Partial resistance of SARS-CoV-2 Delta variants to vaccine-elicited antibodies and convalescent sera.
Highly transmissible SARS-CoV-2 variants identified in India and designated B.1.617, Kappa (B.1.617.1), Delta (B.1.617.2), B.1.618, and B.1.36.29 contain spike mutations L452R, T478K, E484K, E484Q, and N440K located within the spike receptor-binding domain and thus could contribute to increased transmissibility and potentially allow re-infection or cause resistance to vaccine-elicited antibody. To address these issues, we used lentiviruses pseudotyped by variant spikes to measure their neutralization by convalescent sera, vaccine-elicited and Regeneron therapeutic antibodies, and ACE2 affinity. Convalescent sera and vaccine-elicited antibodies neutralized viruses with Delta spike with 2- to 5-fold decrease in titer in different donors. Regeneron antibody cocktail neutralized virus with the Delta spike with a 2.6-fold decrease in titer. Neutralization resistance to serum antibodies and monoclonal antibodies was mediated by L452R mutation. These relatively modest decreases in antibody neutralization titer for viruses with variant spike proteins suggest that current vaccines will remain protective against the family of Delta variants.


Metal-doped carbon dots as peroxidase mimic for hydrogen peroxide and glucose detection.
Carbon dots (CDs) have several superior characteristics including sufficient carbon sources, easy preparation, no toxicity, and high catalytic efficiency as a new kind of nanozyme. Herein, Ce-doped carbon dots (Ce-CDs), Cr-doped carbon dots (Cr-CDs), Cu-doped carbon dots (Cu-CDs), Fe-doped carbon dots (Fe-CDs), Mn-doped carbon dots (Mn-CDs), and non-metal-doped carbon dots (0-CDs) were synthesized to explore the detection of hydrogen peroxide (H2O2) and glucose as peroxidase mimic. The prepared CDs could efficiently oxidize the colorless 3,3',5,5'-tetramethylbenzidine (TMB) into blue oxTMB in the presence of H2O2. After adding glucose oxidase (GOD) to the CDs/TMB system, a colorimetric method for glucose detection was developed. The results show that Fe-CDs possess the highest catalytic activity. When using Fe-CDs as peroxidase mimetics, the detection limit of this assay for glucose was 0.029 mmol L-1. This successfully provides a sensitive and selective colorimetric method for hydrogen peroxide and glucose determination.


For staining of ALK protein, the novel D5F3 antibody demonstrates superior overall performance in terms of intensity and extent of staining in comparison to the currently used ALK1 antibody.
Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm. Approximately 50 % of IMTs show an anaplastic lymphoma kinase (ALK) gene fusion resulting in ALK overexpression on immunohistochemistry (IHC). A novel anti-ALK monoclonal antibody (D5F3) has been suggested to be of superior sensitivity to the ALK1 antibody which is currently used. We compared the performance of D5F3 in detecting ALK protein expression in IMTs from various anatomic sites compared to the currently utilized ALK1. We selected 25 IMTs from our surgical pathology files (2005-2015). The novel rabbit monoclonal anti-human CD246 (clone D5F3) and the currently used mouse monoclonal anti-human CD246 (clone ALK1) were used for immunohistochemical staining (IHC) in an automated slide stainer. The percentage of immunoreactive tumor cells (0, <5 %, 5-50 %, >50 %) and cytoplasmic staining intensity (graded 0-3) were assessed and compared between the two antibodies. Fluorescence in situ hybridization (FISH) studies for ALK gene rearrangement were performed on 11 tumors. D5F3 antibody stained 76 % and ALK1 antibody stained 72 % of IMTs (p = 0.747). Compared to staining with ALK1, D5F3 stained a higher proportion of cases extensively (>50 % cells) (76 vs. 28 %, p < 0.001) and with high intensity (grade 3 76 % vs 0; p < 0.001). FISH and IHC findings (for both antibodies) were concordant in 9/10 (90 %) IMTs, in which results were informative. The novel anti-ALK rabbit monoclonal antibody (D5F3 clone) demonstrates superior overall performance in term of intensity and extent of staining of ALK protein in IMT. We found IHC staining with both antibody clones to correlate equally well with FISH results for detection of ALK rearrangement.


Pitted enamel hypoplasia in tuberous sclerosis patients and first-degree relatives.
Thirty-six families with tuberous sclerosis (TS) including 49 affected persons and 68 apparently unaffected first-degree relatives were examined for dental abnormality. Fifty unrelated controls were similarly examined. Clinically observed multiple enamel pits (pitted enamel hypoplasia) were noted in 71% of persons with typical TS and in one out of 10 "atypical" cases. Enamel pits were rarely seen, and in small numbers only, in the control series, and they were rare in the otherwise apparently normal TS first-degree relatives. However, one parent and one half-sib of persons with typical TS, but themselves without other signs of TS, were found to have multiple enamel pits. Examination for pitted enamel hypoplasia should be made in all persons suspected of having TS and in all close relatives; enamel pits are a valuable clinical sign and may identify otherwise unsuspected carriers of the gene within the family.


Gas chromatography system for the automated, unattended, and cryogen-free monitoring of C2 to C6 non-methane hydrocarbons in the remote troposphere.
An unattended, automated, on-line, cryogen-free, remotely controlled gas chromatography (GC) system was developed and has been deployed for more than 1 year for the continuous determination of C(2) to C(6) hydrocarbons at an observatory located at 2225 m elevation, on the summit caldera of an inactive volcano on the island of Pico, Azores. The GC instrument is tailored to the measurement challenges at this remote and high altitude site. All consumable gases are prepared in situ. Total power use remains below 700 W at all times. Sample collection and analysis is performed without use of cryogen. Hydrocarbons are concentrated on a one-stage trapping/injection system consisting of a Peltier-cooled multi-bed solid adsorbent trap. Analytes are detected after thermal desorption and separation on an alumina-PLOT (porous-layer open tubular) column by flame ionization detection (FID). Sample focusing, desorption, separation and detection parameters were thoroughly investigated to ensure quantitative collection and subsequent injection onto the GC system. GC operation is controlled remotely and data are downloaded daily. Sample volumes (600 and 3000 ml) are alternated for analysis of C(2) to C(3) and C(3) to C(6) hydrocarbons, respectively. Detection limits are in the low parts per trillion by volume (pptv) range, sufficient for quantification of the compounds of interest at their central North Atlantic lower free troposphere background concentrations.


Structural characterization and hepatoprotective effects of polysaccharides from Anoectochilus zhejiangensis.
Two new polysaccharides, AZP-1a and AZP-1d, with molecular weights of 3.41 × 104 and 4568 Da, respectively, were extracted from Anoectochilus zhejiangensis and purified by column chromatography. Their structural characteristics were systematically explored and results indicated AZP-1a and AZP-1d shared a similar backbone consisted of→4)-Galp-(1→, →4)-Glcp-(1→, and →4,6)-Glcp-(1→, with a different terminal residue of Manp-(1 → and Glcp-(1→, respectively. In vivo experiments showed that the crude polysaccharide of A. zhejiangensis (AZP) exhibited significant hepatoprotective effects, decreasing the serum levels of ALT, AST and LDH in CCl4-treated mice, reducing MDA content, promoting SOD and CAT activities, and increasing GSH level in liver. Further in vitro investigation exhibited that AZP, AZP-1a and AZP-1d effectively protected liver cells against CCl4-stimulated oxidative damage, while AZP-1a and AZP-1d functioned mainly through the activation of Nrf2 signaling pathway. Our results suggest that A. zhejiangensis polysaccharides can be applied as a potential resource for the development of hepatoprotective drugs.


Intelligent non-colorimetric indicators for the perishable supply chain by non-wovens with photo-programmed thermal response.
Spoiled perishable products, such as food and drugs exposed to inappropriate temperature, cause million illnesses every year. Risks range from intoxication due to pathogen-contaminated edibles, to suboptimal potency of temperature-sensitive vaccines. High-performance and low-cost indicators are needed, based on conformable materials whose properties change continuously and irreversibly depending on the experienced time-temperature profile. However, these systems can be limited by unclear reading, especially for colour-blind people, and are often difficult to be encoded with a tailored response to detect excess temperature over varying temporal profiles. Here we report on optically-programmed, non-colorimetric indicators based on nano-textured non-wovens encoded by their cross-linking degree. This combination allows a desired time-temperature response to be achieved, to address different perishable products. The devices operate by visual contrast with ambient light, which is explained by backscattering calculations for the complex fibrous material. Optical nanomaterials with photo-encoded thermal properties might establish new design rules for intelligent labels.


Cancelling of Fresnel reflections in in situ, double beam laser, fluorimetry using a single optical fibre.
This paper describes several techniques used to cancel Fresnel reflection on the extremities of the optical fibre in in situ double beam laser fluorimetry when the single optical fibre is adopted. The reasons for the technical choices are exposed and the results on several media are presented (water, air, finger pad, rat heart).


A Ternary Ni46 Co40 Fe14 Nanoalloy-Based Oxygen Electrocatalyst for Highly Efficient Rechargeable Zinc-Air Batteries.
Replacing noble-metal-based oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) electrocatalysts is the key to developing efficient Zn-air batteries (ZABs). Here, a homogeneous ternary Ni46 Co40 Fe14 nanoalloy with a size distribution of 30-60 nm dispersed in a carbon matrix (denoted as C@NCF-900) as a highly efficient bifunctional electrocatalyst produced via supercritical reaction and subsequent heat treatment at 900 °C is reported. Among all the transition-metal-based electrocatalysts, the C@NCF-900 exhibits the highest ORR performance in terms of half-wave potential (0.93 V) in 0.1 m KOH. Moreover, C@NCF-900 exhibits negligible activity decay after 10 000 voltage cycles with minor reduction (0.006 V). In ZABs, C@NCF-900 outperforms the mixture of Pt/C 20 wt% and IrO2 , cycled over 100 h under 58% depth of discharge condition. Furthermore, density functional theory (DFT) calculations and in situ X-ray absorption spectroscopy strongly support the active sites and site-selective reaction as a plausible ORR/OER mechanism of C@NCF-900.


