An acquired Bernard-Soulier-like platelet defect associated with juvenile myelodysplastic syndrome.
Bernard-Soulier syndrome is an inherited bleeding abnormality characterized by thrombocytopenia with large platelets and deficiency of the platelet membrane glycoprotein (GP) Ib-IX complex. We have identified a young female with an acquired Bernard-Soulier-like platelet defect and a coexisting primary myelodysplastic disorder. Abnormal bruising had developed at age 5. A normal platelet count with some giant platelets was noted at age 7. At age 9 she developed a large haematoma following surgery. Laboratory investigation revealed thrombocytopenia and large platelets. Platelet membrane glycoprotein analysis showed a marked deficiency of the components of the GP Ib-IX complex (approximately equal to 25% of normal). Flow cytometry revealed two populations of platelets: a predominant population of large platelets lacking the GP Ib-IX complex and a minor population of normal-sized platelets with normal GP Ib-IX expression. The patient developed progressive anaemia, more severe thrombocytopenia and neutropenia, and circulating blast cells were seen. A bone marrow showed gross hypercellularity with marked dysplasia of all three lineages and increased blasts. Marrow cytogenetic studies showed the presence of monosomy 7 in all metaphases, with an additional trisomy 21 in 10%. Peripheral blood cells were normal 46XX. The above data are consistent with an acquired myelodysplastic syndrome associated with a Bernard-Soulier-like platelet defect.


Current challenges of metastatic breast cancer.
Metastasis is one of the most characteristic yet problematic behaviors of cancer cells. Stage IV breast cancer accounts for a large portion of breast cancer-related morbidity and mortality. Despite early detection and improvement in survival owing to advancements in biomedical research and overall improvement of the health system, 6-10% of patients present with stage IV disease in the developed world, with a higher incidence noted elsewhere. Despite advances in biomedical research into cancer, up to 70-80% of patients with stage IV breast cancer die of cancer in 5 years, a disproportionally higher mortality compared with non-metastatic breast cancer. In this article, we review the incidence, survival, heterogeneity, current practice, and challenges in stage IV breast cancer, and we finish by noting new research initiatives to improve poor survival and suggesting future directions. By doing so, we hope to set the basis of future directions for both treating physicians and translational researchers to relieve the suffering of patients with stage IV breast cancer and improve the survival of patients with this dismal disease.


Computer-aided analysis of the influence of digitizing and surfacing on the accuracy in dental CAD/CAM technology.
In dentistry, ceramic materials with high fracture resistance are needed for all-ceramic fixed partial dentures (FPDs). The sophisticated processing of advanced ceramics that can be used for such dental restorations demands the application of CAD/CAM technologies. These techniques necessitate digitizing of the prepared teeth or the planned restoration itself and surfacing of the acquired digital data before milling paths can be generated. As precision in fit is crucial for dental restorations, a computer-aided method for the quantitative and qualitative 3D analysis has been developed and applied. Factors influencing the obtainable precision in the application of CAD/CAM techniques were taken into consideration.


Cross-sectional area of the anterior belly of the digastric muscle: comparison of MRI and ultrasound measures.
Changes in morphometry of head and neck muscles have received little attention in research relative to limb muscles. While recent literature suggests that high-frequency ultrasound transducers can provide superior spatial resolution compared to that of magnetic resonance imaging (MRI), no studies have compared these imaging methods for investigating the submental muscle group. This preliminary study sought to compare ultrasound and MRI as a method of quantifying the cross-sectional area (CSA) of the submental muscle group. Measurements were taken from coronal ultrasound and MRI images in 11 healthy participants. Comparisons were limited to the anterior belly of the digastric muscle because of differences in imaging resolution. Ultrasound CSA measurements were smaller than MRI measurements (p = 0.01) by 10 % (95% CI = -18 to -2). Correlations were significant and relatively high (left: r = 0.909, p < 0.001; right: r = 0.776, p = 0.005). Ultrasound imaging has the advantages of natural participant positioning, superior clarity of muscle borders of the submental muscles, requires less acquisition time, and is a less expensive method of imaging compared to MRI. This preliminary study has shown that ultrasound is a viable imaging modality for quantitative measurements of the anterior belly of the digastric muscle and has advantages over MRI beyond cost and accessibility.


Perceived location of two-dimensional patterns.
The study attempted to test the possibility that the center of gravity of two-dimensional patterns is the cue used by a human observer for their localization. Four experiments were carried out. The first, using a matching procedure, required the localization of the center of irregular dot patterns, contour and filled polygons which varied in size and orientation. In the other three experiments the subjects had to point to briefly exposed dot patterns in which overall shape (convex and concave in Expts 2 and 3) and dot density (Expt 4) were manipulated. The performance of these direct localization tasks was found to be as accurate as the performance in previous studies of indirect localization or regular patterns. The results consistently supported the claim that information about position of the center of gravity is used for the localization of visual objects.


Higher omega-3 index and DHA status in pregnant women compared to lactating women - Results from a German nation-wide cross-sectional study.
During pregnancy and lactation, there is a high need of long-chain (LC) omega-3 fatty acids (n-3 PUFA), especially docosahexaenoic acid (DHA), for fetus and infant. Also, a low LC n-3 PUFA status during pregnancy is associated with postpartum depression. The aim of this cross-sectional study was to analyze the LC n-3 PUFA status in German women during pregnancy and lactation. As a part of a nationwide cross-sectional study in which the nutrient status of women in different stages of life was determined, 213 pregnant (≥27th week of gestation) and 127 lactating women between 18 and 44 years were evaluated regarding their LC n-3 PUFA status by measuring the omega-3 index (relative eicosapentaenoic acid (EPA) and DHA concentration in erythrocyte fatty acid). The mean omega-3 index of the total study population was 6.23±1.48%. Pregnant women showed significant (p≤0.001) higher omega-3 index values (6.40±1.31%) and DHA concentrations (5.91±1.23%) than lactating women (omega-3 index: 5.50±1.34%; DHA: 4.79±1.27%). Woman with LC n-3 PUFA supplementation showed higher omega-3 index values (7.73±1.28%) vs. women without supplementation (6.04±1.39%, p≤0.001). Week of pregnancy, month of lactation as well as smoking were negatively associated with the omega-3 index. Comprehensive data on the long-term LC n-3 PUFA status of German women during pregnancy and lactation are presented. To evaluate an optimal maternal omega-3 index in view of the fetal and infant development further studies are needed.


Candidate proteomic biomarkers for non-alcoholic fatty liver disease (steatosis and non-alcoholic steatohepatitis) discovered with mass-spectrometry: a systematic review.
Non-alcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in the liver which is accompanied by a series of metabolic deregulations. There are sustained research efforts focusing upon biomarker discovery for NAFLD diagnosis and its prognosis in order investigate and follow-up patients as minimally invasive as possible. The objective of this study is to critically review proteomic studies that used mass spectrometry techniques and summarize relevant proteomic NAFLD candidate biomarkers. Medline and Embase databases were searched from inception to December 2014. A final number of 22 records were included that identified 251 candidate proteomic biomarkers. Thirty-three biomarkers were confirmed - 14 were found in liver samples, 21 in serum samples, and two from both serum and liver samples. Some of the biomarkers identified have already been extensively studied regarding their diagnostic and prognostic capacity. However, there are also more potential biomarkers that still need to be addressed in future studies.


The Australian paradox: a substantial decline in sugars intake over the same timeframe that overweight and obesity have increased.
Ecological research from the USA has demonstrated a positive relationship between sugars consumption and prevalence of obesity; however, the relationship in other nations is not well described. The aim of this study was to analyze the trends in obesity and sugar consumption in Australia over the past 30 years and to compare and contrast obesity trends and sugar consumption patterns in Australia with the UK and USA. Data on consumption of sugar in Australia, the UK and USA were obtained from the Food and Agriculture Organization for the years 1980-2003. The prevalence of obesity has increased 3 fold in Australians since 1980. In Australia, the UK and USA, per capita consumption of refined sucrose decreased by 23%, 10% and 20% respectively from 1980 to 2003. When all sources of nutritive sweeteners, including high fructose corn syrups, were considered, per capita consumption decreased in Australia (-16%) and the UK (-5%), but increased in the USA (+23%). In Australia, there was a reduction in sales of nutritively sweetened beverages by 64 million liters from 2002 to 2006 and a reduction in percentage of children consuming sugar-sweetened beverages between 1995 and 2007. The findings confirm an "Australian Paradox"--a substantial decline in refined sugars intake over the same timeframe that obesity has increased. The implication is that efforts to reduce sugar intake may reduce consumption but may not reduce the prevalence of obesity.


Fos regulates neuronal activity in the nucleus accumbens.
Repeated exposure to drugs of abuse induces a variety of persistent changes in the brain and the dopamine D1 receptor plays a major role in the process. To understand intracellular mechanisms contributing to cocaine-induced neuroadaptations, we previously examined the role of the immediate early gene Fos using a mouse in which Fos is disrupted primarily in D1 receptor-expressing neurons in the brain. We found that both dendritic remodeling of medium spiny neurons and behavioral sensitization induced by repeated exposure to cocaine are attenuated in the mutant mice. Moreover, the expression of genes encoding several transcription factors, neurotransmitter receptors and intracellular signaling molecules following repeated cocaine administration is altered in the mutant mice compared to that in wild-type mice. In the present study, we have investigated the role of Fos in regulating neuronal excitability at a cellular level and found that medium spiny nucleus accumbens neurons in the mutant mice exhibit increased excitability and attenuated inhibitory responses to stimulation of D1 receptors compared to those in wild-type mice. Our findings suggest that Fos functions in D1 receptor-bearing neurons to regulate neuronal activity which may contribute to the persistence of drug-induced changes.


