Skin physiology and safety of microfocused ultrasound with visualization for improving skin laxity.
The efficacy of microfocused ultrasound with visualization (MFU-V; Ultherapy®) has been demonstrated in clinical studies and daily practice. However, data addressing skin physiology after MFU-V treatment are lacking. This observational evaluation was aimed to assess skin physiology before and after MFU-V treatment using noninvasive biophysical measurements. Twenty-two female patients with moderate-to-severe skin sagging at the jawline and submental region on the Merz Aesthetics Scale obtained a single MFU-V treatment according to protocol. Skin function measurements focused on short-term effects up to 3 days and long-term effects up to 24 weeks after treatment. Skin temperature, transepidermal water loss, skin hydration, erythema, elasticity, and skin thickness and density were evaluated under standardized conditions. Pain was assessed using a validated numeric visual analog scale. Skin temperature remained in a physiologic range and no significant increase was noted at day 3 after MFU-V treatment. Transepidermal water loss, hydration, and erythema values were fairly stable and showed no significant differences at short- and long-term measurements vs baseline. At week 4 after a single MFU-V treatment, gross and net elasticity values were significantly decreased (P=0.003 and P=0.0001, respectively), followed by significantly increased values at week 12 (P=0.015, P=0.046) and week 24 (P=0.001, P=0.049). Edema due to MFU-V treatment resolved without sequelae. For all patients, pain diminished shortly after treatment. No adverse events occurred during the 24-week follow-up period. MFU-V treatment is well tolerated and it does not alter the epidermal barrier function or physiology of skin. Significant increase in the elasticity of skin was observed at 12 and 24 weeks after a single treatment, which reflects improvement in dermal tissue function. These short- and long-term effects are congruous with the mode of action of MFU-V due to a proven intrinsic tissue remodeling process.


Genetic manipulation of periostin expression in the heart does not affect myocyte content, cell cycle activity, or cardiac repair.
Following a pathological insult, the adult mammalian heart undergoes hypertrophic growth and remodeling of the extracellular matrix. Although a small subpopulation of cardiomyocytes can reenter the cell cycle following cardiac injury, the myocardium is largely thought to be incapable of significant regeneration. Periostin, an extracellular matrix protein, has recently been proposed to induce reentry of differentiated cardiomyocytes back into the cell cycle and promote meaningful repair following myocardial infarction. Here, we show that although periostin is induced in the heart following injury, it does not stimulate DNA synthesis, mitosis, or cytokinesis of cardiomyocytes in vitro or in vivo. Mice lacking the gene encoding periostin and mice with inducible overexpression of full-length periostin were analyzed at baseline and after myocardial infarction. There was no difference in heart size or a change in cardiomyocyte number in either periostin transgenic or gene-targeted mice at baseline. Quantification of proliferating myocytes in the periinfarct area showed no difference between periostin-overexpressing and -null mice compared with strain-matched controls. In support of these observations, neither overexpression of periostin in cell culture, via an adenoviral vector, nor stimulation with recombinant protein induced DNA synthesis, mitosis, or cytokinesis. Periostin is a regulator of cardiac remodeling and hypertrophy and may be a reasonable pharmacological target to mitigate heart failure, but manipulation of this protein appears to have no obvious effect on myocardial regeneration.


One-Pot Synthesis of Strong Anionic/Charge-Neutral Amphiphilic Block Copolymers.
Despite the ever more versatile polymerization techniques that are becoming available, the synthesis of macromolecules with tailored functionalities can remain a lengthy endeavor. This becomes more conspicuous when the implementation of incompatible chemistries (i.e., strong polyelectrolytes) within sequence-controlled polymers is desired, often requiring (i) polymerization, (ii) chain extension, and (iii) postpolymerization modification. Herein, we explore the production of strong anionic/charge-neutral block copolymers (BCPs) in a one-pot fashion. This straightforward three-step process includes the synthesis of a macroinitiator and chain extension via rapid and efficient photomediated atom transfer radical polymerization, followed by in situ deprotection to expose the polyanionic domains. The resulting BCPs, which are strong amphiphiles by nature, are capable of self-assembly in aqueous media, as evidenced by dynamic light scattering, small-angle X-ray scattering, ζ-potential measurements, and transmission electron microscopy. We further demonstrate the versatility of our methodology by producing several BCPs through sampling of a single reaction mixture, enabling the straightforward production of strong polymer amphiphiles.


Growth inhibitory effects of gastric cancer cells with an increase in S phase and alkaline phosphatase activity repression by aloe-emodin.
Aloe-emodin is a novel active compound found in the root and rhizome of Rheum palmatum. To investigate the effects and mechanisms of aloe-emodin on human gastric cancer, MGC-803 cells were treated with 2.5, 5, 10, 20 and 40 microM aloe-emodin for 1-5 d. The results showed that aloe-emodin inhibited the growth of cancer cells in a dose-dependent manner with an increase in S phase and in the proportion of cells cycling at a higher ploidy level (>G2/M). Moreover, the alkaline phosphatase (ALP) activity, an indicator of cell differentiation, was found decreased. This is one of the first to focus on the effect of ALP activity in human gastric carcinomas cells treated by aloe-emodin. These results indicate that aloe-emodin has a potential value for the treatment of gastric cancer and its mechanisms are by means of cell cycle interruption and induce differentiation.


Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form.
Point mutations in the p53 gene are the most frequently identified genetic change in human cancer. They convert murine p53 from a tumour suppressor gene into a dominant transforming oncogene able to immortalize primary cells and bring about full transformation in combination with an activated ras gene. In both the human and murine systems the mutations lie in regions of p53 conserved from man to Xenopus. We have developed a monoclonal antibody to p53 designated PAb240 which does not immunoprecipitate wild type p53. A series of different p53 mutants all react more strongly with PAb240 than with PAb246. The PAb240 reactive form of p53 cannot bind to SV40 large T antigen but does bind to HSP70. In contrast, the PAb246 form binds to T antigen but not to HSP70. PAb240 recognizes all forms of p53 when they are denatured. It reacts with all mammalian p53 and chicken p53 in immunoblots. We propose that immunoprecipitation of p53 by PAb240 is diagnostic of mutation in both murine and human systems and suggest that the different point mutations which convert p53 from a recessive to a dominant oncogene exert a common conformational effect on the protein. This conformational change abolishes T antigen binding and promotes self-oligomerization. These results are consistent with a dominant negative model where mutant p53 protein binds to and neutralizes the activity of p53 in the wild type conformation.


Uricase-deficient rat is generated with CRISPR/Cas9 technique.
Urate oxidase (uricase, Uox) is a big obstacle for scientists to establish stable animal models for studying hyperuricemia and associated disorders. Due to the low survival rate of uricase-deficient mice, we generated a Uox-knockout model animal from Sprague Dawley (SD) rats using the CRISPR/Cas9 technique by deleting exons 2 to 4 of the Uox gene. The uricase-deficient rats were named "Kunming-DY rats", and were apparently healthy with more than a 95% survival up to one year. The male rats' serum uric acid (SUA) increased to 48.3 ± 19.1 µg/ml, significantly higher than those of wild-type rats. Some indexes of the blood fat like total triglyceride, low density lipoprotein, and renal function indexes including blood urea nitrogen and serum creatinine were significantly different from those of wild-type rats, however, all the indexes were close to or in normal ranges. Histological renal changes including mild glomerular/tubular lesions were observed in these uricase-deficient rats. Thus, "Kunming-DY rats" with stable uricase-deficiency were successfully established and are an alternative model animal to study hyperuricemia and associated diseases mimicking human conditions.


Efficacy and safety of moxibustion in the treatment of female stress urinary incontinence: A protocol for systematic review and meta-analysis.
Stress urinary incontinence (SUI) is one of the common diseases in female urinary system diseases, and the incidence is increasing year by year. Moxibustion therapy, as a kind of acupuncture therapy, has been widely used in the clinical treatment of SUI, but its therapeutic effect and safety have not been scientifically and systematically evaluated. Therefore, the protocol of this systematic review we propose this time is to scientifically evaluate the effectiveness and safety of moxibustion in the treatment of female stress urinary incontinence (FSUI). The following 8 electronic databases will be searched from establishment to December 2021: PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure, VIP Database, Wanfang Database, China Biology Medicine disc. All randomized controlled trials of moxibustion in the treatment of FSUI will be searched in the above electronic databases. Two reviewers will independently complete research selection, data extraction, and research quality evaluation. After screening the studies, the quality of the included studies will be evaluated according to the quality standards specified in the Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0). The primary outcome of included studies is the change from baseline in urine leakage measured by the 1-hour pad test. Secondary outcomes include: the short-form of the International Consultation on Incontinence Questionnaire, the mean 72-hour urinary incontinence episode frequency, self-assessment of the patient's treatment effect, severity of urinary incontinence, and adverse events. Two reviewers will independently conduct study selection, data extraction, risk of bias assessment, and study quality assessment. And the STATA 14.0 software will be implemented for data synthesis and meta-analysis. The result of this meta-analysis will be submitted to peer-reviewed journals for publication, and a comprehensive review of current evidence will be conducted. The conclusion of this systematic review will provide evidence for judging whether moxibustion is a safer and more effective intervention for female stress urinary incontinence. The protocol has been registered on INPLASY2021120052.


Smoking-related attitudes and behaviors of parents of fourth grade students.
In an attempt to determine the effect of tobacco education homework on the smoking behavior and/or attitudes of parents of fourth graders, a sample of students was given homework assignments at the beginning of the school year with which their parents had agreed to help. A control sample had the regular tobacco education unit, with no homework assignments. A follow-up survey at the end of the school year revealed that for parents who had been cigarette smokers at the beginning of the school year, those in the homework sample (n = 215) reported smoking fewer cigarettes and a greater reduction in smoking than those in the nonhomework sample (n = 89). While parents in the two samples did not differ in their general attitude toward cigarette smoking, those in the homework sample were more opposed to their children starting to smoke at a later time and more approving of tobacco education introduced as early as the fourth grade.


