[Regional and general contractile function of the myocardium following myocardial infarct].
A total of 93 patients with myocardial infarction were investigated 3-4 mos. after the beginning of disease by the method of radionuclide ventriculography. Total and regional ejection fractions (for 7 zones), left ventricular functional volumes (end-systolic, end-diastolic and stroke volumes), rates of contraction and expulsion were determined. A certain level of left ventricular pump function in patients after myocardial infarction was determined by the ratio of the number of hypokinetic segments and the expression of a decrease in their contractility and normo- and hyperkinetic segments which are the main compensatory factor. Variations in the structure of formation of the total ejection fraction with relation to a site of myocardial infarction were revealed. Compensatory significance of hyperkinetic zones is decreased with a growing degree of expression of contraction asynergia.


Common evolutionary origin for the rotor domain of rotary ATPases and flagellar protein export apparatus.
The V1- and F1- rotary ATPases contain a rotor that rotates against a catalytic A3B3 or α3β3 stator. The rotor F(1-γ) or V1-DF is composed of both anti-parallel coiled coil and globular-loop parts. The bacterial flagellar type III export apparatus contains a V1/F1-like ATPase ring structure composed of FliI6 homo-hexamer and FliJ which adopts an anti-parallel coiled coil structure without the globular-loop part. Here we report that FliJ of Salmonella enterica serovar Typhimurium shows a rotor like function in Thermus thermophilus A3B3 based on both biochemical and structural analysis. Single molecular analysis indicates that an anti-parallel coiled-coil structure protein (FliJ structure protein) functions as a rotor in A3B3. A rotary ATPase possessing an F1-γ-like protein generated by fusion of the D and F subunits of V1 rotates, suggesting F(1-γ) could be the result of a fusion of the genes encoding two separate rotor subunits. Together with sequence comparison among the globular part proteins, the data strongly suggest that the rotor domains of the rotary ATPases and the flagellar export apparatus share a common evolutionary origin.


A facile approach to tryptophan derivatives for the total synthesis of argyrin analogues.
A facile route has been established for the synthesis of indole-substituted (S)-tryptophans from corresponding indoles, which utilizes a chiral auxiliary-facilitated Strecker amino acid synthesis strategy. The chiral auxiliary reagents evaluated were (S)-methylbenzylamine and related derivatives. To illustrate the robustness of the method, eight optically pure (S)-tryptophan analogues were synthesized, which were subsequently used for the convergent synthesis of a potent antibacterial agent, argyrin A and its analogues.


Neuroendocrine tumor of the appendix-a case report and review of the literature.
Incidental appendiceal neuroendocrine tumors (ANETs) occur in 0.2-0.7% of surgical resections for suspected appendicitis (Moris, Tsilimigras, Vagios, Ntanasis-stathopoulos, Karachaliou, Papalampros, et al. Neuroendocrine neoplasms of the appendix: a review of the literature. Anticancer Res [Internet]. 2018;38:601-11.). It's a rare entity, clinically challenging and has controversy surrounding its management. A 69-year-old male presented to our clinic with acute right lower quadrant abdominal pain with less than 24 hours of evolution. The presumed clinical diagnosis was acute appendicitis. It was performed a laparoscopic appendectomy and the histopathologic result of the specimen showed neuroendocrine tumor of the appendix. ANETs are rare and typically diagnosed as incidental histopathologic finds in appendices specimens. However, they are the most common tumors arising from de appendix, between 30% and 80% of the cases (Pape, Niederle, Costa, Gross, Kelestimur, Kianmanesh, et al. ENETS consensus guidelines for neuroendocrine neoplasms of the appendix (excluding goblet cell carcinomas). Neuroendocrinology. 2016;103:144-52). Appendectomy may be sufficing for tumors <2 cm and they are associated with good long-term outcomes.


Spontaneous seizures in a rat model of multiple prenatal freeze lesioning.
Focal cortical dysplasia (FCD) is an important cause of intractable epilepsy. Previous rat studies have utilized freeze lesioning of neonatal animals to model FCD; however, such models are unable to demonstrate spontaneous seizures without seizure-provoking events. Therefore, we created an animal model with multiple FCD, produced during embryonic development, and observed whether spontaneous seizures occurred. Furthermore, we examined the relationship between FCD and epileptogenesis using immunohistochemistry. At 18 days postconception, a frozen metal probe was placed bilaterally on the scalps of Sprague-Dawley rat embryos through the uterus wall to produce multiple FCD. Electroencephalogram (EEG) and video recording were performed from postnatal day (P) 35 to P77. Brain tissues were examined immunohistochemically at P28 and P78 using semiquantitative densitometry. Eleven of 16 rats (68.8%) showed spontaneous seizures arising in the hippocampus from P47. Movement cessation followed by sniffing and mastication, culminating in wet-dog shaking, was seen during the hippocampal EEG discharges. FCD was observed in the bilateral frontoparietal lobes. The expression levels of N-methyl-d-aspartate receptor (NMDAR) subunits 1, 2A, 2B, the glutamate/aspartate transporter and the glial glutamate transporter 1 (GLT1) at FCD sites were increased at P28 and P78. There were no major histological abnormalities in the hippocampi compared with those in the cortex. However, the expression levels of NMDAR 2A and 2B were increased at P28. Levels of NMDAR1, 2A and 2B, the glutamate/aspartate transporter and GLT1 were also increased at P78. We created an animal model showing spontaneous seizures without a provoking event except for the existence of cortical dysplasia, and without a genetic or general systematic cause like MAM injection or irradiation. The seizures resembled human temporal lobe epilepsy both clinically and on EEG. Alterations in the levels of glutamatergic and GABAergic receptors were investigated during growth. This model should enable better clarification of the mechanisms underlying the development of human epilepsy.


The leaving group in Au(I)-phosphine compounds dictates cytotoxic pathways in CEM leukemia cells and reactivity towards a Cys2His2 model zinc finger.
Gold(i)-phosphine "auranofin-like" compounds have been extensively explored as anticancer agents in the past decade. Although potent cytotoxic agents, the lack of selectivity towards tumorigenic vs. non-tumorigenic cell lines often hinders further application. Here we explore the cytotoxic effects of a series of (R3P)AuL compounds, evaluating both the effect of the basicity and bulkiness of the carrier phosphine (R = Et or Cy), and the leaving group L (Cl-vs. dmap). [Au(dmap)(Et3P)]+ had an IC50 of 0.32 μM against the CEM cell line, with good selectivity in relation to HUVEC. Flow cytometry indicates reduced G1 population and slight accumulation in G2, as opposed to auranofin, which induces a high population of cells with fragmented DNA. Protein expression profile sets [Au(dmap)(Et3P)]+ further apart from auranofin, with proteolytic degradation of caspase-3 and poly(ADP-ribose)-polymerase (PARP), DNA strand-break induced phosphorylation of Chk2 Thr68 and increased p53 ser15 phosphorylation. The cytoxicity and observable biological effects correlate directly with the reactivity trend observed when using the series of gold(i)-phosphine compounds for targeting a model zinc finger, Sp1 ZnF3.


Atovaquone Impairs Growth of Aspergillus and Fusarium Keratitis Isolates by Modulating Mitochondrial Function and Zinc Homeostasis.
Aspergillus and Fusarium molds cause blinding corneal infections as a consequence of ocular trauma and in association with contact lens wear. As these fungi require zinc for fungal growth, we examined the effect of atovaquone, a ubiquinone analog that disrupts zinc homeostasis, on fungal growth in vitro and in vivo. In vitro: Aspergillus and Fusarium germinating conidia were incubated overnight with atovaquone, and hyphal growth was measured by fluorimetry. In vivo: C57BL/6 mouse corneas were infected with Aspergillus or Fusarium conidia. Atovaquone was added topically and corneal opacification and fungal growth were quantified. Atovaquone has antifungal activity against Aspergillus and Fusarium clinical isolates, with Fusarium species being more sensitive to atovaquone than Aspergillus species. Atovaquone also reduced labile intracellular zinc levels and increased the sensitivity of Aspergillus to metal shock. Atovaquone reduced vacuolar acidification, which regulates storage of intracellular free zinc, and also acted synergistically with voriconazole and itraconazole to kill hyphae. Furthermore, mitochondrial potential and ATP production were reduced in both Aspergillus and Fusarium following atovaquone treatment. Finally, topical application of atovaquone to the ocular surface significantly inhibited fungal growth and corneal opacification in murine models of fungal keratitis. These studies demonstrate that atovaquone has pronounced in vitro and in vivo antifungal activity against filamentous fungi by disrupting both metal homeostasis and mitochondrial function, and therefore has potential as a novel antifungal agent.


Modes of Interaction in Naturally Occurring Medical Encounters With General Practitioners: The "One in a Million" Study.
In this article, we qualitatively explore the manner and style in which medical encounters between patients and general practitioners (GPs) are mutually conducted, as exhibited in situ in 10 consultations sourced from the One in a Million: Primary Care Consultations Archive in England. Our main objectives are to identify interactional modes, to develop a classification of these modes, and to uncover how modes emerge and shift both within and between consultations. Deploying an interactional perspective and a thematic and narrative analysis of consultation transcripts, we identified five distinctive interactional modes: question and answer (Q&A) mode, lecture mode, probabilistic mode, competition mode, and narrative mode. Most modes are GP-led. Mode shifts within consultations generally map on to the chronology of the medical encounter. Patient-led narrative modes are initiated by patients themselves, which demonstrates agency. Our classification of modes derives from complete naturally occurring consultations, covering a wide range of symptoms, and may have general applicability.