Molecular characterization of the song control nucleus HVC in Bengalese finch brain.
Songbirds have a specialized neural substrate for learned vocalization, called the song circuit, which consists of several song nuclei in the brain. The song control nucleus HVC (a letter-based name) is the intersection point of the song learning and vocal motor pathways. Knowledge of the types of genes expressed in the HVC is essential in understanding the molecular aspects of the HVC. Gene expression in the HVC under silent conditions shows the competence necessary for singing. To investigate this, we compared the HVC with its adjacent tissues in searching for the molecular specificities of the song nucleus HVC using an in-house cDNA microarray of the Bengalese finch (Lonchura striata var. domestica). Our microarray analysis revealed that 70 genes were differentially expressed in the HVC compared with the adjacent tissue. We investigated 27 of the microarray-selected genes that were enriched or repressed in the HVC by in situ hybridization. We found that multiple calcium-binding proteins (e.g., CAPS2, parvalbumin and ATH) were enriched in the HVC. Meanwhile, the adult HVC showed low expression levels of plasticity-related genes (e.g., CAMK2A and MAP2K1) compared with the juvenile HVC. The HVC plays an important role during song learning, but our results suggest that the plasticity of this nucleus may be suppressed during adulthood. Our findings provide new information about the molecular features that characterize the HVC.


Congenital Chagas disease: diagnostic and clinical aspects in an area without vectorial transmission, Bermejo, Bolivia.
The authors carried out a 1-year study of a population of pregnant women delivering at Bermejo hospital, South Bolivia. In this area, vectorial transmission of Trypanosoma cruzi is negligible and women infect themselves during displacements in close endemic areas. The prevalence of T. cruzi in 508 pregnant women, diagnosed by several serological tests, was 33.9%. In eight infants, we observed T. cruzi in the umbilical cord (congenital transmission rate of 5.2%). The means of birth weights, lengths and hemoglobin rates were similar in the children from both seronegative and seropositive women, and in children infected or not by T. cruzi. This study could confirm a less severity of the congenital disease of Chagas in the absence of re-infestation of the mother during pregnancy. Serological screening of pregnant women by rapid diagnostic tests and examination of babies born from seropositive mothers by microhematocrit method at birth is a suitable strategy to detect and prevent congenital Chagas disease in non-endemic areas.


Impact of Late Referral on Cardiac Transplant Outcomes.
Late referral for heart transplantation (HTx) is associated with worse patient outcomes. There are no universally accepted definitions of what constitutes a timely referral for HTx assessment. To evaluate the impact of late referral (LR) on HTx outcomes. This single-centre retrospective observational study included 80 patients undergoing HTx between 2016-2019. We applied a simple clinical tool, derived from markers of advanced heart failure (HF), to classify LR in HTx patients and assess the impact of LR on HTx outcomes. Outcome measures included duration of intensive care unit (ICU) stay, total hospitalisation stay, cost of transplant admission and one-year mortality. Based upon the clinical profile, LR was defined by the presence of four or more out of 10 criteria for more than 6 months in HTx patients. In this model, 34 patients were timely referrals and 46 were LR. Patients who were LR had: a longer median time between initial diagnosis and referral (3 vs 7 ys; p=0.03); more features of advanced HF, including inotrope requirements (p=0.004); more comorbidities (p=0.014); and hospitalisations (p<0.0001). Late referral was not associated with longer ICU (p=0.14) or hospital stay (p=0.051), however LR incurred greater total in-hospital costs (p=0.011). There was no difference in one-year mortality (6% vs 9%; p=0.64). Patients referred late for HTx are more unwell at time of referral and require greater in-hospital resource usage at the time of transplantation. Earlier referral for transplant assessment in patients with advanced HF should be encouraged.


Intracranial hemorrhage in utero due to isoimmune neonatal thrombocytopenia.
A case is presented of isoimmune neonatal thrombocytopenia complicated by spontaneous intracranial hemorrhage in utero. Maternal platelets were found to be negative for the PLA1, Baka, and HLA-A2 antigens. The present case demonstrates that the classical conservative approach of elective cesarean section can not guarantee against this crippling event.


Monitoring intravesical bacillus Calmette-Guerin treatment of superficial bladder carcinoma by postoperative urinary cytology.
We studied 51 patients with superficial bladder carcinoma who had been treated with transurethral resection of all gross tumor followed by intravesical bacillus Calmette-Guerin weekly for 6 weeks. Within 72 hours of either the first or second quarterly cystoscopic surveillance examination after bacillus Calmette-Guerin therapy, a conventional cytology study was obtained. Of these patients 8 (15.7 per cent) had positive, 9 (17.6 per cent) suspicious and 34 (66.7 per cent) negative postoperative cytology studies. Subsequent tumor recurrence was defined as a positive biopsy or visible papillary tumors on cystoscopic examination. All 8 patients with a positive postoperative cytology study had tumor recurrence at a median interval of 4 months. Of the 9 patients with a suspicious study 7 (77.8 per cent) had recurrent tumor at a median interval of 7 months and 2 (22.2 per cent) had no evidence of disease at 16 and 19 months, respectively. Of the 34 patients with a negative postoperative cytology study 13 (38.2 per cent) had tumor recurrence after a median interval of 4 months and 21 (67.8 per cent) had no evidence of disease after a median of 25 months. The tumor recurrence rate in patients with a positive or suspicious postoperative cytology study was significantly greater than that of patients with a negative study (p equals 0.001, Fisher's exact test). Postoperative cytology appears to be a significant prognostic indicator following transurethral resection and intravesical bacillus Calmette-Guerin treatment of superficial bladder carcinoma.


Stability of single skyrmionic bits.
The switching between topologically distinct skyrmionic and ferromagnetic states has been proposed as a bit operation for information storage. While long lifetimes of the bits are required for data storage devices, the lifetimes of skyrmions have not been addressed so far. Here we show by means of atomistic Monte Carlo simulations that the field-dependent mean lifetimes of the skyrmionic and ferromagnetic states have a high asymmetry with respect to the critical magnetic field, at which these lifetimes are identical. According to our calculations, the main reason for the enhanced stability of skyrmions is a different field dependence of skyrmionic and ferromagnetic activation energies and a lower attempt frequency of skyrmions rather than the height of energy barriers. We use this knowledge to propose a procedure for the determination of effective material parameters and the quantification of the Monte Carlo timescale from the comparison of theoretical and experimental data.


Cerebrospinal Fluid Leak at Percutaneous Exit of Ventricular Catheter as a Crucial Risk Factor for External Ventricular Drainage-Related Infection in Adult Neurosurgical Patients.
The placement of a ventricular catheter for temporary cerebrospinal fluid (CSF) diversion is associated with a considerable risk of CSF infection. The authors investigated the effect of a CSF leak on CSF-related infection and the predisposing factors for a CSF leak. Fifty-two patients who underwent external ventricular drainage (EVD) for acute hydrocephalus associated with a subarachnoid hemorrhage or intraventricular hemorrhage (IVH) were enrolled in this prospective study. A CSF leak-detection paper (small sterilized filter paper) was applied at the percutaneous catheter exit site to check for any bloody CSF leak. In addition, radiologic and clinical data were collected. Four of the 52 patients (7.7%) developed an EVD-related CSF infection from organisms including Staphylococcus epidermidis (n = 3) and Staphylococcus hominis (n = 1). A prolonged CSF leak >1 day was detected in 9 patients (17.3%) and revealed as a significant risk factor for CSF infection with a 44.4% positive predictive value. Moreover, an IVH >10 mL was found in 11 patients (21.2%) and revealed as a significant predisposing factor for a CSF leak at the percutaneous catheter exit. A prolonged CSF leak for >1 day at the percutaneous catheter exit site is a crucial risk factor for EVD-related CSF infection and an IVH >10 mL is a predisposing factor for a CSF leak.


Retrograde neuronal labeling by means of Bisbenzimide and Nuclear Yellow (Hoechst S 769121). Measures to prevent diffusion of the tracers out of retrogradely labeled neurons.
Bisbenzimide and Hoechst S 769121 (Nuclear Yellow, NY), when transported retrogradely through axons to their parent cell bodies, may migrate out of the axons and the cell bodies, as indicated by fluorescence of adjoining glial nuclei. This migration was found to take place both in vivo and in vitro during storage of the sections in water. When using the tracers in 1% concentrations the in vivo migration may be controlled by restricting the survival time. The in vitro migration may be prevented by rapid histological processing of the material.


Electrical detection of spin precession in a metallic mesoscopic spin valve.
To study and control the behaviour of the spins of electrons that are moving through a metal or semiconductor is an outstanding challenge in the field of 'spintronics', where possibilities for new electronic applications based on the spin degree of freedom are currently being explored. Recently, electrical control of spin coherence and coherent spin precession during transport was studied by optical techniques in semiconductors. Here we report controlled spin precession of electrically injected and detected electrons in a diffusive metallic conductor, using tunnel barriers in combination with metallic ferromagnetic electrodes as spin injector and detector. The output voltage of our device is sensitive to the spin degree of freedom only, and its sign can be switched from positive to negative, depending on the relative magnetization of the ferromagnetic electrodes. We show that the spin direction can be controlled by inducing a coherent spin precession caused by an applied perpendicular magnetic field. By inducing an average precession angle of 180 degrees, we are able to reverse the sign of the output voltage.


Autophagy and toll-like receptors: a new link in cancer cells.
In addition to its clean-up function, autophagy is considered as an innate immunity mechanism due to its role in the removal of intracellular pathogens. Toll-like receptors (TLRs) are crucial components of innate immunity involved in the recognition of a diverse array of microbial products. Recent works demonstrated that different pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS) and single-strand RNA are able to induce autophagy via different TLRs in immune cells. In a recent report, we showed that bacterial CpG motifs, another PAMP, can induce autophagy in rodent and human tumor cell lines and that this process is TLR9-dependent. In addition, an increase in the number of autophagosomes can also be observed in vivo after the intratumoral injection of CpG motifs. These results extend the link between TLRs and autophagy to non-immune tumor cells and may be relevant for cancer treatment and more generally for gene therapy approaches in TLR9-positive tissues. In this addendum, we discuss the potential mechanisms and the consequences of the CpG-induced autophagy in tumor cells.


