Robustness of a new three-dimensional echocardiographic algorithm for left ventricular volume and ejection fraction quantification: experts vs. novices.
We evaluated the ability of a new simplified algorithm for three-dimensional echocardiography (3DE) left ventricular (LV) measurements with minimal operator interaction to be reproducible and robust, independently of the experience. A total of 163 subjects were investigated using two-dimensional echocardiography (2DE) and 3DE. The 3D data sets were blindly analysed offline by novice investigators and experts. A subgroup of 30 patients was assessed using cardiac magnetic resonance imaging (CMRI) to compare end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) obtained by 2DE, 3DE, and CMRI. Intra-observer and inter-observer variabilities of 2DE and 3DE measurements were evaluated according to level of experience. Mean time analysis of 3DE data was 23.2 ± 6.3s for the novice and 26.1 ± 4.1 s for the expert (P = ns). Correlations (r) and mean error measurements (MEM) between 3DE analysis by experts and novices were 0.91 and -3.5 mL for EDV, 0.97 and 4.3 mL for ESV, and 0.91 and -2.6% for EF, respectively. Correlations between 3DE and CMRI were good with low variability and greater agreement when compared with those between 2DE and CMRI. For the novice, MEM was -21.3 mL for EDV, -15.0 mL for ESV, and 2.3% for EF. MEM and 95% confidence intervals were wider for 2DE vs. CMRI than for 3DE vs. CMRI in relation to both expert and novice. This new semi-automated algorithm of LV endocardial border detection based on 3DE data appears suitable for clinical use by either expert or novice investigators with greater reproducibility and time of analysis than 2DE.


Computer tablet distraction reduces pain and anxiety in pediatric burn patients undergoing hydrotherapy: A randomized trial.
Distraction is often used in conjunction with analgesics to minimize pain in pediatric burn patients during treatment procedures. Computer tablets provide many options for distraction items in one tool and are often used during medical procedures. Few studies have examined the effectiveness of tablet distraction in improving the care of pediatric burn patients. This study examines the effectiveness of tablet distraction provided by a child life specialist to minimize pain and anxiety in pediatric burn patients undergoing hydrotherapy. Thirty pediatric patients (4-12) undergoing hydrotherapy for the treatment of burns participated in this randomized clinical trial. The tablet distraction group received tablet distraction provided by a child life specialist while those in the control group received standard care. Pain was assessed through self-reports and observation reports. Anxiety was assessed through behavioral observations. Length of procedure was also recorded. Nurses reported significantly less pain for the tablet distraction group compared to the control group. There was no significant difference between groups on self-reported pain. The tablet distraction group displayed significantly less anxiety during the procedure compared to the control group. Also, the tablet distraction group returned to baseline after the procedure while those in the control group displayed higher anxiety post-procedure. There was no difference in the length of the procedure between groups. These findings suggest tablet distraction provided by a child life specialist may be an effective method for improving pain and anxiety in children undergoing hydrotherapy treatment for burns.


Down-regulation of phytochrome mRNA abundance by red light and benzyladenine in etiolated cucumber cotyledons.
Northern blot analysis revealed that a single 4.2 kb phytochrome mRNA species was detectable in cotyledons excised from five-day-old etiolated cucumber seedlings. Intact etiolated five-day-old cucumber seedlings were given a red light or benzyladenine treatment, and cotyledons were harvested at various times following treatment. The abundance of phytochrome mRNA in the cotyledons was quantitated using 32P-labeled RNA probes and slot blot analysis. By 2 h after irradiation the phytochrome mRNA level was reduced to 40% of the initial abundance and reaccumulation began by 3 h after irradiation. Reaccumulation of phytochrome mRNA to the time-zero dark control level was achieved by 10 h after treatment. A decrease in phytochrome mRNA abundance was evident by 2 h after benzyladenine treatment, and a maximal reduction to 45% of the time-zero dark control was attained by 4 h after treatment. No recovery of the phytochrome mRNA level was evident by 8 h after benzyladenine treatment. The abundance of actin mRNA was unaffected by benzyladenine treatment.


A new preparedness policy for EMS logistics.
Response time in emergency medical services (EMS) is defined as the interval for an ambulance to arrive the scene after receipt of a 911 call. When several ambulances are available upon the receipt of a new call, a decision of selecting an ambulance has to be made in an effort to reduce response time. Dispatching the closest unit available is commonly used in practice; however, recently the Preparedness policy was designed that is in a simplistic form yet being capable of securing a long-term efficiency. This research aims to improve the Preparedness policy, resolving several critical issues inherent in the current form of the policy. The new Preparedness policy incorporates a new metric of preparedness based on the notion of centrality and involves a tuning parameter, weight on preparedness, which has to be appropriately chosen according to operational scenario. Computational experiment shows that the new policy significantly improves the former policy robustly in various scenarios.


Interspecies transmission and limited persistence of low pathogenic avian influenza genomes among Alaska dabbling ducks.
The reassortment and geographic distribution of low pathogenic avian influenza (LPAI) virus genes are well documented, but little is known about the persistence of intact LPAI genomes among species and locations. To examine persistence of entire LPAI genome constellations in Alaska, we calculated the genetic identities among 161 full-genome LPAI viruses isolated across 4 years from five species of duck: northern pintail (Anas acuta), mallard (Anas platyrhynchos), American green-winged teal (Anas crecca), northern shoveler (Anas clypeata) and American wigeon (Anas americana). Based on pairwise genetic distance, highly similar LPAI genomes (>99% identity) were observed within and between species and across a range of geographic distances (up to and >1000 km), but most often between isolates collected 0-10 km apart. Highly similar viruses were detected between years, suggesting inter-annual persistence, but these were rare in our data set with the majority occurring within 0-9 days of sampling. These results identify LPAI transmission pathways in the context of species, space and time, an initial perspective into the extent of regional virus distribution and persistence, and insight into why no completely Eurasian genomes have ever been detected in Alaska. Such information will be useful in forecasting the movement of foreign-origin avian influenza strains should they be introduced to North America.


Congenital absence of the flexor pollicis longus--a case report.
Congenital absence of the flexor pollicis longus, associated with hypoplasia of the thumb, is an unusual anomaly. A case of congenital absence of the flexor pollicis longus without hypoplasia or aplasia of the thumb and thenar muscles, which is described, is very rare. Surgical treatment for the transfer of the ring finger flexor superficialis tendon to provide the thumb interphalangeal joint with flexion resulted in a significant improvement in pinch.


Amlodipine has a preventive effect on temporal left ventricular hypokinesia after emotional stress compared with an angiotensin II receptor blocker.
We previously reported that α- and β-blockers protected against emotional stress-induced cardiac dysfunction, but the protective effects of other antihypertensive drugs is unknown. The purpose of this study is to evaluate the ability of a calcium channel blocker, amlodipine, to prevent temporal left ventricular hypokinesia after emotional stress compared with an angiotensin II receptor blocker, olmesartan medoxomil. Rats premedicated with amlodipine (0.2 mg/kg), olmesartan (0.8 mg/kg), or vehicle were restrained for 30 min (immobilization stress: IMO) to reproduce emotional stress and then anesthetized to release stress. We measured the fractional area change (FAC) using echocardiography (SONOS5500) with a s12 probe (frequency 5-12 MHz, frame rate 120 Hz) and blood pressure and heart rate at the end of IMO and every 10 for 60 min after IMO. During IMO, FAC in the amlodipine or the olmesartan group was as high as that in the vehicle group. At 20 min after IMO, FAC in the amlodipine group was significantly higher than in the other two groups (84 ± 8 vs. 60 ± 7 or 68 ± 15 %, p < 0.05). During IMO, blood pressure in the amlodipine or the olmesartan group was significantly lower than with vehicle (119 ± 6 and 110 ± 7 vs. 124 ± 5 mmHg, p < 0.05). After IMO, blood pressure in the olmesartan group was significantly lower than in the other two groups. Acute administration of amlodipine could prevent a sudden drop in cardiac function after acute stress like IMO, but olmesartan did not. Amlodipine might have a protective effect on temporal left ventricular hypokinesia after emotional stress, which might not be related to decreased blood pressure.


Optimization of Gaussian Kernel Function in Support Vector Machine aided QSAR studies of C-aryl glucoside SGLT2 inhibitors.
The present investigations include utility of latest statistical algorithm Support Vector Machine (SVM) to identify non-linear structure activity relationship between IC50 values and structures of C-aryl glucoside SGLT2 inhibitors. Training dataset consisted of forty molecules and the remaining six molecules were chosen for test set validation. SVM under Gaussian Kernel Function yielded non-linear QSAR models. Forward selection algorithm was applied after pruning and redundancy check on molecular descriptors. Internal validations of QSAR models have been achieved using R CV (2) (LOO), PRESS, SDEP and Y-Scrambling. SVM aided non-linear models are more efficient when optimization of Gaussian Kernel Function was introduced. Non-linear QSAR studies further identified atomic van der Waals volumes, atomic masses, sum of geometrical distances between O..S and degree of unsaturation as molecular descriptors and crucial structural requirements to model IC50 of C-aryl glucoside derivatives.


[Anomalous connections of coronary arteries : About 4 cases and litterature review].
Coronary connection anomalies are a rare congenital anatomical aberration with an angiographic incidence of around 1%. In the majority of cases, these anomalies are incidentally discovered during coronary angiography or coro CT and remain silent without clinical translation, while in a certain number of cases, they can be responsible for serious clinical manifestations of up to sudden death. Coronary CT is crucial in the management of its patients since it makes it possible to objectify the presence of a pre-aortic course or the existence of an intramural aortic trajectory, two characteristics associated with the occurrence of sudden death. Through four clinical cases we illustrate the different situations in which we had to manage these anomalies.


[Clinical practice guidelines for assessment and treatment of transsexualism. SEEN Identity and Sexual Differentiation Group (GIDSEEN)].
Transsexual patients can only be diagnosed and treated at functional gender identity Units with provision of high quality care, development of clinical practice guidelines, and interdisciplinary working groups. The therapeutic process has three mainstays: initial psychological diagnostic evaluation and psychotherapy, endocrinological evaluation and hormone therapy, and sex reassignment surgery. Cross-sex hormone therapy is essential for the anatomical and psychological transition process in duly selected patients. Hormones help optimize real-life sex identity, improve quality of life, and limit psychiatric co-morbidities often associated to lack of treatment. Development of this clinical practice guideline addresses the need for implementing a coordinated action protocol for comprehensive health care for transgender people in the National Health System.