Static magnetic field therapy for carpal tunnel syndrome: a feasibility study.
To assess the feasibility of conducting trials of static magnetic field (SMF) therapy for carpal tunnel syndrome (CTS), to collect preliminary data on the effectiveness of 2 SMF dosages, and to explore the influence of an SMF on median nerve conduction. Randomized, double-blind, sham-controlled trial with a 6-week intervention and a 12-week follow-up. University hospital outpatient clinics. Women and men (N=60), ages 21 to 65 years, with an electrophysiologically confirmed CTS diagnosis recruited from the general population. Participants wore nightly either neodymium magnets that delivered either 15 or 45 mTesla (mT) to the contents of the carpal canal or a nonmagnetic disk. Symptom Severity Scale (SSS) and Function Severity Scale (FSS) of the Boston Carpal Tunnel Questionnaire (BCTQ) and 4 median nerve parameters: sensory distal latency, sensory nerve action potential amplitude, motor distal latency and compound motor action potential amplitude. Fifty-eight of 60 randomized participants completed the study. There were no significant between-group differences for change in the primary endpoint SSS or for FSS or median nerve conduction parameters. For the SSS and the FSS, each group showed a reduction at 6 weeks indicating improvement in symptoms. This study showed the feasibility and safety of testing SMF therapy for CTS. There were no between-group differences observed for the BCTQ or median nerve parameters after 6 weeks of SMF therapy. Significant within-group, symptomatic improvements of the same magnitude were experienced by participants in both active and sham magnet groups. Future studies are needed to optimize SMF dosimetry and resolve issues related to the use of sham controls in SMF trials.


Nonlinear analysis of heart rate dynamics in hyperthyroidism.
Studies on the physiology of the cardiovascular system suggested that the generation of the heart rate signal is governed by nonlinear chaotic dynamics. No study investigated the nonlinear dynamics of heart rate in hyperthyroidism. We examined whether the heart rate dynamics of hyperthyroid patients is different from normal controls by the nonlinear analysis of heart rate variability (HRV) with correlation dimension (CD). Thirty-three hyperthyroid Graves' disease patients (30 females and 3 males; age 31 +/- 1 years, means +/- SE) and 33 sex-, age-, and body mass index-matched normal controls were recruited to receive one-channel electrocardiogram recording for 30 min. The CD, an index of complexity, was computed from the sequence of normal R-R intervals by the Grassberger and Procaccia algorithm. Compared to the normal controls, the hyperthyroid patients showed significant reductions (P < 0.001) in the mean R-R interval (hyperthyroid 616 +/- 15 versus control 868 +/- 16 ms), the standard deviation of R-R intervals (25 +/- 2 versus 54 +/- 4 ms) and CD (5.02 +/- 0.11 versus 6.42 +/- 0.16). Our study demonstrated for the first time that hyperthyroid patients and normal controls could be distinguished by CD analysis of HRV. In addition, the decreased CD in hyperthyroid patients implies reduced complexity and impaired tolerance to cardiovascular stresses in hyperthyroidism. This finding helps to explain exercise intolerance and irritability manifested by the hyperthyroid patients.


Protein and amino acid metabolism with reference to aging and the elderly.
In this short review, selected aspects of body protein and amino-acid metabolism during aging in human subjects have been explored. There is a progressive diminution of total body protein with aging, due largely to a loss of skeletal muscle protein. These changes are accompanied by a shift in the overall pattern of whole body protein synthesis and breakdown, with muscle mass estimated to account for about 30 percent of whole body protein turnover in the young adult, as compared with a lower value of 20 percent or less in elderly subjects. There is no evidence that the loss of muscle protein is related to a reduced "amino acid tolerance" to insulin, since leucine-insulin metabolic relationships appear to remain intact during advancing adult age. However, because skeletal muscle mass plays an important role in the response to body protein and amino-acid metabolism to stress, such as that due to infection or trauma, this decline in the contribution of muscle to total body protein metabolism might be a factor responsible for the reduced ability of older people to withstand such unfavorable circumstances. Recent observations on the importance of muscle as a source of glutamine that is essential for immune cell function support this contention. The dietary requirements for individual essential and for total protein are limited and often contradictory (see, for example, Young, et al, 1982). However, elderly individuals are more likely to be affected by various biological, environmental and social factors, which would generally increase protein and amino acid needs above those for younger adults. Thus, in practice, the protein needs in the elderly are likely to be higher than those in the young. The decline in energy intake, together with its possible consequences for reducing the efficiency of dietary protein utilization, also will tend to increase the protein need for elderly subjects, relative to that for physically more active young adults. Until more data become available, it is recommended, for food planning purposes, that an appropriate protein allowance would be about 15 percent of the total energy intake, for mixed food protein sources characteristic of the diets of industrialized countries. Epidemiological surveys of the protein nutritional status of healthy, free living elderly subjects and of institutionalized individuals without clinically apparent terminal or wasting illness are consistent with this recommendation.


[Oral clonidine test for growth hormone release (author's transl)].
Serum growth hormone (GH) was determined in 15 children (three with normal height, one with pituitary dwarfism, and eleven with short stature without endocrinological disturb) after oral clonidine load of 0,15 mg/m2 S.A. Significant GH increase was observed, as other authors have reported. Authors findings confirm that clonidine is a potent stimulus for growth hormone release, without relevant side effects. In two children with short stature without endocrinological disturb, there was a partial failure to increase GH in response to clonidine. Authors conclude that confirmation of GH deficiency in the case of failure to respond to oral clonidine test requires one other stimulation test.


Increased expression of endoplasmic reticulum stress and unfolded protein response genes in peripheral blood mononuclear cells from patients with limited cutaneous systemic sclerosis and pulmonary arterial hypertension.
Pulmonary arterial hypertension (PAH), a common complication of limited cutaneous systemic sclerosis (lcSSc), is associated with alterations of markers of inflammation and vascular damage in peripheral blood mononuclear cells (PBMCs). Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been implicated in autoimmune and inflammatory diseases. The goal of this study was to assess whether markers of ER stress and the UPR are present in PBMCs from lcSSc patients with PAH. PBMCs were purified from 36 healthy controls, 32 lcSSc patients with PAH, and 34 lcSSc patients without PAH. Gene expression in healthy control PBMCs stimulated with thapsigargin was analyzed by DNA microarray. Genes were validated by quantitative real-time reverse transcription-polymerase chain reaction in PBMCs from healthy controls and lcSSc patients. Several ER stress/UPR genes, including BiP, activating transcription factor 4 (ATF-4), ATF-6, and a spliced form of X-box binding protein 1, were up-regulated in PBMCs from lcSSc patients, with the highest levels in patients with PAH. Thapsigargin up-regulated heat-shock proteins (HSPs) and interferon (IFN)-regulated genes in PBMCs from healthy controls. Selected HSP genes (particularly DnaJB1) and IFN-related genes were also found at significantly elevated levels in PBMCs from lcSSc patients, while IFN regulatory factor 4 expression was significantly decreased. There was a positive correlation between DnaJB1 and severity of PAH (measured by pulmonary artery pressure) (r = 0.56, P < 0.05) and between ER stress markers and interleukin-6 levels (r = 0.53, P < 0.0001) in PBMCs from lcSSc patients. This study demonstrates an association between select ER stress/UPR markers and lcSSc with PAH, suggesting that ER stress and the UPR may contribute to the altered function of circulating immune cells in lcSSc.


Cardiovascular magnetic resonance detects the progression of impaired myocardial perfusion reserve and increased left-ventricular mass in mice fed a high-fat diet.
Impaired myocardial perfusion reserve (MPR) is prevalent in obesity and diabetes, even in the absence of obstructive coronary artery disease (CAD), and is prognostic of adverse events. We sought to establish the time course of reduced MPR and to investigate associated vascular and tissue properties in mice fed a high-fat diet (HFD), as they are an emerging model of human obesity, diabetes, and reduced MPR without obstructive CAD. C57Bl/6 mice fed a HFD or a low-fat diet (control) were imaged at 6, 12, 18 and 24 weeks post-diet. The cardiovascular magnetic resonance (CMR) protocol included multi-slice cine imaging to assess ejection fraction (EF), left-ventricular (LV) mass, LV wall thickness (LVWT), and LV volumes, and first-pass perfusion CMR to quantify MPR. Coronary vascular reactivity, aortic atherosclerosis, myocardial capillary density and tissue fibrosis were also assessed. Body weight was increased in HFD mice at 6-24 weeks post-diet (p < 0.05 vs. control). MPR in HFD mice was reduced and LV mass and LVWT were increased in HFD mice at 18 and 24 weeks post-diet (p < 0.05 vs. control). Coronary arteriolar vascular reactivity to adenosine and acetylcholine were reduced in HFD mice (p < 0.05 vs. control). There were no significant differences in cardiac volumes, EF, or capillary density measurements between the two groups. Histology showed interstitial fibrosis in HFD and no aortic atherosclerosis in either group. C57Bl/6 mice fed a HFD for 18-24 weeks have progressively increased LV mass and impaired MPR with fibrosis, normal capillary density and no aortic plaque. These results establish C57Bl/6 mice fed a HFD for 18-24 weeks as a model of impaired MPR without obstructive CAD due to obesity and diabetes.


Collaborative discharge planning: nursing and social services.
Discharge planning impacts hospital costs and patient outcomes. The purpose of this study was to determine the effects of a structured discharge planning program using collaboration between the CNS and the social worker. The quasi-experimental study used a sample of 64 elderly patients. The experimental group (n = 29) had discharge planning directed through collaboration by a CNS and a social worker. After discharge, patients were contacted by telephone about satisfaction and services received. Charts were reviewed for information about length of stay, readmission, and documentation. Data analysis revealed that patients involved in collaborative planning were more satisfied, had a shorter length of stay, had fewer readmissions, and received a higher rate of indicated postdischarge services. Documentation was not significantly affected, except in the area of patient teaching, which was lower in the experimental group. Based on these findings, the collaborative model offers nurse administrators a way to improve outcomes for patients and the organization.


Long-term intra-individual variation of platelet parameters.
Mean platelet volume, platelet count and platelet distribution width were determined in eight male subjects at monthly intervals over a 4-6 month period. Measurements were made on a Coulter S Plus VTM exactly 15 min and 2 h after blood collection. Long-term intra-individual variability for mean platelet volume showed a mean coefficient of variation (CV) of 1.60% at 15 min and 2.01% at 2 h after blood collection; for platelet count a mean CV of 3.18% at 15 min and 2.40% at 2 h; and for platelet distribution width a mean CV of 7.3% at 15 min and 6.5% at 2 h. Platelet parameters are stable over time in the normal male individual.