Expanding the efficacy of Project UPLIFT: Distance delivery of mindfulness-based depression prevention to people with epilepsy.
Depression affects about 16% of the U.S. population over a lifetime. People with chronic diseases have especially high rates of comorbid depression; 32% to 48% of people with epilepsy experience depression. This study evaluated the efficacy of a mindfulness-based cognitive therapy intervention for preventing major depressive disorder (MDD) episodes in people with epilepsy. Participants (n = 128) were adults from Georgia, Michigan, Texas, and Washington with epilepsy and mild/moderate depressive symptoms. The 8-session weekly Project UPLIFT intervention, based on mindfulness-based cognitive therapy, was group-delivered via Web or telephone. Using a randomized, controlled crossover design, participants were assigned to Project UPLIFT or a treatment-as-usual (TAU) waitlist and assessed at baseline, and after intervening in the intervention group (∼10 weeks) and in the TAU group (∼20 weeks). Assessments included valid self-report measures of depression and MDD, knowledge/skills, and satisfaction with life. The incidence of MDD episodes (new or relapse) from baseline to interim assessment was significantly lower in the intervention condition (0.0%) than in TAU (10.7%). Depressive symptoms decreased significantly more in the intervention condition than in TAU; Web and telephone did not differ. Change in knowledge/skills mediated the effect, which persisted over the 10 weeks of follow-up. Knowledge/skills and life satisfaction increased significantly more in the intervention condition than in TAU. Distance delivery of group mindfulness-based cognitive therapy can prevent episodes of MDD, reduce symptoms of depression, and increase life satisfaction in people with epilepsy. This intervention is easily modified for persons with other chronic diseases and other disparity populations. (PsycINFO Database Record


Mild hypoxia and the use of oxygen in flight.
Hypoxia in aviation remains a major hazard. It may be caused by ascent while breathing air, failure of oxygen supply or loss of cabin pressurisation. Malfunction of equipment or its improper use accounted for the majority of hypoxic incidents in one 10-year military study. Symptoms of hypoxia depend on rate of ascent, temperature, and individual variation, as well as altitude. Dyspnoea, lack of coordination and reduction in capacity for skilled performance precede the gross changes which occur at altitudes of over 4572 m (15,000 ft) and lead ultimately to unconsciousness. Studies have shown a significant decrease in psychomotor task ability at altitudes as low as 2438 m (8000 ft). Developments in aircraft oxygen systems are discussed and the importance of adequate crew instruction on hypoxia and their aircraft oxygen equipment is stressed.


Time-resolved compression of a capsule with a cone to high density for fast-ignition laser fusion.
The advent of high-intensity lasers enables us to recreate and study the behaviour of matter under the extreme densities and pressures that exist in many astrophysical objects. It may also enable us to develop a power source based on laser-driven nuclear fusion. Achieving such conditions usually requires a target that is highly uniform and spherically symmetric. Here we show that it is possible to generate high densities in a so-called fast-ignition target that consists of a thin shell whose spherical symmetry is interrupted by the inclusion of a metal cone. Using picosecond-time-resolved X-ray radiography, we show that we can achieve areal densities in excess of 300 mg cm(-2) with a nanosecond-duration compression pulse--the highest areal density ever reported for a cone-in-shell target. Such densities are high enough to stop MeV electrons, which is necessary for igniting the fuel with a subsequent picosecond pulse focused into the resulting plasma.


Magnetic resonance imaging for pathobiological assessment and interventional treatment of the coronary arteries.
X-ray-based fluoroscopy is the standard tool for diagnostics and intervention in coronary artery disease. In recent years, computed tomography has emerged as a non-invasive alternative to coronary angiography offering detection of coronary calcification and imaging of the vessel lumen by the use of iodinated contrast agents. Even though currently available invasive or non-invasive techniques can show the degree of vessel stenosis, they are unable to provide information about biofunctional plaque properties, e.g. plaque inflammation. Furthermore, the use of radiation and the necessity of iodinated contrast agents remain unfavourable prerequisites. Magnetic resonance imaging (MRI) is a radiation-free alternative to X-ray which offers anatomical and functional imaging contrasts fostering the idea of non-invasive biofunctional assessment of the coronary vessel wall. In combination with molecular contrast agents that target-specific epitopes of the vessel wall, MRI might reveal unique plaque properties rendering it, for example, 'vulnerable and prone to rupture'. Early detection of these lesions may allow for early or prophylactic treatment even before an adverse coronary event occurs. Besides diagnostic imaging, advances in real-time image acquisition and motion compensation now provide grounds for MRI-guided coronary interventions. In this article, we summarize our research on MRI-based molecular imaging in cardiovascular disease and feature our advances towards real-time MRI-based coronary interventions in a porcine model.


Teaching strategies to incorporate genomics education into academic nursing curricula.
The translation of genomic science into health care has expanded our ability to understand the effects of genomics on human health and disease. As genomic advances continue, nurses are expected to have the knowledge and skills to translate genomic information into improved patient care. This integrative review describes strategies used to teach genomics in academic nursing programs and their facilitators and barriers to inclusion in nursing curricula. The Learning Engagement Model and the Diffusion of Innovations Theory guided the interpretation of findings. CINAHL, Medline, and Web of Science were resources for articles published during the past decade that included strategies for teaching genomics in academic nursing programs. Of 135 articles, 13 met criteria for review. Examples of effective genomics teaching strategies included clinical application through case studies, storytelling, online genomics resources, student self-assessment, guest lecturers, and a genetics focus group. Most strategies were not evaluated for effectiveness.


[Diabetes mellitus and myocardial infarct].
The data from the case histories of 106 patients with myocardial infarction (MI) and diabetes mellitus (DM) from the intensive care unit of III Internal Clinic of the Medical Faculty of the Higher Medical Institute "I. P. Pavlov"-- Plovdiv are interpreted as well as of the same number of patients with myocardial infarction without diabetes mellitus. The authors found a higher percentage of painless forms of myocardial infarction in diabetics, no matter the duration, form and severity of the diabetes. The patients with DM and MI have a slowed down rehabilitation and reverse ECG dynamics. The complications in both groups observed do not differ. Myocardial rupture is significantly more frequent among the females from both groups. High leukocytosis, with shifting to the left, accelerated ESR, high SGOT and LDH activity and hypercoagulemia as well as their slowed down restoration should be admitted--a constellation with an unfavourable prognostic sign, requiring a cautious treatment and a slower rehabilitation.


Prevalence of alcohol consumption in nursing students.
Alcohol consumption is a public health problem that affects university students. The legality of alcohol facilitates consumption among the young and makes it the most used drug in this population, impacting health and university education. To identify alcohol consumption among nursing students of a public institution in Minatitlán, Veracruz, Mexico. Descriptive cross-sectional study, conducted between October and November 2020. A total of 260 nursing students participated voluntarily and anonymously. The information was collected using two instruments. The first one inquired about personal data, and the second one evaluated drinking through the Alcohol Use Disorders Identification Test (AUDIT). We found that 64.6% of students reported drinking at least once, with a mean age at drinking onset of 16.3 years. The preferred beverage was beer (53.6%), and the main providers of alcoholic beverages were friends (62.5%) and family (34.5%). A total of 59.6% of students had a low risk drinking patter, 4.6% had a high-risk drinking patter, and 0.4% reported dependence. There were no significant differences between drinking patterns and leisure time activities (X2 = 25.970; p = 0.355). There was a significant relationship between students' alcohol consumption patterns and age, current semester, drinking at least once, and drinking with family and friends (p < 0.01). There is a close relationship between the initiation and maintenance of alcohol consumption with nursing students' social, family, and school context. These findings should encourage health programs that follow up on alcohol consumption during university training.


[A case of double cancer: renal pelvic transitional cell carcinoma and lung squamous cell carcinoma].
A 69-year-old woman was admitted with the chief complaint of gross hematuria and left flank pain ten years after curative right pneumonectomy. Retrograde pyelography showed a filling defect of inferior calyx. Computerized tomography revealed a solid tumor with a low density area arising from the left kidney. The tumor was demonstrated hypovascular by angiography. Left radical nephrectomy by a transabdominal approach was performed. Histological diagnosis was primary transitional cell carcinoma of the left renal pelvis largely replacing the renal parenchyma. Twenty six days after the operation she was discharged. Our case was of double cancer consistent with Warren and Gates criteria and was classified into the nonsimultaneous case according to Moertels criteria. Double cancer of the lung and renal pelvis is very rare and our case seems to be the 7th in the Japanese clinical literature.


Correction and updating.
In the heading of David Cassidy's review of The Private Lives of Albert Einstein (18 February, p. 997) the price of the book as sold by its British publisher, Faber and Faber, was given incorrectly; the correct price is pound15.99. The book is also to be published in the United States by St. Martin's Press, New York, in April, at a price of $23.95.


Thromboprophylaxis practice patterns in hip fracture surgery patients: experience in Perth, Western Australia.
International guidelines recommend that all patients undergoing hip fracture surgery receive specific thromboprophylaxis. The purpose of the present study was to examine current thromboprophylaxis practice patterns in patients undergoing hip fracture surgery at Royal Perth Hospital. A total of 129 consecutive patients admitted to Royal Perth Hospital between 4 February and 21 July 2002 for surgical repair of a fractured neck of femur, was studied. The primary outcome was the frequency, type, and duration of thromboprophylaxis use during hospitalization. Mean patient age was 79.4 +/- 13.4 years and 69.8% (90/129) were female. Seventy-four patients (57.8%; 95% confidence interval (CI): 48.8-66.8%) received specific thromboprophylaxis during hospitalization, including 50 patients (39.1%; 95%CI: 30.6-48.1%) who received pharmacological prophylaxis only, three (2.3%; 95%CI: 0.5-6.7%) who received mechanical prophylaxis only, and 21 (16.4%; 95%CI: 10.5-24.0%) who received both mechanical and pharmacological prophylaxis. Of those receiving pharmacological prophylaxis, 35 (49.3%; 95%CI: 37.2-61.4%) received low-molecular-weight heparin, 26 (36.6%; 95%CI: 25.5-48.9%) received low-dose unfractionated heparin, eight (11.3%; 95%CI: 5.0-21.0%) received warfarin, 35 (49.3%; 95%CI: 37.2-61.8%) received aspirin or clopidogrel, and 27 (38.0%; 95% CI: 26.8-50.3%) received combined anticoagulant and antiplatelet prophylaxis. The median duration of mechanical prophylaxis was 8 days (range: 6-12 days) and that of pharmacological prophylaxis was 12 days (range: 6-26 days). When the 32 patients already taking aspirin or warfarin at the time of admission were excluded, only 45 (46.9%; 95%CI: 36.6-57.3%) of the remaining 96 patients received specific thromboprophylaxis. Specific thromboprophylaxis remains under-utilized in patients undergoing surgery for hip fracture at Royal Perth Hospital. These data should prompt the implementation of effective strategies to improve thromboprophylaxis practice patterns in high-risk orthopaedic patients.


