Factors associated with glucose tolerance, pre-diabetes, and type 2 diabetes in a rural community of south India: a cross-sectional study.
India's national rural prevalence of type 2 diabetes has quadrupled in the past 25 years. Despite the growing rural burden, few studies have examined putative risk factors and their relationship with glucose intolerance and diabetes in rural areas. We undertook a cross-sectional study to determine the prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes in a rural area of south India. In addition, we determined which factors were associated with type 2 diabetes. We sampled 2 % of the adult population from 17 villages using a randomized household-level sampling technique. Each participant undertook a questionnaire that included basic descriptive information and an assessment of socioeconomic status, physical activity, and dietary intake. Height, weight, waist and hip circumference, and blood pressure measurements were taken. An oral glucose tolerance test was used to determine diabetes status. We used stepwise logistic model building techniques to determine associations between several putative factors and type 2 diabetes. 753 participants were included in the study. The age- and sex-standardized prevalence of IFG was 3.9 %, IGT was 5.6 %, and type 2 diabetes was 10.8 %. Factors associated with type 2 diabetes after adjusting for confounders included physical activity [OR 0.81], rurality [OR 0.76], polyunsaturated fat intake [OR 0.94], body mass index [OR 1.85], waist to hip ratio [OR 1.62], and tobacco consumption [OR 2.82]. Our study contributes to the growing body of research suggesting that diabetes is a significant concern in rural south India. Associated risk factors should be considered as potential targets for reducing health burdens in India.


Radial artery pseudoaneurysm formation after cat bite to the wrist.
Pseudoaneurysms may occur in the groin after catheterization of the femoral artery but may also occur in arteriovenous shunting for dialysis after placement of indwelling catheters or after direct trauma to an artery. We report a unique cause of radial artery pseudoaneurysm at the wrist related to a cat bite sustained by an elderly woman. The patient underwent successful operative repair of the aneurysm, with ligation of the radial artery.


Targeting nuclear acid-mediated immunity in cancer immune checkpoint inhibitor therapies.
Cancer immunotherapy especially immune checkpoint inhibition has achieved unprecedented successes in cancer treatment. However, there are many patients who failed to benefit from these therapies, highlighting the need for new combinations to increase the clinical efficacy of immune checkpoint inhibitors. In this review, we summarized the latest discoveries on the combination of nucleic acid-sensing immunity and immune checkpoint inhibitors in cancer immunotherapy. Given the critical role of nuclear acid-mediated immunity in maintaining the activation of T cell function, it seems that harnessing the nuclear acid-mediated immunity opens up new strategies to enhance the effect of immune checkpoint inhibitors for tumor control.


Accurate evaluation of combustion enthalpy by ab-intio computations.
Accurate evaluation of combustion enthalpy is of high scientific and industrial importance. Although ab-initio computation of the heat of reactions is one of the promising and well-established approaches in computational chemistry, reliable and precise computation of heat of combustion reactions by ab-initio methods is surprisingly scarce in the literature. A handful of works carried out for this purpose report significant inconsistencies between the computed and experimentally determined combustion enthalpies and suggest empirical corrections to improve the accuracy of the ab-initio predicted data. The main aim of the present study is to investigate the reasons behind those reported inconsistencies and propose guidelines for a high-accuracy estimation of heat of reactions via ab-initio computations. We show comparably accurate prediction of combustion enthalpy of 40 organic molecules based on a DSD-PBEP86 double-hybrid density functional theory approach and CCSD(T)-F12 coupled-cluster computations, with mean unsigned errors with respect to experimental data being below 0.5% for both methods.


Agrin and the molecular choreography of synapse formation.
High concentrations of neurotransmitter receptors characterize neuromuscular junctions as well as neuron-neuron synapses in the brain and periphery. Synaptic function is critically dependent upon this marshalling of neurotransmitter receptors to the post-synaptic membrane. This review discusses agrin's role in orchestrating the molecular topography of the post-synaptic apparatus at nerve-muscle synapses and the emerging evidence suggesting a role for agrin in synaptogenesis in the brain.


Design, synthesis and evaluation of novel hydroxyamides as orally available anticonvulsants.
Themisone, also known as Atrolactamide, was found, in the 1950s, to be a very potent anticonvulsant. It was hypothesized that the -CF(3) substitution would maintain the anticonvulsant activity. Anticonvulsant testing of our novel compounds by the National Institute of Health's Anticonvulsant Screening Project of the Antiepileptic Drug Discovery Program identified analogue 1, 3,3,3-trifluoro-2-hydroxy-2-phenyl-propionamide, to have potent anticonvulsant activity (MES ED(50) of 9.9 mg/kg, ScMET ED(50) of 34 mg/kg and TD(50) of 100 mg/kg). Therefore, a diverse range of analogues were synthesized utilizing multiple synthetic pathways to explore the structure-activity relationship. Patch clamp electrophysiology experiments demonstrate that compound 1 is an effective T-type calcium channel blocker. Altogether, these results suggest these compounds as a class of orally available anticonvulsants.


Cell adhesion molecules and intracellular signalling: from fly to man.
Analysis of the wingless pathway in Drosophila and the Wnt pathway in vertebrates has led to a detailed knowledge of the signalling events involved in this morphogenetic system. Molecules involved in cell-cell adhesion and junction formation are implicated at several steps in the pathway, highlighting the high level of interaction between cell adhesive systems and classical signalling pathways.


Cholinergic Urticaria with Anaphylaxis: An Underrecognized Clinical Entity.
Cholinergic urticaria is a form of physical urticaria triggered by high ambient temperature, strenuous physical activity, and strong emotion. These same triggers may cause multisystem reactions that can be life-threatening. A study of patients with cholinergic urticaria with anaphylaxis was undertaken to describe the demographic and clinical features of this form of anaphylaxis. To describe a cohort of patients with anaphylaxis triggered by high ambient temperature, exertion, and stress. Patients from an academic allergy practice in a university teaching hospital were identified by retrospective chart review. A total of 19 patients with recurrent episodes of anaphylaxis due to cholinergic triggers were identified. The female:male ratio was 15:4 (79% females). The mean age of onset was 27.5 years. Patients experienced a mean of 9.41 episodes per year. All 19 patients (100%) reported anaphylaxis triggered by high ambient temperature, 89.5% reported anaphylaxis triggered by strenuous exertion, and 78.9% reported anaphylaxis triggered by stress. Cutaneous involvement was present in 94.7%; 78.9% had upper airway obstructive symptoms, 78.9% had lower airway involvement, 57.9% had gastrointestinal involvement, and 78.9% had cardiovascular manifestations. Anaphylaxis severity scores were grade 1 (mild) in 11.1%, grade 2 (moderate) in 44.4%, and grade 3 (severe) in 44.4%. Baseline tryptase levels were normal in all but 1 patient. Anaphylaxis due to cholinergic triggers is underreported, with only several case reports in the literature. Reactions are multisystem with cutaneous, upper and lower airway, and cardiovascular involvement in most patients. Manifestations may be life-threatening, and reactions are often severe.


Motor cortical control of vocal interaction in neotropical singing mice.
Like many adaptive behaviors, acoustic communication often requires rapid modification of motor output in response to sensory cues. However, little is known about the sensorimotor transformations that underlie such complex natural behaviors. In this study, we examine vocal exchanges in Alston's singing mouse (Scotinomys teguina). We find that males modify singing behavior during social interactions on a subsecond time course that resembles both traditional sensorimotor tasks and conversational speech. We identify an orofacial motor cortical region and, via a series of perturbation experiments, demonstrate a hierarchical control of vocal production, with the motor cortex influencing the pacing of singing behavior on a moment-by-moment basis, enabling precise vocal interactions. These results suggest a systems-level framework for understanding the sensorimotor transformations that underlie natural social interactions.


The substance P receptor on rat mast cells and in human skin.
(D-Pro4 D- Trp7 ,9,10)SP4-11 (SPA) has been shown to be a competitive antagonist of the histamine releasing action of substance P in rat peritoneal mast cells. Antagonist activity of SPA is expressed in the concentration range 1 to 10 microM, but at higher concentrations SPA releases histamine. SPA inhibits the flare response induced by substance P in human skin but is without effect on the wheal response. Up to 12.5 pmol SPA produces neither wheal nor flare response by itself. The structurally related peptide, kassinin , does not cause histamine release from rat mast cells at concentrations up to 10 microM whereas the methyl ester of substance P was found to 1.6 times more active than substance P in this respect. The findings are discussed in terms of the classification of substance P receptors and the mechanism of wheal and flare in human skin.


Temporal expression profiles of leptin and its receptor genes during early development and ovarian maturation of Cynoglossus semilaevis.
Leptin (Lep) plays a key role in the regulation of food intake and energy homeostasis in vertebrates. Our previous studies have provided evidence for the existence of two leptin genes (lepa and lepb) and one leptin receptor (lepr) gene in a flatfish, the half-smooth tongue sole (Cynoglossus semilaevis). However, the spatial-temporal expression patterns and possible roles of the leptin system during early development and ovarian maturation are still poorly understood in teleosts. In the current study, we evaluated dynamic expression profiles of lepa, lepb, and lepr mRNAs during various developmental stages in this species. Quantitative RT-PCR analysis indicated that both ligand (lepa and lepb) and receptor (lepr) genes were detected in unfertilized eggs and during embryogenesis but with different expression profiles. In addition, lepa, lepb, and lepr transcripts levels increased significantly during larval development, reaching the peak at 10, 25, and 30 days post-hatching (dph), respectively. On the other hand, changes in mRNA expression of these three genes at the brain-pituitary-gonad (BPG) axis were also investigated during ovarian maturation, and lepa, lepb, and lepr mRNAs varied greatly. Taken together, our results encompass the first study reporting the dynamic expression patterns of leptin and its receptor mRNAs in the order Pleuronectiformes, providing evidence that the leptin system could be functional and play important roles during early development and ovarian maturation in tongue sole.


