Association of Serum Vitamin B12 and Circulating Methylmalonic Acid Levels with All-Cause and Cardiovascular Disease Mortality among Individuals with Chronic Kidney Disease.
(1) Background: it is unclear whether serum vitamin B12 and circulating methylmalonic acid (MMA) are related with a poor prognosis among individuals with chronic kidney disease (CKD); (2) Methods: this prospective cohort study included 2589 individuals with CKD who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004, and from 2011 to 2014, respectively. Hazard ratios (HRs) and 95% Cis for the associations of MMA and vitamin B12 levels with the risk of all-cause and cardiovascular disease (CVD) mortality were calculated using multivariable Cox proportional hazards regression models. Restricted cubic spline analyses were used to examine the non-linear association of MMA levels with all-cause and CVD mortality. (3) Results: among the 2589 participants, we identified 1192 all-cause deaths and 446 CVD deaths, respectively, with a median follow-up of 7.7 years. Compared with participants with MMA < 123 nmol/L, those with MMA ≥ 240 nmol/L had an increased all-cause and CVD mortality in the multivariable-adjusted model [HR (95% CI), 2.01 (1.54-2.62) and 1.76 (1.18-2.63), respectively]; (4) Conclusions: higher circulating MMA levels were found to be strongly associated with an elevated all-cause and CVD mortality among individuals with CKD, while serum vitamin B12 levels were not associated.


Fluorescence quenching near small metal nanoparticles.
We develop a microscopic model for fluorescence of a molecule (or semiconductor quantum dot) near a small metal nanoparticle. When a molecule is situated close to metal surface, its fluorescence is quenched due to energy transfer to the metal. We perform quantum-mechanical calculations of energy transfer rates for nanometer-sized Au nanoparticles and find that nonlocal and quantum-size effects significantly enhance dissipation in metal as compared to those predicted by semiclassical electromagnetic models. However, the dependence of transfer rates on molecule's distance to metal nanoparticle surface, d, is significantly weaker than the d(-4) behavior for flat metal surface with a sharp boundary predicted by previous calculations within random phase approximation.


Role of temperature-dependent spin model parameters in ultra-fast magnetization dynamics.
In the spirit of multi-scale modelling magnetization dynamics at elevated temperature is often simulated in terms of a spin model where the model parameters are derived from first principles. While these parameters are mostly assumed temperature-independent and thermal properties arise from spin fluctuations only, other scenarios are also possible. Choosing bcc Fe as an example, we investigate the influence of different kinds of model assumptions on ultra-fast spin dynamics, where following a femtosecond laser pulse, a sample is demagnetized due to a sudden rise of the electron temperature. While different model assumptions do not affect the simulational results qualitatively, their details do depend on the nature of the modelling.


Emergence of chiral magnetism in spinor Bose-Einstein condensates with Rashba coupling.
Hydrodynamic theory of the spinor BEC condensate with Rashba spin-orbit coupling is presented. A close mathematical analogy of the Rashba-Bose-Einstein condensate model to the recently developed theory of chiral magnetism is found. Hydrodynamic equations for mass density, superfluid velocity, and the local magnetization are derived. The mass current is shown to contain an extra term proportional to the magnetization direction, as a result of the Rashba coupling. Elementary excitations around the two known ground states of the Rashba-Bose-Einstein condensate Hamiltonian, the plane-wave, and the stripe states, are worked out in the hydrodynamic framework, highlighting the cross coupling of spin and superflow velocity excitations due to the Rashba term.


[Advances in cutinase research].
Cutinase (EC 18.104.22.168) is a kind of hydrolase capable of catalyzing the cleavage of ester bonds of cutin to release fatty acids. Cutinase displayed hydrolytic activity not only toward cutin but also a variety of soluble synthetic esters, insoluble triglycerides and polyesters. Besides its hydrolytic activity, cutinase also showed synthetic activity and transester activity. Therefore, cutinase was evaluated as a versatile lipolytic enzyme used in food and chemical industry. Recently, it is found that cutinase has potential use in cotton bio-scouring and synthetic fibers modification. Cutinase is the most important enzyme in clean production of textile industry.


The Mental Health Impact of Physical Appearance Concerns in the Context of Other Life Domains Among Australian Gay Men.
Previous studies have identified gay men as a high-risk population for body image disturbances. However, little research has examined the mental health impact of gay men's physical appearance concerns in the context of other major life domains. The present study addressed this gap by investigating how mental health outcomes (satisfaction with life, self-esteem, positive well-being, and psychological distress) were associated with satisfaction with and importance of physical appearance, work, family relationships, friendships, health and fitness, and sex life among Australian gay men aged 18-39. The possible moderating role of intimate relationship status was also examined. Results from an online survey revealed that greater satisfaction with physical appearance, work, family, and friendships all had similar positive associations with mental health. However, more importance placed on physical appearance was more consistently associated with poorer mental health compared with the subjective importance of other domains. Findings also indicated the associations between physical appearance satisfaction and life satisfaction, and between physical appearance importance and positive well-being, were weaker for those in relationships. Thus, physical appearance matters in gay men's lives, but was only one factor when considered in the broader context of other life areas that contributed to overall well-being. These findings suggest the need for a nuanced and contextualized understanding of how physical appearance concerns fit into gay men's lives.


Classification of congenital middle ear anomalies. Report on 144 ears.
The surgical findings in 144 successive ears operated on for congenital conductive hearing loss were analyzed, and the results were evaluated in terms of hearing gain. All the patients underwent middle ear surgery at the University Hospital Nijmegen between 1964 and 1990. A classification system was developed to analyze the findings. Class 1 comprises ears with congenital isolated stapes ankylosis. Class 2 comprises ears with congenital stapes ankylosis in combination with a congenital anomaly of the ossicular chain. Class 3 comprises ears with congenital anomalies of the ossicular chain and at least a mobile stapes footplate. Class 4 comprises ears with aplasia or severe dysplasia of the oval window or round window.


A non healing ulcer on scalp.
Angiosarcoma is a soft tissue tumour with a dismal prognosis. We present a 74 year old male presenting with a non healing ulcer on the scalp. On histopathology a diagnosis of angiosarcoma was made. An early diagnosis and tumour size play a pivotal role in the survival of the patient.


Myocardial perfusion scintigraphy (SPECT) during adenosine stress can be performed safely early on after thrombolytic therapy in acute myocardial infarction.
The objective of this study was to evaluate the safety of myocardial perfusion scintigraphy with Tc-99 m sestamibi during adenosine stress in patients with recent thrombolytically treated myocardial infarction. Eighty-four patients with thrombolytically treated myocardial infarction, 59 males and 25 females, aged 62.9 +/- 8.4, were eligible for myocardial perfusion scintigraphy during adenosine provocation. Exclusion criteria for adenosine stress were hypotension, unstable angina pectoris, cardiac failure, pericarditis and atrioventricular block (AV block) II-III. Adenosine-stress and resting myocardial perfusion scintigraphy was performed 2-5 days after thrombolysis. Scintigraphy at rest was done 24 h after the stress study. Sixty patients (71%) experienced some kind of side-effects during adenosine infusion. The most frequent side-effects were dyspnoea in 43/84 patients (51%) and unspecific chest discomfort in 26/84 patients (31%). During infusion, ST depressions or elevations on ECG were seen in 9 patients (11%), 5 of whom experienced atypical chest discomfort. Five patients (6%) described typical angina but none of them showed electrographic signs of myocardial ischaemia during infusion. Six patients (7%) developed transient AV block I-II. Reversible scintigraphic perfusion defects were seen in 67 patients (79%). No serious complications, such as death, reinfarction or severe arrhythmias, occurred during adenosine infusion or during a 3-day clinical follow-up period. In conclusion, MIBI-SPECT during adenosine stress is a safe diagnostic method that can be performed in most patients early on after thrombolytically treated acute myocardial infarction. Side-effects are common but benign, and not different from those seen in patients with chronic coronary artery disease.


A Retrospective Patient Chart Review and Survey in Patients with Cryopyrin-associated Periodic Syndromes Treated with Anakinra.
Background: Cryopyrin-associated periodic syndromes (CAPS) is a group of rare autoinflammatory diseases. Little is known about the burden of disease, patients' views on treatment, and adverse events (AEs) with current therapy. Objectives: The main study objective was to quantify the patients' burden of disease in terms of flares and resource use and to characterize patient symptomatology and tolerability of treatment with anakinra. A secondary objective included comparing chart review and patient recall of symptoms and AEs. Methods: A retrospective medical chart review and concurrent online patient survey was conducted in four European countries. Data 12 months prior to initiation of/during anakinra treatment were entered into web-based case report forms by study groups. Results: Forty-two patients received/were receiving anakinra as primary treatment for at least 12 months. Patients experienced a 79.5% reduction in flares after commencing anakinra treatment. During the past 12 months on anakinra, four of five (80%) patients who recalled experiencing flares reported cancelling social activities and staying home as the most common courses of action. Most common AEs were injection site pain upon treatment initiation and weight gain. According to patient recall, 12 of 21 patients (57.1%) discontinued anakinra to enter another clinical trial; of the 12, eight (38%) specifically discontinued anakinra only for that reason, and four patients cited entering a clinical trial as one of many reasons for discontinuing anakinra. Conclusions: To our knowledge, this is the most comprehensive survey of patient experience with CAPS. Although improved, CAPS treatment remains suboptimal and a significant burden is placed upon patients, caregivers, and the healthcare system. With new agents available, it will be important to compare outcomes in patients using all therapeutic options.


Efficacy of intravenous adenosine in treatment of paroxysmal supraventricular tachycardia in the local population.
In a prospective study conducted over 4 months at the Accident and Emergency Department, 21 patients with 24 episodes of spontaneous paroxysmal supraventricular tachycardia (PSVT) were treated with intravenous adenosine at incremental doses of 3 mg, 6 mg, 9 mg and 12 mg until termination of the PSVT. There were 6 males and 15 females. The mean age was 54 +/- 17 years (range from 23 to 83 years). The mean QRS rate was 171 +/- 21 per minute. When data were expressed in a cumulative manner, the response to intravenous adenosine 3 mg, 6 mg, 9 mg and 12 mg in the 24 episodes of PSVT were 5 episodes (21%), 16 episodes (67%), 20 episodes (83%) and 20 episodes (83%) respectively. Adverse effects were present in 10 episodes (42%) of the PSVT. They were all mild and transient, lasting less than 1 minute.


