Independent particle theory with electron correlation.
We formulate an effective independent particle model where the effective Hamiltonian is composed of the Fock operator and a correlation potential. Within the model the kinetic energy and the exchange energy can be expressed exactly leaving the correlation energy functional as the remaining unknown. Our efforts concentrate on finding a correlation potential such that exact ionization potentials and electron affinities can be reproduced as orbital energies. The equation-of-motion coupled-cluster approach enables us to define an effective Hamiltonian from which a correlation potential can be extracted. We also make the connection to electron propagator theory. The disadvantage of the latter is the inherit energy dependence of the potential resulting in a different Hamiltonian for each orbital. Alternatively, the Fock space coupled-cluster approach employs an effective Hamiltonian which is energy independent and universal for all orbitals. A correlation potential is extracted which yields the exact ionization potentials and electron affinities and a set of associated molecular orbitals. We also describe the close relationship to Brueckner theory.


Restrictive allograft syndrome after lung transplantation.
Despite recent advances over the past decade in lung transplantation including improved surgical technique and immunotherapy, the diagnosis and treatment of chronic lung allograft dysfunction remains a significant barrier to recipient survival. Aside from bronchiolitis obliterans syndrome, a restrictive phenotype called restrictive allograft syndrome has recently been recognized and affects up to 35% of all patients with CLAD. The main characteristics of RAS include a persistent and unexplained decline in lung function compared to baseline and persistent parenchymal infiltrates on imaging. The median survival after diagnosis of RAS is 6 to 18 months, significantly shorter than other forms of CLAD. Treatment options are limited, as therapies used for BOS are typically ineffective at halting disease progression. Specific medications such as fibrinolytics are lacking large, multicenter prospective studies. In this manuscript, we discuss the definition, mechanism, and characteristics of RAS while highlighting the similarities and differences between other forms of CLAD. We also review the diagnoses along with current and potential treatment options that are available for patients. Finally, we discuss the existing knowledge gaps and areas for future research to improve patient outcomes and understanding of RAS.


The sense of body ownership relaxes temporal constraints for multisensory integration.
Experimental work on body ownership illusions showed how simple multisensory manipulation can generate the illusory experience of an artificial limb as being part of the own-body. This work highlighted how own-body perception relies on a plastic brain representation emerging from multisensory integration. The flexibility of this representation is reflected in the short-term modulations of physiological states and perceptual processing observed during these illusions. Here, we explore the impact of ownership illusions on the temporal dimension of multisensory integration. We show that, during the illusion, the temporal window for integrating touch on the physical body with touch seen on a virtual body representation, increases with respect to integration with visual events seen close but separated from the virtual body. We show that this effect is mediated by the ownership illusion. Crucially, the temporal window for visuotactile integration was positively correlated with participants' scores rating the illusory experience of owning the virtual body and touching the object seen in contact with it. Our results corroborate the recently proposed causal inference mechanism for illusory body ownership. As a novelty, they show that the ensuing illusory causal binding between stimuli from the real and fake body relaxes constraints for the integration of bodily signals.


Reaction mechanism for the diastereocontrolled synthesis of phosphorothioate DNA by the oxazaphospholidine approach.
Reaction mechanisms for the diastereoselective synthesis of deoxyribonucleoside 3'-cyclic phosphoramidites as well as dinucleoside phosphite intermediates by the oxazaphospholidine approach were analyzed by means of ab initio molecular orbital calculations at the HF/6-31G* level. These reactions are essential for the diastereoselective synthesis of phsophorothioate DNA.


Scanning mutagenesis of the putative transmembrane segments of Kir2.1, an inward rectifier potassium channel.
Structural models of inward rectifier K+ channels incorporate four identical or homologous subunits, each of which has two hydrophobic segments (M1 and M2) which are predicted to span the membrane as alpha helices. Since hydrophobic interactions between proteins and membrane lipids are thought to be generally of a nonspecific nature, we attempted to identify lipid-contacting residues in Kir2.1 as those which tolerate mutation to tryptophan, which has a large hydrophobic side chain. Tolerated mutations were defined as those which produced measurable inwardly rectifying currents in Xenopus oocytes. To distinguish between water-accessible positions and positions adjacent to membrane lipids or within the protein interior we also mutated residues in M1 and M2 individually to aspartate, since an amino acid with a charged side chain should not be tolerated at lipid-facing or interior positions, due to the energy cost of burying a charge in a hydrophobic environment. Surprisingly, 17 out of 20 and 17 out of 22 non-tryptophan residues in M1 and M2, respectively, tolerated being mutated to tryptophan. Moreover, aspartate was tolerated at 15 out of 22 and 15 out of 21 non-aspartate M1 and M2 positions respectively. Periodicity in the pattern of tolerated vs. nontolerated mutations consistent with alpha helices or beta strands did not emerge convincingly from these data. We consider the possibility that parts of M1 and M2 may be in contact with water.


Inadequate management of pneumonia among children in South Ethiopia: findings from descriptive study.
Health system support is crucial for quality child healthcare. Therefore, this baseline survey, which is part of the community-based management study of severe pneumonia, was conducted to assess the state of health system support of IMNCI and iCCM, and health workers' knowledge in managing childhood pneumonia at health facilities. A survey was conducted in 99 government health institutions in South Ethiopia from 07 to 14 January, 2018. A questionnaire for health system support and case scenario for the management of severe pneumonia was adapted from the WHO health facility survey tool. The questionnaire's interview, facility observation, case scenario and retrospective record review were all used as data collection methods. Indicators of health system support in the context of an integrated management of childhood illness were used. Proportions for categorical variables and means for continuous variables were also computed for each indicator. Mean score was analysed for assessing the knowledge of health workers in managing the case scenario. In the study area, only 12 (34%) of health centres and 18 (29%) of health posts received supervision, which included the observation of case management. The mean number of essential oral antibiotics for the home treatment of pneumonia available at the facility was 1.1 (95% CI 0.9 to 1.3), whereas the mean number of pre-referral drugs for the treatment of severe pneumonia was 1.3 (95% CI 1.0 to 1.6). Approximately 47 (48%; 95% CI 37.7 to 57.3) of the surveyed health facilities had materials and equipment to support vaccination services, and 71 (72%; 95% CI 62.8 to 80.6) of them had the vaccines on the day of the survey. Only four (4%; 95% CI 0.3 to 8.3) of the health facilities had all the essential job aids and supplies for providing services for pneumonia. The providers' mean knowledge score for the management of severe childhood pneumonia was 14.9 out of 22 correct answers. There is a room to improve the health system support to integrated management of neonatal and childhood illness through supply chain management and knowledge of health workers in the management of severe pneumonia by providing training.


Analytic model for light guidance in single-wall hollow-core anti-resonant fibers.
We report an analytic model for quantitatively calculating the transmission attenuation of single-wall hollow-core anti-resonant fibers. Our calculations unveil the light leakage dependences on azimuthal angle, polarization, and geometrical shape and have been examined in a variety of fiber geometries. Based on our model, a simple and clear picture about light guidance in hollow-core lattice fibers is presented. Formation of equiphase surface at fiber's outermost boundary and light emission ruled by Helmholtz equation in transverse plane constitute the basis of this picture. Using this picture, we explain how the geometrical shape of a single-wall hollow-core fiber influences its transmission properties.


Comparison of three systems of classification in predicting the outcome of diabetic foot ulcers in a Brazilian population.
The aim was to compare three ulcer classification systems as predictors of the outcome of diabetic foot ulcers: the Wagner, the University of Texas (UT) and the size (area, depth), sepsis, arteriopathy, denervation system (S(AD)SAD) systems in a specialist clinic in Brazil. Ulcer area, depth, appearance, infection and associated ischaemia and neuropathy were recorded in a consecutive series of 94 subjects. A novel score, the S(AD)SAD score, was derived from the sum of individual items of the S(AD)SAD system, and was evaluated. Follow-up was for at least 6 months. The primary outcome measure was the incidence of healing. Mean age was 57.6 years; 57 (60.6%) were male. Forty-eight ulcers (51.1%) healed without surgery; 11 (12.2%) subjects underwent minor amputation. Significant differences in terms of healing were observed for depth (P=0.002), infection (P=0.006) and denervation (P=0.002) using the S(AD)SAD system, for UT grade (P=0.002) and stage (P=0.032) and for Wagner grades (P=0.002). Ulcers with an S(AD)SAD score of <or=9 (total possible 15) were 7.6 times more likely to heal than scores >or=10 (P<0.001). All three systems predicted ulcer outcome. The S(AD)SAD score of ulcer severity could represent a useful addition to routine clinical practice. The association between outcome and ulcer depth confirms earlier reports. The association with infection was stronger than that reported from the centres in Europe or North America. The very strong association with neuropathy has only previously been observed in Tanzania. Studies designed to compare the outcome in different countries should adopt systems of classification, which are valid for the populations studied.


Roles of mechanical blood forces in vascular diseases. A clinical overview.
Under the influence of heart and elasticity of arteries, circulating blood constantly acts upon the layers of the vessels, covered by active endothelial cells. The shear stress appears like the most efficient mechanical factor developing a rubbing physical force, the laminar flow. But pulsating and centrifugal forces allow shear to be often unsteady. Mechanobiology investigates receptors and transduction across wall cells, showing that thousands of genes are activated in the endothelium leading to a lot of adaptable functions. Atherosclerosis is due to disturbances of laminar flow in specific areas where low shear allows white cells to adhere and migrate, permeability to increase. Coronaropathies, cerebral vascular accidents, aneurisms are so geometrically local diseases, of which lesions are subsequently enhanced by risk factors. Chronic venous insufficiency is also related to physical forces: hydrostatic and centrifugal pressures, and disruption of shear stress along the wall and around valvulae. Here also similar cells and biochemical phenomenons are the cause of wall remodelling and varicose. At the level of microcirculation the shear stress fall induces hypoxia, accumulation of white cells and hemorheological disorders in microvenulae. This leads to lesions of tissue, small vessel and ulcers. Numerous treatments in vascular diseases tend to restore flow and blood shearing. However a better understanding in the future should open new therapeutic fields and genetic approaches.


