Epithelial-mesenchymal transition, and collective and individual cell migration regulate epithelial changes in the amikacin-damaged organ of Corti.
Characterizing the microenvironment of a damaged organ of Corti and identifying the basic mechanisms involved in subsequent epithelial reorganization are critical for improving the outcome of clinical therapies. In this context, we studied the expression of a variety of cell markers related to cell shape, cell adhesion and cell plasticity in the rat organ of Corti poisoned with amikacin. Our results indicate that, after severe outer hair cell losses, the cytoarchitectural reorganization of the organ of Corti implicates epithelial-mesenchymal transition mechanisms and involves both collective and individual cell migratory processes. The results also suggest that both root cells and infiltrated fibroblasts participate in the homeostasis of the damaged epithelium, and that the flat epithelium that may emerge offers biological opportunities for late regenerative therapies.


Impact of Riehl's melanosis on quality of life in Korean patients: A cross-sectional comparative study.
The prevalence of Riehl's melanosis in Korea is increasing. However, little is known about the psychosocial burden of patients with Riehl's melanosis. This study was aimed to examine the level of psychosocial impact of Riehl's melanosis. A cross-sectional study recruited 52 patients with Riehl's melanosis who were asked to complete questionnaires requesting demographic characteristics, the Dermatology Life Quality Index (DLQI) and Melasma Quality of Life Scale (MELASQOL). The mean score of DLQI and MELASQOL was increased in patients with Riehl's melanosis compared with that of patients with melasma and healthy controls, respectively. Of note, patients with a long duration of illness, of lower educational level and suffering comorbid disease are more associated with impairment in quality of life. Riehl's melanosis poses serious negative impacts on the quality of life of the patients. Therefore, the psychological burden of patients with Riehl's melanosis should be carefully considered.


Cervical cancer screening - The challenges of complete pathways of care in low-income countries: Focus on Malawi.
Cervical cancer is the fourth most common cancer among women globally, with approximately 580,000 new diagnoses in 2018. Approximately, 90% of deaths from this disease occur in low- and middle-income countries, especially in areas of high HIV prevalence, and largely due to limited prevention and screening opportunities and scarce treatment options. In this overview, we describe the opportunities and challenges faced in many low- and middle-income countries in delivery of cervical cancer detection, treatment and complete pathways of care. In particular, drawing on our experience and that of colleagues, we describe cervical screening and pathways of care provision in Malawi, as a case study of a low-resource country with high incidence and mortality rates of cervical cancer. Screening methods such as cytology - although widely used in high-income countries - have limited relevance in many low-resource settings. The World Health Organization recommends screening using human papillomavirus testing wherever possible; however, although human papillomavirus primary testing is more sensitive and detects precancers and cancers earlier than cytology, there are currently costs, infrastructure considerations and specificity issues that limit its use in low- and middle-income countries. The World Health Organization accepts the alternative screening approach of visual inspection with acetic acid as part of 'screen and treat' programmes as a simple and inexpensive test that can be undertaken by trained health workers and hence give wider screening coverage; however, subjectivity and variability in interpretation of findings between providers raise issues of false positives and overtreatment. Cryotherapy using either nitrous oxide or carbon dioxide is an established treatment for precancerous lesions within 'screen and treat' programmes; more recently, thermal ablation has been recognized as suitable to low-resource settings due to lightweight equipment, short treatment times, and hand-held battery-operated and solar-powered models. For larger lesions and cancers, complete clinical pathways (including loop excision, surgery, radiotherapy, chemotherapy and palliative care) are required for optimal care of women. However, provision of each of these components of cancer control is often limited due to limited infrastructure and lack of trained personnel. Hence, global initiatives to reduce cervical mortality need to adopt a holistic approach to health systems strengthening.


Polypharmacy, Infectious Diseases, Sexual Behavior, and Psychophysical Health Among Anabolic Steroid-Using Homosexual and Heterosexual Gym Patrons in San Francisco's Castro District.
Limited studies based in England and Australia reported misuse of anabolic-androgenic steroids (AAS) among homosexual men to enhance body image. Anecdotally, AAS are also being misused by homosexual men in the United States. Since many AAS and certain performance enhancing drugs (PEDs) are administered via injection, this poses a potential vector for the spread of infectious disease in an already at-risk population. This study compared and contrasted homosexual and heterosexual male gym clients regarding use of AAS and PEDs, use of alcohol and illicit drugs, seroprevalence of infectious disease, engagement in risky injection practices and sexual behaviors, and presence of psychiatric conditions. Recruitment and data collection occurred outside four exercise gyms in the San Francisco Castro District area between October 25, 2014 and March 10, 2015. Two hundred and twenty homosexual men and 73 heterosexual men completed the 114-item cross-sectional survey. Ten percent of homosexual men reported lifetime AAS use. Homosexual men had almost four times more sexual partners and were over 14 times more likely to knowingly have unprotected intercourse with a known HIV positive person than heterosexual men. In addition, a quarter of homosexual men who injected drugs admitted to sharing used syringes or needles with another person. Conclusions/Importance: The current study is the first to confirm AAS use among homosexual men in the United States. Homosexual men partook in high-risk sexual behaviors and injection practices which may place them at greater risks for contracting and spreading HIV and other infectious diseases.


Why Do They Just Sit? Apathy as a Core Symptom of Alzheimer Disease.
Apathy is common in Alzheimer disease (AD) and has a far-reaching impact on patients' clinical course and management needs. However, it is unclear if apathy is an integral component of AD or a manifestation of depression in cognitive decline. This study aims to examine interrelationships between apathy, depression, and function. This was a cross-sectional study of well-characterized AD patients in the National Alzheimer's Coordinating Center Uniform Data Set with a Clinical Dementia Rating (CDR) between 0.5 and 2. Participants' function was measured using the Functional Assessment Questionnaire. Apathy and depression were measured using clinician judgment and informant-reported Neuropsychiatric Inventory-Questionnaire. Dementia severity was categorized by CDR. Sample included 7,679 participants (55.7% men) with a mean (standard deviation) age of 74.9 (9.7) years; 3,197 (41.6%) had apathy based on clinician judgment. Among those with apathy, approximately half had no depression. Presence of apathy was associated with 21%, 10%, and 3% worsening in function compared with those without apathy in CDR 0.5, 1, and 2 groups, respectively. Depression was not independently associated with functional status. Results revealed no interaction between apathy and depression. Apathy, but not depression, was significantly associated with worse function, with the strongest effects in mild dementia. Results emphasize the need for separate assessments of apathy and depression in the evaluation and treatment of patients with dementia. Understanding their independent effects on function will help identify patients who may benefit from more targeted management strategies.


Explicitly Correlated Orbital Optimized Contracted Pair Correlation Methods: A Short Overview.
Designing efficient algorithms to apply highly accurate pair correlation methods to large molecules of scientific interest has remained an important field of research for a long period of time. We present a new approach toward fast algorithms, which represents an interesting alternative and extension to currently existing methods. The presented new contraction scheme saves a significant amount of memory and can be easily combined with efficient linear scaling algorithms. Additionally, the extension to orbital optimization and explicitly correlated f12-theory is demonstrated to further improve accuracy and applicablility.


Grounded in Community: Development of a Birth Justice-Focused Volunteer Birth Companion Program.
Continuous labor support is an evidence-based practice demonstrated to improve birth outcomes, particularly when provided by a trained doula or birth companion. Access to doula services designed to meet the needs of historically underserved and diverse communities can mitigate the negative effects of structural racism and health disparities in perinatal care. Unfortunately, continuous labor support by a companion of choice is not universally supported. This leaves individuals with limited resources unable to access services from a trained doula. Volunteer birth companion programs are one model for increasing access to continuous labor support by bringing the community into the hospital. This article describes a birth justice-focused volunteer birth companion program that evolved out of a multistakeholder collaboration between community birth workers, local reproductive justice organizations, and hospital-based providers, staff, and administrators in direct response to community needs. This program is unique in its collaborative development, grounding in core values, and design of a reproductive justice-focused curriculum that includes training in diversity, inclusion, and care for clients with a history of trauma or perinatal substance use. Key takeaways include recommendations to center client needs, consider sustainability, and embrace flexibility and change. Discussion includes recognition of the strengths and limitations of a volunteer-based model, including acknowledgment that volunteer birth work, while filling an important gap, necessitates the privilege of having sufficient time, economic freedom, and social support. Ensuring universal insurance coverage for doula services has the potential to increase access to continuous labor support, improve birth outcomes, and diversify the birth workforce.


Ultra-compact silicon-microcap based improved Michelson interferometer high-temperature sensor.
An ultra-short high-temperature fiber-optic sensor based on a silicon-microcap created by a single-mode fiber (SMF) and simple fusion splicing technology is proposed and experimentally demonstrated. A section of the SMF with a silicon-microcap at one end is connected to the "peanut" structure to build the microcap-based optical fiber improved Michelson interferometer (MI). The optimal discharge parameters of microcap and length of SMF has been investigated to achieve the best extinction ratio of 6.61 dB. The size of this microcap-based improved MI sensor is 560 µm and about 18 times shorter compared to the current fiber tip interferometers (about 10 mm). Meanwhile, it showed good robustness during the two heating-cooling cycles and the duration period stability test at 900 °C. This microcap-based improved MI sensor with the smaller size, simple fabrication, low cost, high reliability, and good linearity within a large dynamic range is beneficial to practical temperature measurement and massive production.


Glucocorticoids may not inhibit plasma exudation by direct vascular antipermeability effects in human airways.
In animal airways, single topical treatment with glucocorticoids produces a prompt vascular anti-permeability effect that may last for several hours. This has been considered a potentially important anti-inflammatory action in human airways. The present study, involving nine healthy subjects, examines whether nasal budesonide application affects histamine-induced mucosal exudation of plasma and plasma-derived mediators in human airways. A selected low concentration (40 micrograms.ml-1) of the vascular permeability-inducing agent histamine was kept in one of the nasal cavities for 10 min, and this challenge was repeated at 50 min intervals over 4 h. Ten minutes after the first histamine-challenge, a clinical dose of budesonide (100 micrograms) was sprayed into the same nasal cavity. Nasal lavage fluid levels of albumin and fibrinogen were measured as indices of mucosal exudation of bulk plasma, and bradykinins were analysed to indicate generation of plasma-derived mediators. The baseline levels of albumin and fibrinogen were evaluated in 24 healthy control subjects by means of a 10 min saline lavage. Histamine produced significant mucosal exudation of albumin and fibrinogen, compared to control subjects. Topical budesonide treatment did not affect the histamine-induced mucosal exudation of albumin or fibrinogen, nor did budesonide affect the mucosal output of bradykinins. The present human airway data do not support the view, based on animal findings, that airway glucocorticoids reduce mucosal exudation of plasma by direct vascular effects. We suggest that anti-exudative effects of topical glucocorticoids in airway diseases indirectly reflect the inhibition of cellular inflammatory processes by these drugs, rather than any direct effects on the airway microcirculation.