Surgeon and SterEOS agreement of spinal sagittal plane parameters in patients with adolescent idiopathic scoliosis.
To compare agreement between surgeons and sterEOS sagittal plane measurements. EOS radiographs of 74 patients with adolescent idiopathic scoliosis were reviewed. The measurements were generated by two surgeons and compared to sterEOS. Intraclass correlations (ICC) were calculated. Agreement was also analyzed for the following subgroups: Cobb angle < 70° vs ≥ 70°, lumbar modifier A vs B/C, and BMI of < 24.5 kg/m2 vs ≥ 24.5 kg/m2. Agreement was poor if the ICC was < 0.5, moderate if 0.5-0.75, good if 0.75-0.9, and excellent if > 0.9. Paired t tests were performed to compare the surgeon's and sterEOS means. For the surgeons, agreement was good (0.75-0.89) except for pelvic tilt (PT) and sacral slope (SS), which were excellent (0.91-0.92). Agreement between the surgeons and sterEOS were good (0.78-0.9) except PT and SS, which were excellent (0.91-0.93). Agreement was negatively affected for T4-T12 kyphosis, PI, and SS in the ≥ 70°group, LL when BMI was ≥ 24.5 kg/m2, and LL, PI, and SS in the lumbar modifier B/C group. The ICCs overlapped with the 95% confidence intervals (95% CI). Paired t-test showed a significant difference for T4-T12 kyphosis (p < 0.001). This was also true in the < 70° group (p < 0.001), the ≥ 70° group (p = 0.04), and the BMI < 24.5 kg/m2 group. PT was significantly different for the ≥ 70° group. There was good to excellent agreement between the surgeons and surgeons and sterEOS. Some variables may affect agreement. The surgeons overestimated T4-T12 kyphosis.


The influence of visual deprivation on the development of the thalamocortical network: Evidence from congenitally blind children and adults.
The thalamus is heavily involved in relaying sensory signals to the cerebral cortex. A relevant issue is how the deprivation of congenital visual sensory information modulates the development of the thalamocortical network. The answer is unclear because previous studies on this topic did not investigate network development, structure-function combinations, and cognition-related behaviors in the same study. To overcome these limitations, we recruited 30 congenitally blind subjects (8 children, 22 adults) and 31 sighted subjects (10 children, 21 adults), and conducted multiple analyses [i.e., gray matter volume (GMV) analysis using the voxel-based morphometry (VBM) method, resting-state functional connectivity (FC), and brain-behavior correlation]. We found that congenital blindness elicited significant changes in the development of GMV in visual and somatosensory thalamic regions. Blindness also resulted in significant changes in the development of FC between somatosensory thalamic regions and visual cortical regions as well as advanced information processing regions. Moreover, the somatosensory thalamic regions and their FCs with visual cortical regions were reorganized to process high-level tactile language information in blind individuals. These findings provide a refined understanding of the neuroanatomical and functional plasticity of the thalamocortical network.


Facile Discovery of a Diverse Panel of Anti-Ebola Virus Antibodies by Immune Repertoire Mining.
The ongoing evolution of Ebolaviruses poses significant challenges to the development of immunodiagnostics for detecting emergent viral variants. There is a critical need for the discovery of monoclonal antibodies with distinct affinities and specificities for different Ebolaviruses. We developed an efficient technology for the rapid discovery of a plethora of antigen-specific monoclonal antibodies from immunized animals by mining the VH:VL paired antibody repertoire encoded by highly expanded B cells in the draining popliteal lymph node (PLN). This approach requires neither screening nor selection for antigen-binding. Specifically we show that mouse immunization with Ebola VLPs gives rise to a highly polarized antibody repertoire in CD138(+) antibody-secreting cells within the PLN. All highly expanded antibody clones (7/7 distinct clones/animal) were expressed recombinantly, and shown to recognize the VLPs used for immunization. Using this approach we obtained diverse panels of antibodies including: (i) antibodies with high affinity towards GP; (ii) antibodies which bound Ebola VLP Kissidougou-C15, the strain circulating in the recent West African outbreak; (iii) non-GP binding antibodies that recognize wild type Sudan or Bundibugyo viruses that have 39% and 37% sequence divergence from Ebola virus, respectively and (iv) antibodies to the Reston virus GP for which no antibodies have been reported.


The value of the post-captopril aldosterone/renin ratio for the diagnosis of primary aldosteronism and the influential factors: A meta-analysis.
The procedure for the captopril challenge test (CCT) in diagnosing primary aldosteronism (PA) is not standardized. We performed a meta-analysis to evaluate the controversial diagnostic value and influential factors of the post-captopril aldosterone/renin ratio (ARR). We searched literature in databases for eligible studies (until October 1, 2020). We extracted information regarding study and patient characteristics, CCT methods, outcome data. We pooled studies using the random-effect model. We performed meta-regression and six pre-specified subgroup analyses to explore heterogeneity. Nineteen studies involving 4568 subjects were included. The pooled sensitivity and specificity were 0.825 (95% CI 0.804-0.844) and 0.919 (95% CI 0.908-0.928). The area under the summary receiver operating characteristic curve was 0.9487 (95% CI 0.9207-0.9767). Meta-regression revealed that heterogeneity might derive from time interval (p = 0.0117) and study population (p = 0.0033). Subgroup analyses showed significant differences between the subgroups stratified by the dose, posture, study region, time interval, cut-off value and study population for sensitivity and/or specificity (p < 0.05). Post-captopril ARR is comparably valuable for diagnosing PA at cut-offs from 12.0 to 50.0. Conducting the CCT in the supine position with 25 mg of captopril may attain greater sensitivity. Conducting the CCT in the seated position with 50 mg of captopril may attain greater specificity. A 90-min time interval may perform best in both the sensitivity and specificity.


Successful Treatment of Digital Ischemia Following a Carbon Dioxide Laser and Tourniquet for a Digital Procedure With Adjuvant Low-Level Laser Therapy.
A digital tourniquet with/without epinephrine is commonly used in local anesthetics when operating on digits. However, such a complication as digital ischemia could occur following tourniquet application. We reported an elderly patient with atherosclerotic risk factors and she subsequently underwent a digital tourniquet, partial nail plate removal, and a carbon dioxide laser treatment for subungual wart with digital gangrene development. The successful treatment consisted of wound-dressing, medication, and adjuvant low-level light therapy (LLLT) to enhance the wound healing process, thereby resulting in almost complete recovery of skin color and function of the digit in 3 months. In conclusion, the digital tourniquet should be cautiously applied, especially in elderly patients with atherothrombosis, under minimal pressure and appropriate length of time. Moreover, LLLT could be an effective adjuvant treatment to prevent the vascular complications of the digit.


Urgent heart transplantation in patients with previous sternotomies. Cardiac Transplant Team.
Critically ill patient status and prior sternotomy have separately been associated with increased risk of mortality and morbidity after heart transplantation. Consequently, the justification of assigning urgent priority for transplantation to critically ill patients with prior sternotomy may be arguable. The authors therefore undertook a retrospective analysis to evaluate the outcome of urgent and elective heart transplantation in 64 patients who had undergone one to four previous sternotomies. Patients in group 1 (n = 23) were critically ill and underwent urgent heart transplantation. Group 2 (n = 41) consisted of more stable patients who received heart transplantation as an elective procedure. Intravenous inotropes or mechanical circulatory support were required by all patients in group 1 but by none in group 2. The mortality rate within 30 days post-transplant was higher in group 1 than in group 2 (22% versus 10%), though the difference was not statistically significant. The 1-year actuarial allograft survival was similar between the two groups (72% versus 74%). In addition, there was no significant difference between groups 1 and 2 in the incidence of postoperative coagulopathy (57% versus 42%), re-exploration (13% versus 15%), early infections (57% versus 49%), renal failure (17% versus 10%) or rejection episodes in the first 3 months (65% versus 78%). The authors' findings suggest that despite higher operative mortality in critically ill patients with previous sternotomies, the intermediate-term outcome of heart transplantation in these patients is similar to that in more stable patients. Critically ill patients with prior sternotomies should therefore continue to be considered for urgent heart transplantation.


Comparative Efficacy of Systemic Agents for Brain Metastases From Non-Small-Cell Lung Cancer With an EGFR Mutation/ALK Rearrangement: A Systematic Review and Network Meta-Analysis.
Brain metastases (BM) from non-small-cell lung cancer (NSCLC) are frequent and carry significant morbidity, and current management options include varying local and systemic therapies. Here, we performed a systematic review and network meta-analysis to determine the ideal treatment regimen for NSCLC BMs with targetable EGFR-mutations/ALK-rearrangements. We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL and references of key studies for randomized controlled trials (RCTs) published from inception until June 2020. Comparative RCTs including ≥10 patients were selected. We used a frequentist random-effects model for network meta-analysis (NMA) and assessed the certainty of evidence using the GRADE approach. Our primary outcome of interest was intracranial progression-free survival (iPFS). We included 24 studies representing 19 trials with 1623 total patients. Targeted tyrosine kinase inhibitors (TKIs) significantly improved iPFS, with second-and third- generation TKIs showing the greatest benefit (HR=0.25, 95%CI 0.15-0.40). Overall PFS was also improved compared to conventional chemotherapy (HR=0.47, 95%CI 0.36-0.61). In EGFR-mutant patients, osimertinib showed the greatest benefit in iPFS (HR=0.32, 95%CI 0.15-0.69) compared to conventional chemotherapy, while gefitinib + chemotherapy showed the greatest overall PFS benefit (HR=0.26, 95%CI 0.10-0.70). All ALKi improved overall PFS compared to conventional chemotherapy, with alectinib having the greatest benefit (HR=0.13, 95%CI 0.07-0.24). In patients with NSCLC BMs and EGFR/ALK mutations, targeted TKIs improve intracranial and overall PFS compared to conventional modalities such as chemotherapy, with greater efficacy seen using newer generations of TKIs. This data is important for treatment selection and patient counseling, and highlights areas for future RCT research. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=179060.


The vitamin D content of fortified milk and infant formula.
The fortification of milk and infant formula with vitamin D has had an important role in eliminating rickets in children and osteomalacia in adults. A recent outbreak of vitamin D intoxication caused by drinking milk fortified with excess vitamin D has led to questions about the level of vitamin D in milk from other producers. We used high-performance liquid chromatography to measure vitamin D in samples of 13 brands of milk with various fat contents and 5 brands of infant formula purchased at random from local supermarkets in five Eastern states. Only 12 (29 percent) of the 42 samples of the 13 brands of milk and none of the 10 samples of the 5 brands of infant formula contained 80 to 120 percent of the amount of vitamin D stated on the label. Twenty-six of the 42 milk samples (62 percent) contained less than 80 percent of the amount claimed on the label. No vitamin D was detected in 3 of the 14 samples of skim milk tested (lower limit of assay, 4.7 IU per quart [5.0 IU per liter]). One milk sample labeled as containing vitamin D2 (ergocalciferol) contained vitamin D3 (cholecalciferol). Seven of the 10 samples of infant formula contained more than 200 percent of the amount stated on the label; the sample with the highest concentration contained 419 percent of the stated amount. None of the samples of infant formula contained less than the amount stated. Milk and infant-formula preparations rarely contain the amount of vitamin D stated on the label and may be either underfortified or overfortified. Since both underfortification and overfortification are hazardous, better monitoring of the fortification process is needed.