Isotachophoretic determination of chromium(VI) at low parts per billion concentrations.
Factors important in the isotachophoretic determination of CrVI at low ppb concentrations were studied. To increase the selectivity of the analysis, the use of photometric detection at a 405 wavelength was preferred. Losses of CrVI due to adsorption were found to be the main potential source of analytical errors at the concentration levels of interest. The presence of sulphate in the sample solution at ca. 10(-4) M concentration eliminated the losses due to adsorption on the walls of the sample handling glassware. In analysis with a low pH of the leading electrolyte, adsorption of CrVI on the walls of the separation compartment also played a role; addition of naphthalene-1,3,6-trisulphonate to the sample solution considerably reduced this disturbance. When the precautions concerning adsorption were taken, the detection limits for CrVI were in the range 4-5 ppb (depending on the pH of the leading electrolyte) for a 30-microliters sample volume. The calibration graphs were linear over the concentration range 10(-7)-5 X 10(-6) M with good correlation coefficients. The reproducibilities of the determinations within this concentration range were 2-3% or better. The practical utility of capillary isotachophoresis in the trace determination of CrVI in drinking water and wastewater samples seems promising.


Misperceptions of peer drinking norms in Canada: another look at the "reign of error" and its consequences among college students.
Much research has documented extensive misperceptions of drinking norms and their negative effects in U.S. student populations. This study provides extensive research evidence documenting this phenomenon in Canadian higher education. Data were collected in a 2003-2004 survey of students (N=5280) attending 11 institutions across Canada. Surveys were administered either to a random sample of students through the mail or to students attending a diverse selection of classes. Regardless of the actual drinking norm on each campus, students most commonly overestimated the alcohol consumption norms (both quantity and frequency levels) in every instance. Students' perception of their campus drinking norm was the strongest predictor of the amount of alcohol personally consumed in comparison with the influence of all demographic variables. Perception of the norm was also a much stronger predictor of personal use than the actual campus norm for consumption on each campus or the actual norm for compliance with campus regulations. Among students who personally abstain or consume lightly, misperceptions of the student drinking norms contribute to alienation from campus life. The data presented here on Canadian students extends the evidence that peer drinking norms are grossly misperceived and that these misperceptions produce a highly detrimental "reign of error" in the lives of college students. The data suggest that a broad range of students--abstainers and light drinkers as well as moderate and heavy drinkers--may benefit from implementing intervention strategies that can correct or reduce these misperceptions.


Cartilage-derived retinoic acid-sensitive protein (CD-RAP): A stage-specific biomarker of heterotopic endochondral ossification (HEO) in fibrodysplasia ossificans progressiva (FOP).
Genesis of a cartilaginous scaffold is an obligate precursor to bone formation in heterotopic endochondral ossification (HEO). We tested the hypothesis that cartilage-derived retinoic acid-sensitive protein (CD-RAP) can serve as a plasma biomarker for the pre-osseous cartilaginous stage of HEO. Palovarotene, a retinoic acid receptor-gamma (RARγ) agonist, has been proposed as a possible treatment for fibrodysplasia ossificans progressiva (FOP) and is a potent inhibitor of HEO in mouse models. Current drug development for FOP mandates the identification of stage-specific biomarkers to facilitate the evaluation of clinical trial endpoints. Here we show in an injury-induced, constitutively-active transgenic mouse model of FOP that CD-RAP levels peaked between day-7 and day-10 during the zenith of histologically-identified chondrogenesis, preceded radiographically apparent HEO, and were diminished by palovarotene. Cross-sectional analysis of CD-RAP levels in plasma samples from FOP patients demonstrated a statistically non-significant trend toward higher levels in the recent flare-up period (three weeks to three months within onset of symptoms). However, in a longitudinal subgroup analysis of patients followed for at least six months after resolution of flare-up symptoms, there was a statistically significant decrease of CD-RAP when compared to levels in the same patients at the time of active or recent exacerbations. These data support the further exploration of CD-RAP as a stage-specific biomarker of HEO in FOP.


Nanocellulose-based Surface-enhanced Raman spectroscopy sensor for highly sensitive detection of TNT.
Surface-enhanced Raman scattering (SERS) has undergone an important development in the detection and identification of extremely low traces of explosives over the past few years. Here we fabricated a new type of three-dimensional (3D) SERS sensors by loading AuNR@AgNCs on bacterial cellulose aerogels for the detection of 2, 4, 6-trinitrotoluene (TNT). The aerogel substrates with hierarchical pore structure are favored by the construction of dense 3D hot-spot distribution and the enrichment of TNT molecules. The retention aid of polyethyleneimine was used to improve the loading capacity as well as prevent the aggregation of nanoparticles. Moreover, AuNR@AgNCs were modified with p-aminobenzenethiol to improve the affinity of SERS substrates to TNT via the formation of Meisenheimer complex. Owing to the unique structure and morphology of AuNR@AgNCs, the composite SERS substrate can detect trace TNT with a limit of detection of 8 × 10-12 g/L and the SERS enhancement factor is high up to 1.87 × 108.


The Effect of Zoledronic Acid on Bone Microarchitecture and Strength after Denosumab and Teriparatide Administration: DATA-HD Study Extension.
The combination of denosumab and teriparatide is an effective treatment strategy in postmenopausal osteoporosis, though skeletal gains are promptly lost when these agents are discontinued. In the DATA-HD study, we reported that a single dose of zoledronic acid (ZOL) maintains the increases in areal spine and hip bone mineral density (BMD) achieved with this combination for at least 12 months. The capacity of ZOL to maintain corresponding improvements in peripheral volumetric BMD and microarchitecture, however, has not been reported. In the 15-month DATA-HD study, 76 postmenopausal osteoporotic women were randomized to receive 9 months of teriparatide (20-μg or 40-μg daily) overlapped with denosumab (60 mg at months 3 and 9). In the Extension study, 53 participants received a single dose of ZOL (5 mg intravenously) 24-35 weeks after the last denosumab dose. We measured volumetric BMD and microarchitecture at the distal radius and tibia using high-resolution peripheral quantitative computed tomography at months 27 and 42. Despite ZOL administration, total and cortical BMD gradually decreased over 27 months resulting in values similar to baseline at the radius but still significantly above baseline at the tibia. At both sites, cortical porosity decreased to values below pretreatment baseline at month 27 but then increased from month 27 to 42. There were no significant changes in trabecular parameters throughout the 27-month post-ZOL observation period. Stiffness and failure load, at both sites, decreased progressively from month 15 42 though remained above baseline at the tibia. These findings suggest that in contrast to the largely maintained gains in dual-energy X-ray absorptiometry (DXA)-derived spine and hip BMD, a single dose of ZOL was not as effective in maintaining the gains in volumetric peripheral bone density and microarchitecture produced by 15 months of overlapping treatment with denosumab and teriparatide. Alternative therapeutic approaches that can fully maintain improvements in peripheral bone parameters require further study. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).


Anti-epileptogenesis: Electrophysiology, diffusion tensor imaging and behavior in a genetic absence model.
The beneficial effects of chronic and early pharmacological treatment with ethosuximide on epileptogenesis were studied in a genetic absence epilepsy model comorbid for depression. It was also investigated whether there is a critical treatment period and treatment length. Cortical excitability in the form of electrical evoked potentials, but also to cortico-thalamo-cortical network activity (spike-wave discharges, SWD and afterdischarges), white matter changes representing extra cortico-thalamic functions and depressive-like behavior were investigated. WAG/Rij rats received either ethosuximide for 2 months (post natal months 2-3 or 4-5), or ethosuximide for 4 months (2-5) in their drinking water, while control rats drank plain water. EEG measurements were made during treatment, and 6 days and 2 months post treatment. Behavioral test were also done 6 days post treatment. DTI was performed ex vivo post treatment. SWD were suppressed during treatment, and 6 days and 2 months post treatment in the 4 month treated group, as well as the duration of AD elicited by cortical electrical stimulation 6 days post treatment. Increased fractional anisotropy in corpus callosum and internal capsula on DTI was found, an increased P8 evoked potential amplitude and a decreased immobility in the forced swim test. Shorter treatments with ETX had no large effects on any parameter. Chronic ETX has widespread effects not only within but also outside the circuitry in which SWD are initiated and generated, including preventing epileptogenesis and reducing depressive-like symptoms. The treatment of patients before symptom onset might prevent many of the adverse consequences of chronic epilepsy.


Isoflurane impairs olfaction by increasing neuronal activity in the olfactory bulb.
General anesthesia can induce cognitive deficits in both humans and rodents, correlating with pathological alterations in the hippocampus. However, whether general anesthesia affects olfactory behaviors remains controversial as clinical studies have produced inconsistent results. Therefore, we aimed to investigate how olfactory behaviors and neuronal activity are affected by isoflurane exposure in adult mice. The olfactory detection test, olfactory sensitivity test, and olfactory preference/avoidance test were used to examine olfactory function. In vivo electrophysiology was performed in awake, head-fixed mice to record single-unit spiking and local field potentials in the olfactory bulb (OB). We also performed patch-clamp recordings of mitral cell activity. For morphological studies, immunofluorescence and Golgi-Cox staining were applied. Repeated exposure to isoflurane impaired olfactory detection in adult mice. The main olfactory epithelium, the first region exposed to anesthetics, displayed increased proliferation of basal stem cells. In the OB, a crucial hub for olfactory processing, repeated isoflurane exposure increased the odor responses of mitral/tufted cells. Furthermore, the odor-evoked high gamma response was decreased after isoflurane exposure. Whole-cell recordings further indicated that repeated isoflurane exposure increased the excitability of mitral cells, which may be due to weakened inhibitory input in isoflurane-exposed mice. In addition, elevated astrocyte activation and glutamate transporter-1 expression in the OB were observed in isoflurane-exposed mice. Our findings indicate that repeated isoflurane exposure impairs olfactory detection by increasing neuronal activity in the OB in adult mice.


PCRCR complex is essential for invasion of human erythrocytes by Plasmodium falciparum.
The most severe form of malaria is caused by Plasmodium falciparum. These parasites invade human erythrocytes, and an essential step in this process involves the ligand PfRh5, which forms a complex with cysteine-rich protective antigen (CyRPA) and PfRh5-interacting protein (PfRipr) (RCR complex) and binds basigin on the host cell. We identified a heteromeric disulfide-linked complex consisting of P. falciparum Plasmodium thrombospondin-related apical merozoite protein (PfPTRAMP) and P. falciparum cysteine-rich small secreted protein (PfCSS) and have shown that it binds RCR to form a pentameric complex, PCRCR. Using P. falciparum lines with conditional knockouts, invasion inhibitory nanobodies to both PfPTRAMP and PfCSS, and lattice light-sheet microscopy, we show that they are essential for merozoite invasion. The PCRCR complex functions to anchor the contact between merozoite and erythrocyte membranes brought together by strong parasite deformations. We solved the structure of nanobody-PfCSS complexes to identify an inhibitory epitope. Our results define the function of the PCRCR complex and identify invasion neutralizing epitopes providing a roadmap for structure-guided development of these proteins for a blood stage malaria vaccine.