A Multimodal Framework Based on Integration of Cortical and Muscular Activities for Decoding Human Intentions About Lower Limb Motions.
In this study, a multimodal fusion framework based on three different modal biosignals is developed to recognize human intentions related to lower limb multi-joint motions which commonly appear in daily life. Electroencephalogram (EEG), electromyogram (EMG) and mechanomyogram (MMG) signals were simultaneously recorded from twelve subjects while performing nine lower limb multi-joint motions. These multimodal data are used as the inputs of the fusion framework for identification of different motion intentions. Twelve fusion techniques are evaluated in this framework and a large number of comparative experiments are carried out. The results show that a support vector machine-based three-modal fusion scheme can achieve average accuracies of 98.61%, 97.78% and 96.85%, respectively, under three different data division forms. Furthermore, the relevant statistical tests reveal that this fusion scheme brings significant accuracy improvement in comparison with the cases of two-modal fusion or only a single modality. These promising results indicate the potential of the multimodal fusion framework for facilitating the future development of human-robot interaction for lower limb rehabilitation.


[Mesangial IgA deposits nephropathy].
Idiopathic IgA nephropathy of Berger's disease is characterized by prominent and diffuse IgA deposits in the mesangium. In many countries, it is the most common type of primary chronic glomerulonephritis. Typically, it is revealed by recurrent episodes of gross hematuria in association with ENT infection, but it can progress insidiously with microscopic hematuria and proteinuria. Serum IgA levels are increased in about 50% of cases. IgA nephropathy is not a minor condition: 20% of patients develop end-stage chronic renal failure 10 years after diagnosis and 50% after 20 years. IgA nephropathy can recur in a transplanted kidney suggesting that this disease is a systemic disorder although it has a remarkable tropism for the kidney. Even though many points remain to be elucidated, its pathogenesis appears to be linked to a genetic factor responsible for a lymphocyte dysfunction and an acquired environmental factor such as penetration of an antigen via the mucosa which may give rise to an excessive and inappropriate IgA immune response with the deposition of IgA in the mesangium and the development of progressive renal alterations. No treatment has been shown to be effective but tonsillectomy advised in case of a recurrent tonsillar focal infection is most often accompanied by a decrease in the incidence of gross hematuria. Corticosteroid therapy can be of benefit in cases involving a nephrotic syndrome associated with minimal glomerular lesions. In all cases, control of possible hypertension is of value in slowing the progression of this disease.


Rotavirus capsid VP6 protein acts as an adjuvant in vivo for norovirus virus-like particles in a combination vaccine.
Rotavirus (RV) and norovirus (NoV) are the 2 leading causes of acute viral gastroenteritis worldwide. We have developed a non-live NoV and RV vaccine candidate consisting of NoV virus-like particles (VLPs) and recombinant polymeric RV VP6 protein produced in baculovirus-insect cell expression system. Both components have been shown to induce strong potentially protective immune responses. As VP6 nanotubes are highly immunogenic, we investigated here a possible adjuvant effect of these structures on NoV-specific immune responses in vivo. BALB/c mice were immunized intramuscularly with a suboptimal dose (0.3 μg) of GII.4 or GI.3 VLPs either alone or in a combination with 10 μg dose of VP6 and induction of NoV-specific antibodies in sera of experimental animals were measured. Blocking assay using human saliva or synthetic histo-blood group antigens was employed to test NoV blocking antibodies. Suboptimal doses of the VLPs alone did not induce substantial anti-NoV antibodies. When co-administered with the VP6, considerable titers of not only type-specific but also cross-reactive IgG antibodies against NoV VLP genotypes not included in the vaccine composition were induced. Most importantly, NoV-specific blocking antibodies, a surrogate for neutralizing antibodies, were generated. Our results show that RV VP6 protein has an in vivo adjuvant effect on NoV-specific antibody responses and support the use of VP6 protein as a part of the NoV-RV combination vaccine, especially when addition of external adjuvants is not desirable.


An Algorithmic Approach to Management of Venous Thromboembolism.
Venous thromboembolism (VTE) is associated with significant morbidity and mortality. Factors such as the presence of transient risk factors for VTE, risk of bleeding, and location of deep vein thrombosis (DVT) determine the duration of anticoagulation. Extended anticoagulation is offered to patients with unprovoked pulmonary embolism (PE) or proximal DVT and a low risk of bleeding. Anticoagulation for 3 months is advised in patients with provoked DVT or PE, high risk of bleeding, and isolated distal or upper extremity DVT. In patients with unprovoked PE or proximal DVT and a low risk of bleeding, who want to stop anticoagulation after 3 months, further risk stratification is necessary. Clinical scoring system, and thrombophilia testing otherwise not routinely performed, may be considered to measure risk of annual recurrence in such cases. Short-term anticoagulation may be considered in subsegmental PE and superficial vein thrombosis, particularly if patients are at low risk of bleeding and have persistent risk factors for recurrent VTE. In cases of catheter-associated thrombosis, the catheter need not be removed routinely, and the patient may be anticoagulated for 3 months or longer if the catheter is maintained in patients with cancer. Extensive screening for occult cancer in cases of unprovoked VTE is not beneficial. New oral anticoagulants such as apixaban, rivaroxaban, or dabigatran may be preferred to vitamin K antagonists in patients without cancer or renal failure, more so after the development of reversal agents such as idarucizumab and andexanet alfa.


Antidepressant use before and after the diagnosis of type 2 diabetes: a longitudinal modeling study.
To examine antidepressant use before and after the diagnosis of diabetes. This study was a longitudinal analysis of diabetic and nondiabetic groups selected from a prospective cohort study of 151,618 men and women in Finland (the Finnish Public Sector Study, 1995-2005). We analyzed the use of antidepressants in those 493 individuals who developed type 2 diabetes and their 2,450 matched nondiabetic control subjects for each year during a period covering 4 years before and 4 years after the diagnosis. For comparison, we undertook a corresponding analysis on 748 individuals who developed cancer and their 3,730 matched control subjects. In multilevel longitudinal models, the odds ratio for antidepressant use in those who developed diabetes was 2.00 (95% CI 1.57-2.55) times greater than that in nondiabetic subjects. The relative difference in antidepressant use between these groups was similar before and after the diabetes diagnosis except for a temporary peak in antidepressant use at the year of the diagnosis (OR 2.66 [95% CI 1.94-3.65]). In incident cancer case subjects, antidepressant use substantially increased after the cancer diagnosis, demonstrating that our analysis was sensitive for detecting long-term changes in antidepressant trajectories when they existed. Awareness of the diagnosis of type 2 diabetes may temporarily increase the risk of depressive symptoms. Further research is needed to determine whether more prevalent use of antidepressants noted before the diagnosis of diabetes relates to effects of depression, side effects of antidepressant use, or a common causal pathway for depression and diabetes.


Secondary Oxalate Nephropathy: Causes and Clinicopathological Characteristics of a Case Series.
Secondary oxalate nephropathy (OxN) is associated with a variety of causes and has not been well characterized in Chinese population. To investigate the etiology, clinicopathological features, and outcomes of secondary OxN, we report a case series from a single center in China. A retrospective analysis of 68 patients diagnosed with secondary OxN by renal biopsy from January 2013 to February 2019 in Jinling Hospital was performed. Secondary OxN accounted for 0.23% of the renal biopsies and 2.31% of patients who received renal biopsies due to acute kidney injury (AKI). A total of 49 men and 19 women with an average age of 51.6 ± 11.8 years were enrolled. The most common cause was iatrogenic medication, followed by oxalate-rich diet and industry exposure. Stage 1, 2, and 3 AKI and AKI on chronic kidney disease (ACKD) were found in 4.4, 8.8, 69.1, and 17.6% of the patients, respectively. The peak serum creatinine during hospitalization was 8.62 ± 4.67 mg/dL. The median urinary oxalate excretion was 51.5 (23.2-147.1) mg/24 h. Kidney biopsy showed extensive calcium oxalate crystal deposits with acute tubulointerstitial nephritis. Thirty-four patients (50.0%) required renal replacement therapy. At the end of a follow-up that lasted 8.7 (0.1-72.1) months, 81.0% of patients achieved renal function recovery in 50 (14-432) days. Patients with renal function recovery had a lower rate of ACKD, a higher level of hemoglobin, a lower level of urine lysozyme, and a lower degree of interstitial fibrosis/tubular atrophy, interstitial inflammation, and global glomerulosclerosis than those in the nonrecovery group. In this case series of secondary OxN, the most common cause was iatrogenic medication, and it presented with AKI or ACKD. Half of the patients required renal replacement therapy, and in most of them, the renal function was reversible. Renal biopsy played an important role in diagnosis and prognosis evaluation.


Relative Contributions of Anatomical and Quantum Noise in Signal Detection and Perception of Tomographic Digital Breast Images.
Anatomical and quantum noise inhibits detection of malignancies in clinical images such as in digital mammography (DM), digital breast tomosynthesis (DBT) and breast CT (bCT). In this work, we examine the relative influence and interactions of these two types of noise on the task of low contrast mass detectability in DBT. We show how the changing levels of quantum noise contributes to the estimated power-law slope β by changing DBT acquisition parameters as well as with spatial filtering like an adaptive Weiner filtering. Finally, we examine via human observer LROC studies whether power spectral parameters obtained from DBT images correlate with mass detectability in those images. Our results show that lower values of power-law slope β can result from heightened quantum noise or image artifacts and do not necessarily imply reduced anatomical noise or improved signal detectability for the given imaging system. These results strengthen the argument that when power-law magnitude K is varying, β is less relevant to lesion detectability. Our preliminary results also point to K values having strong correlation to human observer performance, at least for the task shown in this paper. As a byproduct of these main results, we also show that while changes in acquisition geometry can improve mass detectability, the use of efficient filters like an adaptive Weiner filtering can significantly improve the detection of low contrast masses in DBT.


