MRI Based Radiomics Compared With the PI-RADS V2.1 in the Prediction of Clinically Significant Prostate Cancer: Biparametric vs Multiparametric MRI.
To compare the performance of radiomics to that of the Prostate Imaging Reporting and Data System (PI-RADS) v2.1 scoring system in the detection of clinically significant prostate cancer (csPCa) based on biparametric magnetic resonance imaging (bpMRI) vs. multiparametric MRI (mpMRI). A total of 204 patients with pathological results were enrolled between January 2018 and December 2019, with 142 patients in the training cohort and 62 patients in the testing cohort. The radiomics model was compared with the PI-RADS v2.1 for the diagnosis of csPCa based on bpMRI and mpMRI by using receiver operating characteristic (ROC) curve analysis. The radiomics model based on bpMRI and mpMRI signatures showed high predictive efficiency but with no significant differences (AUC = 0.975 vs 0.981, p=0.687 in the training cohort, and 0.953 vs 0.968, p=0.287 in the testing cohort, respectively). In addition, the radiomics model outperformed the PI-RADS v2.1 in the diagnosis of csPCa regardless of whether bpMRI (AUC = 0.975 vs. 0.871, p= 0.030 for the training cohort and AUC = 0.953 vs. 0.853, P = 0.024 for the testing cohort) or mpMRI (AUC = 0.981 vs. 0.880, p= 0.030 for the training cohort and AUC = 0.968 vs. 0.863, P = 0.016 for the testing cohort) was incorporated. Our study suggests the performance of bpMRI- and mpMRI-based radiomics models show no significant difference, which indicates that omitting DCE imaging in radiomics can simplify the process of analysis. Adding radiomics to PI-RADS v2.1 may improve the performance to predict csPCa.


Understanding How to Support Family Caregivers of Seniors with Complex Needs.
The purpose of this study was to describe the experiences and challenges of supporting family caregivers of seniors with complex needs and to outline support strategies and research priorities aimed at supporting them. A CIHR-funded, two-day conference entitled "Supporting Family Caregivers of Seniors: Improving Care and Caregiver Outcomes" was held. An integrated knowledge translation approach guided this planning conference. Day 1 included presentations of research evidence, followed by participant engagement Qualitative data was collected regarding facilitators, barriers/gaps, and recommendations for the provision of caregiver supports. Day 2 focused on determination of research priorities. Identified facilitators to the provision of caregiver support included accessibility of health-care and community-based resources, availability of well-intended health-care providers, and recognition of caregivers by the system. Barriers/gaps related to challenges with communication, access to information, knowledge of what is needed, system navigation, access to financial resources, and current policies. Recommendations regarding caregiver services and research revolved around assisting caregivers to self-identify and seek support, formalizing caregiver supports, centralizing resources, making system navigation available, and preparing the next generation for caregiving. A better understanding of the needs of family caregivers and ways to support them is critical to seniors' health services redesign.


Effect of puerarin on human choriocarcinoma cells.
To discuss the effect of puerarin on human choriocarcinoma cells. Survival rates under puerarin monotherapy, fluorouracil (5-FU) monotherapy and puerarin in combination with 5-FU were detected by MTT assay. Apoptotic morphology was observed with Hoechst 33258 staining. Apoptosis rates were detected with flow cytometry. Expressions of AKT, mechanistic target of rapamycin (mTOR), and P70S6K mRNAs and phosphorylated proteins were detected by RT-PCR and Western blot. Tumor-bearing mice were administered puerarin and puerarin+5-FU, and serum levels of β-human chorionic gonadotropin (β-HCG) were measured. Proliferation inhibition and apoptosis rates of JEG-3 cells were positively correlated with puerarin concentration, which increased in the puerarin+5-FU group. Expression levels of AKT, mTOR, P70S6K mRNAs, and phosphorylated proteins decreased significantly after action of puerarin at different concentrations. With increasing puerarin concentration, expression of cleaved-caspase-3 in JEG-3 cells increased, whereas that of Bcl-2 decreased. Puerarin significantly inhibited tumor growth in choriocarcinoma-bearing SCID mice. Serum β-HCG levels were significantly lower than those of control group after administration. Magnitude of β-HCG decline was positively correlated with concentration.. Puerarin+5-FU inhibited proliferation of JEG-3 choriocarcinoma cells and promoted their apoptosis, being associated with the mTOR signaling pathway.


First report of Phaeoacremonium oleae and P. viticola associated with olive trunk diseases in Italy.
Over 300 trunk, branch and stem samples with vascular discolouration, necrotic wood and shoot death were collected from olive (Olea europaea) orchards in Lecce, Brindisi, Bari and Foggia provinces (Apulia region, Italy) from October to May from 2013 to 2019. Small chips of symptomatic wood samples were surface sterilised (5% NaOCl, 3 min; 70% ethanol, 30 s), rinsed (sterile distilled water, ×3), and placed onto potato dextrose agar (PDA) plates amended with 500 ppm streptomycin sulphate. After 14 days at 25 °C in the dark, hyphal tips of growing fungi, including different taxa, for instance Phaeoacremonium and Botryosphaeriaceae spp., were transferred to new PDA plates and incubated until sporulation. Monoclonal colonies resembling Phaeoacremonium-like genus (Mostert et al. 2006) were selected for further study, and genomic DNA of 59 representative isolates was extracted (Carlucci et al. 2013). Partial actin and β-tubulin genes were amplified with primers ACT-513F/ACT-783R (Carbone & Kohn 1999), and T1(O'Donnell & Cigelnik 1997) and Bt2b (Glass & Donaldson 1995), respectively. The sequenced amplicons were compared by BLAST algorithms with reference strains of Phaeoacremonium spp. retrieved from GenBank. Forty-four isolates showed 99% to 100% similarity with reference strains P. italicum, P. minimum, P. parasiticum, P. scolyti and P. sicilianum (Carlucci et al. 2015), nine with P. oleae, and six with P. viticola. Actin and β-tubulin sequences of P. oleae (Pm14) and P. viticola (Pm34) were submitted to GenBank (MW714561, MW714563; MZ318697, MZ318696). Microscopy of P. oleae isolates showed: conidiophores branched and unbranched, (18.7-)21.9-57.1(-67.8) × (2.9-)3.3-4.7(-5.2) (mean, 38.9×4.1) μm (n=30); conidia oblong-ellipsoidal to obovoid or subcylindrical 3.4 to 5.5 μm long, and 1.5 to 2.4 (mean, 4.6 × 2.2) μm wide (n=30). Microscopy of P. viticola isolates showed: conidiophores subcylindrical, branched at base (6.7-)8.9-27.2(-29.3) × (2.0-)2.6-3.3(-3.7) (mean, 21.4 × 3.2) μm (n=30); conidia oblong-ellipsoidal to obovoid or subcylindrical 3.3 to 6.8 μm long, and 1.1 to 2.2 (mean, 4.2 × 1.6) μm wide (n=30). In spring 2020, artificial inoculations were carried out with P. oleae (Pm14, Pm46) and P. viticola (Pm34, Pm43) strains on 10 healthy, 2-year-old olive seedlings cultivar 'Coratina'. Agar plugs (diameter, 0.3-0.5 cm) from 10-day-old cultures grown on water agar at 23 (±2) °C were inserted under the bark of small wounds in the stems (length, 0.4-1.0 cm) made with a sterile scalpel. After inoculation, the wounds were wrapped with wet sterile cotton wool and sealed with Parafilm. Ten control olive seedlings were inoculated with sterile agar plugs. The experiment was replicated three times. All inoculated young olive plants were grown in pots in a greenhouse without temperature control. After 120 days, inoculated plants showed decline symptoms, and when cut longitudinally, brown streaks were observed in the wood. For P. oleae these streaks measured 3.0-5.5 cm long (standard deviation [SD], 0.9 cm, and for P. viticola they were 1.8-3.5 cm (SD, 0.62). Both fungal species were re-isolated from the symptomatic wood from 85% and 80%, respectively, of these inoculated olive seedlings, fulfilling Koch's postulates. No symptoms were observed from olive seedlings used as control. P. oleae was first described as a fungal pathogen of wild olive (Olea europaea subsp. cuspidate) in South Africa by Spies et al. (2018), and P. viticola as a fungal pathogen of grapevine in France by Dupont et al. (2000). To the best of our knowledge, this is the first report of P. oleae associated with olive trunk disease in Italy, and the first report of P. viticola associated with olive trunk disease worldwide. References: Carbone I. & Kohn L.M. 1999. Mycologia 91:553. Carlucci A. et al. 2015. Eur. J. Plant Pathol. 141:717. Carlucci A. et al. 2013. Phytopathol. Mediterr. 52:517. Dupont et al. 2000. Mycologia 92:499-504. Glass N. L. & Donaldson G. C. 1995. J. Cl. Microbiol. 41: 1332. Mostert L. et al. 2006. Stud. Mycol. 54:1. O'Donnell K. & Cigelnik E. 1997. Mol. Phylogenetics Evol 7:103. Spies et al. 2018. Persoonia 40:26.