Value of the fT3/fT4 ratio and its combination with the GRACE risk score in predicting the prognosis in euthyroid patients with acute myocardial infarction undergoing percutaneous coronary intervention: a prospective cohort study.
Thyroid hormones deeply influence the cardiovascular system; however, the association between the fT3/fT4 ratio and the clinical outcome in euthyroid patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) is not well defined. Therefore, the present study aimed to assess the prognostic performance of the fT3/fT4 ratio in predicting the long-term prognosis in euthyroid patients with AMI undergoing PCI. In a prospective cohort study with a 1-year follow-up, according to the clinical end point, 953 euthyroid individuals (61.0 ± 11.6; female, 25.8%) were divided into two groups: (1) the survival group (n = 915) and (2) the death group (n = 38). According to Cox regression multivariate analysis, fT4 (HR: 1.249, 95% CI: 1.053-1.480, p = 0.010) and the fT3/fT4 ratio (HR: 3.546, 95% CI: 1.705-7.377, p = 0.001) were associated with an increased risk of 1-year all-cause mortality. The prognostic performance of the fT3/fT4 ratio was similar to the Global Registry of Acute Coronary Events (GRACE) score in predicting 1-year all-cause mortality (C-statistic: z = 0.261, p = 0.794; IDI: -0.017, p = 0.452; NRI: -0.049, p = 0.766), but better than fT4 (C-statistic: z = 2.438, p = 0.015; IDI: 0.053, p = 0.002; NRI: 0.656, p < 0.001). The fT3/fT4 ratio also significantly improved the prognostic performance of the GRACE score (GRACE score vs GRACE score + fT3/fT4 ratio: C-statistic: z = 2.116, p = 0.034; IDI: 0.0415, p = 0.007; NRI: 0.614, p < 0.001). In euthyroid patients with AMI undergoing PCI, the fT3/fT4 ratio was an independent predictor of 1-year all-cause mortality. Its prognostic performance was similar to the GRACE score, and also improved its prognostic performance (GRACE score vs GRACE score + fT3/fT4 ratio).


High-dose follicle-stimulating hormone stimulation at the onset of the menstrual cycle does not improve the in vitro fertilization outcome in low-responder patients.
In an attempt to improve their outcome with in vitro fertilization (IVF), 34 low-responder patients were stimulated with six ampules of follicle-stimulating hormone (FSH) daily starting on day 1 (n = 17) or day 2 (n = 17) of their menstrual cycles. The stimulated cycles showed a mean peak estradiol of 443 +/- 173 pg/mL, mean days of human chorionic gonadotropin of 7.6 +/- 1.4, 2.67 +/- 1.5 preovulatory oocytes per retrieval, and 2.56 +/- 1.3 oocytes per transfer. Three clinical pregnancies resulted after 25 embryo transfer cycles (12%). With paired analysis, we compared 8 patient cycles with prior six ampules of FSH stimulation starting on day 3; all parameters examined showed no significant differences. In a comparison of 22 patient cycles with prior 4 ampules of FSH stimulation on cycle day 3, no significant differences in any parameters were observed except in the higher number of ampules used in the present study. We conclude that high-dose FSH stimulation at the onset of the menstrual cycle does not improve the IVF outcome in low-responder patients.


Automated direct screening for resistance of Gram-negative blood cultures using the BD Kiestra WorkCell.
Early detection of resistance in sepsis due to Gram-negative organisms may lead to improved outcomes by reducing the time to effective antibiotic therapy. Traditional methods of resistance detection require incubation times of 18 to 48 h to detect resistance. We have utilised automated specimen processing, digital imaging and zone size measurements in conjunction with direct disc susceptibility testing to develop a method for the rapid screening of Gram-negative blood culture isolates for resistance. Positive clinical blood cultures with Gram-negative organisms were prospectively identified and additional resistant mock specimens were prepared. Broth was plated and antibiotic-impregnated discs (ampicillin, ceftriaxone, piperacillin-tazobactam, meropenem, ciprofloxacin, gentamicin) were added. Plates were incubated, digitally imaged and zone sizes were measured using the BD Kiestra WorkCell laboratory automation system. Minimum, clinically useful, incubation times and optimised zone size cut-offs for resistance detection were determined. We included 187 blood cultures in the study. At 5 h of incubation, > 90% of plates yielded interpretable results. Using optimised zone size cut-offs, the sensitivity for resistance detection ranged from 87 to 100%, while the specificity ranged from 84.7 to 100%. The sensitivity and specificity for piperacillin-tazobactam resistance detection was consistently worse than for the other agents. Automated direct disc susceptibility screening is a rapid and sensitive tool for resistance detection in Gram-negative isolates from blood cultures for most of the agents tested.


Risk Factors for Postprocedural Arterial Ischemic Stroke in Children With Cardiac Disease.
Cardiac pathologies are the second most frequent risk factor (RF) in children with arterial ischemic stroke (AIS). This study aimed to analyze RFs for AIS in children with cardiac disease and cardiac intervention. Data were drawn from the Swiss Neuropediatric Stroke Registry. Patients with cardiac disease and postprocedural AIS registered from 2000 until 2015 were analyzed for the cause of cardiac disease and for potential RFs. Forty-seven out of 78 children with cardiac disease had a cardiac intervention. Of these, 36 presented a postprocedural AIS. Median time from cardiac intervention to symptom onset was 4 days (interquartile range, 2-8.5); time to diagnosis of AIS was 2 days (interquartile range, 0-5.8). Main RFs for postprocedural AIS were hypotension, prosthetic cardiac material, right-to-left shunt, arrhythmias, low cardiac output, and infections. In children with postprocedural AIS, time to diagnosis was delayed. Most patients presented multiple potentially modifiable RFs as hemodynamic alterations and infections.


Towards an ontological representation of morbidity and mortality in Description Logics.
Despite the high coverage of biomedical ontologies, very few sound definitions of death can be found. Nevertheless, this concept has its relevance in epidemiology, such as for data integration within mortality notification systems. We here introduce an ontological representation of the complex biological qualities and processes that inhere in organisms transitioning from life to death. We further characterize them by causal processes and their temporal borders. Several representational difficulties were faced, mainly regarding kinds of processes with blurred or fiat borders that change their type in a continuous rather than discrete mode. Examples of such hard to grasp concepts are life, death and its relationships with injuries and diseases. We illustrate an iterative optimization of definitions within four versions of the ontology, so as to stress the typical problems encountered in representing complex biological processes. We point out possible solutions for representing concepts related to biological life cycles, preserving identity of participating individuals, i.e. for a patient in transition from life to death. This solution however required the use of extended description logics not yet supported by tools. We also focus on the interdependencies and need to change further parts if one part is changed. The axiomatic definition of mortality we introduce allows the description of biologic processes related to the transition from healthy to diseased or injured, and up to a final death state. Exploiting such definitions embedded into descriptions of pathogen transmissions by arthropod vectors, the complete sequence of infection and disease processes can be described, starting from the inoculation of a pathogen by a vector, until the death of an individual, preserving the identity of the patient.


CXCR4 chemokine receptors (CD184) and alpha4beta1 integrins mediate spontaneous migration of human CD34+ progenitors and acute myeloid leukaemia cells beneath marrow stromal cells (pseudoemperipolesis).
Marrow stromal cells play an important role in regulating the development and proliferation of haematopoietic stem cells (HSC) within the marrow microenvironment. However, the molecular mechanisms of stem cell-stromal cell interactions are not fully understood. We observed that mobilized peripheral blood and cord-blood-derived CD34+ progenitor cells, or CD34+ acute myeloid leukaemia (AML) cells spontaneously migrated beneath marrow stromal cells, an in vitro migration phenomenon termed pseudoemperipolesis. In contrast, the CD34+ myeloid leukaemia cell line, Kasumi-1, did not display pseudoemperipolesis. Cord blood CD34+ cells had a higher capacity than granulocyte-colony-stimulating-factor-mobilized CD34+ cells for pseudoemperipolesis (28.7 +/- 12%vs 18.1 +/- 6.1% of input cells within 24 h, mean +/- SD, n = 8), whereas 9.4 +/- 12.6% (mean +/- SD, n = 10) of input AML cells displayed this phenomenon. Pseudoemperipolesis of CD34+ progenitor and AML cells was significantly inhibited by pertussis toxin and antibodies to the CXCR4 chemokine receptor (CXCR4, CD184), but not control antibodies. Moreover, CD34+ and AML cell migration was significantly inhibited by a CS1 peptide that blocks alpha4beta1 integrin binding, but not by a control peptide, in which the fibronectin binding motif was scrambled. Pseudoemperipolesis was associated with an increased proliferation of migrated CD34+ progenitor cells but not AML cells within the stromal layer, demonstrated by cell cycle analysis and cell division tracking. We conclude that alpha4beta1 integrin binding and CXCR4 chemokine receptor activation are prerequisites for the migration of CD34+ haematopoietic progenitors and AML cells beneath marrow stromal cells. These observations suggest a central role of marrow stromal cells for HSC trafficking and homing within the marrow microenvironment.


Effects of an internet-based self-help intervention for psychological distress due to COVID-19: Results of a randomized controlled trial.
The COVID-19 pandemic and its far-reaching impact on physical and mental health generate high demand and, accordingly, a great need for treatment opportunities that promote well-being and manage psychological distress. Internet-based interventions are particularly suitable for this purpose. They are easily scalable, readily accessible, and the online format allows for adherence to social distancing. For this reason, we developed an internet-based self-help intervention called ROCO to address psychological distress due to the COVID-19 pandemic. This randomized controlled trial aimed to examine the efficacy of the ROCO intervention. A total of 107 German-speaking adults with at least mild depressive symptoms were randomized either to the intervention group with direct access to the three-week ROCO intervention plus care as usual or the waiting control group receiving care as usual. Primary outcome (depressive symptoms) and secondary outcomes (stress, anxiety, resilience, emotion regulation, health-related quality of life, embitterment, loneliness, optimism, and self-efficacy) were assessed pre- and post-treatment and at a 6-week follow-up using self-report questionnaires (e.g. Patient Health Questionnaire-9 for depressive symptoms). The average age was 40.36 years (SD = 14.59) and 81.3% of participants were female. The intervention did not significantly reduce primary depressive symptoms (between-group effect size: d = 0.04) and secondary outcomes such as anxiety and stress symptoms (between-group effect size: d = -0.19). However, the intervention led to a significant increase in emotion regulation skills (between-group effect size d = 0.35) and resilience (between-group effect size d = 0.38). The internet-based self-help intervention cannot be recommended for the purpose of reducing depressive symptoms. However, the increase in emotion regulation skills and resilience suggest that the intervention may be suitable for preventive purposes, like improving overall coping with psychological distress or potential stressors. Future research is needed to examine for whom and how the intervention is most effective.


