Asthma care practices in Chicago-area emergency departments. Chicago Asthma Surveillance Initiative Project Team.
Emergency departments (EDs) represent an important source of asthma care, yet there are few studies detailing how ED asthma practices vary and to what extent EDs meet expectations of national asthma guidelines. The purpose of this study is to characterize ED care for persons with asthma in a single large community. During 1996 and 1997, a cross-sectional, self-administered survey to characterize asthma care practices was conducted among medical directors of the 89 EDs serving the Chicago metropolitan area (six counties). The survey topic areas included asthma-specific demographics and selected utilization statistics; assessment practices; treatment practices; discharge and follow-up activities; and familiarity with, attitudes toward, and utilization of guidelines/ protocols. Sixty-four EDs completed surveys, for a response rate of 71.9%. Ninety-four percent of the respondents were ED medical directors. As part of assessment, peak flow measurements, while common, were used less frequently than pulse oximetry. The average (+/- SE) estimated length of stay for asthma care was 3.0 +/- 0.1 h, and average disposition time (ie, the decision to admit) was 2.5 +/- 0.2 h. Systemic steroids (either i.v. or p.o.) were estimated to be given to 73.2 +/- 3.9% of patients during their ED visits. Systemic steroids were prescribed for 55.9 +/- 3.5% of patients at time of discharge. Only 57.0 +/- 5.4% of patients were estimated to have received any type of written asthma educational materials. Approximately 25% of patients were reported to have been given a detailed follow-up appointment at the time of discharge. The results reveal that the medical directors reported many of the Chicago-area EDs as providing asthma care that is consistent with key aspects of national guidelines. However, in certain critical areas of care, the EDs demonstrate a high degree of variation, often with the community falling short of guideline recommendations. By identifying these variations in asthma care, it is now possible to target specific goals for community-wide asthma quality improvement among the EDs in the Chicago metropolitan area.


Demodicosis in dairy goats.
Multiple nodular skin lesions on an adults Saanen doe were found to be caused by demodectic mites. An identical condition developed in the daughter of the affected goat despite separation from the mother at 24 hours after birth. Of 7 other goats in contact with the doe, 2 had a few demodectic nodules. Of 84 goats examined at a local show, 7 (from 4 herds) were similarly affected. The observations suggested that the nodular form of demodicosis is widespread in Michigan dairy goats and that perinatal transmission may occur..


A novel dual response ratiometric fluorescent probe for the determination of H2O2 and glucose via etching of silver nanoparticles.
Based on the inner filter effect and charge transfer dual response mechanism, a dual response ratiometric fluorescent probe (D-RFP) with two reversible signal changes for sensing H2O2 and glucose was developed. The D-RFP was proposed by embedding glycine-derived carbon dots (CDs) (λem = 400 nm) into silica nanoparticles and covalently linking CdTe quantum dots (QDs) (λem = 600 nm) onto the surface of silica nanoparticles. When silver nanoparticles (Ag NPs) were mixed with D-RFP, the fluorescence intensity of CDs can be quenched by Ag NPs via the inner filter effect. With the addition of H2O2, Ag NPs were etched to silver ions, thus recovering the fluorescence of CDs. In the meantime, fluorescence of QDs was quenched by Ag+via charge transfer. Under optimal conditions, D-RFP displayed high sensitivity toward H2O2 with a detection limit of 0.28 μM. Based on the conversion of glucose into H2O2, D-RFP can also be exploited for glucose sensing with a detection limit of 0.59 μM. The approach developed can be applied to monitor glucose levels in human serum samples with satisfactory results, and the results of the heathy and diabetic patients can be distinguished by the naked eye. Moreover, this method provides a new idea for designing a high-sensitivity D-RFP.


Establishment of a new short, protease-resistant, affinity labeling reagent for the cholecystokinin receptor.
Proteolytic degradation of radioligands is an important source of artifact in affinity labeling of receptor proteins. To complement our previous characterization of the pancreatic acinar cell cholecystokinin (CCK) receptor, we synthesized D-Tyr-Gly[(Nle28,31)CCK-26-33]. The amino terminal D-enantiomer of tyrosine provided a site for oxidative iodination, a free amino group for cross-linking, and rendered the peptide resistant to aminopeptidases. The decapeptide was oxidatively iodinated and purified by reverse-phase HPLC to 2,000 Ci/mmol, to yield a probe which was equal in potency and efficacy to CCK-8, and which bound to rat pancreatic membranes in a rapid, reversible, temperature-dependent, specific, saturable and high affinity manner. This probe was resistant to aminopeptidase degradation, and maintained its ability to bind to receptor after incubation with pancreatic membranes or dispersed cells. Affinity labeling of pancreatic membranes with this analogue identified an Mr = 85,000-95,000 molecule. This analogue offers several advantages over existing probes and should be useful for future studies of this and other CCK receptors.


Exposure to nontraditional pets at home and to animals in public settings: risks to children.
Exposure to animals can provide many benefits during the growth and development of children. However, there are potential risks associated with animal exposures, including exposure to nontraditional pets in the home and animals in public settings. Educational materials, regulations, and guidelines have been developed to minimize these risks. Pediatricians, veterinarians, and other health care professionals can provide advice on selection of appropriate pets as well as prevention of disease transmission from nontraditional pets and when children contact animals in public settings.


Advance care planning and the quality of end-of-life care in older adults.
To determine whether advance care planning influences quality of end-of-life care. In this observational cohort study, Medicare data and survey data from the Health and Retirement Study (HRS) were combined to determine whether advance care planning was associated with quality metrics. The nationally representative HRS. Four thousand three hundred ninety-nine decedent subjects (mean age 82.6 at death, 55% women). Advance care planning (ACP) was defined as having an advance directive (AD), durable power of attorney (DPOA) or having discussed preferences for end-of-life care with a next of kin. Outcomes included previously reported quality metrics observed during the last month of life (rates of hospital admission, in-hospital death, >14 days in the hospital, intensive care unit admission, >1 emergency department visit, hospice admission, and length of hospice ≤ 3 days). Seventy-six percent of subjects engaged in ACP. Ninety-two percent of ADs stated a preference to prioritize comfort. After adjustment, subjects who engaged in ACP were less likely to die in a hospital (adjusted relative risk (aRR) = 0.87, 95% confidence interval (CI) = 0.80-0.94), more likely to be enrolled in hospice (aRR = 1.68, 95% CI = 1.43-1.97), and less likely to receive hospice for 3 days or less before death (aRR = 0.88, 95% CI = 0.85-0.91). Having an AD, a DPOA or an ACP discussion were each independently associated with a significant increase in hospice use (P < .01 for all). ACP was associated with improved quality of care at the end of life, including less in-hospital death and increased use of hospice. Having an AD, assigning a DPOA and conducting ACP discussions are all important elements of ACP.


Indications of symbiotic state influencing melanin-synthesis immune response in the facultative coral Astrangia poculata.
Increased ocean warming is causing detrimental impacts to tropical corals worldwide. Compounding the effects of heat stress, incidences of tropical coral disease have risen concurrently. While tropical coral responses to these impacts are well studied, temperate coral responses remain largely unknown. The present study focused on the immune response of the temperate coral Astrangia poculata to increased temperature and disease. Symbiotic and aposymbiotic A. poculata were collected from Narragansett Bay, Rhode Island (USA) in summer and winter seasons and exposed to control (18°C) versus elevated temperatures (26°C) in the presence of an immune stimulant (i.e. lipopolysaccharide) for a 12 h period. Prophenoloxidase (PPO) and melanin concentrations from the melanin-synthesis pathway were assessed via spectrophotometry to examine immune responses. While PPO measurements were higher on average in symbiotic corals compared with aposymbiotic corals, temperature and season did not significantly affect this metric. Melanin was significantly higher in symbiotic compared to aposymbiotic corals, implying that symbiotic state may be important for melanin-synthesis response. Conversely, melanin as an immune response may be of less importance in aposymbiotic A. poculata due to the potential capacity of other immune responses in this species. In addition, differences in resource allocation to immune investment as a result of symbiosis is plausible given melanin production observed within the present study. However, thermal stressors may reduce the overall influence of symbiosis on melanin production. Future studies should build upon these results to further understand the entirety of innate immunity responses in temperate coral species.


Using next-generation sequencing for characterising HLA-DRB1 and DQB1 loci in a cohort of Colombian women.
The Colombian population is characterised by a high genetic diversity, secondary to the ethnic mixture arising from colonisation. Unfortunately, few reports are available regarding HLA-DRB1 and DQB1 diversity in Colombia to date. HLA-DRB1 and DQB1 diversity was identified in this study using next-generating sequencing (NGS) on a cohort of Colombian women. Cervical samples taken from 276 women were used for typing DRB1 and DQB1 loci by Illumina MiSeq. Allele and haplotype frequencies were calculated using an expectation-maximisation algorithm. Hardy-Weinberg Equilibrium and linkage disequilibrium (LD) between loci were evaluated. Forty-seven DRB1 alleles and 14 DQB1 alleles were identified. DRB1*04:07:01G and DQB1*03:02:01G alleles occurred most frequently in the target population. Significant LD was found in 44 out of the 144 identified haplotypes, within which DRB1*04:07:01G-DQB1*03:02:01G occurred most frequently (6.56%). The alleles and haplotypes found with NGS agreed with that found in previous reports involving lower resolution for the Colombian population, and greater genetic variability was found, especially concerning DRB1. Comparing allele and haplotype frequency distribution in the target population to that of other populations denoted HLA system intra- and inter-population diversity.


Genomic alterations in tubular breast carcinomas.
Tubular carcinoma of the breast is a well-differentiated variant of invasive ductal carcinoma and has been shown to have an exceptionally favorable prognosis, as manifested by a low incidence of lymph node metastases and an excellent overall survival. It is unknown whether this subtype represents an early step along the continuum of development to a more aggressive, poorly differentiated ductal cancer, or whether these cancers are destined to remain well differentiated with limited metastatic potential. We undertook an analysis of 18 pure tubular carcinomas of the breast using comparative genomic hybridization to evaluate the chromosomal changes in these tumors. An average of 3.6 chromosomal alterations of the genome were identified per case. The most frequent change involved loss of 16q (in 78% of tumors) and gain of 1q (in 50% of tumors). All but one case with 1q gain also exhibited a concomitant 16q loss. Other frequent changes involved 16p gain in 7 of 18 cases (39%) and distal 8p loss in 5 of 18 cases (28%). Comparison with known genomic alterations in a mixed group of invasive cancers shows tubular cancer to have fewer overall chromosomal changes per tumor (P <.01), higher frequency of 16q loss (P <.001), and lower frequency of 17p loss (P =.007). These results strongly suggest that tubular carcinomas are a genetically distinct group of breast cancers.