[Transient ischemic stroke].
According to the new definition proposed by the TIA working group, transient ischemic stroke (TIA) is "a brief episode of neurologic dysfunction caused by focal brain or retinal ischemia, with clinical symptoms typically lasting less than one hour, and without evidence of acute infarction." Patient presenting with a TIA should be investigated and treated urgently because the risk of ischemic stroke is about 10% at one month with 50% of these events occurring during the first 48 hours. Atherosclerosis, cardioembolism and small vessel disease account for the majority of TA. Aspirin should be started as soon as possible after brain imaging has been performed. Other treatment such as oral anticoagulants or carotide surgery may be necessary, depending on the result of the electronical work up.


Adenosine deaminase specific activity in normal, benign hypertrophied and neoplastic human prostate tissue.
The finding that deficiency in the purine salvage pathway enzyme, adenosine deaminase (ADA), is associated with immunodeficiency suggests that this enzyme may be crucial for normal function of immunocompetent cells in man. We have therefore examined ADA activity in human prostatic tissue. Mean values were as follows: normal tissue, 0.37 mumol substrate turned over/h/mg protein; carcinoma, 0.33; benign prostatic hypertrophy (BPH), 1.22. ADA activity in normal and carcinoma prostate tissue differed significantly from BPH (p = 0.001), but were individually indistinguishable. Thus, there may be a cellular level of immunostimulation in BPH relative to normal prostatic tissue which is no longer detectable in overt carcinoma.


[Watermelon stomach and scleroderma].
We report here a 72-year-old man with severe, persistent, iron deficiency anaemia. Upper gastrointestinal endoscopy revealed red stripes radiating to the pylorus, characteristic of watermelon stomach (gastric antral vascular ectasia). The patient was found to have scleroderma with calcinosis, sclerodactyly, and telangiectasias, but neither Raynaud's phenomenon nor oesophageal dysmotility. The patient was treated with endoscopic Argon laser therapy, repeated six times, but this did not control the bleeding. Altogether the patient received 62 units of blood transfusions. The patient died after 9 months.


Associations of overweight and metabolic health with successful aging: 32-year follow-up of the Helsinki Businessmen Study.
Prognostic significance of metabolically healthy overweight and obesity (MHO) is under debate. However the relationship between MHO and health-related quality of life (HRQoL) is less studied. We compared successful aging (longevity plus HRQoL) in men with MHO, metabolically healthy normal weight (MHN) and metabolically unhealthy overweight and obesity (MUO). In the Helsinki Businessmen Study longitudinal cohort, consisting of men born 1919 to 1934. In 1985/86, overweight (BMI≥25 kg/m2) and metabolic health were determined in 1309 men (median age 60 years). HRQoL was assessed using RAND-36/SF-36 in 2000 and 2007, and all-cause mortality retrieved from registers up to 2018. The proportion of men reaching 90 years was also calculated. Of the men, 469 (35.8%), 538 (41.1%), 276 (21.1%), and 26 (2.0%) were MHN, MHO, MUO and MUN, respectively. During the 32-year follow-up, 72.3% men died. With MHN as reference, adjusted hazard ratio with all-cause mortality was 1.08 (95% confidence interval [CI] 0.93 to 1.27) for MHO, and 1.18 (95% CI 0.95 to 1.47) for MUO. During follow-up, 273 men reached 90 years. With MHN as reference, adjusted odds ratio for MHO was 0.82 (95% CI 0.59 to 1.14) and 0.62 (95% CI 0.41 to 0.95) for MUO. Men in MHN group scored generally highest in RAND-36 HRQoL subscales in 2000 and 2007, of those significantly better in Physical functioning, Role physical, Role emotional, Bodily Pain, and General health sub-scales compared to MHO group in 2000. As compared to MHN, MHO in late midlife does not increase mortality, but impairs odds for successful aging.


The Application of an Anatomical Database for Fetal Congenital Heart Disease.
Fetal congenital heart anomalies are the most common congenital anomalies in live births. Fetal echocardiography (FECG) is the only prenatal diagnostic approach used to detect fetal congenital heart disease (CHD). FECG is not widely used, and the antenatal diagnosis rate of CHD varies considerably. Thus, mastering the anatomical characteristics of different kinds of CHD is critical for ultrasound physicians to improve FECG technology. The aim of this study is to investigate the applications of a fetal CHD anatomic database in FECG teaching and training program. We evaluated 60 transverse section databases including 27 types of fetal CHD built in the Prenatal Diagnosis Center in Peking University People's Hospital. Each original database contained 400-700 cross-sectional digital images with a resolution of 3744 pixels × 5616 pixels. We imported the database into Amira 5.3.1 (Australia Visage Imaging Company, Australia) three-dimensional (3D) software. The database functions use a series of 3D software visual operations. The features of the fetal CHD anatomical database were analyzed to determine its applications in FECG continuing education and training. The database was rebuilt using the 3D software. The original and rebuilt databases can be displayed dynamically, continuously, and synchronically and can be rotated at arbitrary angles. The sections from the dynamic displays and rotating angles are consistent with the sections in FECG. The database successfully reproduced the anatomic structures and spatial relationship features of different fetal CHDs. We established a fetal CHD anatomy training database and a standardized training database for FECG. Ultrasound physicians and students can learn the anatomical features of fetal CHD and FECG through either centralized training or distance education. The database of fetal CHD successfully reproduced the anatomic structures and spatial relationship of different kinds of fetal CHD. This database can be widely used in anatomy and FECG teaching and training.


Antioxidants alleviate electric field-induced effects on lung tissue based on assays of heme oxygenase-1, protein carbonyl content, malondialdehyde, nitric oxide, and hydroxyproline.
In order to test whether antioxidants have beneficiary effects on electric field induced damage, we determined the pulmonary levels of heme oxygenase-1 (HO-1), protein carbonyl content (PCO), malondialdehyde (MDA), nitric oxide (NO) and hydroxyproline (HP) under extremely low frequency (ELF) electric (E) field exposure (50 Hz, 12 kV/m, 7 days/for 8 h/day). While PCO levels significantly increased (p<0.05), insignificant changes (p>0.05) were observed in HO-1, MDA, NO and HP levels for electric field exposure groups compared to the control group. We have not observed any significant change in these parameters on the electric field group compared to the group where NAC and EGCG were separately applied along with electric field. However, during our previous studies, we have concluded that NAC and EGCG are potent antioxidants and we believe that new studies should be established by way of setting up different experimental conditions.


Apoptosis in colorectal cancer.
Apoptosis is an inborn process that has been preserved during evolution; it allows the cells to systematically inactivate, destroy and dispose of their own components thus leading to their death. This programme can be activated by both intra and extracellular mechanisms. The intracellular components involve a genetically defined development programme while the extracellular aspects regard endogenous proteins, cytokines and hormones as well as xenobiotics, radiations, oxidative stress and hypoxia. The ability of a cell to enter apoptosis as a response to a "death" signal depends on its proliferative status, the position in the cell cycle and also on the controlled expression of those genes that have the capacity of promoting and inhibiting cell death. The fine regulation of these parameters needs to be maintained in order to ensure the physiological environment required for the induction of apoptosis. Any malfunction in any of the steps of controlled cellular death can lead to dysfunctions and, as a consequence, to different pathological conditions. The importance of apoptosis lies in its active nature and in the potential of controlling biological systems.


New technique for inducing reversible obstructive jaundice in the rat.
We present a new animal model of reversible obstructive jaundice, in which two polyethylene tubes were inserted into the common bile duct, one towards the liver and the other towards the duodenum. The ends of the tubes were tunneled subcutaneously and tied shut to establish obstructive jaundice. Biliary drainage was achieved without a second laparotomy by connecting the tubes with a 1-cm segment of a 24-gauge needle. Serum concentrations of total bilirubin (TB), glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), alkaline phosphatase (ALP), and albumin (Alb.) were measured before and after obstruction and decompression. TB, GOT, GPT and ALP increased and Alb. decreased 7 days after the onset of biliary obstruction. All values normalized 14 days after biliary drainage at the latest. Our model is reproducible and allows for evaluation of biliary decompression. Unlike previous models, it can be used for long-term investigation of chronic obstructive jaundice.


First derivative emission spectrofluorimetric method for the determination of LCZ696, a newly approved FDA supramolecular complex of valsartan and sacubitril in tablets.
LCZ696 (sacubitril/valsartan, Entresto™) is a therapy lately approved by United States Food and Drug Administration (US FDA) as a heart failure therapy. It is claimed to decrease the mortality rate and hospitalization for patients with chronic heart failure. This study is considered as the first report to investigate the fluorimetric behavior of sacubitril in addition to pursuing all the different conditions that may affect its fluorescence. Various conditions were studied, for example studying the effects of organized media, solvents and pH, which may affect the fluorescence behavior of sacubitril. For the simultaneous determination of the newly approved supramolecular complex of valsartan (VAL) and sacubitril (SAC) in their tablets, a sensitive and simple first derivative spectrofluorimetric method was developed. The method involved the measurement of native fluorescence at 416 nm and 314 nm (λex 249 nm) for VAL and SAC, respectively. The first (D1) derivative technique was applied to the emission data to resolve a partial overlap that appeared in their emission spectra. The proposed method was successfully applied for the assay of the two drugs in their supramolecular complex LCZ696 with no interference from common pharmaceutical additives. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines were followed in order to validate the proposed method.


Use of program logic models in the Southern Rural Access Program evaluation.
The Southern Rural Access Program (SRAP) evaluation team used program logic models to clarify grantees' activities, objectives, and timelines. This information was used to benchmark data from grantees' progress reports to assess the program's successes. This article presents a brief background on the use of program logic models--essentially charts or diagrams specifying a program's planned activities, objectives, and goals--for evaluating and managing a program. It discusses the structure of the logic models chosen for the SRAP and how the model concept was introduced to the grantees to promote acceptance and use of the models. The article describes how the models helped clarify the program's objectives and helped lead agencies plan and manage the many program initiatives and subcontractors in their states. Models also provided a framework for grantees to report their progress to the National Program Office and evaluators and promoted the evaluators' visibility and acceptance by the grantees. Program logics, however, increased grantees' reporting requirements and demanded substantial time of the evaluators. Program logic models, on balance, proved their merit in the SRAP through their contributions to its management and evaluation and by providing a better understanding of the program's initiatives, successes, and potential impact.