The use of sodium hyaluronate for the treatment of radiation recall dermatitis.
Hyaluronic acid (HA) is a high-molecular weight polysaccharide, a glycosaminoglycan that enhances fibroblast movement and metabolism during wound healing, increasing collagen fibers forming granulation tissue. We describe a 42-year-old female, who developed radiation recall dermatitis following an allogeneic stem cell transplant from an unrelated donor (MUD-PBSCT). Her skin was treated with a topical sodium hyaluronate gel twice daily (RadiaplexRX, MPM Medical). There was marked improvement after 5 days of therapy without discontinuation of any of her therapeutic agents. At a time when the health care providers were faced with considerable treatment dilemmas, this patient demonstrated improvement in the symptoms of radiation recall dermatitis with the topical application of sodium hyaluronate and no change in her medication profile. This agent could successfully allow practitioners to treat radiation recall dermatitis without discontinuation of the recall trigger drug and thus jeopardizing the outcome of the treatment regimen.


Metabolism and disposition of [14C]BMS-690514 after oral administration to rats, rabbits, and dogs.
(3R,4R)-4-Amino-1-((4-((3-methoxyphenyl)amino)pyrrolo[2,1-f] [1,2,4]triazin-5-yl)methyl)-3-piperidinol (BMS-690514) is a potent inhibitor of human epidermal growth factor receptors 1, 2, and 4 and vascular endothelial growth factor receptors 1 through 3. BMS-690514 is an oral oncologic agent currently being developed for the treatment of patients with advanced non-small cell lung cancer and breast cancer. In this investigation, a series of studies was conducted to determine the biotransformation of [(14)C]BMS-690514 after oral administration to rats, rabbits, and dogs. After administration of a single oral dose of [(14)C]BMS-690514 to rats and dogs, the majority of the radioactive dose (61-71%) was recovered in the feces, whereas 18 to 20% was eliminated in urine. In bile duct-cannulated rats, 83 and 17% of the administered radioactivity was recovered in the bile and urine, respectively, suggesting that biliary secretion was a major route for the elimination of BMS-690514-derived radioactivity in rats. The parent compound underwent extensive metabolism in both species, with <12% of the administered radioactivity recovered as BMS-690514 in the excreta samples. Metabolite profiles in plasma were qualitatively similar in rats, rabbits, and dogs. Unchanged BMS-690514 was a prominent drug-related component in the plasma profiles from all the species. However, multiple metabolites contributed significantly to the circulating radioactivity, particularly for rabbit and dog, in which metabolites comprised 73 to 93% of the area under the time curve (0-8 h). Circulating metabolites included M6, a direct O-glucuronide conjugate; M1, a hydroxylated metabolite; and glucuronide conjugates of hydroxylated and O-demethylated metabolites. Overall, the results from these studies suggested that BMS-690514 was well absorbed and highly metabolized through multiple pathways in these preclinical species.


[L-T4 malabsorption determined by intolerance to cow's milk proteins and celiac disease in a patient with congenital hypothyroidism. A clinical case].
An infant with congenital hypothyroidism (CH) is described who in the course of thyroxin replacement therapy developed cow's milk protein intolerance (CMPI) and subsequently coeliac disease (CD). The presence of these two pathologies interfered with the intestinal absorption of L-thyroxin (L-T4) and made the appropriate management of CH difficult. A male patient, formula fed from birth, was screened for CH at 5 days of age. CH was confirmed and L-T4 treatment (6.8 micrograms/kg/day per os) begun at 35 days of age. Seen after 3 weeks because of feeding problems and impaired growth and with a serum T4 concentration of 4.7 micrograms/dl and a TSH of 56 mU/ml, his replacement dose was increased to 12 micrograms/kg/day. One week later, the child was hospitalized because of vomiting, acidosis and shock. CMPI was diagnosed and the child began a diet with a hydrolyzed milk protein food. After 7 weeks the serum T4 improved to 11 micrograms/dl, the TSH decreased to 10 mU/ml, while maintaining the 12 micrograms/kg dose. After 2 months an oral challenge with cow's milk confirmed the diagnosis of CMPI with a concomitant decrease in serum T4 to 6.4 micrograms/dl, while TSH rose to 64 mU/ml. Weight and T4 levels normalised with CMPI diet. At 12 months of age the patient presented anorexia and impaired growth.(ABSTRACT TRUNCATED AT 250 WORDS)


Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes.
Recent studies have implicated fatty acid-dependent activation of the serine kinase IKKbeta, which plays a key role in tissue inflammation, in the pathogenesis of insulin resistance. High doses of salicylates have recently been shown to inhibit IKKbeta activity and might therefore ameliorate insulin resistance and improve glucose tolerance in patients with type 2 diabetes. To test this hypothesis, we studied nine type 2 diabetic subjects before and after 2 weeks of treatment with aspirin ( approximately 7 g/d). Subjects underwent mixed-meal tolerance tests and hyperinsulinemic-euglycemic clamps with [6,6-(2)H2]glucose to assess glucose turnover before and after treatment. High-dose aspirin treatment resulted in a approximately 25% reduction in fasting plasma glucose, associated with a approximately 15% reduction in total cholesterol and C-reactive protein, a approximately 50% reduction in triglycerides, and a approximately 30% reduction in insulin clearance, despite no change in body weight. During a mixed-meal tolerance test, the areas under the curve for plasma glucose and fatty acid levels decreased by approximately 20% and approximately 50%, respectively. Aspirin treatment also resulted in a approximately 20% reduction in basal rates of hepatic glucose production and a approximately 20% improvement in insulin-stimulated peripheral glucose uptake under matched plasma insulin concentrations during the clamp. In conclusion, these data support the hypothesis that IKKbeta represents a new target for treating type 2 diabetes mellitus.


[Investigation of seminal plasma. Value of nuclear magnetic resonance].
The purpose of this study was to investigate whether the measurement by NMR of some biochemical markers such as glycerylphosphorylcholine (GPC), glycerylphosphorylethanolamine (GPE), citrate, and lactate in human seminal plasma may be able to differentiate spermatogenic failure from obstructive azoospermia. The peak area ratios citrate/lactate, between normozoospermic and spermatogenic failure or obstructive azoospermia groups were significantly different. We have also found significant differences in GPE/GPC peak intensity ratio between spermatogenic failure men and obstructive azoospermia patients (P < 0.001). This ratio appears to be a very important parameter to differentiate spermatogenic failure from obstructive azoospermia. These results demonstrate the potential use of 1H NMR on human seminal plasma in male infertility evaluation and such analysis may be used to elucidate the molecular basis of the human pathologic seminal plasma disturbances.


Critical role of calpain in spinal cord degeneration in Parkinson's disease.
While multiple molecular mechanisms contribute to midbrain nigrostriatal dopaminergic degeneration in Parkinson's disease (PD), the mechanism of damage in non-dopaminergic sites within the central nervous system, including the spinal cord, is not well-understood. Thus, to understand the comprehensive pathophysiology underlying this devastating disease, postmortem spinal cord tissue samples (cervical, thoracic, and lumbar segments) from patients with PD were analyzed compared to age-matched normal subjects or Alzheimer's disease for selective molecular markers of neurodegeneration and inflammation. Distal axonal degeneration, relative abundance of both sensory and motor neuron death, selective loss of ChAT(+) motoneurons, reactive astrogliosis, microgliosis, increased cycloxygenase-2 (Cox-2) expression, and infiltration of T cells were observed in spinal cord of PD patients compared to normal subjects. Biochemical analyses of spinal cord tissues revealed associated inflammatory and proteolytic events (elevated levels of Cox-2, expression and activity of μ- and m-calpain, degradation of axonal neurofilament protein, and concomitantly low levels of endogenous inhibitor - calpastatin) in spinal cord of PD patients. Thus, pathologically upregulated calpain activity in spinal cords of patients with PD may contribute to inflammatory response-mediated neuronal death, leading to motor dysfunction. We proposed calpain over-activation and calpain-calpastatin dysregulation driving in a cascade of inflammatory responses (microglial activation and T cell infiltration) and degenerative pathways culminating in axonal degeneration and neuronal death in spinal cord of Parkinson's disease patients. This may be one of the crucial mechanisms in the degenerative process.


Interspecific comparison of the mechanical properties of mussel byssus.
Byssally tethered mussels are found in a variety of habitats, including rocky intertidal, salt marsh, subtidal, and hydrothermal vents. One key to the survival of mussels in these communities is a secure attachment, achieved by the production of byssal threads. Although many studies have detailed the unique biomechanical properties of byssal threads, only a few prevalent species have been examined. This study assesses the variation in the mechanical properties of byssus in a broad range of mussel species from diverse environments, including intertidal and subtidal Mytilus edulis, Modiolus modiolus, Geukensia demissa, Bathymodiolus thermophilus, and Dreissena polymorpha. A tensometer was used to measure quasi-static and dynamic mechanical properties of individual threads, and several aspects of morphology were quantified. The results indicate that thread mechanical properties vary among mussel species, and several novel properties were observed. For example, of the species examined, D. polymorpha threads were the strongest, stiffest, least resilient, and fastest to recover after partial deformation. Threads of M. modiolus were characterized by the presence of two distinct yield regions prior to tensile failure. This comparative study not only provides insight into the ecological limitations and evolution of mussels, but also suggests new models for the design of novel biomimetic polymers.


Optimal scheduling of interleukin-12 and fractionated radiation therapy in the murine Lewis lung carcinoma.
Interleukin-12 (IL-12), a naturally occurring cytokine, has demonstrated antitumor activity in several murine solid tumors. The Lewis lung carcinoma was used to study the most effective scheduling of recombinant murine interleukin-12 (rmIL-12) administration with fractionated radiation therapy. The effect of the schedule of rmIL-12 administration alone or along with a 1- or 2-week fractionated radiation therapy regimen was examined. Beginning rmIL-12 prior to or at the same time as radiation therapy and extending rmIL-12 through the radiation regimen and beyond produced the longest tumor growth delays. Those treatment regimens which were most effective against the primary tumor were also most effective in decreasing the number of lung metastases on day 20. To further assess the immunotherapeutic effects from rmIL-12 administration, the efficacy of rmIL-12 with fractionated radiation therapy delivered to a right hind-limb tumor was measured as tumor growth delay in an unirradiated left hind-limb tumor. There was some difference in the tumor growth delay between the unirradiated tumor in the animals bearing an irradiated tumor in the contralateral leg, and the tumors in animals receiving rmIL-12 only. Recombinant murine granulocyte-macrophage-colony stimulating factor (rmGM-CSF) was also an antitumor agent active against the Lewis lung carcinoma and produced an additive effect in combination with fractionated radiation therapy in this tumor. rmIL-12 was a radiation sensitizer in the Lewis lung carcinoma. When rmIL-12 (45-microg/kg) and rmGM-CSF (45 microg/kg) were administered together with fractionated radiation therapy, a marked increase in tumor growth delay resulted. This treatment combination also nearly ablated lung metastases on day 20 in these animals. These results may serve as a useful guide in developing clinical protocols, including rmIL-12 and fractionated radiation therapy.