Pathology correlations with optical biopsy techniques.
Traditional surgical pathology predicts the future course of a patient's disease based on subjective comparison of the biopsy with the outcome of similar biopsies that have been seen previously. Optical techniques are being designed to aid the clinician in evaluating the patients' tissue in vivo. These technologies assess the disease process itself, associated structural alterations or do not have a known physical basis. These techniques will have an almost immediate application in directing the location to biopsy. The true optical biopsy where a definitive diagnosis is made by in vivo optical technology is a laudable goal, but only a few such applications are likely to become available in the near future. In addition to these approaches, the movement towards telemedicine is going to increase the demand for this type of technology for remote monitoring at home as well as in hospital settings.


Prospective evaluation of digital non-stereo color fundus photography as a screening tool in age-related macular degeneration.
To evaluate mydriatic, non-stereo digital color fundus photographs as a screening tool for identifying and classifying exudative age-related macular degeneration (AMD). Prospective case series. Digital color fundus photographs were obtained from patients seen in the AMD screening clinic over a 9-month period at the Ivey Eye Institute in London, Ontario. Photographs for eligible patients were separated by eye, cataloged, blinded, and randomly labeled before interpretation by an experienced vitreoretinal surgeon. Exact agreement, sensitivity, specificity, positive predictive value, and negative predictive value of the fundus photographs in diagnosing, classifying, and managing cases of suspected exudative AMD were then calculated against gold standard clinical examination and fluorescein angiography. A total of 223 images were used from 118 eligible patients. Exact agreement between photographic evaluation and gold standard ranged from 89.2% (presence of pigment epithelial detachment (PED)) to 82.5% (evidence of retinal pigment epithelium geographic atrophy). Sensitivities ranged from 89.2% (presence of choroidal neovascular membrane (CNVM)) to 40.0% (presence of PED). Specificities ranged from 94.1% (presence of PED) to 86.8% (presence of retinal pigment epithelium geographic atrophy). Positive predictive value ranged from 86.1% (presence of CNVM) to 40.0% (presence of PED). Negative predictive value ranged from 94.1% (presence of PED) to 88.9% (presence of CNVM). As a screening tool for high-risk dry changes and active exudative changes, overall sensitivity specificity, positive predictive value, and negative predictive value were 82.1%, 79.1%, 70.4%, and 88.0%, respectively. Digital, non-stereo color fundus photographs are highly sensitive and have high negative predictive value as a screening tool. Very few treatable lesions are missed using telemedicine in age-related macular degeneration.


Autophagy-mediated NKG2D internalization impairs NK cell function and exacerbates radiation pneumonitis.
Radiation pneumonitis is a critical complication that constrains the use of radiation therapy for thoracic malignancies, leading to substantial morbidity via respiratory distress and lung function impairment. The role of Natural killer (NK) cells in inflammatory diseases is well-documented; however, their involvement in radiation pneumonitis is not fully understood. To explore the involvement of NK cells in radiation pneumonitis, we analyzed tissue samples for NK cell presence and function. The study utilized immunofluorescence staining, western blotting, and immunoprecipitation to investigate CXCL10 and ROS levels, autophagy activity, and NKG2D receptor dynamics in NK cells derived from patients and animal models subjected to radiation. In this study, we observed an augmented infiltration of NK cells in tissues affected by radiation pneumonitis, although their function was markedly diminished. In animal models, enhancing NK cell activity appeared to decelerate the disease progression. Concomitant with the disease course, there was a notable upsurge in CXCL10 and ROS levels. CXCL10 was found to facilitate NK cell migration through CXCR3 receptor activation. Furthermore, evidence of excessive autophagy in patient NK cells was linked to ROS accumulation, as indicated by immunofluorescence and Western blot analyses. The association between the NKG2D receptor and its adaptor proteins (AP2 subunits AP2A1 and AP2M1), LC3, and lysosomes was intensified after radiation exposure, as demonstrated by immunoprecipitation. This interaction led to NKG2D receptor endocytosis and subsequent lysosomal degradation. Our findings delineate a mechanism by which radiation-induced lung injury may suppress NK cell function through an autophagy-dependent pathway. The dysregulation observed suggests potential therapeutic targets; hence, modulating autophagy and enhancing NK cell activity could represent novel strategies for mitigating radiation pneumonitis.


Differential association of socio-economic status with gender- and age-defined suicidal ideation among adult and elderly individuals in South Korea.
South Korea has the highest suicide rate among countries in the Organisation for Economic Co-operation and Development (OECD), with a rising trend that contrasts with the trend in most other OECD countries. This study assessed differential associations of socio-demographic factors with suicidal ideation in South Korea. We used five waves of data from the 2010 Korea National Health and Nutrition Examination Survey. Study subjects included 5803 men and women aged >25 years. We analysed weighted percentages with consideration of the complex survey sample design and unequal weights. Surveylogistic regressions were applied. Protective effects against suicidal ideation were found for higher household income, higher educational attainment, and being married. Functional limitations and depressive symptoms were risk factors for suicidal ideation. However, these significant factors may exert different effects on vulnerability for suicidal ideation among different genders and age groups. Thus, household income was mainly protective for women and subjects aged 25-44 years, and educational attainment was protective for individuals aged >65 years. Our findings suggest the need for extended social protection policies for the less privileged population and special strategies for different groups.


Acute 5-HT reuptake blockade potentiates human amygdala reactivity.
Variability in serotonin (5-HT) function is associated with individual differences in normal mood and temperament, as well as psychiatric illnesses, all of which are influenced by amygdala function. This study evaluated the acute effects of 5-HT reuptake blockade on amygdala function using pharmacological functional MRI. Eight healthy men completed a double-blind balanced crossover study with the selective 5-HT reuptake inhibitor, citalopram (20 mg infused over 30 min), and normal saline. Amygdala reactivity in response to novel facial expressions was assessed on three successive scans, once before drug/placebo infusion, once early in the infusion, and once at the end of infusion. Acute citalopram administration resulted in concentration-dependent increases in human amygdala reactivity to salient stimuli. The current pattern of 5-HT-mediated amygdala reactivity may represent an important pathway through which SSRIs achieve an antidepressant effect. Intriguingly, our data may also reveal a mechanism contributing to clinical observations of extreme agitation, restlessness, and suicidal ideation in some individuals during acute SSRI treatment. Developing a comprehensive model of how 5-HT modulates human amygdala reactivity supporting behavioral and physiological arousal will be instrumental for our understanding of basic neurobehavioral processes, their dysfunction in psychiatric illnesses, and their contribution to mechanism of treatment response.


Modelling molecule-surface interactions--an automated quantum-classical approach using a genetic algorithm.
We present an automated and efficient method to develop force fields for molecule-surface interactions. A genetic algorithm (GA) is used to parameterise a classical force field so that the classical adsorption energy landscape of a molecule on a surface matches the corresponding landscape from density functional theory (DFT) calculations. The procedure performs a sophisticated search in the parameter phase space and converges very quickly. The method is capable of fitting a significant number of structures and corresponding adsorption energies. Water on a ZnO(0001) surface was chosen as a benchmark system but the method is implemented in a flexible way and can be applied to any system of interest. In the present case, pairwise Lennard Jones (LJ) and Coulomb potentials are used to describe the molecule-surface interactions. In the course of the fitting procedure, the LJ parameters are refined in order to reproduce the adsorption energy landscape. The classical model is capable of describing a wide range of energies, which is essential for a realistic description of a fluid-solid interface.


Clinical and genetic heterogeneity of inherited autosomal recessive susceptibility to disseminated Mycobacterium bovis bacille calmette-guérin infection.
Five patients from 4 unrelated Tunisian families who presented with disseminated neonatal infection by Mycobacterium bovis bacille Calmette-Guérin strain were investigated. Two unrelated patients had different homozygous interleukin-12 receptor beta1 subunit gene splice-site mutations (64+5G-->A and 550-2A-->G). Two siblings and 1 unrelated patient, all of whom were from the same town, carried the same mutation (297del8) within the interleukin-12p40 gene. This is the first description of familial cytokine deficiency reported so far. All patients had complete lack of expression of the affected polypeptide and a profound deficiency of in vitro interferon-gamma production. The clinical severity of the mycobacterial infection was heterogeneous, even among affected members of the same family, which suggests the intervention of modifying genes.


Cost-effectiveness analysis of population-based tobacco control strategies in the prevention of cardiovascular diseases in Tanzania.
Tobacco consumption contributes significantly to the global burden of disease. The prevalence of smoking is estimated to be increasing in many low-income countries, including Tanzania, especially among women and youth. Even so, the implementation of tobacco control measures has been discouraging in the country. Efforts to foster investment in tobacco control are hindered by lack of evidence on what works and at what cost. We aim to estimate the cost and cost-effectiveness of population-based tobacco control strategies in the prevention of cardiovascular diseases (CVD) in Tanzania. A cost-effectiveness analysis was performed using an Excel-based Markov model, from a governmental perspective. We employed an ingredient approach and step-down methodologies in the costing exercise following a government perspective. Epidemiological data and efficacy inputs were derived from the literature. We used disability-adjusted life years (DALYs) averted as the outcome measure. A probabilistic sensitivity analysis was carried out with Ersatz to incorporate uncertainties in the model parameters. Our model results showed that all five tobacco control strategies were very cost-effective since they fell below the ceiling ratio of one GDP per capita suggested by the WHO. Increase in tobacco taxes was the most cost-effective strategy, while a workplace smoking ban was the least cost-effective option, with a cost-effectiveness ratio of US$5 and US$267, respectively. Even though all five interventions are deemed very cost-effective in the prevention of CVD in Tanzania, more research on budget impact analysis is required to further assess the government's ability to implement these interventions.


[CT of primary cerebral lymphoma in non-immunosuppressed patients].
In the last 10-15 years primary lymphoma of the brain has tripled in frequency in the non-immunosuppressed population. The correct diagnosis by CT-examination is difficult as primary lymphoma imitates different pathological conditions. Five examples from a series of 13 patients are presented.