Quantification of nitroimidazoles residues in swine liver by liquid chromatography-mass spectrometry with atmospheric pressure chemical ionization.
A liquid chromatography-mass spectrometry method was developed for the simultaneous determination of ronidazole (RNZ), metronidazole (MNZ) and dimetridazole (DMZ) residues in swine liver. Following liquid-liquid extraction, the HLB solid-phase extraction was used for further purification. The targets were detected by atmospheric pressure chemical ionization (APCI) following the reverse phase liquid chromatography separation. Consequently, the detection limits for the method were 0.5 microg/kg for MNZ, 1.0 microg/kg for RNZ and 0.5 microg/kg for DMZ, respectively. The accuracies were determined using swine liver samples fortified at levels of 0.5, 1, 2, and 4 microg/kg and the mean recoveries of the analytes were between 66% and 81%.


Efficacy and safety of oral sildenafil (Viagra) in men with erectile dysfunction caused by spinal cord injury.
To evaluate the efficacy and safety of 50-mg doses of sildenafil during a 28-day period in patients with erectile dysfunction caused by spinal cord injury (cord level range, T6 through L5). Sildenafil is an orally active, potent, and selective inhibitor of phosphodiesterase type 5, an important regulator of cyclic guanosine monophosphate in the human corpus cavernosum. To be included in this double-blind, placebo-controlled study, all patients had to be able to achieve at least a partial reflexogenic erectile response to penile vibratory stimulation. The study utilized a single triangular sequential trial design. A total of 27 patients were randomized to receive 50 mg of sildenafil or placebo, taken orally as required (not more than once daily) approximately 1 hour before sexual activity. After 28 days of treatment, nine of 12 patients (75%) on sildenafil and one of 14 patients (7%) on placebo reported that treatment had improved their erections (p=0.0043). Furthermore, eight of 12 patients (67%) on sildenafil and two of 13 patients (15%) on placebo indicated that they wished to continue treatment (p=0.018). A significant improvement in satisfaction with their sex life was reported by patients taking sildenafil (p=0.012). No patients discontinued treatment due to adverse events. Oral sildenafil, taken as required (not more than once daily), significantly improves the quality of erections and satisfaction with sex life in men with erectile dysfunction caused by a spinal cord injury between T6 and L5.


Compliance with Enhanced Recovery After Surgery (ERAS) protocol recommendations for bariatric surgery in an obesity treatment center.
The higher risk of perioperative complications associated with obesity has made anesthesiologists increasingly concerned with the management of obese patients. Measures that improve bariatric surgery patient safety have become essential. The implementation of ERAS protocols in several surgical specialties has made it possible to achieve appropriate outcomes as to surgery safety. The aim of this study was to evaluate patient compliance with the recommendations of an ERAS protocol for Bariatric Surgery (ERABS) at a hospital specialized in obesity treatment. Cross-sectional study, using a medical record database, in a hospital certified as an International Center of Excellence in Bariatric and Metabolic Surgery. The definition of the variables to be assessed was based on the most recent ERABS proposed by Thorell et al. Results were analyzed using descriptive epidemiology. The study evaluated all patients undergoing bariatric surgery in 2019. Mean compliance with the recommendations per participant was 42.8%, with a maximum of 55.5%, and was distributed as follows: 22.6% of compliance with preoperative recommendations, 60% to intraoperative recommendations, and 58.1% to postoperative recommendations. The anesthesiologist is the professional who provides most measures for the perioperative optimization of bariatric surgery patients. In our study we found that anesthesiologists complied with only 39.5% of ERABS recommendations. Mean compliance with ERABS recommendations per participant was 42.8%. Considering that the study was carried out at a hospital certified as an international center of excellence, the need for introducing improvements in the care of patients to be submitted to bariatric surgery is evident.


Subjective estimation of ergonomic conditions of working with video display units.
In a group of 49 operators entering data into video display units, the type and frequency of subjective complaints were assessed and subjective assessment of ergonomic working conditions was examined. A detailed ergonomic analysis of the equipment and workplaces was done. The results showed a high frequency of subjective complaints. Incompatibility was established between the objectively measured ergonomic features and subjective estimation of the workplaces.


Computer-assisted implantology: historical background and potential outcomes-a review.
The accurate transfer of preoperatively determined implant positions to the patient mouth is very beneficial to the dental practitioner as well as patients. The objective of this paper was to review the gradual development of computer-assisted implant surgery. All of the major data sources including unpublished data in the internet are considered Computer-assisted/-guided/-aided implantology has been founded to overcome the errors encountered during implant osteotomies and to position the implants more precisely. The protocols followed by this sophisticated technique are based upon the advocated concept of prosthetic-driven implantology and CT-scan analysis recently approved. Although several attempts have been made to improve this approach more and more, little has been done regarding the patient's demands, including cost. The inherent complexity of the techniques and materials utilized necessitates several degrees of training before attempting treatment and must be taken into account.


Monocular visual form deprivation in human infants.
A preferential looking technique was used to measure visual acuity in human infants under one year of age who experienced monocular visual form deprivation. Of the 14 cases reviewed, 9 infants had monocular occlusion as therapy for esotropia; 3 infants had unilateral opacities of the ocular media; and 2 infants had unilateral eyelid closure from infection or burns. Despite differences in exact mode of deprivation, the effects on visual acuity were similar. There was a reduction in visual acuity in the deprived eye and a simultaneous increase in acuity of the non-deprived eye. These effects of monocular deprivation were not permanent. Recovery occurred with reverse deprivation or by simple cessation of the deprivation.


A reverse vaccinology approach identifies putative vaccination targets in the zoonotic nematode Ascaris.
Ascariasis is the most prevalent helminthic disease affecting both humans and pigs and is caused by the roundworms Ascaris lumbricoides and Ascaris suum. While preventive chemotherapy continues to be the most common control method, recent reports of anthelminthic resistance highlight the need for development of a vaccine against ascariasis. The aim of this study was to use a reverse vaccinology approach to identify potential vaccine candidates for Ascaris. Three Ascaris proteomes predicted from whole-genome sequences were analyzed. Candidate proteins were identified using open-access bioinformatic tools (e.g., Vacceed, VaxiJen, Bepipred 2.0) which test for different characteristics such as sub-cellular location, T-cell and B-cell molecular binding, antigenicity, allergenicity and phylogenetic relationship with other nematode proteins. From over 100,000 protein sequences analyzed, four transmembrane proteins were predicted to be non-allergen antigens and potential vaccine candidates. The four proteins are a Piezo protein, two voltage-dependent calcium channels and a protocadherin-like protein, are all expressed in either the muscle or ovaries of both Ascaris species, and all contained high affinity epitopes for T-cells and B-cells. The use of a reverse vaccinology approach allowed the prediction of four new potential vaccination targets against ascariasis in humans and pigs. These targets can now be further tested in in vitro and in vivo assays to prove efficacy in both pigs and humans.


Evaluation of linear polyethyleneimine/nitric oxide adduct on wound repair: therapy versus toxicity.
A full-thickness wound model was used to evaluate the effects of a topically applied polyethyleneimine-based nitric oxide donor on wound repair in aged rats. Polymer applications were applied over a 10-day period on days 0, 2, 4, 6, and 8 comparing treatment (linear polyethyleneimine-nitric oxide) and control groups (linear polyethyleneimine). Urinary nitrate excretion was quantified as a measure of nitric oxide released. The nitric oxide released from the linear polyethyleneimine-nitric oxide group was significant compared with controls (p </= 0.001), with a maximal nitrate level of 40 micromol on day 1 and an average sustained delivery of 34 micromol/day for the remainder of the study. Wound closure was examined using a computer-based video-imaging analysis system. The wounds of both the linear polyethyleneimine- nitric oxide treatment and linear polyethyleneimine control groups exhibited minimal wound closure; however, the wound closure of the treatment group was significant as compared with the control group (p </= 0.05). A phosphate- buffered saline solution-wounded control was performed that showed cleaner and faster healing wounds, similar to normal healing, than either of the polymer application groups. The histological data showed very little wound healing, on a cellular level, implicating the linear polyethyleneimine-nitric oxide as well as the carrier compound as contributing to the adverse tissue reactions that occurred in the wound bed. Thus, we report the toxic effects of a polyethyleneimine-based compound, as well as the toxic effects of sustained delivery of excess levels of nitric oxide on the wound- repair process. Our findings suggest that there exists indeterminate parameters between therapy and toxicity of nitric oxide delivery to wounds.


Decolorization of acid black 24 by the FeGAC/H2O2 process.
FeGAC/H2O2 process was developed and employed in this research for the treatment of acid back 24. The removal efficiencies of five treatment processes (GAC, FeGAC, H2O2, GAC/H2O2, and FeGAC/H2O2) were studied in this research. The adsorption capacity of granular activated carbon (GAC) was greatly improved by the coating of iron oxide on GAC surface (FeGAC). The presence of H2O2 significantly improved the removal abilities of FeGAC and GAC. For instance, at solution pH 2, the removal efficiency of FeGAC/H2O2, GAC/H2O2, H2O2, FeGAC, and GAC were 76, 74, 59, 11, and 7%, respectively. The possible removal mechanisms of FeGAC/H2O2 process were proposed in this research. When treating the actual dye contaminated wastewater, the removal efficiencies of FeGAC/H2O2 and GAC/H2O2 were approximately six times greater than that of H2O2 process.


Comparing the Toxicity of Water-Soluble Fractions of Biodiesel, Diesel and 5% Biodiesel/Diesel Blend on Oreochromis niloticus Using Histological Biomarkers.
This study estimated end compared the potential toxic effects of the water-soluble fractions (WSF) of biodiesel (B100), diesel and the commercial biodiesel (B5) on Oreochromis niloticus. After a 24 h-exposition to WSF-0% (control) and WSF-serial concentrations of 4.6%, 10%, 22%, 46% and 100%, samples of gill and liver of the exposed fishes were fixed in Bouin's solution, processed, stained using hematoxylin/eosin and analyzed by light-microscopy. WSF-hydrocarbons and methanol contents, analyzed by gas chromatography, were checked against the occurrence of abnormal histopathological alterations. These were not found in the control and WSF-4.6% exposed fishes, while exposures to or above 10%-WSF resulted in histopathological alterations whose severity increased in a dose-dependent manner, being higher in fishes exposed to WSF-diesel, or WSF-B5 when compared to biodiesel. These results, which were corroborated by the chemical analyses, highlighted the histological technique as an appropriate diagnostic tool that can be used for the preservation of water bodies' quality.