Delayed postpartum hemoperitoneum due to uterine artery pseudoaneurysm rupture.
A 30-year-old woman experienced severe abdominal pain 8 days after vaginal delivery. The patient was diagnosed with hemoperitoneum due to rupture of the left uterine artery pseudoaneurysm, which was confirmed via ultrasound with color Doppler and computed tomography scans. This patient was treated with bilateral uterine artery embolization to maintain fertility. A uterine artery pseudoaneurysm that causes delayed postpartum hemorrhage can occur after cesarean section or vaginal delivery. A uterine artery pseudoaneurysm can be fatal, so its detection and diagnosis are critical. Herein, we report a case of delayed postpartum hemoperitoneum due to uterine artery pseudoaneurysm rupture.


Symptoms of posttraumatic stress disorder and mental health in women who escaped prostitution and helping activists in shelters.
This study compared the mental symptoms, especially symptoms of posttraumatic stress disorder (PTSD), of women who escaped prostitution, helping activists at shelters, and matched control subjects. We assessed 113 female ex-prostitutes who had been living at a shelter, 81 helping activists, and 65 control subjects using self-reporting questionnaires on demographic data, symptoms related to trauma and PTSD, stress-related reactions, and other mental health factors. Female ex-prostitutes had significantly higher stress response, somatization, depression, fatigue, frustration, sleep, smoking and alcohol problems, and more frequent and serious PTSD symptoms than the other 2 groups. Helping activists also had significantly higher tension, sleep and smoking problems, and more frequent and serious PTSD symptoms than control subjects. These findings show that engagement in prostitution may increase the risks of exposure to violence, which may psychologically traumatize not only the prostitutes themselves but also the people who help them, and that the effects of the trauma last for a long time. Future research is needed to develop a method to assess specific factors that may contribute to vicarious trauma of prostitution, and protect field workers of prostitute victims from vicarious trauma.


Synthesis of helical polyacetylene in chiral nematic liquid crystals using crown ether type binaphthyl derivatives as chiral dopants.
A series of crown ether type binaphthyl derivatives (CEBDs) were synthesized and used as chiral dopants to induce chiral nematic (N*) liquid crystals (LCs). The twisting powers of the CEBDs for phenylcyclohexane (PCH)-derived nematic LCs were evaluated. It was found that the twisting powers of the CEBDs increased with decreasing ring size of the crown ether. Helical polyacetylenes were synthesized in the N*-LCs induced by the CEBDs. The relationship between the morphology of the helical polyacetylene and the helical structure of the N*-LC was investigated. The result showed that the interdistance between the fibril bundles of the helical polyacetylene was equal to a half-helical pitch of the N*-LC and the screw direction of the polyacetylene fibrils was opposite to that of the N*-LC.


[Abortion practices in high school students in Yamoussoukro, Côte d'Ivoire].
Induced abortion is illegal in Cote d'Ivoire, except when the mother's life is in danger. The primary objective of this study was to describe abortion practices among Yamoussoukro high school students. More specifically, this study estimated the prevalence of induced abortion, described the pathway and the methods used for abortion and determined any abortion-related complications. This cross-sectional study was conducted in July 2011 on 312 randomly selected girls attending the Lycée Jeunes Filles in Yamoussoukro. These girls had a mean age (SD) of 16.1 (4.7) years; 258 (82.7%) of them had already had sexual intercourse and 81 (31.4%) had already been pregnant. Fifty (61.7% [56.3-67.1%]) of these 81 girls had already had an abortion. The abortion pathway was as follows: the main method was self-prescribed medication (70%) as first attempt, followed, in case of failure, by traditional healers (56.4%). Healthcare practitioners were usually consulted at the third attempt (85.7%). The most commonly used methods of abortion were drugs (91.9%), ingestion of plants/beverages (68.5%) and introduction of devices into the uterine cavity (62.3%). Twenty-two (44%) out of 50 induced abortions resulted in complications, mostly infectious complications (81.8%), and bleeding (68.2%). Complications were significantly associated with self-induced abortions or abortions performed by traditional healers (p < 0.001). More intensive sexual education, access to modern methods of contraception, awareness campaigns concerning the risks related to unwanted pregnancies and abortions performed by non-medical personnel need to be implemented to prevent school abortions. The quality and accessibility of post-abortion services also need to be reinforced.


Endogenous retinoid X receptors can function as hormone receptors in pituitary cells.
Retinoids regulate gene transcription by interacting with both retinoic acid (RA) receptors (RARs) and retinoid X receptors (RXRs). Since unliganded RXRs can act as heterodimerization partners for RARs and other nuclear hormone receptors, it is unclear whether ligand binding by RXRs actually regulates the expression of naturally occurring genes. To address this issue, we synthesized the RXR-selective retinoid SR11237 and confirmed its specificity in transient transfection and proteolytic susceptibility assays before using it to assess the contribution of ligand-activated RXRs to retinoid action. Unlike RAR ligands, SR11237 did not increase endogenous RAR beta mRNA levels in F9 embryonal carcinoma cells, even though it activated transcription of an RXR-responsive reporter gene in these cells. Thus, it is likely that RARs mediate the induction of RAR beta gene expression by RA. In contrast, the RXR-specific ligand induced rat growth hormone mRNA in GH3 pituitary cells, indicating that the effects of RA on growth hormone gene expression at least in part involve ligand binding to endogenous RXRs in vivo. Our results indicate that in addition to serving as cofactors for other nuclear hormone receptors, endogenous RXRs can function as ligand-dependent regulators of gene expression, i.e., classical nuclear hormone receptors.


GUIDELINE FOR THE MANAGEMENT OF BILE DUCT CANCERS BY THE BRAZILIAN GASTROINTESTINAL TUMOR GROUP.
The Brazilian Gastrointestinal Tumor Group developed guidelines for the surgical and clinical management of patients with billiary cancers. The multidisciplinary panel was composed of experts in the field of radiology, medical oncology, surgical oncology, radiotherapy, endoscopy and pathology. The panel utilized the most recent literature to develop a series of evidence-based recommendations on different treatment and diagnostic strategies for cholangiocarcinomas and gallbladder cancers.


Effects of glycerol on 4-nitroquinoline 1-oxide induced pulmonary tumorigenesis in ddY mice.
The effects of glycerol administration on pulmonary tumorigenesis induced by 4-nitroquinoline 1-oxide (4NQO) were examined in male ddY mice, that were given 5% glycerol solution instead of drinking water after a subcutaneous injection of 4NQO. The incidence of pulmonary tumor-bearing mice and the mean number of induced tumors per mouse were significantly enhanced in mice given glycerol after 4NQO treatment, compared with mice given 4NQO alone. The results demonstrate effects including that of promotion by glycerol in 4NQO-induced pulmonary tumorigenesis.


The nuclear 5S RNAs from chicken, rat and man. U5 RNAs are encoded by multiple genes.
Preparations of chicken, rat and human nuclear 5S RNA contain two sets of molecules. The set with the lowest electrophoretic mobility (5Sa) contains RNAs identical or closely related to ribosomal 5S RNA from the corresponding animal species. In HeLa cells and rat brain, we only detected an RNA identical to the ribosomal 5S RNA. In hen brain and liver, we found other species differing by a limited number of substitutions. The results suggest that mutated 5S genes may be expressed differently according to the cell type. The set with the highest mobility corresponds to U5 RNA. In both rat brain and HeLa cells, U5 RNA was found to be composed of 4 and 5 different molecules respectively (U5A, U5B1-4) differing by a small number of substitutions or insertions. In hen brain, no U5B was detected but U5A' differing from U5A by the absence of the 3'-terminal adenosine. All the U5 RNAs contain the same set of modified nucleotides. They also have the same secondary structure which consists of two hairpins joined together by a 17 nucleotide long single-stranded region. The 3' half of the molecule has a compact conformation. Together, the results suggest that U5 RNAs are transcribed from a multigene family and that mutated genes may be expressed as far as secondary structure is conserved. The conformation of U5 RNA is likely to be related to its function and it is of interest to mention that several similarities of structure are found between U5 and U1A RNA.


Recent advances in shotgun lipidomics and their implication for vision research and ophthalmology.
In the past decade, mass spectrometry (MS) has made tremendous advances toward the profiling and identification of lipids from biological samples. MS is attractive for the simplicity it offers toward total profiling of lipids, the identification and characterization of individual entities directly after extraction from complex biological mixtures utilizing an infusion mode. Fundamentally, two types of mass analyzers exist, depending upon whether the fragment ion resolution and analysis occurs in space domain or in time domain within the mass spectrometer. Compared to MS, chromatographic methods are cumbersome. Nuclear magnetic resonance, which provides unequivocal elucidation of structures, necessitates much higher absolute amount and demands purity of lipids. We present here an account of recent developments in class-specific lipid identification strategies, targeted and untargeted lipid analyses, identification and de novo structure elucidation using mass spectrometric and combinatorial chemical derivatization and MS. We have reviewed the strategies with emphasis for spatial domain fragment resolution mass analyzers enabling analysis of lipids in a class-specific manner. We also provide a brief account of database and bioinformatic tools that have been recently developed toward profiling, identification and quantification of lipids in complex biological mixtures.


Getting the most out of all your customers.
Companies spend billions of dollars on direct marketing, targeting individual customers with ever more accuracy. Yet despite the power of the myriad data-collecting and analytical tools at their disposal, they're still having trouble optimizing their direct-marketing investments. Many marketers try to minimize costs by pursuing only those customers who are cheap to find and cheap to keep. Others try to get the most customers they possibly can and keep all of them for as long as they can. But a customer need not be loyal to be highly profitable, and many loyal customers turn out to be highly unprofitable. Companies can get more out of direct marketing if they see it as a single system for generating profits than if they try to maximize performance measures at each stage of the process. This article describes a tool for doing just that. Called ARPRO (Allocating Resources for Profits), the tool is essentially a complex regression analysis that can estimate the impact of a company's direct-marketing investments on the profitability of its customer pool. With data that companies already gather, the tool can show managers how much to spend on acquisition versus retention and even what percentage of their funds they should allocate to the different direct-marketing channels. Using the model, companies can easily see that even small deviations from the optimal levels of customer profitability are expensive. Applying it to one catalog retailer showed, for instance, that a 10% reduction in marketing costs would lead to a 1.8 million dollar drop in long-term customer profits. Conversely, spending 69% less on marketing would actually increase average customer profitability at one B2B service provider by 42%. What's more, the tool can show that finding the optimal balance between investments in acquisition and retention can be more important than finding the optimum amount to invest overall.