A sweet twist gets Bacillus into shape.
A protective organelle that is essential for viability under most conditions, the cell wall is a dynamic structure that is continuously remodelled with the growth of the bacterial cell. Because the cell wall also moulds the bacterium, the mechanisms of cell wall homeostasis can be deciphered using cell shape as a convenient proxy. In this issue of Molecular Microbiology, Foulquier et al. illuminate a connection between cell shape regulation and metabolism in Bacillus subtilis. They find that the putative NAD(P)-binding enzyme YvcK organizes into helical subcellular structures that exert shape control by directing the cell wall biosynthetic enzyme PBP1 along the cell cylinder and to the septum, a function shared with the MreB actin cytoskeleton. Unlike MreB, however, the role of YvcK in cell shape control is manifested only on certain carbon sources, presumably by way of a previously unknown metabolic feed that taps into cell morphogenesis.


[Crystallography in the analysis of urinary calculi in Spain. Historical review of the Spanish contribution to the subject].
We make a review of the Spanish contribution to the field of crystallography applied to the study of Urinary Lithiasis and assess the current state of the same. We emphasize, by virtue of the number and quality of their works, CIFUENTES, DELATTE and COLLS, SOMACARRERA and ALONSO as pioneers of ultramicroscopic studies. GUILEN CAVERO because of his impressive explanation of Lithogenesis and B. PINTO for his contribution to the generalization of the knowledge of analysed calculation by means of crystallographic methods.


Columns and optimum gradient conditions for fast second-dimension separations in comprehensive two-dimensional liquid chromatography.
Gradient elution provides significantly higher peak capacity in comparison to the isocratic elution mode, hence it is very useful in online comprehensive two-dimensional liquid chromatography (LC). We compared suitability of five commercial core-shell columns and one monolithic column for fast gradients in the second LC dimension, where the time of separation is strictly limited by the fraction cycle time. In two-dimensional reversed-phase systems with partially correlated retention, the resolution, the peak capacity, and the regularity of coverage of the second-dimension retention space can be improved by appropriate adjusting the gradient time and the gradient range to suit the sample properties. We developed a new strategy for adjusting the gradient mobile phase composition range in the second-dimension, employing the retention data of representative sample standards characterizing the sample properties, which can be calibrated using the reference alkylbenzene series. Optimized second-dimension gradients with single-step or segmented profiles covering two or more fraction ranges, employed for the separation of subsequent fractions from the first-dimension, improve significantly the resolution, the separation time, and the regularity of coverage of the two-dimensional retention plane. The approach was applied to the two-dimensional comprehensive separation of phenolic acids and flavonoid compounds occurring as natural antioxidants.


Eps15 Homology Domain Protein 4 (EHD4) is required for Eps15 Homology Domain Protein 1 (EHD1)-mediated endosomal recruitment and fission.
Upon internalization, receptors are trafficked to sorting endosomes (SE) where they undergo sorting and are then packaged into budding vesicles that undergo fission and transport within the cell. Eps15 Homology Domain Protein 1 (EHD1), the best-characterized member of the Eps15 Homology Domain Protein (EHD) family, has been implicated in catalyzing the fission process that releases endosome-derived vesicles for recycling to the plasma membrane. Indeed, recent studies suggest that upon receptor-mediated internalization, EHD1 is recruited from the cytoplasm to endosomal membranes where it catalyzes vesicular fission. However, the mechanism by which this recruitment occurs remains unknown. Herein, we demonstrate that the EHD1 paralog, EHD4, is required for the recruitment of EHD1 to SE. We show that EHD4 preferentially dimerizes with EHD1, and knock-down of EHD4 expression by siRNA, shRNA or by CRISPR/Cas9 gene-editing leads to impaired EHD1 SE-recruitment and enlarged SE. Moreover, we demonstrate that at least 3 different asparagine-proline-phenylalanine (NPF) motif-containing EHD binding partners, Rabenosyn-5, Syndapin2 and MICAL-L1, are required for the recruitment of EHD1 to SE. Indeed, knock-down of any of these SE-localized EHD interaction partners leads to enlarged SE, presumably due to impaired endosomal fission. Overall, we identify a novel mechanistic role for EHD4 in recruitment of EHD1 to SE, thus positioning EHD4 as an essential component of the EHD1-fission machinery at SE.


Human papillomavirus and carcinoma of the urinary bladder.
The human papillomaviruses have been strongly associated with anogenital cancers. Sporadic reports have linked papillomavirus infection to bladder neoplasms. We analyzed 27 normal and malignant bladder tissue samples for the presence of human papillomavirus by in situ DNA hybridization and the polymerase chain reaction. Only one invasive, keratinizing squamous cell carcinoma was found to contain human papillomavirus DNA. This occurred in a 61-yr-old female who was immunocompetent and had no previous evidence of papillomavirus-associated disease. This case represents the first invasive carcinoma of the bladder associated with papillomavirus infection.


Tomato carotenoid cleavage dioxygenases 1A and 1B: Relaxed double bond specificity leads to a plenitude of dialdehydes, mono-apocarotenoids and isoprenoid volatiles.
The biosynthetic processes leading to many of the isoprenoid volatiles released by tomato fruits are still unknown, though previous reports suggested a clear correlation with the carotenoids contained within the fruit. In this study, we investigated the activity of the tomato (Solanum lycopersicum) carotenoid cleavage dioxygenase (SlCCD1B), which is highly expressed in fruits, and of its homolog SlCCD1A. Using in vitro assays performed with purified recombinant enzymes and by analyzing products formed by the two enzymes in carotene-accumulating Escherichia coli strains, we demonstrate that SlCCD1A and, to a larger extent, SlCCD1B, have a very relaxed specificity for both substrate and cleavage site, mediating the oxidative cleavage of cis- and all-trans-carotenoids as well as of different apocarotenoids at many more double bonds than previously reported. This activity gives rise to a plenitude of volatiles, mono-apocarotenoids and dialdehyde products, including cis-pseudoionone, neral, geranial, and farnesylacetone. Our results provide a direct evidence for a carotenoid origin of these compounds and point to CCD1s as the enzymes catalyzing the formation of the vast majority of tomato isoprenoid volatiles, many of which are aroma constituents.


Anandamide and its metabolites: what are their roles in the kidney?
Anandamide (AEA) is the N-acyl ethanolamide of arachidonic acid, an agonist of cannabinoid and non-cannabinoid receptors in the body. The kidneys are enriched in AEA and in enzymes that metabolize AEA, but the roles of AEA and its metabolites in the kidney remain poorly understood. This system likely is involved in the regulation of renal blood flow and hemodynamics and of tubular sodium and fluid reabsorption. It may act as a neuromodulator of the renal sympathetic nervous system. AEA and its cyclooxygenase-2 metabolites, the prostamides, in the renal medulla may represent a unique antihypertensive system involved in the long-term control of blood pressure. AEA and its metabolites are also implicated as modulators of inflammation and mediators of signaling in inflammation. AEA and its metabolites may be influential in chronic kidney disease states associated with inflammation and cardiovascular diseases associated with hyperhomocysteinemia. The current knowledge of the roles of AEA and its derivatives highlights the need for further research to define and potentially exploit the role of this endocannabinoid system in the kidney.


[Use of loading doses of bifidumbacterin forte for treatment of patients with acute enteric infections].
The clinical observation of patients with acute enteric infections (AEI), treated with loading doses of Bifidumbacterin forte during the first 2 days of the disease, was carried out. The preparation was shown to produce a positive effect on the course of AEI: salmonellosis, alimentary toxicoinfections, acute, dysentery. The early decrease of the manifestations of intoxication, pain syndrome, diarrhea, as well as the acceleration of convalescence in comparison with standard treatment, were noted. The most essential dynamics was registered in salmonellosis patients. The analysis of clinical results allowed to recommend the use of loading doses of Bifidumbacterin forte, a probiotic with high colonization potential to normalize the microbiocenosis of the intestine in AEI.


Development of ex situ normothermic reperfusion as an innovative method to assess pancreases after preservation.
Static cold storage (SCS) is the standard method for pancreas preservation prior to transplantation; however, it does not permit organ assessment. Normothermic reperfusion (NR) is utilized clinically for other organs to assess viability. Our aim was to develop NR using normothermic machine perfusion technique to simulate reperfusion at the time of transplantation, enabling evaluation of oxygenated hypothermic machine perfusion (HMPO2) as a newer strategy to optimize pancreas preservation. 13 porcine pancreases procured after circulatory death were divided into 3 groups: 4 pancreases preserved using SCS, and 2 groups preserved by HMPO2 (n = 4 and n = 5, differing by type of preservation solution). Duration of perfusion or cold storage was 6 hours before the 1-hour assessment using NR. Outcome measures were perfusion characteristics, biochemistry and change in tissue water mass as oedema assessment. During NR, the HMPO2 groups demonstrated better perfusion characteristics, normal macroscopic appearances, decreased water mass and one HMPO2 group demonstrated a response to glucose stimulation. Conversely, the SCS group showed an increased water mass and developed early macroscopic appearances of oedema, interstitial haemorrhage and minimal portal outflow. This study suggests that ex situ assessment of pancreases by NR is promising, and that HMPO2 may be better than SCS.


Astrocyte-specific activation of TNFR2 promotes oligodendrocyte maturation by secretion of leukemia inhibitory factor.
Tumor necrosis factor (TNF) and its receptors TNFR1 and TNFR2 have pleiotropic effects in neurodegenerative disorders. For example, while TNFR1 mediates neurodegenerative effects in multiple sclerosis, TNFR2 is protective and contributes to remyelination. The exact mode of TNFR2 action, however, is poorly understood. Here, we show that TNFR2-mediated activation of the PI3K-PKB/Akt pathway in primary astrocytes increased the expression of neuroprotective genes, including that encoding the neurotrophic cytokine leukemia inhibitory factor (LIF). To investigate whether intercellular signaling between TNFR2-stimulated astrocytes and oligodendrocytes plays a role in oligodendrocyte maturation, we established an astrocyte-oligodendrocyte coculture model, composed of primary astrocytes from huTNFR2-transgenic (tgE1335) mice and oligodendrocyte progenitor cells (OPCs) from wild-type mice, capable of differentiating into mature myelinating oligodendrocytes. In this model, selective stimulation of human TNFR2 on astrocytes, promoted differentiation of cocultured OPCs to myelin basic protein-positive mature oligodendrocytes. Addition of LIF neutralizing antibodies inhibited oligodendrocyte differentiation, indicating a crucial role of TNFR2-induced astrocyte derived LIF for oligodendrocyte maturation.


