Utility of the PALM-COEIN classification of abnormal uterine bleeding for Indian gynecologists.
To study the clinical utility of the PALM-COEIN classification for abnormal uterine bleeding in day-to-day practice in India. Between April and November 2014, a cross-sectional survey was undertaken of gynecologists practicing in Chittoor and Nellore. Doctors possessing a postgraduate degree in gynecology and obstetrics, and postgraduate students in the gynecology department of medical colleges were invited to participate. A validated questionnaire containing 15 questions was distributed, the opinions were collated, and the results analyzed. Among 150 invited gynecologists, 120 agreed to participate, and 119 completed the survey fully. Overall, 95 (79.8%) respondents were aware of the classification, and 56 (47.1%) responded that the PALM-COEIN system is very good, 46 (38.7%) that it is average, and 17 (14.3%) that it is poor. By subgroup, 16 of 20 (80.0%) faculty members, 46 of 56 (82.1%) postgraduate students, and 33 of 43 (76.7%) practitioners responded that the system is useful. Indian doctors generally believe that the PALM-COEIN system is clinically useful and a step forward in the management of abnormal uterine bleeding.


Thrombolysis for occluded vein bypass grafts through surgical access.
This report describes surgical access to occluded vein grafts for thrombolysis by direct cutdown where indirect angiographic techniques have failed. A sheath is introduced directly into the proximal vein graft. Distal thrombus is lysed following standard protocol. The residual thrombus at the origin of the graft is removed surgically, and the area is closed with a patch angioplasty. Distal thrombus was completely lysed in two vein grafts without bleeding complications. The thrombus "cork" that forms at the upper end of an occluded vein graft may deflect the angiographer's guide wire, but the distal thrombus usually remains soft and amenable to lysis. Angiographic access should not be a limiting factor in thrombolysis of an occluded vein graft.


Economic cost of cyanobacterial blooms.
Cyanobacterial blooms impact upon the water quality, environmental and ecological status of water bodies and affect most of the uses we make of water. The extent of the impact depends upon the type, size and frequency of the blooms, the size of the water body affected, the uses made of the water and the treatment options available to respond to the blooms. The impacts therefore vary considerably from place to place. Overall costs should also account for the planning and remedial actions taken to prevent future blooms.


Photon bound state dynamics from a single artificial atom.
The interaction between photons and a single two-level atom constitutes a fundamental paradigm in quantum physics. The nonlinearity provided by the atom leads to a strong dependence of the light-matter interface on the number of photons interacting with the two-level system within its emission lifetime. This nonlinearity unveils strongly correlated quasiparticles known as photon bound states, giving rise to key physical processes such as stimulated emission and soliton propagation. Although signatures consistent with the existence of photon bound states have been measured in strongly interacting Rydberg gases, their hallmark excitation-number-dependent dispersion and propagation velocity have not yet been observed. Here we report the direct observation of a photon-number-dependent time delay in the scattering off a single artificial atom-a semiconductor quantum dot coupled to an optical cavity. By scattering a weak coherent pulse off the cavity-quantum electrodynamics system and measuring the time-dependent output power and correlation functions, we show that single photons and two- and three-photon bound states incur different time delays, becoming shorter for higher photon numbers. This reduced time delay is a fingerprint of stimulated emission, where the arrival of two photons within the lifetime of an emitter causes one photon to stimulate the emission of another.


Osteoarthritis year in review 2018: biology.
This Year in Review highlights a selection of articles published between the 2017 and 2018 Osteoarthritis Research Society International (OARSI) World Congress meetings within the field of osteoarthritis biology, presented at OARSI 2018. Selected articles were obtained from a PubMed search covering cartilage, subchondral bone, inflammation, ageing, pain and animal models. Studies focused on biomechanics, biomarkers, genetics and epigenetics, imaging and clinical studies were excluded due to their coverage in other articles within the OARSI Year in Review series. Significant themes including the role of progenitor cells in cartilage homeostasis and repair, novel signalling mechanisms controlling chondrocyte phenotypic stability and the influence of disrupted or senescent chondrocytes were identified and are discussed in this review. Overarching conclusions derived from these study areas indicate that promising avenues of intervention are on the horizon, however further understanding is required in order to target therapeutic treatments to suitable patient subgroups and disease stages.


The role of adipokines in cardiovascular disease.
Obesity leads to the development of cardiovascular diseases. Adipose tissue produces various bioactive molecules, also known as adipokines, and imbalanced production of adipokines contributes to the pathogenesis of obesity-linked metabolic and cardiovascular complications. Some adipokines such as adiponectin exert salutary actions on cardiovascular and metabolic disorders. Recent research has been conducted to identify poorly-characterized adipokines involved in cardiovascular regulation. In this review, we focus on the protective role of novel adipokines that are of current interest in the field of cardiology.


Computational and experimental insights into the chemosensory navigation of Aedes aegypti mosquito larvae.
Mosquitoes are prolific disease vectors that affect public health around the world. Although many studies have investigated search strategies used by host-seeking adult mosquitoes, little is known about larval search behaviour. Larval behaviour affects adult body size and fecundity, and thus the capacity of individual mosquitoes to find hosts and transmit disease. Understanding vector survival at all life stages is crucial for improving disease control. In this study, we use experimental and computational methods to investigate the chemical ecology and search behaviour of Aedes aegypti mosquito larvae. We first show that larvae do not respond to several olfactory cues used by adult Ae. aegypti to assess larval habitat quality, but perceive microbial RNA as a potent foraging attractant. Second, we demonstrate that Ae. aegypti larvae use chemokinesis, an unusual search strategy, to navigate chemical gradients. Finally, we use computational modelling to demonstrate that larvae respond to starvation pressure by optimizing exploration behaviour-possibly critical for exploiting limited larval habitat types. Our results identify key characteristics of foraging behaviour in an important disease vector mosquito. In addition to implications for better understanding and control of disease vectors, this work establishes mosquito larvae as a tractable model for chemosensory behaviour and navigation.


A common factors perspective on mindfulness-based interventions.
Mindfulness-based interventions (MBIs) have entered mainstream Western culture in the past four decades. There are now dozens of MBIs with varying degrees of empirical support and a variety of mindfulness-specific psychological mechanisms have been proposed to account for the beneficial effects of MBIs. Although it has long been acknowledged that non-specific or common factors might contribute to MBI efficacy, relatively little empirical work has directly investigated these aspects. In this Perspective, I suggest that situating MBIs within the broader psychotherapy research literature and emphasizing the commonalities rather than differences between MBIs and other treatments might help guide future MBI research. To that end, I summarize the evidence for MBI efficacy and several MBI-specific psychological mechanisms, contextualize MBI findings within the broader psychotherapy literature from a common factors perspective, and propose suggestions for future research based on innovations and challenges occurring within psychotherapy research.


Nematode fauna of high altitude avian hosts in Garhwal Himalayan Ecosystems I. Eustrongylides spinispiculum n. sp. and revised key to the species of genus Eustrongylides Jagerskiold (1909).
Analysis of variance has been applied as a new tool for precise substantiation of taxometric differences between Eustrongylides spinispiculum n. sp. and close species, as indicated by the polythetic divisive classificatory system. A revised key to the species of genus Eustrongylides Jagerskiod (1909) has been presented.


Changes in aortic pulse wave velocity of patients undergoing endovascular repair of abdominal aortic aneurysms.
To assess changes in pulse wave velocity (PWV), a valid index of arterial stiffness, in patients undergoing endovascular repair (EVAR) of abdominal aortic aneurysm (AAA). Arterial stiffness is an independent marker of all-cause mortality and cardiovascular morbidity and mortality. Forty-eight consecutive male patients (mean age 71±4 years) underwent elective EVAR (AAA group) after exclusion of patients with Marfan syndrome or other collagen-related disorders. Thirty-one age-matched men (mean age 69±5 years) without overt cardiovascular disease served as controls. PWV and clinical parameters were determined at baseline in both groups and after 6 months in the AAA group. At baseline, the groups did not differ in demographic characteristics, lipid profile, or blood pressure levels (p>0.05). PWV was considerably higher in AAA than controls (p<0.001). PWV positively correlated with mean blood pressure, AAA diameter, and age in univariate and multivariate analysis (R(2)=0.498, p=0.008). At 6 months after EVAR, PWV significantly increased from 13.11±3.57 m/s to 16.41±2.33 m/s (p<0.001) in the AAA group. Patients with AAA present with significantly elevated PWV levels compared to controls, and stent-graft repair is associated with a significant increase in the PWV. Whether those changes contribute to the cardiovascular risk in AAA patients needs further investigation.


A phase II study of anlotinib combined with etoposide and platinum-based regimens in the first-line treatment of extensive-stage small cell lung cancer.
The aim of this prospective, pilot, single-arm phase II trial was to evaluate the safety and efficacy of anlotinib combined with etoposide and platinum-based regimens in the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC). This phase II study was conducted at Fudan University Shanghai Cancer Center between December 2018 and December 2020. All patients received standard chemotherapy (etoposide plus cisplatin/carboplatin) consisting of four courses and anlotinib at 12 mg once per day for 2 weeks followed by a one-week rest. Anlotinib administration was continued until disease progression, intolerable adverse events (AEs) or patient withdrawal from the study. The primary outcome measure was progression-free survival (PFS). The secondary outcome measures were overall survival (OS), objective control rate (ORR), disease control rate (DCR) and AEs. Thirty-seven patients were included in this study, and 30 patients were eligible for efficacy analysis. ORR and DCR were 90.0% and 96.7%, respectively. The estimated PFS and OS were 6.0 months (95% CI: 1.1-11.9 months) and 14.0 months (95% CI: 8.6-19.4 months), respectively. No unexpected adverse effects were reported. Hypertension (20/37, 54.1%), anemia (16/37, 43.2%), alopecia (15/37, 40.5%), elevated transaminases (9/37, 24.3%) and alkaline phosphatase (9/37, 24.3%) were the most commonly reported AEs. Thirteen patients (35.1%) reported grade 3-5 AEs. No treatment-related deaths occurred during this study. The addition of anlotinib to standard etoposide/platinum chemotherapy achieved encouraging PFS and OS in previously untreated ES-SCLC patients, with an acceptable tolerability profile and no new safety signals observed.


