Pure invasive lobular carcinoma is more difficult to diagnose clinically and mammographically than other invasive breast carcinomas. Our objective was to document the ultrasound appearances of pure invasive lobular carcinoma, to determine whether there were any specific features when compared to similar cases of invasive ductal carcinoma, and to compare the sensitivity of ultrasound with mammography in the diagnosis of invasive lobular carcinoma. We report on 23 cases of invasive lobular carcinoma who were matched for age and presentation with cases of invasive ductal carcinoma. High frequency ultrasound detected lesions in 22 cases of invasive lobular carcinoma and all had features highly suggestive of malignancy. Twenty-one of 23 cases of invasive ductal carcinoma also had malignant features. At mammography, six cases of invasive lobular carcinoma were not detected. Ultrasound is as specific for identifying invasive lobular carcinoma as it is for invasive ductal carcinoma. Ultrasound was more sensitive than mammography for diagnosing invasive lobular carcinoma.


The nurse leader as logistician: optimizing human capital.
Many traditional approaches to planning and deploying human capital have not been effective. Staffing offices are chaotic, budgets are overrun, staffing is frequently misaligned, a growing number of state legislatures are mandating nurse staffing levels, and dissatisfaction with work schedules abounds. The authors explores methodologies used in the science of logistics management, namely, systems theory and mathematical optimization modeling, which, when applied to human capital planning and deployment, can significantly improve business results.


Effects of physical training and potassium supplementation on blood pressure, glucose metabolism and albuminuria of spontaneously hypertensive rats.
It is still controversial whether there are synergistic effects among different non-pharmacological interventions used in the treatment of hypertension. To evaluate the effect of aerobic exercise, oral supplementation of potassium and their combination on blood pressure, glucose metabolism, urinary albumin excretion and glomerular morphology in spontaneously hypertensive rats (SHR). SHR were divided into groups: Control Group (SHR; standard diet and sedentary, n = 10), Exercise Group (SHR + E; trained on a treadmill, standard diet, n = 10), Potassium Group (SHR + K; sedentary, potassium supplementation, n = 10) and Group Exercise + Potassium (SHR + E + K, exercise, potassium supplementation n = 10). Weekly, body weight (BW) and tail blood pressure (TAP) were measured. At the end of 16 weeks, a Oral Glucose Tolerance Test was performed. Albuminuria was determined in the baseline period, at 8th and at 16th week. After sacrifice, the analysis of glomerular sclerosis index and visceral fat weight was performed. The TAP and BW did not change significantly. There was improvement in insulin sensitivity in SHR + E and SHR + K, but not in SHR + E + K. At week 16, albuminuria in all groups was significantly lower than the SHR control. The glomerular sclerosis index and visceral fat content were also significantly lower in all groups compared to control. An oral supplementation of potassium and exercise led to an improvement in glucose metabolism, in albuminuria and glomerular morphology, however, the overlap of the treatments did not show synergism.


Role of beta 1H for the binding of C3b-coated particles to human lymphoid and phagocytic cells.
Coating of EAC14oxy23b with highly purified human serum beta 1H globulin (beta 1H) led to acceleration of rosette formation with human peripheral blood lymphocytes (PBL), tonsil lymphocytes, B lymphoblastoid (Raji) cells, granulocytes and monocytes. This reaction was discernible from C3bi-dependent rosette formation. Enhancement of rosette formation of C3b cells by beta 1H was most effective at limiting amounts of C3 per EAC14oxy23b. The beta 1H effect was not due to trace contamination with C3b inactivator. beta 1H-dependent rosette formation with the various lymphoid and phagocytic cells could be suppressed by the F(ab')2 fragment of anti-beta 1H suggesting beta 1H-mediated binding of beta 1H-coated particles to complement receptor-positive (CR+) cells. In turn, binding of fluid-phase beta 1H to lymphoid and phagocytic cells could be demonstrated by fluorescence and by 14C-labeled beta 1H. In addition, the functional status of these cells with respect to their receptor reactivity was altered. Treatment of normal lymphocytes (PBL, tonsil lymphocytes) and of granulocytes with beta 1H improved their rosette formation with both EAC14oxy23b and EAC14oxy23b-beta 1H. The reaction of monocytes was hardly affected. The beta 1H effect on Raji cells resulted in reduced rosette formation with EAC14oxy23b-beta 1H, while binding of EAC14oxy23b remained unchanged. These results suggest the presence of sites on CR+ cells, to which soluble and particle-bound beta 1H can bind, leading to alteration of the functional status of the cells. In all likelihood, EAC14oxy23bi can attach to the beta 1H-binding sites on CR+ cells.