Recommendations for nurse practitioner residency programs.
The purpose of this study was to identify and prioritize critical aspects needed in the design and execution of new nurse practitioner (NP) residency programs. Subjects answered a series of questions on formulating residency programs and on key outcomes and cost measures related to their sustainability. These results serve as potential guideposts for future work in NP residency standardization and sustainability development.


Effects of varying intraperitoneal pressure on liver function tests during laparoscopic cholecystectomy.
Laparoscopic cholecystectomy at standard-pressure pneumoperitoneum uses a pressure of 12-14 mm Hg, which may cause a variety of adverse physiological changes involving the respiratory, cardiovascular, and hepatorenal systems reflected as subclinical abnormalities in biochemical parameters. The use of low-pressure pneumoperitoneum in the range of 8-10 mm Hg has been shown to reduce the adverse physiological changes without affecting the outcome of surgery. This study was done in a randomized controlled manner. Patients with gallstone disease (n=101) underwent laparoscopic cholecystectomy. Patients were randomly assigned to high-pressure laparoscopic cholecystectomy (HPLC) (n=51) and low-pressure laparoscopic cholecystectomy (LPLC) (n=50) and underwent surgery at pressures of 14 mm Hg and 8 mm Hg, respectively. Liver function tests, including total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase, were obtained preoperatively and on postoperative Days 1 and 7. The two study groups had similar demographic profiles, and there were no significant differences in the operative time (HPLC, 47.25 ± 6.73 minutes; LPLC, 48.00 ± 7.76 minutes; P=.6071) and pneumoperitoneum time (HPLC, 34.02 ± 5.29 minutes; LPLC, 34.60 ± 6.13 minutes; P=.6115). On postoperative Day 1, the total bilirubin levels were 1.0684 ± 0.4108 mg/dL and 0.8926 ± 0.3162 mg/dL for HPLC and LPLC (P=.0179), respectively, AST levels were 66.0810 ± 25.5868 IU/L and 42.2420 ± 14.7301 IU/L (P=.0001), respectively, and ALT levels were 68.1410 ± 31.4572 IU/L and 42.7460 ± 17.9405 IU/L (P=.0001), respectively. Thus, liver enzyme activities were significantly elevated in the HPLC group compared with the LPLC group. LPLC causes less abnormality in liver function tests in the postoperative period compared with HPLC. LPLC should be considered in all patients undergoing laparoscopic cholecystectomy, especially those patients with compromised liver functions.


Reduced-rank hazard regression for modelling non-proportional hazards.
The Cox proportional hazards model is the most common method to analyse survival data. However, the proportional hazards assumption might not hold. The natural extension of the Cox model is to introduce time-varying effects of the covariates. For some covariates such as (surgical)treatment non-proportionality could be expected beforehand. For some other covariates the non-proportionality only becomes apparent if the follow-up is long enough. It is often observed that all covariates show similar decaying effects over time. Such behaviour could be explained by the popular (gamma-) frailty model. However, the (marginal) effects of covariates in frailty models are not easy to interpret. In this paper we propose the reduced-rank model for time-varying effects of covariates. Starting point is a Cox model with p covariates and time-varying effects modelled by q time functions (constant included), leading to a pxq structure matrix that contains the regression coefficients for all covariate by time function interactions. By reducing the rank of this structure matrix a whole range of models is introduced, from the very flexible full-rank model (identical to a Cox model with time-varying effects) to the very rigid rank one model that mimics the structure of a gamma-frailty model, but is easier to interpret. We illustrate these models with an application to ovarian cancer patients.


Quantification of radiation dose savings in cardiac computed tomography using prospectively triggered mode and ECG pulsing: a phantom study.
To quantify radiation dose reduction in cardiac computed tomography (CT) using a prospectively triggered mode compared with a retrospective ECG-gated helical mode. Absorbed organ doses in cardiac 64-row multidetector CT were quantified using an anthropomorphic male Alderson phantom with 74 thermoluminescence dosimeters. Three different imaging protocols were applied: retrospective ECG-gating, retrospective ECG-gating with additional ECG-pulsing, and a prospectively triggered mode. The measured organ doses were compared with dose estimation by a mathematical phantom. Compared with the retrospective ECG-gating mode, the mean relative organ doses were reduced by 44% using ECG pulsing and by 76% using the prospectively triggered mode. The range of dose savings varied from 34% to 49% using ECG pulsing and from 65% to 87% using the prospectively triggered mode. The effective dose was 16.5 mSv using retrospective gating, 9.2 mSv using retrospective gating with ECG pulsing and 4.0 mSv using the prospectively triggered mode. Our measurements confirm the high dose-saving potential of the prospectively triggered technique in cardiac CT. The reduction in the organ doses measured corresponds to estimates determined by the mathematical phantom. The effective dose calculated by the mathematical phantom was, in some cases, significantly lower than that calculated using the anthropomorphic phantom.


Carcinoid tumors. An analysis of 2,837 cases.
Two thousand eight hundred thirty-seven cases of carcinoid tumor from files at the National Cancer Institute were analyzed statistically. Tumors were found in the lung, ovary, and biliary and gastrointestinal tracts. Most were in the appendix, rectum, and ileum. Age-adjusted incidence rates were higher for black males, except for lung carcinoids. Carcinoids showed several differences from other kinds of tumor, including a low age for appendiceal and lung cases and low male/female and black/white ratios in the lung. Percentages of concurrent neoplasms and multiple carcinoids were low compared to other series. Five-year relative survival rates ranged from 99% (appendix) to 33% (sigmoid colon). Survival for colon cases was not so low as expected on the basis of the high rate of metastasis. Some appendiceal carcinoids were metastatic and may have killed 1 patient. Findings are compared with other studies.


The chirality of a twist-bend nematic phase identified by NMR spectroscopy.
One of the defining characteristics of the twist-bend nematic phase, formed by the methylene-linked liquid crystal dimer 1″,7″-bis(4-cyanobiphenyl-4'-yl) heptane (CB7CB), is its chirality. This new nematic phase, predicted by Dozov, is of particular interest because although the constituent molecules are achiral the phase itself is chiral. Here, we describe the use of NMR spectroscopy to determine experimentally whether in reality the phase is chiral or not. The basis of this novel procedure is that the equivalence of the protons or deuterons in a prochiral methylene group in a nematic phase with D∞h symmetry is lost in a chiral phase because its symmetry is reduced to D∞ on removal of the mirror plane. Recording proton-enhanced local field (PELF) NMR experiments shows that in the standard nematic phase all of the methylene groups in the heptane spacer have equivalent pairs of C-H groups but this equivalence is lost for the six prochiral methylene groups with their enantiotopic protons on passing to the twist-bend nematic. Strikingly, this equivalence is not lost for the central methylene group where the two protons are homotopic. We also show how the phase chirality can be demonstrated with probe molecules which contain deuteriated prochiral methylene groups, using 4-octyl-4'-cyanobiphenyl-d2, perdeuteroacenaphthene-d10, and acenaphthene-d4 as examples. For the standard nematic phase deuterium, NMR shows that the deuterons in these methylene groups are equivalent but, as expected, in the twist-bend nematic phase this equivalence is lost. The deuterium NMR spectra of these probe molecules dissolved in CB7CB have been recorded from the isotropic phase, through the nematic and deep into the supercooled twist-bend nematic.


Determination of chiral asymmetries in the valence photoionization of camphor enantiomers by photoelectron imaging using tunable circularly polarized light.
An electron imaging technique has been used to study the full angular distribution of valence photoelectrons produced from enantiomerically pure molecular beams of camphor when these are photoionized with circularly polarized light. In addition to the familiar beta parameter, this provides a new chiral term, taking the form of an additional cosine function in the angular distribution which consequently displays a forward-backward electron ejection asymmetry. Several ionization channels have been studied using synchrotron radiation in the 8.85-26 eV photon energy range. With alternating left and right circularly polarized radiations the photoelectron circular dichroism (PECD) in the angular distribution can be measured and shows some strong dynamical variations with the photon energy, depending in sign and intensity on the ionized orbital. For all orbitals the measured PECD has a quite perfect antisymmetry when switching between R and S enantiomers, as expected from theory. In the HOMO(-1) channel the PECD chiral asymmetry curves show a double maxima reaching nearly 10% close to threshold, and peaking again at approximately 20% some 11 eV above threshold. This is attributed to a resonance that is also visible in the beta parameter curve. Newly optimized CMS-Xalpha photoionization dynamics calculations are also presented. They are in reasonably good agreement with the experimental data, including in the very challenging threshold regions. These calculations show that PECD in such randomly oriented samples can be understood in the electric dipole approximation and that, unlike the case pertaining in core-shell ionization-where a highly localized achiral initial orbital means that the dichroism arises purely as a final state scattering effect-in valence shell ionization there is a significant additional influence contributed by the initial orbital density.


Transcription factors SF1 and cJUN cooperate to activate the Fdx1 promoter in MA-10 Leydig cells.
The Ferredoxin 1 (FDX1) protein supports steroid biosynthesis in steroidogenic cells through electron transfer to the rate-limiting steroidogenic enzyme, CYP11A1. The latter catalyzes the conversion of cholesterol to pregnenolone through side chain cleavage inside the mitochondria. Thus far, only several transcription factors have been implicated in the regulation of mouse Fdx1 promoter activity in Leydig cells. These include the nuclear receptor SF1 and SP1. Since two conserved regulatory elements for AP1 transcription factors have been located at -764 and -617bp of the Fdx1 promoter, we hypothesized that cJUN may cooperate with other partners to regulate Fdx1 in Leydig cells. Indeed, we report that SF1 and cJUN interact and cooperate to activate the Fdx1 promoter in MA-10 and TM3 Leydig cells. Furthermore, we found that such activation requires different regulatory elements located between -124 and -306bp of the Fdx1 promoter and involves recruitment of SF1 to this region. Using RNA interference, the importance of SF1 in transcriptional regulation of Fdx1 was confirmed, whereas cJUN was dispensable even though it cooperated with SF1 to upregulate Fdx1 expression in MA-10 cells. Thus, our data provides new insights in the molecular mechanisms that control mouse Fdx1 transcription, possibly leading to regulation of CYP11A1 enzyme activation, in Leydig cells.