The associations between public stigma and support for others' help-seeking for alcohol use disorder: a cross sectional study in the general Danish population.
A minority of all individuals with alcohol use disorders (AUD) seek treatment, where stigma is one prominent barrier. Social support is important to facilitate health and increase treatment-seeking. Whether there is an association between stigma and attitudes towards others' help-seeking for AUD is unknown. The aim of this study was to investigate the associations between stigma and support towards others' help-seeking for AUD, also to explore possible gender differences. Cross-sectional study, n = 2895, including Danish adults aged 30-65 in the general population. Year 2020, an online questionnaire was administrated, which covered demographics, attitudes towards others' help-seeking for AUD, and stigma measured with the Difference, Disdain & Blame Scales. Analyses were performed with Restricted Cubic Spline models, and odds ratios were calculated. Lower level of stigma was associated with a higher probability for endorsing an "active support strategy". Level of stigma was not associated with "not knowing what to say or do" or "sharing my concern with others". There were few gender differences: among men, higher level of stigma was associated with a higher probability of "avoidance". Among women, lower level of stigma was associated with a lower probability of "avoidance". There is a clear association between stigma and attitudes towards supporting others' help-seeking for AUD. The results highlight the need to reduce stigma and promote engagement towards others' treatment-seeking.


Discovery and optimization of benzenesulfonanilide derivatives as a novel class of 11β-HSD1 inhibitors.
A novel series of benzenesulfonanilide derivatives of 11β-HSD1 inhibitors were identified via modification of the sulfonamide core of the arylsulfonylpiperazine lead structures. The synthesis, in vitro biological evaluation, and structure-activity relationship of these compounds are presented. Optimization of this series rapidly resulted in the discovery of compounds (S)-10 and (S)-23 (11β-HSD1 SPA IC(50)=1.8 and 1.4 nM, respectively).


Enterococcus faecalis thrives in dual-species biofilm models under iron-rich conditions.
Escherichia coli (E. coli) and Enterococcus faecalis (E. faecalis) are pathogenic strains that often coexist in intestinal flora of humans and are prone to cause biofilm-associated infections, such as gastrointestinal tract and urinary tract infections. Earlier studies have demonstrated that E. faecalis biofilm can metabolize ferrous ions in iron-rich environments and promote biofilm growth under in-vivo conditions. However, the influence of iron transporters on dual-species biofilm growth and the nature of molecular-level interactions between iron transporter proteins and Fe2+ remains unknown. Therefore, in this work, co-culture studies were performed and the study indicates that Fe2+ at concentrations of 50-150 µM promotes the colonization of E. coli, and Fe2+ concentrations of 50-200 µM promote the growth of E. faecalis and dual-species colonies. Atomic absorption spectroscopy results reveal that Fe2+ ion augmentation in bacterial cells was increased to 4 folds in the single-species model and 11 folds in the dual-species model under iron-supplemented conditions. Furthermore, Fe2+ augmentation increased the antibiotic resistance of E. faecalis in both single- and dual-species bacterial cultures. In addition, in-silico docking were performed to determine a three-dimensional (3D) structure of ferrous iron-transporter proteins FeoB of E. faecalis and its affinity to extracellular Fe2+. Our model suggests that the FeoB facilitates the Fe2+ uptake in E. faecalis cells in the absence of iron chelator, 2,2-bipyridyl.


Single-Cell Transcriptome Analysis Reveals the Role of Pancreatic Secretome in COVID-19 Associated Multi-organ Dysfunctions.
The SARS-CoV-2 infection affects the lungs, heart, kidney, intestine, olfactory epithelia, liver, and pancreas and brings forward multi-organ dysfunctions (MODs). However, mechanistic details of SARS-CoV-2-induced MODs are unclear. Here, we have investigated the role of pancreatic secretory proteins to mechanistically link COVID-19 with MODs using single-cell transcriptome analysis. Secretory proteins were identified using the Human Protein Atlas. Gene ontology, pathway, and disease enrichment analyses were used to highlight the role of upregulated pancreatic secretory proteins (secretome). We show that SARS-CoV-2 infection shifts the expression profile of pancreatic endocrine cells to acinar and ductal cell-specific profiles, resulting in increased expression of acinar and ductal cell-specific genes. Among all the secretory proteins, the upregulated expression of IL1B, AGT, ALB, SPP1, CRP, SERPINA1, C3, TFRC, TNFSF10, and MIF was mainly associated with disease of diverse organs. Extensive literature and experimental evidence are used to validate the association of the upregulated pancreatic secretome with the coagulation cascade, complement activation, renin-angiotensinogen system dysregulation, endothelial cell injury and thrombosis, immune system dysregulation, and fibrosis. Our finding suggests the influence of an upregulated secretome on multi-organ systems such as nervous, cardiovascular, immune, digestive, and urogenital systems. Our study provides evidence that an upregulated pancreatic secretome is a possible cause of SARS-CoV-2-induced MODs. This finding may have a significant impact on the clinical setting regarding the prevention of SARS-CoV-2-induced MODs.


Early carbohydrate antigen 125 as a mortality predictor in hospitalized patients with coronavirus disease 2019.
Carbohydrate antigen 125 (CA125) is an indicator of inflammation, immune response, and impaired cardiac function. The aim was to investigate whether CA125 behaves as a biomarker of severity and poor clinical outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19). Serum CA125 [Elecsys CA125 II assay-(Roche Diagnostics GmbH)] was measured in stored biobank samples from COVID-19 hospitalized patients between 01 March 2020 and 17 October 2021. Multiple logistic regression models were built to explore the association between CA125 and clinical outcomes [in-hospital all-cause mortality, need for invasive mechanical ventilation (IMV), or non-invasive respiratory support (non-IRS)], estimating odds ratios (ORs; 95% CI). The gradient of risk of CA125 was evaluated by fractional polynomials. A total of 691 patients were included, median age of 63 years (50-76), men (57.2%), with high comorbidity. At admission, 85.8% had pneumonia. Median CA125 was 10.33 U/ml (7.48-15.50). The in-hospital mortality rate was 7.2%. After adjusting for confounding factors, CA125 ≥ 15.5 U/ml (75th percentile) showed an increased risk of death [OR 2.85(1.21-6.71)], as age ≥ 65 years, diabetes, and immunosuppression. Furthermore, CA125 as a continuous variable was positive and significantly associated with the risk of death after multivariate adjustment. The mean hospital stay of the patients with CA125 ≥ 15.5 U/ml was longer than the rest of the study population. CA125 in the first 72 h of hospital admission seems a useful biomarker of mortality in hospitalized patients with moderate-severe COVID-19. If our findings are confirmed, the wide availability of this biomarker would make easy its widespread implementation in clinical practice.


Effect of Streptozotocin on Plasma Insulin Levels of Rats and Mice: A Meta-analysis Study.
In the studies focusing on diabetic organisms, Streprozotocine (STZ) is a frequently used agent to induce diabetes in rats and mice. However the current studies do not represent practical importance of their statistical findings. For showing practical importance of the differences in plasma insulin levels of diabetic rats and mice induced by STZ, there should be a statistical synthesis regarding statistical findings of the studies. The purpose of this study is to make a meta-analysis of the studies on the effect of STZ on plasma insulin levels in diabetic rats and mice. In this study 39 effect sizes (37 studies) about levels of plasma insulin were analyzed by calculating individual effect sizes (d) and mean effect size. The effect sizes were between -13.7 and +65.3 and the mean effect size value (+9.33) represented a large effect indicating that STZ was an effective agent to significantly decrease plasma insulin levels of diabetic rats and mice. It can be said that the differences in plasma insulin levels between STZ-applied and no application groups has a practical importance in making animal model of diabetes.


Conjugate-Driven Electron Density Delocalization of Piperidine Nitroxyl Radical for Stable Aqueous Zinc Hybrid Flow Batteries.
Stable and soluble redox-active nitroxyl radicals are highly desired for high-capacity and long-life aqueous zinc hybrid flow batteries (AZHFBs). Here we report a "π-π" conjugated imidazolium and "p-π" conjugated acetylamino co-functionalized 2,2,6,6-tetramethylpiperidine-N-oxyl (MIAcNH-TEMPO) as stable catholyte for AZHFBs. The incorporation of double-conjugate substituents could delocalize the electron density of the N-O head and thus remarkably stabilize the radical and oxoammonium forms of TEMPO, avoiding the side reaction of ring-opening. Consequently, the applied MIAcNH-TEMPO/Zn AZHFB demonstrates the hardly time-dependent stability with a constant capacity retention of 99.95 % per day over 16.7 days at a high concentration catholyte of 1.5 M and high current density of 50 mA cm-2 . This proposed molecular engineering strategy based on electron density regulation of redox-active structures displays an attractive efficacy and thus represents a remarkable advance in high-performance AZHFBs.


What is the significance of the abnormal oesophageal scintigram?
In a review of 52 oesophageal scintigrams carried out in 46 patients with a variety of oesophageal problems, there was no correlation between the results of this test and the findings in other tests of oesophageal function, or between the scintigram results and the patients' symptoms, with the possible exception of regurgitation. We conclude that the test is of little value.


Exploring Media Representations of the Nexus Between Climate Change and Crime in the United States.
Information on the criminal causes and effects of the climate crisis has the potential to shape public understanding of the problem, influence behavior(s), and prompt policy decisions. This article examines the mediated representation of climate change and crime in the United States to understand whether and how these issues are being portrayed. Using a content analysis of top online media stories in 2018, we found that there is a paucity of coverage on the nexus of climate change and crime. The few stories that did discuss the subject were often oversimplified and showed a lack of critical and informative coverage of the subject. Media coverage of climate change and crime needs more attention. This means that social scientists should dedicate more time to this research and to creating awareness around the climate change-social harm nexus. It also requires that social scientists are actively included in the discussions of the social effects of climate change.


The myth of silent cortex and the morbidity of epileptogenic tissue: implications for temporal lobectomy.
This article reviews two commonly held myths regarding temporal lobe epilepsy-it is a static disorder with minimal morbidity and mortality, and epileptogenic tissue impairs only the functions of the seizure focus-and one myth concerning temporal lobe functions-they contain areas of nonfunctional, "silent" cortex. Chronic temporal lobe epilepsy can cause progressive structural, cognitive, and behavioral changes. Aside from the seizure focus, primary epileptogenic cortex may have a deleterious influence on distant brain areas. Removing this "nociferous" cortex and reducing the antiepileptic drug burden can improve cognitive or behavioral and metabolic function in areas remote from the resection. Anterior temporal lobectomy often removes functional tissue that may or may not be epileptogenic. Because normal brain does not contain functionless, "silent" areas, the procedure can have negative as well as positive cognitive or behavioral consequences. To improve the outcomes of focal cortical resections for seizure control, we need to better define functional and nociferous cortex and more clearly understand their boundaries and interactions.