Pediatric trauma: preparation and management.
1. Trauma causes more than 50% of the deaths in children. The leading cause of pediatric injury is motor vehicle accidents involving children as passengers, pedestrians, or bicycle riders. 2. Trauma is always unexpected; therefore, the most vital aspect of any trauma system is that the system itself never be caught unprepared. Anticipation and preparation are the best first-line defenses against traumatic injury. 3. Because of a child's smaller size, vital organs are in close proximity to one another; multiple organ injuries are common. 4. The team who responds to a pediatric trauma should include nurses and physicians trained in principles of pediatric resuscitation.


A guide to clinical research supervision for psychiatrists: a mentoring approach.
To provide a guide for clinically-based psychiatrist supervisors of research projects for early career researchers. This paper will describe a mentoring framework for supervision, for psychiatrist clinical research supervisors and early career researchers. The domains discussed include, across various aspects of a study: the role of the supervisor, project management, and where and when to seek advice. Supervision of clinical research can be a professionally rewarding experience for psychiatrists, as well as early career researcher supervisees.


Effects of open vs. closed system endotracheal suctioning on cerebral blood flow velocities in mechanically ventilated extremely low birth weight infants.
Endotracheal (ET) suctioning causes cardiovascular side effects and may impair cerebral hemodynamics. Subjectively, these effects are worse if patients are disconnected from the ventilator (open system suctioning, OSS) than if they remain connected to the ventilator during suctioning (closed system suctioning, CSS). It is uncertain whether the response to ET suctioning is similar in conventionally (CV) and high frequency (HF) ventilated patients. To investigate if the mode of suctioning or of mechanical ventilation influences cerebral blood flow velocities (CBFVs) in extremely low birth weight (ELBW) infants. Transcranial Doppler sonography in the middle cerebral artery during OSS and CSS in CV and HF ventilated ELBW infants. Forty-one measurements were performed in 19 infants within the first two weeks of life. Mean CBFVs decreased during suctioning from baseline 18.8 to 14.3 cm/s (-24%), increased thereafter to 24.7 cm/s (73%) and then returned to baseline (20.8 cm/s). Changes in CBFV were less pronounced in infants with higher baseline CBFVs. Heart rate decreased during ET suctioning and thereafter returned to baseline values. The alterations in CBFV and heart rate were both independent of the mode of ventilation or suctioning. The mode of suctioning or ventilation does not influence CBFVs in ELBW infants.


Tau pathogenesis is promoted by Aβ1-42 but not Aβ1-40.
The relationship between the pathogenic amyloid β-peptide species Aβ1-42 and tau pathology has been well studied and suggests that Aβ1-42 can accelerate tau pathology in vitro and in vivo. The manners if any in which Aβ1-40 interacts with tau remains poorly understood. In order to answer this question, we used cell-based system, transgenic fly and transgenic mice as models to study the interaction between Aβ1-42 and Aβ1-40. In our established cellular model, live cell imaging (using confocal microscopy) combined with biochemical data showed that exposure to Aβ1-42 induced cleavage, phosphorylation and aggregation of wild-type/full length tau while exposure to Aβ1-40 didn't. Functional studies with Aβ1-40 were carried out in tau-GFP transgenic flies and showed that Aβ1-42, as previously reported, disrupted cytoskeletal structure while Aβ1-40 had no effect at same dose. To further explore how Aβ1-40 affects tau pathology in vivo, P301S mice (tau transgenic mice) were injected intracerebrally with either Aβ1-42 or Aβ1-40. We found that treatment with Aβ1-42 induced tau phosphorylation, cleavage and aggregation of tau in P301S mice. By contrast, Aβ1-40 injection didn't alter total tau, phospho-tau (recognized by PHF-1) or cleavage of tau, but interestingly, phosphorylation at Ser262 was shown to be significantly decreased after direct inject of Aβ1-40 into the entorhinal cortex of P301S mice. These results demonstrate that Aβ1-40 plays different role in tau pathogenesis compared to Aβ1-42. Aβ1-40 may have a protective role in tau pathogenesis by reducing phosphorylation at Ser262, which has been shown to be neurotoxic.


Genomic alterations of ERBB receptors in cancer: clinical implications.
The ERBB family of receptor tyrosine kinases has been implicated in carcinogenesis for over three decades with rigorous attention to EGFR and HER2. ERBB receptors, consisting of EGFR, HER2, HER3, and HER4 are part of a complicated signaling network that activates downstream signaling pathways including PI3K/AKT, Ras/Raf/MAPK, JAK/STAT and PKC. It is well established that EGFR is amplified and/or mutated in gliomas and non-small-cell lung carcinoma while HER2 is amplified and/or over-expressed in breast, gastric, ovarian, non-small cell lung carcinoma, and several other tumor types. With the advent of next generation sequencing and large scale efforts to explore the entire spectrum of genomic alterations involved in human cancer progression, it is now appreciated that somatic ERBB receptor mutations occur at relatively low frequencies across multiple tumor types. Some of these mutations may represent oncogenic driver events; clinical studies are underway to determine whether tumors harboring these alterations respond to small molecule EGFR/HER2 inhibitors. Recent evidence suggests that some somatic ERBB receptor mutations render resistance to FDA-approved EGFR and HER2 inhibitors. In this review, we focus on the landscape of genomic alterations of EGFR, HER2, HER3 and HER4 in cancer and the clinical implications for patients harboring these alterations.


Study of chondrogenic potential of stem cells in co-culture with chondrons.
Three-dimensional biomimetic scaffolds have widespread applications in biomedical tissue engineering due to similarity of their nanofibrous architecture to native extracellular matrix. Co-culture system has stimulatory effect on chondrogenesis of adult mesenchymal stem cells. This work presents a co-culture strategy using human articular chondrons and adipose-derived stem cells (ASCs) from infrapatellar fat pad (IPFP) for cartilage tissue production. Isolated stem cells were characterized by flowcytometry. Electrospun and polycaprolactone (PCL) scaffolds (900 nm fiber diameter) was obtained from Bon Yakhteh (Tehran-Iran) and human infrapatellar fat pad-derived stem cells (IPFP-ASCs) were seeded on them. IPFP-ASCs on scaffolds were co-cultured with articular chondrons using transwell. After 21 day, chondrogenic differentiation of stem cell was evaluated by determining the genes expression of collagen2, aggrecan and Indian hedgehog using real-time RT-PCR. Genes expression of collagen2, aggrecan by IPFP-ASCs did not alter significantly in comparison with control group. Howevers, expression of Indian hedgehog decreased significantly compared to control group (P< 0.05). These findings indicate that chondrons obtained from osteoarthritic articular cartilage did not stimulate chondrogenic differentiation of IPFP-ASCs in co-culture.


Design and synthesis of a solid-phase fluorescent mass tag.
In this study, we demonstrate the design of a new solid-phase fluorescent mass tag (FMT) that contains the following features: (1) the FMT is synthesized using Fmoc chemistry which is simple, rapid, and cost-effective; (2) lysine is used as a uniformly labeled amino acid (using stable isotopes) to allow 8 Da difference between "heavy" and "light" tags; (3) a fluorescent molecule is coupled to the isotope tag that allows a tagged peptide to be detected by online fluorescence; and (4) an iodoacetyl reactive group provides cysteine reactivity. Using MALDI-TOF MS and HPLC, we show that the FMT reagent can be used to label standard cysteine-containing peptides as well as cysteine-containing peptides from a BSA tryptic digest.


Immediate effects of cryotherapy on static and dynamic balance.
Cryotherapy is commonly used in physical therapy with many known benefits; however several investigations have reported decreased functional performance following therapeutic application thereof. The purpose of this study was to determine the effect of cryotherapy applied to the ankle on static and dynamic standing balance. It was hypothesized that balance would be decreased after cryotherapy application. Twenty individuals (aged 18 to 40 years) participated in this research project. Each participant was tested under two conditions: an experimental condition where subjects received ice water immersion of the foot and ankle for 15 minutes immediately before balance testing and a control condition completed at room temperature. A Biodex® Balance System was used to quantify balance using anterior/posterior (AP), medial/lateral (ML), and overall balance indices. Paired t-tests were used to compare the balance indices for the two conditions with alpha set at 0.05 a priori. Effect size was also calculated to account for the multiple comparisons made. The static balance indices did not display statistically significant differences between the post-cryotherapy and the control conditions with low effect sizes. Dynamic ML indices significantly increased following the cryotherapy application compared to the control exhibiting a moderate effect size indicating decreased balance following cryotherapy application. No differences were noted between experimental and control conditions for the dynamic AP or overall balance indices while a small effect size was noted for both. The results suggest that cryotherapy to the ankle has a negative effect on the ML component of dynamic balance following ice water immersion. Immediate return to play following cryotherapy application is cautioned given the decreased dynamic ML balance and potential for increased injury risk. 3b Case-control study.


