Gyrate atrophy of the choroid and retina. The ocular disease progresses in juvenile patients despite normal or near normal plasma ornithine concentration.
Hyperornithinemia disappeared in three children with Gyrate atrophy of the choroid and retina during a low-arginine diet for 3 to 4 1/2 years. Because of the young age of the patients, we had an exceptional opportunity to follow the progression of the disease during this period. Despite the excellent biochemical control, electroretinographic changes progressed in two patients, and the chorioretinal atrophy progressed steadily in all the patients throughout the diet. Dark adaptation and color vision remained stable. In these patients, the normo-ornithinemia has not been able to halt the progression of the chorioretinal degeneration.


Enhanced remediation of BDE-209 in contaminated mangrove sediment by planting and aquaculture effluent.
Toxic and persistent flame retardant (BDE-209) and aquaculture effluent (AE) are ubiquitous in coastal environments, but how their co-existence influences their fate is not yet investigated. This study investigated AE effects on remediation and uptake of BDE-209 by Kandelia obovata (Ko) and Avicennia marina (Am), true and dominant mangrove species. After 12-months, a significant removal of BDE-209 was achieved in planted mangrove sediment and the removal was significantly enhanced by AE addition, possibly due to the enhancement of nitrogen (N) and phosphorous (P) content in sediment. Residual percentages of parent BDE-209 in Ko and Am planted sediments without AE were 61.4% and 70.9%, respectively, but decreased to 46.9% and 48.0% with AE addition after 12-months. A similar trend was found in unplanted sediment, with 86.5% and 65.3% of BDE-209 retained in sediments without and with AE addition, respectively. The results demonstrated that AE addition not only increased the debromination of BDE-209 in all treated sediments with the production of debrominated congeners (de-PBDEs) like di- to nona-BDEs in unplanted and planted sediments, but also enhanced the take up of BDE-209 in Ko root, and de-PBDEs in both Ko and Am, thus enhancing the phytoremediation of BDE-209 in contaminated sediments.


Modification of postmortem wounds by Dermestes maculatus (Coleoptera: Dermestidae) activity: A preliminary study.
The purpose of this analysis was to evaluate the effects of insect activity on hacking trauma which was inflicted with a small cleaver and a razor blade under controlled conditions. Three pig hooves were each subjected to a blow with a small cleaver and a cut with a razor blade prior to insect exposure. We used Dermestes maculatus DeGeer 1774 species. These beetles made principally depressions and destruction on both wounds, and bites were observed on the edges of the wounds. As time passed and insects fed and refuge, chop marks were deformed and disappeared, taking this less than a month. Thus, D. maculatus could mask postmortem wounds and probably premortem wounds, and so the cause of death.


[Maternal lactation. I. Resistance of maternal milk to bacterial contamination].
Bacteriologic studies in hands, nipples and milk in 10 wet-nurses were done in order to establish regulation for the recollection of breast milk to be used in low -birth-weight infants. The same studies were done in the hands of 10 nurse-aids, that help in the recollection of breast milk. The results depicts that the breast milk has bacteriostatic and bactericidal properties enough to protect against contamination by germs of the mother's bacterial flora. It does not have the same property against germs that are not of their own flora: those of the nurse-aids's hands. The protection is such that is possible to maintain the breast milk at environmental temperature of 4 degrees C, for 72 hours, without having the developing of germs not isolated previously, and even with the disappearance of some strains present in the initial cultures.


Binding of ras p21 to bands 4.2 and 6 of human erythrocyte membranes.
The direct binding protein(s) of ras p21 was (were) investigated in inside-out vesicles of human erythrocyte ghosts using the pure v-Kirsten (Ki)-ras p21 synthesized in E. coli. The bound ras p21 was detected immunochemically using an anti-v-Ki-ras p21 monoclonal antibody, ras p21 bound to vesicles. Prior digestion of the vesicles with trypsin reduced this binding significantly. When ras p21 was laid over vesicle proteins immobilized on a nitrocellulose sheet by transfer from the gel of SDS-polyacrylamide gel electrophoresis, ras p21 bound to bands 4.2 and 6. ras p21 binding to these proteins was reduced by prior incubation of ras p21 with the purified band 4.2 or 6 protein. These results indicate that v-Ki-ras p21 can bind directly to bands 4.2 and 6 of human erythrocyte membranes as far as tested in an in vitro cell-free system.


Surgical anatomy of the hypoglossal nerve: A new classification system for selective upper airway stimulation.
Selective upper airway stimulation (UAS) has shown effectiveness in treating patients with obstructive sleep apnea (OSA). The terminating branches of the hypoglossal nerve show a wide complexity, requiring careful discernment of a functional breakpoint between branches for inclusion and exclusion from the stimulation cuff electrode. The purpose of this study was to describe and categorize the topographic phenotypes of these branches. Thirty patients who received an implant with selective UAS from July 2015 to June 2016 were included. All implantations were recorded using a microscope and resultant tongue motions were captured perioperatively for comparison. Eight different variations of the branches were encountered and described, both in a tabular numeric fashion and in pictorial schema. The examinations showed the complex phenotypic surgical anatomy of the hypoglossal nerve. A schematic classification system has been developed to help surgeons identify the optimal location for cuff placement in UAS.


Advances in non-snake venom L-amino acid oxidase.
L-amino acid oxidase is widely found in diverse organisms and has different properties. It is thought to contribute to antimicrobial activity, amino acid catabolism, and so forth. The purpose of this communication is to summarize the advances in non-snake venom L-amino acid oxidase, including its enzymatic and structural properties, gene cloning and expression, and biological function. In addition, the mechanism of its biological function as well as its application is also discussed.


Exploring the diagnostic value, prognostic value, and biological functions of NPC gene family members in hepatocellular carcinoma based on a multi-omics analysis.
Liver cancer is a cunning malignancy with a high incidence and mortality rate among cancers worldwide. The NPC gene family members (NPCs: NPC1, NPC2, and NPC1L1) are closely linked to the development of multiple cancers, but their role in liver cancer remains unclear. As a result, we must investigate their functions in liver hepatocellular carcinoma (LIHC). NPCs were significantly differentially expressed between normal and LIHC tissues, with a high mutation frequency in LIHC. The ROC curve analysis revealed that NPC1/NPC2 had high diagnostic and prognostic values in LIHC. NPC1 expression was also found to be negatively correlated with its methylation level. The differentially expressed genes between high and low NPC1 expression groups in LIHC were mainly related to channel activity, transporter complexes, and plasma membrane adhesion molecules. Additionally, NPC1 expression was significantly associated with multiple immune cells and immunization checkpoints. It was hypothesized that a TUG1/SNHG4-miR-148a-3p-NPC1 regulatory axis is associated with hepatocarcinogenesis. Finally, the protein expression of NPC1 in LIHC tissues and paraneoplastic tissues was detected, and NPC1-knockdown HepG2 cells (NPC1KO) inhibited the proliferation, migration, and invasion. This study helped to identify new prognostic markers and potential immunotherapeutic targets for LIHC and revealed the molecular mechanisms underlying NPC1 regulation in LIHC. The NPCs play a key role in the prognosis and diagnosis of LIHC and may be an important indicator for LIHC prognosis and diagnosis; NPC1 might be a potential therapeutic target in LIHC.


Logistic regression and machine learning predicted patient mortality from large sets of diagnosis codes comparably.
The objective of the study was to compare the performance of logistic regression and boosted trees for predicting patient mortality from large sets of diagnosis codes in electronic healthcare records. We analyzed national hospital records and official death records for patients with myocardial infarction (n = 200,119), hip fracture (n = 169,646), or colorectal cancer surgery (n = 56,515) in England in 2015-2017. One-year mortality was predicted from patient age, sex, and socioeconomic status, and 202 to 257 International Classification of Diseases 10th Revision codes recorded in the preceding year or not (binary predictors). Performance measures included the c-statistic, scaled Brier score, and several measures of calibration. One-year mortality was 17.2% (34,520) after myocardial infarction, 27.2% (46,115) after hip fracture, and 9.3% (5,273) after colorectal surgery. Optimism-adjusted c-statistics for the logistic regression models were 0.884 (95% confidence interval [CI]: 0.882, 0.886), 0.798 (0.796, 0.800), and 0.811 (0.805, 0.817). The equivalent c-statistics for the boosted tree models were 0.891 (95% CI: 0.889, 0.892), 0.804 (0.802, 0.806), and 0.803 (0.797, 0.809). Model performance was also similar when measured using scaled Brier scores. All models were well calibrated overall. In large datasets of electronic healthcare records, logistic regression and boosted tree models of numerous diagnosis codes predicted patient mortality comparably.


Beta-sheet secondary structure of an LDL receptor domain from complement factor I by consensus structure predictions and spectroscopy.
Low density lipoprotein receptor domains (LDLrs) represent a large cell surface receptor superfamily of consensus length 39 residues. Alignment of 194 sequences indicated highly conserved Cys and Asp/Glu residues, and a consensus secondary structure with three beta-strands was predicted. Sequence threading against known protein folds indicated consistency with small beta-sheet proteins. Complement factor I contains two LDLrs, and the second of these was successfully expressed using a bacterial pGEX system. FT-IR spectroscopy on this indicated a small amount of beta-sheet together with turns and loops. LDLr is proposed to have a beta-sheet structure in which the five biologically important Asp/Glu residues are located on an exposed loop.


Sutureless laparoscopic ventral hernia repair in obese patients.
Transfascial sutures (TFS) are a standard component of laparoscopic ventral herniorrhaphy (LVHR) that contribute to the durability of repair, but also pain and, resultantly, hospital stay. We sought to examine LVHR without TFS in obese patients with small abdominal wall hernias. Between September 2002 and December 2007, 174 patients underwent LVHR at Yale-New Haven Hospital. Patients with BMI >30kg/m(2) and small primary abdominal wall hernias were eligible for repair without TFS. Correlation between BMI, defect surface area, operative time, and postoperative stay was assessed. Fourteen patients underwent LVHR with no TFS, 2 with normal BMI and recurrent hernia after open repair and 12 with BMI >30 kg/m(2) and primary small hernia. Mean age was 38.8 years. The average defect size was 5.3cm(2); mean operative time (OT) was 42 minutes. Eleven patients (92%) were discharged home the day of surgery. No infectious or bleeding complications occurred. One patient required chronic pain management, and 8 patients (67%) developed seromas that resorbed spontaneously. There was no hernia recurrence at 7-month follow-up. LVHR is feasible without TFS provided the hernia defect is small. Surgery can be performed on an outpatient basis in obese individuals with minimal postoperative morbidity.


