Arterial Hypertension and Plasma Glucose Modulate the Vasoactive Effects of Nitroso-Sulfide Coupled Signaling in Human Intrarenal Arteries.
We have investigated the vasoactive effects of the coupled nitro-sulfide signaling pathway in lobar arteries (LAs) isolated from the nephrectomized kidneys of cancer patients: normotensive patients (NT) and patients with arterial hypertension (AH). LAs of patients with AH revealed endothelial dysfunction, which was associated with an increased response to the exogenous NO donor, nitrosoglutathione (GSNO). The interaction of GSNO with the H2S donor triggered a specific vasoactive response. Unlike in normotensive patients, in patients with AH, the starting and returning of the vasorelaxation induced by the end-products of the H2S-GSNO interaction (S/GSNO) was significantly faster, however, without the potentiation of the maximum. Moreover, increasing glycemia shortened the time required to reach 50% of the maximum vasorelaxant response induced by S/GSNO products so modulating their final effect. Moreover, we found out that, unlike K+ channel activation, cGMP pathway and HNO as probable mediator could be involved in mechanisms of S/GSNO action. For the first time, we demonstrated the expression of genes coding H2S-producing enzymes in perivascular adipose tissue and we showed the localization of these enzymes in LAs of normotensive patients and in patients with AH. Our study confirmed that the heterogeneity of specific nitroso-sulfide vasoactive signaling exists depending on the occurrence of hypertension associated with increased plasma glucose level. Endogenous H2S and the end-products of the H2S-GSNO interaction could represent prospective pharmacological targets to modulate the vasoactive properties of human intrarenal arteries.


Lack of Association between Toxocara Exposure and Suicide Attempts in Psychiatric Patients.
Infection with Toxocara may affect the central nervous system. A high seroprevalence of Toxocara infection has been reported in psychiatric patients. To the best of our knowledge, there is no previous report about an association of Toxocara infection with suicide attempts. Therefore, we sought to determine whether Toxocara exposure is associated with suicide attempts in psychiatric patients. We studied 282 psychiatric outpatients (156 with suicide attempts and 126 without suicide attempts). Sera of patients were analyzed for the presence of anti-Toxocara IgG antibodies by using a commercially available enzyme immunoassay. One of the 156 (0.6%) suicide attempters and 1 (0.8%) of the 126 controls were positive for anti-Toxocara IgG antibodies (OR = 0.80; 95% CI: 0.04-13.02; P = 1.00). Toxocara seropositivity was significantly higher (P = 0.01) in male patients with consumption of raw dried goat meat than male patients without this consumption. Results suggest that Toxocara exposure is not associated with suicide attempts in psychiatric outpatients in Durango City, Mexico. However, further studies with larger samples sizes to confirm our results should be conducted. Too few patients were seropositive to assess further associations of Toxocara exposure with sociodemographic, clinical, and behavioral characteristics of the psychiatric patients.


The Impact of Videolaryngoscopy on Endotracheal Intubation Success by a Pediatric/Neonatal Critical Care Transport Team.
Endotracheal intubation may be required for the transport of critically ill neonates and children. Data suggest that first pass success (FPS) is associated with lower rates of complications. Thus, understanding factors associated with FPS can have important implications for clinical outcomes. We aimed to determine the impact of videolaryngoscopy (VL) on FPS by a pediatric critical care transport team (CCTT). Methods: We performed a retrospective cross-sectional study on pediatric patients (≤ 18 years of age) requiring endotracheal intubation by a tertiary care-based pediatric CCTT between 2011 and 2019. Patients were categorized as neonatal (≤ 28 days of age, either preterm or term) or pediatric (> 28 days of age). All intubation attempts using VL were performed with the C-MAC videolaryngoscope. Our primary outcome was rate of FPS. Descriptive statistics of patient, provider, and procedure characteristics were calculated. Multivariate regression was used to test the association between FPS and type of laryngoscope (video versus direct) adjusting for significant clinical predictors. Results: Over the study period, 135 patients were intubated by the CCTT. Sixty percent of these patients were neonates, and 40% were pediatric. The overall FPS rate was 61%, with lower rates in neonates (54%) and higher rates in pediatric patients (70%). Use of videolaryngoscopy increased over the study period. First pass success rate using the C-MAC videolaryngoscope was 72% compared to 42% for direct laryngoscopy across the whole study population. In adjusted analyses, FPS using VL was significantly higher in the pediatric patient population (aOR 12.42 [95%CI 3.33, 46.29]), but not in neonates (aOR 1.08 [0.44, 2.63]). Use of VL increased significantly over the study period. Conclusion: We found use of a C-MAC videolaryngoscope by a critical care transport team was associated with improved FPS during endotracheal intubation of pediatric patients but not neonates, after controlling for other patient and provider characteristics. In addition to the impact on FPS, use of VL may offer additional educational and quality benefits.


Gestational diabetes: risks, management, and treatment options.
Gestational diabetes mellitus (GDM) is commonly defined as glucose intolerance first recognized during pregnancy. Diagnostic criteria for GDM have changed over the decades, and several definitions are currently used; recent recommendations may increase the prevalence of GDM to as high as one of five pregnancies. Perinatal complications associated with GDM include hypertensive disorders, preterm delivery, shoulder dystocia, stillbirths, clinical neonatal hypoglycemia, hyperbilirubinemia, and cesarean deliveries. Postpartum complications include obesity and impaired glucose tolerance in the offspring and diabetes and cardiovascular disease in the mothers. Management strategies increasingly emphasize optimal management of fetal growth and weight. Monitoring of glucose, fetal stress, and fetal weight through ultrasound combined with maternal weight management, medical nutritional therapy, physical activity, and pharmacotherapy can decrease comorbidities associated with GDM. Consensus is lacking on ideal glucose targets, degree of caloric restriction and content, algorithms for pharmacotherapy, and in particular, the use of oral medications and insulin analogs in lieu of human insulin. Postpartum glucose screening and initiation of healthy lifestyle behaviors, including exercise, adequate fruit and vegetable intake, breastfeeding, and contraception, are encouraged to decrease rates of future glucose intolerance in mothers and offspring.


Microglial cell activation in demyelinating canine distemper lesions.
Microglia cells are the principal immune effector elements of the brain responding to any pathological event. To elucidate the possible role of microglia in initial non-inflammatory demyelination in canine distemper virus (CDV) infection, microglia from experimentally CDV infected dogs were isolated ex vivo by density gradient centrifugation and characterized immunophenotypically and functionally using flow cytometry. Results from dogs with demyelinating lesions were compared to results from recovered dogs and two healthy controls. CDV antigen could be detected in microglia of dogs with histopathologically confirmed demyelination. Microglia of these dogs showed marked upregulation of the surface molecules CD18, CD11b, CD11c, CD1c, MHC class I and MHC class II and a tendency for increased expression intensity of ICAM-1 (CD54), B7-1 (CD80), B7-2 (CD86), whereas no increased expression was found for CD44 and CD45. Functionally, microglia exhibited distinctly enhanced phagocytosis and generation of reactive oxygen species (ROS). It was concluded that in CDV infection, there is a clear association between microglial activation and demyelination. This strongly suggests that microglia contribute to acute myelin destruction in distemper.


Insomnia: pathophysiology and implications for treatment.
Interest in developing a greater understanding of the pathophysiogical mechanisms underlying primary insomnia has increased. Recent evidence indicates that there may be some neuroendocrine and clinical similarities between primary insomnia and major depressive disorder, that abnormal corticotropin releasing factor (CRF) activity occurs in major depression, and that CRF hyperactivity appears to mediate the hyperarousal seen in primary insomnia. These findings all point to the possibility of hypothalamic-pituitary-adrenal (HPA) axis and CRF overactivity in both disorders. More recent findings have strengthened the evidence that primary insomnia may be linked with mood disorders and is associated with HPA axis overactivity and excess secretion of CRF, adrenocorticotropin releasing hormone, and cortisol. These insights have implications for managing chronic primary insomnia, such as use of antiglucocorticoid agents.


Incremental effects of concurrent pharmacotherapeutic regimens for heart failure on hospitalizations and costs.
Inappropriate medication use in patients with heart failure (HF) presents challenges in providing optimal, evidence-based care. To evaluate the incremental differences of concurrent and persistent use of angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, loop diuretics, and digoxin on the one-year, all-cause risk of hospitalization and total healthcare costs associated with treatment of HF in patients enrolled in a managed care organization within the US. A retrospective database analysis was conducted spanning from January 1, 1997, to December 31, 1999. Multivariate regression methods were used to examine the association between treatment regimens and hospitalizations or costs after controlling for patient demographics and risk factors. Of the 1903 patients meeting inclusion criteria, 32.3% (n = 615) received none of the 4 HF agents studied and were associated with a 2.5 times greater risk (p < or = 0.001) of hospitalization and 43.6% higher (p < or = 0.001) total costs compared with all other patients with HF. Comparatively, 13.9% (n = 264) utilized the HF medications investigated for at least 6 months. Of those with persistent use of > or =3 agents, approximate decreases in hospitalizations were noted of 80% (p < or = 0.001) and total costs of 70% (p < or = 0.001) relative to patients receiving no HF therapy. A substantial portion of patients with HF may be receiving suboptimal pharmacotherapeutic care in real-world practice settings, potentially incurring large increases in hospitalizations and total costs. Quality improvement initiatives should seek to identify and manage those not being treated according to guideline recommendations.


Genetic deficiency of the fourth component of complement (C4) in Wistar rats.
A chance observation has led to the discovery of single component complement deficiency in Wistar rats. During serial total haemolytic activity (CH50) determinations on 10 male rats, 2 were consistently found to have values 20% or less than that of the others. An additional 30 males (200--220 g) and 20 females (180--200 g) were screened for CH50 and the defect was found in 10 of the males but none of the females. Mixtures of sera of high and low haemolytic activity gave intermediate values between the two populations arguing against the presence of an inhibitor of the complement system. Single component analysis revealed the defect to reside in the fourth component of complement (C4). Highly purified human C4 completely reconstituted the haemolytic activity of the complement deficient rat serum. A linear relationship between C4 and CH50 titres was observed. Data from preliminary selective breeding experiments point toward an autosomal recessive mode of inheritance. Animals with intermediate values were observed indicating a gene dosage effect with which the heterozygote may be recognized.