Adaptation in Caco-2 Human Intestinal Cell Differentiation and Phenolic Transport with Chronic Exposure to Blackberry (Rubus sp.) Extract.
As evidence mounts for a health-protective role of dietary phenolics, the importance of understanding factors influencing bioavailability increases. Recent evidence has suggested chronic exposure to phenolics may impact their absorption and metabolism. To explore alterations occurring from chronic dietary exposure to phenolics, Caco-2 cell monolayers were differentiated on Transwell inserts with 0-10 μM blackberry (Rubus sp.) total phenolics extracts rich in anthocyanins, flavonols, and phenolic acids. Following differentiation, apical to basolateral transport of phenolics was assessed from an acute treatment of 100 μM blackberry phenolics from 0 to 4 h. Additionally, differences in gene expression of transport and phase II metabolizing systems including ABC transporters, organic anion transporters (OATs), and uridine 5'-diphospho (UDP) glucuronosyltransferases (UGTs) were probed. After 4 h, 1 μM pretreated monolayers showed a significant (P < 0.05) decrease in the percentage of cumulative transport including less epicatechin (42.1 ± 0.53), kaempferol glucoside (23.5 ± 0.29), and dicaffeoylquinic acid (31.9 ± 0.20) compared to control. Finally, significant (P < 0.05) alterations in mRNA expression of key phase II metabolizing enzymes and transport proteins were observed with treatment. Therefore, adaptation to blackberry extract exposure may impact intestinal transport and metabolism of phenolics.


Camellia sinensis Prevents Perinatal Nicotine-Induced Neurobehavioral Alterations, Tissue Injury, and Oxidative Stress in Male and Female Mice Newborns.
Nicotine exposure during pregnancy induces oxidative stress and leads to behavioral alterations in early childhood and young adulthood. The current study aimed to investigate the possible protective effects of green tea (Camellia sinensis) against perinatal nicotine-induced behavioral alterations and oxidative stress in mice newborns. Pregnant mice received 50 mg/kg C. sinensis on gestational day 1 (PD1) to postnatal day 15 (D15) and were subcutaneously injected with 0.25 mg/kg nicotine from PD12 to D15. Nicotine-exposed newborns showed significant delay in eye opening and hair appearance and declined body weight at birth and at D21. Nicotine induced neuromotor alterations in both male and female newborns evidenced by the suppressed righting, rotating, and cliff avoidance reflexes. Nicotine-exposed newborns exhibited declined memory, learning, and equilibrium capabilities, as well as marked anxiety behavior. C. sinensis significantly improved the physical development, neuromotor maturation, and behavioral performance in nicotine-exposed male and female newborns. In addition, C. sinensis prevented nicotine-induced tissue injury and lipid peroxidation and enhanced antioxidant defenses in the cerebellum and medulla oblongata of male and female newborns. In conclusion, this study shows that C. sinensis confers protective effects against perinatal nicotine-induced neurobehavioral alterations, tissue injury, and oxidative stress in mice newborns.


Examination of the Borrelia burgdorferi transcriptome in Ixodes scapularis during feeding.
Borrelia burgdorferi gene expression within the guts of engorging Ixodes scapularis ticks was examined by use of differential immunoscreening and differential expression with a customized amplified library. Fourteen chromosomal genes involved in energy metabolism, substrate transport, and signal transduction and 10 (4 chromosomal and 6 plasmid) genes encoding putative lipoproteins and periplasmic proteins were preferentially expressed in engorging ticks. These data demonstrate a new approach to the global analysis of B. burgdorferi genes that are preferentially expressed within the vector during feeding.


Statistical theory of the compensating effect when anchoring with two orthogonal photoaligned polymers.
In this paper we extend a statistical microscopic analysis to the anchoring properties of polymer films obtained by two concomitant or subsequent polymerization processes along two different directions. We can thus explain the recently observed compensating effect of two orthogonal polymerization processes. An expression for the anchoring energy has been evaluated from the extra Helmholtz free energy within an interface layer where the interactions shift from polymer-nematic interactions to nematic-nematic interactions, as in bulk. The result includes the angular dependence on the two photoaligning directions. A procedure of getting controlled anchoring strength in situ is suggested.


Rare extra-adrenal paraganglioma mimicking a painful Schwannoma: case report.
Paragangliomas originate from chromaffin tissue primarily found in the Zuckerkandl body. A 53 years old man, was investigated with abdominal MRI for chronic backache, that had lasted for 2 years. MRI revealed an incidental mass in para-aortic region, at the adrenal lodge, with characteristics of a solid nodular mass, which did not seem to arise from the adrenal gland. An abdominal CT showed a mass localized prior to left adrenal gland; the radiologist reported this mass as a malignant peripheral nerve sheath tumor (Schwannoma). During his stay in hospital, tumoral markers chromogranin and neuron-specific enolase were dosed, with a concentration of 187.00 ng/mL and 7.7 ng/mL. Patient's back pain was treated first with ketorolac, without any resolution of the problem, then with ketorolac plus tramadol in elastomeric pump, again with no relief, and finally with a continuous infusion of morphine. Since the exact nature of the neoplasm was not known and a CT guided biopsy was not technically feasible to do, a laparoscopic excision of the mass, with transperitoneal anterior submesocolic approach, as well as for the left adrenalectomy, was planned. After surgery, the patient no longer needed morphine. The postoperative course was uneventful. Histopathological findings consisted of periadrenal paraganglioma. Extra-adrenal paragangliomas are rarely recognized during preoperative study. This is often due to its capacity of mimicking other type of tumors. Paragangliomas could be successfully resected by laparoscopy, they are difficult to distinguish from other tumor and they should be investigated even if preoperative findings argue for something else.


Optimising retention success: a research team's experience of following-up participants recruited to a pilot trial through community pharmacies in England.
Background: Community pharmacies support a range of patients and medical conditions, and form an important part of comprehensive, holistic healthcare services. The role of a community pharmacist has changed significantly over recent years, developing to include research activities. The CHAMP-1 ( Community pharmacy: Highlighting Alcohol use in Medication a Ppointments) pilot trial aimed to explore an intervention discussing alcohol during medication consultations. It presented various challenges regarding patient retention, and various actions were taken to address these, which are discussed in this manuscript. Methods: Community pharmacists recruited patients aged 18 and over, attending a Medicine Use Review (MUR) or New Medicine Service (NMS) consultation, and drinking alcohol at least twice per week. Pharmacies were randomised to conduct their consultations as usual (control), or to incorporate the Medicines and Alcohol Consultation (MAC) intervention. All participants were followed-up by a researcher after two months to complete data collection via telephone or post. Results: Forty-seven of 51 participants (92%) completed the two month follow-up. Thirty-eight (81%) responses were provided by telephone and nine (19%) by post. Of the 38 follow-up calls completed by telephone, 17 (45%) participants were reached at first attempt; 16 (42%) at second attempt; and five (13%) at the third attempt. Conclusions: The results suggest that patients recruited to a trial by community pharmacists are willing to take part in data collection activities, and follow-up can be successfully conducted by researchers. The techniques employed to encourage high levels of retention should be investigated further in a larger study.


NMR structure of an alpha-L-LNA:RNA hybrid: structural implications for RNase H recognition.
Alpha-L-LNA (alpha-L-ribo configured locked nucleic acid) is a nucleotide analogue that raises the thermostability of nucleic acid duplexes by up to approximately 4 degrees C per inclusion. We have determined the NMR structure of a nonamer alpha-L-LNA:RNA hybrid with three alpha-L-LNA modifications. The geometry of this hybrid is intermediate between A- and B-type, all nucleobases partake in Watson-Crick base pairing and base stacking, and the global structure is very similar to that of the corresponding unmodified hybrid. The sugar-phosphate backbone is rearranged in the vicinity of the modified nucleotides. As a consequence, the phosphate groups following the modified nucleotides are rotated into the minor groove. It is interesting that the alpha-L-LNA:RNA hybrid, which has an elevation in melting temperature of 17 degrees C relative to the corresponding DNA:RNA hybrid, retains the global structure of this hybrid. To our knowledge, this is the first example of such a substantial increase in melting temperature of a nucleic acid analogue that does not act as an N-type (RNA) mimic. alpha-L-LNA:RNA hybrids are recognised by RNase H with subsequent cleavage of the RNA strand, albeit with slow rates. We attempt to rationalise this impaired enzyme activity from the rearrangement of the sugar-phosphate backbone of the alpha-L-LNA:RNA hybrid.