Monitoring pressure changes in the inner ear induced by middle ear pressure therapy with an EFET01 device in guinea pigs.
As a low-cost, portable, handheld air pressure generation tool not requiring a ventilation tube, the EFET01 device has shown clinical effectiveness for intractable Ménière's disease (MD) patients in Japan. However, no animal studies have investigated changes in inner ear pressure (PI) when applying this device. To determine the PI properties in response to middle ear pressure therapy (MEPT) induced by the EFET01 in guinea pigs. In seven healthy guinea pigs, bi-phasic pressure pulses from -5 to 12 cm H2O were delivered to the external ear canal and transmitted to the middle and inner ear cavities with an intact tympanic membrane. Hydrostatic pressure change in the inner ear perilymphatic compartment was measured by a servo-controlled micropipette system. From eight successful ears, pressure changes in the middle ear slightly decreased and were instantly transferred to the inner ear. The EFET01 produces a bi-phasic positive/negative pressure pulse, which is approximately twice as large as the monophasic pressure pulse. Our study clarified the EFET01's ability to transmit pressure and verified its effectiveness in MD patients as observed in clinical studies. The PI properties in guinea pig response to MEPT with the EFET01 device were investigated.


Seizing opportunity: Diverse early-entry nursing students' perceptions of seeking a PhD.
The aging and retirement of the current nursing professoriate and the increasing numbers of nurses pursuing practice doctorates has precipitated decreasing numbers of nurses, specifically diverse nurses pursuing a research doctorate, thus limiting the development of nursing science. To describe factors influencing decisions about entering a PhD program from the perspectives of early-entry PhD nursing students. A qualitative descriptive design using semistructured interviews to explore the perceptions of making the decision to pursue a PhD in nursing of the students who participated in two early-entry mentoring programs. A model, entitled "Seizing Opportunity" was developed from the findings about the process of students deciding to pursue a PhD. Motivators and detractors that can help nursing educators understand how to successfully recruit diverse PhD students were uncovered. Providing knowledge and mentoring for early entry students can increase the numbers of diverse students pursuing a PhD in nursing.


Scanning electron microscopy of congenital corneal leukomas (Peters' anomaly).
Specimens of three corneas in two patients with Peter's anomaly were obtained at the time of penetrating keratoplasty and studied by scanning and transmission electron microscopy. In one patient, the anomaly was monocular, and the endothelial surface showed a central defect in Descemet's layer with isolated rounded defects in the midperiphery. Fine collagenous material covered the posterior surface. The other two specimens were obtained from a patient with rubella syndrome without cataracts. The cornea showed malformation of Descemet's membrane with fibroblastic overgrowth on the endothelial layer. Epithelial-like cells and leukocytes were also found. The congenital central leukoma we believe was caused by adhesion of the pupillary membrane in our first patient, and possibly was inflammatory in our second patient.


Stable rAAV-mediated transduction of rod and cone photoreceptors in the canine retina.
Recombinant adeno-associated virus (rAAV) vectors are attractive candidates for the treatment of inherited and acquired retinal disease. Although rAAV vectors are well characterized in rodent models, a prerequisite to their clinical application in human patients is the thorough evaluation of their efficacy and safety in intermediate animal models. In this study, we describe rAAV-2-mediated expression of GFP reporter gene in retinal cells following local vector delivery in dogs. Subretinal delivery of rAAV.CMV.GFP was performed unilaterally in eight normal dogs from 6 weeks of age. The area of retinal transduction was maximized by the optimization of surgical techniques for subretinal vector delivery by pars-plana vitrectomy and the use of fine-gauge subretinal cannulae to create multiple retinotomies. rAAV-2 vectors mediated efficient stable reporter gene expression in photoreceptors and retinal pigment epithelial cells. We found efficient transduction of cone photoreceptors in addition to rods in both the canine retina and after subretinal vector delivery in another intermediate animal model, the feline retina. GFP expression in dogs was confined to the area of the retinal bleb and was sustained in cells at this site for at least 18 months. Electroretinography demonstrated a modest reduction in global rod-mediated retinal function following subretinal delivery of rAAV.CMV.GFP. Three of the eight animals developed delayed-onset intraocular inflammation, in two cases associated with a serum antibody response to GFP protein. We conclude that rAAV-2 vectors mediate efficient sustained transgene expression in rod and cone photoreceptors following subretinal delivery in this intermediate animal model. The possibility of adverse effects including intraocular immune responses and reduced retinal function requires further investigation prior to clinical applications in patients.


Exploring the influence of nasal vestibule structure on nasal obstruction using CFD and Machine Learning method.
Motivated by clinical findings about the nasal vestibule, this study analyzes the aerodynamic characteristics of the nasal vestibule and attempt to determine anatomical features which have a large influence on airflow through a combination of Computational Fluid Dynamics (CFD) and machine learning method. Firstly, the aerodynamic characteristics of the nasal vestibule are detailedly analyzed using the CFD method. Based on CFD simulation results, we divide the nasal vestibule into two types with distinctly different airflow patterns, which is consistent with clinical findings. Secondly, we explore the relationship between anatomical features and aerodynamic characteristics by developing a novel machine learning model which could predict airflow patterns based on several anatomical features. Feature mining is performed to determine the anatomical feature which has the greatest impact on respiratory function. The method is developed and validated on 41 unilateral nasal vestibules from 26 patients with nasal obstruction. The correctness of the CFD analysis and the developed model is verified by comparing them with clinical findings.


DRAM-3 modulates autophagy and promotes cell survival in the absence of glucose.
Macroautophagy is a membrane-trafficking process that delivers cytoplasmic constituents to lysosomes for degradation. The process operates under basal conditions as a mechanism to turnover damaged or misfolded proteins and organelles. As a result, it has a major role in preserving cellular integrity and viability. In addition to this basal function, macroautophagy can also be modulated in response to various forms of cellular stress, and the rate and cargoes of macroautophagy can be tailored to facilitate appropriate cellular responses in particular situations. The macroautophagy machinery is regulated by a group of evolutionarily conserved autophagy-related (ATG) proteins and by several other autophagy regulators, which either have tissue-restricted expression or operate in specific contexts. We report here the characterization of a novel autophagy regulator that we have termed DRAM-3 due to its significant homology to damage-regulated autophagy modulator (DRAM-1). DRAM-3 is expressed in a broad spectrum of normal tissues and tumor cells, but different from DRAM-1, DRAM-3 is not induced by p53 or DNA-damaging agents. Immunofluorescence studies revealed that DRAM-3 localizes to lysosomes/autolysosomes, endosomes and the plasma membrane, but not the endoplasmic reticulum, phagophores, autophagosomes or Golgi, indicating significant overlap with DRAM-1 localization and with organelles associated with macroautophagy. In this regard, we further proceed to show that DRAM-3 expression causes accumulation of autophagosomes under basal conditions and enhances autophagic flux. Reciprocally, CRISPR/Cas9-mediated disruption of DRAM-3 impairs autophagic flux confirming that DRAM-3 is a modulator of macroautophagy. As macroautophagy can be cytoprotective under starvation conditions, we also tested whether DRAM-3 could promote survival on nutrient deprivation. This revealed that DRAM-3 can repress cell death and promote long-term clonogenic survival of cells grown in the absence of glucose. Interestingly, however, this effect is macroautophagy-independent. In summary, these findings constitute the primary characterization of DRAM-3 as a modulator of both macroautophagy and cell survival under starvation conditions.


A decade at the roadside.
The Mid-Anglia General Practitioner Accident Service (MAGPAS) was formed ten years ago, following the example set by Dr Ken Easton OBE and his Road Accident After Care Scheme in the North Riding of Yorkshire. The following paper outlines the operational details of MAGPAS and analyses the statistics compiled from the accident report forms returned by the participating doctors over the past five years.


Effect of rabbit doe-litter separation on 24-hour changes of luteinizing hormone, follicle stimulating hormone and prolactin release in female and male suckling pups.
The daily pattern of nursing of the rabbit pup by the doe is the most important event in the day for the newborn and is neatly anticipated by them. Such anticipation presumably needs a close correlation with changes in hormones that will allow the pups to develop an appropriate behavior. Although a number of circadian functions have been examined in newborn rabbits, there is no information on 24-h pattern of gonadotropin release or on possible sex-related differences in gonadotropin or prolactin (PRL) release of pups. This study examined the 24-h changes of plasma luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL) in 11 days old suckling female and male rabbits left with the mother or after short-term (i.e., 48 h) doe-litter separation. Animals were kept under controlled light-dark cycles (16 h-8 h; lights on at 08:00 h). On day 9 post partum, groups of 6-7 female or male rabbit pups were separated from their mothers starting at 6 different time intervals in the 24 h cycle. Pups were killed 48 h after separation. At each time interval groups of male or female pups that stayed with the mother were killed as controls. Plasma, LH, FSH and PRL levels were measured by specific radioimmunoassays. In pups kept with their mother plasma FSH and LH maxima occurred at the first and second part of the light phase (at 13:00 and 17:00-21:00 h, respectively) (females) or as two peaks for each of the hormones (at 13:00 and 01:00 h) (males). PRL release was similar in female and male rabbit pups kept with their mother, showing a 24-h pattern with two peaks, at 13:00 and 01:00 h, respectively. Mean 24-h values of gonadotropins and PRL did not differ between sexes. Isolation of pups for 48 h augmented circulating gonadotropin and PRL levels and distorted hormone 24-h pattern to a similar extent in both sexes. Significant sex differences in 24-h changes in LH and FSH, but not in PRL, release occurred in rabbit pups kept with the doe. Separation of newborn pups from their mother augmented circulating gonadotropin and PRL levels and disrupted 24-h rhythmicity of gonadotropin and PRL release similarly in both sexes. The effect of pups' isolation can be attributed either to a modification of the circadian pacemaker or to a masking effect on some of its output overt rhythms.


Covariation patterns of phytoplankton and bacterioplankton in hypertrophic shallow lakes.
The aim of this work was to assess the temporal patterns in the community composition of phytoplankton (PCC) and bacterioplankton (BCC) in two interconnected and hypertrophic Pampean shallow lakes in Argentina. Factors shaping their community dynamics and community temporal covariations were also analysed. We performed 4 years of seasonal samplings (2012-2016) and communities were studied by the Utermöhl approach (PCC) and Illumina MiSeq sequencing (BCC). We found marked seasonal variations in both communities and inter-annual variations with decreasing microbial community similarities during the study. We also observed covariation in community-level dynamics among PCC and BCC within and between shallow lakes. The within-lake covariations remained positive and significant, while controlling for the effects of intrinsic (environmental) and extrinsic (temporal and meteorological) factors, suggesting a community coupling mediated by intrinsic biotic interactions. Algal-bacterial associations between different taxa of phytoplankton and bacterioplankton within each lake were also found. PCC was mainly explained by pure regional extrinsic (17-21%) and intrinsic environmental (8-9%) factors, while BCC was explained by environmental (8-10%) and biotic interactions with phytoplankton (7-8%). Our results reveal that the influence of extrinsic regional factors can be channeled to bacterioplankton through both environmental (i.e. water temperature) and phytoplankton effects.