Association of interleukin-2 and interferon-γ single nucleotide polymorphisms with Juvenile systemic lupus erythematosus.
Juvenile systemic lupus erythematosus (JSLE) is a severe and chronic autoimmune disease of unknown origin. Inflammatory cytokines can play a pivotal role in the pathogenesis of JSLE, while their secretion is under genetic control. The current investigation was performed to analyse the associations of particular single nucleotide polymorphisms (SNPs) of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) genes in a case control study. The allele, genotype and haplotype frequencies of the polymorphic IL-2 (G/T at -330, rs2069762, and G/T at +166, rs2069763) and IFN-γ (A/T at +874, rs2430561) genes were estimated in 59 patients with JSLE by contrast with 140 healthy controls using polymerase chain reaction with sequence-specific primers method. Results of the analysed data revealed a negative allelic association for JSLE in IL-2 -330/T (P=0.02), as well as a positive allelic association for IL-2 -330/G (P=0.02). IL-2 GG genotype (-330) in the patient group was also significantly overrepresented (P<0.001), while IL-2 GT genotype (-330) was notably decreased in the patients with JSLE (P<0.001). Additionally, the frequency of IL-2 (-330, +166) GT haplotype was significantly higher in the patient group (P<0.001). IL-2 cytokine gene polymorphisms could affect individual susceptibility to JSLE and can take on the role of possible genetic markers for vulnerability to JSLE.


In vitro studies of erythropoietic progenitors (CFU-E) in marrow from neonatal and young mice.
Reports that cells from neonatal animals produce CFU-E in response to erythropoietin (Ep) at doses lower than are required by adults indicated that young mice would provide a good system to study the hormone response of erythropoietic progenitors. Studies presented here confirm the increased Ep responsiveness until 3-4 weeks of age reported previously by others. Along with the enhancement in their Ep responsiveness, bone marrow cells from young animals produce many more CFU-E per 10(5) cells plated than do adult animals; i.e., neonates have a higher plating efficiency for CFU-E in the presence of erythropoietin. Neonatal animals, in contrast to adults, contain in addition erythropoietic progenitors in their bone marrow capable of growth in vitro without added hormone. Because of the large numbers of "endogenous" colonies, a study was done to explore the possibility that a small amount of Ep was present in the culture medium. Antiserum to erythropoietin was added directly to cultures in another study to remove any undetected hormone. The results indicate that CFU-E from neonatal mouse bone marrow can develop in culture in the absence of detectable Ep.


Predicting In-State Workforce Retention After Graduate Medical Education Training.
There is a paucity of literature when it comes to identifying predictors of in-state retention of graduate medical education (GME) graduates, such as the demographic and educational characteristics of these physicians. The purpose was to use demographic and educational predictors to identify graduates from a single Michigan GME sponsoring institution, who are also likely to practice medicine in Michigan post-GME training. We included all residents and fellows who graduated between 2000 and 2014 from 1 of 18 GME programs at a Michigan-based sponsoring institution. Predictor variables identified by logistic regression with cross-validation were used to create a scoring tool to determine the likelihood of a GME graduate to practice medicine in the same state post-GME training. A 6-variable model, which included 714 observations, was identified. The predictor variables were birth state, program type (primary care versus non-primary care), undergraduate degree location, medical school location, state in which GME training was completed, and marital status. The positive likelihood ratio (+LR) for the scoring tool was 5.31, while the negative likelihood ratio (-LR) was 0.46, with an accuracy of 74%. The +LR indicates that the scoring tool was useful in predicting whether graduates who trained in a Michigan-based GME sponsoring institution were likely to practice medicine in Michigan following training. Other institutions could use these techniques to identify key information that could help pinpoint matriculating residents/fellows likely to practice medicine within the state in which they completed their training.


[Not Available].
This article sets out to explore the perception of pain during outbreaks of the plague in the early modern period. On the basis of the recent doubts about the mind/body dualism, it holds that both kinds of pain should be investigated and be seen as a whole. In the majority of the autobiographical sources the article relies on, there is no description of pain itself. Instead visual signs and its quantitative dimensions are given: the number of buboes and the length of the illness. This can partly be explained by the perspective of the sources but also points to a more general attitude prevailing at that time. However, that there is no description of pain is a statement which has to be qualified, particularly for those sources which describe the treatment of the buboes by the surgeons. Christian religion was the force that strongly influenced the perception of pain. It gave a meaning to suffering and it made quite a number of the sick concentrate on their duty as Christians and on the death and afterlife, thus partly disregarding pain, in particular when they had done penance and taken Holy Communion before. However, it sometimes also caused doubts about sinful behaviour before the plague. Pain however was aggravated by the way society and the authorities acted or were perceived to act. The pain of separation, and a feeling of loneliness and discrimination were connected with being infected. The article closes with some remarks on plague and gender. The fear of the plague and the plague itself cannot have meant the same to men and women, it argues.


MARTX toxins as effector delivery platforms.
Bacteria frequently manipulate their host environment via delivery of microbial 'effector' proteins to the cytosol of eukaryotic cells. In the case of the multifunctional autoprocessing repeats-in-toxins (MARTX) toxin, this phenomenon is accomplished by a single, >3500 amino acid polypeptide that carries information for secretion, translocation, autoprocessing and effector activity. MARTX toxins are secreted from bacteria by dedicated Type I secretion systems. The released MARTX toxins form pores in target eukaryotic cell membranes for the delivery of up to five cytopathic effectors, each of which disrupts a key cellular process. Targeted cellular processes include modulation or modification of small GTPases, manipulation of host cell signaling and disruption of cytoskeletal integrity. More recently, MARTX toxins have been shown to be capable of heterologous protein translocation. Found across multiple bacterial species and genera--frequently in pathogens lacking Type 3 or Type 4 secretion systems--MARTX toxins in multiple cases function as virulence factors. Innovative research at the intersection of toxin biology and bacterial genetics continues to elucidate the intricacies of the toxin as well as the cytotoxic mechanisms of its diverse effector collection.


Defective natural killer cell activity in a mouse model of eczema herpeticum.
Patients with atopic dermatitis (AD) are susceptible to several viruses, including herpes simplex virus (HSV). Some patients experience 1 or more episodes of a severe skin infection caused by HSV termed eczema herpeticum (EH). There are numerous mouse models of AD, but no established model exists for EH. We sought to establish and characterize a mouse model of EH. We infected AD-like skin lesions with HSV1 to induce severe skin lesions in a dermatitis-prone mouse strain of NC/Nga. Gene expression was investigated by using a microarray and quantitative PCR; antibody titers were measured by means of ELISA; and natural killer (NK) cell, cytotoxic T-cell, regulatory T-cell, and follicular helper T-cell populations were evaluated by using flow cytometry. The role of NK cells in HSV1-induced development of severe skin lesions was examined by means of depletion and adoptive transfer. Inoculation of HSV1 induced severe erosive skin lesions in eczematous mice, which had an impaired skin barrier, but milder lesions in small numbers of normal mice. Eczematous mice exhibited lower NK cell activity but similar cytotoxic T-cell activity and humoral immune responses compared with normal mice. The role of NK cells in controlling HSV1-induced skin lesions was demonstrated by experiments depleting or transferring NK cells. A murine model of EH with an impaired skin barrier was established in this study. We demonstrated a critical role of defective NK activities in the development of HSV1-induced severe skin lesions in eczematous mice.


Impact of parental presence during induction of anesthesia on anxiety level among pediatric patients and their parents: a randomized clinical trial.
Anesthesia induction is a stressful event for children and their parents, and may have potentially harmful consequences on the patient's physiological and mental situation. Stressful anesthesia induction has psychological adverse effects that recur with repeated anesthesia, can lead to increased pediatric discomfort during the recovery period, and may even induce reactionary postoperative behavior. A randomized controlled trial was performed to assess the impact of parental presence during induction of anesthesia (PPIA) on preoperative anxiety of pediatric patients and their parents at three different times, cooperation of child with anesthesiologist at induction of anesthesia, and parental satisfaction. A total of 96 pediatric patients undergoing elective minor surgery (ASA 1-2) were randomly divided into two groups. Both groups received oral midazolam (0.5 mg/kg) at least 20 minutes before surgery, but in the PPIA group, the parents were also present in the operating room until loss of consciousness of child at anesthesia induction. Anxiety in the patients (as measured by the modified Yale Preoperative Anxiety Scale [mYPAS]) and parents (as measured by the State and Trait Anxiety Inventory [STAI]), the Induction Compliance Checklist (ICC), and parental satisfaction (as measured by visual analog scale) were assessed. There was no significant difference in the mean anxiety scores (mYPAS) of participants in the control and PPIA groups at ward T0 and upon arrival to operating room T1 (P>0.05). However, between the PPIA and control groups, mean mYPAS score was different at the time of induction of anesthesia T2 (35.5±16.6 vs 59.8±22.4; P<0.001). The ICC scores showed that perfect score was significantly different in the PPIA and control groups (66.6% vs 6.3%; P<0.01). The STAI scores of the parents in the two groups did not differ in T0, T1, and T2. The mean parental satisfaction score was higher in the PPIA group than in the control group (7.6±7.0 vs 5.8±6.1; P<0.01). PPIA may reduce preoperative state anxiety of pediatric patients and improve quality of anesthesia induction based on ICC scores and higher parental satisfaction, but it does not impact on parental state anxiety.


Saturday-morning television: do sponsors promote high-risk behavior for burn injury?
Television has become an important tool for learning and socialization in children. Although television violence has been associated with adverse effects, data on depiction of fire and burn injury are lacking. We sought to determine whether Saturday-morning television programming, viewed primarily by children, depicts fire and burn injury as safe or without consequence, thus potentially increasing the incidence of burn injury in children. This was a prospective observational study. Saturday-morning children's television programs were videotaped from 7 AM to 11 AM for eight different television networks during a 6-month period. Tapes were scored for scenes depicting fire or smoke by independent observers. Recorded items included show category, scene type, gender target, context of fire, and outcome after exposure to flame. Fire events were documented during programs and their associated commercials. A total of 108 hours of children's programs, 16 hours per network, were recorded. Scenes depicting fire or smoke were identified 1960 times, with 39% of events occurring during the program itself and 61% in commercials. Fire was depicted as either safe or without consequence in 64% of incidents. Action adventure stories accounted for 56% of flame depictions. Overall, one incident involving flame and fire was portrayed for each 3 minutes of television programming. Saturday-morning television programming frequently depicts fire as safe, empowering, or exciting. The incidence of flame use in programming varies between stations but is most prevalent in action/adventure stories. Television commercials, although brief, provide the majority of the misinformation regarding fire. Medical professional societies should alert the public to this potential hazard and recommend responsible portrayal of fire in children's television programming.


Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing.
Massively parallel sequencing of DNA molecules in the plasma of pregnant women has been shown to allow accurate and noninvasive prenatal detection of fetal trisomy 21. However, whether the sequencing approach is as accurate for the noninvasive prenatal diagnosis of trisomy 13 and 18 is unclear due to the lack of data from a large sample set. We studied 392 pregnancies, among which 25 involved a trisomy 13 fetus and 37 involved a trisomy 18 fetus, by massively parallel sequencing. By using our previously reported standard z-score approach, we demonstrated that this approach could identify 36.0% and 73.0% of trisomy 13 and 18 at specificities of 92.4% and 97.2%, respectively. We aimed to improve the detection of trisomy 13 and 18 by using a non-repeat-masked reference human genome instead of a repeat-masked one to increase the number of aligned sequence reads for each sample. We then applied a bioinformatics approach to correct GC content bias in the sequencing data. With these measures, we detected all (25 out of 25) trisomy 13 fetuses at a specificity of 98.9% (261 out of 264 non-trisomy 13 cases), and 91.9% (34 out of 37) of the trisomy 18 fetuses at 98.0% specificity (247 out of 252 non-trisomy 18 cases). These data indicate that with appropriate bioinformatics analysis, noninvasive prenatal diagnosis of trisomy 13 and trisomy 18 by maternal plasma DNA sequencing is achievable.


Isolation of chlorophenoxy herbicides on columns of glass beads.
A method for the analysis of chlorophenoxy herbicide residues has been developed based on the observed adsorptive affinity of chlorophenoxy acids for glass surfaces. Extracted residues of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) herbicides are adsorbed onto a column of fine mesh glass beads, and subsequently esterified with diazomethane for gas-liquid chromatographic quantitation, using an electron capture detector. Prior to injection, the esterified sample is cleaned up by passing through a Florisil column. The method is sensitive to about 0.5 ppm 2,4-D and 0.01 ppm 2,4,5-T. Recoveries averaged from 81 to 101%, depending on the level added and the substrate.


Prevention and treatment of delirium in intensive care: Hermeneutics of experiences of the nursing team.
To understand the experiences in nursing care in the prevention and treatment of delirium in people hospitalized in intensive care units. Hermeneutic phenomenological qualitative study. The selection of participants was by intentional sampling: seven nursing assistants and eight nurses. Theoretical saturation was achieved. The phenomenological interview was applied to collect data from a central question and the analysis was carried out following the approaches of Heidegger's hermeneutical circle. Four significant themes emerged from the analysis: 1) Delirium prevention, 2) Pharmacological treatment, 3) Non-pharmacological treatment, and 4) Barriers to non-pharmacological treatment. These themes were accompanied by 35 interrelated units of meaning: in the first theme, the most repetitive units were communication, orientation, and family bonding; in the second was the use of pharmacological treatment only in the acute phase; in the third was the modification of the environment according to the patient's preference (where the family is a priority and strategies that provide cognitive and social stimulation can be reinforced), and in the fourth was the work overload for the nursing team. The experiences of the nursing team in the prevention and treatment of delirium in critically ill patients highlight that communication allows an approach to the patient as a human being immersed in a reality, with a personal history, needs and preferences. Therefore, family members must be involved in these scenarios, as they can complement and support nursing care.


Computer-simulation methods in the study of noncrystalline materials.
Computer-assisted physics can be considered the third approach besides experimental and theoretical physics. Numerical simulations are especially useful in the study of non-crystalline materials such as liquids, glasses, amorphous solids, and liquid crystals. Some applications of computer simulations to these materials are discussed.


Characterizations of CD4-1, CD4-2 and CD8β T cell subpopulations in peripheral blood leucocytes, spleen and head kidney of Japanese flounder (Paralichthys olivaceus).
In the previous study, antibodies against CD3 molecule have been produced and were used in labeling T cells in Japanese flounder (Paralichthys olivaceus). In this paper, CD4+ and CD8+ lymphocytes subpopulations in peripheral blood leucocytes (PBL), spleen and head kidney of flounder were investigated. The flounder CD4-1, CD4-2 and CD8β recombinant proteins and their antibodies (Abs) were produced, then the cross-reactivity of the Abs to CD4-1, CD4-2 and CD8β was detected by Western blotting, respectively, and the reactions of Abs to PBL were analyzed by immunofluorescence staining (IFS) and flow cytometry (FCM). CD4-1+/CD3+, CD4-2+/CD3+, and CD8β+/CD3+ lymphocytes in PBL, spleen and head kidney were observed by double IFS, then their proportions were analyzed using two-color FCM, respectively. Further, CD4-1/CD8β, CD4-2/CD8β, or CD4-1/CD4-2 lymphocytes were analyzed using double-IFS and two-color FCM. Finally, CD4-1+, CD4-2+, and CD8β+ lymphocytes in spleen and head kidney were observed by immunohistochemistry. The results showed that the Abs were specific for CD4-1, CD4-2 and CD8β molecules, respectively. The proportions of CD4-1+/CD3+, CD4-2+/CD3+, and CD8β+/CD3+ lymphocytes were 6.7±2.0%, 8.6±2.8%, 2.1±1.3% in PBL; 13.6±3.6%, 15.6±5.2%, 2.8±1.4% in spleen; 20.0±4.6%, 20.5±4.6%, 3.2±1.5% in head kidney, respectively. Most CD4+ and CD8+ cell subpopulations belonged to CD3+ cells; there were no cross-reactivity between CD4+ and CD8+ cells. CD4-1+/CD4-2-, CD4-1-/CD4-2+, and CD4-1+/CD4-2+ cells presented different proportions in PBL, spleen and head kidney, among them, CD4-1+/CD4-2+ cell is the majority of CD4T cell subpopulation.


Ulcerative colitis and colon cancer: more controversy than clarity.
Although it is generally accepted that the risk of colorectal cancer in patients with ulcerative colitis is increased compared with the general population, the management of this increased risk remains controversial. Patients with pancolitis of > 8 years duration should consider periodic colonoscopic surveillance or prophylactic colectomy. For patients unwilling to undergo prophylactic colectomy, colonoscopic surveillance annually or biennially is recommended. High-grade dysplasia or low-grade dysplasia in association with a lesion or mass is an indication for colectomy when confirmed by 2 pathologists. Repeat colonoscopic surveillance (in 3-6 months) or colectomy is recommended for confirmed low-grade dysplasia.


[Effect of spironolactone on L-arginine/iNOS/NO pathway of aortic adventitia in spontaneously hypertensive rats].
Adventitia plays an important role in vascular injury diseases. Nitric oxide (NO) from inducible nitric oxide synthase (iNOS) is involved in many cardiovascular diseases. iNOS/NO pathway is activated in aorta of spontaneously hypertensive rats (SHRs). The role of aldosterone in L-arginine (L-Arg)/iNOS/NO pathway of aortic adventitia is uncertain. We investigated the effect of aldosterone antagonist spironolactone on adventitial L-Arg/iNOS/NO pathway in SHRs. Twenty male SHR (10 weeks old, 220-280 g) were randomly divided into 2 groups (10 in each): untreated or treated with the aldosterone receptor antagonist, spironolactone (20 mg/kg per day) for 6 weeks. Age-matched Wistar-Kyoto rats (WKY) were used as control. Systolic blood pressure (tail-cuff method) was measured weekly. Six weeks later, the rats were sacrificed. The whole aorta was collected and aortic adventitia was isolated. iNOS activity, [(3)H]-L-Arg transport assay of aortic adventitia were carried out by isotope-labeled L-arginine conversion rate measurement, and measurement of nitrate/nitrite (NOx), an index of NO production of aortic adventitia was assayed with the Griess reaction. iNOS activity, [(3)H]-L-Arg transport and NO production were greatly increased in aortic adventitia of SHR [(12.55 +/- 2.27) pmol x mg(-1) x min(-1), (0.88 +/- 0.19) pmol x mg(-1) x min(-1) and (2.07 +/- 0.39) micromol/L)] compare versus WKY [(5.96 +/- 1.87) pmol x mg(-1) x min(-1), (0.51 +/- 0.15) pmolxmg(-1) x min(-1) and (1.55 +/- 0.32) micromol/L, P < 0.01], and decreased significantly by spironolactone treatment [(8.32 +/- 1.84) pmol x mg(-1) x min(-1), (0.61 +/- 0.15) pmol x mg(-1) x min(-1) and (1.64 +/- 0.27) micromol/L, P < 0.01]. L-Arg/iNOS/NO is activated in aortic adventitia of SHR. Spironolactone can inhibit the activation of L-Arg/iNOS/NO pathway. Aldosterone may play an important role in some cardiovascular diseases such as atherosclerosis through iNOS/NO pathway.


Endoscopic sclerotherapy of bleeding oesophageal varices in Jamaica.
The results of oesophageal sclerotherapy (OS) in 18 patients with recurrent bleeding varices are compared with 15 patients treated medically. The total transfusion requirement pre-sclerotherapy was 112 units of blood (mean 6/patient) which decreased to 46 units (mean 2.5) after sclerotherapy treatment was started (p = 0.005). In the medically treated group, total transfusion was 74 units (mean 5 units/patient). One hundred and forty-three injection sclerotherapy sessions were given, and all but one patient had significant reduction or eradication of varices. Three patients died of recurrent bleeding (17%) and one other required surgery. In the medically treated group, 3 patients died of bleeding (20%). Complications of sclerotherapy included mild bleeding (39%), chest pain (28%) and oesophageal ulcer (5.5%). OS reduces transfusion requirements in patients with recurrent variceal bleeding.


