The relationship between moral distress, professional stress, and intent to stay in the nursing profession.
Moral distress and professional stress are common problems that can have adverse effects on nurses, patients, and the healthcare system as a whole. Thus, this cross-sectional study aims to examine the relationship between moral distress, professional stress, and intent to stay in the nursing profession. Two hundred and twenty full-time nurses employed at teaching hospitals in the eastern regions of Iran were studied. A 52-item questionnaire based on Corley's Moral Distress Scale, Wolfgang's Health Professions Stress Inventory and Nedd Questionnaire on Intent to Stay in the Profession was used in the study. Additionally, demographic details of the study population were collected. No significant correlation was observed between the intensity and frequency of moral distress, professional stress, and intent to stay in the profession among nurses (P > 0.05). There was a significant correlation between moral distress, professional stress, and age, number of years in service and work setting (P < 0.05). Given the important effect of moral distress and professional stress on nurses, in addition to the educational programs for familiarization of nurses with these concepts, it is recommended that strategies be formulated by the healthcare system to increase nurses' ability to combat their adverse effects.


Acute and Chronic Hyponatremia.
Hyponatremia is the most common electrolyte disorder in clinical practice. Catastrophic complications can occur from severe acute hyponatremia and from inappropriate management of acute and chronic hyponatremia. It is essential to define the hypotonic state associated with hyponatremia in order to plan therapy. Understanding cerebral defense mechanisms to hyponatremia are key factors to its manifestations and classification and subsequently to its management. Hypotonic hyponatremia is differentiated on the basis of urine osmolality, urine electrolytes and volume status and its treatment is decided based on chronicity and the presence or absence of central nervous (CNS) symptoms. Proper knowledge of sodium and water homeostasis is essential in individualizing therapeutic plans and avoid iatrogenic complications while managing this disorder.


Race and ethnic differences and human figure drawings: clinical utility of the DAP:SPED.
This study examined race and ethnic differences on the Draw A Person: Screening Procedure for Emotional Disturbance (DAP:SPED; Naglieri, McNeish, & Bardos, 1991) for youths 6 though 17 years of age for 2 matched samples. Samples were drawn from the DAP:SPED nationally representative standardization sample and matched on gender, grade, and school classroom. No statistically significant differences were found for big figure, small figure, or shading item composites. A statistically significant difference was found between Black-White pairs on figure omissions but showed a small effect size (d value = .25). Further, no statistically significant differences were found between the DAP:SPED Total T scores for Black and White youth (M = 47.67, SD = 10.09; N =138) or Hispanic and White youth (M = 48.20, SD = 9.56; N = 59), showing very small effect sizes. In addition, equivalence testing showed similarities across race and ethnic pairs for all composites and DAP:SPED total score, lending preliminary support to the DAP:SPED's clinical utility as a measure that yields similar scores across these groups.


How the Cerebellum and Prefrontal Cortex Cooperate During Trace Eyeblinking Conditioning.
Several data have demonstrated that during the widely used experimental paradigm for studying associative learning, trace eye blinking conditioning (TEBC), there is a strong interaction between cerebellum and medial prefrontal cortex (mPFC). Despite this evidence, the neural mechanisms underlying this interaction are still not clear. Here, we propose a neurophysiologically plausible computational model to address this issue. The model is constrained on the basis of two critical anatomo-physiological features: (i) the cerebello-cortical organization through two circuits, respectively, targeting M1 and mPFC; (ii) the different timing in the plasticity mechanisms of these parallel circuits produced by the granule cells time sensitivity according to which different subpopulations are active at different moments during conditioned stimuli. The computer simulations run with the model suggest that these features are critical to understand how the cooperation between cerebellum and mPFC supports motor areas during TEBC. In particular, a greater trace interval produces greater plasticity changes at the slow path synapses involving mPFC with respect to plasticity changes at the fast path involving M1. As a consequence, the greater is the trace interval, the stronger is the mPFC involvement. The model has been validated by reproducing data collected through recent real mice experiments.


ACCEPTANCE OR REJECTION OF MALE SKIN BY ISOLOGOUS FEMALE MICE: EFFECT OF INJECTION OF SPERM.
Female C57B1/6J mice given one intraperitoneal injection of 1 to 8 million isologous epididymal sperm cells may exhibit either delayed or accelerated rejection of isologous male skin, depending on both the number of sperm cells injected and the time of application of the graft. A long time interval or a large dose of sperm cells results in maintenance of the male graft or delayed rejection, while a small dose and short time interval produces an accelerated rejection phenomenon.


[Sudden death in epilepsy: clinical experience].
The disconcerting experience of sudden unexpected death in epilepsy (SUDEP) obliges the clinician to consider the differential diagnosis and study the mechanisms by which it may be prevented. A 13 year old patient with idiopathic generalized epilepsy and a history of febrile convulsions, both also described in the family history, who suddenly died at his home from no apparent cause. The legal autopsy findings were normal. The serum levels of valproic acid, previously normal, were non existent at death. In this case the differential diagnosis included intentional causes, ingestion of toxic substances, feeding disorders, long QT syndrome and SUDEP. After considering the available evidence we suggest that this was a case of SUDEP. Epidemiological studies specifically designed to seek risk factors may suggest preventive measures even when the causes and pathogenic mechanisms of the disorder are not known. The creation of a national SUDEP register would be a great step in this direction.


Emergency strategies and trends in the management of liver trauma.
The liver is the most frequently injured organ during abdominal trauma. The management of hepatic trauma has undergone a paradigm shift over the past several decades, with mandatory operation giving way to nonoperative treatment. Better understanding of the mechanisms and grade of liver injury aids in the initial assessment and establishment of a management strategy. Hemodynamically unstable patients should undergo focused abdominal sonography for trauma, whereas stable patients may undergo computed tomography, the standard examination protocol. The grade of liver injury alone does not accurately predict the need for operation, and nonoperative management is rapidly becoming popular for high-grade injuries. Hemodynamic instability with positive focused abdominal sonography for trauma and peritonitis is an indicator of the need for emergent operative intervention. The damage control concept is appropriate for the treatment of major liver injuries and is associated with significant survival advantages compared with traditional prolonged surgical techniques. Although surgical intervention for hepatic trauma is not as common now as it was in the past, current trauma surgeons should be familiar with the emergency surgical skills necessary to manage complex hepatic injuries, such as packing, Pringle maneuver, selective vessel ligation, resectional debridement, and parenchymal sutures. The present review presents emergency strategies and trends in the management of liver trauma.


Accelerated Progression to Type 1 Diabetes in the Presence of HLA-A*24 and -B*18 Is Restricted to Multiple Islet Autoantibody-Positive Individuals With Distinct HLA-DQ and Autoantibody Risk Profiles.
We investigated the effect of HLA class I risk alleles on disease progression in various phases of subclinical islet autoimmunity in first-degree relatives of patients with type 1 diabetes. A registry-based group of siblings/offspring (aged 0-39 years) was monitored from single- to multiple-autoantibody positivity (n = 267) and from multiple-autoantibody positivity to clinical onset (n = 252) according to HLA-DQ, -A*24, -B*18, and -B*39 status. Genetic markers were determined by PCR sequence-specific oligotyping. Unlike HLA-B*18 or -B*39, HLA-A*24 was associated with delayed progression from single- to multiple-autoantibody positivity (P = 0.009) but not to type 1 diabetes. This occurred independently from older age (P < 0.001) and absence of HLA-DQ2/DQ8 or -DQ8 (P < 0.001 and P = 0.003, respectively), and only in the presence of GAD autoantibodies. In contrast, HLA-A*24 was associated with accelerated progression from multiple-autoantibody positivity to clinical onset (P = 0.006), but its effects were restricted to HLA-DQ8+ relatives with IA-2 or zinc transporter 8 autoantibodies (P = 0.002). HLA-B*18, but not -B*39, was also associated with more rapid progression, but only in HLA-DQ2 carriers with double positivity for GAD and insulin autoantibodies (P = 0.004). HLA-A*24 predisposes to a delayed antigen spreading of humoral autoimmunity, whereas HLA-A*24 and -B*18 are associated with accelerated progression of advanced subclinical autoimmunity in distinct risk groups. The relation of these alleles to the underlying disease process requires further investigation. Their typing should be relevant for the preparation and interpretation of observational and interventional studies in asymptomatic type 1 diabetes.


[Indications for antireflux surgery of the esophagus].
In the Western world gastroesophageal reflux disease constitutes the single most common benign disorder of the upper gastrointestinal tract. Current medical therapy with proton pump inhibitors allows physicians to provide complete symptom relief and healing of acute esophageal mucosal injury in practically all affected patients. However, up to 50% of patients require maintenance therapy to prevent relapse. In these patients laparoscopic antireflux surgery offers an attractive and cost-effective alternative to potentially life-long medical therapy. Consequently, every patient with persistent or recurrent symptoms and/or complications of gastroesophageal reflux who depends on maintenance medical therapy to remain in remission is a potential candidate for laparoscopic antireflux surgery, particularly if of young age, suffering from side effects of medical therapy or worrying about long-term safety of the conservative treatment alternatives. A careful selection of patients, objective documentation of gastroesophageal reflux disease by 24-h esophageal pH monitoring, and meticulous attention to the technical details of the procedure are essential for a successful outcome of antireflux surgery.


Rapid differentiation of bacterial communities using high resolution melting analysis.
Analysis of microbial communities is of broad interest in biology and high throughput sequencing is now the preferred method. However, some studies may not need the level of detail high throughput sequencing provides and its cost may limit the number of samples that can be sequenced. High resolution melting analysis (HRM) of 16S rRNA gene variable regions has been proposed as an efficient and low cost method to prioritize samples for sequencing but more specific primers are needed and its efficacy needs to be confirmed. We tested a more specific pair of primers and compared results concerning the structure of microbial communities in tadpole intestine and feces obtained using HRM, denaturing gradient gel electrophoresis (DGGE) and high-throughput sequencing performed in parallel. All three methods showed similar conclusions concerning the communities and revealed communities that differed among intestinal regions and feces. The improved HRM method targets a shorter amplicon in the V3 region of the 16S rRNA gene and uses non-degenerate primers, both of which increase the sensitivity of HRM. The HRM approach was shown to be as effective as DGGE for comparing microbial communities, is considerably easier to perform, and can be used to assess differences in microbial community structure among a large number of samples before committing to sequencing.