Government intervention, market development, and pollution emission efficiency: Evidence from China.
The government and the market are the two main means for resource allocation, and both play important roles in economic development and environmental protection. Based on the theoretical mechanism analysis, this study empirically investigated the relationship between government intervention, market development, and China's provincial pollution emission efficiency by using the static panel OLS, system generalized method of moments (SYS-GMM), and panel threshold effect model during the period 2000-2017. The results show that the impact of government intervention on China's provincial pollution emission efficiency shows a non-linear U-shaped curve relationship, and there is a positive correlation between market development and provincial pollution emission efficiency in China. Government intervention and market development are complementary, rather than a substitute for each other, in promoting China's provincial pollution emission efficiency. When government intervention is set as the threshold variable, the impact of government intervention on China's provincial pollution emission efficiency shows the feature of "promotes first, then inhibits." However, when market development is set as the threshold variable, government intervention is only conducive to the improvement of China's provincial pollution emission efficiency at a moderate marketization level. Lastly, some policy implications related to the government and the market in enhancing China's provincial pollution emission efficiency are presented.


Rheumatoid arthritis associated with bronchiolitis obliterans and immunoblastic sarcoma.
A case is reported of a 72 year old man suffering from classical seropositive RA for 10 years. Two months before admission he experienced general illness, fever and itching. Lymph nodes enlargement and hepatosplenomegaly were found. Histologic features of lymph node biopsy were compatible with angioimmunoblastic lymphadenopathy and Lennert lymphoma. Rapidly progressive pulmonary deterioration followed with hilar invasion and honeycombing. Sternal punction, bone biopsy, bronchus biopsy and blind lung biopsy however, did not reveal lymphomatous invasion. On the contrary, lung biopsy, showed bronchiolitis obliterans, an often fatal, small airway disease whose connection with RA is discussed. Plasmapheresis induced a correction of leucopenia and thrombocytopenia. A fatal evolution evolved within six months. Autopsy revealed diffuse invasion by immunoblastic sarcoma. The clinicopathological entities angioimmunoblastic lymphadenopathy and Lennert lymphoma are referred to. The relationship with autoimmune disorders is stressed.


Scaling-up of natural products isolation.
Scaling-up is a way of increasing the quantity without losing the quality. The scaling-up is not always straightforward as the yield of the target compound becomes more important. The factors that influence scaling-up in a medium scale are outlined in this chapter. An example of a scale-up is also provided to illustrate some of the principles.


Clinical management of older persons with haemophilia.
Life expectancy for people with haemophilia (PWH) has improved and is now approaching that of the general population. The growing population of elderly PWH will therefore increasingly face the age-related morbidities such as cardiovascular diseases, malignant disease, liver disease, and bone and joint related diseases, as well as the lifestyle and psychosocial factors that accompany many of these conditions. For many PWH, frequent contact with haemophilia specialists within the comprehensive care centres supplants the relationship that individuals in the general population have with their general practitioners. As a result, there is a risk that elderly PWH may miss the chronic disease screening opportunities offered to the general population. This review focuses on the screening tests and examinations recommended for age-related comorbidities in the general population that may be applicable to the growing population of older people with haemophilia.


Awareness, emotional adjustment, and injury severity in postacute brain injury.
Relationships among awareness of deficits, injury severity, and emotional adjustment in patients with traumatic brain injury were explored. One hundred sixty-six individuals were referred for postacute neurocognitive assessment. Retrospective file analysis identified injury severity, and data from the Patient Competency Rating Scale and Katz Adjustment Scale-Revised, utilizing self-ratings and significant others' ratings, were gathered. Significant others described emotional adjustment difficulties, regardless of the severity of injury. A positive association was noted between patients' acknowledgment of neurobehavioral problems and ratings of their emotional adjustment. Severity of TBI appeared less important than emotional adjustment in the awareness of deficit; mildly injured patients were more likely to report neurobehavioral deficits than were moderately and severely injured patients, relative to the reports of significant others.


Differentiation between specific and nonspecific reactions of bovine sera and foot and mouth disease virus (FMDV) in immunodiffusion tests.
The precipitating and neutralizing activities of normal bovine sera with FMDV were studied and compared. Twenty-two out of 79 normal bovine sera gave a positive reaction in micro neutralization tests with FMDV type O, while six did so with type A. In RID tests 32 sera were positive with type O and 28 with type A virus. Almost all of the 79 sera gave a positive reaction in the RID with trypsin treated virus of both types. After three to four fold concentration most sera also gave visible reactions in ID tests when tested against complete virus. When O virus was used the ID patterns produced by most normal sera clearly differed from those obtained with early and late convalescent sera from FMDV infected steers. When type A materials were employed this was also the case but to a lesser extent. The patterns obtained with concentrated normal sera showed, in general a strong line with trypsin treated virus and no line or a weaker one with complete virus. The substances in normal bovine sera precipitating trypsin treated O virus were different from those reacting with trypsinized virus of type A.


Antipsychotic use in the elderly: shifting trends and increasing costs.
The purpose of this study was to assess trends in utilization and costs of antipsychotic drugs among a population of older adults over time, with respect to the prevalence of users, shifts in prescribing patterns, and related financial implications. Cross-sectional time series of quarterly and annual antipsychotic utilization and cost were obtained from administrative databases for calendar years 1993 through 2002. A population-based study of more than 1.4 million residents of the province of Ontario aged 65 years or older. Data sources used included the Ontario Drug Benefits (ODB) database and Statistics Canada census data. The prevalence of antipsychotic users increased by 34.8% over the study period from 2.2% at the beginning of 1993 to 3.0% of the elderly at the end of 2002 (p < 0.01). This was associated with a 749% increase in total cost (from $3.7 million in 1993 to $31.4 million in 2002; p < 0.01). The atypical antipsychotics, which were not available in 1993, made up 82.5% of the antipsychotics dispensed and 95.2% of costs in 2002. The modest increase in antipsychotic prevalence in the elderly over the last ten years has been associated with a substantial increase in cost, with a significant shift towards use of the atypical antipsychotics. As the atypical antipsychotics are increasingly used for patients with dementia, which is becoming more prevalent in the aging population, an understanding of the benefits of these medications must be balanced with a detailed understanding of the material and financial implications.


[Gas-permeable scleral lens for management of severe keratoconjunctivitis sicca secondary to chronic graft-versus-host disease].
Graft-versus-host disease is a major complication of allogeneic hematopoietic stem cell transplantation. Severe keratoconjunctivitis sicca is common in patients with chronic GVH disease. The goal of this study was to evaluate the safety and efficacy of a gas-permeable scleral lens in the management of severe dry eye disease associated with chronic GVH. This is a retrospective study from June 2009 to November 2013. Patients fitted with scleral lenses for severe keratoconjunctivitis sicca associated with chronic GVH were included. The main outcomes measured were best-corrected visual acuity and quality of life (OSDI and NEI-VFQ25) composite scores before and six months after scleral lens fitting. Sixteen patients were included. The mean age was 52 years (19-69 years). Mean follow-up was 20 months (3-48 months). All patients reported improvement of their ocular symptoms. Best corrected visual acuity improved from 0.21 ± 0.26 to 0.1 ± 0.14 logMAR (P = 0.002), OSDI score improved from 92.1 ± 11.3 to 23.5 ± 11.2 (P = 0.002) and NEI-VFQ25 improved from 41.3 ± 7 to 83.1 ± 15.9 (P = 0.003), 6 months after scleral lens fitting. No serious adverse events, infectious, hypoxemic or allergic complications attributable to the scleral lens occurred. Gas-permeable scleral lens use appears to be safe and effective in patients with severe dry eye related to chronic GVH.


Diagnostic significance of myeloperoxidase assay in neuronal ceroid-lipofuscinoses (Batten-Vogt syndrome).
In 13 patients with morphologically established juvenile neuronal ceroid lipofuscinosis and 13 controls, the activity of leukocyte peroxidase (myeloperoxidase) was determined under various conditions: Measurement of water-soluble enzyme, the buffer-soluble enzyme, and the leukocyte homogenate; application of phosphate buffer (pH7.0) and borate buffer (pH7.6); employment of 9mM, 28mM, and 55mMp-phenylenediamine as hydrogen donor; and measurement of the specific enzyme extinction at 10, 60, and 180 seconds. A significant difference between mean values for patients and controls could not be established. In both groups, single individuals exhibited definitely increased or reduced enzyme concentrations, leaving us, however, without an adequate explanation for these observations. Our studies indicate that determination of myeloperoxidase has no value in establishing the diagnosis of neuronal ceroid-lipofuscinoses.


[Diagnosis, treatment and prevention of Ixodes tick-borne borreliosis in the Ul'ianovsk region].
The level of morbidity in Ixodes tick-borne borreliosis, the analysis of the quality of diagnostics and the results of treatment are presented. The necessity of taking prophylactic measures is substantiated.


[Diagnosis and follow-up of Russel's diencephalic cachexia by echography, x-ray computed tomography and nuclear magnetic resonance].
A diencephalic astrocytoma was diagnosed by ultrasonography in a 5 months old girl with nystagmus and emaciation. A 27 months follow-up with ultrasonography, computed tomography and magnetic resonance imaging, showed an initial improvement after irradiation and afterwards the development of complications with ventricular dilatation and parenchymal calcifications.


Tensional acoustomechanical soft metamaterials.
We create acoustomechanical soft metamaterials whose response to uniaxial tensile stressing can be easily tailored by programming acoustic wave inputs, resulting in force versus stretch curves that exhibit distinct monotonic, s-shape, plateau and non-monotonic snapping behaviors. We theoretically demonstrate this unique metamaterial by considering a thin soft material sheet impinged by two counter-propagating ultrasonic wave inputs across its thickness and stretched by an in-plane uniaxial tensile force. We establish a theoretical acoustomechanical model to describe the programmable mechanics of such soft metamaterial, and introduce the first- and second-order tangential stiffness of its force versus stretch curve to boundary different behaviors that appear during deformation. The proposed phase diagrams for the underlying nonlinear mechanics show promising prospects for designing tunable and switchable photonic/phononic crystals and microfluidic devices that harness snap-through instability.