[Expression of human leucocyte antigen G in peripheral blood of kidney transplantation recipients].
To investigate the expression of non-classical major histocompatibility complex (MHC)-I molecule, human leucocyte antigen (HLA) G, including membrane-bound HLA-G (mHLA-G), intracellular HLA-G (iHLA-G) and soluble HLA-G (sHLA-G), in peripheral blood of surviving kidney transplantation recipients and understand the relevance between HLA-G and the function of transplanted organ, as well as the onset of acute rejection. A longitudinal study was performed on 175 kidney transplantation recipients. Three groups were involved in this study, including acute rejection group (n = 36), function stable group (n = 139) and healthy control group (n = 30). The expression of mHLA-G1 and iHLA-G1 in the T lymphocytes of peripheral blood was detected by flow cytometry analysis and the sHLA-G5 level detected by ELISA. The average rate of CD4(+)mHLA-G1(+), CD8(+)mHLA-G1(+), CD4(+)iHLA-G1(+), CD8(+)iHLA-G1(+) in T lymphocytes of healthy control group was 0.43% +/- 0.19%, 1.23% +/- 0.41%, 27% +/- 13% and 36% +/- 14% respectively. That of acute rejection group was 0.57% +/- 0.34%, 1.31% +/- 0.56%, 26% +/- 8% and 37% +/- 17%; that of function stable group was 0.61% +/- 0.43%, 1.39% +/- 0.47%, 26% +/- 9% and 37% +/- 17% respectively. There was no significant difference among the three groups (all P > 0.05). The average of sHLA-G5 levels in plasma of control group was (25 +/- 14) ng/ml, acute rejection group (24 +/- 15) ng/ml (pre-operative) and (34 +/- 21) ng/ml (post-operative), function stable group (25 +/- 11) ng/ml (pre-operative) and (56 +/- 32) ng/ml (post-operative). There was no significant difference among the three groups (pre-operative, P > 0.05). The average of sHLA-G5 levels in plasma of function stable group was higher than that of acute rejection group (post-operative, P < 0.05). There is a subset of CD4(+)HLA-G1(+) and CD8(+)HLA-G1(+)T lymphocytes with low percentage in peripheral blood of those surviving kidney transplantation recipients. The expressions of mHLA-G1 and iHLA-G1 have no relevance with the onset of acute rejection. sHLA-G5 is correlated with acute rejection in peripheral blood of surviving transplantation recipients.


Ejection of the Massive Hydrogen-rich Envelope Timed with the Collapse of the Stripped SN 2014C.
We present multi-wavelength observations of SN 2014C during the first 500 days. These observations represent the first solid detection of a young extragalactic stripped-envelope SN out to high-energy X-rays ~40 keV. SN 2014C shows ordinary explosion parameters (Ek ~ 1.8 × 1051 erg and Mej ~ 1.7 M⊙). However, over an ~1 year timescale, SN 2014C evolved from an ordinary hydrogen-poor supernova into a strongly interacting, hydrogen-rich supernova, violating the traditional classification scheme of type-I versus type-II SNe. Signatures of the SN shock interaction with a dense medium are observed across the spectrum, from radio to hard X-rays, and revealed the presence of a massive shell of ~1 M⊙of hydrogen-rich material at ~6 × 1016 cm. The shell was ejected by the progenitor star in the decades to centuries before collapse. This result challenges current theories of massive star evolution, as it requires a physical mechanism responsible for the ejection of the deepest hydrogen layer of H-poor SN progenitors synchronized with the onset of stellar collapse. Theoretical investigations point at binary interactions and/or instabilities during the last nuclear burning stages as potential triggers of the highly time-dependent mass loss. We constrain these scenarios utilizing the sample of 183 SNe Ib/c with public radio observations. Our analysis identifies SN 2014C-like signatures in ~10% of SNe. This fraction is reasonably consistent with the expectation from the theory of recent envelope ejection due to binary evolution if the ejected material can survive in the close environment for 103-104 years. Alternatively, nuclear burning instabilities extending to core C-burning might play a critical role.


DIYABC v2.0: a software to make approximate Bayesian computation inferences about population history using single nucleotide polymorphism, DNA sequence and microsatellite data.
DIYABC is a software package for a comprehensive analysis of population history using approximate Bayesian computation on DNA polymorphism data. Version 2.0 implements a number of new features and analytical methods. It allows (i) the analysis of single nucleotide polymorphism data at large number of loci, apart from microsatellite and DNA sequence data, (ii) efficient Bayesian model choice using linear discriminant analysis on summary statistics and (iii) the serial launching of multiple post-processing analyses. DIYABC v2.0 also includes a user-friendly graphical interface with various new options. It can be run on three operating systems: GNU/Linux, Microsoft Windows and Apple Os X. Freely available with a detailed notice document and example projects to academic users at http://www1.montpellier.inra.fr/CBGP/diyabc CONTACT: email@example.com Supplementary information: Supplementary data are available at Bioinformatics online.


Altered expression of Akt signaling pathway parameters in prostate needle biopsies derived from benign, adjacent and cancerous tissue.
PTEN, p-Akt and p27kip1 are known to be altered in prostate cancer. The aim of the present study was to determine the addition of molecular markers to a classical histopathological approach to enhance the sensitivity in detection of malignant or premalignant lesions within prostatic biopsies. Forty-two fine needle biopsies from malignant, tumor adjacent and benign areas were obtained from 14 patients scheduled for a prostatic biopsy. Biomarker expression was determined by immunohistochemistry and correlated to different localizations. We observed a reduction of Akt signaling proteins in cancer tissue compared to benign controls with significantly lower expression of p27kip1 (P=0.0024), PTEN (P=0.0045) and p-Akt (P=0.028). A pathologist histopathologically classified the tumor adjacent tissue obtained from areas distinctly apart from the primary tumor as benign in all cases. In these regions we observed an intermediate expression of Akt signaling proteins without significant difference in relation to the findings in the malignant samples. The expression of Akt signaling proteins is reduced in prostate cancer compared to normal prostate tissue. The intermediate expression of these proteins in tumor adjacent tissue warrants further investigations into the role of Akt signaling in the carcinogenesis and early detection of prostate cancer. There seems to be a marked difference between the molecular and histopathological characterization of prostate tissue. Molecular markers might further augment the histopathological diagnosis suggesting the need for earlier repeated prostate biopsy in case of microscopic malignancy.


[Reopening of chronic coronary occlusions--initial references for prognostic indications].
Today indication for percutaneous transluminal coronary angioplasty is based on typical chest pain and objective signs of myocardial ischemia during exercise. Especially in chronic coronary occlusions, however, prognostic implications may play an increasing role in the future. The case report describes long-term follow-up of a patient in whom a chronic complete occlusion of the right coronary artery could be reopened successfully back in September 1988. At this time, the peripheral part of the occluded RCA was filled retrogradely by septal collaterals from the LAD. After reopening the patient remained symptom-free for more than two years. In January 1991 again severe angina recurred and ECG showed a non-transmural anterior myocardial infarction. The LAD was occluded proximal and the peripheral part was filled retrogradely by septal collaterals coming from the right coronary artery which was still open (flow reversal). Left ventricular function was only slightly impaired and the LAD occlusion could be reopened successfully too. The case suggests that prognostic implications should be taken into consideration in addition to symptoms especially in complete coronary occlusions.


Catastrophic long-term care expenditure: associated socio-demographic and economic factors.
An increasing number of persons across the world require long-term care (LTC). In Spain, access to LTC involves individuals incurring out-of-pocket (OOP) expenditure. There is a large body of literature on the incidence of catastrophic OOP payments in access and participation in health systems, but not in the field of LTC nor the determinants of these expenses. Our aim was to analyse the socio-demographic and economic factors associated with different levels of catastrophic LTC expenditure in the form of private out-of-pocket payments among dependent persons in Spain. The study used the Spanish Disability and Dependency Survey (SDDS) conducted by the Spanish National Statistics Institute to obtain the socioeconomic, demographic and health profiles. The households were classified into those below the poverty threshold and those above the threshold of catastrophe, using measures of impoverishment and catastrophe. We estimated two logistic regression models, one binary (impoverishment) and one ordinal (catastrophe). The results show that OOP expenditure on LTC increases the probability of impoverishment by 18.90%. The factors associated with higher probability of experiencing catastrophe were age, being single, widowed or separated, lower levels of household income and education, higher level of dependence and living in an autonomous community with lower per capita income. These findings highlight the need to include exemptions or insurance in the design of LTC policies to protect dependent persons from the risk of financial burden.


Chemical and biological methods to evaluate the availability of heavy metals in soils of the Siena urban area (Italy).
A biogeochemistry field study was conducted in the Siena urban area (Italy) with the main objective of establishing the relationship between available amounts of heavy metals in soil assessed by a chemical method (soil fractionation) and bioavailability assessed by a biological method (bioaccumulation in earthworm tissues). The total content of traffic-related (Cd, Cu, Pb, Sb, Zn) and geogenic (Co, Cr, Ni, U) heavy metals in uncontaminated and contaminated soils and their concentrations in soil fractions and earthworms were used for this purpose. The bioavailability of heavy metals assessed by earthworms did not always match the availability defined by soil fractionation. Earthworms were a good indicator to assess the bioavailability of Pb and Sb in soil, while due to physiological mechanisms of regulation and excretion, Cd, Cu and Zn tissue levels in these invertebrates gave misleading estimates of their bioavailable pool. No relationship was identified between chemical and biological availability for the geogenic heavy metals, characterized by a narrow range of total contents in soil. The study highlighted that chemical and biological methods should be combined to provide more complete information about heavy element bioavailability in soils.