Ultrastructure of the main excretory duct epithelia of the rat parotid and submandibular glands with a review of the literature.
The fine structure of the main excretory duct (MED) epithelia of the rat parotid and submandibular glands was investigated by scanning and transmission electron microscopy. The structure of these two MED epithelia was compared. Five principal cell types were observed in the MED epithelium of the parotid gland--cuboidal, basal, light (types I and II), dark, and tuft cells. The cuboidal cells, which were stratified in two or three layers, were the most numerous. Basal cells were situated adjacent to the basal lamina of the epithelium. The type I light cells had well-developed basal plasma membrane infoldings. The type II light cells had poorly developed basal plasma membrane infoldings. The dark and tuft cells resembled those of the MED epithelium of the rat submandibular gland. Four principal cell types were observed in the MED epithelium of the submandibular gland--light cells (types I and II), dark, tuft, and basal cells. The two types of light cells were the most numerous. Dark cells with regular and dense microvilli were relatively narrow in shape and had complicated basal plasma membrane infoldings. There were numerous vesicles or channel-like vesicles in their apical cytoplasm. Tuft cells were characterized by prominent microvilli, many vesicles of various sizes in the apical cytoplasm, and no basal infoldings. Peroxisomes were present in the MED epithelia of the rat parotid and submandibular glands, especially in light and cuboidal cells.


CD44 is a key player in non-alcoholic steatohepatitis.
Cluster of differentiation (CD)44 regulates adipose tissue inflammation in obesity and hepatic leukocyte recruitment in a lithogenic context. However, its role in hepatic inflammation in a mouse model of steatohepatitis and its relevance in humans have not yet been investigated. We aimed to evaluated the contribution of CD44 to non-alcoholic steatohepatitis (NASH) development and liver injury in mouse models and in patients at various stages of non-alcoholic fatty liver disease (NAFLD) progression. The role of CD44 was evaluated in CD44-/- mice and after injections of an αCD44 antibody in wild-type mice challenged with a methionine- and choline-deficient diet (MCDD). In obese patients, hepatic CD44 (n=30 and 5 NASH patients with a second liver biopsy after bariatric surgery) and serum sCD44 (n=64) were evaluated. Liver inflammation (including inflammatory foci number, macrophage and neutrophil infiltration and CCL2/CCR2 levels), liver injury and fibrosis strongly decreased in CD44-/- mice compared to wild-type mice on MCDD. CD44 deficiency enhanced the M2 polarization and strongly decreased the activation of macrophages by lipopolysaccharide (LPS), hepatocyte damage-associated molecular patterns (DAMPs) and saturated fatty acids. Neutralization of CD44 in mice with steatohepatitis strongly decreased the macrophage infiltration and chemokine ligand (CCL)2 expression with a partial correction of liver inflammation and injury. In obese patients, hepatic CD44 was strongly upregulated in NASH patients (p=0.0008) and correlated with NAFLD activity score (NAS) (p=0.001), ballooning (p=0.003), alanine transaminase (p=0.005) and hepatic CCL2 (p<0.001) and macrophage marker CD68 (p<0.001) expression. Correction of NASH was associated with a strong decrease in liver CD44+ cells. Finally, the soluble form of CD44 increased with severe steatosis (p=0.0005) and NASH (p=0.007). Human and experimental data suggest that CD44 is a marker and key player of hepatic inflammation and its targeting partially corrects NASH. Human and experimental data suggest that CD44, a cellular protein mainly expressed in immune cells, is a marker and key player of non-alcoholic steatohepatitis (NASH). Indeed, CD44 enhances the non-alcoholic fatty liver (NAFL) (hepatic steatosis) to NASH progression by regulating hepatic macrophage polarization (pro-inflammatory phenotype) and infiltration (macrophage motility and the MCP1/CCL2/CCR2 system). Targeting CD44 partially corrects NASH, making it a potential therapeutic strategy.


Assessment of Hyperthermic Intraperitoneal Chemotherapy to Eradicate Intraperitoneal Free Cancer Cells.
To assess the effect of hyperthermic intraperitoneal chemotherapy (HIPEC) to eradicate intraperitoneal free cancer cells and to explore the feasibility of cytological cure for peritoneal carcinomatosis (PC). The peritoneal lavage fluid (or ascites) from 50 PC patients was collected before and after intraoperative HIPEC, respectively, for conventional cytology test, and conventional and real-time quantitative reverse transcript polymerase chain reaction detecting carcinoembryonic antigen (CEA) mRNA and cytokeratin-20 (CK20) mRNA. The blood samples 3 days before and 7 days after intraoperative HIPEC were also collected for detecting the serum tumor markers, including CEA, carbohydrate antigen (CA) 125, and CA19-9. The positive rate of conventional cytology test before HIPEC versus after HIPEC was100.0% versus 22.0% (P = .000). The positive rates of CEA mRNA and CK20 mRNA before HIPEC versus after HIPEC were 100.0% versus 86.0% (P = .012) and 100.0% versus 96.0% (P = .495), respectively. Moreover, after HIPEC, 18 (36.0%) patients had a decline in CEA mRNA (P = .000), and 17 (34.0%) patients had a decline in CK20 mRNA (P = .000). The positive rates of serum CEA, CA125, and CA199 before HIPEC versus after HIPEC were 52.0% versus 28.0% (P = .014), 52.0% versus 44.0% (P = .423), and 40.0% versus 28.0% (P = .205), respectively. HIPEC could effectively eradicate intraperitoneal free cancer cells and partially achieve cytological cure for PC.


Accelerating microbial iron cycling promotes re-cementation of surface crusts in iron ore regions.
Accelerating microbial iron cycling is an innovative environmentally responsible strategy for mine remediation. In the present study, we extend the application of microbial iron cycling in environmental remediation, to include biocementation for the aggregation and stabilization of mine wastes. Microbial iron reduction was promoted monthly for 10 months in crushed canga (a by-product from iron ore mining, dominated by crystalline iron oxides) in 1 m3 containers. Ferrous iron concentrations reached 445 ppm in treatments and diverse lineages of the candidate phyla radiation dominated pore waters, implicating them in fermentation and/or metal cycling in this system. After a 6-month evaporation period, iron-rich cements had formed between grains and 20-cm aggregates were recoverable from treatments throughout the 1-m depth profile, while material from untreated and water-only controls remained unconsolidated. Canga-adapted plants seeded into one of the treatments germinated and grew well. Therefore, application of this geobiotechnology offers promise for stabilization of mine wastes, as well as re-formation of surface crusts that underpin unique and threatened plant ecosystems in iron ore regions.


Inhibition of antigen-induced airway inflammation and hyperresponsiveness in guinea pigs by a selective antagonist of "chemoattractant receptor homologous molecule expressed on Th2 cells" (CRTH2).
Chemoattractant receptor homologous molecule expressed on T helper type 2 cells (CRTH2) is a PGD2 receptor found on eosinophils, basophils, and Th2 type T cells which exhibits chemotaxis and functions in activation cascades. However, while a number of CRTH2 antagonists, including ramatroban, are known to exert activity in certain animal models, activity in a guinea pig model of EA-induced airway hyperresponsiveness has not been demonstrated. The newly developed CRTH2 antagonist ASP5642 has shown antagonistic activity against human and guinea pig CRTH2 in previous studies and has also been found effective in treating guinea pig models of airway inflammation and airway hyperresponsiveness. While previous studies have used animals such as rats and mice to evaluate CRTH2 antagonist effects, ours is the first attempt to evaluate CRTH2 function in a guinea pig asthma model, which may prove useful in evaluating the compound's effects in humans, given the comparable airway function between the two species taken together, these data from the present study strongly suggest the utility of ASP5642 in investigating the role of CRTH2 in inflammatory responses and as a drug treatment for human asthma.


Correction to: Oxidizable Phenolic Concentrations Do Not Affect Development and Survival of Paropsis Atomaria Larvae Eating Eucalyptus Foliage.
Ian Wallis was inadvertently omitted as an author in this study. Ian Wallis assisted with the collection of the leaf samples that were used in this study, and built the chambers that the insects were housed in.


Chemotherapy-induced cardiotoxicity.
Anthracycline-based chemotherapeutics have long been recognized as effective agents for treating a wide range of malignancies. However, their use is not without significant adverse cardiotoxic side effects. Strategies for prevention involve limiting free-radical production and subsequent cardiac myocyte damage. Dexrazoxane remains the most widely studied cardioprotective medication. Alternative agents may reduce cardiotoxicity but may still cause significant cardiovascular problems. The role of β-blockers and angiotensin-converting enzyme inhibitors in the treatment of heart failure is well proven. The role of these medications in the prevention and treatment of chemotherapy-induced cardiotoxicity is not well established.


Effects of aging on lens transmittance and retinal input to the suprachiasmatic nucleus in golden hamsters.
Old animals are less sensitive by almost an order of magnitude to the phase-shifting effects of a low intensity light pulse on the locomotor activity rhythm and the associated induction of immediate early genes in the circadian clock. The transmittance of energy from 200 to 700 nm through the excised lens of the eyes of young and old golden hamsters was measured to determine if an age-related difference exists in the transmittance of light. There is only a small decrease (8-50%) in transmittance, with the magnitude being dependent upon wavelength. No significant differences were detected between young and old animals in the retinal innervation of the suprachiasmatic nucleus (SCN). These results support the hypothesis that the observed decrease in sensitivity to light in the aged circadian system occurs within the SCN itself and/or retino-hypothalamic tract photoreceptors.


Three-dimensional structure of an antigenic mutant of the influenza virus haemagglutinin.
Antigenic variation in the haemagglutinin (HA) glycoprotein of influenza virus is associated with recurrent epidemics of respiratory disease in man (for review see ref. 1). We have examined the size of structural changes necessary to alter the antigenicity of HA by determining the three-dimensional structure of the HA from an antigenic mutant containing a single amino acid substitution which was selected by growth of virus in the presence of monoclonal antibodies. Here we present evidence that the simple addition of an amino acid side chain which results in only minor local distortions of the structure of the HA is sufficient structural alteration for a virus to escape neutralization by a monoclonal antibody. Our results also demonstrate that single amino acid substitutions can cause only local changes in the HA structure, verifying the assumption made in several studies to locate antigenic sites on the HA and other molecules, and indicate that proposals of large conformational changes to account for variations in HA antigenicity are unnecessary in this case. The structure of the variant antigen has independently been successfully predicted (M. Karplus, personal communication).