[Home hemodialysis].
Home hemodialysis (HHD) is the cornerstone of renal replacement therapy in Germany. From 1969, it enabled survival with a diagnosis that up to then had been fatal; however, with the development of a good network of dialysis centers, the knowledge and experience of HHD was increasingly lost. Today, HHD is practically no longer included in the education. Insufficient information and a lack of HHD services are the result. Currently, less than 0.8% of patients in Germany are treated with HHD. In the development of dialysis machines, the industry focused on stand-alone machines for the centers. This form of treatment hinders mobility and limits the activities of patients with renal insufficiency requiring dialysis. Starting with the Advancing American Kidney Health Initiative there has been a welcome momentum in the development of innovative, wearable and implantable artificial kidneys. This can improve the quality of life and reduce the mortality rate. The first initiatives have also emerged in Germany and Europe. These innovative devices and the associated transition in renal replacement therapy will solve many problems of the nephrology community, such as personnel shortages or the lack of donor organs and death on the waiting list and give patients independence and mobility. The cost burden on healthcare systems can be reduced. In addition, the immense water and electricity consumption will be dramatically reduced by the regenerative techniques of the new machines.


Cardiolipin occupancy profiles of YidC paralogs reveal the significance of respective TM2 helix residues in determining paralog-specific phenotypes.
YidC belongs to an evolutionarily conserved family of insertases, YidC/Oxa1/Alb3, in bacteria, mitochondria, and chloroplasts, respectively. Unlike Gram-negative bacteria, Gram-positives including Streptococcus mutans harbor two paralogs of YidC. The mechanism for paralog-specific phenotypes of bacterial YidC1 versus YidC2 has been partially attributed to the differences in their cytoplasmic domains. However, we previously identified a W138R gain-of-function mutation in the YidC1 transmembrane helix 2. YidC1W138R mostly phenocopied YidC2, yet the mechanism remained unknown. Primary sequence comparison of streptococcal YidCs led us to identify and mutate the YidC1W138 analog, YidC2S152 to W/A, which resulted in a loss of YidC2- and acquisition of YidC1-like phenotype. The predicted lipid-facing side chains of YidC1W138/YidC2S152 led us to propose a role for membrane phospholipids in specific-residue dependent phenotypes of S. mutans YidC paralogs. Cardiolipin (CL), a prevalent phospholipid in the S. mutans cytoplasmic membrane during acid stress, is encoded by a single gene, cls. We show a concerted mechanism for cardiolipin and YidC2 under acid stress based on similarly increased promoter activities and similar elimination phenotypes. Using coarse grain molecular dynamics simulations with the Martini2.2 Forcefield, YidC1 and YidC2 wild-type and mutant interactions with CL were assessed in silico. We observed substantially increased CL interaction in dimeric versus monomeric proteins, and variable CL occupancy in YidC1 and YidC2 mutant constructs that mimicked characteristics of the other wild-type paralog. Hence, paralog-specific amino acid- CL interactions contribute to YidC1 and YidC2-associated phenotypes that can be exchanged by point mutation at positions 138 or 152, respectively.


Pathology of the Trachea and Central Bronchi.
A wide variety of disorders can affect the trachea and central bronchi. Computed tomography is the imaging modality of choice in the evaluation of tracheobronchial disease. Tracheobronchial abnormalities are sometimes incidentally detected on routine imaging or when imaging is performed for another reason. Abnormalities of the tracheobronchial tree, however, can be easily missed because they can be subtle. Furthermore, because symptoms in patients with tracheobronchial disorders often overlap symptoms of lung disease, radiologists may focus their attention on the lungs and overlook the tracheobronchial tree. In this article, we review a wide range of tracheobronchial diseases with emphasis on their computed tomographic appearances.


Structure and assembly of PEO-PPO-PEO co-polymers in mammalian cell-culture media.
We investigate the structure of a poly(ethylene oxide)-poly(propylene oxide)-poly (ethylene oxide) co-polymer, Pluronic F127, in mammalian cell-culture media. It is well known that aqueous solutions of F127 gel at physiological temperatures with this transition, which corresponds to the formation of a close-packed cubic assembly of spherical micelles. Previous work has shown that in both mammalian cell minimum essential medium (MEM) and MEM with added fetal bovine serum, the gel phase boundary shifts to lower temperatures and concentrations as compared to pure water. Using DLS, we have found that at 25 degrees C the critical micelle concentration (CMC) decreases in the presence of MEM. Our SANS studies at 25 degrees C indicate that F127 in MEM-D2O also forms a close-packed cubic micellar gel, suggesting that the mechanism of gelation is the same in both pure water and MEM. Fits to the neutron spectra on 2 wt% F127 in D2O and MEM-D2O show a large difference in the micelle aggregation number (Nagg) and a small difference in the micelle size, with both Nagg and the micelle size larger in the presence of MEM. In addition, our SANS spectra in MEM-D2O indicate repulsive interactions between micelles at 2 wt% polymer, whereas no correlation peak is observed for this concentration in water. Finally, moderately concentrated samples (5-18 wt% polymer) in MEM exhibit slightly stronger ordering and sharper peaks, perhaps indicating stronger intermicellar interactions in the presence of MEM. This stronger repulsive interaction may be the cause of the shift in the liquid-gel phase boundary that is observed.


Fringe jump analysis and implementation of polarimetry on the ASDEX Upgrade DCN interferometer.
The ASDEX Upgrade tokamak is equipped with a 5-channel DCN interferometer with a probing wavelength of 195 μm. Up to now, phase measurement and density calculation have been accomplished by hard-wired phase counting electronics. Meanwhile, a fast digitizer has been installed which acquires the raw signals. That way, the various causes of counting errors by integer multiples of 2π, so-called fringe jumps, can be analyzed, and phase reconstruction schemes based on digital signal processing can be developed. In addition, a prototype polarimeter setup has been installed on one channel and allows for measurement of the Faraday rotation experienced by the probing beam.


A disconnect between high-affinity binding and efficient regulation by antifolates and purines in the tetrahydrofolate riboswitch.
The tetrahydrofolate (THF) riboswitch regulates folate transport and metabolism in a number of Firmicutes by cooperatively binding two molecules of THF. To further understand this riboswitch's specificity for THF, binding and regulatory activity of a series of THF analogs and antifolates were examined. Our data reveal that although binding is dominated by the RNA's interactions with the pterin moiety, the para-aminobenzoic acid (pABA) moiety plays a significant role in transcriptional regulation. Further, we find that adenine and several other analogs bind with high affinity by an alternative binding mechanism. Despite a similar affinity to THF, adenine is a poor regulator of transcriptional attenuation. These results demonstrate that binding alone does not determine a compound's effectiveness in regulating the activity of the riboswitch-a complication in current efforts to develop antimicrobials that target these RNAs.


Selective changes in mu, delta and kappa opioid receptor binding in certain limbic regions of the brain in Alzheimer's disease patients.
Total opioid binding and levels of the three major types of opioid binding sites were measured in homogenates of various limbic structures from post-mortem brains of Alzheimer's disease patients and age-matched control individuals. The most consistent finding in Alzheimer's disease brains was an increase in kappa binding in all 6 areas of the limbic system examined, with the putamen and caudate regions showing significant increases of 114% and 53%, respectively. In addition, the Alzheimer's disease putamen showed a significantly higher level of total binding (85% increase). The amygdala of Alzheimer's disease patients exhibited significantly lower levels of mu and delta binding (41% and 55% decrease, respectively). Total binding and binding to mu and delta receptors in frontal cortex, caudate and hippocampus of Alzheimer's disease brains was indistinguishable from levels seen in these brain areas from control individuals.


Compact high-resolution spectrometer based on super-prism and local-super-collimation effects of photonic crystal.
We propose a design of the compact high-resolution photonic crystal (PhC) spectrometer with a wide working bandwidth based on both super-prism and local-super-collimation (LSC) effects. The optimizing methods, finding the ideal incident angle and oblique angle of PhC for a wider working bandwidth and ideal incident beam width and PhC size for a certain resolution requirement, are developed. Besides the theoretical work, for the first time, the experiment of such a PhC spectrometer is conducted in the microwave frequency range, and the beam-splitting effects for different frequencies in a wide working bandwidth agree very well with the theoretical predictions. According to the scalability, with the condition to control the deviations in the fabrication processes the design could be extended to optical frequency ranges, e.g., infrared, visible-light, and ultraviolet ranges. The spectrometer in optical frequencies can be implemented on silicon-on-insulator (SOI) chips as a thin-slab structure so that the operating bandwidth can be expanded further through the multi-layer design. Theoretically, the size of the ultra-high-resolution PhC spectrometer in optical frequency ranges based on our design could be two orders smaller than the traditional design.


Soluble urokinase plasminogen activator receptor and incidence of venous thromboembolism.
Raised plasma levels of the soluble urokinase plasminogen activator receptor (suPAR) have been associated with increased incidence of cardiovascular diseases. Whether suPAR is associated with venous thromboembolism (VTE) is largely unknown. The purpose of the present study was to investigate the relationship between suPAR and incidence of VTE in a cohort study. suPAR was measured in 5,203 subjects (aged 46-68 years, 58 % women) from the general population, who participated in the Malmö Diet and Cancer (MDC) study between 1991 and 1994. Incident cases of VTE were identified from the Swedish patient register during a mean follow-up of 15.7 years. Of 5,203 subjects with measurements of suPAR, 239 had VTE during follow-up (127 venous thrombosis, 86 lung embolism, 26 both). Incidence of VTE was significantly higher in subjects with suPAR levels in the top quartile. Adjusted for age and sex, the HR (4th vs 1st quartile) was 1.74 (95 %CI: 1.2-2.6, p for trend=0.003). After adjustments for risk factors, the HR was 1.66 (95 %CI: 1.1-2.5, p for trend=0.016). High level of suPAR was a risk indicator for incidence of VTE in this population-based cohort study. The causal relationships between suPAR and VTE remain to be explored.


3D Printing of Physical Organ Models: Recent Developments and Challenges.
Physical organ models are the objects that replicate the patient-specific anatomy and have played important roles in modern medical diagnosis and disease treatment. 3D printing, as a powerful multi-function manufacturing technology, breaks the limitations of traditional methods and provides a great potential for manufacturing organ models. However, the clinical application of organ model is still in small scale, facing the challenges including high cost, poor mimicking performance and insufficient accuracy. In this review, the mainstream 3D printing technologies are introduced, and the existing manufacturing methods are divided into "directly printing" and "indirectly printing", with an emphasis on choosing suitable techniques and materials. This review also summarizes the ideas to address these challenges and focuses on three points: 1) what are the characteristics and requirements of organ models in different application scenarios, 2) how to choose the suitable 3D printing methods and materials according to different application categories, and 3) how to reduce the cost of organ models and make the process simple and convenient. Moreover, the state-of-the-art in organ models are summarized and the contribution of 3D printed organ models to various surgical procedures is highlighted. Finally, current limitations, evaluation criteria and future perspectives for this emerging area are discussed.