Quarantine for contaminated pathogens in transplantable human tumors or infections in tumor bearing mice.
To quarantine human tumor samples for transplantation into immune deficient mice or tumor xenograft lines established and introduced from other institutions, we performed isolated implantation and passaging of tumors in a vinyl isolator, and microbiological examinations of sentinel mice kept together with tumor bearing mice. We examined 105 pairs of sentinel mice used to quarantine 907 tumors, and found six cases of contamination or infection with Staphylococcus aureus, 20 cases with Pseudomonas aeruginosa and one case with mouse hepatitis virus (MHV). It was, however, possible that Mycoplasma pulmonis contamination was overlooked because the microbe had been isolated from tumors passaged after quarantine, even though the results of the quarantine of these tumors showed no sign of pathogens. Direct culture of tumors for the microbe was recommended to improve the quarantine system.


Requirements for an accurate dispersion-corrected density functional.
Post-self-consistent dispersion corrections are now the norm when applying density-functional theory to systems where non-covalent interactions play an important role. However, there is a wide range of base functionals and dispersion corrections available from which to choose. In this work, we opine on the most desirable requirements to ensure that both the base functional and dispersion correction, individually, are as accurate as possible for non-bonded repulsion and dispersion attraction. The base functional should be dispersionless, numerically stable, and involve minimal delocalization error. Simultaneously, the dispersion correction should include finite damping, higher-order pairwise dispersion terms, and electronic many-body effects. These criteria are essential for avoiding reliance on error cancellation and obtaining correct results from correct physics.


MicroRNAs and Cardiovascular Disease in Diabetes Mellitus.
Cardiovascular disease (CVD) is the major macrovascular complication of diabetes mellitus. Recently, although CVD morbidity and mortality have decreased as a result of comprehensive control of CVD risk factors, CVD remains the leading cause of death of patients with diabetes in many countries, indicating the potential underlying pathophysiological mechanisms. MicroRNAs are a class of noncoding, single-stranded RNA molecules that are involved in β-cell function, insulin secretion, insulin resistance, skeletal muscle, and adipose tissue and which play an important role in glucose homeostasis and the pathogenesis of diabetic complications. Here, we review recent progress in research on microRNAs in endothelial cell and vascular smooth muscle cell dysfunction, macrophage and platelet activation, lipid metabolism abnormality, and cardiomyocyte repolarization in diabetes mellitus. We also review the progress of microRNAs as potential biomarkers and therapeutic targets of CVD in patients with diabetes.


Determination of glyphosate and its metabolites in plant material by reversed-polarity CE with indirect absorptiometric detection.
A simple CE method for simultaneous determination of glyphosate and its metabolites (i.e. aminomethylphosphonic acid, glyoxylate, sarcosine and formaldehyde) in plants is reported here. A BGE of pH 7.5, 10% ACN, 7.5 mM phthalate, containing 0.75 mM hexadecyltrimethylammonium bromide as an electro-osmotic flow modifier, an applied voltage of -20 kV and absorptiometric monitoring at 220 nm were the optimal chemical and instrumental parameters. The method, with development time 20 min, shows linear calibrations within the range 5-500 microg/mL (for all target analytes) with correlation coefficients between 0.999 and 0.998. It has been validated by application to samples of Lolium spp. The electroinjection mode hinders most interferents to enter the capillary, thus providing a clean electropherogram and making unnecessary long sample-preparation steps.


On hearing and inspiration in the composition of music.
The observation that composers experience inspiration as a source external to the self is considered, using reports of early and modern composers. This is related both to earlier psychoanalytic work on creative inspiration and to modern ego psychology. The postulation that an auditory sensory style in composers has early developmental roots and becomes their primary sensory mode is considered together with some possible determinants in its development.


Association of Central Retinal Arteriolar and Venular Equivalents with Brain-aging and Macular Ganglion Cell-inner Plexiform Layer Thickness.
Neurodegeneration and cognitive decline in aging are growing public health concerns. This study investigates associations between central retinal arteriolar and venular equivalents (CRAE, CRVE) and brain-aging, a sensory and cognitive test composite measure, and macular ganglion cell-inner plexiform layer (mGCIPL) thickness, a biomarker of neurodegeneration. Beaver Dam Offspring Study (BOSS) participants are adult children (baseline (2005-2008) age 21-84 years) of the population-based Epidemiology of Hearing Loss Study participants. Follow-up occurred every 5 years. In 2010-2013, fundus photographs were used to measure retinal vessels. A brain-aging score was constructed by principal component analysis using sensorineural and cognitive data. Associations between incident brain-aging and vessel measures were investigated using logistic regression. Associations between CRAE and CRVE and mGCIPL thickness, measured in 2015-2017, were also investigated. Participants (N = 2381; mean age: 53.9 years (SD = 9.8); 54% women) had a mean CRAE and CRVE of 148.8 µm (SD = 14.5) and 221.7 µm (SD = 20.7), respectively. Among those without ocular conditions, wider CRAE was associated with decreased 5-year brain-aging risk (33% per SD CRAE increase). Both vessel measures were independently associated with mGCIPL thickness. The mGCIPL thickness increased by approximately 1.7 µm and 2.0 µm per SD increase in CRAE and CRVE, respectively. The association of CRAE with incident brain-aging indicates its potential use as a screening tool among those without eye disease. The associations between CRAE and CRVE and mGCIPL thickness indicate narrower vasculature could affect neuronal health. These associations point to potential usefulness of retinal vessel measurements to identify people at higher risk of sensorineural declines and neurodegeneration.


Cloning and analysis of a Trichinella pseudospiralis muscle larva secreted serine protease gene.
Nematode parasites of the genus Trichinella are intracellular and distinct life cycle stages invade intestinal epithelial and skeletal muscle cells. Within the genus, Trichinella spiralis and Trichinella pseudospiralis exhibit species-specific differences with respect to host-parasite complex formation and host immune modulation. Parasite excretory-secretory (ES) proteins play important roles at the host-parasite interface and are thought to underpin these differences in biology. Serine proteases are among the most abundant group of T. spiralis ES proteins and multiple isoforms of the muscle larvae-specific TspSP-1 serine protease have been identified. Recently, a similar protein (TppSP-1) in T. pseudospiralis muscle larvae was identified. Here we report the cloning and characterisation of the full-length transcript of TppSP-1 and present comparative data between TspSP-1 and TppSP-1.


Clinical use of anticonvulsants: a neurologist's perspective.
Seizures may have an acute, reversible cause; antiepileptic drugs (AEDs) are not needed for every patient who presents with a seizure. The neurologist's decision concerning whether to initiate drug therapy depends on verifying that one or more seizures has occurred, on determining the likelihood of recurrence, and on balancing the risks of future seizures against the risks of treatment. Choice of AED is guided by classification of the seizure type and epilepsy syndrome, and by assessment of the likelihood of successful use based on patient characteristics such as age, childbearing potential, and comorbidities, balanced against drug characteristics such as pharmacokinetic profile and common side effects. Dose adjustment depends on communication between the physician and patient regarding seizure control and adverse drug effects. Patients who do not respond adequately to the first two or three appropriate AEDs should be referred for a comprehensive evaluation to verify the diagnosis and determine suitability for alternative treatments such as epilepsy surgery.


A probe into effect of Shoutai pill on endometrial receptivity.
The effect of Shoutai pill on endometrial receptivity was analyzed. A total of 160 patients with spontaneous abortion were enrolled in this study. They were treated in the Fifth People's Hospital of Jinan (Shandong, China) from February 2014 to June 2016. The following treatment regimen was performed for the patients: after menstruation, Shoutai pill was taken as continuous medication for more than 5 menstrual cycles, the pill was taken 20 days per month, medication was stopped during menstruation, and contraceptive measures were taken during this period. Statistics were recorded of endometrial thickness and morphology, hemodynamic parameters of uterine spiral artery, including pulsatility index (PI) and resistance index (RI), endometrial LIF levels before and after treatment, and follicular development and ovulation were strictly monitored, and statistics of pregnancy were recorded. The endometrial thickness, type A endometrium and endometrial spiral arterial PI and RI levels, endometrial LIF levels were significantly improved after treatment (P<0.05); at the same time, pregnancy rate was 85%; during this treatment, patients had no significant side effects. In conclusion, improvement of endometrial acceptability with Shoutai pills can receive good effect, significantly promote embryo implantation and enhance pregnancy rate.


Noise estimation in infrared image sequences: a tool for the quantitative evaluation of the effectiveness of registration algorithms.
Dynamic infrared imaging has been proposed in literature as an adjunctive technique to mammography in breast cancer diagnosis. It is based on the acquisition of hundreds of consecutive thermal images with a frame rate ranging from 50 to 200 frames/s, followed by the harmonic analysis of temperature time series at each image pixel. However, the temperature fluctuation due to blood perfusion, which is the signal of interest, is small compared to the signal fluctuation due to subject movements. Hence, before extracting the time series describing temperature fluctuations, it is fundamental to realign the thermal images to attenuate motion artifacts. In this paper, we describe a method for the quantitative evaluation of any kind of feature-based registration algorithm on thermal image sequences, provided that an estimation of local velocities of reference points on the skin is available. As an example of evaluation of a registration algorithm, we report the evaluation of the SNR improvement obtained by applying a nonrigid piecewise linear algorithm.


Emodiversity and the emotional ecosystem.
[Correction Notice: An Erratum for this article was reported in Vol 143(6) of Journal of Experimental Psychology: General (see record 2014-49316-001). There is a color coding error in Figure 2. The correct color coding is explained in the erratum.] Bridging psychological research exploring emotional complexity and research in the natural sciences on the measurement of biodiversity, we introduce--and demonstrate the benefits of--emodiversity: the variety and relative abundance of the emotions that humans experience. Two cross-sectional studies across more than 37,000 respondents demonstrate that emodiversity is an independent predictor of mental and physical health--such as decreased depression and doctor's visits--over and above mean levels of positive and negative emotion. These results remained robust after controlling for gender, age, and the 5 main dimensions of personality. Emodiversity is a practically important and previously unidentified metric for assessing the health of the human emotional ecosystem.