Usefulness of the accelerated idioventricular rhythm as a marker for myocardial necrosis and reperfusion during thrombolytic therapy in acute myocardial infarction.
The value of the accelerated idioventricular rhythm (AIVR) as a marker for myocardial necrosis and/or reperfusion was prospectively studied in 87 patients admitted with persistent ischemic chest pain. All patients received streptokinase. Necrosis was diagnosed by new Q waves and an increase in plasma enzymes. Reperfusion was documented angiographically. Myocardial necrosis occurred in 72 patients and reperfusion in 70 patients, 58 of whom had myocardial necrosis. Of 27 patients with AIVR, 26 had both necrosis and reperfusion (p less than 0.001). AIVR started after a long coupling interval to the preceding sinus rhythm and was regular. Configuration depended on the reperfused infarct vessel. Reperfusion of the left anterior descending branch showed most configurations of AIVR and with the least QRS width. Reperfusion of the circumflex branch never had a left bundle branch block-like configuration. AIVR from reperfusion of the right coronary artery never had an inferior axis. AIVR occurring during persistent ischemic chest pain is a marker for both myocardial necrosis and reperfusion of the infarct vessel. AIVR starts with a long coupling interval and is regular. The QRS configuration may be useful for the noninvasive identification of the infarct vessel.


The results of arthroscopic debridement of glenoid labral tears based on tear location.
A retrospective, average 2-year review of 14 patients with a primary glenoid labral tear treated by arthroscopic debridement was conducted to evaluate the long-term results of labral debridement based on tear location in preoperatively stable shoulders. All patients with concomitant pathology requiring an additional open or arthroscopic procedure were eliminated from this study. Every patient complained of shoulder pain mainly with overhead activities and nine patients (64%) also described "clicking" with shoulder movement. All shoulders were stable to translation in all quadrants during the preoperative examination and examination under anesthesia. The functional results at 6 months' follow-up were 93% excellent or good. However, the results at > 1 year's follow-up (average 2 years) were only 71% excellent or good, with a statistically significant 50% of patients decreased in function. The best results were in the superior and anterior-inferior regions. Three patients with large anterior-superior lesions (60%) developed postoperative instability noted at > 6 months postsurgery, representing a significant difference between groups. One of these patients was able to regain a good functional result with rotator cuff strengthening therapy. Close observation of patients after large anterior-superior labral tear arthroscopic debridement is advised because they are at risk for the delayed onset of instability.


Quantitative assays of enzyme activity in single cells: early prenatal diagnosis of genetic disorders.
The combined use of special cell culture techniques and biochemical ultramicromethods permits one to handle very small amounts of materials, to reduce the costs of chemicals, and more accurately to assess gene dosage effects by expressing enzyme activities per cell instead of per total cell protein. An alkaline phosphatase induction test has been developed which allows one to screen small numbers of fibroblasts for lysosomal storage diseases, cystic fibrosis, and chromosomal disorders. A successful attempt has been made to automate the microtechniques. Combining the alkaline phosphatase induction with the ultramicro automatization should eventually permit one to screen all pregnancies for major possible fetal genetic defects. Automated ultramicro enzyme assays should contribute to the general development of clinical chemistry.


Calibration of the KRISS reference ionization chamber for certification of ²²²Rn gaseous sources.
A primary measurement system for gaseous (222)Rn based on the defined solid angle counting method has recently been constructed at KRISS and the reference ionization chamber used to measure the activities of gamma-emitting single radionuclides was adopted as a secondary standard for gaseous (222)Rn. A 20 mL flame-sealed glass ampoule source from the primary measurement system was used to calibrate the ionization chamber for (222)Rn. The (222)Rn efficiency of the ionization chamber was compared with that calculated by using a photon energy-dependent efficiency curve and that measured by using a standard (226)Ra solution. From the comparisons we draw the conclusion that the reference ionization chamber for gamma-emitting radionuclides can be a suitable secondary measurement system for gaseous (222)Rn sources.


Nanostructure and β1-integrin distribution analysis of pig's spermatogonial stem cell by atomic force microscopy.
Spermatogonial stem cells (SSCs) provide the foundation for spermatogenesis and male fertility. However, spermatogenesis has direct links with some adhesion molecules on SSCs membrane. Β1-integrin (CD29) is such a kind of adhesion molecule and a biomarker of pig's SSCs. Therefore, quantitative characteristics of β1-integrin expression level in a single cell could help us to capture the signal switch and understand the mechanism of spermatogenesis. In this study, atomic force microscopy (AFM) was used to obtain the morphology and ultrastructure of SSCs at nanometer level, and the CD29 Ab-functionalized AFM tip was used to examine β1-integrin distribution on the cell membrane. There were many force-binding spots on about 50% of cell membrane binding to the CD29 Ab-functionalized AFM tip, and the mean bind rupture force was 283.63±12.56PN which was much larger than the non-specific average force 70.75±10.95PN. Meanwhile, β1-integrin on SSCs membrane was distributed non-uniformly, and there were some β1-integrins appeared to be expressed as 150-350 nm nanoclusters on the membrane. Our results discovered the structure of SSCs at nanometer level by AFM. The force between β1-integrin antigen-antibody interactions and the distribution of β1-integrin protein on SSCs membrane were also firstly demonstrated.


Endometriosis of the ureter can present as renal failure: a case report and review of endometriosis affecting the ureters.
Of the female subjects with pelvic endometriosis 1.2 per cent are found to have involvement of the genitourinary tract. Ureteral obstruction secondary to endometriosis is uncommon and usually is unilateral. We report a case of renal failure with hypertension due to bilateral ureteral obstruction from pelvic endometriosis. Ureteral endometriosis and its treatment are discussed. In premenopausal women presenting with bilateral obstruction of the distal ureters endometriosis should be part of the differential diagnosis.


Neural and non-neural mediation of propionate-induced contractile responses in the rat distal colon.
Short-chain fatty acids (SCFAs), including propionate, butyrate and acetate, are fermentation products of carbohydrates in the colon. We investigated the contractile effects of SCFAs on the rat distal colon. Mechanical activity of the circular muscle in strip preparations was recorded in vitro. Propionate and butyrate concentration-dependently (10 micromol L(-1)-10 mmol L(-1)) induced rapid, large amplitude phasic contractions (the first phase) followed by tonic contractions (the second phase). Acetate itself had no effect on muscle activity, although preincubation with acetate attenuated both phases of the propionate-induced response. The propionate-induced phasic contraction was attenuated by atropine, tetrodotoxin and the 5-HT4 receptor antagonist SB-204070. The propionate-induced tonic contraction was attenuated by the cyclo-oxygenase inhibitor piroxicam. Antagonists of 5-HT1A, 5-HT2A and 5-HT3 receptors had no effect on the responses. Propionate-induced responses were not observed in mucosa-free preparations. These results suggest that propionate acts on receptors in the mucosa causing the release of 5-HT from enterochromaffin cells. 5-HT acts through 5-HT4 receptors on the endings of intrinsic primary afferent neurones that in turn activate cholinergic motor neurones that contract the circular muscle. Propionate also causes tonic contraction, via prostaglandin release, in the rat distal colon.


Evaluation of the intramuscular administration of Cervarix™ vaccine on fertility, pre- and post-natal development in rats.
Cervarix™ is a prophylactic human papillomavirus (HPV)-16/18 vaccine for the prevention of cervical cancer. It contains GSK Biologicals' proprietary Adjuvant System AS04. The objective of this study was to investigate the effects of Cervarix™ and of AS04 on female fertility and pre- and post-natal development in Sprague Dawley rats. Female rats were injected with vaccine, AS04, or saline 30 days before mating and on Gestation Days 6, 8, 11 and 15. Each dose of vaccine was one-fifth the human dose volume. Treatment of rats with vaccine or AS04 was not associated with any systemic toxicity and had no impact on female fertility. There were no adverse effects on pre- or post-natal development of litters from treated rats, as judged by fetal evaluation at Gestation Day 20, and growth and survival of pups to postnatal Day 25. These results support the use of the vaccine in the targeted human population.


Is convergence surprising? An examination of the frequency of convergence in simulated datasets.
Although convergence is recognized as a central concept in evolutionary biology, very few tools are available for the quantitative study of this phenomenon. Moreover, although many evolutionary assertions assume that convergence should be rare in the absence of influences on organismal phenotypes such as natural selection or constraint, no studies have tested whether this is the case. I simulate random evolution (Brownian motion model) of quantitative characters along phylogenies with varying numbers of terminal taxa, numbers of traits, variance structure, and tree balance, and quantify the amount of convergence observed in these datasets using four metrics. The amount of convergence observed in a dataset increases with increasing number of taxa and decreasing number of traits, approaching the maximum possible amount of convergence under certain circumstances. Some convergence is expected in almost all datasets. Comparison of empirical datasets to those produced by random evolution provides a test of whether empirical datasets actually show elevated levels of convergence. Out of three test datasets, two show more convergence than expected. Given that high levels of convergence can be produced simply by random evolution, no explanation may be necessary for instances of convergence discovered in an evolutionary investigation.


[Multicentric clinical trial of a new combination of a broad spectrum antimycotic and a dermocorticoid (author's transl)].
After having reviewed the conditions of use of an antimycotic-corticoid combination, the authors are reporting their clinical results on 183 patients of a new drug combining econazole and triamcinolon. This clinical trial demonstrates that the own activity of each component of the combination is entirely maintained, and that the new combination shows an original interest in the treatment of all inflammatory dermatomycoses, as well as inflammatory supra-infected dermatoses.


Variations on the staining method in quantitative indirect immunofluorescence assays for Bacillus spores, and the use of fluorescein--protein A.
Quantitative indirect immunofluorescence assays for B. anthracis and B. cereus spores fixed on multispot microscope slides have been performed using a microfluorometer to measure the fluorescence of individual bacteria. A study has been made of variations of the indirect assay sequence, in which the washing operation between application of 1st and 2nd antibody types was omitted. In one modification the addition of the indirect antibody was deferred, and in the second the direct and indirect reagents were added simultaneously to the spores at the start of the incubation period. This simultaneous addition method shows promise for wide application in diagnostic serology. Evidence is presented that fluorescein-protein A (F-PA) can be successfully substituted for fluorescein/sheep anti-rabbit antibody (F-SAR) in the indirect spore assay, and that it is far more active than the F-SAR on a weight basis. About twice as many F-PA molecules as F-SAR molecules are bound to the spore at saturation.


B cells in clinical transplantation tolerance.
The rarity of tolerance following clinical transplantation has complicated the study of the responsible mechanisms. Several recent studies of kidney transplant recipients have demonstrated an association between increased numbers of B cells with less mature, inhibitory phenotypes and a state of tolerance. While a growing body of evidence from experimental models supports a role for B cells in regulating or suppressing immune responses, a causative role for B cells in clinical transplantation tolerance has yet to be proven. If B cells are conclusively shown to participate in the development of transplantation tolerance, it will be important to define the responsible mechanisms in order to design monitoring assays and immunosuppressive regimens that favor the development of tolerance.