Hypotensive epidural anesthesia for total hip arthroplasty: a review.
Hypotensive epidural anesthesia provides arterial hypotension to maintain a mean arterial pressure of 50 mmHg and it can be used to reduce blood loss during total hip replacement. The technique combines an extensive epidural blockade with an intravenous infusion of low-dose epinephrine. This results in arterial hypotension, but with preservation of central venous pressure, heart rate, stroke volume, cardiac output, and an augmentation of blood flow to the lower extremity. The technique does not appear to adversely affect cardiac, renal, or cerebral function and is used safely in patients with hypertension, ischemic heart disease, and in the elderly. Intraoperative blood losses during primary total hip replacement are between 100 and 300 mL. Perioperative transfusions have declined with the introduction of the technique. Radiological evidence of improved fixation of cemented acetabular components has been observed. Rates of deep-vein thrombosis are low: 2-3% proximal deep-vein thrombosis with an overall rate of 10%. In-hospital mortality is 0.1%; lower than previously published rates. In conclusion, hypotensive epidural anesthesia is safe and provides a number of advantages over conventional anesthetic techniques for total hip replacement.


Drug-induced handwriting changes: an empirical review.
Since handwriting is a highly complex, coordinated motor activity, handwrits of pharmacological agents. Its potential has been most evident in research involving therapeutic administrations of anti-psychotic an anti-Parkinsonian drugs, from which consistent and systematic handwriting changes have been observed. This relationship has been found to be particularly significant among the anti-psychotics, since the onset of these graphomotor alterations appear to mark the optmal dose of the drug. Consistent and systematic handwriting changes have not been as evident in inivestigations of drugs used in a nontherapeutic atmosphere. Psychiatric assessments of subjects in ths type of research provided data which indicated that psychological stability may be a factor influencing the susceptibility of one's handwriting to drug induced changes.


The plastic pandemic: COVID-19 has accelerated plastic pollution, but there is a cure.
Plastic pollution is now present in all areas of our planet, including its last wilderness, Antarctica, and the plastic crisis has further escalated because of COVID-19. The pandemic has caused a significant increase in the global consumption of single-use protective items such as masks and gloves. These and other plastic items add to the suite of plastic pollution issues, from entanglement of wildlife to microplastic bioaccumulation. Given plastics are a major threat facing humans and wildlife, swift action to reduce plastic pollution is urgently needed. Solutions to plastic pollution are within reach. With collective, impactful action we will ensure a better future for our planet and ourselves. Here, we propose several measures for decision-makers to implement to achieve a solution and tackle plastic pollution as a united, global community.


Skipping Breakfast and Its Association with Health Risk Behaviour and Mental Health Among University Students in 28 Countries.
The study aimed to investigate the associations between skipping breakfast and various health risk behaviours and mental health in university students in 28 countries. Using a cross-sectional study design, 21,972 university students with a median age of 20 years from 28 countries in Africa, the Americas and Asia, replied to self-reported measures of breakfast consumption, health compromising behaviours, mental health measures and protective factors. In adjusted logistic regression analysis, infrequent and/or frequent breakfast skipping was associated with inadequate fruit and vegetable intake, frequent soft drink intake, not avoiding fat and cholesterol, current binge drinking, current tobacco use, gambling, not always wearing a seatbelt, inadequate physical activity, inadequate tooth brushing, not seeing a dentist in the past year and having been in a physical fight. In addition, infrequent and/or frequent breakfast skipping was associated with depression, lower happiness, posttraumatic stress disorder, loneliness, short sleep, long sleep, sleep problem, restless sleep, sleep problem due to traumatic event, and poor academic performance. We found evidence that skipping breakfast was associated with 10 of 15 health risk behaviours, all of nine poor mental health indicators and poor academic performance.


Polyphenol profiles of apple juices.
Focusing on 17 constituents, the polyphenol profiles of juices freshly made from various dessert (n = 4) and cider apple cultivars (n = 7) as well as commercially available apple juices (n = 24) were investigated using high-performance liquid chromatography-photodiode array detection (HPLC-DAD) and (HPLC)-electrospray ionization-tandem mass spectrometry (ESI(neg)-MS/MS) analyses. Significant differences in the total polyphenol content as well as the profiles of the apple cultivars under study were observed. For dessert apples the total polyphenol content ranged from 154 to 178 mg/L, whereas for 'old' German cider apple cultivars 261-970 mg/L were determined. Boskoop showed the highest (970 mg/L) and Granny Smith the lowest (154 mg/L) polyphenol content of the freshly prepared samples under study. Hydroxycinnamic acids, with chlorogenic acid as dominating constituent, ranged from 57 to 68 mg/L as well as from 134-593 mg/L in juices made from dessert apples and that from cider apples, respectively. Dessert apple juices showed lower contents of dihydrochalcones (10-35 mg/L) and flavan-3-ols (50-95 mg/L) compared to that of cider apples (34-171 mg/L and 70-393 mg/L, respectively). Quercetin and its derivatives were found from 0.4-4 mg/L and 0.4-27 mg/L in juices made from dessert apples and that of cider apples, respectively. Compared with freshly made juices, lower contents of polyphenols were determined in the commercial samples under study. Amounts ranging from 110-459 mg/L, dominated by chlorogenic acid with concentrations from 53-217 mg/L, were determined. Information about cultivar-typical apple polyphenol content and profile is important for bioactivity studies and, consequently, essential for the development of consumer-relevant products with particular nutritional functionalities.


Immunologic identification of Epstein-Barr virus early antigen in a P3HR-1 cell extract.
We extracted the Epstein-Barr soluble antigen (EBSA) from the P3HR-1 human lymphoid cell line, which carries the Epstein-Barr virus (EBV), after P3HR-1 cells were activated with 5-iodo-2'-deoxyuridine. EBSA was identified as the early antigen (EA) complex by immunodiffusion and blocking immunofluorescence tests with high-titered human antiserum to EA. The identity of the EA complex was confirmed with antiserum to EA prepared in rabbits and adsorbed to assure its immunologic specificity. The EA was partially purified on Sephadex G-200. Further characterization by immunoelectrophoresis showed that the EBSA moved rapidly toward the anode. This indicated a highly negative charge. EBSA appeared to be distinct from the previously described complement-fixing S-antigen. It was demonstrable only in EA-producer lymphoid cell lines and reacted specifically with human antiserum to EA, whereas the S-antigen was found in all EBV-carrying lymphoid cell lines and reacted with all EBV antibody-positive human antisera.


Design of a Low-Cost Miniature Robot to Assist the COVID-19 Nasopharyngeal Swab Sampling.
Nasopharyngeal (NP) swab sampling is an effective approach for the diagnosis of coronavirus disease 2019 (COVID-19). Medical staffs carrying out the task of collecting NP specimens are in close contact with the suspected patient, thereby posing a high risk of cross-infection. We propose a low-cost miniature robot that can be easily assembled and remotely controlled. The system includes an active end-effector, a passive positioning arm, and a detachable swab gripper with integrated force sensing capability. The cost of the materials for building this robot is 55 USD and the total weight of the functional part is 0.23kg. The design of the force sensing swab gripper was justified using Finite Element (FE) modeling and the performances of the robot were validated with a simulation phantom and three pig noses. FE analysis indicated a 0.5mm magnitude displacement of the gripper's sensing beam, which meets the ideal detecting range of the optoelectronic sensor. Studies on both the phantom and the pig nose demonstrated the successful operation of the robot during the collection task. The average forces were found to be 0.35N and 0.68N, respectively. It is concluded that the proposed robot is promising and could be further developed to be used in vivo.


[Early ischemic lesion demonstrated by ictal diffusion-weighted MRI during prior TIA in a patient with cerebral infarction].
We reported a patient with transient ischemic attack (TIA), subsequently evolving to a cerebral infarction, in whom ictal diffusion-weighted magnetic resonance imaging (MRI) detected early ischemic lesion in the left hemisphere. The patient was a 30-year-old right-handed male medical doctor, who had an in-hospital episode of TIA with obtundation and right hemiparesis, which lasted for 150 minutes. Ictal diffusion-weighted MRI obtained 110 minutes after symptom onset demonstrated an area of high signal intensity in the left striatum and corona radiata, whereas T 2-weighted and FLAIR images were entirely normal. Ictal magnetic resonance angiography (MRA) showed occlusive lesions in the M 2 branches of the left middle cerebral artery. The second MRA obtained 90 minutes after resolution of the symptoms showed nearly complete recanalization of the left middle cerebral artery, suggesting that the TIA was embolic mechanism. However the patient rapidly developed similar neurological symptoms again 58.5 hours after the TIA episode, evolving finally to a completed stroke. A brain CT obtained 1 hour after the second episode demonstrated diffuse hypodense lesions in the left basal ganglia and corona radiata, and in the left temporal lobe. MRIs 3 and 7 days later displayed completed infarcts, of which distribution was consistent with that of the hypodense lesions on the earlier CT. The left middle cerebral artery remained patent on the follow-up MRAs. The patient fairly recovered and returned to his premorbid position as medical doctor with a mild residual right hand clumsiness. In this patient, ictal and post-ictal MRAs documented an occlusion and a reopening of the middle cerebral artery. The embolic mechanism remains unknown despite detailed cardiac, vascular, and hematological examinations. In addition to recurrent embolism, we would like to point out that the reperfusion injury, secondary delayed neuronal death, and other factors may be involved in the second exacerbation evolving to the completed stroke.


The Trihelix transcription factor GT2-like 1 (GTL1) promotes salicylic acid metabolism, and regulates bacterial-triggered immunity.
The Trihelix Transcription factor GT2-like 1 (GTL1) was previously shown to be a key regulator of ploidy-dependent trichome growth and drought tolerance. Here, we report that GTL1 plays an important role in coordinating plant immunity. We show that gtl1 mutants are compromised in the regulation of basal immunity, microbial pattern-triggered immunity (PTI) and effector-triggered RIN4-mediated immunity. Transcriptome analysis revealed that GTL1 positively regulates defense genes and inhibits factors that mediate growth and development. By performing hormonal measurements and chromatin-immunoprecipitation studies, we found GTL1 to coordinate genes involved in salicylic acid metabolism, transport and response. Interaction studies and comparative transcriptomics to known data sets revealed that GTL1 is part of the MPK4 pathway and regulates oppositely the expression of differentially expressed genes in mpk4 plants. We introduced the gtl1 mutation in the mpk4 mutant and thereby partially suppressed its dwarfism and the high resistance against a bacterial invader. Our data show that GTL1 is part of the MPK4 pathway and acts as a positive regulator of bacterial-triggered immunity and SA homeostasis.