Trauma-Focused Cognitive Behavioral Therapy for Youth: Effectiveness in a Community Setting.
The current investigation examined the effectiveness of Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) in treating child traumatic stress when implemented in community settings on a state-wide level. Seventy-two youths (ages 7-16 years) with a history of documented trauma (sexual or physical abuse, traumatic loss, domestic or community violence) and symptoms of Posttraumatic Stress Disorder (PTSD) received an average of 10 sessions delivered in a state-contracted mental health agency. PTSD symptoms and internalizing and externalizing behavior problems were assessed at pre-treatment and then at 3-, 6-, 9-, and 12-months after intake. Piecewise hierarchical linear modeling revealed that symptoms of PTSD, as well as internalizing and externalizing problems, decreased significantly over the six months after intake (pretreatment, 3-month, 6-month assessments), and these gains were maintained over the next 6 months (6, 9, and 12 month assessments). Symptoms of externalizing symptoms increased somewhat during the follow-up period, but this change was not statistically significant. These findings suggest that TF-CBT can be implemented effectively in community settings. Treatment outcomes were similar to those reported in efficacy trials of TF-CBT delivered in specialty clinic settings. Improvements in PTSD symptoms and internalizing and externalizing problems were maintained up to one year after treatment began, although the changes in externalizing symptoms were the least stable.


Dynamic reconfiguration of the language network preceding onset of speech in picture naming.
Language production is a complex neural process that requires the interplay between multiple specialized cortical regions. We investigated modulations in large-scale cortical networks underlying preparation for speech production by contrasting cortico-cortical coherence for overt and silent picture naming in an all-to-all connectivity analysis. To capture transient, frequency-specific changes in functional connectivity we analyzed the magnetoencephalography data in two consecutive 300-ms time windows. Within the first 300 ms following picture onset beta frequency coherence was increased for overt naming in a network of regions comprising the bilateral parieto-temporal junction and medial cortices, suggesting that overt articulation modifies selection processes involved in speech planning. In the late time window (300-600 ms after picture onset) beta-range coherence was enhanced in a network that included the ventral sensorimotor and temporal cortices. Coherence in the gamma band was simultaneously reduced between the ventral motor cortex and supplementary motor area, bilaterally. The results suggest functionally distinct roles for beta (facilitatory) and gamma (suppressive) band interactions in speech production, with strong involvement of the motor cortex in both frequency bands. Overall, a striking difference in functional connectivity between the early and late time windows was observed, revealing the dynamic nature of large-scale cortical networks that support language and speech. Our results demonstrate that as the naming task evolves in time, the global connectivity patterns change, and that these changes occur (at least) on the time-scale of a few hundred milliseconds. More generally, these results bear implications for how we view large-scale neural networks underlying task performance.


Budd-Chiari syndrome treated by Senning's procedure.
Two patients with Budd-Chiari syndrome who underwent a new surgical procedure developed by Senning are reported. A 33-year-old man was diagnosed as having Budd-Chiari syndrome with a membranous obstruction of the inferior vena cava (IVC) and right hepatic vein and short segmental obstruction of the left hepatic vein. Removal of the obstruction by dorsocranial resection of the liver and reconstruction of the veins by hepatoatrial anastomosis was carried out. In a 53-year-old female, the same procedure was carried out for a short segmental obstruction of the IVC and left hepatic vein. In both patients, postoperative examination revealed good patency of the IVC and the hepatic veins and increased portal venous flow as measured by Doppler-echography. This procedure is considered the method of choice for Budd-Chiari syndrome with membranous and/or short segmental obstruction of the IVC and hepatic veins.


Construction of a vertical undulator at SPring-8.
A new-type insertion device (ID) has been constructed for the structural-biology beamline (BL45XU) at SPring-8. The ID consists of two undulators which can provide vertical polarized radiation (vertical undulators). By changing the individual gap of each undulator independently, photons with two different energies can be obtained. Magnetic field measurements show that the maximum horizontal field is 0.49 T and the magnetic performance is as good as expected.


An Unusual Presentation of Recurrent Childhood Kimura Disease: Ileocecal Involvement.
Kimura disease commonly presents as an isolated swelling over the head and neck region. Intestinal involvement by Kimura disease in children is uncommonly reported. We report a 10-year-old boy who had presented with an ileocaecal mass with peripheral blood eosinophilia and elevated immunoglobulin E levels. The histopathologic examination from the ileocaecal mass was suggestive of Kimura disease. He had 2 recurrences once in the left axillary region and once in the bilateral cervical region. Ileocaecal involvement in Kimura disease is an uncommon presentation in childhood. Careful evaluation of complete blood count is critical in making diagnosis and avoiding unnecessary invasive procedures.


Effect of Heterogeneous Sediment Distributions on Hyporheic Flow in Physical and Numerical Models.
Variations in permeability have been found to significantly affect the flow of water though hyporheic systems, especially in regions with discontinuous transitions between distinct streambed lithologies. In this study, we probabilistically arranged two sediments (sand and sandy gravel) in a grid framework and imposed a single hyporheic flow cell across the grid to investigate how discontinuous permeability fields influence volumetric flow and residence time distributions. We used both a physical system and computer simulations to model flow through this sediment grid. A solution of blue dye and salt was pumped into the system and used to detect flow. We recorded the dye location using time-lapse photography and measured the electrolytic conductivity levels as the water exited the system as a proxy for salt concentration. We also used a computer simulation to calculate dye-fronts, residence times, and exiting salt concentrations for the modeled system. Comparison between simulations and physical measurements yielded strong agreement. In further simulations with 300 different grids, we found a strong correlation between volumetric flow rate and the placement of high permeability grid cells in regions of high hydraulic head gradients. One implication is that small anomalies in streambed permeability have a disproportionately large influence on hyporheic flows when located near steep head gradients such as steps. We also used moving averages with varying window sizes to investigate the effect of the abruptness of transitions between sediment types. We found that smoother permeability fields increased the volumetric flow rate and decreased the median residence times.


Spreading Depolarizations: A Therapeutic Target Against Delayed Cerebral Ischemia After Subarachnoid Hemorrhage.
Delayed cerebral ischemia is the most feared cause of secondary injury progression after subarachnoid hemorrhage. Initially thought to be a direct consequence of large artery spasm and territorial ischemia, recent data suggests that delayed cerebral ischemia represents multiple concurrent and synergistic mechanisms, including microcirculatory dysfunction, inflammation, and microthrombosis. Among these mechanisms, spreading depolarizations (SDs) are arguably the most elusive and underappreciated in the clinical setting. Although SDs have been experimentally detected and examined since the late 1970s, their widespread occurrence in human brain was not unequivocally demonstrated until relatively recently. We now know that SDs occur with very high incidence in human brain after ischemic or hemorrhagic stroke and trauma, and worsen outcomes by increasing metabolic demand, decreasing blood supply, predisposing to seizure activity, and possibly worsening brain edema. In this review, we discuss the causes and consequences of SDs in injured brain. Although much of our mechanistic knowledge comes from experimental models of focal cerebral ischemia, clinical data suggest that the same principles apply regardless of the mode of injury (i.e., ischemia, hemorrhage, or trauma). The hope is that a better fundamental understanding of SDs will lead to novel therapeutic interventions to prevent SD occurrence and its adverse consequences contributing to injury progression in subarachnoid hemorrhage and other forms of acute brain injury.


Using cultured canine cardiac slices to model the autophagic flux with doxorubicin.
Chemotherapy-induced impairment of autophagy is implicated in cardiac toxicity induced by anti-cancer drugs. Imperfect translation from rodent models and lack of in vitro models of toxicity has limited investigation of autophagic flux dysregulation, preventing design of novel cardioprotective strategies based on autophagy control. Development of an adult heart tissue culture technique from a translational model will improve investigation of cardiac toxicity. We aimed to optimize a canine cardiac slice culture system for exploration of cancer therapy impact on intact cardiac tissue, creating a translatable model that maintains autophagy in culture and is amenable to autophagy modulation. Canine cardiac tissue slices (350 μm) were generated from left ventricular free wall collected from euthanized client-owned dogs (n = 7) free of cardiovascular disease at the Foster Hospital for Small Animals at Tufts University. Cell viability and apoptosis were quantified with MTT assay and TUNEL staining. Cardiac slices were challenged with doxorubicin and an autophagy activator (rapamycin) or inhibitor (chloroquine). Autophagic flux components (LC3, p62) were quantified by western blot. Cardiac slices retained high cell viability for >7 days in culture and basal levels of autophagic markers remained unchanged. Doxorubicin treatment resulted in perturbation of the autophagic flux and cell death, while rapamycin co-treatment restored normal autophagic flux and maintained cell survival. We developed an adult canine cardiac slice culture system appropriate for studying the effects of autophagic flux that may be applicable to drug toxicity evaluations.


[Binding of protein SCP to myelin, its identity with protein P2. A simple method of protein P2 isolation].
Protein SCP is found in myelin of spinal cord and spinal roots. It is shown that its amount accounts for 12% of the total protein content in myelin of spinal roots and only for 2% in myelin of spinal cord. Almost all the studied protein is extracted from myelin with 0.1 M NaCl (80-90%). The absolute identity of protens SCP and P2 is established using the cross reaction immunodiffusion with monospecific antisera. It is shown that- N-terminal amino acid in protein SCP, like in protein P2 is blocked. On the basis of the data obtained a conclusion is made that protein P2 is not an integral protein of myelin. However, myelin is capable under conditions of a nonionic medium of binding protein which then may be easily extracted by increasing the medium ionic strength. This gave reasons to propose a method for protein P2 isolation from myelin using 0.15 M NaCl with the subsequent purification by means of Sephadex G-50 gelfiltration.