Crucial roles of UCH-L1 on insulin-producing cells and carbohydrate metabolism in Drosophila melanogaster model.
Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a highly expressed protein in β cells and has been implicated in β cells' viability and function, however, the role of UCH-L1 in β cells remains unclear. Herein, we examined the functions of UCH-L1 in β cells by utilizing the Drosophila melanogaster model. Our results showed that specific knockdown of dUCH (D.melanogaster homolog of UCH-L1) in Drosophila Insulin-producing cells (D.melanogaster homolog of β cells) induced mitochondria fusion, IPCs death/degeneration, interfered with DILP2 secretion, and triggered the rise of glycogen storage and body weight. Strikingly, the impairment in IPCs cellular activities can be rescued by vitamin C- a strong antioxidant compound, which suggested the relationship between knockdown dUCH and oxidative stress in IPCs; and the potential of this model in screening compounds for β cells function moderation. Since carbohydrate metabolism is an important function of beta cells, we continued to examine the ability to regulate carbohydrate metabolism of knockdown dUCH flies. Our results showed that knockdown dUCH caused the decline of IPCs number under a high-sucrose diet, which finally led to metabolic and physiological disturbances, including total lipid rise, glycogen storage reduction, circulating carbohydrate increase, and weight loss. These symptoms could be early indications of metabolic disorders, particularly β cell dysfunction-related diseases. Taken together, our results indicate that dUCH is essential in the viability and functions of IPCs through the regulation of carbohydrate metabolism in the Drosophila model.


Machine learning models for efficient characterization of Schottky barrier photodiode internal parameters.
We propose ANN-based models to analyze and extract the internal parameters of a Schottky photodiode (SPD) without presenting them with any knowledge of the highly nonlinear thermionic emission (TE) expression of the device current. We train, evaluate and demonstrate the ML models on thirty-six private datasets from three previously published devices, which denote current responses under illumination and ambient temperature of graphene oxide (GO) doped p-Si Schottky barrier diodes (SBDs). The GO doping levels are 0%, 1%, 3%, 5%, and 10%. The illumination ranged from dark (0 mW/cm2) to 30 mW/cm2. The predictions are then made completely at the intensity of 60 mW/cm2. For each diode, some values of the barrier height ([Formula: see text]), ideality factor (n), and series resistance ([Formula: see text]) independently calculated using the Cheung-Cheung method were included in the training dataset. The predictions are done at unspecified intensities on the model development data at 80 and 100 mW/cm2, and on external data at 5% and 20% GO doping which were not part of the development dataset. The ANN achieved a mean square error and mean absolute error score below 0.003 across all datasets. This demonstrates the effective learning capabilities of the ANN models in accurately capturing the photo responses of the photodiodes and accurately predicting the internal parameters of the Schottky Barrier Diodes (SBDs), all without relying on an inherent understanding of the thermionic emission (TE) equation for SBDs. The ANN models achieved high accuracy in this process. The proposed ML models can significantly reduce analysis time in device development cycles and can be applied to other datasets in various fields.


The association between pre-operative pain sensitisation and chronic pain after knee replacement: an exploratory study.
Chronic pain after total knee replacement (TKR) is a prevalent condition, affecting about 20% of patients. The aim of this study was to explore the relationship between pre-operative pain thresholds and chronic pain after TKR. Patients listed for a TKR because of osteoarthritis participated in a Quantitative Sensory Testing (QST) session prior to surgery. Pressure pain thresholds (PPTs) and hot pain thresholds were assessed at the osteoarthritic knee and the forearm. Patients were followed-up at 1-year after TKR, and the severity of pain in the replaced knee was assessed using the WOMAC Pain score. Pre-operative median QST thresholds were compared to thresholds from a normative database collected from 50 people with no knee pain. The relationship between pre-operative pain thresholds and pain severity post TKR were tested using correlations. Fifty-one patients participated in a pre-operative QST session and completed a 1-year WOMAC Pain score. Pre-operatively, patients demonstrated evidence of localised (knee) and widespread (forearm) pain sensitisation in response to pressure stimuli compared to healthy participants. Pre-operative PPTs at the forearm were found to be significantly correlated with 1-year WOMAC Pain scores (r = 0.37, P = 0.008). This study provides preliminary evidence that pre-operative widespread pain sensitisation, measured using pressure algometry, may be associated with chronic pain after TKR. Further research is needed to explore the predictive value of an assessment of pre-operative widespread pain sensitisation in identifying who is likely to develop chronic pain after TKR.


Intraoperative molecular imaging of colorectal lung metastases with SGM-101: a feasibility study.
Metastasectomy is a common treatment option for patients with colorectal lung metastases (CLM). Challenges exist with margin assessment and identification of small nodules, especially during minimally invasive surgery. Intraoperative fluorescence imaging has the potential to overcome these challenges. The aim of this study was to assess feasibility of targeting CLM with the carcinoembryonic antigen (CEA) specific fluorescent tracer SGM-101. This was a prospective, open-label feasibility study. The primary outcome was the number of CLM that showed a true positive fluorescence signal with SGM-101. Fluorescence positive signal was defined as a signal-to-background ratio (SBR) ≥ 1.5. A secondary endpoint was the CEA expression in the colorectal lung metastases, assessed with the immunohistochemistry, and scored by the total immunostaining score. Thirteen patients were included in this study. Positive fluorescence signal with in vivo, back table, and closed-field bread loaf imaging was observed in 31%, 45%, and 94% of the tumors respectively. Median SBRs for the three imaging modalities were 1.00 (IQR: 1.00-1.53), 1.45 (IQR: 1.00-1.89), and 4.81 (IQR: 2.70-7.41). All tumor lesions had a maximum total immunostaining score for CEA expression of 12/12. This study demonstrated the potential of fluorescence imaging of CLM with SGM-101. CEA expression was observed in all tumors, and closed-field imaging showed excellent CEA specific targeting of the tracer to the tumor nodules. The full potential of SGM-101 for in vivo detection of the tracer can be achieved with improved minimal invasive imaging systems and optimal patient selection. The study was registered in ClinicalTrial.gov under identifier NCT04737213 at February 2021.


Pseudoaneurysm in a chronic pancreatitis patient: report of a case, with emphasis on contrast-enhanced sonograms.
The association between pseudoaneurysm of the splenic artery and pancreatitis is now established. Rupture of an aneurysm is a lethal condition, and early diagnosis and treatment are required to prevent this hazardous life-threatening complication. In our case, early detection of pseudoaneurysm of the splenic artery enabled us to start prompt embolization, which yielded good results. Splenic infarction is known to be an important and frequent complication of transarterial embolization of splenic artery aneurysms. Thus, when performing transarterial embolization of a splenic artery aneurysm, this complication must be kept in mind and it is absolutely necessary to confirm the presence or absence of this complication after embolization of the aneurysm. In our case of pseudoaneurysm of the splenic artery due to acute aggravation of chronic pancreatitis, contrast-enhanced ultrasonography confirmed the spleen to be free from infarction. Thus, this technique is strongly recommended in such instances.


Radiofrequency catheter ablation of an orthodromic tachycardia in a patient with single ventricle.
Radiofrequency catheter ablation of a recurrent orthodromic tachycardia was performed in a 10-year-old child with single ventricle and bidirectional Glenn procedure before a Fontan operation. Identification of a His bundle electrogram was achieved at the postero-inferior atrioventricular (AV) groove by the inferior vena cava route, and electrophysiological demonstration of a concealed accessory pathway-mediated tachycardia was possible when a ventricular extrastimuli given during the His bundle refractoriness showed advancement of the atrium. A single energy application during tachycardia in the right antero-superior region of the AV groove resulted in the definitive interruption of the accessory pathway.


Evaluation of cellulose and carboxymethyl cellulose/poly(vinyl alcohol) membranes.
Cellulose was isolated from rice straw and converted to carboxymethyl cellulose (CMC). Both polymers were crosslinked with poly(vinyl alcholo) (PVA). The physical properties of the resulting membranes were characterized by FT-IR, TGA, DSC and SEM. The cellulose and CMC were first prepared from bleached rice straw pulp. The infrared spectroscopy of the resulting polymer membranes indicated a decrease in the absorbance of the OH group at 3300-3400 cm(-1), which is due to bond formation with either the cellulose or CMC with the PVA. The thermal stability of PVA/cellulose and PVA/CMC membranes was lower than PVA membrane. The surface of the resulting polymer membranes showed smooth surface in case of the PVA/CMC membrane and rough surface in case of the PVA/cellulose membrane. Desalination test, using 0.2% NaCl, showed that pure PVA membranes had no effect while membranes containing either cellulose or CMC as filler were able to decrease the content of the NaCl from the solution by 25% and 15%, respectively. Transport properties, including water and chloroform vapor were studied. The moisture transport was reduced by the presence of both cellulose and CMC. Moreover, the membranes containing cellulose and CMC showed significantly reduced flux compared to the pure PVA. The water sorption, solubility and soaking period at different pH solutions were also studied and showed that the presence of both cellulose and CMC influences the properties.


Major histocompatibility complex (MHC) class II antigen (HLA-DR, DQ, and DP) expression in human fetal endocrine organs and gut.
Monoclonal antibodies were used to analyse adrenal, pancreas, thyroid, and gut samples from human fetuses (14-19 weeks estimated gestational age; EGA) for the presence of class II major histocompatibility complex (MHC) antigens (HLA-DR, DQ, DP) by immunohistochemistry. In the adrenal definitive and fetal cortex, HLA-DR+, DP-, DQ- cells were clearly demonstrated. These DR+ cells were identified, phentotypically, as predominantly tissue macrophages and a small population of CD45R+, IgM+ lymphoid cells. Within the pancreas, numerous cells throughout the tissue were strongly DR+ but DQ-; DP+ cells were not observed until 17 weeks EGA. Using a double-labelling procedure, minor proportions of these DR+ cells were identified as macrophages or as (CD19+) B cells, while endocrine and endothelial cells were negative. Throughout the thyroid, small numbers of DR+ macrophages and small lymphoid cells were detected, although the thyroid epithelial cells were DR-, DP-, and DQ-. Large numbers of DR+, DP+, DQ- cells were observed in the stomach wall and mucosa. In the intestine, DR+, DP+, DQ+ cells positive for all MHC class II loci products were abundant throughout the lamina propria and lymphoid aggregates. The class II antigens appeared in the proportion DR greater than DP greater than DQ and expression was most prevalent in the mid-gut region. A small proportion of epithelial cells of the villi along the gut were weakly DR+ but DQ-, DP-. These results show that DR+ cells in fetal endocrine tissue are mainly 'passenger leucocytes' and that, in contrast to recent reports concerning normal adult tissue, the adrenal and pancreatic endothelial cells are DR-.