Gene replacement by homologous recombination in the multicellular green alga Volvox carteri.
With only two different cell types, the haploid green alga Volvox represents the simplest multicellular model system. To facilitate genetic investigations in this organism, the occurrence of homologous recombination events was investigated with the intent of developing methods for gene replacement and gene disruption. First, homologous recombination between two plasmids was demonstrated by using overlapping nonfunctional fragments of a recombinant arylsulfatase gene (tubulin promoter/arylsulfatase gene). After bombardment of Volvox reproductive cells with DNA-coated gold microprojectiles, transformants expressing arylsulfatase constitutively were recovered, indicating the presence of the machinery for homologous recombination in Volvox. Second, a well characterized loss-of-function mutation in the nuclear nitrate reductase gene (nitA) with a single G --> A nucleotide exchange in a 5'-splice site was chosen as a target for gene replacement. Gene replacement by homologous recombination was observed with a reasonably high frequency only if the replacement vector containing parts of the functional nitrate reductase gene contained only a few nucleotide exchanges. The ratio of homologous to random integration events ranged between 1:10 and 1:50, i.e., homologous recombination occurs frequently enough in Volvox to apply the powerful tool of gene disruption for functional studies of novel genes.


Growth characteristics of influenza virus concerning the binding of virus by host cells.
Under certain conditions, influenza virus may bind to chorioallantoic membrane and the infectious property is retained upon prolonged incubation of the complex. Apparently the bound active virus is not functioning in the initiation of viral increase. The bound infectious virus may be partially removed by extensive washing. The characteristics of the washing are suggestive of a reversible equilibrium type of binding. Binding will also occur when the tissue has been pretreated with RDE or in the presence of AMPS. However, under these conditions the binding is of a lesser degree. When the tissue has been treated with RDE and AMPS is present, no stable binding occurs. In the presence of AMPS, the initiating activity is bound but cannot function in promoting viral increase. It is proposed that active virus is held by two types of binding at the same site; one type of binding is sensitive to the action of RDE; the second type is sensitive to the blocking effect of AMPS. Virus can be held to the receptor site by either type of binding or both. It is further suggested that the bound infectious virus is a result of an abortive attempt at initiating infection. The nature of the binding of infectious virus is of significance for understanding the binding of initiating activity.


Analysis of C3 suggests three periods of positive selection events and different evolutionary patterns between fish and mammals.
The third complement component (C3) is a central protein of the complement system conserved from fish to mammals. It also showed distinct characteristics in different animal groups. Striking features of the fish complement system were unveiled, including prominent levels of extrahepatic expression and isotypic diversity of the complement components. The evidences of the involvement of complement system in the enhancement of B and T cell responses found in mammals indicated that the complement system also serves as a bridge between the innate and adaptive responses. For the reasons mentioned above, it is interesting to explore the evolutionary process of C3 genes and to investigate whether the huge differences between aquatic and terrestrial environments affected the C3 evolution between fish and mammals. Analysis revealed that these two groups of animals had experienced different evolution patterns. The mammalian C3 genes were under purifying selection pressure while the positive selection pressure was detected in fish C3 genes. Three periods of positive selection events of C3 genes were also detected. Two happened on the ancestral lineages to all vertebrates and mammals, respectively, one happened on early period of fish evolutionary history. Three periods of positive selection events had happened on C3 genes during history and the fish and mammals C3 genes experience different evolutionary patterns for their distinct living environments.


The extracellular matrix environment in suture morphogenesis and growth.
Sutures are the major bone growth sites of the craniofacial skeleton and form in response to developmental approximation of and interaction between two opposing osteogenic fronts. Premature obliteration of these craniofacial bone growth sites or craniosynostosis results in compensatory growth at other bone growth sites, with concomitant craniofacial dysmorphology. While much is now known about the growth and transcriptional factor regulation of suture formation and maintenance, little about the nature of the extracellular environment within sutures and their surrounding bones has been described. This review elucidates the nature of the sutural extracellular matrix and its role in mediating suture maintenance and growth through the regulation of cellular and biomechanical signaling.


Glycerolipid biosynthesis in porcine adipose tissue in vitro. II. Synthesis by various types of cellular preparations.
Glycerolipid biosynthesis by porcine adipose tissue homogenates did not yield the 90+% triacylglycerol observed in situ. Consequently, we compared intact tissue slices and various subcellular fractions to characterize the usefulness of such systems to assess glycerolipid biosynthesis in vitro. Glycerolipid biosynthesis by porcine adipose tissue homogenates was measured in vitro using either [14C]-fatty acid or [14C]-glycerol-3-phosphate (G3P) as a radiolabelled substrate. Removal of residual 14C-labelled fatty acid from lipid extracts was difficult. Because G3P is soluble in water, residual [14C]-G3P separated easily from the glycerolipid-containing organic phase and, thus, was the preferred radiolabelled substrate. With tissue slices, glycerol and G3P were minimally incorporated into lipid so that [14C]-fatty acid was the preferred radiolabelled tracer. A washing procedure followed by thin layer chromatography was devised to separate residual [14C]-fatty acid from glycerolipids, including phospholipids. Fatty acid esterification into glycerolipids in tissue slices yielded about 4% phospholipids, whereas with homogenates, esterification yielded up to 50% phospholipids. Comparison of several subcellular fractions indicated that microsomes contained most of the glycerolipid biosynthetic activity when activity was expressed on a protein basis. However, when activities were expressed on a tissue wet weight basis, the 700 x g infranate and the 10,000 x g supernate had about equal activity that was far greater than the microsomes. The 700 x g infranate was the preferred enzyme preparation for assay of the entrance of G3P into the pathway as well as the capacity to synthesize triacylglycerol. Several methods of freezing and storing tissue or 700 x g infranates were not acceptable. Freezing of the 700 x g infranate in liquid N2 with storage at -80 degrees C may be an acceptable procedure.


Validity and reliability on three European language versions of the Safety Organizing Scale.
The Safety Organizing Scale (SOS) offers a reliable snapshot of nurses' engagement in unit-level safety behaviors in hospitals. As no comparable questionnaire exists in German, French and Italian, we explored the psychometric properties of SOS translations into each of those languages. The psychometric properties of the nine-item SOS were tested according to American Educational Research Association guidelines. Between October 2009 and June 2010, 1633 registered medical and/or surgical nurses in 35 Swiss hospitals completed translated SOS questionnaires. For each translation, psychometric evaluation revealed evidence based on content (scale-content validity index >0.89), response patterns (e.g. average of missing values across all items = 0.80%), internal structure (e.g. comparative fit indices >0.90, root mean square error of approximation <0.08) and reliability (Cronbach's alpha >0.79). We differentiated the scale regarding one related concept (implicit rationing of nursing care). Higher SOS scores correlated with supportive leadership and lower nurse-reported medication errors, but not with nurse-reported patient falls. The SOS offers a valuable measurement of engagement in safety practices that might influence patient outcomes. Initial evidence regarding the validity and reliability of the translated versions supports their use in German, French and Italian. Concurrent validity will require confirmation via further analysis using more reliable outcome measures (e.g. mortality rates). The translated versions' predictive validity needs to be established in prospective studies.


Does Addition of Propolis to Glass Ionomer Cement Alter its Physicomechanical Properties? An in Vitro Study.
Propolis is a natural resinous substance produced by honey bees. The antimicrobial effects of glass ionomer cement have been shown to improve with the addition of propolis; however its effect on the physicomechanical properties of the cement is not known. The purpose of this study was to evaluate the compressive strength and solubility of conventional restorative glass ionomer cement following the addition of propolis. Twenty half cylindrical samples were prepared with conventional restorative glass ionomer cement formed the control group. Another twenty samples were prepared with propolis added to conventional restorative glass ionomer cement formed the experimental group. The compressive strength was assessed using universal testing machine. To assess solubility, the samples were immersed in deionised water at room temperature, for 7 days. The solubility was measured as a difference in the weight of the sample; prior to immersion and following immersion at the end of each day. The control group had a significantly higher mean compressive strength of 146.26 Mpa as compared to the experimental group (135.06 Mpa). The solubility between the groups was significant. In comparison to the control group, incorporation of propolis to conventional restorative glass ionomer cement decreased the compressive strength significantly. The solubility of the cement in the experimental group increased significantly over 7day period as compared to the control group.


Nevirapine significantly reduces the levels of racemic methadone and (R)-methadone in human immunodeficiency virus-infected patients.
Methadone is metabolized by various isoforms of the cytochrome P450 family, which can be induced by many drugs, including nevirapine. The objective of the present study was to determine the effects of coadministration of nevirapine and methadone on the dose-adjusted areas under the concentration-time curves (AUCs) of racemic and (R)-methadone. Twenty-five human immunodeficiency virus-infected subjects taking stable single daily doses of racemic methadone or (R)-methadone were included in this prospective, single-crossover trial. At the baseline, nevirapine was either started as part of a new regimen containing two nucleoside reverse transcriptase inhibitors (NRTIs) or added to an ongoing NRTI regimen. Patients could increase their methadone doses if withdrawal symptoms developed. Twelve-hour pharmacokinetic profiles were obtained before and 28 days after the start of nevirapine treatment. The total concentrations of methadone and its inactive metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), in serum were determined by liquid chromatography-tandem mass spectrometry. Among the 20 evaluable patients, coadministration of nevirapine significantly decreased the mean dose-adjusted AUC of methadone by 41%. AUC reductions were similar for patients taking racemic methadone (37%; n = 11) and (R)-methadone (44%; n = 9). AUC changes ranged from mild increases in three patients to decreases of up to 70%. Fourteen of 20 patients required additional methadone due to withdrawal symptoms. However, the median dose increase was only 15%, which was less than that which would have been expected from the pharmacokinetic data. The AUC of EDDP increased significantly, by 35%. Methadone dose adjustments are justified when methadone is coadministered with nevirapine. Due to extensive variability, the adjustments must be tailored to the individual patient's needs.