The Human-Animal Interface.
The human-animal interface is as ancient as the first bipedal steps taken by humans. Born with the human species, it has grown and expanded with the human species' prehistoric and historical development to reach the unprecedented scope of current times. Several facets define the human-animal interface, guiding the scope and range of human interactions with animal species. These facets have not ceased to evolve and expand since their emergence, all the more favoring disease emergence. Placing the human-animal interface in its historical perspective allows us to realize its versatile and dynamic nature. Changes in the scope and range of domestication, agriculture, urbanization, colonization, trade, and industrialization have been accompanied by evolving risks for cross-species transmission of pathogens. Because these risks are unlikely to decrease, improving our technologies to identify and monitor pathogenic threats lurking at the human-animal interface should be a priority.


Nerve Transfers After Cervical Spine Surgery: Multi-Institutional Case Series and Review of the Literature.
Up to 10% of cervical spine surgeries are complicated by postoperative weakness. Although many patients recover with nonoperative management, some require surgery for restoration of function. To present the indications and outcomes of patients undergoing nerve transfers after developing weakness secondary to cervical spine decompression. A retrospective review of patients from 2 academic medical centers who underwent nerve transfer for C5-6 root injury after cervical spine surgery was performed. Of the 10 treated patients, 9 experienced recovery at last follow-up, demonstrating improvements in strength and motion in the affected muscles. Successful nerve transfers occurred between 3 and 8 months after the index spinal surgery and included spinal accessory nerve to suprascapular nerve, triceps branch to anterior division of the axillary nerve, and/or ulnar or median fascicles to motor branches of the musculocutaneous nerve. The unsuccessful patient underwent nerve transfer surgery approximately 11 months after the index operation and failed to obtain functional recovery. Patients who experience C5-6 weakness after cervical spine surgery should be evaluated and considered for nerve transfer surgery if they have continued severe functional deficits at 6 months postoperatively. Earlier referral for nerve transfer is associated with improved functional outcomes in this cohort.


The influence of different mode of power density during antimicrobial photodynamic therapy for photokilling of Streptococcus mutans.
The aim of this study was to evaluate the inactivation potency of riboflavin and curcumin plus blue diode laser against Streptococcus mutans with different power densities. In this in vitro study, standard-strain S. mutans was exposed to curcumin and riboflavin plus blue diode laser with different power densities (0.4-1.0 W/cm2) as well as chlorhexidine (CHX). The colony forming units (CFUs)/mL was calculated. Data were analyzed by one-way ANOVA. Antibacterial analysis indicated that the blue diode laser irradiation with curcumin and riboflavin provided a satisfactory reduction of the S. mutans level. In addition, S. mutans was more affected by curcumin + blue diode laser when the power density was set to 1.0 W/cm2 (P < 0.0001). Meanwhile, bacterial suspensions treated with CHX showed maximum colony number reduction, compared with the control (P < 0.0001). This study showed the blue diode laser along with curcumin had strong bactericidal effect on S. mutans, and this effect improved by increasing the power density.


The importance of pancreatic inflammation in endosonographic diagnostics of solid pancreatic masses.
Endosonography (EUS) is one of the main diagnostic tools for the differential diagnosis of pancreatic masses. The aim of our study was to describe the value of this technique in the work-up of solid pancreatic lesions, considering the influence of the morphological evidence of pancreatic inflammation in the diagnostic process. Retrospective analysis of prospectively collected data in our tertiary University center. From March 2007 to October 2015, 218 patients underwent EUS for a suspected solid pancreatic neoplasm (based on previous cross-sectional imaging results, idiopatic acute pancreatitis, weight loss, pancreatic hyperenzymemia, painless jaundice or elevated Ca 19-9 values). Malignant lesions were diagnosed in 98 (45%) patients. Sensitivity of EUS for malignancy was 91% and specificity 89.2%. Signs of pancreatic inflammation in the surrounding pancreatic parenchyma around the focal lesion were present in 97 patients (44.4%)(more often in men, smokers and drinkers, and the most common etiology was focal chronic pancreatitis) and in these patients the sensitivity and sensibility dropped to 44% and 87.1%, respectively. In patients without signs of pancreatic inflammation, the pancreatic focal lesions were adenocarcinoma, neuroendocrine tumor, ventral/dorsal split, non-pancreatic pathology, pancreatic lipomatosis and autoimmune pancreatitis. Pancreatic inflammation (either focal or involving the whole gland) lowers the diagnostic sensibility of EUS in the work- up of pancreatic masses suspected for cancer, requiring further invasive diagnostic methods. Focal autoimmune pancreatitis and paraduodenal pancreatitis are still confused with pancreatic cancer, even in the absence of pancreatic inflammation.


Object-related brain potentials associated with the perceptual segregation of a dichotically embedded pitch.
The cortical mechanisms of perceptual segregation of concurrent sound sources were examined, based on binaural detection of interaural timing differences. Auditory event-related potentials were measured from 11 healthy subjects. Binaural stimuli were created by introducing a dichotic delay of 500-ms duration to a narrow frequency region within a broadband noise, and resulted in a perception of a centrally located noise and a right-lateralized pitch (dichotic pitch). In separate listening conditions, subjects actively discriminated and responded to randomly interleaved binaural and control stimuli, or ignored random stimuli while watching silent cartoons. In a third listening condition subjects ignored stimuli presented in homogenous blocks. For all listening conditions, the dichotic pitch stimulus elicited an object-related negativity (ORN) at a latency of about 150-250 ms after stimulus onset. When subjects were required to actively respond to stimuli, the ORN was followed by a P400 wave with a latency of about 320-420 ms. These results support and extend a two-stage model of auditory scene analysis in which acoustic streams are automatically parsed into component sound sources based on source-relevant cues, followed by a controlled process involving identification and generation of a behavioral response.


Application of pulsed-field gel electrophoresis and binary typing as tools in veterinary clinical microbiology and molecular epidemiologic analysis of bovine and human Staphylococcus aureus isolates.
Thirty-eight bovine mammary Staphylococcus aureus isolates from diverse clinical, temporal, and geographical origins were genotyped by pulsed-field gel electrophoresis (PFGE) after SmaI digestion of prokaryotic DNA and by means of binary typing using 15 strain-specific DNA probes. Seven pulsed-field types and four subtypes were identified, as were 16 binary types. Concordant delineation of genetic relatedness was documented by both techniques, yet based on practical and epidemiological considerations, binary typing was the preferable method. Genotypes of bovine isolates were compared to 55 previously characterized human S. aureus isolates through cluster analysis of binary types. Genetic clusters containing strains of both human and bovine origin were found, but bacterial genotypes were predominantly associated with a single host species. Binary typing proved an excellent tool for comparison of S. aureus strains, including methicillin-resistant S. aureus, derived from different host species and from different databases. For 28 bovine S. aureus isolates, detailed clinical observations in vivo were compared to strain typing results in vitro. Associations were found between distinct genotypes and severity of disease, suggesting strain-specific bacterial virulence. Circumstantial evidence furthermore supports strain-specific routes of bacterial dissemination. We conclude that PFGE and binary typing can be successfully applied for genetic analysis of S. aureus isolates from bovine mammary secretions. Binary typing in particular is a robust and simple method and promises to become a powerful tool for strain characterization, for resolution of clonal relationships of bacteria within and between host species, and for identification of sources and transmission routes of bovine S. aureus.


In vitro degradation behavior of a hydroxyapatite/poly(lactide-co-glycolide) composite reinforced by micro/nano-hybrid poly(glycolide) fibers for bone repair.
A poly(glycolide) (PGA) fiber-reinforced hydroxyapatite/poly(lactide-co-glycolide) (HA/PLGA) composite with high mechanical strength has been prepared previously. In this paper, in vitro degradation of ternary composites with different contents of PGA fibers (0, 30, 50 and 70 wt%) was investigated. Water absorption showed a marked increase as the degradation progressed, and the composite with 70 wt% PGA fibers showed the highest final water uptake which was 3.89 times higher than the initial value. The mass loss of the composite with 70 wt% PGA fibers was 79.3 ± 6.47% at 16 weeks, which was the highest among all the composites. The molecular weight of the PLGA matrix decreased over time especially for the composites containing 70 wt% PGA fibers. The lowest pH of the buffer solution was also observed in the composite with 70 wt% PGA fibers. Environmental scanning electron microscopy (ESEM) and micro-computed tomography (micro-CT) results demonstrated that the porosity of the composites and the size of the pores gradually increased as the degradation progressed. The most significant change in compression strength was observed for the composite with 70 wt% PGA fibers which was reduced from an initial value of 20 MPa to approximately 1 MPa at 16 weeks. The results indicated that the in vitro degradation of the composites could be accelerated by increasing the content of PGA fibers. It implied that the ternary composites might be a candidate for the repair of non-load bearing or cancellous bone which needs high initial strength and fast degradation rate.


DIFFUSE: predicting isoform functions from sequences and expression profiles via deep learning.
Alternative splicing generates multiple isoforms from a single gene, greatly increasing the functional diversity of a genome. Although gene functions have been well studied, little is known about the specific functions of isoforms, making accurate prediction of isoform functions highly desirable. However, the existing approaches to predicting isoform functions are far from satisfactory due to at least two reasons: (i) unlike genes, isoform-level functional annotations are scarce. (ii) The information of isoform functions is concealed in various types of data including isoform sequences, co-expression relationship among isoforms, etc. In this study, we present a novel approach, DIFFUSE (Deep learning-based prediction of IsoForm FUnctions from Sequences and Expression), to predict isoform functions. To integrate various types of data, our approach adopts a hybrid framework by first using a deep neural network (DNN) to predict the functions of isoforms from their genomic sequences and then refining the prediction using a conditional random field (CRF) based on co-expression relationship. To overcome the lack of isoform-level ground truth labels, we further propose an iterative semi-supervised learning algorithm to train both the DNN and CRF together. Our extensive computational experiments demonstrate that DIFFUSE could effectively predict the functions of isoforms and genes. It achieves an average area under the receiver operating characteristics curve of 0.840 and area under the precision-recall curve of 0.581 over 4184 GO functional categories, which are significantly higher than the state-of-the-art methods. We further validate the prediction results by analyzing the correlation between functional similarity, sequence similarity, expression similarity and structural similarity, as well as the consistency between the predicted functions and some well-studied functional features of isoform sequences. https://github.com/haochenucr/DIFFUSE. Supplementary data are available at Bioinformatics online.