Nonlinear neural control using feedback linearization explains task goals of central nervous system for trunk stability in sitting posture.
Objective.Characterizing the task goals of the neural control system for achieving seated stability has been a fundamental challenge in human motor control research. This study aimed to experimentally identify the task goals of the neural control system for seated stability.Approach.Ten able-bodied young individuals participated in our experiments, which allowed us to measure their body motion and muscle activity during perturbed sitting. We used a nonlinear neuromechanical model of the seated human, along with a full-state feedback linearization approach and optimal control theory for identifying the neural control system and characterizing its task goals.Main results.We demonstrated that the neural feedback for trunk stability during seated posture uses angular position, velocity, acceleration, and jerk in a linearized space. The mean squared error between the predicted and measured motor commands was less than 0.6% among all trials and participants, with a median correlation coefficientrof more than 0.9. Our identified optimal neural control primarily used trunk angular acceleration and near-minimum muscle activation to achieve seated stability while keeping the deviations of the trunk angular position and acceleration sufficiently small.Significance.Our proposed approach to neural control system identification relied on a performance criterion (e.g. cost function) explaining what the functional goal is and subsequently, finds the control law that leads to the best performance. Therefore, instead of assuming what control schemes the neural control might utilize (e.g. proportional-integral-derivative control), optimal control allows the motor task and the neuromechanical model to dictate a control law that best describes the physiological process. This approach allows for a mechanistic understanding of the neuromuscular mechanisms involved in seated stability and for inferring the task goals used by the neural control system to achieve the targeted motor behavior. Such neural control characterization can contribute to the development of objective balance evaluation tools and of bio-inspired assistive neuromodulation technologies.


Tracking HOCl concentrations across cellular organelles in real time using a super resolution microscopy probe.
BODIPY derivative, SF-1, exclusively shows a fluorescence ON response to HOCl and images endogenously generated HOCl in RAW 264.7 macrophages. Widefield and super resolution structured illumination microscopy images confirm localization in the Golgi complex and lysosomes, and hence specifically detects HOCl generated in these organelles. SF-1 is compatible with 3D-SIM imaging of individual cells.


Modulation of differentiation in PA-1 human teratocarcinoma cells after N-ras oncogene-induced tumorigenicity.
We have been studying the effect of oncogenes on differentiation using the human ovarian teratoma-derived cell line PA-1. From this study we have characterized variants representing four stages relevant to multistage carcinogenesis, two non-tumorigenic and two tumorigenic. The two non-tumorigenic cell variants differ in that one is resistant to transformation by ras oncogenes whereas the other can be transformed to tumorigenicity. When these non-tumorigenic PA-1 variants are treated with retinoic acid (RA), a morphogen, they stop dividing, begin to express homeobox genes, and change in morphology. Transfection of an activated N-ras oncogene into ras-resistant non-tumorigenic PA-1 cells does not alter the RA responsiveness of the cells, indicating that expression of the activated oncogene is not sufficient for blocking RA-induced differentiation. Spontaneous activation of an N-ras oncogene leading to tumorigenic transformants and gene transfer-induced N-ras transformants are resistant to these effects of RA. However, another spontaneous transformant of PA-1 cells that does not contain an activated N-ras is responsive to RA. We prepared somatic cell hybrids of the RA-non-responsive, N-ras-transformed and tumorigenic PA-1 cell and the RA-responsive, ras-resistant non-tumorigenic PA-1 cell; the hybrid cell lines continue to express the oncogene but are non-tumorigenic. These non-tumorigenic hybrids are responsive to RA with regard to morphological changes, growth arrest and induction of homeobox gene expression. Tumorigenic revertants of these hybrids arise as a result of the loss of some chromosomes; these hybrid cells express the oncogene but have lost RA responsiveness. These results indicate that tumorigenic transformation in general is not sufficient to induce RA resistance, and resistance to differentiation may be oncogene-specific. In addition, the expression of an activated N-ras oncogene alone is insufficient to induce resistance to RA and ras-induced tumorigenicity is necessary. Therefore, some feature of cellular metabolism that is altered by and discordantly segregates with tumorigenic transformation controls responsiveness to RA. This controlling element is presumably a tumor suppressor.


Limits of identification using VUV spectroscopy applied to C8H18 isomers isolated by GC×GC.
The vacuum ultraviolet detector for gas chromatography can be used to identify structural differences between isomers with similar chromatographic elution times, which adds detail to characterization, valuable for prescreening of sustainable aviation fuel candidates. Although this capability has been introduced elsewhere, vacuum ultraviolet spectroscopy for saturated hydrocarbons has been examined minimally, as the similarities between their spectra are much less significant than their aromatic counterparts. The fidelity with which structural differences can be identified has been unclear. In this work, all possible structural isomers of C8H18 are measured and determined to have unambiguously unique vacuum ultraviolet spectra. Using a statistically based residual comparison approach, the concentration limits at which the spectral differences are interpretable are tested in both a controlled study and a real fuel application. The concentration limit at which the spectral differences between C8H18 isomers are unambiguous is below 0.40% by mass and less than 0.20% with human discretion in our experimental configuration.


Exploring the Effect of Ligand Structural Isomerism in Langmuir-Blodgett Films of Chiral Luminescent Eu(III) Self-Assemblies.
Here we have investigated the influence of the antenna group position on both the formation of chiral amphiphilic Eu(III) -based self-assemblies in CH3 CN solution and, on the ability to form monolayers on the surface of quartz substrates using the Langmuir-Blodgett technique, by changing from the 1-naphthyl (2(R), 2(S)) to the 2-naphthyl (1(R), 1(S)) position. The evaluation of binding constants of the self- assemblies in CH3 CN solution was achieved using conventional techniques such as UV/Visible and luminescence spectroscopies along with more specific circular dichroism (CD) spectroscopy. The binding constants obtained for EuL, EuL2 and EuL3 species in the case of 2-naphthyl derivatives were comparable to those obtained for 1-naphthyl derivatives. The analysis of the changes in the CD spectra of 1(R) and 1(S) upon addition of Eu(III) not only allowed us to evaluate the values of the binding constants but the resulting recalculated spectra may also be used as fingerprints for assignment of the chiral self-assembly species formed in solution. The obtained monolayers were predominantly formed from EuL3 (≈85 %) with the minor species present in ≈15 % EuL2 .


Regulations with plenty of loopholes--the doctors' prescription rights during the era of prohibition 1916-1926.
In Norway, the sale of distilled spirits was prohibited from 1916 to 1926, and fortified wines were banned from 1917 to 1923. This period is often referred to as The Prohibition. The consumption of alcohol declined somewhat, but at a high price: Increased smuggling, moonshining and abuse of prescriptions. The latter was caused by the doctors' exclusive right to prescribe alcohol, which some doctors abused for the sake of personal gain. KNOWLEDGE BASIS: The article is based on a review of the records of the Storting's deliberations concerning prescription practices in the period 1916-1926, as well as articles on alcohol issues in the Journal of the Norwegian Medical Association from the same period. With the aid of increasingly strict regulations, the authorities sought to stem the activities of the so-called «whisky doctors». The restrictions and controls imposed on their prescribing rights turned out not to be very effective, however, since the doctors' rights were firmly established. In combination with weaknesses in the legislative base, this hampered the criminal prosecution of doctors who wrote prescriptions in a big way. The abuse reached its climax in 1923. It was only with the enactment of the Prescription Act which came into force on 1 March 1924 that the authorities finally succeeded in gaining control of the abuse of prescriptions. The sale of spirits on prescription subsequently dropped sharply. The prescription of spirits had gradually spiralled out of control, and the repeated control measures enacted by the authorities proved insufficient. When the Prescription Act was finally adopted after three attempts in the Storting, time was in reality up for the prohibition.


Keloids and hypertrophic scars.
Keloids and hypertrophic scars are benign fibrous growths which usually occur after trauma in predisposed individuals. Their etiology, clinical manifestations and treatment are diverse. The purpose of this article is to review the pertinent literature concerning keloids and hypertrophic scars as well as present my own perspective on the subject. It is my hope that the information contained herein will help both the dermatologist and dermatologic surgeon better understand and manage these vexing lesions. Medline literature search as well as original material. There is no one right way to treat all keloids and hypertrophic scars. Treatment results have been variable. The management of keloids and hypertrophic scars can be difficult and frustrating for both patient and physician. A better understanding of keloid pathogenesis may lead to improved therapies by which keloid growth and regrowth may be obviated.


The UA_handle: a versatile submotif in stable RNA architectures.
Stable RNAs are modular and hierarchical 3D architectures taking advantage of recurrent structural motifs to form extensive non-covalent tertiary interactions. Sequence and atomic structure analysis has revealed a novel submotif involving a minimal set of five nucleotides, termed the UA_handle motif (5'XU/AN(n)X3'). It consists of a U:A Watson-Crick: Hoogsteen trans base pair stacked over a classic Watson-Crick base pair, and a bulge of one or more nucleotides that can act as a handle for making different types of long-range interactions. This motif is one of the most versatile building blocks identified in stable RNAs. It enters into the composition of numerous recurrent motifs of greater structural complexity such as the T-loop, the 11-nt receptor, the UAA/GAN and the G-ribo motifs. Several structural principles pertaining to RNA motifs are derived from our analysis. A limited set of basic submotifs can account for the formation of most structural motifs uncovered in ribosomal and stable RNAs. Structural motifs can act as structural scaffoldings and be functionally and topologically equivalent despite sequence and structural differences. The sequence network resulting from the structural relationships shared by these RNA motifs can be used as a proto-language for assisting prediction and rational design of RNA tertiary structures.


[Ocular defects associated with a duplication of the distal part of the long arm of chromosome 1: a case report].
The authors report a case of de novo duplication 1q32-qter present in a patient with dysmorphic syndrome and developmental delay. This article describes the eighth case of partial trisomy 1q32-qter "pure", without chromosomal abnormalities. In the literature, a dysmorphic "syndrome" is described for trisomy 1q32-qter: hypertelorism, low set and malformed ears, prominent forehead, long philtrum, antimongoloid slanting, foot and digital malformations, cardiovascular abnormalities, urogenital abnormalities, and mental retardation. The ocular defects described in previously reported cases include: cataract, strabismus, hypoplasia of the optic disk, microphthalmia, epicanthal folds, ptosis, persistent tunica vasculosa lentis, and hyaloid vessels, but this seems to be nonspecific of this chromosomal abnormality.


