Acid-catalyzed condensed-phase reactions of limonene and terpineol and their impacts on gas-to-particle partitioning in the formation of organic aerosols.
We investigated the condensed-phase reactions of biogenic VOCs with C double bond C bonds (limonene, C(10)H(16), and terpineol, C(10)H(18)O) catalyzed by sulfuric acid by both bulk solution (BS) experiments and gas-particle (GP) experiments using a flow cell reactor. Product analysis by gas chromatography-mass spectrometry (GC-MS) showed that cationic polymerization led to dimeric and trimeric product formation under conditions of relative humidity (RH) <20% (in the GP experiments) and a sulfuric acid concentration of 57.8 wt % (in the BS experiments), while hydration occurred under conditions of RH > 20% (in the GP experiments) and sulfuric acid concentrations of 46.3 wt % or lower (in the BS experiments). Apparent partitioning coefficients (K(p,rxn)) were estimated from the GP experiments by including the reaction products. Only under extremely low RH conditions (RH < 5%) did the values of K(p,rxn) ( approximately 5 x 10(-6) m(3)/microg for limonene and approximately 2 x 10(-5) m(3)/microg for terpineol) substantially exceed the physical partitioning coefficients (K(p) = 6.5 x 10(-8) m(3)/microg for limonene and =2.3 x 10(-6) m(3)/microg for terpineol) derived from the absorptive partitioning theory. At RH higher than 5%, the apparent partitioning coefficients (K(p,rxn)) of both limonene and terpineol were in the same order of magnitude as the K(p) values derived from the absorptive partitioning theory. Compared with other conditions including VOC concentration and degree of neutralization (by ammonium) of acidic particles, RH is a critical parameter that influences both the reaction mechanisms and the uptake ability (K(p,rxn) values) of these processes. The finding suggests that RH needs to be considered when taking the effects of acid-catalyzed reactions into account in estimating organic aerosol formation from C double bond C containing VOCs.


Inhibition of protein kinase CK2 by flavonoids and tyrphostins. A structural insight.
Sixteen flavonoids and related compounds have been tested for their ability to inhibit three acidophilic Ser/Thr protein kinases: the Golgi apparatus casein kinase (G-CK) recently identified with protein FAM20C, protein kinase CK1, and protein kinase CK2. While G-CK is entirely insensitive to all compounds up to 40 μM concentration, consistent with the view that it is not a member of the kinome, and CK1 is variably inhibited in an isoform-dependent manner by fisetin and luteolin, and to a lesser extent by myricetin and quercetin, CK2 is susceptible to drastic inhibition by many flavonoids, displaying with six of them IC(50) values < 1 μM. A common denominator of these compounds (myricetin, quercetin, fisetin, kaempferol, luteolin, and apigenin) is a flavone scaffold with at least two hydroxyl groups at positions 7 and 4'. Inhibition is competitive with respect to the phospho-donor substrate ATP. The crystal structure of apigenin and luteolin in complex with the catalytic subunit of Zea mays CK2 has been solved, revealing their ability to interact with both the hinge region (Val116) and the positive area near Lys68 and the conserved water W1, the two main polar ligand anchoring points in the CK2 active site. Modeling experiments account for the observation that luteolin but not apigenin inhibits also CK1. The observation that luteolin shares its pyrocatechol moiety with tyrphostin AG99 prompted us to solve also the structure of this compound in complex with CK2. AG99 was found inside the ATP pocket, consistent with its mode of inhibition competitive with respect to ATP. As in the case of luteolin, the pyrocatechol group of AG99 is critical for binding, interacting with the positive area in the deepest part of the CK2 active site.


New adaptive mesh development for accurate near-field enhancement computation.
An accurate computation of the near-field enhancement is a key factor for the optimization of nanostructures in plasmonics. This problem has been addressed for Green's dyadic method but remains open for finite element method (FEM) where the use of non-Cartesian meshes is known to be the most efficient. We present a new adaptive mesh process based on the a posteriori error indicator estimation on the physical solution. This new procedure accelerates drastically the convergence of the solution and minimizes both the memory requirement and the computational time.


Stochastic dynamics of Francisella tularensis infection and replication.
We study the pathogenesis of Francisella tularensis infection with an experimental mouse model, agent-based computation and mathematical analysis. Following inhalational exposure to Francisella tularensis SCHU S4, a small initial number of bacteria enter lung host cells and proliferate inside them, eventually destroying the host cell and releasing numerous copies that infect other cells. Our analysis of disease progression is based on a stochastic model of a population of infectious agents inside one host cell, extending the birth-and-death process by the occurrence of catastrophes: cell rupture events that affect all bacteria in a cell simultaneously. Closed expressions are obtained for the survival function of an infected cell, the number of bacteria released as a function of time after infection, and the total bacterial load. We compare our mathematical analysis with the results of agent-based computation and, making use of approximate Bayesian statistical inference, with experimental measurements carried out after murine aerosol infection with the virulent SCHU S4 strain of the bacterium Francisella tularensis, that infects alveolar macrophages. The posterior distribution of the rate of replication of intracellular bacteria is consistent with the estimate that the time between rounds of bacterial division is less than 6 hours in vivo.


Conventional and maximum length sequences middle latency response in patients with central nervous system lesions.
Conventional and maximum length sequence (MLS) middle latency response (MLR) procedures were compared across several parameters for control patients and patients with central nervous system lesions. There were similar findings for both populations and both types of MLR for the absolute latencies of Na and Pa waves. Middle latency waves were absent more often in the neurologic than control subjects for both the conventional and MLS-MLR procedures. Overall, more MLR waves were present for the MLS technique than for the conventional MLR technique. Differences in wave amplitude were significant for several recording sites when comparing neurologic with control groups, but findings were similar for wave amplitude when comparing the two types of MLR procedures for the neurologic population. Based on these findings, no clear diagnostic advantage was shown for using the MLS-MLR technique. These findings are further discussed.


Remodeling yeast gene transcription by activating the Ty1 long terminal repeat retrotransposon under severe adenine deficiency.
The Ty1 long terminal repeat (LTR) retrotransposon of Saccharomyces cerevisiae is a powerful model to understand the activation of transposable elements by stress and their impact on genome expression. We previously discovered that Ty1 transcription is activated under conditions of severe adenine starvation. The mechanism of activation is independent of the Bas1 transcriptional activator of the de novo AMP biosynthesis pathway and probably involves chromatin remodeling at the Ty1 promoter. Here, we show that the 5' LTR has a weak transcriptional activity and is sufficient for the activation by severe adenine starvation. Furthermore, we demonstrate that Ty1 insertions that bring Ty1 promoter sequences into the vicinity of a reporter gene confer adenine starvation regulation on it. We provide evidence that similar coactivation of genes adjacent to Ty1 sequences occurs naturally in the yeast genome, indicating that Ty1 insertions can mediate transcriptional control of yeast gene expression under conditions of severe adenine starvation. Finally, the transcription pattern of genes adjacent to Ty1 insertions suggests that severe adenine starvation facilitates the initiation of transcription at alternative sites, partly located in the 5' LTR. We propose that Ty1-driven transcription of coding and noncoding sequences could regulate yeast gene expression in response to stress.


Magnesium status in patients with acute myocardial infarction: a pilot study.
The magnesium retention test (MRT) was used together with muscle quadriceps lateralis biopsy in a pilot study of 5 patients with acute myocardial infarction (AMI) and 6 healthy control persons. Included were men aged 35-65 years with no prior medication and/or diseases. The magnesium retention was 42% in the infarction group and 22% in the control group (p less than 0.01). A lower muscle content of magnesium in the AMI group confirms the MRT and indicates a magnesium deficiency. The bleeding time after the magnesium load was prolonged.


Understanding the expression of loneliness on Twitter across age groups and genders.
Some individuals seek support around loneliness on social media forums. In this work, we aim to determine differences in the use of language by users-in different age groups and genders (female, male), who publish posts on Twitter expressing loneliness. We hypothesize that these differences in the use of language will reflect how these users express themselves and some of their support needs. Interventions may vary depending on the age and gender of an individual, hence, in order to identify high-risk individuals who express loneliness on Twitter and provide appropriate interventions for these users, it is important to understand the variations in language use by users who belong to different age groups and genders and post about loneliness on Twitter. We discuss the findings from this work and how they can help guide the design of online loneliness interventions.


Physicochemical and biological characterization of sustained isopropyl unoprostone-release device made of poly(ethyleneglycol) dimethacrylates.
Transscleral drug delivery is becoming increasingly popular to manage posterior eye diseases. To evaluate the clinical application of a transscleral, sustained, unoprostone (UNO)-release device (URD) constructed of photopolymerized tri(ethyleneglycol) dimethacrylate and poly(ethyleneglycol) dimethacrylate, we evaluated physicochemical and biological properties of this device. The URD consists of a drug-impermeable reservoir and a semi-permeable cover. The in vitro release rate of UNO from the URD increased with increasing temperatures from 20 to 45 °C. Scanning electron microscopy and atomic-force microscopy showed that the border between the reservoir and drug formulation was sharply defined but that between the cover and drug was poorly determined, indicating that UNO could permeate only through the cover. For stability tests, the URDs were sterilized with ethylene oxide gas and stored at 40 °C/75% for 3 and 6 months and at 25 °C/60% for 3, 6, 9, 12, 18, and 24 months; UNO content and release rate at 37 °C were then evaluated. There was no significant decrease in either UNO content or release rate after the storage conditions. Cytotoxicity was evaluated by examining the colony formation of Chinese hamster fibroblast V79 cells in a media extract of the URD without UNO. This extract did not affect colony formation of V79 cells, indicating the cytocompatibility of the URD. In conclusion, the URD was physically stable for 24 months and is potentially useful for clinical application.


Management and prevention of herpes zoster: A Canadian perspective.
Varicella-zoster virus reactivation leads to herpes zoster - the main complication of which is postherpetic neuralgia (PHN). Rapid antiviral therapy initiated within 72 h of rash onset has been shown to accelerate rash healing, reduce the duration of acute pain and, to some extent, attenuate the development and duration of PHN. Other adjunctive therapies such as analgesics, antidepressants and some anticonvulsants are frequently required in the management of severe PHN. A live, attenuated zoster vaccine has been recently shown to significantly decrease herpes zoster incidence, PHN and the overall burden of illness when administered to adults older than 60 years of age. This new prophylactic modality has been reported to be cost-effective in the Canadian context, especially in the 60- to 75-year-old age group.