Antinutrients in amphidiploids (black gram x Mung bean): varietal differences and effect of domestic processing and cooking.
Phytic acid, saponin and polyphenol contents in grains of various varieties of black gram (Vigna mungo) Mung bean (Vigna radiata L.) amphidiploids ranged from 697 to 750, 2746 to 2972 and 702 to 783 mg/100 g, respectively. Domestic processing and cooking methods including soaking, ordinary and pressure cooking of soaked and unsoaked seeds, and sprouting significantly lowered phytic acid, saponin and polyphenol contents of the amphidiploid seeds. Soaking for 18 h removed 31 to 37% of the phytic acid; the extent of removal was higher with long periods of soaking. Saponins and polyphenols were relatively less affected. Loss of the antinutrients was greater when soaked instead of unsoaked seeds were cooked. Pressure cooking had a greater effect than ordinary cooking. Antinutrient concentrations declined following sprouting; the longer the period of germination the greater was the reduction.


[Common epitopes of protein antigens in Neisseria and Moraxella].
Cross reactions between N. meningitidis and M. catarrhalis proteins were studied with the use of a panel of monoclonal antibodies to M. catarrhalis protein antigens. All antigenic preparations under study were shown to give cross reactions between N. meningitidis serotype porin of 39 kD (strain B125) and M. catarrhalis proteins of 40-41 kD. These M. catarrhalis proteins belonged to main proteins of class F and had the function of porins in the cell. In addition, the epitope of 41-kD antigen, detected by monoclonal antibodies 3E10, is common for both N. meningitidis porin and N. meningitidis iron-regulated proteins of 70 and 50 kD. The epitope of M. catarrhalis protein of 67 kD, detected by monoclonal antibodies 1G6, is common for N. meningitidis porin and N. meningitidis iron-regulated proteins of 50 and 55 kD.


[First-line chemo-radiotherapy neoadjuvant treatment in locally advanced (T4) epidermoid carcinoma of the esophagus].
In the period 1993-1997 we performed two phase II pilot studies of first-line chemo-radiotherapy in patients with locally advanced (T4) SCC of the esophagus. The first protocol (3 cycles of DDP-VP16 + 45 Gy) was used in 37 patients: toxicity was not negligible; a clinical tumor downstaging was obtained in 54% of cases; an R0 resection surgery was performed in 40% of patients. The overall median survival of the whole group of 37 patients was 11 months, while it was > 36 months for patients undergoing R0 resection. The second protocol (4 cycles of DDP-5FU + 45 Gy) was used in 25 patients: a clinical tumor downstaging was obtained in 55% of cases, and R0 resection surgery was performed in 45% of patients. The overall median survival of the whole group was 11 months. To date, all patients but one (who died after 13 months) are alive with a median follow up of 13 months. The prognosis of both groups of patients was improved compared to patients with T4 SCC of the esophagus who did not undergo chemo and/or radiotherapy. The survival advantage was especially evident for those who were able to undergo an R0 resection. First line chemo-radiotherapy should be considered the standard treatment for locally advanced esophageal SCC.


Microwave Simulation Experiments on Regolith (Lunar Dust) Deposition on Stainless Steel.
In this article, results are presented of experiments on depositing charged particles, which imitate the levitating dust on the Moon, on stainless steel. Ensembles of particles are created above the surface of laboratory regolith whose composition and particle size distribution imitate the dust that covers the Moon's surface. Under the action of the gyrotron radiation on regolith, non-linear physical-chemical processes develop (breakdown, chain plasmachemical reactions, and particle scattering by the Coulomb mechanism), which lead to the appearance of a levitating cloud of particles. The simulation experiment is based on the similarity between the processes that develop in the laboratory experiments with regolith and the processes that occur on the Moon during its bombardment by micrometeorites. The effect of the levitating cloud on stainless steel plates is studied and it is shown that regolith particles in the shape of spheroids of different sizes are deposited on the surface of the plates. The dimensions of the deposited particles and the density of their placement depend on the quality of treatment of the plate surface. It is shown that the laboratory-produced dusty plasma can be used in simulation experiments to study the modification of surfaces of different materials for space technology.


Diagnostic sonography in general surgery.
Eighty-seven patients who had sonographic examinations at the Orange County Medical Center were studied retrospectively to evaluate the usefulness and reliability of this noninvasive technique, and sonographic results were compared with findings at operation or findings made using other diagnostic methods. With a variety of lesions, the overall accuracy of diagnosis by sonography was 85%. In the remaining 15% of studies, false-positive or false-negative results were observed. The accuracy varied with the organ involved, the greatest being renal and hepatic masses. Ultrasound, when used in addition to careful surgical assessment of the patient, was found to be most useful in the diagnosis and follow-up of abdominal problems in surgical patients.


New translocation sequence mediating tetracycline resistance found in Escherichia coli pathogenic for piglets.
A discrete piece of deoxyribonucleic acid coding for tetracycline (Tc) resistance was found to move from one R plasmid to another in an Escherichia coli strain which is pathogenic for piglets. Since this phenomenon took place also in rec strains, the Tc segment was classified as a transposon and called Tn804. Restriction enzyme analysis with EcoRI, BglII, and HindIII indicated that Tn804 is related to Tn10, a well-known transposon that codes for resistance to tetracycline. Hybridization between plasmids carrying the two transposons provided proof of homology between Tn10 and prt of Tn804. Electron microscopic studies showed a transposon-like structure composed of one loop-stem structure with inverted repetitions of approximately 0.9 megadaltons inserted into the loop of a second loop-stem structure. It is suggested that Tn804 is composed of Tn10 plus another transposable sequence.


Molecular cloning, functional expression and characterization of d-limonene synthase from Schizonepeta tenuifolia.
Limonene is one of the most simple cyclic monoterpenes, and two enantiomers, d- and l-limonene occur due to the chiral carbon at 4-position. Cyclization of GPP into limonene is catalyzed by the limonene synthase, and some l-limonene synthase cDNAs have already been cloned from several species of plants, mainly from Labiatae family. However, the d-limonene synthase gene has not yet been obtained, therefore, no information is available on the molecular mechanism of stereochemical regulation in limonene formation. To resolve this, we cloned the d-limonene synthase gene (dLMS) from Schizonepeta tenuifolia (Labiatae) by a reverse genetic approach, and we found that both d- and l-limonene synthase share similar features such as a transit peptide, an arginine rich domain, and a metal cation binding site in their structures. Here, we report on the cloning of dLMS, and the putative stereochemical regulation mechanism is discussed based on the comparison of the deduced amino acid sequence of dLMS with those of known l-limonene synthases.


Initial response to salvage therapy determines prognosis in relapsed pediatric Hodgkin lymphoma patients.
Pediatric Hodgkin lymphoma (HL) is a highly curable disease; however, prognostic factors for the survival of patients who develop recurrent disease have not been clearly defined. This was a retrospective analysis of 50 pediatric patients with HL who relapsed or progressed between 1990 and 2006 and who were retrieved with intense cytoreductive treatment regimens followed by autologous stem cell transplantation and radiation therapy. A Cox proportional hazards model was used to determine risk factors for second treatment failure and death. The median patient age was 16.1 years (range, 4.9-22.1 years) at the time of HL diagnosis. Fifteen patients developed progressive disease during therapy, 14 patients relapsed early, and 21 patients relapsed late. Patients who remained alive at the time of this study had been followed for a median of 4.4 years (range, 1.2-16.6 years). The 5-year overall survival rate for patients who had an inadequate response (n = 14) to initial salvage therapy was only 17.9% (95% confidence interval [CI], 3.1%-42.5%) compared with 97.2% (95% CI, 81.9%-99.6%) for patients who responded (n = 36; P < .0001). In a multivariate Cox regression analysis of overall survival, an inadequate response to initial salvage therapy was the only significant variable (hazard ratio, 43.6; 95% CI, 5.4-354; P = .0004). The current results indicated that pediatric patients with relapsed HL who have an inadequate response after initial primary salvage chemotherapy have a very poor prognosis and should be considered for novel therapies directed at biologic or immunologic targets.


Food supplementation with milk fermented by Lactobacillus casei DN-114 001 protects suckling rats from rotavirus-associated diarrhea.
Group A rotavirus is the leading cause of diarrhea among children aged 3-36 mo worldwide. Introducing fermented milk products into the infant diet has been proposed for the prevention or treatment of rotavirus diarrhea. The preventive effect of milk fermented by the Lactobacillus casei strain DN-114 001 was studied in a model of germfree suckling rats supplemented daily from d 2 of life and infected with SA11 rotavirus at d 5 (RF group). One group was supplemented with nonfermented milk (RM) and two uninfected groups (CM and CF) received either nonfermented or fermented milk. Frequency and severity of diarrhea were observed. Rats were killed at various times from 0 to 120 h postinfection (p.i.). Bacteria were measured in the intestine, and rotavirus antigens were detected by ELISA in fecal samples and in different parts of the intestine. Histologic observations were made, including vacuolation, morphology of intestinal villi and number of mucin cells. RM rats had diarrhea for 6 d; compared with the CM group, they had alterations of the intestinal mucosa characterized by cellular vacuolation 48 and 72 h p.i. and a lower number of sulfated mucin cells 72 and 96 h p.i. (P: < 0.05). Early supplementation with fermented milk significantly decreased the clinical signs of diarrhea from 24 to 144 h p.i. (P: < 0.05) and prevented rotavirus infection in all sections of the intestine. Histologic lesions of the small intestine were greatly reduced (P: < 0.05) and the number of mucin cells remained unchanged. The data are discussed with respect to the possibility of reducing rotavirus diarrhea in young children by consumption of fermented milk.


Can the electrically stimulated manual muscle test differentiate upper from lower motor neuron injury in persons with acute SCI?
To determine if the motor response on the stimulated manual muscle test (SMMT) in muscles with a grade 0 motor score on the manual muscle test (MMT) can differentiate lower motor neuron (LMN) from upper motor neuron (UMN) injury based on the presence of spontaneous activity (SA) with needle EMG. Prospective Study. Twenty-one subjects with acute traumatic cervical SCI. An upper extremity International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) evaluation was completed on all subjects. A needle EMG and an electrically stimulated manual muscle test (SMMT) were completed on all key upper extremity muscles with a MMT motor score of zero. The MMT, SMMT and Needle EMG were done on 77 muscles. The SMMT motor score was 0 on 10 muscles and >1 on 67 muscles. The needle EMG identified spontaneous activity (SA) in 55/77 muscles. Seventy percent (7/10) of the muscles with MMT and SMMT motor score of zero demonstrated SA on EMG. Seventy-two percent (48/67) of the muscles with MMT motor score = 0 and SMMT motor score ≥1 demonstrated SA on EMG. In our study, 70% of the muscles with a SMMT motor response of zero and 72% of the muscles with a SMMT motor response greater than or equal to one demonstrated SA on EMG. The use of the SMMT as a clinical measure to differentiate LMN from UMN integrity may be limited when applied.


