Modeling healthcare expenditures: overview of the literature and evidence from a panel time-series model.
The rapid growth of healthcare expenditures in the past 40 years in many industrial countries has contributed to an improvement in life expectancy and the quality of life, but has also jeopardized the sustainability of public budgets. For the future, it is important to get more insight into the determinants of this growth. Factors, such as aging, income growth and technological development have been discussed extensively. In this review, we want to pay attention to a somewhat neglected factor: the increase in the relative price of healthcare. Owing to the Baumol effect, healthcare tends to become more expensive over time. How does the demand for healthcare react to this price increase?


Oral antihypertensive trial design and analysis under the pediatric exclusivity provision.
The Best Pharmaceuticals for Children Act provides a 6-year extension to the economic incentives offered to drug manufacturers under the Pediatric Exclusivity Provision, for providing requested information on drugs used in children, which includes >50 oral antihypertensive medications. Guidelines were published outlining specific requirements for the design and analysis of trials to provide the requested information. We review the design and analysis requirements, along with recruitment and eligibility guidelines, for dose-ranging studies of oral antihypertensives in children in light of ethical and methodologic issues unique to pediatric research. We also discuss examples of trials conducted to date and the implications and limitations of legislative efforts. Four possible trial types are outlined in the guidelines. Trial C, which uses a randomized withdrawal phase after treatment, has been used most often. Avoidance of a true placebo arm may enhance patient recruitment and minimize ethical concerns at the expense of a more complicated design and analysis. In addition, this trial involves little risk for manufacturers because patent extension does not depend on the outcome of the trial. Studies being conducted under the Pediatric Exclusivity Provision will provide valuable information concerning dosing and efficacy for several antihypertensive medications used in children. New legislation may stimulate study of drugs without remaining patent life, but data on safety, long-term outcomes, and the youngest pediatric age groups are also needed for a full understanding of all issues pertinent to pediatric use.


Oedipus again: a critical study of Charles Laughton's The Night of the Hunter.
In this paper the Oedipus complex is reexamined through a film, The Night of the Hunter. Study reveals a concealed fairy tale structure, a structure that, when presented against a mythic backdrop, is ideal for presenting a certain kind of oedipal situation, that of a vulnerable damaged father and couple (indeed, couples), revealing a skewed oedipal situation. The film, produced in 1954 and looked at forty years later in the context of psychoanalytic writings of the last decade (Bergmann, Feldman, Herman, Simon), provides a matrix with which to reexamine a fundamental psychoanalytic concept, the Oedipus complex. It is the mutual enrichment of art and psychoanalysis that this paper addresses.


Geographical distribution of acute lymphoblastic leukaemia subtypes: second report of the collaborative group study.
Childhood acute lymphoblastic leukemia (ALL) T and B precursor subtypes have been identified by standardised immunophenotyping in different geographic and ethnic settings. Comparison of the relative frequencies and estimated incidence rates of the major subtypes indicates very similar values, with the striking exception of black childhood populations in Africa in which there appears to be a significant and selective deficit in the incidence of the common (B-cell precursor) subset of ALL. There is suggestive evidence for a similar bias in ALL subtypes in South Africans of mixed ethnic origin and in Mapuche Indians from Chile. Several interpretations of these data are possible but the one favoured attributes these differences primarily to socio-economic factors and patterns of infection in infancy.


Light-induced electron spin polarization in vanadyl octaethylporphyrin: I. Characterization of the excited quartet state.
Laser flash induced spin-polarized transient electron paramagnetic resonance (TREPR) spectra for vanadyl octaethylporphyrin in isotropic and partially ordered frozen solutions are presented and compared with corresponding luminescence data. The TREPR spectra show well-resolved hyperfine couplings to the vanadium nucleus and a multiplet polarization pattern with features typical of zero-field splitting (ZFS). The principal values of the vanadium hyperfine coupling tensor evaluated from the spectra are 1/3 of the corresponding values found from steady-state EPR spectra of the ground state. On the basis of these characteristics and numerical simulations, the polarization patterns are assigned to the excited quartet state. The values of the ZFS parameters of the trip-quartet obtained from simulation of the spectra (D = 17.5 mT and E = 1.5 mT) are comparable to those of the triplet state of the zinc and free base octaethyl porphyrin. The lifetime of the spin polarization is found to be temperature dependent and is essentially the same as that of the optical emission. The temperature dependence is rationalized using a model in which the decay to the ground state occurs from both the trip-quartet and trip-doublet, which are in thermal equilibrium even at 15 K. A fit of the model to the observed spin polarization lifetimes yields an energy gap of 47 cm(-1) between the trip-quartet and trip-doublet. It is shown that the spin polarization evolves from a multiplet pattern at early times to a net absorptive pattern at late times following the laser flash. It is proposed that the establishment of thermal equilibrium leads to the evolution of the spin from multiplet to net polarization.


Immune cell subtyping in the cerebrospinal fluid of patients with neurological diseases.
The analysis of cerebrospinal fluid (CSF) with the assessment of CSF cell counts and proteins is an important method in the diagnostic workup of neurological diseases. As an addition to this standard approach, we here present data on the distribution of CSF immune cell subsets in common neurological diseases, and provide reference values along with cases of rare neurological diseases. CD4+ and CD8+ T cells, the CD4/CD8 ratio, B cells, plasmablasts, monocytes and NK cells in the CSF of 319 patients with inflammatory or non-inflammatory neurological diseases were analysed by seven-color flow cytometry. Diagnoses included headache, idiopathic intracranial hypertension, Guillain-Barré syndrome, multiple sclerosis, Lyme neuroborreliosis, bacterial and viral meningitis, human immunodeficiency virus (HIV) infection, stroke, and CNS malignancies, among others. T cells were the predominant population in the CSF with CD4+ T cells being more prevalent than CD8+ T cells. Mostly in HIV patients, and under other conditions of immunosuppression, CD4+ and CD8+ T cells were significantly altered and the CD4/CD8 ratio reduced. B cells and plasmablasts could hardly be detected in non-inflammatory diseases but were consistently elevated in inflammatory diseases. Monocytes were reduced in neuroinflammation and showed a negative correlation with B cells. NK cells were slightly elevated in neuroinflammation. Both monocytes and NK cells were slightly elevated in CNS malignancies. The analysis of immune cell subsets in the CSF adds valuable information to clinicians and is a promising tool for the differential diagnosis of neurological diseases.


Randomized Controlled Trial of Lifestyle Walking for African American Women: Blood Pressure Outcomes.
The aim of this study was to test the effects of a lifestyle physical activity intervention (group meetings alone vs supplemented by personal or automated calls) on changes in systolic/diastolic blood pressures from baseline to 24 and 48 weeks among African American women. This was a randomized controlled trial with intervention conditions randomly assigned across 6 community health care sites. Participants were 288 sedentary African American women without major signs/symptoms of cardiovascular disease. Each intervention had 6 group meetings over 48 weeks, with 1 of 3 options between meetings: (1) no calls, (2) personal motivational calls, or (3) automated motivational calls. Blood pressures were taken at baseline, 24 weeks, and 48 weeks. Separate analyses were conducted using blood pressure classifications from the 2003 and 2017 high blood pressure guidelines. Average blood pressures decreased approximately 3 mm Hg for systolic and 2 mm Hg for diastolic from baseline to 48 weeks, with no differences between conditions. For both 2003 and 2017 blood pressure classifications, the risk ratio (odds of moving to a lower classification) was 1.44 for each assessment (P < .001). This lifestyle walking intervention appears beneficial in lowering blood pressure across blood pressure classifications in midlife African American women.


A nod factor binding lectin with apyrase activity from legume roots.
A lectin isolated from the roots of the legume, Dolichos biflorus, binds to Nod factors produced by rhizobial strains that nodulate this plant and has a deduced amino acid sequence with no significant homology to any lectin reported to date. This lectin also is an enzyme that catalyzes the hydrolysis of phosphoanhydride bonds of nucleoside di- and triphosphates; the enzyme activity is increased in the presence of carbohydrate ligands. This lectin-nucleotide phosphohydrolase (LNP) has a substrate specificity characteristic of the apyrase category of phosphohydrolases, and its sequence contains four motifs characteristic of this category of enzymes. LNP is present on the surface of the root hairs, and treatment of roots with antiserum to LNP inhibits their ability to undergo root hair deformation and to form nodules on exposure to rhizobia. These properties suggest that this protein may play a role in the rhizobium-legume symbiosis and/or in a related carbohydrate recognition event endogenous to the plant.


[Restorative microsurgery in severe injury and traumatic amputation of the distal portions of the extremities].
Application of microsurgical methods and free grafting of the compound complexes of tissues with the vessels and nerves in particular with microanastomoses permitted to achieve high functional results in traumatic amputation of extremities in contiguity, severe destroying traumas and their consequences. Experience of 1000 urgent microsurgical operations, including 638 replantations of digits and their blocks for various kinds of amputation on the palm level was summarized. Classification of amputation, taking into account the injury mechanism and character, promoting the choice of optimal tactic and technique of restoration operation was elaborated. Indication for replantation are substantiated, the results of restoration operation, complications occurring after large segments of extremities replantation and measures for their treatment are analysed. Definite success of operation is determined by the extent of first operation and by subsequent rehabilitation measures conduction including the correcting operations and various conservative methods.


[Study on immunoglobulin allotypes in the Chinese: a hypothesis of the origin of the Chinese nation].
This paper reports the distribution of immunoglobulin Gm and Km allotypes in 74 Chinese geographic populations. These populations are derived from 24 nationalities comprising 96.6% of the total population of China. A total of 9,560 individuals were phenotyped for Gm (1,2,3,5,21) factors and 9,611 for Km(1). Phylogenetic trees were constructed on the basis of Gm haplotype frequencies and genetic distances. The results of clustering analysis show the heterogeneity of the Chinese nation, and confirm the hypothesis that the modern Chinese nation originated from two distinct populations. One population originating in the Yellow River valley, and the other originating, in the Yangtze River valley during the early part of neolithic times (to date 3,000--7,000). Frequencies of the Gm haplotype of 74 Chinese populations were compared with those from 33 populations from major racial groups. The results suggest that during human evolution, the Negroid group and Caucasoid-Mongoloid group diverged first, followed by a divergence between the Caucasoid and Mongoloid. Interrace divergences are high in comparison with interrace divergences. There appear to be two distinct subgroups of Mongoloid, Northern and Southern Mongoloid. The Northern and Southern Mongoloid have Gm1;21 and Gm1,3;5 haplotypes as race associated markers, respectively. Furthermore, the Caucasian associated haplotype Gm3;5 was found in several of the minorities living in the northwest part of China. The amount of Caucasian admixture has been estimated. The presence of the Gm3;5 haplotype is attributed to the Caucasians living in Central Asia throughout the "Silk Road." In contrast to the Gm haplotype distribution, Km1 gene frequencies showed a random distribution in the populations studied.