Transfer of skills between laparoscopic and robot-assisted surgery: a systematic review.
Robot-assisted surgery is today well-implemented in many surgical specialties, but requires another skill set than laparoscopy. Most often, robot-assisted surgery is considered add-on to laparoscopic skills but very little is known about the transfer of skills. The aim of the study was to examine to what extent surgical skills are transferable between laparoscopic and robot-assisted surgery. A systematic search was conducted in three databases (Ovid Medline, Embase, and Web of Science). Studies investigating transfer of skills between laparoscopy and robot-assisted surgery in either a phantom-based, simulation-based, animal model, or clinical setting were eligible for inclusion. Quality assessment was done using the Medical education research study quality instrument and educational New Ottawa Scale. Of 15,610 studies identified, 89 studies continued to full-text reading, and 37 studies were included. Four studies were found non-comparable and were left out of the results for the primary outcome. All 33 studies explored transfer from laparoscopy to robot-assisted surgery and 17 found a positive transfer whereas 15 did not. Only 11 studies explored transfer from robot-assisted surgery to laparoscopy, of which only three found a positive transfer. An almost equal number of publications found a positive transfer and no transfer from laparoscopic to robot-assisted surgery. Fewer studies explored the transfer from robot-assisted surgery to laparoscopy. Very little evidence supports that surgeons trained solely in robot-assisted surgery can perform laparoscopy. This must be considered in future training programs as robot-assisted surgery is expected to become the first-in-line modality for many future surgeons.


Some implications of Bion's thought: the waking dream and narrative derivatives.
Following up Bion's idea that dreaming is a continuous process that takes place in waking life as well as in sleep, the author develops its theoretical and technical implications. He describes the narrative derivatives of waking dream thought as the means, or interface, whereby access may be had, albeit indirectly, to the constantly forming sequences of alpha-elements. Examples of the formation of these sequences out of childhood memories, present-day experiences and sexual feelings are given. Reference is also made to the notion of the analytic field. The author goes on to demonstrate the clinical value of these concepts both for studying the session's microtransformations and as a means of in-depth examination of the analyst's own mental functioning, including its lapses, in a session. Abundant clinical material is presented to help analysts who normally apply different models of the mind share these ideas. Finally, it is suggested that night dreams result from a further elaboration of the elements formed during waking life.


[Inactivated sodium channels are blocked by the anti-arrhythmic cordaron].
The blocking action of the antiarrhythmic cordaron (amiodaron hydrochloride) on Na currents in the frog node of Ranvier was studied by the voltage-clamp technique. It was established that the degree of the cordaron-induced block can be reversibly increased by long-term (1 s and more) membrane depolarization. The time constants of both the development and recovery from the block caused by membrane depolarization are of the order of hundreds of seconds ("induced slow sodium inactivation"). The fraction of blocked channels rises to some limiting level with an increase in the magnitude of the depolarizing step, the region of strong voltage dependency being between -130 and -70 mv. The inhibition of outward potassium current by 7.10(-4) M cordaron does not exceed 15%. The time- and voltage-dependent block of Na channels is supposed to result from interaction of the antiarrhythmic with inactivated channels.


Dispositional optimism and all-cause mortality after esophageal cancer surgery: a nationwide population-based cohort study.
To examine the association between dispositional optimism and all-cause mortality after esophageal cancer surgery and whether pathological tumor stage and the COVID-19 pandemic modified this association. This nationwide, population-based prospective cohort study included 335 patients undergoing esophageal cancer surgery in Sweden between January 1, 2013, and December 31, 2019. Dispositional optimism was measured 1 year post-surgery using Life Orientation Test-Revised (LOT-R). A higher LOT-R sum score represents higher dispositional optimism. Mortality information was obtained from the Swedish Register of the Total Population. All patients were followed up until death or until December 31, 2020, whichever occurred first. Cox regression with adjustments for confounders was used. The median follow-up was 20.8 months, during which 125 (37.3%) patients died. Among the included 335 patients, 219 (65.4%) patients had tumor pathologically staged Tis-II, and 300 (89.6%) patients entered the cohort before the COVID-19 pandemic. Both tumor stage and the COVID-19 pandemic were effect modifiers. For each unit increase in LOT-R sum score, the risk of all-cause mortality decreased by 11% (HR 0.89, 95% CI 0.81 to 0.98) among patients with tumor staged Tis-II before the COVID-19 pandemic. This association was non-significant in patients with tumor staged III-IV (HR 0.99, 95% CI 0.92 to 1.07) and during the COVID-19 pandemic (HR 1.08, 95% CI 0.94 to 1.25). Assessing dispositional optimism may help predict postoperative survival, especially for patients with early and intermediate esophageal cancer. Increasing dispositional optimism might be a potential intervention target to improve survival after esophageal cancer surgery.


Post-infarction exercise testing in patients under 55 years. Relation between ischaemic abnormalities and the extent of coronary artery disease.
Previous studies have suggested that the early post-infarction exercise test is useful in predicting the extent of coronary artery disease. The results of a heart rate limited exercise test three weeks after infarction and a symptom limited exercise test six weeks after infarction obtained by both standard lead electrocardiograms and 16 lead precordial maps were compared in 100 consecutive survivors of acute myocardial infarction under 55 years of age. Exercise tests were defined as being positive on the basis of angina, ST segment depression greater than or equal to 1 mm in any electrocardiogram lead, or exertional hypotension. Multivessel disease, that is two or three vessel disease, was present in 60 patients, and three vessel disease in 22 patients. The sensitivity, specificity, and predictive value for multivessel disease of the three week test were 38%, 83%, and 76% respectively; and results for the six week test were 55%, 75%, and 77% respectively. Only 32% of patients with three vessel disease were identified at the three week test, and 59% at the six week test. Significantly more patients with multivessel and three vessel disease were identified by the symptom limited six week test. Precordial mapping offered no advantages over the standard 12 lead electrocardiogram in either the identification of patients with multivessel disease or the prediction of the distribution of coronary artery disease. Angina pectoris during the exercise test at six weeks was the single most useful predictor of multivessel disease. Multivessel disease was found in 27 (87%) of the 31 patients with angina with or without ST depression during the test at six weeks compared with 33 (48%) of the 69 patients who did not have angina during the test at six weeks. Exercise testing in the early post-infarction period in patients under 55 years of age is of limited value in predicting the extent of coronary artery disease. It is, therefore, unreasonable to use such exercise tests to select patients for coronary arteriography after myocardial infarction. None the less angina pectoris occurring during a symptom limited exercise test six weeks after infarction is a strong predictor of multivessel disease, and coronary arteriography is recommended in these patients.


Form-deprivation myopia in chick induces limited changes in retinal gene expression.
Evidence has implicated the retina as a principal controller of refractive development. In the present study, the retinal transcriptome was analyzed to identify alterations in gene expression and potential signaling pathways involved in form-deprivation myopia of the chick. One-week-old white Leghorn chicks wore a unilateral image-degrading goggle for 6 hours or 3 days (n = 6 at each time). Total RNA from the retina/(retinal pigment epithelium) was used for expression profiling with chicken gene microarrays (Chicken GeneChips; Affymetrix, Santa Clara, CA). To identify gene expression level differences between goggled and contralateral nongoggled eyes, normalized microarray signal intensities were analyzed by the significance analysis of microarrays (SAM) approach. Differentially expressed genes were validated by real-time quantitative reverse transcription-polymerase chain reaction (qPCR) in independent biological replicates. Small changes were detected in differentially expressed genes in form-deprived eyes. In chickens that had 6 hours of goggle wear, downregulation of bone morphogenetic protein 2 and connective tissue growth factor was validated. In those with 3 days of goggle wear, downregulation of bone morphogenetic protein 2, vasoactive intestinal peptide, preopro-urotensin II-related peptide and mitogen-activated protein kinase phosphatase 2 was validated, and upregulation of endothelin receptor type B and interleukin-18 was validated. Form-deprivation myopia, in its early stages, is associated with only minimal changes in retinal gene expression at the level of the transcriptome. While the list of validated genes is short, each merits further study for potential involvement in the signaling cascade mediating myopia development.


Sitting Posture During Occupational Driving Causes Low Back Pain; Evidence-Based Position or Dogma? A Systematic Review.
In this review, we determine if there is evidence to demonstrate a relationship between occupational driving posture and low back pain. The burden of low back pain is increasing. An understanding of this relationship is required to enable the development of recommendations for clinicians and policy-makers for the driving industry. Five databases were searched up to March 12, 2018. Study quality was assessed using the National Heart, Lung, and Blood Institute's Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies, followed by a GRADE analysis to consider the evidence as a whole. A narrative, critical synthesis was completed that considered the methods by which driving posture and low back pain were measured and analyzed. There were 653 articles identified, with seven eligible for review. Four articles identified an association between occupational driving posture and low back pain, yet this was based on the use of measurement tools lacking validity. Although a relationship may exist, the specific driving postures associated with low back pain and the strength of this relationship have not been confirmed. Future research needs to employ validated and reliable, real-time qualitative methods for measuring occupational driving posture to advance our understanding of this relationship. Clinical and policy recommendations regarding driving posture and low back pain should be used with caution, as they are guided by evidence incorporating bias. Future studies are required to confirm the specific postures assumed while occupational driving and their relationship with low back pain, before recommendations can be made.


Molding of hydrogel microstructures to create multiphenotype cell microarrays.
The fabrication of mammalian cell-containing poly(ethylene glycol) (PEG) hydrogel microstructures on glass and silicon substrates is described. Using photoreaction injection molding in poly(dimethylsiloxane) microfluidic channels, three-dimensional hydrogel microstructures encapsulating cells (fibroblasts, hepatocytes, macrophage) were fabricated with cells uniformly distributed to each hydrogel microstructure, and the number of cells in each hydrogel microstructure was controlled by changing the cell density of the precursor solution. PEG hydrogels were modified using an Arg-Gly-Asp (RGD) peptide sequence, with the incorporation of RGD into the hydrogel matrix promoting the spreading of encapsulated fibroblasts over a 24-h period in culture. Cells remained viable encapsulated in these hydrogel microstructures for a period in excess of 1 week in culture. Arrays of hydrogel microstructures encapsulating two or more phenotypes on a single substrate were successfully fabricated using multimicrofluidic channels, creating the potential for multiphenotype cell-based biosensors.