The X-Linked Intellectual Disability Protein IL1RAPL1 Regulates Dendrite Complexity.
Mutations and deletions of the interleukin-1 receptor accessory protein like 1 (IL1RAPL1) gene, located on the X chromosome, are associated with intellectual disability (ID) and autism spectrum disorder (ASD). IL1RAPL1 protein is located at the postsynaptic compartment of excitatory synapses and plays a role in synapse formation and stabilization. Here, using primary neuronal cultures and Il1rapl1-KO mice, we characterized the role of IL1RAPL1 in regulating dendrite morphology. In Il1rapl1-KO mice we identified an increased number of dendrite branching points in CA1 and CA2 hippocampal neurons associated to hippocampal cognitive impairment. Similarly, induced pluripotent stem cell-derived neurons from a patient carrying a null mutation of the IL1RAPL1 gene had more dendrites. In hippocampal neurons, the overexpression of full-length IL1RAPL1 and mutants lacking part of C-terminal domains leads to simplified neuronal arborization. This effect is abolished when we overexpressed mutants lacking part of N-terminal domains, indicating that the IL1RAPL1 extracellular domain is required for regulating dendrite development. We also demonstrate that PTPδ interaction is not required for this activity, while IL1RAPL1 mediates the activity of IL-1β on dendrite morphology. Our data reveal a novel specific function for IL1RAPL1 in regulating dendrite morphology that can help clarify how changes in IL1RAPL1-regulated pathways can lead to cognitive disorders in humans.SIGNIFICANCE STATEMENT Abnormalities in the architecture of dendrites have been observed in a variety of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. Here we show that the X-linked intellectual disability protein interleukin-1 receptor accessory protein like 1 (IL1RAPL1) regulates dendrite morphology of mice hippocampal neurons and induced pluripotent stem cell-derived neurons from a patient carrying a null mutation of IL1RAPL1 gene. We also found that the extracellular domain of IL1RAPL1 is required for this effect, independently of the interaction with PTPδ, but IL1RAPL1 mediates the activity of IL-1β on dendrite morphology. Our data reveal a novel specific function for IL1RAPL1 in regulating dendrite morphology that can help clarify how changes in IL1RAPL1-regulated pathways can lead to cognitive disorders in humans.


Elimination of Hepatitis B: Is It a Mission Possible?
Chronic hepatitis B virus (HBV) infection is a global public health issue. Although the disease cannot be cured effectively, disease management has been improved over the past decade. The introduction of potent nucleos(t)ide analogues (NAs) to suppress viral replication represented a giant leap in the control of this disease. It has been shown that tenofovir treatment, a potent NA, complements current immunoprophylaxis to diminish mother-to-infant transmission in pregnant women with a high viral load. For patients with chronic HBV infection, quantitative hepatitis B surface antigen is a useful tool to define inactive carriers and to guide antiviral therapy. Quantification of HBV mutants is also useful in predicting long-term outcomes more precisely than ever. The next challenge is how to achieve an HBV cure; although immunotherapy is a promising strategy, the current results from two clinical trials using therapeutic vaccines to induce HBV-specific immune response in patients with chronic HBV infection are disappointing. In the coming years, we are expecting to see a combination of therapeutic agents with various modes of action to complete the mission of HBV elimination.


Inter-identity autobiographical amnesia in patients with dissociative identity disorder.
A major symptom of Dissociative Identity Disorder (DID; formerly Multiple Personality Disorder) is dissociative amnesia, the inability to recall important personal information. Only two case studies have directly addressed autobiographical memory in DID. Both provided evidence suggestive of dissociative amnesia. The aim of the current study was to objectively assess transfer of autobiographical information between identities in a larger sample of DID patients. Using a concealed information task, we assessed recognition of autobiographical details in an amnesic identity. Eleven DID patients, 27 normal controls, and 23 controls simulating DID participated. Controls and simulators were matched to patients on age, education level, and type of autobiographical memory tested. Although patients subjectively reported amnesia for the autobiographical details included in the task, the results indicated transfer of information between identities. The results call for a revision of the DID definition. The amnesia criterion should be modified to emphasize its subjective nature.


Development of an immuno tandem mass spectrometry (iMALDI) assay for EGFR diagnosis.
The epidermal growth factor receptor (EGFR) is highly expressed in a variety of tumors, and is therefore an important biomarker for cancer diagnosis and a target for cancer therapy. We have developed a novel peptide-based immuno tandem mass spectrometry (iMALDI) diagnostic assay for highly sensitive, highly specific, and quantitative analysis of EGFR, which we have applied to the detection of the EGFR peptide in three cell lines and in a tumor biopsy sample. This assay is capable of detecting the EGFR target peptide bound to the antibody beads at attomole levels. The ability to directly obtain amino acid sequence data by MS/MS on any affinity-captured peptides provides specificity to this diagnostic technique. This avoids the problem of "false positives" which can result from the nonspecific binding that can occur with any affinity-based technique. The addition of stable-labeled versions of the target peptide (synthesized from stable-isotope coded amino acids) as internal standards allows absolute quantitation of the target protein.


[Biological properties of the causative agents of salmonellosis in young children].
The study of the biological properties of 161 Salmonella strains isolated from the feces and faucial mucus of 121 young children revealed that at the initial period of salmonellosis the occurrence of Salmonella strains in these materials was the same. Salmonella strains sensitive to antibiotics, as well as group C salmonellae, were shown to be capable of causing hospital infections. Statistically significant results revealed that Salmonella strains isolated from the nasopharynx were more virulent than those isolated simultaneously from the feces of the same children.


Study on the Integration Strategy of Online EOL Testing of Pure Electric Vehicle Power Battery.
This paper analyzes the electrical test items of the EOL testing line in automotive manufacturers. On this basis, this paper proposes and designs an integrated and automated testing strategy to deal with the problems of slow testing speed, high dependence on manual labor and low efficiency. This article mainly analyzes the various tests of the two main tests in battery EOL testing: Battery Management System (BMS) testing and electrical testing. We propose an innovative integrated solution based on various testing items, including the reception, transmission, and self-analysis of different UDS protocol messages, a unique automated electrical performance measurement scheme, and a requirement and logic design of an integrated software end based on Python. The experimental results of actual testing show that the implementation of the integrated strategy greatly reduces the complexity of the testing steps, improves the testing efficiency, and reduces errors caused by human operation.


Lignan Dimers from Forsythia viridissima Roots and Their Antiviral Effects.
Six new dimeric lignans (1-6) and one new lignan glycoside (16) were isolated from Forsythia viridissima roots along with nine known lignans (7-15). Spectroscopic analyses and chemical methods were used to determine these new structures and their absolute configurations. Among these compounds, dimatairesinol (1) and viridissimaols A-E (2-6) were assigned as dimers of dibenzylbutyrolactone analogues. Furthermore, the isolated compounds were evaluated for their antiviral activities against coxsackievirus B3 (CVB3) and human rhinovirus 1B (HRV1B). In these tests, compounds 12 and 15 showed antiviral effects against CVB3 infection with IC50 values of 15.4 and 36.4 μM, respectively, while 2, 3, 8, and 9 showed activities against HRV1B with IC50 values of 45.7, 47.5, 13.0, and 43.2 μM, respectively.


Flexor tendon graft through intact superficialis tendon.
During a 14-year period, the flexor profundus mechanism was reconstructed with a free tendon graft in 25 fingers. The graft was passed either through or alongside the intact superficialis tendon. Five of the profundus tendons had ruptured, and 21 had been severed. One patient was under 10 years of age and only three were over 21 years of age. The result was considered to be satisfactory if the finger flexed to 3.2 cm or less of the mid-palm, had at lease 20 degrees of voluntary flexion of the distal joint, and lacked no more than 30 degrees of extension of the proximal interphalangeal joint. Additionally, to be satisfactory, the combined loss of extension of the proximal interphalangeal and distal interphalangeal joints ahd to be 40 degrees or less for an index or middle finger, and 60 degrees or less for a ring or little finger. Using these criteria, 20 patients were satisfactory, four were unsatisfactory, and one was unchanged. Selected patients who are between the ages of 10 and 21 years will benefit from this operation, providing that the finger had limber joints and minimal scar, and the superficialis tendon flexes the proximal interphalangeal joint at least 80 degrees.


Phylogenetic analysis of Monascus and new species from honey, pollen and nests of stingless bees.
The genus Monascus was described by van Tieghem (1884) to accommodate M. ruber and M. mucoroides, two species with non-ostiolate ascomata. Species delimitation in the genus is still mainly based on phenotypic characters, and taxonomic studies that include sequence data are limited. The genus is of economic importance. Species are used in fermented Asian foods as food colourants (e.g. 'red rice' (ang-kak, angka)) and found as spoilage organisms, and recently Monascus was found to be essential in the lifecycle of stingless bees. In this study, a polyphasic approach was applied combining morphological characters, ITS, LSU, β-tubulin, calmodulin and RNA polymerase II second largest subunit sequences and extrolite data, to delimit species and to study phylogenetic relationships in Monascus. Furthermore, 30 Monascus isolates from honey, pollen and nests of stingless bees in Brazil were included. Based on this polyphasic approach, the genus Monascus is resolved in nine species, including three new species associated with stingless bees (M. flavipigmentosus sp. nov., M. mellicola sp. nov., M. recifensis sp. nov., M. argentinensis, M. floridanus, M. lunisporas, M. pallens, M. purpureus, M. ruber), and split in two new sections (section Floridani sect. nov., section Rubri sect. nov.). Phylogenetic analysis showed that the xerophile Monascus eremophilus does not belong in Monascus and monophyly in Monascus is restored with the transfer of M. eremophilus to Penicillium (P. eremophilum comb. nov.). A list of accepted and excluded Monascus and Basipetospora species is given, together with information on (ex-)types cultures and barcode sequence data.