[Therapeutic interchange of drugs not included in the hospitaĺs pharmacotherapeutic guide: a quality program].
Standardised substitution of those drugs not included in the hospitaĺs formulary constitutes one of several methods used to improve therapeutic efficiency, due to reduction of variability in pharmaceutical practice and prevention of potential medication errors. To evaluate quality of drug substitution procedures in those drugs not included in the hospital's formulary. Assessment study in a surgical hospital with 314 beds, using structural, process and outcome criteria from 1998 to 2002. Compliance degree for structure, process and outcome criteria were 100, 89 and 35%, respectively, while the established standards were 100%. Prevalence values for patients with substituted medication, increased from 2.9 (95%CI, 2.4-3.6) in 1998 to 11.1% (95%CI, 10.2-12.1) in 2002. Non-substituted drugs annual cost decreased from 20,199 in 1998 to 12,356 Euro in 2002. Drug substitution made by the pharmacist had an acceptance degree of 82.5%. No interchange errors were found in 126 replaced drugs. The development of quality programs to improve drug prescription adherence to the hospitaĺs formulary, specially those that promote therapeutic interchange under the Pharmacy Committee guidance, are helpful strategies to make a proficient management of patients pharmacotherapy.


[The evaluation of the Harrington technique in the treatment of double-curved scoliosis (author's transl)].
Double-curved scoliosis was present in 18.5 of 750 scolioses operated on at the St. Justine Hospital in Montreal. 128 cases were reviewed with a follow up of more than 3 years. Pre-operative curves measured 61 and 58 degrees on average and post-operative curves measured 27 and 23 degrees. At the time of review, the curves were 39 and 36 degrees. The loss of correction varied with the age of the patient and the severity of deformity. The technique of early ambulation improved the post-operative results. However, it was concluded that compression rods did not provide a better correction of the curve or of the thoracic kyphosis.


Corticosteroid injection therapy for overuse injuries.
Local corticosteroid injection therapy may be considered for many conditions commonly treated by the primary care physician. Chronic overuse and flawed biomechanics may lead to inflammation in areas easily accessible to injected local corticosteroids, including bursae, tendon sheaths and joints. It is generally preferable to mix the steroid preparation with an anesthetic agent to minimize the injection pain, provide immediate symptom relief and confirm the diagnosis. Local complications of corticosteroid injection include tendon and ligament weakening, bacterial infections of joints and related structures, and subcutaneous tissue atrophy. Systemic complications are rare but reportedly include hyperglycemia and adrenal axis suppression.


Association between SPARC mRNA expression, prognosis and response to neoadjuvant chemotherapy in early breast cancer: a pooled in-silico analysis.
SPARC is an important regulator of the extracellular matrix and has been suggested to improve delivery of albumin-bound cytotoxics. However, little is known regarding its role in breast cancer (BC). We conducted a pooled analysis of publically available datasets, in which BC patients who received no systemic therapy or received neoadjuvant chemotherapy were eligible. Patients were assigned to molecular subtypes using PAM-50. We computed a SPARC module (SPARC7), composed of genes with an absolute correlation with SPARC >0.7. In the systemically untreated cohort, we evaluated 1) expression of SPARC/SPARC7 according to breast cancer subtype, 2) association between SPARC/SPARC7 and biological processes related to proliferation, immune and stroma, and 3) association between SPARC/SPARC7 and relapse-free survival in a Cox model in all patients and in the different molecular subtypes adjusted for tumor size, nodal status, histological grade, and age. In the neoadjuvant cohort, we evaluated the association between SPARC and pCR in a logistic regression model, adjusted for the same clinicopathologic factors. 948 (10 datasets), and 791 (8 datasets) patients were included in the systemically untreated and neoadjuvant cohorts, respectively. High SPARC expression was associated with small tumor size, low histological grade and luminal-A tumors (all p<0.0001). There was a positive correlation between SPARC and stroma-related modules but negative correlation with proliferation modules. High SPARC expression was associated with poor prognosis in patients with basal and HER2+ breast cancer even after adjusting for clinicopathologic parameters. In the neoadjuvant cohort, a subgroup analysis suggested that high SPARC is associated with low rates of pCR in the HER2 subtype. Same results were observed on replacing SPARC by SPARC7. This analysis suggests a potential role of SPARC in determining prognosis and response to primary chemotherapy in early BC. This information could guide further development of albumin-bound cytotoxics in BC.


Testicular germ cell tumor: Short and long-term side effects of treatment among survivors.
Long-term prognosis of germ cell tumor (GCT) types is excellent, however, treatment is associated with non-negligible complication rates and a negative impact on quality of life. The present study described treatment results in terms of survival, both short and long-term toxicity, and paternity rates in a cohort of patients treated at Jules Bordet Institute, University ULB of Brussels (Brussels, Belgium). The present study analyzed the data of a cohort of patients with GCT types. Pre-operative patient and tumor characteristics were described. Performance status, pulmonary function tests and renal clearance prior to chemotherapy were noted. Chemotherapeutic regimens and their associated toxicities were analyzed. The duration to event-free, cancer-specific and overall survivals were estimated using Kaplan-Meier curves. A total of 115 patients (median age, 31-years-old) were treated for a GCT at Jules Bordet Institute. At a median follow-up of 6-years, 11 (10%) patients had relapsed and 2 (2%) developed a second malignant neoplasm. At the final follow-up, 97 (89%) and 6 (5.5%) patients exhibited complete and partial remission, respectively. A total of 6% of patients exhibited a progressive disease. In terms of short-term toxicity, 11% of patients presented with febrile neutropenia. The 10-year overall survival rate and relapse-free survival rate were 93.4 and 89.8%, respectively. The paternity rate post-treatment was 27%. Testicular GCT survivors suffered from short- and long-term treatment-associated side effects on both a physical and psychological level. A long-term close follow-up is necessary in order to assist the patient with these treatment-induced complications.


Kappa statistics as indicators of quality assurance in histopathology and cytopathology.
Kappa statistics are widely-used to assess performance in quality assurance schemes. Low values, however, are difficult to interpret, especially when confidence intervals have not been calculated. A model of a dichotomous decision in pathology (benignancy or malignancy in fine needle aspirates of the breast) was used to calculate kappa statistics (with confidence limits) for increasing false positive rates. It was found that the level at which the upper 95% confidence interval for the kappa statistic fell below 1 was an insensitive method of detecting unsatisfactory performance as at that level the false positive rate was unacceptably high (> 1%) for all populations of specimens less than 800 in number. Either large populations of samples are required in quality assurance schemes which use kappa statistics (which may well be impractical) or other methods of assessing performance, possibly with weighted outcomes, are required.


Turkish validity and reliability study for the person-centered maternity care scale.
The objective was to adapt the person-centered maternity care scale (PCMCS) developed by Afulani et al. in 2017 to Turkish and to perform the validity and reliability study of this scale. The population of this methodological study consisted of 280 mothers who were referred to the postpartum service of a public hospital in eastern Turkey. Linguistic validity, context validity, and pilot practice studies regarding the PCMCS that could be used in the first nine postpartum weeks were performed. Explanatory factor analysis and confirmatory factor analysis were performed to assess the construct validity of the form. Reliability of PCMCS was tested through the Cronbach's α internal consistency coefficient, total item correlation, and test-retest analysis. The Turkish version of the PCMCS a 21-item scale with three sub-dimensions was obtained. These three sub-dimensions found as a result of explanatory factor analysis and confirmatory factor analysis supported the scale structure. Cronbach's α reliability coefficient scale was adequate for total and sub-dimensions. Turkish version of PCMCS was found to be a valid and reliable instrument to be used for assessing the person-centered maternity care for women in the postpartum period.


Fluoride-releasing removable appliances.
A method was developed to give removable appliances a fluoride-releasing capability. Visible light-cured glass-ionomer cement inserts were made, placed in resins commonly used for removable appliances, and evaluated for fluoride release over a 2-month period. Fluoride release was measured daily for 7 days, weekly for 4 weeks, and monthly for 1 month. All specimens released fluoride at every time period. There was a "burst effect" in which more fluoride was released the first day, but the amount released decreased significantly on the second day. The amount of fluoride released decreased at each of the daily and weekly measurements, but became relatively stable after 7 days. All specimens were still releasing fluoride at the end of the 2-month test period.


Ecology of Powassan Virus in the United States.
Zoonotic viruses threaten the lives of millions of people annually, exacerbated by climate change, human encroachment into wildlife habitats, and habitat destruction. The Powassan virus (POWV) is a rare tick-borne virus that can cause severe neurological damage and death, and the incidence of the associated disease (Powassan virus disease) is increasing in the eastern United States. The mechanisms by which POWV is maintained in nature and transmitted to humans are complex and only partly understood. This review provides an overview of what is known about the vector species, vector-host transmission dynamics, and environmental and human-driven factors that may be aiding the spread of both the vector and virus.


Minoxidil and male-pattern alopecia: a potential role for a local regulator of sebum secretion with vasoconstrictive effects?
Regulation of the hair cycle takes place at the pilo-sebaceous unit with the sebaceous gland as a sex hormone-dependent part. Although minoxidil stimulates proliferation of follicular cells and activation of prostaglandin endoperoxide synthase-1, it was suggested that other mechanisms, such as an increase in the local blood flow, might mediate the drug effect on hair growth. If that is the case, it is possible that minoxidil counteracts some vasoconstrictive mediator of male-pattern alopecia. This hypothetical vasoconstrictive mediator X would have to meet some criteria: (I) vasoconstriction both in the general circulation and in the hair-growing skin; (II) local vasoconstrictive activity in the hair growing skin should be related to the circulating testosterone level; (III) only an increase in the local mediator X activity causes male-pattern alopecia, since hypertensive patients are not balder than expected. The sebaceous gland is a possible place of the mediator X secretion since it is a sex-hormone-dependent part of the pilo-sebaceous unit. ET-1 might be a suitable candidate for the mediator X, since male hormones raise ET-1 plasma levels and female hormones lower them. The speculation presented here is that ET-1, beside vasoconstriction in the general circulation, might also regulate the sebum secretion, by triggering contractions of the myoepithelial cells. This hypothetical mechanism would normally remain confined to the sebaceous gland. During puberty, sex hormones stimulate growth of sebaceous glands in both sexes. In women hypertrophied sebaceous glands under estrogen control would not increase its ET-1 content, while in men, testosterone would increase ET-1 secretion that might affect the neighboring arterioles. Induced vasoconstriction might reduce the hair growth and promote hair loss. If ET-1 plays the described role, then an ET-1 antagonist, i.e. bosentane, should also have some hair-growing properties.