Pharmacologic profiles of KRH-594, a novel nonpeptide angiotensin II-receptor antagonist.
We studied pharmacologic profiles of KRH-594, dipotassium (Z)-2-[[5-ethyl-3-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl-1,3,4 -thiadiazolin-2-ylidene]aminocarbonyl]-1-cyclopentenecarb oxylate, a novel angiotensin II (AII)-receptor antagonist. KRH-594 potently displaced specific binding of [125I]-AII from AT1 receptor with a Ki of 0.39 nM in rat liver membranes, but not from AT2 receptor in bovine cerebellar membranes (Ki > 10 microM). KRH-594 exhibited no affinity for 21 other receptors and two enzymes [50% inhibitory concentration (IC50) > 10 microM], demonstrating its high specificity toward AT1 receptors. In isolated rabbit aorta, KRH-594 caused nonparallel shifts to the right of the dose-response curve to AII and decreased the maximal response with a pK(B) of 10.4. We evaluated the in vivo efficacy and the duration of action in freely moving rats under nonfasting conditions. In normotensive rats, orally administered KRH-594 inhibited AII-induced pressor responses with a 50% inhibitory dose (ID50) of 0.39 mg/kg. In spontaneously hypertensive rats (SHRs), both KRH-594 (1 mg/kg p.o.) and losartan (10 mg/kg p.o.) exerted similar blood pressure-reducing effects, and their effects were still significant at 24 h after drug administration. We concluded that KRH-594 is a specific and efficacious AT1 antagonist that may find its use in the treatment of human hypertension.


Insights into the antimicrobial properties of a cationic steroid and antibiofilm performance in PDMS-based coatings to potentially treat urinary infections.
Currently, multidrug-resistant (MDR) infections are one of the most important threats, driving the search for new antimicrobial compounds. Cationic peptide antibiotics (CPAs) and ceragenins (CSAs) contain in their structures cationic groups and adopt a facially amphiphilic conformation, conferring the ability to permeate the membranes of bacteria and fungi. Keeping these features in mind, an amine steroid, DOCA-NH2, was found to be active against reference strains and MDR isolates of Gram-positive Enterococcus faecalis and Staphylococcus aureus and Gram-negative Escherichia coli and Pseudomonas aeruginosa. The compound was active against all the tested microorganisms, having bactericidal and fungicidal activity, displaying minimal inhibitory concentrations (MICs) between 16 and 128 μg mL-1. No synergy with clinically relevant antibacterial drugs was found. However, the compound was able to completely inhibit the biofilm formation of bacteria exposed to the MIC of the compound. For E. coli and E. faecalis, inhibition of biofilm formation occurred at half the MIC. Besides, DOCA-NH2 inhibited the dimorphic transition of Candida albicans at concentrations 4 times lower than the MIC, and can reduce the microorganism virulence and biofilm formation was significantly reduced at both MIC and half the MIC. Polydimethylsiloxane-based coatings containing DOCA-NH2 (0.5, 1.0, and 1.5 wt%) were prepared and tested against the E. coli biofilm formation under hydrodynamic conditions similar to those prevailing in ureteral stents. A biofilm reduction of approximately 80% was achieved when compared to the control.


Predation risk influences adaptive morphological variation in fish populations.
Predators can cause a shift in both density and frequency of a prey phenotype that may lead to phenotypic divergence through natural selection. What is less investigated is that predators have a variety of indirect effects on prey that could potentially have large evolutionary responses. We conducted a pond experiment to test whether differences in predation risk in different habitats caused shifts in behavior of prey that, in turn, would affect their morphology. We also tested whether the experimental data could explain the morphological variation of perch in the natural environment. In the experiment, predators caused the prey fish to shift to the habitat with the lower predation risk. The prey specialized on habitat-specific resources, and there was a strong correlation between diet of the prey fish and morphological variation, suggesting that resource specialization ultimately affected the morphology. The lack of differences in competition and mortality suggest that the morphological variation among prey was induced by differences in predation risk among habitats. The field study demonstrated that there are differences in growth related to morphology of perch in two different habitats. Thus, a trade-off between foraging and predator avoidance could be responsible for adaptive morphological variation of young perch.


Detection of lumbosacral nerve root compression with a novel composite nerve conduction measurement.
Multivariate logistic regression techniques were used to develop a composite nerve conduction measurement that detects lumbosacral (L5, S1, or both) nerve root compression. To evaluate the diagnostic efficacy of a composite nerve conduction measurement for detection of lumbosacral nerve root compression. Nerve root involvement is characterized by clinical abnormalities and confirmed by radiologic and electrodiagnostic studies. Imaging studies visualize structural abnormalities; however, they are associated with high false-positive rates. Electrodiagnostic methods assess the physiologic integrity of the nerve roots. One form of electrodiagnostic testing, nerve conduction studies, is widely used for evaluation of musculoskeletal and neuromuscular complaints. Although similar clinical value is expected for the evaluation of nerve root compromise, prior applications of nerve conduction studies have yielded widely varying results. Two groups of subjects were compared. The L5-S1 compression group was composed of 25 patients with magnetic resonance imaging-confirmed lumbosacral (L5, S1, or both) nerve root compression and symptoms in the appropriate segmental distribution. The majority of subjects (22) had at least one of the following findings on physical examination: positive straight-leg raise test, diminished ankle reflexes, sensory loss, or weakness. The control group consisted of 35 asymptomatic individuals with no history of radiculopathy or potentially confounding neuropathology. The posterior tibial and deep peroneal nerves were evaluated bilaterally in all study subjects using standard nerve conduction procedures, which consisted of the measurement of distal motor latencies and F-wave latencies that assess nerve root pathophysiology. A composite nerve conduction measurement was determined using multivariate logistic regression analysis. The efficacy of the composite measurement was assessed by receiver operating characteristic curve analysis and by the diagnostic sensitivity and specificity. Five F-wave latency parameters (peroneal mean F-wave latency, odds ratio = 0.42; peroneal seventh F-wave latency decile, odds ratio = 2.71; tibial mean F-wave latency, odds ratio = 8.90; tibial first F-wave latency decile, odds ratio = 0.47; tibial maximum F-wave latency, odds ratio = 0.44) were found to be predictive of nerve root compression. A composite nerve conduction measurement, NC composite, constructed from these five parameters (NC composite = exp(phi)/(1 + exp(phi)), phi = -31.2 + 1.0 * Per7 Decile - 0.88 * PerMean + 2.2 * TibMean - 0.88 * Tib1 Decile - 0.83 * TibMax) yielded an area under the receiver operating characteristic curve of 0.91. At a threshold of 0.20, NC composite had a diagnostic specificity of 84.3% and a sensitivity of 83.3%. This preliminary study suggests that a novel composite nerve conduction measurement, based on F-wave latency parameters, may be highly effective at detecting magnetic resonance imaging-confirmed lumbosacral nerve root compression. Because these measurements provide objective evidence of functional nerve root compromise and are noninvasive, they may be of diagnostic value to clinicians evaluating patients presenting with low back and leg pain.