Effect of five genetic variants associated with lung function on the risk of chronic obstructive lung disease, and their joint effects on lung function.
Genomic loci are associated with FEV1 or the ratio of FEV1 to FVC in population samples, but their association with chronic obstructive pulmonary disease (COPD) has not yet been proven, nor have their combined effects on lung function and COPD been studied. To test association with COPD of variants at five loci (TNS1, GSTCD, HTR4, AGER, and THSD4) and to evaluate joint effects on lung function and COPD of these single-nucleotide polymorphisms (SNPs), and variants at the previously reported locus near HHIP. By sampling from 12 population-based studies (n = 31,422), we obtained genotype data on 3,284 COPD case subjects and 17,538 control subjects for sentinel SNPs in TNS1, GSTCD, HTR4, AGER, and THSD4. In 24,648 individuals (including 2,890 COPD case subjects and 13,862 control subjects), we additionally obtained genotypes for rs12504628 near HHIP. Each allele associated with lung function decline at these six SNPs contributed to a risk score. We studied the association of the risk score to lung function and COPD. Association with COPD was significant for three loci (TNS1, GSTCD, and HTR4) and the previously reported HHIP locus, and suggestive and directionally consistent for AGER and TSHD4. Compared with the baseline group (7 risk alleles), carrying 10-12 risk alleles was associated with a reduction in FEV1 (β = -72.21 ml, P = 3.90 × 10(-4)) and FEV1/FVC (β = -1.53%, P = 6.35 × 10(-6)), and with COPD (odds ratio = 1.63, P = 1.46 × 10(-5)). Variants in TNS1, GSTCD, and HTR4 are associated with COPD. Our highest risk score category was associated with a 1.6-fold higher COPD risk than the population average score.


Perioperative patient education for retinal surgery.
Anticipation of retinal surgery and fear of permanent vision loss can be stressful for patients. When patients first are diagnosed with retinal problems and informed that ocular surgery is required, they may not be psychologically or emotionally ready to absorb the information needed to prepare them for the postoperative recovery phase. Perioperative nurses have an opportunity to affect patient outcomes by providing information to patients before, during, and after surgery. Well-educated patients have the necessary knowledge to maximize compliance and afford themselves an optimal surgical outcome.


Malignant pheochromocytoma. Severe clinical exacerbation and release of stored catecholamines during lymphoma chemotherapy.
The association of malignant pheochromocytoma and poorly differentiated lymphocytic lymphoma has not previously been reported. A case is presented of a 58-year old man with a 20-year history of malignant pheochromocytoma well controlled on Dibenzyline who was found to have poorly differentiated lymphocytic lymphoma. During lymphoma chemotherapy with cyclophosphamide, vincristine and prednisone (VCP) he developed tachycardia and syncope accompanied by severe hypertension. During the next course of chemotherapy one month later, 24-hour urinary VMA, metanephrine and catecholamine values were determined before, during and after the chemotherapy and were found to have increased two- to ten-fold. This suggests that VCP caused tumor lysis with release of catecholamines into the circulation.


The effects of reward and frustration in patients with bipolar disorder: Evidence from a computerized task with non-contingent feedback.
Bipolar disorder (BD) is characterized by mood changes that implies alterations in reward sensitivity and frustration tolerance. This study examined the effects of monetary reward and frustration on attentional performance and on affective experience across mood states in BD. An Affective Posner Task in which the nature of contingencies are divided in the three successive blocks (baseline condition, monetary reward and non-contingent feedback) was applied to BD individuals in their different episodes: mania (n = 30), depression (n = 30), and euthymia (n = 30) as well as to a group of healthy controls (n = 30). Monetary reward improved performance (in terms of faster response times) in the euthymic group and the control group, whereas it impaired performance in the manic group and has not significant effect in the depressed group. In addition, an increased interference of frustration on response accuracy was exhibited in the three groups of BD patients (including euthymia) compared with healthy controls. Participants' affective experience was self-informed by a Likert scale, so the reliability of this measure can be undermined in symptomatic patients in terms of stability and objectivity. Although it was statistically controlled, at the time of testing, all BD patients were medicated. A dissociated effect of reward and frustration was found between symptomatic and euthymic states in BD: whereas the benefit from monetary reward is affected only during symptomatic episodes (i.e., a state), the notably increased interference of frustration is exhibited also during euthymia (i.e., a trait).


Factor analysis of climacteric symptoms in Japan.
To identify menopausal and climacteric symptoms among midlife Japanese women by factor analysis of symptom frequency and severity data. Demographic information, anthropometric data, 2-week recalls of 82 symptoms, and assessment of epidemiological menopausal and self-defined konenki (climacteric) status were collected from 140 Japanese women living in Kyoto and Fukushima prefectures. Factor analysis was performed using symptom frequency scores and frequency-severity scores. To identify the symptoms constituting menopausal and climacteric syndromes in Japan, regression scores for individual factors were compared by menopausal and konenki status groups using non-parametric tests. Among 140 women aged 49.5+/-3.0 years (mean+/-S.D.), the three most prevalent symptoms were shoulder stiffness, memory loss, and stress. Analysis of frequency data resulted in an eight-factor solution, and frequency-severity data in a seven-factor solution. Anxiety and depression factors and a sexual-vasomotor factor were observed in almost all factor solutions, with additional factors comprised of psychosomatic and somatic symptoms. Anxiety scores differed by menopausal status, depression scores by konenki status, and sexual-vasomotor scores by both. Chilliness was highly correlated with sexual-vasomotor symptoms and frequency scores differed significantly between menopausal but not konenki groups. Sexual-vasomotor symptoms constitute a robust menopausal and konenki symptom grouping among Japanese women, but do not include night sweats or the foreign word hotto furasshu, yet do include chilliness, which may reflect thermoregulatory instability. Overlap of factors displaying significant differences between menopausal and konenki groups indicate a transition to a more medicalized concept of konenki in use by Japanese women.


Relation of hepcidin gene expression in blood mononuclear cells with iron overload severity among β-thalassemia major patients.
Iron overload is the main cause of morbidity and mortality in β-thalassemia major patients, and cardiac iron overload is the most common reason for death in these transfusion-dependent patients. Hepcidin, a liver-derived peptide hormone, plays a key role in plasma iron levels regulation by controlling two main stages, digestive iron absorption in enterocytes, and iron recycling in macrophages. Although hepcidin is mainly secreted from hepatocytes in the liver, it is also synthesized from mononuclear cells consisting of monocytes and lymphocytes. Binding of this molecule to ferroportin, a specific cellular exporter of iron, leads to degradation of the ligand-receptor complex, which reduces the iron overload by lowering the amounts of iron released into the plasma. Likewise, the same mechanism has been proved to be true for lymphocyte-drived hepcidin. The expression levels of hepcidin mRNA were evaluated using quantitative real time PCR (qRT-PCR) in 50 β-thalassemia major patients, as well as 25 healthy volunteers as the group of control. There was a significantly positive correlation between the cardiac iron concentration, showed by higher T2 values, and hepcidin levels in the patients (p = 0.028; r = 0.311). However, hepcidin expression levels did not significantly correlate with ferritin and liver iron concentrations. Hepcidin can act as a beneficial marker to determine iron overload degrees, particularly in the heart, in β-thalassemia major patients and be used as a logical therapeutic agent for treatment of β-thalassemia disorders.


Blood alcohol in sudden and unexpected deaths.
Blood alcohol concentration was determined in 1672 sudden and unexpected natural and non-natural out-of-hospital deaths. The material covered all medicolegal autopsies in the province of Uusimaa which has a population of approximately 1.1 million inhabitants. In general, the prevalence of cases with alcohol in the blood at the time of death was high but varied considerably according to sex, age, and the cause and manner of death. The blood alcohol result was positive in 36% of the male and in 15% of the female material. In 59% of the alcohol-positive male and in 54% of the alcohol-positive female cases the actual concentrations were at least 1.5%. Acute use of alcohol was regarded as a significant condition contributing to death in 23% of the whole male and in 8% of the whole female material. These gross results and the details presented indicate that the acute use of excess alcohol is a factor contributing to non-natural but also to sudden and unexpected natural deaths to an extent that is not generally known. The results also emphasize that simple blood alcohol determination should be a routine procedure in the autopsy praxis of all sudden and unexpected natural and non-natural out-of-hospital deaths.


Do patients with ankylosing spondylitis adapt to their disease? Evidence from a 'then-test' in patients treated with TNF inhibitors.
To investigate whether patients with ankylosing spondylitis (AS) adapt to their disease, using the 'then-test'. Data from patients participating in the AS Study for Evaluation of Recombinant Infliximab Therapy (ASSERT) and continuing in the European AS Infliximab Cohort (EASIC) were used. At 5 assessments in EASIC, patients were asked to rerate their global well-being before the start of infliximab in ASSERT. The patients evaluated their past situation by using a 'then-test' ('retrospective patient global'). Initial and retrospective patient global were compared using a paired t test, and mixed linear models investigated whether the retrospective score of well-being was stable at all follow-up assessments in EASIC. Linear regression analysis explored whether treatment response was associated with the difference between the initial and retrospective score ('gap') while adjusting for possible confounders. 86 patients (mean age 39.8 years (SD=10.4), mean disease duration 10.8 years (SD=8.5)) contributed to the current analyses. At the time of starting infliximab, patients judged their global at 7.0 (SD=1.6), and with the 'then-test' at 7.2 (SD=2.3) (p=0.45). Time elapsed did not influence the 'then-test' (p=0.13). Multivariably, the gap was irrespective of treatment response, but associated with initial patient global (p<0.01) and initial Bath AS Disease Activity Index (p=0.02). Patients with AS accurately judged their global well-being before starting treatment with tumour necrosis factor inhibition, even though substantial time had elapsed. The difference between initial and retrospective judgment was irrespective of treatment response. In this setting, the 'then-test' could not prove adaptation in AS. NCT01286545.