Phenytoin intoxication.
We studied the clinical features of 85 cases of phenytoin toxicity in 76 patients treated at a general hospital. Serum levels of phenytoin on admission ranged from 30.3 to 95.0 micrograms/mL (median, 46.5). Iatrogenic causes of intoxication were common and included increased daily dosage and intravenous loading in the emergency room for single seizures in patients with subtherapeutic serum phenytoin levels. The most frequent neurologic findings were nystagmus (95%), ataxia (88%), lethargy (22%), and seizures (19%). Outcome was usually good, but three patients had serious complications.


The signaling pathways and targets of natural products from traditional Chinese medicine treating gastric cancer provide new candidate therapeutic strategies.
Gastric cancer (GC) is one of the severe malignancies with high incidence and mortality, especially in Eastern Asian countries. Significant advancements have been made in diagnosing and treating GC over the past few decades, resulting in tremendous improvements in patient survival. In recent years, traditional Chinese medicine (TCM) has garnered considerable attention as an alternative therapeutic approach for GC due to its multicomponent and multitarget characteristics. Consequently, natural products found in TCM have attracted researchers' attention, as growing evidence suggests that these natural products can impede GC progression by regulating various biological processes. Nevertheless, their molecular mechanisms are not systematically uncovered. Here, we review the major signaling pathways involved in GC development. Additionally, clinical GC samples were analyzed. Moreover, the anti-GC effects of natural products, their underlying mechanisms and potential targets were summarized. These summaries are intended to facilitate further relevant research, and accelerate the clinical applications of natural products in GC treatment.


Comparative Evaluation of Efficacy of Iontophoresis with 0.33% Sodium Fluoride Gel and Diode Laser Alone on Occlusion of Dentinal Tubules.
Dentinal Hypersensitivity (DH) is one of the most commonly encountered clinical problems. Literature reveals no specific therapy to satisfactorily eliminate dentinal hypersensitivity. The aim of this study was to assess and compare the efficacy of iontophoresis with 0.33% Sodium Fluoride (NaF) gel and diode laser alone in dentinal tubule occlusion. This in vitro study included 20 teeth with intact root surfaces unaltered by extraction procedure for specimen preparation. Each tooth was cleaned, air dried and cut into three sections. Total 60 sections were prepared (30 longitudinal and 30 transverse sections), which were acid etched. In control group, no treatment was carried. In iontophoresis treatment group, samples were inserted into a foam tray containing 0.33 % NaF Gel and subjected to 1.5 mA output current for three minutes. In laser treatment group, specimens were lased with 980 nm diode laser at 0.5 W/PW (62.2J /cm2) in a noncontact mode for 30 seconds. Specimens were evaluated under Scanning Electron Microscope (SEM) at 10KV to 20KV under x 2000, x5000 magnification for surface characteristics and patency of dentinal tubules. Total number of tubules visible, open, completely and partially occluded were recorded in each microphotograph and compared. On comparison, laser group showed the least number of open tubules i.e., 130 (31.1%) followed by iontophoresis group, 155 (51.32%) and control group 417 (100%). Diode laser application provided better results as compared to iontophoresis on occlusion of dentinal tubules. Hence, it can be used to treat the patients with DH.


Technetium-99m-DMSA studies in pediatric urinary infection.
Urinary tract infection (UTI) is a common condition in children and may lead to renal scarring with a risk of later hypertension and renal insufficiency. We made a cross-sectional study of the 99mTc-DMSA findings in 496 children referred for following symptomatic UTI to a Department of Nuclear Medicine and we categorized the results, to provide a framework for further study. A standard 99mTc-DMSA protocol was used to study 496 children (157 males, 339 females) aged from birth to 14 yr. Findings were classified according to the image appearance and relative function of each kidney. These were related to age, sex, history and timing of UTI and the results on micturating cysto-urethrography (MCU). Images were normal, with function within limits (45%-50% in one kidney), in approximately half the boys and girls studied. The other images were classified as equivocal in 68 children, abnormal unilaterally in 105 and bilaterally in 76, and they were subdivided according to the image appearance. No image changes could be identified that were specifically associated with acute UTI. Diffuse change alone was uncommon. A high proportion of abnormal images was found in infant boys, older girls with recurrent UTI and those children with vesico-ureteric reflux (VUR). Of the bilateral abnormal images, 98% were seen in children with VUR. Our findings suggest that infective renal change may be superimposed on underlying congenital lesions (perhaps detectable antenatally) or may be acquired following UTI in the presence of reflux and are thus potentially preventable. This study also suggests that VUR is almost certain to have occurred in a child who has bilateral abnormal 99mTc-DMSA images following UTI and is also commonly present in those with definite unilateral defects.


COVID-19 vaccines and risks of hematological abnormalities: Nested case-control and self-controlled case series study.
Several studies reported hematological abnormalities after vaccination against the coronavirus disease 2019 (COVID-19). We evaluated the association between COVID-19 vaccines (CoronaVac and BNT162b2) and hematological abnormalities. We conducted nested case-control and self-controlled case series analyses using the data from the Hong Kong Hospital Authority and the Department of Health, HKSAR. Outcomes of interest were thrombocytopenia, leukopenia, and neutropenia. Adjusted odds ratios (aORs), incidence rate ratios (IRRs), and 95% confidence intervals (CIs) were estimated using conditional logistic regression. In total, 1 643 419 people received COVID-19 vaccination (738 609 CoronaVac; 904 810 BNT162b2). We identified 457 and 422 cases after CoronaVac and BNT162b2 vaccination, respectively. For CoronaVac, the incidence of thrombocytopenia, leukopenia, and neutropenia was 2.51, 1.08, and 0.15 per 10 000 doses. For BNT162b2, the corresponding incidence was 1.39, 1.17, and 0.26 per 10 000 doses. The incidence per 10 000 COVID-19 cases were 1254, 2341, and 884, respectively. We only observed an increased risk of leukopenia following the second dose of BNT162b2 (aOR 1.58, 95% CI 1.24-2.02; day 0-14, IRR 2.21; 95% CI 1.59-3.08). There was no increased risk of any hematological abnormalities after CoronaVac vaccination. We observed an increased risk of leukopenia shortly after the second dose of BNT162b2. However, the incidence was much lower than the incidence following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. There was no association between CoronaVac and hematological abnormalities. The benefits of vaccination against COVID-19 still outweigh the risk of hematological abnormalities.


Distinct Roles of Catalytic Cysteine and Histidine in the Protease and Ligase Mechanisms of Human Legumain As Revealed by DFT-Based QM/MM Simulations.
The cysteine protease enzyme legumain hydrolyzes peptide bonds with high specificity after asparagine and under more acidic conditions after aspartic acid [Baker E. N.J. Mol. Biol.1980, 141, 441-484; Baker E. N.; J. Mol. Biol.1977, 111, 207-210; Drenth J.; Biochemistry1976, 15, 3731-3738; Menard R.; J. Cell. Biochem.1994, 137; Polgar L.Eur. J. Biochem.1978, 88, 513-521; Storer A. C.; Methods Enzymol.1994, 244, 486-500. Remarkably, legumain additionally exhibits ligase activity that prevails at pH > 5.5. The atomic reaction mechanisms including their pH dependence are only partly understood. Here we present a density functional theory (DFT)-based quantum mechanics/molecular mechanics (QM/MM) study of the detailed reaction mechanism of both activities for human legumain in solution. Contrasting the situation in other papain-like proteases, our calculations reveal that the active site Cys189 must be present in the protonated state for a productive nucleophilic attack and simultaneous rupture of the scissile peptide bond, consistent with the experimental pH profile of legumain-catalyzed cleavages. The resulting thioester intermediate (INT1) is converted by water attack on the thioester into a second intermediate, a diol (INT2), which is released by proton abstraction by Cys189. Surprisingly, we found that ligation is not the exact reverse of the proteolysis but can proceed via two distinct routes. Whereas the transpeptidation route involves aminolysis of the thioester (INT1), at pH 6 a cysteine-independent, histidine-assisted ligation route was found. Given legumain's important roles in immunity, cancer, and neurodegenerative diseases, our findings open up possibilities for targeted drug design in these fields.


Distribution and Clearance of Blood Constituents after Intracerebral Hemorrhage in Rats: Mechanisms and Relevance for Functional Outcomes.
Background and Objective To evaluate the impact of blood clearance mechanisms on neurologic damage and functional outcomes after intracerebral hemorrhage (ICH) in rats. Methods A rat model of ICH was established through pre-cannulation and injection of autologous arterial blood into the caudate nucleus. Blood was supplemented with 6-amino-caproic acid (a procoagulant), low-molecular-weight heparin (an anticoagulant), or vehicle. Relationships between hematoma volume and edema size and neurologic damage were assessed at different times. Results At 6 hours and 24 hours, hematoma volume was greater in rats that received anticoagulant than in the other two groups (p < 0.01). No significant differences were observed at 3 days, 5 days, or 7 days (p > 0.05). At 6 hours and 24 hours, the Neurological Severity Score in the procoagulant group was significantly higher than in the other two groups (comparison between groups, p < 0.01); and no significant differences were found at other times (p > 0.05). Conclusion Enhanced clearance of leaked blood was associated with larger hematomas within the first 3 days of ICH and with less neurologic damage. The capacity to clear blood is an important determinant of functional recovery after ICH. Enhanced clearance may help reduce neurologic damage.