Discovery of long-acting N-(cyanomethyl)-N-alkyl-L-prolinamide inhibitors of dipeptidyl peptidase IV.
Details of structure-activity relationships (SAR) for P2 moiety of a P1 2-cyanopyrrolidine dipeptidyl peptidase IV (DPP-IV) inhibitor 4a including stereochemistry are presented. Based on this information, a series of P1 (N-alkyl)aminoacetonitrile analogs 9-20 possessing optimal P2 structure were synthesized and evaluated as inhibitors of DPP-IV. Among them, a representative compound 11, N-(cyanomethyl)-N-ethyl-L-prolinamide, was further evaluated to determine its effect on the plasma glucose level. Also 4a, 10, and 11 were evaluated for their isozyme selectivity to predict their safety problems.


Urinary steroid profile of a newborn suffering from pseudohypoaldosteronism.
A case is described of a newborn, admitted to hospital because of severe salt loss at the age of 1 month. Subsequent analysis of urinary steroid excretion, by gas chromatography and gas chromatography-mass spectrometry, revealed that the patient suffered from pseudohypoaldosteronism. However, it was difficult to interpret the results unambiguously, since the first urinary analysis appeared to suggest 21-hydroxylase- or 18-hydroxylase deficiency. The final diagnosis was possible only after detecting high urinary levels of aldosterone and tetrahydroaldosterone. It is concluded that neonatal urinary steroid profiles should be interpreted cautiously in order to arrive at the correct diagnosis.


Validation of a chronic dietary cadmium bioaccumulation and toxicity model for Hyalella azteca exposed to field-contaminated periphyton and lake water.
A model previously developed in the laboratory to predict chronic bioaccumulation and toxicity of cadmium to Hyalella azteca from a diet of periphyton was validated by comparing predictions with measurements of Cd in two exposure scenarios: laboratory-cultured H. azteca exposed for 28 d to field-contaminated water and periphyton, and Cd measured in field-collected H. azteca. In both exposure scenarios, model predictions of bioaccumulation were shown to be robust; however, effects on Cd bioaccumulation from complexation with dissolved organic carbon (DOC) and inhibition of Cd bioaccumulation by Ca²⁺ must be incorporated into the model to permit its wider application. The model predicted that 80 to 84% of Cd in H. azteca came from periphyton when H. azteca were chronically exposed to dissolved Cd in lake water at 2.63 to 3.01 nmol/L and periphyton at 1,880 to 2,630 nmol/g ash-free dry mass. Dietary Cd contributed markedly to the model-predicted decrease in 28-d survival to 74% at environmental Cd concentrations in food and water. In reality, survival decreased to 10%. The lower than predicted survival likely was due to the higher nutritional quality of periphyton used to develop the model in the laboratory compared with the field-collected periphyton. Overall, this research demonstrated that Cd in a periphyton diet at environmental concentrations can contribute to chronic toxicity in H. azteca.


Temporal patterns of selected late toxicities in patients treated with brachytherapy or brachytherapy plus external beam radiation for prostate adenocarcinoma.
What's known on the subject? and What does the study add? While the frequencies and severity of late toxicities following prostate brachytherapy are well known, less has been published with regard to time to first onset. Several series with limited median follow-up have published time to onset. An extensive analysis of timing to late toxicity following brachytherapy for cervical cancer has also been published. This study is the largest of its kind with the longest median follow-up to capture very late events. It can provide a basis for physician and patient education about when late toxicities can reasonably be expected to occur. The study also shows that a significant amount of erectile dysfunction might be more age related than radiation induced. • To assess the timing of first onset of late rectal bleeding, late haematuria and erectile dysfunction (ED) following brachytherapy with or without external beam radiation therapy (EBRT) for prostate adenocarcinoma. • To identify treatment factors and patient characteristics that affect the time to first onset. • In all, 2046 patients were definitively treated for prostate adenocarcinoma with a full (125) I or (103) Pd implant or a partial (103) Pd implant followed by EBRT with 6 years median follow-up (range 2-17 years). • Patients were selected for an event of Radiation Therapy Oncology Group (RTOG) grade 2 or greater rectal bleeding, ≥RTOG grade 2 haematuria, or a drop in the Mount Sinai Erectile Dysfunction Score from potent to impotent (excluding patients who received androgen deprivation therapy). • Life tables were generated to calculate actuarial incidence rates of toxicity. • Wilcoxon rank sum and Cox regression were utilized to identify treatment factors affecting time to onset. • The incidence rate per 1000 patients for 0-2 years, 2-5 years and 5-10 years following radiation for rectal bleeding is 14.3, 15.9 and 6.5, respectively; for haematuria, 14.0, 8.2 and 1.3, respectively; and for ED, 82.4, 48.2 and 42.2, respectively. • Just 5% of rectal bleeding occurs after 5 years from radiation vs 18% of haematuria cases and 22% of ED. • On multivariate analysis, time to first onset of rectal bleeding was affected by the addition of EBRT only whereas the time to onset of haematuria was affected by the biological effective dose of the radiation and the addition of EBRT. • The only factor on multivariate analysis to affect time to onset of ED was the age of the patient at treatment, independent of radiation dose or technique. • Unique temporality to first onset of selected toxicities was observed in patients after radioactive implant for prostate adenocarcinoma with or without EBRT. • Clinicians and patients should be counselled when to expect late toxicities. • The only factor to affect time to onset of ED is the age of the patient, suggesting possible over-reporting of radiation-induced ED in the light of normal age-related events.


1H-13C heteronuclear single quantum coherence NMR evidence for iodination of natural organic matter influencing organo-iodine mobility in the environment.
The complex biogeochemical behavior of iodine (I) isotopes and their interaction with natural organic matter (NOM) pose a challenge for transport models. Here, we present results from iodination experiments with humic acid (HA) and fulvic acid (FA) using 1H-13C heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR) spectroscopy. Even though not a quantitative approach, 1H-13C HSQC NMR corroborated that iodination of NOM occurs primarily through aromatic electrophilic substitution of proton by I, and also revealed how iodination chemically alters HA and FA in a manner that potentially affects the mobility of iodinated NOM in the environment. Three types of iodination experiments were conducted with HA and FA: a) non-enzymatic iodination by IO3- (pH 3) and I- (pH 4 and 7), b) addition of lactoperoxidase to promote I--iodination in the presence of the co-substrate, H2O2 (pH 7), and c) addition of laccase for facilitating I--iodination in the presence of O2, with or without a mediator (pH 4). When mediators or H2O2 were present, extracellular oxidases and peroxidases enhanced I- incorporation into NOM by between 54% and 3400%. Iodination of HA, which was less than that of FA, enhanced HA's stability (inferred from increases in aliphatic compounds, decreases in carbohydrate moieties, and thus increased molecular hydrophobicity) yet reduced HA's tendency to incorporate more iodine. As such, HA is expected to act more as a sink for iodine in the environment. In contrast, iodination of FA appeared to generate additional iodine binding sites, which resulted in greater iodine uptake capability and enhanced mobility (inferred from decreases in aliphatic compounds, increases in carbohydrates, and thus decreases in molecular hydrophobicity). These results indicate that certain NOM moieties may enhance while others may inhibit radioiodine mobility in the aqueous environment.


Illicit drug use and acute kidney injury in patients admitted to hospital with rhabdomyolysis.
Severe rhabdomyolysis is associated with acute kidney injury, but it is unclear if patients developing rhabdomyolysis after illicit drug use have a higher risk of acute kidney injury compared to other causes. To provide a descriptive analysis of patients admitted with rhabdomyolysis, with a focus on illicit drug use, and to determine if illicit drug use was an independent predictor for acute kidney injury or renal replacement therapy. We conducted a 5-year cohort study of patients admitted to Monash Health, a tertiary referral hospital network. We identified adult patients with muscle injury from ICD-10 AM codes, serum creatine kinase level greater than 1000 U/mL, and a clinical history consistent with rhabdomyolysis. We determined the prevalence and type of illicit drug involved and determined the association between illicit drug use and renal outcomes by logistic regression. Of 643 patients, illicit drug use was identified in 12%. Acute kidney injury developed in 51%, and 5% required renal replacement therapy. Compared to the rest of the cohort, patients who used illicit drugs were younger and had higher peak serum creatine kinase, and developed a higher severity of acute kidney injury. In multivariable analysis, the factors associated with acute kidney injury were illicit drug use, peak creatine kinase, cardiovascular disease, concurrent sepsis and a clinically-evident pressure injury. Chronic kidney disease and need for fasciotomy were additional risk factors for renal replacement therapy. Illicit drug use was associated with acute kidney injury and renal replacement therapy independent of creatine kinase levels.


Cdc42 Couples T Cell Receptor Endocytosis to GRAF1-Mediated Tubular Invaginations of the Plasma Membrane.
: T cell activation is immediately followed by internalization of the T cell receptor (TCR). TCR endocytosis is required for T cell activation, but the mechanisms supporting removal of TCR from the cell surface remain incompletely understood. Here we report that TCR endocytosis is linked to the clathrin-independent carrier (CLIC) and GPI-enriched endocytic compartments (GEEC) endocytic pathway. We show that unlike the canonical clathrin cargo transferrin or the adaptor protein Lat, internalized TCR accumulates in tubules shaped by the small GTPase Cdc42 and the Bin/amphiphysin/Rvs (BAR) domain containing protein GRAF1 in T cells. Preventing GRAF1-positive tubules to mature into endocytic vesicles by expressing a constitutively active Cdc42 impairs the endocytosis of TCR, while having no consequence on the uptake of transferrin. Together, our data reveal a link between TCR internalization and the CLIC/GEEC endocytic route supported by Cdc42 and GRAF1.


Endotracheal suction for adult, non-head-injured, patients. A review of the literature.
The procedure for endotracheal suctioning was perceived as a problem by the members of a quality circle in the intensive care unit (ICU). Endotracheal suction, when performed in the unit, appeared to be carried out according to the nurses' experience and expertise, and had no formal research backing. An extensive literature search was undertaken, and a framework for endotracheal suction was formulated based on the available evidence. Some of the aspects of endotracheal suction represented in the research evidence appear contradictory, and nurses must make a professional judgement about their suction technique based on the individual circumstances of patients. The wealth of evidence available regarding endotracheal suctioning allows nurses to make an informed decision about care.


Vasoactive intracavernous pharmacotherapy--the nursing role in teaching self-injection therapy.
Our physician-nurse team management of a program in vasoactive intracavernous pharmacotherapy to treat male impotence has provided a high degree of patient and partner satisfaction. Nurses participate in the assessment of the ability of a patient or partner to master the self-injection technique, and the potential of a couple for compliance with and commitment to the program, all of which are key factors for successful home therapy. A nurse also teaches the self-injection technique. Audiovisual materials and handouts are used as teaching aids to ensure that complete and consistent information is given. The patient or partner is required to perform a self-injection under nursing supervision before a prescription for home use written. Initial followup visits are scheduled with a nurse at 1 to 2-week intervals. At these visits the nurse identifies possible patient errors in self-injection technique, dose or frequency, and answers questions about the therapy. After the couple has mastered and is comfortable with home injection, followup appointments are scheduled with the physician at 4-week intervals to monitor for possible changes in response to treatment and for an examination of the phallus.