Who Expressed What Emotion? Men Grab Anger, Women Grab Happiness.
When anger or happiness flashes on a face in the crowd, do we misperceive that emotion as belonging to someone else? Two studies found that misperception of apparent emotional expressions - "illusory conjunctions" - depended on the gender of the target: male faces tended to "grab" anger from neighboring faces, and female faces tended to grab happiness. Importantly, the evidence did not suggest that this effect was due to the general tendency to misperceive male or female faces as angry or happy, but instead indicated a more subtle interaction of expectations and early visual processes. This suggests a novel aspect of affordance-management in human perception, whereby cues to threat, when they appear, are attributed to those with the greatest capability of doing harm, whereas cues to friendship are attributed to those with the greatest likelihood of providing affiliation opportunities.


A monotopic aluminum telluride with an Al=Te double bond stabilized by N-heterocyclic carbenes.
Aluminum chalcogenides are mostly encountered in the form of bulk aluminum oxides that are structurally diverse but typically consist of networks with high lattice energy in which the chalcogen atoms bridge the metal centres. This makes their molecular congeners difficult to synthesize because of a pronounced tendency for oligomerization. Here we describe the isolation of the monotopic aluminum chalcogenide (L(Dip)N)AlTe(L(Et))2 (L(Dip)=1,3-(2,6-diisopropylphenyl)-imidazolin-2-imine, L(Et)=1,3-diethyl-4,5-dimethyl-imidazolin-2-ylidene). Unique features of (L(Dip)N)AlTe(L(Et))2 are the terminal position of the tellurium atom, the shortest aluminum-tellurium distance hitherto reported for a molecular complex and the highest bond order reported for an interaction between these elements, to the best of our knowledge. At elevated temperature (L(Dip)N)AlTe(L(Et))2 equilibrates with dimeric {(L(Dip)N)AlTe(L(Et))}2 in which the chalcogen atoms assume their common role as bridges between the metal centres. These findings demonstrate that (L(Dip)N)AlTe(L(Et))2 comprises the elusive Al=Te double bond in the form of an N-heterocyclic carbene-stabilized species.


Examining the influence of acute instructional approaches on the decision-making performance of experienced team field sport players.
We examined the influence of instructions on decision-making accuracy using video simulations of game-specific scenarios in Australian football. Skilled performers (average age of 23.4 ± 4.2 years) differing in experience (range 0 to 339 Australian Football League (AFL) matches) assumed the role of the key attacker and verbally indicated their kicking decision. Participants were randomly stratified into three groups: (1) LOOSE (n = 15)--instructed to "keep the ball away from the loose defender"; (2) TTF (n = 15) - instructed to "take the first option"; and (3) NI (control) (n = 16)--given no instructions. Gaze behaviour for a subset of participants (n = 20) was recorded. In the scenarios with an even number of attacking and defensive players, the decision-making accuracy of LOOSE was greater than TTF. This difference was most evident for lesser experienced performers, highlighting that lesser experienced performers are more affected by instructional foci than experienced performers. Gaze behaviour was not affected by instructional foci, but visual search rate was greater in scenarios of greater player number and complexity.


Alpha-1 anti-trypsin and CD30 expression occur in parallel in activated T cells.
We have performed an immunohistochemical study of immunoblastic T cell lymphoma and enteropathy-associated T cell lymphoma for alpha-1 anti-trypsin and CD30. Cytoplasmic staining for alpha 1 anti-trypsin is present in the malignant cells in both types of T cell neoplasm which also express CD30, a marker of lymphoid activation. Peripheral blood T lymphocytes on stimulation with mitogen also show granular cytoplasmic expression of alpha 1 anti-trypsin. Time course studies show that this parallels the expression of CD30. Alpha 1 anti-trypsin expression appears therefore to be associated with activation in T cells. Further studies of sub-fractionated T lymphocytes in vitro suggest that the expression of alpha 1 anti-trypsin on activation is not restricted to an individual lymphocyte subset.


Modified Linggui Zhugan Decoction () Ameliorates Glycolipid Metabolism and Inflammation via PI3K-Akt/mTOR-S6K1/AMPK-PGC-1 α Signaling Pathways in Obese Type 2 Diabetic Rats.
To investigate the protective effects of modified Linggui Zhugan Decoction (, MLZD), a traditional Chinese medicine formula, on obese type 2 diabetes mellitus (T2DM) rats. Fifty Sprague-Dawley rats were randomly divided into 5 groups by a random number table, including normal, obese T2DM (ob-T2DM), MLZD low-dose [MLDZ-L, 4.625 g/(kg·d)], MLZD middle-dose [MLD-M, 9.25 g/(kg·d) ] and MLZD high-dose [MLD-H, 18.5 g/(kg·d)] groups, 10 rats in each group. After 4-week intervention, blood samples and liver, pancreas, muscle tissues were collected to assess the insulin resistance (IR), blood lipid, adipokines and inflammation cytokines. The alteration of phosphatidylinositol 3 kinase (PI3K)-protein kinase B (PKB or Akt)/the mammalian target of rapamycin (mTOR)-ribosome protein subunit 6 kinase 1 (S6K1 )/AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 α) pathways were also studied. MLZD dose-dependently reduced fasting blood glucose, fasting insulin, homeostasis model of assessment for IR index and increased insulin sensitive index compared with ob-T2DM rats (P<0.05). Similarly, total cholesterol, triglyceride, low-density lipoprotein cholesterol and free fatty acids were also decreased compared with ob-T2DM rats after 4-week treatment (P<0.05 or P<0.01). Improvements in adipokines and inflammatory cytokines were observed with a raised level of adiponectin and a reduced level of leptin, resistin, tumor necrosis factor-α and interleukin-6 (P<0.05 or P<0.01). MLZD regulated the PI3K-Akt/mTOR-S6K1/AMPK-PGC-1 α pathways and restored the tissue structure of liver and pancreas (P<0.05 or P<0.01). MLZD ameliorated glycolipid metabolism and inflammation, which may be attributed to the regulation of PI3K-Akt/mTOR-S6K1/AMPK-PGC-1 α pathways.


Cell Biology: Hacking Alpha Satellites out of the HAC.
Human artificial chromosomes (HACs) are a potentially powerful technique for genomic engineering, but their use is limited by the repetitive centromeric alpha-satellite DNA needed to form a centromere. A new study presents a method to induce HAC centromere formation on non-repetitive templates through sequence-directed CENP-A nucleosome seeding.


Correlates of estimated lifetime cruciate ligament survival inform potential rupture risk reduction strategies: findings from the Exceptional Aging in Rottweilers Study.
Cranial cruciate ligament (CCL) rupture is one of the most commonly diagnosed orthopedic conditions of pet dogs, making estimated lifetime cruciate ligament survival an attractive endpoint for studies attempting to define clinical and genetic correlates of rupture risk reduction. Early life experiences contribute significantly to the origins of adult health outcomes, yet our current understanding of modifiable susceptibility factors that drive the high frequency of CCL rupture remains limited. We reasoned that combining lifetime medical history with standardized late-life assessment of lifetime cruciate ligament survival and detailed phenotyping of each dog for selected risk variables would provide a sensitive approach to identify factors that would differentiate between lifelong avoidance versus susceptibility to ligament rupture. Here, we report results of Kaplan-Meier analysis of estimated lifetime cruciate ligament survival and Cox proportional hazards modeling to assess risk variables in a lifetime cohort study of 123 purebred Rottweilers, a breed at high risk for veterinarian-diagnosed CCL rupture. We show that gonad removal during the 24-month developmental period is adversely associated with three measures of susceptibility-increased incidence of CCL rupture, multiplicity (bilateral rupture), and accelerated time to initial CCL failure. Our analysis reveals two other phenotypes-short adult height and the production of offspring (in females)-are associated with significant CCL rupture risk reduction. Together, the results provide clues to an early endocrine influence on lifetime cruciate ligament survival. Further, we identify two distinct clinical syndromes of CCL failure, providing a disease subtyping framework to advance future progress in genetic epidemiology, pathogenesis, and prediction. By conducting an evaluation of estimated lifetime CCL survival in dogs, we show that cruciate ligament survival may be jeopardized by gonad removal during the developmental period. Avoidance of such early environmental adversity may represent an actionable method for the control of canine CCL disease in certain breeds.


A glass intraocular lens.
We designed a glass and polyimide iris-plane, iris-clip intraocular lens. It is sterilized in the autoclave and weighs approximately 6 mg in water. The optic is 0.3 mm thick for a 19-diopter lens and the flexible haptic is 0.05 mm thick. Two identical haptics and the optic are joined mechanically to form the intraocular lens. The round spatula-like portion of an insertional instrument secures the intraocular lens by passing through two opposing flexible haptic loops and behind the optic. Fluid or air is irrigated through the cannula as the implant is inserted in order to protect the endothelium.


Compound-specific isotopic analysis to characterize the photocatalytic reaction of TiO2 nanoparticles with diethyl phthalate.
In this study compound-specific isotope analysis (CSIA) has been used to explore the degradation mechanism of nano titanium dioxide (TiO2) catalyzes photodegradation of diethyl phthalate (DEP). TiO2 is a popular photosensitizer with potential in waste water treatment and application in advanced oxidation processes. The degradation process of DEP can be described with a first-order kinetics in the applied concentration ranges. The larger degradation rate constant has been found at neutral conditions. The 13C and 2H isotope fractionation associated with the nano TiO2 catalyzes photodegradation of DEP at pH 3, 7 and 11 yield normal isotope effects. In the TiO2/UV/DEP and TiO2/H2O2/UV/DEP systems, the correlation of 13C and 2H fractionation (Λ) were calculated to be 2.7 ± 0.2, 2.8 ± 0.2 at pH 3, 2.2 ± 0.4, 2.5 ± 0.2, 2.3 ± 0.6 at pH 7 and 2.6 ± 0.3, 2.2 ± 0.3, 2.7 ± 0.2 and 2.3 ± 0.3 at pH11, respectively. The dominant free radical species in studied systems were explored by combining free radical quenching method and electron paramagnetic resonance analysis. The hydroxyl radicals have been found as the main radical species at all pH conditions studied. Furthermore, the 13C and 2H fractionation suggested that the addition of •OH on the benzene ring of DEP is the main conversion pathway. Therefore, CSIA is a promising technology for the identification of reaction pathways of DEP for example in water treatment systems.