A Case of Chronic Mesenteric Ischemia: Complete Revascularization Using Multiple Procedures.
Chronic mesenteric ischemia (CMI) involving occlusion and/or stenosis of multiple mesenteric arteries is rare. We report our experience with a 66-year-old man who presented with a more than 3 months history of abdominal pain and vomiting/diarrhea. A diagnosis of CMI due to occlusion of the superior mesenteric artery (SMA) and severe stenosis of the celiac artery by median arcuate ligament syndrome was made. Complete revascularization through iliac artery-SMA bypass grafting and arcuate ligament dissection assisted with staged-catheter intervention successfully alleviated the patient's symptoms. The patient has maintained a normal daily diet for 6 months postoperatively.


Effect of Ensiling Density and Storage Temperature on Fermentation Quality, Bacterial Community, and Nitrate Concentration of Sorghum-Sudangrass Silage.
This study aimed to evaluate the fermentation quality, bacterial community, and nitrate content of sorghum-sudangrass silage with two ensiling densities [550 kg fresh weight (FW)/m3 (low density, LD) and 650 kg FW/m3 (high density, HD)] stored at two temperatures [10°C (low temperature, LT) and 25°C (normal temperature, NT)] for 60 days. The fermentation parameters, microbial counts, bacterial community, nutritional composition, and nitrate and nitrite levels were assessed. The pH and ammonia nitrogen (N) in all silages were below 4.0 and 80 g/kg total N, respectively. Compared with LT treatments, NT treatments had lower pH and lactic acid (LA) bacteria and yeasts counts and contained higher LA and LA/acetic acid (LA/AA) (p < 0.05). The LT-LD contained more ammonia-N than LT-HD (p < 0.05) and had higher nitrate and lower nitrate degradation than other treatments (p < 0.05). Lactobacillus was the most dominant genus with all treatments (57.2-66.9%). The LA, LA/AA, and abundances of Pantoea, Pseudomonas, and Enterobacter in the silage negatively correlated with nitrate concentration and positively correlated with nitrate degradation (p < 0.05). Moreover, pH and ammonia-N were positively correlated with nitrate concentration and negatively correlated with nitrate degradation (p < 0.05). Overall, all silage had satisfactory fermentation quality, and the silage with HD and NT had better fermentation quality and higher nitrate degradation. The bacterial communities in all silages were dominated by Lactobacillus. The nitrate degradation during the fermentation process might be related to the fermentation quality and the activity of Pantoea, Pseudomonas, and Enterobacter in silage.


Reed's syndrome: segmental piloleimyomas type 1 and uterus myomatosus.
Cutaneous mosaicism is a possible cause of segmental skin diseases. Cutaneous leiomyomatosis represent a spectrum of conditions ranging from single lesions to disseminated wide distribution. Reed's syndrome, is an autosomal dominant disorder characterized by multiple cutaneous and uterine leiomyomas. We observed a segmental cutaneous piloleimyomatosis type 1 in a 55-year old female who had an uterus extirpation because of uterine leiomyomas. The cutaneous lesions were moderately painful and localized on her left upper trunk. They presented as firm nodules and small plaques in a linear arrangement. Renal cancer was excluded. In patients with multiple cutaneous (pilo)leiomyomas a search for underlying systemic diseases is necessary in order to not miss benign or malignant tumors of internal organs.


[A case of bronchial lipoma treated by Nd-YAG laser surgery].
A 59-year-old man was referred to our hospital with complaint of cough. On physical examination the patient was 159 cm tall and weighted 68 kg. Chest X-ray showed an infiltrative shadow in the left lower lung field. Bronchoscopic findings revealed a polypoid tumor with smooth surface, located at the lower part of the left main bronchus and occupying over two-thirds of the left basal bronchus. A hamartoma was suspected as the result of bronchial biopsy. Endoscopic Nd-YAG laser surgery was performed. The left basal bronchus was opened. Histologically the tumor consisted mainly of mature fat tissue with collagen fibers and was diagnosed as a bronchial lipoma. Bronchial lipoma arising from the submucosal tissue of a large bronchus, occurs mainly in obese and middle-aged men. It is a rare benign tumor of the lung and only 38 cases have been reported in Japan.


Detection and characterization of fumonisin mycotoxins by liquid chromatography/electrospray ionization using ion trap and triple quadrupole mass spectrometry.
Electrospray ionization (ESI) high-performance liquid chromatography/mass spectrometry using both ion trap and triple quadrupole mass spectrometers has been utilized for the detection and characterization of fumonisin mycotoxin impurities in a purified sample of fumonisin B1 (FB1). Multi-stage tandem mass spectrometry (MSn) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) of FB1 and the fifteen synthetically prepared methyl esters of FB1 on the ion trap instrument allowed investigation of the numerous fragmentation pathways available for this compound class. Data-dependent LC/MS/MS precursor-ion scan to product-ion scan experiments, based on the ion trap MSn experiments, were carried out on a triple quadrupole instrument and facilitated the detection of twelve, and the structural characterization of eight, minor impurities on the purified sample of FB1. Data-dependent LC/MS/MS full scan to product-ion scan experiments on the ion trap instrument resulted in the detection and characterization of fifteen further impurities in the purified sample of FB1; this number included the four uncharacterized impurities detected in the triple quadrupole LC/MS/MS experiments.


Effect of cytokines on production of insulin-like growth factor binding proteins (IGFBPs) from human fibroblasts in culture.
Bioactivity of Insulin-like growth factors (IGEs) are positively or negatively regulated by IGF binding proteins (IGFBPs). Like IGFs, production of IGFBPs are influenced by a number of hormonal factors. We studied the effects of cytokines on production of IGFBPs in human fibroblasts in culture. Both IL-1beta and TNF-alpha inhibited IGFBP-3 (42/38 KDa species) production in a concentration dependent manner judged by Western ligand blot. Expression of IGFBP-3 mRNA was also decreased by these cytokines. Moreover, the treatment with IL-1beta and TNF-alpha resulted in appearance of smaller mol weight (26 KDa) immunoreactive IGFBP-3 fragment(s) which lacked the ability to bind 125I-IGFs, indicating that these cytokines degrade IGFBP-3 via activation of proteases. Both IL-1beta and TNF-alpha decreased production of IGFBP-4, whereas they increased that of IGFBP-6, IL-6 had little effect on production of IGFBPs. Likewise, interferon-gamma failed to affect of production of IGFBPs except at high concentrations. The present data demonstrate that cytokines, especially IL-1beta and TNF-alpha are potent regulators of IGFBPs production and degradation. These cytokines may alter tissue uptake of IGFs and help to counteract the catabolic state induced by them.


Glymphatic Pathway of Gadolinium-Based Contrast Agents Through the Brain: Overlooked and Misinterpreted.
The "glymphatic system" (GS), a brain-wide network of cerebrospinal fluid microcirculation, supplies a pathway through and out of the central nervous system (CNS); malfunction of the system is implicated in a variety of neurological disorders. In this exploratory study, we analyzed the potential of a new imaging approach that we coined delayed T2-weighted gadolinium-enhanced imaging to visualize the GS in vivo. Heavily T2-weighted fluid-attenuated inversion recovery (hT2w-FLAIR) magnetic resonance imaging was obtained before, and 3 hours and 24 hours after intravenous gadolinium-based contrast agent (GBCA) application in 33 neurologically healthy patients and 7 patients with an impaired blood-brain barrier (BBB) due to cerebral metastases. Signal intensity (SI) was determined in various cerebral fluid spaces, and white matter hyperintensities were quantified by applying the Fazekas scoring system. Delayed hT2w-FLAIR showed GBCA entry into the CNS via the choroid plexus and the ciliary body, with GBCA drainage along perineural sheaths of cranial nerves and along perivascular spaces of penetrating cortical arteries. In all patients and all sites, a significant SI increase was found for the 3 hours and 24 hours time points compared with baseline. Although no significant difference in SI was found between neurologically healthy patients and patients with an impaired BBB, a significant positive correlation between Fazekas scoring system and SI increase in the perivascular spaces 3 hours post injection was shown. Delayed T2-weighted gadolinium-enhanced imaging can visualize the GBCA pathway into and through the GS. Presence of GBCAs within the GS might be regarded as part of the natural excretion process and should not be mixed up with gadolinium deposition. Rather, the correlation found between deep white matter hyperintensities, an imaging sign of vascular dementia, and GS functioning demonstrated feasibility to exploit the pathway of GBCAs through the GS for diagnostic purposes.


Risk indices associated with the insulin resistance syndrome, cardiovascular disease, and possible protection with yoga: a systematic review.
To conduct a systematic review of published literature regarding the effects of yoga, a promising mind-body therapy, on specific anthropometric and physiologic indices of cardiovascular disease (CVD) risk and on related clinical endpoints. We performed a literature search using 4 computerized English and Indian scientific databases. The search was restricted to original studies (1970 to 2004) evaluating the effects of yoga on CVD or indices of CVD risk associated with the insulin resistance syndrome (IRS). Randomized controlled trials (RCTs), nonrandomized controlled trials, uncontrolled (pre and post) clinical trials, and cross-sectional (observational) studies were included if they met specific criteria. Data were extracted regarding study design, setting, population size and characteristics, intervention type and duration, comparison group or condition, outcome assessment, data analysis and presentation, follow-up, and key results, and the quality of each study was evaluated according to specific predetermined criteria. We identified 70 eligible studies, including 1 observational study, 26 uncontrolled clinical trials, 21 nonrandomized controlled clinical trials, and 22 RCTs. Together, the reported results of these studies indicate beneficial changes overall in several IRS-related indices of CVD risk, including glucose tolerance and insulin sensitivity, lipid profiles, anthropometric characteristics, blood pressure, oxidative stress, coagulation profiles, sympathetic activation, and cardiovagal function, as well as improvement in several clinical endpoints. Collectively, these studies suggest that yoga may reduce many IRS-related risk factors for CVD, may improve clinical outcomes, and may aid in the management of CVD and other IRS-related conditions. However, the methodologic and other limitations characterizing most of these studies preclude drawing firm conclusions. Additional high quality RCTs are needed to confirm and further elucidate the effects of standardized yoga programs on specific indices of CVD risk and related clinical endpoints.


