Distinct roles of intracellular heat shock protein 70 in maintaining gastrointestinal homeostasis.
The inducible heat shock protein 70 (Hsp70) is both cytoprotective and immunomodulatory, potentially accounting for its critical role in maintaining gastrointestinal homeostasis. When levels are reduced in conditions like inflammatory bowel diseases (IBD), loss of function contributes to the severity and chronicity of these diseases, although through which cell types and mechanisms remains unclear. Here, the role of Hsp70-mediated intestinal epithelial protection and immune regulation in experimental colitis was examined by using a villin promoter-driven Hsp70 transgene in the 2,4,6-trinitrobenzene sulfonic acid (TNBS) and dextran sodium sulfate (DSS) models and in IL-10/Hsp70 double knockout (IL10-/-/Hsp70-/-) mice. In addition, Hsp70-mediated IL-10 production and immune protection were investigated using a CD45RBhigh transfer model and measuring colonic and immune cell cytokine expression during colitis. We found that the epithelial-specific expression of Hsp70 transgene attenuated DSS-induced colitis in Hsp70-/- mice by protecting tight junctions (TJ) and their interaction with the TJ-associated protein ZO-1. In the TNBS colitis and CD45RBhigh model, Hsp70 carried out its intracellular anti-inflammatory function by maintaining IL-10 production. Impaired ERK phosphorylation, but not p38 or JNK phosphorylation pathways, was associated with decreased IL-10 production in Hsp70-deficient cells. Together, these actions can be leveraged in the context of cellular specificity to develop complementary strategies that can lead to reduction in mucosal injury and immune activation in colonic colitis development. NEW & NOTEWORTHY Using four different experimental colitis models, we filled an important gap in knowledge by defining essential roles of intracellular heat shock protein 70 in different cell types in maintaining intestinal integrity and immune regulation. These findings are relevant to human inflammatory bowel diseases and represent potential avenues for developing therapeutic strategies, not only to counter the destructive processes of inflammation but also to promote tissue healing and prevent complications frequently associated with chronic intestinal inflammation.


[Current surgical approach in the treatment of pancreatic pseudocysts].
The paper evaluates the role of surgery in the treatment of pancreatic pseudocysts in the light of current knowledge. The authors underline the important part played by ultrasonography and CT in monitoring the evolution of pseudocysts: ETG on account of its high levels of sensitivity and specificity and CT due to its diagnostic accuracy which is equivalent to almost 100%; these methods allow the surgeon to decide if and when to operate. A series of operations were carried out by the authors' division in 15 patients suffering from pancreatic pseudocysts. Emphasis is placed on the high percentage of emergency operations, 40%, due to complicated pseudocysts. External drainage was always used in emergency surgery, whereas in elective surgery it was preferred to use cystojejunostomy with a Roux-en-Y loop, followed by cystogastrostomy; cystoduodenostomy was only chosen in one case. The operative mortality rate was 20%. In elective surgery the operation which currently gives the best results is cystojejunostomy with a Roux-en-Y loop, but cystogastrostomy should not be overlooked due to the ease with which it is performed. A recent acquisition is the use of needle aspiration and CT- or ETG-guided percutaneous drainage in the treatment of post-necrotic pseudocysts, therefore after 4-8 weeks' maturity, both in a rapid-growth from and in the event of suppuration. Pancreatic resection is indicated for multiple atypical pseudocysts caused by retention, and this also serves to treat the underlying pancreopathy. Duodenocephalopancreatectomy is now considered to be excessive by the majority of authors. In emergency surgery, drainage of the pseudocysts is the method of choice using either a surgical or percutaneous method.


Purification, cloning, and properties of the tRNA psi 55 synthase from Escherichia coli.
tRNA pseudouridine 55 (psi 55) synthase, the enzyme that is specific for the conversion of U55 to psi 55 in the m5U psi CG loop in most tRNAs, has been purified from Escherichia coli and cloned. On SDS gels, a single polypeptide chain with a mass of 39.7 kDa was found. The gene is a previously described open reading frame, p35, located at 68.86 min on the E. coli chromosome between the infB and rpsO genes. The proposed name for this gene is truB. There is very little protein sequence homology between the truB gene product and the hisT (truA) product, which forms psi in the anticodon arm of tRNAs. However, there was high homology with a fragment of a Bacillus subtilis gene that may produce the analogous enzyme in that species. The cloned gene was fused to a 5'-leader coding for a (His)6 tract, and the protein was overexpressed > 400-fold in E. coli. The recombinant protein was purified to homogeneity in one step from a crude cell extract by affinity chromatography using a Ni(2+)-containing matrix. The SDS mass of the recombinant protein was 41.5 kDa, whereas that calculated from the gene was 37.3. The recombinant protein was specific for U55 in tRNA transcripts and reacted neither at other sites for psi in such transcripts nor with transcripts of 16S or 23S ribosomal RNA or subfragments. The enzyme did not require either a renatured RNA structure or Mg2+, and prior formation of m5U was not required. Stoichiometric formation of psi occurred with no requirement for an external source of energy, indicating that psi synthesis is thermodynamically favored.


Relationship between oxidative stress parameters and cystatin C levels in patients with severe preeclampsia.
Oxidative stress is believed to play a role in the development of preeclampsia (PE). It is known that an increased cystatin C level is also associated with PE. The aim of this study was to investigate the relationship between oxidative stress parameters and cystatin C levels in patients with severe PE. Forty-four patients with severe PE and 40 healthy pregnant women were recruited for the study. All study subjects were divided into 2 groups: group 1 (n=44) consisted of patients with severe PE, and group 2 (n=40) included healthy pregnant subjects. Blood samples were obtained from all subjects in order to measure the cystatin C level, total antioxidant status, and total oxidant status. The oxidative stress index was calculated. The group 1 had significantly higher cystatin C, total oxidant status, oxidative stress index levels and lower total antioxidant status level as compared with the group 2 (P=0.001, P<0.001, P<0.001, P=0.036, respectively). The serum cystatin C level was significantly correlated with the oxidative stress index (r=0.609, P<0.001). The present study demonstrated that both oxidative stress and cystatin C levels were increased in patients with PE, and the increased cystatin C levels seem to be a consequence of oxidative stress.


Alternative delivery systems for agents to treat acute agitation: progress to date.
Psychomotor agitation is often associated with aggression. It is important to identify agitation early and achieve results quickly in order to prevent aggressive behavior. Strategies may include verbal de-escalation techniques, reduced stimulation, medications, or a combination of approaches. Historically, pharmacological treatments for agitation have been delivered using oral and intramuscular formulations. Although the types of medication available have not changed dramatically, different formulations have been developed recently to aid in treating this difficult condition. This paper will detail some of the newer, more novel formulations used to deliver medications to treat agitation. Formulations to be described include orally disintegrating tablets, sublingual, buccal and intranasal forms, as well as an inhalation form. Each form has a unique purpose and will aid in treatment of different populations at different levels of agitation. Of note, of the medication formulations to be discussed, only inhaled loxapine is FDA approved for acute agitation in schizophrenia and bipolar disorder and no medications are approved for 'agitation' outside of a specific disease state. The orally disintegrating tablets of olanzapine, risperidone, and aripiprazole are swallowed and enter the circulation via the portal system. They do not have a more rapid onset of action than the standard oral tablets but are useful for patients that might otherwise divert the medication. The sublingual, buccal and intranasal formulations include asenapine and midazolam. Absorption by this route is more rapid and avoids first-pass metabolism. Finally, inhaled loxapine enters the alveoli and appears quickly in the arterial circulation. All of these novel formulations require at least some cooperation but have the potential to prevent escalation and improve the experience of patients and could be considered when negotiation is possible.


Hepatitis C infection, time in renal-replacement therapy, and outcome after kidney transplantation.
Hepatitis C virus (HCV) infection is common in kidney transplantation and is known to affect long-term patient and graft survival, as is time in renal-replacement therapy (RRT). The aim of this study was to investigate HCV in relation to time in RRT and its impact on outcome after transplantation. A follow-up cohort study using Kaplan-Meier analysis and Cox proportional hazards model was performed in 545 kidney and 26 kidney-pancreas transplant recipients receiving transplants between 1989 and 1997, with last follow-up on December 31, 2002. HCV status at transplantation and time in RRT were analyzed. Time in RRT was significantly longer (P<0.0001), and previous transplantations were more common (P=0.04) in the HCV-positive group. HCV significantly reduced patient (P=0.0012) and graft survival (P=0.0003) after transplantation. Adjustment for age, sex, diabetes, previous transplantations, type of transplant, and time in RRT resulted in a relative risk (RR) for death of 2.23, 1.92, and 1.07 for HCV, diabetes, and age, respectively. The RR for graft loss was 1.96 and 1.03 for HCV and age. Sex, previous transplants, and time in RRT did not affect HCV as an independent risk factor for patient or graft survival. The leading cause of death was cardiovascular disease in both groups. HCV was, in our series, more important than time in RRT for patient death and graft loss posttransplant. Successful pretransplant antiviral therapy could be more beneficial for HCV-infected patients rather than early transplantation for long-term outcome, but this needs to be studied prospectively.


Bidirectional linear inertial impact piezoelectric motor with multimodal resonance.
A new multimodal bidirectional linear inertial impact motor with bidirectional motion based on self-clamping control driven by a single-harmonic signal was designed and manufactured. By applying driving signals of different resonant frequencies to the piezoelectric plate of a piezoelectric motor combined with the unique structural design of the motor, the piezoelectric motor has multiple modes and has the ability of two-way movement. First, the overall structure of the motor is introduced, and its working principle and theoretical displacement characteristics are presented through the periodic motion diagram of the piezoelectric motor. Second, the simulation analysis is carried out to determine the working modal of the proposed motor with COMSOL5.2. Finally, a motor prototype is developed, and the accuracy of the working principle and the simulation analysis is verified through experimental tests. When the motor has no load, the driving voltage is 200 Vp-p. The maximum speed when moving to the right reached 3.125 mm/s when the preload is 2 N, and the driving frequency is 96 Hz. The maximum speed when moving to the left reached 4.301 mm/s when the preload is 4 N, and the driving frequency is 148 Hz. In the load capacity test of the motor prototype, the maximum load of the piezoelectric motor prototype moving to the right and left can reach 0.4 and 0.6 N, respectively. Compared with similar inertial impact motors, the proposed motor achieves flexible control of driving and switching of two-way movement conveniently and has a certain driving ability.