Bis(mu-oxo)dicopper(III) complexes of a homologous series of simple peralkylated 1,2-diamines: steric modulation of structure, stability, and reactivity.
We have synthesized and characterized bis(mu-oxo)dicopper(III) dimers 1b-4b (Os) based on a core family of peralkylated trans-(1R,2R)-cyclohexanediamine (CD) ligands, self-assembled from the corresponding [LCu(MeCN)]CF3SO3 species 1a-4a and O2 at 193 K in aprotic media; additional Os based on peralkylated ethylenediamine and tridentate polyazacyclononane ligands were synthesized analogously for comparative purposes (5b-7b and 8b-9b, respectively). Trigonal-planar [LCu(MeCN)]1+ species are proposed as the active O precursors. The 3-coordinate Cu(I) complexes [(L(TE))Cu(MeCN)]CF3SO3 (4a) and [(L(TB))Cu(MeCN)]CF3SO3 (10a) were structurally characterized; the apparent O2-inertness of 10a correlates with the steric demands of its four benzyl substituents. The rate of O formation, a multistep process that likely proceeds via associative formation of a 1:1 [LCu(O2)]1+ intermediate, exhibits significant dependence upon ligand sterics and solvent: oxygenation of 4a-the slowest-reacting O precursor of the CD series-is first-order with respect to [4a] and proceeds at least 300 times faster in tetrahydrofuran than in CH2Cl2. The EPR, UV-vis, and resonance Raman spectra of 1b-9b are all characteristic of the diamagnetic bis(mu-oxo)dicopper(III) core. The intense ligand-to-metal charge transfer absorption maxima of CD-based Os are red-shifted proportionally with increasing peripheral ligand bulk, an effect ascribed to a slight distortion of the [Cu2O2] rhomb. The well-ordered crystal structure of [(L(ME))2Cu2(mu-O)2](CF3SO3)2.4CH2Cl2 ([3b. 4CH2Cl2]) features the most metrically compact [Cu2O2]2+ core among structurally characterized Os (av Cu-O 1.802(7) A; Cu...Cu 2.744(1) A) and exemplifies the minimal square-planar ligation environment necessary for stabilization of Cu(III). The reported Os are mild oxidants with moderate reactivity toward coordinating substrates, readily oxidizing thiols, certain activated alkoxides, and electron-rich phenols in a net 2e-, 2H+ process. In the absence of substrates, 1b-9b undergo thermally induced autolysis with concomitant degradation of the polyamine ligands. Ligand product distribution and primary kinetic isotope effects (kobsH/kobsD approximately 8, 1b/d24-1b, 293 K) support a unimolecular mechanism involving rate-determining C-H bond cleavage at accessible ligand N-alkyl substituents. Decomposition half-lives span almost 3 orders of magnitude at 293 K, ranging from approximately 2 s for 4b to almost 30 min for d(24)-1b, the most thermally robust dicationic O yet reported. Dealkylation is highly selective where ligand rigidity constrains accessibility; in 3b, the ethyl groups are attacked preferentially. The observed relative thermal stabilities and dealkylation selectivities of 1b-9b are correlated with NC(alpha)-H bond dissociation energies, statistical factors, ligand backbone rigidity, and ligand denticity/axial donor strength. Among the peralkylated amines surveyed, bidentate ligands with oxidatively robust NC(alpha)-H bonds provide optimal stabilization for Os. Fortuitously, the least sterically demanding N-alkyl substituent (methyl) gives rise to the most thermally stable and most physically accessible O core, retaining the potential for exogenous substrate reactivity.


In silico validation of the non-antibiotic drugs acetaminophen and ibuprofen as antibacterial agents against red complex pathogens.
Acetaminophen (APAP) and ibuprofen (IB) are drugs commonly used to alleviate pain due to their anti-inflammatory, anti-pyretic, and analgesic effect. The aim of the present study is to unravel the molecular mechanisms underlying the antimicrobial potential of these two drugs against red complex pathogens, namely, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, by using in silico tools, since they are potentially associated with inflammatory conditions related to periodontal infections. The STITCH v5.0 pipeline was primarily used for identifying drug-protein interactions; VirulentPred and VICMPred were used for elucidating the virulence property and functional class of the proteins. The subcellular localization of virulent proteins was assessed using PSORTb v3.0 and the epitopes were identified using BepiPred v1.0 Linear Epitope Prediction tool. APAP and IB were found to interact with proteins involved in cellular process, metabolism, and virulence. The virulent proteins targeted by the drugs were located in the cytoplasm, which would further add to the effectiveness of the drugs to serve as antimicrobial agents. Finally, epitope prediction revealed multiple epitopes in the virulent proteins which can be specifically focused on. APAP and IB were found to target vital proteins involved in the cellular process, metabolism, and virulence of red complex pathogens. An in-depth knowledge on the interaction of these drugs and their antibacterial activity would add to the plethora of merits gained by these drugs in clinical settings. Further in vitro studies on a wide range of pathogens are warranted to substantiate the true interactions between the drugs and the protein repertoire of pathogens.


[Relation of the major connector of a removable partial denture (RPD) with mandibular mucosal tissue; clinical case].
When the performance of removable partial prosthesis is analyzed, it can be seen that failures outnumber the successes. These failures, however, should not be imputed to the prostheses themselves, but rather to the fact that proper biomechanical principles were not observed in the planning of these devices. Each component of a prosthesis should be carefully planned in order to obtain maximum stability with respect to the supporting tissues. One of these principles is concevued to the relieve that must be established between major connectors and mandibular mucosae. It is important to remember that mandibular mucosae is fine, moveable, very sensitive and weak, so that this mucosae be considered very susceptible to mechanical aggression. In this work the authors emphasize the necessity of relieve in the mandibular major connector in order not to pressure the investing tissues. Otherwise serious periodontal damage can occur.


Transduction of Amine-Phosphate Supramolecular Interactions and Biosensing of Acetylcholine through PEDOT-Polyamine Organic Electrochemical Transistors.
Organic electrochemical transistors (OECTs) are important devices for the development of flexible and wearable sensors due to their flexibility, low power consumption, sensitivity, selectivity, ease of fabrication, and compatibility with other flexible materials. These features enable the creation of comfortable, versatile, and efficient portable devices that can monitor and detect a wide range of parameters for various applications. Herein, we present OECTs based on PEDOT-polyamine thin films for the selective monitoring of phosphate-containing compounds. Our findings reveal that supramolecular single phosphate-amino interaction induces higher changes in the OECT response compared to ATP-amino interactions, even at submillimolar concentrations. The steric character of binding anions plays a crucial role in OECT sensing, resulting in a smaller shift in maximum transconductance voltage and threshold voltage for bulkier binding species. The OECT response reflects not only the polymer/solution interface but also events within the conducting polymer film, where ion transport and concentration are affected by the ion size. Additionally, the investigation of enzyme immobilization reveals the influence of phosphate species on the assembly behavior of acetylcholinesterase (AchE) on PEDOT-PAH OECTs, with increasing phosphate concentrations leading to reduced enzyme anchoring. These findings contribute to the understanding of the mechanisms of OECT sensing and highlight the importance of careful design and optimization of the biosensor interface construction for diverse sensing applications.


Diagnosis of B cell lymphoma by analysis of immunoglobulin gene rearrangements in biopsy specimens obtained by fine needle aspiration.
Histologic diagnosis of lymphoma is far more difficult in the disaggregated cells obtained by percutaneous aspiration of lymph nodes than in tissue sections prepared from excisional biopsy specimens. However, the simplicity, economy, and safety of aspiration biopsy makes this an attractive diagnostic option in certain situations. In the present study, we demonstrate that lymph node aspirates provide material that is both suitable and sufficient for accurately detecting clonal proliferations of B cells by analysis of immunoglobulin gene rearrangements. The rearrangements detected in aspirated tissue serve as clonal markers that can be directly compared with the rearrangements found in histologically confirmed lymphoma removed by open biopsy. The application of gene rearrangements to aspirated material therefore offers a useful method of diagnosing lymphoma, particularly for the purposes of more thorough staging at initial presentation or the evaluation of tissues for possible relapse.


Stability Optimization Strategies of Cathode Materials for Aqueous Zinc Ion Batteries: A Mini Review.
Among the new energy storage devices, aqueous zinc ion batteries (AZIBs) have become the current research hot spot with significant advantages of low cost, high safety, and environmental protection. However, the cycle stability of cathode materials is unsatisfactory, which leads to great obstacles in the practical application of AZIBs. In recent years, a large number of studies have been carried out systematically and deeply around the optimization strategy of cathode material stability of AZIBs. In this review, the factors of cyclic stability attenuation of cathode materials and the strategies of optimizing the stability of cathode materials for AZIBs by vacancy, doping, object modification, and combination engineering were summarized. In addition, the mechanism and applicable material system of relevant optimization strategies were put forward, and finally, the future research direction was proposed in this article.


Purinoceptor-mediated, capsaicin-resistant excitatory effect of allyl isothiocyanate on neurons of the guinea-pig small intestine.
Allyl isothiocyanate (AITC; 200 μM) caused atropine- and tetrodotoxin-sensitive longitudinal muscle contraction on the guinea-pig small intestine. The response was not influenced by hexamethonium, a functional blockade of capsaicin-sensitive neurons or by antagonists acting at TRPV1 or TRPA1, but was abolished by the P2 purinoceptor antagonist PPADS (50 μM). It is concluded that cholinergic motoneurons are activated by a purinergic mechanism in the course of the AITC response, independently of capsaicin-sensitive processes or even TRPA1.


Clinics in diagnostic imaging (183).
Hydrocoele of the canal of Nuck is a rare condition in adult women caused by a failure of complete obliteration of the canal of Nuck. It may be likened to a patent processus vaginalis in men. In most cases, the diagnosis is made during surgery as it is often mistaken for an inguinal hernia. We report a case where the diagnosis of this condition was made preoperatively on imaging. The salient anatomy, clinical features, radiological images and surgical management are discussed and the medical literature reviewed.


A Risk-Based Approach for Managing Affinity Resin Contaminations.
This commentary outlines a proposed approach for navigating remediation (non-routine sanitization) of contaminated affinity-based resins. The methodology for collection of relevant information and for subsequent decision-making is presented, along with a tool for determining risk to the process associated with proposed return-to-use of remediated resin.