[Adjuvant chemotherapy for non-small cell lung cancer].
Recently, several randomized trials with a large number of enrolled patients have shown that postoperative adjuvant treatment improves survival among patients with completely resected non-small cell lung cancer (NSCLC). Platinum-based chemotherapy has been reported to be effective for patients with postoperative stage I to IIIA NSCLC in western countries. On the other hand, uracil-tegafur was also shown to improve survival among patients with stage I adenocarcinoma in Japan. We reviewed the results of recent randomized trials and meta-analyses, and discuss the current role and problems related to adjuvant chemotherapy in NSCLC.


Significance of Laurén's classification in chemotherapy of gastric carcinoma.
The effects of anticancer agents were studied on the basis of survival rates following surgery for gastric carcinomas in different histologic types of Laurén's classification. It was revealed that Laurén's classification would provide an index to the use of anticancer agents to a certain extent. Anticancer agents were effective against diffuse gastric carcinoma, and should therefore be intensively used for treatment of this malignancy. For female patients with diffuse gastric carcinoma, careful selection of adequate anticancer agents is highly necessary. Anticancer agents were less effective against intestinal-type carcinoma, and it would therefore be necessary to use anticancer agents on the aged male patients with this malignancy by taking his age and side effects of the agents into consideration.


Supramolecular Macrocyclic Pd(II) and Pt(II) Squares and Rectangles with Aryldithiolate Ligands and their Excellent Catalytic Activity in Suzuki C-C Coupling Reaction.
Addition of 1,4-benezenedithiol and 4,4'-biphenyldithiol to M(OTf)2 (M = cis-[Pt(PEt3)2](2+) or cis-[Pd(dppe)](2+)) (dppe = 1,2-bis(diphenylphosphino)ethane) gave self-assembled tetranuclear complexes [M2{S(C6H4)nS}]2(OTf)4 (n = 1, 2). The same reaction with 1,4-benezenedimethanethiol yielded octanuclear supramolecular coordination complexes (SCC) [M2{SCH2C6H4CH2S}]4(OTf)8. These complexes were characterized by NMR, mass, and UV-vis spectroscopies, cyclic voltammetry, as well as density functional theory studies and represent the first examples of SCCs constructed by thiolate groups and square-planar metal ions. The rectangular shape of tetranuclear complexes and square shape of octanuclear complex are confirmed by single-crystal structures and computational studies. The palladium complexes showed excellent catalytic activity in Suzuki C-C cross-coupling reactions with high turnover numbers (2 × 10(7)), even with low catalyst loading.


Executive function impairment and recidivism in adult protective services clients referred for a decision making capacity assessment.
The objective of this study was to determine if recidivistic Adult Protective Services (APS) cases referred for a decision-making capacity assessment were more cognitively impaired than nonrecidivistic cases. A retrospective medical record review of neuropsychological and demographic data was gathered during decisional capacity assessments. Recidivistic clients were those referred to APS more than once; those with a single open case were nonrecidivistic. Mean neuropsychological test scores were compared between recidivistic (n = 138) and nonrecidivistic (n = 95) subjects. No significant differences were found for age, gender, ethnicity, education, or dwelling status. Both recidivistic and nonrecidivistic cases performed poorly in all cognitive domains. Recidivistic clients performed significantly worse on measures of executive function (CLOX1, EXIT25). Executive function impairments seem to be one risk factor for recidivism in APS referrals. With 60% of cases referred for decision capacity assessments being recidivistic, identifying risk factors may help identify when targeted interventions are indicated to preclude recurrence of abuse.


Diversity of vibrios in the haemolymph of the spider crab Maja brachydactyla.
The aim of this study was to characterise and identify vibrios isolated from the haemolymph of apparently healthy adult spider crabs (Maja brachydactyla) wild-caught in the Spanish localities of Galician coast and in the Canary Islands and also from captive animals held at IRTA's facilities in the Ebro Delta of Catalonia, north-west Spanish Mediterranean coast. A total of 277 bacterial isolates were obtained, and of these, 171 were characterised with rep-PCR, resulting electrophoretic bands were analysed and clusters formed. Identification of representative strains of each cluster was made by sequencing the 16S rRNA. Samples from animals caught in Galicia and captive at IRTA (around 15-18°C) rendered mostly species belonging to the Splendidus clade (72·2 and 76·6% respectively), commonly found in cold waters (below 20°C). Higher species diversity was found in the haemolymph of the captive animals. In the warmer Canary Islands waters (around 21°C), the diversity of vibrios is dominated by three clades, Harveyi (Vibrio core group, 39·3%), Orientalis (23·2%) and Splendidus (21·4%) with a species diversity that equals that of the colder captive animals. Differences in the vibrios populations were found in the haemolymph extracted from animals collected from the three localities. Potential new species were found, and their description is under way. As with other invertebrates, spider crabs also contain a diverse population of vibrios. These findings should help researchers to diagnose when a crab is infected.


The questionable wisdom of a low-fat diet and cholesterol reduction.
The prevalent wisdom that a low-fat diet and cholesterol reduction are essential to good cardiovascular health is coming under increased scrutiny. An examination of the foundations of this view suggests that in many respects it was ill-conceived from the outset and, with the accumulation of new evidence, it is becoming progressively less tenable. Cross-sectional, longitudinal and cross-cultural investigations have variously suggested that the relationship between dietary fat intake and death from heart disease is positive, negative and random. These data are incompatible with the view that dietary fat intake has any causal role in cardiovascular health. Although hypercholesterolemia is associated with increased liability to death from heart disease, it is as frequently associated with increased overall life expectancy as with decreased life expectancy. These findings are incompatible with labelling hypercholesterolemia an overall health hazard. Moreover, it is questionable if the cardiovascular liability associated with hypercholesterolemia is either causal or reversible. The complex relationships between diet, serum cholesterol, atherosclerosis and mortality and their interactions with genetic and environmental factors suggest that the effects of simple dietary prescriptions are unlikely to be predictable, let alone beneficial. These cautions are borne out by numerous studies which have shown that multifactorial primary intervention to lower cholesterol levels is as likely to increase death from cardiovascular causes as to decrease it. Importantly, the only significant overall effect of cholesterol-lowering intervention that has ever been shown is increased mortality. The stress and helplessness associated with misapprehensions as to the dangers of dietary fat and the asceticism inherent in the war on cholesterol have considerable implications for health practices. Recent research in behavioral immunology suggests that stress and helplessness are likely to compromise immunity and promote ill-health.


Morphological and stereological characterization of hepatic foci of cellular alteration in control Fischer 344 rats.
Quantitative evaluation of altered hepatocellular foci (AHF), followed by stereological analysis was performed on standard hematoxylin and eosin-stained liver sections from control Fischer 344 (F344) rats of both sexes from seven 2-yr carcinogenicity studies conducted by the National Toxicology Program (NTP). Liver samples were collected at 6, 9, 12, 15, 18, and/or 24 months on study. Although AHF had a broad spectrum of morphological features, they could be classified into the following 5 types using previously published criteria: basophilic, eosinophilic, clear, vacuolated, mixed cell foci. Approximately 50% of the animals had foci at 6 months, and the incidence reached nearly 100% at 15 months in both sexes. The number, size and volume fraction of AHF increased with age in both sexes; these changes were most evident for basophilic and clear cell foci. The number of basophilic foci was significantly greater in females than in males while clear cell foci were more numerous in males. This sex difference was observed at each time point. Mean number of all types of AHF in males and females at 24 months was 547 and 460 per cubic centimeter of liver, respectively. Despite the high incidence of AHF in control rats, the incidence of hepatocellular neoplasms is low. The implication is that most foci do not progress to neoplasia in control F344 rats used in 2-yr studies.


Three-dimensional stereotactic anatomy of the human trigeminal nerve nuclear complex.
The trigeminal nuclear complex and its spinal tract extend throughout the greater part of the brain-stem and at medullary levels form the target site for producing stereotactic lesions. This paper describes a method for three-dimensional drawings of this nuclear complex. A stereotactic atlas of the human brain-stem and cerebellar nuclei has formed the data base. The two-dimensional composite transverse sections, at 1-mm intervals have been digitized using an X-Y coordinate plotting microscope. Computer programs have been written to generate drawings of a single transverse hemisection as well as regeneration of the opposite hemibrain-stem section. Specific programs were used to reconstruct serial transverse section outlines and incorporate the trigeminal nuclear complex with and without hidden line removal techniques and colour graphic display facilities. Rotation about the x, y and z axes was possible and permits any view of the reconstructed specimen to be computer-generated. A further program for reconstructing structures as stereopairs is presented.


Hand discomfort following heliox chamber dives.
During a series of dry chamber dives using compressed heliox, five attendants and one wet diver experienced eight episodes of hand discomfort, the character of which was atypical of limb pain during decompression sickness. Although immersed for most of the dive, during the compression and decompression phases, the wet diver's hands were out of the water and hence exposed to the helium-containing chamber atmosphere. In all cases, symptoms resolved within a maximum of 48 h. There was no response to hyperbaric oxygen therapy in the three cases that presented before spontaneous resolution. While the attendants wore dry suits to minimize skin absorption of helium, their hands, were exposed to the heliox atmosphere. After the first six cases of hand symptoms, a dry glove assembly was added to prevent helium absorption through the exposed hand. Two cases of hand discomfort occurred following the addition of the dry glove assembly to the dry suit. In both cases, the symptoms were less severe and resolved over a significantly shorter time period. Adoption of the dry gloves resulted in the incidence of hand discomfort among attendants falling from 25% (5/20) to 2.4% (2/84) (p = 0.005). Possible mechanisms of causation of this hand discomfort, thought to be the result of local tissue absorption of helium, are discussed.