IgE class switching is critically dependent upon the nature of the B cell activator, in addition to the presence of IL-4.
Cross-linkage of membrane IgD on resting murine B cells, by anti-IgD mAb conjugated to dextran (alpha delta-dex), induces high levels of proliferation, and in the presence of IL-2 or IL-5, Ig secretion in vitro. The structural and functional similarities between alpha delta-dex and TNP-Ficoll for B cell responses led us to propose that alpha delta-dex could provide a model system for studying B cell activation induced by T cell-independent, type II Ag. In this report, we study the effects of Ig class switch and differentiation factors on Ig isotype production by murine B cells activated by alpha delta-dex, and directly compare these to responses obtained after activation by LPS. We show that an IL-4-containing CD4+ T cell supernatant (Th2 SN) stimulates large increases in IgG1 and IgE production by LPS-activated B cells, but fails to stimulate detectable levels of IgE by alpha delta-dex-activated cells, despite inducing high levels of secreted IgM and IgG1. This is correlated with undetectable steady state levels of both germ-line and rearranged (productive) IgE-specific RNA in B cells stimulated with alpha delta-dex + Th2 SN. Alpha delta-dex is selective in its failure to costimulate IgE production in that IFN-gamma-containing T cell supernatant (Th1 SN) and transforming growth factor-beta-supplemented Th2 SN selectively stimulate a large IgG2a and IgA secretory response, respectively. Anti-IgD conjugated to Sepharose beads, in distinct contrast to dextran, costimulates a strong IgE response. These findings underscore the importance of the specific B cell activator, in addition to IL-4, in the regulation of IgE production.


Progress toward global eradication of dracunculiasis.
The plan for the global eradication of dracunculiasis (i.e., Guinea worm disease) was developed in October 1980, when dracunculiasis was known to be endemic in 16 African countries, India, and Pakistan. In 1991, the World Health Assembly adopted a resolution to eradicate dracunculiasis by the end of 1995. This report summarizes the substantial progress toward eradication of dracunculiasis since the beginning of this effort.


Toward the locomotion of two contemporaneous Adapis species.
The morphological differences between the limb bones of two Adapis species from two localities in Southern France are analyzed for their functional significance. The study focuses on the distal humerus, proximal femur, astragalus and calcaneum. The Escamps species Adapis aff. betillei shows more extreme flexion at the elbow, lateral mobility at the hip, and more rotation at the calcaneocuboid joint than in the other species. The species from Rosières 2 A. cf. parisiensis shows increased emphasis on parasagittal movements, restrictions of lateral mobility in the hindlimb, enhanced capacity for rapid flexion and powerful extension of the thigh, and powerful rapid foot extension. The Rosières species probably engaged in more frequent branch walking and running, and the Escamps species probably included more climbing in its locomotor repertoire. In the general Adapis genus morphology, the large tuber calcanei, short astragalus, and the presence of a calcaneal "pressure facet" are similarities shared with living cercopithecids. Along with other characters, these suggest that horizontal running was possibly an important means of locomotion in the Adapis and adapine morphotypes, and may even indicate a degree of terrestraility. Contrary to the most common view, the euprimate morphotype was probably not a specialized leaper.


[Oxidized LDL and anti-oxidized LDL antibodies according uric acid levels in overweight women].
To establish whether increased serum uric acid is associated with higher levels of oxidized LDL (oxLDL), antibodies against human oxidized LDL (oxLDL Ab) and ratios of LDL oxidation in overweight women. Cross-sectional study that included 114 women with body mass index ? 25 kg/m2. We determined weight, height, waist circumference, blood pressure, glycemia, uric acid, lipid profile, creatinine, Apolipoprotein B (ApoB), oxLDL, oxLDL Ab, insulin and insulin resistance was estimated using HOMA. Body mass index, LDL-associated ApoB, rates of LDL oxidation and tertiles of uric acid were calculated. Metabolic syndrome was defined using NCEP/ATP III criteria. Of the women studied 51.8% were overweight and the rest was classified as obese; 66.7% had metabolic syndrome. In the total group and overweight group, only the oxLDL/HDL cholesterol ratio was significantly higher in the last tertile of uric acid. The serum levels of circulanting oxLDL and oxLDL/cholesterol, oxLDL/HDL cholesterol, oxLDL/ApoB and oxLDL/ LDL-associated ApoB ratios were significantly higher among obese women located in the highest tertile of uric acid. Concentrations of oxLDL Ab and oxLDL/oxLDL Ab were not related to the uric acid. Serum uric acid and ApoB predicted the elevation of oxLDL. Increased serum uric acid was associated with more oxidation of LDL among obese women. This suggests the importance of regular monitoring of uric acid in overweight women. Prospective research should be conducted.