Tissue-specific activation of cardiac angiotensin converting enzyme in experimental heart failure.
In addition to the circulating renin-angiotensin system, recent data demonstrate the existence of tissue renin-angiotensin systems that may be important in cardiovascular homeostasis. However, the relative activities of the circulating and tissue renin-angiotensin systems have not been examined previously in pathophysiological states, such as congestive heart failure. The present study was performed to examine the status of plasma and tissue angiotensin converting enzyme (ACE) activities in compensated experimental heart failure induced by coronary artery ligation in the rat. Three groups of male Sprague-Dawley rats were examined: 1) nonoperated rats (NO, n = 5), 2) sham-operated rats (SO, n = 5), and 3) heart failure rats (HF, n = 11). Rats were studied an averaged of 85 days postoperatively. In HF animals, plasma renin concentration and serum ACE activities were not different compared with NO and SO control animals. Cardiac ACE activity was 50% greater in the right ventricle than the interventricular septum in NO and SO rats. Both right ventricular and interventricular septal ACE activity increased approximately twofold in HF animals as compared with NO and SO groups (p less than 0.05). In contrast, pulmonary, aortic, and renal ACE activities were not altered in HF rats compared with control animals. A positive correlation existed between the histopathological size of myocardial infarction and the level of right ventricular ACE activity (r = 0.75, p less than or equal to 0.05). Such a relation between infarct size and either serum or noncardiac tissue ACE activities was not observed.(ABSTRACT TRUNCATED AT 250 WORDS)


How much energy should manipulative parasites leave to their hosts to ensure altered behaviours?
Although host manipulation is likely to be costly for parasites, we still have a poor understanding of the energetic aspects underlying this strategy. It is traditionally assumed that physiological costs are inevitably associated with mechanisms evolved by parasites to induce the required changes in host behaviours. While most energetic expenditures of parasites relate primarily to bringing about the altered behaviours, manipulative parasites also have to consider the condition of their host during the manipulation. Here, we suggest that because of this trade-off, the energy required to accomplish parasite-induced behaviours may represent a key energetic constraint for parasites. Depending on the energetic expenditures specific to each type of manipulation, parasites should undergo selection to secure resources for their host to allow them to perform manipulated behaviours.


Inhibition of protein glycation by essential oils of branchlets and fruits of Juniperus communis subsp. hemisphaerica.
Oxidative stress and protein glycation play pivotal roles in the pathophysiology of diabetes mellitus and its vascular complications. The present study aimed to investigate the anti-glycation properties of essential oils obtained from different parts of Juniperus communis subsp. hemisphaerica. The branchlets of male tree (BMT) and branchlets of female (BFT) tree, and fruits of J. communis subsp. hemisphaerica were extracted using steam distillation method. The oils were phytochemically analyzed using gas chromatography-mass spectrometry. Anti-glycation properties were evaluated using hemoglobin and insulin glycation assays. Overall, 18 volatile components were identified in the J. communis subsp. hemisphaerica oils, amounting to 82.1%, 100.0% and 96.4% of the BMT, BFT and fruit oils, respectively. Promising inhibitory activity was observed from all concentrations of the tested oils in the hemoglobin and insulin glycation assays. The inhibitory activities peaked to 89.9% (BFT oil; 200 μg mL(-1)) and 81.0% (BFT oil; 600 μg mL(-1)) in the hemoglobin and insulin glycation assays, respectively. The evidence from this study suggests that essential oils obtained from the fruits and branchlets of J. communis subsp. hemisphaerica possess anti-glycation properties. These activities may find implication for the prevention and treatment of diabetic complications.


Modeling variably saturated subsurface solute transport with MODFLOW-UZF and MT3DMS.
The MT3DMS groundwater solute transport model was modified to simulate solute transport in the unsaturated zone by incorporating the unsaturated-zone flow (UZF1) package developed for MODFLOW. The modified MT3DMS code uses a volume-averaged approach in which Lagrangian-based UZF1 fluid fluxes and storage changes are mapped onto a fixed grid. Referred to as UZF-MT3DMS, the linked model was tested against published benchmarks solved analytically as well as against other published codes, most frequently the U.S. Geological Survey's Variably-Saturated Two-Dimensional Flow and Transport Model. Results from a suite of test cases demonstrate that the modified code accurately simulates solute advection, dispersion, and reaction in the unsaturated zone. Two- and three-dimensional simulations also were investigated to ensure unsaturated-saturated zone interaction was simulated correctly. Because the UZF1 solution is analytical, large-scale flow and transport investigations can be performed free from the computational and data burdens required by numerical solutions to Richards' equation. Results demonstrate that significant simulation runtime savings can be achieved with UZF-MT3DMS, an important development when hundreds or thousands of model runs are required during parameter estimation and uncertainty analysis. Three-dimensional variably saturated flow and transport simulations revealed UZF-MT3DMS to have runtimes that are less than one tenth of the time required by models that rely on Richards' equation. Given its accuracy and efficiency, and the wide-spread use of both MODFLOW and MT3DMS, the added capability of unsaturated-zone transport in this familiar modeling framework stands to benefit a broad user-ship.


Functional properties of human auditory cortical fields.
While auditory cortex in non-human primates has been subdivided into multiple functionally specialized auditory cortical fields (ACFs), the boundaries and functional specialization of human ACFs have not been defined. In the current study, we evaluated whether a widely accepted primate model of auditory cortex could explain regional tuning properties of fMRI activations on the cortical surface to attended and non-attended tones of different frequency, location, and intensity. The limits of auditory cortex were defined by voxels that showed significant activations to non-attended sounds. Three centrally located fields with mirror-symmetric tonotopic organization were identified and assigned to the three core fields of the primate model while surrounding activations were assigned to belt fields following procedures similar to those used in macaque fMRI studies. The functional properties of core, medial belt, and lateral belt field groups were then analyzed. Field groups were distinguished by tonotopic organization, frequency selectivity, intensity sensitivity, contralaterality, binaural enhancement, attentional modulation, and hemispheric asymmetry. In general, core fields showed greater sensitivity to sound properties than did belt fields, while belt fields showed greater attentional modulation than core fields. Significant distinctions in intensity sensitivity and contralaterality were seen between adjacent core fields A1 and R, while multiple differences in tuning properties were evident at boundaries between adjacent core and belt fields. The reliable differences in functional properties between fields and field groups suggest that the basic primate pattern of auditory cortex organization is preserved in humans. A comparison of the sizes of functionally defined ACFs in humans and macaques reveals a significant relative expansion in human lateral belt fields implicated in the processing of speech.


Gemfibrozil in a group of diabetics.
A group of 14 diabetic patients was treated with gemfibrozil during a variable length of time ranging from nine to 23 weeks in order to establish if a lowering effect on the cholesterol and triglyceride levels could be achieved, as it had been in the case of another group of non-diabetic patients. The present results showed that: (1) The drug is remarkably well tolerated. (2) With doses ranging between 400 and 800 mg per day the magnitude of the effect of the drug was less than that observed in our previous trial with non-diabetic subjects. The effect upon triglycerides seemed to be reduced more than that upon cholesterol when compared with results in higher-dose studies. (3) In this group of diabetic patients (3 insulin dependent, 11 maturity-onset type) control of the diabetic condition was never impaired and appeared in some cases to be slightly improved by gemfibrozil. (4) There was no evidence of undesirable interaction with any of the anti-diabetic drugs used.


Biosensor-assisted selection of optimal parameters for designing molecularly imprinted polymers selective to phosmet insecticide.
Molecularly imprinted polymers (MIPs) for phosmet insecticide were synthesized by batch polymerization. The affinity of functional monomers to phosmet was tested using an original method involving an electrochemical biosensor based on acetylcholinesterase inhibition. It was demonstrated that association of phosmet with appropriate functional monomers resulted in a decrease of enzyme inhibition. Using this method, it was shown that N,N-methylenebis(acrylamide) displayed the highest interactions with phosmet using DMSO as solvent. These results were in good accordance with those obtained by conventional computational modeling. Molecularly imprinted polymers (MIPs) and non-imprinted polymers (NIPs) were synthesized and adsorption isotherms were studied to describe their interaction with phosmet. Freundlich isotherm was able to fit phosmet adsorption on MIPs with good agreement (R2 = 0.9). The pre-exponential factor KF determined for MIPs was 1.439mg(1-N)g-1LN, more that 10 times higher than for NIPs (0.125mg(1-N)g-1. LN), indicating an increase of binding sites number and average affinity.


Spatiotemporal gait parameters and recurrent falls in community-dwelling elderly women: a prospective study.
Falling is a common but devastating and costly problem of aging. There is no consensus in the literature on whether the spatial and temporal gait parameters could identify elderly people at risk of recurrent falls. To determine whether spatiotemporal gait parameters could predict recurrent falls in elderly women. One hundred and forty-eight elderly women (65-85 years) participated in this study. Seven spatiotemporal gait parameters were collected with the GAITRite(r) system. Falls were recorded prospectively during 12 months through biweekly phone contacts. Elderly women who reported two or more falls throughout the follow-up period were considered as recurrent fallers. Principal component analysis (PCA) and discriminant analysis followed by biplot graph interpretation were applied to the gait parameters. After 12 months, 23 elderly women fell twice or more and comprised the recurrent fallers group and 110 with one or no falls comprised the non-recurrent fallers group. PCA resulted in three components that explained 88.3% of data variance. Discriminant analysis showed that none of the components could significantly discriminate the groups. However, visual inspection of the biplot showed a trend towards group separation in relation to gait velocity and stance time. PC1 represented gait rhythm and showed that recurrent fallers tend to walk with lower velocity and cadence and increased stance time in relation to non-recurrent fallers. The analyzed spatiotemporal gait parameters failed to predict recurrent falls in this sample. The PCA-biplot technique highlighted important trends or red flags that should be considered when evaluating recurrent falls in elderly females.


Self-emulsified annatto tocotrienol improves bone histomorphometric parameters in a rat model of oestrogen deficiency through suppression of skeletal sclerostin level and RANKL/OPG ratio.
Menopause is the leading cause of osteoporosis for elderly women due to imbalanced bone remodelling in the absence of oestrogen. The ability of tocotrienol in reversing established bone loss due to oestrogen deficiency remains unclear despite the plenitude of evidence showcasing its preventive effects. This study aimed to investigate the effects of self-emulsified annatto tocotrienol (SEAT) on bone histomorphometry and remodelling in ovariectomised rats. Female Sprague Dawley rats (n=36) were randomly assigned into baseline, sham, ovariectomised (OVX) control, OVX-treated with annatto tocotrienol (AT) (60 mg/kg), SEAT (60 mg/kg) and raloxifene (1 mg/kg). Daily treatment given through oral gavage was started two months after castration. The rats were euthanised after eight weeks of treatment. Blood was collected for bone biomarkers. Femur and lumbar bones were collected for histomorphometry and remodelling markers. The results showed that AT and SEAT improved osteoblast numbers and trabecular mineralisation rate (p<0.05 vs untreated OVX). AT also decreased skeletal sclerostin expression in OVX rats (p<0.05 vs untreated OVX). Similar effects were observed in the raloxifene-treated group. Only SEAT significantly increased bone formation rate and reduced RANKL/OPG ratio (p<0.05 vs untreated OVX). However, no changes in osteoclast-related parameters were observed among the groups (p>0.05). In conclusion, SEAT exerts potential skeletal anabolic properties by increasing bone formation, suppressing sclerostin expression and reducing RANKL/OPG ratio in rats with oestrogen deficiency.