Randomized, Double Blind, Placebo Controlled, Clinical Trial to Study Ashwagandha Administration in Participants Vaccinated Against COVID-19 on Safety, Immunogenicity, and Protection With COVID-19 Vaccine-A Study Protocol.
Vaccines have emerged as the most effective tool in the fight against COVID-19. Governments all over the world have rolled out the COVID-19 vaccine program for their populations. Oxford-AstraZeneca COVID-19 vaccine (COVISHIELD™) is widely used in India. A large number of Indian people have been consuming various traditional medicines in the hope of better protection against COVID-19 infection. Several studies have reported immunological benefits of Withania somnifera (Ashwagandha) and its potential as a vaccine adjuvant. We propose to study the safety, immunogenicity and clinical protection offered by a 6-month regimen of Ashwagandha in participants who volunteer to be vaccinated against COVID-19 (COVISHIELDTM) in the ongoing national program of vaccination. We designed a prospective, randomized, double-blind, parallel-group, placebo-controlled, two-arm, exploratory study on healthy volunteers receiving the COVISHIELDTM vaccine. The administration of Ashwagandha will begin within 7 days of the first or second dose of COVISHIELDTM. Primary outcome measure is immunogenicity as measured by SARS-CoV-2 spike (S1) and RBD-specific IgG antibody titres. Secondary outcome measures are safety, protective immune response and quality of life measures. All adverse events will be monitored at each time throughout the study. Participants will be tracked on a daily basis with a user-friendly mobile phone application. Following power calculation 600 participants will be recruited per arm to demonstrate superiority by a margin of 7% with 80% power. Study duration is 28 weeks with interim analysis at the end of 12 weeks. Ethics approval was obtained through the Central and Institutional Ethics Committees. Participant recruitment commenced in December 2021. Results will be presented in conferences and published in preprints followed by peer-reviewed medical journals. [www.ClinicalTrials.gov], identifier [CTRI/2021/06/034496].


Adenoid Cystic Carcinoma With Sialolithiasis of the Left Submandibular Gland: A Case Report and Literature Review.
Adenoid cystic carcinoma is one of the most common salivary gland malignancies with poor long-term prognosis, but the coexistence of sialoliths is extraordinarily rare. In this article, we report a case of 30-year-old woman with a history of submandibular area swelling with intermittent pain increasing during mealtimes that had led her attending physician to diagnose a sialolith in the left submandibular gland on a radiograph 10 years before. However, the surgical specimen proved to be an adenoid cystic carcinoma accompanied with a sialolith. Histopathologically, the submandibular gland was displaced with a fibrous granulation tissue containing a small cribriform carcinoma invading the extracapsular region of the gland. We performed fluorescence in situ hybridization examination with an MYB-NFIB fusion probe of the lesion, with positive results. The patient underwent a supraomohyoid neck dissection as additional procedure because of the possibility of the extracapsular cancer nest remaining around the submandibular gland, but she remains well and disease free 11 years after the first operation.


Behavioral development and sociodemographics of infants and young children at higher and lower risk for autism spectrum disorders.
Identification of early signs of Autism Spectrum Disorder (ASD) could lead to earlier diagnosis and intervention. This cross-sectional study used the Parent Observation of Early Markers Scale (POEMS, Feldman et al. in J Autism Dev Disord 42:13-12, 2012) to identify early signs of ASD in 69 ASD high-risk (older sibling diagnosed with ASD) and 69 sex and aged-matched ASD low-risk second-born or later infants (no family history of ASD) between 6 and 36 months of age. Family sociodemographic comparisons were also made between the risk groups. The high-risk children had significantly more elevated POEMS items than the low-risk children at 12, 18, 24, 30 and 36 months of age, even when the children subsequently diagnosed with ASD were removed from the analyses. Families of the high-risk group had older parents, lower family income and fewer mothers working out of the home than the low-risk group. These sociodemographic variables were not significantly correlated with POEMS scores. The results suggest that high-risk infants may show signs of the broader ASD phenotype as early as 12 months of age that may be unrelated to observed sociodemographic family differences.


The importance of mangrove forest in tsunami disaster mitigation.
Tsunamis and storm surges have killed more than one million people and some three billion people currently live with a high risk of these disasters, which are becoming more frequent and devastating worldwide. Effective mitigation of such disasters is possible via healthy coastal forests, which can reduce the energy of tsunamis. In recent years, these natural barriers have declined due to adverse human and natural activities. In the past 20 years, the world has lost almost 50 per cent of its mangrove forests, making them one of the most endangered landscapes. It is essential to recover them and to use them as a shield against a tsunami and as a resource to secure optimal socio-economic, ecological and environmental benefits. This paper examines the emerging scenario facing mangrove forests, discusses protection from tsunamis, and proposes a way to improve the current situation. We hope that practical tips will help communities and agencies to work collectively to achieve a common goal.


Port-access thoracoscopic anatomical right anterior segmentectomy.
Thoracoscopic lung segmentectomy is a complicated and thus controversial procedure. The term "segment" comprises several genres. Each segment or subsegment is defined anatomically as the lung area for ventilation of the bronchial branches. Human lungs consist of 18 segments as well as block segments such as lingular or basal segments. Therefore, thoracoscopic lung segmentectomy includes various types of procedures. We developed pulmonary segmentectomy method under three-dimensional multidetector computed tomography simulation and so far performed 248 port access thoracoscopic anatomic lung segmentectomies. Also we developed a slip-knot technique for creating the inflation-deflation line to delineate the intersegmental plane and used this method as standard since 2010. The intersegmental plane was identified using the intersegmental veins as landmarks and the demarcation between the resected (inflated) and preserved (collapsed) lungs. The success rate of segmentectomy performed under complete thoracoscopy was 99%. Minithoracotomy was required for two patients because of arterial bleeding. The chest tubes were left in place for 1-8 d (median duration, 1 d). There were no recurrences of the primary tumor in the curative-intent resection group patients for lung cancer treatment. Thoracoscopic lung segmentectomy achieved by multidetector computed tomography for use in respective anatomical interpretation enabled precise parenchymal dissection. Our slip-knot technique facilitated the creation of inflation-deflation line under thoracoscopic surgery and shortened the surgical time consequently. Herein, we present the representative case of an 84-year-old man who underwent port-access anatomical resection of the anterior segment of right upper lobe (S3). In this patient, we used a vessel sealing system for cutting the vessels and dissecting the parenchyma.


Modeling performance of sample collection sites using whole exome sequencing metrics.
Although next-generation sequencing assays are routinely carried out using samples from cancer trials, the sequencing data are not always of the required quality. There is a need to evaluate the performance of tissue collection sites and provide feedback about the quality of next-generation sequencing data. This study used a modeling approach based on whole exome sequencing quality control (QC) metrics to evaluate the relative performance of sites participating in the Bristol Myers Squibb Immuno-Oncology clinical trials sample collection. We identified several events for the sample swap. Overall, most sites performed well and few showed poor performance. These findings can increase awareness of sample failure and improve the quality of samples.


Pharmacokinetics, stability, and blood partition of DA-8159, a new phosphodiesterase V inhibitor.
The pharmacokinetics of DA-8159, a new phosphodiesterase V inhibitor, after 1 min intravenous, 30 mg/kg, and oral, 30 mg/kg, administration of the drug to rats, the stability of DA-8159 in various pH solutions ranging from 1 to 13, and human and rat plasma and urine, and the blood partition of DA-8159 between plasma and blood cells of rabbit were evaluated. After intravenous administration, DA-8159 was eliminated fast with the mean total body clearance of 126 ml/min/kg, and was almost completely metabolized in rats; 5.98% of intravenous dose of DA-8159 were excreted unchanged in 24-hr urine. The extent of absolute oral bioavailibility of DA-8159 was approximately 25%. The apparent volume of distribution at steady state was considerably large, 15048 ml/kg, suggesting that DA-8159 has a good affinity to rat tissues. DA-8159 was relatively stable in various pH solutions, and human and rat plasma and urine for up to 48 h incubation in a water-bath shaker kept at 37 degrees C and at a rate of 50 oscillations per min. DA-8159 reached equilibrium fast (within 30 sec mixing manually) between plasma and blood cells of rabbit blood and the plasma-to-blood cell concentration ratios were independent of initial blood concentrations of DA-8159, 1, 5, and 10 microg/ml, when the rabbit whole blood was incubated for up to 120 min; the ratios were in the range of 0.662-0.812. There was no in vitro 'blood storage effect' in the plasma concentration of DA-8159.


Pressure adaptation is linked to thermal adaptation in salt-saturated marine habitats.
The present study provides a deeper view of protein functionality as a function of temperature, salt and pressure in deep-sea habitats. A set of eight different enzymes from five distinct deep-sea (3040-4908 m depth), moderately warm (14.0-16.5°C) biotopes, characterized by a wide range of salinities (39-348 practical salinity units), were investigated for this purpose. An enzyme from a 'superficial' marine hydrothermal habitat (65°C) was isolated and characterized for comparative purposes. We report here the first experimental evidence suggesting that in salt-saturated deep-sea habitats, the adaptation to high pressure is linked to high thermal resistance (P value = 0.0036). Salinity might therefore increase the temperature window for enzyme activity, and possibly microbial growth, in deep-sea habitats. As an example, Lake Medee, the largest hypersaline deep-sea anoxic lake of the Eastern Mediterranean Sea, where the water temperature is never higher than 16°C, was shown to contain halopiezophilic-like enzymes that are most active at 70°C and with denaturing temperatures of 71.4°C. The determination of the crystal structures of five proteins revealed unknown molecular mechanisms involved in protein adaptation to poly-extremes as well as distinct active site architectures and substrate preferences relative to other structurally characterized enzymes.


Toxic effect of scopolamine eye drops in children.
Five children, admitted with acute psychotic reactions after use of Scopolamine eye drops 0.2%, are presented. The predominant symptoms were visual hallucinations, strange behaviour, and restlessness. In one case peripheral symptoms were observed. Recovery was complete in 24 h. Prescription of Scopolamine eye drops should be followed by information of possible adverse effects. Cyclopentolate might be used instead.