What Is Being Measured with P-Bearing NMR Probe Molecules Adsorbed on Zeolites?
Elucidating the nature, strength, and siting of acid sites in zeolites is fundamental to fathom their reactivity and catalytic behavior. Despite decades of research, this endeavor remains a major challenge. Trimethylphosphine oxide (TMPO) has been proposed as a reliable probe molecule to study the acid properties of solid acid catalysts, allowing the identification of distinct Brønsted and Lewis acid sites and the assessment of Brønsted acid strengths. Recently, doubts have been raised regarding the assignment of the 31P NMR resonances of TMPO-loaded zeolites. Here, it is shown that a judicious control of TMPO loading combined with two-dimensional 1H-31P HETCOR solid-state NMR, DFT, and ab initio molecular dynamics (AIMD)-based computational modeling provides an unprecedented atomistic description of the host-guest and guest-guest interactions of TMPO molecules confined within HZSM-5 molecular-sized voids. 31P NMR resonances usually assigned to TMPO molecules interacting with Brønsted sites of different acid strength arise instead from both changes in the probe molecule confinement effects at ZSM-5 channel system and the formation of protonated TMPO dimers. Moreover, DFT/AIMD shows that the 1H and 31P NMR chemical shifts strongly depend on the siting of the framework aluminum atoms. This work overhauls the current interpretation of NMR spectra, raising important concerns about the widely accepted use of probe molecules for studying acid sites in zeolites.


The vomeronasal organ of wild canids: the fox (Vulpes vulpes) as a model.
The vomeronasal system (VNS) has been extensively studied within specific animal families, such as Rodentia. However, the study of the VNS in other families, such as Canidae, has long been neglected. Among canids, the vomeronasal organ (VNO) has only been studied in detail in the dog, and no studies have examined the morphofunctional or immunohistochemical characteristics of the VNS in wild canids, which is surprising, given the well-known importance of chemical senses for the dog and fox and the likelihood that the VNS plays roles in the socio-reproductive physiology and behaviours of these species. In addition, characterising the fox VNS could contribute to a better understanding of the domestication process that occurred in the dog, as the fox would represent the first wild canid to be studied in depth. Therefore, the aim of this study was to analyze the morphological and immunohistochemical characteristics of the fox VNO. Tissue dissection and microdissection techniques were employed, followed by general and specific histological staining techniques, including with immunohistochemical and lectin-histochemical labelling strategies, using antibodies against olfactory marker protein (OMP), growth-associated protein 43 (GAP-43), calbindin (CB), calretinin (CR), α-tubulin, Gαo, and Gαi2 proteins, to highlight the specific features of the VNO in the fox. This study found significant differences in the VNS between the fox and the dog, particularly concerning the expression of Gαi2 and Gαo proteins, which were associated with the expression of the type 1 vomeronasal receptors (V1R) and type 2 vomeronasal receptors (V2R), respectively, in the vomeronasal epithelium. Both are immunopositive in foxes, as opposed to the dog, which only expresses Gαi2. This finding suggests that the fox possesses a well-developed VNO and supports the hypothesis that a profound transformation in the VNS is associated with domestication in the canid family. Furthermore, the unique features identified in the fox VNO confirm the necessity of studying the VNS system in different species to better comprehend specific phylogenetic aspects of the VNS.


Alfvén limit in fast ignition.
Fast ignition inertial confinement fusion relies on rapidly heating the compressed fuel to ignition using a laser-generated electron beam. The current required far exceeds the Alfvén limit, so it can only propagate while the plasma provides a nearly coincident return current. The resistive decay of the return current is shown to be too rapid for the originally proposed scheme to work. Possible solutions to this problem are to increase the mean energy of the beam, to heat the fuel to a higher temperature by lowering the beam radius and duration, to use multiple beams, and to use an annular beam. Considering the laser wavelength required shows that increasing the mean energy and number of beams are the most practical solutions.


Acneiform eruption induced by vedolizumab.
The development of new biological drugs for the treatment of advanced oncological processes or severe inflammatory diseases brings with it the appearance of new adverse effects. Vedolizumab, an α4β7 integrin inhibitor antibody, is approved for induction and maintenance therapy in both Crohn disease and ulcerative colitis. We report a case of severe acneiform eruption induced by vedolizumab in a 17-year-old woman with ulcerative colitis.


Performance and implementation of low impact development - A review.
Climate change, urbanization, and ecological concerns are all driving the need for new stormwater management strategies. The effects of urbanization are exaggerated by climate change and thus the development of innovative stormwater management techniques are necessary to mitigate these impacts. One emerging stormwater management philosophy is low impact development (LID). LID utilizes distributed stormwater controls (often green infrastructure) as well as green spaces and natural hydrologic features in order to bring the hydrology of urban catchments closer to pre-development conditions. The review provides a summary of the knowledge of LID as a stormwater management technique and climate change mitigation measure as well as the current state of research and implementation of this topic. In order to provide a better understanding of the extensive scope that should be considered for design of low impact developments, methods of optimization, modelling, monitoring and the performance of LID alternatives is covered. LID has been widely adopted and proven successful in many cases; however, there remains uncertainty of its benefits. This review brings together knowledge from many sources in order to provide an overview of LID and examine its performance and implementation.


Electroretinogram (ERG) to photic stimuli should be carefully distinct from photic brainstem reflex in patients with deep coma.
Patient 1: A 35-year-old woman became deep coma because of intracranial hemorrhage after pulmonary surgery. Patient 2: A 39-year-old woman became deep coma because of cerebellar hemorrhage after hepatic surgery. Scalp-recorded digital electroencephalography (EEG) showed electrocerebral inactivity in both cases. In addition, both EEG showed repetitive discharges at bilateral frontopolar electrodes in response to photic stimuli. The amplitude and latency of the discharges was 17 μV and 24 msec in case 1, and 9 μV and 27 msec in case 2 respectively. The activity at left frontopolar electrode disappeared after coverage of the ipsilateral eye. Based on these findings, we could exclude the possibility of brainstem response and judged it as electroretinogram (ERG). Photic stimulation is a useful activation method in EEG recording, and we can also evaluate brainstem function by checking photic blink reflex if it is evoked. However, we should be cautious about the distinction of ERG from photic blink reflex when brain death is clinically suspected.


Depression, anxiety and their associated factors among medical students.
To determine the frequency of anxiety and depression among medical students of Wah Medical College and their associations with sociodemographic and educational characteristics if any. Cross-sectional survey. Wah Medical College, from September 2007 to March 2008. A sample of 279 students was included in the study after excluding first year medical students because they were admitted for less than 6 months. A self administered Encounter Form was administered. Sociodemographic and educational characteristics included age, gender, birth order, number of siblings, monthly income, monthly expenditure on education, academic performance in professional examination, past medical and past psychiatric history, substance abuse and family history of psychiatric illness. Beck depression inventory and beck anxiety inventory were used to assess the level of depression and anxiety. The chi-square test was applied at 5% level of significance to determine associated factors for anxiety and depression respectively. The mean age of students was 21.4+/-1.41 years with female preponderance i.e. 202 (72.4%). Anxiety was present in 133 (47.7%) students and depression in 98 (35.1%) students. Both were found concomitantly in 68 (24.37%) students. Age (p=0.013), gender (p=0.016), examination criteria dissatisfaction (p=0.002) and overburden with test schedule (p=0.002) were significantly associated with depression. Anxiety was significantly associated with gender (p=0.007), birth order (p=0.049), year of study (p=0.001), examination criteria dissatisfaction (p=0.010) and overburden with test schedule (p=0.006). One third of students were found to have anxiety and depression which was associated with the sociodemographic and educational factors as stated above.


The Greenville gastric bypass. Progress report at 3 years.
Two hundred and ten morbidly obese patients underwent a standardized gastric bypass procedure between February 1980 and November 1983. We conclude, based on 100% follow-up, that the operation is safe (operative mortality--1%, significant complications--10%) and effective (reoperation rate--4%). Only one patient failed to lose more than 25% of preoperative weight. The operation produced a mean weight loss in the group from 289 pounds (202-505) before surgery to 176 pounds (118-308) at 18 months after surgery. Stated as "per cent of ideal weight," patients lost from a preoperative mean of 214% (153-350) to 130% (88-189) at 18 months. Maximum weight loss was reached by 18 months after the procedure and was maintained during 36 months of observation in over 95% of patients. When patients were divided into four groups according to preoperative weight, weight loss occurred at a roughly similar rate, but heavier patients, although they lost more weight, plateaued at a higher weight than patients originally less obese. Striking and objective benefits were seen in patients with diabetes, hypertension, heart disease, and pulmonary insufficiency.


Frog ventricle: participation of SR in excitation-contraction coupling.
Activation of the first beat (B1) following a 60-s pause is diminished in isometrically contracting frog ventricular strips, in contrast to the augmentation documented for sarcoplasmic reticulum (SR)-dependent mammalian myocardium. However, treatment of frog ventricular strips with ouabain, an indirect inhibitor of the sarcolemmal Na+-Ca2+ exchanger, selectively enhanced postpause beats suggesting that in the absence of ouabain significant extrusion of cellular Ca2+ occurred during the pause. Because resting tension did not increase during the pause in ouabain-treated strips, the nonextruded Ca2+ must have been sequestered into a compartment such as SR. Steady-state beats were not affected by ouabain; its actions appeared to be separate from its known positive inotropism. Caffeine, a direct SR stimulus, initially enhanced B1 and subsequently decreased activation of all beats, which was consistent with initial augmentation of SR Ca2+ release and subsequent depletion of SR Ca2+ stores. Ouabain both potentiated the stimulatory effects and blocked the inhibitory effects of caffeine, suggesting that ouabain increased Ca2+ stores in the same intracellular Ca2+ pool as that acted on by caffeine, the SR. Ryanodine, an inhibitor of SR in mammalian myocardium, did not affect activation of frog myocardium. SR may be an important site for activator Ca2+ cycling in frog myocardium under control conditions as well as after long diastolic intervals in the presence of ouabain.