Precise control of plant stem cell activity through parallel regulatory inputs.
The regulation of columella stem cell activity in the Arabidopsis root cap by a nearby organizing centre, the quiescent centre, has been a key example of the stem cell niche paradigm in plants. Here, we investigate interactions between transcription factors that have been shown to regulate columella stem cells using a simple quantification method for stem cell activity in the root cap. Genetic and expression analyses reveal that the RETINOBLASTOMA-RELATED protein, the FEZ and SOMBRERO NAC-domain transcription factors, the ARF10 and ARF16 auxin response factors and the quiescent centre-expressed WOX5 homeodomain protein each provide independent inputs to regulate the number of columella stem cells. Given the tight control of columella development, we found that these inputs act in a surprisingly parallel manner. Nevertheless, important points of interaction exist; for example, we demonstrate the repression of SMB activity by non-autonomous action of WOX5. Our results suggest that the developmental progression of columella stem cells may be quantitatively regulated by several more broadly acting transcription factors rather than by a single intrinsic stem cell factor, which raises questions about the special nature of the stem cell state in plants.


[Atheroma plaque of the carotid bifurcation: how to identify an "active" lesion?].
The identification of carotid atheromatous plaques associated to a higher neurologic risk may be important in therapeutic decision making for asymptomatic patients and symptomatic patients with 50%-70% stenosis. The introduction of high-definition ultrasonography (HDU) and computer-assisted image analysis provides the possibility of a standard, objective and detailed characterization of the structure of the carotid plaque. The aim of this study is to analyse the relationship between the ultrasonographic characteristics of a group of plaques and the risk of associated cerebrovascular events and cerebral infarction. One hundred carotid bifurcation plaques (in 68 patients) were studied for the presence of ipsilateral cerebrovascular events. In 61 patients (87 plaques), a correlation with CT scan for the presence of cerebral infarction was possible. The lesions were studied by HDU (ATL-HDI 3000) and digitalized for computer-assisted standardization of the image. The analysis included the appreciation of the histogram of the image gray-scale pixel distribution by use of commercial software Adobe Photoshop 3.0. The parameters analysed for global echogenicity were the median of the histogram and the percentage of percentile 40 hypoechogenic pixels (40). Statistical analysis was made with STATA 4.0 software with categorical variables analysed by chi-square and Fisher's exact test and continuous variables analysed by variance analysis and Student's t test. Thirty eight (38%) plaques were symptomatic and 34 (39.1%) were associated to cerebral infarction. The degree of stenosis was > 70% in 51%; between 50 and 69% in 27% and < 50% in 22%. The mean of the median and P40 values was 33.9 and 60.3% in the symptomatic and 46.8 (p = 0.005) and 46.6% (p = 0.001) in the asymptomatic plaques respectively. In the plaques associated to cerebral infarction, it was 32.7 and 61.6% respectively, and in the ones with negative CT scan, it was 44.6 (p = 0.005) and 48.1% (p = 0.002). The mean of the median in the plaques vs. degree of stenosis was: > 70%--33.3; 50-69%--45.1; < 49%--57.7 (p < 0.001). In the series the cut-off point for the median value was 32 and for P40 it was 43 (for any degree of stenosis): G1--plaques < 32 (echolucent); G2--plaques > 32 (echogenic). In G1 symptoms occurred in 60% of the plaques and in 26% of the plaques in G2 (p = 0.0001). CT scan was positive in 66% of the echolucent plaques and in 25% of the echogenic plaques (p = 0.0238). 1. The more echolucent plaques are associated with a significantly higher neurological risk. 2. The plaques associated with higher degrees of stenosis are more echolucent. 3. The use of a standard and objective methodology in the analysis of the echographic structure of carotid plaques is important and limits the known intra and inter-observer variability of subjective appreciation.


Root Architecture and Functional Traits of Spring Wheat Under Contrasting Water Regimes.
Wheat roots are known to play an important role in the yield performance under water-limited (WL) conditions. Three consecutive year trials (2015, 2016, and 2017) were conducted in a glasshouse in 160 cm length tubes on a set of spring wheat (Triticum aestivum L.) genotypes under contrasting water regimes (1) to assess genotypic variability in root weight density (RWD) distribution in the soil profile, biomass partitioning, and total water used; and (2) to determine the oxygen and hydrogen isotopic signatures of plant and soil water in order to evaluate the contribution of shallow and deep soil water to plant water uptake and the evaporative enrichment of these isotopes in the leaf as a surrogate for plant transpiration. In the 2015 trial under well-watered (WW) conditions, the aerial biomass (AB) was not significantly different among 15 wheat genotypes, while the total root biomass and the RWD distribution in the soil profile were significantly different. In the 2016 and 2017 trials, a subset of five genotypes from the 2015 trial was grown under WW and WL regimes. The water deficit significantly reduced AB only in 2016. The water regimes did not significantly affect the root biomass and root biomass distribution in the soil depths for both the 2016 and 2017 trials. The study results highlighted that under a WL regime, the production of thinner roots with low biomass is more beneficial for increasing the water uptake than the production of large thick roots. The models applied to estimate the relative contribution of the plant's primary water sources (shallow or deep soil water) showed large interindividual variability in soil, and plant water isotopic composition resulted in large uncertainties in the model estimates. On the other side, the combined information of root architecture and the leaf stable isotope signatures could explain plant water status.


Evidence-based treatment of anorexia nervosa.
This paper addresses the question "Is evidence-based treatment of anorexia nervosa possible?" "Barely" is the conclusion drawn. New forms of treatment are needed for adults with anorexia nervosa, and the true value of family-based treatment for adolescents has yet to be established.


[Human embryonic stem cells: possibilities for future cell transplantation therapy].
Human embryonic stem cells are of great importance, and Parkinson's disease is given as an example of a condition that could benefit from the development of stem cell-based transplantation therapies. The reason for this is fairly obvious: the disease is caused by the loss of only one cell type from the brain that has one major function, namely the production of dopamine. Replacement of these cells should in principle cure the disease. But what are stem cells and how far is scientific research from being able to offer stem cell-based therapy in the clinic to patients suffering from Parkinson's disease, and other chronic diseases? These questions are addressed here together with a critical evaluation of short and long-term clinical perspectives, and a discussion of possible alternatives such as adult stem cells.


The relationship between living in urban and rural areas of Scotland and children's physical activity and sedentary levels: a country-wide cross-sectional analysis.
Living in urban or rural environments may influence children's levels of physical activity and sedentary behaviours. We know little about variations in device-measured physical activity and sedentary levels of urban and rural children using nationally representative samples, or if these differences are moderated by socioeconomic factors or seasonal variation. Moreover, little is known about the influence of 'walkability' in the UK context. A greater understanding of these can better inform intervention strategies or policy initiatives at the population level. Country-wide cross-sectional study in Scotland in which 774 children (427 girls, 357 boys), aged 10/11 years, wore an accelerometer on one occasion for at least four weekdays and one weekend day. Mean total physical activity, time spent in sedentary, light, and moderate-to-vigorous physical activity (MVPA), per day were extracted for weekdays, weekend days, and all days combined. Regression analyses explored associations between physical activity outcomes, urban/rural residence, and a modified walkability index (dwelling density and intersection density); with interactions fitted for household equivalised income and season of data collection. Sensitivity analyses assessed variation in findings by socioeconomic factors and urbanicity. Rural children spent an average of 14 min less sedentary (95% CI of difference: 2.23, 26.32) and 13 min more in light intensity activity (95% CI of difference, 2.81, 24.09) per day than those from urban settlements. No urban-rural differences were found for time spent in MVPA or in total levels of activity. Our walkability index was not associated with any outcome measure. We found no interactions with household equivalised income, but there were urban/rural differences in seasonal variation; urban children engaged in higher levels of MVPA in the spring months (difference: 10 mins, p = 0.06, n.s) and significantly lower levels in winter (difference: 8.7 mins, p = 0.036). Extrapolated across one-year, rural children would accumulate approximately 79 h (or just over 3 days) less sedentary time than urban children, replacing this for light intensity activity. With both outcomes having known implications for health, this finding is particularly important. Future work should prioritise exploring the patterns and context in which these differences occur to allow for more targeted intervention/policy strategies.


Using the Extended Parallel Process Model to Frame E-Professionalism Instruction in Healthcare Education.
Issue: With the proliferation of social media and the blurring of online and real-world lives, today's healthcare professionals must constantly work to protect and manage their online reputation. Unfortunately, they are often not taught this skill as part of their healthcare education. Although many healthcare educators agree that this topic needs to be taught to students, researchers have not presented a formalized pathway to support this type of instruction. Evidence: Research on e-professionalism, a concept that addresses an individual's online professional image, was originally presented in 2009 and has continued to be investigated with research supporting its importance. Scholars in the field have found that the cost of having a nonexistent or poor online reputation can cause a lack of trust in the patient-provider relationship and, in extreme situations, can cause healthcare providers to face criminal charges, lose their jobs, or be expelled from healthcare programs. For example, in 2014 an emergency room nurse posted a photo to Instagram of an empty trauma room and was fired from her position for what the hospital called "insensitivity." These types of social media posts have occurred consistently over the last decade, highlighting the need for formalized online professionalism instruction in healthcare education. Implications: This article suggests the use of the extended parallel process model as a guide for healthcare educators to use when creating instruction on issues related to e-professionalism and online reputation management. The extended parallel process model has been successfully used to create health campaigns since the 1970s and is a respected and frequently used health communication model. This article shows that the extended parallel process model supports a systematic approach to e-professionalism instruction that allows it to be easily integrated into existing healthcare curricula.