[Effects of clinorotation-induced weightlessness on growth factor and ERK signal transduction in cultured cardiac fibroblasts].
To study the changes of expression and secretion of some growth factors and ERK1/2 activation in cardiac fibroblasts under clinorotation conditions. Primary cultured neonatal rat cardiac fibroblasts were clinorotated to simulate weightlessness. The bFGF and TGF(beta)1 expressions in the cells and Ang II concentration in the medium were detected by western blotting and radioimmunoassay respectively. The expression and phosphorylated level of ERK1/2 were analyzed by western blotting. Compared to the control group, bFGF expression and Ang II concentration increased in clinorotation group, but there was no evident change in TGF(beta)1 expression. At the same time, the expression of ERK1/2 increased but their phosphorylated level decreased. Different growth factors responds to clinorotation by different ways. As one of the most important reactions of growth factor signal downstream pathways, ERK1/2 activation is inhibited in clinorotation.


Clinical and epidemiological features of ulcerative colitis patients in Sardinia, Italy: Results from a multicenter study.
There are little data on the epidemiological and clinical features of adult patients with ulcerative colitis (UC) in the different Italian regions, mainly derived from the absence of a national registry. This prevents correct interpretation of the disease burden. To assess the main clinical and epidemiological features of adult patients diagnosed with UC in Sardinia, Italy. We performed a multicenter, observational, cross-sectional study that included adult patients with UC enrolled in seven gastroenterology unit centers in Sardinia. Data were obtained from the patients' medical records and from a questionnaire administered at the inclusion visit. Four hundred and forty-two patients with UC were included. The median age at diagnosis was 39 years (interquartile range 28-48). After a median disease duration of 10 years, 53 patients experienced proximal extension of proctitis or left-sided colitis. Seventy-five patients developed extraintestinal manifestations. Nineteen patients (4.3%) developed cancer: two with colorectal cancer and seventeen with extracolonic cancers. Mesalazine (5-ASA) remains the mainstay of treatment for UC. Overall, 95 patients (21.5%) were treated with one or more biologic agents, whereas 15 patients (3.4%) underwent surgery, mostly colectomy. Our results provide important insights into the clinical and epidemiological features of patients with UC, and while waiting for a national Italian registry, present eligible data on the UC population in Sardinia.


Corticosterone implants in the paraventricular nucleus inhibit ACTH and corticosterone responses and the release of corticotropin-releasing factor following neural stimuli.
Experiments were conducted on the possible role of corticosterone (CS), at the level of the paraventricular nucleus of the hypothalamus (PVN) and dorsal hippocampus (D.HIPP), in the negative feedback effects following neural stimuli. In rats with bilateral PVN cholesterol (CHO) implants, acoustic and photic stimuli caused a significant rise in serum CS and ACTH and depletion of median eminence (ME) CRF-41 content. CS PVN implants have prevented the rise in serum CS, ACTH and ME CRF-41 depletion. Bilateral CHO or CS implants in the D.HIPP did not modify the responses of the hypothalamo-pituitary-adrenal axis to the above neural stimuli. In PVN CS-implanted rats, i.v. injection of CRF-41 increased serum CS similar to that observed in PVN CHO-implanted animals. These data are discussed in view of previous experiments on corticosteroid implants in the brain. It is concluded that CS PVN implants, by acting possibly via type II hypothalamic receptors, have prevented the release of ME CRF-41 following neural stimuli and consequently the secretion of ACTH and CS.


A review of implantable sensors.
Solid state sensors offer high performance, small size, lower cost, and compatibility with computing circuits. The current status of these sensors for biomedical applications is reviewed. Physical transducers may be used to measure pressure, flow, acceleration, velocity, etc. Chemical transducers may measure H+, K+, Na+, etc. Research required for their implantation is suggested.


Excellent PROM results after fast-track hip and knee arthroplasty with no postoperative restrictions: a cohort study validation of fast-track surgery without postoperative restrictions.
Fast-track hip and knee arthroplasty (HA and KA) has been increasingly common over the last decade. In the same time period, there was a strong trend toward less restrictive mobilization. However, few reports have been published on combining these novel programs while measuring the postoperative results by patient-reported outcome measures (PROMs). Descriptions of fast-track surgery programs and their results are warranted. The aim of this retrospective cohort study was to examine if it is possible to achieve excellent PROM results for hip and knee arthroplasty patients in a fast-track pathway without postoperative restrictions. During 2014-2017, the stepwise introduction of a PROM program was implemented at Stavanger University Hospital for all scheduled HA and KA patients, with preoperative assessments and postoperative follow-ups at the outpatient clinic. Standardized information with a focus on early mobilization and no postoperative restrictions was also initiated for the same patients. The generic EuroQol questionnaire (EQ-5D) and either the Hip or Knee disability/injury and Osteoarthritis Outcome Score (HOOS or KOOS) were used. PROM response rates varied from 80 to 99%. The median (interquartile range) change from preoperative to one-year postoperative results were as follows for HA and KA patients, respectively: pain, 55 (43-68) and 47 (31-61); other symptoms, 50 (40-65) and 36 (19-50); function in daily living, 54 (41-65) and 44 (31-55); function in sports and recreation, 56 (38-75) and 40 (15-64); joint-related quality of life, 69 (50-81) and 56 (38-75). The length of stay (LOS) was reduced by 1.9 days (mean), corresponding to a 40% reduction for HA patients and a 37% reduction for KA patients. We found excellent PROM results after fast-track HA and KA with no postoperative restrictions. We believe that a fast-track program focusing on mobilization without any postoperative restrictions is superior for most patients, but further comparative studies are warranted.


Nonvisualization of the intravenous pyelogram--a poor prognostic sign in Wilms' tumor?
In a series of 49 consecutive cases of Wilms' tumor from a single institution, there was a 20% incidence of nonvisualization on the initial intravenous pyelogram. Even though nonvisualization was secondary to either gross or microscopic invasion of the renal vein or renal pelvis, this did not forecast a grim progosis. Seven of the nine patients with nonvisualization are presently alive and tumor-free at least 5 yr after resection. The only two deaths in this particular group were unrelated to the Wilms' tumor.


Total Composite Flap Facelift and the Deep-Plane Transition Zone: A Critical Consideration in SMAS-Release Midface Lifting.
Recent anatomic studies suggest the superficial musculoaponeurotic system (SMAS) layer attenuates in the midface. This led the author to switch from a bilamellar high SMAS dissection to a "total composite flap" technique, preserving skin and SMAS/platysma as one layer in a critical "deep-plane transition zone" (DTZ) lateral to the zygomaticus major muscle. This allows traction on the SMAS to translate to the malar fat pad via a "cantilever bridge" effect, which is lost when skin is undermined in the DTZ. This paper attempts to answer the question of whether the composite flap or bilamellar technique better lifts the midface, comparing groups where the DTZ was undermined: (1) only at a sub-SMAS level; or (2) at both subcutaneous and sub-SMAS levels. Thirty-five patients underwent bilamellar facelifts with skin and SMAS separated in the DTZ. Midfacial elevation was measured using size-matched preoperative and 18-month (average) postoperative photographs for the 70 hemi-midfaces. The same analysis was done for 35 patients undergoing total composite flap facelift, maintaining skin and SMAS as one layer in the DTZ. The two groups were compared. In the bilamellar group, the mean percentage of midfacial elevation at 18 months postoperative was 5.5% (range, 0.0%-17.8%). In the composite flap group, the percentage was 11.7% (range, 0.1%-32.3%). The difference was statistically significant. Maintaining skin-SMAS attachments in the DTZ improves midface elevation during SMAS facelifting, exploiting a "cantilever bridge" effect of the skin transferring traction on the SMAS to the malar fat pad.


The PERK/eIF2 alpha signaling pathway of Unfolded Protein Response is essential for N-(4-hydroxyphenyl)retinamide (4HPR)-induced cytotoxicity in cancer cells.
N-(4-hydroxyphenyl)retinamide (4HPR) is a synthetic retinoid that has been tested in clinical trials as a cancer chemopreventive drug. 4HPR is cytotoxic to cancer cells but the underlying molecular mechanisms are at present only partially understood. Here we demonstrate that in the human cervical cancer cell line HeLa and the human leukemia cell line HL-60, 4HPR caused rapid, Reactive Oxygen Species (ROS)-dependent activation of the Unfolded Protein Response (UPR). In HeLa cells, 4HPR was shown to induce cell death and activation of procaspases. These effects of 4HPR could be abolished by the over-expression of dominant negative mutants of PERK or eIF2 alpha. HeLa cells incubated with 4HPR were found to form autophagosomes that were also mediated by the PERK/eIF2 alpha pathway. While 4HPR-induced cell death could be significantly prevented by the presence of specific caspase inhibitors, 3-methyladenine (3-MA) that inhibits autophagosome formation enhanced 4HPR-induced cell death. Examination of individual 4HPR-treated HeLa cells revealed that those without the development of autophagosomes hence exhibiting an incomplete UPR were caspase-active and were not viable, while those with autophagosomes were caspase-inactive and retained cell viability. Our data suggest that the PERK/eIF2 alpha pathway is essential for the cytotoxicity of 4HPR that targets on cancer cells with malfunctional UPR.


Determining Copper and Zinc Content in Superoxide Dismutase Using Electron Capture Dissociation Under Native Spray Conditions.
Localizing metal binding to specific sites in proteins remains a challenging analytical problem in vitro and in vivo. Although metal binding can be maintained by "native" electrospray ionization with intact proteins for quantitation by mass spectrometry, subsequent fragmentation of proteins with slow-heating methods like collision-induced dissociation (CID) can scramble and detach metals. In contrast, electron capture dissociation (ECD) fragmentation produces highly localized bond cleavage that is well known to preserve posttranslational modifications. We show how a newly available ECD tool that can be retrofitted on standard QTOF mass spectrometers allows the sites of copper and zinc binding to be localized in the antioxidant enzyme Cu, Zn superoxide dismutase (SOD1). The loss of zinc from Cu, Zn SOD1 has been shown to induce motor neuron death and could have a causal role in the fatal neurodegenerative disease, amyotrophic lateral sclerosis (ALS). The methods described enable copper loss to be distinguished from zinc using distinct ECD fragments of SOD1 and are broadly applicable to other metalloproteins.


Effects of low potassium or magnesium concentrations on isolated cardiac tissue.
Low potassium and magnesium concentrations not only cause cardiac arrhythmias, but also interfere with the efficacy or enhance the toxicity of drugs commonly used to treat patients with heart disease. Arrhythmias may develop in hypokalemia due to enhanced normal automaticity, abnormal automaticity, or slowed conduction; moreover, hypokalemia is associated with enhanced digitalis toxicity, quinidine-related Torsades de pointes, and interference with the antiarrhythmic activity of quinidine. Hypomagnesemia, especially in the presence of other electrolyte abnormalities, also affects automaticity and is associated with decreased efficacy of digitalis and with quinidine-related Torsades de pointes. Therefore, treatment that controls hypertension without causing electrolyte abnormalities is preferable for patients who are at risk of arrhythmias, or who are receiving drugs such as digitalis or quinidine.