Postural control in girls with adolescent idiopathic scoliosis while wearing a Chêneau brace or performing active self-correction: a pilot study.
It is known that adolescent idiopathic scoliosis (AIS) is often accompanied by balance deficits. This reciprocal relationship must be taken into account when prescribing new therapeutic modalities because these may differently affect postural control, interacting with therapy and influencing its results. The purpose was to compare postural control in girls with AIS while wearing the Chêneau brace (BRA) or performing active self-correction (ASC) with their postural control in a quiet comfortable stance. Nine subjects were evaluated on a force plate in three series of two 20-s quiet standing trials with eyes open or closed; three blocks were randomly arranged: normal quiet stance (QST), quiet stance with BRA, and quiet stance with ASC. On the basis of centre-of-pressure (COP) recordings, the spatial and temporal COP parameters were computed. Performing ASC was associated with a significant backward excursion of the COP mean position with eyes open and closed (ES = 0.56 and 0.65, respectively; p < 0.05). This excursion was accompanied by an increase in the COP fractal dimension (ES = 1.05 and 0.98; p < 0.05) and frequency (ES = 0.78; p = 0.10 and ES = 1.14; p < 0.05) in the mediolateral (ML) plane. Finally, both therapeutic modalities decreased COP sample entropy with eyes closed in the anteroposterior (AP) plane. Wearing BRA resulted in ES = 1.45 (p < 0.05) while performing ASC in ES = 0.76 (p = 0.13). The observed changes in the fractal dimension (complexity) and frequency caused by ASC account for better adaptability of patients to environmental demands and for their adequate resources of available postural strategies in the ML plane. These changes in sway structure were accompanied by a significant (around 25 mm) backward excursion of the mean COP position. However, this improvement was achieved at the cost of lower automaticity, i.e. higher attentional involvement in postural control in the AP plane. Wearing BRA may have an undesirable effect on some aspects of body balance.


Osteoprecursor cell response to strontium-containing hydroxyapatite ceramics.
The objective of this study was to investigate the in vitro bioactivity of strontium-containing hydroxyapatite (Sr-HA), and its effect on cellular attachment, proliferation, and differentiation. The effect of Sr-HA has been compared with that of hydroxyapatite (HA), which is widely used in orthopedics and dentistry. Sr-HA ceramic containing 10 mol % was prepared. The bioactivity of Sr-HA was evaluated in vitro by immersion in simulated body fluid (SBF). After immersion in SBF, Sr-HA exhibited greater ability to induce apatite precipitation on its surface than did HA. The possible effects on cell behavior of Sr-HA were examined by culturing osteoprecursor cells (OPC1) on materials surfaces. Cell shape and cell-material interactions were analyzed by scanning electron microscope (SEM) and the MTT assay was used to determine cell proliferation on samples. When compared with HA, Sr-HA promoted better OPC1 cell attachment and proliferation, and showed no deleterious effects on extracellular matrix formation and mineralization. Confocal scanning microscopy was used to assess the expression of specific osteoblast proteins: alkaline phosphatase (ALP) and osteopontin (OPN). The results obtained indicate that the presence of Sr stimulates OPC1 cell differentiation, and enhances ALP and OPN expression.


In vivo evaluation of postoperative immunosuppression by means of Multitest system.
The Multitest System, a new standardized method for evaluating delayed hypersensitivity and cell mediated immunity was carried out before surgery and throughout the postoperative care in subjects undergoing gastrointestinal surgery. In all patients significantly depressed cutaneous reactions were found in the first day after operation. Immunosuppression lasted more than four days when postoperative infection has set up, while in uneventful patients delayed hypersensitivity has returned to preoperative values from the fourth day. It would be suggested that Multitest System data in fourth postoperative day could identify subjects with uneventful recovery after surgery.


Antidiabetic Activity of Ergosterol from Pleurotus Ostreatus in KK-Ay Mice with Spontaneous Type 2 Diabetes Mellitus.
The number of people with diabetes is increasing rapidly in the world. In the present study, the hypoglycemic activity and potential mechanism of ergosterol (ERG), a phytosterol derived from the edible mushroom Pleurotus ostreatus are investigated in vitro and in vivo. ERG is isolated from Pleurotus ostreatus and identified by NMR spectra. The effects of ERG on the glucose uptake, glucose transporter 4 (GLUT4) translocation, GLUT4 expression, and the phosphorylation of AMPK, Akt and PKC in L6 cells are evaluated. ERG enhances glucose uptake and displays a GLUT4 translocation activity with up-regulating GLUT4 expression and phosphorylation of Akt and PKC in L6 cells. In vivo, antidiabetic activity of ERG is examined. The phosphorylation of Akt and PKC in different tissues from KK-Ay mice is assessed. ERG significantly improves insulin resistance and blood lipid indices while reducing fasting blood glucose levels and protecting pancreas and liver in the mice. Moreover, the phosphorylation of Akt and PKC is increased in different tissues. The results suggest that ERG may be a potential hypoglycemic agent for the treatment of T2DM with the probable mechanism of stimulating GLUT4 translocation and expression modulated by the PI3K/Akt pathway and PKC pathway.