Pervasive lncRNA binding by epigenetic modifying complexes--The challenges ahead.
Epigenetic modifying factors are fundamental regulators of chromatin structure and gene expression during development and differentiation through the induction of chemical modifications on histones, DNA or via remodeling of the chromatin structure. Protein complexes involved in these three processes contain non-canonical RNA-binding components that interact with long non-coding RNAs, in many cases in the absence of any sequence or structural signatures. However, there is growing evidence of the role of such protein-lncRNA interactions in the regulation of the epigenetic landscape in vivo. This review summarizes the growing number of epigenetic modifying factors described to interact with lncRNAs in mouse and human, and then discusses the challenges that lay ahead in understanding lncRNAs as part of the intricate networks of epigenetic regulation. A combination of protein and RNA-centric approaches is required for this purpose. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa.


Bleomycin--mode of action with particular reference to the cell cycle.
Over the last four years, investigations into the mechanism of interaction between bleomycin and DNA have been pursued at a rapid pace. This is, no doubt, because of the potential of bleomycin as a tool for molecular biology. It seems likely that the precise nature of the interaction between Fe(II), oxygen and bleomycin will be elucidated in the near future together with the nature of the binding between the complex and DNA. More information on the mechanism of strand scission including the involvement of free radical mechanisms and sequence specificity may also be expected. In contrast to this picture of rapid progress at the molecular level, interest in studies of bleomycin action at the cellular level appears to have waned. This is despite the fact that most of the important questions which have been raised regarding effects of the drug on cell cycle progression, the possibility of a selective action on on-cycling cells and the nature of 'recovery from potentially-lethal damage' remain unresolved. There is no doubt that, for most cell types, bleomycin produces a block at the early G2 stage of the cell cycle. There is considerable doubt, however, as to how many of the cells blocked for a significant period remain clonogenically viable. This question is amenable to being answered using a vital DNA stain, such as Hoechst 33342, and cell sorting but this does not appear to have been done. The relationship between G2 blockage and repair of DNA damage has also not been resolved. Neither has the question of whether or not DNA breaks which remain unrepaired are different in nature from the majority of repairable lesions. The data on the relative sensitivity of exponential and plateau phase cells are conflicting and their in vivo significance unclear. Well designed experiments to examine the bleomycin sensitivity of those cells in solid tumors which survive radiation treatment could help to answer this question. Evidence that the phenomenon of 'recovery from potentially lethal damage' is therapeutically-exploitable is mainly lacking. It would be of great relevance to known whether or not the effect can be observed in normal tissues. However, the evidence that the effect is not simply an artefact of clonogenic assay procedures is scanty and this possibility must be borne in mind.(ABSTRACT TRUNCATED AT 400 WORDS)


Stereoselective synthesis of trisubstituted alkenylboranes by palladium-catalysed reaction of alkynyltriarylborates with aryl halides.
The palladium-catalysed reaction of alkynyltriarylborates with aryl halides afforded trisubstituted alkenylboranes, in which two different aryl groups were installed across the carbon-carbon double bond in a cis arrangement.


The effect of immunosuppression on protective immunity of turkey poults against infection with turkey coronavirus.
The objective of the present study was to evaluate the protective effect of humoral and cellular immunities on turkeys infected with turkey coronavirus (TCV). Two trials were conducted with two separate hatches of turkey poults. Turkey's were experimentally immunosuppressed with cyclosporin A (CsA) or cyclophosphamide (CY) and infected with TCV. Prior to infection, treatment with CsA selectively suppressed T cell activity as revealed by 2-3 fold decreased (p < 0.1) lymphocyte proliferation responses to a T cell mitogen, concanavalin A (Con A). Treatment with CY mainly induced B cell deficiency as indicated by significant reductions (p < 0.05) in antibody responses to sheep erythrocytes 7 days after injection. Body weight gain of turkeys treated with CY was significantly lower (p < 0.05) than that of untreated turkeys at 9 days post-infection (PI). Turkeys treated with CY had 1-2 fold higher immunofluorescent antibody assay (IFA) scores for TCV antigens (p < 0.05) in the intestine than untreated turkeys at 9 or 14 days PI. These results suggested that humoral immunity against TCV infection may be important in turkeys.


Photo-induced intermolecular electron transfer from electron donating solvents to Coumarin dyes in bile salt aggregates: role of diffusion in electron transfer reaction.
The photo-induced electron transfer between Coumarin dyes and aromatic amines has been investigated using steady state and time-resolved fluorescence quenching studies. We have observed a Marcus type inversion in the electron transfer rate in correlation of quenching constant to the free energy change occurred during reaction. To justify the "inverted region" obtained in the correlation of quenching constant versus free energy curve, we have performed anisotropy measurement and estimated the several diffusional parameters. The translational diffusion coefficients exhibit a similar picture like electron transfer rate constant when it is plotted against free energy. Thus we argued that the diffusion has played an important role in the electron transfer kinetics.


Initial experience with polytetrafluoroethylene leaflet extensions for aortic valve repair.
The purpose of this study is to evaluate our initial experience with aortic valve repair using polytetraflouroethylene (PTFE) leaflet extensions in congenital valvular disease. From October 2008 through February 2011, 13 patients underwent aortic valvuloplasty by PTFE leaflet extensions. All valves were repaired in a tri-leaflet configuration using PTFE leaflet extensions. The median age at operation was 14 years (1.8-19.7 years) and the median weight was 58 kg (9.5-86 kg). Previous interventions included balloon valvuloplasty in two patients, aortic valvuloplasty in one and coarctation repair in one patient. Eight (73%) patients had combined aortic stenosis and insufficiency, three (23%) had isolated insufficiency and two (15%) had stenosis only. In 10 (77%) patients, a bicuspid aortic valve was present. The follow-up ranged from 2 to 30 months (mean follow-up 14.8 ± 9 months). At the latest echocardiography follow-up, six patients had none or trace aortic insufficiency, six patients had a mild aortic insufficiency and one patient had a mild-to-moderate insufficiency. The mean aortic insufficiency degree decreased from 1.8 ± 1.2 preoperatively to 0.8 ± 0.6 at the follow-up (P < 0.01). The mean gradient across the aortic valve decreased from 56 ± 40 mmHg preoperatively to 12 ± 13 mmHg at the follow-up (P < 0.0008). All patients are alive. There were no reoperations. The median hospital stay was 9 days (4-21 days). The use of PTFE leaflet extensions is an effective technique for aortic valve reconstruction in congenital valvular disease. Long-term follow-up is necessary to assess the durability of this type of repair.


The impact of climate change on water provision under a low flow regime: a case study of the ecosystems services in the Francoli river basin.
Mediterranean basin is considered one of the most vulnerable regions of the world to climate change and with high probability to face acute water scarcity problem in the coming years. Francolí River basin (NE Spain), located in this vulnerable region is selected as a case study to evaluate the impact of climate change on the delivery of water considering the IPCC scenarios A2 and B1 for the time spans 2011-2040, 2041-2070 and 2071-2100. InVEST model is applied in a low flow river as a new case study, which reported successful results after its model validation. The studied hydrological ecosystem services will be highly impacted by climate change at Francolí River basin. Water yield is expected to be reduced between 11.5 and 44% while total drinking water provisioning will decrease between 13 and 50% having adverse consequences on the water quality of the river. Focusing at regional scale, Prades Mountains and Brugent Tributary provide most of the provision of water and also considered highly vulnerable areas to climate change. However, the most vulnerable part is the northern area which has the lowest provision of water. Francolí River basin is likely to experience desertification at this area drying Anguera and Vallverd tributaries.


Can we safely accommodate larger volume implants in inframammary fold nipple sparing mastectomy compared to nipple sacrificing mastectomy in implant-based reconstruction with acellular dermal matrix?
The aim of this study was to analyse if inframammary fold nipple sparing mastectomy (IMF NSM) could safely accommodate larger implants in relation to weight of the breast as opposed to nipple sacrificing mastectomy (NSacriM) in implant reconstruction with biological mesh. A review of prospectively collected data of implant-based reconstruction using biological mesh between Nov 2016 and December 2019 by a single surgeon. The volume of the implant was measured against the weight of the breast. The data was analysed using Chi-squared test and independent t-test, and a P value of < 0.05 was considered significant. Sixty-five patients had 86 implant reconstructions during this period. Median follow-up was 18 months (1-38). There was no statistical difference between IMF NSM and NSacriM with regard to smoking, obesity (BMI>30) and radiotherapy (P>0.05). The volume of the implants was more than the weight of the breast in IMF NSM group compared to the NSacriM group (22/34 vs 21/52; P = 0.026). Significantly more patients in IMF NSM group had an implant volume within 100 g of the mastectomy weight compared to NSacriM group (31/34 vs 33/52; P = 0.003). None of the 34 IMF NSM had wound necrosis or threatened wound compared to 7/52 in NSacriM group (P = 0.025); 4 were managed in the clinic and 3 were managed in theatre. One patient in the NSacriM group lost her implant post radiotherapy at 5 months, and another patient lost her implant at 3 years. Comparisons were made between IMF-NSM and skin sparing mastectomy (SSM) having fixed volume silicone implants. The analysis showed that 22/33 (67%) IMF-NSM, had a volume of the implant more than the weight of the breast compared to 15/35 (43%) having SSM, this was statistically significant. There was a statistical difference between these two groups with regard to ischemic complications in favour of IMF-NSM. IMF NSM allows safer insertion of larger volume implants in relation to the weight of the breast as opposed to NSacriM.


Outcome, risk factors and therapeutic strategies in carbapenem-resistant Gram-negative bacteraemia from Pakistan.
Carbapenem-resistant Gram-negative (CRGN) bacteraemia has high mortality and limited therapeutic options. We assessed the risk factors and outcome of CRGN bacteraemia treated with limited options. A prospective cohort study done at a tertiary care hospital in Pakistan, from October 2021 to August 2022. All patients >18 years with CRGN bacteraemia were assessed for demographics, source, risk factors and treatment received. Outcome was assessed as bacterial clearance and all-cause mortality at Day 14 of bacteraemia. We included 175 patients. Median age was 45 years (IQR 30-58) and the majority of our patients were on haemodialysis (75%). We found 14 day mortality in 26.8% of our patients; in addition, microbiological clearance was achieved in 95%. The central line (49.7%) was the most common source and Klebsiella spp. (47%) the most common organism. On multivariate analysis, risk factors for mortality were Foley's catheter [aOR 2.7 (95% CI 1.1-6.5)], mechanical ventilation [aOR 5.1 (95% CI 1.6-15.8)] and Pitt bacteraemia score >4 [aOR 3.48 (95% CI 1.1-10.5)]. Source control was a significant protective factor [aOR 0.251 (95% CI 0.09-0.6)]. The majority received a colistin-based regimen with no difference in mortality between monotherapy and combination therapy. Our cohort of CRGN bacteraemia is unique, comprising younger patients mostly on haemodialysis with a central line as the source of bacteraemia and we have found 14 day mortality of 27%. Colistin with various combinations can be an effective option in patients with renal failure having prompt source control.