Cell membrane integrity and lysis in Lactococcus lactis: the detection of a population of permeable cells in post-logarithmic phase cultures.
A method was developed that enabled an analysis of the proportion of permeable cells in a culture of Lactococcus lactis. This used the fluorescence of propidium iodide (PI) when in contact with DNA and the impermeability of the intact cell membrane to this compound. A permeability index was suggested that expresses the PI-induced fluorescence of a cell suspension as a percentage of the value obtained from wholly permeabilized cells after treatment with cetyltrimethylammonium bromide. This method was applied to the determination of cell permeability in death phase cultures. A large proportion of unlysed cells was freely permeable to PI, a finding that may have some significance for the investigation of the role of cell lysis in cheese maturation. This method is suggested as a useful addition to the techniques available for the study of cell damage in a variety of fields, and for the screening of cheese starter bacteria.


Sample sizes for batch acceptance from single- and multistage designs using two-sided normal tolerance intervals with specified content.
One quality control test in the pharmaceutical industry is a test for uniformity of content of a batch prior to release of the batch to market. For batch acceptance by this or other quantitative tests of batch quality, one approach uses two-sided tolerance intervals of specified content. If the tolerance interval falls entirely within an acceptance interval, the batch is accepted. This has the form of a statistical hypothesis test. Once we recognize this approach as a statistical test, we can ask what sample size is required to be able to accept the batch with a desired power. The power for a single-stage design is a bivariate noncentral t probability and can be determined using previously published algorithms. Using standard methods for interim analyses, the approach is extended to multistage designs. Power and sample size for multistage designs are validated with simulations. We demonstrate it is possible to design one- and two-stage designs for batch acceptance with desired power and specified type I level.


The trend of osteoporosis and osteoporotic fragility fractures in inpatients: results from a national database.
Osteoporosis is associated with an increased risk of pathologic fractures; however, most patients do not receive diagnosis and adequate treatment. The aim of our study was to compare the yearly trends of osteoporosis and osteoporotic fragility fractures in the USA (US) inpatients. We used National (Nationwide) Inpatient Sample database to identify adults ≥18 years with diagnoses of osteoporosis and pathologic fractures and excluded pathologic fractures due to other etiologies. We then studied the annual trends, in terms of annual percentage change (APC), of osteoporosis and osteoporotic fractures. Among overall hospitalizations, osteoporosis was noted to have an increasing trend from 2000 to 2009 (APC = 5.81, p < 0.05) with a decline thereafter (APC = - 3.88, p < 0.05). In contrast, osteoporotic fracture showed an initial downward trend from 2000 to 2010 (APC = -7.31, p < 0.05), followed by a slowly rising trend (APC = 2.0, p = NS). The initially increasing trend of osteoporosis was followed by a decreasing trend thereafter. In contrast, there was a halt in a previously declining trend of osteoporotic fracture. Potential explanations include inadequate screening and treatment per guidelines along with decreasing patient compliance. In conclusion, primary and secondary prevention measures for osteoporosis have been underutilized by both physicians and patients alike.


Pluralistic Ignorance of Physical Attractiveness in the Gay Male Community.
Researchers have found that a disproportionate percentage of men diagnosed with eating disorders identify as gay, and there is extensive evidence that gay men have significantly more body image concerns than heterosexual men (Bosley, 2011). The current studies investigated whether pluralistic ignorance exists about what is considered attractive in the gay community. It was hypothesized that gay males would privately reject the notion that only a mesomorphic (thin and muscular) body type is attractive, yet incorrectly assume that their peers are attracted primarily to a mesomorphic body type. The studies found evidence for the existence of pluralistic ignorance about what is considered attractive in the gay community. Further, there was evidence for a significant association between pluralistic ignorance and body image concerns, particularly among men who were not in committed romantic relationships.


Differential distribution of alpha and beta isoforms of p21-activated kinase in the monkey cerebral neocortex and hippocampus.
The present study aimed to elucidate the subcellular distribution of the Cdc42 and Rac activated alpha and beta isoforms of p21-activated kinase (PAK) in the monkey cerebral neocortex and hippocampus. These proteins have been shown to play morphological roles through effects on the actin cytoskeleton. alphaPAK immunoreaction product was concentrated in regions of axon terminals or dendrites, some distance (0.2-1 microm) away from the synapse. The labeled portion of dendrite often appeared with "ruffled" cell membranes or resembling non-synapse forming "buds." betaPAK immunoreaction product was concentrated in cell bodies and larger diameter dendrites. Immunogold labeled sections showed that most of the label for both alphaPAK and betaPAK was present in a perisynaptic or extrasynaptic location, and relatively little staining was present on the postsynaptic density. Because alphaPAK has been shown to be associated with new membrane structures involving the Rho family GTPase Rac1, which controls dendritic morphology, these observations suggest alphaPAK positive regions of axons and dendrites may mark new areas of neurite extension.


Usefulness of the most popular neurodevelopmental tests in preschool assessment of children born with very low birth weight.
The aim of our study was multifaceted neurodevelopmental examination of children born prematurely with very low birth weight (VLBW) in order to evaluate the usefulness of popularly used tests. The second aim of the study was exploration of risk and protective factors of neurodevelopmental impairment. Eighty-nine VLBW patients were evaluated at the age of 50 months. All children underwent anthropometric measurements and psychomotor tests: functional independence measure scale (WeeFIM), Gross Motor Function Measurement (GMFM), non-verbal psychometric evaluation (Leiter test), Developmental Test of Visual Perception (DTVP-2), temperament questionnaire (EAS-C) and children vocabulary test (TSD). Most severe deficits in ex-preterms' neurodevelopment were associated with verbal abilities, visual perception and temper abnormalities. WeeFIM, DTVP-2, Leiter and vocabulary tests' results correlated with each other. The lowest percent of children with deficits in WeeFIM test indicates, that it seems to be the most valuable tool for identification of the most seriously impaired children. Due to the highest percent of children with visual perception deficits, DTVP test seems to be good second choice in assessment of children born prematurely. In motor assessment GMFM appears to be more adequate than cerebral palsy (CP) diagnosis. Almost one fifth of VLBW did not reach 85% in Gross Motor Function Measurement, although only 9% of children had CP. Children born with VLBW had deficits in every part of psychometric evaluation. We believe that the most useful tests in assessment VLBW patients are WeeFIM, GMFM and DTVP. Children with severe prematurity complications could require more precise evaluation.


[Modern aspects of shoulder injury treatment].
The article describes injuries of soft and bone structures of the shoulder region, with special emphasis on the following clinical forms: instabilities and luxations of the glenohumeral joint, fractures of the proximal humerus, clavicle and the states of painful shoulder. Fractures and dislocations, but also significant entities - painful states caused not only by fractures but also by minor trauma such as tendinitises and m.supraspinatus tendon and bicipital tendon ruptures are discussed in more detail. Moreover, their consequences - painful and stiff shoulder - as well as modern diagnostic and therapeutic procedures applied in the painful shoulder treatment are also discussed.


Lignans from the tuber-barks of Colocasia antiquorum var. esculenta and their antimelanogenic Activity.
Colocasia antiquorum var. esculenta , a variant of C. antiquorum , commonly known as "Imperial Taro", is an edible vegetable in many tropical and subtropical regions of the world. This study with the aim of evaluating the potential of C. antiquorum var. esculenta as a functional food with a depigmenting effect resulted in the identification of a new sesquilignan, named colocasinol A (1), and a new acyclic phenylpropane lignanamide, named cis-grossamide K (2), together with 10 known compounds (3-12). The identification and structural elucidation of these compounds were based on 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data analysis as well as high-resolution fast atom bombardment mass spectrometry (FABMS) and electron impact mass spectrometry (EIMS). Quantitation of the melanin contents and cell viability in murine melanocyte melan-a cells was used to assess the antimelanogenic activities of the isolated compounds. Among them, cis-grossamide K (2), isoamericanol A (3), americanol A (4), 2-hydroxy-3,2'-dimethoxy-4'-(2,3-epoxy-1-hydroxypropyl)-5-(3-hydroxy-1-propenyl)biphenyl (5), and (-)-pinoresinol (6) showed inhibitory effects on melanin production. Compounds 2, 5, and 6 exerted a particularly strong antimelanogenic activity on the cells without high cell toxicity (IC(50) = 54.24, 53.49, and 56.26 microM, and LD(50) = 163.60, 110.23, and >500 microM, respectively).


Congenital aniridia: etiology, manifestations and management.
Congenital aniridia manifests as total or partial absence of the iris caused most commonly by mutations in PAX6, FOXC1, PITX2, and CYP1B1. Recently two new genes, FOXD3 and TRIM44, have also been implicated in isolated studies. We discuss the genotype-phenotype correlations for the main implicated genes. Classic aniridia is a panocular condition, which includes aniridia, cataract, corneal pannus, foveal, and optic nerve hypoplasia associated with mutations in the PAX6 gene. Classical aniridia is due to PAX6 mutations, while other genes contribute to aniridia-like phenotypes. We review the challenges involved in the management of aniridia, and discuss various surgical interventions. The clinical importance of defining the genotype in cases of congenital aniridia has become acutely apparent with the advent of possible therapies for classical aniridia, which are discussed.


Classics in Neuroimaging: Imaging the Dopaminergic Pathway with PET.
The success of positron emission tomography (PET) for observing molecular processes underlying brain function and disease is underpinned by radiotracer chemistry. From the earliest applications of PET to measure dopamine synthesis capacity and the abundance of neuroreceptors and transporters, to the more recent topic of dynamic neurochemical imaging, interrogation of brain dopamine in conditions such as neurodegenerative diseases, schizophrenia, mood disorders, and addictions has been a driving force that challenges the ingenuity of radiopharmaceutical scientists. In fact, the pursuit of new ligands and reaction methods to address longstanding challenges has often been pioneered in the context of dopamine imaging. From this viewpoint, we highlight the unique history of imaging the dopaminergic pathway with PET, and present our interpretation of how this worldwide effort shaped and continues to drive the field of molecular imaging.