Mechanisms of drug-eluting stent restenosis.
Drug-eluting stents (DES) were developed to overcome in-stent restenosis (ISR), which has long been considered the main complication limiting the long-term efficacy of coronary stenting. New-generation DES which composed of advanced stent design with and without specific biocompatible polymer contributes a reduction of the incidence of ISR to rate ranging from 5 to 10%. The precise reasons of DES restenosis are still controversial and not fully understood. Angiographic and coronary images at the index procedure, systemic status of patients, medications, and intracoronary imaging at ISR site are all considered to find the possible mechanisms of DES restenosis. Multiple biological, genetic, mechanical, and technical factors might intricately contribute to DES restenosis. Biological and genetic factors of ISR are not able to be sufficiently modified by the current medical approaches. Tailored treatments avoiding mechanical and technical factors of ISR are required to reduce DES restenosis. Elucidation of DES restenosis leads to further improvement in the current DES system and finds the optimal approach to treat DES restenosis. The possible mechanisms of DES restenosis are discussed in this review.


Differential staining of collagens and non-collagens with Coomassie Brilliant Blue G and R.
The following proteins were subjected to electrophoresis in SDS gels and stained with both Coomassie Brilliant Blue R and Coomassie Brilliant Blue G: the pepsin-treated collagen types I, II, III and V, and non-pepsin-treated type IV collagen, and the non-collagens, laminin, fibronectin, myosin, beta-galactosidase, fibrin, phosphorylase b and serum albumin. The Coomassie Brilliant Blue G stain was formulated as in the dye-binding protein assay reagent of Bradford (Anal. Biochem. 72: 248-254, 1976). Coomassie Brilliant Blue R prominently stained all polypeptides, but the collagen chains, including the type IV chains, stained metachromatically (red or pink) while the non-collagens stained orthochromatically (blue-violet). In the Bradford reagent, however, only the non-collagens and the intact type IV chains were prominently stained; the pepsin-treated collagen chains were virtually undetectable provided that detergent had been exhaustively removed prior to immersion in the stain. Metachromatic staining with Coomassie Brilliant Blue R is attributed to the presence of closely-spaced proline and hydroxyproline residues in sequences from triple-helical domains. The staining of type IV chains with the Bradford reagent is attributed to the presence of binding sites in the sequences from the non-triple-helical domains only, since such binding sites are absent from chains derived from the pepsin-treated collagens.


Efficiency of skeletal and cardiac muscle.
In the human physiology literature values for skeletal and cardiac mechanical efficiency are being reported that seem to be much higher than are found in isolated tissue studies. We consider some of the different efficiency definitions and explore some possible reasons for low isolated tissue values, these include the experimental protocols used, the time at which measurements are made, afterloaded versus sinusoidal contractions, the effects of varying activation levels and recovery heat uncertainty. We examine some of the mechanical and energetic differences between cardiac and skeletal muscle--the absence of shortening heat, the linear relationship between energy per beat and pressure-volume area, constant contractile efficiency, and a larger crossbridge (CB) working stroke. Some observations are made on muscle energetics and loose and tight coupling CB models.


Multiple treatment approach to limit cardiac ischemia-reperfusion injury.
This study evaluates a multiple treatment approach (ie, pharmacologic preconditioning [diazoxide], sodium-proton exchange inhibition [cariporide], and controlled reperfusion) to improve the outcome from severe cardiac ischemia-reperfusion injury that occurs during a cardiac operation. Five groups of 10 pigs (group 1: control, group 2: diazoxide, group 3: cariporide, group 4: controlled reperfusion, and group 5: combination of diazoxide and cariporide-controlled reperfusion) underwent 75 minutes of left anterior descending occlusion, 1 hour of cardioplegic arrest, and 2 hours of reperfusion. Prior to occlusion, each group received an infusion of vehicle alone (ie, dimethylsulfoxide for the control and the controlled reperfusion groups) or vehicle with drug (ie, diazoxide or cariporide, or both for all other groups). Infarct size (primary outcome) was measured and was normalized to the region at risk. Regional function (secondary outcome) was measured using preload recruitable work area. Infarct size as a function of area at risk was decreased by cariporide-controlled reperfusion, and combination treatment compared with the control group (14 +/- 6%, 15 +/- 8%, and 9 +/- 4% vs 24 +/- 9%; p < 0.02), and variation in infarct size was decreased by combination treatment compared with the controlled reperfusion group alone (p < 0.02). Recovery of systolic function during reperfusion significantly improved in the left anterior descending region in the cariporide and combination groups compared with the control, controlled reperfusion, or diazoxide groups (group-time effect, p < 0.05). Combined use of controlled reperfusion, cariporide, and diazoxide decreases myocyte necrosis and loss of systolic function compared with an untreated control group. Combination treatment has the potential to improve the results of cardiac surgery, however further improvements are needed before clinical application.


Comparative analysis of naphthodianthrone and phloroglucine derivatives in St. John's Wort extracts by near infrared spectroscopy, high-performance liquid chromatography and capillary electrophoresis.
A near infrared spectroscopic (NIRS) method is established for quantitative determination of naphthodianthrones and phloroglucine derivatives in St. John's Wort extracts. The validated NIRS method is compared with optimised liquid chromatography (LC) and capillary electrophoresis (CE), applying UV as a detection tool. Optimisation of stationary and mobile phase conditions in reversed-phase liquid chromatography (RP-LC) allow separating the derivatives of interest with high peak symmetry and robustness. Elution takes 15 and 25 min on non-porous or porous silica C18 with different porosities, respectively. Capillary electrophoresis (CE) is used for cross-validation of RP-LC. CE enables baseline separation of hypericine and pseudohypericine in less than 2min, but is ten times less sensitive. The validated RP-LC is chosen as a reference method for calibration of the NIRS-system. Analysis of 80 St. John's Wort extracts (320 NIR spectra) and the subsequent chemometric calculations of the best regression model show that NIRS is suitable for analysis of hypericine, pseudohypericine and hyperforine. RP-LC or CE must be employed for the other remaining lower concentrated naphthodianthrone and phloroglucine derivatives. Hypericine and hyperforine are analysed via NIRS with a standard error of estimation (SEE) of 0.52 and 0.50 microg mL(-1) and standard error of prediction (SEP) of 0.64 and 0.71 microg mL(-1) within few seconds. The current study demonstrates the suitability of NIRS as an alternative to LC and CE for St. John's Wort producing phytopharmaceutical industry. The short analysis time of few seconds' assures high sample throughput in routine analysis.


An analytic approach to optimized retracted missing tissue compensators.
The introduction of an attenuating medium into a photon beam serves both to reduce the intensity of the primary beam and to create secondary radiation due to scatter. When retracted missing tissue compensators are employed to compensate for irregular surface contour or internal inhomogeneities, they are often fabricated without regard to the scattered radiation that they introduce into the system. The study of a mathematically describable conical geometry has clearly demonstrated the need for improved compensator design. Experimental results obtained with this geometry can be reproduced with good agreement, using theoretical calculations based on primary and first order scattered radiation. This method of analysis may be extended to predict the shape of a compensator which will produce an optimized dose distribution at a given depth in a phantom, equivalent to that which would be obtained when an irregular surface is filled with unit density material (bolus), producing a flat surface. An optimized compensator was constructed based on these theoretical considerations and excellent agreement was observed between theory and experiment. Dramatic improvement in the restoration of bolus dose is obtained with this optimized compensator. Finally, an anthropomorphic phantom of the neck region has been constructed and the performance of a compensator designed according to current clinical methods for this geometry has been evaluated. The performance of an optimized compensator specific to this geometry is presented and good agreement between theoretical predictions and experimental results is observed. Dramatic improvement in bolus dose restoration over that obtained with the clinically designed compensator is realized.


An exploratory study evaluating the effects of macular carotenoid supplementation in various retinal diseases.
The aim of this study was to assess the impact of daily oral supplementation with Macushield (10 mg/d meso-zeaxanthin, 10 mg/d lutein, and 2 mg/d zeaxanthin) on eye health in patients with retinal diseases by assessing the macular pigment (MP) profile, the visual function, and the quality of life. Fifty-one patients with various retinal diseases were supplemented daily and followed up for 6 months. The MP optical density was measured using the customized heterochromatic flicker photometry and dual-wavelength autofluorescence. Visual function was evaluated by assessing the change in best corrected visual acuity, contrast sensitivity, and glare sensitivity in mesopic and photopic conditions. Vision-related and general quality of life changes were determined using the National Eye Insititute- Visual Function Questionnaire-25 (NEI-VFQ-25) and EuroQoL-5 dimension questionnaires. A statistically significant increase in the MP optical density was observed using the dual-wavelength autofluorescence (P=0.04) but not with the customized heterochromatic flicker photometry. Statistically significant (P<0.05) improvements in glare sensitivity in low and medium spatial frequencies were observed at 3 months and 6 months. Ceiling effects confounded other visual function tests and quality of life changes. Supplementation with the three carotenoids enhances certain aspects of visual performance in retinal diseases.


The Synovium Attenuates Cartilage Degeneration in KOA through Activation of the Smad2/3-Runx1 Cascade and Chondrogenesis-related miRNAs.
Knee osteoarthritis (KOA) is a highly prevalent disabling joint disease in aged people. Progressive cartilage degradation is the hallmark of KOA, but its deeper mechanism remains unclear. Substantial evidence indicates the importance of the synovium for joint homeostasis. The present study aimed to determine whether the synovium regulates cartilage metabolism through chondrogenesis-related microRNAs (miRNAs) in the KOA microenvironment. Clinical sample testing and in vitro cell experiments screened out miR-455 and miR-210 as effective miRNAs. The levels of both were significantly reduced in KOA cartilage but increased in KOA synovial fluid compared with controls. We further revealed that transforming growth factor β1 (TGF-β1) can significantly upregulate miR-455 and miR-210 expression in synoviocytes. The upregulated miRNAs can be secreted into the extracellular environment and prevent cartilage degeneration. Through bioinformatics and in vitro experiments, we found that Runx1 can bind to the promoter regions of miR-455 and miR-210 and enhance their transcription in TGF-β1-treated synoviocytes. Collectively, our findings demonstrate a protective effect of the synovium against cartilage degeneration mediated by chondrogenesis-related miRNAs, which suggests that Runx1 is a potential target for KOA therapy.


Pretransfer CT scans are frequently performed, but rarely helpful in rural trauma systems.
Rural trauma patients often undergo workup prior to transfer to a trauma center. Repeat and redundant imaging at the trauma center is common. Two hundred consecutive adult trauma patients transferred to a regional trauma center were retrospectively evaluated. 197 patients met criteria. 152 underwent CT scan prior to transfer and CT was the indication for transfer in 88 patients (44.7%). One intervention was performed as a result of CT imaging. 84 patients (55.3%) received repeat CT imaging. There were no statistically significant differences in rates of CT imaging at the outside facility based on injury severity, mechanism of injury, or age. The most common reason for repeat CT scans was incomplete initial imaging. The ability to obtain initial imaging was not a significant factor. Repeat CT imaging in transferred trauma patients is very common. The majority of reimaging is done for incomplete initial imaging. Rural trauma systems may benefit from improved protocols for more efficient care.