Identification of novel tumor-associated antigens and evaluation of a panel of autoantibodies in detecting oral cancer.
We aimed to identify tumor-associated antigen (TAA) biomarkers through bioinformatic analysis and experimental verification, and to evaluate a panel of autoantibodies against tumor-associated antigens (TAAbs) for the detection of oral cancer (OC). GEO and TCGA databases were used to screen significantly up-regulated genes related to OC, and protein-protein interaction (PPI) analysis and Cystoscope software were used to identify key genes. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of autoantibodies in 173 OC patients and 173 normal controls, and binary logistic regression analysis was used to build a diagnostic model. Using bioinformatics, we identified 10 key genes (AURKA, AURKB, CXCL8, CXCL10, COL1A1, FN1, FOXM1, MMP9, SPP1 and UBE2C) that were highly expressed in OC. Three autoantibodies (anti-AURKA, anti-CXCL10, anti-FOXM1) were proven to have diagnostic value for OC in the verification set and the validation set. The combined assessment of these three autoantibodies improved the diagnostic value for OC, with an area under the curve (AUC), sensitivity and specificity of 0.741(95%CI:0.690-0.793),58.4% and 80.4%, respectively. In addition, the combination of these three autoantibodies also had high diagnostic value for oral squamous cell carcinoma (OSCC), with an AUC, sensitivity and specificity of 0.731(95%CI:0.674,0.786), 53.8% and 82.1%, respectively. Our study revealed that AURKA, CXCL10 and FOXM1 may be potential biomarkers and the panel of three autoantibodies (anti-AURKA, anti-CXCL10 and anti-FOXM1) had good diagnostic value for OC.


Balloon-occluded Retrograde Transvenous Obliteration of Portovenous Shunts During Endoscopic Therapy for the Treatment of Gastric Varices.
To explore the safety and feasibility of balloon-occluded retrograde transvenous obliteration (BRTO) of portovenous shunts during endoscopic cyanoacrylate injection for the treatment gastric varices (E-BRTO) secondary to portal hypertension. A total of 28 cirrhotic patients with gastroesophageal varices and concurrent gastrorenal or gastrosplenorenal shunt, treated with E-BRTO, were enrolled. Operative details were recorded to evaluate the safety, feasibility, and efficacy of the procedure. Short-term follow-up was conducted to denote any incidence of distant emboli, variceal rebleeding, or mortality (Video, Supplemental Digital Content 1, http://links.lww.com/SLE/A179). All the patients successfully received E-BRTO without intraoperative complications. The average volume of cyanoacrylate was 2.4±1.3 mL. During the 90 days follow-up, none of the patients experienced distant systemic emboli. However, 8 patients suffered from gastrointestinal rebleeding, including one death, while 2 patients were lost to follow-up. The short-term rebleeding rate (intention to treat) was about 36% in E-BRTO for this subset of patients. BRTO during endoscopic cyanoacrylate injection is an alternative selection for cirrhotic patients with portovenous shunts. The procedure is feasible and procedurally safe, but the associated high rebleeding rate may require a multimodality approach.


Cerebral sinus venous thrombosis in a subject with thyrotoxicosis and MTHFR gene polymorphism.
We report a case of cerebral venous thrombosis (CVT) due to tyrotoxicosis in a patient with methylenetetrahydro-folate-reductase (MTHFR) gene polymorphism C677T, (genotype 677TT), in which discontinuation of intravenous heparin was followed by clinical and radiological worsening despite warfarin treatment. We discuss the relationship between CVT, MTHFR hyperthiroidism and anticoagulant therapy.


Relative displacements in muscle and tendon during human arm movements.
1. X-ray, cine and video recordings were made of the movement of radio-opaque markers injected into the musculo-tendinous junctions of biceps brachii muscle. 2. In strong isometric contractions, the distal tendon of the long head of biceps lengthened by about 2% of its estimated rest length. 3. During voluntary isotonic elbow flexion-extension movements at frequencies up to 5.5 Hz there was no detectable phase shift between intramuscular and joint displacements. 4. In the fastest alternating movements (5.5-6.7 Hz) small phase advances developed in the muscle. 5. We conclude that human tendons do stretch during muscle contraction, but not enough to cause intramuscular phase reversals in rapid unloaded movements. This in turn means that muscle spindles shorten and lengthen virtually in phase with joint movements under most conditions.


Food robbing in ants, a form of interference competition.
Food robbing is a special form of interference competition in ants. It has been frequently observed in Myrmecocystus mimicus, which waylay returning foragers of several Pogonomyrmex species at their nests and take insect prey, particularly termites, away from them. Myrmecocystus more successfully robs prey from P. desertorum and P. maricopa than from P. barbatus. Usually only those Pogonomyrmex nests are affected by Myrmecocystus prey robbing that are not farther away than 10 m from the Myrmecocystus nest. Some M. mimicus workers show a high specialization in prey robbing. Other cases of food robbing in ants are described.


The effects of streptozotocin diabetes on sodium-glucose transporter (SGLT1) expression and function in rat jejunal and ileal villus-attached enterocytes.
Rats treated with streptozotocin for 17 days were used to determine the cellular origin of enhanced brush border glucose transport in the diabetic small intestine. In the jejunum of both normal and diabetic rats, phlorizin-sensitive (SGLT1-mediated) glucose transport was shown, by section autoradiography, to take place in upper villus enterocytes. The distribution of brush border SGLT1 transporters along villi, determined using immunogold cytochemistry, was similar to that found for glucose uptake. Longer villi, supporting a larger number of absorbing enterocytes in the diabetic jejunum, appeared to be responsible for increased glucose uptake in this condition. SGLT1 protein and SGLT1-mediated glucose transport were undetectable in normal distal ileal villi. However, following treatment with streptozotocin, both SGLT1 protein and SGLT1-mediated glucose transport were found to be present in basal ileal villus enterocytes. SGLT1 protein and SGLT1-mediated glucose transport both increased during enterocyte migration to the villus tip. Cellular induction of the SGLT1 transporter, as well as longer villi contribute to enhanced glucose transport in diabetic rat distal ileum. Close correlation between the positional expression of SGLT1 protein and absorptive function suggests that transporter density is an important determinant for up-regulation of sodium-dependent glucose transport in diabetes.


Tomoelastography Paired With T2* Magnetic Resonance Imaging Detects Lupus Nephritis With Normal Renal Function.
The aim of this study was to test multiparametric magnetic resonance imaging including blood oxygen level-dependent (BOLD) imaging by T2* mapping, magnetic resonance elastography (MRE) by tomoelastography, and diffusion-weighted imaging (DWI) for detecting nephropathy in patients with lupus nephritis (LN). Forty-one subjects (25 patients with LN and 16 age- and sex-matched healthy volunteers; LN: mean age, 47.3 ± 14.8 years; 22 female subjects; volunteers: mean age, 43.9 ± 11.6 years; 13 female subjects) were prospectively enrolled. The LN group was further divided into subgroups with normal (LN-nRF, GFR > 90 mL/min per 1.73 m) and compromised renal function (LN-cRF, GFR < 90 mL/min per 1.73 m). All subjects were examined by multifrequency MRE, BOLD imaging, and DWI, yielding shear wave speed (SWS; in meter per second), T2* relaxation times (in millisecond), and apparent diffusion coefficient (ADC; in millimeter square per second), respectively. Renal subregional analysis was performed for the medulla (ME), inner cortex (CoI), and outer cortex (CoO). Imaging markers were correlated to clinical parameters such as GFR and protein-to-urine creatinine ratio. Cutoffs and area under the receiver operating curve (AUROC) were computed to test diagnostic performances. Compared with CoI and CoO, LN-nRF predominantly affects ME tissue (SWS: -7%, P < 0.01; T2*: +9%, P < 0.05; ADC: -5%, P = 0.27). Detection of LN-nRF was better with MRE compared with BOLD imaging and DWI (AUROC = 0.81, 0.76, not significant), whereas pairing MRE with T2* further increased diagnostic power (AUROC = 0.91). Disease progression was associated with reduction of SWS also in CoI (LN-nRF, 3.04 ± 0.38 m/s; LN-cRF, 2.60 ± 0.26 m/s; p = 0.013), allowing distinction of LN-nRF from LN-cRF (AUROC = 0.83). Diffusion-weighted imaging was only sensitive to LN-cRF in ME tissue (ADC, -12%; P < 0.05). Lupus nephritis with normal renal function first arises in MRE and BOLD images within ME tissue, progressing to CoI tissue once renal function becomes impaired and diffusion of tissue water changes.


X-linked ocular albinism: prevalence and mutations--a national study.
In a national retrospective register study 112 patients with ocular albinism (OA) were identified, including 60 male patients with proven or presumed X-linked ocular albinism (XLOA). Based on the birth year cohorts 1960-1989, an XLOA point prevalence at birth of 1 in 60,000 live-born was calculated. We identified 14 XLOA families in the Danish population, and obtained DNA from affected persons in nine families. Mutation analysis of the OA1 gene demonstrated seven presumed pathogenic mutations in the nine families with XLOA: five single nucleotide substitutions predicting a change of conserved amino acids (G35D, L39R, D78V, W133R and E233K) when compared with the mouse OA1 homologue, one deletion leading to the skipping of exon 2, and one single nucleotide substitution expected to affect the 5' splice site of intron 2 were found. Subsequent genealogical investigations in the three families harbouring the same mutation disclosed that two of the three pedigrees belonged to the same family. All mutations predict crucial changes in the protein structure. Clinical examination failed to identify any phenotype-genotype pattern except a milder phenotype devoid of iris translucency in the patient with the 5'splice site mutation of intron 2.


Syntheses and Properties of (Nitronyl nitroxide)-substituted Tri-phenylamine ortho-Bridged by Two Oxygen and Sulfur Atoms.
A nitronyl nitroxide unit (NN) was linked with a triphenylamine-based condensed polycyclic skeleton DOTT to form a radical substituted donor NN-DOTT. X-ray crystal structure analysis demonstrated a flat bowl shape of the DOTT unit. EPR spectra showed the localization of electron spin on the NN unit. Chemical oxidation of the DOTT unit produced radical-substituted radical cation salts NN-DOTT+ ⋅ SbF6 - and NN-DOTT+ ⋅ FeBr4 - that are stable under ambient conditions. The magnetic behavior of NN-DOTT+ ⋅ SbF6 - is characterized by the strong intramolecular ferromagnetic interaction between NN and DOTT+ . The X-ray structural analysis of NN-DOTT+ ⋅ FeBr4 - shows planar structure of DOTT and 1D mixed-stack column of NN-DOTT+ and FeBr4 - . Magnetic measurements established that NN-DOTT+ ⋅ FeBr4 - undergoes magnetic phase transition into a weak ferromagnet at 7 K.