Cancer from exposure to 50/60 Hz electric and magnetic fields--a major scientific debate.
Millions of dollars are presently being spent on both laboratory and epidemiological studies to determine if an association exists between the exposure of humans to 50/60 Hz electromagnetic fields and cancer incidence. This review discusses findings from both of these areas of study and focuses attention on their relevance to the electromagnetic field-cancer debate. So far, the conflicting results from epidemiology have succeeded only in raising the concerns of both occupationally exposed groups and the general public. A few hypotheses have suggested possible mechanisms by which fields could exert biological effects. However the studies on which these hypotheses are based require substantiation and further, there is insufficient evidence to indicate if the biological effects observed in these studies have any relevance to human health. It will be at least another three to five years before there are results from large scale human studies presently being designed or undertaken. From an objective review of existing scientific data it can only be concluded that exposure to 50/60 Hz electric and magnetic fields at levels occurring in our environment have not been established to lead to cancer in humans. Sufficient gaps in our knowledge exist however to recommend that research continue, especially in areas identified in the text. To assist the casual reader of this subject the complex issues of cancer initiation and promotion are considered.


Duration of Device-Based Fever Prevention after Cardiac Arrest.
Guidelines recommend active fever prevention for 72 hours after cardiac arrest. Data from randomized clinical trials of this intervention have been lacking. We randomly assigned comatose patients who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause to device-based temperature control targeting 36°C for 24 hours followed by targeting of 37°C for either 12 or 48 hours (for total intervention times of 36 and 72 hours, respectively) or until the patient regained consciousness. The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category of 3 or 4 (range, 1 to 5, with higher scores indicating more severe disability; a category of 3 or 4 indicates severe cerebral disability or coma) within 90 days after randomization. Secondary outcomes included death from any cause and the Montreal Cognitive Assessment score (range, 0 to 30, with higher scores indicating better cognitive ability) at 3 months. A total of 393 patients were randomly assigned to temperature control for 36 hours, and 396 patients were assigned to temperature control for 72 hours. At 90 days after randomization, a primary end-point event had occurred in 127 of 393 patients (32.3%) in the 36-hour group and in 133 of 396 patients (33.6%) in the 72-hour group (hazard ratio, 0.99; 95% confidence interval, 0.77 to 1.26; P = 0.70) and mortality was 29.5% in the 36-hour group and 30.3% in the 72-hour group. At 3 months, the median Montreal Cognitive Assessment score was 26 (interquartile range, 24 to 29) and 27 (interquartile range, 24 to 28), respectively. There was no significant between-group difference in the incidence of adverse events. Active device-based fever prevention for 36 or 72 hours after cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).


[HBs antigenemia in glomerulonephritis in children].
Altogether 194 glomerulonephritis patients were examined by three methods: countercurrent immunoelectrophoresis, passive hemagglutination test, and enzyme immunoassay. Use of the most sensitive method, viz. enzyme immunoassay, has yielded the highest HBsAg detection rate: 29.1% in acute glomerulonephritis and 21.4% in chronic glomerulonephritis. This method may be recommended for the examination of glomerulonephritis patients whose sera contain HBsAg in low titers.


"I don't care about you as a person": Sexual minority women objectified.
This study investigates sexual minority women's experiences of objectification in the United States. Data from 5 focus groups with 33 sexual minority women were analyzed using thematic analysis (Braun & Clarke, 2006, 2012). Results revealed 6 themes and 34 subthemes grouped into "manifestations of objectification: general and explicit intersections," "immediate context of relational and situational characteristics," and "broader context of oppression and privilege along gender and sexualities." First, sexual minority women's experiences of objectification included both general manifestations described in prior research with heterosexual women and manifestations of objectification that reflected intersections of systems of inequality based on sexual orientation, gender identity, race, ethnicity, culture, and age. Second, participants identified novel relational and situational characteristics of objectification. Finally, participants included experiences of stereotyping, discrimination, and dehumanization in their conceptualizations of objectification, connecting their experiences of objectification with broader dynamics of power related to gender and sexuality. Centralizing sexual minority women's experiences, this study produced a fuller understanding of objectification experiences in general and of sexual minority women's experiences in particular. (PsycINFO Database Record


Fluorescent antibody detection of the antigens of the Shope papilloma virus in papillomas of the wild and domestic rabbit.
The results obtained by a fluorescent antibody study of the Shope papilloma virus in papillomas of the wild and domestic rabbit are presented. In the wild rabbit papillomas the viral antigens occurred exclusively in the nucleus and were present in the differentiating cells of the keratohyaline layers and in the keratinized layers. The antigens were not present in the deeper proliferating epithelial cells of the papillomas. The Shope viral antigens were present in very minute amounts in papillomas of the domestic rabbit, as compared with papillomas of the wild rabbit, and were only detected in the superficial keratinized layers. It is postulated that virus is present in the nuclei of the proliferating cells of the papillomas of the wild and domestic rabbit but exists there in an early stage of development, consisting mainly of nucleic acid and deficient in protein, therefore non-antigenic and not demonstrable by fluorescent antibody. The nucleic acid moiety of the virus may be infective, and the protein component may provide immunologic specificity and serve to preserve transmissibility. The protein-deficient virus can be referred to as masked virus.


Charge injection and transport properties of large area organic junctions based on aryl thin films covalently attached to a multilayer graphene electrode.
The quantum interaction between molecules and electrode materials at molecule/electrode interfaces is a major ingredient in the electron transport properties of organic junctions. Driven by the coupling strength between the two materials, it results mainly in the broadening and energy shift of the interacting molecular orbitals. Using new electrode materials, such as the recently developed semi-conducting two-dimensional nanomaterials, has become a significant advancement in the field of molecular/organic electronics that opens new possibilities for controlling the interfacial electronic properties and thus the charge injection properties. In this article, we report the use of atomically thin two-dimensional multilayer graphene films as the base electrode in organic junctions with a vertical architecture. The interfacial electronic structure dominated by the covalent bonding between bis-thienyl benzene diazonium-based molecules and the multilayer graphene electrode has been probed by ultraviolet photoelectron spectroscopy and the results are compared with those obtained on junctions with standard Au electrodes. Room temperature injection properties of such interfaces have also been explored by electron transport measurements. We find that, despite strong variations of the density of states, the Fermi energy and the injection barriers, both organic junctions with Au base electrodes and multilayer graphene base electrodes show similar electronic responses. We explain this observation by the strong orbital coupling occurring at the bottom electrode/bis-thienyl benzene molecule interface and by the pinning of the hybridized molecular orbitals.


Neuropsychological sequelae of PTSD and TBI following war deployment among OEF/OIF veterans.
Posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) are highly prevalent among Veterans of the conflicts in Iraq and Afghanistan. These conditions are associated with common and unique neuropsychological and neuroanatomical changes. This review synthesizes neuropsychological and neuroimaging studies for both of these disorders and studies examining their co-occurrence. Recommendations for future research, including use of combined neuropsychological and advanced neuroimaging techniques to study these disorders alone and in concert, are presented. It is clear from the dearth of literature that addiitonal studies are required to examine and understand the impact of specific factors on neurocognitive outcome. Of particular relevance are temporal relationships between PTSD and mTBI, risk and resilience factors associated with both disorders and their co-occurrence, and mTBI-specific factors such as time since injury and severity of injury, utilizing comprehensive, yet targeted cognitive tasks.


Comparison of Decompression With and Without Fusion for Patients With Synovial Facet Cysts.
This is a retrospective study. To compare (1) recurrence of radiculopathy and (2) back pain after decompression with and without fusion for patients with a symptomatic synovial cyst. Previous work described favorable outcomes following cyst excision with and without fusion. Because of the association of facet cysts with spinal instability it is hypothesized that a decompression with fusion will lead to better outcomes. However, previous studies present contradicting results. We included 314 consecutive patients that underwent operative treatment for a facet cyst between 2003 and 2013 at 2 tertiary spine referral centers: 224 (71%) underwent decompression without fusion (35% spondylolisthesis), 90 (29%) underwent decompression with fusion (63% spondylolisthesis). Baseline data were compared between the groups. Bivariate log-rank analysis was used to compare outcomes between groups, followed by multivariable Cox regression analysis accounting for differences in baseline characteristics. Patients undergoing decompression with fusion presented with a higher incidence of back pain (P=0.004) and spondylolisthesis (P<0.001), had more often bilateral decompressions (P<0.001), more facetectomies (P<0.001), and more levels of decompression (P=0.004) than those who underwent decompression alone. We found a difference in recurrence of radiculopathy (no fusion: 25% vs. fusion: 9.4%, P=0.029) in bivariate analysis. However, this difference did not hold when accounting for confounders (hazard ratio, 0.50, 95% confidence interval, 0.19-1.31, P=0.16). There was no difference in recurrence of back pain in bivariate (no fusion: 29% vs. fusion: 22%, P=0.51) and multivariable analysis (hazard ratio 0.51, 95% confidence interval, 0.23-1.14, P=0.10). We found, with the numbers evaluated, no difference in recurrence of radiculopathy or back pain between patients undergoing decompression with or without fusion after accounting for confounders. The decision for fusion should be considered in light of the extent of decompression and the existence of other pathology. Level III-therapeutic study.


Identification of New Soluble Factors Correlated With the Development of Graft Failure After Haploidentical Hematopoietic Stem Cell Transplantation.
Graft failure is a severe complication of allogeneic hematopoietic stem cell transplantation (HSCT). The mechanisms involved in this phenomenon are still not completely understood; data available suggest that recipient T lymphocytes surviving the conditioning regimen are the main mediators of immune-mediated graft failure. So far, no predictive marker or early detection method is available. In order to identify a non-invasive and efficient strategy to diagnose this complication, as well as to find possible targets to prevent/treat it, we performed a detailed analysis of serum of eight patients experiencing graft failure after T-cell depleted HLA-haploidentical HSCT. In this study, we confirm data describing graft failure to be a complex phenomenon involving different components of the immune system, mainly driven by the IFNγ pathway. We observed a significant modulation of IL7, IL8, IL18, IL27, CCL2, CCL5 (Rantes), CCL7, CCL20 (MIP3a), CCL24 (Eotaxin2), and CXCL11 in patients experiencing graft failure, as compared to matched patients not developing this complication. For some of these factors, the difference was already present at the time of infusion of the graft, thus allowing early risk stratification. Moreover, these cytokines/chemokines could represent possible targets, providing the rationale for exploring new therapeutic/preventive strategies.