Transient Receptor Potential (TRP) Channels in Drug Discovery: Old Concepts & New Thoughts.
2017 marks the 20th anniversary of the molecular cloning by David Julius and colleagues (1997) of the long sought-after capsaicin receptor, now known as TRPV1 (Transient Receptor Potential Vanilloid 1) [1]. This seminal discovery has opened up a "hot" new field of basic research and launched drug discovery efforts into the large family (by the latest count 28 mammalian members, 27 in humans) of TRP ion channels [2]. Indeed, it took less than a decade for the first potent, small molecule TRPV1 antagonists to enter phase 1 clinical trials [3]. Yet, despite the large amount of resources that has been invested in TRPV1 research, there are currently no TRPV1-targeted drugs in phase 3 clinical trials. In this special issue of Pharmaceuticals, we aim to capture the progress in the TRP channel field over the past twenty years, with 15 articles covering a variety of TRP channels and potential relevant disease states and applications.


Transcriptome analysis of Apis mellifera antennae reveals molecular divergence underlying the division of labour in worker bees.
The olfactory system plays a fundamental role in mediating insect behaviour. Worker bees exhibit an age-dependent division of labour, performing discrete sets of behaviours throughout their lifespan. The behavioural states of bees rely on their sense of the environment and chemical communication via their olfactory system, the antennae. However, the olfactory adaptation mechanism of worker bees during their behavioural development remains unclear. In this study, we conducted a comprehensive and quantitative analysis of antennal gene expression in the Apis mellifera of newly emerged workers, nurses, foragers and defenders using RNA-seq. We found that the antenna tissues of honey bees continued developing after transformation from newly emerged workers to adults. Additionally, we identified differentially expressed genes associated with bee development and division of labour. We validated that major royal jelly protein genes are highly and specifically expressed in nurse honey bee workers. Furthermore, we identified and validated significant alternative splicing events correlated with the development and division of labour. These findings provide a comprehensive transcriptome profile and a new perspective on the molecular mechanisms that may underlie the worker honey bee division of labour.


Confusion surrounding repetitive strain injury highlighted at conference.
Uncertainty about disorders that account for many of the claims related to job injury at work became clear during a recent meeting, when speakers referred to the same disorders by several different names, including repetitive strain injury. Speakers discussed different types of injuries and reasons why they appear to be coming more common.


Social support of people with HIV/AIDS: the Social Determinants of Health Model.
To analyze the social support of people with HIV/AIDS from the perspective of the Social Determinants of Health Model. This was a cross-sectional study conducted in 2015 in an infectious disease outpatient clinic. The sample was made up of 116 people with HIV/AIDS. The data was collected through interviews, using a sociodemographic form and a social support scale. The data was analyzed using descriptive statistics, and Student's t-tests and Mann-Whitney tests were performed to determine the association between social support and the social determinants of health. Total social support was satisfactory, emotional support was influenced by smoking (p=0.0432) and instrumental support, by the number of people in the household (p=0.0003). The main source of instrumental and emotional support was relatives living outside the household, corresponding to 66.7% and 56.1%, respectively. It was found that smokers havelower emotional support and people living alone received less instrumental support.


Treponema denticola infection is not a cause of false positive Treponema pallidum serology.
It has long been assumed that parodontal disease can be a cause of false positive results in syphilis serology, but so far there are no definitive data supporting this hypothesis. In this study we tested 250 serum samples obtained from blood donors. All of them were negative when routinely screened for antibodies against Treponema pallidum. Then, all these samples were tested by immunoenzymatic (ELISA) and Western Blot (WB) assays to investigate reactivities against T. denticola. Thirteen samples showed a strong positivity when tested by both methods. When tested by WB against T. pallidum no sample met the positivity criteria. Nevertheless, bands with molecolar weights of about 30-35 KDa (endoflagellar core antigens) were recognized. All the 13 subjects serologically T. denticola positive underwent oral clinical and radiological observation: all showed a very poor parodontal status (CPSS > 103). Eleven crevicular fluid samples out of the total of 13 patients were T. denticola positive by Real Time PCR carried out using a LightCycler system. In this study we demonstrated that the presence of T. denticola in the crevicular fluid samples obtained from patients with a severe periodontal status and/or a positive serology against T. denticola is not a cause of false positive results in syphilis serology.


Maintenance of Remission with Partial Enteral Nutrition Therapy in Pediatric Crohn's Disease: A Retrospective Study.
Partial enteral nutrition (PEN) may be helpful for the maintenance of remission in pediatric Crohn's disease patients. To evaluate the efficacy of PEN treatment for preventing clinical relapse. We retrospectively assessed 42 pediatric Crohn's disease patients who entered clinical remission on 4-12 weeks of exclusive enteral nutrition (EEN) and were maintained on PEN as a supplementary diet. We evaluated the efficacy of the treatment at different time points using the weighted Pediatric Crohn Disease Activity Index (wPCDAI), Physician Global Assessment, laboratory parameters, and growth of each patient. Additionally, we assessed the use of concomitant medications. The median length of remission with PEN was 6 (0-36) months. Patients' remission was maintained on PEN without concomitant medications for a median time of zero months (0-16). The mean body mass index in the PEN group increased from 18.1 to 18.8 after six months of PEN. The median wPCDAI decreased from 30 at diagnosis to 5.0 after EEN and increased to 7.5 after three months of PEN. Overall, the median wPCDAI decreased by 26.2. PEN treatment was partially effective in maintaining remission and was able to increase BMI and lower wPCDAI. Most patients required concomitant medication after PEN initiation.


[CHYLOUS LEAKAGE AFTER LAPAROSCOPIC RENAL AND ADRENAL SURGERY].
(Objectives) It is recognized that Chylous leakage is a rare complication but is a relevant clinical problem after major abdominal surgery. It was occasionally reported in urologic surgery, but the data about its incidence and treatment outcome is still lacking. In this study, we reviewed our cases of chylous leakage after laparoscopic adrenalectomy or nephrectomy. (Patients and methods) From January 2005 to September 2014, laparoscopic adrenalectomies or nephrectomies were performed in 300 patients. The factors that affected the development of chylous leakage were analyzed. (Results) The overall incidence of chylous leakage was 4.3% (13 of 300 cases). All chylous leakage was seen on the left side, and it was commonly developed in patients with lymph node dissection or excessive hilar dissection around the left renal pedicle. Importantly, all cases were successfully managed conservatively by a low fat diet with or without octreotide. (Conclusions) Our results suggest that chylous leakage is not a rare complication after laparoscopic adrenalectomy or nephrectomy, but most cases can be treated conservatively. Chylous leakage can occur in patients with lymphadenectomy or hilar dissection on the left side.


New-onset postpartum hypertension in women without a history of hypertensive disorders of pregnancy: a multicenter study in Japan.
The aim of this study was to investigate the prevalence and risk factors of new-onset postpartum hypertension (PPHTN), defined as new-onset hypertension during the postpartum period, among women without a history of hypertension during pregnancy and labor. A multicenter retrospective study was conducted using clinical data of women who delivered at term between 2011 and 2018 at 12 maternity hospitals. A total of 18,295 normotensive women were eligible, after excluding those with hypertensive disorders of pregnancy or hypertension during labor. New-onset PPHTN was defined as multiple blood pressure readings of ≥ 140/90 mmHg between 1 d and 4 weeks postpartum among normotensive women throughout pregnancy. Multivariate regression analyses were performed to evaluate the risk factors for new-onset PPHTN. Among the 18,295 normotensive women, 227 (1.2%) presented with new-onset PPHTN. The prevalence was higher in women who delivered via cesarean section than in those who delivered vaginally (7.0% and 1.0%, respectively). The independent risk factors were maternal age ≥ 35 years (adjusted odds ratio 1.67, 95% confidence interval [1.10-2.53]), nulliparity (1.83 [1.24-2.71]), high normal blood pressure (systolic blood pressure [SBP] 120-129 and diastolic blood pressure [DBP] < 80) at the last prenatal check-up (1.96 [1.23-3.13]), elevated blood pressure (SBP 130-139 and/or DBP 80-89) (6.42 [4.15-9.95]), urinary protein 1+ (1.99 [1.27-3.11]), scheduled cesarean section (4.05 [1.69-9.69]), and emergency cesarean section (10.02 [5.10-19.70]). New-onset PPHTN was observed in 1.2% of the normotensive women, with women who delivered via cesarean section having the highest risk. Close postpartum blood pressure monitoring may be required for women with multiple risk factors to identify new-onset PPHTN in a timely manner and reduce adverse maternal consequences.