Effects of Electroacupuncture on Gut Microbiota and Fecal Metabolites in Rats with Poststroke Depression.
Poststroke depression (PSD) is the most frequent neuropsychiatric consequence of stroke. Electroacupuncture (EA) has been found to be an effective therapy for treating PSD. However, the underlying mechanisms of EA's efficacy remain unclear. This research aimed to investigate the effects of EA on alterations in gut microbiota and fecal metabolome in PSD rats. Analyses of gut microbiome and fecal metabolome were performed to identify gut microbes and their functional metabolites in a sham group, PSD group, and EA group. We conducted enrichment analysis to identify the differential metabolic pathways in three groups. Correlations between altered gut microbes and differential metabolites after EA treatment were studied. PSD showed decreased species-richness/diversity indices of microbial composition, characterized by an increase in Muribaculaceae, Peptostreptococcaceae, Oscillospiraceae, Ruminococcaceae, and Clostridiaceae and a decrease in Lactobacillaceae, Lachnospiraceae, and Bacteroidaceae. Of these, the abundance of Muribaculaceae, Lactobacillaceae, Lachnospiraceae, Peptostreptococcaceae, and Clostridiaceae were reversed by EA. Furthermore, PSD was associated with 34 differential fecal metabolites, mainly belonging to steroid hormone biosynthesis, that could be regulated by EA. Regulation of gut microbiome and lipid metabolism could be one of the potential mechanisms for EA treatment for alleviating the depressive behaviors of PSD.


Does early adolescent sex cause depressive symptoms?
A recent study by the Heritage Foundation (Rector, Johnson, & Noyes, 2003) found evidence of a positive relationship between early sexual intercourse and depressive symptoms. This finding has been used to bolster support for funding abstinence only sex education. However, promoting abstinence will only yield mental health benefits if there is a causal link between sexual intercourse and depression. Using the National Longitudinal Study of Adolescent Health (Add Health), I carefully examine the relationship between early teen sex and several measures of depression. Controlling for a wide set of individual level and family level observable characteristics, cross section estimates consistently show a significant positive relationship between early sexual activity for females and three measures of adverse mental health: self reported depression, a belief that one's life is not worth living, and serious thoughts of suicide. However, difference-in-difference estimates reflect no evidence of a significant relationship between early teen sex and depressive symptoms. These findings suggest that the positive association observed by Rector et al. (2003) can be explained by unmeasured heterogeneity. Thus, promoting abstinence among adolescents is unlikely to alleviate depressive symptoms


Reversal of end-stage heart failure in juvenile hemochromatosis with iron chelation therapy: a case report.
Juvenile hemochromatosis is the most severe form of iron overloading phenotype. Although rare, it should be suspected in patients who present with hypogonadotropic hypogonadism, diabetes mellitus, or cardiomyopathy without a clear cause. A young Serbian male presenting with end-stage heart failure was referred for extracorporeal membrane oxygenation. An endomyocardial biopsy revealed cytoplasmic iron deposits in myocytes. His condition was stabilized with biventricular assist devices and he was listed for heart transplantation. Iron chelation therapy was commenced and resulted in rapid removal of iron burden. Serial outpatient echocardiograms demonstrated myocardial recovery such that a successful biventricular assist device explant occurred 131 days after initial implant. Targeted gene sequencing revealed a loss-of-function mutation within the HJV gene, which is consistent with juvenile hemochromatosis. This rare case of a patient with juvenile hemochromatosis associated with a HJV mutation provides histologic evidence documenting the reversal of associated end-stage heart failure, requiring emergent mechanical circulatory support, with iron chelation therapy.


Comparative hemodynamic studies of isradipine and dihydralazine in atherosclerotic and normal rabbits.
The hemodynamic effects of the calcium antagonist isradipine (code name PN 200-110) and the arteriolar vasodilator dihydralazine were compared in atherosclerotic (cholesterol-fed) and normal conscious rabbits with implanted catheters. Regional blood flows were measured using the microsphere technique. Cardiac output and blood flow to several organs, especially to the gastrointestinal system, but not to the heart and brain, were lower in atherosclerotic rabbits than in normal ones. Intravenous isradipine (10 and 30 micrograms/kg) increased heart rate less in atherosclerotic than in normal rabbits. Isradipine had no effect on the surface electrocardiogram (ECG). In contrast, 0.4 mg/kg dihydralazine caused depression of the ST segment while decreasing blood pressure similarly. This was explained partly by an intramyocardial maldistribution of coronary blood flow (using microspheres). Isradipine increased and dihydralazine decreased flow to the brain. Isradipine redistributed cardiac output in atherosclerotic and normal animals in favor of the heart, brain, and skeletal muscle. However, in atherosclerotic animals, the high dose was less effective than the low dose in some vascular beds. Thus, isradipine is not a general vasodilator in either atherosclerotic or in normal animals, but favors the vital organs. This redistribution of cardiac output contrasts favorably with that induced by dihydralazine.


Quality control and validation.
This chapter discusses two important aspects of the structure determination process that are related to the accuracy and reliability of the crystallographic model under investigation. Quality control is defined as the analysis of an intermediate model to identify aspects of it that are unusual in some sense and that could, therefore, be a result of errors in the model building or refinement process. Any such errors need to be fixed, if at all possible, prior to analysis and publication of the model. Validation is the process of assessing the reliability of the final model (or certain aspects of it, e.g., the active site residues) that is about to be analyzed, published, deposited, and possibly used in follow-up studies.


Transfusion of bone marrow red cells during bone marrow harvests.
Large volumes of bone marrow may be required for certain types of autologous bone marrow transplants. The present study was done to determine whether red cells obtained during a bone marrow harvest would be useful in reducing homologous transfusion requirements. A group of patients receiving standard transfusion support during the harvest (group 1) was compared to a group that received processed bone marrow red cells (PBMRBC) (group 2). Using the Cobe 2991 cell processor, 90% of the harvested bone marrow red cells were extracted and transfused during the procedure. Group 2 received a median of 1500 ml of blood processed from the bone marrow or 413 ml (volume of marrow processed x hematocrit) of red cells. Infusion of the PBMRBC reduced the homologous transfusion requirement from 6.5 units to 3.0 units (p = 0.02). In addition, group 1 had a 20% decrease in hematocrit following transfusion compared to the pre-harvest hematocrit, as opposed to an 8% decrease in group 2 (p = 0.02). This study indicates that PBMRBC can reduce the homologous transfusion requirements during an autologous bone marrow harvest.


Membranoproliferative glomerulonephritis in association with chronic lymphocytic leukaemia: a report of three cases.
The reported association of glomerular disease with chronic lymphocytic leukaemia (CLL) is rare despite the relative frequency of this type of leukaemia. Hence, we have examined the renal biopsies in three patients with CLL and glomerulonephritis. Renal biopsies were examined by light microscopy, immunofluorescence microscopy and electron microscopy. One of two patients with mild impairment of renal function and an active urinary sediment had ultrastructural features of idiopathic type I membranoproliferative glomerulonephritis (MPGN), and the other had features of fibrillary/ immunotactoid glomerulonephritis with deposits of IgG and C3. One patient with nephrotic syndrome had characteristic electron microscopic appearances of type III MPGN. In all three there was an association with monoclonal gammopathy. The parameters of glomerular damage improved in association with response to drug treatment of the CLL. There is a spectrum of types of MPGN seen in patients with CLL and there appears to be an association with the presence of monoclonal gammopathy. This is the first reported case of type III MPGN in CLL.


A suggested classification for two groups of Campylobacter myoviruses.
Most Campylobacter bacteriophages isolated to date have long contractile tails and belong to the family Myoviridae. Based on their morphology, genome size and endonuclease restriction profile, Campylobacter phages were originally divided into three groups. The recent genome sequencing of seven virulent campylophages reveal further details of the relationships between these phages at the genome organization level. This article details the morphological and genomic features among the campylophages, investigates their taxonomic position, and proposes the creation of two new genera, the "Cp220likevirus" and "Cp8unalikevirus" within a proposed subfamily, the "Eucampyvirinae"


Post-CABG Deep Sternal Wound Infection: A Retrospective Comparative Analysis of Early versus Late Referral to a Plastic Surgery Unit in a Tertiary Care Center.
Background Deep sternal wound infections (DSWI) following median sternotomy are initially treated by the cardiothoracic surgeons and are referred to a plastic surgical unit late in the course of time. Methods This is a retrospective review done in a tertiary care teaching institute from January 2005 to June 2018 and the data of 72 patients who had DSWI out of 4,214 patients who underwent median sternotomy for coronary artery bypass grafting (CABG) was collected with respect to the duration between CABG and presentation of DSWI as well as time of referral to a plastic surgery unit. We defined early referral as < or equal to 15 days from presentation and late referral as > 15 days. Both groups were compared with respect to multiple parameters as well as early and late postoperative course, postoperative complications, and mortality. Results The early group had 33 patients, while the late group had 39 patients. The number of procedures done by the cardiothoracic team before referral to the plastic surgery unit is significant ( p = 0.002). The average duration from the presentation of DSWI to definitive surgery was found to be 16.58 days in the early group and 89.36 days in the late group. The rest of the variables that were compared in both the groups did not have significant differences. Conclusion There is no statistical difference between early and late referral to plastic surgery in terms of mortality and morbidity. Yet, early referrals could lead to highly significant reduction in total duration of hospital stay, wound healing, and costs. Early referral of post-CABG DSWIs to Plastic surgeons by the cardiothoracic surgeons is highly recommended.


Effects of cigarette smoking on lexical decision-making.
10 habitual smokers, aged 19-25 yr., were randomly assigned to smoke either a very low nicotine "Placebo" cigarette (.05-mg nicotine delivery as estimated by the FTC method) or a Nicotine cigarette (.7-mg estimated nicotine delivery). Each participant was asked to abstain from smoking for 4 to 7 hr. prior to testing. After completing a presmoking test of lexical decision-making, participants smoked either a Nicotine or Placebo cigarette and were then retested for reaction times and accuracy on the lexical decision test. When presented the most difficult lexical decisions, participants responded significantly faster after smoking a Nicotine cigarette than they did before smoking; smoking a Placebo cigarette did not affect reaction times. Response accuracy was unaffected by smoking either kind of cigarette. These results suggest that smoking a nicotine cigarette may improve attention or memory retrieval after several hours of smoking abstinence.


Rat basophilic leukemia cell lines defective in phospholipid methyltransferase enzymes, Ca2+ influx, and histamine release: reconstitution by hybridization.
Variants of the rat basophilic leukemia (RBL) cell line were isolated and screened for phospholipid methyltransferase I and II activities, enzymes that convert phosphatidylethanolamine to phosphatidylcholine. Two variants were found that had decreased phospholipid methyltransferase enzyme levels and were unable to cause an influx of Ca2+ or release histamine in an IgE-mediated reaction. However, these cells were able to release histamine through an ionophore-induced reaction, indicating that the releasing mechanism distal to the Ca2+ channel was intact. One cell line, 1C1.B1, had low specific activity for phospholipid methyltransferase I. A second variant, 2H3.B6, had reduced phospholipid methyltransferase II activity. Although both variants were unable to incorporate label from [methyl-3H]methionine or [3H]serine into phosphatidylcholine, they were able to incorporate [methyl-3H]choline and myo-[2-3H(N)]inositol into phospholipids. Fusion of the two cell lines and isolation on selective media resulted in the growth of eight independent hybrids. All eight had an increased number of chromosomes and normal phospholipid methyltransferase activities. Stimulation of the hybrids with IgE resulted in CA2+ influx and histamine release. These results indicate that phospholipid methylation precedes and is necessary for Ca2+ influx, and they further support the hypothesis that methylation is a necessary early step in the IgE-mediated histamine release reaction in RBL cells.