DIRECT2: A novel platform for a CRISPR-Cas12-based assay comprising universal DNA-IgG probe and a direct lateral flow test.
CRISPR-Cas12-based biosensors are a promising tool for the detection of nucleic acids. After dsDNA-target-activated Cas12 cleaves the ssDNA probe, a lateral flow test (LFT) is applied for rapid, simple, and out-of-laboratory detection of the cleaved probe. However, most of the existing approaches of LFT detection have disadvantages related to inverted test/control zones in which the assay result depends not only on the cleavage of the probe but also on the second factor: the binding of the non-cleaved probe in the control zone. We proposed a novel platform for the detection of trans-cleaved DNA using a universal DNA-IgG probe and LFT with the sequential direct location of test and control zones. The advantage of the platform consists of the assay result depending only on the cleaved probe. For this, we designed a composite probe that comprise two parts: the DNA part (biotinylated dsDNA connected to ssDNA with fluorescein) (FAM), and the antibody part (mouse anti-FAM IgG). The Cas12, with guide RNA, was activated by the dsDNA-target. The activated Cas12 cleaved the probe, releasing the ssDNA-FAM-IgG reporter that was detected by the LFT. The sandwich LFT was proposed with anti-mouse IgG adsorbed in the test zone and on the surface of gold nanoparticles. We called the platform with direct location zones and direct analyte-signal dependence the DNA-Immunoglobulin Reporter Endonuclease Cleavage Test (DIRECT2). Therefore, this proof-of-concept study demonstrated that the combination of the proposed DNA-IgG probe and direct LFT opens new opportunities for CRISPR-Cas12 activity detection and its bioanalytical applications.


Single-cell characterization and metabolic profiling of in vitro cultured human skeletal progenitors with enhanced in vivo bone forming capacity.
Cell populations and their interplay provide the basis of a cell-based regenerative construct. Serum-free preconditioning can overcome the less predictable behavior of serum expanded progenitor cells, but the underlying mechanism and how this is reflected in vivo remains unknown. Herein, the cellular and molecular changes associated with a cellular phenotype shift induced by serum-free preconditioning of human periosteum-derived cells were investigated. Following BMP-2 stimulation, preconditioned cells displayed enhanced in vivo bone forming capacity, associated with an adapted cellular metabolism together with an elevated expression of BMPR2. Single-cell RNA sequencing confirmed the activation of pathways and transcriptional regulators involved in bone development and fracture healing, providing support for the augmentation of specified skeletal progenitor cell populations. The reported findings illustrate the importance of appropriate in vitro conditions for the in vivo outcome. In addition, BMPR2 represents a promising biomarker for the enrichment of skeletal progenitor cells for in vivo bone regeneration.


Making rural Young Vet Network events a success.
Becky Richardson, Young Vet Network representative on BVA Council, discusses the anxieties and joys of hosting a rural YVN event.


Doppler echocardiographic study of left ventricular diastole in non-anaesthetized healthy cats.
The current study: (1) describes the Doppler technique for the assessment of diastolic function in feline patients; (2) reports normal Doppler diastolic values; and (3) determines the effect of ageing on these parameters. Doppler echocardiography was performed on 20 non-anaesthetized healthy cats. Each diastolic parameter was correlated with age, body weight, body surface area and R-R interval. To assess the isovolumetric relaxation phase of diastole, isovolumetric relaxation time was measured. To assess the filling phase of diastole, we measured peak flow velocities of the E and A waves, diastolic filling time, acceleration and deceleration time of the E wave and the E/A ratio of transmitral flow, peak flow velocity of the S, D and the A retrograde waves, as well as the S/D ratio and the systolic fraction of pulmonary venous flow. We found a significant correlation between age and peak flow velocity of the A wave, normalized peak flow velocity of the A wave, the E/A ratio, the acceleration time of the E wave, the diastolic filling time, the velocity time integral of the E wave, the peak flow velocity of the S wave and the systolic fraction. It was concluded that Doppler echocardiographic analysis of diastole is possible in the cat and that age has most effect on filling parameters.


Use of parenteral colistin for the treatment of multiresistant Gram-negative organisms in major burn patients in South Korea.
To assess the therapeutic effect and toxicity of intravenous colistin in the treatment of multidrug-resistant (MDR) Gram-negative bacteria in patients with severe burns. The medical records of 930 patients admitted to the Burn Intensive Care Unit (ICU) at Hallym University Hangang Sacred Heart Hospital, Seoul, South Korea between April 2007 and December 2009 were retrospectively reviewed. Of these, the 104 patients who had received intravenous colistin treatments (104 courses) during this period were enrolled in the study. Changes in creatinine level were analyzed in three groups: all patients receiving colistin (n = 104), patients with undergoing continuous renal replacement therapy (CRRT group; n = 38), and patients not undergoing CRRT (non-CRRT group; n = 66). Among these patients, the burnt body surface area ranged from 5 to 96% (mean 49.7%). Thirty-five patients (33.7%) suffered inhalation injury, and CRRT was administered to 38 patients. The mean duration of colistin treatment was 14.7 (range 4-71) days. The total dose of colistin was 3,045.7 mg (range 100-13,800). The length of ICU stay was 48.9 (range 7-154) days. Forty patients (38.5%) died. The mean pre-colistin creatinine level of all patients was 1.04 mg/dL, and the mean post-colistin level was 1.34 mg/dL. The mean pre-colistin creatinine level of the CRRT group and non-CRRT group was 1.68 and 0.66 mg/dL, and the mean post-colistin level was 1.68 and 1.14 mg/dL, respectively. Colistin appears to be a relatively safe and effective treatment for major burn patients with infections caused by MDR Gram-negative bacteria when no other drug is available. Additionally, we found no statistically significant impairment of creatinine levels.


Dynein light chain 1 induces assembly of large Bim complexes on mitochondria that stabilize Mcl-1 and regulate apoptosis.
The Bcl-2 family protein Bim triggers mitochondrial apoptosis. Bim is expressed in nonapoptotic cells at the mitochondrial outer membrane, where it is activated by largely unknown mechanisms. We found that Bim is regulated by formation of large protein complexes containing dynein light chain 1 (DLC1). Bim rapidly inserted into cardiolipin-containing membranes in vitro and recruited DLC1 to the membrane. Bim binding to DLC1 induced the formation of large Bim complexes on lipid vesicles, on isolated mitochondria, and in intact cells. Native gel electrophoresis and gel filtration showed Bim-containing mitochondrial complexes of several hundred kilodaltons in all cells tested. Bim unable to form complexes was consistently more active than complexed Bim, which correlated with its substantially reduced binding to anti-apoptotic Bcl-2 proteins. At endogenous levels, Bim surprisingly bound only anti-apoptotic Mcl-1 but not Bcl-2 or Bcl-XL, recruiting only Mcl-1 into large complexes. Targeting of DLC1 by RNAi in human cell lines induced disassembly of Bim-Mcl-1 complexes and the proteasomal degradation of Mcl-1 and sensitized the cells to the Bcl-2/Bcl-XL inhibitor ABT-737. Regulation of apoptosis at mitochondria thus extends beyond the interaction of monomers of proapoptotic and anti-apoptotic Bcl-2 family members but involves more complex structures of proteins at the mitochondrial outer membrane, and targeting complexes may be a novel therapeutic strategy.


The knockout of the lprG-Rv1410 operon produces strong attenuation of Mycobacterium tuberculosis.
P27 lipoprotein was previously described as an antigen in the Mycobacterium tuberculosis complex, encoded by the lprG gene, also named Rv1411 in the TubercuList (http://genolist.pasteur.fr/TubercuList) gene bank. It forms an operon with Rv1410 that encodes for an efflux pump, P55. A mutant of the H37Rv strain of M. tuberculosis not producing P27 (strain DeltaP27) was obtained by two-step mutagenesis using the counterselectable marker sacB and a thermosensitive origin of replication in the shuttle plasmid pPR27. By RT-PCR, we observed no lprG or Rv1410 mRNA in the DeltaP27 mutant strain compared with the wild type and complemented strains. Western blot experiments using anti-P27 polyclonal sera showed that the P27 protein was present both in the parental and in a complemented strain, in which the entire lprG-Rv1410 operon was reintroduced, but absent in the mutant strain. The three strains showed similar growth kinetics and characteristics in culture broth. To study the effect of the lprG mutation on M. tuberculosis virulence, BALB/c mice were inoculated to determine bacterial loads in spleens. At days 15 and 35 after infection, decreases of 1.5 and 2.5 logs in the bacterial load were found, respectively, in animals inoculated with the DeltaP27 mutant strain or with the wild type. This attenuation was reverted in the complemented strain. These results demonstrated that lprG gene is required for growth of M. tuberculosis in immunocompetent mice. The reversion of attenuation in the complemented strain indicates that the attenuated phenotype resulted from disruption of the lprG-Rv1410 operon.


Subsequent infection differentially affects the proteome of Caenorhabditis elegans by abrogating the intestinal cell proliferation.
With a wide range of bacterial infections growing, it has become a big challenge to the research field to combat the newly emerging diseases. Immuno-compromised patients are vulnerable to opportunistic infections. P. mirabilis, an opportunistic pathogen infects the nematode when the immune system is compromised. In the present study, the C. elegans was pre-exposed to S. aureus for a short term, and then consecutively infected with P. mirabilis. The primary infection caused by S. aureus makes the immune system of C. elegans vulnerable making it easy for P. mirabilis to colonize efficiently during subsequent exposure, thereby stimulating the immune system of the nematode. In this study, the C. elegans exposed to the pathogens (S. aureus 4 h/P. mirabilis 40 h and S. aureus 8 h/P. mirabilis 60 h time points) showed a substantial difference in the banding patterns of SDS-PAGE gel, when compared to their respective OP50 fed controls. 2-DE identified a total of 235 proteins from all the time points which had >2 fold regulation. The regulated protein spots were identified by MALDI-ToF/ToF analysis and one common protein CDC-25.1 was found to be regulated in all the comparative time points. CDC-25.1 seemed to down regulate during subsequent infection and up regulate in single infection. The transcriptomic regulation of cdc-25.1 also reflects the protein regulation. In addition to it, survival assay in cdc-25.1 mutant nematodes confirm the susceptibility of host during subsequent infection.