Handedness and the 2016 U.S. Primaries: consistent handedness predicts support for Donald Trump among republicans, but gender predicts support for Hillary Clinton among democrats.
A growing number of studies demonstrate that consistent handers, people who use their dominant hand for all or most manual tasks, are less cognitively flexible than inconsistent handers, people who use their non-dominant hands at least some of the time. A recent hypothesis suggests that differences in handedness emerged evolutionarily because populations benefited from a balance between cognitively rigid and cognitively flexible people. One expectation is that cognitively rigid consistent handers would support more authoritarian policies or candidates. To test this idea, we looked at handedness, gender, and political affiliation as predictors of support for Donald Trump, a candidate whose supporters self-report being more authoritarian, in the 2016 primary. Our data show that in the Republican Primary, consistent handers report more support than inconsistent for Donald Trump. When authoritarianism was added as a covariate, the handedness effect disappeared. Further analyses showed that authoritarianism mediates the relationship between handedness and support for Donald Trump. In the Democratic Primary, there was a main effect of gender. Women reported more support than men for Hillary Clinton.


Radiation Protection in Interventional Radiology.
There has been a rapid development in the field of interventional radiology over recent years, and this has led to a rapid increase in the number of interventional radiology procedures being performed. There is, however, a growing concern regarding radiation exposure to the patients and the operators during these procedures. In this article, we review the basics of radiation exposure, radiation protection techniques, radiation protection tools available to interventional radiologists, and radiation protection during pregnancy.


The effect of thalidomide on BCG-induced granulomas in mice.
Granuloma proliferation is the result of a series of complex biological events in which a variety of cell types and cytokines are involved. Tumor necrosis factor alpha (TNF-alpha) plays a central role. In the present study, we investigated the effect of thalidomide (alpha-N-pthalimidoglutarimide), a selective inhibitor of TNF-alpha synthesis, on granuloma formation during BCG infection in Oncins France 1 (OF-1) mice. Subcutaneous injections of 30 mg/kg body weight of thalidomide daily for 14, 21 or 28 days into the mice resulted in the reduction of the size and total number of liver granulomas. The most striking effect of thalidomide was observed after 28 days, when the total number of liver granulomas was reduced by as much as 40% (P < 0.05). Serum TNF-alpha levels of thalidomide-treated mice were significantly lower (85%) than control mice on day 14 and remained lower (55%) on days 21 and 28. Positive immunohistochemical staining specific for TNF-alpha were demonstrable only in well-developed granulomas in which central mononuclear cells presented extensive differentiation into epithelioid cells. Daily administration of thalidomide for 21 to 28 days to the BCG-infected mice inhibited local TNF-alpha expression in well-developed granulomas. The mechanisms by which thalidomide modulates the granuloma proliferation are discussed.


Phylogeographic history of South American populations of the silky anteater Cyclopes didactylus (Pilosa: Cyclopedidae).
Cyclopes didactylus, commonly called silky anteater, is the smallest and least studied of the anteaters. It is an arboreal species occurring in rainforests, ranging from southern Mexico to Central and South America, with an apparently disjoint distribution between Amazon and Atlantic rainforests in Brazil. Although seven subspecies are recognized, little is known about its geographical variation. Thus, to evaluate the population dynamics and evolutionary history of the South American silky anteater, we analyzed 1542 bp sequences of the mitochondrial control region (CR), COI and Cyt-b genes of 32 individuals. Haplotype network, AMOVA and molecular dating analyses were performed and identified seven geographic clusters. The split of lineages separating Cyclopedidae (Cyclopes) and Myrmecophagidae (Myrmecophaga and Tamandua genera) was estimated around 41 million years ago (mya), and the intraspecific lineage diversification of C. didactylus began in the Miocene around 13.5 mya, likely in southwestern Amazonia. Tectonic and climatic events that took place in South America during the Tertiary and Quaternary seem to have influenced the evolutionary history of the species at different levels. This is the first study to investigate the population dynamics and phylogeography of the silky anteater, which contributes to a better comprehension of the biogeography of South America.


Challenges to antagonist blockade during sustained-release naltrexone treatment.
Naltrexone is a competitive opioid antagonist that effectively blocks the action of heroin and other opioid agonists. Sustained-release naltrexone formulations are now available that provide long-acting opioid blockade. This study investigates the use of heroin and other opioids among opioid-dependent patients receiving treatment with long-acting naltrexone implants, their subjective experience of drug 'high' after opioid use, and factors associated with opioid use. Participants (n = 60) were opioid-dependent patients receiving treatment with naltrexone implants. Outcome data on substance use, drug 'high', depression and criminal activity were collected over a 6-month period. Blood samples were taken to monitor naltrexone plasma levels, and hair samples to verify self-reported opioid use. More than half [n = 34 or 56%; 95% confidence interval (CI) 44-68%)] the patients challenged the blockade with illicit opioids during the 6-month treatment period; 44% (n = 26; 95% CI 32-56%) were abstinent from opioids. Mean opioid use was reduced from 18 [standard deviation (SD)13] days during the month preceding treatment to 6 days (SD 11) after 6 months. Of the respondents questioned on opioid 'high' (n = 31), nine patients (30%; 95% CI 16-47%) reported partial drug 'high' following illicit opioid use, and three (12%; 95% CI 3-26%) reported full 'high'. Opioid use was associated with use of non-opioid drugs and criminal behaviour. Challenging naltrexone blockade with heroin on at least one occasion is common among sustained-release naltrexone patients, but only a minority of patients use opioids regularly. Challenges represent a warning sign for poor outcomes and often occur in the context of polydrug use and social adjustment problems.


Impact of intracoronary ultrasound guidance on long-term outcome of percutaneous coronary interventions in diabetics--insights from the randomized SIPS trial.
The Strategy for Intravascular ultrasound (IVUS) guided PTCA and Stenting (SIPS) trial included a prospectively designed subgroup analysis to investigate whether routine IVUS-guidance during percutaneous intervention improves long-term outcome in diabetics. Consecutive diabetic patients (n = 43) with 57 lesions were randomly assigned to receive provisional stenting with angiographic guidance only (ANGIO) or with IVUS guidance provided by a combined IVUS/variable diameter balloon catheter (IVUS). The combined primary endpoint included death, nonfatal myocardial infarction and target vessel revascularisation (TVR) and was recorded for 28 months. The re-stenosis rate at 6-month follow-up angiography was defined as a secondary endpoint. A primary endpoint occurred in 6 diabetic patients (31.6%) in the IVUS-group and 11 diabetic patients (45.8%) in the ANGIO-group (relative risk for IVUS, 0.83, 95% confidence interval 0.28-2.35, p = 0.83). Kaplan-Meier analysis suggested that IVUS did slightly attenuate the negative effect of diabetes on long-term event-free survival. The quantitative assessment of follow-up angiography revealed that the incidence of re-stenosis was high in both groups (IVUS: 53% versus ANGIO: 52%, p = 0.94). There was no difference in the mean duration of hospitalisation (11.8 days with IVUS versus 11.2 days with ANGIO, p = 0.83) or total cost (US dollars 16,725 with IVUS versus US dollars 16,230 with ANGIO, p = 0.83) during follow-up. Routine IVUS-guidance during provisional stenting seems to slightly attenuate the negative effect of diabetes on long-term outcome. However, the re-stenosis rate remains very high.


Symptomatic tachydysrhythmias after esophagectomy: incidence and outcome measures.
Supraventricular tachydysrhythmias (SVT) after esophageal operations for carcinoma occur frequently and may be associated with increased morbidity. Prospective data on the etiology, incidence, and importance of these dysrhythmias are sparse. In 100 consecutive patients undergoing esophagectomy without prior history of atrial dysrhythmias or receiving antiarrhythmics, we prospectively examined the effects of predefined risk factors by history and pulmonary function on the 30-day incidence of symptomatic postoperative SVT, need for intensive care unit admission, and mortality rate. Symptomatic postoperative SVT occurred in 13 (13%) of the 100 patients studied at a median of 3 days after operation and was accompanied by hypotension in 9/13 (69%). Univariate correlates of SVT were older age (p = 0.03), perioperative use of theophylline (p = 0.044), and a low carbon monoxide diffusion capacity (measured in 56% of patients) on preoperative pulmonary function. Patients in whom SVT developed had a higher rate of intensive care unit admission (p = 0.0001) and a longer hospital stay (p = 0.036). Although patients in whom SVT developed had a higher (p = 0.013) 30-day mortality rate, SVT was not the direct cause of death. These prospective data show that the true incidence of symptomatic SVT within 30 days of esophagectomy is lower than previously reported. Occurrence of SVT was associated with significant morbidity. Older age was the strongest predictor of SVT after esophagectomy. In high-risk patients, continued monitoring (48 to 72 hours) and early interventions to decrease the incidence of postoperative SVT may improve overall surgical outcomes.


Preparation for caregiving: a study of multigeneration families.
The impact of providing care to the frail elderly on individual caregivers and their families has been discussed at length, but few researchers have investigated the events and circumstances preceding the onset of caregiving. In addition, although there is evidence that several family members are usually involved in planning and decision making about caregiving, the majority of studies in this area include only one generation. Based on a larger theoretical framework of preparation for caregiving [1, 2], the extent to which family members anticipate and plan for future caregiving is investigated. In addition, the extent to which they are satisfied with these preparations is studied. Interviews were conducted with mothers, daughters, and granddaughters in thirty-three multigeneration families. While substantial numbers of both mothers and daughters anticipated the need for care for the oldest generation, few made concrete plans about how to organize future care provision. Planners were more satisfied with the amount of discussion and planning in their family than non-planners. Implications for future research and practice applications are discussed.


Increased responsiveness of human coronary artery endothelial cells in inflammation and coagulation.
The effects of anti-inflammatory plant extracts, such as black tea extract (BTE) and resveratrol (RSV) could modulate cell activation leading to atherosclerosis, however there is little comparative information about how different endothelial cell types are affected by these compounds. In order to compare human endothelial cells derived from different origins (umbilical vein or HUVEC, coronary artery or HCAEC, microvascular or HMVEC) and their interleukin-1beta (IL-1beta) responsiveness, IL-6 ELISA, RT-PCR, tissue factor assay, and prostacyclin responses using 6-keto PGF1alpha ELISA were determined. The IL-1beta-induced IL-6 levels were dose-dependent with highest responses seen in HCAEC. Significant inhibition of IL-1beta responses was achieved with BTE and RSV, with the largest decrease of IL-6 and TF seen in HCAEC. Prostacyclin levels were highest in HUVEC and were inhibited by RSV in all cell types. The differences between the endothelial cell types could account for greater susceptibility of coronary arteries to inflammation and atherogenesis.