Method of measuring the coupled lattice functions at the interaction point in e+e- storage rings.
We have investigated a method of measuring the complete lattice functions including the coupling parameters at any azimuthal position in a periodic and symplectic system. In particular, the method is applied to measure the lattice functions at the interaction point where the beams collide. It has been demonstrated that a complete set of lattice functions can be accurately measured with two adjacent beam position monitors and the known transformation matrix between them. As a by-product, the method also automatically measures the complete one-turn matrix.


Nuclear distribution of glutamate, gamma-aminobutyrate and aspartate within the normal human thalamus.
Detailed mapping of amino acid neurotransmitter candidates, glutamate, gamma-aminobutyrate and aspartate within the human thalamus, was performed with a grid microdissection method using two horizontal slices of the right thalamus from four neurologically normal cases. Although the fine distribution of these amino acids varied considerably from case to case, characteristic patterns of distribution for each amino acid could be demonstrated by superimposing maps of each case. Glutamate was high around a caudal part of nucleus medialis and a rostral part of nucleus pulvinaris. Interestingly enough, gamma-aminobutyrate distributed in a similar manner to glutamate, suggesting the possible interaction between glutamate and gamma-aminobutyrate in these areas of the thalamus. The distribution of aspartate was different from the former two amino acids and highly concentrated areas were patchy and scattered in the middle part of the thalamus. The results were discussed in relation to the recently accumulated evidence obtained from animal brains for neurotransmitter roles of these amino acids in the thalamus.


Genetic transformation of Robinia pseudoacacia by Agrobacterium tumefaciens.
Transgenic Robinia pseudoacacia plants were obtained by Agrobacterium tumefaciens mediated gene transfer. Agrobacterium strain LBA4404 harbouring a binary vector that contained the chimeric neomycin phosphotransferase II (NPTII) and beta-glucuronidase (GUS) genes was co-cultivated with hypocotyl segments of in vitro raised seedlings of Robinia. Parameters important for high efficiency regeneration and transformation rates included type of explant, pre-conditioning of explants and appropriate length of co-cultivation period with Agrobacterium. A transformation frequency 16.67% was obtained by 48 hr of pre-conditioning followed by 48 hr of co-cultivation. Transformed tissue was selected by the ability to grow on kanamycin containing medium. Successful regeneration was followed after histochemical GUS assay for the detection of transgenic tissue. This transformation procedure has the potential to expand the range of genetic variation in Robinia.


Rationally Targeted Mutations at the V1V2 Domain of the HIV-1 Envelope to Augment Virus Neutralization by Anti-V1V2 Monoclonal Antibodies.
HIV-1 envelope glycoproteins (Env) are the only viral antigens present on the virus surface and serve as the key targets for virus-neutralizing antibodies. However, HIV-1 deploys multiple strategies to shield the vulnerable sites on its Env from neutralizing antibodies. The V1V2 domain located at the apex of the HIV-1 Env spike is known to encompass highly variable loops, but V1V2 also contains immunogenic conserved elements recognized by cross-reactive antibodies. This study evaluates human monoclonal antibodies (mAbs) against V2 epitopes which overlap with the conserved integrin α4β7-binding LDV/I motif, designated as the V2i (integrin) epitopes. We postulate that the V2i Abs have weak or no neutralizing activities because the V2i epitopes are often occluded from antibody recognition. To gain insights into the mechanisms of the V2i occlusion, we evaluated three elements at the distal end of the V1V2 domain shown in the structure of V2i epitope complexed with mAb 830A to be important for antibody recognition of the V2i epitope. Amino-acid substitutions at position 179 that restore the LDV/I motif had minimal effects on virus sensitivity to neutralization by most V2i mAbs. However, a charge change at position 153 in the V1 region significantly increased sensitivity of subtype C virus ZM109 to most V2i mAbs. Separately, a disulfide bond introduced to stabilize the hypervariable region of V2 loop also enhanced virus neutralization by some V2i mAbs, but the effects varied depending on the virus. These data demonstrate that multiple elements within the V1V2 domain act independently and in a virus-dependent fashion to govern the antibody recognition and accessibility of V2i epitopes, suggesting the need for multi-pronged strategies to counter the escape and the shielding mechanisms obstructing the V2i Abs from neutralizing HIV-1.


Interfacial charge-transfer transitions in a TiO2-benzenedithiol complex with Ti-S-C linkages.
Interfacial charge-transfer (ICT) transitions between organic materials and inorganic semiconductors are a new mechanism for light absorption at organic-semiconductor interfaces. ICT transitions cause one-step interfacial charge separation without loss of energy. This feature is potentially useful to realize efficient organic-inorganic hybrid solar cells. ICT transitions have been examined by employing titanium dioxide (TiO2) nanoparticles chemisorbed with π-conjugated molecules via Ti-O-C linkages. Here, we report ICT transitions in a TiO2 and 1,2-benzenedithiol (BDT) complex with Ti-S-C linkages. BDT adsorbs on TiO2 by the bridging bidentate coordination of the sulfur atoms to surface titanium atoms. The TiO2-BDT complex shows ICT transitions from the BDT moiety to the conduction band of TiO2 in the visible region. The ICT transitions occur by orbital overlaps between the d orbitals of the surface titanium atoms and the π orbitals of the benzene ring. Our density-functional-theory (DFT) analysis reveals that the 3p valence orbitals of the sulfur bridging atoms contribute to more than 50% of the highest occupied molecular orbital (HOMO) and the 3d-3p(sulfur)-π interaction via the Ti-S-C linkage enhances the electronic mixing between the titanium atoms and the benzene moiety as compared to the 3d-2p(oxygen)-πvia the Ti-O-C linkage. This result indicates the important role of the heavier-atom linkers for strong organic-inorganic electronic couplings.


Prolonged induction activates Cebpα independent adipogenesis in NIH/3T3 cells.
3T3-L1 cells are widely used to study adipogenesis and insulin response. Their adipogenic potential decreases with time in the culture. Expressing exogenous genes in 3T3-L1 cells can be challenging. This work tries to establish and characterize an alternative model of cultured adipocytes that is easier to work with than the 3T3-L1 cells. INDUCED CELLS WERE IDENTIFIED AS ADIPOCYTES BASED ON THE FOLLOWING THREE CHARACTERISTICS: (1) Accumulation of triglyceride droplets as demonstrated by oil red O stain. (2) Transport rate of 2-deoxyglucose increased after insulin stimulation. (3) Expression of fat specific genes such as Fabp4 (aP2), Slc2a4 (Glut4) and Pparg (PPARγ). Among the cell lines induced under different conditions in this study, only NIH/3T3 cells differentiated into adipocytes after prolonged incubation in 3T3-L1 induction medium containing 20% instead of 10% fetal bovine serum. Rosiglitazone added to the induction medium shortened the incubation period from 14 to 7 days. The PI3K/AKT pathway showed similar changes upon insulin stimulation in these two adipocytes. C/EBPα mRNA was barely detectable in NIH/3T3 adipocytes. NIH/3T3 adipocytes induced in the presence of rosiglitazone showed higher 2-deoxyglucose transport rate after insulin stimulation, expressed less Agt (angiotensinogen) and more PPARγ. Knockdown of C/EBPα using shRNA blocked 3T3-L1 but not NIH/3T3 cell differentiation. Mouse adipose tissues from various anatomical locations showed comparable levels of C/EBPα mRNA. NIH/3T3 cells were capable of differentiating into adipocytes without genetic engineering. They were an adipocyte model that did not require the reciprocal activation between C/EBPα and PPARγ to differentiate. Future studies in the C/EBPα independent pathways leading to insulin responsiveness may reveal new targets to diabetes treatment.


[Epidemiology of diarrhea caused by Escherichia coli and rotavirus in calves and lambs in Morocco].
An epidemiological survey on E coli and rotavirus associated diarrheas in one to twenty five days old calves and lambs was made in three regions: Rabat-Kenitra, Marrakech and Agadir. Isolated E coli K99 stains have been studied of a biochemical, serotypical (O antigen) and antibiotypical point of view. The identification of rotavirus was made by ELISA test. Persistence of K99 antigen and heat stable toxin A was examined after a conservation of 5 weeks at - 18 degrees C. The frequency of E coli K99 or rotavirus associated diarrheas is respectively 26.9% and 29.7% in calf, 10% and 30% in lamb. This incidence considerably decreases from the 20th day in calf and from the 11th day in lamb. It must be observed that 34.8% of cases of diarrheas in calf and 55% in lamb cannot be ascribed to investigated agents. Only 12 out of 42 E coli K99 strains belong to serogroups O101, O8 and O9. Preservation of strains to - 18 degrees C comes with the loss of K99 antigen. These strains are not toxinogens. Among the strains having kept this antigen, 29% are toxinogens. Surveyings of antibiotics resistance was discussed.


[Difficulties in diagnosing a case of chronic necrotic aspergillosis with an unfavorable course].
A case of chronic necrotic aspergillosis was discussed. Diagnostic and therapeutic difficulties were described in patient with an insufficiency of immune response mainly in polymorphonuclear leukocytes function.


Paracoccus tegillarcae sp. nov., isolated from the gastrointestinal tract of a blood cockle (Tegillarca granosa).
A novel bacterial isolate, designated as strain BM15T, was isolated from the gastrointestinal tract of a blood cockle, Tegillarca granosa, which was collected from the foreshore of Beolgyo-eup, Republic of Korea. Strain BM15T was Gram-stain-negative, non-motile, strictly aerobic and short-rod-shaped. Optimum growth of the isolate occurred at 20 °C, in the presence of 4 % (w/v) NaCl and at pH 6. The 16S rRNA gene sequence analysis showed that strain BM15T belonged to the genus Paracoccus and had more than 97 % 16S rRNA gene sequence similarity to 'Paracoccus zhejiangensis' J6 (97.40 % similarity) and Paracoccus lutimaris HDM-25T (97.04 %). The polar lipid profile of strain BM15T comprised phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, an unidentified glycolipid and two unidentified lipids. The predominant respiratory quinone was ubiquinone-10. The major cellular fatty acid (>20 %) was summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). The complete genome sequence of strain BM15T comprised 3,759,866 bp with 62.2 mol% G+C content. The results of the phylogenetic, phenotypic and genotypic analyses indicated that strain BM15T represents a novel species in the genus Paracoccus, for which the name Paracoccus tegillarcae is proposed. The type strain is BM15T (=KCTC 72032T=JCM 33289T).