Diversification of Orientia tsutsugamushi genotypes by intragenic recombination and their potential expansion in endemic areas.
Scrub typhus is a mite-borne febrile disease caused by O. tsutsugamushi infection. Recently, emergence of scrub typhus has attracted considerable attention in several endemic countries in Asia and the western Pacific. In addition, the antigenic diversity of the intracellular pathogen has been a serious obstacle for developing effective diagnostics and vaccine. To understand the evolutionary pathway of genotypic diversification of O. tsutsugamushi and the environmental factors associated with the epidemiological features of scrub typhus, we analyzed sequence data, including spatiotemporal information, of the tsa56 gene encoding a major outer membrane protein responsible for antigenic variation. A total of 324 tsa56 sequences covering more than 85% of its open reading frame were analyzed and classified into 17 genotypes based on phylogenetic relationship. Extensive sequence analysis of tsa56 genes using diverse informatics tools revealed multiple intragenic recombination events, as well as a substantially higher mutation rate than other house-keeping genes. This suggests that genetic diversification occurred via frequent point mutations and subsequent genetic recombination. Interestingly, more diverse bacterial genotypes and dominant vector species prevail in Taiwan compared to other endemic regions. Furthermore, the co-presence of identical and sub-identical clones of tsa56 gene in geographically distant areas implies potential spread of O. tsutsugamushi genotypes. Fluctuation and diversification of vector species harboring O. tsutsugamushi in local endemic areas may facilitate genetic recombination among diverse genotypes. Therefore, careful monitoring of dominant vector species, as well as the prevalence of O. tsutsugamushi genotypes may be advisable to enable proper anticipation of epidemiological changes of scrub typhus.


Epithelial uptake and transport of cell-free human immunodeficiency virus type 1 and gp120-coated microparticles.
Cell-free human immunodeficiency virus type 1 (HIV-1) can be taken up and released by a monolayer of primary human gingival cells and remain infectious for CD4+ cells. Virus-sized latex particles covalently coated with purified native HIV-1 envelope glycoprotein gp120 are also transported through the primary epithelial cells. This process is significantly stimulated by increasing the intracellular cyclic AMP (cAMP) concentration. Inhibition experiments with mannan and alpha-methyl-mannopyranoside indicated that mannosyl groups are involved in the interaction between gp120 and gingival cells. An increase of cellular oligomannosyl receptors by incubation with the mannosidase inhibitor deoxymannojirimycin augmented transcellular transport of the gp120-coated particles. The results suggest that infectious HIV can penetrate gingival epithelia by a cAMP-dependent transport mechanism involving interaction of the lectin-like domain of gp120 and mannosyl residues on glycoproteins on the mucosal surface. Penetration of HIV could be inhibited by soluble glycoconjugates present in oral mucins.


Conformational Isomerization Involving Conserved Proline Residues Modulates Oligomerization of the NS1 Interferon Response Inhibitor from the Syncytial Respiratory Virus.
Interferon response suppression by the respiratory syncytial virus relies on two unique nonstructural proteins, NS1 and NS2, that interact with cellular partners through high-order complexes. We hypothesized that two conserved proline residues, P81 and P67, participate in the conformational change leading to oligomerization. We found that the molecular dynamics of NS1 show a highly mobile C-terminal helix, which becomes rigid upon in silico replacement of P81. A soluble oligomerization pathway into regular spherical structures at low ionic strengths competes with an aggregation pathway at high ionic strengths with an increase in temperature. P81A requires higher temperatures to oligomerize and has a small positive effect on aggregation, while P67A is largely prone to aggregation. Chemical denaturation shows a first transition, involving a high fluorescence and ellipticity change corresponding to both a conformational change and substantial effects on the environment of its single tryptophan, that is strongly destabilized by P67A but stabilized by P81A. The subsequent global cooperative unfolding corresponding to the main β-sheet core is not affected by the proline mutations. Thus, a clear link exists between the effect of P81 and P67 on the stability of the first transition and oligomerization/aggregation. Interestingly, both P67 and P81 are located far away in space and sequence from the C-terminal helix, indicating a marked global structural dynamics. This provides a mechanism for modulating the oligomerization of NS1 by unfolding of a weak helix that exposes hydrophobic surfaces, linked to the participation of NS1 in multiprotein complexes.


[Therapy of chronic myeloid leukemia. Uncommon view of the modern approaches].
Chronic myeloid leukemia has got an outstanding position among the other oncology diseases, particularly due to specific chromosomal abnormality called Philadelphia chromosome, its molecular consequence BCR/ABL fusion gene and its biologic product BCR/ABL tyrosinekinase, which is responsible for the leukemic transformation of the hematopoetic cells. We can see a real revolution in the treatment of the chronic myeloid leukemia in the last few years. The authors pay attention to the developement of the new drugs in the large historical consequences from the beginning in the 19th century (describing leukemia first time) to the introduction of the new small specific molecules into the clinical practice.


Biochemical and pharmacological characterization of mu, delta and kappa 3 opioid receptors expressed in BE(2)-C neuroblastoma cells.
Total opioid binding in the human neuroblastoma cell line BE(2)-C has a density similar to that found in brain, with a Bmax value of 383 +/- 60 fmol/mg protein and a KD of 0.4 +/- 0.07 nM for the nonselective opioid antagonist 3H-diprenorphine. Selective assays reveal a binding distribution of mu (38%), delta (16%) and kappa 3 (43%) opioid receptors. There is no observable kappa 1 or kappa 2 binding. The sum of the Bmax values in the selective binding assays (370 +/- 39 fmol/mg protein) approximates closely that observed with 3H-diprenorphine, suggesting that mu, delta and kappa 3 sites account for most of the binding. The binding selectivities of various opiates and opioid peptides in the BE(2)-C cells are similar to those in rat brain. Delta and mu binding are defined easily by traditional selective ligands. The binding profiles also distinguish clearly mu from kappa 3 binding. The selective mu ligand DAMGO competes with mu binding over 35-fold more potently than kappa 3 binding, whereas morphine shows a 10-fold selectivity. Functionally, selective mu, delta and kappa 3 agonists inhibit forskolin-stimulated cAMP accumulation through distinct receptor mechanisms that are pertussis toxin-sensitive. In addition to demonstrating that BE(2)-C cells provide a useful model system for studying mu, kappa 3 and delta receptors, these studies confirm that kappa 3 receptors represent a pharmacologically distinct receptor class in this cell line.


Integration host factor stimulates both FimB- and FimE-mediated site-specific DNA inversion that controls phase variation of type 1 fimbriae expression in Escherichia coli.
The site-specific DNA inversion that controls phase variation of type 1 fimbriation in E. coli is catalysed by two recombinases, FimB and FimE. Efficient inversion by either recombinase also requires the leucine-responsive regulatory protein (Lrp). In addition, FimB recombination is stimulated by the integration host factor (IHF). The effect of IHF on FimE inversion has not previously been reported. Here it is shown that IHF stimulates FimE recombination; In strain MG1655, mutants containing lesions in either the alpha (ihfA) or beta (ihfB) subunits of IHF show a marked decrease in both FimB- (100-fold) and FimE (15,000-fold)-promoted switching. IHF is shown to bind with high affinity to sites both adjacent to (site I) and within (site II) the fim invertible element. Furthermore, mutations in site I or site II that lower the affinity of IHF binding In vitro were found to lower the frequency of FimE and/ or FimB recombination in vivo. Although site I and site II mutations in combination have an effect on FimB-promoted switching comparable to that of IHF knockout mutations (100-fold), the cis site mutations have a much less marked effect (100-fold) on FimE-promoted switching.


Eosinophilic fasciitis.
Eosinophilic fasciitis is a rare sclerodermiform syndrome of unknown etiology. It is characterized by the thickening of the muscular fascia and subcutaneous tissue, with a variable infiltration of eosinophils. Peripheral eosinophilia, poly or monoclonal hypergammaglobulinemia and increased erythrocyte sedimentation rate can be seen. Clinical features begin acutely, with local edema and a painful and symmetrical stiffening of the limbs, progressing rapidly to fibrosis, which can limit joint movements. Some cases have a history of strenuous physical exercise or trauma. The diagnosis is confirmed by a deep skin biopsy. Glucocorticoids in high doses is the treatment of choice. We report a typical eosinophilic fasciitis case with peripheral eosinophilia and dramatic response to pulse therapy with methylprednisolone.


The doctor's dilemma: challenges for the primary care physician caring for the child with special health care needs.
To identify barriers to providing quality primary care to children with special health care needs (CSHCN). Descriptive cross-sectional needs assessment of primary care physicians caring for CSHCN. The population consists of 30 physicians from 2 health centers and 4 private offices participating in an intervention study designed to enhance primary care for CSHCN and 20 physicians from comparable sites (2 health centers, 5 private offices). An 86-item questionnaire was administered to participants. Among these physicians who care for large numbers of CSHCN, over 70% were satisfied with specialist care, emergency room, and hospital care. By contrast, fewer than 50% reported satisfaction with mental health services, information available for families, access to case managers, and resources for transition-to-adult services. Seventy-one percent reported that compensation systems affected care, and more than half the physicians reported needing more time or staff to provide optimal care for CSHCN. Experienced physicians providing primary care for large numbers of CSHCN report that their care is adversely affected by compensation systems. There is extensive dissatisfaction with the availability of mental health services, access to community resources, transition services, and availability of written information for families.


A review of emerging physical transfection methods for CRISPR/Cas9-mediated gene editing.
Gene editing is a versatile technique in biomedicine that promotes fundamental research as well as clinical therapy. The development of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) as a genome editing machinery has accelerated the application of gene editing. However, the delivery of CRISPR components often suffers when using conventional transfection methods, such as viral transduction and chemical vectors, due to limited packaging size and inefficiency toward certain cell types. In this review, we discuss physical transfection methods for CRISPR gene editing which can overcome these limitations. We outline different types of physical transfection methods, highlight novel techniques to deliver CRISPR components, and emphasize the role of micro and nanotechnology to improve transfection performance. We present our perspectives on the limitations of current technology and provide insights on the future developments of physical transfection methods.