Hydration status, fluid intake, and electrolyte losses in youth soccer players.
The purpose of the study was to determine the hydration status, fluid intake, and electrolyte losses of 21 male professional youth soccer players (age 17.1 ± 0.7 y) training in a cool environment. Pretraining and posttraining measurements of body mass, urine (freezing-point osmolality method), and sweat concentration (flame-emission spectroscopy) were collected. Fourteen players were found to be hypohydrated before training. The amount of fluid lost due to exercise equated to a 1.7% loss in body mass, which equated to a gross dehydration loss of 0.5%. Overall, the soccer players replaced 46% ± 88% of sweat loss during training, and only 4 remained hypohydrated after training. No significant correlations between sweat loss and sweat concentrations of Na+ (r = -.11, P = .67) or K+ (r = .14, P = .58) were found, but there was a significant correlation with Mg2+ (r = -.58, P < .009). This study found large variability in pretraining hydration status that the players were able to rehydrate during the training sessions. However, given the numbers starting training in a hypohydrated state, adequate hydration status before training should be considered by youth players, coaches, and sports-science support staff.


Lipotropes, immunocompetence, and cancer.
Lipotropes (choline, methionine, folic acid, and vitamin B12) are required for normal metabolic function at the cellular and subcellular levels. Deficiencies of any or all of them to a point of influence on methyl group metabolism has a profound effect on synthesis of cellular macromolecules and on cell proliferation. Lipotrope deficiency results in a diminished immunocompetence and an increased susceptibility to a number of types of cancer in experimental animals. A challenge now being addressed is to identify the linkage between lipotropes, the immune system, and cancer and to determine mechanisms which can be useful in cancer prevention.


Comparative analysis of Constitutive and fiber-specific promoters under the expression pattern of Expansin gene in transgenic Cotton.
Promoters are specified segments of DNA that lead to the initiation of transcription of a specific gene. The designing of a gene cassette for plant transformation is significantly dependent upon the specificity of a promoter. Constitutive Cauliflower mosaic virus promoter, CaMV35S, due to its developmental role, is the most commonly used promoter in plant transformation. While Gossypium hirsutum (Gh) being fiber-specific promoter (GhSCFP) specifically activates transcription in seed coat and fiber associated genes. The Expansin genes are renowned for their versatile roles in plant growth. The overexpression of Expansin genes has been reported to enhance fiber length and fineness. Thus, in this study, a local Cotton variety was transformed with Expansin (CpEXPA1) gene, in the form of two separate cassettes, each with a different promoter, named as 35SEXPA1 and FSEXPA1 expressed under CaMV35S and GhSCFP promoters respectively. Integration and Spatiotemporal relative expression of the transgene were studied in an advanced generation. GhSCFP bearing transgene expression was significantly higher in Cotton fiber than other plant parts. While transgene with CaMV35S promoter was found to be continually expressing in all tissues but the expression was lower in fiber than that expressed under GhSCFP. The temporal expression profile was quite interesting with a gradual increasing pattern of both constructs from 1DPA (days post anthesis) to 18DPA and decreased expression from 24 to 30 DPA. Besides the relative expression of promoters, fiber cellulose quantification and fluorescence intensity were also observed. The study significantly compared the two most commonly used promoters and it is deduced from the results that the GhSCFP promoter could be used more efficiently in fiber when compared with CaMV35S which being constitutive in nature preferred for expression in all parts of the plant.


Association of Abdominal Aorta Calcium and Coronary Artery Calcium with Incident Cardiovascular and Coronary Heart Disease Events in Black and White Middle-Aged People: The Coronary Artery Risk Development in Young Adults Study.
Background Assessing coronary artery calcium (CAC) is among AHA/ACC prevention guidelines for people at least 40 years old at intermediate risk for coronary heart disease (CHD). To study enhanced risk stratification, we investigated the predictive value of abdominal aorta calcium (AAC) relative to CAC for cardiovascular disease (CVD) and CHD events in Black and White early middle-aged participants, initially free of overt CVD. Methods and Results In the CARDIA (Coronary Artery Risk Development in Young Adults) study, a multi-center, community-based, longitudinal cohort study of CVD risk, the CAC and AAC scores were assessed in 3011 participants in 2010-2011 with follow-up until 2019 for incident CVD and CHD events. Distributions and predictions, overall and by race, were computed. During the 8-year follow-up, 106 incident CVD events (55 were CHD) occurred. AAC scores tended to be much higher than CAC scores. AAC scores were higher in Black women than in White women. CAC predicted CVD with HR 1.77 (1.52-2.06) and similarly for AAC, while only CAC predicted CHD. After adjustment for risk factors and calcium in the other arterial bed, the association of CAC with CVD was independent of risk factors and AAC, while the association of AAC with CVD was greatly attenuated. However, AAC predicted incident CVD when CAC was 0. Prediction did not vary by race. Conclusions AAC predicted CVD nearly as strongly as CAC and could be especially useful as a diagnostic tool when it is an incidental finding or when no CAC is found.


New methods for estimating follow-up rates in cohort studies.
The follow-up rate, a standard index of the completeness of follow-up, is important for assessing the validity of a cohort study. A common method for estimating the follow-up rate, the "Percentage Method", defined as the fraction of all enrollees who developed the event of interest or had complete follow-up, can severely underestimate the degree of follow-up. Alternatively, the median follow-up time does not indicate the completeness of follow-up, and the reverse Kaplan-Meier based method and Clark's Completeness Index (CCI) also have limitations. We propose a new definition for the follow-up rate, the Person-Time Follow-up Rate (PTFR), which is the observed person-time divided by total person-time assuming no dropouts. The PTFR cannot be calculated directly since the event times for dropouts are not observed. Therefore, two estimation methods are proposed: a formal person-time method (FPT) in which the expected total follow-up time is calculated using the event rate estimated from the observed data, and a simplified person-time method (SPT) that avoids estimation of the event rate by assigning full follow-up time to all events. Simulations were conducted to measure the accuracy of each method, and each method was applied to a prostate cancer recurrence study dataset. Simulation results showed that the FPT has the highest accuracy overall. In most situations, the computationally simpler SPT and CCI methods are only slightly biased. When applied to a retrospective cohort study of cancer recurrence, the FPT, CCI and SPT showed substantially greater 5-year follow-up than the Percentage Method (92%, 92% and 93% vs 68%). The Person-time methods correct a systematic error in the standard Percentage Method for calculating follow-up rates. The easy to use SPT and CCI methods can be used in tandem to obtain an accurate and tight interval for PTFR. However, the FPT is recommended when event rates and dropout rates are high.


Flight metabolic rate has contrasting effects on dispersal in the two sexes of the Glanville fritillary butterfly.
Evolution of dispersal is affected by context-specific costs and benefits. One example is sex-biased dispersal in mammals and birds. While many such patterns have been described, the underlying mechanisms are poorly understood. Here, we study genetic and phenotypic traits that affect butterfly flight capacity and examine how these traits are related to dispersal in male and female Glanville fritillary butterflies (Melitaea cinxia). We performed two mark-recapture experiments to examine the associations of individuals' peak flight metabolic rate (MR(peak)) and Pgi genotype with their dispersal in the field. In a third experiment, we studied tethered flight in the laboratory. MR(peak) was negatively correlated with dispersal distance in males but the trend was positive in females, and the interaction between MR(peak) and sex was significant for long-distance dispersal. A similar but nonsignificant trend was found in relation to molecular variation at Pgi, which encodes a glycolytic enzyme: the genotype associated with high MR(peak) tended to be less dispersive in males but more dispersive in females. The same pattern was repeated in the tethered flight experiment: the relationship between MR(peak) and flight duration was positive in females but negative in males. These results suggest that females with high flight capacity are superior in among-population dispersal, which facilitates the spatial spreading of their reproductive effort. In contrast, males with high flight capacity may express territorial behaviour, and thereby increase the number of matings, whereas inferior males may be forced to disperse. Thus, flight capacity has opposite associations with dispersal rate in the two sexes.


Mild parkinsonian signs and psycho-behavioral symptoms in subjects with mild cognitive impairment.
Mild cognitive impairment (MCI) may be accompanied by extra pyramidal signs (EPS), which are related to the severity and type of cognitive impairment. We aimed to elucidate further the relationship between MCI and EPS, analyzing the correlation between the severity of EPS and cognitive functions, and the presence of EPS and neuro-psychiatric features. Data were obtained from a longitudinal study of 150 MCI outpatients. Participants underwent a clinical assessment including the Unified Parkinson Disease Rating Scale, the Neuropsychiatric Inventory, the Tinetti Scale, and a standardized neuropsychological battery. Mild EPS could be defined as being present (MCI with mild EPS) using a subscale of UPDRS, based on three specific symptoms: bradykinesia, rigidity and tremor. The two groups, one with mild EPS (24%) and one without EPS (76%), differed in gait abnormalities and presence of extrapyramidal symptoms. Groups did not differ in terms of general cognitive functions evaluated using the Mini-mental State Examination, while subjects with MCI with mild EPS performed significantly worse than those with MCI without EPS in total global score and in non-memory items of the Alzheimer's Disease Assessment Scale. Moreover, severity of EPS was significantly correlated with low performance on executive functions and with high performance on episodic memory. The group with MCI with mild EPS were observed to have a greater prevalence of patients with anxiety, depression, apathy and sleep disturbances than in MCI without EPS. MCI may be associated with mild parkinsonian signs, the severity of which are related to the severity of cognitive impairment, in particular of non-memory functions, and to a differential pattern of psycho-behavioral symptoms.