Red cell enzyme deficiencies: from genetic basis to gene transfer.
Features of some of the more common erythrocyte enzyme deficiencies that may be relevant to possible future attempts to correct the deficiencies by gene transfer approaches are considered. The last few years have seen rapid progress in our understanding of the molecular basis of these diseases and the regulation of the genes underlying these deficiencies is now coming into focus. Animal models for some of the conditions are available and others can be produced by homologous recombination techniques. Although considerable improvements in gene transfer vectors and protocols are required, this research may lead eventually to gene replacement therapy for these severe conditions.


[Renal disorders induced by organic solvents].
Organic solvents are a class of chemical substances that are widely used in large volume in various manufacturing plants. Due to their high lipophilicity, organic solvents may produce physicochemical damage to renal glomeruli and tubuli. Many reports have been published abroad, though only a few in Japan, on organic solvent-induced nephropathy such as Goodpasture syndrome, a form of renal damage mediated by anti-basement membrane antibodies. This article reviews the epidemiological studies published in the literature and stresses that organic solvent exposure is one of the etiological factors involved in the development of chronic nephropathy. At present in Japan there are 60,000 patients with terminal renal failure undergoing hemodialysis, 50,000 young men placed under observation each year for abuse of organic solvents, and one million workers exposed to organic solvents in factories. Attention should be focused on the occurrence of renal damage due to organic solvents in Japan.


Survival After Sentinel Lymph Node Biopsy Compared with Axillary Lymph Node Dissection for Female Patients with T3-4c Breast Cancer.
For patients with cN0 and T1-2 breast cancer, sentinel lymph node biopsy (SLNB) can provide survival results equivalent to axillary lymph node dissection (ALND). However, whether it can be performed on T3-4c patients is still controversial. Female patients diagnosed with cN0, T3-4c, and M0 breast cancer from 2004 to 2019 were identified using the surveillance, epidemiology and end results (SEER) database and divided into 2 groups, the SLNB group (1-5 regional lymph nodes examined) and the ALND group (≥10 regional lymph nodes examined). Finally, only those with pN0 disease were included in the SLNB group. The baseline differences in clinicopathological characteristics between groups were eliminated by propensity score matching (PSM). We also conducted subgroup analyses according to age, overall TNM stage, breast cancer subtypes, surgical approaches, radiation therapy, and chemotherapy. The primary endpoint was survival. With a mean follow-up of 75 months, a total of 186 deaths were reported among 864 patients. The overall survival (OS) and breast cancer-specific survival (BCSS) in the SLNB group were 78.2% and 87.5%, respectively, and that in the ALND group were 78.7% and 87.3%, respectively. The unadjusted hazard ratio (HR) for OS and BCSS in the SLNB group (vs. the ALND group) was 0.922 (95% CI, 0.691-1.230, P = .580) and 0.874 (95% CI, 0.600-1.273, P = .481), respectively. Besides, the OS and BCSS between the 2 groups were also similar in all subgroup analyses. SLNB may be performed on female patients with cN0, T3-4c, and M0 breast cancer.


Optimizing acceleration-based ethograms: the use of variable-time versus fixed-time segmentation.
Animal-borne accelerometers measure body orientation and movement and can thus be used to classify animal behaviour. To univocally and automatically analyse the large volume of data generated, we need classification models. An important step in the process of classification is the segmentation of acceleration data, i.e. the assignment of the boundaries between different behavioural classes in a time series. So far, analysts have worked with fixed-time segments, but this may weaken the strength of the derived classification models because transitions of behaviour do not necessarily coincide with boundaries of the segments. Here we develop random forest automated supervised classification models either built on variable-time segments generated with a so-called 'change-point model', or on fixed-time segments, and compare for eight behavioural classes the classification performance. The approach makes use of acceleration data measured in eight free-ranging crab plovers Dromas ardeola. Useful classification was achieved by both the variable-time and fixed-time approach for flying (89% vs. 91%, respectively), walking (88% vs. 87%) and body care (68% vs. 72%). By using the variable-time segment approach, significant gains in classification performance were obtained for inactive behaviours (95% vs. 92%) and for two major foraging activities, i.e. handling (84% vs. 77%) and searching (78% vs. 67%). Attacking a prey and pecking were never accurately classified by either method. Acceleration-based behavioural classification can be optimized using a variable-time segmentation approach. After implementing variable-time segments to our sample data, we achieved useful levels of classification performance for almost all behavioural classes. This enables behaviour, including motion, to be set in known spatial contexts, and the measurement of behavioural time-budgets of free-living birds with unprecedented coverage and precision. The methods developed here can be easily adopted in other studies, but we emphasize that for each species and set of questions, the presented string of work steps should be run through.


GSK3beta inhibitor-induced dental mesenchymal stem cells regulate ameloblast differentiation.
Epithelial-mesenchymal interactions are extremely important in tooth development and essential for ameloblast differentiation, especially during tooth formation. We aimed to identify the type of mesenchymal cells important in ameloblast differentiation. We used two types of cell culture systems with chambers and found that a subset of debtal mesenchimal cells is important for the differentiatiuon of dental spithelial cells into ameloblasts. Further, we induced dental pulp stem cell-like cells from dental pulp stem cells using the small molecule compound BIO ( a GSK-3 inhibitor IX) to clarify the mechanism involved in ameloblast differentiation induced by dental pulp stem cells. The BIO-induced dental pulp cells promoted the expression of mesenchymal stem cell markers Oct3/4 and Bcrp1. Furthermore, we used artificial dental pulp stem cells induced by BIO to identify the molecules expressed in dental pulp stem cells required for ameloblast differentiation. Panx3 expression was induced in the dental pulp stem cell through interaction with the dental epithelial cells. In addition, ATP release from cells increased in Panx3-expressing cells. We also confirmed that ATP stimulation is accepted in dental epithelial cells. These results showed that the Panx3 expressed in dental pulp stem cells is important for ameloblast differentiation and that ATP release by Panx3 may play a role in epithelial-mesenchymal interaction.


[Fever of unknown origin in rheumatology].
Fever occurs frequently in several rheumatic disorders, and remains a diagnostic and therapeutic challenge to the rheumatologist in spite of the great advances made in the fields of medical diagnosis and technology. It can be the initial symptom of a rheumatic disease, but it can also be the expression of a disease flare, of an infectious complication, of a secondary neoplasm or be of iatrogenic origin. The pathogenesis of fever in rheumatic diseases is still quite unclear; however, recently IL-1, IL-6 and other endogenous pyrogens, such as Tumor necrosis factor, have been shown to play a pivotal role in causing pyrexia during inflammatory conditions. In the presence of longstanding fever of unknown origin, it is mandatory to carry out a number of selected appropriate examinations with the patient's informed consent. The aim of this study was to review the frequency and the characteristics of fever at the onset and in the course of a number of rheumatic diseases, such as chronic inflammatory arthropathies, connective tissue diseases, reactive arthritis and dysmetabolic arthropathies. Finally, we have reviewed the features of fever during arthritis complicating non-rheumatic diseases and during adverse reactions related to drugs that are widely prescribed for the treatment of rheumatic disorders.


Aseptic polyurethane carotid patch rejection: complication, allergy or miraculous healing?
Carotid endarterectomy plays an important role in the prevention of ischemic stroke; patching could reduce the risk of intra- and postoperative complications and late restenosis among primary closure. Materials actually available for the patch tailoring are synthetic or biological: which is the best is still debated. We present the case of a polyurethane (PU) carotid patch rejection three years after its implant, with no evident arterial discontinuity and no sign of infection. Histopathological analysis on hematoxylin-eosin stained sections of the regenerated arterial wall tissue removed revealed plasma cell infiltration and clusters of foreign body giant cells. PU patch rejection has been seldom described in literature. This is an unusual late complication that should be considered at long-term follow-up evaluation of these patients.


Preparation, Structural Determination, and Characterization of Electronic Properties of Bis-silylated and Bis-germylated Lu3 N@Ih -C80.
Bis-silylated and bis-germylated derivatives of Lu3 N@Ih -C80 (3, 4, 5) were successfully synthesized by the photochemical addition of disiliranes 1 a, 1 b or digermirane 2, and fully characterized by spectroscopic, electrochemical, and theoretical studies. Interestingly, digermirane 2 reacts more efficiently than disiliranes 1 a and 1 b because of its good electron-donor properties and lower steric hindrance around the Ge-Ge bond. The 1,4-adduct structures of 3, 4, 5 were unequivocally established by single-crystal X-ray crystallographic analyses. The electrochemical and theoretical studies reveal that the energy gaps between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of the 1,4-adducts are remarkably smaller than those of Lu3 N@Ih -C80 , because the electron-donating groups effectively raise the HOMO levels. It is also observed that germyl groups are slightly more electron-donating than the silyl groups on the basis of the redox properties and the HOMO-LUMO energies of 4 and 5. Bis-silylation and bis-germylation are effective and versatile methods for tuning the electronic characteristics of endohedral metallofullerenes.


Platelet glycoprotein VI-related clinical defects.
Human patients with defects associated with the platelet collagen receptor, glycoprotein (GP)VI, are rare and usually described as having a mild bleeding disorder. However, here we review clinical profiles of patients with familial or acquired GPVI defects, revealing the bleeding defect is often severe and associated with immune dysfunction. GPVI is a member of the immunoreceptor family, and co-expressed on platelets with Fc receptor gamma-chain (FcRgamma). Ligand binding to GPVI leads to activation of platelet integrins, in particular alpha(IIb)beta(3) that mediates platelet aggregation; and activation of endogenous platelet metalloproteinases resulting in ectodomain shedding and release of a soluble GPVI fragment. Increasing evidence supports the functional importance of GPVI/FcRgamma in thrombus formation at arterial shear rates, and expression levels of platelet GPVI may be a marker of thrombotic risk. Over the past 20 years, patients have been reported with GPVI-related defects involving: (i) an acquired deficiency, resulting from (a) anti-GPVI autoantibodies or (b) other causes; or (ii) a congenital deficiency, where (c) GPVI is not expressed or (d) is expressed in a dysfunctional form with defective signalling to alpha(IIb)beta(3). Clinical consequences of GPVI-related defects may be uniquely informative about the role of platelet GPVI in health and disease.