An almost general theory of mean size perception.
A general explanation for the observer's ability to judge the mean size of simple geometrical figures, such as circles, was advanced. Results indicated that, contrary to what would be predicted by statistical averaging, the precision of mean size perception decreases with the number of judged elements. Since mean size discrimination was insensitive to how total size differences were distributed among individual elements, this suggests that the observer has a limited cognitive access to the size of individual elements pooled together in a compulsory manner before size information reaches awareness. Confirming the associative law of addition means, observers are indeed sensitive to the mean, not the sizes of individual elements. All existing data can be explained by an almost general theory, namely, the Noise and Selection (N&S) Theory, formulated in exact quantitative terms, implementing two familiar psychophysical principles: the size of an element cannot be measured with absolute accuracy and only a limited number of elements can be taken into account in the computation of the average size. It was concluded that the computation of ensemble characteristics is not necessarily a tool for surpassing the capacity limitations of perceptual processing.


Self-enhancement lateral flow immunoassay for COVID-19 diagnosis.
Equipment-free colorimetric-based lateral flow immunoassay (LFIA) is the most convenient and popular tool for various applications, including diagnostic tools requiring high sensitivity for the detection of pathogens. Thus, improvements and developments of LFIA are constantly being reported. Herein, we enriched the sensitivity of LFIA using the gold enhancement principle, emphasizing needlessly complicated apparatus, only one step for the strip test operation, and typical time incubation (15 min) process. Self-enhanced LFIA was then executed for subsequent flows by overlapping the additionally enhanced pad composed of gold ions and reducing agent on the conjugate pad and the sample pad. Self-enhanced LFIA was performed to detect SARS-CoV-2 antigens in saliva. The obtained result depicted that the achieved sensitivity was up to tenfold compared with that of conventional LFIA by visual measurements. The detection limits of self-enhanced LFIA detecting nucleocapsid protein antigens in the saliva sample was 0.50 and 0.10 ng/mL employed by naked eye detection and calibration curve-based calculation, respectively. When the proposed device was applied to 207 human saliva samples, the diagnostic performance presented a 96.10 % sensitivity and 99.23 % specificity. This self-enhanced LFIA could be implemented in large-scale production and demonstrates higher sensitivity with effortless use, which meets the requirements for point-of-care testing and on-field mass screening.


HPLC method for determination of biologically active epoxy-transformers of treosulfan in human plasma: pharmacokinetic application.
Clinical trials demonstrated treosulfan (TREO) as a promising myeloablative agent prior to hematopoietic stem cell transplantation (HSCT). TREO is a specific pro-drug from which biologically active mono- (S,S-EBDM) and diepoxybutane (S,S-DEB) derivatives are formed in vitro or in vivo by a non-enzymatic pH and temperature-dependent intramolecular nucleophilic substitution. Following extraction of the plasma samples with a mixture of dichloromethane and acetonitrile, S,S-EBDM and S,S-DEB were derivatized with 3-nitrobenzenesulfonic acid (3-NBS) to UV-absorbing esters. Optimal temperature and time of derivatization as well as extraction method and also the effect of pH on TREO stability in plasma were established. Identity of the synthesized derivatives was confirmed by mass spectrometry. The post-derivatization mixture was purified from the excess of unreacted 3-NBS by extraction with water. The derivatization products and 2,2'-dinitrobiphenyl (internal standard) were separated on Nucleosil 100 C18 column using a mobile phase consisted of acetonitrile and water. The developed method was validated and demonstrated adequate accuracy and precision. Limit of quantification for both S,S-EBDM and S,S-DEB amounted to 2.5 μM. The method was applied in clinical conditions to quantify the levels of TREO activation products in plasma of children undergoing HSCT. The methodology for simultaneous determination of TREO epoxy-transformers in human plasma is described for the first time.


Spatiotemporal organization of frog respiratory neurons visualized on the ventral medullary surface.
We visualized the spatiotemporal activity of respiratory-related neurons in the frog using the isolated brainstem spinal cord preparation. We recorded optical signals from the ventral surface of the medulla using a voltage-sensitive dye, and calculated cross-correlations with the integrated respiratory activity of the trigeminal nerve. Lung burst-related depolarizing optical signals were observed bilaterally as longitudinal columns in the ventrolateral medulla between the levels of trigeminal and hypoglossal rootlets, mostly caudal to the vagal rootlet. However, we could not differentiate between neurons involved in rhythm generation and motoneurons. The dye weakened the buccal rhythm and slowed the lung rhythm, which might have influenced the results. Extracellular recording of respiratory neurons verified the optically identified area. Strychnine disrupted the spatiotemporal organization of optical signals, although trigeminal periodic bursts persisted. We conclude that the pattern generator but not the rhythm generator of lung burst in the frog involves glycinergic mechanisms and lies as longitudinal columns in the reticular formation of the ventrolateral medulla.


Assessment of comparative toxicities of lead and copper using plant assay.
The acute toxicities of lead (Pb) and copper (Cu) to important crop plants Sorghum bicolor, Cucumis sativus, Triticum aestivum, and Zea mays were compared. The EC50 values (the concentration of metals in the soil that reduces the growth of shoots and roots by 50%) were derived using the Trimmed Spearman-Karber method. The EC50s-shoot (root) in mg Pb kg-1 dry soil and mg Cu kg-1 dry soil were in the range of 519 to >1280 (285-445), and 48-232 (<40-110), respectively. Those concentrations are likely to occur in some abandoned mine areas in Korea. The figures indicate that Cu is more toxic than Pb to the plants in this study, and that root growth is more sensitive to the toxicity endpoint than shoot growth in Cu- or Pb-amended soils. On the other hand, seed germination is insensitive to both Pb and Cu toxicities. The Pb- and Cu-sensitive plants were also identified. Among the plants tested, T. aestivum and S. bicolor were most sensitive to Pb and Cu, respectively. Z. mays was most resistant to both Pb and Cu. The combined effects of Pb and Cu depend on the plant species, and no general phenomenon was observed. Bioaccumulations of Pb and Cu were observed in all test species, and they are concentration-dependent. These differences in the toxicities of Pb and Cu in plant species should be taken into account in biomonitoring and ecological risk assessment.


Influence of chondroitin sulfate, heparin sulfate, and citrate on Proteus mirabilis-induced struvite crystallization in vitro.
Struvite crystals were produced by Proteus mirabilis growth in artificial urine, in the presence of a number of naturally occurring crystallization inhibitors. The use of phase contrast light microscopy enabled the effects of added chondroitin sulfate A, chondroitin sulfate C, heparin sulfate, or sodium citrate, on struvite crystal growth rates to be rapidly monitored as changes in crystal habit. Struvite crystals formed as a consequence of the urease activity of P. mirabilis under all chemical conditions. In the absence of inhibitor, early crystal development was marked by large quantities of amorphous precipitate, followed immediately by the appearance of rapidly growing X-shaped or planar crystals. Addition of the glycosaminoglycans, chondroitin sulfate A, chondroitin sulfate C, or heparin sulfate to the artificial urine mixture had no effect on the rate of crystal growth or appearance. When sodium citrate was present in elevated concentrations, crystal appearance was generally slowed, and the crystals assumed an octahedral, slow growing appearance. None of the added compounds had any influence on bacterial viability, pH, or urease activity. It is therefore likely that the inhibitory activity displayed by sodium citrate might be related to its ability to complex magnesium or to interfere with the crystal structure during struvite formation. From these experiments it would appear that citrate may be a factor in the natural resistance of whole urine to struvite crystallization.


Aneurysm of the sinus of Valsalva with coexistent coronary atherosclerosis.
Unruptured aneurysm of the sinus of Valsalva coexistent with extensive coronary atherosclerosis was noted in a 65-year-old man. He underwent transaortic patch repair of the aneurysm and quadruple aortocoronary bypass. The essential features of adequate management of this association are discussed.


Chromosome analysis of human oocytes failing to fertilize in vitro.
To assess the contribution of chromosome anomalies to the high failure of in vitro fertilization (IVF), 94 unfertilized eggs from 43 women participating in the IVF program were cytogenetically investigated. The mean age of the oocyte donors was 33.6 years. Chromosome karyotypes were obtained in 65 of 94 oocytes: 34 oocytes (52.3%) had a normal haploid chromosome complement; 10 (15.4%) were hypohaploid; 7 (10.8%) were hyperhaploid; 8 were diploid; and 6 were hypodiploid or hyperdiploid (from 36 to 53). Eleven eggs showed prematurely condensed chromosomes of the G1-phase from sperm, as well as a set of maternal metaphase II chromosomes. These results are compared to similar reports in the literature.


Nitrogen and water recovery from animal slurries by a new integrated ultrafiltration, reverse osmosis and cold stripping process: a case study.
The correct management of livestock manure represents one of the major challenge for the agricultural sector development, as it may ensure environmental and economic sustainability of livestock farming. In this work, a new treatment process called N-Free(®), was monitored on two plants treating digested cattle manure (DCM) and digested swine manure (DSM). The process is characterized by sequential integration of solid/liquid separations, ultrafiltration, reverse osmosis and cold ammonia stripping. Solid and liquid streams were characterized regarding TS, TKN, N-NH4(+), P and K content allowing to draw a complete mass balance. The main results were a substantial reduction of initial digestate volume (38 and 51% in DCM and DSM respectively) as clean water and a high N-NH4(+) removal percentage (47 and 71% in DCM and DSM respectively), through cold ammonia stripping, allowing the production of up to 1.8 m(3) concentrated ammonium sulfate, every 100 m(3) of treated digestate. The concentrated streams, rich in either organic or mineral N, P and K, can be efficiently used for land application. The N-Free(®) technology demonstrated to be a valuable candidate for the path toward nutrient and water recycle, in a new sustainable agriculture and farming concept.


Ciraparantag, an anticoagulant reversal drug: mechanism of action, pharmacokinetics, and reversal of anticoagulants.
Ciraparantag, an anticoagulant reversal agent, is a small molecule specifically designed to bind noncovalently by charge-charge interaction to unfractionated heparin and low-molecular-weight heparin. It shows binding characteristics that are similar to those of direct oral anticoagulants (DOACs). A dynamic light-scattering methodology was used to demonstrate ciraparantag's binding to the heparins and DOACs and its lack of binding to a variety of proteins including coagulation factors and commonly used drugs. Ciraparantag reaches maximum concentration within minutes after IV administration with a half-life of 12 to 19 minutes. It is primarily hydrolyzed by serum peptidases into 2 metabolites, neither of which has substantial activity. Ciraparantag and its metabolites are recovered almost entirely in the urine. In animal models of bleeding (rat tail transection and liver laceration), a single IV dose of ciraparantag given at peak concentrations of the anticoagulant, but before the bleeding injury, significantly reduced the blood loss. Ciraparantag, given after the bleeding injury, also significantly reduced blood loss. It appears to have substantial ability to reduce blood loss in animal models in which a variety of anticoagulants are used and has potential as a useful DOAC reversal agent.