University hospitals reach out.
University of Iowa Hospitals and Clinics extends its services throughout Iowa to support community physicians and the hospitals in which they serve their patients.


Retrolental fibroplasia in full-term infants without exposure to supplemental oxygen.
We observed retinal folds identical in appearance to Grade 3 cicatricial retrolental fibroplasia in three infants at birth. In two of them we observed the active lesion of acute retrolental fibroplasia in the fellow eye at birth. These observations lead us to suggest that the active lesion of retrolental fibroplasia can occur in utero and progress to cicatrization in the absence of any obvious precipitating factor.


Biosynthesis of basement membrane molecules by salivary adenoid cystic carcinoma cells: an immunofluorescence and confocal microscopic study.
The biosynthesis of basement membrane molecules and fibronectin was studied in vitro in the two different human cell systems (ACC2 and ACC3) established from adenoid cystic carcinomas (ACC) of the salivary gland using immunofluorescence and confocal microscopy. When cells were attached and spread on dishes, fine granular immunofluorescence for type IV collagen, laminin, heparan sulphate proteoglycan, entactin, and fibronectin first appeared diffusely in the cytoplasm, and then changed in aggregation of coarse granules in the perinuclear area. With formation of colonies, these signals were present in the extracellular space, initially in the basal aspect of attached cells and consequently in the lateral intercellular space. After the cells formed a confluent monolayer, extracellular signals started to decrease in inverse proportion to the reappearance of intracellular ones. The results indicate that the parenchymal cells of ACC synthesize these five extracellular matrix molecules, secrete them into the extracellular milieu and remodel the extracellular deposits. It is suggested that the characteristic stromal architecture of ACC, represented by stromal pseudocysts, results from their own secretion of the basement membrane molecules and fibronectin.


Serum creatine kinase levels after succinylcholine in children with "muscle, eye and brain disease".
Four boys belonging to a group of children affected by a rare form of muscular dystrophy with eye and brain involvement, termed the "muscle, eye and brain disease" (MEB), were anaesthetized for various eye examinations and surgery. On some occasions succinylcholine was used during anaesthesia and the initially elevated serum creatine kinase (CK) values increased from a range of 122 to 1200 units.L-1 to a range of 4350 to 9690 units.L-1 22 hours after anaesthesia. CK values after anaesthesia without succinylcholine remained at the initially elevated levels. Rectal temperatures of the children were normal. These findings suggest that succinylcholine should be avoided in patients with MEB disease.


Characterization of a subset of oligodendrocytes separated on the basis of selective adherence properties.
A subset of oligodendrocytes (B3,f) was isolated by taking advantage of selective cell-substratum interaction. B3,f cells were characterized morphologically, biochemically, and immunocytochemically. Oligodendrocytes were isolated from 4-to-6-month-old lamb brains by a modified version of our published procedure [Szuchet et al, J Neurosci Methods 3:7-19, 1980]. Freshly isolated cells from band III were plated on plastic culture plates at a concentration of 2 X 10(6) cells/ml. Approximately 40% of the cells attached to the plate under these conditions. The remaining cells formed small floating clusters. We refer to the latter as B3,f oligodendrocytes. After 4 to 5 days, the supernatant containing B3,f cells was removed and centrifuged, and the pellet was resuspended in culture medium and replated on polylysine-coated petri dishes. B3,f oligodendrocytes attached to this surface and extended an intricate network of processes. The purity of the cultures, judged by the number of cells staining with a monoclonal antibody against galactocerebroside was 98-99%. This high degree of cell homogeneity was maintained throughout the life of the cultures. B3,f cells appeared to be highly differentiated and remained so in vitro. This is surmised by the expression of oligodendrocytic characteristic functions such as high levels of CNPase activity typically, 5 microM/min/mgP; high incorporation of H2 35SO4 into sulfatides, an overall lipid metabolism that mimics events associated with myelinogenesis [Szuchet et al, PNAS 80:7019-7023, 1983]; the presence, detected immunocytochemically, of myelin-associated glycoprotein and myelin basic proteins. It is concluded that this culture system offers an opportunity for studying the biology of interfascicular oligodendrocytes and their interaction with neurons and/or astrocytes. It also should open up a way of examining the relevance of oligodendrocyte polymorphism.


Use of T-2 toxin-immobilized amine-activated beads as an efficient affinity purification matrix for the isolation of specific IgY.
An affinity purification method that isolates T-2 toxin-specific IgY utilizing a T-2-toxin-immobilized column was developed. The T-2 toxin was covalently coupled via a carbonyldiimidazole-activated hydroxyl functional group to amine-activated sepharose beads. The affinity-purified IgY was characterized by gel electrophoresis, fast protein liquid chromatography, enzyme-linked immunosorbant assay, surface plasmon resonance and mass spectrometry. A competitive inhibition ELISA (CI-ELISA) was performed using affinity-purified IgY with a T-2 toxin detection sensitivity of 30 ng/mL, which falls within the maximum permissible limit of 100 ng/mL. The cross reactivity of IgY towards deoxynivalenol, zearalenone, fumonisin B1 and HT-2 was significantly reduced after affinity purification. A surface plasmon resonance (SPR)-based inhibition assay was also applied for quantitative determination of T-2 toxin in spiked wheat samples. The results obtained indicate the feasibility of utilizing this IgY-based assay for the detection of T-2 toxin in food samples.


Development of sleep/wake, activity and temperature rhythms in newborns maintained in a neonatal intensive care unit and the impact of feeding schedules.
Biological rhythms in infants are described as evolving from an ultradian to a circadian pattern along the first months of life. Recently, the use of actigraphy and thermistors with memory has contributed to the understanding of temporal relations of different variables along development. The aim of this study was to describe and compare the development of the rhythmic pattern of wrist temperature, activity/rest cycle, sleep/wake and feeding behavior in term and preterm newborns maintained in a neonatal intensive care unit (NICU). Nineteen healthy preterm and seven fullterm newborns had the following variables monitored continuously while they were in the NICU: activity recorded by actigraphy, wrist temperature recorded with a thermistor and observed sleep and feeding behavior recorded by the NICU staff with diaries. Subjects were divided in 3 groups according to their gestational age at birth and rhythmic parameters were compared. A dominant daily rhythm was observed for wrist temperature since the first two weeks of life and no age relation was demonstrated. Otherwise, a daily pattern in activity/rest cycle was observed for most preterm newborns since 35 weeks of postconceptional age and was more robust in term babies. Feeding and sleep/wake data showed an almost exclusive 3h rhythm, probably related to a masking effect of feeding schedules. We found that wrist temperature develops a daily pattern as soon as previously reported for rectal temperature, and with acrophase profile similar to adults. Moreover, we were able to find a daily rhythm in activity/rest cycle earlier than previously reported in literature. We also suggest that sleep/wake rhythm and feeding behavior follow independent developmental courses, being more suitable to masking effects.


Atypical antipsychotics and effects of adrenergic and serotonergic receptor binding on insulin secretion in-vivo: an animal model.
Atypical antipsychotics (AAPs) are associated with several metabolic sequelae including increased risk of type 2 diabetes. Growing evidence points to a direct drug effect of these compounds on glucose homeostasis, independent of weight gain. While the responsible mechanisms have yet to be elucidated, the heterogeneous binding profiles of AAPs likely include receptors involved in glucose metabolism. This study aimed to clarify weight-gain independent mechanisms of AAP-induced alterations in insulin secretion. Deconstruction of the receptor binding profiles of these agents was done using representative antagonists. Healthy rats were pre-treated with a single subcutaneous dose of prazosin 0.25mg/kg (n = 16), a selective α1 antagonist; idazoxan 0.5mg/kg (n = 10), a selective α2 antagonist; SB242084 0.5mg/kg (n = 10), a selective 5HT2C antagonist; WAY100635 0.1mg/kg (n = 10), a selective 5HT1A antagonist; MDL100907 0.5mg/kg (n = 8), a selective 5HT2A antagonist; or vehicle: 0.9% NaCl saline (n = 8), DMSO (n = 8), or cyclodextrin (n = 5). Hyperglycemic clamps were employed following injection, providing an index of secretory capacity of pancreatic β-cells. Treatment with prazosin and MDL100907 resulted in significant decreases in both insulin and C-peptide secretion compared to their respective controls, DMSO and saline. These findings were corroborated with decreased glucose infusion rate and disposition index in the prazosin group. Results suggest that α1 and 5HT2A receptor antagonism may be involved in glucose dysregulation with AAP treatment, however, the exact mechanisms involved remain unknown.


Development and validation of an automated solid-phase extraction and liquid chromatographic method for determination of lumefantrine in capillary blood on sampling paper.
A bioanalytical method for the determination of lumefantrine in 100 microl blood applied onto sampling paper, by solid-phase extraction and liquid chromatography, has been developed and validated. Whatman 31 ET Chr sampling paper was pre-treated with 0.75 M tartaric acid before sampling capillary blood to enable a high recovery of lumefantrine. Lumefantrine was extracted from the sampling paper, then further purified using solid-phase extraction and finally quantified with HPLC. The between-day variation was below 10% over the range 0.4-25 microM. The lower limit of quantification was 0.25 microM in 100 microl capillary blood. No decrease in lumefantrine concentration in dried blood spot is seen after 4 months storage at 22 degrees C. The method was also evaluated in field samples from patients in Tanzania after treatment with lumefantrine/artemether. Lumefantrine could be estimated accurately enough to assess bioavailability and treatment compliance on day 7 (i.e. 4 days after the last dose) after a standard regimen with the lumefantrine/artemether combination.