Structural characterization of an immunoenhancing heteroglycan of a hybrid mushroom (pfls1h) of Pleurotus florida and Lentinus squarrosulus (Mont.) Singer.
An immunostimulating water-soluble heteroglycan (PS-II) was isolated from an aqueous extract of the fruit bodies of a hybrid mushroom, pfls1h produced by intergeneric protoplast fusion between Pleurotus florida and Lentinus squarrosulus (Mont.) Singer. Structural characterization of PS-II was carried out using sugar analysis, methylation experiment, periodate oxidation and 1D/2D NMR studies. Sugar analysis indicated the presence of glucose, mannose and galactose in a molar ratio of 1:1:2. Methylation analysis revealed that PS-II was composed of (1→6)- and (1→2,4,6)-α-D-galactopyranosyl, terminal β-D-mannopyranosyl and terminal β-D-glucopyranosyl residues in a relative proportion of approximately 1:1:1:1. On the basis of chemical analysis and NMR studies, the structure of the repeating unit of the heteroglycan was established to consist of a backbone chain of two (1→6)-α-D-galactopyranosyl residues, one of which is branched at O-2 with terminal β-D-Manp and at O-4 with terminal β-D-Glcp. This heteroglycan (PS-II) showed in vitro splenocyte, thymocyte and macrophage activations.


Diarrhoea, vomiting and reduced wet nappies - a familiar story with unexpected twists.
Vomiting and diarrhoea is a common presenting complaint in paediatrics. Most often it is due to a benign and self-limiting infectious illness. Here, we explore the diagnostic journey of a 7-month-old infant with these symptoms presenting in a secondary care hospital and the overnight clinical problem solving involved in tackling the unexpected complexities.


Tumor metabolic and secondary lymphoid organ metabolic markers on 18F-fludeoxyglucose positron emission tomography predict prognosis of immune checkpoint inhibitors in advanced lung cancer.
The purpose of this study was to investigate the predictive value of tumor metabolic parameters in combination with secondary lymphoid metabolic parameters on positron emission tomography (PET)/computed tomography (CT) for immune checkpoint inhibitor (ICI) prognosis in advanced lung cancer. This study retrospectively included 125 patients who underwent 18F-fludeoxyglucose (FDG) PET/CT before ICI therapy, including 41 patients who underwent a second PET/CT scan during ICI treatment. The measured PET/CT parameters included tumor metabolism parameters [maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), total lesion glycolysis (TLG), and total metabolic tumor volume (TMTV)] and secondary lymphoid organ metabolism parameters [spleen-to-liver SUVmax ratio (SLR) and bone marrow-to-liver SUVmax ratio (BLR)]. The correlation of PET/CT metabolic parameters with early ICI treatment response, progression-free survival (PFS), and overall survival (OS) was analyzed. Within a median follow-up of 28.7 months, there were 44 responders and 81 non-responders. The median PFS was 8.6 months (95% confidence interval (CI): 5.872-11.328), and the median OS was 20.4 months (95% CI: 15.526-25.274). Pretreatment tumor metabolic parameters were not associated with early treatment responses. The high bone marrow metabolism (BLR >1.03) was significantly associated with a shorter PFS (p = 0.008). Patients with a high TMTV (>168 mL) and high spleen metabolism (SLR >1.08) had poor OS (p = 0.019 and p = 0.018, respectively). Among the 41 patients who underwent a second PET/CT scan, the ΔSUVmax was significantly lower (p = 0.01) and the SLR was significantly higher (p = 0.0086) in the responders. Populations with low-risk characteristics (low TMTV, low SLR, and ΔSLR > 0) had the longest survival times. High pretreatment TMTV and SLR are associated with poor OS, and increased spleen metabolism after ICI therapy predicts treatment benefit. This indicates that the combination of tumor and spleen metabolic parameters is a valuable prognostic strategy.


[Isolation of foamy virus type II out of haematopoetic cells from baboons with haematoblastoses and from healthy animals (author's transl)].
Foamy virus Type II persists in the haematopoetic organs of 75 percent of baboons in the Suchumi flock. A mixed infection with foamy virus types I and II seems to be possible. Foamy viruses are isolated as well from monkeys with haemoblastoses as from healthy animals. New information concerning the intrauterine transmission of foamy viruses were obtained.


Effect of hemorrhagic hypotension on hydroxyl radicals in cat brain.
This study investigated the relationships between blood pressure, cortical oxygen pressure and hydroxyl radicals in the brain of adult cats during hemorrhagic hypotension and retransfusion. Oxygen pressure in the blood of the cortex was measured optically by the oxygen dependent quenching of phosphorescence and hydroxyl radicals by in vivo microdialysis. Following a 2 h stabilization period after implantation of the microdialysis probe in the striatum, the mean arterial blood pressure (MAP) was decreased in a stepwise manner from 132 +/- 2 Torr (control) to 90 +/- 1 Torr, 70 +/- 3 Torr and 50 +/- 3 Torr, holding the pressure at each level for 15 min. The whole blood was then retransfused and measurements were continued for 90 min. Cortical oxygen pressure progressively decreased with decrease in MAP, decreasing from 50 +/- 2 Torr (control) to 42 +/- 1 Torr, 31 +/- 2 Torr and 22 +/- 2 Torr, respectively. The level of hydroxyl radical increased by 20-25% following first 15 min of bleeding and stay on this level during the remaining period of hypotension. Maximal increase (by 78%) in level of hydroxyl radicals was observed after 15 min of retransfusion. The present study demonstrated that during hypotension and retransfusion there was an increase in the level of hydroxyl radicals in striatum. These can be important mediators of postischemic injury to the striatum.


The role of sphingolipid metabolism in cutaneous permeability barrier formation.
The epidermal permeability barrier of mammalian skin is localized in the stratum corneum. Corneocytes are embedded in an extracellular, highly ordered lipid matrix of hydrophobic lipids consisting of about 50% ceramides, 25% cholesterol and 15% long and very long chain fatty acids. The most important lipids for the epidermal barrier are ceramides. The scaffold of the lipid matrix is built of acylceramides, containing ω-hydroxylated very long chain fatty acids, acylated at the ω-position with linoleic acid. After glucosylation of the acylceramides at Golgi membranes and secretion, the linoleic acid residues are replaced by glutamate residues originating from proteins exposed on the surface of corneocytes. Removal of their glucosyl residues generates a hydrophobic surface on the corneocytes used as a template for the formation of extracellular lipid layers of the water permeability barrier. Misregulation or defects in the formation of extracellular ceramide structures disturb barrier function. Important anabolic steps are the synthesis of ultra long chain fatty acids, their ω-hydroxylation, and formation of ultra long chain ceramides and glucosylceramides. The main probarrier precursor lipids, glucosylceramides and sphingomyelins, are packed in lamellar bodies together with hydrolytic enzymes such as glucosylceramide-β-glucosidase and acid sphingomyelinase and secreted into the intercelullar space between the stratum corneum and stratum granulosum. Inherited defects in the extracellular hydrolytic processing of the probarrier acylglucosylceramides impair epidermal barrier formation and cause fatal diseases: such as prosaposin deficiency resulting in lack of lysosomal lipid binding and transfer proteins, or the symptomatic clinical picture of the "collodion baby" in the absence of glucocerebrosidase. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.


Studies on crystal growth, vibrational and optical properties of organic nonlinear optical crystal: p-aminoazobenzene.
p-Aminoazobenzene (p-AAZB), an organic nonlinear optical (NLO) crystal having good optical quality has been grown by slow evaporation solution technique using ethanol as a solvent. Solubility studies were performed at different temperatures. The structural characterization of the grown crystals was carried out by X-ray diffraction. Group theoretical analysis was carried out to calculate the number of modes of vibration. The lowering of the wave numbers of azo group suggests the existence of strong intermolecular N-H...H hydrogen bonding. This has been analysed based on the vibrational spectral features. Optical absorption studies show the effective transmission in the entire UV-vis region. The second harmonic generation results show the suitability of this material for NLO applications.


Prenatal Education Intervention for Increasing Knowledge and Changing Attitude Toward Offspring Obesity Risk Factors.
This pre- and post-test quasi-experimental design study pilot tested an educational intervention designed to increase knowledge of and change attitudes toward prenatal factors that increase risk of childhood offspring obesity in 36 pregnant women. Educational intervention content included monitoring blood glucose, gestational weight gain in pregnancy, healthy lifestyle choices, and breastfeeding. Education intervention delivery method included: Verbal, written, and video. Participants' knowledge improved after the intervention for most topics (p = .03-.000). Their attitude score also differed before and after intervention (p = .002). Video delivery mode was the most useful, attractive, and most helpful method. This study showed an education intervention could potentially increase pregnant women's knowledge and attitudes toward offspring obesity risk factors.


Macrophage Migration Inhibitory Factor (MIF) Deficiency Exacerbates Aging-Induced Cardiac Remodeling and Dysfunction Despite Improved Inflammation: Role of Autophagy Regulation.
Aging leads to unfavorable geometric and functional sequelae in the heart. The proinflammatory cytokine macrophage migration inhibitory factor (MIF) plays a role in the maintenance of cardiac homeostasis under stress conditions although its impact in cardiac aging remains elusive. This study was designed to evaluate the role of MIF in aging-induced cardiac anomalies and the underlying mechanism involved. Cardiac geometry, contractile and intracellular Ca(2+) properties were examined in young (3-4 mo) or old (24 mo) wild type and MIF knockout (MIF(-/-)) mice. Our data revealed that MIF knockout exacerbated aging-induced unfavorable structural and functional changes in the heart. The detrimental effect of MIF knockout was associated with accentuated loss in cardiac autophagy with aging. Aging promoted cardiac inflammation, the effect was attenuated by MIF knockout. Intriguingly, aging-induced unfavorable responses were reversed by treatment with the autophagy inducer rapamycin, with improved myocardial ATP availability in aged WT and MIF(-/-) mice. Using an in vitro model of senescence, MIF knockdown exacerbated doxorubicin-induced premature senescence in H9C2 myoblasts, the effect was ablated by MIF replenishment. Our data indicated that MIF knockout exacerbates aging-induced cardiac remodeling and functional anomalies despite improved inflammation, probably through attenuating loss of autophagy and ATP availability in the heart.