Interchange reaction of disulfides and denaturation of oxytocin by copper(II)/ascorbic acid/O2 system.
The interchange reaction of disulfides was caused by the copper(II)/ascorbic acid/O2 system. The incubation of two symmetric disulfides, L-cystinyl-bis-L-phenylalanine (PP) and L-cystinyl-bis-L-tyrosine (TT), with L-ascorbic acid and CuSO4 in potassium phosphate buffer (pH 7.2, 50 mM) resulted in the formation of an asymmetric disulfide, L-cystinyl-L-phenylalanine-L-tyrosine (PT), and the final ratio of PP:PT:TT was 1:2:1. As the reaction was inhibited by catalase and DMSO only at the initial time, hydroxyl radical generated by the copper(II)/ascorbic acid/O2 system seemed to be responsible for the initiation of the reaction. Oxytocin and insulin were denatured by this system, and catalase and DMSO similarly inhibited these denaturations. As the composition of amino acids was unchanged after the reaction, hydroxyl radical was thought to cause the cleavage and/or interchange reaction of disulfides to denature the peptides.


Abnormal expression of the KLF8 (ZNF741) gene in a female patient with an X;autosome translocation t(X;21)(p11.2;q22.3) and non-syndromic mental retardation.
Non-syndromic X linked mental retardation (MRX) is a heterogeneous group of conditions in which all patients have mental retardation as the only constant phenotypic feature. We have identified a female patient with mental retardation and a balanced translocation involving chromosomes X and 21, t(X;21)(p11.2;q22.3). Physical mapping of the translocation breakpoint on the human X chromosome was performed using fluorescence in situ hybridisation. We have mapped the X chromosome breakpoint to a 21 kb DNA fragment upstream of the first exon of the KLF8 (ZNF741) gene in Xp11.21. We have subsequently shown that the KLF8 transcript is no longer detected in cells from the patient, although KLF8 expression is otherwise normally present in control lymphoblasts. Mutation screening of probands from 20 unrelated XLMR families linked to the proximal short arm of the human X chromosome failed to show any mutation in the coding region of the KLF8 gene.


Behavioral responses to prey density by three acarine predator species with different degrees of polyphagy.
Behavioral responses by three acarine predators, Phytoseiulus persimilis, Typhlodromus occidentalis, and Amblyseius andersoni (Acari: Phytoseiidae), to different egg and webbing densities of the spider mite Tetranychus urticae (Acari: Tetranychidae) on rose leaflets were studied in the laboratory. Prey patches were delineated by T. urticae webbing and associated kairomones, which elicit turning back responses in predators near the patch edge. Only the presence of webbing affected predator behavior; increased webbing density did not increase patch time. Patch time increased with increased T. urticae egg density in the oligophagous P. persimilis, but was density independent in the polyphagous species T. occidentalis and A. andersoni. Patch time in all three species was more strongly correlated with the number of prey encounters and attacks than with the actual prey number present in the patch. Patch time was determined by (a) the turning back response near the patch edge; this response decayed through time and eventually led to the abandonment of the patch, and (b) encounters with, and attacks upon, prey eggs; these prolonged patch time by both an increment of time spent in handling or rejecting prey and an increment of time spent searching between two successive prey encounters or attacks. Although searching efficiency was independent of prey density in all three species, the predation rate by P. persimilis decreased with prey density because its searching activity (i.e. proportion of total patch time spent in searching) decreased with prey density. Predation rates by T. occidentalis and A. andersoni decreased with prey density because their searching activity and success ratio both decreased with prey density. The data were tested against models of predator foraging responses to prey density. The effects of the degree of polyphagy on predator foraging behavior were also discussed.


Elective nodal irradiation mitigates local and systemic immunity generated by combination radiation and immunotherapy in head and neck tumors.
In the setting of conventional radiation therapy, even when combined with immunotherapy, head and neck cancer often recurs locally and regionally. Elective nodal irradiation (ENI) is commonly employed to decrease regional recurrence. Given our developing understanding that immune cells are radio-sensitive, and that T cell priming occurs in the draining lymph nodes (DLNs), we hypothesize that radiation therapy directed at the primary tumor only will increase the effectiveness of immunotherapies. We find that ENI increases local, distant, and metastatic tumor growth. Multi-compartmental analysis of the primary/distant tumor, the DLNs, and the blood shows that ENI decreases the immune response systemically. Additionally, we find that ENI decreases antigen-specific T cells and epitope spreading. Treating the primary tumor with radiation and immunotherapy, however, fails to reduce regional recurrence, but this is reversed by either concurrent sentinel lymph node resection or irradiation. Our data support using lymphatic sparing radiation therapy for head and neck cancer.


Grass pollen immunotherapy for hayfever is associated with increases in local nasal but not peripheral Th1:Th2 cytokine ratios.
Grass pollen immunotherapy is the only treatment for hayfever that is both effective and confers long-term benefit. Immunotherapy may act by altering the local nasal mucosal T helper type 2 (Th2) to type 1 (Th1) cytokine balance either by down-regulation and/or immune deviation of T-lymphocyte responses. There is controversy as to whether these changes are detectable in peripheral blood. We therefore examined both local nasal and peripheral T-cell responses to allergen exposure in the same subjects before and after immunotherapy. In a double-blind trial of grass pollen immunotherapy, nasal biopsies were obtained at baseline and during the peak pollen season following 2 years of immunotherapy. Placebo-treated patients showed a seasonal increase in CD3(+) T cells (P = 0.02) and in interleukin-5 (IL-5) mRNA(+) cells (P = 0.03) and no change in interferon-gamma (IFN-gamma ) mRNA(+) cells (P = 0.2) in the nasal mucosa. In contrast, in the immunotherapy-treated group, there were no changes in the number of CD3(+) T cells (P = 0.3) and IL-5 mRNA+ cells (P = 0.2) but a significant increase in the number of IFN-gamma mRNA(+) cells (P = 0.03). Furthermore, clinical improvement in the immunotherapy-treated group was accompanied by a seasonal increase in the ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa (P = 0.03). In contrast, there were no significant changes in peripheral T-cell proliferative responses or cytokine production for IFN-gamma or IL-5 in response to grass pollen either within or between the two treatment groups. We conclude that successful grass pollen immunotherapy was associated with an increase in the ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa, whereas these changes were not reflected by alterations in peripheral blood T-cell proliferative responses or cytokine production before/after treatment.


Guideline adherence among prehospital emergency nurses when caring for patients with chest pain: a prospective cohort study.
The emergency medical services (EMS) use guidelines to describe optimal patient care for a wide range of clinical conditions and symptoms. The intent is to guide personnel to provide patient care in line with best practice. The aim of this study is to describe adherence to such guidelines among prehospital emergency nurses (PENs) when caring for patients with chest pain. To describe guideline adherence among PENs when caring for patients with chest pain. To investigate whether guideline adherence is associated with patient age, sex or final diagnosis of acute myocardial infarction on hospital discharge. Guideline adherence in terms of patient examination and pharmaceutical treatment was analysed in a cohort of 2092 EMS missions carried out in 2018 in Region Halland, Sweden. Multivariate regression was used to describe how guideline adherence is associated with patient age, sex and diagnosis on hospital discharge. Guideline adherence was high regarding examination of vital signs (93%) and electrocardiogram (ECG) registration (96%) but lower in terms of pharmaceutical treatment (ranging from 28 to 90%). Adherence was increased in cases in which the patient ended up with acute myocardial infarction (AMI) as diagnosis on discharge. Patients with AMI were given acetylsalicylic acid by PENs in 50% of cases. Women were less likely than men to receive treatment with acetylsalicylic acid and oxycodone. Guideline adherence among PENs when caring for patients with chest pain is satisfactory in terms vital signs and ECG registration. Regarding pharmaceutical treatment guideline adherence is defective. Improved adherence is mainly associated with male sex in patients and a diagnosis of AMI on hospital discharge. Defective adherence excludes measures known to improve patients' prognoses such as treatment with acetylsalicylic acid.


Superior enhancement in thermal conductivity of epoxy/graphene nanocomposites through use of dimethylformamide (DMF) relative to acetone as solvent.
This method article describes the fabrication of graphene-epoxy nanocomposites using two different solvents, dimethylformamide (DMF) and acetone, and validates the resulting thermal conductivity improvements. The study compared the two solvents at a filler composition of 7 wt% and found that DMF resulted in more uniform dispersion of graphene nanoparticles in the epoxy matrix, leading to a 44% improvement in thermal conductivity compared to acetone. Laser scanning confocal microscopy (LSCM) imaging showed that DMF-based composites had more evenly dispersed graphene nanoplatelets than acetone-based composites, which exhibited larger graphene agglomerations. Effective medium theory calculations showed that DMF led to almost 35% lower interface thermal resistance between graphene and epoxy compared to acetone. The validated fabrication method and findings provide new possibilities for developing high thermal conductivity graphene-epoxy nanocomposites for various thermal management applications.•This article describes methods for fabricating graphene-epoxy composites using acetone and DMF as solvents, and validates that DMF is better for achieving higher thermal conductivity in the composite.


Rapid effects of triiodothyronine on hepatic gene expression. Hybridization analysis of tissue-specific triiodothyronine regulation of mRNAS14.
We recently reported that 3,5,3'-triiodothyronine (T3) causes a rapid increase in the translational activity of a specific mRNA (mRNAS14) coding for a protein designated "Spot 14" (Mr = 18,000; 4.9 pI) using two-dimensional gel electrophoresis of in vitro translated proteins. The current studies suggest that Spot 14 is a cytosolic protein. Using a plasmid-derived cDNAS14 and dot hybridization, we have directly measured changes in hepatic mRNAS14 levels in response to T3 and other physiologic stimuli. Following injection of hypothyroid rats with a receptor-saturating dose of T3, a 20-min lag preceded the induction of hepatic mRNAS14 to levels 16-fold above basal values within 4 h. This is the most rapid effect of T3 on hepatic gene expression documented to date. Both during time course studies in hypothyroid animals injected with T3 as well as in the intact euthyroid rat, hepatic mRNAS14 levels varied up to 3-fold over a 24-h period in a pattern consistent with circadian variation. A lipogenic diet also significantly elevated hepatic mRNAS14. Thus, T3, dietary, and the unknown factors responsible for circadian variation influence hepatic mRNAS14 expression. Blot and dot hybridization analysis indicated that mRNAS14 expression in nonhepatic tissues was significantly below euthyroid hepatic values. Responsivity of mRNAS14 in nonhepatic tissue to in vivo T3 administration was also either substantially diminished or totally absent. Thus, expression and regulation of mRNAS14 is tissue specific.