Late developmental dislocation of the hip after initial normal evaluation: a report of five cases.
Developmental dysplasia of the hip (DDH) denotes a wide spectrum of pathologies ranging from hip instability to frank dislocation. The current understanding is that cases of late diagnosis were missed during the newborn period. However, there is some evidence that a number of hip subluxations or dislocations may have been clinically stable in the neonatal period, but dislocate late. We present 5 cases of otherwise healthy children with normal physical examinations and hip radiographs in the first 3 months of life who later developed hip dislocations. Four of the 5 cases required surgical open reduction. In light of these cases and others in the literature, normal neonatal screening for DDH does not assure that continued normal development of the hip joint will happen. Our study confirms the existence of another entity in the wide spectrum of DDH: the late hip dislocation. Therefore, hip evaluations should be continued beyond the neonatal period until the child begins to walk. Parents should be informed that hip dislocation can occur in a late form, and they should be encouraged to take their children for repeated evaluations even if the neonatal screening is normal.


[Changes in sweating during exertion. Effects of beta-blocker treatment].
Eccrine sweat secretion is studied during physical stress after the administration of a B-blocking agent: Butofilolol. 20 voluntary normotensive subjects, age 24 + 2 ans are submitted to 2 exercises stress test (ergometric bicycle) performed at on week interval. Butofilolol is administrated at a posology of 200 mg, 24 hours and 2 hours, before the test as well as placebo (double blind). Local sweat output is measured 1 min after stress and in the interscapulary region with an evaporimeter. Sweat weight, sweat electrolyte concentrations (sodium, chloride) are analysed from filters papers placed on the forehead. With butofilolol, significative increases of sweet output (+13%), sweat weight (+20%), and sodium (+20%), chloride (+26%) elimination are observed. The subjective observation of the effects of B-blocking agents is confirmed. The way of action of Butofilolol discussed.


A systematic review and meta-analysis of the impact of cornelian cherry consumption on blood lipid profiles.
Polyphenolic and flavonoid compounds are claimed to improve blood lipid profiles and to provide protective effects against cardiovascular disease. For this reason, we conducted a systematic review and meta-analysis of studies that comprehensively investigated the effects of cornelian cherry supplementation on lipid profiles in rat models. Up to December 2020, 855 articles were screened, and finally, seven articles were selected as eligible for the meta-analysis. This meta-analysis revealed that cornelian cherry supplementation significantly decreased low-density lipoprotein (LDL) (WMD = -6.38 mg/dl; 95% CI, -9.93 to-2.84; p < .001), triglyceride (TG) (WMD = -52.36 mg/dl; 95% CI, -80.50 to -24.22; p < .005), and cholesterol level (WMD = -37.16 mg/dl; 95% CI, -51.19 to -23.13; p < .005) in treated rats compared with control groups. A nonsignificant increase in high-density lipoprotein (HDL) level was observed (WMD = 4.21 mg/dl; 95% CI, -3.25 to 11.66; p = .268). These results suggest that cherry supplementation may have health effects by modifying lipid profiles. However, there is a need for more well-controlled human clinical trials to make more definitive conclusions about the potential health benefits of cherry supplementation.


Activation of tyrosine hydroxylase by nicotine in rat adrenal gland.
The administration of nicotine activates tyrosine hydroxylase in the rat adrenal gland. This activation is apparently maximal 25 min after a single subcutaneous injection of nicotine at 2.3 mg/kg. Repeated injections of nicotine (seven injections once every 30 min) are associated with a persistent activation of adrenal tyrosine hydroxylase for at least 3 h. The nicotinic receptor antagonist hexamethonium does not significantly inhibit the nicotine-mediated activation of tyrosine hydroxylase in innervated adrenal glands. However, hexamethonium completely blocks the activation of adrenal tyrosine hydroxylase by nicotine in denervated adrenal glands. Furthermore, even though a single injection of nicotine activates tyrosine hydroxylase in both innervated and denervated adrenal glands, repeated injections of nicotine do not activate tyrosine hydroxylase in denervated adrenal glands. Our results suggest that the systemic administration of nicotine activates adrenal tyrosine hydroxylase by two mechanisms: (1) via direct interaction with adrenal chromaffin cell nicotinic receptors; and (2) via stimulation of the CNS leading to the release from the splanchnic nerve of substances that interact with adrenal chromaffin cell receptors other than the nicotinic receptor.


Differences in pain and nausea in children operated on by Tonsillectomy or Tonsillotomy - a prospective follow-up study.
To evaluate the differences in postoperative pain, nausea and time of discharge in children 3-12 years old after Tonsillectomy or Tonsillotomy at the postanaesthetic care unit, children's ward and at home. Tonsillectomy involves risk of bleeding, severe postoperative pain and nausea. Tonsillotomy is a less invasive method with lower risk of bleeding, postoperative pain and nausea according to previous studies. A prospective, comparative follow-up study design. From December 2008-April 2009 following parental agreement, 87 children in the ages 3-12 undergoing Tonsillectomy or Tonsillotomy participated. Visual analogue scale was used for children's pain and nausea reports. Significantly, fewer children operated on by the Tonsillotomy reported postoperative pain ≥ 3 according to the visual analogue scale than children operated on by the Tonsillectomy at the postanaesthetic care unit and the children's ward. A statistically significant difference of postoperative nausea was only present during the care at the postanaesthetic care unit and children's ward with fewer Tonsillotomy children reporting nausea ≥ 3. The time of postoperative care was shorter among the Tonsillotomy children in both the postanaesthetic care unit and the children's ward. Postoperative pain and pain related difficulties in eating after discharge was significantly more present among the Tonsillectomy children compared with the Tonsillotomy children. The results of our study showed duration of postoperative pain and nausea in both groups, but indicated that Tonsillotomy is a more favourable alternative than Tonsillectomy in children.


Efficacy of non-heme iron fortified diets: a review.
Iron deficiency anemia (IDA) is prevailing around the globe at variable extent. To combat this phenomenon various strategies are popular. One effective strategy is food fortification. A number of reviews are available to discuss the bioavailability of food fortificants exclusively or in special dietary arrangements with specific food vehicles to access their performance in order to overcome the iron deficiency problem. However, little consideration is given to the efficacy studies of these dietary settings. This review is meant for discussing the efficacy of non-heme iron fortified diets.


Is the cytologic diagnosis of esophageal glandular dysplasia feasible?
Barrett's esophagus is a premalignant condition in which the normal stratified squamous epithelium of the esophagus is replaced by metaplastic glandular epithelium. Patients with Barrett's esophagus are at increased risk for the development of esophageal adenocarcinoma. Because dysplasia precedes the development of frank adenocarcinoma, the cytologic detection of esophageal glandular dysplasia represents a potentially inexpensive and efficient means of monitoring disease progression to adenocarcinoma and identifying high-risk patients. This article discusses the current status of exfoliative cytology as a screening test for glandular dysplasia of the esophagus.


The role of nitric oxide in modulating ischaemia-induced arrhythmias in rats.
The effect of a nitric oxide (NO) donor and the influence of endogenous NO in modulating ischaemia-induced arrhythmias was assessed in anaesthetised rats. The nitric oxide donor C87-3754 (1 mg/kg) caused a significant reduction in arterial blood pressure before coronary artery ligation but did not influence the incidence or severity of ventricular arrhythmias during a 30-min period of myocardial ischaemia [60 and 58% incidence of ventricular fibrillation (VF) in control and treated rats, respectively]. When the hearts were preconditioned by a short (3 min) coronary artery occlusion before the 30-min period of ischaemia, there was a marked reduction in both the number of ventricular ectopic beats (260 +/- 65 vs. 812 +/- 256 beats/min in controls; p < 0.05) and the incidence of ventricular fibrillation (9 vs. 67% in controls; p < 0.05). Neither NG-nitro-L-arginine methyl ester (L-NAME; 10-100 mg/kg) nor methylene blue (1-50 mg/kg) attenuated this marked antiarrhythmic effect of preconditioning. L-NAME caused a significant increase in blood pressure with all doses used, whereas methylene blue did not increase blood pressure. Both L-NAME and methylene blue attenuated ventricular arrhythmias in non-preconditioned hearts. L-NAME reduced the number of ventricular ectopic beats (from 812 +/- 256 to 318 +/- 81 beats/min at 10 mg/kg; p < 0.05), whereas methylene blue decreased the incidence of VF from 67 to 20% at a dose of 50 mg/kg (p < 0.05). These findings suggest that neither endogenous nor exogenously administered NO reduces ischaemic arrhythmias in anaesthetised rats. Furthermore, the antiarrhythmic effect of preconditioning in this species appears to be independent of NO. The antiarrhythmic effects seen with both methylene blue and L-NAME may be the result of actions other than inhibition of the production or actions of NO.


Specificity of action on neuropeptides of an endopeptidase from the synaptosomal membranes of guinea pig brain.
An endopeptidase was solubilized and highly purified from the synaptosomal membrane fraction of guinea pig brain, and its specificity of action on various neuropeptides was investigated. It hydrolyzed specifically the Pro10-Tyr11 bond of neurotensin and showed a marked specificity toward Pro-X bonds present in the interior parts of various neuropeptides and related peptides. No cleavage, however, was observed at the first and second peptide bonds from the NH2-termini or from the COOH-termini of the peptides examined, suggesting that the enzyme requires both NH2- and COOH-terminal extentions of at least 3 residues from the scissile bond for its action. In addition, a limited number of other peptide bonds were cleaved, indicating that the enzyme is not strictly specific to Pro-X bonds. These results suggest the possible implication of this enzyme in the specific degradation of neurotensin and other peptide neurotransmitters in the synaptic cleft.


Enhancement of the endosomal endocytic pathway increases quantal size.
We combined recordings of spontaneous quantal events with electron microscopy analysis of synaptic ultrastructure to demonstrate that the size of a neurosecretory quantum increases following an activation of the endosomal endocytic pathway. We reversibly activated the endosomal endocytic pathway in Drosophila motor boutons by application of high K+ solution. This treatment produced the formation of numerous cisternae, vacuoles and enlarged vesicles. Spontaneous quantal events recorded immediately after the cessation of high K+ application were significantly enlarged, and this increase in quantal size was reversed after a 10 minute resting period. Actin depolymerization produced by latrunculin B pretreatment inhibited both the formation of endosome-like structures and the increase in quantal size. Loading the preparations with the dye FM1-43 followed by photoconversion of the dye combined with electron microscopy analysis revealed that the observed cisternae are likely to be the product of both bulk membrane retrieval and vesicle fusion.