Detecting gene expression in buccal mucosa in subjects with asthma versus subjects without asthma.
Differences in mRNA expression for inflammatory markers have been observed between subjects with asthma vs. controls and in relation to corticosteroid response. However, these studies utilized methods (e.g., bronchoscopy) that are too invasive to be used routinely in children and in the clinic. The primary purpose of this study was to determine the feasibility of obtaining RNA of adequate quantity and quality from buccal mucosa of children and adults for gene expression studies. Secondly, this study aimed to determine whether gene expression patterns in buccal mucosa are similar to those that have been observed in respiratory epithelium. We enrolled 94 subjects with and without asthma between 5 and 54 years of age. Relative gene expression in buccal mucosa was determined with quantitative RT-PCR for the following genes: CCL2, EDN1, FKBP5, IL8, IFNAR2, NFKB1, RELA, SERPINB2, DENND1B, HRH1, ICAM1, ORMDL3, NR3C1, CLCA1, CRHR1, MUC5B, FCER2, POSTN, GAPDH, PPIA. mRNA Expression of the following genes was detected in buccal mucosa: CCL2, EDN1, FKBP5, IL8, IFNAR2, NFKB1, RELA, SERPINB2, DENND1B, HRH1, ICAM1, ORMDL3, NR3C1, GAPDH, PPIA. HRH1 was differentially expressed in adults with asthma vs. controls (p = 0.04), and EDN1 was differentially expressed in children with asthma vs. controls 12-18 years old (p = 0.03). A similar trend for HRH1 was observed in children 12-18 years old. Buccal mucosa sampling is a reliable method for detecting changes in gene expression in patients with asthma. This non-invasive technique may serve as a valuable tool for diagnosing asthma and evaluating therapeutic response.


Effects of smoking specified as cigarettes per day and maternal body mass index on hypertensive disorders of pregnancy.
We have previously described the prevalence in pregnancy of hypertension, proteinuria, oedema and preeclampsia/eclampsia according to maternal body mass index (BMI) and smoking status. We found that these disorders were less frequent among smoking women. To investigate whether this relationship is causal or a chance finding, we here present an analysis according to BMI and smoking specified according to the number of cigarettes consumed per day. Data were from the German Perinatal Survey of 1998-2000. We classified women by BMI as underweight (BMI<18.5 kg/m2), normal weight (BMI 18.5-24.99 kg/m2), overweight (25.0-29.99 kg/m2), or obese (BMI≥30 kg/m2). Smoking was categorised as being a non-smoker or smoking 1-7, 8-14 or ≥ 15 cigarettes per day. Datasets from 433 669 singleton pregnancies with information on maternal BMI and smoking were included in the analysis. In all BMI categories hypertension, moderate to severe oedema, and preeclampsia/eclampsia became less prevalent with increasing maternal cigarette consumption. Dose-dependence was not convincing for proteinuria.Dose-dependence in the relationship between smoking and hypertensive disorders of pregnancy argues against a chance finding and for a causal relationship.


Clinical and histopathological review of 24 cases of sarcoma of the corpus uteri.
The Authors report their experience in 24 cases of sarcoma of the corpus uteri observed between 1971 and 1981. After pointing out that their experiences confirm the extreme rareness of these neoplastic forms they dwell on diagnostic, prognostic and histologic criteria of classification and conclude that sarcomas of the corpus uteri - mostly leiomyosarcomas - of fibromatous origin - are always potentially very malignant with low 5-year survival rates despite combined treatment with surgery + radiotherapy + antiblastic therapy.


The electron affinity of the uranium atom.
The results of a combined experimental and computational study of the uranium atom are presented with the aim of determining its electron affinity. Experimentally, the electron affinity of uranium was measured via negative ion photoelectron spectroscopy of the uranium atomic anion, U-. Computationally, the electron affinities of both thorium and uranium were calculated by conducting relativistic coupled-cluster and multi-reference configuration interaction calculations. The experimentally determined value of the electron affinity of the uranium atom was determined to be 0.309 ± 0.025 eV. The computationally predicted electron affinity of uranium based on composite coupled cluster calculations and full four-component spin-orbit coupling was found to be 0.232 eV. Predominately due to a better convergence of the coupled cluster sequence for Th and Th-, the final calculated electron affinity of Th, 0.565 eV, was in much better agreement with the accurate experimental value of 0.608 eV. In both cases, the ground state of the anion corresponds to electron attachment to the 6d orbital.


Evaluation and medical management of benign prostatic hyperplasia.
Benign prostatic hyperplasia (BPH) is common among aging men. Untreated BPH may lead to complications including urinary tract infection, acute urinary retention, and obstructive nephropathy. Diagnosing BPH can be challenging because lower urinary tract symptoms are found in conditions other than BPH, and prostate size correlates poorly with symptoms of obstruction. Nonetheless, a careful medical history and physical examination, along with prudent use of diagnostic tests, can yield an accurate diagnosis. We review the evaluation of men with suspected BPH and indications for referral to a urologist for invasive therapy. We also review supporting evidence and treatment considerations for saw palmetto and the 2 major classes of prescription medications, alpha1-adrenergic antagonists and 5alpha-reductase inhibitors.


Category length produces an inverted-U discriminability function in episodic recognition memory.
Four experiments used signal detection analyses to assess recognition memory for lists of words consisting of differing numbers of exemplars from different semantic categories. The results showed that recognition memory performance, measured by d(a), (a) increased as category length (CL, the number of study-list items selected from the same semantic category) increased from 1 to 8 but then decreased as CL further increased from 8 to 14, (b) was greater when 2 studied items from the same category occurred back to back, rather than being separated by 5-11 items from other categories, and (c) was greater for the first studied 2 exemplars than for the last studied 2 exemplars from blocked categories with CLs of 8 or 14. For all CLs, all z-coordinate receiver operating characteristic (z-ROC) functions were linear with slopes significantly less than 1.0, and none had a significant quadratic component. These results pose a challenge for three major classes of recognition memory models: item-noise, context-noise, and dual-process models.


[Clinical and pathophysiologic problems associated with smoke inhalation injury].
Smoke inhalation injury is one of the primary determinants of survival following major burn injury. The primary site of injury in smoke inhalation appears to be the small airway rather than the alveoli, and thus small airway occlusion caused by edema and pseudomembrane formation are the primary mechanisms of progressive hypoxia. Ventilation-perfusion (VA/Q) alterations after smoke inhalation are characterized by increased blood flow to low VA/Q compartments, although an increase in true shunt (VA/Q = 0) was not a consistent finding. This differs considerably from most adult respiratory distress syndrome (ARDS) patients or oleic acid-induced lung edema models, in which an increase in true shunt is the major mechanism of hypoxia. Such differences lead to different responses to nitric oxide (NO) inhalation therapy, and NO does not improve oxygenation and outcome in patients with smoke inhalation injury. In the treatment of inhalation injury, meticulous removal of pseudomembrane by fiberoptic bronchoscopy is essential, the use of high concentrations of oxygen should be avoided since it can cause absorption atelectasis. High-frequency percussive ventilation is a suitable treatment for inhalation injury, as it improves oxygenation and facilitates removal of pseudomembrane.


Three-dimensional dose reconstruction of breast cancer treatment using portal imaging.
In this study, we present an algorithm for three-dimensional (3-D) dose reconstruction using portal images obtained with an electronic portal imaging device (EPID). For this purpose an algorithm for 2-D dose reconstruction, which was previously developed in our institution, was adapted. The external contour of the patient was used to correct for absorption of primary photons, but the presence of inhomogeneities was not taken into account. The accuracy of the algorithm was determined by irradiating two anthropomorphic breast phantoms with 6 MV photons. The dose values derived from portal images were compared with results from 3-D dose calculations, which, in turn, were verified with data obtained with an ionization chamber and film dosimetry. It was found that the application of contour information significantly improves the accuracy of 2-D dose reconstruction. If the total dose at the isocenter plane resulting from all treatment beams is reconstructed, the average deviation from the planned dose is 0.1%+/-1.7% (1 SD). If contour information is not available, the differences increase up to +/-20% for the individual beams. In that case, the dose can only be reconstructed with reasonable accuracy when (nearly) opposing beams are used. The average deviation of the 3-D reconstructed dose from the planned dose in the irradiated volume is 1.4%+/-5.4% (1 SD). If the irradiated volume is enclosed by planes less than 5 cm distant from the isocenter plane, then the average deviation is only 0.5%+/-3.4% (1 SD). It can be concluded that the proposed algorithm for a 3-D dose reconstruction allows a determination of the dose at the isocenter plane and the dose-volume histogram with an accuracy acceptable for an independent verification of the treatment.


False-positive urine opiate screening associated with fluoroquinolone use.
To review the literature regarding false-positive urine opiate screens associated with the use of fluoroquinolones. Literature was identified using MEDLINE (1966-February 2004), EMBASE, and all EBM Reviews with the terms quinolones, substance abuse detection, opiates, cross-reactions, false-positive reactions, and each fluoroquinolone. Article references were also reviewed. Various settings utilize the practice of screening for drugs of abuse, such as opiates. These screening procedures can impact aspects of one's life, such as employment; therefore, accuracy is of the utmost importance. Two clinical trials were evaluated which showed that certain fluoroquinolone antibiotics cross-react with some of the commonly used urine opiate screening immunoassays. This suggests the importance of verifying positive results in instances where one's livelihood can be affected. Fluoroquinolones can cause false-positive urine opiate screens. Clinicians should be aware of this potential interaction and may need to verify positive results.