Roles of tumour necrosis factor in the illness and pathology of malaria.
Evidence is accumulating that the illness and pathology observed in malaria are not caused directly by parasite products, but by normal components of the immune response, mainly monokines such as tumor necrosis factor (TNF), produced in excess. These mediators are released from the host's monocytes and macrophages, apparently in response to stimulation by parasite products. Recombinant TNF, if injected into a range of animal species or into tumour patients, is demonstrably toxic, giving rise to changes typical of acute malaria, and several groups have detected circulating TNF in serum from patients acutely ill with malaria. The short serum clearance time of TNF and TNF tolerance have to be considered when interpreting such data. Current studies indicate that some malarial antigens, in the absence of lipopolysaccharide, can trigger release of TNF. This and other monokines could contribute to cerebral malaria in at least 2 ways: by increasing thrombospondin secretion, and hence favouring local sequestration of knob-bearing parasitized red cells, and, as has been demonstrated in clinical trials in tumour patients, by causing neurological symptoms directly. In addition, it seems that TNF does not act alone, but as part of an interdependent synergizing network of polypeptide mediators. These evidently act together to induce secretion of other cell products, such as platelet-activating factor, prostaglandins, reactive oxygen species and procoagulant activity, that actually cause illness, biochemical change and tissue damage. Understanding these processes should lead to a range of new therapeutic interventions.


Chronic active Epstein-Barr virus infection presenting as refractory chronic sinusitis.
A 44-year-old Japanese man presented with fever and sore throat. He had a history of refractory chronic sinusitis that did not respond to several years of pharmacotherapy, and underwent endoscopic sinus surgery (ESS) 5 months prior to his presentation, but his symptoms persisted. A biopsy specimen was taken from the right nasal cavity, and extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) was diagnosed. Two years after complete remission was achieved by chemoradiation therapy, he developed hemophagocytic lymphohistiocytosis (HLH) without recurrence of ENKTL. Epstein-Barr virus (EBV)-DNA copy number was relatively high and EBV-infected lymphocytes (CD8 + T cells) were detected in the peripheral blood. Pathological review of the biopsy specimens taken during ESS showed that CD8 + T cells with slightly atypia infiltrating the stroma were EBV positive. These findings suggested that the patient had underlying chronic active EBV infection (CAEBV) that caused the refractory chronic sinusitis, eventually developed into ENKTL, and also caused HLH. Clinicians should consider adult-onset CAEBV in the differential diagnosis of patients with refractory chronic sinusitis.


Coumarin glycosides and iridoid glucosides with neuroprotective effects from Hydrangea paniculata.
Five new coumarin glycosides, umbelliferone 7-O-sophoroside (1), umbelliferone 7-O-β-D-glucopyranosyl(1 → 3)-β-D-glucopyranoside (2), umbelliferone 7-O-β-D-glucopyranosyl(1 → 3)-[β-D-apiofuranosyl(1 → 6)]-β-D-glucopyranoside (3), umbelliferone 7-O-β-D-glucopyranosyl(1 → 2)-β-D-apiofuranosyl(1 → 6)-β-D-glucopyranoside (4), and umbelliferone 7-O-β-D-glucopyranosyl(1 → 5)-β-D-apiofuranosyl(1 → 6)-β-D-glucopyranoside (5), and two new iridoid glucosides, 7-O-E-isoferuloyl loganic acid (6) and 7-O-β-D-glucopyranosyl loganin (7), together with eight known compounds (8-15) were isolated from the stems of Hydrangea paniculata. Their structures were established by spectroscopic analysis and chemical methods. At 10 µM, compounds 1, 3, 5, 6, 8, 9, and 13 showed neuroprotective effects against serum deprivation-induced PC12 cell damage.


Spatiotemporal reorganization of corticostriatal networks encodes motor skill learning.
Motor skill learning requires the activity of the dorsal striatum, with a differential global implication of the dorsomedial and dorsolateral territories. We investigate here whether and how specific striatal neurons encode the acquisition and consolidation of a motor skill. Using ex vivo two-photon calcium imaging after rotarod training, we report that highly active (HA) striatal populations arise from distinct spatiotemporal reorganization in the dorsomedial (DMS) and dorsolateral (DLS) striatum networks and are correlated with learning performance. The DMS overall activity decreases in early training, with few and sparsely distributed HA cells, while the DLS shows a progressive and long-lasting formation of HA cell clusters. These reorganizations result from reinforcement of synaptic connections to the DMS and anatomical rearrangements to the DLS. Targeted silencing of DMS or DLS HA cells with the cFos-TRAP strategy strongly impairs individual performance. Our data reveal that discrete domains of striatal populations encode acquisition and long-lasting retention of a motor skill.


The effect of haemorrhage on renal blood flow and intrarenal flow distribution.
Bleeding of dogs to constant arterial pressure of 90 mm/g and 60 mmHg respectively decreased renal blood flow in proportion to pressure reduction. There was no evidence of autoregulation of renal blood flow or of selective renal vasoconstriction. With the radioactive microsphere technique a moderate shift of blood flow from the outer to the inner cortex was observed. In the renal 133Xe wash-out curves exponent 1(attributed to the elimination of the indicator from the cortex) was more reduced than exponents 2 and 3 (medulla). These findings may not indicate a redistribution of renal blood flow through resistance changes in specific parts of the renal vasculature but may represent the consequences of focal cortical ischaemia, most prominent in the outer cortex.


Outcomes of methicillin-resistant Staphylococcus aureus infection after kidney and/or pancreas transplantation.
The true extent of Methicillin-Resistant Staphylococcus aureus (MRSA) colonization and incidence of infection after solid organ transplantation in adults and children is not well-known. The aim of this study was to evaluate the incidence and the outcomes of MRSA infection following kidney and/or pancreas transplantation. We reviewed the case notes of all patients who developed MRSA colonization and infection within the first year of transplantation between September 2002 and December 2009. The primary endpoint of this study was mortality. The secondary endpoints included morbidity, graft failure, and length of hospital stay. During the study period 1116 transplantations were performed. MRSA colonization was detected in 14 patients (1.25%) and infection occurred in 6 cases (0.53%) post-transplantation. Graft failure was not associated with MRSA colonization/infection in any of the cases. The mortality rate attributed to MRSA was 10% (n = 2). The overall median length of stay was 16 days (range, 6-243 days). Our study demonstrates that the prevalence of MRSA colonization and infection in our unit is low in spite of immunosuppression. The incidence of MRSA infection was higher among patients who underwent pancreas transplantation. Patients who had MRSA colonization and then developed infection had higher morbidity and mortality rates.


The effect of external salts on the aggregation of the multiheaded surfactants: All-atom molecular dynamics studies.
Tailoring the molecular design of the surfactants leads to changes in the aggregation properties. The role of external salts on the aggregation properties of the multiheaded surfactants is investigated using molecular dynamics simulations. The multiheaded surfactants show differential aggregation properties on addition of external salts, as reported earlier from experimental studies. We have modelled the multiheaded surfactants to study the effect of external salts (potassium bromide and sodium salicylate) at three different concentrations using the all-atom modelling and explicit solvation. The influence of external salts on the hydration and aggregation propensity, hydrogen bonding, and the structural characteristics of the surfactant aggregates are probed using various analyses across the four groups of multiheaded surfactants. The larger salicylate ion masks the repulsion between the cationic head groups and acts as an effective promoter of aggregation.


Effects of temperature on the energy budgets of Hydra pseudoligactis.
Dry matter, nitrogen, and energy budgets were determined for laboratory cultures of Hydra pseudoligactis reared at 10, 15, 20, and 25° C, and fed freshly collected zooplankton. Maximum specific feeding rates increased from 0.24 to 0.91 (KJ food/KJ Hydra) with increasing rearing temperature. The corresponding growth rates increased from 0.14 to 0.29 but gross (growth/ingestion), net (growth/(ingestion-egestion)), and assimilation (gross/net) efficiencies decreased with increasing temperatures. The requisite food densities to maintain maximum ingestion rates (when permitted to feed for 3 hrs day-1) increased from 0.0056 to 0.021 KJ of zooplankton/KJ of Hydra. The combination of increasing energy requirements, decreasing food supply, and efficiencies of food utilization, with increasing water temperatures may contribute to the rapid declines of Hydra populations that are often observed in temperate lakes.


Numerical analysis of the relationship between mixing regime, nutrient status, and climatic variables in Lake Biwa.
As awareness of climate-related freshwater quality problems increases, more research is needed to better understand how climate impacts water quality. Climate has significant impacts on the mixing regime and nutrient status of lakes. However, the relationship between climatic variables, mixing regime, and nutrient status in large monomictic lakes requires further study. Here we applied a three-dimensional ecosystem model to the large monomictic Lake Biwa, where hypoxia had recurred over the past 60 years. The model was validated using monitoring data, and the relationships among mixing regime, nutrient status, and climatic variables have been investigated. The turnover timing, which represented the mixing regime, varied by 36 days and depended most on wind speed but least on air temperature. In the early period prior to waste-water treatment there was a strong linear relationship between phosphorus and deep-water dissolved oxygen (DO) concentrations. Following this period, the relationship weakened but remained significant. In addition, we find a weak relationship between turnover timing and deep-water DO concentrations. We suggest that later turnover timing may favor lower deep-water DO concentrations, which in turn may favor release of legacy nutrients from sediments. Although waste-water treatment has improved conditions in the lake, climate change induced alteration of turnover timing may adversely influence water quality. Maintaining water quality under continued warming may require more rigorous controls on phosphorus loading to the lake.


Current and future recombinant viral vaccines for poultry.
The use of biotechnology to create recombinant viral vaccines holds many promises for the future. But, to be practical, new vaccines must have a selective advantage over traditional vaccines. A vaccine that is novel because it is a recombinant vaccine is not enough. Recombinant vaccines must be safer, or more efficacious, or less expensive to produce in order for them to gain a niche in the marketplace.


[Nanomedicine in otorhinolaryngology--future prospects].
Nanotechnology becomes more and more important in the world of today. Equally, it does generally in medicine and of course specifically in otorhinolaryngology. Essentially, there are the following fields: Diagnostics, new therapies and agents, drug delivery and medical implants. An extensive literature research on nanomedicine in otorhinolaryngology was carried out in the standard online medical reference databases "PubMed/Medline" and "Web of Science". Furthermore, we are giving an overview of the work of the Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), University Hospital Erlangen. A lot of new and innovative studies on nanotechnology in diagnostics and therapy were recovered. Depending on the variety in otorhinolaryngology, there are numerous versatile approaches, according to the different areas. The main part is engaged in drug delivery. The efforts to exploit the potential of nanotechnology in otorhinolaryngology are multifaceted, innovative and seminal. The best perspective of success is attributed to nanoparticulate drug delivery systems.