Efficacy of High-Intensity Local Treatment for Metastatic Urothelial Carcinoma of the Bladder: A Propensity Score-Weighted Analysis From the National Cancer Data Base.
Purpose Evidence from studies of other malignancies has indicated that aggressive local treatment (LT), even in the presence of metastatic disease, is beneficial. Against a backdrop of stagnant mortality rates for metastatic urothelial carcinoma of the bladder (mUCB) at presentation, we hypothesized that high-intensity LT of primary tumor burden, defined as the receipt of radical cystectomy or ≥ 50 Gy of radiation therapy delivered to the bladder, affects overall survival (OS). Patients and Methods We identified 3,753 patients within the National Cancer Data Base who received multiagent systemic chemotherapy combined with high-intensity versus conservative LT for primary mUCB. Patients who received no LT, transurethral resection of the bladder tumor alone, or < 50 Gy of radiation therapy delivered to the bladder were included in the conservative LT group. Inverse probability of treatment weighting (IPTW) -adjusted Kaplan-Meier curves and Cox regression analyses were used to compare OS of patients who received high-intensity versus conservative LT. Results Overall, 297 (7.91%) and 3,456 (92.09%) patients with mUCB received high-intensity and conservative LT, respectively. IPTW-adjusted Kaplan-Meier curves showed that median OS was significantly longer in the high-intensity LT group than in the conservative LT group (14.92 [interquartile range, 9.82 to 30.72] v 9.95 [interquartile range, 5.29 to 17.08] months, respectively; P < .001). Furthermore, in IPTW-adjusted Cox regression analysis, high-intensity LT was associated with a significant OS benefit (hazard ratio, 0.56; 95% CI, 0.48 to 0.65; P < .001). Conclusion We report an OS benefit for individuals with mUCB treated with high-intensity versus conservative LT. Although the findings are subject to the usual biases related to the observational study design, these preliminary data warrant further consideration in randomized controlled trials, particularly given the poor prognosis associated with mUCB.


Restenosis after carotid endarterectomy in patients with paired vein and Dacron patch reconstruction.
This is an analysis of restenosis after bilateral carotid endarterectomy (CEA) with saphenous vein patch reconstruction on one side and Dacron patch reconstruction on the other. The possibility that differences in reconstruction geometry between vein and Dacron patched sides effected restenosis outcomes was evaluated as was the value of serial common carotid wall thickness measurements in predicting restenosis. Between 1990 and 1997, 33 bilateral CEA were performed within one year on 22 men and 11 women using a greater saphenous vein patch on one side and a knitted Dacron patch on the other. Interoperative post-CEA geometry was measured. Follow-up was by duplex scans that included wall thickness measurements in the endarterectomized common carotid bulb. Over a mean follow-up of 43 months 10 (30%) Dacron patched and one (3%) vein patched CEA developed > or = 25% restenosis (p = 0.001), seven (21%) Dacron patched and no vein patched CEA developed > or = 50% restenosis (p = 0.01) and four (12%) Dacron patched and no vein patched CEA developed > or = 70% restenosis (p = 0.11). The Kaplan-Meier cumulative > or = 25% restenosis rates for Dacron and vein patched CEA were 22% and 0% at 2 years and 41% and 5% at 5 years respectively (p = 0.002). The cumulative > or = 50% restenosis rates for Dacron and vein patched CEA were 16% and 0% at 2 years and 34% and 0% at 5 years respectively (p = 0.003). The cumulative > or = 70% restenosis rates for Dacron and vein patched CEA were 8% and 0% at 2 years and 20% and 0% at 5 years respectively (p = 0.02). For both patients with and without recurrent stenosis the mean within patient between sides differences of the diameters of the internal carotid, internal carotid bulb, common carotid bulb, and common carotid arteries and the lengths of the internal carotid and total patch segments were not significantly different and all were less than 5%. Common carotid bulb wall thickness measured at the time of identification of the nine unilateral Dacron patched CEA restenosis was 1.5 +/-0.5 mm compared to 1.4 +/-0.4 mm (m +/-1 SD) for the contralateral vein patched CEA (p = 0.45 by paired t test). Dacron patched CEA have a significantly higher incidence of mild, moderate and severe restenosis than do saphenous vein patched CEA independent of systemic risk factors. The within patient equality of Dacron and vein patched carotid reconstruction geometry in patients with unilateral restenosis indicates that patch material is the major local risk factor, not adverse hemodynamics produced by variance in geometry. Common carotid bulb wall thickness measurements after CEA are not predictors or indicators of recurrent stenosis.


Efficacy of rifabutin in the treatment of disseminated infection due to Mycobacterium avium complex. The Rifabutin Treatment Group.
The incidence of infection with Mycobacterium avium complex (MAC) is increasing among patients with AIDS. Although numerous antimicrobial regimens have been proposed as treatment for this infection, it is unclear which therapy is most effective. For this reason, we prospectively evaluated rifabutin (600 mg/d) vs. a placebo, each in combination with clofazimine and ethambutol, for the treatment of MAC bacteremia. Patients in the rifabutin group had a significantly higher rate of microbiological response (defined as either sterilization of the blood or at least a 2-log10 reduction in mycobacterial titers). By week 4 of therapy, 7 of 11 patients receiving rifabutin, vs. 0 of 13 in the placebo group, had responded (P < .001). Similar results were seen at later time points (7 of 10 vs. 1 of 8 responded to rifabutin by week 8, and 6 of 9 vs. 1 of 7 responded to a placebo by week 12). These results indicate that, in combination with other antimicrobial agents, rifabutin may be effective in the treatment of disseminated MAC infection.


Non-Conduit Repair of Truncus Arteriosus.
The procedure of choice for treatment of truncus arteriosus is one-stage repair within the first few months of life. Establishing right ventricle-pulmonary artery direct continuity without conduit can be a good alternative in the absence of valved conduits in developing centers. Between January 2021 and June 2021, a total of five patients (three males, two females) underwent definitive repair of truncus arteriosus without an extracardiac conduit. We used the Barbero-Marcial technique to allow age-related growth, eliminate the risk of conduit-related complications, and to avoid forcing a conduit to place in a very small mediastinal space. The patients' mean age was 31.2 days (11-54 days). Their mean bodyweight was 3.2 kg (2.7-3.8kg). Mean postoperative intensive care unit stay was 39.6 days (7-99 days). There were two mortalities in the intensive care unit on postoperative days 12 and 61 due to lung-related problems. The remaining three cases' mean ventilation time was 15.6 days (8-22 days). Having access to a valved conduit is still challenging for some centers, and the non-conduit repair technique defined by Barbero-Marcial can be a successful, life-saving alternative easy for young surgeons to perform in newly based centers.


Products of 5-lipoxygenase and myeloperoxidase activities are increased in young male cigarette smokers.
The significance of 5-lipoxygenase and myeloperoxidase activities has not been extensively studied among young male smokers. Leukotriene B(4), 20-hydroxy-leukotriene B(4), 20-carboxy-leukotriene B(4) and 3-chlorotyrosine were measured in plasma and urinary samples of young male smokers at 8 hours following cigarette abstinence and an hour after cigarette smoking. Leukotriene B(4) and 3-chlorotyrosine were determined in neutrophils isolated from these individuals. The levels of these markers were compared with those of age-matched controls. In vitro studies were performed to evaluate the production of leukotriene B(4) and 3-chlorotyrosine from human neutrophils following exposure to nicotine and cotinine. Thirty male smokers (mean age, 27.4 years) and 28 male non-smokers (mean age, 28.7 years) were studied. Plasma levels of leukotriene B(4), 20-carboxy-leukotriene B(4) and 3-chlorotyrosine were higher in smokers than in non-smokers; leukotriene B(4) and 20-carboxy-leukotriene B(4) levels increased further an hour after cigarette smoking. Peripheral neutrophils isolated from smokers showed greater expressions of myeloperoxidase and 5-lipoxygenase activities compared with non-smokers, while plasma leukotriene B(4) and 3-chlorotyrosine were correlated significantly with high-sensitivity C-reactive protein and plasma nicotine concentrations. Exposure of human neutrophils to nicotine and cotinine resulted in a higher production of leukotriene B(4) and 3-chlorotyrosine. To conclude, leukotriene B(4) and 3-chlorotyrosine levels are increased in young male cigarette smokers. These results suggest that cigarette smoking aggravates neutrophil-mediated inflammation by modulating the activities of myeloperoxidase and 5-lipoxygenase pathways.


Synchrotron Radiation Lithography for Manufacturing Integrated Circuits Beyond 100 nm.
Extreme ultraviolet lithography is a powerful tool for printing features of 0.1 micro m and below; in Japan and the USA there is a growing tendency to view it as the wave of the future. With Schwarzschild optics, replication of a 0.05 micro m pattern has been demonstrated in a 25 micro m square area. With a two-aspherical-mirror system, a 0.15 micro m pattern has been replicated in a ring slit area of 20 mm x 0.4 mm; a combination of this system with illumination optics and synchronized mask and wafer stages has enabled the replication of a 0.15 micro m pattern in an area of 10 mm x 12.5 mm. Furthermore, in the USA, the Sandia National Laboratory has succeeded in fabricating a fully operational NMOS transistor with a gate length of 0.1 micro m. The most challenging problem is the fabrication of mirrors with the required figure error of 0.28 nm. However, owing to advances in measurement technology, mirrors can now be made to a precision that almost satisfies this requirement. Therefore, it is time to move into a rapid development phase in order to obtain a system ready for practical use by the year 2004. In this paper the status of individual technologies is discussed in light of this situation, and future requirements for developing a practical system are considered.


Clearance of 9-micron spheres and rubidium in the intestinal circulation.
Rubidium clearance and 9-micron-sphere entrapment were studied and compared in isolated intestinal preparations under various physiological conditions in 10 dogs anesthetized with intravenous pentobarbital sodium. The chosen intestinal segment was pumped with aortic blood at a constant rate and pressure of about 90-100 mmHg. The temperature of the isolated loop was maintained at 37-38 degrees C with an electrical pad. A mixture of 86Rb and 9-micron-spheres labeled with 141Ce was injected into the arterial cannula supplying the intestinal loop while mesenteric venous blood was collected for activity counting. Three to four intestinal segments were used from each dog. The following three experimental conditions were randomly used for each intestinal segment preparation: 1) a mesenteric venous pressure (MVP) equaling 0 cmH2O and warmed normal saline infused into the lumen of segment; 2) an MVP equaling 0 cmH2O and 5% glucose in saline infused into the intestinal lumen; and 3) the reservoir with venous blood elevated to provide an MVP equaling 17 cmH2O and warmed normal saline infused into the intestinal lumen. A very strong and significant correlation was found between rubidium and microsphere clearances (r = 0.99, P less than 0.0001). Rubidium extraction was inversely associated with blood flow through the intestinal segment (r = 0.49, P = 0.02), while microsphere entrapment (extraction) was independent from intestinal blood flow (r = 0.16). The data suggest that the shunting of 9-micron spheres through tissue reflects the arteriovenous shunting of blood and, therefore, can be used as a tool to study the nutritive and nonnutritive blood flows in tissues.