The Wearable Cardioverter Defibrillator: an Early Single Centre Australian Experience. Some Pitfalls and Caveats for Use.
Wearable Cardioverter Defibrillators (WCD) have been effectively used for more than a decade in North America and Europe for prevention of sudden cardiac death (SCD) due to ventricular arrhythmias. This device has only recently been available in Australia. At Westmead hospital, WCD has been used since 2013 as a bridging therapy to an implantable cardioverter defibrillator (ICD) for those at high risk, but are temporarily not suitable for an implantable device. Indications for use were explanted infected ICD, dilated cardiomyopathy, post partum cardiomyopathy, valvular heart disease and myocarditis. The default device settings were: ventricular tachycardia (VT) and ventricular fibrillation (VF) threshold of 150 bpm and 200 bpm respectively and response times were 60 secs for VT and 25 secs for VF. WCD was used in eight patients. Duration of use ranged from five to 180 days with median of 77 days. Daily usage averaged 23.4±0.6hours. All except one were compliant with the device and none of our patients received shock or died during device usage. Four of the eight patients received ICD, two declined ICD, one was judged to no longer require ICD and one remains under assessment. WCD is easy to use, well tolerated and is effective for SCD prevention in patients who are temporarily not suitable for ICD. However patients need to be actively followed-up to reduce the duration of WCD usage and thereby be cost effective.


A code within the genetic code: codon usage regulates co-translational protein folding.
The genetic code is degenerate, and most amino acids are encoded by two to six synonymous codons. Codon usage bias, the preference for certain synonymous codons, is a universal feature of all genomes examined. Synonymous codon mutations were previously thought to be silent; however, a growing body evidence now shows that codon usage regulates protein structure and gene expression through effects on co-translational protein folding, translation efficiency and accuracy, mRNA stability, and transcription. Codon usage regulates the speed of translation elongation, resulting in non-uniform ribosome decoding rates on mRNAs during translation that is adapted to co-translational protein folding process. Biochemical and genetic evidence demonstrate that codon usage plays an important role in regulating protein folding and function in both prokaryotic and eukaryotic organisms. Certain protein structural types are more sensitive than others to the effects of codon usage on protein folding, and predicted intrinsically disordered domains are more prone to misfolding caused by codon usage changes than other domain types. Bioinformatic analyses revealed that gene codon usage correlates with different protein structures in diverse organisms, indicating the existence of a codon usage code for co-translational protein folding. This review focuses on recent literature on the role and mechanism of codon usage in regulating translation kinetics and co-translational protein folding. Video abstract.


The efficacy of oral Zhizhu Kuanzhong, a traditional Chinese medicine, in patients with postprandial distress syndrome.
The treatment of patients with functional dyspepsia (FD) remains unsatisfactory. We assessed the efficacy of Zhizhu Kuanzhong (ZZKZ) capsule, a traditional Chinese medicine formula, in patients with postprandial distress syndrome (PDS) of FD. The study was designed as a multicenter, randomized, double-blinded, controlled clinical trial. Three-hundred ninety-two patients with PDS defined by Rome III criteria from 16 centers in China were randomly assigned to receive either ZZKZ or placebo. The proportion of the responders at 4 weeks after randomization was considered primary endpoint. Secondary endpoint was the symptom score reduction of each dyspeptic symptom relative to the baseline at 4 weeks after randomization in all subjects. In terms of the primary endpoint, the proportion of the responders concerning the composite PDS symptom score was 38.8% and 54.7% in placebo group and ZZKZ group, respectively (P = 0.003), in per protocol analysis at 4 weeks after randomization. Concerning the individual evaluated upper gastrointestinal symptoms, only postprandial fullness and early satiety showed significant difference in symptom score reduction at 4 weeks after randomization between placebo and ZZKZ groups. Zhizhu Kuanzhong is superior to placebo in the treatment of PDS with FD. The exact mechanisms by which ZZKZ improves symptoms remain to be established (http://www.chictr.org.cn/ChinCTR-TRC-14004714).


Rerouting vessels and nerves from other digits in replanting an avulsed and degloved thumb.
In avulsion and degloving injuries of amputated thumbs, we have rotated nearby neurovascular bundles and dorsal digital vessels to restore circulation and sensation. This has been done in 5 patients, and 3 thumbs survived with preservation of length and good function.


High-speed submillimeter magnetic-driven rotational scanning side-imaging OCT probe.
A high-speed side-imaging magnetic-driven scanning (MDS) probe is proposed for endoscopic optical coherence tomography (OCT). In the distal end of the probe, a reflecting micromirror is attached to a tiny magnet, which is driven by an external fast-rotating magnetic field to achieve unobstructed 360-degree side-view scanning. A prototype probe was fabricated with an outer diameter of 0.89 mm. Using the prototype probe, OCT images of an ex vivo porcine artery with implanted stent were acquired in 100 frames per second. The OCT engine was a swept-source system, and the system sensitivity with the prototype probe was 95 dB with an output power of 6 mW. The axial and lateral resolutions of the system were 10.3 and 39.7 μm, respectively. The high-speed submillimeter MDS-OCT probe provides a promising alternative endoscopic OCT solution for intravascular imaging applications.


FRESC: French Real world Extensive stage SCLC Cohorts: A retrospective study on patient characteristics and treatment strategy based on KBP-2010.
FRESC reanalyzed extensive-stage small-cell lung cancer (ES-SCLC) patient data from the French KBP-2010 cohort to describe the characteristics and therapeutic management of ES-SCLC and provide real-world estimates of survival. A target population of first line (1L) ES-SCLC was identified at initial diagnosis in KBP-2010 (KBP population, N = 796). A KBP-2010 subpopulation was defined as patients who also met the IMpower133 clinicaltrial PS ≤ 1 inclusion criteria (KBP-PS_0/1 population, N = 394). Subgroups were defined according to the 1L ES-SCLC chemotherapy regimens: carboplatin or cisplatin with etoposide (Carb-E or Cisp-E subgroups). The vast majority of KBP populations exhibited stage IV ES-SCLC (84.9%) at initial diagnosis. Median age was 66 years; patients were mostly male and smokers. Patients receiving Cisp + Eto were younger (median age 61 years [55.0-67.0]) and fitter (25.5% had PS ≥ 2) than those receiving Carb + Eto (71 years [62.5-77.5]; 44.1%had PS ≥ 2). Median overall survival (OS) of chemotherapy-treated 1L ES-SCLC patients varied from 7.0 months [95% CI, 6.1; 7.8] in the KBPCarb-Esubgroups to 9.6 months [95% CI, 8.4;10.8] in the KBP Cisp-E subgroup. KBP-PS_0/1 population showed better median OS, especially for the Cisp-E subgroup (10 months [95% CI, 8.7; 11.3]). In the KBP-PS_0/1 population, median OS was close to the one that was found in the IMpower133 control arm. Although this needs to be confirmed by further research, it suggests the transposability of the IMpower133 results to real-life conditions.


Nonhuman Primate Models to Explore Mechanisms Underlying Early-Life Temperamental Anxiety.
Anxiety disorders are among the most prevalent psychiatric disorders, causing significant suffering and disability. Behavioral inhibition is a temperament that is linked to an increased risk for the later development of anxiety disorders and other stress-related psychopathology, and understanding the neural systems underlying this dispositional risk could provide insight into novel treatment targets for anxiety disorders. Nonhuman primates (NHPs) have anxiety-related temperaments that are similar to those of humans with behavioral inhibition, facilitating the design of translational models related to human psychopathology. Characterization of our NHP model of behavioral inhibition, which we term anxious temperament (AT), reveals that it is trait-like. Exploration of the neural substrates of AT in NHPs has revealed a distributed neural circuit that is linked to individual differences in AT, which includes the dorsal amygdala. AT-related metabolism in the dorsal amygdala, including the central nucleus, is stable across time and can be detected even in safe contexts, suggesting that AT has trait-like neural signatures within the brain. The use of lesioning and novel chemogenetic methods allows for mechanistic perturbation of the amygdala to determine its causal contribution to AT. Studies characterizing the molecular bases for individual differences in AT in the dorsal amygdala, which take advantage of novel methods for probing cellular and molecular systems, suggest involvement of neurotrophic systems, which point to the importance of neuroplasticity in AT. These novel methods, when used in combination with translational NHP models such as AT, promise to provide insights into the brain systems underlying the early risk for anxiety disorder development.


Therapeutic inertia and intensified treatment in diabetes mellitus prescription patterns: A nationwide population-based study in Taiwan.
Objective To measure therapeutic inertia by characterizing prescription patterns using secondary data obtained from the nationwide diabetes mellitus pay-for-performance (DM-P4P) programme in Taiwan. Methods Using reimbursement claims from Taiwan's National Health Insurance Research Database, a nationwide retrospective cohort study was undertaken of patients with diabetes mellitus who participated in the DM-P4P programme from 2006-2008. Glycosylated haemoglobin results were used to evaluate modifications in therapy in response to poor diabetes control. Prescription patterns were used to assign patients to either a therapeutic inertia group or an intensified treatment group. Therapeutic inertia was defined as the failure to act on a known problem. Results The research sample comprised of 168 876 patients with diabetes mellitus who had undergone 899 135 tests. Of these, 37.4% (336 615 visits) of prescriptions were for a combination of two types of drug and 27.7% (248 788 visits) were for a combination of three types of drug. The proportion of patients in the intensified therapy group who were prescribed more than two types of drug was considerably higher than that in the therapeutic inertia group. Conclusion In many cases in the therapeutic inertia group only a single type of hypoglycaemic drug was prescribed or the dosage remained unchanged.


Exemplary attributes: how to prepare for an audit.
Experts discuss one of the biggest challenges to any research site implementing a clinical trial program: the audit process.


Erratum: CNN-based Deformable Registration Facilitates Fast and Accurate Air Trapping Measurements at Inspiratory and Expiratory CT.
[This corrects the article DOI: 10.1148/ryai.2021210211.].