Comparison of Functional Capacity and Symptoms of COPD Patients with and without Pulmonary Hypertension.
Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD) associated with a decrease in the survival rate of patients with COPD. Our aim was to investigate whether PH impairs the functional capacity and symptoms in patients with COPD. In addition, we aimed to evaluate the correlation between the functional capacity and symptoms score in patients with COPD. This prospective cross-sectional study enrolled 64 patients with moderate to severe COPD, prospectively. All patients underwent the pulmonary function test, echocardiography, 6-minute walk test (6MWT), and cardiopulmonary exercise testing (CPET). We applied the modified Medical Research Council (mMRC) dyspnea scale and COPD Assessment Test (CAT) to all patients. The mean pulmonary arterial pressure (mPAP) >30 mmHg with echocardiography was considered as PH. The patients were grouped according to the presence of PH as COPD-PH (n=30) and COPD-nonPH (n=34). Hospitalization rate was higher in the COPD-PH group than in the COPD-nonPH group (p=0.006). The 6MWT results were lower in the COPD-PH group compared to the COPD-nonPH group (325±61 m vs. 354±46 m, respectively, p=0.025). In the COPD-PH group, the maximum oxygen consumption (VO2max) was lower, but the difference did not reach statistical significance (p=0.118). Although the maximum load and minute ventilation were lower in the COPD-PH group, the end-tidal pressure of CO2 (PETCO2) was higher (p=0.033, p=0.036, and p=0.009, respectively). However, the CAT score and mMRC were similar between the groups (p=0.405 and p=0.238, respectively). An elevated PAP in patients with COPD limits the exercise capacity. Using CPET in the functional evaluation of patients with COPD may be beneficial in the early detection of PH.


Association between the intraoperative fluid balance during cardiac surgery and postoperative sequential organ failure assessment score: a post hoc analysis of the BROTHER study, a retrospective multicenter cohort study.
Although intraoperative intravenous fluids are commonly administered to reverse intraoperative hypotension during cardiac surgery, the appropriate volume remains unclear. This study aimed to evaluate the relationship between the intraoperative fluid balance and sequential organ failure assessment (SOFA) score in patients undergoing cardiac surgery to determine the impact of intraoperative intravenous fluids on their organs. This was a post hoc analysis using data from a multicenter, retrospective, observational study across 14 intensive care units (ICUs) in Japan. Adult patients admitted to ICUs after elective coronary artery bypass grafting or valve surgery from January 1 to December 31, 2018 were enrolled. We compared patients with intraoperative fluid balance < 20 ml/kg to those with fluid balance ≥ 20 ml/kg and conducted a multiple regression analysis for the SOFA score within 24 h of ICU admission. Of the 1567 included patients, 870 met the eligibility criteria. A total of 725 patients (83%) had an intraoperative fluid balance of ≥ 20 ml/kg. In the univariate analysis, the SOFA score (interquartile range) was 7 (6-8) and 7 (6-9) in the intraoperative fluid balance < 20 ml/kg and ≥ 20 ml/kg groups, respectively (p = 0.017). Multiple regression analysis showed a positive association between intraoperative fluid balance and SOFA score within 24 h of ICU admission [standardized coefficient 0.0065 (95% confidence interval 0.0036-0.0095), p < 0.001]. Intraoperative fluid balance in patients undergoing cardiac surgery was significantly associated with higher SOFA scores within 24 h of ICU admission.


Allogeneic bone marrow transplantation for childhood leukemia following a busulfan and melphalan preparative regimen.
Thirty children with leukemia underwent allogeneic bone marrow transplantation (BMT) following a radiation-free preparative regimen, from July 1988 to January 1996. Twelve males and 18 females, ages 9 months to 15 years (median 8.5 years), received busulfan (BU, 4 mg/kg/day for 4 days by mouth), followed by melphalan (L-PAM, 60-70 mg/m2/day i.v. for 3 days), and infusion of allogeneic marrow from an HLA-matched related donor. Diagnoses included acute myelogenous leukemia (n = 20), acute lymphoblastic leukemia (n = 8) and chronic myelogenous leukemia (n = 2). Twenty-five patients were transplanted in first complete remission (CR), three in second CR, and two patients with chronic myelogenous leukemia in the first chronic phase. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate (MTX) alone in 27 patients and short-term MTX and cyclosporin A in three patients. Engraftment was achieved in all patients. Toxicities were mild or moderate. Six patients developed acute GVHD: four had grade I and two had grade II. Chronic GVHD was documented in eight patients. Three patients relapsed. As of September 1997, 27 patients were alive and well at 22-110 months (median 61) of follow-up. The disease-free survival rate at 5 years after BMT was 90%. A regimen consisting of high-dose BU and L-PAM without total body irradiation is useful for conditioning for allogeneic BMT in children with leukemia.


Direct evidence that decreased serum opsonization of Streptococcus pneumoniae via the alternative complement pathway in sickle cell disease is related to antibody deficiency.
Two approaches were used to demonstrate that reduction in serum opsonization of Streptococcus pneumoniae via the alternative complement pathway in children with sickle cell disease is related to a deficiency of antibodies to pneumococcal capsular polysaccharide. First, opsonization of S. pneumoniae mediated by the alternative pathway in patients' sera was restored to normal by addition of the purified IgG or IgM fraction of goat antiserum to capsular polysaccharide of the homologous serotype. Secondly, IgG antibody titers to capsular polysaccharide in patients' sera correlated significantly with alternative pathway-mediated opsonization; the correlation between titers of IgM anticapsular antibodies and opsonization approached statistical significance. The sum of the IgG and IgM anticapsular antibody titers correlated most significantly with opsonization. Our results suggest that reduction in alternative pathway-mediated opsonization in sera from children with sickle cell disease is related to low levels of both IgG and IgM anticapsular antibodies.


Habituation of the landing response of Drosophila wild-type and mutants defective in olfactory learning.
Habituation of the landing response of Drosophila is described by two behavioural variables. The landing activity and the time till the onset of the response. These data are described in the framework of a leaky integrator model. It is shown that the course of habituation can be simulated by varying only one of the parameters of the model, the output of the detector for landing stimuli. The two other parameters, the leakiness and the degree of biological variance, are kept at fixed values. With the exception of the data for mutant rutabaga, the same values for the constant parameters can be used to describe the data for two wildtype strains and mutants defective in olfactory learning. Duerr and Quinn (1982) have shown that these mutants habituate slower than the corresponding wildtype to chemosensory stimuli. In contrast habituation to visual stimuli of the mutants dunce amnesiac and rutabaga is faster than that of wildtype Canton-S. The theoretical description shows that this can not be attributed to leakier integrators of the mutants, but rather to a faster decrease of the output of the landing detector.


Swellable molecularly imprinted polyN-(N-propyl)acrylamide particles for detection of emerging organic contaminants using surface plasmon resonance spectroscopy.
Lightly crosslinked theophylline imprinted polyN-(N-propyl)acrylamide particles (ca. 300nm in diameter) that are designed to swell and shrink as a function of analyte concentration in aqueous media were spin coated onto a gold surface. The nanospheres responded selectively to the targeted analyte due to molecular imprinting. Chemical sensing was based on changes in the refractive index of the imprinted particles that accompanied swelling due to binding of the targeted analyte, which was detected using surface plasmon resonance (SPR) spectroscopy. Because swelling leads to an increase in the percentage of water in the polymer, the refractive index of the polymer nanospheres decreased as the particles swelled. In the presence of aqueous theophylline at concentrations as low as 10(-6)M, particle swelling is both pronounced and readily detectable. The full scale response of the imprinted particles to template occurs in less than 10min. Swelling is also reversible and independent of the ionic strength of the solution in contact with the polymer. Replicate precision is less than 10(-4) RI units. By comparison, there is no response to caffeine which is similar in structure to theophylline at concentrations as high as 1x10(-2)M. Changes in the refractive index of the imprinted polymer particles, as low as 10(-4) RI units could be readily detected. A unique aspect of the prepared particles is the use of light crosslinking rather than heavy crosslinking. This is a significant development as it indicates that heavy crosslinking is not entirely necessary for selectivity in molecular imprinting with polyacrylamides.


EFFECTS OF BACTERIAL ENDOTOXIN ON WATER INTAKE, FOOD INTAKE, AND BODY TEMPERATURE IN THE ALBINO RAT.
Intraperitoneal injections of Escherichia coli endotoxin in albino rats produces a decrease in food and water intake and a drop in body temperature. The drop in temperature and in water intake is probably proportional to the size of the dose. Using a behavioral test in which animals are trained to press a bar at a steady rate for intermittent food or water reward, it is possible to demonstrate the sudden onset of the toxin effect at 30 to 45 minutes after injection. In any group of rats, all of whom were presumably exposed to E. coli, three types of response to toxin can be found: (a) Sharp reduction in water intake 30 minutes after injection. (b) Little or no change in intake or rate of working for water reward. (c) Immediate depression of work rate. These three types of reaction appear related to previous experience with the toxin. The "normal" or "inexperienced" reaction a was seen in animals who had not been given toxin before. The "protected" reaction b, with little or no effect of toxin injection on response rate was frequently found 4 to 5 days after a previous injection. The "susceptible" reaction c was found in three animals after 14 or more days had passed since a previous injection. Injections of toxin into the lateral hypothalamic region of four animals through implanted cannulae had no effect on the rate of bar pressing for water. Control injections of lidocaine blocked response rate completely for brief periods in three animals.


Training of interventional cardiologists in radiation protection--the IAEA's initiatives.
The International Atomic Energy Agency (IAEA) has initiated a major international initiative to train interventional cardiologists in radiation protection as a part of its International Action Plan on the radiological protection of patients. A simple programme of two days' training has been developed, covering possible and observed radiation effects among patients and staff, international standards, dose management techniques, examples of good and bad practice and examples indicating prevention of possible injuries as a result of good practice of radiation protection. The training material is freely available on CD from the IAEA. The IAEA has conducted two events in 2004 and 2005 and number of events are planned in 2006. The survey conducted among the cardiologists participating in these programmes indicates that over 80% of them were attending such a structured programme on radiation protection for the first time. As the magnitude of X-ray usage in cardiology grows to match that in interventional radiology, the standards of training on radiation effects, radiation physics and radiation protection in interventional cardiology should also match those in interventional radiology.