as-PSOCT: Volumetric microscopic imaging of human brain architecture and connectivity.
Polarization sensitive optical coherence tomography (PSOCT) with serial sectioning has enabled the investigation of 3D structures in mouse and human brain tissue samples. By using intrinsic optical properties of back-scattering and birefringence, PSOCT reliably images cytoarchitecture, myeloarchitecture and fiber orientations. In this study, we developed a fully automatic serial sectioning polarization sensitive optical coherence tomography (as-PSOCT) system to enable volumetric reconstruction of human brain samples with unprecedented sample size and resolution. The 3.5 μm in-plane resolution and 50 μm through-plane voxel size allow inspection of cortical layers that are a single-cell in width, as well as small crossing fibers. We show the abilities of as-PSOCT in quantifying layer thicknesses of the cerebellar cortex and creating microscopic tractography of intricate fiber networks in the subcortical nuclei and internal capsule regions, all based on volumetric reconstructions. as-PSOCT provides a viable tool for studying quantitative cytoarchitecture and myeloarchitecture and mapping connectivity with microscopic resolution in the human brain.


Extra-abdominal infections due to Gemella species.
To understand the role of Gemella species as a pathogen causing extra-abdominal infections in the Hospital General Universitario Gregorio Marañón. Between 1994 and 1998, one or more isolates of Gemella sp. were found in 128 patients. The 113 patients with isolates from nonsignificant specimens or representing intra-abdominal infections were excluded. The clinical records of the remaining 15 patients were reviewed as well as the more recent literature. Mean age of patients was 41 years. The underlying conditions most frequently noted were intravenous drug users (n=6; 3 positive for human immunodeficiency virus), alcoholism (n=2), cardiovascular disease (n=2), chronic lung disease (n=2), diabetes (n=1), kidney transplant (n=1). The extra-abdominal infections were skin and soft tissue abscess (n=5), empyema (n=4), brain abscess (n=2), primary bacteremia (n=1), lung abscess (n=1), septic thrombophlebitis (n=1), complicated urinary tract infection (n=1). The infection was monomicrobial in six and polymicrobial in nine cases. Surgical drainage and betalactam antibiotics were used. The outcome was favorable in almost all cases. Gemella sp. should be included as a cause of localized soft-tissue abscesses, empyema, and bloodstream infection. No case of infective endocarditis was found. Although it is susceptible to several antibiotics, Gemella sp. requires a careful microbiologic diagnosis and a subtle clinical interpretation.


Invertases of Lilium Pollen : Characterization and Activity during In Vitro Germination.
Two different forms of invertase are found in pollen of lily (Lilium auratum). One form is cytoplasmic (Invertase 1) and the other is bound to the pollen wall (Invertase 2). Invertase 1 has been partially purified and is a glycoprotein (apparent molecular weight, 450 kilodaltons) with a K(m) of 0.65 millimolar for sucrose. The two invertases differ in pH optimum and thermal stability. Invertases of lily pollen are beta-fructofuranosidases which can hydrolyze sucrose but not melizitose. The mature pollen grains have enzyme activity in both cytoplasmic and wall fractions, and no increase in the activity of either occurs during germination. The wall-bound enzyme could not be released by treatments with detergents or high salt concentrations.


Insulin-like growth factor-I and estrogen interactions in breast cancer.
There is increasing evidence that estradiol and insulin-like growth factor-I (IGF-I) act through a complex cross-talk mechanism to stimulate the proliferation of normal mammary epithelium to increase the risk of breast cancer. The emerging model of cross-talk suggests that estradiol regulates the expression of IGF-I and the IGF receptor I. The subsequent binding of IGF-I to its receptor initiates an intracellular signal transduction pathway that activates transcription factors, including the estrogen receptor. Recent studies show that the effects of IGF-I on estrogen receptor activity are mediated in part by the protein kinase A and phosphatidylinositol-3-kinase/Akt pathways.


Leadership Principles to Decrease Psychological Casualties in COVID-19 and Other Disasters of Uncertainty.
Coronavirus disease (COVID-19) is a "disaster of uncertainty" with ambiguity about its nature and trajectory. These features amplify its psychological toxicity and increase the number of psychological casualties it inflicts. Uncertainty was fueled by lack of knowledge about the lethality of a disaster, its duration, and ambiguity in messaging from leaders and health care authorities. Human resilience can have a buffering effect on the psychological impact. Experts have advocated "flattening the curve" to slow the spread of the infection. Our strategy for crisis leadership is focused on flattening the rise in psychological casualties by increasing resilience among health care workers. This paper describes an approach employed at Johns Hopkins to promote and enhance crisis leadership. The approach is based on 4 factors: vision for the future, decisiveness, effective communication, and following a moral compass. We make specific actionable recommendations for implementing these factors that are being disseminated to frontline leaders and managers. The COVID-19 pandemic is destined to have a strong psychological impact that extends far beyond the end of quarantine. Following these guidelines has the potential to build resilience and thus reduce the number of psychological casualties and speed the return to normal - or at least the new normal in the post-COVID world.