Identifying primary aldosteronism patients who require adrenal venous sampling: a multi-center study.
Adrenal venous sampling (AVS) is crucial for subtyping primary aldosteronism (PA) to explore the possibility of curing hypertension. Because AVS availability is limited, efforts have been made to develop strategies to bypass it. However, it has so far proven unsuccessful in applying clinical practice, partly due to heterogeneity and missing values of the cohorts. For this purpose, we retrospectively assessed 210 PA cases from three institutions where segment-selective AVS, which is more accurate and sensitive for detecting PA cases with surgical indications, was available. A machine learning-based classification model featuring a new cross-center domain adaptation capability was developed. The model identified 102 patients with PA who benefited from surgery in the present cohort. A new data imputation technique was used to address cross-center heterogeneity, making a common prediction model applicable across multiple cohorts. Logistic regression demonstrated higher accuracy than Random Forest and Deep Learning [(0.89, 0.86) vs. (0.84, 0.84), (0.82, 0.84) for surgical or medical indications in terms of f-score]. A derived integrated flowchart revealed that 35.2% of PA cases required AVS with 94.1% accuracy. The present model enabled us to reduce the burden of AVS on patients who would benefit the most.


Clinical usefulness of anaerobic blood culture in pediatric patients with bacteremia.
The purpose of this study is to evaluate the usefulness of anaerobic blood culture in pediatric patients by comparing the detection rate and distribution of bacteria between aerobic and anaerobic blood culture bottles. A retrospective analysis was conducted on 11,664 blood cultures obtained from children under the age of 14 between January 2013 and June 2020. The positive rate of total, aerobic, and anaerobic blood culture, as well as the species distribution of each blood culture bottle, were investigated. The positive rate of blood culture was 2.4 % (N = 281). Among them, 67 (23.8 %), 85 (30.3 %) and 129 (45.9 %) organisms were grown in only aerobic, only anaerobic, and both blood culture bottles, respectively. Gram-positive cocci were cultured on both, only aerobic, and only anaerobic blood culture bottles in proportions of 46.4 %, 23.4 %, and 30.2 %, respectively. Gram-negative bacilli were cultured on both, only aerobic, and only anaerobic blood culture bottles in proportions of 58.5 %, 12,3 %, and 29.2 %, respectively. Gram positive bacilli grew best in aerobic bottle only. There were seven strains of obligate anaerobes. Because many facultative anaerobic bacteria are recognized primarily from anaerobic blood culture bottles, combining aerobic and anaerobic blood culture bottles might be beneficial in pediatric patients with suspected blood stream infection.


Regeneration of the adult zebrafish brain from neurogenic radial glia-type progenitors.
Severe traumatic injury to the adult mammalian CNS leads to life-long loss of function. By contrast, several non-mammalian vertebrate species, including adult zebrafish, have a remarkable ability to regenerate injured organs, including the CNS. However, the cellular and molecular mechanisms that enable or prevent CNS regeneration are largely unknown. To study brain regeneration mechanisms in adult zebrafish, we developed a traumatic lesion assay, analyzed cellular reactions to injury and show that adult zebrafish can efficiently regenerate brain lesions and lack permanent glial scarring. Using Cre-loxP-based genetic lineage-tracing, we demonstrate that her4.1-positive ventricular radial glia progenitor cells react to injury, proliferate and generate neuroblasts that migrate to the lesion site. The newly generated neurons survive for more than 3 months, are decorated with synaptic contacts and express mature neuronal markers. Thus, regeneration after traumatic lesion of the adult zebrafish brain occurs efficiently from radial glia-type stem/progenitor cells.


In vitro mitochondrial toxicity of metacavir, a new nucleoside reverse transcriptase inhibitor for treatment of hepatitis B virus.
Therapy with nucleoside reverse transcriptase inhibitors (NRTIs) can be associated with mitochondrial toxicity. In vitro studies have been used to predict the predisposition for and characterize the mechanisms causing mitochondrial toxicity. Metacavir (PNA) is a novel synthetic nucleoside analog for oral administration with potent and specific antiviral activity against hepatitis B virus (HBV). We assessed the potential for mitochondrial toxicity of PNA in long-term cultures of HepG2 hepatoma cells by measuring mitochondrial function (through lactate secretion), levels of mitochondrial DNA (mtDNA), and the activities of respiratory-chain complexes I to IV. Exposure of HepG2 cells to PNA at concentrations up to 50 μM for 15 days resulted in no deleterious effect on cell proliferation, levels of lactate or mtDNA, or enzyme activities of respiratory-chain complexes I to IV. In contrast, dideoxycytosine at 10 μM and zidovudine at 50 μM have significant effects on cell proliferation, levels of lactate and mtDNA, and enzyme activities of respiratory-chain complexes I to IV. However, PNA at a supratherapeutic concentration of 250 μM could result in significant alterations in the levels of mtDNA and the activities of respiratory-chain complex enzymes, revealing evidence of the potential mitochondrial toxicity of PNA. In summary, these in vitro results indicate that the potential for PNA to interfere with mitochondrial functions is low.


Inequality in quality: addressing socioeconomic, racial, and ethnic disparities in health care.
Socioeconomic and racial/ethnic disparities in health care quality have been extensively documented. Recently, the elimination of disparities in health care has become the focus of a national initiative. Yet, there is little effort to monitor and address disparities in health care through organizational quality improvement. After reviewing literature on disparities in health care, we discuss the limitations in existing quality assessment for identifying and addressing these disparities. We propose 5 principles to address these disparities through modifications in quality performance measures: disparities represent a significant quality problem; current data collection efforts are inadequate to identify and address disparities; clinical performance measures should be stratified by race/ethnicity and socioeconomic position for public reporting; population-wide monitoring should incorporate adjustment for race/ethnicity and socioeconomic position; and strategies to adjust payment for race/ethnicity and socioeconomic position should be considered to reflect the known effects of both on morbidity. JAMA. 2000;283:2579-2584


The Impact of Intense Exercise on Semen Quality.
With expanding knowledge on the health benefits of exercise, there is an increasing demand for information on the andrological consequences of participating in sports. These consequences are especially important in the context of infertility problems worldwide. The so-called "male factor" is reported in up to 50% of couples having trouble with conception. The answer to the question, "Is physical activity good for male reproductive health?" is not straightforward. A number of studies have suggested that significant changes in semen parameters may occur due to sports training of certain types, intensities, and durations. The changes to these parameters vary in scope, direction, and magnitude. Findings in recreational athletes have also differed from those in professional athletes. This review of the current literature suggests that intense physical activity may affect the semen concentration, as well as the number of motile and morphologically normal spermatozoa. Training at higher intensities and with increased loads seems to be associated with more profound changes in semen quality. In recreational athletes, exercise has either a positive or neutral effect on semen parameters. Due to many limitations (e.g., global sperm count trends, concerns about the quality control of sperm evaluations, and new standards for semen analysis), comparisons among historical data and their interpretation are difficult.


Safety and effectiveness of drug-eluting stents among diabetic patients: a propensity analysis.
Diabetic patients frequently receive drug-eluting stents (DES) during percutaneous coronary interventions (PCI), but recent data have raised concerns as to whether DES are associated with increased risk of myocardial infarction or death. Accordingly, we sought to evaluate the long-term safety and effectiveness of DES in diabetic patients. We used a propensity score matching method to create and analyze a well-balanced cohort that included 2,374 diabetic patients who received PCI in Ontario, Canada, from December 1, 2003, to March 31, 2005. Primary outcomes of interest were repeat target-vessel revascularization, myocardial infarction, and death after the index PCI. The mean age of our diabetic cohort was 64 years, and 68% of the patents were male. At 2 years, rates of repeat target-vessel revascularization were significantly lower among diabetic patients treated with DES compared with those treated with bare metal stents (BMS) (7.1% vs 14.4%, P < .001). Myocardial infarction rates were not significantly different between the 2 groups after 2 years (6.6% in DES group vs 4.5% in BMS group, P = .45). In addition, mortality was not statistically different among diabetic patients treated with DES (7.6%) and BMS (9.5%) (P = .086). Drug-eluting stents are effective among diabetic patients in substantially reducing the need for repeat target-vessel revascularization. The overall rates of myocardial infarction were not significantly different between DES and BMS. In addition, the mortality of diabetic patients who received DES was not significantly increased compared with BMS.


EphA7 regulates spiral ganglion innervation of cochlear hair cells.
During the development of periphery auditory circuitry, spiral ganglion neurons (SGNs) form a spatially precise pattern of innervation of cochlear hair cells (HCs), which is an essential structural foundation for central auditory processing. However, molecular mechanisms underlying the developmental formation of this precise innervation pattern remain not well understood. Here, we specifically examined the involvement of Eph family members in cochlear development. By performing RNA-sequencing for different types of cochlear cell, in situ hybridization, and immunohistochemistry, we found that EphA7 was strongly expressed in a large subset of SGNs. In EphA7 deletion mice, there was a reduction in the number of inner radial bundles originating from SGNs and projecting to HCs as well as in the number of ribbon synapses on inner hair cells (IHCs), as compared with wild-type or heterozygous mutant mice, attributable to fewer type I afferent fibers. The overall activity of the auditory nerve in EphA7 deletion mice was also reduced, although there was no significant change in the hearing intensity threshold. In vitro analysis further suggested that the reduced innervation of HCs by SGNs could be attributed to a role of EphA7 in regulating outgrowth of SGN neurites as knocking down EphA7 in SGNs resulted in diminished SGN fibers. In addition, suppressing the activity of ERK1/2, a potential downstream target of EphA7 signaling, either with specific inhibitors in cultured explants or by knocking out Prkg1, also resulted in reduced SGN fibers. Together, our results suggest that EphA7 plays an important role in the developmental formation of cochlear innervation pattern through controlling SGN fiber ontogeny. Such regulation may contribute to the salience level of auditory signals presented to the central auditory system.