The novel calpain inhibitor A-705253 potently inhibits oligomeric beta-amyloid-induced dynamin 1 and tau cleavage in hippocampal neurons.
We have previously shown that beta-amyloid (Abeta) oligomers induced dynamin 1 and tau cleavage in cultured hippocampal neurons. As a result of this cleavage, dynamin 1 levels decreased and a toxic tau fragment was generated. Abeta-induced cleavage of these proteins was calpain-mediated and impacted both synaptic vesicle recycling and the integrity of neuronal processes [Kelly, B.L., Vassar, R., Ferreira, A., 2005. Beta-amyloid-induced dynamin 1 depletion in hippocampal neurons. A potential mechanism for early cognitive decline in Alzheimer disease. J. Biol. Chem. 280, 31746-31753; Park, S.Y., Ferreira, A., 2005. The generation of a 17kDa neurotoxic fragment: an alternative mechanism by which tau mediates beta-amyloid-induced neurodegeneration. J. Neurosci. 25, 5365-5375; Kelly, B.L., Ferreira, A., 2006. Beta-amyloid-induced dynamin 1 degradation is mediated by N-methyl-d-aspartate receptors in hippocampal neurons. J. Biol. Chem. 281, 28079-28089, Kelly, B.L., Ferreira, A., 2007. Beta-amyloid disrupted synaptic vesicle endocytosis in cultured hippocampal neurons. Neuroscience 147, 60-70]. Building on previous reports, these results identified calpain as a potential target for therapeutic intervention in Alzheimer's disease. In the present study, we tested the ability of A-705253, a novel water-soluble calpain inhibitor with oral availability and enhanced metabolic stability, to prevent Abeta-induced dynamin 1 and tau cleavage in cultured hippocampal neurons. Quantitative Western blot analysis indicated that the incubation of these cells with A-705253 prior to the addition of oligomeric Abeta reduced both dynamin 1 and tau cleavage in a dose-dependent manner. In addition, our results showed that this calpain inhibitor significantly ameliorated the cleavage of these proteins when added simultaneously with oligomeric Abeta. Furthermore, our data indicated that the use of this calpain inhibitor could have some beneficial effects even when added after the cleavage of these proteins have been triggered by Abeta. Collectively, these results suggest that, indeed, specific calpain inhibitors could play an important role in the treatment of Alzheimer's disease.


A Design-Adaptive Local Polynomial Estimator for the Errors-in-Variables Problem.
Local polynomial estimators are popular techniques for nonparametric regression estimation and have received great attention in the literature. Their simplest version, the local constant estimator, can be easily extended to the errors-in-variables context by exploiting its similarity with the deconvolution kernel density estimator. The generalization of the higher order versions of the estimator, however, is not straightforward and has remained an open problem for the last 15 years. We propose an innovative local polynomial estimator of any order in the errors-in-variables context, derive its design-adaptive asymptotic properties and study its finite sample performance on simulated examples. We provide not only a solution to a long-standing open problem, but also provide methodological contributions to error-invariable regression, including local polynomial estimation of derivative functions.


The immunophenotypic characterization of bovine lymphomas.
A prospective analysis of 38 cases of bovine lymphoma was performed. Thirty-five of the lymphomas were considered enzootic because of serologic or molecular biologic association with the bovine leukemia virus (BLV). The three remaining cases were in cattle < 1 year of age and were not associated with BLV and hence were considered sporadic lymphomas. Utilizing the national cancer Institute Working Formulation for the morphologic classification of human non-Hodgkin's lymphoma, 54.3% (19/35) of the enzootic lymphomas were classified as the diffuse large cleaved cell type. The cells of the 35 enzootic lymphomas expressed a consistent immunophenotype represented by MHCII+, gamma-heavy chain+, and lambda-light chain+; this constellation of markers indicated a mature B-cell phenotype. The three sporadic lymphomas failed to express MHCII antigen despite the presence of other B-cell antigens. There was no correlation between morphologic cell type and immunophenotype in these bovine lymphomas.


Cancellation of the zeroth order in a phase mask by mode interplay in a high index contrast binary grating.
A new grating phase mask is designed that allows the cancellation of the zeroth transmitted order in a diffraction configuration where the grating period is smaller than twice the exposure wavelength. An analytical treatment based on the true-mode method delivers the structure parameters, achieving 100% interference contrast. This modal approach is used to describe the modal operation of the giant reflection to zero-order device.


Probes for measuring fluctuation-induced Maxwell and Reynolds stresses in the edge of the Madison Symmetric Torus reversed field pinch.
Several probes have been constructed to measure fluctuation-induced Maxwell and Reynolds stresses in the edge of the Madison Symmetric Torus reversed field pinch (RFP). The magnetic probe is composed of six magnetic pickup coil triplets. The triplets are separated spatially, which allows for local measurements of the Maxwell stress. To measure the plasma flow components for evaluation of the Reynolds stress, we employ a combination of an optical probe [Kuritsyn et al., Rev. Sci. Indrum. 77, 10F112 (2006)] and a Mach probe. The optical probe measures the radial ion flow locally using Doppler spectroscopy. The Mach probe consists of four current collectors biased negatively with respect to a reference tip and allows for measurements of the poloidal and toroidal components of the bulk plasma flow. The stresses are observed to play an important role in the momentum balance in the RFP edge during internal reconnection events.


Navigating Human Immunodeficiency Virus and Primary Care Concerns Specific to the Transgender and Gender-Nonbinary Population.
Human immunodeficiency virus (HIV) prevention and treatment remain critically important to outpatient care among transgender and gender-nonbinary individuals. Epidemiologically, trans men and trans women are significantly more likely to have HIV compared with all adults of reproductive age. Here, we provide an overview of unique primary care considerations affecting transgender and gender-nonbinary individuals, including screening and treatment of HIV and other sexually transmitted infections as well as cancer screening and fertility preservation options. We also seek to review current literature and clinical practice guidelines related to drug-drug interactions between antiretroviral therapy (ART) and gender-affirming hormonal therapy (GAHT). In short, integrase strand transfer inhibitor-based therapy is not expected to have significant drug interactions with most GAHT and is preferred in most transgender individuals, including those on GAHT. Clinicians should also remain aware of current GAHT regimens and consider tailoring ART and GAHT to reduce cardiovascular and other risk factors.


Myosin Light Chain Kinase: A Potential Target for Treatment of Inflammatory Diseases.
Myosin light chain kinase (MLCK) induces contraction of the perijunctional apical actomyosin ring in response to phosphorylation of the myosin light chain. Abnormal expression of MLCK has been observed in respiratory diseases, pancreatitis, cardiovascular diseases, cancer, and inflammatory bowel disease. The signaling pathways involved in MLCK activation and triggering of endothelial barrier dysfunction are discussed in this review. The pharmacological effects of regulating MLCK expression by inhibitors such as ML-9, ML-7, microbial products, naturally occurring products, and microRNAs are also discussed. The influence of MLCK in inflammatory diseases starts with endothelial barrier dysfunction. The effectiveness of anti-MLCK treatment may depend on alleviation of that primary pathological mechanism. This review summarizes evidence for the potential benefits of anti-MLCK agents in the treatment of inflammatory disease and the importance of avoiding treatment-related side effects, as MLCK is widely expressed in many different tissues.


Preparation of a Water-Soluble Glycopolymer Bearing Porphyrin Skeletons and Its Biological Properties.
A known tetraphenyl porphyrin (TPP) having an amino functional group [5-(4-aminophenyl)-10,15,20-(triphenyl)porphyrin] was converted into the corresponding monomer by means of condensation with acryloyl chloride. Simple radical polymerization of the porphyrin monomer and a glycosyl monomer in the presence of acrylamide as a regulator monomer in order to avoid steric interference gave a water-soluble glycopolymer bearing porphyrin moieties. Spectroscopic analyses suggested incorporation of porphyrin moieties in the glycopolymer. The physical properties of the water-soluble glycopolymer bearing porphyrin moieties were examined in aqueous media, and the results also indicated the incorporation of TPP moieties in the polymer. Uptake of the polymer into HeLa cells was observed, and the cytotoxicity of the polymer was confirmed by microscopic analyses. The glycopolymer bearing porphyrin moieties is promising not only for photodynamic therapy but also as an anti-cancer reagent.


Description-based reappraisal regulate the emotion induced by erotic and neutral images in a Chinese population.
Previous emotion-regulation research has shown that the late positive potential (LPP) is sensitive to the down-regulation of emotion; however, whether LPP is also sensitive to the up-regulation of emotion remains unclear. The present study examined the description-based reappraisal effects on the up-regulation of positive emotions induced by erotic and neutral images in a Chinese population. Self-reported ratings and event-related potential (ERP) were recorded when subjects viewed pleasant and neutral images, which were shown after either a neutral or positive description. Self-reported results showed that images following positive descriptions were rated as more pleasant compared to images following neutral descriptions. ERP results revealed that the P2, P3, and slow wave (SW) components were larger for erotic pictures than for neutral pictures, while the positive description condition yielded attenuated erotic image-induced P2, P3 and SW and increased SW induced by neutral images. The results demonstrated that description-based reappraisal, as a method of reappraisal, significantly modulates the emotional experience and ERP responses to erotic and neutral images.


Role of osteoclast differentiation in the occurrence of osteoarthritis of temporomandibular joint.
This study aimed to explore the role of osteoclast differentiation in the occurrence of temporomandibular joint osteoarthritis (TMJOA). A mouse TMJOA model was constructed. Micro-CT was used to observe the changes in condylar bone during the development of TMJOA. Hematoxylin-eosin (HE) staining was used to observe the histological structure changes of the condyle of TMJOA mice. Tartrate resistant acid phosphatase (TRAP) staining was used to observe the presence of osteoclasts in TMJOA joint tissue. The synovial fluid of patients with TMJ-OA was collected to determine the effect on osteoclast differentiation. Micro-CT revealed that the condyle of the TMJOA group had the most obvious damage in the second and third weeks, and the shape of the condyles also changed in a beak-like manner. HE staining showed that the condyle cartilage and subchondral bone structure of TMJOA mice were disordered in the second week. TRAP tissue staining showed that the number of osteoclasts of the TMJOA group obviously increased in the second week. Results of cell experiments showed that the number of osteoclast differentiation significantly increased after stimulation of synovial fluid from TMJOA patients, and the cell volume increased. TMJOA animal models and TMJOA patient synovial cell experiments could induce osteoclast differentiation, indicating that osteoclast differentiation plays an important role in TMJOA occurrence.


Identification and quantification of microbial populations in activated sludge and anaerobic digestion processes.
Eight different phenotypes were studied in an activated sludge process (AeR) and anaerobic digester (AnD) in a full-scale wastewater treatment plant by means of fluorescent in situ hybridization (FISH) and automated FISH quantification software. The phenotypes were ammonia-oxidizing bacteria, nitrite-oxidizing bacteria, denitrifying bacteria, phosphate-accumulating organisms (PAO), glycogen-accumulating organisms (GAO), sulphate-reducing bacteria (SRB), methanotrophic bacteria and methanogenic archaea. Some findings were unexpected: (a) Presence of PAO, GAO and denitrifiers in the AeR possibly due to unexpected environmental conditions caused by oxygen deficiencies or its ability to survive aerobically; (b) presence of SRB in the AeR due to high sulphate content of wastewater intake and possibly also due to digested sludge being recycled back into the primary clarifier; (c) presence of methanogenic archaea in the AeR, which can be explained by the recirculation of digested sludge and its ability to survive periods of high oxygen levels; (d) presence of denitrifying bacteria in the AnD which cannot be fully explained because the nitrate level in the AnD was not measured. However, other authors reported the existence of denitrifiers in environments where nitrate or oxygen was not present suggesting that denitrifiers can survive in nitrate-free anaerobic environments by carrying out low-level fermentation; (e) the results of this paper are relevant because of the focus on the identification of nearly all the significant bacterial and archaeal groups of microorganisms with a known phenotype involved in the biological wastewater treatment.