The GluR5 subtype of kainate receptor regulates excitatory synaptic transmission in areas CA1 and CA3 of the rat hippocampus.
Activation of kainate receptors depresses excitatory synaptic transmission in the hippocampus. In the present study, we have utilised a GluR5 selective agonist, ATPA [(RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid], and a GluR5 selective antagonist, LY294486 [(3SR,4aRS,6SR,8aRS)-6-([[(1H-tetrazol-5-y l)methyl]oxy]methyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3 -carboxylic acid], to determine whether GluR5 subunits are involved in this effect. ATPA mimicked the presynaptic depressant effects of kainate in the CA1 region of the hippocampus. It depressed reversibly AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor-mediated field excitatory postsynaptic potentials (field EPSPs) with an IC50 value of approximately 0.60 microM. The dual-component excitatory postsynaptic current (EPSC) and the pharmacologically isolated NMDA (N-methyl-D-aspartate) receptor-mediated EPSC were depressed to a similar extent by 2 microM ATPA (61 +/- 7% and 58 +/- 6%, respectively). Depressions were associated with an increase in the paired-pulse facilitation ratio suggesting a presynaptic locus of action. LY294486 (20 microM) blocked the effects of 2 microM ATPA on NMDA receptor-mediated EPSCs in a reversible manner. In area CA3, 1 microM ATPA depressed reversibly mossy fibre-evoked synaptic transmission (by 82 +/- 10%). The effects of ATPA were not accompanied by any changes in the passive properties of CA1 or CA3 neurones. However, in experiments where K+, rather than Cs+, containing electrodes were used, a small outward current was observed. These results show that GluR5 subunits comprise or contribute to a kainate receptor that regulates excitatory synaptic transmission in both the CA1 and CA3 regions of the hippocampus.


Inactivation of SARS-CoV-2 by commercially available alcohol-based hand sanitizers.
Alcohol-based hand sanitizers are being recommended as an infection prevention measure for COVID-19. Recently published data indicates that ethanol effectively inactivates the SARS-CoV-2 virus, but there is a lack of data for formulated hand sanitizer products currently used in U.S. healthcare and general settings. This study demonstrates a commercially available foam and gel alcohol-based hand sanitizer are effective in inactivating SARS-CoV-2 in suspension.


Mechanosensitive activation of CFTR by increased cell volume and hydrostatic pressure but not shear stress.
The cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl(-) channel that is essential for electrolyte and fluid homeostasis. Preliminary evidence indicates that CFTR is a mechanosensitive channel. In lung epithelia, CFTR is exposed to different mechanical forces such as shear stress (Ss) and membrane distention. The present study questioned whether Ss and/or stretch influence CFTR activity (wild type, ∆F508, G551D). Human CFTR (hCFTR) was heterologously expressed in Xenopus oocytes and the response to the mechanical stimulus and forskolin/IBMX (FI) was measured by two-electrode voltage-clamp experiments. Ss had no influence on hCFTR activity. Injection of an intracellular analogous solution to increase cell volume alone did not affect hCFTR activity. However, hCFTR activity was augmented by injection after pre-stimulation with FI. The response to injection was similar in channels carrying the common mutations ∆F508 and G551D compared to wild type hCFTR. Stretch-induced CFTR activation was further assessed in Ussing chamber measurements using Xenopus lung preparations. Under control conditions increased hydrostatic pressure (HP) decreased the measured ion current including activation of a Cl(-) secretion that was unmasked by the CFTR inhibitor GlyH-101. These data demonstrate activation of CFTR in vitro and in a native pulmonary epithelium in response to mechanical stress. Mechanosensitive regulation of CFTR is highly relevant for pulmonary physiology that relies on ion transport processes facilitated by pulmonary epithelial cells.


Randomized placebo controlled clinical trial of an enteric coated micro-pelleted formulation of a pancreatic enzyme supplement in dogs with exocrine pancreatic insufficiency.
Pancreatic enzyme supplements for the treatment of exocrine pancreatic insufficiency (EPI) in dogs can be uncoated or enteric coated. Enteric coated supplements might be advantageous. Enteric coated enzyme supplements are superior to uncoated supplements in dogs with clinical EPI. Eleven dogs with naturally occurring EPI that were apparently free from other diseases. Randomized, blinded, controlled cross-over clinical trial comparing a novel micro-encapsulated enteric coated enzyme supplement to a commercially available uncoated product in dogs with clinical EPI. Search of serum canine serum trypsin-like immunoreactivity concentration ≤ 2.5 µg/L in the Gastrointestinal Laboratory database was used to identify dogs with EPI. There was no difference -4.46% (95% CI: -7.97%--0.96%; P = .15) in the % acid hydrolysis fecal fat (primary outcome) between the enteric coated formulation (median: 11.8%; range 6.4%-17.0%) and the uncoated pancreatic enzyme replacement product (median: 17.5%; range: 5.2%-24.9%) in the 11 dogs that completed the study. Other variables did not differ between treatments. This study, which had low statistical power, did not detect a difference between formulations.


How events are reviewed matters: effects of varied focus on eyewitness suggestibility.
Witnesses to a crime or an accident perceive that event only once, but they are likely to think or talk about it multiple times. The way in which they review the event may affect their later memory. In particular, some types of review may increase suggestibility if the witness has been exposed to postevent misleading information. In Experiment 1, participants viewed a videotaped crime and then received false suggestions about the event. We found that participants who were then asked to focus on specific details when reviewing the event were more suggestible on a later source memory test than participants asked to review the main points. The findings of Experiment 2 suggest that this effect was not due to a criterion shift at test. These findings indicate that the type of rehearsal engaged in after witnessing an event can have important consequences for memory and, in particular, suggestibility.


[Microcirculation characteristics and humoral factors of healthy people from different populations at high altitude (4 100 m)].
The present study was aimed to observe the characteristics of sublingual microcirculation and the changes of humoral factors in healthy people of three different high altitude populations. Three groups of healthy subjects in Guoluo area of Qinghai province (4 100 m) were included: Tibetan group: 30 Tibetans, (45.62 ± 10.15) years old; Han group: 22 two-generation of Han immigrants, (46.23 ± 8.59) years old; migrant group: 23 migrants living at high altitude for 2-5 years, (43.45 ± 8.31) years old. Blood routine test was performed to determine white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (HGB), hematocrit (HCT), platelet (PLT) count, and neutrophil (NEUT) count. The changes of serum humoral factors including endothelin-1 (ET-1), CD31, CD34, CD105, vascular endothelial growth factor (VEGF), nitric oxide (NO) and noradrenaline (NE) were detected by ELISA. Continuous noninvasive hemodynamics monitor was used to continuously measure the changes of systemic circulation indexes: cardiac output (CO), cardiac index (CI), heart rate (HR), stroke volume (SV), pulse pressure variation (PPV), systemic vascular resistance index (SVRI), and mean arterial pressure (MAP). Blood oxygen was measured by pulse oximeter. Sublingual microcirculation indexes including total vascular density (TVD), perfused vessel density (PVD), proportion of perfused vessels (PPV), and microvascular flow index (MFI) were determined by sidestream dark field imaging. The results showed that there were no difference in systemic circulation among the 3 groups. Compared with Tibetan group, TVD and PVD of microcirculation in Han group and migrant group were significantly increased (P < 0.05). Compared with Tibetan group and Han group, WBC, RBC, HGB and HCT of migrant group were significantly increased (P < 0.05). Compared with Han group and Migrant group, PLT of Tibetan group was significantly increased (P < 0.05). Compared with the Tibetan group, the levels of serum humoral factors CD105 and VEGF were significantly higher in the migrant group (P < 0.05), while compared with Han and migration groups, NO in Tibetan group was significantly increased (P < 0.05). It is suggested that there were significant differences in microcirculation (TVD, PVD), blood routine (WBC, RBC, HGB, HCT) and humoral factors (CD105, VEGF) among different populations in high altitude area. Importantly, the increased microcirculation, erythrocytosis and increased pro-angiogenic factors due to hypoxic environment were observed in long-term residents and migrants, except for permanent residents. These physiological changes have clinical significance in the treatment of septic shock and chronic altitude sickness for different plateau populations.


Intravoxel incoherent motion (IVIM) MRI in pediatric patients with synovitis of the knee joint: a prospective pilot study.
Diagnosing synovial inflammation by administration of gadolinium-based contrast agents is limited by invasiveness and possible side effects, especially in children and adolescents. We investigated diagnostic accuracy of diffusion-weighted (DWI) MRI with intravoxel incoherent motion (IVIM) imaging compared to contrast-enhanced MRI for detecting synovitis of the knee in a population of pediatrics and young adults. In addition we compared quantitative measures of synovial diffusion and perfusion to a group of healthy volunteers. In this prospective study, 8 pediatric patients with 10 symptomatic knees (6 girls and 2 boys, mean age 13 years) with known or suspected synovitis underwent pre- and post-contrast 3.0 T MRI of the knee joint and additional DWI sequences between October 2016 and July 2019. For comparison we enrolled 5 healthy young adults (2 women and 3 men, median age 27 years) with contrast-free MRI of both knees. Post-contrast T1w images and DWI images at b = 1000s/mm2 with apparent diffusion coefficient (ADC) maps of patients were separately rated by two independent and blinded readers with different levels of experience for the presence or absence and degree of synovitis along with the level of confidence. We measured signal intensity on DWI of synovium, joint effusion and muscle with regions of interests and calculated the IVIM-parameters tissue diffusion coefficient (D) and perfusion fraction (f) for patients and volunteers. All patients showed at least some synovial contrast enhancement, 8 (80%) children knees were diagnosed with synovitis on contrast-enhanced (= ce)-T1w, the diagnostic standard. Ratings by the first and second reader on ce-T1w and DWI showed full agreement (kappa = 1) in diagnosing synovitis and substantial agreement (k = 0,655) for the degree of synovial enhancement. Interobserver agreement on DWI showed fair agreement (k = 0,220) between both readers. Diagnostic confidence was lower on DWI. Mean D- and f-values of muscle was comparable between patients and volunteers. Effusion mean D was higher, mean f was lower, synovial mean D was lower, mean f higher in patients than in volunteers. All differences were statistically significant (p < 0.001). Diffusion-weighted MRI with IVIM imaging remains a promising, though reader-dependent alternative to i.v. contrast-enhanced imaging in pediatric patients to reliably diagnose, or rule out, synovitis of the knee joint. We detected significantly restricted synovial diffusion and increased perfusion in patients compared to healthy volunteers. Ethical Comitee University Hospital Ulm, Nr. 320/16.