Extensive acquired cholesteatoma in children: when the penny drops.
To determine the factors associated with the diagnosis of acquired cholesteatoma (AC) in children, we performed a retrospective chart review at a tertiary care center. We reviewed children with a diagnosis of AC that extended beyond the mesotympanum in the presence of a nonintact tympanic membrane who underwent surgical treatment over a 14-year period. There were 116 children (78 male, 38 female) between 3 and 18 years of age (mean, 9.5 years). Their average period of management in a specialist otolaryngology clinic before the diagnosis of cholesteatoma was made was 3.2 years, and 68% of the children had previously undergone insertion of tympanostomy tubes. Symptoms and signs included chronic otorrhea (59%), recurrent acute otitis media (58%), and conductive hearing loss (51%). The diagnosis of AC was eventually made after office otoscopy (26%), temporal bone computed tomography (24%), or examination under anesthesia (17%). In 33% of children, the diagnosis was made only after surgical exploration of the middle ear and mastoid. Our data underscore the importance of maintaining a high index of suspicion for AC in managing children with long-standing otologic symptoms, and considering otomicroscopy, computed tomographic scanning, or tympanomastoid exploration if medical treatment fails.


Electromagnetic field-assisted cell-laden 3D printed poloxamer-407 hydrogel for enhanced osteogenesis.
3D bioprinted hydrogel has gained enormous attention, especially in tissue engineering, owing to its attractive structure and excellent biocompatibility. In this study, we demonstrated that 3D bioprinted cell-laden 'thermoresponsive' poloxamer-407 (P407) gels have the potential to stimulate osteogenic differentiation of apical papilla stem cells (SCAPs) under the influence of low voltage-frequency (5 V-1 Hz, 0.62 mT) electromagnetic fields (EMFs). SCAPs were initially used for cell-laden 3D printing to biomimic the apical papilla of human teeth. The developed hydrogel exhibited higher mechanical strength as well as good printability, showing high-quality micro-architecture. Moreover, the as-printed hydrogels (5 mm × 5 mm) were loaded with plasminogen activator inhibitor-1 (PAI-1) for testing the combined effect of PAI-1 and EMFs on SCAP differentiation. Interestingly, the 3D hydrogels showed improved viability and differentiation of SCAPs under EMFs' influence as examined by live/dead assay and alizarin Red-S staining, respectively. Therefore, our results confirmed that P407 hydrogels are non-toxic for encapsulation of SCAPs, yielding high cell viability and accelerate the cell migration potential. The 3D hydrogels with PAI-1 exhibited high mRNA expression levels for osteogenic/odontogenic gene markers (ALP, Col-1, DSPP, and DMP-1) vis-à-vis control after 14 days of in vitro culture. Our findings suggest that 3D bioprinted P407 hydrogels are biocompatible for SCAP encapsulation, and the applied low voltage-frequency EMFs could effectively improve dental tissue regeneration, particularly for oral applications.


Fluctuations in dietary intake during treatment for childhood leukemia: A report from the DALLT cohort.
Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Nutritional morbidities are a persistent problem facing pediatric patients during and after treatment and age-gender groups that are at risk for nutritional conditions have not been clearly identified. Therapy is a contributing factor; however, the role of dietary intake remains largely unknown. Prior to conduct of interventional trials, an understanding of the effects of treatment on fluctuations in dietary intake is necessary. We enrolled 794 children with ALL in a prospective clinical trial. Dietary intake was collected with a food frequency questionnaire at diagnosis and throughout the course of treatment for pediatric ALL. Reported values were compared to the Dietary Recommended Intake (DRI), and normative values (NHANES). Hierarchical linear models and multilevel mixed-effects ordered logistic regression models were used to evaluate longitudinal changes in dietary intake; independent samples t-test with Bonferroni correction was performed to compare to NHANES. Of the evaluable participants at each timepoint, dietary intake was obtained on 81% (n = 640), 74% (n = 580) and 74% (n = 558) at diagnosis, end of induction phase of treatment, and continuation, respectively. Despite exposure to corticosteroids, caloric intake decreased over therapy for most age-gender groups. Predictive models of excess intake found reduced odds of over-consuming calories (OR 0.738, P < 0.05); however, increased odds of over-consuming fat (OR 6.971, P < 0.001). When compared to NHANES, we consistently found that ≥1/3 of children were consuming calories in excess of normative values. For select micronutrients, a small proportion of participants were above or below the DRI at each time evaluated. Our study suggests that dietary intake fluctuates during treatment for ALL as compared to age-gender recommended and normative values. Improving our understanding of nutrient fluctuations and dietary quality will facilitate subsequent analyses addressing relationships of dietary intake, toxicity, and survival.


Effects of cell Ca and pH on Na channels from rat cortical collecting tubule.
The patch-clamp technique was used to identify individual Na channels in the apical membrane of the rat cortical collecting tubule and to evaluate the effects of cytoplasmic Ca2+ and pH on channel activity. In excised, inside-out patches, the probability of a channels's being open (P0) increased with alkalinization of the solution bathing the cytoplasmic side of the patch. Estimates of P0 were 0.05 at pH 6.4, 0.19 at pH 6.9, and 0.41 at pH 7.4. Varying the free Ca2+ concentration of the solution bathing the cytoplasmic side of the patch had no measurable effect on P0. In cell-attached patches, addition of the Ca2+ ionophore ionomycin to the solution bathing the tubules to a final concentration of either 1 or 10 microM decreased channel activity measured as the mean number of open channels (no. open) = n X P0 where n is the number of channels in the membrane. (no. open) was significantly decreased at 3 min after addition of ionomycin and fell to less than 10% of control values after 10 min incubation. There was no fall in (no. open) either in time controls or in tubules exposed to ionomycin in the presence of low bath Ca2+ concentrations [no added Ca2+ with 1 mM ethyleneglycol-bis-(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA)]. The results suggest that cytoplasmic pH can directly influence channel activity. Cytoplasmic Ca2+ does not interact directly with the channels, but increased cytoplasmic Ca2+ produces a fall in channel activity through an indirect process.


Physicians' perceptions of the implementation of the serious illness care program: a qualitative study.
Conversations about goals, values and priorities with patients that are seriously ill are associated with improved palliative healthcare. The Serious Illness Care Program is a multi-component program that can facilitate more, better, and earlier conversations between clinicians and seriously ill patients. For successful and sustainable implementation of the Serious Illness Care Program, it is important to consider how stakeholders perceive it. The aim of our study was to explore physicians' perceptions and experiences of implementing the Serious Illness Care Program. Data were collected through four focus group discussions with physicians (n = 14) working at a hospital where the Serious Illness Care program was in the process of being implemented. Data were analyzed with inductive thematic analysis. Physicians' perceptions of the implementation encompassed three thematic areas: hovering between preparedness and unpreparedness, being impacted and being impactful, and picking pieces or embracing it at all. This study identified key aspects related to the individual physician, the care team, the impact on the patient, and the organizational support that were perceived to influence the implementation and sustainable integration of the Serious Illness Care Program. Describing these aspects provides insight into how the Serious Illness Care Program is implemented in practice and indicates areas for future training and development. Not applicable.


Replication and external validation of a bi-factor parameterization of attention deficit/hyperactivity symptomatology.
This study evaluated the fit and criterion validity of a recently proposed bi-factor structure for attention deficit/hyperactivity disorder (ADHD) symptoms. Participants were 1,093 children, drawn from an ongoing prospective longitudinal study, whose ADHD symptoms were rated by parents and teachers when children were in 1st grade. The criterion validity of the bi-factor model was established using a range of school-based outcomes that included treatment utilization, teacher perceptions of the need for treatment, academic functioning, and peer and teacher relationship quality. Results indicated that a bi-factor model parameterization provided an equally good fit to parent, teacher, and combined reports of ADHD symptoms as did traditional 1-, 2-, and 3-factor models. However, in contrast to traditional models, the bi-factor parameterization acknowledged both the unity and diversity of ADHD symptoms. The general ADHD latent factor explained the vast majority of the observed variation in every symptom. Whereas the general ADHD latent factor was significantly associated with all 15 outcomes, the specific Inattentive factor explained unique variation in 9 (primarily the academically oriented) outcomes and the specific Hyperactive-Impulsive factor explained unique variation in 2 outcomes. The general ADHD factor was more strongly correlated with each of the observed ADHD symptom scores (total, inattentive, hyperactive-impulsive) than was either specific factor. Results are discussed with respect to how changes in the conceptualization of the factor structure correspond to recent changes to the diagnostic criteria for ADHD, as well as whether/how individual differences in inattention and hyperactivity-impulsivity might be used to differentiate children who are diagnosed with ADHD.


Nobiletin Inhibits Helicobacterium pylori Infection-Induced Gastric Carcinogenic Signaling by Blocking Inflammation, Apoptosis, and Mitogen-Activated Protein Kinase Events in Gastric Epithelial-1 Cells.
Helicobacter pylori causes a Gram-negative bacterial infection that can increase the risk of gastric cancer. Consequently, meticulous prevention of an H. pylori infection is significant for averting gastric cancer in humans. Nobiletin, an important dietary polymethoxylated flavonoid in citrus fruits, possesses multidimensional pharmaceutical properties, including its ability to act as an anticancer, anti-inflammatory, antioxidative, cardiovascularly defensive, neuroprotective, and antimetabolic agent. Our study evaluates the role of nobiletin in inflammation-mediated gastric carcinogenic signaling of H. pylori-arbitrated coculture in the human gastric epithelial (GES)-1 cell line. Our results show that the culture system of H. pylori-tainted GES-1 cells demonstrates maximum fabrication of reactive oxygen species (ROS), mediating DNA injury and augmenting nuclear fragmentations. Treatment with nobiletin reduces ROS levels and apoptotic morphological changes by dual staining and decreases levels of lipid peroxides and glutathione content in H. pylori-infected GES-1 cells. Phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/phosphatase and tensin homolog signaling have been implicated to affect cell endurance, inflammation, proliferation, and carcinogenic activity in gastric GES-1 cells. We find that nobiletin strongly impedes tumor necrosis factor-α, interleukin-6, cyclooxygenase-2, PI3K, AKT, and mitogen-activated protein kinase molecules, including p38, extracellular receptor kinase 1, and c-Jun amino-terminal expression in H. pylori-infected GES-1 cells. We conclude that nobiletin potentially impedes H. pylori infection and its related activation, likely preventing H. pylori infection-mediated gastric cancer.