Simultaneous analysis of two urinary biomarkers of oxidative damage to DNA and RNA based on packed-fiber solid phase extraction coupled with high-performance liquid chromatography.
The determination of the concentrations of urinary biomarkers of oxidative damage to DNA and RNA is difficult due to the low content of targets and the complex matrix of urine. A method using polystyrene/polypyrrole (PS/PPY) electronspun nanofibers as the adsorbent was introduced to the routine urinary treatment and determination of 8-OHdG and 8-oxoG for the first time. And 2-aminoethyl diphenylborate (DPBA) solution was creatively used in the loading and rinsing steps in order to promote the retention of the analytes as well as remove impurities. Under optimal conditions, 8-OHdG, 8-oxoG and IS were separated very well and exhibited a good linearity in the range of 0.5-50 ng mL-1, with correlation coefficients of R2 > 0.996. Limits of detection (LOD) were 0.058 ng mL-1 and 0.093 ng mL-1, and limits of quantification (LOQ) were 0.195 ng mL-1 and 0.309 ng mL-1, respectively. The recoveries were 88.8-104.9%. The proposed method was so simple and economical that it had the potential to be applied to batch quantitative analysis of 8-OHdG and 8-oxoG in urine. And it was successfully applied to real urine samples of cancer patients.


A novel online multi-task learning for COVID-19 multi-output spatio-temporal prediction.
In light of the ongoing COVID-19 pandemic, predicting its trend would significantly impact decision-making. However, this is not a straightforward task due to three main difficulties: temporal autocorrelation, spatial dependency, and concept drift caused by virus mutations and lockdown policies. Although machine learning has been extensively used in related work, no previous research has successfully addressed all three challenges simultaneously. To overcome this challenge, we developed a novel online multi-task regression algorithm that incorporates a chain structure to capture spatial dependency, the ADWIN drift detector to adapt to concept drift, and the lag time series feature to capture temporal autocorrelation. We conducted several comparative experiments based on the number of daily confirmed cases in 20 areas in California and affiliated cities. The results from our experiments demonstrate that our proposed model is superior in adapting to concept drift in COVID-19 data and capturing spatial dependencies across various regions. This leads to a significant improvement in prediction accuracy when compared to existing state-of-the-art batch machine learning methods, such as N-Beats, DeepAR, TCN, and LSTM.


Safety and efficacy of single incision laparoscopic surgery for total extraperitoneal inguinal hernia repair.
Almost 20 years after the first laparoscopic inguinal hernia repair was performed, single incision laparoscopic surgery (SILS™) is set to revolutionize minimally invasive surgery. However, the loss of triangulation must be overcome before the technique can be popularized. This study reports the first 100 laparoscopic total extraperitoneal hernia repairs using a single incision. The study cohort comprised 68 patients with a mean age of 44 (range, 18 to 83): 36 unilateral and 32 bilateral hernias. Twelve patients also underwent umbilical hernia repair with the Ventralex patch requiring no additional incisions. A 2.5-cm to 3-cm crescentic incision within the confines of the umbilicus was performed. Standard dissecting instruments and 52-cm/5.5-mm/30(0) laparoscope were used. Operation times were 50 minutes for unilateral and 80 minutes for bilateral. There was one conversion to conventional 3-port laparoscopic repair and none to open surgery. Outpatient surgery was achieved in all (except one). Analgesic requirements were minimal: 8 Dextropropoxyphene tablets (range, 0 to 20). There were no intraoperative or postoperative complications with a high patient satisfaction score. Single-incision laparoscopic hernia repair is safe and efficient simply by modifying dissection techniques (so-called "inline" and "vertical"). Comparable success can be obtained while negating the risks of bowel and vascular injuries from sharp trocars and achieving improved cosmetic results.


Disparate Na+-requirement of taurocholate and indocyanine green uptake by isolated hepatocytes.
Uptake of both taurocholate and indocyanine green (ICG) by isolated rat hepatocytes was saturable and obeyed Michaelis-Menten kinetics. Only uptake of taurocholate exhibited Na+-dependence, a phenomenon compatible with active membrane transport. These findings suggest that the mechanisms responsible for hepatocellular uptake of bile acids and anionic dyes differ fundamentally.


Cold active hydrolytic enzymes production by psychrotrophic Bacilli isolated from three sub-glacial lakes of NW Indian Himalayas.
The diversity of culturable, cold-active enzymes producing Bacilli was investigated from three sub-glacial lakes of north western Indian Himalayas. Amplified ribosomal DNA restriction analysis (ARDRA) using three restriction enzymes Alu I, Msp I, and Hae III led to the clustering of 136 Bacilli into 26, 23, and 22 clusters at 75% similarity index from Chandratal Lake, Dashair Lake, and Pangong Lake, respectively. Phylogenetic analysis based on 16S rRNA gene sequencing led to the identification of 35 Bacilli that could be grouped in seven families viz.: Bacillaceae (48%), Staphylococcaceae (14%), Bacillales incertae sedis (13%), Planococcaceae (12%), Paenibacillaceae (9%), Sporolactobacillaceae (3%), and Carnobacteriaceae (1%), which included twelve different genera Bacillus, Desemzia, Exiguobacterium, Jeotgalicoccus, Lysinibacillus, Paenibacillus, Planococcus, Pontibacillus, Sinobaca, Sporosarcina, Staphylococcus, and Virgibacillus. Based on their optimal temperature for growth, 35 Bacilli were grouped as psychrophilic (11 strains), psychrotrophic (17 strains), or psychrotolerant (7 strains), respectively. The representative isolates from each cluster were screened for cold-active enzyme activities. Amylase, β-glucosidase, pectinase, and protease activities at 4 °C were detected in more than 80% of the strains while approximately 40, 31, 23, 14, 11, and 9% of strains possessed cellulase, xylanase, β-galactosidase, laccase, chitinase, and lipase activity, respectively. Among 35 Bacilli, Bacillus amyloliquefaciens, Bacillus marisflavi, Exiguobacterium indicum, Paenibacillus terrae, Pontibacillus sp., Sporosarcina globispora, and Sporosarcina psychrophila were efficient producers of different cold-active enzymes. These cold-adapted Bacilli could play an important role in industrial and agricultural processes.


Synthesis and antimicrobial activity of novel 5-(1-adamantyl)-2-aminomethyl-4-substituted-1,2,4-triazoline-3-thiones.
The reaction of 5-(1-adamantyl)-4-substituted-1,2,4-triazoline-3-thione 5a,b and 10a,b with formaldehyde solution and various primary aromatic amines or 1-substituted piperazines yielded the corresponding N-Mannich bases 6a-o, 7a-g and 11a-i. The newly synthesized N-Mannich bases 6a-o, 7a-g and 11a-i were tested for in vitro inhibitory activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. The compounds 6j, 6l, 6m, 7a, 7b, 7c, 7d, 7f, 11a, 11b, 11c, 11d, 11e, 11f, 11h and 11i displayed moderate to good activity against the tested Gram-positive bacteria, while compounds 7c, 11c, 11d, 11f and 11h showed potent broad spectrum antibacterial activity. None of the newly synthesized compounds were proved to possess marked activity against C. albicans.


Non-steroidal anti-inflammatory drugs and slow-acting anti-rheumatic drugs in juvenile rheumatoid arthritis.
The preferred drugs for the initial treatment of juvenile rheumatoid arthritis (JRA) are salicylates or other non-steroidal anti-inflammatory drugs (NSAID) such as tolmetin or naproxen. If the disease activity does not respond adequately to the treatment, slow-acting anti-rheumatic drugs (SAARD) such as oral gold agents, low-dose D-penicillamine, or sulfasalazine should be given in addition to NSAID. If the systemic manifestations are severe, corticosteroid therapy may be commenced. Furthermore, if the joint destruction is progressive, immunosuppressants such as methotrexate would be selected as the third-line drugs of choice. The safety and efficacy of SAARD and immunosuppressants for the treatment of children with JRA, however, have not yet been confirmed, as the adverse effects such as bone marrow suppression, oncogenicity and mutagenicity are sometimes intense. Consequently, the strict indications for use and new therapeutic concepts for the management of JRA based on its pathogenesis are required.


Papillary muscle ischemia on high-resolution cine imaging of nitrogen-13 ammonia positron emission tomography: Association with myocardial flow reserve and prognosis in coronary artery disease.
The evaluation of papillary muscle (PM) perfusion through existing perfusion imaging, including single-photon emission computed tomography and magnetic resonance imaging, is not possible. Therefore, this study sought to investigate the detection of PM ischemia in coronary artery disease (CAD) using nitrogen-13 (N-13) ammonia positron emission tomography (NH3 PET) and its association with global myocardial flow reserve (MFR) and major adverse cardiac events (MACE). Data of adenosine-stress NH3 PET for 263 consecutive patients with known or suspected CAD were retrospectively analyzed. PM ischemia was defined as the absence of PM accumulation under stress conditions and PM presence at rest on high-resolution cine imaging derived from PET-computed tomography scanner with time-of-flight technology. The primary outcome was MACE. Of 263 patients, 30 experienced mean follow-up period of 910 days (MACE), while 31 (11.8%) presented PM ischemia. Compared to patients without PM ischemia, those with PM ischemia reported a significantly lower global MFR and a significantly higher rate of MACE (P < .0001). NH3 PET enables the detection of PM ischemia in approximately 10% of patients with known or suspected CAD. PM ischemia is associated with reduced global MFR and is an important sign in predicting prognosis.


Herbs and Medicinal Plants in Jordan.
The presence of phenolic acids in edible products for human consumption is considered in relation to the production of odorant substances, with a variety of different aromas. Phenolic substances anthocyanidins, anthocyanins, flavanols, flavones and isoflavones, flavones, flavonols, etc. - are extremely interesting as flavor additives, anti-aging or maturing agents, and color and aroma enhancers. The connection between flavoring properties on one hand and the presence of phenolic compounds on the other can be discussed in terms of food acceptance by consumers, especially with relation to the "Mediterranean Diet" lifestyle. The health perspectives of these and other food products related to Mediterranean Diet should be evaluated in the geographical ambit of the Mediterranean Basin, including several particular food and vegetable preparations - herbs and medicinal plants - of the Middle East. The aim of this paper is to give a presentation on these specialties in relation to Jordan. Medicinal herbs have interesting health properties against digestive problems, parasitic worms, liver diseases, diabetes, skin problems, nervous, cardiocirculatory, and respiratory diseases.