Digital Technology Use and BMI: Evidence From a Cross-sectional Analysis of an Adolescent Cohort Study.
The use of digital technology such as mobile phones is ubiquitous in adolescents. However, excessive use may have adverse health effects, possibly partially mediated by disruptions to sleep. This study aims to assess the social predictors of digital technology use and their cross-sectional association with BMI z scores and being overweight in a large sample of adolescents. We used baseline data from a subset of a large adolescent cohort from 39 schools across Greater London who participated in the Study of Cognition, Adolescents and Mobile Phones (n=1473). Digital technology use included phone calls, internet use on mobile phones, and video gaming on any device. Multilevel regression was used to assess the associations between digital technology use and age-specific and sex-specific BMI z scores and being overweight (including obesity). Measurements were derived from height and weight, obtained by the Tanita BC-418 Body Composition Analyzer. We examined whether these associations were mediated by insufficient sleep. Generally, participants with lower socioeconomic status reported more use of digital technology. Controlling for socioeconomic status, internet use on mobile phones for more than 3 hours per day was associated with higher BMI z scores (adjusted β=.30, 95% CI 0.11-0.48) and greater odds of being overweight (adjusted odds ratio 1.60, 95% CI 1.09-2.34), compared with low use (≤30 minutes). Similar associations were found between video gaming and BMI z scores and being overweight. The BMI z score was more strongly related to weekday digital technology use (internet use on mobile phones and video gaming) than weekend use. Insufficient sleep partly mediated the associations between digital technology use and BMI z scores (proportion of mediation from 8.6% to 17.8%) by an indirect effect. We found an association between digital technology use and BMI in adolescents, partly mediated by insufficient sleep, suggesting that the underlying mechanisms may be multifactorial. Further research with longitudinal data is essential to explore the direction of the relationships.


[Effectiveness of mesoglycan topical treatment of leg ulcers in subjects with chronic venous insufficiency].
Aim of the present comparative clinical study was to demonstrate the efficacy of the topical application of mesoglycan, a profibrinolytic agent, for healing of leg ulcers in patients with chronic venous insufficiency. Forty patients, observed in our outpatients department, with venous leg ulcers have been randomized in two groups of twenty subjects, each treated with topical application of mesoglycan (1 or 2 vials/day) or vegetal stimulins and followed for two months, with controls after 15, 30 and 60 days. At the end of the observation period, ulcer healing rate was 95% in the mesoglycan group, while a lower healing rate was obtained in the stimulins group (80%). The present study confirms previous clinical experiences with mesoglycan and suggests its application in the topical treatment of venous ulcers.


Effects of long-term, low-fat diet on plasma apo E in familial LCAT deficiency.
To study the metabolic abnormalities in familial lecithin-cholesterol acyltransferase (LCAT) deficiency, the effects of a long-term, low-fat diet and LCAT replacement therapy on plasma lipids and apolipoproteins were investigated in a patient with LCAT deficiency. The patient had elevated triglycerides (TG, 543.7 mg/dl) and phospholipids (PL, 350.3 mg/dl) and normal total cholesterol (TC, 206.9 mg/dl). Change to a low-fat diet reduced TC and TG by 20% and 75%, respectively. These reductions occurred mainly in the d < 1.006 fraction. At baseline, the patient had normal apolipoprotein B (apo B), low apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II) and elevated apolipoprotein E (apo E). Long-term treatment with a low-fat diet increased plasma apoA-I and decreased apo E. However, urinary protein excretion did not change throughout the observed period. LCAT replacement with fresh frozen plasma (FFP) after the low-fat diet further reduced plasma apo E to the normal range. These results indicate that the elevated plasma apo E in LCAT deficiency was related not only to the lack of LCAT in the plasma, but also to fat intake. A low-fat diet may be effective in correcting lipid abnormalities. Moreover, plasma apo E may be a good indicator of the efficacy of diet therapy.


Cooperative regulation of cytoplasmic streaming and ca fluxes by pfr and photosynthesis in vallisneria mesophyll cells.
In mesophyll cells of Vallisneria gigantea Graebner, Ca(2+) regulates the induction and cessation of cytoplasmic streaming. Streaming is induced when the level of calcium in the cytoplasm is lowered through light-accelerated release of Ca(2+) from the cells (S Takagi, R Nagai [1988] Plant Physiol 88: 228-232). We have now initiated an investigation on the nature of the photoreceptor(s) that are involved in the regulation of Ca(2+) movements across the cell membrane and of streaming. Streaming is induced only when phytochrome exists in the phytochrome-far redabsorbing form (Pfr)-and photosynthesis is allowed to take place for at least 4 minutes. The former effect is typically photoreversible by red and far-red light, and phytochrome is spectro-photometrically detectable in the crude extract from the leaves. The latter effect is assessed in terms of the wavelength dependency and the effects of diuron and atrazine, two inhibitors of photosynthesis. A similar requirement for Pfr and photosynthesis is found to be associated with the acceleration of Ca(2+) efflux in the protoplasts. The results suggest that phytochrome and photosynthetic pigment(s) cooperatively regulate cytoplasmic streaming via modulation of the Ca(2+) transport in the cell membrane.


Toward integration of in vivo molecular computing devices: successes and challenges.
The computing power unleashed by biomolecule based massively parallel computational units has been the focus of many interdisciplinary studies that couple state of the art ideas from mathematical logic, theoretical computer science, bioengineering, and nanotechnology to fulfill some computational task. The output can influence, for instance, release of a drug at a specific target, gene expression, cell population, or be a purely mathematical entity. Analysis of the results of several studies has led to the emergence of a general set of rules concerning the implementation and optimization of in vivo computational units. Taking two recent studies on in vivo computing as examples, we discuss the impact of mathematical modeling and simulation in the field of synthetic biology and on in vivo computing. The impact of the emergence of gene regulatory networks and the potential of proteins acting as "circuit wires" on the problem of interconnecting molecular computing device subunits is also highlighted.


Cutaneous Leukocytoclastic Vasculitis Induction Following ChAdOx1 nCoV-19 Vaccine.
The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented event, and in order to control its spread and minimize its damages, all efforts are immediately mobilized. Mass vaccination is considered a promising solution to combat this universal issue. However, given the urgent need for vaccine production, some of the side effects may not have been presented during trials and will only appear during the mass vaccination. Limited vasculitis cases have been reported so far following vaccination against COVID-19. We present a case of cutaneous leukocytoclastic vasculitis (LCV) induced following the first dose of the ChAdOx1 nCoV-19 vaccine in an otherwise healthy individual.


Long-term effects of parental divorce timing on depression: A population-based longitudinal study.
We examined the long-term effects of parental divorce timing on depression using longitudinal data from the Korean Welfare Panel Study. Depression symptoms were measured using the 11 items of Center for Epidemiologic Scale for Depression (CES-D-11), and we categorized parental divorce timing into 'early childhood', 'adolescent' and 'none'. Although participants who experienced parental divorce during adolescence exhibited a significantly higher CES-D-11 score ( p = .0468), 'early childhood' participants displayed the most increased CES-D-11 score compared to the control group ( p = .0007). Conversely, among participants who were unsatisfied with their marriage, those who experienced parental divorce in early childhood showed lower CES-D-11 scores, while 'adolescent period' participants exhibited significantly higher CES-D-11 scores ( p = .0131). We concluded that timing of parental divorce exerts substantial yet varied effects on long-term depression symptoms and future marriage satisfaction.


What Is Not Yet: cultivating the imagination.
In this column, the author describes imaginative capacities that encourage imaginative thinking and creating anew. Concepts from the nursing theory of humanbecoming are presented to further explore the applicability of focusing on cultivating the imagination in nursing curricula. A nursing seminar is proposed, entitled What Is Not Yet, that could foster the creative potential of nurse leaders.


Action of vibration on the response of cat muscle spindle Ia afferents to low frequency sinusoidal stretching.
1. A study has been made of the effect of continuous vibration, at 150 Hz, upon the response of muscle spindle afferents to low frequency sinusoidal stretching (1 and 8 Hz). Using the soleus muscle of the anaesthetized cat, with severed ventral roots, recordings were made of single Ia afferents and of the massed Ia afferent discharges in the main bulk of the cut L7 dorsal root. 2. When the amplitude of vibration was large (50 micrometers, short pulses) and that of the sinusoidal stretching was not too great (50-100 micrometers, peak-to-peak) the discharge of the afferents was largely locked 1:1 to the vibration and the response to the sinusoidal stretching was abolished. 3. When the amplitude of the vibration was reduced to below that eliciting continuous afferent driving, then the response to sinusoidal stretching of any amplitude was often markedly increased. This arose through the vibration having a much more powerful excitatory action during the rising phase of the sinusoidal stretch than it did during the falling phase. 4. Averaged over a full cycle, the phase of the response to the sinusoidal stretching tended to be delayed during the vibration in comparison with the normal. This was largely dependent upon the afferents continuing to respond maximally to the vibration around the peak of the sinusoidal stretch, at which stage their unvibrated response is declining, rather than to a phase lag of the whole pattern of response. 5. The results are discussed in relation to the effects of vibration on tremor and the human stretch reflex, and on the determination of the frequency-response of spindle afferents.


Photo-catalytic oxidation of a di-nuclear manganese centre in an engineered bacterioferritin 'reaction centre'.
Photosynthesis involves the conversion of light into chemical energy through a series of electron transfer reactions within membrane-bound pigment/protein complexes. The Photosystem II (PSII) complex in plants, algae and cyanobacteria catalyse the oxidation of water to molecular O2. The complexity of PSII has thus far limited attempts to chemically replicate its function. Here we introduce a reverse engineering approach to build a simple, light-driven photo-catalyst based on the organization and function of the donor side of the PSII reaction centre. We have used bacterioferritin (BFR) (cytochrome b1) from Escherichia coli as the protein scaffold since it has several, inherently useful design features for engineering light-driven electron transport. Among these are: (i.) a di-iron binding site; (ii.) a potentially redox-active tyrosine residue; and (iii.) the ability to dimerise and form an inter-protein heme binding pocket within electron tunnelling distance of the di-iron binding site. Upon replacing the heme with the photoactive zinc-chlorin e6 (ZnCe6) molecule and the di-iron binding site with two manganese ions, we show that the two Mn ions bind as a weakly coupled di-nuclear Mn2II,II centre, and that ZnCe6 binds in stoichiometric amounts of 1:2 with respect to the dimeric form of BFR. Upon illumination the bound ZnCe6 initiates electron transfer, followed by oxidation of the di-nuclear Mn centre possibly via one of the inherent tyrosine residues in the vicinity of the Mn cluster. The light dependent loss of the MnII EPR signals and the formation of low field parallel mode Mn EPR signals are attributed to the formation of MnIII species. The formation of the MnIII is concomitant with consumption of oxygen. Our model is the first artificial reaction centre developed for the photo-catalytic oxidation of a di-metal site within a protein matrix which potentially mimics water oxidation centre (WOC) photo-assembly.