Hippocampal CA3 pyramidal cells selectively innervate aspiny interneurons.
The specific connectivity among principal cells and interneurons determines the flow of activity in neuronal networks. To elucidate the connections between hippocampal principal cells and various classes of interneurons, CA3 pyramidal cells were intracellularly labelled with biocytin in anaesthetized rats and the three-dimensional distribution of their axon collaterals was reconstructed. The sections were double-stained for substance P receptor (SPR)- or metabotropic glutamate receptor 1alpha (mGluR-1alpha)-immunoreactivity to investigate interneuron targets of the CA3 pyramidal cells. SPR-containing interneurons represent a large portion of the GABAergic population, including spiny and aspiny classes. Axon terminals of CA3 pyramidal cells contacted SPR-positive interneuron dendrites in the hilus and in all hippocampal strata in both CA3 and CA1 regions (7.16% of all boutons). The majority of axons formed single contacts (87.5%), but multiple contacts (up to six) on single target neurons were also found. CA3 pyramidal cell axon collaterals innervated several types of morphologically different aspiny SPR-positive interneurons. In contrast, spiny SPR-interneurons or mGluR-1alpha-positive interneurons in the hilus, CA3 and CA1 regions were rarely contacted by the filled pyramidal cells. These findings indicate a strong target selection of CA3 pyramidal cells favouring the activation of aspiny classes of interneurons.


Antisense protein kinase A RIalpha inhibits 7,12-dimethylbenz(a)anthracene-induction of mammary cancer: blockade at the initial phase of carcinogenesis.
There are two types of cyclic AMP (cAMP)-dependent protein kinase (PKA), type I (PKA-I) and type II (PKA-II), which share a common catalytic (C) subunit but contain distinct regulatory (R) subunits, RI versus RII, respectively. Evidence suggests that increased expression of PKA-I and its regulatory subunit (RIalpha) correlates with tumorigenesis and tumor growth. We investigated the effect of sequence-specific inhibition of RIalpha gene expression at the initial phase of 7,12-dimethylbenz(alphaa)anthracene (DMBA)-induced mammary carcinogenesis. Antisense RIalpha oligodeoxynucleotide (ODN) targeted against PKA RIalpha was administered (0.1 mg/day/rat, i.p.) 1 day before DMBA intubation and during the first 9 days post-DMBA intubation to determine the anticarcinogenic effects. Antisense RIalpha, in a sequence-specific manner, inhibited the tumor production. At 90 days after DMBA intubation, untreated controls and RIalpha-antisense-treated rats exhibited an average mean number of tumors per rat of 4.2 and 1.8, respectively, and 90% of control and 45% of antisense-treated animals had tumors. The antisense also delayed the first tumor appearance. An increase in RIalpha and PKA-I levels in the mammary gland and liver preceded DMBA-induced tumor production, and antisense down-regulation of RIalpha restored normal levels of PKA-I and PKA-II in these tissues. Antisense RIalpha in the liver induced the phase II enzymes, glutathione S-transferase and quinone oxidoreductase, c-fos protein, and activator protein 1 (AP-1)- and cAMP response element (CRE)-directed transcription. In the mammary glands, antisense RIalpha promoted DNA repair processes. In contrast, the CRE transcription-factor decoy could not mimic these effects of antisense RIalpha. The results demonstrate that RIalpha antisense produces dual anticarcinogenic effects: (a) increasing DMBA detoxification in the liver by increasing phase II enzyme activities, increasing CRE-binding-protein phosphorylation and enhancing CRE- and Ap-1-directed transcription; and (b) activating DNA repair processes in the mammary gland by down-regulating PKA-I.


[Neuropsychological alterations in narcolepsy with cataplexy: a review].
To describe the current state of the art about the main cognitive deficits that appear in patients affected with narcolepsy with cataplexy (NT1). The majority of the studies have found that the most impaired cognitive functions are attention (especially maintenance of attention or sustained attention), speed of information processing and executive functions (in particular, verbal fluency and resistance to the stimuli interference). These data indicate the difficulty to use the available cognitive resources of the patient. These alterations are similar to those present in other hypersomnias, although they might differ in intensity. Moreover, most of the studies emphasize a high prevalence of different depressive and anxious disorders. It has been suggested that predisposition to anxiety could be part of the characteristic phenotype of these patients. Anxiety could act either as a trigger for the disease or a consequence of the disease. Cognitive deficits in patients with NT1 appear in long lasting and/or monotonous tasks and in high cognitive demanding tasks. The presence of depressive symptomatology, together with excessive daytime sleepiness in these patients could affect their performance in neuropsychological test, and it might be related to their subjective perception of the cognitive deficits.


Detecting COVID-19 in Chest X-Ray Images via MCFF-Net.
COVID-19 is a respiratory disease caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2). Due to the rapid spread of COVID-19 around the world, the number of COVID-19 cases continues to increase, and lots of countries are facing tremendous pressure on both public and medical resources. Although RT-PCR is the most widely used detection technology with COVID-19 detection, it still has some limitations, such as high cost, being time-consuming, and having low sensitivity. According to the characteristics of chest X-ray (CXR) images, we design the Parallel Channel Attention Feature Fusion Module (PCAF), as well as a new structure of convolutional neural network MCFF-Net proposed based on PCAF. In order to improve the recognition efficiency, the network adopts 3 classifiers: 1-FC, GAP-FC, and Conv1-GAP. The experimental results show that the overall accuracy of MCFF-Net66-Conv1-GAP model is 94.66% for 4-class classification. Simultaneously, the classification accuracy, precision, sensitivity, specificity, and F1-score of COVID-19 are 100%. MCFF-Net may not only assist clinicians in making appropriate decisions for COVID-19 diagnosis but also mitigate the lack of testing kits.


Comparison of zotarolimus-eluting and sirolimus-eluting stents in patients with native coronary artery disease: a randomized controlled trial.
This trial examined the relative clinical efficacy, angiographic outcomes, and safety of zotarolimus-eluting coronary stents (ZES) with a phosphorylcholine polymer versus sirolimus-eluting stents (SES). Whether a cobalt-based alloy stent coated with the novel antiproliferative agent, zotarolimus, and a phosphorylcholine polymer may provide similar angiographic and clinical benefit compared with SES is undetermined. A prospective, multicenter, 3:1 randomized trial was conducted to evaluate the safety and efficacy of ZES (n = 323) relative to SES (n = 113) in 436 patients undergoing elective percutaneous revascularization of de novo native coronary lesions with reference vessel diameters between 2.5 mm and 3.5 mm and lesion length > or =14 mm and < or =27 mm. The primary end point was 8-month angiographic in-segment late lumen loss. Angiographic in-segment late lumen loss was significantly higher among patients treated with ZES compared with SES (0.34 +/- 0.44 mm vs. 0.13 +/- 0.32 mm, respectively; p < 0.001). In-hospital major adverse cardiac events were significantly lower among patients treated with ZES (0.6% vs. 3.5%, p = 0.04). In-segment binary angiographic restenosis was also higher in the ZES cohort (11.7% vs. 4.3%, p = 0.04). Total (clinically and non-clinically driven) target lesion revascularization rates at 9 months were 9.8% and 3.5% for the ZES and SES groups, respectively (p = 0.04). However, neither clinically driven target lesion revascularization (6.3% zotarolimus vs. 3.5% sirolimus, p = 0.34) nor target vessel failure (12.0% zotarolimus vs. 11.5% sirolimus, p = 1.0) differed significantly. Compared with SES, treatment with a phosphorylcholine polymer-based ZES is associated with significantly higher late lumen loss and binary restenosis at 8-month angiographic follow-up. (The Endeavor III CR; http://clinicaltrials.gov/ct/show/NCT00265668?order=1?).


How a Thermally Unstable Metal Hydrido Complex Can Yield High Catalytic Activity Even at Elevated Temperatures.
Despite their instability in ethereal solvents, organotitanium hydride catalysts are successfully employed in catalysis at moderate to high temperatures (110 °C), even in the presence of alcohols. It is shown computationally (bond dissociation energy (BDE) analysis and energetic profile for regeneration) and experimentally (EPR studies and kinetic studies), with the specific example of hydrodefluorination (HDF), that despite the long standing belief, regeneration of Ti-H bonds from Ti-F bonds using silanes is endergonic. The resulting low concentration of Ti-H species is crucial for the catalytic stability of those systems. The resting state in the catalysis is a Ti-F species. The most promising silanes for regeneration are not the ones that have the strongest Si-F bond, but the ones that show the largest difference in Si-F and Si-H BDEs.