Induction of gastric lesions and hypoglycemic response by food deprivation in streptozotocin-diabetic rats.
Overnight fasting causes hemorrhagic lesions in the stomach of streptozotocin (STZ)-induced diabetic rats, but the pathogenetic mechanism remains unknown. The present study was performed to investigate the pathogenesis of such lesions developed in STZ-diabetic rats after starvation, mainly in relation to blood glucose changes. A single injection of STZ (70 mg/kg, intraperitoneally) induced hyperglycemic conditions one week after the administration, and high blood glucose levels (BGL: > 350 mg%) remained up to three weeks later. The STZ-diabetic rats developed gastric lesions with the marked reduction of BGL after 18 hr of fasting, depending upon the duration of diabetes; the lesion score and delta BGL reduction in the 3-week-old STZ rats were 32.0 +/- 7.8 mm and > 250 mg/100 ml, respectively. Acid secretion in the pylorus-ligated rats was not significantly changed in the STZ-induced diabetic conditions for the initial two weeks but slightly decreased at three weeks when compared with normal rats. Fasting of normal rats for 18 hr did not cause either BGL reduction or any lesion in the stomach. In the 3-week-old STZ animals, the severity of gastric lesions increased with the duration of fasting (4-18 hr) and was again closely associated with the degree of delta BGL reduction. These lesions induced by 18 hr of starvation in 3-week-old STZ rats were significantly inhibited by pretreatment with insulin (4 units/rat/day) for the last one week to maintain BGL within normal ranges or by intravenous infusion of 25% glucose during fasting period. Both of these treatments significantly prevented BGL reduction in response to fasting.(ABSTRACT TRUNCATED AT 250 WORDS)


Miniaturized Self-Resonant Micro Coil Array with A Floating Structure for Wireless Multi-Channel Transmission.
Micro size antennas have significant merits due to the small size effect, enabling new device concepts. However, the low-quality factor (Q-factor), the large size of impedance matching components, and the poor selectivity of the multi-array design remain challenging issues. To solve these issues, a floating coil structure stacked on a loop micro-antenna is suggested. Various floating coil designs are prepared with appropriate matching conditions at specific target frequencies, using an easy fabrication process without the need for additional space. A simple one-loop antenna design shows a higher Q-factor than other, more complicated designs. The micro-sized loop antenna with the 80 µm trace width design exhibits the highest Q-factor, around 31 within 7 GHz. The 8 different floating coil designs result in high-frequency selectivity from 1 to 7 GHz. The highest selectivity contrast and WPT efficiency are above 7 and around 1%, respectively. Considering the size of the antenna, the efficiency is not low, mainly due to the good matching effect with the high Q-factor of the floating coil and the loop antenna. This micro-antenna array concept with high integration density can be applied for advanced wireless neural stimulation or in wireless pixel array concepts in flexible displays.


Genome-scale analysis of evolutionary rate and selection in a fast-expanding Spanish cluster of HIV-1 subtype F1.
This work is aimed at assessing the presence of positive selection and/or shifts of the evolutionary rate in a fast-expanding HIV-1 subtype F1 transmission cluster affecting men who have sex with men in Spain. We applied Bayesian coalescent phylogenetics and selection analyses to 23 full-coding region sequences from patients belonging to that cluster, along with other 19 F1 epidemiologically-unrelated sequences. A shift in the overall evolutionary rate of the virus, explained by positively selected sites in the cluster, was detected. We also found one substitution in Nef (H89F) that was specific to the cluster and experienced positive selection. These results suggest that fast transmission could have been facilitated by some inherent genetic properties of this HIV-1 variant.


The impact of different service states of tunnel lighting on traffic safety.
The service states of tunnel lighting will directly affect the lighting conditions, which affect traffic safety. Therefore, it is imperative to evaluate and predict traffic safety accurately in different lighting states. In this research, three hundred experimental scenarios of the service states of tunnel lighting were designed and implemented to evaluate the impact of different service states of tunnel lighting on traffic safety. The evaluation was achieved through a visual identification experiment in a physical tunnel. The experimental results show higher simulated vehicle speeds pose a greater threat to traffic safety. The severity of lighting attenuation contributes to an increased risk to traffic safety. An increase in the number of luminaires failure also poses a greater threat to traffic safety. The newly proposed traffic safety factor was employed to evaluate traffic safety quantitatively in road tunnels. To improve the accuracy and comprehensiveness of the traffic safety factor prediction in different lighting service states, an advanced neural network prediction system was developed. The prediction system was constructed using the Sparrow Search Algorithm (SSA) to optimize Extreme Learning Machine (ELM) neural network, and the dataset from the experiment was used for the prediction model. The SSA-ELM neural network model is a reliable model that can predict the traffic safety factor comprehensively and accurately. The recommended threshold value for the traffic safety factor is 0.6. When the value falls below 0.6, it shows that the service states of tunnel lighting pose a threat to traffic safety in the tunnel. These findings can provide insights into the safe and energy-efficient maintenance of road tunnels.


Target contrast affects reaching and grasping in the visually impaired subjects.
The aim of this study is to investigate whether subjects with central visual impairment (VI) show different reaching and grasping behavior for targets of different contrasts compared with visually normal age-matched subjects. Reaching and grasping performance was measured in 14 subjects with VI and 14 normal subjects. Subjects were asked to pick up a cylindrical target. Three different targets were used: black (low contrast), white (high contrast), and transparent, placed against a black background. A motion analysis system (Vicon 460) recorded and reconstructed the hand and finger movements. Significantly longer onset times, total movement duration, and time after maximum grip aperture were obtained for subjects with VI compared with normal subjects (p < 0.002). No significant differences existed in maximum velocity and grip aperture between the two groups for any of the targets. Subjects with VI took longer to initiate and to complete the movement. Maximum velocity and grip aperture were not different suggesting that once the target was "seen" by subjects with VI performance was similar to normal subjects. Time after maximum grip aperture was longer in subjects with VI indicating the need for "online" modifications in these subjects. Contrast sensitivity was significantly correlated to more indices than visual acuity.


Biotransformation of caffeine by microsomes from human liver. Kinetics and inhibition studies.
The nature of the cytochrome P-450-dependent enzyme reactions giving rise to four primary metabolites of caffeine was investigated using microsomes isolated from livers of human kidney donors. Metabolite formation proceeded at a lower rate than that predicted from in vivo caffeine elimination half-lives, as has been observed in other species using this compound as a substrate in microsomal incubations. Kinetic experiments indicated that the formation of each of the N-demethylated metabolites paraxanthine, theobromine and theophyline was mediated by both a high- and a low-affinity catalytic site over a substrate concentration range from 0.05 mM to 80.0 mM, although only the high-affinity component is likely to be of any importance at normally encountered in vivo caffeine concentrations. 7-Ethoxyresorufin and acetanilide, selective substrates for two polycyclic aromatic hydrocarbon (PAH)-inducible isozymes of cytochrome P-450 in the mouse (P1-450 and P3-450, respectively) were each able to inhibit competitively the formation of caffeine metabolites by human liver microsomes, while caffeine could in turn similarly inhibit the biotransformations of these two compounds. The isozyme-selective P-450 inhibitor alpha-naphthoflavone (ANF) potently inhibited the high-affinity component of caffeine N-demethylations, while 1-phenylimidazole (PI) was a more potent inhibitor of the low-affinity component. The inhibition studies also indicated that the formation of 1,3,7-trimethyluric acid was mediated by both ANF-sensitive and PI-sensitive sites. Taken together, the data support suggestions from in vivo studies that a PAH-inducible isozyme of cytochrome P-450 plays a significant role in the biotransformation of caffeine in man.


Functional surgery in pediatric drug-resistant posterior cortex epilepsy: Electro-clinical findings, cognitive and seizure outcome.
Epilepsies originated from the occipital, parietal and/or the posterior edge of the temporal lobe are grouped together into posterior cortex epilepsy (PCE). Our objective was firstly to describe electro-clinical and imaging findings in the presurgical evaluation of children with PCE, and secondly to identify potential factors associated with surgical and cognitive outcomes. From the total of patients referred to the Epilepsy Monitoring Unit of 'Hospital Universitario Niño Jesús' from 2003 to 2016, 55 had drug-resistant PCE. Different variables obtained from the multimodal presurgical work-up were analyzed among patients achieving seizure freedom after surgery (ILAE class 1) and patients with persistent seizures. Categorical variables were compared with Fisheŕs exact test and numeric variables with t-Student for independent samples, and multiple logistic regression were used to analyze predictive values. Median duration of epilepsy until surgery was 5 years [3-10 years]. Fifty patients showed lesions in the MRI, and 62.5% had concordant MRI-PET corregistration. 37 (67%) patients were operated (lesionectomy in 21 subjects, tailored resection based on intracranial studies in 16), and 23 (62,2%) reached ILAE class 1, with a mean follow-up period of 3.51 [1-12] years. A lower number of basal seizures and antiepileptic drugs, a well-defined lesion on the MRI, an epileptogenic zone (EZ) restricted to the posterior quadrant and the normalization of postsurgical EEGs were associated with seizure freedom (p<0.05). Additionally, 65% of patients had a long-term improvement of cognitive performances. Epilepsy surgery should be considered in children with drug-resistant PCE, especially in those with a restricted EZ.


Apc+/Min colonic epithelial cells express TNF receptors and ICAM-1 when they are co-cultured with large intestine intra-epithelial lymphocytes.
Adenomatous polyposis coli (APC) functions are involved in the heterotypic interactions occurring between intestinal epithelial cells (IECs) and intra-epithelial lymphocytes (IELs). These interactions may be of interest in cancer prevention, since recent data provide evidence for lymphocyte mediated immunosurveillance of epithelial cancers. The present study attempts to determine if APC inactivation induces changes in the cross-talk between IEC and large intestine IEL (LI-IEL) through intercellular adhesion molecule (ICAM-1)/leukocyte function-associated (LFA-1) interactions. Mouse Apc+/+ and Apc+/Min colonocytes were co-cultivated with LI-IEL. When co-cultured with LI-IEL Apc+/Min IEC but not Apc+/+ IEC expressed high levels of ICAM-1. The presence of ICAM-1 was linked to TNFalpha production in both co-cultures and TNFR expression only in co-cultivated Apc+/Min IEC. Finally, butyrate enhanced the expression of ICAM-1 in Apc+/Min IEC co-cultured with LI-IEL, and the secretion of TNFalpha by both types of co-cultures. These events could participate in determining the Apc+/Min IEC immunogenicity under different in vivo conditions.