Epidemiology and susceptibility to antimicrobials in community, hospital and long-term care facility bacteremia in northern Israel: a 6 year surveillance.
Identification of pathogens and their susceptibility to antimicrobials is mandatory for successful empiric antibiotic treatment. To compare the clinical characteristics of patients with bacteremia, as well as the bacterial distribution and antimicrobial susceptibility in community, hospital and long-term care facilities during two periods (2001-2002 and 2005-2006). The study was conducted at the HaEmek Medical Center, a community 500-bed teaching hospital in northern Israel serving a population of approximately 500,000 inhabitants. All episodes of bacteremia (n = 1546) during two 2 year periods (2001-2 and 2005-6) were prospectively recorded, evaluated and compared (755 in 2001-2 and 791 in 2005-6). In both periods the urinary tract was the main port of entry in community and long-term care facility bacteremia, while the urinary tract--primary and catheter-related--were similar in frequency as sources of hospital bacteremia. Escherichia coli was the most frequent pathogen isolate. No significant changes in the frequency of methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase-producing bacteria were seen between the two 2 year periods (2001-2 and 2005-6). The susceptibility of non-ESBL-producing E. coli decreased for some antibiotics while non-ESBL-producing Klebsiella pneumoniae susceptibility profile improved in the same period. A non-statistically significant trend of increased resistance in gram-negative isolates to quinolones, piperacillin and piperacillin-tazobactam was observed, but most isolates still remained highly susceptible to carbapenems. There was a small increase in mortality rate in hospital bacteremia during the second period. Continuous surveillance is imperative for monitoring the local epidemiology and for developing local treatment guidelines.


Utility of intraoperative transesophageal echocardiography during endovascular stent-graft repair of acute thoracic aortic dissection.
This study was undertaken to evaluate the utility and efficacy of intraoperative transesophageal echocardiography (TEE) in the endovascular management of patients with acute type B aortic dissection. Twelve consecutive patients with acute type B aortic dissection underwent elective endoluminal stent-graft repair in the operating room under angiographic and TEE guidance. The follow-up protocol included spiral CT scanning before discharge from the hospital to assess thrombosis exclusion of the aortic false lumen, perfusion of branch vessels, and the absence of perigraft leak. No complications related to the use of TEE were encountered. TEE clearly demonstrated the presence and extent of the dissection flap in all patients. After the procedure a persistent perigraft leak or residual flow into the false lumen was diagnosed by TEE in 6 patients, whereas intraoperative angiography visualized only 3 cases. Postoperative CT scan confirmed these findings. One patient died 2 months later by aortic rupture secondary to a persistent perigraft leak not treated (8.3% mortality). No postoperative paraplegia or visceral ischaemia were registered, although an asymptomatic occlusion of left subclavian artery was observed. TEE monitoring detects perigraft leakage, identifies the entry tear, and accurately demonstrates sealing of the false lumen. TEE is essential in our practice as an adjuvant to fluoroscopy to achieve optimal results during endovascular stent-graft repair of acute thoracic aortic dissection.


Consumer trust in the dairy value chain in China: The role of trustworthiness, the melamine scandal, and the media.
This study provides a deep insight into Chinese consumer trust in the Chinese dairy value chain, as a lack of trust due to the 2008 melamine scandal has been widely recognized as a barrier to the development of the domestic dairy industry in China. Based on face-to-face interviews with 954 Chinese consumers in Beijing, Shanghai, and Shijiazhuang, this study measured consumer trust in farmers, manufacturers, retailers, the government, and third parties. Consumer trust was studied by measuring the effect of beliefs on the trustworthiness of actors (i.e., competence, benevolence, integrity, credibility, and openness), and current experiences regarding the melamine scandal and the media. The results showed that the level of trust in dairy chain actors varied. The government and third parties were relatively highly trusted, whereas retailers were considered less trustworthy. The importance of consumer beliefs about trustworthiness are different among actors. Consumer belief of competence determines trust in farmers and manufacturers. For retailers, the government, and third parties, respectively, benevolence, credibility, and openness are the most important factors. Trust in dairy chain actors is still strongly negatively affected by current experiences regarding the melamine scandal, even though it occurred more than 10 years ago. Using social media to directly provide more information and establish continuous daily communication with consumers could help manufacturers and third parties to strengthen consumer trust.


In vivo optical molecular imaging of inflammation and immunity.
Inflammation is the phenotypic form of various diseases. Recent development in molecular imaging provides new insights into the diagnostic and therapeutic evaluation of different inflammatory diseases as well as diseases involving inflammation such as cancer. While conventional imaging techniques used in the clinical setting provide only indirect measures of inflammation such as increased perfusion and altered endothelial permeability, optical imaging is able to report molecular information on diseased tissue and cells. Optical imaging is a quick, noninvasive, nonionizing, and easy-to-use diagnostic technology which has been successfully applied for preclinical research. Further development of optical imaging technology such as optoacoustic imaging overcomes the limitations of mere fluorescence imaging, thereby enabling pilot clinical applications in humans. By means of endogenous and exogenous contrast agents, sites of inflammation can be accurately visualized in vivo. This allows for early disease detection and specific disease characterization, enabling more rapid and targeted therapeutic interventions. In this review, we summarize currently available optical imaging techniques used to detect inflammation, including optical coherence tomography (OCT), bioluminescence, fluorescence, optoacoustics, and Raman spectroscopy. We discuss advantages and disadvantages of the different in vivo imaging applications with a special focus on targeting inflammation including immune cell tracking.


Effects of long-term treatment with melatonin or melatonin plus ectopic pituitary transplants on testicular LH/hCG and prolactin receptors in juvenile Syrian hamsters (Mesocricetus auratus).
Juvenile hamsters were injected daily with melatonin and some were also given transplants of 2 pituitaries under the kidney capsule. Weights of the testes and the accessory reproductive glands were reduced after 8 and after 12 weeks of melatonin treatment, but remained unaltered in animals treated with ectopic pituitary transplants. Levels of testicular LH/hCG receptors were significantly reduced by daily melatonin injections for 8 and 12 weeks. The presence of pituitary transplants in melatonin-injected hamsters prevented these reductions, and increased LH/hCG receptors above control levels. These changes in testicular LH/hCG receptors were closely related to alterations in serum prolactin concentration induced by melatonin and pituitary transplants. After 8, but not after 12 weeks of treatment, testicular prolactin receptor levels were reduced by melatonin and maintained by the presence of pituitary transplants. We conclude that: juvenile male hamsters become sensitive to the effects of daily melatonin injections when they reach maturity; daily melatonin injections can reduce the levels of testicular LH/hCG and prolactin receptors; and the effects of melatonin on LH/hCG and prolactin receptors are probably due to suppression of endogenous prolactin release.


Factors that predict the success of cyclosporine treatment for chronic urticaria.
Chronic urticaria (CU) is a frequent, difficult clinical problem. When first-line therapy fails, patients are often treated with alternative therapies that either have a poor side effect profile or little evidence to support effectiveness. To describe our low-dose cyclosporine-treated CU population and factors predicting a positive outcome. A retrospective chart review was conducted of adult CU patients treated with cyclosporine. Elements of the history, physical examination, diagnostic testing, efficacy, and side effects were extracted for statistical analysis. Chronic urticaria was defined as having urticaria more than 3 days per week for 6 consecutive weeks. Sixty-eight adults with CU who fulfilled the intake criteria and completed a course of cyclosporine were identified. After taking cyclosporine at an average dose of 1.8 ± 1.1 mg/kg, 53 (78%) patients attained complete remission defined as ≤ 1 day of hives per month. Recurrence occurred in only 7 patients; all achieved remission with resumption of cyclosporine. A history of hives (P = .01), shorter duration of urticaria (mean: 55.2 weeks vs 259.63 weeks; P = .03), and positive CU Index (P = .05) predicted a favorable response to cyclosporine. Notably, autologous serum skin testing, prior response to steroids, atopic status, or presence of antithyroid antibodies was not predictive. Male sex and a positive ANA trended toward significance (P = .1). Side effects were generally mild and seen in 35% of patients; all were reversible by dose reduction. Cyclosporine is an effective treatment for CU, and a history of hives, shorter duration of disease, and CU index ≥10 predict a successful response.


Application of the Inverted Classroom Model for Teaching Pathophysiology to Chinese Undergraduate Medical Students: Usability Study.
The inverted classroom model differs from the traditional teaching model as it reverses the pattern of knowledge transfer and internalization. In recent years, this new teaching model has received much attention in undergraduate medical education. Pathophysiology is a course in the undergraduate Chinese medical curriculum that is critical in bridging basic medical science and clinical medicine. The purpose of this study was to investigate the application of inverted classroom in delivering the course on pathophysiology to Chinese undergraduate medical students. In the spring semester of 2018, inverted classroom teaching was implemented for second-year clinical medicine students at the College of Medicine at Nanchang University. The topics of hypoxia and respiratory failure were selected for the inverted classroom study. The effect of the inverted classroom on teaching pathophysiology was evaluated using classroom performance metrics, a final examination, and questionnaires. This study found that students in the inverted classroom group achieved higher scores in their in-course assessments (82.35 [SD 11.45] vs 81.33 [SD 9.51], respectively) and in their final exams (73.41 [SD 10.37] vs 71.13 [SD 11.22], respectively) than those in the traditional lecture-based group, but the scores were not significantly different (P=.13, unpaired two-tailed t test). There was also no significant difference in the distribution of the score segments in the class quiz (P=.09, chi-square test) and in the final exams (P=.25, chi-square test) between the 2 groups. Further, most of the students reported that the inverted classroom increased their learning motivation, made them more confident, and helped them understand the content on pathophysiology better. The students in the inverted classroom also improved in their problem-solving skills and teamwork abilities. However, some students from the inverted classroom group also reported that the self-learning and preparatory work before class increased their learning burden. This study shows the feasibility and promise of inverted classroom for teaching pathophysiology to undergraduate Chinese medical students. The inverted classroom improves students' learning interests and attitudes toward learning. However, further studies are required to assess the benefits of broader acceptance and implementation of the inverted classroom among Chinese undergraduate medical students.