[Application of quantitative electroencephalogram monitoring in evaluating thrombolytic effect of acute cerebral infarction].
To investigate the value of quantitative electroencephalography (qEEG) in the evaluation of thrombolytic efficacy in acute cerebral infarction. A prospective cohort study was conducted. Ninety-four patients with acute cerebral infarction who received intravenous thrombolysis admitted to the department of emergency of Qinhuangdao First Hospital from October 2019 to September 2020 were enrolled. The relative energy values of δ, θ, α and β waves in qEEG before and 2 hours, 24 hours and 7 days after intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis were dynamically monitored, and the power ratio index [DTABR, DTABR = (δ+θ)/(α+β)] was calculated. The National Institutes of Health stroke scale (NIHSS) score was also recorded. The reduction of NIHSS score ≥ 3 or the disappearance of neurological symptoms were regarded as effective thrombolytic therapy. The changes of DTABR before and after thrombolysis in patients with effective and ineffective thrombolysis were analyzed, and the correlation between DTABR and NIHSS score was analyzed by Pearson method. A total of 94 patients were enrolled, including 64 males and 30 females. The average age was (61.71±10.11) years from 36 to 89 years old. Thrombolysis was effective in 57 cases and ineffective in 37 cases. Compared with before thrombolysis, DTABR of the effective group was significantly decreased at 2 hours, 24 hours and 7 days after thrombolysis (left cerebral infarction: 1.87±1.45, 1.59±0.88, 1.58±0.90 vs. 3.82±2.60; right cerebral infarction: 1.55±0.57, 1.41±0.50, 1.35±0.44 vs. 3.20±1.63, all P < 0.05). DTABR did not change or increase significantly at 2 hours, 24 hours and 7 days after thrombolysis compared with before thrombolysis (left cerebral infarction: 3.56±2.57, 3.48±2.19, 3.54±2.50 vs. 3.11±1.62; right cerebral infarction: 5.29±3.93, 5.33±3.94, 5.19±4.52 vs. 4.73±2.43, all P > 0.05). Pearson correlation analysis showed a significant positive correlation between DTABR and NIHSS score in patients with acute cerebral infarction (r = 0.691, P < 0.01). The quantitative index of qEEG, DTABR, can accurately and quickly monitor the process of thrombolysis in acute cerebral infarction, and can effectively evaluate the effect of thrombolysis in patients.


Forgone care among middle aged and elderly with chronic diseases in China: evidence from the China Health and Retirement Longitudinal Study Baseline Survey.
In general, published studies analyse healthcare utilisation, rather than foregone care, among different population groups. The assessment of forgone care as an aspect of healthcare system performance is important because it indicates the gap between perceived need and actual utilisation of healthcare services. This study focused on a specific vulnerable group, middle-aged and elderly people with chronic diseases, and evaluated the prevalence of foregone care and associated factors among this population in China. Data were obtained from a nationally representative household survey of middle-aged and elderly individuals (≥45 years), the China Health and Retirement Longitudinal Study, which was conducted by the National School of Development of Peking University in 2013. Descriptive statistics were used to analyse sample characteristics and the prevalence of foregone care. Andersen's healthcare utilisation and binary logistic models were used to evaluate the determinants of foregone care among middle-aged and elderly individuals with chronic diseases. The prevalence of foregone outpatient and inpatient care among middle-aged and elderly people was 10.21% and 6.84%, respectively, whereas the prevalence of foregone care for physical examinations was relatively high (57.88%). Predisposing factors, including age, marital status, employment, education and family size, significantly affected foregone care in this population. Regarding enabling factors, individuals in the highest income group reported less foregone inpatient care or physical examinations compared with those in the lowest income group. Social healthcare insurance could significantly reduce foregone care in outpatient and inpatient situations; however, these schemes (except for urban employee medical insurance) did not appear to have a significant impact on foregone care involving physical examinations. In China, policy-makers may need to further adjust healthcare policies, such as health insurance schemes, and improve the hierarchical medical system, to promote reduction in foregone care and effective utilisation of health services.


Is cervical cancer in Ethiopian women the result of a sexually transmitted disease?
Cervical cancer is the most prevalent cancer of women in Ethiopia and sexually transmitted diseases are highly prevalent in the country. In order to establish a possible cause and effect relationship between sexually transmitted diseases and cervical cancer, likely etiological socio-economic factors for these two conditions have been analysed. While residence, income, age at first coitus, age, number of sexual partners, marital status/profession and duration of sexual life affect both conditions, there is a significant difference between the most important factors in the etiology of the separate conditions. Serological testing shows a high prevalence of gonorrhea, which was used as a marker of STD. Women with gonococcal antibodies had evidence of increased exposure to other STD; there was no such correlation for cervical cancer. Our results indicate that STD per se is unlikely to be a primary cause of CC in Ethiopia. It appears probable that the etiology of CC in Ethiopia is multifactorial. Early exposure of the immature cervical epithelium to STD, the trauma of repeated childbirth, and multiple sexual partners in women whose defence factors are impaired by chronic malnutrition, add up to a major medico-socio-economic factor. The evidence presented here suggests that CC in Ethiopia is not so much the result of a sexually transmitted disease, but a sociosexual disease.


Orbitide Composition of the Flax Core Collection (FCC).
The flax (Linum usitatissimum L.) core collection (FCC) was regenerated in Saskatoon, Saskatchewan and Morden, Manitoba in 2009. Seed orbitide content and composition from successfully propagated plants of 391 accessions were analyzed using high-throughput analyses employing high-performance liquid chromatography (HPLC) with reverse-phase monolithic HPLC columns and diode array detection (HPLC-DAD). Seed from plants regenerated in Morden had comparatively higher orbitide content than those grown in Saskatoon. Concentrations of orbitides encoded by contig AFSQ01016651.1 (1, 3, and 8) were higher than those encoded by AFSQ01025165.1 (6, 13, and 17) for most accessions in both locations. The cultivar 'Primus' from Poland and an unnamed accession (CN 101580 of unknown origin) exhibited the highest ratio of sum of [1,3,8] to a sum of [6,13,17]. Conversely, the lowest orbitide concentrations and ratio of [1,3,8] to [6,13,17] were observed in cultivars 'Hollandia' and 'Z 11637', both from The Netherlands. Orbitide expression did not correlate with flax morphological and other chemical traits.


Minimally invasive colon resection (laparoscopic colectomy).
The successful application of laparoscopic surgery to gallbladder disease and acute appendicitis has encouraged clinical investigators to develop this technology further in an attempt to manage other pathologic disorders of the gastrointestinal (GI) tract. After gaining experience with various laparoscopic skills while performing clinical biliary tract surgery, appendectomy and then in a controlled animal laboratory, a pilot program for laparoscopic colonic surgery was initiated. Twenty patients with ages ranging from 43 to 88 years (mean age of 57 years) underwent laparoscope-assisted colon resection. In nine patients, a right hemicolectomy was performed and a sigmoid colectomy in eight. A low anterior resection, Hartman's procedure, and abdominal perineal resection were each performed in one patient. Indications for surgery were large villous adenomas or adenocarcinoma in 12, diverticular disease in 5, sigmoid endometrioma in 1, cecal volvulus in 1, and inflammatory bowel disease in 1. Eighty percent of patients were able to tolerate a liquid diet on the first postoperative day and 70% were discharged within 96 h eating a regular diet and having normal bowel movements. There were three operative complications: a 3 unit postoperative bleed managed without surgery, one patient developed marked edema of the rectosigmoid anastomosis requiring decompression with a rectal tube, and one individual with metastatic colon cancer was operated on for a mechanical small bowel obstruction 7 days after the initial laparoscopic surgery. Although laparoscope-assisted colonic surgery may still be considered a procedure in evolution, we feel that in time it has the potential to be as popular as laparoscopic cholecystectomy.


Hemimethylated duplex DNAs prepared from 5-azacytidine-treated cells.
Duplex heavy-light (HL) DNAs synthesized in the presence of brdUrd and methylation inhibitors were separated from bulk cellular DNA by CsCl density gradient centrifugation and analysed for 5-methylcytosine (5mC) contents by HPLC. DNAs synthesized in the presence of 5 mM ethionine or 2 mg/ml cycloleucine were not detectably hypomethylated, was undermethylated with respect to control DNA. The heavy, or H-strand, in which up to 5% of the cytosine residues were replaced by intact 5-azacytosine, was undermethylated and the HL duplex DNA was therefore strand asymmetrically methylated. This duplex DNA served as an efficient substrate for a crude DNA methyltransferase preparation which transferred the methyl group from S-adenosylmethionine specifically into cytosine residues within the hypomethylated H strand. Increasing levels of incorporated 5-azacytosine inhibited the action of the methyltransferase suggesting that incorporation of 5-azacytosine into DNA may be responsible for the inhibitory effect of 5-azacytidine on DNA methylation.


Susceptibility to Klebsiella pneumonaie infection in collaborative cross mice is a complex trait controlled by at least three loci acting at different time points.
Klebsiella pneumoniae (Kp) is a bacterium causing severe pneumonia in immunocompromised hosts and is often associated with sepsis. With the rise of antibiotic resistant bacteria, there is a need for new effective and affordable control methods; understanding the genetic architecture of susceptibility to Kp will help in their development. We performed the first quantitative trait locus (QTL) mapping study of host susceptibility to Kp infection in immunocompetent Collaborative Cross mice (CC). We challenged 328 mice from 73 CC lines intraperitoneally with 104 colony forming units of Kp strain K2. Survival and body weight were monitored for 15 days post challenge. 48 of the CC lines were genotyped with 170,000 SNPs, with which we mapped QTLs. CC lines differed significantly (P < 0.05) in mean survival time, between 1 to 15 days post infection, and broad sense heritability was 0.45. Distinct QTL were mapped at specific time points during the challenge. A QTL on chromosome 4 was found only on day 2 post infection, and QTL on chromosomes 8 and 18, only on day 8. By using the sequence variations of the eight inbred strain founders of the CC to refine QTL localization we identify several candidate genes. Host susceptibility to Kp is a complex trait, controlled by multiple genetic factors that act sequentially during the course of infection.


Selection and Validation of Reference Genes for Quantitative Real-Time Polymerase Chain Reaction Studies in Mossy Maze Polypore, Cerrena unicolor (Higher Basidiomycetes).
With its ability to produce ligninolytic enzymes such as laccases, white-rot basidiomycete Cerrena unicolor, a medicinal mushroom, has great potential in biotechnology. Elucidation of the expression profiles of genes encoding ligninolytic enzymes are important for increasing their production. Quantitative real-time polymerase chain reaction (qPCR) is a powerful tool to study transcriptional regulation of genes of interest. To ensure accuracy and reliability of qPCR analysis of C. unicolor, expression levels of seven candidate reference genes were studied at different growth phases, under various induction conditions, and with a range of carbon/nitrogen ratios and carbon and nitrogen sources. The stability of the genes were analyzed with five statistical approaches, namely geNorm, NormFinder, BestKeeper, the ΔCt method, and RefFinder. Our results indicated that the selection of reference genes varied with sample sets. A combination of four reference genes (Cyt-c, ATP6, TEF1, and β-tubulin) were recommended for normalizing gene expression at different growth phases. GAPDH and Cyt-c were the appropriate reference genes under different induction conditions. ATP6 and TEF1 were most stable in fermentation media with various carbon/nitrogen ratios. In the fermentation media with various carbon or nitrogen sources, 18S rRNA and GAPDH were the references of choice. The present study represents the first validation analysis of reference genes in C. unicolor and serves as a foundation for its qPCR analysis.