Specific effects of neuregulin-1β on the communication between DRG neurons and skeletal muscle cells in vitro.
The communication between primary afferent neuron and skeletal muscle (SKM) is one of the important factors on maintaining the structure and function of SKM cells. Neuregulin-1β (NRG-1β) signaling is essential for regulating synaptic neurotransmission. Here, we established a neuromuscular coculture model of dorsal root ganglion (DRG) sensory neurons and SKM cells to explore the nerve-muscle communication in the presence of exogenous NRG-1β. The expression of three distinct subtypes (TrkA, TrkB, and TrkC) of tyrosine kinase receptors was monitored for the phenotypical alterations of the neurons. The aggregation extent of acetylcholine receptor (AChR) represents the specific changes of SKM cells after NRG-1β incubation in this neuromuscular coculture model. The results showed that NRG-1β not only enhanced neurite outgrowth of DRG neurons but also increased the length and branches of SKM cells. NRG-1β treatment not only induced expression of all the three subtypes of Trk receptors in neurons but also promoted AChR aggregation on the surface of SKM cells. The effects of NRG-1β could be blocked by administration of ERK1/2 inhibitor PD98059, PI3K inhibitor LY294002, and JAK2 inhibitor AG490, respectively. These data imply that NRG-1β is essential for the nerve-muscle communication by enhancing growth and modifying phenotypes of the two different kinds of cells. The specific effects produced by NRG-1β add novel interpretation for nerve-muscle communication between sensory neurons and SKM cells.


Gastrointestinal motility disorders during pregnancy.
To review the pathophysiology of gastrointestinal motility disorders during pregnancy, their clinical manifestations, and their management. Studies published from 1963 to 1992 identified by computerized literature searches of Index Medicus and MEDLINE; hand searches; contact with pharmaceutical representatives for information on drug therapy during pregnancy; and selected texts on drugs and obstetrics. Selected studies were those involving controlled design of physiology related to pregnancy or to hormonal effects on the gastrointestinal tract or both, and clinical studies or previous reviews that contributed to the understanding of the gastrointestinal effects of pregnancy. Data concerning the epidemiology, causes, clinical manifestations, and complications of altered gastrointestinal motility during pregnancy as well as the strength of association between gastrointestinal disorders of pregnancy and hormonal changes were evaluated and used to develop a practical approach to evaluate and manage these patients. Effects on the gastrointestinal tract during pregnancy are caused primarily by hormonal changes and not the physical effects of the gravid uterus. Motility changes occur throughout the gastrointestinal tract, including a reduction in lower esophageal sphincter pressure and its physiologic function with resulting gastroesophageal reflux and the risk for aspiration; alterations in gastric motor function associated with nausea and vomiting; and a decrease in the rate of small-bowel and colonic transit manifested primarily as abdominal bloating and constipation. These effects are mediated by progesterone, with estrogen probably acting as a primer. Given the large number of pregnancies each year complicated by gastrointestinal motility disorders, many physicians (including internists and gastroenterologists) must manage these problems. Knowledge of the underlying physiologic alterations in gastrointestinal motility during pregnancy and of safe treatment options is essential to the care of the pregnant patient.


Concurrent fast and slow synchronized efferent phrenic activities in time and frequency domain.
In urethane-anesthetized or decerebrated vagotomized rabbits efferent multifiber activity of the phrenic nerve was investigated for synchronized activities both in time and frequency domains. When respiratory drive was steadily increased by either an elevation of end-tidal CO2 concentration or i.v. administration of 4-aminopyridine, medium-frequency oscillations (MFO) first increased, then decreased and finally became absent. The power of high-frequency oscillations (HFO) steadily rose with increasing respiratory drive. In contrast to HFO which revealed a unimodal spectral peak of mostly small bandwidth, the MFO spectrum in most cases consisted of a broad complex. This complex in some cases was composed of two distinct peaks, i.e. MFO were heterogenous. The low- and high-frequency fractions of the MFO complex were related predominantly to the first and last third of inspiration, respectively. Examination of the on-going multifiber activity of the phrenic nerve with an expanded time scale revealed that lower frequency MFO probably result from synchronized ramp-like wave activity during early and mid-inspiration. The duration of the observed ramps well matched the corresponding MFO frequency. We suggest that these ramps might result from propagated synchronized waves of high-threshold phrenic motoneurons. During the last part of inspiration, however, MFO, like HFO, resulted from burst-like synchronized discharge of phenic motoneurons. Thus HFO are superimposed on ramp-like and burst-like activity of the MFO. It is assumed that the decline of MFO at high respiratory drive may be due to the increasing strength of HFO bursts which interrupt ramp activity in the MFO range and thus let MFO appear 'invisible' to the recording electrode. Both MFO and HFO were visually detectable in postinspiration.


Peripheral and central conduction times in hereditary pressure-sensitive neuropathy.
Seven members of a family with histologically proven hereditary pressure-sensitive neuropathy (HPSN) agreed to be examine clinically and electrophysiologically. A sural nerve biopsy specimen taken from the propositus who suffered from a partial brachial plexus palsy showed typical 'sausage-like' myelin sheath thickenings reflecting a failure of axon-adjusted myelination. Reduced motor and sensory conduction velocities involving several nerves were found in the four family members with clinical signs of HPSN. In addition, central conduction times in the auditory and somatosensory pathways were determined measuring the interwave latency I-V in brainstem auditory-evoked potentials and the interpeak latency N14-N20 in median nerve sensory-evoked potentials. Central conduction times in both afferent systems were within normal limits. The absolute delay of peak N14 and N20 in median and P40 in tibial nerve-evoked potentials was probably due to an impaired conduction in the peripheral branch of the bipolar ganglion cell. Whether the central axon branch in the dorsal columns was also involved could not be decided.


Retention and selectivity of flavanones on homopolypeptide-bonded stationary phases in both normal- and reversed-phase liquid chromatography.
Three linear polymers of repeating amino acid units, or homopolypeptides, have been individually covalently bonded to microparticulate silica and evaluated for liquid chromatographic separations. The retention and selectivity of seven flavanones were investigated on these stationary phases and a structurally similar, commercially available reference stationary phase, Chiraspher. All three of the homopolypeptide stationary phases retain solutes in the normal-phase mode. The aromatic-containing homopolypeptide stationary phases also retain solutes in the reversed-phase mode. Selectivity values for the flavanones were higher in the normal-phase mode; chiral selectivity was observed for the amphiphilic homopolypeptide stationary phase in the reversed-phase mode. The retention mechanism of each stationary phase is suggested based on the chemical nature and conformation of the corresponding homopolypeptide ligand.


Prolonged potentiation of transmission through a withdrawal reflex pathway after noxious stimulation of the heel in the rabbit.
The sural-gastrocnemius reflex of the spinalized rabbit was potentiated to an average of 3-6 times control levels after the application of noxious mechanical, thermal or chemical stimuli to the skin of the heel. Facilitation of the reflex was maximal within 1 min of the noxious stimulus, and in many cases persisted for more than 1 h. Prolonged increases in the excitability of the sural-gastrocnemius reflex were not seen after innocuous mechanical or thermal stimulation of the heel. Repetitive electrical stimulation of the sural nerve (100 shocks given at 0.5 Hz) caused persistent facilitation of the reflex when small myelinated A delta fibres or non-myelinated C-fibres were recruited by the conditioning stimulus. Such protracted increases in the excitability of the sural-gastrocnemius pathway would enhance the protective functions of this reflex. The mechanisms described here have probably evolved to provide a high level of reflex protection to the heel after tissue damage has occurred at that site.


A Real-world Evidence-based Management of HIV by Differential Duration HAART Treatment and its Association with Incidence of Oral Lesions.
The efficacy of highly active antiretroviral therapy (HAART) can be estimated by the immunological response and the incidence of opportunistic infections. This study aimed at evaluating the effectiveness of different durations of HAART in terms of immunological response markers (CD4 count and CD4/CD8 ratio) along with disease progression markers (incidence of oral lesions) in Chinese patients with HIV. This single-center, retrospective, and real-world study included patients with HIV, grouped into a treatment group and treatment-naïve group, of which the former was further divided into 6, 12, and 18 months based on the treatment duration. The CD4 and CD8 cell counts were analyzed by the FACSCalibur flow cytometry. Kruskal-Wallis test was applied to determine the outcome of different duration of HAART. Oral examination was carried out according to the WHO type IV examination. In 246 patients with HIV, CD4 counts increased significantly post-HAART compared to pre-HAART in all three treatment groups (P<.001), while CD8 count decreased significantly (P<.05) in all three treated groups. A significant association of HAART with the CD4/CD8 ratio was observed (P<.001). A significant increase in CD4 count was observed between 12-months and 18-months treatment groups (P<.05). The occurrence of oral lesions reduced significantly in the treatment group. We observed a better response to the HAART regimen with 18-months of duration than 12-months and 6-months therapies and reduction in oral lesions.


Colloid-SEM method for the investigation of magnetic domain structures.
The paper presents scanning electron microscopy (SEM) studies on the magnetic domain structure (DS) using magnetic colloid. The possibility of colloid-SEM method for observing the DS of mono- and polycrystalline samples in the secondary (SEI) and backscattered electrons modes (BEC) is demonstrated. Owing to the large focal depth of SEM, it is possible to observe the overall DS and fine features, even in unpollished samples.


[Epidemiology and diagnosis of cervical cancer].
The authors study 567 medical histories of women with cancer of the uterine cervix. They describe the data in relation to epidemiology and cytology, colposcopy, and the procedure for an early diagnosis.


Food insecurity is associated with maternal depression and child pervasive developmental symptoms in low-income Latino households.
The objective of this study was to investigate associations between household food insecurity, maternal clinical depression, and child behavior problems in low-income Latino households. Data were collected from a cohort of 168 children and their Latina mothers recruited prenatally at two San Francisco hospitals from 2006 to 2007. Food insecurity at year four was associated with increased odds of maternal clinical depression at years four to five (adjusted OR 1.22, 95% confidence interval 1.03 to 1.43). Food insecurity at year four was associated with child pervasive developmental problems at year five (B=0.21, p=0.041) in adjusted models. The association between food insecurity at year four and oppositional defiant problems at year five was partially mediated (28.7% mediation, p=0.046) by maternal clinical depression in years four and five. Our results suggest that household food insecurity is associated with greater maternal depression, and both food insecurity and maternal depression uniquely predict certain types of child behavior problems. Assessing for and addressing household food insecurity may be beneficial additions to psychosocial interventions targeting maternal and child mental health.