Health and Healthcare Utilization among Asylum-Seekers from Berlin's LGBTIQ Shelter: Preliminary Results of a Survey.
LGBTIQ asylum-seekers face multiple health risks. Yet, little is known about their healthcare needs. In 2016, Berlin opened the only major shelter for LGBTIQ asylum-seekers in Germany. This preliminary study describes health and healthcare utilization by asylum-seekers living in Berlin's LGBTIQ shelter. To identify particular healthcare needs, we compared our results to asylum-seekers from other shelters. We surveyed residents of the LGBTIQ shelter and 21 randomly selected shelters in Berlin, using a validated questionnaire in nine languages (n = 309 respondents, including 32 respondents from the LGBTIQ shelter). Bivariate tests and generalized linear mixed models were applied to examine differences in health and healthcare utilization between the two groups. Residents of the LGBTIQ shelter show high rates of chronic and mental illness. They use ambulatory and mental health services more frequently than asylum-seekers from other shelters, including a significantly higher chance of obtaining psychotherapy/psychiatric care in case of need. Emergency room utilization is also higher in the LGBTIQ group. Asylum-seekers from the LGBTIQ shelter face high chronic and mental health burdens. Tailored services in the LGBTIQ shelter help obtain adequate healthcare; they should be scaled up to maximize their potential. Yet, unmet needs remain and warrant further research.


Practical aspects in the management of statin-associated muscle symptoms (SAMS).
Statin-associated muscle symptoms (SAMS) frequently cause statin non-adherence, switching and discontinuation, contributing to adverse cardiovascular (CV) outcomes. Therefore, the management of SAMS is key in the effective treatment of patients with cardiovascular disease (CVD), through achievement of maximum-tolerated statin dosing and other practical aspects. The aim of this article is to provide practical, focused advice for healthcare professionals on the management of patients with SAMS. An expert working group combined current evidence, published guidelines and experiences surrounding a number of topics concerning SAMS to provide recommendations on how to best assess and manage this condition and reach the highest tolerated dose of statin for each individual patient. The group collaborated to provide guidance on definitions in the SAMS field, psychological issues, re-challenging and switching treatments, as well as interpretation of current guidelines and optimal treatment of SAMS in different patient populations. An algorithm was developed to guide the management of patients with SAMS. In addition, the expert working group considered some of the more complex scenarios in a series of frequently asked questions and suggested answers. The expert working group gave recommendations for healthcare professionals on the management of SAMS but highlighted the importance of tailoring the treatment approach to each individual patient. Evidence supporting the role of nutraceuticals and complementary therapies, such as vitamin D, was lacking, however the majority of the group favoured combination therapy with ezetimibe and the addition of PCSK9 inhibitors in high-risk patients.


Analysis of an HIV infection model incorporating latency age and infection age.
There is a growing interest to understand impacts of latent infection age and infection age on viral infection dynamics by using ordinary and partial differential equations. On one hand, activation of latently infected cells needs specificity antigen, and latently infected CD4+ T cells are often heterogeneous, which depends on how frequently they encountered antigens, how much time they need to be preferentially activated and quickly removed from the reservoir. On the other hand, infection age plays an important role in modeling the death rate and virus production rate of infected cells. By rigorous analysis for the model, this paper is devoted to the global dynamics of an HIV infection model subject to latency age and infection age from theoretical point of view, where the model formulation, basic reproduction number computation, and rigorous mathematical analysis, such as relative compactness and persistence of the solution semiflow, and existence of a global attractor are involved. By constructing Lyapunov functions, the global dynamics of a threshold type is established. The method developed here is applicable to broader contexts of investigating viral infection subject to age structure.


Extracorporeal membrane modality conversions.
We report the case of a patient with cardiovascular and respiratory failure due to severe anaphylaxis requiring multiple extracorporeal membrane oxygenation (ECMO) cannulation strategies to provide adequate oxygen delivery and ventilatory support during a period of rapid physiological change. ECMO provides partial or complete support of oxygenation-ventilation and circulation. The choice of which ECMO modality to use is governed by anatomical (vessel size, cardiovascular anatomy and previous surgeries) and physiological (respiratory and/or cardiac failure) factors. The urgency with which ECMO needs to be implemented (emergency cardiopulmonary resuscitation (eCPR), urgent, elective) and the institutional experience will also influence the type of ECMO provided. Here we describe a 12-year-old schoolgirl who, having been resuscitated with peripheral veno-venous (VV) ECMO for severe hypoxemia due to status asthmaticus in the setting of acute anaphylaxis, required escalation to peripheral veno-arterial (VA) ECMO for precipitous cardiovascular deterioration. Insufficient oxygen delivery for adequate cellular metabolic function and possible cerebral hypoxia due to significant differential hypoxia necessitated ECMO modification. After six days of central (transthoracic) VA ECMO support and 21 days of intensive care unit (ICU) care, she made a complete recovery with no neurological sequelae. The use of ECMO support warrants careful consideration of the interplay of a patient's pathophysiology and extracorporeal circuit dynamics. Particular emphasis should be placed on the potential for mismatch between cardiovascular and respiratory support as well as the need to meet metabolic demands through adequate cerebral, coronary and systemic oxygenation. Cannulation strategies occasionally require alteration to meet and anticipate the patient's evolving needs.


MiRNA landscape in stage I epithelial ovarian cancer defines the histotype specificities.
Epithelial ovarian cancer (EOC) is one of the most lethal gynecologic diseases, with survival rate virtually unchanged for the past 30 years. EOC comprises different histotypes with molecular and clinical heterogeneity, but up till now the present gold standard platinum-based treatment has been conducted without any patient stratification. The aim of the present study is to generate microRNA (miRNA) profiles characteristic of each stage I EOC histotype, to identify subtype-specific biomarkers to improve our understanding underlying the tumor mechanisms. A collection of 257 snap-frozen stage I EOC tumor biopsies was gathered together from three tumor tissue collections and stratified into independent training (n = 183) and validation sets (n = 74). Microarray and quantitative real-time PCR (qRT-PCR) were used to generate and validate the histotype-specific markers. A novel dedicated resampling inferential strategy was developed and applied to identify the highest reproducible results. mRNA and miRNA profiles were integrated to identify novel regulatory circuits. Robust miRNA markers for clear cell and mucinous histotypes were found. Specifically, the clear cell histotype is characterized by a five-fold (log scale) higher expression of miR-30a and miR-30a*, whereas mucinous histotype has five-fold (log scale) higher levels of miR-192/194. Furthermore, a mucinous-specific regulatory loop involving miR-192/194 cluster and a differential regulation of E2F3 in clear cell histotype were identified. Our findings showed that stage I EOC histotypes have their own characteristic miRNA expression and specific regulatory circuits.


The molecular cloning of a type II regulatory subunit of the cAMP-dependent protein kinase from rat skeletal muscle and mouse brain.
A cDNA clone for a type II regulatory (R) subunit of the cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC 18.104.22.168) was isolated from a rat skeletal muscle library using a specific 47-base oligonucleotide probe. The rat cDNA was 1.2 kilobases (kb) in length and contained an open reading frame of 1.113 kb representing 92% of the coding region of the molecule. Nick-translated rat cDNA was then used to isolate a mouse RII cDNA clone from a brain library that contained an open reading frame of 1.143 kb. Because both cDNAs lacked complete coding sequences, the remainder of the RII coding region was obtained from a 15-kb mouse genomic clone. The mouse RII coding region contains 1.2 kb corresponding to a 400-amino acid protein of 51.141 kDa. The mouse cDNA hybridizes to two mRNA species, a 2.4-kb form that was only observed in testis and a 6.0-kb form found in a wide range of tissues, including testis.


Subject-domain approach to the study of air pollution effects on schoolchildren's illness absence.
In this paper, the authors propose a new statistical modeling technique, the subject-domain approach, which is theoretically proven to be equivalent to the time-domain approach in detecting an association between exposure and response with time trends. The authors use an empirical data set from a school absence monitoring study conducted during the 1994-1995 school year in Taiwan to demonstrate this subject-domain approach's application to environmental epidemiologic studies. Because the subject-domain models can control the influential personal confounding factors in the models, they show greater statistical power than the traditional time-domain approaches in determining the relation between air pollution and illness absences. The authors' models found that the schoolchildren's risks of illness absence were significantly related to acute exposures to nitrogen dioxide and nitrogen oxides with a 1-day lag (p < 0.01) at levels below the World Health Organization's guidelines. By contrast, the authors could not detect significant associations between air pollution and schoolchildren's absenteeism using time-domain approaches. Such findings imply that the models built on subject domain may be a general solution to the problem of the ecologic fallacy, which is commonly encountered in environmental and social epidemiologic studies.


Modeling geriatric depression in animals: biochemical and behavioral effects of olfactory bulbectomy in young versus aged rats.
Geriatric depression exhibits biological and therapeutic differences relative to early-onset depression. We studied olfactory bulbectomy (OBX), a paradigm that shares major features of human depression, in young versus aged rats to determine mechanisms underlying these differences. Young OBX rats showed locomotor hyperactivity and a loss of passive avoidance and tactile startle. In contrast, aged OBX animals maintained avoidance and startle responses but showed greater locomotor stimulation; the aged group also exhibited decreased grooming and suppressed feeding with novel presentation of chocolate milk, effects which were not seen in young OBX. These behavioral contrasts were accompanied by greater atrophy of the frontal/parietal cortex and midbrain in aged OBX. Serotonin transporter sites were increased in the cortex and hippocampus of young OBX rats, but were decreased in the aged OBX group. Cell signaling cascades also showed age-dependent effects, with increased adenylyl cyclase responses to monoaminergic stimulation in young OBX but no change or a decrease in aged OBX. These data indicate that there are biological distinctions in effects of OBX in young and aged animals, which, if present in geriatric depression, provide a mechanistic basis for differences in biological markers and drug responses. OBX may provide a useful animal model with which to test therapeutic interventions for geriatric depression.