[Use of an evaluation score for rectal mucosal prolapse].
Rectal mucosal prolapse is characterised by the protrusion of the mucosa alone in the rectal lumen. The authors, after an experience conducted in ambulatory patients, have produced a score to classify the extent of rectal mucosal prolapse based on evaluation of qualitative and quantitative factors that should help in the correct management of proctological patients. A total of 30 patients with proctological symptoms during outpatient visits were submitted to a minimally invasive test in comparison to the traditional ones, using a simple gauze plug connected to the end of a suture thread, inserted in the rectal lumen and removed via the anus. The score designed by the authors made it possible to classify 96.6% of patients accurately. In 4 patients the score was equal to zero. In 12 patients there was a mucosal prolapse of less than 25% with a reduction score equal to 2.4 and therefore these were treated with a single rubber ligature (7 patients with classes a and b) and 5 patients were treated with the transfixed stitch technique (TST) (class c). In 10 patients a 50% mucosal prolapse of the anal circumference and a mean reduction score of 5.6 were found. In 5 of these patients (classes a and b) it was possible to perform a multiple ligature while the other 5 (class c) were treated with TST. In 3 patients a prolapse ranging from 50 to 75% with a mean reduction index of 8.1 was found. The therapeutic procedure preferred for these patients was TST. In one patient a circumferential prolapse was diagnosed with a reduction score of 11 treated with Longo's surgical technique. The mucosal prolapse score seems to be useful to stratify patients more precisely in the choice of surgical intervention and during follow-up. The plug test is a minimally invasive test, useful for the application of the rectal mucosal prolapse score.


Migraine among university students in Cotonou (Benin).
Few data are available on migraine among students in Africa. The aim of this study was to estimate the prevalence of migraine and describe its clinical features and associated conditions among students of the Faculty of Health Sciences of Abomey-Calavi University, in Cotonou, Benin. A cross-sectional study was prospectively conducted during the academic year 2002-2003 and included 336 students selected using systematic random sampling. Migraine was defined according International Headache Society criteria 1988. The lifetime prevalence of migraine was 11.3% (95% CI: 8.2-15.3%). The prevalence was significantly higher in females (18.3%) than males (6.8%), in married-widowed (30.4%) than single (9.9%). The mean age at onset of the disease was 15.0 years +/- 2.5. Migraine without aura was the more frequent form (57.9%). The mean attack frequency per month was 3.8 (+/-3.4) and the peak attack duration was between 4 and 6 hours. Psychological tiredness was the most frequent triggering factors (92.1%). The factors associated with migraine in multivariate analysis were female sex (OR = 2.6 [95% CI: 1.2-5.3]), single marital status (OR = 3.7 [95% CI: 1.2-11.9]) and presence of a family history of headache (OR = 2.9 [95% CI: 1.0-8.1]) Migraine was frequent in students in Cotonou (Benin) compared with other studies in Africa.


Delays in diagnosis and treatment of extrapulmonary tuberculosis in Guatemala.
A 23-year-old indigenous Guatemalan man presented in 2016 to our clinic in Sololá, Guatemala, with 10 months of recurrent neck swelling, fevers, night sweats and weight loss. Previously, he had sought care in three different medical settings, including a private physician-run clinic, a tertiary private cancer treatment centre and, finally, a rural government health post. With assistance from our institution's accompaniment staff, the patient was admitted to a public tertiary care hospital for work-up. Rifampin-susceptible tuberculosis was diagnosed, and appropriate treatment was begun. The case illustrates how low tuberculosis recognition among community health workers and health system segmentation creates obstacles to appropriate care, especially for patients with limited means. As a result, significant diagnostic and treatment delays can occur, increasing the public health burden of tuberculosis.


Megalencephalic leukodystrophy in an Asian Indian ethnic group.
Over a 10-year period, we reviewed 30 patients with leukodystrophy, megalencephaly, and a relatively benign course. Most of these patients (26) belonged to a distinctive ethnic group called the Agrawals. Head circumference exceeded the 95th percentile in 28 patients; 22 patients had seizures; 22 had pyramidal signs (16 more pronounced and 6 mild); and 16 had cerebellar ataxia. The median age of onset of symptoms was 1.8 years. Interictal electroencephalogram (EEG) was abnormal in 21 of 23 patients. The inheritance is possibly autosomal recessive.