Optical Coherence Tomography and Visual Evoked Potentials as Prognostic and Monitoring Tools in Progressive Multiple Sclerosis.
Understanding the mechanisms underlying progression and developing new treatments for progressive multiple sclerosis (PMS) are among the major challenges in the field of central nervous system (CNS) demyelinating diseases. Over the last 10 years, also because of some technological advances, the visual pathways have emerged as a useful platform to study the processes of demyelination/remyelination and their relationship with axonal degeneration/protection. The wider availability and technological advances in optical coherence tomography (OCT) have allowed to add information on structural neuroretinal changes, in addition to functional information provided by visual evoked potentials (VEPs). The present review will address the role of the visual pathway as a platform to assess functional and structural damage in MS, focusing in particular on the role of VEPs and OCT, alone or in combination, in the prognosis and monitoring of PMS.


Increased intra-articular substance P and prostaglandin E2 following injection of interleukin-1 in rabbits.
Inflammation was induced by intra-articular injection of 100 ng recombinant human interleukin-1 alpha (rhIL-1) into rabbit knees. Substance P (SP) and prostaglandin E2 (PGE2) were measured by radioimmunoassay (RIA) in the joint fluid at 4, 24 and 48 h after rhIL-1 injection. SP was increased by 4 h, further increased at 24 h and remained elevated at 48 h. PGE2 concentration was highest at 4 h and remained elevated at 48 h after rhIL-1 injection. Because of the proinflammatory activities of SP and PGE2, our studies suggest that the elevated SP and PGE2, in the joint may amplify or sustain an initial receptor-mediated inflammatory response to IL-1.


Doctor-patient interaction in Finnish primary health care as perceived by first year medical students.
In Finland, public health care is the responsibility of primary health care centres, which render a wide range of community level preventive, curative and rehabilitative medical care. Since 1990's, medical studies have involved early familiarization of medical students with general practice from the beginning of the studies, as this pre-clinical familiarisation helps medical students understand patients as human beings, recognise the importance of the doctor-patient relationship and identify practicing general practitioners (GPs) as role models for their professional development. Focused on doctor-patient relationship, we analysed the reports of 2002 first year medical students in the University of Kuopio. The students observed GPs' work during their 2-day visit to primary health care centres. We analysed systematically the texts of 127 written reports of 2002, which represents 95.5% of the 133 first year pre-clinical medical students reports. The reports of 2003 (N = 118) and 2004 (N = 130) were used as reference material. Majority of the students reported GPs as positive role models. Some students reported GPs' poor attitudes, which they, however, regarded as a learning opportunity. Students generally observed a great variety of responsibilities in general practice, and expressed admiration for the skills and abilities required. They appreciated the GPs' interest in patients concerns. GPs' communication styles were found to vary considerably. Students reported some factors disturbing the consultation session, such as the GP staring at the computer screen and other team members entering the room. Working with marginalized groups, the chronically and terminally ill, and dying patients was seen as an area for development in the busy Finnish primary health care centres. During the analysis, we discovered that medical students' perceptions in this study are in line with the previous findings about the importance of role model (good or bad) in making good doctors. Therefore, medical students' pre-clinical primary health care centre visits may influence their attitudes towards primary health care work and the doctor-patient relationship. We welcome more European studies on the role of early pre-clinical general practice exposure on medical students' primary care specialty choice.


Adapting a grid into a microswitch to suit simple hand movements of a child with profound multiple disabilities.
We adapted a grid into a microswitch for the hand movements of a girl with profound multiple disabilities who lay on her back. The grid, suspended above the girl's face, was equipped with two mercury devices, i.e., small sealed ampoules containing a mercury drop and ending with conductive leads. A lateral or forward movement of the grid would make the mercury drop of at least one device slide to the conductive leads and activate the device. During the intervention, activations of the devices, i.e., microswitch activations, produced the occurrence of favorite stimuli. Analysis showed that the girl increased the frequency of hand movements and microswitch activations during the intervention phases compared to the baseline phases (when the favorite stimuli were not available). The increase was retained at a 1-mo. postintervention check.


Placebo in the evaluation of antiulcer drugs.
According to the most recent definition, "placebo" is any substance devoid of specific activity, which nevertheless is given in order to obtain an effect. It is used to advantage in identifying active drugs (controlled clinical trials). It has an effect which is usually (though not always) favourable and has its own pharmacology closely resembling that of active substances. In view of the consistency of the placebo effect, any substance tried in the treatment of the various diseases of the alimentary tract must prove superior to placebo in order to be considered an "active" substance. It is only on the basis of this criterion that we may accept the risk of side-effects which, though they may be slight, are nevertheless unjustified if the drugs we are administering are inactive. This drug vs placebo comparison classically takes the form of so-called "double-blind" controlled studies, but for digestive diseases these are far less numerous than the many unreliable, uncontrolled studies available. Generally, the use of a placebo control has led to the elimination of numerous substances characterized by purely alleged efficacy, and to the identification of efficacious compounds or acceptable therapeutic trends. In peptic ulcer, controlled studies vs placebo have also contributed towards the acquisition and definition of useful pathophysiological, clinical and therapeutic notions.(ABSTRACT TRUNCATED AT 250 WORDS)


Action of prostanoids on the emetic reflex of Suncus murinus (the house musk shrew).
Several prostanoids were investigated for a potential to induce emesis in Suncus murinus. The TP receptor agonist 11alpha,9alpha-epoxymethano-15S-hydroxyprosta-5Z,13E-dienoic acid (U46619) induced emesis at doses as low as 3 microg/kg, i.p. but the DP receptor agonist 5-(6-Carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl) hydantoin (BW245C) was approximately 1000 times less potent. The emetic action of U46619 (300 microg/kg, i.p.) was antagonized significantly by the TP receptor antagonist, vapiprost (P<0.05). EP (prostaglandin E(2), 17-phenyl-omega-trinor prostaglandin E(2), misoprostol and sulprostone), FP (prostaglandin F(2alpha) and fluprostenol) and IP (iloprost and cicaprost) receptor agonists failed to induce consistent emesis at doses up to 300-1000 microg/kg, i.p. Fluprostenol reduced nicotine (5 mg/kg, s.c.)-but not copper sulphate (120 mg/kg, intragastric)-induced emesis; the other inconsistently emetic prostanoids were inactive to modify drug-induced emesis. The results indicate an involvement of TP and possibly DP and FP receptors in the emetic reflex of S. murinus.


Mycobacterium Chimaera: A Rare Presentation.
Mycobacterium chimaera is an indolent nontuberculous mycobacterium which is abundant in soil, dust, and water. Although lacking recognition garnered by other mycobacteria (i.e., M. tuberculosis), it has been recognized as an emerging opportunistic threat to patients undergoing coronary bypass surgery and open heart procedures requiring extracorporeal devices. Here, we present a case of an individual initially seen in the inpatient setting without a history of such procedures or other risk factors commonly associated with mycobacterium-laden infections.


Pathophysiology of congestive heart failure secondary to congestive and ischemic cardiomyopathy.
Dilated cardiomyopathy, owing to any cause, usually culminates in the clinical syndrome of congestive heart failure. Heart failure is characterized by exertional dyspnea and fatigue, but the precise mechanisms that produce these symptoms are still not clear. Sodium retention occurs early in heart failure, but this disturbance is dynamic in nature and is not always present in the patient. The mechanism of early salt and water retention in heart failure is not defined. Gross edema and ascites occur much later, undoubtedly owing to the convergence of a number of factors. The peripheral adaptations to heart failure include activation of the renin-angiotensin system and the sympathetic nervous system, and the release of AVP. The result is an increase in preload with a resultant increase in stroke volume for some patients, but the price is paid in the form of heightened impedance to ejection and circulatory congestion. The sympathetic nervous system disturbances in heart failure are striking, as disturbances in both circulating and myocardial NE levels are consistently found. Vasorelaxant and natriuretic hormones, as well as certain prostaglandins, may be released in an attempt to offset excessive "compensatory" pressor-sodium retentive mechanisms, but the net result seems to be excessive peripheral vasoconstriction and a downward spiral of deterioration in many patients. One would hope that an unraveling of the complex pathophysiology of heart failure would lead to therapy that would change the natural history of the disease. The results of the first V-HeFT trial give room for cautious optimism in this regard.


GLTM: A Global-Local Attention LSTM Model to Locate Dimer Motif of Single-Pass Membrane Proteins.
Single-pass membrane proteins, which constitute up to 50% of all transmembrane proteins, are typically active in significant conformational changes, such as a dimer or other oligomers, which is essential for understanding the function of transmembrane proteins. Finding the key motifs of oligomers through experimental observation is a routine method used in the field to infer the potential conformations of other members of the transmembrane protein family. However, approaches based on experimental observation need to consume a lot of time and manpower costs; moreover, they are hard to reveal the potential motifs. A proposed approach is to build an accurate and efficient transmembrane protein oligomer prediction model to screen the key motifs. In this paper, an attention-based Global-Local structure LSTM model named GLTM is proposed to predict dimers and screen potential dimer motifs. Different from traditional motifs screening based on highly conserved sequence search frame, a self-attention mechanism has been employed in GLTM to locate the highest dimerization score of subsequence fragments and has been proven to locate most known dimer motifs well. The proposed GLTM can reach 97.5% accuracy on the benchmark dataset collected from Membranome2.0. The three characteristics of GLTM can be summarized as follows: First, the original sequence fragment was converted to a set of subsequences which having the similar length of known motifs, and this additional step can greatly enhance the capability of capturing motif pattern; Second, to solve the problem of sample imbalance, a novel data enhancement approach combining improved one-hot encoding with random subsequence windows has been proposed to improve the generalization capability of GLTM; Third, position penalization has been taken into account, which makes a self-attention mechanism focused on special TM fragments. The experimental results in this paper fully demonstrated that the proposed GLTM has a broad application perspective on the location of potential oligomer motifs, and is helpful for preliminary and rapid research on the conformational change of mutants.


Clinical management of immuno-suppression in athletes associated with exercise training: sports medicine considerations.
The Overtraining Syndrome (OTS) is a physically debilitating medical condition that results in athletes being totally compromised in their capacity to perform and compete. Many physiological systems are affected by the process of overtraining and the development of the OTS which results from it; but one system in particular, the immune, is highly susceptible to degradation resulting in a reduction in overall health and physical performance. The aim of this paper is to review; 1) the evidence-based proactive steps and actions to take to greatly reduce the risk of development of an infection or a compromised immune system in athletes; and 2) the course of action for clinicians to take when they are dealing with an athlete displaying overt signs of an infection and, or inflammation. Evidenced reported here within support that it is essential for clinicians to take practical preventative and management steps - actions with athletes (involved in intensive exercise training) in order to help preserve and maintain a healthy and robust immune system if they are going to perform optimally.