No Modifying Effect of Antioxidant N-Acetyl-L-Cysteine on Fenofibrate-induced Hepatocarcinogenesis in Rats.
To clarify the modifying effect of N-Acetyl-L-Cysteine (NAC), which has antioxidative ability, on hepatocarcinogenesis promoted by fenofibrate (FF), a peroxisome proliferator-activated receptor (PPAR) alpha agonist , male F344/N rats were administered a single intraperitoneal injection of N-diethylnitrosamine (DEN) as an initiator followed by administration of a diet containing 3,000 ppm of FF for 16 weeks. Two-thirds partial hepatectomy was performed 1 week after the FF treatment. Additionally, NAC treatments for 14 weeks from 2 weeks after the FF treatment were performed. Although the expression level of tumor protein p53 (Tp53) mRNA decreased in the DEN+FF+NAC group as compared with that in the DEN+FF group, no significant differences between the DEN+FF and DEN+FF+NAC groups were observed in the number of hepatocellular altered foci and activities of hepatocellular proliferation. In addition, the results of an antioxidant enzyme assay and measurement of the amounts of total glutathione in the liver revealed no significant difference between the DEN+FF and DEN+FF+NAC groups; although no significant differences were observed in many genes between the DEN+FF and DEN+FF+NAC groups, only glutathione peroxidase 2 (Gpx2) mRNA increased in the DEN+FF+NAC group as compared with the DEN+FF group. The results under the present experimental conditions indicate no obvious modifying effect of NAC on liver tumor promotion by FF in rats.


Autocatalysis in a reconstituted chloroplast system.
In whole plants and intact chloroplasts, photosynthesis does not reach its full rate immediately upon illumination but only after a lag which is believed to reflect an autocatalytic increase in the concentration of carbon cycle intermediates. Autocatalysis has now been observed in a reconstituted system containing envelope-free chloroplasts augmented with ferredoxin and other stromal proteins but only catalytic amounts of ATP and NADP. With ribose 5-phosphate as substrate, the CO(2) dependent O(2) evolution recorded for such mixtures implies rates of "endogenous" or ferredoxin-dependent photophosphorylation as high as 360 mumoles of orthophosphate esterified mg(-1) chlorophyll hr(-1).


Microscopic and chemical characterization of PVC tube used for dialysis lines: A new approach.
Polyvinylchloride is universally agreed upon to be the material of choice for tubings and for containers for medical application. Many alterations of the chemical/physical surface conditions, mainly due to an altered extrusion process, could influence its biocompatibility by promoting platelet aggregation. Biocompatibility and safety of the medical device must be preserved, also monitoring the migration of additives within polyvinylchloride during the diffusion process. A large variety of methods are used to verify the correct composition and extrusion of polyvinylchloride but, generally, they need long experimental time and are expensive. The aim of the study is to propose a simple, economic and rapid approach based on Fourier transform-infrared spectroscopy and Coomassie Blue staining. The method has been used to detect chemical and morphological defects caused by an altered extrusion process on 20/75 polyvinylchloride tubings in a blind test. This approach positively identified altered samples in 80% of the cases. The suggested approach represents a reliable and versatile method to detect and monitor surface defects by an easy, inexpensive and reproducible method.


Pre and Postoperative Sexual Dysfunction in Patients with Leriche Syndrome-A Prospective Pilot Study.
Background: Recovery of normal arterial inflow in the lower limbs after Leriche's syndrome surgery does not always improve erection. This study assesses the effects of Leriche syndrome on erectile and ejaculatory dysfunction in patients awaiting surgical treatment and the impact of treatment used on sexual dysfunctions. Methods: 35 men with Leriche syndrome aged 61.3 years (SD = 7.74) were assessed for erectile dysfunction. The patients were classified into three groups: aortofemoral bypass (group 1); stenting of the iliac artery (group 2) and aortobifemoral bypass (group 3). The patients were qualified for surgery based on the TASC II guidelines. Follow-up was done 3 months after treatment. Results: The mean preoperative IIEF-5 score was 14. 69 (+/- 5.30), with better preoperative scores obtained by 54.3% of patients. A total of 51.4% and 48.6% of patients, respectively, reported normal erection enabling satisfactory penetration and normal ejaculation before treatment. After surgical treatment, satisfactory erection was reported by 60% of all surgically treated patients, whereas the presence of ejaculation was reported by only 14.2% of patients. Conclusions: The IIEF-5 score is a tool for careful assessment of vascular erectile dysfunctions, it allows for the evaluation of erectile dysfunctions in relation to atherosclerosis risk factors. The treatment strategy used allowed for slight improvement as evidenced to erection but decreasing normal ejaculation.


The Rise of Total Ankle Arthroplasty Use: A Database Analysis Describing Case Volumes and Incidence Trends in the United States Between 2009 and 2019.
Ankle arthrodesis has been the mainstay treatment for end-stage ankle arthritis. The popularity of total ankle arthroplasty (TAA) has been on the rise due to improved implant design and postoperative outcomes. The purpose of this study was to describe the basic epidemiology and trends of annual procedure volumes and incidence in the general American population as well as in different population subgroups from 2009 to 2019. We hypothesize that the incidence of TAA has significantly risen while the median length of hospital stay has decreased nationwide. The IBM MarketScan database was queried for patients who underwent TAA from January 2009 to December 2019 based on Current Procedural Terminology coding. Population estimates from the US Census Bureau were used to calculate the annual incidence of TAA. Procedural volume and incidence were calculated for annual sums, gender, age subgroups, inpatient and outpatient TAA, as well as in four statistical geographic regions in the United States. Median length of hospital stay was calculated and trended annually for inpatient TAA. A total of 41,060 primary TAAs were identified in the database from 2009 to 2019, in which 52.5% were performed in males. Annual volumes increased by 136.1%, from 2180 to 5147 procedures nationwide. Incidence reported per 100 000 population increased by 120.8%. Both inpatient and outpatient procedures have increased, by 242.5% and 86.6%, respectively. Median length of hospital stay decreased from 3 days in 2009 to 1 day in 2019 and did not differ between genders. Growth in incidence was demonstrated in males and females above the age of 54 years with the largest growth in annual incidence found between 65 and 74 years. Incidence rose in the South and West of the United States by 111.8% and 136.5%, respectively. We found that annual volumes and incidence rates of primary TAA has increased between 2009 and 2019. Although both inpatient and outpatient surgery have become more frequent, inpatient volumes and incidence have increased almost 3 times more than those of outpatient surgery. Length of hospital stay decreased over the study years. When adjusted for the same study period, the cumulative annual growth rates of TAA were found to be 2 times greater than total knee arthroplasty and 3.6 times greater than total hip arthroplasty. Level III, retrospective database review.


[The surgical management of spastic foot deformities].
Any surgical treatment of spastic foot deformities must be preceded by an exact preoperative analysis of every aspect of the deformity and its functional consequences. The goals of surgical treatment are correction of the deformity, reestablishment of the stability of the foot and preservation of functionally important ranges of motion and muscle strength. These goals can usually be achieved only by a package of several simultaneous procedures. The foot must never be treated in isolation. Proximal joints have to be considered as well as the opposite side, because a plantigrade position of the foot is only possible when the leg is straight. Any postoperative evaluation must also take into account the proximal joints and the opposite leg in unilateral cases. The mere static evaluation of the postoperative results by reporting clinical and radiographic values should be supplemented by dynamic measurements which allow more insight into the functional results.


Adherence to prophylaxis and bleeding outcome in haemophilia: a multicentre study.
Prevention of bleeding and joint damage in severe haemophilia is dependent on adherence to prophylactic replacement therapy. The aim of this study was to assess adherence to prophylaxis, including associations with age, bleeding and clotting factor consumption (CFC). In three Dutch haemophilia centres, semi-structured interviews about adherence to prophylaxis in the previous 2 weeks were conducted with patients or parents of a child with haemophilia. Patients were classified, according to pre-specified definitions, as adherent, sub-optimally adherent or non-adherent based on missing, timing, and dose of infusions. Association of annual bleeding rates, mean CFC, person performing the infusion (parents verus patients) with adherence categories were analysed. Overall, 241 patients with haemophilia using prophylaxis were studied. Parents were more adherent (66%; n = 48/73) than patients (43%; n = 72/168). Sub-optimal adherence occurred in 29% of parents and 37% of patients and was characterized by changes in timing of infusion (mostly from morning to evening), while missing <6% of infusions. Non-adherence occurred less often: in 5% of parents and 20% of patients. Reduced adherence was associated with lower CFC, but not with joint bleeding. In conclusion, non-adherence in haemophilia was relatively rare, yet 1/3 of patients struggled to administer prophylaxis at the appropriate time of day.


Interfacial forces between a silica particle and phosphatidylcholine monolayers at the air-water interface.
Interfacial forces between a silica or borosilicate particle in water and phospholipids at the air-water interface were studied using the Monolayer Particle Interaction Apparatus. This instrument allowed the forces to be measured as the colloidal probe approached the monolayer from the liquid phase. The proper working principle of this setup was demonstrated by measuring the forces between a particle and a mica plate in 0.1 mM NaCl. The effect of the alkyl chain length on the adhesion between the particle and the monolayer was investigated using four different 1,2-dialkyl-sn-glycero-3-phosphocholines (DMPC, DPPC, DSPC, and DBPC), which had 14, 16, 18, and 22 carbon atoms per alkyl chain, respectively. The adhesion force increased with the square of the particle radius. The lipids in the liquid-expanded (LE) phase showed an attraction to the particle, explained by an electrostatic attraction and/or the formation of a three-phase contact line that lead to a capillary force. All monolayers showed an adhesion in their retract force curve, which decreased with an increased chain length and surface pressure. Interfacial stiffness was generally seen to increase with the phospholipid chain length and to decrease with surface pressure, explained by an increase in the intermolecular van der Waals interaction and a decrease in the interfacial tension, respectively. The adhesion between the particle and monolayer was concluded to be controlled by the contact area between the particle and monolayer, and therefore the monolayer stiffness and the electrostatic interactions.