[Nutritional care in the cardiac rehabilitation program].
There is some evidence of the efficacy of nutritional care in modifying eating habits and behavior in patients undergoing cardiac rehabilitation: nutritional care has a relevant role in the secondary prevention of cardiovascular disease. The dietitian is the qualified sanitary professional for nutritional care. The aim of this study was to define the role of dietitians within a health care team in programs of cardiac rehabilitation. In this setting, nutritional care starts with a dietary assessment, which includes a measurement of the anthropometric parameters, and a survey of the patient knowledge and eating habits. If there is no need for change in the patient lifestyle, the patient is addressed to the normal cardiac rehabilitation program with no further nutritional intervention except one session of counseling. When lifestyle changes are needed, the dietitian defines, together with the patient, therapeutic aims and expected results. The following phase is represented by group session with patients and their relatives during which nutritional topics are discussed and nutritional education is provided Afterwards, self-monitoring sheets of eating habits are individually discussed in one visit; a last individual visit is used for a final assessment of nutritional knowledge, dietary habits, and anthropometric parameters. In case of unsatisfactory results, patients are invited to participate to three group session to be held biweekly, during which they interact with the dietitian and take part to exercises and group discussions. When the established targets are reached, the nutritional program includes individual follow up visits at six and twelve months for further assessment of medium term results.


HPV Infection, HPV Vaccines and Cervical Cancer Awareness: A Multi-Centric Survey Study in Istanbul, Turkey.
Our purpose was to examine the level of knowledge and awareness about HPV (Human papillomavirus) infection, HPV vaccines, and cervical cancer of participants. This study was conducted at students and healthcare workers of Uskudar University as well as the healthcare workers of Umraniye Training and Research Hospital and patients admitted to the gynecology outpatient clinics. A 41-question survey was conducted that investigated the 700 participants' demographic characteristics, HPV infection and cervical cancer status, and attitudes toward vaccination. 44.1% of the participants stated that they knew the cause of cervical cancer, 42.8% did not. 55.9% of those who went to regular doctor control, 38.5% of those who did not, knew that the HPV vaccine prevented warts and cervical cancer. 63.4% of men and 75.4% of women stated that they did not know whether the vaccine was effective against penile, anal and laryngeal cancer. All these were found to be statistically significant (P < .05). Lack of knowledge on vaccine protection, insufficient knowledge regarding HPV, prevalence of prejudices, and overall opinions about health are the most prevalent public health concerns in Turkey.


Lactate and malate dehydrogenase and alpha-esterases in oligospermia.
Lactate dehydrogenase (LDH), malate dehydrogenase, and alpha-esterase were studied electrophoretically in a total of 99 semen samples obtained from normal, vasectomized, oligospermic, and infertile males. The enzymatic patterns were compared with total sperm count and percentage sperm motility. Lactate dehydrogenase X was absent in semen samples from oligospermic as well as vasectomized males. An extra LDH band (between the second and third LDH bands) was detectable in samples which had a low sperm count but higher motility (80 to 90%). This extra band was absent in samples with higher sperm count regardless of the level of percentage motility, suggesting that the extra band possibly may be related to motility factors of low sperm count but not normal sperm count. The fastest moving alpha-esterase bands were absent in samples from oligospermic or vasectomized males. These bands were also absent in samples from infertile patients having a very low sperm count. It is not clear whether the fast-moving esterase bands are related to sperm count or possible differences in hormonal levels of individuals with low or zero sperm count samples. The patterns of malate dehydrogenase did not differ in individuals with zero, low, or normal sperm count.


The sense of self in anorexia-nervosa patients: a psychoanalytically informed method for studying self-representation.
This paper has two purposes: to study a central psychological feature of anorexia nervosa, the disturbed sense of self, and to demonstrate the utility of an empirical research method to explore a psychoanalytic concept such as self-representation. The aim of the study was to distinguish the sense of self of anorexia-nervosa patients from that of other psychiatric patients, as well as from non-patients. We obtained open-ended self-descriptions, which provide access to self-representations, from 77 young women between the ages of 14 and 24 who made up three groups-anorexia-nervosa patients (n = 15), control psychiatric patients (n = 15), and control non-patients (n = 48). The self-descriptions, when rated on 18 scales that fell into four factors (Agency, Reflectivity, Differentiation, and Relatedness) and two affective scales (Anxiety and Depression), showed that the two patient groups shared characteristics that significantly differentiated them from women who were not patients-a lower sense of agency and relatedness. What significantly differentiated the anorexia-nervosa patients from the other psychiatric patients, as well as from the nonpatients, were a heightened and harsh self-reflectivity and more openly expressed depressive and anxious affect in the self-descriptions. The implications for treatment and for understanding eating disorders are discussed.


Mental hygiene movement as a (r)evolutionary trend in public health in interwar Kaunas and Vilnius from 1918 to 1939.
The health care system of the interwar period is distinguished by its revolutionary attempts to overcome social diseases and social hardships in general. In the researches published after the Second World War, different and in some cases even contradicting ideas on mental hygiene and eugenics were mixed together and were associated - almost exclusively - with the Nazi's racist ideology, totalitarian, or authoritarian regimes. The assessments of social-medical policy of the interwar period in the Baltic region also became rather one-sided. Felder's recent study (1) gives the impression that changes in psychiatry in Lithuania were caused by the Nazi's eugenics as a single agent. However, there were other factors. One of the most significant ones was the mental hygiene movement that will be discussed in this paper. In this research we used descriptive and comparative methods. After the First World War, the problem of treatment of the mentally ill was a medical and a social issue that required a completely new approach both in Lithuania and in Vilnius. The most notable manifestation of such a new attitude in psychiatry was a mental hygiene movement. University scientists in Vilnius and Kaunas were discussing issues of mental hygiene. The mental hygiene movement of the early 20th century played an important role in the later development in psychiatry and medical sciences. The ideas published by the medical doctors in Kaunas and Vilnius were partly characteristic of the interwar period, although some of them went far ahead of their times.


Spin label EPR-based characterization of biosystem complexity.
Following the widely spread EPR spin-label applications for biosystem characterization, a novel approach is proposed for EPR-based characterization of biosystem complexity. Hereto a computational method based on a hybrid evolutionary optimization (HEO) is introduced. The enormous volume of information obtained from multiple HEO runs is reduced with a novel so-called GHOST condensation method for automatic detection of the degree of system complexity through the construction of two-dimensional solution distributions. The GHOST method shows the ability of automatic quantitative characterization of groups of solutions, e.g. the determination of average spectral parameters and group contributions. The application of the GHOST condensation algorithm is demonstrated on four synthetic examples of different complexity and applied to two physiologically relevant examples--the determination of domains in biomembranes (lateral heterogeneity) and the study of the low-resolution structure of membrane proteins.


Pharmacokinetics in rats of a long-acting human parathyroid hormone-collagen binding domain peptide construct.
The pharmacokinetics of a hybrid peptide consisting of the N-terminal biologically active region of human parathyroid hormone (PTH) linked to a collagen-binding domain (CBD) were evaluated in female Sprague-Dawley rats. The peptide, PTH-CBD, consists of the first 33 amino acids of PTH linked as an extension of the amino acid chain to the CBD peptide derived from ColH collagenase of Clostridium histolyticum. Serum concentrations arising from single dose administration by the subcutaneous and intravenous routes were compared with those measured following route-specific mole equivalent doses of PTH(1-34). Population-based modeling demonstrated similar systemic absorption kinetics and bioavailability for both peptides. Exposure to PTH-CBD was sixfold higher because of a systemic clearance of approximately 20% relative to PTH(1-34); however, these kinetics were consistent with more than 95% of a dose being eliminated from serum within 24 h. Results obtained support continued investigation of PTH-CBD as a bone-targeted anabolic agent for the treatment of postmenopausal osteoporosis.


Non-Noble Metal Oxide Catalysts for Methane Catalytic Combustion: Sonochemical Synthesis and Characterisation.
The aim of this study was to obtain nanocrystalline mixed metal-oxide-ZrO₂ catalysts via a sonochemically-induced preparation method. The effect of a stabiliser's addition on the catalyst parameters was investigated by several characterisation methods including X-ray Diffraction (XRD), nitrogen adsorption, X-ray fluorescence (XRF), scanning electron microscopy (SEM) equipped with energy dispersive X-ray spectrometer (EDS), transmission electron microscopy (TEM) and µRaman. The sonochemical preparation method allowed us to manufacture the catalysts with uniformly dispersed metal-oxide nanoparticles at the support surface. The catalytic activity was tested in a methane combustion reaction. The activity of the catalysts prepared by the sonochemical method was higher than that of the reference catalysts prepared by the incipient wetness method without ultrasonic irradiation. The cobalt and chromium mixed zirconia catalysts revealed their high activities, which are comparable with those presented in the literature.


Temperature dependence of droplet breakup in 8CB and 5CB liquid crystals.
Droplet breakup of many Newtonian fluids is well described by current experiments, theory, and simulations. Breakup in complex fluids where interactions between mesoscopic structural features can affect the flows remains poorly understood and a burgeoning area of research. Here, we report on our investigations of droplet breakup in thermotropic liquid crystals. We investigate breakup in the smectic, nematic, and isotropic phases of 4-cyano 4-octylbiphenyl (8CB) and the nematic and isotropic phases of 4-cyano 4-pentylbiphenyl (5CB). The experiment consists of varying the ambient temperature to control liquid crystalline phase and imaging breakup using a fast video camera at up to 110000 frames/s. We expand on previous work [John R. Savage et al., Soft Matter 6, 892 (2010)] that shows breakup in the smectic phase is symmetric, producing no satellite droplets, and is well described by a similarity solution for a shear-thinning power-law fluid. We show that in the nematic phase the breakup occurs in two stages. In the first stage, the breakup is symmetric and the power-law exponent for the minimum radius dependence on the time left to breakup is 1.2<n<1.9. In the second stage the drop develops two minima and the minimum radii shrink with a power-law exponent 0.6<n<1. We find that the exponents vary with temperature across the nematic phase. These results are surprising because rheological measurements of 8CB and 5CB in the nematic phases indicate Newtonian behavior that cannot account for the observed breakup dynamics. Finally, in the isotropic phase, the exponents are consistent with theoretical predictions and experiments for Newtonian fluid breakup in the inertial viscous regime.