Characteristics and Outcomes of Patients Treated With Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (The Mayo Clinic Experience).
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors represent a novel addition to the lipid-lowering armamentarium. We attempted to characterize a real-world group of patients with a clinical indication for PCSK9 inhibitors and describe their clinical outcomes and adverse effect profile. A retrospective chart review was conducted, evaluating all patients referred to preventive cardiology at the Mayo Clinic (Minnesota) between September, 2015 and December, 2018 for management of severe dyslipidemia. A total of 222 patients were referred and a recommendation to start a PCSK9 inhibitor was given to 164 patients (73.9%). Of these, 28 patients (17.1%) declined the use of a PCSK9 inhibitor. A total of 136 previous authorizations were submitted. Of these applications, 96 (70.6%) were approved and 17 (12.5%) were rejected. The cohort's mean age was 64.1 years (range 39 to 91). High-intensity statins and ezetimibe were used in 50 (52.1%) and 80 (83.3%) of the treated patients. Mean pretreatment low-density lipoprotein cholesterol was 167.9 mg/dl. At a median follow-up of 19.0 months, the mean low-density lipoprotein reduction was 60.9% (range 0 to 90.3%). Higher low-density lipoprotein cholesterol percent reductions were seen in younger patients (p value 0.048), patients on high-intensity statins (p value 0.027), those with statin intolerance (p value 0.046), and individuals with a higher baseline triglycerides (p value 0.047). Two (2.1%) patients underwent coronary revascularization, and 1 (1.0%) patient was hospitalized for unstable angina. No cardiovascular deaths occurred. Adverse events were reported in 12 (12.5%) patients, and were all minor (injection site reactions, myalgias, and flu-like illness). In conclusion, our study shows an efficacy and safety profile that is concordant with previous investigations. The use of a standardized application form was associated with a high insurance approval rate.


Immunological response of female macaques to the PH-20 sperm protein following injection of recombinant proteins or synthesized peptides.
Because of its location on the sperm surface and its multiple functions during fertilization, the PH-20 protein is a potential target for contraceptive vaccines. Cynomolgus macaques were immunized using four different adjuvants together with synthesized peptides or recombinant proteins representing selected regions of macaque PH-20. The synthesized peptide (amino acids 387-412, designated Peptide 4) was used as a linear molecule in a 1:1 ratio with a peptide sequence of tetanus toxoid, as well as a multiple antigenic peptide (MAP) matrix held together by scaffolding lysine residues. In the MAP construct, the ratio of Peptide 4 to tetanus peptide was 4:1. To circumvent the poor production of recombinant PH-20 in bacterial cells, two truncated forms of the molecule were expressed in Escherichia coli, G18 (encoding amino acids 143-510) and E10 (encoding amino acids 291-510). The adjuvants were Montanide ISA 51, Titermax Gold, Syntex adjuvant formulation (SAF), and QS-21. All of the antigen/adjuvant combinations produced significant immune responses as measured by ELISA. The circulating antibodies from immunized animals recognized macaque sperm surface PH-20 on Western blots and were shown by indirect immunofluorescence to bind to the surface of macaque sperm. Montanide and Titermax were associated with higher titers of anti-PH-20 antibodies than QS-21 and SAF adjuvants. Immunization with Titermax, however, resulted in sterile abscesses in 4 of 8 animals injected. We conclude that antigens derived from synthesized peptides and recombinant proteins representing selected regions of the PH-20 molecule can be used as vaccine components in combination with the adjuvant Montanide to elicit a significant sperm-directed antibody response in immunized macaques.


Predicting Alzheimer dementia in mild cognitive impairment patients. Are biomarkers useful?
A correct clinical diagnosis in the early stage of Alzheimer disease is not only of importance given the current available treatment with acetylcholine esterase inhibitors, but would be the basis for disease-modifying therapy slowing down or arresting the degenerative process. Moreover, in the last years, several efforts have been made to determine if a patient with mild cognitive impairment has incipient Alzheimer disease, i.e. will progress to Alzheimer disease with dementia, or have a benign form of mild cognitive impairment. In this review, the recent published reports regarding progress in early and preclinical Alzheimer disease diagnosis are discussed and the role of peripheral and cerebrospinal fluid biomarkers highlighted. Approaches combining panels of different biomarkers show promise for discovering profiles that are characteristic of Alzheimer disease, even in the pre-symptomatic stage. More work is needed but available novel perspectives offered by recent introduced technologies shed some lights in identifying incipient Alzheimer disease in mild cognitive impairment subjects.


Compensation mechanism for membrane potential against hypoosmotic stress in the Onchidium neuron.
The effect of acute hypoosmotic stress on the neural response was investigated using the neurons identified in the abdominal ganglion of the amphibious mollusk Onchidium. The membrane potential of an identified neuron (Ip-1/2) was not significantly altered in 50% hypoosmotic artificial sea water. In isotonic 50% artificial seawater (ASW) with osmolarity that was compensated for using glycerol or urea, the membrane potentials of Ip-1/2 were also not altered compared to those in 50% hypoosmotic ASW. However, hyperpolarization was induced in isotonic 50% ASW when osmolarity was compensated for using sucrose or mannose. In the presence of volume-regulated anion channel (VRAC) inhibitors (niflumic acid and glibenclamide), the Ip-1/2 membrane potentials were hyperpolarized in 50% hypoosmotic ASW. These results suggest that there is a compensatory mechanism involving aquaglyceroporin and VRAC-like channels that maintains membrane potential under hypoosmotic conditions. Here, we detected the expression of aquaglyceroporin mRNA in neural tissues of Onchidium.


Imaging blood-brain barrier disruption: an evolving tool for assessing the risk of hemorrhage after thrombolysis.
This Practice Point commentary discusses a study by Kastrup et al. that demonstrates that the early detection of blood-brain barrier (BBB) disruption as detected on post-contrast enhanced T1-weighted MRI after thrombolysis for acute ischemic stroke predicts subsequent intracerebral hemorrhage. No parenchymal enhancements were detected on scans before thrombolysis; however, after thrombolysis, 3 of 48 patients had parenchymal enhancement in the areas of the initial insult and these patients later developed symptomatic hemorrhages at these sites. These data suggest that assessment of BBB integrity might be a useful addition to a multimodal MRI study, potentially improving the overall efficacy of thrombolysis and broadening the effective time window. Further work is needed to optimize an imaging sequence that will be short and sufficiently sensitive to detect early damage to the BBB before treatment. Meanwhile, prudent clinicians should select patients for therapy on the basis of accepted guidelines and best clinical judgment.


Fabrication of small-structure red-emissive fluorescent probes for plasma membrane enables quantification of nuclear to cytoplasmic ratio in live cells and tissues.
Nuclear to cytoplasmic ratio is one of the vital parameters in diagnosis of cancer by means of hematoxylin-eosin (HE) stained histopathology. However, HE histopathology dependent on mechanical tissue slice damages biosamples and exhibits insufficient accuracy. Herein, we rationally prepared two small-molecule plasma membrane fluorescent probes with red-emitting fluorescence for visualizing plasma membrane in living cells and tissues. Their fluorescence intensities are strongly affected by environmental viscosity, which enables the exclusive imaging of plasma membrane in high fidelity. The probes can visualize plasma membrane in SiHa and rat blood red cells. Particularly, the probes are able to visualize T-tubule (transverse tubule) in skeletal muscle tissues successfully, suggesting their ability to image plasma membrane in tissues. In cooperation with Hoechst 33342, the nuclear to cytoplasmic ratio was successfully qualified in live cells and tissues. We believe these probes may have potential applications in facilitating the study on histopathology and the related areas.


Depolarization-induced decreases in fluroescence intensity of gastro-intestinal quinacrine-binding nerves.
Quinacrine, a fluorescent antimalarial acridine derivative, selectively binds to a population of nerve cell bodies and nerve fibers in Auerbach's plexus and elsewhere in the gut. This quinacrine-binding, as measured by fluorescence intensity, is reduced if the nervous elements are depolarized by high K+ (80--150 MM) or veratridine (5 x 10(-5) M) during quinacrine incubation. A reduction of quinacrine-content in nerve terminals is also seen when depolarization (veratridine) takes place for 2 min after quinacrine-incubation, indicating a release of already bound quinacrine. If terminals are depolarized (high K+ or veratridine) before quinacrine incubation, a reduction of quinacrine content is also seen. The depolarization-induced reduction of quinacrine-binding is blocked by Ca2+-removal and, in the case of veratridine by tetrodotoxin. Our findings suggest that quinacrine binds to a compound that is released by nervous activity. Binding mechanism remains to be elucidated. The possibility that quinacrine visualized purine-rich structures is discussed.


Sodium and blood pressure: positive associations in a north London population with consideration of the methodological problems of within-population surveys.
Blood pressure (BP) and 24-hr urinary sodium (Na) and potassium (K) excretion were measured in 58 men and women aged 40 and above who were selected randomly from the age-sex register of a general practice in North London. All 58 urine collections were reported as complete, but only 28/56 (50%) were classified as 'complete' by the excretion of a biological marker, p-aminobenzoic acid (PABA). Reliability of Na excretion estimated from repeated urine collections was 0.86, indicating that variability of Na excretion within individuals in this middle-aged and elderly population was low. Systolic blood pressure (SBP) was significantly related to 24-hr Na excretion and to 24-hr Na/creatinine ratio. After adjustment for age, sex and body mass index, a SBP-Na regression coefficient of 0.091 mmHg/mmol Na (P = 0.02) was observed. On simple regression analysis, a significant association was also found between diastolic blood pressure and Na (P = 0.04). In the sub-group classified as 'complete' collectors by PABA excretion, BP-Na regression coefficients were larger than in analyses of the sample as a whole. BP was not significantly related to K or Na/K.