Biocontrol of Bacterial Leaf Blight of Rice and Profiling of Secondary Metabolites Produced by Rhizospheric Pseudomonas aeruginosa BRp3.
Xanthomonas oryzae pv. oryzae (Xoo) is widely prevalent and causes Bacterial Leaf Blight (BLB) in Basmati rice grown in different areas of Pakistan. There is a need to use environmentally safe approaches to overcome the loss of grain yield in rice due to this disease. The present study aimed to develop inocula, based on native antagonistic bacteria for biocontrol of BLB and to increase the yield of Super Basmati rice variety. Out of 512 bacteria isolated from the rice rhizosphere and screened for plant growth promoting determinants, the isolate BRp3 was found to be the best as it solubilized 97 μg/ mL phosphorus, produced 30 μg/mL phytohormone indole acetic acid and 15 mg/ L siderophores in vitro. The isolate BRp3 was found to be a Pseudomonas aeruginosa based on 16S rRNA gene sequencing (accession no. HQ840693). This bacterium showed antagonism in vitro against different phytopathogens including Xoo and Fusarium spp. Strain BRp3 showed consistent pathogen suppression of different strains of BLB pathogen in rice. Mass spectrometric analysis detected the production of siderophores (1-hydroxy-phenazine, pyocyanin, and pyochellin), rhamnolipids and a series of already characterized 4-hydroxy-2-alkylquinolines (HAQs) as well as novel 2,3,4-trihydroxy-2-alkylquinolines and 1,2,3,4-tetrahydroxy-2-alkylquinolines in crude extract of BRp3. These secondary metabolites might be responsible for the profound antibacterial activity of BRp3 against Xoo pathogen. Another contributing factor toward the suppression of the pathogen was the induction of defense related enzymes in the rice plant by the inoculated strain BRp3. When used as an inoculant in a field trial, this strain enhanced the grain and straw yields by 51 and 55%, respectively, over non-inoculated control. Confocal Laser Scanning Microscopy (CLSM) used in combination with immunofluorescence marker confirmed P. aeruginosa BRp3 in the rice rhizosphere under sterilized as well as field conditions. The results provide evidence that novel secondary metabolites produced by BRp3 may contribute to its activity as a biological control agent against Xoo and its potential to promote the growth and yield of Super Basmati rice.


Electrophysiological response of rat ventricular myocytes to acidosis.
The effects of acidosis on the action potential, resting potential, L-type Ca(2+) (I(Ca)), inward rectifier potassium (I(K1)), delayed rectifier potassium (I(K)), steady-state (I(SS)), and inwardly rectifying chloride (I(Cl,ir)) currents of rat subepicardial (Epi) and subendocardial (Endo) ventricular myocytes were investigated using the patch-clamp technique. Action potential duration was shorter in Epi than in Endo cells. Acidosis (extracellular pH decreased from 7.4 to 6.5) depolarized the resting membrane potential and prolonged the time for 50% repolarization of the action potential in Epi and Endo cells, although the prolongation was larger in Endo cells. At control pH, I(Ca), I(K1), and I(SS) were not significantly different in Epi and Endo cells, but I(K) was larger in Epi cells. Acidosis did not alter I(Ca), I(K1), or I(K) but decreased I(SS); this decrease was larger in Endo cells. It is suggested that the acidosis-induced decrease in I(SS) underlies the prolongation of the action potential. I(Cl,ir) at control pH was Cd(2+) sensitive but 4,4'-disothiocyanato-stilbene-2,2'-disulfonic acid resistant. Acidosis increased I(Cl,ir); it is suggested that the acidosis-induced increase in I(Cl,ir) underlies the depolarization of the resting membrane potential.


Pharmacological attributes of Bacopa monnieri extract: Current updates and clinical manifestation.
Bacopa monnieri has been used for centuries in Ayurvedic medicine, alone or in combination with other herbs, as a memory and learning enhancer, sedative, and anti-epileptic. This review aimed to highlight the health benefits of B. monnieri extracts (BME), focusing on anti-cancer and neurodegenerative diseases. We examined the clinical studies on phytochemistry and pharmacological application of BME. We further highlighted the mechanism of action of these extracts in varying types of cancer and their therapeutic implications. In addition, we investigated the underlying molecular mechanism in therapeutic interventions, toxicities, safety concerns and synergistic potential in cognition and neuroprotection. Overall, this review provides deeper insights into the therapeutic implications of Brahmi as a lead formulation for treating neurological disorders and exerting cognitive-enhancing effects.


Effect of arm rotation on MR imaging of the rotator cuff.
The effect of humeral rotation on the appearance of the rotator cuff tendon in oblique coronal magnetic resonance images was evaluated in 70 such images. Internal rotation produced overlap of the supraspinatus and infraspinatus tendons with soft-tissue interposition or apparent discontinuity of the tendon in 22 cases, including 14 of 15 shoulders positioned in the first 30 degrees between extreme internal and external rotation. Imaging in internal rotation makes assessment of the tendon difficult and should be avoided.


Evaluation of single-cell gel electrophoresis data: combination of variance analysis with sum of ranking differences.
Specimens of the mussel Mytilus galloprovincialis were collected from five sites in the Boka Kotorska Bay (Adriatic Sea, Montenegro) during the period summer 2011-autumn 2012. Three types of tissue, haemolymph, digestive gland were used for assessment of DNA damage. Images of randomly selected cells were analyzed with a fluorescence microscope and image analysis by the Comet Assay IV Image-analysis system. Three parameters, viz. tail length, tail intensity and Olive tail moment were analyzed on 4200 nuclei per cell type. We observed variations in the level of DNA damage in mussels collected at different sites, as well as seasonal variations in response. Sum of ranking differences (SRD) was implemented to compare use of different types of cell and different measure of comet tail per nucleus. Numerical scales were transferred into ranks, range scaling between 0 and 1; standardization and normalization were carried out. SRD selected the best (and worst) combinations: tail moment is the best for all data treatment and for all organs; second best is tail length, and intensity ranks third (except for digestive gland). The differences were significant at the 5% level. Whereas gills and haemolymph cells do not differ significantly, cells of the digestive gland are much more suitable to estimate genotoxicity. Variance analysis decomposed the effect of different factors on the SRD values. This unique combination has provided not only the relative importance of factors, but also an overall evaluation: the best evaluation method, the best data pre-treatment, etc., were chosen even for partially contradictory data. The rank transformation is superior to any other way of scaling, which is proven by ordering the SRD values by SRD again, and by cross validation.