Consultation planning to help breast cancer patients prepare for medical consultations: effect on communication and satisfaction for patients and physicians.
To measure the prevalence of communication barriers between breast cancer patients and their physicians and to present the results of a study evaluating the impact of two visit preparation techniques on communication and satisfaction for breast cancer patients and their physicians. We recruited 132 breast cancer patients from two outpatient cancer centers in a sequential, controlled trial. Ninety-four consented and completed the trial. Patients were assigned to one of two visit preparation interventions before their appointment with either a surgeon or a medical oncologist. In the control intervention, called Productive Listening, a researcher listened to and prompted patients to reflect on their experiences communicating with physicians. In the experimental intervention, called Consultation Planning, a researcher elicited questions and concerns, generated a printed agenda for the upcoming consultation, and engaged patients in techniques to improve communication with their physicians. Valid and reliable surveys measured communication barriers, satisfaction with the intervention, and patients' and physicians' satisfaction with the consultation. Sixty-four percent of the patients reported three or more communication barriers. Patients reported a significant reduction in communication barriers after both the intervention and the control session. Patients reported significantly higher satisfaction after the Consultation Planning sessions. Physicians reported significantly higher satisfaction with those patients who had participated in a Consultation Planning session. Visit preparation sessions help patients prepare for medical consultations and reduce barriers to communication. Consultation Planning sessions, in which a researcher solicited the patient's agenda, were more satisfying to patients and physicians than the Productive Listening sessions.


Total Synthesis and Stereochemical Assignment of Delavatine A: Rh-Catalyzed Asymmetric Hydrogenation of Indene-Type Tetrasubstituted Olefins and Kinetic Resolution through Pd-Catalyzed Triflamide-Directed C-H Olefination.
Delavatine A (1) is a structurally unusual isoquinoline alkaloid isolated from Incarvillea delavayi. The first and gram-scale total synthesis of 1 was accomplished in 13 steps (the longest linear sequence) from commercially available starting materials. We exploited an isoquinoline construction strategy and developed two reactions, namely Rh-catalyzed asymmetric hydrogenation of indene-type tetrasubstituted olefins and kinetic resolution of β-alkyl phenylethylamine derivatives through Pd-catalyzed triflamide-directed C-H olefination. The substrate scope of the first reaction covered unfunctionalized olefins and those containing polar functionalities such as sulfonamides. The kinetic resolution provided a collection of enantioenriched indane- and tetralin-based triflamides, including those bearing quaternary chiral centers. The selectivity factor (s) exceeded 100 for a number of substrates. These reactions enabled two different yet related approaches to a key intermediate 28 in excellent enantiopurity. In the synthesis, the triflamide served as not only an effective directing group for C-H bond activation but also a versatile functional group for further elaborations. The relative and absolute configurations of delavatine A were unambiguously assigned by the syntheses of the natural product and its three stereoisomers. Their cytotoxicity against a series of cancer cell lines was evaluated.


[Possibilities of early diagnosis of left-heart insufficiency in acute myocardial infarction].
In 84 patients with an acute myocardial infarction clinical signs, measurement of the pressure of the pulmonary arteries and radiogramme of the thorax were used and compared for the estimation of the left heart insufficiency-particularly of an increase of a preload. The value of a standardized course series of radiogrammes of the thorax as a non-invasive investigation method in contrast to the invasive method of the pressure measurement of the pulmonary arteries was discussed. Advantages and disadvantages of the two methods were critically shown, since only in about 60% a correspondence was to be recognized.


A new skink of the genus Sphenomorphus Fitzinger, 1843 (Squamata: Scincidae) from Hon Ba Nature Reserve, southern Vietnam.
A new forest skink of the genus Sphenomorphus Fitzinger, 1843 is described from Khanh Hoa Province, southern Vietnam based on morphological characters of four specimens and a fragment of 653 nucleotides of the gene COI. Sphenomorphus yersini sp. nov. is characterized by the following morphological characters: medium size in adults (snout-vent length up to 55 mm); tail length/snout-vent length ratio 1.81; toes reach to fingers when limbs adpressed; midbody scale rows 32-34, smooth; paravertebral scales 61-69; ventral scale rows 58-67; subcaudal scales 112; supraoculars four, rarely five; prefrontals in broad contact with one another; loreal scales two; tympanum deeply sunk; smooth lamellae beneath finger and toe IV 10-12 and 18-20 respectively; a pair of enlarged precloacal scales; hemipenis deeply forked and asymmetrical with two differently sized smooth lobes. The new species differs from its most similar congener, Sphenomorphus buenloicus Darevsky Nguyen, 1983, by 16.4-16.7% uncorrected p-distance in COI sequences.


Aggregation-induced emission of tetraphenylethene derivative as a fluorescence method for probing the assembling/disassembling of amphiphilic molecules.
The aggregation-induced emission (AIE) of a 1,2-diphenyl-1,2-di(p-tolyl)ethene (TPE) was explored as a novel fluorescence method for probing the assembling/disassembling of amphiphilic molecules. The fluorescence intensity was able to monitor the formation of micelles and determine the critical micelle concentration (CMC) of surfactants. The temperature-dependent micellization of the pharmaceutically important PEO-PPO-PEO copolymer, Pluronic F127, was further studied by using the TPE fluorescence spectrum intensity. Our results showed good agreement with those reported in the literature by using other methods. The special advantage of the AIE probe method was further explored to determine the assembling/disassembling process of the colored amphiphilic molecule, 1-[4-(3-phenylazophenoxy)butyl]triethylamine bromide (AzoC4), whose CMC value has not previously been described. Since the TPE fluorescence signal mainly comes from the aqueous phase, not from the inside of hydrophobic core, it provides a possible platform to study the CMC of those colored surfactants. Based on the novel fluorescence properties of TPE in the aggregated and dispersed states, one can conclude that the TPE method is a promising method for the determination of the CMC and critical micellization temperature (CMT), particularly having a special advantage to determine the assembling/disassembling process of colored amphiphilic molecules.


A registration-based propagation framework for automatic whole heart segmentation of cardiac MRI.
Magnetic resonance (MR) imaging has become a routine modality for the determination of patient cardiac morphology. The extraction of this information can be important for the development of new clinical applications as well as the planning and guidance of cardiac interventional procedures. To avoid inter- and intra-observer variability of manual delineation, it is highly desirable to develop an automatic technique for whole heart segmentation of cardiac magnetic resonance images. However, automating this process is complicated by the limited quality of acquired images and large shape variation of the heart between subjects. In this paper, we propose a fully automatic whole heart segmentation framework based on two new image registration algorithms: the locally affine registration method (LARM) and the free-form deformations with adaptive control point status (ACPS FFDs). LARM provides the correspondence of anatomical substructures such as the four chambers and great vessels of the heart, while the registration using ACPS FFDs refines the local details using a constrained optimization scheme. We validated our proposed segmentation framework on 37 cardiac MR volumes on the end-diastolic phase, displaying a wide diversity of morphology and pathology, and achieved a mean accuracy of 2.14 +/- 0.63 mm (rms surface distance) and a maximal error of 4.31 mm.


Escherichia coli MW005: lambda Red-mediated recombineering and copy-number induction of oriV-equipped constructs in a single host.
Escherichia coli strain EL350 contains chromosomally integrated phage lambda Red recombinase genes enabling this strain to be used for modifying the sequence of resident clones via recombineering. BAC and fosmid clones are highly suitable for modification by recombineering but, because they are present at low (1-2) copies per cell, the DNA is difficult to isolate in high yield and purity. To overcome this limitation vectors, e.g. pCC1FOS, have been constructed that contain the additional replication origin, oriV, which permits copy-number to be induced transiently when propagated in a suitable host strain, e.g. EPI300, that supplies the cognate trans-replication protein TrfA. Previously, we used EL350 and EPI300 sequentially to recombineer oriV-equipped fosmid genomic clones and, subsequently, to induce copy-number of the resulting recombinant clone. To eliminate these intervening DNA isolation and transformation steps we retrofitted EL350 with a PBAD-driven trfA gene generating strain MW005 that supports, independently, both recombineering and copy-number induction. The PBAD-driven copy of cre in EL350 was replaced seamlessly with a copy of trfA, PCR-amplified from EPI300 chromosomal DNA, to generate MW005. This new strain has been used to both generate, via recombineering, a number of reporter gene fusions directly from pCC1FOS-based Caenorhabditis elegans genomic clones and to transiently induce copy-number of fosmid and BAC clones prior to DNA preparation. By retrofitting EL350, an established 'recombineering' E. coli strain, with a tightly regulated copy of trfA we have produced a new strain, MW005, which combines recombineering capacity with the useful ability to transiently induce copy-number of oriV-equipped clones. By coupling these two steps in a single strain, use of MW005 will enable the more rapid recombineering-mediated production of recombinant clones in the yield and quality necessary for many downstream purposes.


Renal Dysfunction was an Independent Predictor of In-Hospital Death and Ventricular Rupture in Patients With Acute Myocardial Infarction.
Apart from the severity of myocardial infarction and coronary artery disease, several predictors of in-hospital death (In-HD) are suggested in patients with acute myocardial infarction (AMI). We investigated predictors of In-HD and ventricular rupture (VR) including ventricular septal rupture (VSR) and free wall rupture (FWR) with stepwise multivariable logistic regressions in 1,042 patients admitted to our Cardiovascular Center within 48 hours from symptom onset for the first attack of AMI. In-HD, VSR, and FWR were observed in 78 cases (7.5%), 14 cases of which 13 cases were In-HD, and 13 cases of which 6 cases were In-HD, respectively. Apart from the disease severity, age and renal dysfunction (RD) defined by estimated glomerular filtration rate of lower than 60 mL/min/ 1.73 m2 were independent positive predictors of In-HD (the odds ratios (ORs) (95% confidence interval (CI)): 1.04 (1.01 - 1.06) P = 0.0069 and 5.75 (3.12 - 10.59) P < 0.0001, respectively) and hypercholesterolemia was an independent negative predictor for In-HD (OR (95% CI): 0.34 (0.17 - 0.67) P = 0.0017). After including the categories of coronary disease, ventricular rupture, and ejection fraction in predictors, RD remained an independent predictor of In-HD (OR (95% CI): 6.65 (2.67 - 16.60) P < 0.0001). Age (OR (95% CI): 1.07 (1.02 - 1.12) P = 0.0064), RD (OR (95% CI): 2.77 (1.18 - 6.49) P = 0.019), and diabetes (OR (95% CI): 2.52 (1.12 - 5.71) P = 0.026) were independent predictors of VR. RD was an independent predictor of In-HD and VR in patients with initial AMI.