Intrinsic risk factors for inversion ankle sprains in females--a prospective study.
Ankle sprains are extremely common. However, very little is known about the variables that predispose individuals to these injuries. The purpose of this study was to examine prospectively intrinsic risk factors for inversion sprains in a young physically active female population. One hundred and fifty-nine female physical education students were evaluated for several possible intrinsic risk factors for inversion sprains at the beginning of their academic study. The evaluated intrinsic risk factors included anthropometrical and physical characteristics, ankle joint position sense, isokinetic ankle muscle strength, lower leg alignment characteristics, postural control and muscle reaction time during a sudden inversion perturbation. All sports injuries were registered during 1-3 years and exposure to sport was recorded (mean: 15.33+/-4.33 h a week). Thirty-two (20%) of the 159 females sprained their ankle. The number of ankle sprains per 1000 h of sports exposure was 0.75. The Cox regression analysis revealed that females with less accurate passive joint inversion position sense [hazard ratio (HR): 1.08, 95% confidence interval (CI): 1.02-1.14 for absolute error at 15 degrees inversion], a higher extension range of motion at the first metatarsophalangeal joint (HR: 1.03, 95% CI: 1.00-1.06) and less coordination of postural control (HR: 0.96, 95% CI: 0.93-1.00 for endpoint excursion; HR: 0.94, 95% CI: 0.89-0.99 for maximal endpoint excursion) are at greater risk of an ankle sprain. The findings of this study suggest that effective prevention and conservative rehabilitation of ankle inversion sprains should include attention to these variables.


Correlation of crevicular fluid and serum levels of retinol-binding protein 4 and leptin in chronic periodontitis and obesity.
Retinol-binding protein 4 (RBP4) and leptin are both adipokines and involved in the pathophysiology of different vascular and inflammatory diseases and selectively elevated in patients with obesity. The aim of the present study was to determine and correlate the levels of RBP4 and leptin in gingival crevicular fluid (GCF) and serum in patients with chronic periodontitis (CP) and obesity. A total of 70 patients with age group 25 to 45 years were divided into four groups based on gingival index (GI), probing depth (PD), clinical attachment level (CAL), body mass index (BMI) and radiographic evidence of bone loss. The groups were (1) group I (non-obese periodontally healthy), (2) group II (obese periodontally healthy), (3) group III (non-obese with chronic periodontitis) and (4) group IV (obese with chronic periodontitis). The GCF and serum levels of human RBP4 and leptin were quantified using ELISA. An increase in RBP4 levels from group I to group IV was found in both GCF and serum. However, GCF leptin levels was found to be greatest in group II, then group I, group IV and group III showing the least while an increase in serum levels from group I to group IV was found. The GCF and serum values of the inflammatory mediator correlated with the evaluated periodontal parameters and with each other (p < 0.05). RBP4 and leptin can be considered as possible GCF and serum markers of inflammatory activity in CP and obesity, which further longitudinal studies are needed.


QT Interval Monitoring and Drugs Management During COVID-19 Pandemic.
While facing potentially high morbidity from COVID-19 without known effective therapies, the off-label use of several non-specific drugs has been advocated, including re-purposed anti- viral (e.g., remdesivir or the lopinavir/ritonavir combination), biologic agents (e.g., tocilizumab), and antimalarial drugs such as chloroquine and hydroxychloroquine, in association with or without azithromycin. Data regarding the effectiveness of these drugs in treating COVID-19 has been shown in some trials and clinical settings, but further randomised controlled trials are still being carried out. One of the main concerns regarding their widespread use, however, is their possible effects on the QT interval and arrhythmogenic potential. Some of these drugs have been associated with QT prolongation and Torsades de Point, a potentially lethal ventricular arrhythmia. The review aims to highlight the magnitude of this problem, to quickly refresh clinically impacting cornerstones of QT interval and TdP pathophysiology, to summarize the available evidence regarding the QT and arrhythmia impact of drugs used in different clinical settings in COVID-19 patients, and to help the physicians dealing with the knowledge needed in the everyday clinical duties in case of doubts regarding QT-induced arrhythmias in this time of emergency.


The impact of radioactive steel recycling on the public and professionals.
The decommissioning of nuclear power plants represents a complex process resulting in the generation of large amounts of waste materials, e.g. steel scrap containing various concentrations of radionuclides. Recycling some of these materials is highly desirable due to numerous reasons. Herein presented scenarios of recycling of radioactive steel within the nuclear as well as civil engineering industry are analyzed from the radiation protection point of view. An approach based on the dose constraints principle is chosen. The aim of the study is to derive conditional clearance levels (maximal specific mass activity of material allowing its recycling/clearance) for analyzed radionuclides ensuring that the detrimental impact on human health is kept on a negligible level. Determined conditional clearance levels, as the result of performed software calculations, are valid for the reuse of radioactive steel in four selected scenarios. Calculation results indicate that the increase of the amount of recyclable radioactive steel due to its reuse in specific applications may be feasible considering the radiation impact on the public and professionals. However, issues connected with public acceptance, technical difficulties and financing of potential realization are still open and they have to be examined in more detail.


Behavioral and biochemical analysis of GABA-mediated inhibition in the early chick embryo.
Exogenous gamma-aminobutyric acid (GABA) decreased spontaneous motility in 4-, 6-, 7-, 9-, and 13-day chick embryos; the younger embryos were more sensitive. Neither the positional isomers of GABA, alpha-aminobutyric acid (AABA) and beta-aminobutyric acid, nor the principle GABA catabolite, succinic acid, decreased motility in 4-day embryos. Several semi-rigid GABA analogues decreased motility in 4-day embryos with a potency that paralleled their effectiveness in displacing [3H]GABA in ligand-binding studies. The effects of AABA and GABA on hind-limb motility were quantitatively similar in thoracic spinal and sham-operated 7-day embryos. Bicuculline and picrotoxin elicited absolute motility increases at 6, 7 and 9 days of incubation. Picrotoxin and two bicyclophosphate GABA antagnoists elicited relative motility increases while bicuculline elicited an absolute motility increase at 4 days. The two bicyclophosphates increased motility with a potency that paralleled their electrophysiological effectiveness. L-Glutamic acid decarboxylase (GAD) activity was detected in the embryonic lumbar spinal cord at all ages examined (3--7 days) using a new radiometric cation-exchange method. Gamma-Aminobutyric acid transaminase (GABA-T) activity was detected in the lumbar spinal cord at the earliest age examined (day 5). Both GAD and GABA-T activity were detected at earlier ages than previously reported. GABA receptors, and the enzymes necessary for the synthesis and degradation of GABA, all appear to be present at (or before) the onset of spontaneous motility. GABA-mediated transmission appears to be present at 6 days and perhaps as early as 4 days.


Fibrinolysis inhibits shear stress-induced platelet aggregation.
Shear stress-induced platelet aggregation may initiate arterial thrombosis at sites of pathological blood flow. Shear stress-induced platelet aggregation is mediated by von Willebrand factor (vWf) binding to platelet membrane glycoprotein (GP) Ib and GP IIb/IIIa. Tissue-type plasminogen activator (TPA) induces thrombolysis in coronary arteries through the local generation of plasmin. Plasmin also proteolyses GP Ib and plasma vWf. Because these effects could mitigate shear stress-induced platelet aggregation, we investigated the effect of fibrinolytic agents on platelet aggregation in response to a pathological shear stress of 120 dynes/cm2 generated by a cone-and-platen rotational viscometer. Plasmin inhibited shear stress-induced aggregation of washed platelets, and this was associated with a decrease in GP Ib. TPA, at concentrations > or = 2000 IU/mL, significantly inhibited shear stress-induced platelet aggregation of platelet-rich plasma without a decrease in platelet GP Ib. In plasma-platelet mixing experiments, we determined that the TPA effect was localized to plasma. Purified vWf multimer degradation by TPA (in the presence of exogenous plasminogen) was associated with the loss of the capacity of vWf to support shear stress-induced platelet aggregation. These results demonstrate that TPA inhibits platelet aggregation in response to pathological shear stress by altering the multimeric composition of vWf. This effect of TPA on shear stress-induced platelet aggregation may contribute, along with fibrinolysis, to the therapeutic effect of TPA in restoring blood flow during acute coronary artery thrombosis.


Divergent and sex-dimorphic expression of the paralogs of the Sox9-Amh-Cyp19a1 regulatory cascade in developing and adult atlantic cod (Gadus morhua L.).
The factors of the Sox9-Amh-Cyp19a1 cascade play a crucial role in the complex process of sex differentiation in mammals. The involvement of Sox9 and Cyp19a1 paralogs and the single Amh ortholog in sex differentiation and development of the gonads and the brain in Atlantic cod was examined by analyzing bimodal and sex-dimorphic gene expression patterns, respectively, during early stages and in maturing males and females. Expression of sox9a and sox9b were initiated at blastulation, and both paralogs were expressed in chondrogenic tissue in the hatched larvae. The male-specific expression of sox9a in the adult gonads supports a conserved role in testis function, while sox9b was expressed in the maturing testes and ovaries at similar levels. Amh was expressed at low, but variable, levels from late gastrulation prior to the onset of cyp19a1a and cyp19a1b expression. Male-biased amh expression was found in the maturing gonads, but the increased ovarian levels during maturation suggest a role also in females. The larval expression of cyp19a1a and cyp19a1b increased at the expected time of sex differentiation, but showed large individual variation. The ovarian expression of cyp19a1a and amh increased concomitant with increased plasma estradiol levels during vitellogenesis. The testis-specific cyp19a1b expression supports the importance of estrogen in the spermatogenesis, while abundant expression in the male and female brain is probably related to the continuous neurogenesis in fish. These divergent and sex-dimorphic expression patterns of the cod sox9 and cyp19a1 paralogs demonstrate the complexity of the genetic network regulating sexual development in fish.