Dyslipidemias and the primary prevention of cardiovascular disease: analysis of the FAMUS primary care register.
Primary prevention of cardiovascular disease with a pharmacological approach to dyslipidemias is controversial. Little is known about the clinical management by general practitioners in this area. To evaluate the patterns of treatment of patients in primary prevention who were entered in the FAmily Medicine, Université de Sherbrooke (FAMUS) register and to calculate the probability of their receiving a hypolipidemic agent according to the presence of various risk profiles. Descriptive study based on the FAMUS prospective primary care register. Data from patients in primary prevention (those who had not sustained a cardiovascular event) were extracted and analyzed. Of the 52,505 patients in the register, 48, 190 were identified as being in primary prevention. Of these, 22,250 (46.2%) had a complete lipid profile on record, and 2300 had received a prescription for a hypolipidemic agent (4.8%). Patients under pharmacological treatment had significantly higher lipid values. The adjusted relative risk of being treated with a hypolipidemic agent was 1.3 for smokers, 1.3 for diabetic patients, 2.0 for those with a positive family history of premature cardiovascular disease, 2.2 for hypertensives and 3.3 for men over 45 years of age or women over 55 years, compared with patients who were not taking lipid-lowering medications. The number of risk factors was even more strongly associated with the probability of being treated. Overall, few patients in primary prevention in the register were treated with a pharmacological agent. The presence of associated risk factors in this study was an important predictor for treatment, suggesting that patients in primary prevention are being evaluated globally as a function of all of their risk factors, not just their lipid and lipoprotein levels. Further attention, nonetheless, needs to be directed to the segment of the population with multiple risk factors whose lipoprotein profile is unknown or who are not being treated to guideline target levels.


Induction of caspase-3 and nitric oxide synthase-2 during gastric mucosal inflammatory reaction to Helicobacter pylori lipopolysaccharide.
Helicobacter pylori lipopolysaccharide is recognized as a primary virulence factor evoking acute mucosal inflammatory reaction associated with H. pylori infection. We investigated the activity of a key apoptotic protease, caspase-3, and the expression of inducible nitric oxide synthase (NOS-2) during H. pylori lipopolysaccharide-induced acute gastritis. The assays conducted 4 days following intragastric dose of the lipopolysaccharide revealed a pattern of acute mucosal responses characterized by an 11.2-fold increase in epithelial cells apoptosis, inflammatory infiltration of the lamina propria, hyperemia, and epithelial hemorrhage. This was accompanied by a 5.4-fold increase in caspase-3 activity, while the mucosal expression of NOS-2 showed a 6.5-fold induction. The results implicate H. pylori lipopolysaccharide in the induction of NOS-2 expression, and point to its effect on activation of the signaling cascade involving caspase-3 in the process gastric epithelial cells apoptosis.


Aortic arch thrombosis in the neonate.
Thrombotic occlusion of the aortic arch in the neonate is a rare lesion for which successful operative repair with survival beyond the immediate postoperative period has not been previously reported. We report a case in which surgical repair of this lesion with survival was achieved and discuss the diagnostic and technical aspects of management of aortic arch thrombosis in the neonate.


Development of perifocal edema in experimental epilepsy induced by cobalt-gelatin.
Two blood-borne tracers, Evans-blue albumin (EBA) and colloidal-iron (Ferrlecit) were applied to visualize the development of perifocal edema in experimental epilepsy induced by cobalt-gelatin (Co-gelatin). This model is known to produce central necrosis with gliomesenchymal scar and peripheral transitory zone in the brain cortex. Characteristic red fluorescence of EBA was detected diffusely in the necrotic area surrounding the Co-gelatin implant and EBA labelled individual neurons reflecting cell membrane injury in the transitory zone. The colloidal iron tracer was localized mainly in the gliomesenchymal scar. It is proposed that neurons with altered membrane permeability to EBA in the transitory zone may play a role in the genesis of epileptic spike activity. The marked labelling of the gliomesenchymal scar by colloidal-iron indicates furthermore that this newly vascularized tissue with leaky capillaries may be a source of perifocal edema.


High-volume hemofiltration after out-of-hospital cardiac arrest: a randomized study.
The study examined the effect of isovolumic high-volume hemofiltration (HF) alone or combined with mild hypothermia (HT) on survival after out-of-hospital cardiac arrest (OHCA) with initial ventricular fibrillation or asystole. Global inflammation in response to whole-body ischemia-reperfusion is common after OHCA and may worsen the overall prognosis. Sixty-one patients admitted between May 2000 and March 2002 in the intensive care units of two hospitals in France were randomized to one of three groups: control, HF (200 ml/kg/h over 8 h) or HF+HT (32 degrees C for 24 h) induced by cooling the HF substitution fluid. Standard supportive care was provided in all three groups. The primary end point was survival with a follow-up time of six months. The effect of HF on death by intractable shock was the secondary end point. The six-month survival curves of the three groups were significantly different, with better survival in the HF group (p = 0.026) and in the HF+HT group (p = 0.018). After adjustment on baseline characteristics of cardiac arrest, HF (with or without HT) was associated with improved survival (logistic regression odds ratio, 4.4; 95% confidence interval [CI], 1.1 to 16.6). Compared to control group, the relative risk of death by intractable shock was 0.29 (95% CI, 0.09 to 0.91) in the HF+HT group and 0.21 (95% CI, 0.05 to 0.85) in the HF group. The HF may improve the overall prognosis after resuscitation from OHCA. Combination of HF with mild HT is feasible and should be evaluated in larger trials.


Gasoline consumption and leukemia mortality and morbidity in 19 European countries: an ecological study.
It is widely recognized that exposure to benzene is a risk factor for leukemia; however, much remains to be clarified about the possible long-term health effects of exposures to low concentrations of benzene. With this in mind an ecological study was carried out in which both gasoline consumption data and data on leukemia mortality and incidence were collected for 19 European countries. Gasoline consumption was taken as an indication for exposure to benzene in ambient air. There appeared to be a weak inverse association between temporal trends in gasoline consumption and temporal trends in leukemia mortality. On the other hand, a weak positive association was found between the age-adjusted myeloid leukemia incidence in 14 areas and the gasoline consumption per square kilometer. However, both findings can easily be explained by other factors, such as changes in prognosis or differences in leukemia case ascertainment. This study is not supportive of an association between gasoline consumption and reported leukemia incidence and mortality rates.


Effects of gamma radiation on wastewater microbiota.
Wastewater treatment by gamma radiation is a promising technology, with the capacity to reduce the impact of chemical and biological pollution of effluents in the environment. The aim of this study was to find out the effect of gamma radiation on the inactivation response of wastewater microorganisms. Wastewater samples were irradiated at a Co-60 facility, at different dose rates and at sublethal doses. The D10-values of total coliforms and mesophilic microbiota were determined for each sample and dose rate. Radio-resistant microorganisms in wastewater samples were isolated and their growth and inactivation kinetics in different composition substrates were determined, to find out the capacity of these bacteria to biodegrade the organic content of the wastewater. The results obtained suggest that irradiation substrate and dose rate influence the response of microorganisms to gamma radiation and could be also important factors for bioremediation.


Large-scale phosphorylation mapping reveals the extent of tyrosine phosphorylation in Arabidopsis.
Protein phosphorylation regulates a wide range of cellular processes. Here, we report the proteome-wide mapping of in vivo phosphorylation sites in Arabidopsis by using complementary phosphopeptide enrichment techniques coupled with high-accuracy mass spectrometry. Using unfractionated whole cell lysates of Arabidopsis, we identified 2597 phosphopeptides with 2172 high-confidence, unique phosphorylation sites from 1346 proteins. The distribution of phosphoserine, phosphothreonine, and phosphotyrosine sites was 85.0, 10.7, and 4.3%. Although typical tyrosine-specific protein kinases are absent in Arabidopsis, the proportion of phosphotyrosines among the phospho-residues in Arabidopsis is similar to that in humans, where over 90 tyrosine-specific protein kinases have been identified. In addition, the tyrosine phosphoproteome shows features distinct from those of the serine and threonine phosphoproteomes. Taken together, we highlight the extent and contribution of tyrosine phosphorylation in plants.


n-TiO2 and CdCl2 co-exposure to titanium dioxide nanoparticles and cadmium: Genomic, DNA and chromosomal damage evaluation in the marine fish European sea bass (Dicentrarchus labrax).
Due to the large production and growing use of titanium dioxide nanoparticles (n-TiO2), their release in the marine environment and their potential interaction with existing toxic contaminants represent a growing concern for biota. Different end-points of genotoxicity were investigated in the European sea bass Dicentrarchus labrax exposed to n-TiO2 (1mgL(-1)) either alone and combined with CdCl2 (0.1mgL(-1)) for 7 days. DNA primary damage (comet assay), apoptotic cells (diffusion assay), occurrence of micronuclei and nuclear abnormalities (cytome assay) were assessed in peripheral erythrocytes and genomic stability (random amplified polymorphism DNA-PCR, RAPD assay) in muscle tissue. Results showed that genome template stability was reduced after CdCl2 and n-TiO2 exposure. Exposure to n-TiO2 alone was responsible for chromosomal alteration but ineffective in terms of DNA damage; while the opposite was observed in CdCl2 exposed specimens. Co-exposure apparently prevents the chromosomal damage and leads to a partial recovery of the genome template stability.


Update in treatment options in pulmonary hypertension.
Significant developments have occurred in the field of pulmonary hypertension (PH) in the past 2 years, especially in terms of treatment options available. These include: approval of new drugs; evidence for use of initial combination therapies in pulmonary arterial hypertension; approved drugs for use in chronic thromboembolic disease not amenable to, or persistent after surgical thromboendarterectomy; and ongoing clinical trials in PH related to left heart disease and hypoxia. The field continues to evolve and address the challenges in treatment of this multifaceted disease with the aim to provide novel solutions and meet the needs of a growing population with PH. This has led to an extensive body of literature, ranging from case series to prospective, multicenter clinical trials, which will enhance the future of patient outcomes in PH. This contemporary review highlights the key articles in treatment updates for PH for the years 2013 to 2015.


Student preferences regarding teaching methods in a drug-induced diseases and clinical toxicology course.
To determine which teaching method in a drug-induced diseases and clinical toxicology course was preferred by students and whether their preference correlated with their learning of drug-induced diseases. Three teaching methods incorporating active-learning exercises were implemented. A survey instrument was developed to analyze students' perceptions of the active-learning methods used and how they compared to the traditional teaching method (lecture). Examination performance was then correlated to students' perceptions of various teaching methods. The majority of the 107 students who responded to the survey found traditional lecture significantly more helpful than active-learning methods (p=0.01 for all comparisons). None of the 3 active-learning methods were preferred over the others. No significant correlations were found between students' survey responses and examination performance. Students preferred traditional lecture to other instructional methods. Learning was not influenced by the teaching method or by preference for a teaching method.