The effect of varying glucose levels on the ex vivo crystalline lens: implications for hyperglycaemia-induced refractive changes.
Refractive changes in diabetic eyes have long been reported but with equivocal results. The lens has been a more recent focus as the source of any change but it is possible that multiple sources of variation have made it difficult to demonstrate a systematic change clinically. The aim of this study was therefore to use a bovine lens model to investigate the optical changes in hyperglycaemia and when lenses are returned to normal glucose levels as would occur following commencement of treatment. Bovine eyes were obtained and their lenses excised under sterile conditions before placing them in culture medium within an incubator using standard tissue culture techniques. In the first experiment, lenses were transferred into culture medium containing 5 mm (n = 12), 15 mm (n = 12) and 30 mm (n = 12) glucose. Measurements were made of the change in back vertex focusing distance with equatorial lens diameter using the ScanTox(™) measurement system. From these measurements, the back vertex focal length and primary longitudinal spherical aberration were derived. In a second experiment, lenses maintained at 30 mm glucose (n = 7) were stepped down to 5 mm glucose to simulate starting diabetic therapy and measured in the same way. Changes over time were assessed with a linear regression model. A trend towards myopia was observed with increasing hyperglycaemia, this was not statistically significant. When lenses were stepped-down from hyperglycaemia to normal physiological levels of glucose, a hyperopic shift was observed in line with published clinical studies that again failed to reach statistical significance. High variability in the measurement on longitudinal spherical aberration prevented any significant trends being measured. Our results suggest that there are no consistent crystalline lens-induced refractive changes following exposure to hyperglycaemia for time-periods up to 5 days used in the current study. It is possible that bovine lenses are able to offset the raised osmotic pressure from high glucose levels in the short-term by a process of osmoregulation and that repeated osmotic stress or longer term exposure may be required to induce the changes in refraction that are seen clinically.


Substrate interactions during the biodegradation of benzene, toluene, ethylbenzene, and xylene (BTEX) hydrocarbons by the fungus Cladophialophora sp. strain T1.
The soil fungus Cladophialophora sp. strain T1 (= ATCC MYA-2335) was capable of growth on a model water-soluble fraction of gasoline that contained all six BTEX components (benzene, toluene, ethylbenzene, and the xylene isomers). Benzene was not metabolized, but the alkylated benzenes (toluene, ethylbenzene, and xylenes) were degraded by a combination of assimilation and cometabolism. Toluene and ethylbenzene were used as sources of carbon and energy, whereas the xylenes were cometabolized to different extents. o-Xylene and m-xylene were converted to phthalates as end metabolites; p-xylene was not degraded in complex BTEX mixtures but, in combination with toluene, appeared to be mineralized. The metabolic profiles and the inhibitory nature of the substrate interactions indicated that toluene, ethylbenzene, and xylene were degraded at the side chain by the same monooxygenase enzyme. Our findings suggest that soil fungi could contribute significantly to bioremediation of BTEX pollution.


Dyschondroplasias, including osteochondrosis, in boars between 25 and 169 days of age: histologic changes.
Microscopic sections of physeal and articular-epiphyseal (A-E) cartilages from major limb bones of 60 boars between 25 and 169 days of age were examined. The objectives in this study were to determine the age of onset and pathogenesis of osteochondrosis, a defect of endochondral ossification. Lesions regarded as typical of osteochondrosis were associated with physes of pigs from 25 days of age, indicating an earlier age of onset than has generally been documented. Two morphologically distinct lesions were observed, but both had areas with increased depth of the zone of hypertrophying chondrocytes. Some lesions were repairing. With increasing age of the pigs, the number of involved physes increased in each of 6 different age groups up to 169 days. Lesions associated with physes were observed in boars younger than those with lesions associated with A-E complexes. A few pigs at, or older than, 53 days of age, had osteochondrosis-like lesions involving epiphyseal growth cartilages. However, a dyschondroplasia different from osteochondrosis and typified by chondrolysis was more frequently associated with A-E complexes of pigs at or greater than 79 days of age. The number of affected cartilages and sites with this type of lesion also increased with age. Although osteoarthrosis had not developed in any of the pigs, it is probable that chondrolytic areas were precursors of degenerative joint disease. To date, osteochondrosis has been used to encompass lesions involving physes and A-E complexes. However, in view of the findings in the present study, dyschondroplasia is the preferred term to be used generically and then qualified by morphologic description, since causations may be different.


Generalizability of studies on mental health treatment and outcomes, 1981 to 1996.
This study operationalized and measured the external validity, or generalizability, of studies on mental health treatment and outcomes published in four journals between 1981 and 1996. MEDLINE was searched for articles on mental health treatment and outcomes that were published in four leading psychiatry and psychology journals between 1981 and 1996. A 156-item instrument was used to assess generalizability of study findings. Of more than 9,000 citations, 414 eligible studies were identified. Inclusion of community sites and patients from racial or ethnic minority groups were documented in only 12 and 25 percent of studies, respectively. Random or systematic sampling methods were rare (3 percent), and 75 percent of studies did not explicitly address sample representativeness. Studies with funding from the National Institute of Mental Health (NIMH) were more likely than those without NIMH funding to document the inclusion of patients from minority groups (30 percent compared with 20 percent). Randomized studies were more likely than nonrandomized studies to document the inclusion of patients from minority groups (28 percent compared with 17 percent), include patients with comorbid psychiatric conditions (31 percent compared with 19 percent), and attend to sample representativeness (28 percent compared with 15 percent). Modest improvements were seen over time in inclusion of patients from minority groups, inclusion of patients with psychiatric comorbidities, and attention to sample representativeness. Generalizability of studies on treatments and outcomes, whether experimental or observational, remained low and poorly documented over the 16-year period.


Radiographic dental implants recognition for geographic evaluation in human identification.
Dental implants for prosthetic rehabilitation with fixed crown or mobile partial/total dentures is a very common oral treatment among the population in Italy as elsewhere. There is a great number of implant systems of different designs. However, a catalogue of radiographic images and a description of the dental implants available in Italy would be useful in order to identify the manufacturer and the type of implant encountered in forensic casework. When an unidentified body is found with one or more implants in the jaws, and no dental record is available, clues gleaned from the type of implants used could give direction to the investigation. In this study Italian implant manufactures were contacted and asked to provide specimen implants. Digital radiographs were taken of all the implants donated at 0º, 30º, and 60º horizontal rotation, combined with -20º, -10º, 0º, +10º, and +20º vertical inclination relative to the radiographic beam and the X-ray sensor. A total of 15 images per implant were taken and examined to identify consistent, unique features that would aid in implant recognition. Only those observations made from radiographs between -10º and +10º vertical inclination would ever be used for definite identification of any implant. The information from this study should be considered a survey of the commercial distribution of dental implants in Italy through their digital radiographic images. It is also a starting point for a wider geographical evaluation of different manufacturers in other countries and continents. The radiographic images provided should help both the forensic odontologist and the prosthodontist to identify pre-existing implants which they may discover from their radiographic images.


Patterns of Influenza Vaccination and Vaccine Effectiveness Among Young US Children Who Receive Outpatient Care for Acute Respiratory Tract Illness.
The burden of influenza among young children is high, and influenza vaccination is the primary strategy to prevent the virus and its complications. Less is known about differences in clinical protection following 1 vs 2 doses of initial influenza vaccination. To describe patterns of influenza vaccination among young children who receive outpatient care for acute respiratory tract illness in the US and compare vaccine effectiveness (VE) against medically attended laboratory-confirmed influenza by number of influenza vaccine doses received. This test-negative case-control study was conducted in outpatient clinics, including emergency departments, at 5 sites of the US Influenza Vaccine Effectiveness Network during the 2014-2015 through 2017-2018 influenza seasons. The present study was performed from November 5, 2014, to April 12, 2018, during periods of local influenza circulation. Children aged 6 months to 8 years with an acute respiratory tract illness with cough who presented for outpatient care within 7 days of illness onset were included. All children were tested using real-time, reverse-transcriptase polymerase chain reaction for influenza for research purposes. Vaccination in the enrollment season with either 1 or 2 doses of inactivated influenza vaccine as documented from electronic medical records, including state immunization information systems. Medically attended acute respiratory tract infection with real-time, reverse-transcriptase polymerase chain reaction testing for influenza. Of 7533 children, 3480 children (46%) were girls, 4687 children (62%) were non-Hispanic white, and 4871 children (65%) were younger than 5 years. A total of 3912 children (52%) were unvaccinated in the enrollment season, 2924 children (39%) were fully vaccinated, and 697 children (9%) were partially vaccinated. Adjusted VE against any influenza was 51% (95% CI, 44%-57%) among fully vaccinated children and 41% (95% CI, 25%-54%) among partially vaccinated children. Among 1519 vaccine-naive children aged 6 months to 2 years, the VE of 2 doses in the enrollment season was 53% (95% CI, 28%-70%), and the VE of 1 dose was 23% (95% CI, -11% to 47%); those who received 2 doses were less likely to test positive for influenza compared with children who received only 1 dose (adjusted odds ratio, 0.57; 95% CI, 0.35-0.93). Consistent with US influenza vaccine policy, receipt of the recommended number of doses resulted in higher VE than partial vaccination in 4 influenza seasons. Efforts to improve 2-dose coverage for previously unvaccinated children may reduce the burden of influenza in this population.


Influences of membrane mimetic environments on membrane protein structures.
The number of membrane protein structures in the Protein Data Bank is becoming significant and growing. Here, the transmembrane domain structures of the helical membrane proteins are evaluated to assess the influences of the membrane mimetic environments. Toward this goal, many of the biophysical properties of membranes are discussed and contrasted with those of the membrane mimetics commonly used for structure determination. Although the mimetic environments can perturb the protein structures to an extent that potentially gives rise to misinterpretation of functional mechanisms, there are also many structures that have a native-like appearance. From this assessment, an initial set of guidelines is proposed for distinguishing native-like from nonnative-like membrane protein structures. With experimental techniques for validation and computational methods for refinement and quality assessment and enhancement, there are good prospects for achieving native-like structures for these very important proteins.