Cognitive Processes of Cancer Patients: A Major Threat to Patients' Quality of Life.
To explore the effects of intrusive and deliberate rumination on the quality of life of cancer patients. Descriptive cross-sectional design. PIMS and NORI Hospital between July to September 2016. A sample of 100 cancer patients participated in the study. The patients fulfilling the inclusion criteria were given a written consent form. Event related Rumination Inventory and WHO Quality of Life-Bref scale was used for data collection. There were 57 male and 43 female patients within the age range of 18 to 66 years (mean = 36.62 +13.77 years). A significant negative correlation was found between intrusive rumination and all domains of quality of life as physical (r = -0.28, p<0.01), psychological (r = -0.19, p<0.01), social (r = -0.20, p<0.01), environmental (r = -0.17, p<0.05), and global (r = -0.26, p<0.01) functioning. Furthermore, results on regression analysis showed the significant prediction of the intrusive rumination on all domains of quality of life. The effect of deliberate rumination was found to be non-significant. Intrusive rumination significantly negatively predicted all domains of quality of life, whereas, quality of life of cancer patients was not significantly predicated by deliberate rumination.


Update on Transanal NOTES for Rectal Cancer: Transitioning to Human Trials.
The feasibility of natural orifice translumenal endoscopic surgery (NOTES) resection for rectal cancer has been demonstrated in both survival swine and fresh human cadaveric models. In preparation for transitioning to human application, our group has performed transanal NOTES rectal resection in a large series of human cadavers. This experience both solidified the feasibility of resection and allowed optimization of technique prior to clinical application. Improvement in specimen length and operative time was demonstrated with increased experience and newer platforms. This extensive laboratory experience has paved the way for successful clinical translation resulting in an ongoing clinical trial. To date, based on published reports, 4 human subjects have undergone successful hybrid transanal NOTES resection of rectal cancer. While promising, instrument limitations continue to hinder a pure transanal approach. Careful patient selection and continued development of new endoscopic and flexible-tip instruments are imperative prior to pure NOTES clinical application.


Risk of technique failure and death in fungal peritonitis is determined mainly by duration on peritoneal dialysis: single-center experience of 24 years.
Fungal peritonitis (FP) is an infrequent cause of peritonitis in peritoneal dialysis (PD), but it has high morbidity and mortality. We analyzed the experience with FP in a single PD unit over a 24-year period. We identified 671 episodes of peritonitis that occurred in 496 patients during the study period. Of these episodes, 23 (3.4%) were FP episodes occurring in 21 patients. In the FP episodes, the patients' mean time on PD was 29.2 +/- 27 months. In 5 episodes, the patients had experienced a peritonitis episode within the preceding month, and in 11 episodes, the patients had used antibiotics within the preceding month. The FP diagnosis was made a mean of 3.17 +/- 3 days after the diagnosis of peritonitis, and in 1 patient, the diagnosis was made after death. Candida spp. were isolated in 82.6% of patients. In 91.3%, the peritoneal catheter was removed. After the FP diagnosis, 15 patients dropped out of PD, but in only 8 patients (34.7%) was drop-out related to FP. In 4 patients, drop-out occurred because of peritoneal membrane failure, and 4 patients (17.4%) died. Time on PD was significantly higher in the group of patients that dropped out of PD because of the FP (45.7 +/- 31 months vs. 19 +/- 18 months, p = 0.02). Fungal peritonitis is a rare cause of peritonitis in PD patients, but it is associated with high morbidity and mortality. Longer time on PD is the main factor in technique failure and mortality.


A Hyperspectral Data 3D Convolutional Neural Network Classification Model for Diagnosis of Gray Mold Disease in Strawberry Leaves.
Gray mold disease is one of the most frequently occurring diseases in strawberries. Given that it spreads rapidly, rapid countermeasures are necessary through the development of early diagnosis technology. In this study, hyperspectral images of strawberry leaves that were inoculated with gray mold fungus to cause disease were taken; these images were classified into healthy and infected areas as seen by the naked eye. The areas where the infection spread after time elapsed were classified as the asymptomatic class. Square regions of interest (ROIs) with a dimensionality of 16 × 16 × 150 were acquired as training data, including infected, asymptomatic, and healthy areas. Then, 2D and 3D data were used in the development of a convolutional neural network (CNN) classification model. An effective wavelength analysis was performed before the development of the CNN model. Further, the classification model that was developed with 2D training data showed a classification accuracy of 0.74, while the model that used 3D data acquired an accuracy of 0.84; this indicated that the 3D data produced slightly better performance. When performing classification between healthy and asymptomatic areas for developing early diagnosis technology, the two CNN models showed a classification accuracy of 0.73 with regards to the asymptomatic ones. To increase accuracy in classifying asymptomatic areas, a model was developed by smoothing the spectrum data and expanding the first and second derivatives; the results showed that it was possible to increase the asymptomatic classification accuracy to 0.77 and reduce the misclassification of asymptomatic areas as healthy areas. Based on these results, it is concluded that the proposed 3D CNN classification model can be used as an early diagnosis sensor of gray mold diseases since it produces immediate on-site analysis results of hyperspectral images of leaves.


Approach to and management of abnormalities in plasma sodium.
The differential diagnosis between hypertonic, isotonic and hypotonic hyponatremia are presented. The help of some usual serum (urea, uric acid and TCO2) and urine parameters (mainly osmolality and sodium concentration) are discussed and help to determine the best treatment. Morbidity associated with untreated hyponatremia and with the different treatment available is also discussed. Who to prevent and treat ODS (osmotic demyelating syndrome) is recalled. The pathophysiology and treatment of hypernatremia are also discussed.


Epidemiology and distribution of tick-borne encephalitis.
Tick-borne encephalitis (TBE) is the main tick-borne virus infection in Eurasia. It is prevalent across the entire continent from Japan to France and occurs in endemic foci. Expansion of prevalence in areas including northern Russia, Sweden, and Finland has been observed in recent years. Ticks are the most important vectors and may transmit the TBE virus to animals and humans. TBE can also be transmitted to humans in milk containing the virus. TBE has been implicated as a travel-acquired illness and there are isolated reports of its occurrence in countries outside the known areas of prevalence. Therefore, TBE should be included in the differential diagnosis for all central nervous system diseases inside or outside endemic areas.


Comparison and Validation of Putative Pathogenicity-Related Genes Identified by T-DNA Insertional Mutagenesis and Microarray Expression Profiling in Magnaporthe oryzae.
High-throughput technologies of functional genomics such as T-DNA insertional mutagenesis and microarray expression profiling have been employed to identify genes related to pathogenicity in Magnaporthe oryzae. However, validation of the functions of individual genes identified by these high-throughput approaches is laborious. In this study, we compared two published lists of genes putatively related to pathogenicity in M. oryzae identified by T-DNA insertional mutagenesis (comprising 1024 genes) and microarray expression profiling (comprising 236 genes), respectively, and then validated the functions of some overlapped genes between the two lists by knocking them out using the method of target gene replacement. Surprisingly, only 13 genes were overlapped between the two lists, and none of the four genes selected from the overlapped genes exhibited visible phenotypic changes on vegetative growth, asexual reproduction, and infection ability in their knockout mutants. Our results suggest that both of the lists might contain large proportions of unrelated genes to pathogenicity and therefore comparing the two gene lists is hardly helpful for the identification of genes that are more likely to be involved in pathogenicity as we initially expected.


Poisoning with organophosphorus insecticides.
Because of an increasing incidence of poisoning with the newer organophosphorus anticholinesterase insecticides, these compounds have been reviewed in terms of their history and pharmacology, relationship with other drugs, factors affecting toxicity, mechanism of action, toxic signs and treatment. The modern organophosphorus pesticide requires metabolic conversion before toxicity develops. Insects have a greater propensity for this conversion than humans. Nevertheless, this conversion does occur in humans and can be potentiated by other drugs. Toxicity also varies with age, sex, route and frequency of administration, and previous exposure. The mechanism of toxicity is inhibition of acetylcholinesterase, causing an intoxicating build-up of acetylcholine. Signs and symptoms consist of the clinical manifestations of unopposed parasympathetic and central activity. Treatment must be initiated early. Respiration must be maintained and the effects of acetylcholine must be counteracted by massive doses of atropine. Metaraminol enhances the antagonistic action of atropine against acetylcholine and may also be given. Once acetylcholinesterase is inactivated, restoration is slow. Recovery can be accelerated by enzyme reactivators like the oxime compounds. Pyridine aldoxime (Pralidoxime, Protopam, P(2)S and 2-PAM) can be given in combination with atropine and metaraminol (AMP therapy) and may be the treatment of choice.


Five New Limonoids from Peels of Satsuma Orange (Citrus reticulata).
Five new: 21,23-dihydro-21-hydroxy-23-oxonomilin (1), 21,23-dihydro-23-methoxy-21-oxonomilin (2), 21,23-dihydro-21-hydroxy-23-oxonomilinic acid methyl ester (3), 21,23-dihydro-23-methoxy-21-oxolimonin (4), and 21,23-dihydro-21-oxolimonin (5), and seven known limonoids were isolated from peels of satsuma orange (Citrus reticulata). The isolated compounds were evaluated for their inhibitory effects on macrophage activation by an inhibitory assay of nitric oxide (NO) production. Among them, compound (2) exhibited NO inhibitory activity without cytotoxicity.


Evaluation of adverse effects in intracarotid propofol injection for Wada test.
The authors evaluated adverse effects of intracarotid propofol injection during a Wada test and their risk factors in 58 patients. Nineteen patients had an adverse effect, mostly in patients receiving more than 10 mg. For patients older than age 55 years or those requiring an injection dose greater than 20 mg to produce hemiplegia, propofol should be injected slowly and patients monitored for excitatory movements.


The Impact of Chronic Disease on the Corrected QT (QTc) Value in Women in a British Columbia First Nations Population.
Indigenous women have higher rates of chronic disease than Indigenous men and non-Indigenous women. Long QT syndrome (LQTS) can be inherited or acquired; the latter may occur with chronic disease. A prolonged corrected QT value (QTc) is an independent risk factor for ventricular arrhythmias and sudden death, but few studies have quantified the impact of chronic disease on the QTc. We assessed the association between chronic disease and QTc prolongation in a population of First Nations women previously ascertained to study a high rate of inherited LQTS due to a unique genetic (founder) variant in their community. This substudy focusing on women expands on the original research where patients with clinical features of LQTS and their relatives were assessed for genetic variants discovered to affect the QTc. Medical records were retrospectively reviewed and chronic diseases documented. Using multivariate linear regression, adjusting for the effect of genetic variants, age, and QTc-prolonging medications, we evaluated the association between chronic disease and the QTc. In total, 275 women were included. After adjustments, a prolonged QTc was associated with coronary artery disease (26.5 ms, 95% confidence interval [CI] 9.0-44.1 ms; P = 0.003), conduction system disease (26.8 ms, 95% CI 2.2-51.4 ms; P = 0.033), rheumatoid arthritis (28.9 ms, 95% CI 12.7-45.1 ms; P = 0.001), and type 2 diabetes mellitus (17.9 ms, 95% CI 3.6-32.3 ms; P = 0.015). This quantification of the association between chronic disease and QTc prolongation in an Indigenous cohort provides insight into the nongenetic determinants of QTc prolongation. Corroboration in other populations will provide evidence for generalisability of these results.