Chemoselective samarium-mediated benzoyloxysulfone eliminations.
An investigation of the substrate dependence on the rate of samarium-mediated reductive elimination of β-acyloxysulfones has provided insights into the mechanism of this transformation and allowed for the development of a chemoselective elimination process.


Effects of diet and exercise on the density and composition of the fat-free mass in obese women.
The purpose of this study was to determine whether the density (D(FFM)) and composition of the fat-free mass (FFM) and the accuracy of estimates of body composition from body density (%Fat(d)) are affected by diet and exercise. Twenty-nine obese women (body mass index (BMI) = 25.0-43.7 kg x m(-2) and %Fat(d) = 35.7-47.1%) were assigned to one of three groups: diet only (DO, N = 9); diet and aerobic exercise (DE, N = 9); or control (C, N = 11). Measures of body density by hydrostatic weighing, body water by deuterium dilution, and bone mineral by whole-body dual-energy x-ray absorptiometry, and estimates of body composition from body density and from a four-component model were obtained before and after a 16-wk diet and exercise intervention. Mean (+/- SD) changes in body mass were -7.2 +/- 7.4, -3.9 +/- 3.3, and +1.2 +/- 2.8 kg for the DO, DE, and C, respectively. The density and composition of the FFM did not change significantly (P > 0.05) in any of the groups. Individual changes in D(FFM) (-0.011 to +0.011 g x mL(-1)), and differences between changes in %Fat estimated using a four-component model and %Fat(d) (-2.1 to +2.7% body mass) were not related to changes in body mass (r = -0.08). Individual changes in D(FFM) were most strongly related to changes in water fraction (r = -0.95) and protein fraction (r = +0.88), and were unrelated to changes in the mineral fraction (r = +0.04) of the FFM. We conclude that in obese women, the density and composition of the FFM are unaltered and densitometry correctly assesses group mean changes in body composition with moderate weight loss induced by diet or diet and aerobic exercise. However, individual deviations in D(FFM) from the assumed value of 1.1 g x mL(-1) are substantial, and a multi-component model in which body water is measured is needed to accurately assess individual body composition changes resulting from diet and exercise.


[Prenatal genetic analysis of two fetuses with Miller-Dieker syndrome].
To perform molecular cytogenetic study on two fetuses with abnormal ultrasound findings and analyze their genotype-phenotype correlation. G-banded karyotyping, single nucleotide polymorphism array (SNP array) and fluorescence in situ hybridization (FISH) were performed on amniotic fluid cells from both fetuses and peripheral blood samples from their parents. Results of SNP array were analyzed with bioinformatics software. G-banded karyotyping failed to detect any abnormalities in both fetuses and their parents. SNP array detected a 2.484 Mb terminal deletion at 17p13.3 [arr[hg19] 17p13.3 (83 035-2 567 405)×1] in fetus 1 and a 3.295 Mb terminal deletion at 17p13.3p13.2 [arr[hg19] 17p13.3p13.2 (83 035- 3 377 560)×1] in fetus 2. Both deletions have overlapped with the critical region of Miller-Dieker syndrome (MDS) and involved candidate genes such as PAFAH1B1, YWHAE and CRK. In addition, SNP array and FISH analyses on the parental peripheral blood samples demonstrated that both 17p13.3 and 17p13.3p13.2 deletions were of de novo origin. Metaphase FISH performed on amniotic fluid cells confirmed the presence of 17p13.3 and 17p13.3p13.2 deletions detected by the SNP array, while metaphase FISH performed on the parents excluded any potential chromosome rearrangements. Abnormal ultrasound features for fetuses with MDS mainly include central nervous system anomalies. SNP array can efficiently detect 17p13.3 microdeletions underlying MDS, and accurately map the breakpoints and involved genes, which may facilitate understanding of the genotype and phenotype correlations for MDS.


Intra-articular plica causing ankle impingement in a young handball player: a case report.
Ankle sprains are common injuries that respond well to rehabilitation. In the case of persisting symptoms, the differential diagnosis should include osteochondral defects, tendon injury, mechanical instability, and ankle impingement. In the present case report, we describe a 16-year-old male handball player who presented with persisting pain and locking in the right ankle 3 years after having sustained multiple minor inversion trauma. The clinical examination and conventional radiography showed no abnormalities. On magnetic resonance imaging, a flake fracture at the anteromedial talar dome and/or loose body was assumed. Arthroscopic examination revealed an intra-articular plica originating from an osteochondral fossa at the anteromedial tibial plafond. The plica was debrided. Retrospectively, the arthroscopic findings matched the radiographs and magnetic resonance images. The postoperative protocol consisted of early mobilization. At 6 weeks of follow-up, the patient had no pain and had returned to his sports activities. The present case report illustrates, to the best of our knowledge, the first case of ankle impingement due to a, most likely congenital, intra-articular plica arising from an osteochondral fossa at the anteromedial tibial plafond. This rare clinical condition can be diagnosed with magnetic resonance imaging. Arthroscopic debridement will effectively relieve the symptoms.


Creatine Transporter Deficiency: Screening of Males with Neurodevelopmental Disorders and Neurocognitive Characterization of a Case.
Creatine transporter deficiency (CTD) is an X-linked, neurometabolic disorder associated with intellectual disability that is characterized by brain creatine (Cr) deficiency and caused by mutations in SLC6A8, the Cr transporter 1 protein gene. CTD is identified by elevated urine creatine/creatinine (Cr/Crn) ratio or reduced Cr peak on brain magnetic resonance spectroscopy; the diagnosis is confirmed by decreased Cr uptake in cultured fibroblasts, and/or identification of a mutation in the SLC6A8 gene. Prevalence studies suggest this disorder may be underdiagnosed. We sought to identify cases from a well-characterized cohort of children diagnosed with neurodevelopmental disorders. Urine screening for CTD was performed on a cohort of 46 males with autism spectrum disorder (ASD) and 9 males with a history of non-ASD developmental delay (DD) classified with intellectual disability. We identified 1 patient with CTD in the cohort based on abnormal urine Cr/Crn, and confirmed the diagnosis by the identification of a novel frameshift mutation in the SLC6A8 gene. This patient presented without ASD but with intellectual disability, and was characterized by a nonspecific phenotype of early language delay and DD that persisted into moderate-to-severe intellectual disability, consistent with previous descriptions of CTD. Identification of patients with CTD is possible by measuring urine Cr and Crn levels and the current case adds to the growing literature of neurocognitive deficits associated with the disorder that affect cognition, language and behavior in childhood.


Ubiquitous cancer genes: multipurpose molecules for protein micro-arrays.
Multipurpose genes in the human genome which are over-expressed in a large variety of different cancers have been identified. Forty-two of the 19,016 human genes annotated to date (0.2%) are ubiquitously over-expressed in half or more of the 36 investigated human cancers. Of these genes, 15 are involved in protein biosynthesis and folding, six of them in glycolysis. A group of 13 solid tumours over-express almost all (39-42 of 42) ubiquitous cancer genes, suggesting a common mechanism underlying these cancers. Others, such as endocrine cancers, have only a few over-expressed ubiquitous cancer genes. The proteins for which these genes code or the corresponding antibodies are candidates for small protein microarrays aiming at maximum information with only a limited number of proteins. Since the over-expression pattern varies from cancer to cancer, distinction between different cancer classes is possible using one single set of protein or antibody molecules.


Use of the babinet compensator for anomalous dispersion measurements.
Reorientation of the optical elements in a standard experimental setup that utilizes a Babinet compensator to measure the anomalous dispersion of a birefringent mediumn results in a useful trade-off between the intensity and visibility of the polarization fringes produced by the apparatus. The fringe pattern is analyzed and numerical results are presented that illustrate the nature of the trade-off and its application to measurements near the center of a strong absorption line.


Myocardial Infarction (MI) presenting as acute limb: an extremely rare presentation of MI.
Acute embolic occlusion of the bilateral lower limbs from the left ventricular thrombus is an extremely rare medical condition that is not only limb threatening but also potentially life threatening. Several strategies are available but not even a single treatment modality is clearly the best. Here, we present an interesting case that presented with bilateral lower limb ischemia and was later found to have a big thrombus in the left ventricle as the source of the emboli.


Brain activity during observation of actions. Influence of action content and subject's strategy.
PET was used to map brain regions that are associated with the observation of meaningful and meaningless hand actions. Subjects were scanned under four conditions which consisted of visually presented actions. In each of the four experimental conditions, they were instructed to watch the actions with one of two aims: to be able to recognize or to imitate them later. We found that differences in the meaning of the action, irrespective of the strategy used during observation, lead to different patterns of brain activity and clear left/right asymmetries. Meaningful actions strongly engaged the left hemisphere in frontal and temporal regions while meaningless actions involved mainly the right occipitoparietal pathway. Observing with the intent to recognize activated memory-encoding structures. In contrast, observation with the intent to imitate was associated with activation in the regions involved in the planning and in the generation of actions. Thus, the pattern of brain activation during observation of actions is dependent both on the nature of the required executive processing and the type of the extrinsic properties of the action presented.


FDG-PET for prediction of tumour aggressiveness and response to intra-arterial chemotherapy and radiotherapy in head and neck cancer.
The aim of this study was to evaluate the possible usefulness of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) for predicting tumour aggressiveness and response to intra-arterial chemotherapy (THP-ADM + 5-FU + carboplatin) and radiotherapy in head and neck carcinomas. Twenty patients with squamous cell carcinoma (SCC) of the head and neck were included in the study. All patients completed the treatment regimen, and each patient underwent two FDG-PET studies, one prior to and one at 4 weeks after the chemoradiotherapy. For the quantitative evaluation of regional FDG uptake in the tumour, standardised uptake values (SUVs) with an uptake period of 50 min were used. The pre-treatment SUV (pre-SUV) and post-treatment SUV (post-SUV) were compared with immunohistologically evaluated tumour proliferative potential (MIB-1 and PCNA), tumour cellularity and other parameters including histological grade, tumour size and stage, clinical response and histological evaluation after therapy. All neoplastic lesions showed high SUVs (mean, 9.75 mg/ml) prior to the treatment, which decreased significantly after the therapy (3.41 mg/ml, P<0.01). Pre-SUV did not show any correlation with MIB-1, PCNA, cellularity or other parameters. However, lower post-SUV was significantly correlated with good histological results after therapy (no viable tumour cells, n=16). In comparison with moderately differentiated SCCs, well-differentiated SCCs exhibited significantly lower post-SUV and a larger difference between pre- and post-SUVs. Lesions with a high pre-SUV (>7 mg/ml) showed residual tumour cells after treatment in 4 out of 15 patients, whereas patients whose lesions showed a low pre-SUV (<7 mg/ml, five patients) were successfully treated. Four out of six tumours with a post-SUV higher than 4 mg/ml had viable tumour cells, whereas all tumours (14/14) with a post-SUV lower than 4 mg/ml showed no viable tumour cells. Computational multivariate analysis using multiple regression revealed four factors (MIB-1 labelling index, cellularity, the number of MIB-1 labelled tumour cells and tumour size grade) contributing to pre-SUV and pre-post SUV (difference between pre-treatment SUV and post-treatment SUV in each patient) with statistical significance. FDG uptake in the tumour might reflect tumour aggressiveness, which is closely related to the proliferative activity and cellularity. Pre-treatment FDG-PET is useful in predicting the response to treatment, and post-treatment FDG-PET is of value in predicting residual viable tumours. FDG-PET has a profound impact on the treatment strategy for head and neck carcinomas.