Posterior medial meniscus-femoral insertion into the anterior cruciate ligament. A case report.
Medial meniscal anomalies are rare. The anterior horn insertion into the anterior cruciate ligament is the most common. In the course of an arthroscopy for torn lateral meniscus, an anomalous band in continuity with the posterior horn of the medial meniscus was observed to insert into the anterior cruciate ligament. Although the tibial portion of the anterior cruciate was redundant, the anomalous band provided tension to the anterior cruciate ligament and a negative pivot shift. A previously unreported posterior medial meniscal femoral insertion is described.


[Developmental change of self-evaluation maintenance process and childhood depression].
The purpose of this study was to elucidate developmental changes in self-evaluation maintenance processes, and examine their relationship to childhood depression. Two questionnaires were administered to two hundred and one (201) elementary school children and three hundred and one (301) junior high school students. They were asked to rate their own performance on school subjects and school-related activities and those of close and distant classmates, as well as the degree of relevance to their selves of each school subject and school-related activity. Their actual school performance indicated that not only fifth and sixth graders and junior high school students, but also third and fourth grade children showed self-evaluation maintenance. In addition, it was found that self-evaluation maintenance was related to some indices, separately measured, of childhood depression, especially cognitive measures.


Phase-change memtransistive synapses for mixed-plasticity neural computations.
In the mammalian nervous system, various synaptic plasticity rules act, either individually or synergistically, over wide-ranging timescales to enable learning and memory formation. Hence, in neuromorphic computing platforms, there is a significant need for artificial synapses that can faithfully express such multi-timescale plasticity mechanisms. Although some plasticity rules have been emulated with elaborate complementary metal oxide semiconductor and memristive circuitry, device-level hardware realizations of long-term and short-term plasticity with tunable dynamics are lacking. Here we introduce a phase-change memtransistive synapse that leverages both the non-volatility of the phase configurations and the volatility of field-effect modulation for implementing tunable plasticities. We show that these mixed-plasticity synapses can enable plasticity rules such as short-term spike-timing-dependent plasticity that helps with the modelling of dynamic environments. Further, we demonstrate the efficacy of the memtransistive synapses in realizing accelerators for Hopfield neural networks for solving combinatorial optimization problems.


[Comparison of standard prognostic factors with the deletion of 13q14 detected by interphase fluorescence in situ hybridization on separated and unseparated bone marrow cells in multiple myeloma].
Cytogenetic abnormalities of chromosome 13 are emerging as important prognostic factors in multiple myeloma and have been associated with poor prognosis. The occurrence of 13q14 deletion and other standard laboratory parameters were determined in 40 patients with multiple myeloma. We found that interphase fluorescence in situ hybridization using a locus specific probe for RB1 gene on immunomagnetically selected myeloma cells was more sensitive than non selected cells. The 13q14 deletion was found in 10 of 40 (25.0%) of bone marrow samples without cell selection and in 25 of 40 (62.5%) of samples with CD138+ enriched myeloma cells. Negative correlation was found between albumin and the 13q14 deletion in separated (p = 0.003) as well as in cells without selection (p = 0.010). No significant correlation was found in overall survival of separated and unseparated cells (p = 0.830; p = 0.260) and a similar result was obtained for treatment response after transplantation of separated cells (p = 0.520) or non-separated cells (0.190). Our results confirm that immunomagnetic selection of CD138+ cells increases the probability of detection of the 13q14 deletion in bone marrow samples. The correlation was found between albumin and the 13q14 deletion in both of type of cells.


Noise and chemical induced hearing loss: special considerations for farm youth.
Farm youth face multiple risks for injury and illness in agriculture. Reviewed here is evidence from current literature illustrating the noise and chemical exposure hearing risks that farm youth potentially face. Sources of noise (e.g., machinery) and potentially toxic chemical exposures (e.g. solvents and pesticides) common in the farm environment are reviewed, illustrating the need for heightened research attention to a problem that may affect up to 2 million children in the United States alone and that requires both public and occupational health solutions. As existing studies have not sufficiently explored potential ototoxic effects of these exposures on children and adolescents, recommendations are outlined for research characterizing both chemical and noise exposures to farm youth and their combined effects on hearing.


Impact of the non-contributory social pension program 70 y más on older adults' mental well-being.
In 2007, a non-contributory pension program was launched in rural areas of Mexico. The program consisted in a non-conditional cash transfer of US$40 monthly to all older adults (OA) aged 70 and over. We evaluate the effect of the program on mental well-being of its beneficiaries. Quantitative and qualitative methods were used. For the quantitative component, we used the selection criteria established by the program (age and locality size) to form the Intervention (OA aged 70-74 residing in rural localities, <2500 inhabitants) and Control groups (OA aged 70-74, in localities with 2501-2700 inhabitants). Baseline data collection was conducted in 2007 where 5,465 OA were interviewed. The follow-up survey was conducted in 2008, and it was possible to interview 5,270 OA, with a response rate of 96%. A difference-in-difference linear probability model with individual fixed effect was used to estimate the impact of the program on mental well-being indicators. In 2009 a qualitative component was designed to explore possible causal pathways of such effect. After a year of exposure, the program had a significant effect on reduction of depressive symptoms (β = -0.06, CI95% -0.12; -0.01) and an increase in empowerment indicators: OA participated in important household decisions (β = 0.09, CI95% 0.03;0.15); and OA participated in household decisions pertaining to expenses (β = 0.11, CI95% 0.05;0.18). Qualitative analysis found a strong trend showing a reduction of sadness, and feeling of increasing empowerment. These results suggest that a non-conditional transfer in older ages have an impact beyond the economic sphere, impacting even the mental well-being. This effect could be explained because the pension produces feelings of safety and welfare. It is recommendable that governments should invest efforts towards universalizing the non-contributory pension programs in order to ensure a basic income for the elderly.


The quality and outcomes framework in the United kingdom: indicators in transition.
The United Kingdom's pay-for-performance system, the Quality and Outcomes Framework, continues to evolve. Since its inception in 2004, the Quality and Outcomes Framework has provided a strong focus on evidence-based performance targets that remains a dominant theme. Strengthening of the evidence base has resulted in the appearance of several new clinical indicators. Increasingly, change has been driven by explicit public health goals with targets incentivized according to their potential for mortality reduction. In 2011, a new policy direction became apparent. New indicators accounting for almost 10% of the Quality and Outcomes Framework will be determined by achievement of targets reflecting the efficient use of health service resources.


Detection of Yersinia enterocolitica in food by PCR amplification.
A polymerase chain reaction (PCR) assay was developed for detection of pathogenic, virulent strains of Yersinia enterocolitica. By using both virulence loci virF and ail as markers for pathogenicity, detection of species with a virulence factor present was possible. DNA preparation in the presence of hexadecyl trimethy ammonium bromide (CTAB) was followed by two 44 cycle amplification reactions, one for each of the markers. As few as 10(2) Y. enterocolitica cells were detected in ground pork in the presence of 10(5)-10(6) bacteria of other species. The described PCR assay provides a sensitive robust assay for the detection of virulent Y. enterocolitica in food.


Patterns of bleaching and mortality following widespread warming events in 2014 and 2015 at the Hanauma Bay Nature Preserve, Hawai'i.
Drastic increases in global carbon emissions in the past century have led to elevated sea surface temperatures that negatively affect coral reef organisms. Worldwide coral bleaching-related mortality is increasing and data has shown even isolated and protected reefs are vulnerable to the effects of global climate change. In 2014 and 2015, coral reefs in the main Hawaiian Islands (MHI) suffered up to 90% bleaching, with higher than 50% subsequent mortality in some areas. The location and severity of bleaching and mortality was strongly influenced by the spatial and temporal patterns of elevated seawater temperatures. The main objective of this research was to understand the spatial extent of bleaching mortality in Hanauma Bay Nature Preserve (HBNP), O'ahu, Hawai'i to gain a baseline understanding of the physical processes that influence localized bleaching dynamics. Surveys at HBNP in October 2015 and January 2016 revealed extensive bleaching (47%) and high levels of coral mortality (9.8%). Bleaching was highly variable among the four HBNP sectors and ranged from a low of ∼31% in the central bay at Channel (CH) to a high of 57% in the area most frequented by visitors (Keyhole; KH). The highest levels of bleaching occurred in two sectors with different circulation patterns: KH experienced comparatively low circulation velocity and a low temperature increase while Witches Brew (WB) and Backdoors (BD) experienced higher circulation velocity and higher temperature increase. Cumulative mortality was highest at WB (5.0%) and at BD (2.9%) although WB circulation velocity is significantly higher. HBNP is minimally impacted by local factors that can lead to decline such as high fishing pressure or sedimentation although human use is high. Despite the lack of these influences, high coral mortality occurred. Visitor impacts are strikingly different in the two sectors that experienced the highest mortality evidenced by the differences in coral cover associated with visitor use however, coral mortality was similar. These results suggest that elevated temperature was more influential in coral bleaching and the associated mortality than high circulation or visitor use.


Development of a bladder instillation of the indoloquinone anticancer agent EO-9 using tert-butyl alcohol as lyophilization vehicle.
The purpose of this research was to develop a stable bladder instillation of EO-9 for the treatment of superficial bladder cancer. First, stability and dissolution studies were performed. Subsequently, the freeze-drying process was optimized by determination of the freeze-drying characteristics of the selected cosolvent/water system and differential scanning calorimetry analysis of the formulation solution. Furthermore, the influence of the freeze-drying process on crystallinity and morphology of the freeze-dried product was determined with x-ray diffraction analysis and scanning electron microscopy, respectively. Subsequently, a reconstitution solution was developed. This study revealed that tert-butyl alcohol (TBA) can be used to both dramatically improve the solubility and stability of EO-9 and to shorten the freeze-drying cycle by increasing the sublimation rate. During freeze drying, 3 TBA crystals were found: TBA hydrate-ice crystals, crystals of TBA hydrate, and a third crystal, probably composed of TBA hydrate crystals containing approximately 90% to 95% TBA. Furthermore, it was shown that crystallization of TBA hydrate was inhibited in the presence of both sodium bicarbonate (NaHCO3) and mannitol. Addition of an annealing step resulted in a minor increase in the crystallinity of the freeze-dried product and formation of the delta-polymorph of mannitol. A stable bladder instillation was obtained after reconstitution of the freeze-dried product (containing 8 mg of EO-9, 20 mg of NaHCO3, and 50 mg of mannitol per vial) to 20 mL with a reconstitution solution composed of propylene glycol/water for injection (WfI)/NaHCO3/sodium edetate 60%/40%/2%/0.02% vol/vol/wt/wt, followed by dilution with WfI to a final volume of 40 mL.