Mentoplasty: a new approach.
In search of a better, more natural appearing mentoplasty prosthesis, a new material, Silastic X7-2524 carvable soft elastomer, has been combined with a new design in a chin implant. In 50 patients over the last 2 years, a submental, subperiosteal approach with protection of the mental nerves during dissection under direct vision was utilized. Results have been excellent and complications to date insignificant. Over the 2-year follow-up period, there has been no clinical evidence of distortion or bone resorption.


The 'active ingredients' for successful community engagement with disadvantaged expectant and new mothers: a qualitative comparative analysis.
To explore which conditions of community engagement are implicated in effective interventions targeting disadvantaged pregnant women and new mothers. Adaptive experiences during pregnancy and the early years are key to reducing health inequalities in women and children worldwide. Public health nurses, health visitors and community midwives are well placed to address such disadvantage, often using community engagement strategies. Such interventions are complex; however, and we need to better understand which aspects of community engagement are aligned with effectiveness. Qualitative comparative analysis conducted in 2013, of trials data included in a recently published systematic review. Two reviewers agreed on relevant conditions from 24 maternity or early years intervention studies examining four models of community engagement. Effect size estimates were converted into 'fuzzy' effectiveness categories and truth tables were constructed. Using fsQCA software, Boolean minimization identified solution sets. Random effects multiple regression and fsQCA were conducted to rule out risk of methodological bias. Studies focused on antenatal, immunization, breastfeeding and early professional intervention outcomes. Peer delivery (consistency 0·83; unique coverage 0·63); and mother-professional collaboration (consistency 0·833; unique coverage 0·21) were moderately aligned with effective interventions. Community-identified health need plus consultation/collaboration in intervention design and leading on delivery were weakly aligned with 'not effective' interventions (consistency 0·78; unique coverage 0·29). For disadvantaged new and expectant mothers, peer or collaborative delivery models could be used in interventions. A need exists to design and test community engagement interventions in other areas of maternity and early years care and to further evaluate models of empowerment.


[Vertebral metrics: application of a new mechanical instrument to evaluate the spinal column].
To present the results of the first application of the new technology - Vertebral Metrics - the analysis of the 3D position of the vertex of each spinous process in pregnant women. The Vertebral Metrics was applied to women without associated pathology in four stages of pregnancy (12, 20, 32, 37 weeks gestation). We applied univariate linear models. We found that the differences that occur during pregnancy are more significant at the position y (anteroposterior). It was found also that there is a positive correlation between the biomechanical position of the vertex of each of the vertebrae with the homologous position of rest. Through Vertebral Metrics innovative results could be obtained in analyzing biomechanics of the spine. A device that has different applications can be easily adopted in areas such as orthopedics, neurosurgery, pediatrics and rehabilitation. It should also be noted that this instrument is not exhausted in the sample of this research because it can be further applied to the general population.


Prognostic role of glutathione S-transferase polymorphisms in acute myeloid leukemia.
Glutathione S-transferases (GSTs) are phase II detoxification enzymes involved in the metabolism of carcinogens and anticancer drugs, known also to interact with kinase complexes during oxidative or chemical stress-induced apoptosis. We were interested whether their polymorphic variants may account for differences in outcome of patients with acute myeloid leukemia (AML) following chemotherapy. We studied the prognostic role of polymorphisms in three GST genes (GSTP1/M1/T1) in a large patient cohort of the German Austrian Acute Myeloid Leukemia Study Group, treated according to prospective multicenter clinical trials (AML HD98A: 254 patients; AML HD98-B: 100 patients), with a median follow-up of 46 months. Looking at short-term adverse drug reactions, homozygous carriers of the GSTP1*105 Val allele had a faster neutrophil and platelet recovery (P=0.002 and 0.02, respectively) and a reduced need of red cell and platelet transfusions (P=0.01 and 0.03, respectively). Response to induction chemotherapy did not vary according to GST polymorphisms. Multivariable Cox regression models revealed a significant better relapse-free (RFS) and overall survival for the GSTP1(*)105 Val (P=0.003 and 0.03, respectively), whereas GSTT1 and GSTM1 genotypes had no significant impact. The favorable impact of GSTP1(*)105 Val on RFS seems to be restricted to the subgroup of patients exhibiting a normal karyotype.


Breastfeeding During Early Infancy is Associated with Higher Weight-Based World Health Organization Anthropometry.
The World Health Organization (WHO) Expert Committee on Physical Status: The Use and Interpretation of Anthropometry established reference anthropometric standards for the growth of healthy infants and children. As part of a prospective clinical study of dengue virus infections in infants, we measured the length and weight of healthy infants in San Pablo, Laguna, Philippines at two scheduled study visits. We examined the correlation between breastfeeding and WHO anthropometric z scores during early infancy in San Pablo, Laguna, Philippines. We found that breastfeeding status and the frequency of breastfeeding during early infancy positively correlated with weight-based WHO anthropometric z scores.


Effect of renal denervation on the development of cellophane-wrap hypertension in rabbits.
The development of hypertension in rabbits with bilateral cellophane wrapping of the kidneys was studied in animals with and without surgical denervation of the kidneys. Mean arterial pressure was measured before and 14 and 28 days after surgery. After 14 and 28 days of wrapping, mean arterial pressure had increased 12 +/- 3 mmHg and 31 +/- 3 mmHg in rabbits with innervated kidneys and 7 +/- 2 mmHg and 26 +/- 2 mmHg in rabbits with denervated kidneys, respectively. The increases in arterial pressure were significantly less in the denervated animals. In sham wrap animals, renal denervation also resulted in significantly lower arterial pressure than in sham wrap+sham denervated rabbits. Noradrenaline concentration of denervated kidneys averaged only 4% of that measured in kidneys subjected to sham denervation. The results show that renal denervation slightly attenuated the degree of hypertension developed following renal wrapping. Since renal denervation produced a similar small decrease in arterial pressure in normotensive rabbits it is suggested that the effect is non-specific and probably due to loss of efferent renal sympathetic nerves.


Relation between work function and structural properties of triangular defects in 4H-SiC epitaxial layer: Kelvin probe force microscopic and spectroscopic analyses.
To understand the relationship between the work function and structural properties of sufficiently expanded triangular defects (size: ∼250 μm) in the 4H-SiC epitaxial layer, Kelvin probe force microscopy (KPFM) and spectroscopic [micro-Raman spectroscopy and photoluminescence (PL)] analyses were performed. Spectroscopic analysis demonstrated that the triangular defects mostly comprise the 3C polytypes and that it experiences internal stress, defects, and defect-induced carrier generation. The distinguishable areas in the triangular defects had surface potential values different from those of the 4H-SiC matrix; this could be explained by the work function difference, which arises from variations in the electron affinity of the 3C polytype as well as the positional variations of the Fermi energy level in terms of electron concentration. In addition, tensile-stress-induced surface disorder leading to variations in electron affinity was discussed. The mechanical properties of the triangular defects measured by a nanoindenter were significantly deteriorated because of many dislocation arrays and stacking faults with many broken and/or strained bonds.


Norepinephrine metabolism in brainstem of spontaneously hypertensive rats.
Concentrations of norepinephrine in lower brainstem and hypothalamus of genetically hypertensive rats are significantly lower than in control rats. There is a concomitant reduction (50 percent) in aromatic L-amino acid decarboxylase but not in tyrosine hydroxylase activity. A possible relation of this central catecholamine deficiency to the hypertension is discussed.


Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial.
Patients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiation have an improved prognosis. The need for surgery in these patients has been questioned, but the proportion of patients achieving a pathological complete response is small. We aimed to assess whether adding cycles of mFOLFOX6 between chemoradiation and surgery increased the proportion of patients achieving a pathological complete response. We did a phase 2, non-randomised trial consisting of four sequential study groups of patients with stage II-III locally advanced rectal cancer at 17 institutions in the USA and Canada. All patients received chemoradiation (fluorouracil 225 mg/m(2) per day by continuous infusion throughout radiotherapy, and 45·0 Gy in 25 fractions, 5 days per week for 5 weeks, followed by a minimum boost of 5·4 Gy). Patients in group 1 had total mesorectal excision 6-8 weeks after chemoradiation. Patients in groups 2-4 received two, four, or six cycles of mFOLFOX6, respectively, between chemoradiation and total mesorectal excision. Each cycle of mFOLFOX6 consisted of racemic leucovorin 200 mg/m(2) or 400 mg/m(2), according to the discretion of the treating investigator, oxaliplatin 85 mg/m(2) in a 2-h infusion, bolus fluorouracil 400 mg/m(2) on day 1, and a 46-h infusion of fluorouracil 2400 mg/m(2). The primary endpoint was the proportion of patients who achieved a pathological complete response, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00335816. Between March 24, 2004, and Nov 16, 2012, 292 patients were registered, 259 of whom (60 in group 1, 67 in group 2, 67 in group 3, and 65 in group 4) met criteria for analysis. 11 (18%, 95% CI 10-30) of 60 patients in group 1, 17 (25%, 16-37) of 67 in group 2, 20 (30%, 19-42) of 67 in group 3, and 25 (38%, 27-51) of 65 in group 4 achieved a pathological complete response (p=0·0036). Study group was independently associated with pathological complete response (group 4 compared with group 1 odds ratio 3·49, 95% CI 1·39-8·75; p=0·011). In group 2, two (3%) of 67 patients had grade 3 adverse events associated with the neoadjuvant administration of mFOLFOX6 and one (1%) had a grade 4 adverse event; in group 3, 12 (18%) of 67 patients had grade 3 adverse events; in group 4, 18 (28%) of 65 patients had grade 3 adverse events and five (8%) had grade 4 adverse events. The most common grade 3 or higher adverse events associated with the neoadjuvant administration of mFOLFOX6 across groups 2-4 were neutropenia (five in group 3 and six in group 4) and lymphopenia (three in group 3 and four in group 4). Across all study groups, 25 grade 3 or worse surgery-related complications occurred (ten in group 1, five in group 2, three in group 3, and seven in group 4); the most common were pelvic abscesses (seven patients) and anastomotic leaks (seven patients). Delivery of mFOLFOX6 after chemoradiation and before total mesorectal excision has the potential to increase the proportion of patients eligible for less invasive treatment strategies; this strategy is being tested in phase 3 clinical trials. National Institutes of Health National Cancer Institute.