Hydroxylation catalysis by mononuclear and dinuclear iron oxo catalysts: a methane monooxygenase model system versus the Fenton reagent Fe(IV)O(H2O)5(2+).
Hydroxylation of aliphatic C-H bonds is a chemically and biologically important reaction, which is catalyzed by the oxidoiron group FeO(2+) in both mononuclear (heme and nonheme) and dinuclear complexes. We investigate the similarities and dissimilarities of the action of the FeO(2+) group in these two configurations, using the Fenton-type reagent [FeO(2+) in a water solution, FeO(H(2)O)(5)(2+)] and a model system for the methane monooxygenase (MMO) enzyme as representatives. The high-valent iron oxo intermediate MMOH(Q) (compound Q) is regarded as the active species in methane oxidation. We show that the electronic structure of compound Q can be understood as a dimer of two Fe(IV)O(2+) units. This implies that the insights from the past years in the oxidative action of this ubiquitous moiety in oxidation catalysis can be applied immediately to MMOH(Q). Electronically the dinuclear system is not fundamentally different from the mononuclear system. However, there is an important difference of MMOH(Q) from FeO(H(2)O)(5)(2+): the largest contribution to the transition state (TS) barrier in the case of MMOH(Q) is not the activation strain (which is in this case the energy for the C-H bond lengthening to the TS value), but it is the steric hindrance of the incoming CH(4) with the ligands representing glutamate residues. The importance of the steric factor in the dinuclear system suggests that it may be exploited, through variation in the ligand framework, to build a synthetic oxidation catalyst with the desired selectivity for the methane substrate.


In silico identification of small molecule protein-protein interaction inhibitors: targeting hotspot regions at the interface of MXRA8 and CHIKV envelope protein.
Chikungunya virus (CHIKV) is an arthritogenic arbovirus responsible for re-emerging epidemics of Chikungunya fever around the world for centuries. Chikungunya has become endemic in Africa, Southeast Asia, the Indian subcontinent, and subtropical regions of the Americas. The unavailability of antiviral therapy or vaccine against the CHIKV and its continuous re-emergence demands an urgent need to develop potential candidate therapeutics. CHIKV entry into the host cell is mediated by its envelope proteins engaging the cellular receptor MXRA8 to invade the susceptible cells. We report here two essential target binding sites at the CHIKV E1-E2 proteins by identifying hotspot regions at the E1-E2-MXRA8 binding interface. Further, we employed high throughput computational screening to identify potential small molecule protein-protein interaction (PPI) modulators which could effectively bind at the identified target sites. Molecular dynamics simulations and binding free energy calculations confirmed the stability of three compounds, viz., ZINC299817498, ZINC584908978, and LAS52155651, at both the predicted interface binding sites. The polar and charged residues at the interface were responsible for energetically holding the ligands at the binding sites. Altogether, our findings suggest that the predicted target binding sites at the E1-E2 dimer could be essential to block the receptor interaction as well as the fusion process of the CHIKV particles. Thus, we identified a few small molecule PPI inhibitors with great potential to block the E1-E2-MXRA8 interaction and act as promising templates to design anti-CHIKV drugs.Communicated by Ramaswamy H. Sarma.


A surgical case of cerebellar tuberculoma caused by a paradoxical reaction while on therapy for tuberculosis spondylitis.
A paradoxical reaction (PR) is a phenomenon in which the primary tuberculous lesion worsens or another de novo tuberculous lesion appears while on anti-tuberculosis therapy. Here, we report a rare case of cerebellar tuberculoma caused by a PR during therapy for lumbar tuberculous spondylitis (Pott's disease). A 47-year-old male with human immunodeficiency virus seronegative was diagnosed with lumber tuberculous spondylitis (Pott's disease) and prescribed anti-tuberculous agents. His lower back pain and inflammatory condition recovered after initiation of anti-tuberculous therapy. Two months later, he complained of headache, nausea, and staggering. Magnetic resonance images revealed a ring-enhanced lesion located at the cerebellar hemisphere extending to the vermis, which caused perifocal edema and bilateral ventriculomegaly. These findings were consistent with his symptoms of hydrocephalus. He did not have preceding clinical findings of meningitis, and a PR was suggested to cause de novo aggregation of cerebellar tuberculoma. A lesionectomy was performed, and the surgical specimen was pathologically diagnosed as a tuberculoma. He recovered well from neurological disorders after the resection. De novo formation of intracranial tuberculoma alone caused by a PR without preceding meningitis is very rare. Lesionectomy is needed for intracranial tuberculoma, which manifests as a mass effect, as well as antituberculous therapy.


[Cleistogenes squarrosa population at different restorative succession stages in Inner Mongolia of China: a point pattern analysis].
In this paper, the spatial pattern of Cleistogenes squarrosa population in different restorative succession communities of the typical steppe dominated by Stipa grandis and Leymus chinensis in Inner Mongolia was measured by photography orientation, and analyzed by complete spatial randomness model, Poisson cluster process, and nested double-cluster process. In severely degraded community, C. squarrosa population fitted well nested double-cluster process for all scales, i. e., high density small clusters existed at the centers of large clusters; whereas in 5-, 8-, and 21-year-old restored communities, C. squarrosa population fitted well Poisson cluster process for all scales, i. e. , high density small clusters did not exist at the centers of the clusters. It was suggested that facilitation was the dominant interaction in severely degraded community, while competition dominated in restored communities. The differences in the spatial pattern of C. squarrosa population during the restorative succession could be induced by the shift from facilitation to competition along the gradient of grazing stress.


Successful treatment of a VIPoma by continuous subcutaneous infusion of somatostatin analogue (SMS 201-995).
A case with WDHA syndrome due to VIPoma is reported. Injection of somatostatin analogue SMS 201-995 was followed by prompt suppression of vasoactive intestinal polypeptide levels (VIP), decreased stool volume, and restoration of the serum potassium concentration to normal. Long-term treatment with SMS 201-995 for up to 20 weeks produced excellent clinical control and a decrease in tumour size. No adverse effects were noted except for localized pain at the site of injection. This was overcome by using a continuous subcutaneous infusion pump which also enabled the effective daily dosage to be reduced and thereby adverse reactions to be avoided.


Serving rural families of developmentally disabled children: a case management model.
Family-centered, community-based case management is a key feature of new federal legislation mandating educational and preschool services for all developmentally disabled children. Social work skills, including counseling, planning, coordination, and knowledge of family and community dynamics, are germane to this task. The goal of family-centered case management is the empowerment of parents as caretakers and planners for their children. Highly skilled case managers will be particularly needed in rural areas where families must deal with scarce resources and other environmental constraints. The authors describe a program employing master's-level social work case managers who serve rural Appalachian families with developmentally disabled children. Included is a case illustration that delineates both case management activities and the contextual elements important in working in an Appalachian rural community.


Pulmonary sequestration diagnosed by contrast enhanced three-dimensional MR angiography.
Pulmonary sequestration is a congenital bronchopulmonary foregut malformation in which a segment of lung parenchyma is not connected to the tracheobronchial tree. This abnormal segment receives a blood supply from the systemic circulation. Multiple imaging modalities have been used to demonstrate the vascular anatomy of the sequestration. Different magnetic resonance angiography (MRA) techniques have been employed in the identification of these anomalous vessels. We report a case of pulmonary sequestration diagnosed by MRI with the use of contrast enhanced three-dimensional MRA.


[Adult living donor liver transplantation].
The number of adult living-donor liver transplantations is rapidly increasing world wide. Donor selection, technical innovation, and postoperative management are important for donor safety. The adequacy of graft size is the major limitation and the most critical issue in adult living-donor liver transplantation. The outcome of this surgery is significantly influenced by the pretransplant patient condition and the original patient disease. Further study is needed to clarify the indications for and timing of living-donor transplantation for adult recipients.


Sarcopenia of thoracic muscle mass is not a risk factor for survival in lung transplant recipients.
In lung transplantation (LTx), patients with thoracic muscle sarcopenia may have to require longer to recovery. We measured thoracic muscle volume by using the cross sectional area (CSA) and assessed its effect on early outcomes after LTx. A retrospective analysis was conducted to evaluate the effect of thoracic sarcopenia in patients undergoing LTx between January 2010 and July 2015. The lowest CSA quartile (Q1) was defined as sarcopenia. In total, 109 patients were enrolled. The mean CSA was 58.24±15.82 cm(2). Patients in the highest CSA quartile were more likely to be male (92.6% vs. 17.9%, P<0.001), older (55.2±10.1 vs. 43.2±14.9 years, P=0.001), to have a higher body mass index (BMI) (22.3±4.0 vs. 19.4±3.7 kg/m(2), P=0.007), and to have pulmonary fibrosis (85.2% vs. 35.7%, P=0.003) compared with the lowest CSA quartile. Early outcomes including ventilator support duration [32.9±49.2 vs. 24.5±39.9 days, P= not significant (ns)], intensive care unit (ICU) stay duration (28.4±43.7 vs. 24.4±35.9 days, P= ns) and hospital stay duration (61.4±48.2 vs. 50.8±37.2 days, P= ns) tended to be longer in Q1 than Q4, but the difference was not significant. However, the 1-year survival rate was better in Q1 compared with Q4 (66.6% vs. 46.0%, P=0.04). Although patients with thoracic sarcopenia seem to require a longer post-operative recovery time after LTx, this does not compromise their early outcomes. By contrast, patients with larger thoracic muscle volume (Q4) showed poorer survival times.