Species sensitivity distributions for use in environmental protection, assessment, and management of aquatic ecosystems for 12 386 chemicals.
The present study considers the collection and use of ecotoxicity data for risk assessment with species sensitivity distributions (SSDs) of chemical pollution in surface water, which are used to quantify the likelihood that critical effect levels are exceeded. This fits the European Water Framework Directive, which suggests using models to assess the likelihood that chemicals affect water quality for management prioritization. We derived SSDs based on chronic and acute ecotoxicity test data for 12 386 compounds. The log-normal SSDs are characterized by the median and the standard deviation of log-transformed ecotoxicity data and by a quality score. A case study illustrates the utility of SSDs for water quality assessment and management prioritization. We quantified the chronic and acute mixture toxic pressure of mixture exposures for >22 000 water bodies in Europe for 1760 chemicals for which we had both exposure and hazard data. The results show the likelihood of mixture exposures exceeding a negligible effect level and increasing species loss. The SSDs in the present study represent a versatile and comprehensive approach to prevent, assess, and manage chemical pollution problems. Environ Toxicol Chem 2019;38:905-917. © 2019 SETAC.


Transthyretin (prealbumin) in health and disease: nutritional implications.
The name "transthyretin" reflects the dual physiological roles of this tetrameric unglycosylated plasma protein. TTR is one of three specific carrier proteins involved in the transport of both thyroid hormones and of retinol through the mediation of RBP. TTR is a product of the visceral compartment, and its hepatic synthesis is exquisititely sensitive to both the adequacy and levels of protein and energy intakes--hence the proposal of TTR as a nutritional marker. To date, 38 TTR variants have been described, most of which are associated with variable degrees of cardiac and/or neural tissue amyloid deposits. All known variants arise from a single AA substitution due to single point mutation in the coding region of the TTR gene. Under acute stress conditions, the synthesis of TTR, RBP, and CBG is abruptly depressed by a cytokine-directed orchestration of new metabolic priorities, with a redistribution of organ and tissue protein pools. It is proposed that TTR, RBP, and CBG behave as acute-booster reactants (ABRs), actively participating in the cascade of metabolic events characterizing the stress reaction along pathways best explained by the free hormone/vitamin hypothesis. The latter is governed by the law of mass action--the spontaneous dissociation and instant uptake by hepatocytes of the ligands freed from their specific carrier proteins, which creates a transient hyperthyroid, hyperretinoid, and hypercortisolic climate. This response generally does not exceed four or five days because the initial impact of injury normally subsides, but it may last longer if complications occur. The magnitude and adequacy of the stress responses depend on the preceding nutritional status as assessed by TTR plasma levels and are proportionate to the severity of insult. Clinical, animal, and molecular studies concur to demonstrate the dualistic stimulatory or inhibitory effects triggered by the ligands, whose unmetabolized fractions are excreted in the urinary output. Thyroid hormones and retinoids appear to control the early maturation processes and the synthesis of primary transcripts, whereas cortisol preferentially modulates the secondary responses and confers a protective effect on healthy tissues. During acute stress, the evolutionary patterns of visceral proteins and inflammatory markers exhibit compulsory mirror images. However, they change in independent ways under more chronic circumstances. A relatively simple biochemical micromethod based on the simultaneous measurement of plasma TTR, albumin, CRP, and orosomucoid aggregated into a PINI is proposed for the early recognition and follow-up of both nutritional and inflammatory facets of the disease spectrum.


Structural Insights into Methylated DNA Recognition by the Methyl-CpG Binding Domain of MBD6 from Arabidopsis thaliana.
Cytosine methylation is an epigenetic modification essential for formation of mature heterochromatin, gene silencing, and genomic stability. In plants, methylation occurs not only at cytosine bases in CpG but also in CpHpG and CpHpH contexts, where H denotes A, T, or C. Methyl-CpG binding domain (MBD) proteins, which recognize symmetrical methyl-CpG dinucleotides and act as gene repressors in mammalian cells, are also present in plant cells, although their structural and functional properties still remain poorly understood. To fill this gap, in this study, we determined the solution structure of the MBD domain of the MBD6 protein from Arabidopsis thaliana and investigated its binding properties to methylated DNA by binding assays and an in-depth NMR spectroscopic analysis. The AtMBD6 MBD domain folds into a canonical MBD structure in line with its binding specificity toward methyl-CpG and possesses a DNA binding interface similar to mammalian MBD domains. Intriguingly, however, the binding affinity of the AtMBD6 MBD domain toward methyl-CpG-containing DNA was found to be much lower than that of known mammalian MBD domains. The main difference arises from the absence of positively charged residues in AtMBD6 that supposedly interact with the DNA backbone as seen in mammalian MBD/methyl-CpG-containing DNA complexes. Taken together, we have established a structural basis for methyl-CpG recognition by AtMBD6 to develop a deeper understanding how MBD proteins work as mediators of epigenetic signals in plant cells.


Anencephalic infants as organ sources.
Liveborn anencephalic infants cannot be used legally as sources for vital organs in the United States and Canada. Understandably, knowledgeable physicians and bioethicists are divided over the ethics of such use and hold various views on whether the legal status of anencephalic newborns should ever be changed. Even if anencephalic newborns could be utilized as organ sources, at best a few hundred infants needing transplant organs would be saved each year. Primarily, this is because the number of anencephalic newborns is likely to diminish due to prenatal diagnosis resulting in abortions. However, the case of anencephalic infants and their treatment is paradigmatic in raising questions far beyond mere organ transplantation.... This analytical report is given against the backdrop of a burgeoning medical technology which can sustain human life far beyond that generally regarded as a meaningful, functional life. The report has three sections: first, a description of the approaches to the use of anencephalic infants in North America over the last five years; second, a summary of the results of a survey of informed clinicians and ethicists; and third, an indication of the leading ethical issues raised by human individuals at the border of life.


[Characteristics of the water-electrolyte regulation in experimental hyperthyroidization and hyperthyroidism].
In experiments on rats the effect of hyperthyroidization (induced by thyroidin, 1-thyroxin) and hyperthyrosis (induced by TSH, cold exposure) on volume natriuresis was studied. As revealed, after expansion of extracellular space natriuresis increased under hyperthyroidization and hyperthyrosis, and was much higher than in control rats. Natriuresis elevation in response to increased volume of extracellular fluid in rats under hyperthyroidization resulted from the rise of natriuretic factor in the blood.


Substance P mediates cerulein-induced pancreatic microcirculatory dysfunction in mice.
The present study was conducted to examine the contribution of substance P to the pancreatic microcirculatory dysfunction during acute pancreatitis. Pancreatitis was elicited by up to 6 hourly injections of cerulein (50 microg/kg IP) in male C57Bl/6 mice. At 0, 1, 3, and 6 hours after cerulein treatment, the pancreatic microvasculature in anesthetized mice was studied using established high-resolution in vivo microscopic methods. Treatment of mice with cerulein for 6 hours caused a 30% decrease in capillary perfusion and the diameter of the capillaries and an increase in microvascular permeability (20%) and interstitial space (30-fold). The administration of the substance P receptor antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11) (2 mg/kg IP) minimized the pancreatic microcirculatory dysfunction 3 hours after cerulein treatment. The superfusion of substance P for 0.5 hours decreased the diameter (by 22%) and increased microvascular permeability (by 23%) along with interstitial space (22-fold increase). Blockade of substance P receptor attenuated substance P-induced pancreatic microcirculatory dysfunction. These results suggest that substance P mediates pancreatic microcirculatory dysfunction during the development of acute pancreatitis.


Release of hydrolases and acetylcholine sensitivity in rat skeletal muscle.
Cytosol prepared from the hind-limb muscles of the rat contained factors which increased the acetylcholine (ACh) contractures in intact normally innervated muscles in vitro. Muscles which had been denervated 4-6 days previously and normally innervated muscles released a factor upon incubation which increased the ACh responses of normal muscles. The normal muscles, however, also released an inhibitor of this effect. The medium obtained after incubation of the muscles contained a variety of hydrolytic enzymes including phospholipase C, acid protease and calcium-activated neutral protease. The amounts of phospholipase C released by normal and denervated muscles were similar, but approximately four times more of the two proteases was released from the denervated muscles than from normal muscles. The possibility that these hydrolases could be the factors which increased the ACh sensitivity in normal muscles is discussed.


Characterization and functional analysis of porcine estrogen-related receptors and their alternative splicing variants.
Estrogen-related receptors (ESRR) are orphan nuclear hormone receptors with unidentified ligands; they play important roles in tissue regulation and development and maintenance of pluripotent cell identity. The splicer variant, genomic organization, and physiological roles of ESRR have been elucidated in the human and the mouse. However, in livestock, they remain elusive. In this study, we cloned porcine ESRR family members , , and . Two alternative splicing variants, and , and a novel were identified. To determine the domain function, we constructed vectors with sequential deletions of the ESRRB coding sequence. The functional analysis showed that the C domain of ESRR plays a core role in promoting the activation of estrogen response elements that are found in all kinds of ESRR-targeting genes, whereas the E domain is not essential for transcription regulation of ESRR unless a specific and identified ligand is applied.


Urine-derived stem cells: A novel and versatile progenitor source for cell-based therapy and regenerative medicine.
Engineered functional organs or tissues, created with autologous somatic cells and seeded on biodegradable or hydrogel scaffolds, have been developed for use in individuals with tissue damage suffered from congenital disorders, infection, irradiation, or cancer. However, in those patients, abnormal cells obtained by biopsy from the compromised tissue could potentially contaminate the engineered tissues. Thus, an alternative cell source for construction of the neo-organ or functional recovery of the injured or diseased tissues would be useful. Recently, we have found stem cells existing in the urine. These cells are highly expandable, and have self-renewal capacity, paracrine properties, and multi-differentiation potential. As a novel cell source, urine-derived stem cells (USCs) provide advantages for cell therapy and tissue engineering applications in regeneration of various tissues, particularly in the genitourinary tract, because they originate from the urinary tract system. Importantly, USCs can be obtained via a non-invasive, simple, and low-cost approach and induced with high efficiency to differentiate into three dermal cell lineages.