Granulopoietic effects of lithium on human bone marrow in vitro.
Although studies in mice suggest that lithium enhances granulopoiesis by increasing the production of colony stimulating factor (CSF), results using human assay systems have varied. We have studied the action of lithium on the in vitro proliferation of normal human bone marrow (BM) granulocytic progenitor cells (CFUc) and on CSF production by human peripheral blood (PB) mononuclear cells (MNC). In the absence of exogenous CSF, lithium increased the number of "spontaneous" BM CFUc (P less than 0.05). This effect was abolished by removal of phagocytic cells, suggesting that lithium does not affect CFUc directly, but rather acts via a phagocytic cell. Lithium variably increased BM CFUc when PB MNC feeder layers were employed as the CSF source. This stimulation was most pronounced when the number of cells in the feeder layer was low, i.e., suboptimal CSF. Incubation with 1 meq/L lithium, increased (P less than 0.05) CSF production by PB MNC. Addition of lithium to BM cultures containing optimum CSF did not increase, but in fact decreased, the number of CFUc. These studies indicate that lithium increases CSF production by both PB and BM MNC. Furthermore, the stimulatory effects of lithium occur when CSF levels in the culture system are low.


Targeting epigenetic mechanisms as an emerging therapeutic strategy in pulmonary hypertension disease.
Pulmonary arterial hypertension (PAH) is a multifactorial cardiopulmonary disease characterized by an elevation of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR), which can lead to right ventricular (RV) failure, multi-organ dysfunction, and ultimately to premature death. Despite the advances in molecular biology, the mechanisms underlying pulmonary hypertension (PH) remain unclear. Nowadays, there is no curative treatment for treating PH. Therefore, it is crucial to identify novel, specific therapeutic targets and to offer more effective treatments against the progression of PH. Increasing amounts of evidence suggest that epigenetic modification may play a critical role in the pathogenesis of PAH. In the presented paper, we provide an overview of the epigenetic mechanisms specifically, DNA methylation, histone acetylation, histone methylation, and ncRNAs. As the recent identification of new pharmacological drugs targeting these epigenetic mechanisms has opened new therapeutic avenues, we also discuss the importance of epigenetic-based therapies in the context of PH.


A bilingual advantage in visual language discrimination in infancy.
The origins of the bilingual advantage in various cognitive tasks are largely unknown. We tested the hypothesis that bilinguals' early capacities to track their native languages separately and learn about the properties of each may be at the origin of such differences. Spanish-Catalan bilingual and Spanish or Catalan monolingual infants watched silent video recordings of French-English bilingual speakers and were tested on their ability to discern when the language changed from French to English or vice versa. The infants' performance was compared with that of previously tested French-English bilingual and English monolingual infants. Although all groups of monolingual infants failed to detect the change between English and French, both groups of bilingual infants succeeded. These findings reveal that bilingual experience can modulate the attentional system even without explicit training or feedback. They provide a basis for explaining the ontogeny of the general cognitive advantages of bilinguals.


Shoulder dystocia in diabetic and non-diabetic pregnancies.
Shoulder dystocia remains an obstetric emergency. Maternal diabetes is considered to be one of the major risk factors for shoulder dystocia. The aim of this study was to analyze antepartum and peripartum risk factors and complications of shoulder dystocia in diabetic and non-diabetic women. We performed a retrospective analysis of 48 shoulder dystocia cases out of 28,485 vaginal deliveries of singleton, live-born infants over a 13 year period: 13 cases were diagnosed in diabetic women and 35 cases in non-diabetic women. The study was conducted in the 2nd Department of Obstetrics and Gynecology, Medical University of Warsaw, Poland, from January 2000 to December 2012. Compared to non-diabetic women, diabetic patients had significantly higher pre-pregnancy body weight (83.4±23.8 kg vs. 62.5±10.9 kg, p=0.002), higher pre-pregnancy BMI (30.2±6.8 kg/m2 vs. 22.9±4.3 kg/m2, p=0.0003), and lower gestational weight gain (11.4±6.2 kg vs. 16.0±4.7 kg, p=0.01). Diabetic women with shoulder dystocia were more likely to deliver before completion of the 38th week of gestation (30.8% vs. 5.7%, p=0.02) and had a higher incidence of 1st and 2nd stage perineal tears compared with the non-diabetic group (23.1% vs. 0%, p=0.02). There were two cases of symphysis pubis dehiscence in non-diabetic women. Children of diabetic mothers had a significantly higher birth weight (4,425.4±561.6 g vs. 4,006.9±452.8 g, p=0.03). Children of diabetic mothers with dystocia were at significantly higher risk of peripartum injuries (92.3% vs. 45.7%). A significant difference was observed in the percentage of brachial plexus palsy (61.5% vs. 17.1%). Children of diabetic women experiencing shoulder dystocia were more frequently affected by Erb's brachial plexus palsy and respiratory disturbances. These children had an increased likelihood of birth weights above the 90th percentile (not necessarily reaching 4,000 g) compared to children born to non-diabetic mothers. Shoulder dystocia in women with diabetes mellitus during pregnancy was associated with earlier gestational age of labor, and these women were more frequently overweight. The newborns of diabetic mothers after shoulder dystocia appeared to be at an increased risk for perinatal morbidity compared to the newborns of non-diabetic mothers experiencing this complication.


[Polymorphisms in the genes of cytochrome oxidase P450 2D6 (CYP2D6), paraoxonase 1 (PON1) and apolipoprotein E (APOE) as risk factors for Parkinson's disease].
The presence of Parkinson's disease (PD) among the members of a family is a clear indication of the significance of genetics in its development. In spite of that, the majority of patients with PD shows a sporadic form of the disease induced as a result of interaction of both environmental and genetic factors. The aim of this study was to examine the effects of polymorphisms in the genes of cytohrome P450 2D6(CYP2D6), paraoxonase 1 (PON 1) and apolipoprotein E (APOE), as risk factors for PD. We examined 106 patients with PD (65 men and 41 women) and 75 ethnically matched control subjects. The mean age at onset of PD in the patients was 46.9+/-9.4 years (ranging from 30 to 70 years). Genotyping was performed using standard PCR amplification and restriction endonuclease digestion protocols described for known polymorphism in the candidate genes under study. The genotype A/A polymorphisms 2D6* gene of CYP2D6 and genotype M/M polymorphisms L54M gene of PON1 were significantly more frequent in the patients with PD than in the control group. The patients with genotypes A/A and M/M had 3.4 and 3.2 higher risk of PD, respectively than the control group (p = 0.01). The relation between genotypes A/A gene of CYP2D6 and M/M gene of PON1 was modified by the age at onset. The genotypes were associated with early onset of PD (P = 0.001, p = 0.004). The carriers of the A and M alleles in homozygote had 2.4 and 4.2 years respectively earlier onset of PD than carriers of other genotypes with these polymorphisms. The frequency allele e4 gene of APOE was higher in the PD patients with early onset (20%) than in PD with later onset (7.4%), while the genotype epsilon3/epsilon3 was associated with PD late onset (p = 0.024). Combined genotype I (carriers of the two risk allels in homozygote and one alleles risk in heterozygote) and combined genotype II (carriers of the three alleles risk in homozygote) caused early PD. Combined genotype II was detected in 12.7% of the patients in the group of early onset, and in 2.4% of the patients with the onset after 45 years. The results of our study suggest that the genotypes A/A and M/M genes of CYP2D6 and PON1, and allele epsilon4 gene are an important risk for the development of PD, causing its early onset. The cumulative effects of the risk genes cause an early onset of PD.


Optical wireless communication performance enhancement using Hamming coding and an efficient adaptive equalizer with a deep-learning-based quality assessment.
Optical wireless communication (OWC) technology is one of several alternative technologies for addressing the radio frequency limitations for applications in both indoor and outdoor architectures. Indoor optical wireless systems suffer from noise and intersymbol interference (ISI). These degradations are produced by the wireless channel multipath effect, which causes data rate limitation and hence overall system performance degradation. On the other hand, outdoor OWC suffers from several physical impairments that affect transmission quality. Channel coding can play a vital role in the performance enhancement of OWC systems to ensure that data transmission is robust against channel impairments. In this paper, an efficient framework for OWC in developing African countries is introduced. It is suitable for OWC in both indoor and outdoor environments. The outdoor scenario will be suitable to wild areas in Africa. A detailed study of the system stages is presented to guarantee the suitable modulation, coding, equalization, and quality assessment scenarios for the OWC process, especially for tasks such as image and video communication. Hamming and low-density parity check coding techniques are utilized with an asymmetrically clipped DC-offset optical orthogonal frequency-division multiplexing (ADO-OFDM) scenario. The performance versus the complexity of both utilized techniques for channel coding is studied, and both coding techniques are compared at different coding rates. Another task studied in this paper is how to perform efficient adaptive channel estimation and hence equalization on the OWC systems to combat the effect of ISI. The proposed schemes for this task are based on the adaptive recursive least-squares (RLS) and the adaptive least mean squares (LMS) algorithms with activity detection guidance and tap decoupling techniques at the receiver side. These adaptive channel estimators are compared with the adaptive estimators based on the standard LMS and RLS algorithms. Moreover, this paper presents a new scenario for quality assessment of optical communication systems based on the regular transmission of images over the system and quality evaluation of these images at the receiver based on a trained convolutional neural network. The proposed OWC framework is very useful for developing countries in Africa due to its simplicity of implementation with high performance.


Synthesis and evaluation of anti-acetylcholinesterase activity of some benzothiazole based new piperazine-dithiocarbamate derivatives.
In this present study some benzothiazole derivatives bearing piperazine and thiocarbamate moieties were synthesized and their potential anticholinesterase properties were investigated. A set of 30 new compounds of 2-[(6-substituted benzothiazol-2-yl)amino]-2-oxoethyl 4-substituted piperazine-1-carbodithioate derivatives were synthesized by reacting 2-chloro-N-(6-substituted benzothiazole-2-yl)acetamide derivatives derivatives and sodium salts of appropriate N,N-disubstituted dithiocarbamic acids in acetone. The structures of the obtained compounds were elucidated using FT-IR, (1)H-NMR and MS spectral data and elemental analyses result. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) using a modificated Ellman's spectrophotometric method. Some of the compounds can be identified as anticholinesterase agents due to their inhibitory effect when compared with Donepezil. Compounds with dimethylamino ethyl or dimethylamino propyl substituents were defined as the anticholinesterase active compounds.