Iterative approach for the numerical simulation of scattering from one- and two-dimensional rough surfaces.
We describe the use of iterative techniques for the solution of the integral equation that arises in an exact treatment of scalar wave scattering from randomly rough surfaces. The surfaces vary in either one or two dimensions, and the special case of a Dirichlet boundary condition is treated. It is found that these techniques, particularly when preconditioning is applied, are much more efficient than direct inversion techniques. Moreover, convergence is obtained for rms roughness of the order of 1, so the techniques have applicability over a wide parameter regime. Convergence is always to the exact solution found by direct inversion, exceptly for cases of extremely large-scaled rms surface heights in which the iterative techniques fail. In addition, by monitoring the residuals in the iteration process, it is immediately clear if the iterative techniques are failing, or performing badly in any given case. Finally, numerical results are compared with existing data in the enhanced backscattering regime.


The ER membrane protein complex is required to ensure correct topology and stable expression of flavivirus polyproteins.
Flaviviruses translate their genomes as multi-pass transmembrane proteins at the endoplasmic reticulum (ER) membrane. Here, we show that the ER membrane protein complex (EMC) is indispensable for the expression of viral polyproteins. We demonstrated that EMC was essential for accurate folding and post-translational stability rather than translation efficiency. Specifically, we revealed degradation of NS4A-NS4B, a region rich in transmembrane domains, in absence of EMC. Orthogonally, by serial passaging of virus on EMC-deficient cells, we identified two non-synonymous point mutations in NS4A and NS4B, which rescued viral replication. Finally, we showed a physical interaction between EMC and viral NS4B and that the NS4A-4B region adopts an aberrant topology in the absence of the EMC leading to degradation. Together, our data highlight how flaviviruses hijack the EMC for transmembrane protein biogenesis to achieve optimal expression of their polyproteins, which reinforces a role for the EMC in stabilizing challenging transmembrane proteins during synthesis.


Treatment of neuroterrorism.
Bioterrorism is defined as the intentional use of biological, chemical, nuclear, or radiological agents to cause disease, death, or environmental damage. Early recognition of a bioterrorist attack is of utmost importance to minimize casualties and initiate appropriate therapy. The range of agents that could potentially be used as weapons is wide, however, only a few of these agents have all the characteristics making them ideal for that purpose. Many of the chemical and biological weapons can cause neurological symptoms and damage the nervous system in varying degrees. Therefore, preparedness among neurologists is important. The main challenge is to be cognizant of the clinical syndromes and to be able to differentiate diseases caused by bioterrorism from naturally occurring disorders. This review provides an overview of the biological and chemical warfare agents, with a focus on neurological manifestation and an approach to treatment from a perspective of neurological critical care.


Prognostic significance of admission troponin T concentrations in patients with myocardial infarction.
New, highly specific cardiac structural proteins can now be measured. The early presence of one of these proteins, troponin T, has been found to have important prognostic significance in patients with unstable angina pectoris. The prognostic significance of its presence on admission was assessed in patients with myocardial infarction. Two hundred forty patients admitted with myocardial infarction were studied and followed prospectively for a median of 3 years. The prognostic significance of an admission troponin T concentration > or = 0.2 ng/mL for subsequent cardiac death and/or reinfarction was assessed and compared with other variables in a regression model. Any detectable troponin T on admission was associated with a worse prognosis on follow-up. An admission concentration of > or = 0.2 ng/mL was associated with a higher risk of subsequent cardiac death (chi 2, 13.3; P = .0002) and death or nonfatal reinfarction (chi 2, 16; P = .00006). The excess risk was seen primarily in patients with admission ECG ST-segment elevation (cardiac death chi 2, 9.7; P = .001; death or nonfatal reinfarction chi 2, 10.3; P = .001). In a stepwise regression model for cardiac death or nonfatal reinfarction, troponin T was superior to most of the other variables entered in both myocardial infarction subgroups. The presence of admission troponin T in patients with myocardial infarction defines a subgroup, particularly those with ST-segment elevation, at increased risk of subsequent cardiac events and identifies a group that may benefit from alternative early management strategies.


Introduction: Value of epidemiological research for clinical practice.
Epidemiology is the scientific analysis of the occurrence of diseases in the general population in relationship to the characteristics of the individual subjects and their environment. Traditional epidemiology is concerned with discovering basic truths on the frequencies of diseases and their aetiology; clinical epidemiology represents a special field that translates clinical practice into quantitative science; public health epidemiology is the basis of knowledge, prevention and treatment of diseases in the population. Epidemiology has an important clinical impact for it can be used to understand the pathogenesis of diseases, improve diagnostic accuracy, help the patient to reduce risk factors and the physician to choose the correct therapeutic approach.


MicroRNAs: shortcuts in dealing with molecular complexity?
Recent studies from Clarke's group published in the journal Cell indicate that miRNAs may be the elusive universal stem cell markers that the field of cancer stem cell biology has been seeking. Distinct profiles of miRNAs appear to reflect the state of cell differentiation not only in breast cancer cells, but also in normal mammary epithelial cells. Moreover, they are conserved across tissues and species. The authors of this work also show evidence that downregulation of miRNA-200c in normal and malignant breast stem cells and in embryonal carcinoma cells has functional relevance, being responsible for the proliferative potential of these cells in vitro and in vivo.


Establishing Healthcare Worker Performance and Safety in Providing Critical Care for Patients in a Simulated Ebola Treatment Unit: Non-Randomized Pilot Study.
Improving the provision of supportive care for patients with Ebola is an important quality improvement initiative. We designed a simulated Ebola Treatment Unit (ETU) to assess performance and safety of healthcare workers (HCWs) performing tasks wearing personal protective equipment (PPE) in hot (35 °C, 60% relative humidity) or thermo-neutral (20 °C, 20% relative humidity) conditions. In this pilot phase to determine the feasibility of study procedures, HCWs in PPE were non-randomly allocated to hot or thermo-neutral conditions to perform peripheral intravenous (PIV) and midline catheter (MLC) insertion and endotracheal intubation (ETI) on mannequins. Eighteen HCWs (13 physicians, 4 nurses, 1 nurse practitioner; 2 with prior ETU experience; 10 in hot conditions) spent 69 (10) (mean (SD)) minutes in the simulated ETU. Mean (SD) task completion times were 16 (6) min for PIV insertion; 33 (5) min for MLC insertion; and 16 (8) min for ETI. Satisfactory task completion was numerically higher for physicians vs. nurses. Participants' blood pressure was similar, but heart rate was higher (p = 0.0005) post-simulation vs. baseline. Participants had a median (range) of 2.0 (0.0-10.0) minor PPE breaches, 2.0 (0.0-6.0) near-miss incidents, and 2.0 (0.0-6.0) health symptoms and concerns. There were eight health-assessment triggers in five participants, of whom four were in hot conditions. We terminated the simulation of two participants in hot conditions due to thermal discomfort. In summary, study tasks were suitable for physician participants, but they require redesign to match nurses' expertise for the subsequent randomized phase of the study. One-quarter of participants had a health-assessment trigger. This research model may be useful in future training and research regarding clinical care for patients with highly infectious pathogens in austere settings.


Large and Reconfigurable Infrared Photothermoelectric Effect at Oxide Interfaces.
To maximize the photovoltaic efficiency, it is highly desirable to enable the electricity conversion from low energy photons and to extract the excessive energy from hot carriers. Here we report a large photovoltage generation at the LaAlO3/SrTiO3 interfaces from infrared photons with energies far below the oxide bandgaps. This effect is a result of the photoexcitation of hot carriers in metasurface electrical contacts and the subsequent thermoelectric charge separations by the interfacial two-dimensional electron gas (2DEG). Reaching a room-temperature responsivity of 4.4 V/W, such light-to-charge conversion can be spatially controlled and reconfigured through the patterning of 2DEG using conducting atomic force microscope. Compatible for broadband applications, our results demonstrate a new path toward efficient and programmable light sensing using oxide-based low-dimensional electron systems.


Feedforward neural control of toe walking in humans.
Activation of ankle muscles at ground contact during toe walking is unaltered when sensory feedback is blocked or the ground is suddenly dropped. Responses in the soleus muscle to transcranial magnetic stimulation, but not peripheral nerve stimulation, are facilitated at ground contact during toe walking. We argue that toe walking is supported by feedforward control at ground contact. Toe walking requires careful control of the ankle muscles in order to absorb the impact of ground contact and maintain a stable position of the joint. The present study aimed to clarify the peripheral and central neural mechanisms involved. Fifteen healthy adults walked on a treadmill (3.0 km h-1 ). Tibialis anterior (TA) and soleus (Sol) EMG, knee and ankle joint angles, and gastrocnemius-soleus muscle fascicle lengths were recorded. Peripheral and central contributions to the EMG activity were assessed by afferent blockade, H-reflex testing, transcranial magnetic brain stimulation (TMS) and sudden unloading of the planter flexor muscle-tendon complex. Sol EMG activity started prior to ground contact and remained high throughout stance. TA EMG activity, which is normally seen around ground contact during heel strike walking, was absent. Although stretch of the Achilles tendon-muscle complex was observed after ground contact, this was not associated with lengthening of the ankle plantar flexor muscle fascicles. Sol EMG around ground contact was not affected by ischaemic blockade of large-diameter sensory afferents, or the sudden removal of ground support shortly after toe contact. Soleus motor-evoked potentials elicited by TMS were facilitated immediately after ground contact, whereas Sol H-reflexes were not. These findings indicate that at the crucial time of ankle stabilization following ground contact, toe walking is governed by centrally mediated motor drive rather than sensory driven reflex mechanisms. These findings have implications for our understanding of the control of human gait during voluntary toe walking.


Intravitreal dexamethasone implant - a new treatment for idiopathic posterior scleritis: A case report.
Posterior scleritis is one of the most easily missed and misdiagnosed diseases in ophthalmology. In this case we treated a patient with intravitreal dexamethasone implant that has not been extensively studied before. A 40-year-old female patient who had anxiety, palpitation, and insomnia presented with eye pain and decreased vision in the left eye. An eye examination indicated that her visual acuity (VA) was 40/100. Her left eye presented conjunctival edema, mild exophthalmos, clear cornea, KP(-), and clear aqueous humor. In the fundus, there was a cinerous retinal protuberance. Ultrasonography showed "T-sign" and no systemic association was detected in laboratory examination. One month after injection of dexamethasone implant, the patient exhibited VA of 20/20, fundus serous retinal detachment disappeared, and intraocular pressure of both eyes was at the normal level. Intravitreal injection of dexamethasone implant may be a safe and effective treatment for patients with idiopathic posterior scleritis.