Afferent signals from the extraocular muscles of the pigeon modify the electromyogram of these muscles during the vestibulo-ocular reflex.
There is no general agreement on whether afferent signals from the extraocular muscles play any part in oculomotor control. However, we have previously shown that they modify the responses of cells in the oculomotor control system during the vestibulo-ocular reflex (VOR). If, as we suspect, these signals have an important role in the control of the VOR from moment-to-moment, we should be able to demonstrate similar, functionally significant, modifications at the output of the reflex. We have recorded the electromyographic activity of several extraocular muscles of the right eye during the VOR and while imposing movements on the left eye. We describe how the activity of the muscles, reflected in the electromyogram, is modified in specific ways depending on the parameters of the imposed eye movements. The effects of the extraocular afferent signals on the eye-muscle responses to vestibular drive during the slow phase of the VOR appear to be corrective. Thus the present results provide strong evidence that afferent signals from the extraocular muscles are concerned in the control of the reflex from moment-to-moment, and suggest that the wider question of their role in oculomotor control merits further consideration.


Dynamics of kink-dark solitons in Bose-Einstein condensates with both two- and three-body interactions.
The matter-wave solutions of Bose-Einstein condensates with three-body interaction are examined through the one-dimensional Gross-Pitaevskii equation. By using a modified lens-type transformation and a further extension of the tanh-function method we obtain the exact analytical solutions which describe the propagation of kink-shaped solitons, anti-kink-shaped solitons, and other families of solitary waves. We realize that the shape of a kink solitary wave depends on both the scattering length and the parameter of atomic exchange with the substrate. The stability of the solitary waves is examined using analytical and numerical methods. Our results can also be applied to nonlinear optics in the presence of cubic-quintic media.


Computer-based blood donor screening: a status report.
There is a substantial literature suggesting that computer-assisted interviewing has advantages over face-to-face and written self-administration of interviews in venues eliciting sensitive information similar to that sought in blood donor history screening. We review some of the recent developments in blood donor history screening, the evidence suggesting that automated interviews should be useful, and the experience to date using computer interviews for blood donation. These data suggest that automated computer-assisted interviewing increases the elicitation of behaviors associated with the risk of transfusion-transmissible infection in donors, improves donor and staff satisfaction, and reduces errors and omissions that frequently accompany traditional interviewing methods. Food and Drug Administration-cleared systems for computer-assisted self-interview of blood donors are briefly described.


Plasma lipids in genetically hypertensive rats of the Lyon strain.
Of the four standardized strains of genetically hypertensive rats, only the Lyon hypertensive rats spontaneously exhibit a higher body weight than their normotensive controls. In order to determine if this increased body weight is associated with alterations in the lipid metabolism, plasma triglycerides (TG), phospholipids (PL), total cholesterol (TPC), and high-density lipoprotein cholesterol (CHDL) were followed in Lyon hypertensive (LH), normotensive (LN), and hypotensive (LL) male rats between 5 and 32 weeks of age. TG were stable with age in LL and LN but increased in LH rats. PL decreased in LL, remained stable in LN, but increased with age in LH rats. TPC and CHDL were stable in LL and LN and increased with age in LH rats. Plasma lipids were not related to the blood pressure level, but were positively related to the body weight in the hypertensive strain. Thus, starting at the age of 5 weeks, LH rats exhibit spontaneously a significant increase in blood pressure, body weight, and plasma lipid concentrations.


Dental Procedures.
Dental problems are a common complaint in emergency departments in the United States. There are a wide variety of dental issues addressed in emergency department visits such as dental caries, loose teeth, dental trauma, gingival infections, and dry socket syndrome. Review of the most common dental blocks and dental procedures will allow the practitioner the opportunity to make the patient more comfortable and reduce the amount of analgesia the patient will need upon discharge. Familiarity with the dental equipment, tooth, and mouth anatomy will help prepare the practitioner for to perform these dental procedures.


Law, ethics and research ethics committees.
This paper examines the view of the operational management of the UK Research Ethics Committee (REC) system that RECs may not reject applications on purely legal grounds. Two arguments are offered for this view: the first rests on the contention that being lawful and being ethical are not the same thing; the second is that RECs lack expertise and authority to base their decisions on legal considerations. However, whatever the philosophical standing of the first argument, it is contrary to published guidance, the basis of RECs' official authority, unethical, and politically imprudent to permit RECs not to consider conformity with the law to be at least a necessary condition for REC approval. In any event, RECs can obtain competent and authoritative advice on the law (though the Department of Health has been remiss in this regard), and they do not exceed their authority by applying the law, because this is within their ethical remit. When current guidance to RECs about advising researchers on whether or not breaches of confidence are permissible in the public interest is linked to the view of the REC management that the role of RECs is to facilitate research (albeit ethical research), this raises serious doubts about the integrity of the system of ethical review currently in place, which is illustrated by a recent "agreement" of the Chairmen of the MRECs not to consider the Data Protection Act 1998 in their ethical review.


Measurement of brevetoxin levels by radioimmunoassay of blood collection cards after acute, long-term, and low-dose exposure in mice.
We developed a radioimmunoassay (RIA) using a sheep anti-brevetoxin antiserum to evaluate detection of brevetoxin on blood collection cards from mice treated with the brevetoxin congener PbTx-3. The RIA has high affinity for PbTx-3 [half-maximal effective concentration (EC(50)) +/- SE = 1.2 +/- 0.2 nM; n = 10] and recognizes both type 1 and type 2 brevetoxins, but not ciguatoxin. Direct comparison of the RIA with a radiolabeled [(3)H]-PbTx-3 receptor-binding assay (RBA) revealed excellent sensitivity, congener selectivity, and minimal interference from blood matrix. We first analyzed blood samples from an acute time course exposure, using a maximal nonlethal dose [180 microg/kg body weight (bw)] for 0.5, 1, 2, 4, and 24 hr. Mean blood brevetoxin levels were 36 nM at 30 min and stayed above 20 nM during the 1-4 hr time points. We next analyzed blood brevetoxin levels after longer exposure (0.5, 1, 2, 3, 4, or 7 days). Mean blood brevetoxin levels were 26.0 nM at 0.5 days, decreased to 8.2 nM at 1.0 day, and maintained a significant level (p < 0.05) of 1.3 nM at day 2. We next determined the lowest measurable dose using increasing concentrations of PbTx-3 (10-300 micro g/kg bw). Analysis of the blood samples at 60 min revealed a linear relationship between administered and internal doses (r(2) = 0.993). All doses of brevetoxin administered were detectable at 1 hr, with significant levels found for the lowest administered dose of 10 micro g/kg bw--a dose that was 10-fold lower than the lowest observable effect level. This RIA provides an optimal first-tier detection of brevetoxin from blood collection cards and, used in combination with the RBA and liquid chromatography-mass spectrometry, should provide a complete panel of methods to biomonitor brevetoxin exposure.


Insulin pumps.
Insulin pump therapy is now more than 30 years old, and is an established part of the routine care of selected people with type 1 diabetes. Nevertheless, there are still significant areas of concern, particularly how pumps compare with modern injection therapy, whether the increasingly sophisticated pump technologies like onboard calculators and facility for computer download offer any real benefit, and whether we have a consensus on the clinical indications. The following papers offer some insight into these and other current questions.


Decreased health care utilization and health care costs in the inpatient and emergency department setting following initiation of ketogenic diet in pediatric patients: The experience in Ontario, Canada.
To assess the change in inpatient and emergency department utilization and health care costs in children on the ketogenic diet for treatment of epilepsy. Data on children with epilepsy initiated on the ketogenic diet (KD) Jan 1, 2000 and Dec 31, 2010 at Ontario pediatric hospitals were linked to province wide inpatient, emergency department (ED) data at the Institute for Clinical Evaluative Sciences. ED and inpatient visits and costs for this cohort were compared for a maximum of 2 years (730days) prior to diet initiation and for a maximum of 2 years (730days) following diet initiation. KD patient were compared to matched group of children with epilepsy who did not receive the ketogenic diet (no KD). Children on the KD experienced a mean decrease in ED visits of 2.5 visits per person per year [95% CI (1.5-3.4)], and a mean decrease of 0.8 inpatient visits per person per year [95% CI (0.3-1.3)], following diet initiation. They had a mean decrease in ED costs of $630 [95% CI (249-1012)] per person per year and a median decrease in inpatient costs of $1059 [IQR: 7890; p<0.001] per child per year. Compared with the no KD children, children on the diet experienced a mean reduction of 2.1 ED visits per child per year [95% CI (1.0-3.2)] and a mean decrease of 0.6 [95% CI (0.1-1.1)] inpatient visits per child per year. Patients on the KD experienced a reduction of $442 [95% CI (34.4-850)] per child per year more in ED costs than the matched group. The ketogenic diet group had greater median decrease in inpatient costs per child per year than the matched group [p<0.001]. Patients initiated on ketogenic diet, experienced decreased ED and inpatient visits as well as costs following diet initiation in Ontario, Canada.


N-Acetyl-beta-D-glucosaminyl-binding properties of the envelope glycoprotein of human immunodeficiency virus type 1.
The effect of carbohydrate structures on the adsorption of HIV-1 or of recombinant envelope glycoprotein gp 160 (rgp 160) to cells of the CEM line was investigated with an indirect immunofluorescence assay using gp 120-specific mouse monoclonal antibodies (mAbs) directed to envelope gp 120. The beta-D-galactosyl, alpha-D-mannosyl, beta-D-glucosyl, N-acetyl-beta-D-glucosaminyl, sialosyl, and L-fucosyl derivatives tested had no effect on this binding. However, preincubation of HIV-1 (or rgp 160) with the neoglycoprotein, beta-D-GlcNAc47-BSA, specifically inhibited the labeling, by some of the mAb used, of HIV-1 (or rgp 160) bound at the cell membrane. This inhibition occurred only with mAbs that were specific for the immunodominant "neutralizing" third variable region (V3) of gp 120. Competition for the binding to rgp 160 between beta-D-GlcNAc47-BSA and mAb was further demonstrated by use of affinity matrices substituted with one of the relevant mAb (110-4), or with beta-D-GlcNAc47-BSA. Besides beta-D-GlcNAc47-BSA-Sepharose, rgp 160 also bound with low affinity, but high specificity, to two other N-acetyl-beta-D-glucosaminyl affinity matrices, beta-D-GlcNAc-divinylsulfone-agarose and asialoagalactothyroglobulin-agarose. Conversely, beta-D-[125I]GlcNAc47-BSA bound specifically to gp 160-Sepharose. These results indicated that rgp 160 behaves as a N-acetyl-beta-D-glucosaminyl-binding protein for GlcNAc residues presented at high density on a carrier, the carbohydrate-binding site of which is close to, or located on the V3 region of gp 120.