Prevalence of problem gambling among the prison population in Hamburg, Germany.
Despite the increasing research in gambling, the prevalence of problem gambling in the criminal justice population is rarely investigated, especially in Europe. Given the lack in knowledge the Hamburg study aimed at identifying the prevalence of problem gambling in the whole regional prison population. For this purpose two major approaches were used: a 10 months long-term screening of pre-trial detainees at prison entry through the Lie/Bet Questionnaire, and full-scale survey of inmate personnel records of prisoners being in prison on a defined reporting date. Based on 792 valid screening files 6.6 % of the pre-trial detainees were positive on the Lie/Bet Questionnaire, and these problem gamblers were male only. Among the 1,236 inmate personnel records reviewed in 7.3 % the records indicated problem gambling (90 prisoners). This indication was found in 7.5 % males and 3.6 % females. For almost half of the prisoners with problem gambling their prison sentence was related to their gambling behavior (46.7 %). These results are representative for the regional prison population, and the first of its kind in Europe.


Sorbitol production in charged membrane bioreactor with coenzyme regeneration system: I. Selective retainment of NADP(H) in a continuous reaction.
The concept of a charged membrane bioreactor (CMBR) has been proposed for continuous reactions of enzymatic reduction dependent upon the nicotinamide coenzyme NADP(H). It was found that a composite membrane with a negative charge, NTR 7410, could retain NADP(H) selectively without any chemical modification. Several permeation experiments have revealed that the retainment of a coenzyme is based on electrostatic repulsion of negative charges between the membrane and the phosphate moiety of NADP(H). The retainment ratio was reduced by the addition of inorganic salt, although it could be restored to 0.8 in the presence of albumin. A reactor equipped with a charged membrane as the coenzyme separator module was constructed and used in the continuous production of sorbitol. NADPH-dependent aldose reductase isolated from Candida tropicalis IAM 12202 was used for the production of sorbitol from glucose. The coenzyme oxidized in this reaction was enzymatically regenerated by conjugation with glucose dehydrogenase, together with the coproduction of gluconic acid from glucose. With a substrate conversion of 85%, 100 g/L sorbitol was produced and equimolar gluconic acid was coproduced for more than 800 h, indicating that the reaction was efficiently coupled to the enzymatic regeneration. The initial high retainment ratio of the membrane was almost maintained throughout the entire reaction. Consequently, the turnover number of the coenzyme reached 106,000.


Effects of age, speech rate, and environmental support in using telephone voice menu systems.
Age differences in the use of telephone menu systems were investigated in two experiments. Participants from three age groups (younger: 18-39; middle-aged: 40-59; older: 60+ years) were required to obtain specified information or perform some action using simulated voice menu systems. Measures reflecting task performance, menu navigation, and subjective responses were collected. The focus in Experiment 1 was on examining the effect of speech rate. Data from 196 participants indicated age differences in performance, especially for complex problems. There was no effect of speech rate on any of the performance measures. Experiment 2 examined two types of support devices: a screen phone and a graphical aid. Data from 114 participants indicated that the screen phone provided some benefits in navigational efficiency. In terms of performance, the older participants benefited more from the graphical aid and the younger participants performed better with the screen phone. Actual or potential applications of this research include guidance in the use of support devices that can reduce memory demands and the identification of appropriate speech rates.


Folic acid supplementation and risk for congenital limb reduction defects in China.
Folic acid (FA) supplementation prevents neural tube defects, but there are mixed results for its ability to prevent limb reduction defects. We examined whether a preventive effect of FA supplementation exists for congenital limb reduction defects in a large population in China. Data from a large population-based cohort study in China were used to evaluate the effects of FA supplementation on birth defects. All births at 20 complete gestational weeks, including live births, stillbirths and pregnancy terminations, and all structural congenital anomalies, regardless of gestational week, were recorded. A total of 247 831 singleton live births delivered at gestational ages of 20-42 weeks to women from northern and southern China with full information on FA intake were included. Limb reduction defects were classified by subtype and maternal FA supplementation. The prevalence of limb reduction defects was 2.7 per 10 000 births among women who took FA compared with 9.7 per 10 000 births among those who did not take FA in northern China; the prevalence was 4.5 and 3.8 per 10 000 births, respectively, in southern China. In both unadjusted and adjusted analyses, the estimated relative risk for upper limb reduction defects [odds ratio (OR) = 0.17, 95% confidence interval (CI): 0.04, 0.63] and total limb reduction defects (OR = 0.24, 95% CI: 0.08, 0.70) in northern China, but not for lower limb reduction defects ,was significantly decreased in association with FA supplementation in northern China. There was no association between FA supplementation and either an increased or decreased risk for limb reduction defects in southern China. FA supplementation successfully reduces the prevalence of limb reduction defects in northern China, whose population has low folate concentrations.


Unraveling the Photodeprotection Mechanism of Anthraquinon-2-ylmethoxycarbonyl-Caged Alcohols Using Time-Resolved Spectroscopy.
Anthraquinone (AQ) compounds have been used as photolabile protecting groups (PPGs) to protect alcohols, ketones, and carboxylic acids. However, because of the lack of direct spectroscopic information for the transient species and intermediates related with the deprotection reaction(s), the photorelease mechanism(s) of these systems are still largely unknown. In this contribution, we detail a time-resolved spectroscopic investigation using anthraquinone-protected galactose (1) and adenosine (2) to investigate the photodeprotection reaction mechanism(s) of these kinds of AQ-PPGs. It was found that, in THF-H2O solvents, the ketyl radical species generated for 1 and 2 was found to be a reactive intermediate that then formed a dihydroxyanthracene species. The photodeprotection then occurred with the accompaniment of a decarboxylation process. These results provide an improved understanding for how AQ-PPGs work and will help assist in the design and applications of selected anthraquinone derivatives as a PPG platform, especially in aqueous environments more relevant for use in biological systems.


The half-truth of first-mover advantage.
Many executives take for granted that the first company in a new product category gets an unbeatable head start and reaps long-lasting benefits. But that doesn't always happen. The authors of this article discovered that much depends on the pace at which the category's technology is changing and the speed at which the market is evolving. By analyzing these two factors, companies can improve their odds of succeeding as first movers with the resources they possess. Gradual evolution in both the technology and the market provides a first mover with the best conditions for creating a dominant position that is long lasting (Hoover in the vacuum cleaner industry is a good example). In such calm waters, a company can defend its advantages even without exceptional skills or extensive financial resources. When the market is changing rapidly and the product isn't, a first entrant with extensive resources can obtain a long-lasting advantage (as Sony did with its Walkman personal stereo); a company with only limited resources probably must settle for a short-term benefit. When the market is static but the product is changing constantly, first-mover advantages of either kind--durable or short-lived--are unlikely. Only companies with very deep pockets can survive (think of Sony and the digital cameras it pioneered). Rapid churn in both the technology and the market creates the worst conditions. But if companies have an acute sense of when to exit-as Netscape demonstrated when it agreed to be acquired by AOL-a worthwhile short-term gain is possible. Before venturing into a newly forming market, you need to analyze the environment, assess your resources, then determine which type offirst-mover advantage is most achievable. Once you've gone into the water, you have no choice but to swim.


New staff and a team approach boost morale.
Your staff's work environment can have a significant impact on how they view their jobs and how they deal with patients. Here are some strategies for improving this all-important area of ED management: When possible, increase the number of physicians in your staff while keeping the total number of hours worked constant. Invite nurses to social gatherings to meet new physicians, to help engender a sense of teamwork. Showing flexibility when nursing staff requests personal time off will be rewarded by an enthusiastic response when you need additional coverage.


Toll-like receptor 9 activation with CpG oligodeoxynucleotides for asthma therapy.
Prokaryotic DNA has long been recognized as immunostimulatory. In the last decade the role played by CpG motifs (nucleotide sequence motifs centered on a cytosine-guanine dinucleotide) in bacterial and viral DNA has been elucidated. CpG motifs are detected by the innate immune pattern recognition receptor Toll-like receptor (TLR) 9, the ligation of which activates multiple signal cascades in responding cells. A restricted pattern of TLR9 expression to certain dendritic cells and B cells appears to provide relative specificity in responses, especially in comparison to other TLR ligands. TLR9 activation induces a Th1-like pattern of cytokine release which led to interest in the use of synthetic CpG oligodeoxynucleotides (CpG ODN) for the prevention and treatment of Th2-associated atopic disorders such as asthma. Interestingly, Th1 cytokines do not appear to be necessary for a therapeutic response in preclinical models of atopic asthma. Additional potential mechanisms of action include induction of regulatory-type responses (involving interleukin-10 release), and expression of indoleamine 2,3-dioxygenase. CpG ODN have been shown to prevent and reverse antigen-induced eosinophilic airway inflammation in animal models; human trials are ongoing with encouraging early results when used as a ragweed vaccine adjuvant in allergic upper airway disease.


Cyclic fluctuation of blood pressure in neonatal neuroblastoma.
Herein is described a case of neonatal neuroblastoma with cyclic blood pressure fluctuation and elevated catecholamines. The fluctuations stabilized after treatment with α-adrenergic blocker and the perioperative course was uneventful. The possibility of catecholamine-related symptoms including hypertension, heart failure, and blood pressure fluctuations should be considered in the treatment for neuroblastoma; if they are present, treatment with α-blockers is effective.