No-Insulation Coil Under Time-Varying Condition: Magnetic Coupling With External Coil.
This paper presents experimental and analytical studies on the time-varying behavior of an NI (no-insulation) high-temperature superconductor pancake coil, alone or magnetically coupled to an external coil. An NI coil and another insulated coil (as an external), both of identical winding i.d. and number of turns, were fabricated. Another external coil used in this study was a 300-mm/5-T low-temperature superconductor magnet. An equivalent circuit model is proposed to simulate the NI coil, and the external coil, under time-varying conditions. Good agreement between experiment and simulation shows that the proposed equivalent circuit model is valid to characterize the time-varying electromagnetic behavior of an NI coil, alone or magnetically coupled to an external coil.


Effects of differential feedback on students' examination performance.
The effects of feedback on performance and factors associated with it were examined in a large introductory psychology course. The experiment involved college students (N = 464) working on an essay examination under 3 conditions: no feedback, detailed feedback that was perceived by participants to be provided by the course instructor, and detailed feedback that was perceived by participants to be computer generated. Additionally, these conditions were crossed with factors of grade (receiving a numerical grade or not) and praise (receiving a statement of praise or not). The task under consideration was a single-question essay examination administered at the beginning of the course. Detailed feedback on the essay, specific to individual's work, was found to be strongly related to student improvement in essay scores, with the influence of grades and praise being more complex. Generally, receipt of a tentative grade depressed performance, although this effect was ameliorated if accompanied by a statement of praise. Overall, detailed, descriptive feedback was found to be most effective when given alone, unaccompanied by grades or praise. It was also found that the perceived source of the feedback (the computer or the instructor) had little impact on the results. These findings are consistent with the research literature showing that descriptive feedback, which conveys information on how one performs the task and details ways to overcome difficulties, is far more effective than evaluative feedback, which simply informs students about how well they did.


Pituitary volumes in hypochondriac patients.
To date, no study has examined the pituitary volumes in patients with hypochondriasis. In the present study, we evaluated pituitary volumes in patients with hypochondriasis and healthy controls. Twenty individuals with hypochondriasis (ten males, ten females), aged 20 to 48 years, and healthy controls were included into the study. The pituitary volumes were obtained. Volumetric measurements were made with T1-weighted coronal MRI images, with 2.4-mm-thick slices, at 1.5 T, and were done blindly. Volumetric measurements did not demonstrate group differences in the brain measurements, i.e., whole brain volume, white, and gray matter volumes (P>0.05). We found significantly smaller pituitary volumes of the whole group of hypochondriac patients compared to healthy controls (age and ICV as covariates). To conclude, the results from the current investigation suggest that hypochondriac patients had smaller pituitary volumes compared with healthy controls. This could be the keystone to a better understanding of the neurobiological basis of hypochondriasis.


The Utility of Penile Bulb Contouring to Localise the Prostate Apex as Compared to Urethrography.
High-precision radiotherapy relies on accurate anatomic localisation. Urethrography is often used to localise the prostatic apex. However, urethrography is an invasive localisation procedure and may introduce a systemic error. The penile bulb (PB) is contoured to minimise the risk of erectile dysfunction. The purpose of this study is to assess the value of using the PB, as an alternative to urethrography, to localise the prostate. The PB was localised on 10 patients treated with simplified intensity-modulated arc radiotherapy at computed tomography simulation during treatment weeks 1 and 7. All patients underwent placement of fiducial markers. Urethrography was used only at simulation. Distances from the superior PB contour to the inferior prostate contour, the apex fiducial marker, and to the inferior prostate contour were obtained as well. The PB was contoured by two observers independently. Agreement coefficients and analysis of variance were used to assess reliability between rates and consistency of measurements over time. The PB-apex distance was greater than or equal to the urethrogram-apex distance in 24/30 (80%) measurements, and the median difference was 3 mm and was consistent between raters. The greatest variation in PB-IM distance between weeks was 6 mm, the median was 3 mm, and the agreements of measurements between weeks for raters 1 and 2 were 0.79 and 0.69, respectively. These differences were not statistically different and were consistent with the computed tomography slice thickness. The PB can be used to identify the prostate apex and can be reliably contoured between observers. Measurements are consistent between patients and through the duration of treatment. The PB distance measurements support studies indicating that urethrography causes a shift of the prostate superiorly. The distance from the PB to prostate apex remains stable during treatment for individual patients but varies between patients.


Investigation of MALDI-TOF Mass Spectrometry for Assessing the Molecular Diversity of Campylobacter jejuni and Comparison with MLST and cgMLST: A Luxembourg One-Health Study.
There is a need for active molecular surveillance of human and veterinary Campylobacter infections. However, sequencing of all isolates is associated with high costs and a considerable workload. Thus, there is a need for a straightforward complementary tool to prioritize isolates to sequence. In this study, we proposed to investigate the ability of MALDI-TOF MS to pre-screen C. jejuni genetic diversity in comparison to MLST and cgMLST. A panel of 126 isolates, with 10 clonal complexes (CC), 21 sequence types (ST) and 42 different complex types (CT) determined by the SeqSphere+ cgMLST, were analysed by a MALDI Biotyper, resulting into one average spectra per isolate. Concordance and discriminating ability were evaluated based on protein profiles and different cut-offs. A random forest algorithm was trained to predict STs. With a 94% similarity cut-off, an AWC of 1.000, 0.933 and 0.851 was obtained for MLSTCC, MLSTST and cgMLST profile, respectively. The random forest classifier showed a sensitivity and specificity up to 97.5% to predict four different STs. Protein profiles allowed to predict C. jejuni CCs, STs and CTs at 100%, 93% and 85%, respectively. Machine learning and MALDI-TOF MS could be a fast and inexpensive complementary tool to give an early signal of recurrent C. jejuni on a routine basis.


Phospholamban gene dosage effects in the mammalian heart.
Phospholamban ablation has been shown to result in significant increases in cardiac contractile parameters and loss of beta-adrenergic stimulation. To determine whether partial reduction in phospholamban levels is also associated with enhancement of cardiac performance and to further examine the sensitivity of the contractile system to alterations in phospholamban levels, hearts from wild-type, phospholamban-heterozygous, and phospholamban-deficient mice were studied in parallel at the subcellular, cellular, and organ levels. The phospholamban-heterozygous mice expressed reduced cardiac phospholamban mRNA and protein levels (40 +/- 5%) compared with wild type mice. The reduced phospholamban levels were associated with significant decreases in the EC50 of the sarcoplasmic reticulum Ca2+ pump for CA2+ and increases in the contractile parameters of isolated myocytes and beating hearts. The relative phospholamban levels among wild-type, phospholamban-heterozygous, and phospholamban-deficient mouse hearts correlated well with the (1) EC50 of the Ca(2+)-ATPase for Ca2+ in sarcoplasmic reticulum, (2) rates of relaxation and contraction in isolated cardiac myocytes, and (3) rates of relaxation and intact beating hearts. These findings suggest that physiological and pathological changes in the levels of phospholamban will result in parallel changes in sarcoplasmic reticulum function and cardiac contraction.


A {Ni12 }-Wheel-Based Metal-Organic Framework for Coordinative Binding of Sulphur Dioxide and Nitrogen Dioxide.
Air pollution by SO2 and NO2 has caused significant risks on the environment and human health. Understanding the mechanism of active sites within capture materials is of fundamental importance to the development of new clean-up technologies. Here we report the crystallographic observation of reversible coordinative binding of SO2 and NO2 on open NiII sites in a metal-organic framework (NKU-100) incorporating unprecedented {Ni12 }-wheels; each wheel exhibits six open NiII sites on desolvation. Immobilised gas molecules are further stabilised by cooperative host-guest interactions comprised of hydrogen bonds, π⋅⋅⋅π interactions and dipole interactions. At 298 K and 1.0 bar, NKU-100 shows adsorption uptakes of 6.21 and 5.80 mmol g-1 for SO2 and NO2 , respectively. Dynamic breakthrough experiments have confirmed the selective retention of SO2 and NO2 at low concentrations under dry conditions. This work will inspire the future design of efficient sorbents for the capture of SO2 and NO2 .


Croser to retire as Executive Director of AAIDD.
Washington, DC-Doreen Croser retired as Executive Director of the American Association on Intellectual and Developmental Disabilities (AAIDD) in June, 2010, following a distinguished 22-year tenure in the position. Past presidents of AAIDD have issued statements in Doreen's honor.


Bilateral volleyball-related deformity of the little fingers: mallet finger and clinodactyly mimic.
A 14-year-old male high school volleyball player was seen to evaluate right- and left-hand little-finger distal interphalangeal joint deformity and pain. His symptoms began during his second season of competitive play. The distal interphalangeal (DIP) joints of the little fingers flexed 20-30°, and a 10-15° valgus deformity was seen at the same joints. Pain was relieved with rest but returned immediately after playing volleyball, so plain radiographs were obtained. The flexion and valgus deformity was obvious on plain radiographs and through a clinical examination. Thus, a bilateral little-finger distal phalanx base epiphysis injury was seen. This injury is characterized by a biplanar Salter Harris physeal injury; type 5 on anteroposterior radiographs and type 2 on lateral plain radiographs. The deformity occurred as a result of competitive volleyball play. To our knowledge, this is the first reported case of a bilateral biplanar physial injury of the base of distal phalanges of the little fingers. Flexion and valgus deformities of DIP joints are a result of repeated micro traumas around the physis. Key pointsAs a result of repeated micro traumas to the physial region, flexion and valgus deformities of the distal interphalangeal (DIP) joints should be occurred.Sports injuries to the hand often require treatment in orthopedic departments to avoid permanent deformities.Short- or long-term functional results can be gained by simple splinting procedures and abstention from play.


[The comparative study on selective alpha1-blocker and behavioural therapy in the treatment of discoordinated voiding in children].
To compare the efficiency of selective alpha1-blocker and behavioural therapy in the treatment of detrusor-sphincter discoordination in children. Prospective, randomized study, approval of Ethics Committee, group of 60 children, age: 5 to 17, detrusor-sphincter discoordination. All children had a history of: recurrent UTI, irregular mictions with or without incontinence in "voiding diary". All have normal upper urinary tract in USG. Dicoordination was diagnosed by pathologic uroflowmetry curve and results with significant postvoiding residual urine in USG. Treatment group 1 (n=30): treatment with selective alpha1-blocker (doxazosin) in age related dosage. Group 2 (n=30): behavioral therapy and rehabilitation with conducting "voiding diary" with timed voiding. All children were also instructed on proper toilet posture, relaxation of the pelvic-floor muscles. After 6 weeks: changes in voiding patterns: No. of micturitions/day, average voided volume were estimated. Uroflowmetry was performed and voided volume, Av. flow rate, shape of the curve (1=normal, 2=flatened, irregular, 3=portions), residual urine (10% of Void.vol.) were calculated. Urinalysis and urin culture were obtained. Of 60 children 57 completed the study: Group 1 (n=30), Group2 (n=27). In Group 1 (alpha1-blocker): improvement in voiding patterns n=21, improvement in UF parameters n=20. In Group 2 (rehabilitation): improvement was estimated in 17 patients. Side effects were noted in 6 children from Group 1 (alpha1-blockers) (headache, hypotonia, vertigo, epistaxis), and non from the Group 2 (rehabilitation). Both treatment methods seemes to be effective in detrusor-sphincter discoordination. Selective alpha1-blockers alone are more effective than training and rehabilitation exercises.