Four distinct photoreceptors contribute to light-induced side branch formation in the moss Physcomitrella patens.
Side branch formation in the moss, Physcomitrella patens, has been shown to be light dependent with cryptochrome 1a and 1b (Ppcry1a and Ppcry1b), being the blue light receptors for this response (Imaizumi et al. in Plant Cell 14:373, 2002). In this study, detailed photobiological analyses were performed, which revealed that this response involves multiple photoreceptors including cryptochromes. For light induction of branches, blue light of a fluence rate higher than 6 micromol m(-2) s(-1) for period longer than 3 h is required. The number of branches increased with the increase in fluence rate and in the irradiation period. The number of branches also increased when red light was applied together with the blue light, although red light alone had a very few effect. By partially irradiating a cell, both receptive sites for blue and red light were found to be located around the nucleus. Further, both red and blue light determine the positions of branches being dependent upon the vibration plane of polarized light. Red light control of branch position was nullified by simultaneous far-red light irradiation. A blue light effect on branch position was not found in lines with disrupted phototropin genes. Thus, dichroic phytochrome and phototropin, possibly on the plasma membrane, regulate branch position. These results indicate that at least four distinct photoreceptor systems, namely, cryptochromes and red light receptor around or in the nucleus, dichroic phytochrome and phototropin around the cell periphery, are involved in the light induction of side branches in the moss Physcomitrella patens.


Cardiorespiratory reflexes and aquatic surface respiration in the neotropical fish tambaqui (Colossoma macropomum): acute responses to hypercarbia.
We examined the cardiorespiratory responses to 6 h of acute hypercarbia (1, 2.5, and 5% CO(2)) in intact and gill-denervated (bilateral denervation of branchial branches of cranial nerves IX and X) tambaqui, Colossoma macropomum. Intact fish exposed to 1 and 2.5% CO(2) increased respiratory frequency ( f(R)) and ventilation amplitude ( V(AMP)) slowly over a 1- to 3-h period. Denervated fish did not show this response, suggesting that tambaqui possess receptors in the gills that will produce excitatory responses to low levels of hypercarbia (1 and 2.5% CO(2)) if the exposure is prolonged. The cardiac response to stimulation of these receptors with this level of CO(2) was a tachycardia and not a bradycardia. During exposure to 5% CO(2), intact fish increased f(R) and V(AMP), and showed a pronounced bradycardia after 1 h. After 2 h, the heart rate ( f(H)) started to increase, but returned to control values after 6 h. In denervated fish, the increase in f(R) was abolished. The slow increase in V(AMP) and the bradycardia were not abolished, suggesting that these changes arose from extra-branchial receptors. Neither intact nor denervated fish developed the swelling of the lower lip or performed aquatic surface respiration, even after 6 h, suggesting that these are unique responses to hypoxia and not hypercarbia.


Neurobiological underpinnings of cognitive subtypes in psychoses: A cross-diagnostic cluster analysis.
Schizophrenia and bipolar disorder include patients with different characteristics, which may hamper the definition of biomarkers. One of the dimensions with greater heterogeneity among these patients is cognition. Recent studies support the identification of different patients' subgroups along the cognitive domain using cluster analysis. Our aim was to validate clusters defined on the basis of patients' cognitive status and to assess its relation with demographic, clinical and biological measurements. We hypothesized that subgroups characterized by different cognitive profiles would show differences in an array of biological data. Cognitive data from 198 patients (127 with chronic schizophrenia, 42 first episodes of schizophrenia and 29 bipolar patients) were analyzed by a K-means cluster approach and were compared on several clinical and biological variables. We also included 155 healthy controls for further comparisons. A two-cluster solution was selected, including a severely impaired group and a moderately impaired group. The severely impaired group was associated with higher illness duration and symptoms scores, lower thalamus and hippocampus volume, lower frontal connectivity and basal hypersynchrony in comparison to controls and the moderately impaired group. Moreover, both patients' groups showed lower cortical thickness and smaller functional connectivity modulation than healthy controls. This study supports the existence of different cognitive subgroups within the psychoses with different neurobiological underpinnings.


Modulation of gene expression by DNA-protein and protein-protein interactions in the promoter region of the zein multigene family.
A common cis-acting element in the promoter region of many genes expressed during endosperm development of cereal seeds, the prolamine-box or P-box, is only 20bp upstream of the alpha-class 22-kDa zein gene-specific cis element, the O2-box, which is recognized by the b-ZIP transcription factor, Opaque-2 (O2). The proximity of these two boxes has prompted a study of how two DNA-binding proteins of a different hierarchy might be involved in the activation and modulation of the 22-kDa zein-encoding genes. This was accomplished by utilizing a highly purified P-box-binding-factor-1 (PBF-1) and a bacterially expressed truncated form of the O2 protein. After adding the recombinant O2 to the purified fraction of PBF-1, binding studies were performed with a series of DNA probes combining the P- and O2-boxes from zein promoters. These studies have revealed an interesting inhibitory effect of PBF-1 over O2 function dependent on their ratio, consistent with its in-vivo properties and the developmental expression profiles of zein genes. We also could show that the P-box is specifically recognized by topoisomerase II and single-strand DNA-binding proteins, indicating a possible additional linkage between P-box and the scaffold-attachment-region (SAR).


The Role of the "Traditional Chinese Medicine Proclamation" in Cholera Prevention and Control in Modern China.
During the period of social transformation in modern China, the sudden onslaught of malignant infectious diseases, the helplessness of the public, and the impact of the modern Western medical system promoted the profound self-revolution of traditional Chinese medicine (TCM). Multiple factors, including politics, economy or religion contributed to the formulation of paper-based "TCM proclamation". This paper, based on the prevention and control of cholera advocated in TCM proclamation, analyzes the new ways of cholera spread in China in early modern times and the complicated "country-region-medical institutions-other institutions-individuals" correlations.


Unattended uterine prolapse during pregnancy in a low-income setting: a case report.
Uterine prolapse (UP) is rare during pregnancy. It sometimes leads to serious complications such as abortion, preterm labor, and maternal death. The main risk factor for UP is previous vaginal childbirth and is usually managed conservatively. However, surgery should be considered in cases of unavailability or failure of conservative approaches. A 34-year-old Gravid4Para3 pregnant woman in the 33rd week of gestation presented with refractory vaginal pain. She had a remarkable history of second-degree UP. Upon presentation, the anterior and posterior cervical lips were swollen, bluish, and protruding through the vagina. Considering the severe pain, the alarming examination findings, and the impossibility of pushing back the protruding mass, a total vaginal hysterectomy was performed. The postoperative pathological study revealed a massive hemorrhage with edematous changes in the vaginal cuff and cervical mucosa in addition to features of placenta accreta, placenta previa, and placenta abruption. UP is a rare but potentially serious condition, especially if it is related to pregnancy. Moreover, managing UP could be challenging in low-income settings, where even simple conservative methods might be unavailable or financially unattainable.


Protective effects of fargesin on cadmium-induced lung injury through regulating aryl hydrocarbon receptor.
Fragesin, a traditional Chinese medicine, has been shown to exert anti-inflammatory effect. The aim of this study was to figure out the possible effectiveness of the fargesin, and to invest the mechanisms by which it works in the cadmium-induced lung injury in mice. Fargesin was given 1 h before cadmium treatment for 7 days. Then, the bronchoalveolar lavage fluid (BALF) were harvested to test inflammatory cells and pro-inflammatory cytokine production. Lung histopathological changes, myeloperoxidase (MPO) activity, and aryl hydrocarbon receptor (AhR) and nuclear factor kappa B (NF-κB) activation were measured. Fargesin dose-dependently reduced inflammatory cells and pro-inflammatory cytokines in BALF, improved lung histopathological injury, and inhibited lung wet/dry ratio and MPO activity. Furthermore, fargesin inhibited cadmium-induced NF-κB activation. In addition, fargesin was found to increase AhR expression. In conclusion, fargesin attenuates cadmium-induced lung injury may be via activating AhR, which subsequently suppressing the inflammatory response.


Hemangiopericytoma of bone.
Primary hemangiopericytoma of bone is a rare malignant tumor. Forty-one cases from the literature were reviewed, and four additional cases are reported. The peak incidence is in fourth and fifth decades. The pelvis and lower extremities are the most common locations. The radiographic features are nonspecific, although angiography may aid in the diagnosis. Based on a limited number of evaluable cases, the prognosis seems to correlate with the histologic grade of the tumor. Late recurrence and distant metastases are common.


Perceptions of nurses working in mental health services regarding the recovery-oriented care approach: Findings from Africa.
The recovery-oriented care approach in mental health is recognised as the vision for mental health. People with a diagnosis of mental illness value the support and the individualistic approach emphasised in the recovery-oriented mental health care approach as they believe it facilitates their recovery. However, as a developing country, Botswana has a long way to go in availing mental health care resources to people with mental illness, let alone adopting new mental health approaches such as recovery. The study aimed to explore the perceptions of nurses working in mental health care facilities of recovery-oriented mental health care. Four mental health facilities from Botswana consented to participate in the study. A descriptive qualitative approach was utilised to explore nurses' views on how they perceive recovery from mental illness. Thirty nurses participated in the focus group discussions across the four study sites. All participants consented to participate and to be recorded. Tesch's (in Qualitative enquiry and research design: Choosing among five approaches. 3th ed. SAGE, 2013:198) thematic analysis was used for this study. Three main themes were identified in participants' perceptions of recovery-oriented care mental health: Recovery from mental illness is possible, the Meaning of recovery from mental illness and Factors facilitating recovery from mental illness. The study offers a perspective into how nurses perceive recovery-oriented approaches from a developing country and add to the gap existing in recovery-oriented mental health care approach from the African context.


Palliative urinary conduit diversion in cases of intolerable urinary discomfort.
Fifteen patients with incurable gynecological cancers, all primary radiation treated and all having severe urinary discomfort due to urinary tract injuries were retrospectively examined after urinary conduit diversion. All have been followed-up until termination or until all survivors had lived for 6 months after the operation. Twelve of the 15 were discharged from the hospital, 10 of whom survived the first 6 months. Of those discharged 82% of the cumulated sum of postoperative observations days was spent out of the hospital. At the end of the observation period nine patients had been supplied with a colostomy as well, thus having double stomas. All six patients still alive declared in retrospect that given the choice again, they would still be willing to undergo the operation.