[Effect of metastasis suppressor gene KAI1 on the proliferation and invasive ability of cervical carcinoma cells].
To explore the effect of metastasis suppressor gene KAI1 on the proliferation and invasive ability of cervical cancer cell line CaSki. pCMV-KAI1 cDNA plasmid was transferred into cervical carcinoma cell line CaSki by liposome, which had low level of endogenous KAI1 expression. The expressions of KAI1 protein and mRNA were determined by immunohistochemistry and real-time fluorescence quantitative PCR (RT-PCR), the proliferation of KAI1-transfected CaSki cells was investigated by MTT assay and the invasive ability of these cells was evaluated by in vitro invasion assays. After the transfection of pCMV-KAI1 cDNA, the level of KAI1 mRNA and protein expression in CaSki cell were increased (P < 0.05), while the cell proliferation was suppresssed, and the migrative ability of passing through the membrane filte also decreased evidently (P < 0.05). The KAI1 metastasis suppressor gene suppressed the ability of proliferation and invasion of cervical cancer cell CaSki in vitro.


Surgical treatment of pulmonary embolism with recent intracranial hemorrhage.
Massive pulmonary embolism (PE) with concomitant intracranial hemorrhage (ICH) has a high mortality rate. Although thrombolytic therapy is generally accepted as emergent treatment for massive PE, the risk of bleeding complications are significant. A 69-year-old woman presented with acute PE 11 days after onset of ICH. Thrombolysis was deferred, and emergent surgical embolectomy with cardiopulmonary bypass (CPB) was elected. Patient outcome was favorable without recurrence of ICH.


Ontogenetic limb bone scaling in basic fibroblast growth factor (FGF-2) transgenic mice.
Basic fibroblast growth factor (FGF-2) is a potent mitogen which is required for normal development, particularly the development of the skeletal system, where the inhibition of FGF binding to its receptor results in various skeletal malformations. The present study employed a newly engineered line of FGF-2 transgenic mice to determine the effects of overexpressing FGF-2 on limb bone ontogeny. We collected radiographic and weight data longitudinally and obtained the length, proximal, distal, and minimum diaphyseal widths of the humerus, femur, and tibia. Because growth is nonlinear with respect to time, we used the Gompertz mathematical model to obtain parameters describing rate and timing for each individual for each measurement. Differences in the parameters due to genotype and sex were subsequently tested with ANOVA. Transgenic animals exhibited consistently shorter limb bones which were generally wider at the epiphyses than those of controls. Parameters of early growth, including initial size and proportional rate of growth, appeared to be most directly responsible for significant differences in final size; however, exponential decay of growth was also a marginally significant factor. There were no differences between the genotypes in body weight, indicating that the shape anomalies observed in transgenic mice were a direct result of the action of FGF-2 rather than a general runting phenomenon.


Electrokinetic-Enhanced Bioremediation of Trichloroethylene-Contaminated Low-Permeability Soils: Mechanistic Insight from Spatio-Temporal Variations of Indigenous Microbial Community and Biodehalogenation Activity.
Electrokinetic-enhanced bioremediation (EK-Bio), particularly bioaugmentation with injection of biodehalogenation functional microbes such as Dehalococcoides, has been documented to be effective in treating a low-permeability subsurface matrix contaminated with chlorinated ethenes. However, the spatio-temporal variations of indigenous microbial community and biodehalogenation activity of the background matrix, a fundamental aspect for understanding EK-Bio, remain unclear. To fill this gap, we investigated the variation of trichloroethylene (TCE) biodehalogenation activity in response to indigenous microbial community succession in EK-Bio by both column and batch experiments. For a 195 day EK-Bio column (∼1 V/cm, electrolyte circulation, lactate addition), biodehalogenation activity occurred first near the cathode (<60 days) and then spread to the anode (>90 days), which was controlled by electron acceptor (i.e., Fe(III)) competition and microbe succession. Amplicon sequencing and metagenome analysis revealed that iron-reducing bacteria (Geobacter, Anaeromyxobacter, Geothrix) were enriched within initial 60 d and were gradually replaced by organohalide-respiring bacteria (versatile Geobacter and obligate Dehalobacter) afterward. Iron-reducing bacteria required an initial long time to consume the competitive electron acceptors so that an appropriate reductive condition could be developed for the enrichment of organohalide-respiring bacteria and the enhancement of TCE biodehalogenation activity.


Achieving donor-specific hyporesponsiveness is associated with FOXP3+ regulatory T cell recruitment in human renal allograft infiltrates.
Exploring new immunosuppressive strategies inducing donor-specific hyporesponsiveness is an important challenge in transplantation. For this purpose, a careful immune monitoring and graft histology assessment is mandatory. Here, we report the results of a pilot study conducted in twenty renal transplant recipients, analyzing the immunomodulatory effects of a protocol based on induction therapy with rabbit anti-thymocyte globulin low doses, sirolimus, and mofetil mycophenolate. Evolution of donor-specific cellular and humoral alloimmune response, peripheral blood lymphocyte subsets and apoptosis was evaluated. Six-month protocol biopsies were performed to assess histological lesions and presence of FOXP3+ regulatory T cells (Tregs) in interstitial infiltrates. After transplantation, there was an early and transient apoptotic effect, mainly within the CD8+ HLADR+ T cells, combined with a sustained enhancement of CD4+ CD25(+high) lymphocytes in peripheral blood. The incidence of acute rejection was 35%, all steroid sensitive. Importantly, only pretransplant donor-specific cellular alloreactivity could discriminate patients at risk to develop acute rejection. Two thirds of the patients became donor-specific hyporesponders at 6 and 24 mo, and the achievement of this immunologic state was not abrogated by prior acute rejection episodes. Remarkably, donor-specific hyporesponders had the better renal function and less chronic renal damage. Donor-specific hyporesponsiveness was inhibited by depleting CD4+ CD25(+high) T cells, which showed donor-Ag specificity. FOXP3+ CD4+ CD25(+high) Tregs both in peripheral blood and in renal infiltrates were higher in donor-specific hyporesponders than in nonhyporesponders, suggesting that the recruitment of Tregs in the allograft plays an important role for renal acceptance. In conclusion, reaching donor-specific hyporesponsiveness is feasible after renal transplantation and associated with Treg recruitment in the graft.


Human vasculature-on-a-chip with macrophage-mediated endothelial activation: The biological effect of aerosol from heated tobacco products on monocyte adhesion.
Heated tobacco products (HTPs) are expected to have the potential to reduce risks of smoking-associated cardiovascular disease (CVD). However, mechanism-based investigations of the effect of HTPs on atherosclerosis remain insufficient and further studies under human-relevant situations are desired for deeper understanding of the reduced risk potential of HTPs. In this study, we first developed an in vitro model of monocyte adhesion by considering macrophage-derived proinflammatory cytokine-mediated endothelial activation using an organ-on-a-chip (OoC), which provided great opportunities to mimic major aspects of human physiology. Then biological activities of aerosol from three different types of HTPs in terms of monocyte adhesion were compared with that of cigarette smoke (CS). Our model showed that the effective concentration ranges of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were close to the actual condition in CVD pathogenesis. The model also showed that monocyte adhesion was less induced by each HTP aerosol than CS, which may be caused by less proinflammatory cytokine secretion. In summary, our vasculature-on-a-chip model assessed the difference in biological effects between cigarettes and HTPs, and suggested a reduced risk potential of HTPs for atherosclerosis.


Kawasaki disease in Hong Kong, 1994 to 2000.
To describe the epidemiology, clinical characteristics, and management of Kawasaki disease in children in Hong Kong. Retrospective survey of medical records from July 1994 to June 1997, and prospective data collection from July 1997 to June 2000. Hospitals with a paediatric unit in Hong Kong. Patients diagnosed with Kawasaki disease between July 1994 and June 2000 in public hospitals in Hong Kong. Incidence of Kawasaki disease and coronary artery aneurysm rates. A total of 696 cases of Kawasaki disease were reported. There were 435 (62.5%) boys and 261 (37.5%) girls giving a male to female ratio of 1.7:1. The age ranged from 1 month to 15 years 5 months with a median of 1.7 years. Infants (<1 year) constituted the largest group of patients (223, 32.0%) and overall, 638 (91.7%) were younger than 5 years. Skin rash, conjunctivitis, and oral signs were among the principal clinical features present in over 80% of cases. Prominent cervical lymph nodes larger than 1.5 cm were less commonly found (24%). Coronary artery aneurysms or ectasia were present in 15.7% (109/696), 8.5% (59/696), and 5.0% (35/696) of patients at 2, 4, and 8 weeks, respectively. The incidence of Kawasaki disease per 100,000 children under 5 years was significantly higher in the prospective study period than in the retrospective period (39 vs 26, P<0.001). The incidence of Kawasaki disease is high in Hong Kong and is 39 per 100,000 children below 5 years of age. The coronary artery aneurysm prevalence is 5%. Intravenous gamma-globulin and high-dose aspirin is the mainstay of treatment.


Viral diarrhea.
Viral diarrhea is a frequent, self-limited illness that may occur sporadically or in epidemic fashion. Nosocomial outbreaks have been reported. Rotavirus and Norwalk virus are the two most important agents causing this disease. Clinical illness is usually mild but may be quite severe in selected infants or elderly or debilitated persons. Specific diagnosis has been advanced by the use of immunoassays. Treatment is supportive, and most patients recover completely. Good hygienic measures are effective in preventing the transmission of the infection. Rotavirus vaccine trials are under way.


Influence of the vagus nerve upon the reflex control of the lower oesophageal sphincter.
In 24 control patients the lower oesophageal sphincter responded to graded increments in intra-abdominal pressure by a significant and sustained rise in tone. This response was abolished by atropine and was also absent in nine of 11 patients who had previously undergone truncal vagotomy for duodenal ulcer but not in the remaining two who had recurrent ulceration. In six patients studied after proximal gastric vagotomy a variable response was seen. Gastric efferent vagal function was assessed by a combined insulin/pentagastrin gastric secretory test and did not correlate closely with the lower oesophageal sphincteric response to increased intra-gastric pressure. These findings are explicable if it is assumed that truncal vagotomy interrupts the afferent limb of a reflex arc regulating lower oesophageal sphincteric tone.