Dreaming during the Covid-19 pandemic: Computational assessment of dream reports reveals mental suffering related to fear of contagion.
The current global threat brought on by the Covid-19 pandemic has led to widespread social isolation, posing new challenges in dealing with metal suffering related to social distancing, and in quickly learning new social habits intended to prevent contagion. Neuroscience and psychology agree that dreaming helps people to cope with negative emotions and to learn from experience, but can dreaming effectively reveal mental suffering and changes in social behavior? To address this question, we applied natural language processing tools to study 239 dream reports by 67 individuals, made either before the Covid-19 outbreak or during the months of March and April, 2020, when lockdown was imposed in Brazil following the WHO's declaration of the pandemic. Pandemic dreams showed a higher proportion of anger and sadness words, and higher average semantic similarities to the terms "contamination" and "cleanness". These features seem to be associated with mental suffering linked to social isolation, as they explained 40% of the variance in the PANSS negative subscale related to socialization (p = 0.0088). These results corroborate the hypothesis that pandemic dreams reflect mental suffering, fear of contagion, and important changes in daily habits that directly impact socialization.


DNA hybridization using surface plasmon-coupled emission.
We describe a new approach to measuring DNA hybridization using surface plasmon-coupled emission (SPCE). Excited fluorophores are known to couple with surface oscillations of electrons in thin metal films, typically 50 nm thick silver on a glass prism. These surface plasmons then radiate into the glass at a sharply defined angle determined by the emission wavelength and the optical properties of the glass and metal. This radiation has the same spectral profile as the emission spectrum of the fluorophores. We studied the emission due to Cy3-labeled DNA oligomers bound to complementary unlabeled oligomers which were themselves bound to the metal surface. Hybridization resulted in SPCE due to Cy3-DNA into the prism. Directional SPCE was observed whether the sample was illuminated from the sample side or through the glass substrate at the surface plasmon angle for the excitation wavelength. A large fraction of the total potential emission is coupled to the surface plasmons resulting in improved sensitivity. When illuminated through the prism at the surface plasmon angle, the sensitivity is increased due to the enhanced intensity of the resonance evanescent field. It is known that SPCE depends on proximity to the silver surface. As a result, changes in emission intensity are observed due to fluorophore localization even if hybridization does not affect the quantum yield of the fluorophore. The use of SPCE resulted in suppression of interfering emission from a noncomplementary Cy5-DNA oligomers due to weaker coupling of the more distant fluorophores with the surface plasmons. We expect SPCE to have numerous applications to nucleic acid analysis and for the measurement of bioaffinity reactions.


Chain length recognition: core-shell supramolecular assembly from oppositely charged block copolymers
Molecular recognition based on length was found to occur between oppositely charged pairs of flexible and randomly coiled block copolymers in an aqueous milieu. Matched pairs with the same block lengths of polyanions and polycations exclusively formed even in mixtures with different block lengths. These assemblies of the charged segments with matched chain lengths then formed larger core-shell-type supramolecular assemblies with an extremely narrow size distribution due to the strict phase separation between core- and shell-forming segments.


The sensitivity and specificity of "caterpillar bodies" in the differential diagnosis of subepidermal blistering disorders.
Caterpillar bodies are eosinophilic, elongated, segmented bodies located within the roofs of blisters and are considered to represent a specific histopathologic feature of porphyric bullous eruptions, including porphyria cutanea tarda and erythropoietic protoporphyria. The possibility that similar or identical bodies may be present in other disorders prompted further study exploring the specificity of caterpillar bodies in the differential diagnosis of subepidermal vesiculobullous disorders. Seventy-six cases exhibiting subepidermal clefting were reviewed by light microscopy. "Classic" caterpillar bodies were present in porphyria cutanea tarda (6 of 14) and 1 case representing either venous stasis-associated bulla or possibly bullosis diabeticorum. Caterpillar body-like clusters were present in porphyria cutanea tarda (5 of 14), erythropoietic protoporphyria (1 of 3), bullous pemphigoid (7 of 24), and junctional or dystrophic epidermolysis bullosa (3 of 5). In some cases, classic caterpillar body and caterpillar body-like clusters coexisted in a blister roof. Caterpillar bodies or caterpillar body-like clusters were not identified in any cases of dermatitis herpetiformis, linear IgA bullous dermatosis, bullous erythema multiforme, epidermolysis bullosa acquisita, or wound-healing reactions. In contrast to caterpillar bodies, caterpillar body-like clusters were negative for PAS or Type IV collagen stains. In conclusion, caterpillar bodies appear to represent a specific feature of porphyria cutanea tarda (specificity, 98%) but were present in less than half of those cases in this study (sensitivity, 43%). Caterpillar body-like clusters are less specific and may be present in porphyria cutanea tarda, erythropoietic protoporphyria, pseudoporphyria, bullous pemphigoid, epidermolysis bullosa, and epidermolysis bullosa acquisita.


Code Status Blues: Do Legal Nudges Discourage Doctors From Ordering Do-Not-Resuscitate?
BackgroundLaws influence human behavior, including practitioners' behavior, and legal nudges may affect bedside patient care practices. Do-not-resuscitate (DNR) practices are one such example. Ensuring that practitioners order DNR for patients who request it is a crucial part of providing quality end-of-life care. On April 1, 2018, in the state of Texas, Senate Bill 11 (SB 11) took effect. This law did not make DNR orders illegal, but it constrained and complicated the process for issuing them. This study aimed to determine if DNR order utilization decreased after the law's implementation. MethodsThe authors conducted a retrospective cohort chart review of all adult patients admitted to a single academic urban tertiary care hospital in Texas before and after the state's DNR law went into effect. The authors reviewed code status orders for the 5426 sickest patients. The primary outcome is the proportion of patients who had DNR orders in effect at the end of their hospitalizations. ResultsImplementation of the DNR law's cumbersome documentation and witnessing requirements correlated with a substantial decline in DNR orders for patients at the highest risk of dying from chronic or severe illness. ConclusionThis is the first study the authors know of that examines whether DNR usage declined after implementation of a DNR law. A troubling implication of this study is that the Texas law has had a chilling effect on doctors' willingness and ability to place medically and ethically appropriate DNR orders and has threatened the right of patients with serious illness to forgo cardiopulmonary resuscitation.


[Sleep quality of obese workers of a teaching hospital: acupuncture as a complementary therapy].
The objective of this study was to verify the effect of acupuncture on the sleep quality of obese workers in a teaching hospital. Data were collected from July to October 2009, focusing on 37 workers who attended eight weekly acupuncture sessions. The Pittsburgh Sleep Quality Index was used to assess their sleep quality before and after the intervention. Results show that before the intervention, five (13.5%) people experienced good quality of sleep whereas at the end of the study 14 (37.8%) showed this condition. Statistic significance (p=0.0001) was found in comparing the mean scores obtained before and after acupuncture. Acupuncture had effects on the quality of sleep in the studied sample, presenting itself as a complementary technique for treating sleep disorders and consequently improving the quality of life in this population.


Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes.
Programmed cell death can be divided into several categories including type I (apoptosis) and type II (autophagic death). The Bcl-2 family of proteins are well-characterized regulators of apoptosis, and the multidomain pro-apoptotic members of this family, such as Bax and Bak, act as a mitochondrial gateway where a variety of apoptotic signals converge. Although embryonic fibroblasts from Bax/Bak double knockout mice are resistant to apoptosis, we found that these cells still underwent a non-apoptotic death after death stimulation. Electron microscopic and biochemical studies revealed that double knockout cell death was associated with autophagosomes/autolysosomes. This non-apoptotic death of double knockout cells was suppressed by inhibitors of autophagy, including 3-methyl adenine, was dependent on autophagic proteins APG5 and Beclin 1 (capable of binding to Bcl-2/Bcl-x(L)), and was also modulated by Bcl-x(L). These results indicate that the Bcl-2 family of proteins not only regulates apoptosis, but also controls non-apoptotic programmed cell death that depends on the autophagy genes.


Chronic persistent Epstein-Barr virus infection of natural killer cells and B cells associated with granular lymphocytes expansion.
B lymphocytes and epithelial cells are the only cell types known to be infected with Epstein-Barr virus (EBV) in normal individuals. Rarely, EBV also infects other cells, including natural killer (NK) cells, almost always in the context of fatal leukaemias or lymphoproliferative disorders. We report on a 6-year-old previously healthy girl who developed fevers and liver function abnormalities for 3 months. The peripheral blood revealed an abnormal expansion of large granular lymphocytes, comprising 24% of the white blood cells. Flow cytometric analysis of the peripheral blood mononuclear cells showed an abnormal increase of CD16-positive NK cells, 62% of which were EBV-infected by in situ EBER-1 hybridization. The circulating B cells were normal in number, but 18% were infected with EBV by in situ EBER-1 hybridization. Approximately 2 years after resolution of all symptoms and continued good health. 35% of the circulating mononuclear cells were EBV-infected, indicative of persistent expansion of EBV-infected cells. We conclude that abnormal expansions of EBV-infected NK and B cells can be associated with a chronic benign course.


Complementary roles of laparoscopic abdominal exploration and diagnostic peritoneal lavage for evaluating abdominal stab wounds: a prospective study.
To determine the roles of laparoscopic abdominal exploration (LE) and diagnostic peritoneal lavage (DPL) in the evaluation of abdominal stab wounds, we prospectively compared LE with mandatory celiotomy (MC) in 76 patients having anterior abdominal stab wounds penetrating the fascia over a 22-month period. Twenty-two patients underwent emergency celiotomy. The remaining patients were subjected to DPL and assigned to treatment by either celiotomy or initial LE with subsequent conversion to open exploration at the discretion of the attending surgeon. Laparotomy was avoided in 55% of the 31 patients undergoing initial laparoscopy, and this group demonstrated a significant decrease in the incidence of nontherapeutic celiotomy, from 19% to 57% (P < 0.05), as well as decreased length of hospital stay (4 +/- 0.6 v 5.9 +/- 0.4 days; P < 0.05), and total hospital cost ($6119 +/- 756 v $8312 +/- 627; P < 0.05). There were no missed intraabdominal injuries or morbidity from laparoscopy identified in follow-up. The DPL (N = 36) was positive in 11 of the 12 patients with injury requiring surgical repair and was negative in 16 of the 25 patients not requiring repair. The sensitivity and specificity of DPL were 0.91 and 0.64 compared with 1.0 and 0.74 for laparoscopy. An algorithm to evaluate stable patients with anterior abdominal stab wounds and minimize overall costs of care, incidence of nontherapeutic celiotomy, and rate of missed injuries is suggested consisting of DPL followed by observation in patients with negative DPL and by laparoscopy in patients with positive DPL. Wounds to the thoracoabdominal region may be best evaluated by initial LE, as diaphragmatic wounds may result in a false-negative DPL.