Accelerated radiation damping for increased spin equilibrium (ARISE): a new method for controlling the recovery of longitudinal magnetization.
Control of the longitudinal magnetization in fast gradient-echo (GRE) sequences is an important factor in enabling the high efficiency of balanced steady-state free precession (bSSFP) sequences. We introduce a new method for accelerating the return of the longitudinal magnetization to the +z-axis that is independent of externally applied RF pulses and shows improved off-resonance performance. The accelerated radiation damping for increased spin equilibrium (ARISE) method uses an external feedback circuit to strengthen the radiation damping (RD) field. The enhanced RD field rotates the magnetization back to the +z-axis at a rate faster than T(1) relaxation. The method is characterized in GRE phantom imaging at 3T as a function of feedback gain, phase, and duration, and compared with results from numerical simulations of the Bloch equations incorporating RD. A short period of feedback (10 ms) during a refocused interval of a crushed GRE sequence allowed greater than 99% recovery of the longitudinal magnetization when very little T(2) relaxation had time to occur. An appropriate application might be to improve navigated sequences. Unlike conventional flip-back schemes, the ARISE "flip-back" is generated by the spins themselves, thereby offering a potentially useful building block for enhancing GRE sequences.


Immune response as a possible mechanism of long-lasting disease control in spontaneous remission of MLL/AF9-positive acute myeloid leukemia.
Spontaneous complete remission (CR) is a rare, poorly understood phenomenon in acute myeloid leukemia (AML). We describe the 10-year follow-up of a patient with MLL-AF9-positive AML (Müller et al. Eur J Haematol 73:62-66, 2004), including ex vivo antileukemic immune responses which may contribute to the long-lasting spontaneous CR (tantamount to cure). We could demonstrate strong in vitro cytotoxic activity mediated by the patient's serum (cryopreserved at diagnosis 2001) against myeloid cell lines. We also addressed cellular cytotoxic activity against myeloid leukemia cells. When the patient's natural killer (NK) cells (obtained in 2007) were tested against the K562 cell line, upregulation of CD107 occurred, implying that long-term CR in this patient could be due to NK cell-mediated disease control.


Cyproheptadine exhibits antitumor activity in urothelial carcinoma cells by targeting GSK3β to suppress mTOR and β-catenin signaling pathways.
Cyproheptadine, a serotonin antagonist, has recently been reported to function as a novel therapeutic agent by inhibiting PI3K/AKT signaling in several human cancers. However, the therapeutic effect of cyproheptadine in urothelial carcinoma (UC) has never been explored. In this study, we determined the effect of cyproheptadine on the growth of five human UC cell lines and an in vivo xenograft model. The results showed that cyproheptadine exerted an inhibitory effect on the proliferation of UC cells both in vitro and in vivo. Cyproheptadine also induced cell cycle arrest in the G1 phase, subsequently followed by apoptosis and necrosis. The underlying mechanisms of cell cycle arrest were associated with the reduction of c-Myc, induction of p21 and p27, and the stabilization of Rb expression. In addition, the suppression of the GSK3β/TSC2/mTOR pathway and deregulation of the GSK3β/β-catenin signaling were observed in cyproheptadine-treated UC cells. Furthermore, cyproheptadine-induced apoptosis was associated with ANGPTL4 expression followed by activation of caspase3 and PARP in UC cells. Our experimental results provide evidence that cyproheptadine is a suitable therapeutic agent for the treatment of UC.


Calf deep vein thrombosis: frequency, therapeutic management, early outcomes and all-causes mortality in a cohort of hospitalized patients.
Isolated distal deep vein thromboses (IDDVT) are frequent; however, their optimal management is still controversial. We performed a retrospective study on inpatients undergoing ultrasound for suspected deep vein thrombosis (DVT) or with a particular risk profile, during 2016. This study aimed to assess the frequency of proximal deep vein thromboses (PDVT) and IDDVT; to evaluate therapeutic management and identify variables associated with early outcomes and mortality among IDDVT patients; to compare all-causes mortality between subjects with PDVT and IDDVT. Among 21594 patients hospitalized in the study period 251 IDDVT and 149 PDVT were diagnosed; the frequency was 1.2% and 0.7% respectively. 19% of IDDVT patients died compared to 25.5% of PDVT subjects (OR=0.72; 95% CI=0.44-1.17; P=0.19). In IDDVT patients, age ≥80, cancer and intracranial bleeding increased the risk of death (OR=2; 95% CI=1.07-3.75, P=0.001; OR=8.47; 95% CI=3.28-21.88, P=0.0000003; OR=2.33; 95% CI=1.18-4.58, P=0.0003). A significant association between intracranial hemorrhage and both proximal extension by using the Fisher's exact test (P=0.031; OR=16.11; 95% CI=0.80-321.2), and composite of propagation to popliteal or to other calf veins (OR=8.28, 95% CI=2.07-33 P=0.001) was observed. Standard anticoagulation significantly reduced the composite of propagation to popliteal or to other calf veins (OR=0.07; 95% CI=0.009-0.61, P=0.007), and all-causes mortality (OR=0.37; 95% CI=0.17-0.8; P=0.02), without a significant increase of bleeding. Among inpatients, IDDVT exceeded 60% of DVT. Mortality was not significantly different between IDDVT and PDVT subjects. Intracranial bleeding significantly increased the risk of propagation and death. Although standard anticoagulation decreased both these complications, further targeted studies are needed.


Rethinking the gold standard - The feasibility of randomized controlled trials within health services effectiveness research.
An evidence-based randomized controlled trial for a novel Pharmacy Asthma Service was tested in 3 Australian states. Positive asthma outcomes were achieved after the 12-month intervention, albeit in both the intervention and comparator arms. The current investigation uses a mixed methods approach to 1) qualitatively explore how comparator arm pharmacists implemented the trial protocol and 2) quantitatively examine how this may have impacted patient outcomes in this trial. Post-intervention semi-structured qualitative interviews were conducted with 20 pharmacists, representing 21 of 37 (57%) comparator arm pharmacies that completed the trial. Based on these interviews, pharmacies were classified as 'adherent' to the trial protocol (reporting no interventions other than general practitioner referral) or 'non-adherent' (reporting at least one extra intervention to the trial protocol), or 'inconclusive'. These subgroups were compared descriptively in relation to patient outcomes. Overall, 33% (n = 8/24) of the comparator pharmacies who were interviewed (n = 21) or determined to have monitoring by a project officer to ensure adherence to the protocol (n = 3) were classified as adherent), 58% (n = 14/24) as non-adherent, 8% inconclusive (n = 2/24). While all patients commenced with uncontrolled asthma (Asthma Control Questionnaire score (ACQ) > 1.5), after 12 months the mean ACQ score for patients from adherent comparator pharmacies ('true control') was 1.8 (still uncontrolled asthma) compared to a score of 1.4 (controlled asthma) in the non-adherent comparator group. Quality of life significantly improved in the non-adherent comparator group over the 12 months of the trial. The majority of pharmacists in the comparator arm who were interviewed, introduced their own interventions, which may have influenced the outcomes of the trial. The naturalistic setting of the study was not protective against these confounders. These findings question the feasibility of comparator arms within primary care settings and that alternative study designs should be considered when designing future intervention studies in pharmacy practice.


Clinical spectrum and diagnostic techniques of coronary heart disease in the elderly.
Coronary heart disease is a major cause of morbidity and mortality in the older population. The recognition of such disease in the elderly varies in a number of parameters from that noted in younger patients. There are a number of physiologic changes in cardiac function as a result of aging, and they have an important bearing on the recognition of cardiac disease in the elderly. This review stresses the particular features of coronary disease in the aged and contrasts them with features more readily recognized in younger patients. Changes in the development of angina pectoris, heart failure, and the diagnosis of myocardial infarction vary significantly in the elderly population. The role of diagnostic modalities varies considerably in sensitivity and specificity when comparing younger and older patients. Potential areas for further research are stressed.


Molecular epidemiology of African swine fever in East Africa.
African swine fever (ASF) a lethal, viral hemorrhagic disease of domestic pigs, first reported from East Africa in 1921, is still widespread in this region. In order to assess field heterogeneity at the regional level, nucleotide sequences corresponding to the C-terminal end of the p72 gene were determined for 77 ASF viruses of diverse temporal and species origin occurring in eight East African countries. The number of sites completely conserved across all East African sequences characterized in this study was 84.2% and 86.8% on nucleotide and amino acid level, respectively. Phylogenetic analysis of a homologous 404 bp region revealed the presence of thirteen East African genotypes, of which eight appear to be country specific. An East African, pig-associated, homogeneous virus lineage linked to outbreaks in Mozambique, Zambia and Malawi over a 23 year period was demonstrated. In addition, genotype I (ESACWA) viruses were identified in East African sylvatic hosts for the first time which is significant as this genotype was previously thought to be restricted to the West African region where it occurs only in domestic pigs. The presence of discrete epidemiological cycles in East Africa and recovery of multiple genotypes affirms the epidemiological complexity of ASF in this region.