Valerian extract Ze 911 inhibits postsynaptic potentials by activation of adenosine A1 receptors in rat cortical neurons.
In this study we evaluated the adenosine A1 receptor-mediated effect of valerian extract (Ze 911) on postsynaptic potentials (PSPs) in pyramidal cells of the rat cingulate cortex in a slice preparation. We first observed that N6-cyclopentyladenosine (CPA, 0.01 - 10 microM), an adenosine A1 receptor agonist, inhibited PSPs in a concentration-dependent manner. The CPA (10 microM)-induced inhibition was antagonized by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.1 microM), an adenosine A1 receptor antagonist. Ze 911 concentration dependently (0.1 - 15 mg/mL) inhibited PSPs in the presence of the adenosine A2A receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (CSC, 0.2 microM) and adenosine deaminase (1 U/mL). The maximal inhibition induced by 10 mg/mL was completely antagonised by DPCPX (0.1 microM), an A1 receptor blocker. The data suggest that activation of adenosine A1 receptors is involved in the pharmacological effects of the valerian extract Ze 911.


The impact of peripheral vascular disease on long-term survival after coronary artery bypass graft surgery.
Although peripheral vascular disease is known to negatively affect overall survival, its effects on survival after surgical myocardial revascularization have not been well described. The objective of this study was to examine the impact of peripheral vascular disease on long-term survival after coronary artery bypass grafting. We reviewed records of 1,164 consecutive patients (370 with peripheral vascular disease and 794 without it) who underwent primary isolated coronary artery bypass graft surgery between 1997 and 2007. Univariate and multivariate logistic regression methods were used to analyze variables associated with early outcomes. We assessed long-term survival by using Kaplan-Meier curves generated by log-rank tests, adjusting for confounding factors with Cox proportional hazards regression analysis. Patients with peripheral vascular disease were generally sicker and had more comorbidities than patients without peripheral vascular disease. The presence of peripheral vascular disease does not predict increased rates of 30-day mortality or major adverse cardiac events. However, after controlling for potential confounding factors, patients with peripheral vascular disease had a significantly worse 9-year survival rate than patients without peripheral vascular disease (72.9% +/- 4.1% versus 82.8% +/- 2.4%; adjusted hazard ratio, 1.7; 95% confidence interval: 1.2 to 2.4; p = 0.004). Although peripheral vascular disease does not affect early outcomes in coronary artery bypass operations, it is an independent predictor of poor long-term survival among patients undergoing coronary artery bypass graft surgery. Identifying the mechanism that underlies this difference is important for improving survival in patients with peripheral vascular disease who undergo surgical myocardial revascularization.


Malt1 protease inactivation efficiently dampens immune responses but causes spontaneous autoimmunity.
The protease activity of the paracaspase Malt1 has recently gained interest as a drug target for immunomodulation and the treatment of diffuse large B-cell lymphomas. To address the consequences of Malt1 protease inactivation on the immune response in vivo, we generated knock-in mice expressing a catalytically inactive C472A mutant of Malt1 that conserves its scaffold function. Like Malt1-deficient mice, knock-in mice had strong defects in the activation of lymphocytes, NK and dendritic cells, and the development of B1 and marginal zone B cells and were completely protected against the induction of autoimmune encephalomyelitis. Malt1 inactivation also protected the mice from experimental induction of colitis. However, Malt1 knock-in mice but not Malt1-deficient mice spontaneously developed signs of autoimmune gastritis that correlated with an absence of Treg cells, an accumulation of T cells with an activated phenotype and high serum levels of IgE and IgG1. Thus, removal of the enzymatic activity of Malt1 efficiently dampens the immune response, but favors autoimmunity through impaired Treg development, which could be relevant for therapeutic Malt1-targeting strategies.


Carbon dots hybrid for dual fluorescent detection of microRNA-21 integrated bioimaging of MCF-7 using a microfluidic platform.
MicroRNAs have short sequences of 20 ~ 25-nucleotides which are similar among family members and play crucial regulatory roles in numerous biological processes, such as in cell development, metabolism, proliferation, differentiation, and apoptosis. We reported a strategy for the construction of a dual-emission fluorescent sensor using carbon dots (CDs) and confirmed their applications for ratiometric microRNA-21 sensing and bioimaging of cancer cells in a microfluidic device. The composition of blue CDs (B-CDs) and yellow CDs (Y-CDs) depicts dual-emission behavior which is centered at 409 and 543 nm under an excitation wavelength of 360 nm. With increasing microRNA-21 concentration, the robust and specific binding of DNA probe functionalized B-CDs to complementary microRNA-21 target induced perturbations of probe structure and led to changing fluorescence intensity in both wavelengths. Consequently, the ratio of turn-on signal to turn-off signal is greatly altered. With monitoring of the inherent ratiometric fluorescence variation (ΔF540nm/ΔF410nm), as-prepared BY-CDs were established as an efficient platform for ratiometric fluorescent microRNA-21 sensing, with a wide linear range of 0.15 fM to 2.46 pM and a detection limit of 50 aM. Furthermore, the proposed assay was applied for detecting microRNA-21 in dilute human serum samples with satisfactory recovery and also in MCF-7 cell lines in the range 3000 to 45,000 (cell mL-1) with a detection limit (3 cells in 10 μL), demonstrating the potential of the assay for clinic diagnosis of microRNA-associated disease. More importantly, the images revealed that MCF-7 cells well labeled with BY-CDs could exhibit the applicability of the proposed microfluidic system as an effective cell trapping device in bioimaging.


1-[2-(1H-Benzimidazol-2-yl)eth-yl]-1H-1,2,3-benzotriazole.
In the title compound, C(15)H(13)N(5), the N-containing heterocycles are linked by an ethyl-ene spacer in a gauche conformation, the N-C-C-C torsion angle along the linker being 60.1 (3)°. The dihedral angle between the terminal benzotriazole and benzimidazole rings is 39.02 (6)°. In the crystal, adjacent mol-ecules are connected by N-H⋯N hydrogen bonds, forming an infinite chain along the c axis. π-π stacking inter-actions [centroid-centroid distance = 3.8772 (7) Å] between the benzotriazole rings of neighbouring chains extend these chains into a supra-molecular sheet in the bc plane. Weak inter-molecular C-H⋯N inter-actions further stabilize the crystal structure.


Feasibility of a break-in period of less than 24 hours for urgent start peritoneal dialysis: a multicenter study.
Urgent start peritoneal dialysis (USPD) is an effective therapeutic method for end-stage renal disease (ESRD). However, whether it is safe to initiate peritoneal dialysis (PD) within 24 h unclear. We examined the short-term outcomes of a break-in period (BI) of 24 h for patients undergoing USPD. This real-world, multicenter, retrospective cohort study evaluated USPD patients from five centers from January 2013 to August 2020. Patients were divided into BI ≤ 24 h or BI > 24 h groups. The Primary outcomes included incidence of mechanical and infectious complications. The secondary outcome was technique failure. Moreover, we presented a subgroup analysis for patients who did not receive temporary hemodialysis (HD). A total of 871 USPD patients were included: 470 in the BI ≤ 24 h and 401 in the BI > 24 h groups. Mechanical and infectious complications did not differ between the two groups across the follow-up timepoints (2 weeks, 1 month, 3 months, and 6 months) (p > 0.05). Multiple logistic regression analysis revealed that BI ≤ 24 h was not an independent risk factor for mechanical complications, catheter migration, or infectious complications (p > 0.05). A BI ≤ 24 h was not an independent significant risk factor for technique failure by multivariate Cox regression analysis (p > 0.05). The subgroup analysis of patients who did not receive temporary HD returned the same results. Initiating PD within 24 h of catheter insertion was not associated with increased mechanical complications, infectious complications, or technique failures.


Lipoproteins Contribute to the Anti-inflammatory Capacity of Lactobacillus plantarum WCFS1.
Bacterial lipoproteins are well-recognized microorganism-associated molecular patterns, which interact with Toll-like receptor (TLR) 2, an important pattern recognition receptor of the host innate immune system. Lipoproteins are conjugated with two- or three-acyl chains (di- or tri-acyl), which is essential for appropriate anchoring in the cell membrane as well as for the interaction with TLR2. Lipoproteins have mostly been studied in pathogens and have established roles in various biological processes, such as nutrient import, cell wall cross-linking and remodeling, and host-cell interaction. By contrast, information on the role of lipoproteins in the physiology and host interaction of probiotic bacteria is scarce. By deletion of lgt, encoding prolipoprotein diacylglyceryl transferase, responsible for lipidation of lipoprotein precursors, we investigated the roles of the collective group of lipoproteins in the physiology of the probiotic model strain Lactobacillus plantarum WCFS1 using proteomic analysis of secreted proteins. To investigate the consequences of the lgt mutation in host-cell interaction, the capacity of mutant and wild-type bacteria to stimulate TLR2 signaling and inflammatory responses was compared using (reporter-) cell-based models. These experiments exemplified the critical contribution of the acyl chains of lipoproteins in immunomodulation. To the best of our knowledge, this is the first study that investigated collective lipoprotein functions in a model strain for probiotic lactobacilli, and we show that the lipoproteins in L. plantarum WCFS1 are critical drivers of anti-inflammatory host responses toward this strain.


Tumor-necrosis factor-alpha modulates mitogen-activated protein kinase activity of epidermal-growth-factor-stimulated MCF-7 breast cancer cells.
Tumor-necrosis factor(TNF)-alpha inhibited in a dose-dependent fashion the proliferation of epidermal-growth-factor(EGF)-stimulated MCF-7 breast cancer cells with an IC50 of 0.25 nM. A comparable TNF-alpha-mediated inhibition of p42/44 mitogen-activated protein (MAP) kinase activity was observed in 10 nM EGF-stimulated cells. The MAP kinase activity dropped 50% within 3 min of TNF-alpha (1 nM) addition to EGF-stimulated MCF-7 cells. EGF and TNF-alpha, when added independently, led to a transient stimulation of MAP kinase activity with maximal activations within 6-8 min and 1-2 min, respectively. These observations suggest that MAP kinase activity in EGF-stimulated MCF-7 cells is modulated by the growth-inhibitory receptor pathways of TNF-alpha. Phosphorylation measurements on western blots determined the involvement of several individual MAP kinases, namely p42/44 MAP kinases, p38 MAP kinase and c-Jun N2-terminal kinase 1 (JNK1), in EGF and TNF-alpha-induced signalling. Phosphorylation of p42 and p38 MAP kinases only was observed after treatment with either TNF-alpha or EGF. A combination of both ligands inhibited p42 and p38 MAP kinase phosphorylation in MCF-7 cells. In contrast, no JNK1 phosphorylation was detected in these cells. Simultaneous addition of okadaic acid, a potent inhibitor of phosphatases 1 and 2A, blocked the decay of EGF-stimulated MAP kinase activity over 40 min. TNF-alpha added to EGF-stimulated and okadaic-acid-treated cells increased the MAP kinase activity twofold within 1 min. Similarly, okadaic acid treatment partly reverted the TNF-alpha-inhibited growth of MCF-7 cells. These experiments suggest that phosphatases are involved in the rapid shut-down by TNF-alpha of p42 MAP kinase activity.