Pre-engraftment syndrome after myeloablative dual umbilical cord blood transplantation: risk factors and response to treatment.
High fevers and/or rashes prior to neutrophil engraftment are frequently observed after umbilical cord blood (UCB) transplantation, and the condition is referred to as pre-engraftment syndrome (PES). Few studies have evaluated the risk factors for and treatment response to PES. Therefore, we retrospectively characterized PES in 57 consecutive engrafted patients (≥ 12 years old) who received myeloablative dual UCB transplantation. All patients received TBI (≥ 13.2 Gy)-based myeloablative conditioning. Tacrolimus (n=35) or CYA (n=22) combined with mycophenolate mofetil was used as GVHD prophylaxis. PES was defined as the presence of non-infectious fever (≥ 38.5 °C) and/or rash prior to or on the day of neutrophil engraftment. The incidence (95% confidence interval) of PES was 77% (66-88%). The incidence of PES was significantly higher in patients who received CYA as a GVHD prophylaxis than those who received tacrolimus (P<0.001), and this association was confirmed in the multivariate analysis. The occurrence of PES did not impact OS or tumor relapse, although it may have increased non-relapse mortality (P=0.071). The incidence of acute GHVD or treatment-related mortality was not influenced by the choice to use corticosteroids to treat PES. This study suggests that use of CYA for GVHD prophylaxis increases the risk of PES following dual UCB transplantation.


Elasticity of crystalline beta-sheet monolayers.
Designed amphiphilic beta-sheet peptides with the sequence Pro-Glu-(Phe-Glu)(n)-Pro (n = 2-7) were previously shown by grazing incidence X-ray diffraction (GIXD), to form ordered two-dimensional (2-D) monolayer structures at interfaces induced by the proline residues at peptide termini. The GIXD diffraction pattern was modeled with two coexisting lattice arrangements, suggesting structural flexibility exhibited in the multiple ways by which beta-strands and their amino acid side chains pack into ordered 2-D structures. Here, we find by in-situ GIXD measurements that the ordered beta-sheet assemblies may undergo a quasi-reversible compression and expansion cycle at the air-water interface. The diffraction measurements indicate that on compression the repeat distance that corresponds to the long axes of the peptide strands may decrease by up to 37% in length. Upon expansion the compressed beta-sheet assemblies revert elastically to their original conformation. The interstrand repeat distance along the peptide hydrogen bonds apparently does not change along the film compression and expansion. Based on the GIXD data, at surface pressures higher than approximately 3 mN/m, beyond the peptide limiting area per molecule, the compressibility is 7.4 +/- 0.6 m/N. The out-of-plane Bragg rod diffraction patterns imply that in the compressed state the beta-strands buckle up in reaction to the increase in surface pressure. At low surface pressure, the 2-D compressibility of the crystalline beta-sheet was estimated at approximately 32 m/N attributed to interdomain rearrangements.


A 'chemotactic dipole' mechanism for large-scale vortex motion during primitive streak formation in the chick embryo.
Primitive streak formation in the chick embryo involves significant coordinated cell movement lateral to the streak, in addition to the posterior-anterior movement of cells in the streak proper. Cells lateral to the streak are observed to undergo 'polonaise movements', i.e. two large counter-rotating vortices, reminiscent of eddies in a fluid. In this paper, we propose a mechanism for these movement patterns which relies on chemotactic signals emitted by a dipolar configuration of cells in the posterior region of the epiblast. The 'chemotactic dipole' consists of adjacent regions of cells emitting chemo-attractants and chemo-repellents. We motivate this idea using a mathematical analogy between chemotaxis and electrostatics, and test this idea using large-scale computer simulations. We implement active cell response to both neighboring mechanical interactions and chemotactic gradients using the Subcellular Element Model. Simulations show the emergence of large-scale vortices of cell movement. The length and time scales of vortex formation are in reasonable agreement with experimental data. We also provide quantitative estimates for the robustness of the chemotaxis dipole mechanism, which indicate that the mechanism has an error tolerance of about 10% to variation in chemotactic parameters, assuming that only 1% of the cell population is involved in emitting signals. This tolerance increases for larger populations of cells emitting signals.


Aprepitant as salvage therapy in patients with chemotherapy-induced nausea and emesis refractory to prophylaxis with 5-HT(3) antagonists and dexamethasone.
Despite prophylaxis with 5-HT(3) antagonists and dexamethasone, nausea/emesis are common chemotherapy- induced toxicities. The aim of this trial was to evaluate the efficacy of adding the NK1 antagonist aprepitant in patients refractory to standard prophylaxis. Patients with significant nausea/vomiting despite prophylaxis with 5-HT(3) antagonists and dexamethasone were eligible. Aprepitant was added to the same antiemetic regimen used during previous cycles. 34 patients received 92 cycles of chemotherapy with aprepitant which was applied orally at 125 mg on day 1 and 80 mg on days 2 and 3. All patients were refractory to standard antiemetic prophylaxis during cisplatin-based (n = 12) or other chemotherapy (n = 22). With the addition of aprepitant, all patients reported subjective improvement. The number of patients with nausea for >4 days decreased from 24 (71%) to 4 (12%) (p < 0.001), and the number of those with emesis for >2 days decreased from 26 (77%) to 0 (0%) (p < 0.001). In 12 patients receiving aprepitant for >2 cycles (3-8) the efficacy was maintained. No toxicity possibly related to aprepitant was observed. Aprepitant demonstrated significant activity in patients with nausea/vomiting refractory to prophylaxis with 5-HT(3) antagonists and dexamethasone.


The characterization of gefitinib sensitivity and adverse events in patients with non-small cell lung cancer.
Factors predicting gefitinib sensitivity and adverse events in non-small cell lung cancer (NSCLC) remain controversial. Correlations among clinicopathological characteristics, gefitinib sensitivity and adverse events were studied in 154 patients with NSCLC, whereas epidermal growth factor receptor (EGFR) mutations were analyzed in 44 patients. Female, non-smoker, adenocarcinoma of stage I-II, and gefitinib effectiveness correlated with longer time to progression (TTP) and overall survival (OS), while the rate of interstitial lung disease in patients undergoing thoracic radiotherapy and stomatitis in females or those who never smoked were significantly higher. EGFR mutations were identified in 18 cases, and among 34 gefitinib-treated patients, 16 patients harboring mutations tended to do better, both in terms of TTP and OS. The results of the mutation analysis from surgical and non-surgical specimens were identical. Certain clinicopathological characteristics and EGFR mutations can be either predictive of gefitinib sensitivity or adverse events.


Effectiveness of cefamandole against methicillin-resistant strains of Staphylococcus aureus in vitro and in experimental infections.
An investigation was carried out into the effectiveness of cefamandole as compared to that of cephalothin against methicillin-sensitive and methicillin-resistant strains of Staphylococcus aureus both in vitro and in mice with the experimental peritonitis-induced septicaemia as a model for a generalized infection. In the agar-diffusion test 95% of 118 and in the broth-dilution test 80% of 30 methicillin-resistant strains were sensitive to cefamandole. In experimental infections the ED50 with methicillin-resistant strains was 20 times greater than that required for the methicillin-sensitive strain although the MIC was only twice that for the latter. Doses of cephalothin required for treatment of infections due to methicillin-resistant strains were also twenty times greater than for those due to the methicillin-sensitive strain. But these differences were consistent with those in MIC (by factors of 16-32). Thus, the results of in-vitro testing of cefamandole are not predictive for its therapeutic efficacy in staphylococcal infections with methicillin-resistant strains. Therefore, rather than relying on inhibition zone diameter and MIC, the information that a staphylococcal strain is methicillin-resistant should be used as an indication not to choose cefamandole for chemotherapy.


Galactomyces geotrichum - moulds from dairy products with high biotechnological potential.
The article reviews the properties of the Galactomyces geotrichum species, the mould that is most important for the dairy industry. G. geotrichum mould has been isolated from milk, cheeses and alcoholic beverage. Its presence in food products makes it possible to obtain a characteristic aroma and taste, which corresponds to the needs and preferences of consumers. G. geotrichum plays an important role in ecology, where the mould is employed for the degradation of various hazardous substances and wastewater treatment. It has also been found to have potential for biofuel production. In addition to this, G. geotrichum can be applicable in two further major areas: agriculture and health protection.


Haemoccult screening for colorectal cancer: the effect of dietary restriction on compliance.
The aim of this study was to examine the effect of dietary restrictions on compliance with Haemoccult screening for colorectal carcinoma. One-hundred-and-fifty-three individuals were randomly allocated to perform Haemoccult tests with or without dietary restrictions, over 3 or 6 days. Those who failed to return completed tests within 6 weeks were sent a reminder letter. A small but significant improvement in compliance when testing over a 3-day period has been previously demonstrated but this difference was not seen in this study because of the small sample size. Overall, 72.8% compliance was achieved in those who were not asked to exclude certain foods during the test period compared with 51.8% in those in whom dietary restriction was requested (chi 2 = 7.45, P < 0.01). In a British population compliance with Haemoccult screening is adversely affected by the imposition of dietary restrictions.