Investigation of germanium Raman lasers for the mid-infrared.
In this paper we present a detailed theoretical investigation of integrated racetrack Raman lasers based on the germanium material system operating in the mid-infrared beyond the germanium two-photon absorption cut-off wavelength of 3.17 μm. The effective Raman gain has been estimated in waveguides based on germanium-on-silicon, germanium-on-SOI and germanium-on-Si3N4 technology platforms as a function of their crystallographic orientations. Furthermore, general design guidelines have been determined by means of a comparative analysis of Raman laser performance, i.e. the threshold power, polarization and directionality of the excited Stokes signals as a function of racetrack cavity length and directional-coupler dimensions. Finally, the emitted Raman laser power has been evaluated as a function of overall propagation losses and operative wavelengths up to 3.8 μm, while the time dynamics of Raman lasers has been simulated assuming continuous and pulse waves as input pump signals.


Why is Mendelian segregation so exact?
The precise 1:1 segregation of Mendelian heredity is ordinarily taken for granted, yet there are numerous examples of 'cheating' genes that perpetuate themselves in the population by biasing the Mendelian process in their favor. One example is the Segregation Distortion system of Drosophila melanogaster, in which the distorting gene causes its homologous chromosome to produce a nonfunctional sperm. This system depends on three closely linked components, whose molecular basis is beginning to be understood. The system is characterized by numerous modifiers changing the degree of distortion. Mathematical theory shows that unlinked modifiers that change the degree of distortion in the direction of Mendelism always increase in the population. This provides a mechanism for removing cheaters and preserving the honesty of the Mendelian gene-shuffle.


Purification and characterization of arcelin seed protein from common bean.
Arcelin, a seed protein originally discovered in wild bean accessions, was purified, characterized, and compared to phaseolin, the major seed protein of common bean, and to phytohemagglutinin (PHA), the major bean seed lectin. Arcelin and PHA has several characteristics in common. Both were glycoproteins having similar subunit M(r), deglycosylated M(r), and amino acid compositions. The two proteins were related antigenically and they had the same developmental timing of accumulation. Arcelin also had some hemagglutinating activity, a characteristic associated with lectins. However, several features distinguished arcelin from PHA. Arcelin had a more basic isoelectric point than PHA, greater numbers of basic amino acid residues, additional cysteine residues, and one methionine residue, which PHA lacks. Native PHA protein is a tetramer of subunits, and although a small component of native arcelin protein was also tetrameric, most of the arcelin preparation was dimeric. The hemagglutinating activity of arcelin was specific only for some pronase-treated erythrocytes. It did not agglutinate native erythrocytes, nor did it bind to thyroglobulin or fetuin affinity resins as did PHA. Although arcelin has lectin-like properties, we believe the distinctions between arcelin and PHA warrant the designation of arcelin as a unique bean seed protein.


Passive leg raising is predictive of fluid responsiveness in spontaneously breathing patients with severe sepsis or acute pancreatitis.
Rapid fluid loading is standard treatment for hypovolemia. Because volume expansion does not always improve hemodynamic status, predictive parameters of fluid responsiveness are needed. Passive leg raising is a reversible maneuver that mimics rapid volume expansion. Passive leg raising-induced changes in stroke volume and its surrogates are reliable predictive indices of volume expansion responsiveness for mechanically ventilated patients. We hypothesized that the hemodynamic response to passive leg raising indicates fluid responsiveness in nonintubated patients without mechanical ventilation. Prospective study. Intensive care unit of a general hospital. We investigated consecutive nonintubated patients, without mechanical ventilation, considered for volume expansion. We assessed hemodynamic status at baseline, after passive leg raising, and after volume expansion (500 mL 6% hydroxyethyl starch infusion over 30 mins). We measured stroke volume using transthoracic echocardiography, radial pulse pressure using an arterial catheter, and peak velocity of femoral artery flow using continuous Doppler. We calculated changes in stroke volume, pulse pressure, and velocity of femoral artery flow induced by passive leg raising (respectively, Deltastroke volume, Deltapulse pressure, and Deltavelocity of femoral artery flow). Among 34 patients included in this study, 14 had a stroke volume increase of >or=15% after volume expansion (responders). All patients included in the study had severe sepsis (n = 28; 82%) or acute pancreatitis (n = 6; 18%). The Deltastroke volume >or=10% predicted fluid responsiveness with sensitivity of 86% and specificity of 90%. The Deltapulse pressure >or=9% predicted fluid responsiveness with sensitivity of 79% and specificity of 85%. The Deltavelocity of femoral artery flow >or=8% predicted fluid responsiveness with sensitivity of 86% and specificity of 80%. Changes in stroke volume, radial pulse pressure, and peak velocity of femoral artery flow induced by passive leg raising are accurate and interchangeable indices for predicting fluid responsiveness in nonintubated patients with severe sepsis or acute pancreatitis.