Usefulness of a novel ultrasound transducer for continuous monitoring treadmill exercise echocardiography to assess coronary artery disease.
The feasibility of a novel ultrasound probe, which can be attached to the left ventricular (LV) apex chest wall and allows free rotation around its long axis direction for the continuous monitoring of LV wall motion, was tested. There were 36 subjects who had coronary artery disease (CAD). By attaching a novel ultrasound probe to the chest wall, the LV apical views were recorded during treadmill exercise stress echocardiography (Echo). The continuous monitoring of LV wall motion was satisfactorily feasible in 30 of 36 patients. The visualization rate of the overall LV segments was higher at rest (90%) compared to that during peak exercise (77%). The segments were better visualized in apical portions (90-100%) than in mid (77-96%) or basal portions (68-87%). The sensitivity, specificity, and accuracy for detecting CAD were 61, 100 and 77%, respectively. The wall motion score index 3 and 6 min after exercise decreased significantly compared to those at peak exercise. The number of segments with dyssynergy was highest at the peak exercise. Ischemic ST-T depression on electrocardiography was observed only at peak stress periods. Continuous monitoring treadmill exercise Echo using a novel ultrasound probe seems feasible for the non-invasive and physiological assessment of CAD.


Expansion and Purification Are Critical for the Therapeutic Application of Pluripotent Stem Cell-Derived Myogenic Progenitors.
Recent reports have documented the differentiation of human pluripotent stem cells toward the skeletal myogenic lineage using transgene- and cell purification-free approaches. Although these protocols generate myocytes, they have not demonstrated scalability, safety, and in vivo engraftment, which are key aspects for their future clinical application. Here we recapitulate one prominent protocol, and show that it gives rise to a heterogeneous cell population containing myocytes and other cell types. Upon transplantation, the majority of human donor cells could not contribute to myofiber formation. As a proof-of-principle, we incorporated the inducible PAX7 lentiviral system into this protocol, which then enabled scalable expansion of a homogeneous population of skeletal myogenic progenitors capable of forming myofibers in vivo. Our findings demonstrate the methods for scalable expansion of PAX7+ myogenic progenitors and their purification are critical for practical application to cell replacement treatment of muscle degenerative diseases.


[Unconditioned logistic regression and sample size: a bibliographic review].
Unconditioned logistic regression is a highly useful risk prediction method in epidemiology. This article reviews the different solutions provided by different authors concerning the interface between the calculation of the sample size and the use of logistics regression. Based on the knowledge of the information initially provided, a review is made of the customized regression and predictive constriction phenomenon, the design of an ordinal exposition with a binary output, the event of interest per variable concept, the indicator variables, the classic Freeman equation, etc. Some skeptical ideas regarding this subject are also included.


Machine Learning and Data Analytics in Pervasive Health.
This accompanying editorial provides a brief introduction to this focus theme, focused on "Machine Learning and Data Analytics in Pervasive Health". The innovative use of machine learning technologies combining small and big data analytics will support a better provisioning of healthcare to citizens. This focus theme aims to present contributions at the crossroads of pervasive health technologies and data analytics as key enablers for achieving personalised medicine for diagnosis and treatment purposes. A call for paper was announced to all participants of the "11th International Conference on Pervasive Computing Technologies for Healthcare", to different working groups of the International Medical Informatics Association (IMIA) and European Federation of Medical Informatics (EFMI) and was published in June 2017 on the website of Methods of Information in Medicine. A peer review process was conducted to select the papers for this focus theme. Four papers were selected to be included in this focus theme. The paper topics cover a broad range of machine learning and data analytics applications in healthcare including detection of injurious subtypes of patient-ventilator asynchrony, early detection of cognitive impairment, effective use of small data sets for estimating the performance of radiotherapy in bladder cancer treatment, and the use negation detection in and information extraction from unstructured medical texts. The use of machine learning and data analytics technologies in healthcare is facing a renewed impulse due to the availability of large amounts and new sources of human behavioral and physiological data, such as that captured by mobile and pervasive devices traditionally considered as nonmainstream for healthcare provision and management.


Predominant mycotoxins, mycotoxigenic fungi and climate change related to wine.
Wine is a significant contributor to the economies of many countries. However, the commodity can become contaminated with mycotoxins produced by certain fungi. Most information on mycotoxins in wine is from Spain, Italy and France. Grapes can be infected by mycotoxigenic fungi, of which Aspergillus carbonarius producing ochratoxin A (OTA) is of highest concern. Climate is the most important factor in determining contamination once the fungi are established, with high temperatures being a major factor for OTA contamination: OTA in wine is at higher concentrations in warmer southern Europe than northern. Contamination by fumonisins is a particular concern, related to Aspergillus niger producing these compounds and the fungus being isolated frequently from grapes. Aflatoxins can be present in wine, but patulin is seldom detected. Alternaria mycotoxins (e.g. alternariol) have been frequently observed. There are indications that T-2 toxin may be common. Also, the combined effects of mycotoxins in wine require consideration. No other mycotoxins are currently of concern. Accurate fungal identifications and mycotoxin detection from the fungi are important and a consideration of practical methods are required. There is a diversity of wines that can be contaminated (e.g. red, white, sweet, dry and fortified). The occurrence of OTA is higher in red and sweet than white wines. Steps to control mycotoxins in wine involve good agriculture practices. The effect of climate change on vines and mycotoxins in wine needs urgent consideration by well-constructed modelling studies and expert interpretation of existing data. Reliable models of the effect of climate change on vines is a priority: the health of vines affects mycotoxin contamination. A modelling study of OTA in grapes at higher temperatures over 100years is required. Progress has been made in reducing OTA in wine. The other mycotoxins require consideration and the effects of climate change will become crucial.


Does dietary salt increase the risk for progression of kidney disease?
Due to the inconsistent observations and suboptimal quality of the study designs, there is insufficient clinical evidence to suggest that increased salt intake may adversely modify the rate of progression of kidney disease. However, there is experimental evidence to suggest a link between increased salt exposure and kidney tissue injury. Further clinical trials are needed to evaluate the relationship between dietary salt and risk for progression of chronic kidney disease.


Non-IgE-mediated food allergy during infancy.
Is to highlight the recent advances in the diagnosis and management of non-IgE-mediated food allergy which is a common consideration in primary care and in allergy and gastroenterology subspecialty practices evaluating infants. The review focuses on food protein-induced enterocolitis syndrome (FPIES) and includes other non-IgE-mediated food allergy in nursing infants, food protein-induced allergic proctocolitis, and food protein-induced enteropathy. For FPIES, we review the 2017 International Consensus Guidelines that provided the first comprehensive framework for its diagnosis and management and that were supplemented by a 2019 position paper by the European Academy of Allergy and Clinical Immunology. We review recent reports that support FPIES as a diagnosis of primarily infants, highlight the problem of delayed diagnosis, reveal the need for improved biomarkers, emphasize new and common food protein triggers, and identify new approaches for evaluation of tolerance. As formal diagnostic criteria for non-IgE-mediated food allergies are defined and prevalence data is increasingly reported, there will likely be improved recognition and evaluation of these conditions. Currently, large-scale prospective studies evaluating their incidence and prevalence, associated risk factors, and natural history are needed. Although avoidance of the suspected trigger food protein remains the cornerstone of management, additional studies of underlying pathophysiology and biomarkers of disease will likely reveal new avenues for therapeutics.


Acetone/periodate-lysine-paraformaldehyde (PLP) fixation and improved morphology of cryostat sections for immunohistochemistry.
Cryostat sections are extensively used in the study of lymphoid tissues because the majority of antigens do not survive routine fixation and processing. A major disadvantage of cryostat section immunohistochemistry is their poor morphology. The use of periodate-lysine-paraformaldehyde (PLP) fixation regimes for cryostat sections was evaluated and compared with conventional acetone immersion. This fixation gives excellent morphology but poor immunostaining. The quality of immunostaining with a panel of 31 antibodies was good with brief acetone fixation followed by PLP fixation. Morphological preservation was very good. We suggest that acetone-PLP fixation is an improvement over acetone alone for cryostat section immunohistochemistry.


Improvement in β-cell function after diet-induced weight loss is associated with decrease in pancreatic polypeptide in subjects with type 2 diabetes.
The aim of our study was to evaluate the effect of a lifestyle intervention program on β-cell function and to explore the role of gastrointestinal peptides in subjects with T2D. Subjects with T2D (n=74) received 24 weeks of intervention: 12 weeks of slimming diet (-500 kcal/day) and the subsequent 12 weeks of diet were combined with aerobic exercise. All subjects were examined at weeks 0, 12 and 24. β-cell function was assessed during standard meal tests. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution, and β-cell function was quantified with a mathematical model. Plasma concentrations of gastrointestinal peptides were measured in a fasting state and during hyperinsulinemia induced by hyperinsulinemic isoglycemic clamp. Mean weight loss was 5.03±4.38 kg (p<0.001) in weeks 0-12. Weight did not change significantly in weeks 12-24. Both insulin secretion at the reference level and glucose sensitivity increased in weeks 0-12 (by 33%±54% and by 26%±53%, respectively, p<0.001) and remained unchanged in weeks 12-24. Both fasting and hyperinsulinemic plasma concentrations of pancreatic polypeptide (PP) decreased in weeks 0-12 (p<0.05 for both) and did not change significantly in weeks 12-24. Changes in insulin secretion at the reference level correlated negatively with plasma concentrations of PP during hyperinsulinemia (r=-0.36; p<0.001). Changes in glucose sensitivity correlated negatively with changes in plasma concentrations of PP, both in fasting and during hyperinsulinemia (r=-0.2; p=0.01 for both). The correlations remained significant after adjustment for changes in body-mass-index. After diet-induced weight loss, β-cell function improved in T2D subjects and remained unchanged after the addition of exercise. We demonstrate for the first time that these changes are associated with a decrease in PP secretion.