A low-cost mesocosm for the study of behaviour and reproductive potential in Afrotropical mosquito (Diptera: Culicidae) vectors of malaria.
A large-scale mesocosm was constructed and tested for its effectiveness for use in experiments on behaviour, reproduction and adult survivorship in the Afrotropical malaria vector Anopheles gambiae s.s. Giles (Diptera: Culicidae) in temperate climates. The large space (82.69 m(3) ) allowed for semi-natural experiments that increased demand on a mosquito's energetic reserves in an environment of widely distributed resources. A one-piece prefabricated enclosure, made with white netting and vinyl, prevented the ingress of predators and the egress of mosquitoes. Daylight and white materials prompted the mosquitoes to seclude themselves in restricted daytime resting sites and allowed the easy collection of dead bodies so that daily mortality could be assessed accurately using a method that accounts for the loss of a proportion of bodies. Here, daily, age-dependent mortality rates of males and females were estimated using Bayesian Markov chain Monte Carlo simulation. In overnight experiments, mosquitoes successfully located plants and took sugar meals. A 3-week survival trial with a single cohort demonstrated successful mating, blood feeding, oviposition and long life. The relatively low cost of the mesocosm and the performance of the mosquitoes in it make it a viable option for any behavioural or ecological study of tropical mosquitoes in which space and seasonal cold are constraining factors.


A novel 3D non-autonomous system with parametrically excited abundant dynamics and bursting oscillations.
In this paper, a novel non-autonomous chaotic system with rich dynamical behaviors is proposed by introducing parametric excitation to a Lorenz-like system, and the effect of the initial value of the excitation system on the resulting system dynamics is then thoroughly investigated. The attractors resulting from the proposed chaotic system will enter different oscillating states or have topological change when the initial value varies. Furthermore, some novel bursting oscillations and bifurcation mechanism are revealed. Stability and bifurcation of the proposed 3D non-autonomous system are comprehensively investigated to analyze the causes of the observed dynamics through a range of analytical methods, including bifurcation diagram, Lyapunov exponent spectrum, and sequence and phase diagrams. Software simulation and hardware experimentation are conducted in this study, which verify the dynamic behaviors of the proposed chaotic system. This study will create a new perspective and dimension of perceiving non-autonomous chaotic systems and exploring their applicability in real-world engineering applications.


Immunostimulatory effect of Tinospora cordifolia Miers leaf extract in Oreochromis mossambicus.
Immunostimulatory effect of leaf extract of T. cordifolia on (i) specific immunity (antibody response), (ii) non-specific immunity (neutrophil activity) and (iii) disease resistance against Aeromonas hydrophila was investigated in O. mossambicus. Ethanol and petroleum ether extracts of the leaves were used. Both ethanol and petroleum ether extracts administered at doses of 0.8, 8 or 80 mg/kg body weight, prolonged the peak primary antibody titres upto one to three weeks. Ethanol extract at the dose of 8 mg/kg and petroleum ether extract at the doses of 0.8 or 8 mg/kg enhanced the secondary antibody response. All the doses of ethanol extract significantly enhanced neutrophil activity. Fish injected with petroleum ether or ethanol extract at a dose of 8 mg/kg were protected against experimental infection with virulent A. hydrophila. The results indicates the potential of T. cordifolia leaf extracts for use as an immunoprophylactic to prevent diseases in finfish aquaculture.


Three-dimensional transesophageal echocardiographic demonstration of intraatrial baffle obstruction.
We report an adult patient with transposition of the great arteries status post-Mustard procedure in whom three-dimensional transesophageal echocardiography demonstrated intraatrial baffle obstruction. The baffle could be visualized in both long-axis and "en face" short-axis views.


Expression of interferon receptor genes (IFNAR1 and IFNAR2 mRNA) in the liver may predict outcome after interferon therapy in patients with chronic genotype 2a or 2b hepatitis C virus infection.
Hepatitis C virus (HCV) genotype 2a or 2b is associated with a favorable outcome after interferon therapy. However, 19% to 33% of patients do not respond to therapy. We investigated whether interferon receptor gene (IFNAR1 and IFNAR2 mRNA) expression in the liver before interferon therapy predicts long-term response to therapy in patients with genotype 2a or 2b HCV infection. Twenty-seven patients who subsequently received interferon-alpha therapy underwent liver biopsies before interferon therapy. Hepatic IFNAR1 and IFNAR2 mRNA were determined using a reverse transcription-polymerase chain reaction assay. Twenty (74%) patients responded to interferon therapy, while the remaining seven (26%) patients were nonresponders. The expression rates of IFNAR1 and IFNAR2 mRNA in the liver were significantly higher in responders than nonresponders (p < 0.01, by chi-square test). The presence of either IFNAR1 or IFNAR2 mRNA predicted complete response to interferon treatment, with a positive predictive value of 100%. Multiple logistic regression analysis showed that IFNAR1 and/or IFNAR2 mRNA expression was the only significant predictor of the effectiveness of IFN therapy (p = 0.0002). We conclude that expression of interferon receptor genes in the liver is a useful index for predicting the long-term efficacy of interferon therapy in patients with chronic genotype 2a or 2b HCV infection.


Relationships and revised status of Nagathrips (Thysanoptera: Phlaeothripinae).
The generic name Nagathrips was erected as a sub-genus of Mesothrips for the single species, crenulatus Varatharajan and Singh (2000). Subsequent studies revealed character states that were not included in the original description. These are: prosternal basantra absent; antennal segment III with one slender sense cone, segment IV with three similar sense cones; fore wings parallel-sided with no median constriction. These character states are not found in any species of Mesothrips, a genus of the Tribe Haplothripini (Mound & Minaei 2007), but are typical of members of the Liothrips-lineage (Dang et al. 2014). To confirm such a relationship partial sequence data of the mitochondrial gene (CO1) was obtained and compared with that of Gynaikothrips species.


Antibiotic Utilization and Prophylaxis in Paediatric Cardiac Surgery: A Retrospective Observational Study at a Rural Tertiary Care Hospital in India.
Introduction Antimicrobial prophylaxis, involving short antibiotic courses preceding surgical procedures, is recommended to minimize postoperative infections. Paediatric cardiac surgeries are classified as clean procedures, though infection challenges persist due to illness severity and extended ICU stays. Antimicrobial prophylaxis varies, ranging from single doses to extended administration until catheters are removed. Typically lasting 24 to 48 hours, it has proven infection-reduction benefits. Despite these practices, uncertainties surround the optimal nature, timing, and duration of administration. This concern is amplified by escalating antimicrobial resistance driven by antibiotic overuse. Vulnerable paediatric populations bear heightened consequences of irrational antimicrobial use, contributing to global resistance trends. Yet, a defined optimal prophylaxis schedule for paediatric cardiac surgery is lacking. Importing adult guidelines may be inadequate due to paediatric research complexities and population diversity. Developing effective prophylaxis protocols is crucial for children undergoing cardiac surgery, given global antibiotic overuse and evolving drug resistance. Establishing an optimal prophylactic strategy remains a challenge, necessitating further research for evidence-based protocols to mitigate infections in this vulnerable patient cohort. Methods This study investigates antibiotic use in paediatric cardiac surgery. A retrospective analysis of 100 patients from a rural Indian hospital (2017-2018) assesses antibiotic patterns, including type, dose, duration, and adherence to prophylaxis protocols. Results In the studied cohort of paediatric cardiac surgery patients, complete compliance (100%) with antibiotic prophylaxis was observed. However, deviations were identified: 30% received antibiotics prematurely, and 30% did not align with institutional protocol criteria. Concerning antibiotic selection, 87% followed hospital policy with the recommended cefoperazone and sulbactam combination plus amikacin, while 9% received piperacillin/tazobactam + amikacin due to sepsis. Irregular use (22%) based on clinical records occurred. Furthermore, 4% received piperacillin/tazobactam + teicoplanin, with one instance of inappropriate higher antibiotic use. Regarding prophylaxis duration, only 27% adhered to the appropriate timeline, with 40% exceeding 48 hours, indicating extended use. Upon discharge, a notable proportion (45 patients) received antibiotic prescriptions. Among them, 73% were prescribed rationally, while 27% exhibited irrational antibiotic use. Conclusion The findings of this study shed a significant light on the issue of antibiotic misuse within the context of paediatric cardiac surgery. It underscores the pressing need for more stringent measures to regulate and address this concerning trend. The study underscores the pivotal importance of adhering rigorously to established protocols and guidelines for antibiotic prophylaxis. This adherence not only holds the potential to elevate the overall quality of patient care but also plays a critical role in combating the escalating challenge of antibiotic resistance. Through a concerted effort to optimize antibiotic usage, we can simultaneously enhance patient outcomes and contribute to the ongoing fight against the emergence of antibiotic-resistant strains, thus preserving the efficacy of these vital medications for future generations.


Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial.
Hepatitis C virus (HCV) infection is a leading cause of morbidity and mortality in patients with HIV-1. The C-EDGE CO-INFECTION study assessed the efficacy, safety, and tolerability of grazoprevir (MK-5172) plus elbasvir (MK-8742) in patients with HCV and HIV co-infection. In this uncontrolled, non-randomised, phase 3, open-label, single-arm study, treatment-naive patients with chronic HCV genotype 1, 4, or 6 infection and HIV co-infection, with or without cirrhosis, were enrolled from 37 centres in nine countries across Europe, the USA, and Australia. Patients were either naive to treatment with any antiretroviral therapy (ART) or stable on ART for at least 8 weeks. All patients received grazoprevir 100 mg plus elbasvir 50 mg in a fixed-dose combination tablet once daily for 12 weeks. The primary endpoint was sustained virological response (HCV RNA <15 IU/mL) 12 weeks after the end of therapy (SVR12). The primary population for efficacy analyses was all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, number NCT02105662. Between June 11, 2014, and Aug 29, 2014, 218 patients were enrolled and received grazoprevir plus elbasvir for 12 weeks, all of whom completed follow-up at week 12. SVR12 was achieved by 210 (96%) of 218 patients (95% CI 92·9-98·4). One patient did not achieve SVR12 because of a non-virological reason, and seven patients without cirrhosis relapsed (two subsequently confirmed as reinfections). All 35 patients with cirrhosis achieved SVR12. The most common adverse events were fatigue (29; 13%), headache (27; 12%), and nausea (20; 9%). No patient discontinued treatment because of an adverse event. Two patients receiving ART had transient HIV viraemia. This HCV treatment regimen seems to be effective and well tolerated for patients co-infected with HIV with or without cirrhosis. These data are consistent with previous trials of this regimen in the monoinfected population. This regimen continues to be studied in phase 3 trials. Merck Sharp & Dohme Corp.