Heat-stable (STa) enterotoxin of enterotoxigenic Escherichia coli: binding of the enterotoxin to coagulated milk and casein.
Oral or intragastric inoculation of the STa enterotoxin of Escherichia coli has been the standard laboratory test for that toxin. We demonstrated that the severity of the secretory response of 2-4-day-old mice to a single dose of the toxin was influenced by weaning of these mice. After oral application of 50-250 fmol of purified, radioiodinated STa toxin (12-13 Ci mmol-1) approximately 55-65% of the administered toxin bound to the stomach contents. Binding of the toxin did not destroy its biological activity. The binding was pH dependent; stomach contents bound 75% of the toxin at pH 2.3 and only 7.4% at pH 10.1. The principle in the stomach contents which bound the toxin was also demonstrated in murine and bovine milk. Further studies with renin-coagulated milk and commercial casein indicated that milk casein bound the toxin. Based on these findings, we speculate that in cases of food-poisoning involving casein-containing foods STa toxin may be present in the absence of cultivable enterotoxigenic E. coli.


Automatic small bowel tumor diagnosis by using multi-scale wavelet-based analysis in wireless capsule endoscopy images.
Wireless capsule endoscopy has been introduced as an innovative, non-invasive diagnostic technique for evaluation of the gastrointestinal tract, reaching places where conventional endoscopy is unable to. However, the output of this technique is an 8 hours video, whose analysis by the expert physician is very time consuming. Thus, a computer assisted diagnosis tool to help the physicians to evaluate CE exams faster and more accurately is an important technical challenge and an excellent economical opportunity. The set of features proposed in this paper to code textural information is based on statistical modeling of second order textural measures extracted from co-occurrence matrices. To cope with both joint and marginal non-Gaussianity of second order textural measures, higher order moments are used. These statistical moments are taken from the two-dimensional color-scale feature space, where two different scales are considered. Second and higher order moments of textural measures are computed from the co-occurrence matrices computed from images synthesized by the inverse wavelet transform of the wavelet transform containing only the selected scales for the three color channels. The dimensionality of the data is reduced by using Principal Component Analysis. The proposed textural features are then used as the input of a classifier based on artificial neural networks. Classification performances of 93.1% specificity and 93.9% sensitivity are achieved on real data. These promising results open the path towards a deeper study regarding the applicability of this algorithm in computer aided diagnosis systems to assist physicians in their clinical practice.


'It's only felophiles who think about doing feline research'.
While there are many passionate researchers out there, those wanting to carry out research for the benefit of cats face multiple obstacles.


Influence of pregnancy on diurnal and seasonal changes in cortisol, T3 and T4 levels in the mare blood serum.
1. The diurnal changes in the level of total protein, cortisol, T3 and T4 were studied in four barren and four pregnant standard-bred mares, kept and examined under the same conditions. 2. Blood samples were taken every 4 hr. for one day each month, throughout one year. 3. In barren mares, a diurnal rhythm in cortisol level (acrophase at 0530 hr in summer and at 0830 hr in winter) and in T3 level (acrophase at 1330 hr in summer and at 1800 hr in winter) was found. 4. In pregnant mares, a diurnal rhythm in cortisol level only till 5th month of pregnancy was observed. 5. A diurnal rhythm in T3 level was found throughout the pregnancy, with acrophase always at 1400 hr. 6. No diurnal rhythm in the total protein content and in the T4 level was observed. 7. In both groups of mares the seasonal cyclicity in T3 and T4 levels were found. A seasonal cyclicity in cortisol level was found only in pregnant mares. 8. Pregnancy abolished seasonal cyclicity in total protein and showed it in cortisol level. 9. Pregnancy in mares modifies diurnal rhythms as well as seasonal cycles in secretion and metabolism of the hormones studied.


The Top 30 Rising Stars Program: an inter-organizational approach to leadership succession planning.
An effective leadership development program is an organizational investment that advances individual performance while strengthening organizational capabilities. The Top 30 Rising Stars Program is a leadership succession program designed to enable leadership capacity building within and across organizations. Key components of the program include formal learning, stretch opportunities, and mentorship. Evaluation results reveal high participant satisfaction and an increase in reported self-confidence in their ability to assume a formal leadership position.


Ammoniagenesis in mudskippers Boleophthalmus boddaerti and Periophthalmodon schlosseri.
1. Glutamate dehydrogenase, aspartate transaminase and alanine transaminase were present in the gill, liver and muscle tissues of Periophthalmodon schlosseri and Boleophthalmus boddaerti. Both transaminases were found in the cytosol and mitochondria. 2. A complete purine nucleotide cycle was not present in the tissues studied. 3. Glutamine synthetase was not detected. Phosphate-dependent glutaminase was detected in both the cytosol and mitochondria. 4. Aspartate was the major substrate of ammoniagenesis in the mudskippers, though glutamate and glutamine were also oxidised. 5. Transdeamination was the major pathway for ammoniagenesis in the mudskippers studied.


Interaction of monosulfonate tetraphenyl porphyrin, a competitive inhibitor, with acetylcholinesterase.
Monosulfonate tetraphenyl porphyrin (TPPS(1)) forms a 1:1 complex with electric eel acetylcholinesterase (AChE) inducing a loss in TPPS(1) absorbance at 402 nm and the appearance of a new absorbance centered at 442 nm. In the presence of AChE, the fluorescence of TPPS(1) at 652 nm is slightly narrowed, with the maximal 652 nm fluorescence shifted from 407 to 412 nm excitation wavelength. The fluorescence peak of TPPS(1) at 712 nm shifts to 716 nm in the presence of AChE. TPPS(1) is a competitive inhibitor of AChE. The addition of acetylcholine iodide (AChI) or the competitive inhibitor tetracaine to the preformed AChE-TPPS(1) complex results in a loss of the 442 nm absorbance band as the porphyrin is displaced from AChE. The absorbance peak does not decrease in the presence of procaine, a non-competitive inhibitor.


Transfusion of plasma from a blood donor induced hepatitis E in Rhesus monkey.
Hepatitis E virus (HEV) infection is normally transmitted via the faeco-oral route. The possibility that the infection might be transmissible by blood has been suggested. Direct evidence of blood-borne transmission of hepatitis E infection is, however, absent. In this report, 10 ml of plasma obtained from a healthy, but hepatitis E viraemic, blood donor was transfused to a Rhesus monkey. Acute hepatitis E developed following transfusion of blood from the hepatitis E viraemic donor. This was confirmed by virological, immunological, biochemical and histopathological data. These results, combined with other epidemiological findings previously reported, indicate that transfusion-associated hepatitis E can occur. The risk of transfusion-associated HEV infection in endemic areas should be assessed and strategies developed to reduce it.


An early preceptorship and medical students' beliefs, values, and career choices.
Curriculum influence on career choice is difficult to determine. In this study we explored the impact of a summer rural/underserved preceptorship on the residency choices of participants and on the beliefs and attitudes of participating students about rural underserved primary care practices. Two data sets are used to examine the Rural/Underserved Opportunities Program (R/UOP). Matriculation and residency selection information is analyzed to compare R/UOP participants with nonparticipants. Second, a survey eliciting beliefs and attitudes about various career choices was given to participants before and after the experience and to a sample of non-participating classmates matched for age, race, and ethnicity. At matriculation, R/UOP participants gave higher rankings to primary care specialties as possible career choices. They were more likely to be matched in a primary care residency than nonparticipants. R/UOP participants expressed belief in more differences between urban and rural practice than did nonparticipants. They maintained their higher attitudes towards rural practice. R/UOP supports preexisting beliefs and positive attitudes towards rural underserved primary care careers. Participating students do not have large differences at entry into medical school. They are more likely to select primary care residencies, compared with nonparticipants.


Hepatic portocholecystostomy for biliary atresia: a 25-year follow-up and review.
We report the successful salvage of a patient's native liver 25 years after hepatic portocholecystostomy for biliary atresia. Our case demonstrates the effectiveness of biliary specific, high-resolution CT imaging in the diagnosis of, and operative planning for complex cases of biliary obstruction. We also report the longest-term pathologic follow-up of biliary atresia after hepatic portocholecystostomy. Life-long follow-up of patients with biliary atresia is important to prevent life-threatening complications of biliary stasis/obstruction.


Course of prevalence of scar contractures limiting function: A preliminary study in children and adolescents after burns.
Scar contracture is a well-known sequela of burns that is specifically relevant as it may limit function. Reports regarding the course of scar contractures, however, are scarce and, moreover, not focussed on function. This study describes the course of prevalence of scar contractures that limit function in children and adolescents after burns. Range of motion (ROM) of extremity joints of 20 children and adolescents after burns were assessed at discharge (T0) and at six weeks (T1), three months (T2), and six months (T3) after discharge. A scar contracture limiting function was defined as a measured ROM lower than the functional ROM, i.e., ROM used to perform daily activities by unimpaired subjects. At discharge (T0), 89.5% of the subjects had one or more scar contractures that limited function. Six months later (T3), this prevalence was 76.5%. At discharge (T0), less function limiting scar contractures were found for the upper extremity (29.7%) than the lower extremity (53.3%). Over time, prevalence of contractures in both extremities fluctuated between 22% and 35%. The majority of children and adolescents (13/17) still had scar contractures limiting function six months after discharge (T3). Substantial longitudinal studies over a longer period of time are needed to increase our knowledge on the course of these scar contractures in order to support improvements in burn care. The study is approved by the Regional Committee for Patient-Oriented Research Leeuwarden in the Netherlands (NL45917.099.13).


A follow-up study of adults with learning disabilities and epilepsy.
A programme to review the drug treatment of 215 adults with epilepsy and learning disabilities occurred in Leicestershire between 1982 and 1985. In 1997, a Leicestershire-wide study of epilepsy suffered by adults with learning disabilities was undertaken. The study sought information about many aspects of the epilepsy including the prescribing of medicines. One hundred and thirty-eight adults were common to both studies. A greater proportion was suffering active epilepsy in 1997 than in 1985. The deterioration in seizure control occurred despite an increase in polypharmacy, the introduction of new antiepileptic drugs and in some cases increases in dosage.


Emerging role of T3-binding protein μ-crystallin (CRYM) in health and disease.
Thyroid hormones are essential metabolic and developmental regulators that exert a huge variety of effects in different organs. Triiodothyronine (T3) and thyroxine (T4) are synthesized in the thyroid gland and constitute unique iodine-containing hormones that are constantly regulated by a homeostatic feedback mechanism. T3/T4 activity in cells is mainly determined by specific transporters, cytosolic binding proteins, deiodinases (DIOs), and nuclear receptors. Modulation of intracellular T3/T4 level contributes to the maintenance of this regulatory feedback. μ-Crystallin (CRYM) is an important intracellular high-affinity T3-binding protein that buffers the amount of T3 freely available in the cytosol, thereby controlling its action. In this review, we focus on the molecular and pathological properties of CRYM in thyroid hormone signaling, with emphasis on its critical role in malignancies.