A case of non-Hodgkin lymphoma in a patient with chronic myeloid leukemia.
Chronic myeloid leukemia is a clonal expansion of hematopoietic progenitor cells characterized by exaggerated proliferation of granulocytic lineage, with chronic phase, accelerated phase and blast crisis. Accelerated phase and blast crisis may be associated with extramedulary disease. Extramedullary transformation of CML can be determined both in nodal and extranodal sites. Non-Hodgkin lymphoma is rare in chronic myeloid leukemia and may be misdiagnosed as an extramedullary lymphoid blast transformation; the majorities are T-cell lymphomas with an immature thymic phenotype, while peripheral B-cell lymphomas are rarer. We report the case of a 79-year-old woman carrier Ph+ chronic myeloid leukemia who developed at eight months of diagnosis an accelerated phase of CML associated simultaneous with a tumor of soft palate, which was initial considering an extramedullary disease. The patient was treated with specific chemotherapy for accelerated phase of CML (Cytosinarabinoside) + Anagrelide, and reversed to secondary chronic phase of CML, but soft palate tumor persists. The immunohistochemical findings of bone marrow trephine biopsy examination showed chronic phase of CML (negativity for immature cells such as CD34, Tdt) and the biopsy of soft palate tumor and immunohistochemical findings revealed a primitive non-Hodgkin lymphoma (NHL) with medium B-cells (CD20, CD79a positive) and excluding an extramedullary blast crisis (CD34 negative, Tdt negative). Cytogenetic analysis in tumor revealed absence of Philadelphia chromosome. The patient was treated with local radiotherapy for NHL, with a favorable evolution and Hydroxyurea 1 g/day for CML with hematological remission. A localized lymphoid neoplasm may be an extramedullary localized blast crisis of CML or a distinct malignancy, with distinguished therapy and prognosis. A correct diagnosis based on a complex investigation: immunohistochemistry, conventional cytogenetic analysis and fluorescence in situ hybridization (FISH), molecular analysis (Southern blot and RT-PCR) is necessary. Further studies are required to clarify the pathogenetic relationship between chronic myeloid leukemia and non-Hodgkin lymphomas.


Enhancement of Arabidopsis growth characteristics using genome interrogation with artificial transcription factors.
The rapidly growing world population has a greatly increasing demand for plant biomass, thus creating a great interest in the development of methods to enhance the growth and biomass accumulation of crop species. In this study, we used zinc finger artificial transcription factor (ZF-ATF)-mediated genome interrogation to manipulate the growth characteristics and biomass of Arabidopsis plants. We describe the construction of two collections of Arabidopsis lines expressing fusions of three zinc fingers (3F) to the transcriptional repressor motif EAR (3F-EAR) or the transcriptional activator VP16 (3F-VP16), and the characterization of their growth characteristics. In total, six different 3F-ATF lines with a consistent increase in rosette surface area (RSA) of up to 55% were isolated. For two lines we demonstrated that 3F-ATF constructs function as dominant in trans acting causative agents for an increase in RSA and biomass, and for five larger plant lines we have investigated 3F-ATF induced transcriptomic changes. Our results indicate that genome interrogation can be used as a powerful tool for the manipulation of plant growth and biomass and that it might supply novel cues for the discovery of genes and pathways involved in these properties.


Activity-dependent expression of occ1 in excitatory neurons is a characteristic feature of the primate visual cortex.
occ1 is a gene whose expression is particularly abundant in neurons in the macaque primary visual cortex (V1). In the present study, we report that the expression of occ1 mRNA in the macaque neocortex can be classified into two modes. The first mode is associated with excitatory neurons distributed in the major thalamocortical recipient layers that exhibit strong cytochrome oxidase activity. This is highly prominent in V1. The second mode is associated with parvalbumin-positive GABAergic interneurons and is distributed across the macaque neocortex. In V1, monocular deprivation showed that occ1 mRNA expression in excitatory neurons was markedly dependent on afferent activity, whereas that in GABAergic interneurons was not. Cross-species comparison showed specific differences in expression. In marmosets, a strong expression was observed in V1 similarly to macaques. The occ1 mRNA expression, however, was generally weak in the mouse neocortex. In rabbit and ferret cortices, the strong expression was observed only in GABAergic interneurons. We conclude that activity-dependent occ1 mRNA expression in the excitatory neurons of V1 was caused by a novel mechanism acquired by primates after their separation from other lineages.


Complement biosynthesis in human breast-milk macrophages and blood monocytes.
The availability of techniques for establishment of primary, long term monolayers of breast milk macrophages and blood monocytes permitted a direct comparison of biosynthetic functions of human tissue macrophage and its progenitor. In addition to previously described morphological differences, four specific characteristics of the breast milk macrophage were identified: (i) a reduced rate of total protein secretion relative to the monocyte; (ii) abrogation of the 3 day lag in complement secretion regularly observed in blood monocyte cultures; (iii) an increase in the secretion of complement proteins C2 and factor B; and (iv) an increase in the ratio of C2 : factor B secretion. These differences did not result from cell-cell interactions between monocytes and macrophages, stable factors elucidated by monocyte or macrophage monolayers, or heat-stable factors in breast milk. In addition, both monocytes and macrophages synthesized and secreted C3 in an apparently native but haemolytically inactive form. The differences observed suggest that macrophages may modulate local availability of complement proteins in tissues or in the early phase of an inflammatory response.


[Terson's syndrome. Its surgical resolution].
The observation of 50-year-old patient is presented. Following a traffic crash, he had suffered a left cranial fracture, right subdural hematoma, cranial base fracture and vitreous hemorrhages at the both eyes. Right ocular vision was 1/500, left ocular vision was 1/200. The vitrectomy through pars plana with Tollentino lens at the right eye, without scleral indentation, is made. The postoperative evolution was good, 21 days after the intervention the visual acuity of the right eye reaching 16/20. The role of vitrectomy in vitreous hemorrhages of Terson syndrome is emphasized.


Visualization of highly dynamic F-actin plus ends in growing phaseolus vulgaris root hair cells and their responses to Rhizobium etli nod factors.
Legume plants secrete signaling molecules called flavonoids into the rhizosphere. These molecules activate the transcription of rhizobial nod genes, which encode proteins involved in the synthesis of signaling compounds named Nod factors (NFs). NFs, in turn, trigger changes in plant gene expression, cortical cell dedifferentiation and mitosis, depolarization of the root hair cell membrane potential and rearrangement of the actin cytoskeleton. Actin polymerization plays an important role in apical growth in hyphae and pollen tubes. Using sublethal concentrations of fluorescently labeled cytochalasin D (Cyt-Fl), we visualized the distribution of filamentous actin (F-actin) plus ends in living Phaseolus vulgaris and Arabidopsis root hairs during apical growth. We demonstrated that Cyt-Fl specifically labeled the newly available plus ends of actin microfilaments, which probably represent sites of polymerization. The addition of unlabeled competing cytochalasin reduced the signal, suggesting that the labeled and unlabeled forms of the drug bind to the same site on F-actin. Exposure to Rhizobium etli NFs resulted in a rapid increase in the number of F-actin plus ends in P. vulgaris root hairs and in the re-localization of F-actin plus ends to infection thread initiation sites. These data suggest that NFs promote the formation of F-actin plus ends, which results in actin cytoskeleton rearrangements that facilitate infection thread formation.


Parietaria pollinosis in an Atlantic area: clinical and palynological data.
Parietaria pollen is considered as one of the most common causes of allergic respiratory symptoms in the Mediterranean area but its presence is limited in the Atlantic area. Some leading patients from Muros, a small town on the Spanish Atlantic coast, complaining of nearly all year round respiratory symptoms happened to be allergic to Parietaria pollen. To evaluate the prevalence of Parietaria sensitization among patients from this Atlantic town, and its correlation with aerobiological data (concentration of Urticaceae pollen). Eighty-nine patients suffering from rhinoconjunctivitis and/or asthma from the area of Muros between January 1998 and January 1999 were included. Skin prick tests and serum-specific IgE (CAP Pharmacia) to Parietaria judaica and a battery of perennial or seasonal allergens were performed. Information about the seasonal and hourly rhythm of symptoms was obtained in each patient sensitized to Parietaria pollen. Atmospheric pollen was collected, using a Hirst-type volumetric pollen sampler, during 1998. Parietaria allergy was detected in 22 patients (25%) and represented the second most important aeroallergen after mites and along with grass pollen. The total atmospheric pollen recorded in Muros during the study period was 27,515 pollen grains, Urticaceae being the most important one (18,554 grains, 67% of the total). The proportion of Urticaceae pollen found in Muros was the highest among all samplers belonging to the Spanish Aerobiology Network. Maximum values of Urticaceae pollen were recorded during May and June. Intradiurnal variation of pollen counts showed maximum values between 11 a.m. and 1 p.m. A parallelism was observed between the rate of symptomatic patients and Parietaria type grain pollen count. The prevalence of Parietaria pollen sensitization seems to be very important in this Atlantic area. The presence of very high levels of this pollen in its atmosphere explains this fact. Such sensitization should be taken into account concerning specific diagnostic tests.