Significance of soil moisture on temperature dependence of Hg emission.
Soil moisture is a key factor for mercury (Hg) emission from soil. Despite its significance for Hg emissions, the effect of soil moisture on Hg flux and fractions has not been thoroughly investigated. The objective of this study was to elucidate the influences of soil moisture and temperature on Hg fluxes from soils and Hg fractions. A kinetic study was performed to measure Hg emission fluxes of six soil samples under different temperature (T) (15 °C, 20 °C, 25 °C, 30 °C, and 35 °C) and moisture conditions (0%, 10%, and 20% added water). The results showed that the Hg fluxes increased with increases in T and soil moisture. A linear correlation was found between ln (Hg emission flux) and 1/T for the six soil samples at different moisture contents (R2 = 0.73-0.99). The range of activation energy (Ea) values was 25.31-57.86 kJ/mol. The Hg fractions in soils of different moisture content were determined by a sequential extraction method. The results demonstrated that soil moisture affected the Hg fractions in soils. The Ea values had different relationships with soil moisture in different soils. There were correlations between Ea and the elemental and mercuric sulfide fractions for air-dried soils. However, for moist soils, Ea was negatively correlated with the water-soluble and acid-soluble fractions. Collectively, the combination of the Hg emission kinetics and Hg fraction measurement of different moist soils indicated that Hg emission was affected by both total Hg concentration and Hg fractions.


Trunk Growth in Early-Onset Idiopathic Scoliosis Measured With Biplanar Radiography.
Cross-sectional and longitudinal retrospective study. To measure thoracic dimensions and volume during growth in early-onset idiopathic scoliosis (EOIS) patients and to compare them to a population of asymptomatic adults and to the previous literature. Data on trunk growth for scoliotic children between 6 and 14 years of age is sparse in the literature. Thirty-six patients (29 girls and 7 boys, between 3 and 14 years old, average Cobb angle 33°±15°) were included, all with a minimum two-year follow-up. Sixty-one asymptomatic girls and 54 asymptomatic adults were included as control groups. All subjects underwent biplanar radiography and 3D reconstruction of the spine, pelvis, and rib cage. EOIS patients repeated their radiologic examination every six months. Cobb angle, rib cage volume, anteroposterior and transverse diameters, thoracic index, thoracic perimeter, pelvic incidence, and T1-T12 and T1-S1 distance were calculated. Reproducibility of measurement was assessed. Measurement reliability in such young patients was comparable to previous studies in adolescents and adults. Geometrical parameters of EOIS patients increased linearly with age. For instance, rib cage volume in girls with EOIS increased from 2200 cm3 at six to seven years of age to 4100 cm3 at 13-14 years (65% of adult values, 294 cm3/y). Comparison with asymptomatic girls showed that EOIS could affect growth spurt. Longitudinal analysis on a cohort of six girls who had a follow-up of six years confirmed the cross-sectional data. In this longitudinal and cross-sectional study, trunk growth between 3 and 14 years of age was characterized, for the first time, with biplanar radiography and 3D reconstruction. The results can be useful to estimate patient growth and thus have potential application in the surgical planning of EOIS patients. Level II, retrospective study.


Cerebrovascular Time Constant in Patients with Head Injury.
The cerebrovascular time constant (τ) theoretically estimates how fast the cerebral arterial bed is filled by blood volume after a sudden change in arterial blood pressure during one cardiac cycle. The aim of this study was to assess the time constant of the cerebral arterial bed in patients with traumatic brain injury (TBI) with and without intracranial hematomas (IH). We examined 116 patients with severe TBI (mean 35 ± 15 years, 61 men, 55 women). The first group included 58 patients without IH and the second group included 58 patients with epidural (7), subdural (48), and multiple (3) hematomas. Perfusion computed tomography (PCT) was performed 1-12 days after TBI in the first group and 2-8 days after surgical evacuation of the hematoma in the second group. Arteriovenous amplitude of regional cerebral blood volume oscillation was calculated as the difference between arterial and venous blood volume in the "region of interest" of 1 cm(2). Mean arterial pressure was measured and the flow rate of the middle cerebral artery was recorded with transcranial Doppler ultrasound after PCT. The time constant was calculated by the formula modified by Kasprowicz. The τ was shorter (p = 0.05) in both groups 1 and 2 in comparison with normal data. The time constant in group 2 was shorter than in group 1, both on the side of the former hematoma (р = 0.012) and on the contralateral side (р = 0.044). The results indicate failure of autoregulation of cerebral capillary blood flow in severe TBI, which increases in patients with polytrauma and traumatic IH.


Mesenteric appendicitis strangulating small bowel: an exceptional internal herniation.
Primitive internal hernias are a rare cause of intestinal obstruction. They are often paraduodenal even transmesocolic, but only rarely transomental. We present a rare case of an internal abdominal hernia in a young man. The small bowel was strangulated by an intra mesenteric appendicitis. This hernia was revealed by abdominal pain, nausea and vomiting. Plain X-ray of the abdomen showed dilated jejunal and ileal loops with multiple air-fluid levels. The diagnosis of appendicitis was suggested by ultrasound but the internal hernia was found only upon surgical exploration. An appendicectomy and adhesiolysis were performed. The patient recovered fully after 3 days, and had an uneventful postoperative course. The authors discuss the possible cause of this rare intestinal obstruction.


Systemic cyclosporine and corneal transplantation.
Corneal transplantation is the most commonly performed tissue transplant boasting over a century of history, science, and tradition. While favorable outcomes have been reported after penetrating keratoplasty, rejection remains a major cause of graft failure. The long-term survival rates of this relatively immunologically privileged tissue are only just comparable to those of vascularized organs. While corticosteroids treatment remains the gold standard for postoperative immunomodulation, other agents have been utilized in an ongoing effort to improve graft survival and patient outcomes. One of the most promising immunomodulatory substances whose immunosuppressive effect has revolutionized solid organ transplantation is cyclosporine (CsA). A calcineurin inhibitor, cyclosporine has been used as an immunosuppressive agent in corneal transplantation since the 1980's. Although some studies have shown beneficial effects of cyclosporine in both low- and high-risk corneal transplant patients the use of cyclosporine in rejection prophylaxis and treatment remain controversial and disputable. We herein present a literature review on the role of systemic cyclosporine in corneal transplantation.


The analysis of dose-response curve from bioassays with quantal response: Deterministic or statistical approaches?
Dose-response relations can be obtained from systems at any structural level of biological matter, from the molecular to the organismic level. There are two types of approaches for analyzing dose-response curves: a deterministic approach, based on the law of mass action, and a statistical approach, based on the assumed probabilities distribution of phenotypic characters. Models based on the law of mass action have been proposed to analyze dose-response relations across the entire range of biological systems. The purpose of this paper is to discuss the principles that determine the dose-response relations. Dose-response curves of simple systems are the result of chemical interactions between reacting molecules, and therefore are supported by the law of mass action. In consequence, the shape of these curves is perfectly sustained by physicochemical features. However, dose-response curves of bioassays with quantal response are not explained by the simple collision of molecules but by phenotypic variations among individuals and can be interpreted as individual tolerances. The expression of tolerance is the result of many genetic and environmental factors and thus can be considered a random variable. In consequence, the shape of its associated dose-response curve has no physicochemical bearings; instead, they are originated from random biological variations. Due to the randomness of tolerance there is no reason to use deterministic equations for its analysis; on the contrary, statistical models are the appropriate tools for analyzing these dose-response relations.


Spatial variation and association between maternal chemical fertilizer exposure and preterm birth in a rural area in Northern China.
Whether maternal macro-environmental chemical fertilizer exposure has an association with the risk of preterm birth remains unclear. This study aimed to investigate the association between maternal exposure to chemical fertilizer during pregnancy and the risk of preterm birth. A total of 13,861 births, including 402 preterm birth from 313 villages in Pingding County, Shanxi Province, China, were analyzed to explore spatial variations of preterm birth risks at the village level. Spatial variations of preterm birth were visualized and tested with Disease Mapping, Moran's I and G* Statistic. The spatial zero-inflated negative binomial model was used to evaluate the incidence rate ratio (IRR) of preterm birth in different chemical fertilizer consumption levels at the village level. A population-based case-control study was conducted including 153 preterm births cases and 204 controls at the household level. The two-level logistic regression model was performed to estimate the association between risks of preterm birth and maternal exposure to chemical fertilizer after adjusting confounding factors. The findings indicated a remarkably clustering effect in relative risks of preterm birth and identified a high-risk clustering region of preterm birth from the south-central to the southwest and a low-risk clustering region in the northern Pingding county. The results of the spatial zero-inflated negative binomial model showed that the risk of preterm birth in the villages with chemical fertilizer consumption≥100 tons was 2.82 (95% CI: 1.50-5.57) times higher than those with <50 tons. Maternal exposure to chemical fertilizer ≥100 tons at village level was associated with an increased risk of preterm birth (aOR 2.14, 95%CI: 1.18-3.96), compared with exposure <50 tons after adjusting for confounding variables. The findings suggests that chemical fertilizers deserve more attention as a potential risk factor of preterm birth.


Application of an automatic adaptive filter for Heart Rate Variability analysis.
The presence of artifacts and noise effects in temporal series can seriously hinder the analysis of Heart Rate Variability (HRV). The tachograms should be carefully edited to avoid erroneous interpretations. The physician should carefully analyze the tachogram in order to detect points that might be associated with unlikely biophysical behavior and manually eliminate them from the data series. However, this is a time-consuming procedure. To facilitate the pre-analysis of the tachogram, this study uses a method of data filtering based on an adaptive filter which is quickly able to analyze a large amount of data. The method was applied to 229 time series from a database of patients with different clinical conditions: premature newborns, full-term newborns, healthy young adults, adults submitted to a very-low-calorie diet, and adults under preoperative evaluation for coronary artery bypass grafting. This proposed method is compared to the demanding conventional method, wherein the corrections of occasional ectopic beats and artifacts are usually manually executed by a specialist. To confirm the reliability of the results obtained, correlation coefficients were calculated, using both automatic and manual methods of ltering for each HRV index selected. A high correlation between the results was found, with highly significant p values, for all cases, except for some parameters analyzed in the premature newborns group, an issue that is thoroughly discussed. The authors concluded that the proposed adaptive filtering method helps to efficiently handle the task of editing temporal series for HRV analysis.