Modeling CRISPR gene drives for suppression of invasive rodents using a supervised machine learning framework.
Invasive rodent populations pose a threat to biodiversity across the globe. When confronted with these invaders, native species that evolved independently are often defenseless. CRISPR gene drive systems could provide a solution to this problem by spreading transgenes among invaders that induce population collapse, and could be deployed even where traditional control methods are impractical or prohibitively expensive. Here, we develop a high-fidelity model of an island population of invasive rodents that includes three types of suppression gene drive systems. The individual-based model is spatially explicit, allows for overlapping generations and a fluctuating population size, and includes variables for drive fitness, efficiency, resistance allele formation rate, as well as a variety of ecological parameters. The computational burden of evaluating a model with such a high number of parameters presents a substantial barrier to a comprehensive understanding of its outcome space. We therefore accompany our population model with a meta-model that utilizes supervised machine learning to approximate the outcome space of the underlying model with a high degree of accuracy. This enables us to conduct an exhaustive inquiry of the population model, including variance-based sensitivity analyses using tens of millions of evaluations. Our results suggest that sufficiently capable gene drive systems have the potential to eliminate island populations of rodents under a wide range of demographic assumptions, though only if resistance can be kept to a minimal level. This study highlights the power of supervised machine learning to identify the key parameters and processes that determine the population dynamics of a complex evolutionary system.


In silico studies of interactions of peptide-conjugated cholesterol metabolites and betulinic acid with EGFR, LDR, and N-terminal fragment of CCKA receptors.
In this work, we designed three new ligands by conjugating cholesterol metabolites 3-hydroxy-5-cholestenoic acid (3-HC) and 3-oxo-4-cholestenoic acid (3-OC) and the natural tri-terpenoid betulinic acid with the tumor-targeting peptide YHWYGYTPQNVI. Molecular interactions with the unconjugated peptide and the conjugates were examined with three receptors that are commonly overexpressed in pancreatic adenocarcinoma cells using ligand docking and molecular dynamics. This study demonstrated the utility of the designed conjugates as a valuable scaffold for potentially targeting EGFR and LDLR receptors. Our results indicate that the conjugates showed strong binding affinities and formation of stable complexes with EGFR, while the unconjugated peptide, BT-peptide conjugate, an 3-HC-peptide conjugate showed the formation of fairly stable complexes with LDLR receptor. For EGFR, two receptor kinase domains were explored. Interactions with the N-terminal domain of CCKA-R were relatively weaker. For LDLR, binding occurred in the beta-propeller region. For the N-terminal fragment of CCKA-R, the conjugates induced significant conformational changes in the receptor. The molecular dynamic simulations for 100 ns demonstrate that BT-peptide conjugates and the unconjugated peptide had the highest binding and formed the most stable complexes with EGFR. RMSD and trajectory analyses indicate that these molecules transit to a dynamically stable configuration in most cases within 60 ns. NMA analysis indicated that amongst the conjugates that showed relatively higher interactions with the respective receptors, the highest potential for deformability was seen for the N-terminal-47 amino acid region of the CCKA-R receptor with and the lowest for the LDLR-receptor. Thus, the newly designed compounds may be evaluated in the future toward developing drug delivery materials for targeting tumor cells overexpressing LDLR or EGFR.


Stem cell transplantation in noise induced hearing loss.
To investigate efficacy of bone marrow stem cell implantation in rehabilitation of noise induced hearing loss in rats. Hearing loss was induced in male rats by a continuous wide-band noise (8-16 kHz/120 dB/120 min). Ten microliter of stem cell containing solution was injected by a Hamilton syringe with 30 G needle through the round window membrane. Hearing status was examined by, distortion product otoacoustic emissions using DP-OAE. Animals were studied in 4 different groups: (1) Normal hearing animals, undergoing sham surgery (no injection done, only round window membrane ruptured and sealed). (2) Deaf animals, undergoing sham surgery. (3) Deaf animals undergoing surgery and injection of solvent (artificial perilymph). (4) Deaf animals undergoing surgery and injection of artificial perilymph containing BMSCs. DP-Gram in rat with normal hearing undergoing sham surgery show that procedure has neither negative impact on normal cochlear nor on deaf cochleas. No significant difference (p=0.25) between ears excludes artificial perilymph as a confounding factor. There is no significant difference between ears in animals receiving BMSCs. Implanted cells with normal histologic structures have no physiologic function and hearing rehabilitation. Further studies by monitoring the survival of these cells with histologic and appropriate biomarkers will help to investigate differentiation process of these cells.


Documentation and coding education in emergency medicine residency programs: a national survey of residents and program directors.
To assess attitudes and practices of documentation and coding education for emergency medicine residents (EMRs). Questions regarding documentation teaching methods were formulated into online surveys for program directors (PDs) and EMRs. Fifty-three of 104 PDs and 446 of 576 EMRs who received the survey completed it. Although 93% of EMRs and 63% of PDs believe proper chart documentation is an important skill, only 18% of EMRs and 25% of PDs believe their program's teaching was adequate. Eleven percent of EMRs reported that they were comfortable with their knowledge of documentation. EMRs who received formal lectures and feedback reported higher comfort levels with their knowledge of documentation (3.3 ± 1.1 vs. 4.5 ± 1.4, p < 0.05) than those who did not receive formal lectures and feedback. Although most physicians who were surveyed agreed that documentation and coding is a vital skill, many EMRs and PDs report inadequate instruction. Resident education may benefit from broader implementation of formal lectures and formal feedback on documentation and coding skills.


A Rare Presentation of Intraosseous Sarcoidosis of the Mandible Presenting as Peri-Implantitis: A Case Report and Literature Review.
We describe a rare case of intraosseous sarcoidosis initially presenting as peri-implantitis, perform a review and analysis of 27 cases of intraosseous sarcoidosis, and provide a clinical review of this condition. We searched the literature for patients presenting with intraosseous sarcoidosis of the jaw through June 2020 using key phrases. Additional papers were included via a search of references and citing papers. Data including patient demographic characteristics and diagnostic tests were manually extracted from the cases and then qualitatively coded by the authors. Descriptive statistical analysis was performed to elucidate general themes and characteristics. A total of 27 cases, dating as early as 1943 and as recent as this case, were identified in the literature, including our case. The average age of these patients was 39 years old, with a range of 16 to 75 years. Eighteen (67%) cases were identified as female and nine (33%) as male. Fourteen cases were reported with localized mandibular involvement. Ten had maxillary disease; 3 cases were generalized to both regions. Nine cases presented anteriorly, 12 posteriorly, and 6 extended across both regions. Eight patients received surgical interventions, such as tooth extractions or lesion removal. Five patients received nonsurgical interventions, such as steroids. Ten patients received combination therapy, often involving surgical intervention and steroid therapy. Our patient had an unusual presentation of intraosseous sarcoidosis mimicking peri-implantitis. To our knowledge, no case in the English literature describes a patient with sarcoidosis presenting with peri-implantitis. Based on the literature review and analysis of our patient's experience, sarcoidosis should be considered on the differential diagnosis for patients with persistent, nonhealing bony lesions in the maxillofacial region, particularly when patients have not been exposed to osteoclast inhibitory therapy or radiation. Pathologic analysis of bone and surrounding tissue in these scenarios is essential.


Extracranial metastasizing solitary fibrous tumors (SFT) of meninges: histopathological features of a case with long-term follow-up.
Extrapleural solitary fibrous tumors are uncommon mesenchymal neoplasms frequently observed in middle-aged adults and are classified, according to the WHO classification of soft tissue tumors, as part of the hemangiopericytoma tumor group. However, these two entities remain separated in the WHO classification of tumors of the central nervous system. In fact, meningeal solitary fibrous tumors are believed to be benign lesion and only in a minority of cases local relapses have been described, although detailed survival clinical studies on solitary fibrous tumors of meninges are rare. In contrast to hemangiopericytoma, which frequently shows distant extracranial metastases, such an event is exceptional in patients with meningeal solitary fibrous tumors and has been clinically reported in a handful of cases only and their histopathological features have not been investigated in detail. In this report, we describe the detailed clinico-pathological features of a meningeal solitary fibrous tumor presenting during a 17-year follow-up period, multiple intra-, extracranial relapses and lung metastases.


Enzymes of collagen synthesis in lung tissues of bleomycin-induced pulmonary fibrosis.
The activities of prolyl hydroxylase (Pro-OHase), galactosylhydroxylysyl glucosyltransferase (Glu-Gal-Hyl-Tase), and hydroxylysyl galactosyltransferase (Gal-Hyl-Tase) were assayed in lung tissues of hamsters with bleomycin-induced experimental pulmonary fibrosis. Serum Glu-Gal-Hyl-Tase and aspartate transaminase (Asp-NH2-Tase) were measured in the same animals. Lung fibrosis was induced by intratracheal bleomycin instillation, and the enzyme activities were assayed 2, 3, and 4 weeks after bleomycin administration. The activities of the three lung enzymes increased significantly after bleomycin instillation. However, no difference in the values of serum Glu-Gal-Hyl-Tase or Asp-NH2-Tase were observed. Histologic examination of lung sections indicated progressive fibrotic foci. These results thus indicate that the activities of collagen processing enzymes are elevated in the fibrotic lung tissues as a reflection of the increased rate of collagen synthesis during the period of active fibrogenesis, but unlike liver fibrosis, the elevation of tissue Glu-Gal-Hyl-Tase is not predicted by a corresponding increase in serum levels of this enzyme.


Cerebral ammonia production during hypoglycemia in the newborn calf.
The effect of insulin hypoglycaemia on cerebral blood flow, and cerebral metabolic rates of glucose, oxygen and ammonia was investigated in the unanaesthetized newborn calf. A net loss of ammonia from the brain occurred during hypoglycaemia, and was greater in convulsing than in comatose animals.


A non-lethal method to estimate CYP1A expression in laboratory and wild Atlantic salmon (Salmo salar).
Expression of cytochrome P4501A (CYP1A) has been used as a biomarker for possible exposure to contaminants such as PCBs and dioxins in teleost fish. Using a quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR) and a non-lethal gill biopsy, we estimated levels of CYP1A mRNA expression in Atlantic salmon (Salmo salar). Groups of ten Atlantic salmon juveniles (48-76 g) received an intraperitoneal injection of 50 microg g(-1) beta-naphthoflavone (BNF) or vehicle. Their gill tissues were repeatedly sampled by non-lethal biopsies on day 0, 1, 2 and 7. Control fish expressed basal levels of CYP1A over the duration of sampling. BNF-treated salmon demonstrated similar levels of CYP1A to control fish at day 0 and higher levels over the course of each additional sampling point. Gill biopsies from wild salmon sampled from Millers River (South Royalston, Worcester County, MA, USA), known to contain PCBs, showed significantly higher CYP1A levels over an uncontaminated reference stream, Fourmile Brook (Northfield, Franklin County, MA, USA). We conclude that gill biopsies coupled with Q-RT-PCR analysis is a valuable tool in environmental assessment of wild Atlantic salmon populations and has the potential to be applied to other populations of fish as well.