Peroxisome proliferator-activated receptor delta-agonist, GW501516, ameliorates insulin resistance, improves dyslipidaemia in monosodium L-glutamate metabolic syndrome mice.
We evaluated the effects of GW501516, a specific peroxisome proliferator-activated receptor beta/delta (PPARdelta) agonist in metabolic syndrome mice, obtained by perinatal injection of monosodium L-glutamate, to investigate the efficacy of GW501516 against metabolic syndrome and the effectiveness of PPARdelta activation as therapeutic target for metabolic syndrome. After 14 days treatment, GW501516 effectively improved the glucose intolerance, normalized the fasted blood glucose, and increased the serum high-density lipoprotein cholesterol (HDL-C) level. Postprandial blood glucose, serum insulin, leptin, free fatty acid (FFA) levels, and total cholesterol/HDL-C ratio were also significantly decreased. Moreover, semiquantitative reverse transcription-polymerase chain reaction results indicated that the above phenotypes might be due to (i) enhancement of fatty acid oxidation in muscle, adipose tissue and the liver; (ii) improvement of insulin-stimulated glucose transportation in skeletal muscle and adipose tissue; and (iii) reduced local glucocorticoid synthesis. Therefore, GW501516 could significantly ameliorate dyslipidaemia and insulin resistance in monosodium L-glutamate mice and activation of PPARdelta could be envisioned as a useful strategy against human metabolic syndrome and related diseases.


Dietary Supplementation of Lauric Acid Alleviates the Irregular Estrous Cycle and the Impaired Metabolism and Thermogenesis in Female Mice Fed with High-Fat Diet (HFD).
Lauric acid (LA) has been implicated in the prevention/treatment of obesity. However, the role of LA in modulating an obesity-related female reproductive disorder remains largely unknown. Here, female mice were fed a control diet, high-fat diet (HFD), or HFD supplemented with 1% LA. The results demonstrated that the HFD-induced estrous cycle irregularity and the reduction of serum follicle-stimulating hormone (FSH) were alleviated by LA supplementation. In possible mechanisms, LA supplementation led to significant increase in serum lipid metabolites such as sphingomyelin and lysophosphatidylcholine containing LA (C12:0) and the improvement of glucose metabolism in mice fed HFD. Moreover, impaired body energy metabolism and weakened brown adipose tissue (BAT) thermogenesis of HFD-fed mice were improved by LA supplementation. Together, these findings showed that LA supplementation alleviated HFD-induced estrous cycle irregularity, possibly associated with altered serum lipid metabolites, improved glucose metabolism, body energy metabolism, and BAT thermogenesis. These findings suggested the potential application of LA in alleviating obesity and its related reproductive disorders.


[Nephrotic syndrome with minimal glomerular lesions, sensitive to corticoids, disclosing a chordoid sarcoma].
A 65 year old woman had a minimal changes nephrotic syndrome (MCNS) with steroid-induced remission. An underlying malignancy was discovered at the time of relapse of proteinuria: it was a retroperitoneal chordoid sarcoma. Even though the tumor could not be excised, complete remission was again observed with corticosteroids. There was no second relapse when prednisone was discontinued and during the seven months before the patient died. This is a new unusual case of MCNS associated with carcinoma. The response of nephrotic syndrome steroid therapy is further suggestive evidence that deficiency in T-cell function may be involved.


Current status of radical prostatectomy for high-risk prostate cancer.
Despite the wide application of prostate-specific antigen-based screening leading to a profound stage migration in prostate cancer (PC), a significant percentage of men are still being diagnosed with clinically high-risk disease that requires aggressive treatment. Optimal management in these patients remains challenging, and strong advocates for radical prostatectomy (RP), radiotherapy, androgen deprivation therapy, and, increasingly, a multimodal approach abound. Currently, surgery for high-risk PC is frequently applied. RP offers an attractive opportunity for tumor excision either as a definitive management or as a first step in multimodal therapy. Nevertheless, this approach is still controversial. In this review, we discuss the current evidence for the role of RP in this clinical setting, including surgical considerations and outcomes. The role of robot-assisted RP, which is increasingly utilized in Korea in this clinical scenario, is discussed.


History of Family Involvement with Child Protective Services as a Risk Factor for Bullying in Ontario Schools.
The relationship between history of family involvement with child protective services (CPS) and bullying was examined. Data were obtained from 2,516 pupils aged 12-19 in the 2007 Ontario Student Drug Use and Health Survey. The association between self-reported history of family involvement with CPS and bullying was estimated using negative binomial hurdle regression models. Females who reported family CPS involvement were more likely to have bullied and been bullied compared with females without CPS involvement. Among males, family CPS involvement was only significantly associated with bully victimisation. A history of family CPS involvement was a risk factor for bullying victimisation and perpetration.


[Relationship of hypoxia-induced factor with tumor angiogenesis in early liver metastasis in colonic cancer].
To study the relationships of hypoxia-induced factor (HIF) with tumor angiogenesis and early liver metastasis in colonic cancer. Thirty three cases of colon cancer undergoing radical surgery were divided into two groups according to liver metastasis or not within half a year after operation. Expressions of HIF and vascular endothelial growth factor (VEGF) were examined using immunohistochemical method and tumor microvessel density (MVD) was measured in colonic cancer specimens. Fifteen cases developed early liver metastasis, while 18 did not. The positive rates of HIF and VEGF, and MVD were 86.7%, 66.7%, (57.9+/- 12.7)% respectively in the group with early liver metastasis, significantly higher than 44.4% (P< 0.05), 27.8% (P< 0.05) and (22.3+/- 10.2)% (P< 0.01) respectively in the group without early liver metastasis respectively. HIF can promote tumor angiogenesis in colonic cancer, and is closely related with early liver metastasis.


Spatial cognitive performance after chronic focal cerebral ischemia in rats.
The authors investigated the impairment of spatial cognitive performance in rats with chronic focal cerebral ischemia using the Morris maze, and examined the correlation between this deficit and other behavioral changes, such as step-through latency in passive avoidance task and neurologic score, or pathologic changes. The authors focused on the relationship between the damaged brain region and the affected spatial learning behavior. In the Morris maze task at 8 weeks after the middle cerebral artery (MCA) occlusion, escape latency, swimming path length, and percent time spent in goal quadrant of MCA-occluded rats were impaired, which correlated with shrinkage of the cortex involving parietal cortex, but not caudate-putamen (CP). Middle cerebral artery-occluded rats were also impaired in the percent time spent in the outermost annulus and in turning ratio, which significantly correlated with shrinkage of CP, but not cortex. Middle cerebral artery-occluded rats showed two typical search patterns; one was almost the same as that of sham-operated and intact rats, and the other was round shaped and had less turning behavior. Both subgroups of MCA-occluded rats divided by turning ratio had significantly impaired spatial cognitive performance, which indicates that the changes of search pattern did not affect cognitive performance in the Morris maze. The neurologic deficits recovered gradually after MCA occlusion, which correlated with shrinkage of cortex and CP. The step-through latency in passive avoidance task of the MCA-occluded rats was impaired, but did not correlate with shrinkage of cortex or CP. These results suggest that the long-term spatial cognitive deficit of MCA-occluded rats is in part associated with damage to the cortex involving parietal cortex, and that the change of search strategies is associated with damage to CP. These findings support the idea that different brain regions contribute differently to cognitive performance, search strategies, avoidance task, and neurologic performance, and may be useful for estimating the related region of functional disorder in the clinical situation.


Sexual selection can increase the effect of random genetic drift--a quantitative genetic model of polymorphism in Oophaga pumilio, the strawberry poison-dart frog.
The variation in color pattern between populations of the poison-dart frog Oophaga pumilio across the Bocas del Toro archipelago in Panama is suggested to be due to sexual selection, as two other nonsexually selecting Dendrobatid species found in the same habitat and range do not exhibit this variation. We theoretically test this assertion using a quantitative genetic sexual selection model incorporating aposematic coloration and random drift. We find that sexual selection could cause the observed variation via a novel process we call "coupled drift." Within our model, for certain parameter values, sexual selection forces frog color to closely follow the evolution of female preference. Any between-population variation in preference due to genetic drift is passed on to color. If female preference in O. pumilio is strongly affected by drift, whereas color in the nonsexually selecting Dendrobatid species is not, coupled drift will cause increased between-population phenotypic variation. However, with different parameter values, coupled drift will result in between-population variation in color being suppressed compared to its neutral value, or in little or no effect. We suggest that coupled drift is a novel theoretical process that could have a role linking sexual selection with speciation both in O. pumilio, and perhaps more generally.


Extended lower lid blepharoplasty for eyelid and midface rejuvenation.
Many techniques have been described for lower eyelid surgery, and the evolution of these procedures has seen significant advances, from simple skin excision to fat preservation and repositioning. Lower lid blepharoplasty can address lid-cheek junction and tear-trough deformities, which cause significant aesthetic concerns for patients, giving the appearance of fatigue and sadness. However, there is potential for serious functional and aesthetic complications, including dry eyes, scleral show, and ectropion. In addition, many surgeons perceive a steep learning curve and difficulty of reliably obtaining excellent cosmetic results. However, the authors have found that an extended lower blepharoplasty can significantly improve eyelid and midface contour, creating substantial aesthetic improvements without visible scars or an operated appearance. In this article, the authors review the relevant pathoanatomical causes of periorbital contour deformities and the evolution and history of lower eyelid surgery, and present the results of their extended blepharoplasty technique in over 300 patients. Therapeutic, V.