Microglia depletion increase brain injury after acute ischemic stroke in aged mice.
Microglia are one of the first responders to ischemic injury. Aged microglia acquire a senescent phenotype and produce more inflammatory cytokines after stroke. Depletion of microglia in young mice worsens post-ischemic damage by increasing inflammation. However, young mice do not have dysfunctional microglia. Hence, we hypothesized that depletion of microglia in older mice will contribute to improved early recovery after ischemic stroke injury. Aged (18-19 month) mice were fed with either control chow diet (CD) or PLX5622 chow diet (PLXD) for 21 days. On day 22, a 60-min middle cerebral artery occlusion (MCAo) surgery or sham surgery was performed. Twenty-four and 72 h after stroke immunohistochemistry and flow cytometry were performed. AFS98, a monoclonal antibody against CSF1R was used to specifically deplete brain macrophages by injection into the right hemisphere. Two days after AFS98 injections, mice underwent one-hour MCAo. Twenty-four hours later mice were euthanized and flow cytometry was performed. An increase in infarct volume (p < 0.05) was seen in the PLXD versus CD after stroke in aged mice at 24 and 72 h. An increase (p < 0.05) in infiltrating monocytes was observed after microglial depletion in aged stroke mice suggesting a differential monocyte response. An increase in astrocyte numbers was evident in the PLXD sham mice compared to CD sham, reflecting the off-target effects of PLX5622 treatment. In conclusion, PLX5622 and AFS98 treatment depleted microglia in aged animals but resulted in increased neuroinflammation after ischemic stroke.


Primary prevention of behavior problems in Mexican-American children.
A primary prevention program, the Houston Parent-Child Development Center, directed towards infants and their parents, has effectively reduced the frequency of behavior problems for these children 5 to 8 years after the program's completion. Teacher ratings showed significantly fewer acting-out, aggressive behaviors for program children. Ratings of classroom behaviors found program children significantly less hostile and more considerate than control boys. This appears to be the first primary prevention program to have demonstrated effectiveness in reducing behavior problems over such a long time.


An uncommon variant of the Essex-Lopresti injury.
The Essex-Lopresti injury is an extremely rare condition combining radial head or neck fracture, distal radio-ulnar joint dislocation and rupture of the interosseous membrane. However, there are rare or unusual varieties or associated injuries. We report a case of a 46-year-old woman with a posterior dislocation of the radio-humeral joint, a radial shaft fracture, and a distal radio-ulnar joint dislocation. She underwent open reduction and internal fixation of the radial shaft fracture followed by an immobilization by a long elbow splint in supination for 6 weeks. At 18 months of follow-up, she was asymptomatic and she had a full range of elbow and wrist motion and had resumed thoroughly her previous job. The Essex-Lopresti injury results from a complex injury to the forearm axis with resultant longitudinal instability, which can be challenging to treat. There are some variations that can lead to a missed diagnosis resulting in persistent pain and instability of the wrist. The best outcomes are reached with early diagnosis and prompt management.


Female sex steroid receptors in gynecological malignancies: clinical correlates.
Cytosol estrogen (ERc) and progestin (PRc) receptors were measured in 135 endometrial carcinoma specimens from 127 patients, and in 84 ovarian carcinoma specimens from 84 patients before any treatment. In endometrial carcinoma, early clinical stages (I and II) were more often receptor-rich (ERc and PRc greater than or equal to 30 fmol/mg cytosol protein) than stage III-IV tumors, or metastatic and recurrent lesions. Anaplastic lesions (grade 3) had lower receptor concentrations than moderately (grade 2) and well (grade 1) differentiated stage I lesions. PRc concentrations of the stage I malignancies clearly infiltrating into the myometrium were lower than those in superficial tumors. Our follow-up (24 months or more) data of 41 patients with clinical stage I disease, and of 21 patients with clinical stage III or IV disease show that the receptor-poor tumors tend to behave more aggressively than receptor-rich malignancies in relation to patient survival. In 59 primary epithelial ovarian carcinomas, there were no significant differences in ERc and PRc concentrations in the four clinical stages. In contrast to this, the concentrations of these receptors were significantly lower in recurrent than in primary epithelial carcinomas. In anaplastic serous carcinomas, PRc was significantly lower than in differentiated tumors, and in anaplastic endometrioid carcinomas, ERc and PRc were lower than in corresponding differentiated tumors. Follow-up (24 months or more) data of 22 patients show that patients with advanced ovarian malignancy characterized by low ERc and/or PRc concentrations survive for a shorter time than the other patients.


Integrative Review of Reproductive Decision Making of Women Who Are BRCA Positive.
To synthesize research findings about reproductive decision making among women who are BRCA positive. PubMed and CINAHL. Articles published in English between 2000 and June 28, 2020, about the reproductive decision making of women with a confirmed BRCA1 or BRCA2 mutation. We extracted data about participants, study design, analysis, follow-up, and results. We used the modified Downs and Black checklist and Kennelly's qualitative data analysis to rate studies for quality and applicability by using. We included five of 257 screened articles in our synthesis. The total sample size of the five studies was 1,468 women. The most prevalent factors related to reproductive decision making were the impending decisions regarding childbearing and family choices, including decisions about biological children, preventive surgery, preimplantation genetic diagnosis, and prenatal diagnosis to prevent further transmission of a BRCA mutation, and family planning. A lack of knowledge exists about the reproductive decision-making processes of women who are BRCA positive. A better understanding of this process would provide nurses and other clinicians with the knowledge needed to support these women through their reproductive life choices.


Imaging of myocardial sympathetic innervation with metaiodobenzylguanidine.
The sympathetic nervous system has profound influences on myocardial function and pathophysiology. The heart is densely innervated with sympathetic nerves, which are distributed on a regional basis. Heterogeneity of myocardial sympathetic innervation, or autonomic imbalance, has long been hypothesized as a major mechanism underlying sudden cardiac death. Only in the past few years has it been possible to evaluate abnormalities in heart innervation in the intact animal. Recent developments in cardiac imaging have lead to the ability to map the distribution of the sympathetic nerves in vivo, with radiolabeled metaiodobenzylguanidine. As a result, pathophysiologic mechanisms that relate alterations in sympathetic nerve activity to disease processes are now being explored.


The Venezuela eye evaluation study.
One-thousand-eighty-one rural and urban inhabitants of Venezuela were discovered to have good uncorrected visual acuity. This was especially noted among the males who were examined. More myopia was seen than previously reported, while earlier presbyopia was confirmed. There was a relatively low prevalence of glaucoma among men and women. Correction of refractive errors, cataracts, glaucoma and pterygia remains a challenge. To determine the frequency of ocular disease in rural and urban Venezuela. Participants in a cross-sectional health screening study were examined. The main outcome measured was external eye disease: allergic conjunctivitis, dry eyes and pterygia. A total of 1,281 individuals participated. All agreed to screening and eye examinations. Open-angle glaucoma was present in 1.2% of women and 1% of men. For participants age > 45, this increased to 1.9% of women and 2.8% of men. Rural and urban inhabitants of Venezuela were determined to have good uncorrected visual acuity, especially among males. More myopia was noted than previously reported, while earlier presbyopia was confirmed. There was a relatively low frequency of glaucoma among men and women as compared to Barbados, and a U.S.-based study of Mexican Americans.


Sex-Related Differences in Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage.
Several population-based studies found a higher case fatality after aneurysmal subarachnoid hemorrhage (ASAH) in women than in men. This may relate to differences in prognostic characteristics. We therefore assessed sex differences in prognosticators and outcome in ASAH patients. From a prospectively collected ASAH database, we retrieved data on patients admitted from 1990 to 2010. We calculated prevalence ratios (PRs) with corresponding 95% confidence intervals (CIs) for prognosticators (clinical condition on admission, site and treatment of the aneurysm, and complications during the clinical course) and risk ratios (RRs) for in-hospital death and poor outcome (death or dependence) at 3 months. RRs were adjusted for possible confounding with Poisson regression analysis. Of the 1761 included patients, 1211 (68.8%) were women, who were 1.9 (95% CI: .5↔3.3) years older than men. PRs for women for the site of the aneurysm were 1.71 (95% CI: 1.38↔2.13) for the carotid artery, .68 (95% CI: .60↔.77) for the anterior communicating artery, 1.14 (95% CI: .92↔1.41) for the middle cerebral artery, and .85 (95% CI: .63↔1.13) for posterior circulation. PRs of other prognosticators were similar between sexes. The crude RR for in-hospital death for women was .91 (95% CI: .78↔1.05) and for poor outcome at 3 months was .95 (95% CI: .85↔1.06); both remained similar after adjustment. In this study, in-hospital death and poor outcome at 3 months did not differ between men and women. Women were slightly older than men and had different distributions of aneurysm sites, but not to an extent that it explained a sex difference in outcome.


Population pharmacokinetics analysis of camidanlumab tesirine in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma.
The objective of this analysis was to develop a population pharmacokinetic (PPK) model to characterize camidanlumab tesirine (Cami) pharmacokinetics based on the phase 1 study in relapsed/refractory lymphoma (NCT02432235). An initial PPK model was developed based on a two-compartment model with parallel linear and nonlinear elimination pathways. Pharmacokinetic parameters were evaluated for correlation with potential demographic covariates; significant covariates were retained in the final model. In the final PPK model, baseline weight effects were included on clearance (CL), intercompartmental clearance (Q), and the volumes of distribution in the central (V1) and peripheral (V2) compartments. The baseline soluble CD25 (sCD25) effect was included on CL and maximum velocity of saturable clearance (Vmax); sex effect was included on CL and V1; and ethnicity effect was included on deconjugation clearance (CLdec). For a typical patient, CL and CLdec were 0.516 and 0.21 L/day, respectively (tAb elimination half-life: 18.72 days); V1 and V2 were 4.41 and 2.67 L, respectively; Vmax was 0.49 mg/day; the Michaelis-Menten constant (Km) was 0.409 µg/mL; and the first-order rate for decrease of Vmax (KDES) was 0.0197/day. Cami exposure was higher for patients with low baseline sCD25, higher body weight, and females. The final model described the observed data well, estimates of PK parameters were obtained, and covariates with significant effects on Cami exposure were identified. Altogether, this final PPK model provides a robust basis for analysis of Cami exposure-response relationships and further supports identification of the optimal Cami dosing schedule for patients with relapsed/refractory lymphoma.