Experimental prosthetic vein valve.
Medical and surgical management of venous insufficiency syndrome (VIS) has produced disappointing results despite the recent introduction of new surgical techniques. This has prompted the investigation of a sutureless prosthetic vein valve. Ten prosthetic sutureless vein valves have been tested to date. The valves are of two types, one constructed of platinum, the other of titanium. Fourteen to eighteen months post-insertion into the femoral vein or vena cava of mongrel dogs, five valves remain patent as shown be venography. The sutureless prosthetic vein valve is a promising development in the treatment of venous insufficiency.


Immunohistochemical expression of core 2 β1,6-N-acetylglucosaminyl transferase 1 (C2GnT1) in endometrioid-type endometrial carcinoma: a novel potential prognostic factor.
It has been reported that the expression of core 2 β1,6-N-acetylglucosaminyl transferase 1 (C2GnT1), which synthesizes the core 2 branching structure on O-glycans, may be associated with the biological aggressiveness of tumour cells. Therefore, the aim of this study was to examine the relationship between the expression of C2GnT1 and clinicopathological parameters of patients with endometrial carcinoma. The immunohistochemical expression of C2GnT1 was examined in 84 cases of endometrioid-type endometrial carcinoma, 15 cases of endometrial hyperplasia, and 30 normal endometria. The staining intensity was reported according to a positivity index (PI, full score 100), calculated from the percentage of positive cells. The expression of C2GnT1 was significantly higher in endometrial carcinoma (PI = 8.31 ± 15.29) than in normal endometrium (PI = 0.52 ± 1.24) (P < 0.0005). In carcinomas, the PI was higher in high-grade or advanced-stage tumours, but not significantly. Topologically, C2GnT1 was strongly expressed at sites of deep myometrial invasion. In addition, patients with C2GnT1 overexpression (PI ≥ 10) had significantly shorter survival (P < 0.0005). Multivariable analysis also indicated that C2GnT1 overexpression was an independent prognostic factor (P = 0.017). C2GnT1 appears to be involved in the biological aggressiveness of endometrial carcinoma. C2GnT1 might become a novel prognostic factor for endometrial carcinoma.


Shifts in hemispheric advantage during familiarization with complex visual patterns.
Twenty females unfamiliar with kanji were given a recognition task involving tachistoscopic presentation of kanji to the right and left visual fields. Repeated exposure to these novel stimuli resulted in significantly increased competence at the task. To analyze different approaches to the task, subjects were divided into an initial left visual field advantage and an initial right visual field advantage group. Over the course of the experiment subjects in the initial left visual field advantage group shifted from a left to a right visual field advantage, showing both a linear trend and a quadratic trend, while the initial right visual field advantage group showed only a quadratic trend. The results are consistent with observations in other novel stimuli situations which have demonstrated a shift in hemispheric advantage from right to left with increased competence and which have demonstrated individual differences in the pattern of shifting hemispheric advantage.


Lipopolysaccharide modulation of thyrotropin-releasing hormone (TRH) and TRH-like peptide levels in rat brain and endocrine organs.
Lipopolysaccharide (LPS) is a proinflammatory and depressogenic agent whereas thyrotropin-releasing hormone (TRH; pGlu-His-Pro-NH2) is an endogenous antidepressant and neuroprotective peptide. LPS and TRH also have opposing effects on K+ channel conductivity. We hypothesized that LPS can modulate the expression and release of not only TRH but also TRH-like peptides with the general structure pGlu-X-Pro-NH2, where "X" can be any amino acid residue. The response might be "homeostatic," that is, LPS might increase TRH and TRH-like peptide release, thereby moderating the cell damaging effects of this bacterial cell wall constituent. On the other hand, LPS might impair the synthesis and release of these neuropeptides, thus facilitating the induction of early response genes, cytokines, and other downstream biochemical changes that contribute to the "sickness syndrome." Sprague-Dawley rats (300 g) received a single intraperitoneal injection of 100 microg/kg LPS. Animals were then decapitated 0, 2, 4, 8, and 24 h later. Serum cytokines and corticosterone peaked 2 h after intraperitoneal LPS along with a transient decrease in serum T3. TRH and TRH-like peptides were measured by a combination of high-performance liquid chromatography and radioimmunoassay. TRH declined in the nucleus accumbens and amygdala in a manner consistent with LPS-accelerated release and degradation. Various TRH-like peptide levels increased at 2 h in the anterior cingulate, hippocampus, striatum, entorhinal cortex, posterior cingulate, and cerebellum, indicating decreased release and clearance of these peptides. These brain regions are part of a neuroimmunomodulatory system that coordinates the behavioral, endocrine, and immune responses to the stresses of sickness, injury, and danger. A sustained rise in TRH levels in pancreatic beta-cells accompanied LPS-impaired insulin secretion. TRH and Leu-TRH in prostate and TRH in epididymis remained elevated 2-24 h after intraperitoneal LPS. We conclude that these endogenous neuroprotective and antidepressant-like peptides both mediate and moderate some of the behavioral and toxic effects of LPS.


A rapid vectorial back reaction at the reaction centers of photosystem II in tris-washed chloroplasts induced by repetitive flash excitation.
In Tris-washed chloroplasts, completely lacking the oxygen-evolving capacity, absorption changes in the range of 420--560 nm induced by repetitive flash excitation have been measured in the presence and absence of electron donors. It was found: (1) At 520 nm flash-induced absorption changes are observed, which predominantly decay via a 100--200-mus exponential kinetics corresponding to that of the back reaction between the primary electron donor and acceptor of Photosystem II (Haveman, J. and Mathis, P. (1976) Biochim. Biophys. Acta 440, 346--355; Renger, G. and Wolff, Ch. (1976) Biochim. Biophys. Acta 423, 610--614). In the presence of hydroquinone/ascorbate as donor couple the amplitude is nearly doubled and the decay becomes significantly slowed down. (2) The difference spectrum of the absorption changes obtained in the presence of hydroquinone/ascorbate, which are sensitive to ionophores, is nearly identical with that of normal chloroplasts in the range of 460--560 nm (Emrich, H.M., Junge, W. and Witt, H.T. (1969) Z. Naturforsch. 24b, 114--1146). In the absence of hydroquinone/ascorbate the difference spectrum of the absorption changes, characterized by a 100--200-mus decay kinetics, differs in the range of 460--500 nm and by a hump in the range of 530--560 nm. The hump is shown to be attributable to the socalled C550 absorption change, which reflects the turnover of the primary acceptor of Photosystem II (van Gorkom, H.J.(1976) Thesis, Leiden), while the deviations in the range of 460--500 nm are understandable as to be due to the overlapping absorption changes of chlorphyll alpha II+. The problems arising with the latter explanation are discussed. (3) The electron transfer due to the rapid turnover at Photosystem II, which can be induced by flash groups with a short dark time between the flashes, is not able to energize the ATPase and to drive photophosphorylation. On the basis of the present results it is inferred, that in Tris-washed chloroplasts under repetitive flash excitation a rapid transmembrane vectorial electron shuttle takes place between the primary acceptor (X320) and donor (Chl alpha II) of Photosystem II, which is not able to energize the photophosphorylation. Furthermore, the data are shown to confirm the localization of X320 and Chl alpha II within the thylakoid membrane at the outer and inner side, respectively.


[Acute disturbances of cerebral blood circulation in the dynamics of pathological process in systemic rheumatic diseases].
Three hundred and twenty-nine patients with systemic rheumatic diseases have been studied using a complex clinical and neurological as well as instrumental examinations. Frequency of stroke and transient ischemic attacks has been estimated. Characteristic features of acute cerebrovascular pathology and risk factors for stroke and transient ischemic attacks in patients with systemic rheumatic diseases are presented.


Separation and biological properties of Phaseolus vulgaris isolectins.
Two isolectins (L4E0-PHA and L0E4-PHA) from red kidney beans (Phaseolus vulgaris) were isolated by affinity chromatography on immobilized thyroglobulin and by chromatography on hydroxyapatite. The L4E0-PHA isolectin was not retarded on the affinity column and was eluted from the hydroxyapatite column with a 0.1 M Phosphate buffer. This isolectin had no erythroagglutinating activity but had high lymphoagglutinating and lymphocyte stimulating activities. The L0E4-PHA isolectin was adsorbed on the affinity column and was eluted from the hydroxyapatite column with a 0.25 M Phosphate buffer. This isolectin has a higo lymphocyte stimulating activity. These two isolectins are shown however to be closely related with respect to their oligomeric structure and reactivity towards anti-PHA antibodies. The lack of mitogenic activity of the L0E4-PHA isolectin suggests that in the other isolectins, the E monomer is not responsible for their mitogenic activity and that the membrane glycoproteins, which contain the E monomer - specific oligosaccharide, are not involved in the process inducing mitosis.


Prognostic factors of sorafenib therapy in hepatocellular carcinoma patients with failure of transarterial chemoembolization.
There is no approved therapy for patients with failed transarterial chemoembolization (TACE) and progression of hepatocellular carcinoma. We aimed to investigate the efficacy and prognostic factors in patients with TACE failure who received sorafenib rescue therapy. We investigated 54 patients who met the criteria of TACE failure as defined by the international guidelines of Europe and Japan. Sorafenib was used as a rescue therapy. Overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier methods, and multivariate analysis was performed to find prognostic factors. The patients were followed for a median 5.5 months, and the median duration of sorafenib administration was 3.3 months. The presence of main (or lobar) portal vein invasion (PVI) (3.7 versus 8.4 months, p = 0.004), dose reduction of sorafenib (4.0 versus 8.8 months, p = 0.002) and Child-Pugh class B (5.3 versus 8.9 months, p = 0.004) were associated with shorter OS compared to the presence of segmental PVI (or absence of macroscopic vascular invasion, MVI), full dosage of sorafenib and Child-Pugh class A, respectively. The presence of main (or lobar) PVI was associated with poorer PFS compared to the presence of segmental PVI (or absence of MVI) (2.1 versus 3.8 months p = 0.010). Sorafenib is a potential rescue therapy in patients with TACE failure. However, the clinical benefits need to be further evaluated for patients with main (or lobar) PVI or those treated with reduced doses of sorafenib.