Solvent-free microwave-assisted peroxidative oxidation of secondary alcohols to the corresponding ketones catalyzed by copper(ii) 2,4-alkoxy-1,3,5-triazapentadienato complexes.
A facile, efficient and selective solvent-free synthesis of ketones from secondary alcohols with tert-butylhydroperoxide (TBHP) as the oxidant under microwave irradiation is achieved, where the copper(ii) 2,4-alkoxy-1,3,5-triazapentadienato complexes are efficient catalysts providing high yields (up to 100%), TONs (up to 890) and TOFs (up to 1780 h(-1)).


New themes in the biological functions of 5-methylcytosine and 5-hydroxymethylcytosine.
5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) play a critical role in development and normal physiology. Alterations in 5-mC and 5-hmC patterns are common events in hematopoietic neoplasms. In this review, we begin by emphasizing the importance of 5-mC, 5-hmC, and their enzymatic modifiers in hematological malignancies. Then, we discuss the functions of 5-mC and 5-hmC at distinct genic contexts, including promoter regions, gene bodies, intron-exon boundaries, alternative promoters, and intragenic microRNAs. Recent advances in technology have allowed for the study of 5-mC and 5-hmC independently and specifically permitting distinction between the bases that show them to have transcriptional effects that vary by their location relative to gene structure. We extend these observations to their functions at enhancers and transcription factor binding sites. We discuss dietary influences on 5-mC and 5-hmC levels and summarize the literature on the effects of folate and vitamin C on 5-mC and 5-hmC, respectively. Finally, we discuss how these new themes in the functions of 5-mC and 5-hmC will likely influence the broader research field of epigenetics.


Sensitization of hypoxic normal tissue.
The radiosensitization by misonidazole of three normal tissues in the unanaeshtetized mouse (femoral marrow, intestinal crypts and the target tissue for tail necrosis) has been studied. At 1 mg/g body weight, no sensitization was observed for the former two tissues, and no cytotoxicity for marrow was demonstrated. Sensitization of fully anoxic marrow or tail shown, by a factor of 1.8--1.9, in comparison with normal tails (factor 1.5). Clamping experiments revealed the homogenous nature of the natural hypoxia in the tissue responsible for tail necrosis, and an effective increase in the oxygenation was seen at Day 7 after a large priming dose.


[Plasmids and mobile genetic elements of pathogenic Yersinia bacteria].
The review of literature is devoted to molecular and genetic organization of movable genetic elements responsible for synthesis of pathogenicity factors of Yersinia bacteria. General characterization of Yersinia pathogenicity factors is given. We analysed the role of plasmids in expression of the pathogenic properties of these bacteria and the role of IS elements of Yersinia in expression of genes encoding synthesis of the pathogenicity factors. Replicative properties of Yersinia plasmids are described. The role of chromosomal genes in regulation of synthesis of the plasmid-specific pathogenicity factors is discussed.


A new genus and species of marine catfishes (Siluriformes; Ariidae) from the upper Eocene Birket Qarun Formation, Wadi El-Hitan, Egypt.
Wadi El-Hitan, the UNESCO World Heritage Site, of the Fayum Depression in the northeast part of the Western Desert of Egypt, has produced a remarkable collection of Eocene vertebrates, in particular the fossil whales from which it derives its name. Here we describe a new genus and species of marine catfishes (Siluriformes; Ariidae), Qarmoutus hitanensis, from the base of the upper Eocene Birket Qarun Formation, based on a partial neurocranium including the complete left side, partial right dentary, left suspensorium, two opercles, left pectoral girdle and spine, nuchal plates, first and second dorsal spines, Weberian apparatus and a disassociated series of abdominal vertebrae. All of the elements belong to the same individual and some of them were found articulated. Qarmoutus gen. nov. is the oldest and the most complete of the Paleogene marine catfishes unearthed from the Birket Qarun Formation. The new genus exhibits distinctive features not seen in other African Paleogene taxa, such as different sculpturing on the opercle and pectoral girdle with respect to that on the neurocranium and nuchal plates, denticulate ornamentation on the skull bones arranged in longitudinal rows and forming a radiating pattern on the sphenotic, pterotic, extrascapular and the parieto-supraoccipital, indentations or pitted ornamentation on the nuchal plates as well as the parieto-supraoccipital process, strut-like radiating pattern of ornamentation on the opercle from the proximal articulation to margins, longitudinal, curved, reticulate ridges and tubercular ornamentations on the cleithrum, sinuous articulation between the parieto-supraoccipital process and the anterior nuchal plate, long, narrow, and arrowhead shaped nuchal shield, very small otic capsules restricted to the prootic. Multiple parsimony and Bayesian morphological phylogenetic analyses of Ariidae, run with and without "molecular scaffolds", yield contradictory results for the placement of Qarmoutus; the genus is either a phylogenetically basal ariid, or it is deeply nested within the ariid clade containing New World species of Sciades.


Acute toxic hepatitis induced by a herbal medicine : Anchusa Boraginaceae.
Herbal treatments are becoming increasingly popular in many countries. Anchusa Boraginaceae (also called Tort plant and beef tongue) is commonly used as a herbal medicine in Elazıg region as diuretic and in the treatment of ulcers, and it is stated that this has no adverse effect. We report a case of acute hepatitis associated with long time use of high doses of Anchusa Boraginaceae. A 43-year-old male patient is drinking water of Anchusa Boraginaceae that is boiling for 14 days to dissolve the stones in the gallbladder. He had no medical history and did not take any other drugs or toxins. Two weeks later ; he admitted with developed tea colored like urine and yellowing of the body. Three weeks later; he was referred to the our department from the epicenter. Blood tests showed aspartate aminotransferase : 37 U/L, alanine aminotransferase : 66 U/L, gama glutamyl transferase : 23 U/L, total bilirubin : 16.9 mg/dL, direct bilirubin : 12 mg/dL, and INR : 1.3 Viral and autoimmune hepatitis were eliminated. Upper abdominal ultrasound was normal. After the herbal medicine was stopped on admission, the patient's laboratory tests didn't recover. Then; the support treatment was performed. The clinical and the laboratory values returned to normal after 2 months after the acute episode. The consumption of herbal medicines containing Anchusa Boraginaceae can induce toxic hepatitis. Recovery can be complete after discontinuation. This case report highlights the risk and lytic effect on gallstone associated with Anchusa Boraginaceae.


Comparison of contractile behavior of native murine ventricular tissue and cardiomyocytes derived from embryonic or induced pluripotent stem cells.
Cardiomyocytes generated from embryonic stem cells (ESCs) and induced pluripotent stem (iPS) cells are suggested for repopulation of destroyed myocardium. Because contractile properties are crucial for functional regeneration, we compared cardiomyocytes differentiated from ES cells (ESC-CMs) and iPS cells (iPS-CMs). Native myocardium served as control. Murine ESCs or iPS cells were differentiated 11 d in vitro and cocultured 5-7 d with irreversibly injured myocardial tissue slices. Vital embryonic ventricular tissue slices of similar age served for comparison. Force-frequency relationship (FFR), effects of Ca(2+), Ni(2+), nifedipine, ryanodine, beta-adrenergic, and muscarinic modulation were studied during loaded contractions. FFR was negative for ESC-CMs and iPS-CMs. FFR was positive for embryonic tissue and turned negative after treatment with ryanodine. In all groups, force of contraction and relaxation time increased with the concentration of Ca(2+) and decreased with nifedipine. Force was reduced by Ni(2+). Isoproterenol (1 microM) increased the force most pronounced in embryonic tissue (207+/-31%, n=7; ESC-CMs: 123+/-5%, n=4; iPS-CMs: 120+/-4%, n=8). EC(50) values were similar. Contractile properties of iPS-CMs and ESC-CMs were similar, but they were significantly different from ventricular tissue of comparable age. The results indicate immaturity of the sarcoplasmic reticulum and the beta-adrenergic response of iPS-CMs and ESC-CMs.


Anti-apoptotic potential of several antidiabetic medicinal plants of the eastern James Bay Cree pharmacopeia in cultured kidney cells.
Our team has identified 17 Boreal forest species from the traditional pharmacopeia of the Eastern James Bay Cree that presented promising in vitro and in vivo biological activities in the context of type 2 diabetes (T2D). We now screened the 17 plants extracts for potential anti-apoptotic activity in cultured kidney cells and investigated the underlying mechanisms. MDCK (Madin-Darnby Canine Kidney) cell damage was induced by hypertonic medium (700 mOsm/L) in the presence or absence of maximal nontoxic concentrations of each of the 17 plant extracts. After 18 h' treatment, cells were stained with Annexin V (AnnV) and Propidium iodide (PI) and subjected to flow cytometry to assess the cytoprotective (AnnV-/PI-) and anti-apoptotic (AnnV+/PI-) potential of the 17 plant extracts. We then selected a representative subset of species (most cytoprotective, moderately so or neutral) to measure the activity of caspases 3, 8 and 9. Gaultheria hispidula and Abies balsamea are amongst the most powerful cytoprotective and anti-apoptotic plants and appear to exert their modulatory effect primarily by inhibiting caspase 9 in the mitochondrial apoptotic signaling pathway. We conclude that several Cree antidiabetic plants exert anti-apoptotic activity that may be relevant in the context of diabetic nephropathy (DN) that affects a significant proportion of Cree diabetics.


Final-Year Dental Undergraduate Attitudes towards Specialisation.
The aim of this study was to explore the attitudes towards postgraduate specialisation of final-year students at one UK dental school and to identify any possible influencing factors. A cross-sectional survey of all 73 final-year students using an anonymous self-report questionnaire was carried out. The response rate was 79%, of which nearly two-thirds were female. Age, ethnicity and parental occupation did not have an effect on the intention to specialise, although student gender did, with more females not wishing to specialise (p = 0.006). Having a 'talent in the field' had the largest positive influence on pursuing a specialist career (37.9% of responses), whilst the length of time needed to obtain a specialist qualification was seen as the largest negative influence (41.1% of responses). The two most popular subjects were Restorative Dentistry and Orthodontics with 24.1% and 20.7% of students listing them as their first choices, respectively. Further research could be carried out to determine if the intentions of UK undergraduates to specialise will meet the increasing specialist oral health needs of the population and which could ultimately influence future dental workforce planning.