Hormone sensitivity predicts the beneficial effects of transdermal estradiol on reward-seeking behaviors in perimenopausal women: A randomized controlled trial.
Depression is highly prevalent during the menopause transition (perimenopause), and often presents with anxious and anhedonic features. This increased vulnerability for mood symptoms is likely driven in part by the dramatic hormonal changes that are characteristic of the menopause transition, as prior research has linked fluctuations in estradiol (E2) to emergence of depressed mood in at risk perimenopausal women. Transdermal estradiol (TE2) has been shown to reduce the severity of depression in clinically symptomatic women, particularly in those with recent stressful life events. This research extends prior work by examining the relation between E2 and reward seeking behaviors, a precise behavioral indicator of depression. Specifically, the current study utilizes a randomized, double blind, placebo-controlled design to investigate whether mood sensitivity to E2 flux ("hormone sensitivity") predicts the beneficial effects of TE2 interventions on reward seeking behaviors in perimenopausal women, and whether recent stressful life events moderate any observed associations. Participants were 66 women who met standardized criteria for being early or late perimenopausal based on bleeding patterns. Participants were recruited from a community sample; therefore, mood symptoms varied across the continuum and the majority of participants did not meet diagnostic criteria for a depressive or anxiety disorder at the time of enrollment. Hormone sensitivity was quantified over an 8-week baseline period, using within-subjects correlations between repeated weekly measures of E2 serum concentrations and weekly anxiety (State Trait Anxiety Inventory) and anhedonia ratings (Snaith-Hamilton Pleasure Scale). Women were then randomized to receive 8 weeks of TE2 (0.1 mg) or transdermal placebo, and reward-seeking behaviors were assessed using the Effort-Expenditure for Rewards Task (EEfRT). Participants who were randomized to receive transdermal estradiol and who demonstrated greater anxiety sensitivity to E2 fluctuations at baseline, demonstrated more reward seeking behaviors on the EEfRT task. Notably, the strength of the association between E2-anxiety sensitivity and post-randomization EEfRT for TE2 participants increased when women experienced more recent stressful life events and rated those events as more stressful. E2-anhedonia sensitivity was not associated with reward-seeking behaviors. Perimenopausal women who are more sensitive to E2 fluctuations and experienced more recent life stress may experience a greater benefit of TE2 as evidenced by an increase in reward seeking behaviors.


Age-related Macular Degeneration: Nutrition, Genes and Deep Learning-The LXXVI Edward Jackson Memorial Lecture.
To evaluate the importance of nutritional supplements, dietary pattern, and genetic associations in age-related macular degeneration (AMD); and to discuss the technique of artificial intelligence/deep learning to potentially enhance research in detecting and classifying AMD. Retrospective literature review. To review the studies of both prospective and retrospective (post hoc) analyses of nutrition, genetic variants, and deep learning in AMD in both the Age-Related Eye Disease Study (AREDS) and AREDS2. In addition to demonstrating the beneficial effects of the AREDS and AREDS2 supplements of antioxidant vitamins and zinc (plus copper) for reducing the risk of progression to late AMD, these 2 studies also confirmed the importance of high adherence to Mediterranean diet in reducing progression of AMD in persons with varying severity of disease. In persons with the protective genetic alleles of complement factor H (CFH), the Mediterranean diet had further beneficial effect. However, despite the genetic association with AMD progression, prediction models found genetic information added little to the high predictive value of baseline severity of AMD for disease progression. The technique of deep learning, an arm of artificial intelligence, using color fundus photographs from AREDS/AREDS2 was superior in some cases and noninferior in others to clinical human grading (retinal specialists) and to the gold standard of the certified reading center graders. Counseling individuals affected with AMD regarding the use of the AREDS2 supplements and the beneficial association of the Mediterranean diet is an important public health message. Although genetic testing is important in research, it is not recommended for prediction of disease or to guide therapies and/or dietary interventions in AMD. Techniques in deep learning hold great promise, but further prospective research is required to validate the use of this technique to provide improvement in accuracy and sensitivity/specificity in clinical research and medical management of patients with AMD.


A retrospective analysis of the women hospitalized and treated due to anemia caused by gynecological pathologies: the role of intravenous iron (ferric carboxymaltose) and blood transfusion in clinical practice.
Gynecological pathologies are an important cause of anemia in women. In this study, we aimed to evaluate women who had been hospitalized because of anemia (Hb level <10 g/dL) caused by gynecologic pathologies and treated with either intravenous iron (ferric carboxymaltose) or blood transfusion. This retrospective cross-sectional study was performed in a tertiary care center. Women who were hospitalized with the diagnosis of anemia with Hb level<10 g/dL and abnormal uterine bleeding between March 2015- September 2017 in the gynecology clinic were enrolled in the study. Hemoglobin levels, hemoglobin changes, uterine pathology and treatment of patients were recorded and compared. One hundred and fifteen women received red blood cell transfusion and 100 women were treated with intravenous ferric carboxymaltose. The mean age of the women was 45.1±6.1 (22-57) years. Although the mean Hb levels were higher in the iv-iron replacement group at the end of the one month (P=0.001), the mean increase in Hb levels was similar between two treatment modalities (P=0.101). Among the anemic women who required surgery, iv iron replacement was the first choice in 75.9% of women; 34.1% received red blood cell transfusion in the preoperative period. Gynecological pathologies are a common cause of anemia in reproductive age women and intravenous carboxymaltose treatment is a safe and cheaper alternative of blood-transfusion in appropriate cases to elevate the Hb levels in the preoperative period.


Psychosomatic illness as a result of a deficit in ego-structure under consideration of the genetic. Dynamic, structural, and group dynamic point of view.
Psychosomatic illness is an illness of ego-structure as a result of a narcissistic deficit reassembling the phenomenology of anaclitic depression in regard to the mother and the primary group. Psychosomatic illness has to be understood on a scale of ego-illnesses related to identity defects. The psychosomatic symptom restitutes the integration of the personality and constitutes the identity of a psychosomatic patient. The role of group dynamics is particularly stressed in relation to psychogenetics, psychodynamics, and the change of symptoms.


Effect of cigarette smoking on quality of life in small cell lung cancer patients.
Continued cigarette smoking after small cell lung cancer (SCLC) diagnosis has been shown to shorten patients' survival, but little is known about the impact of smoking and cessation on quality of life (QOL) profile (e.g., overall QOL, pain, fatigue, cough, dyspnea, appetite change, and performance status) in SCLC survivors (who survived at least 6 months post initial diagnosis). In this study, we sought to evaluate the relationship between cigarette smoking and QOL profiles in SCLC patients. A total of 223 survivors were classified into five groups: never smokers, former smokers (quit more than 1 year prior to diagnosis), recent quitters (quit within 1 year surrounding diagnosis), late quitters (quit after 1 year post diagnosis) and never quitters. One hundred and sixty-eight of these survivors were matched with 334 lung-cancer-free controls on age, gender, and smoking status for comparative analysis. QOL scales were scored from 0 (worse) to 100 (best). Conditional logistic regression, linear mixed-effect models, and Wilcoxon signed rank tests were used. SCLC survivors consistently showed a significant deficit in QOL profile; e.g., mean overall QOL in patients was 17.5 points worse than the controls (p<0.0001). Among all smokers, former smokers reported the best QOL profile, while late or never quitters reported the worst. The recent quitters showed an improving trend in QOL profile and lower percent of reduced appetite (an average of 43%) compared to the late or never quitters (58%). Our study confirmed the negative impact of smoking on SCLC survivors' QOL and found that smoking cessation surrounding the time of diagnosis could improve overall QOL and symptoms. The findings of this study provide evidence for oncologists to recommend smoking cessation to their SCLC patients.


Cloud point extraction of uranium using H₂DEH[MDP] in acidic conditions.
A procedure has been developed for the cloud point extraction (CPE) of uranium (VI) using H2DEH[MDP] (P,P-di(2-ethylhexyl) methanediphosphonic acid) with inductively coupled plasma coupled to mass spectrometry (ICP-MS). The method is based on the modification of the cloud point temperature using cetyl trimethyl ammonium bromide (CTAB) and KI. Optimal conditions of extraction were found using a cross-optimization of every parameter (non-ionic and ionic surfactant concentrations, chelating agent concentration, pH and the extraction, and phase separation temperatures). Furthermore, the figures of merit of the methodology were assessed (limit of detection, limit of quantification, recovery, sensibility, and linear range) and are reported. Quantitative extraction (99 ± 0.5%) was obtained in drinking water samples over a wide range of uranium concentrations. The approach was also validated using drinking (SCP EP-L-3 and SCP EP-H-3), and wastewater (SCP EU-L-3) certified materials. Interferences from most critical anions and cations were evaluated to determine the reliability of the method. The proposed method showed robustness since its performance is maintained over a wide range of pH and metal ion concentrations.


[The neuropathies of monoclonal gammapathies. Immunofluorescence and immunolabelling in the electron microscopy of immunoglobulins with amyloid structure (author's transl)].
Five cases of peripheral neuropathies occurring with monoclonal gammapathies are studied by means of nerve biopsies. Immunofluorescence and HRP-immunolabelling with the electron microscope are performed. The direct pathogenic role of a subperineurial immunoglobulin deposit is pointed out. The relationship of the heavy chain monoclonal immunoglobulin with amyloid fibrils is discussed.


Variant histology of pediatric nodular lymphocyte-predominant Hodgkin lymphoma with IgD and CD30 expression.
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), recently known as nodular lymphocyte-predominant B-cell lymphoma (NLPBL), accounts for 5%-10% of Hodgkin lymphoma (HL). Different morphologic patterns of NLPBL are identified and categorized as typical patterns (type A and B) and variant histologic patterns (types C, D, E, and F). We investigated different morphologic patterns, CD30 and IgD expression in pediatric patients with NLPBL diagnosed at the Children's Cancer Hospital Egypt. Forty-six (53%) of the patients exhibited a typical histologic pattern, whereas the remaining (47%) exhibited variant histologic pattern. Variant histology is associated with unfavorable clinical characteristics, such as advanced stages, B-symptoms, and extranodal involvements, particularly bone marrow and bone infiltration, with p-values of .06, .05, and 0.01%, respectively. Additionally, 39% of patients with variant histology experienced disease progression or relapse, compared to only 15.2% of patients with typical patterns (p = .009). Types C and D are related to decreased event-free survival (EFS), as shown by a p-value of .05. The 5-year EFS for patients with variant histology was 94.4% for the rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone (RCHOP) versus 33.3% for the adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). IgD expression in lymphocyte-predominant (LP) cells was detected in 44 (50%) patients, while CD30 expression in LP cells was found in 39 (44%) patients. Variant histology of NLPBL was associated with advanced disease stages and a poor prognosis, while expression of IgD and CD30 in LP cells was not. The poor outcome of variant histology improved with the RCHOP regimen.


Ubiquitin-proteasome: pallbearer carries the deceased to the grave.
Phagocytosis is a complex process that involves multiple cellular functions. In this issue of Immunity, Silva et al. (2007) report that a protein ubiquitylation complex and the proteasome are required for the clearance of apoptotic cells in Drosophila.