Ambivalence and Interpersonal Liking: The Expression of Ambivalence as Social Validation of Attitudinal Conflict.
Literature on attitude similarity suggests that sharing similar attitudes enhances interpersonal liking, but it remains unanswered whether this effect also holds for ambivalent attitudes. In the present research, we shed light on the role attitudinal ambivalence plays in interpersonal liking. Specifically, we examine whether people express ambivalence strategically to generate a positive or negative social image, and whether this is dependent on the attitudinal ambivalence of their perceiver. We test two alternative hypotheses. In line with the attitude-similarity effect, people should express ambivalence toward ambivalent others to enhance interpersonal liking, as sharing ambivalence might socially validate the latter's experience of attitudinal conflict. On the other hand, people might express more univalence, as ambivalence may drive ambivalent others toward the resolution of their attitudinal conflict, and univalent stances could help to achieve that goal. In two studies (N = 449, 149), people expressed similar attitudes to those of their perceivers, even when the latter experienced attitudinal conflict (Studies 1 and 2). Moreover, they composed an essay, the message of which validated their perceiver's attitudinal conflict (Study 2). In line with these results, we further observe that the more people experienced their ambivalence as conflicting, the more they liked others who similarly experienced attitudinal conflict (Study 1). These findings suggest that the expression of ambivalence can have important interpersonal functions, as it might lead to an enhanced social image when interacting with those coping with attitudinal conflict.


Rheumatic Heart Disease is Missing from the Global Health Agenda.
Rheumatic heart disease (RHD) is a complication of untreated throat infection by Group A beta-hemolytic streptococcus with a high prevalence among socioeconomically disadvantaged populations. Despite its high incidence and prevalence, RHD prevention is not a priority in major global health discussions. The reasons for the apparent neglect are multifactorial, including underestimated morbidity and mortality burden, underappreciated economic burden, lack of public awareness, and lack of sustainable investment. In this review, we recommend multisectoral collaboration to tackle the burden of RHD by engaging the public, health experts, and policymakers; augmenting funding for clinical care; improving distribution channels for prophylaxis, and increasing research and innovation as critical interventions to save millions of people from preventable morbidity and mortality.


Heparin promotes the formation of extracardiac to coronary anastomoses in a canine model.
We developed a canine model for the in vivo utilization of angiogenesis factors to promote revascularization of a collateral-dependent area of the heart and assessed the potential of heparin in this preparation. Ameroids were placed on the proximal left anterior descending coronary artery (LAD) of 29 dogs, and the left internal mammary artery (IMA) was implanted in an intramyocardial tunnel in proximity to the LAD. A tube positioned in the distal IMA provided a continuous retrograde infusion directly into the vessel from an implanted pump. Heparin (15 or 150 U/h) or saline vehicle was infused. After 8 wk, regional myocardial blood flow was assessed in the anesthetized state during adenosine-induced vasodilatation, before and during occlusion of the IMA. The IMA provided a greater proportion of maximal collateral flow in heparin-treated dogs (22 +/- 5%, n = 17) than in saline-treated dogs (9 +/- 2%, n = 12, P less than 0.05). Thus continuous infusion of heparin promotes the formation of collaterals between the extracardiac artery and the myocardial circulation, establishing the feasibility of targeting angiogenic agents for myocardial revascularization.


A Survey of Dementia Knowledge and Recognition of Dementia Prevention and Practice in Healthy Older Adults.
The aim of this study was to investigate the level of dementia knowledge and behaviors recognized as dementia-preventive and the practice thereof among healthy older adults who are highly motivated to engage in activities. The participants were older adults registered at the Silver Human Resource Center of city A, and participants anonymously filled questionnaires through the aggregation method in January 2020. The analysis included 78 participants (the effective response rate was 49.7%). All participants were aware of at least 4 dementia-preventive behaviors, and about 80% of all participants practiced at least 1 preventive behavior. Approximately 20% of participants were not practicing preventive behaviors at all. The elderly aged 65 to 74 years had more knowledge about dementia and more types of behavior perceived as dementia-preventive than the elderly aged 75 years and older. There was no significant correlation between the level of dementia knowledge and the number of types of dementia-preventive behaviors. Healthy older adults were aware of numerous behaviors for dementia prevention, and most older adults practiced preventive behaviors. In contrast, even with a high amount of knowledge about dementia, a small number of healthy older adults did not translate this knowledge into preventative behavioral practices. High levels of dementia knowledge do not translate into preventive behavioral practices.


Telecar: an Italian telecardiology project.
The Telecar (tele-assistance cardiology) project was an example of tele-assistance between health centres of the Regione Lazio in Italy. The project was approved by the Ministry of Health, financed with 500,000,000 lire and carried out by an operative station within 'La Sapienza' University (Rome). About 40 of the health centres in Lazio that did not have cardiologists or electrocardiography (ECG) equipment were provided with telematic instruments (Cardiophone and fax). With this equipment, they were able to transmit ECG signals and receive copies of ECG reports. The 40 health centres included first-aid clinics, 'guardia medica' surgeries and community centres. The project was carried out between 1989 and 1992. During these three years the health centres transmitted a total of 4807 ECGs, 2057 (43%) of which were routine, the remaining 2750 (57%) being suspected emergencies. Of the suspected emergencies, 681 cases (25%) had a confirmed abnormality. We can confirm that telematic aids are very important for an operative station, where all kinds of emergencies must be dealt with.


Autografting for chronic myeloid leukaemia.
For most chronic myeloid leukaemia (CML) patients the option of a potentially 'curative' allogeneic stem cell transplant is not available because of age or lack of donor. Interferon alpha appears to extend survival when used in the chronic phase of the disease but probably does not produce long-term disease-free survivors. Autografting is being actively explored as a therapeutic option which may improve on the survival data seen with interferon and numerous different autografting methodologies are being investigated. While it seems reasonable to hope that a suitably robust and safe approach to autografting may improve survival it is unlikely with current technology that long-term disease-free survival will be achieved. To date no compelling trial data are available to confirm the efficacy of autografting but large prospective randomized studies are underway to investigate whether autografting can indeed extend survival for CML patients who do not have the option of an allograft.


Acute infectious bursal disease in poultry: protection afforded by maternally derived antibodies and interference with live vaccination.
Maternally derived antibodies (MDA) were found insufficient to protect broiler chicks against a highly pathogenic strain of IBDV during the growing period even if the parent flocks had been boostered at point of lay by using oil emulsion vaccines. Whatever the vaccination scheme of the parent flocks, maximum mortality was observed after a challenge performed at 38 days of age in broiler and layer chicks, suggesting that the offspring need to be vaccinated with live vaccines before that age. MDA were demonstrated to interfere with live vaccination but strain D78 was shown to be more efficient as it could establish an infection even at higher antibody levels than the other strains. Given this pathogenicity and the lack of uniformity in the transmitted immunity, there is always a critical period where immune and susceptible birds coexist in the same flock. This period seems to be broader when parental flocks were vaccinated with an inactivated oil emulsion vaccine before lay.


Sodium-1,2-C Acetate Incorporation in Roots of Frost-hardy and Less Hardy Alfalfa Varieties under Hardening Conditions.
When the temperature of incorporation of sodium acetate-1, 2-(14)C into lipids of alfalfa (Medicago media Pers. var. Rambler and Medicago sativa L. var. Caliverde) roots was lowered from 22 C to 1 C, elongation and desaturation of fatty acids and the labeling of phosphatidylcholine were strongly stimulated.Controlled hardening of alfalfa stimulated strongly the incorporation of sodium acetate-1, 2-(14)C into root lipids of the hardy variety Rambler, but only slightly in the case of the frost-sensitive variety Caliverde. When incorporation was done at 1 C at various times of hardening, labeling decreased significantly in linoleic acid with a corresponding increase in oleic acid. Hardening, therefore, repressed specifically the initial low temperature stimulation of oleic acid desaturation, without affecting the stimulation of elongation of palmitic acid and the desaturation of stearic acid at low temperature. The radioactivity in linoleic acid was slightly greater in hardy Rambler than in Caliverde throughout hardening.When feedings were done at 1 C at various times of hardening, labeling of phosphatidylcholine increased in Rambler while it decreased in Caliverde. Throughout the hardening period, when incorporation was done at 1 C, linoleic acid represented a higher percentage of the label in phosphatidylcholine than in phosphatidylethanolamine or triglycerides and its specific radioactivity was much greater in phosphatidylcholine than in phosphatidylethanolamine and triglycerides and in Rambler than in Caliverde. Phosphatidylcholine seems, therefore, to play a special part in linoleic acid synthesis and in its control during the acquisition of frost hardiness.


Experimental Models of Maternal Obesity and Neuroendocrine Programming of Metabolic Disorders in Offspring.
Evidence from epidemiological, clinical, and experimental studies have clearly shown that disease risk in later life is increased following a poor early life environment, a process preferentially termed developmental programming. In particular, this work clearly highlights the importance of the nutritional environment during early development with alterations in maternal nutrition, including both under- and overnutrition, increasing the risk for a range of cardiometabolic and neurobehavioral disorders in adult offspring characterized by both adipokine resistance and obesity. Although the mechanistic basis for such developmental programming is not yet fully defined, a common feature derived from experimental animal models is that of alterations in the wiring of the neuroendocrine pathways that control energy balance and appetite regulation during early stages of developmental plasticity. The adipokine leptin has also received significant attention with clear experimental evidence that normal regulation of leptin levels during the early life period is critical for the normal development of tissues and related signaling pathways that are involved in metabolic and cardiovascular homeostasis. There is also increasing evidence that alterations in the epigenome and other underlying mechanisms including an altered gut-brain axis may contribute to lasting cardiometabolic dysfunction in offspring. Ongoing studies that further define the mechanisms between these associations will allow for identification of early risk markers and implementation of strategies around interventions that will have obvious beneficial implications in breaking a programmed transgenerational cycle of metabolic disorders.