Control of rubella and congenital rubella syndrome (CRS) in developing countries, Part 1: Burden of disease from CRS.
Congenital rubella syndrome (CRS) can lead to deafness, heart disease, and cataracts, and a variety of other permanent manifestations. In developing countries, the burden of CRS has been assessed as follows: by surveillance of CRS; by surveillance of acquired rubella; by age-stratified serosurveys; and by serosurveys documenting the rubella susceptibility of women of childbearing age. During rubella outbreaks, rates of CRS per 1000 live births were at least 1.7 in Israel, 1.7 in Jamaica, 0.7 in Oman, 2.2 in Panama, 1.5 in Singapore, 0.9 in Sri Lanka, and 0.6 in Trinidad and Tobago. These rates are similar to those reported from industrialized countries during the pre-vaccine era. Special studies of CRS have been reported from all WHO regions. Rubella surveillance data show that epidemics occur every 4-7 years, similar to the situation in Europe during the pre-vaccination era. In developing countries, the estimated average age at infection varies from 2-3 years to 8 years. For 45 developing countries we identified serosurveys of women of childbearing age that had enrolled > or = 100 individuals. The proportion of women who remained susceptible to rubella (e.g. seronegative) was < 10% in 13 countries. 10-24% in 20 countries, and > or = 25% in 12 countries. Discussed are methods to improve the surveillance of rubella and CRS in developing countries.


The differential diagnosis and surveillance of hereditary gastrointestinal polyposis syndromes.
Hereditary gastrointestinal polyposis syndromes account for about 1% of all cases of colorectal cancer and are associated with a broad spectrum of extracolonic tumors. The early detection and accurate classification of these syndromes are essential, since effective methods for surveillance and treatment are available. This review article is based on a selective literature search, the author's own work, and evidence-based guidelines and recommendations. The diagnosis is initially suspected on the basis of the endoscopic findings and polyp histology. Because different syndromes can resemble each other phenotypically, e.g., autosomal dominant familial adenomatous polyposis and autosomal recessive MUTYH-associated polyposis, molecular genetic studies are important for differential diagnosis and for assessing the risk of recurrence. Identification of the familial mutation in an affected patient is a prerequisite for predictive testing in asymptomatic persons at risk and sometimes enables prognostication. In recent years, the rate of detection of mutations has risen by 10% to 30%, and clinically relevant genotype-phenotype correlations have been described for juvenile polyposis syndrome. Except in cases of mild adenomatous polyposis, phenotypic overlap among the hamartomatous polyposes often causes difficulties in differential diagnosis. Thus, in unclear cases, a pathologist with special expertise in gastrointestinal disorders should be consulted for the evaluation of polyp tissue. Aside from the monogenic polyposes, there are many other types of polyposis that are non-hereditary or of unknown cause, including the hyperplastic and mixed polyposis syndromes. Risk-adapted surveillance programs have been established for the more frequently occurring polyposes.


Laparoscopic surgery in a patient with Fontan physiology.
Laparoscopic surgery represents a significant advance in surgical technique, but a number of physiologic sequelae result from positioning and insufflation. These physiologic changes may be more significant in patients with complex congenital heart disease. We present the anesthetic management of a patient with Fontan physiology who successfully underwent two separate laparoscopic procedures.


Isolation of lipoxygenase isoforms from Glycine max embryo axes based on apparent cross-reactivity with anti-myosin antibodies.
Three lipoxygenase isoforms were isolated from Glycine max embryo axes. A number of proteins around 97 kDa cross-reacted with several anti-actin and anti-myosin antibodies and these were used to follow their purification through gel filtration, hydroxyapatite and anion exchange columns. The 97-kDa cross-reactive material eluted in the unbound fractions of the last anion exchange column, and displayed two components of pI's 6.2 and 6.3. Further phase partition of this fraction in TX-114 yielded a hydrophobic 97 kDa protein. Additionally, a 95-kDa protein was retained and eluted from this last column. Partial peptide sequences indicated that the 95 kDa protein was soybean lipoxygenase-1, the first 97 kDa protein was lypoxygenase-3, and the hydrophobic 97 kDa protein was lipoxygenase-2. Several possible reasons for the cross-reactivity with the antibodies are discussed. To our knowledge, this is the first example of individual lipoxygenase isoforms isolated from soybean embryo axes.


Vitamin D in the news: A call for clear public health messaging during Covid-19.
Background: The public are increasingly reliant on the internet and media to access healthcare related information during the Covid-19 pandemic. Vitamin D is essential for musculoskeletal and immune health, with daily supplementation advised by public health bodies. Several studies assessing a possible link between vitamin D and Covid-19 severity have arrived at conflicting results and news articles have been rapidly disseminating such research to the public. There has been little focus on studying the quality of information available. Aim: To identify if online search interest in vitamin D increased with pandemic burden and analyse the accuracy of public health messaging relating to vitamin D in online news articles. Methods: Online search interest data for vitamin D was correlated with pandemic burden, defined as the number of Covid-19 deaths. Online news articles discussing vitamin D and Covid-19 were analysed using qualitative coding. Results: Online search interest for vitamin D increased as pandemic burden increased (p < 0.0001, Spearman's rank). Of the 72 articles identified, most (50%) offered a mixed opinion on the benefit of vitamin D in Covid-19. From articles making a recommendation for vitamin D supplementation, 23% of articles gave mixed messaging or advised against supplementation. 16% of articles recommended a dose which exceeded the safe limit of 4000 IU/day, risking toxicity. Conclusion: A significant number of articles provided mixed messaging or incorrectly advised supratherapeutic doses. This study highlights an opportunity for public health bodies to utilise the increased interest in vitamin D during the pandemic to raise awareness with accurate information.


Public availability of results of trials assessing cancer drugs in the United States.
To evaluate to what extent results of completed trials of cancer drugs conducted in the United States are publicly available at ClinicalTrials.gov, as required by the Food and Drug Administration Amendments Act (FDAAA), or are published in journals. We searched ClinicalTrials.gov for cancer trials governed by the FDAAA: phase II to IV trials assessing drugs in the United States with a primary completion date between December 26, 2007, and May 31, 2010. For each trial, we also searched PubMed to identify the publication of results. We assessed the cumulative percentages of posted or published results over time by using the Kaplan-Meier method. We identified 646 trials, including 209 randomized controlled trials (RCTs). At 12 months after completion of the trials, the cumulative percentages of trials with results posted at ClinicalTrials.gov, published in journals, and available either at ClinicalTrials.gov or in journals were 9% (95% CI, 7% to 11%), 12% (95% CI, 10% to 15%), and 20% (95% CI, 17% to 23%), respectively, and for RCTs, the percentages were 12% (95% CI, 8% to 16%), 5% (95% CI, 2% to 8%), and 17% (95% CI, 12% to 22%), respectively. At 36 months, these percentages were 31% (95% CI, 28% to 35%), 35% (95% CI, 31% to 39%), and 55% (95% CI, 51% to 59%), respectively, and for RCTs, they were 38% (95% CI, 31% to 45%), 32% (95% CI, 25% to 39%), and 56% (95% CI, 48% to 62%), respectively. Public availability of phase III trials was 15% (95% CI, 7% to 23%) at 12 months, 39% (95% CI, 27% to 49%) at 24 months, and 64% (95% CI, 50% to 73%) at 36 months. Despite the FDAAA, results for nearly half the trials of cancer drugs in the United States were not publicly available 3 years after completion of the trials.


Improved eradication rate of standard triple therapy by adding bismuth and probiotic supplement for Helicobacter pylori treatment in Thailand.
Helicobacter pylori (H. pylori) remains an important cause of gastric cancer and peptic ulcer disease worldwide. Treatment of H. pylori infection is one of the effective ways to prevent gastric cancer. However, standard triple therapy for H. pylori eradication is no longer effective in many countries, including Thailand. This study was designed to evaluate the efficacy of adding bismuth and probiotic to standard triple therapy for H. pylori eradication. In this prospective single center study, H. pylori infected gastritis patients were randomized to receive 7- or 14-day standard triple therapy plus bismuth with probiotic or placebo. Treatment regimen consisted of 30 mg lansoprazole twice daily, 1 g amoxicillin twice daily, 1 g clarithromycin MR once daily and 1,048 mg bismuth subsalicylate twice daily. Probiotic bacteria composed of Bifidobacterium lactis, Lactobacillus acidophilus and Lactobacillus paracasei. Placebo was conventional drinking yogurt without probiotic. CYP2C19 genotyping and antibiotic susceptibility tests were also done. H pylori eradication was defined as a negative 13C-urea breath test at least 2 weeks after completion of treatment. One hundred subjects were enrolled (25 each to 7- and 14-day regimens with probiotic or placebo). Antibiotic susceptibility tests showed 36.7% metronidazole and 1.1% clarithromycin resistance. CYP2C19 genotyping revealed 40.8%, 49% and 10.2% were rapid, intermediate and poor metabolizers, respectively. The eradication rates of 7- or 14 regimens with probiotics were 100%. Regarding adverse events, the incidence of bitter taste was significantly lower in the 7- day regimen with the probiotic group compared with 7- day regimen with placebo (40% vs. 64%; p=0.04). The 7-day standard triple therapy plus bismuth and probiotic can provide an excellent cure rate of H. pylori (100%) in areas with low clarithromycin resistance such as Thailand, regardless of CYP2C19 genotype. Adding a probiotic also reduced treatment-related adverse events.


Activation of adenosine A2A or A2B receptors causes hypothermia in mice.
Extracellular adenosine is a danger/injury signal that initiates protective physiology, such as hypothermia. Adenosine has been shown to trigger hypothermia via agonism at A1 and A3 adenosine receptors (A1AR, A3AR). Here, we find that adenosine continues to elicit hypothermia in mice null for A1AR and A3AR and investigated the effect of agonism at A2AAR or A2BAR. The poorly brain penetrant A2AAR agonists CGS-21680 and PSB-0777 caused hypothermia, which was not seen in mice lacking A2AAR. MRS7352, a likely non-brain penetrant A2AAR antagonist, inhibited PSB-0777 hypothermia. While vasodilation is probably a contributory mechanism, A2AAR agonism also caused hypometabolism, indicating that vasodilation is not the sole mechanism. The A2BAR agonist BAY60-6583 elicited hypothermia, which was lost in mice null for A2BAR. Low intracerebroventricular doses of BAY60-6583 also caused hypothermia, indicating a brain site of action, with neuronal activation in the preoptic area and paraventricular nucleus of the hypothalamus. Thus, agonism at any one of the canonical adenosine receptors, A1AR, A2AAR, A2BAR, or A3AR, can cause hypothermia. This four-fold redundancy in adenosine-mediated initiation of hypothermia may reflect the centrality of hypothermia as a protective response.