Thermochemical evidence for strong iodine chemisorption by ZIF-8.
For the first time, using aqueous solution calorimetry, we clearly identify the chemisorption of an unusually strong iodine charge-transfer (CT) complex within the cages of a metal-organic framework. Specifically, we studied the sorption of iodine gas in zeolitic imidazolate framework-8 (ZIF-8, Zn(2-methylimidazolate)2). Two iodine-loaded ZIF-8 samples were examined. The first, before thermal treatment, contained 0.17 I2/Zn on the surface and 0.59 I2/Zn inside the cage. The second sample was thermally treated, leaving only cage-confined iodine, 0.59 I2/Zn. The energetics of iodine confinement per I2 (relative to solid I2) in ZIF-8 are ΔHads = -41.47 ± 2.03 kJ/(mol I2) within the cage and ΔHads = -18.06 ± 0.62 kJ/(mol I2) for surface-bound iodine. The cage-confined iodine exhibits a 3-fold increase in binding energy over CT complexes on various organic adsorbents, which show only moderate exothermic heats of binding, from -5 to -15 kJ/(mol I2). The ZIF-8 cage geometry allows each iodine atom to form two CT complexes between opposing 2-methylimidazolate linkers, creating the ideal binding site to maximize iodine retention.


IgG subclass and heavy chain domains contribute to binding and protection by mAbs to the poly γ-D-glutamic acid capsular antigen of Bacillus anthracis.
Bacterial capsules are common targets for antibody-mediated immunity. The capsule of Bacillus anthracis is unusual among capsules because it is composed of a polymer of poly-γ-d-glutamic acid (γdPGA). We previously generated murine IgG3 monoclonal antibodies (mAbs) to γdPGA that were protective in a murine model of pulmonary anthrax. IgG3 antibodies are characteristic of the murine response to polysaccharide antigens. The goal of the present study was to produce subclass switch variants of the γdPGA mAbs (IgG3 → IgG1 → IgG2b → IgG2a) and assess the contribution of subclass to antibody affinity and protection. Subclass switch antibodies had identical variable regions but differed in their heavy chains. The results showed that a switch from the protective IgG3 to IgG1, IgG2b or IgG2a was accompanied by i) a loss of protective activity ii) a change in mAb binding to the capsular matrix, and iii) a loss of affinity. These results identify a role for the heavy chain constant region in mAb binding. Hybrid mAbs were constructed in which the CH1, CH2 or CH3 heavy chain constant domains from a non-protective, low binding IgG2b mAb were swapped into the protective IgG3 mAb. The IgG3 mAb that contained the CH1 domain from IgG2b showed no loss of affinity or protection. In contrast, swapping the CH2 or CH3 domains from IgG2b into IgG3 produced a reduction in affinity and a loss of protection. These studies identify a role for the constant region of IgG heavy chains in affinity and protection against an encapsulated bacterial pathogen.


Revision of the family Sphyriocephalidae Pintner, 1913 (Cestoda: Trypanorhyncha), with the description of Heterosphyriocephalus encarnae n. sp. and redescriptions of two species of Sphyriocephalus.
The family Sphyriocephalidae Pintner, 1913, which comprises the genera Hepatoxylon Bosc, 1811, Sphyriocephalus Pintner, 1913 and Heterosphyriocephalus Palm, 2004, is revised from newly-collected and museum material. Heterosphyriocephalus encarnae n. sp. is described from the pelagic thresher, Alopias pelagicus Nakamura (Lamniformes: Alopiidae) collected from the Pacific Ocean off Boca del Alamo, Mexico. This species can be readily distinguished from the rest of sphyriocephalids by its small size, low number of proglottids and long velum with a characteristically irregular and folded border, among other features. The tentacles show a distinctive basal armature, and a heteroacanthous typical metabasal armature with heteromorphous hooks. Redescriptions are provided for Sphyriocephalus tergestinus Pintner, 1913 and S. viridis (Wagener, 1854) Pintner 1913 based on novel morphological data. A phylogenetic analysis including the available sequences of sphyriocephalid species plus new generated sequences of S. tergestinus has been performed, from which S. tergestinus is allocated into Heterosphyriocephalus as H. tergestinus n. comb. New dichotomous keys for the determination of genera of Sphyriocephalidae are provided, as well as new generic diagnoses for Sphyriocephalus and Heterosphyriocephalus and keys for the determination of species within both genera. Although the morphology of the genus Hepatoxylon is not addressed in the present study, the available sequence of the type-species has been incorporated in the phylogenetic analysis and its relationship to the other two genera of the family is discussed.


Giordano Bruno and the heresy of many worlds.
This paper analyses the importance of Giordano Bruno's belief in many worlds, including the Moon, the planets and the stars, in the context of his trial by the Inquisitions in Venice and Rome. Historians have claimed that this belief was not heretical and therefore was not a major factor in Bruno's trial or execution. On the contrary, by examining neglected treatises on theology, heresies and Catholic canon law, I show that the belief in many worlds was formally heretical. Multiple Christian authorities denounced it. A systematic analysis of the extant primary sources shows that Bruno's belief in many worlds was, surprisingly, of primary importance in his trial and execution. The evidence includes recent and newly discovered primary sources.


Gender disparities in the National Institutes of Health funding for hematologic malignancies and cellular therapies.
We investigated gender inequality in the National Institutes of Health (NIH) funding for hematologic malignancies and cellular therapies (HMCT). The data were retrieved from the NIH Research Portfolio Online Reporting Tools (RePORT). In 2018-2019, 1834 grants totaling $799 million were awarded (men 71% vs. women 29%) to 975 principal investigators (PIs), including 680 (70%) male PIs and 295 (30%) female PIs. There was no significant gender difference in the mean grant amount per PI. Male PIs as compared to female PIs had a higher h-index (44 vs 31, p < 0.001), a higher number of publications (159.5 vs 94, p < 0.001), and higher years of active research (26 vs 21, p < 0.001). In multivariate analyses, a higher h-index independently predicted a higher mean grant amount per PI (p = 0.010), and female PIs were independently less likely to have a higher h-index (p < 0.001). Our study shows significant gender disparity in the NIH funding for HMCT research.


The radiographic detection of initial carious lesions on the proximal surfaces of teeth. Part I. The influence of exposure conditions.
The relationship between a number of technical exposure conditions and the diagnostic value of bitewing radiographs in the interpretation of initial proximal carious lesions was evaluated. The most important exposure factors for radiographs are tube voltage, filtration, and exposure time. Tube voltage and filtration were found to have an insignificant influence on the diagnostic quality. Exposure time proved to be the most critical factor in influencing diagnostic quality. The greatest difference in diagnostic quality, however, was caused by differences between observers.


Oats Tolerant of Pseudomonas syringae pv. tabaci Contain Tabtoxinine-beta-Lactam-Insensitive Leaf Glutamine Synthetases.
Pseudomonas syringae pv. tabaci, a commonly recognized leaf pathogen of tobacco, can infest the rhizosphere of many plants, including oats. Normal oat plants do not survive this infestation as a consequence of the complete and irreversible inactivation of all of their glutamine synthetases by tabtoxinine-beta-lactam (TbetaL), a toxin released by pv. tabaci. We have identified a population of oat (Avena sativa L. var Lodi) plants that are tolerant of pv. tabaci. The tolerant plants had no detectable TbetaL-detoxification mechanisms. Pathogen growth on these plant roots was not inhibited. These plants contain leaf glutamine synthetases (GS(1) and GS(2)) that were less sensitive to inactivation by TbetaL in vitro; these GSs have normal K(m) values for glutamate and ATP when compared with those of GS in control plants. Root glutamine synthetase of the tolerant plants was inactivated in vivo during infestation by the pathogen or by TbetaL in vitro. When growing without pv. tabaci, the tolerant plants contained normal levels of glutamine synthetase in their roots and leaves and normal levels of protein, ammonia, glutamate, and glutamine in their leaves. However, when the tolerant plants' rhizosphere was infested with pv. tabaci, the plant leaves contained elevated levels of glutamine synthetase activity, protein, ammonia, glutamate, and glutamine. No changes in glutamate dehydrogenase activity were detected in leaves and roots of pathogen-infested tolerant plants.


RFLP markers show genetic recombination in Botryotinia fuckeliana (Botrytis cinerea) and transposable elements reveal two sympatric species.
Molecular markers revealed that Botryotinia fuckeliana (the teleomorph of Botrytis cinerea), a haploid, filamentous, heterothallic ascomycete, contained a large amount of intrapopulation genetic variation. The markers were used to determine the mode of reproduction and the population structure of this fungus. We did not detect any differentiation between isolates from different organs, collection dates, varieties of grape, or locations in the Champagne region of France, but two unexpected sympatric populations were identified. One group of isolates (transposa) contained the transposable elements Boty and Flipper; the other (vacuma) did not. These groups differed from one another for all the other markers. RFLP markers showed that there was genetic recombination in both groups of isolates. We conclude that there are two sympatric populations of B. fuckeliana in Champagne. One species (transposa) seems to be local and well adapted, while the other one (vacuma) is presumably a heterogeneous migrant population.


Aggravation of ovalbumin-induced murine asthma by co-exposure to desert-dust and organic chemicals: an animal model study.
The organic chemicals present in Asian sand dust (ASD) might contribute to the aggravation of lung eosinophila. Therefore, the aggravating effects of the Tar fraction from ASD on ovalbumin (OVA)-induced lung eosinophilia were investigated. The Tar fraction was extracted from ASD collected from the atmosphere in Fukuoka, Japan. ASD collected from the Gobi desert was heated at 360°C to inactivate toxic organic substances (H-ASD). ICR mice were instilled intratracheally with 12 different test samples prepared with Tar (1 μg and 5 μg), H-ASD, and OVA in a normal saline solution containing 0.02% Tween 80. The lung pathology, cytological profiles in the bronchoalveolar lavage fluid (BALF), inflammatory cytokines/chemokines in BALF and OVA-specific immunoglobulin in serum were investigated. Several kinds of polycyclic aromatic hydrocarbons (PAHs) were detected in the Tar sample. H-ASD + Tar 5 μg induced slight neutrophilic lung inflammation. In the presence of OVA, Tar 5 μg increased the level of eosinophils slightly and induced trace levels of Th2 cytokines IL-5 and IL-13 in BALF. Also mild to moderate goblet cell proliferation and mild infiltration of eosinophils in the submucosa of airway were observed. These pathological changes caused by H-ASD + OVA were relatively small. However, in the presence of OVA and H-ASD, Tar, at as low a level as 1 μg, induced severe eosinophil infiltration and proliferation of goblet cells in the airways and significantly increased Th2 cytokines IL-5 and IL-13 in BALF. The mixture showed an adjuvant effect on OVA-specific IgG1 production. These results indicate that H-ASD with even low levels of Tar exacerbates OVA-induced lung eosinophilia via increases of Th2-mediated cytokines. These results suggest that ASD-bound PAHs might contribute to the aggravation of lung eosinophila.