Epidemiología y mortalidad hospitalaria por evento vascular cerebral en un hospital de la Ciudad de México: estudio prospectivo de 2 años.
To describe patient characteristics, case fatality rate, and assess predictors of in-hospital acute ischemic (IS) or hemorrhagic stroke (HS) mortality. Adult patients with confirmed stroke were recruited from January 1st, 2018 to December 31st, 2019.Data collect included demographic and laboratory characteristics, risk factors, and clinical outcome. A binary logistic regression model with relative risk and 95% confidence interval was performed. A total of 172 patients were recruited; IS was present in 78.5% of patients. The mean of age was 75.27 ± 11.44 years in IS group and 71.62 ± 11.72 years in HS group. Hypertension was present in > 70% of patients in both groups; the in-hospital case fatality rate was 15.5% for IS and 21.5% for HS. Severe NIHSS score (> 13) was significantly associated with in-hospital mortality in both stroke types. Hypertension was the most common risk factor in patients with stroke. The in-hospital case fatality rate was lower to previously reported in Mexico. Nevertheless, it remains high compared to reported in developed countries. NIHSS scale was the strongest predictor of mortality. There is a need to develop more effective stroke management services in Mexico.


Effect of decreased umbilical blood flow and hemorrhage, and decreased prostaglandins on the ductus venosus diameter in the rat.
The closing mechanisms of the ductus venosus (DV) have not yet been revealed. The aims of this study were to document the perinatal closing process of the DV, to study the suppression of prostaglandins by indomethacin, and to determine the effects of umbilical blood flow to the fetal DV. The proximal and distal DV diameters were studied in near-term fetal and neonatal rats with the rapid whole-body freezing method. The DV diameter changed sensitively at birth, and decreased by 10% immediately after the cessation of the umbilical circulation. Umbilical hemorrhage caused an additional decrease in the DV diameter compared with neonate without the hemorrhage. The neonates showed a DV diameter decreased by 20% at 30 min and 30% at 60 min after birth. The fetal DV was tubular, and the neonatal DV was horn-shaped with a smaller inlet than outlet. A small dose (0.1 mg/kg) of indomethacin administered to the pregnant rats induced a reduction in prostaglandins and decreased the fetal DV diameter to 80% of the control. Indomethacin at a large dose (10 mg/kg), administered to the dams, induced a reduction in prostaglandins, severe constriction of the ductus arteriosus, and decreased blood flow through the descending aorta umbilicus, and caused a further reduction in the DV diameter to 70-80% of the control. A large dose of nifedipine (10 mg/kg), which causes cardiac suppression and heart failure in the fetus, was administered to near-term rats to study the effect of decreased fetal cardiac output and blood flow passing through the DV. Nifedipine induced a 20% decrease in the DV diameter for 2-8 h. In all 1-hour-old neonates with or without pretreatment, the inlet diameter of the DV was reduced more than the outlet diameter, and the DV showed a horn-shaped morphology. In conclusion, perinatal cessation of the umbilical circulation and umbilical hemorrhage are associated with an immediate decrease in DV diameter. The DV diameter is also reduced in other conditions associated with decreased umbilical blood flow, such as induced by nifedipine which leads to heart failure and constricting of the ductus arteriosus induced by indomethacin. The constricting effect of a small dose of indomethacin suggests that prostaglandins dilate the DV physiologically.


Bilayer rigidity of the erythrocyte membrane2H-NMR of a perdeuterated palmitic acid probe.
Perdeuterated palmitic acid was intercalated into the human erythrocyte membrane and its motion studied by dueterium nuclear magnetic resonance (2H-NMR). From analysis of temperature dependent changes in the 2H-NMR spectra and from an analysis of derived moments we conclude that the acyl chains of the erythrocyte lipids do not exhibit a detectable phase transition.


Effect of fenestrated sterile drape and face mask on bacterial dispersion toward the periocular area during intravitreal injection.
This experimental crossover study was performed to investigate whether fenestrated surgical drapes (covering the nose and mouth but with an opening over the periorbital area) with or without patients' surgical face masks increase periorbital bacterial dispersion during simulated intravitreal injection conditions. Each of the 16 healthy volunteers performed 14 scenarios involving different mask and drape conditions in both silent and speaking situations. In each scenario, the subject lay down flat on the back with a blood agar plate being held at the inferior orbital rim perpendicular to the face to capture airflow from breathing/speaking. Another blood agar plate placed 50 cm away from the subject served as an experimental control. A total of 224 experiments were performed. Speaking situations significantly showed more colony forming units (CFUs) compared with their controls (P = 0.014). There were no significant differences in CFUs between wearing vs not wearing the masks (P = 0.887 for speaking and P = 0.219 for silent) and using vs not using the drapes (P = 0.941 for speaking and P = 0.687 for silent). Reusable and disposable drapes were also not significantly different (P = 1.00 for speaking and P = 0.625 for silent). Streptococcus spp., the oropharyngeal microbiota, were only cultivated from speaking scenarios. While refraining from speaking (for both practitioners and patients) is the mainstay of reducing bacterial dispersion and risks of post-injection endophthalmitis, the use of fenestrated surgical drapes or patients' face masks did not significantly affect the amount of bacterial dispersion toward the periorbital area.


doublesex alters aggressiveness as a function of social context and sex in the polyphenic beetle Onthophagus taurus.
Despite sharing nearly the same genome, individuals within the same species can vary drastically in both morphology and behaviour as a function of developmental stage, sex or developmental plasticity. Thus, regulatory processes must exist that enable the stage-, sex- or environment-specific expression of traits and their integration during ontogeny, yet exactly how trait complexes are co-regulated and integrated is poorly understood. In this study, we explore the developmental genetic basis of the regulation and integration of environment-dependent sexual dimorphism in behaviour and morphology in the horn-polyphenic dung beetle Onthophagus taurus through the experimental manipulation of the transcription factor doublesex (dsx). The gene dsx plays a profound role in the developmental regulation of morphological differences between sexes as well as alternative male morphs by inhibiting horn formation in females but enabling nutrition-responsive horn growth in males. Specifically, we investigated whether experimental downregulation of dsx expression affects male and female aggressive and courtship behaviours in two social contexts: interactions between individuals of the same sex and interactions between males and females. We find that dsx downregulation significantly alters aggressiveness in both males and females, yet does so differently for both sexes as a function of social context: dsxRNAi males exhibited elevated aggression towards males but showed reduced aggression towards females, whereas dsxRNAi females became more aggressive towards males, while their aggressiveness towards other females was unaffected. Moreover, we document unexpectedly high levels of female aggression independent of dsx treatment in both wild-type and control-injected individuals. Lastly, we found no effects of dsxRNAi on courtship and mating behaviours. We discuss the role of dsx in the regulation of sex-specific and plastic behaviours, the unexpectedly high levels of aggression of hornless dsxRNAi males in relation to the well-established description of the hornless sneaker phenotype and the potential ecological function of high female aggression.


Multidimensional prognostic index (MPI) predicts successful application for disability social benefits in older people.
The economic recognition of disability is of importance in daily practice, but the tools used in older people are still limited. Therefore, we aimed to investigate the effectiveness of the multidimensional prognostic index (MPI) to identify frail older subjects to be submitted to civil invalidity application for disability benefits including Attendance Allowance (AA) indemnity, Carer's Leave (Law 104) and/or Parking Card for people with disabilities. From March 2018 to January 2019, 80 older people were included. The MPI was calculated from comprehensive geriatric assessment information including eight different domains. Civil benefits included attendance allowance (AA) indemnity by the Local Medico-Legal Committee (MLC-NHS) and by the National Institute of Social Security Committee (INPS), Carer's Leave (Law 104), and Parking Card for people with disabilities. MPI values were associated with an increased probability to obtain a 100% civil disability, AA indemnity, Carer's Leave and a parking card for people with disabilities. MPI score showed a very good accuracy in predicting the civil invalidity benefits with a area-under-curve (AUC) of 87.3 (95% CI 80.6-97.4) to predict the release of AA indemnity, 81.3 (95% CI 68.5-91.1) to predict Care's leave and 70.7 (95% CI 59.4-84.7) to predict the Parking Card release. Moreover, data showed that a cut-off score of MPI ≥ 0.75 could identify the 100% of older subjects who successfully obtained the indemnity release. MPI is an excellent predictor of social benefits' release by local and national agencies.


A Bayesian switching linear dynamical system for estimating seizure chronotypes.
Epilepsy is a disorder characterized by paroxysmal transitions between multistable states. Dynamical systems have been useful for modeling the paroxysmal nature of seizures. At the same time, intracranial electroencephalography (EEG) recordings have recently discovered that an electrographic measure of epileptogenicity, interictal epileptiform activity, exhibits cycling patterns ranging from ultradian to multidien rhythmicity, with seizures phase-locked to specific phases of these latent cycles. However, many mechanistic questions about seizure cycles remain unanswered. Here, we provide a principled approach to recast the modeling of seizure chronotypes within a statistical dynamical systems framework by developing a Bayesian switching linear dynamical system (SLDS) with variable selection to estimate latent seizure cycles. We propose a Markov chain Monte Carlo algorithm that employs particle Gibbs with ancestral sampling to estimate latent cycles in epilepsy and apply unsupervised learning on spectral features of latent cycles to uncover clusters in cycling tendency. We analyze the largest database of patient-reported seizures in the world to comprehensively characterize multidien cycling patterns among 1,012 people with epilepsy, spanning from infancy to older adulthood. Our work advances knowledge of cycling in epilepsy by investigating how multidien seizure cycles vary in people with epilepsy, while demonstrating an application of an SLDS to frame seizure cycling within a nonlinear dynamical systems framework. It also lays the groundwork for future studies to pursue data-driven hypothesis generation regarding the mechanistic drivers of seizure cycles.


Workplace Bullying and Violence on Burnout Among Bangladeshi Registered Nurses: A Survey Following a Year of the COVID-19 Pandemic.
Objectives: To investigate burnout among Bangladeshi nurses and the factors that influence it, particularly the association of workplace bullying (WPB) and workplace violence (WPV) with burnout. Methods: This cross-sectional study collected data from 1,264 Bangladeshi nurses. Mixed-effects Poisson regression models were fitted to find the adjusted association between WPB, WPV, and burnout. Results: Burnout was found to be prevalent in 54.19% of 1,264 nurses. 61.79% of nurses reported that they had been bullied, and 16.3% of nurses reported experience of "intermediate and high" levels of workplace violence in the previous year. Nurses who were exposed to "high risk bullying" (RR = 2.29, CI: 1.53-3.41) and "targeted bullying" (RR = 4.86, CI: 3.32-7.11) had a higher risk of burnout than those who were not. Similarly, WPV exposed groups at "intermediate and high" levels had a higher risk of burnout (RR = 3.65, CI: 2.40-5.56) than WPV non-exposed groups. Conclusion: Nurses' burnout could be decreased if issues like violence and bullying were addressed in the workplace. Hospital administrators, policymakers, and the government must all promote and implement an acceptable working environment.