Randomized comparison of home uterine activity monitoring and routine care in patients discharged after treatment for preterm labor.
To determine whether home uterine activity monitoring reduces the likelihood of preterm birth in women successfully treated for preterm labor in their current pregnancies. Women between 20-34 weeks' gestation who had been treated successfully for preterm labor were solicited to participate in a randomized clinical trial of home uterine activity monitoring versus routine high-risk care. The sample size of 56 was based on power calculations using the results of earlier investigators. Twenty-eight women were randomized to home uterine activity monitoring and 29 were assigned to the type of care appropriate for women discharged after hospitalization for parenteral treatment of preterm labor. One of the routine-care subjects was lost to follow-up. The two groups were comparable in distribution for race, insurance status, multiple gestation, marital status, gestational age at beginning of the study, and incidence of prior preterm birth. The 28 women receiving routine care had a 54% incidence of preterm birth, whereas the incidence was 57% in monitored women (relative risk 1.08, 95% confidence interval 0.6-1.9; P = .79). The incidences of delivery before 32 weeks and 34 weeks also were unaffected by the intervention. Home uterine activity monitoring is not effective in reducing the likelihood of preterm delivery in patients successfully treated for preterm labor in their current pregnancies.


Cloning of sea urchin actin gene sequences for use in studying the regulation of actin gene transcription.
In order to investigate the regulation of actin gene transcription during early sea urchin development, a specific hybridization probe for actin sequences is required. Such a probe was produced by cloning cDNA transcribed from a sea urchin poly(A)-containing mRNA preparation enriched for actin message. Double-stranded DNA was ligated into the BamHI restriction site of plasmid pBR322, and the resulting hybrid molecules were used to transform the Escherichia coli strain ML100. After preliminary screening of bacterial colonies by antibiotic sensitivity and hybridization back to the original cDNA, clones containing sea urchin DNA were further characterized by a positive translation assay in which total sea urchin mRNA was hybridized to plasmid, and the hybridized message then was eluted and translated in a reticulocyte cell-free protein-synthesizing system. In this way, one clone (pSA38) was found to hybridize selectively to sea urchin mRNA coding for a protein of 43,000 daltons. This protein was identified as actin by three criteria: electrophoretic migration in two-dimensional polyacrylamide gels, affinity for DNase I, and peptide mapping. Restriction endonuclease and heteroduplex mapping of pSA38 indicate that it contains a 1.5-kilobase-pair insert and is therefore likely to contain a large portion of the actin coding sequence. By using pSA38 as a hybridization probe, it has been found that the level of actin-specific RNA sequences increases dramatically during early sea urchin development.


High quality polyacrylic acid modified multifunction luminescent nanorods for tri-modality bioimaging, in vivo long-lasting tracking and biodistribution.
Polyacrylic acid (PAA) modified NaYF4:Gd/Yb/Er upconversion nanorods (denoted as PAA-UCNRs) are demonstrated for tri-modal upconversion (UC) optical, computed X-ray tomography (CT), and magnetic resonance imaging (MRI). The hydrophilic PAA-UCNRs were obtained from hydrophobic oleic acid (OA) capped UCNRs (denoted as OA-UCNRs) using a ligand exchange method. The as-prepared UCNRs with a hexagonal phase structure present high monodispersity. These PAA-UCNRs are successfully used as ideal probes for in vivo UC luminescence bioimaging and synergistic X-ray and UC bioimaging. Moreover, X-ray CT imaging reveals that PAA-UCNRs can act as contrast agents for improved detection of the liver and spleen. In addition, a significant signal enhancement in the liver is observed in in vivo MRI, indicating that PAA-UCNRs are ideal T1-weighted MRI agents. More importantly, in vivo long-term tracking based on these PAA-UCNRs in the live mice and the corresponding ex vivo bioimaging of isolated organs also verify the translocation of PAA-UCNRs from the liver to the spleen, and the observed intense UC signals from the feces reveal the biliary excretion mechanism of these UCNRs. These findings contribute to understanding of the translocation and potential route for excretion of PAA-UCNRs, which can provide an important guide for the diagnosis and detection of diseases based on these UCNRs.


Antiviral effects of natural small molecules on aquatic rhabdovirus by interfering with early viral replication.
Spring viremia of carp virus (SVCV) is globally widespread and poses a serious threat to aquatic ecology and aquaculture due to its broad host range. To develop effective agents to control SVCV infection, we selected 16 naturally active small molecules to assess their anti-SVCV activity. Notably, dihydroartemisinin (DHA) (100 µmol/L) and (S, S)-(+)-tetrandrine (TET) (16 µmol/L) exhibited high antiviral effects in epithelioma papulosum cyprinid (EPC) cells, with inhibitory rates of 70.11% and 73.54%, respectively. The possible antiviral mechanisms were determined as follows: 1. Pre-incubation with DHA and TET decreased viral particle infectivity in fish cells, suggesting that horizontal transmission of SVCV in the aquatic environment was disrupted; 2. Although neither had an effect on viral adhesion, TET (but not DHA) interfered with SVCV entry into host cells (>80%), suggesting that TET may have an antiviral function in early viral replication. For in vivo study, both agents enhanced the survival rate of SVCV-infected zebrafish by 53.3%, significantly decreased viral load, and modulated the expression of antiviral-related genes, indicating that DHA and TET may stimulate the host innate immune response to prevent viral infection. Overall, our findings indicated that DHA and TET had positive effects on suppressing SVCV infection by affecting early-stage viral replication, thus holding great potential as immunostimulants to reduce the risk of aquatic rhabdovirus disease outbreaks.


[Ileus caused by V-loc sutures].
A laparoscopic bilateral inguinal hernia repair was performed on a 62-year-old man. The peritoneum was sutured on both sides laterally to medial with the V-loc unidirectional barbed suture. An end of approximately 2 cm was left on both sides. Five days later the patient returned to hospital with intestinal obstruction. Exploratory laparoscopy revealed that the two ends of the sutures had formed a string medially, and the small intestine was caught over the string, causing the obstruction. This case demonstrates the need for fast diagnosis in our patients after surgery, when introducing new surgical material.


How parents can affect excessive spending of time on screen-based activities.
The aim of this study is to explore the association between family-related factors and excessive time spent on screen-based activities among school-aged children. A cross-sectional survey using the methodology of the Health Behaviour in School-aged Children study was performed in 2013, with data collected from Slovak (n = 258) and Czech (n = 406) 11- and 15-year-old children. The effects of age, gender, availability of a TV or computer in the bedroom, parental rules on time spent watching TV or working on a computer, parental rules on the content of TV programmes and computer work and watching TV together with parents on excessive time spent with screen-based activities were explored using logistic regression models. Two-thirds of respondents watch TV or play computer games at least two hours a day. Older children have a 1.80-times higher chance of excessive TV watching (CI: 1.30-2.51) and a 3.91-times higher chance of excessive computer use (CI: 2.82-5.43) in comparison with younger children. More than half of children have a TV (53%) and a computer (73%) available in their bedroom, which increases the chance of excessive TV watching by 1.59 times (CI: 1.17-2.16) and of computer use by 2.25 times (CI: 1.59-3.20). More than half of parents rarely or never apply rules on the length of TV watching (64%) or time spent on computer work (56%), and their children have a 1.76-times higher chance of excessive TV watching (CI: 1.26-2.46) and a 1.50-times greater chance of excessive computer use (CI: 1.07-2.08). A quarter of children reported that they are used to watching TV together with their parents every day, and these have a 1.84-times higher chance of excessive TV watching (1.25-2.70). Reducing time spent watching TV by applying parental rules or a parental role model might help prevent excessive time spent on screen-based activities.


Update on medical and regulatory issues pertaining to compounded and FDA-approved drugs, including hormone therapy.
We review the historical regulation of drug compounding, concerns about widespread use of non-Food and Drug Admiistration (FDA)-approved compounded bioidentical hormone therapies (CBHTs), which do not have proper labeling and warnings, and anticipated impact of the 2013 Drug Quality and Security Act (DQSA) on compounding. US government websites were searched for documents concerning drug compounding regulation and oversight from 1938 (passage of Federal Food, Drug, and Cosmetic Act [FDCA]) through 2014, including chronologies, Congressional testimony, FDA guidelines and enforcements, and reports. The FDCA and DQSA were reviewed. PubMed and Google were searched for articles on compounded drugs, including CBHT. Congress explicitly granted the FDA limited oversight of compounded drugs in a 1997 amendment to the FDCA, but the FDA has encountered obstacles in exercising that authority. After 64 patient deaths and 750 adversely affected patients from the 2012 meningitis outbreak due to contaminated compounded steroid injections, Congress passed the DQSA, authorizing the FDA to create a voluntary registration for facilities that manufacture and distribute sterile compounded drugs in bulk and reinforcing FDCA regulations for traditional compounding. Given history and current environment, concerns remain about CBHT product regulation and their lack of safety and efficacy data. The DQSA and its reinforcement of §503A of the FDCA solidifies FDA authority to enforce FDCA provisions against compounders of CBHT. The new law may improve compliance and accreditation by the compounding industry; support state and FDA oversight; and prevent the distribution of misbranded, adulterated, or inconsistently compounded medications, and false and misleading claims, thus reducing public health risk.


Controllable Regiodivergent Alkynylation of 1,3-Bis(Boronic) Esters Activated by Distinct Organometallic Reagents.
1,3-Bis(boronic) esters can be readily synthesized from alkylBpin precursors. Selective transformations of these compounds hold the potential for late-stage functionalization of the remaining C-B bond, leading to a diverse array of molecules. Currently, there are no strategies available to address the reactivity and, more importantly, the controllable regiodivergent functionalization of 1,3-bis(boronic) esters. In this study, we have achieved controllable regiodivergent alkynylation of these molecules. The regioselectivity has been clarified based on the unique chelation patterns observed with different organometallic reagents. Remarkably, this methodology effectively addresses the low reactivity of 1,3-bis(boronic) esters and bridges the gap in radical chemistry, which typically yields only the classical products formed via stable radical intermediates. Furthermore, the compounds synthesized through this approach serve as potent building blocks for creating molecular diversity.


Bilateral anterior segment dysgenesis in a 7-week-old domestic shorthaired cat.
A 7-week-old, intact, female domestic shorthaired cat was presented to the Atlantic Veterinary College (AVC) Ophthalmology service for a 1-week history of buphthalmia in the left eye and bilateral elevated intraocular pressures. Ocular examination revealed bilateral non-visual glaucomatous eyes. Bilateral enucleations were performed without complications and histopathology revealed anterior segment dysgenesis of varying degrees in both eyes. Key clinical message: Anterior segment dysgenesis is a developmental condition that can result in primary congenital glaucoma for which the best course of treatment is enucleation.