Serum microRNA-92 expression in patients with ovarian epithelial carcinoma.
Studies have reported the significance of circulating microRNAs (miRNAs) as biochemical markers of cancer. Few reports demonstrate the significance of miRNAs in the serum of patients with ovarian epithelial carcinoma (EOC). The present study prospectively investigated the status of miRNA-92 (miR-92) in the serum of EOC patients and healthy controls, and examined the potential usefulness of this molecule as a biomarker for EOC diagnosis. Levels of miR-92 in serum samples from EOC patients and controls were measured by quantitative real time reverse transcription-polymerase chain reaction (RT-PCR). Associations between serum miR-92 concentrations and clinical parameters were assessed by Fisher's exact probability test. The serum concentration of miR-92 in EOC patients (n = 50) was significantly higher than in controls (n = 50). There were significant correlations between miR-92 expression and regional lymph node involvement and clinical stage of the tumour. There was no significant association between expression of miR-92 and age. The detection of miR-92 levels in the serum might serve as a new tumour biomarker in the diagnosis and assessment of prognosis of EOC.


A Poiseuille-based coronary angiographic index for prediction of fractional flow reserve.
Coronary revascularization is commonly based on the angiographic finding of percent diameter stenosis (%DS) >50 while lesion length (LL), which contributes to flow-limitation according to Poiseuille's equation, is disregarded. Fractional flow reserve (FFR) is superior to assessment of %DS for identifying flow-limiting lesions, but the technology is invasive and relatively expensive. We developed a Poiseuille-based angiographic index, incorporating both minimal lumen diameter (MLD) and LL, for improved assessment of the hemodynamic significance of intermediate coronary lesions. The present study was designed to test the hypothesis that the Poiseuille-based angiographic index correlated better with FFR measurements than angiographic assessment of %DS. We performed quantitative coronary angiography (QCA) and FFR measurements in 46 intermediate coronary lesions in 41 symptomatic patients referred for diagnostic coronary angiography. From QCA we determined LL, MLD and %DS and calculated an angiographic index, the LL/MLD(4) ratio. Mean LL was 14.2 ± 7.8 (range: 4.3-38.8) mm, MLD 1.4 ± 0.4 (range: 0.6-2.3) mm, %DS 46 ± 12 (range: 25-74) and FFR 0.85 ± 0.09 (range: 0.55-1.00). Fractional flow reserve correlated inversely with %DS (R=-0.39, p=0.008) and with the LL/MLD(4) ratio (R=-0.66, p<0.0001). An FFR cut-off value of 0.80 corresponded with a LL/MLD(4) ratio of 12 (p=0.003) but not with a %DS of 50 (p=NS). A LL/MLD(4) ratio ≤ 12 had a specificity of 94% and negative predictive value of 82% for excluding hemodynamically significant lesions with FFR (≥ 0.80). The LL/MLD(4) ratio was superior to standard angiographic measurement of %DS for exclusion of hemodynamically significant coronary lesions.


High-fidelity direct contrast synthesis from magnetic resonance fingerprinting.
This work was aimed at proposing a supervised learning-based method that directly synthesizes contrast-weighted images from the Magnetic Resonance Fingerprinting (MRF) data without performing quantitative mapping and spin-dynamics simulations. To implement our direct contrast synthesis (DCS) method, we deploy a conditional generative adversarial network (GAN) framework with a multi-branch U-Net as the generator and a multilayer CNN (PatchGAN) as the discriminator. We refer to our proposed approach as N-DCSNet. The input MRF data are used to directly synthesize T1-weighted, T2-weighted, and fluid-attenuated inversion recovery (FLAIR) images through supervised training on paired MRF and target spin echo-based contrast-weighted scans. The performance of our proposed method is demonstrated on in vivo MRF scans from healthy volunteers. Quantitative metrics, including normalized root mean square error (nRMSE), peak signal-to-noise ratio (PSNR), structural similarity (SSIM), learned perceptual image patch similarity (LPIPS), and Fréchet inception distance (FID), were used to evaluate the performance of the proposed method and compare it with others. In-vivo experiments demonstrated excellent image quality with respect to that of simulation-based contrast synthesis and previous DCS methods, both visually and according to quantitative metrics. We also demonstrate cases in which our trained model is able to mitigate the in-flow and spiral off-resonance artifacts typically seen in MRF reconstructions, and thus more faithfully represent conventional spin echo-based contrast-weighted images. We present N-DCSNet to directly synthesize high-fidelity multicontrast MR images from a single MRF acquisition. This method can significantly decrease examination time. By directly training a network to generate contrast-weighted images, our method does not require any model-based simulation and therefore can avoid reconstruction errors due to dictionary matching and contrast simulation (code available at:https://github.com/mikgroup/DCSNet).


Chromosome analyses of human mammary epithelial cells at stages of chemical-induced transformation progression to immortality.
Benzo(a)pyrene induced extended life (EL) (i.e., a longer than normal proliferative lifespan before senescence) of human breast cells in culture. From many EL cell cultures immortalized cells emerged only once in each of two separate experiments. The original EL cells were mostly normal diploid with only a small percentage of tetraploid cells. The two immortalized cell lines, however, were near diploid, each containing a set of chromosomal aberrations that were present in all the cells analyzed, confirming the clonal origin of both cell lines. For cell line 184A1 the aberrations consisted of deficiencies only, whereas a combination of deficiencies and duplications characterized the 184B5 line. None of the individual aberrations of each set were shared by both cell lines. Both sets of aberrations have remained stable for over 150 population doublings, while some of the other chromosomes showed breakage and reunions. These data are discussed in regard to types of mutations in the sequence of changes from primary to immortalized cells, and it is concluded that the sets of aberrations most likely originated as multiple events in a single cell.


Solvent effect on phosphatidylcholine headgroup dynamics as revealed by the energetics and dynamics of two gel-state bilayer headgroup structures at subzero temperatures.
The packing and dynamics of lipid bilayers at the phosphocholine headgroup region within the temperature range of -40 to -110 degrees C have been investigated by solid-state nuclear magnetic resonance (NMR) measurements of selectively deuterium-labeled H2O/dimyristoylphosphatidylcholine (DMPC) bilayers. Two coexisting signals with 2H NMR quadrupolar, splittings of 36.1 and 9.3 (or smaller) kHz were detected from the -CD3 of choline methyl group. These two signals have been assigned to two coexisting gel-state headgroup structures with fast rotational motion of -CD3 and -N(CD3)3 group, respectively, with a threefold symmetry. The largest quadrupolar splitting of the NMR signal detected from the -CD2 of C alpha and C beta methylene segment was found to be 115.2 kHz, which is 10% lower than its static value of 128.2 kHz. Thus, there are extensive motions of the entire choline group of gel-state phosphatidylcholine bilayers even at a subzero temperature of -110 degrees C. These results strongly support the previous suggestion (E. J. Dufourc, C. Mayer, J. Stohrer, G. Althoff, and G. Kothe, 1992, Biophys. J. 61:42-57) that 31P chemical shift tensor elements of DMPC determined under similar conditions are not the rigid static values. The free energy difference between the two gel-state headgroup structures was determined to be 26.3 +/- 0.9 kJ/mol for fully hydrated bilayers. Furthermore, two structures with similar free energy difference were also detected for "frozen" phosphorylcholine chloride solution in a control experiment, leading to the conclusion that the two structures may be governed solely by the energetics of fully hydrated phosphocholine headgroup. The intermolecular interactions among lipids, however, stabilize the static headgroup structure as evidenced by the apparently lower free energy difference between the two structures for partially hydrated lipid bilayers. Evidence is also presented to suggest that one of the headgroup structures with trimethylammonium group rotation, which is not compatible with the static headgroup structure in crystals, is due to the dielectric relaxation of the slowly reorienting inter bilayer water molecules near the physical edge of membrane surface. Finally, a molecular model of the hydration-induced conformational changes at the torsion angle a5 of the O-C-CN+ bond is proposed to explain the two detected coexisting headgroup structures. These results emphasize the important role of the trimethylammonium group in monitoring the structure and dynamics of the lipid headgroup.


Ocular myasthenia gravis accompanied by anosmia.
We report a case of ocular myasthenia gravis (MG) accompanied by anosmia. A 76-year-old man had idiopathic anosmia of 2-year duration. Four months before consultation, he began to have drooping in the right upper eyelid along with muscle soreness, distension, and pain in the nape. His tongue was dark-red with a thin and white coating; his pulse was wiry and slippery. According to Traditional Chinese Medicine, eyelid drooping and anosmia are the main signs of liver constraint and spleen deficiency. In Western Medicine, the diagnosis was ocular MG and idiopathic anosmia. Our patient, along with the literature, suggests that anosmia may be an early symptom before MG. MG accompanied by anosmia could be a special subtype of MG according to antibody production and symptoms.


Guidelines and recommendations for MR imaging safety and patient management. III. Questionnaire for screening patients before MR procedures. The SMRI Safety Committee.
The authors present the third installment of the guidelines and recommendations from the Safety Committee of the Society for Magnetic Resonance Imaging (now the Society of Magnetic Resonance) concerning various issues related to the safety and management of patients undergoing magnetic resonance (MR) procedures. This document was developed to provide standardized and consistent information for use by health practitioners involved in screening patients or other individuals for MR procedures.


Tizanidine is mainly metabolized by cytochrome p450 1A2 in vitro.
To identify the cytochrome p450 (CYP) enzyme(s) that catalyze the metabolism of tizanidine in vitro. The effect of CYP isoform inhibitors on the elimination of tizanidine was studied using pooled human liver microsomes. The metabolism of the drug by a range of human recombinant CYP isoforms was then investigated. Incubation of tizanidine (80 nm) with human liver microsomes resulted in time- and NADPH-dependent substrate consumption with a half-life of 50 min, initial reaction velocity of 1.1 pmol x min-1 x mg-1 protein and intrinsic clearance of 17 ml x min-1 x kg-1. The predicted in vivo hepatic clearance (CLh) of tizanidine using the well-stirred and parallel-tube model was close (68% and 82%, respectively) to its estimated in vivo CLh. Fluvoxamine and furafylline strongly inhibited tizanidine metabolism. Inhibitors specific to isoforms other than CYP1A2 had no substantial effect. Recombinant CYP1A2 metabolized tizanidine to a substantial degree (35% in 45 min), but other recombinant CYPs had little metabolic capacity for the drug. CYP1A2 is primarily responsible for the metabolism of tizanidine. CYP1A2 inhibitors may inhibit its metabolism also in vivo.


Spontaneous dissection of the abdominal aorta: experience with five patients.
Spontaneous dissection of the infradiaphragmatic abdominal aorta is a rare form of aortic dissection. Its natural history and management are not well defined. We have recently treated five patients with spontaneous aortic dissection. Two patients had acute dissections and three had chronic dissections. Three patients developed saccular aneurysms and underwent resection. Two patients had stable dissections and were treated medically. All patients are alive and well at 6 months to 5 years. We think that spontaneous aortic dissection can be treated as a variant of type III dissection with initial medical management, reserving surgery for those patients in whom a saccular aneurysm or a complication of the dissection develops.