Preservation of Field-Collected Mosquito Blood Meals.
All PCR- and DNA-based blood meal analyses require host DNA from a mosquito blood meal to be effectively preserved between the time when the specimen is collected and the extraction of DNA. As soon as a mosquito ingests blood from a host animal, digestion of host cells and cellular components within the blood meal by enzymes in the mosquito midgut begins to degrade the host DNA templates that are the targets of polymerase chain reaction (PCR) amplification. Without effective preservation, host DNA is typically undetectable by PCR 48 h after feeding, because of digestion. Preservation methods for mosquito blood meals vary in their efficacy, and the logistics of fieldwork can limit the options for preservation of blood meals and maintenance of the integrity of host DNA. This protocol describes a method of blood meal preservation that is effective, convenient, and amenable to fieldwork in remote locations where cryopreservation at -20°C or -80°C may not be feasible. It uses a Flinders Technology Associates (FTA) card, which is a chemically treated card that lyses cells and allows nucleic acids to be preserved. This method is also expected to preserve the DNA or RNA of pathogens present within the engorged mosquito abdomen, including RNA viruses.


The effects of community interventions on unplanned healthcare use in patients with multimorbidity: a systematic review.
To summarise the impact of community-based interventions for multimorbid patients on unplanned healthcare use. The prevalence of multimorbidity (co-existence of multiple chronic conditions) is rapidly increasing and affects one-third of the global population. Patients with multimorbidity have complex healthcare needs and greater unplanned healthcare usage. Community-based interventions allow for continued care of patients outside hospitals, but few studies have explored the effects of these interventions on unplanned healthcare usage. A systematic review was conducted. MEDLINE, EMBASE, PsychINFO and Cochrane Library online databases were searched. Studies were screened and underwent risk of bias assessment. Data were synthesised using narrative synthesis. Community-based interventions. Patients with multimorbidity. Unplanned healthcare usage. Thirteen studies, including a total of 6148 participants, were included. All included studies came from high-income settings and had elderly populations. All studies measured emergency department attendances as their primary outcome. Risk of bias was generally low. Most community interventions were multifaceted with emphasis on education, self-monitoring of symptoms and regular follow-ups. Four studies looked at improved care coordination, advance care planning and palliative care. All 13 studies found a decrease in emergency department visits post-intervention with risk reduction ranging from 0 (95% confidencec interval [CI]: -0.37 to 0.37) to 0.735 (95% CI: 0.688-0.785). Community-based interventions have potential to reduce emergency department visits in patients with multimorbidity. Identification of specific successful components of interventions was challenging given the overlaps between interventions. Policymakers should recognise the importance of community interventions and aim to integrate aspects of these into existing healthcare structures. Future research should investigate the impact of such interventions with broader participant characteristics.


Fusion of Structure and Ligand Based Methods for Identification of Novel CDK2 Inhibitors.
Cyclin dependent kinases play a central role in cell cycle regulation which makes them a promising target with multifarious therapeutic potential. CDK2 regulates various events of the eukaryotic cell division cycle, and the pharmacological evidence indicates that overexpression of CDK2 causes abnormal cell-cycle regulation, which is directly associated with hyperproliferation of cancer cells. Therefore, CDK2 is regarded as a potential target molecule for anticancer medication. Thus, to decline CDK2 activity by potential lead compounds has proved to be an effective treatment for cancer. The availability of a large number of X-ray crystal structures and known inhibitors of CDK2 provides a gateway to perform efficient computational studies on this target. With the aim to identify new chemical entities from commercial libraries, with increased inhibitory potency for CDK2, ligand and structure based computational drug designing approaches were applied. A druglike library of 50,000 compounds from ChemDiv and ChemBridge databases was screened against CDK2, and 110 compounds were identified using the parallel application of these models. On in vitro evaluation of 40 compounds, seven compounds were found to have more than 50% inhibition at 10 μM. MD studies of the hits revealed the stability of these inhibitors and pivotal role of Glu81 and Leu83 for binding with CDK2. The overall study resulted in the identification of four new chemical entities possessing CDK2 inhibitory activity.


Moderate beer consumption and the risk of colorectal cancer.
The relationship between beer consumption and the risk of colon and rectal cancer was considered in a case-control study conducted in northern Italy. The study was based on 828 histologically confirmed incident cases of colon cancer, 498 of rectal cancer, and 2,024 controls in hospital for a wide spectrum of acute, nonneoplastic, nonalcohol-related diseases. Beer drinking was reported by 6% of colon cancer cases, 7% of rectal cancer cases, and 10% of controls; regular beer drinkers (> or = 1 drinks/day) made up 2.6% of colon cancer cases, 3.2% of rectal cancer cases, and 4.1% of controls. Thus the multivariate relative risks (RR) for irregular drinkers were 0.6 [95% confidence interval (CI) 0.4-1.0] for colon and 0.7 (95% CI 0.4-1.2) for rectum. Corresponding values for regular drinkers were 0.7 (95% CI 0.4-1.2) for colon and 0.9 (95% CI 0.5-1.5) for rectal cancer. Despite the low frequency of beer drinking in this study, and hence its limited statistical power, the originality of the population in terms of colorectal cancer incidence, patterns of risk factor exposure, and the large dataset provide interesting and useful confirmation that moderate beer drinking is not associated with elevated colon or rectal cancer risk.


Factors associated with perceived need for mental health care in multiple sclerosis.
Within the multiple sclerosis (MS) population, depression and anxiety are highly prevalent comorbidities that are associated with adverse outcomes such as diminished quality of life and disability progression. In the general population, many people who do not meet formal diagnostic criteria for depression or anxiety disorders still identify a need for mental health care. Limited data are available regarding the perceived need for mental health care among persons with MS. We aimed to determine factors associated with a perceived need for mental health care in the MS population. Participants with MS completed the Hospital Anxiety and Depression Scale (HADS) to assess severity of depression and anxiety symptoms, and reported whether they perceived a need for mental health care, in the context of a larger study examining the burden of psychiatric disorders in immune-mediated inflammatory disease. Participants were also evaluated using the Structured Clinical Interview for DSM-IV-TR (SCID) to diagnose depression or anxiety disorders. Participants reported their sociodemographic characteristics, and underwent physical assessments to determine their disability status. Descriptive analyses and binary logistic regression models were used to determine sociodemographic and clinical factors associated with perceived need for mental health care. Of 255 participants enrolled, 251 were included in this analysis. Most participants were women, Caucasian, with post-secondary education, with a mean (SD) age at enrollment of 50.9 (12.9) years. They predominantly had a relapsing-remitting MS course. Nearly one-quarter of participants had a current SCID diagnosis of depression or anxiety (n = 57, 22.7%). Overall, 31.8% (n = 80) of participants reported a need for mental health care. These individuals were slightly younger at enrollment (p = 0.037), but otherwise did not differ with respect to sociodemographic characteristics, compared to participants not reporting this need. Those identifying need for mental health care also had an earlier age of MS symptom onset (p = 0.011). After adjusting for sociodemographic and clinical factors, elevated symptoms of depression (odds ratio [OR] 2.36; 95%CI: 1.06, 5.25) and anxiety (OR 6.08; 95%CI: 2.78, 13.3) were associated with an increased likelihood of reporting a need for mental health care. Any current SCID diagnosis of depression or anxiety was not associated with perceived need for mental health care after accounting for symptoms of depression and anxiety. One-third of people with MS identified a need for mental health care. Symptoms of anxiety and depression, but not current diagnosed mental health disorders, were the predominant factors associated with a perceived need for care.


The efficacy of diabetic foot care education.
To survey the efficacy of education about factors that influence the learning process and behaviour of diabetics following a nursing interventional project in diabetic foot care education. Educating diabetics can change their behaviour, which may contribute to the prevention of diabetic foot ulcer and amputation. However, there is little information on the factors that contribute to effectiveness of foot care education. Survey. The data before education were collected by using structured assessment based on a practical reasoning scheme. The interventional diabetic foot care education project immediately followed. We used verbal and written patient education material. After education (six months), we used a questionnaire by postadministration. The data were analysed using content analysis, descriptive statistics and inferential statistics. We discovered a rise of knowledge, willingness and motivation to learn and to change the behaviour of diabetics after education. The clinical parameters (weight, Body Mass Index, blood pressure) demonstrated a statistically significant positive change six months after education. The findings after education show a rise in knowledge, willingness and motivation, which are important factors that contribute to changing behaviour of diabetics in diabetic foot care. After education, we identified better results in terms of weight and blood pressure, both of which play a role in the prevention of diabetic ulcer. The education valuable tool ensures knowledge, motivation and willingness to change behaviour in order to prevent diabetic foot complications of diabetics. By using structured assessment, nurses are able to modify their educational interventions.


Processing mutations located throughout the human multidrug resistance P-glycoprotein disrupt interactions between the nucleotide binding domains.
The most common cause of cystic fibrosis is misfolding of the cystic fibrosis transmembrane conductance regulator (CFTR) protein because of deletion of residue Phe-508 (DeltaF508). P-glycoprotein (P-gp) is an ideal model protein for studying how mutations disrupt folding of ATP-binding cassette proteins such as CFTR because specific chemical chaperones can be used to correct folding defects. Interactions between the nucleotide binding domains (NBDs) are critical because ATP binds at the interface between the NBDs. Here, we used disulfide cross-linking between cysteines in the Walker A sites and the LSGGQ signature sequences to test whether processing mutations located throughout P-gp disrupted interactions between the NBDs. We found that mutations present in the cytoplasmic loops, transmembrane segments, and linker regions or deletion of Tyr-490 (equivalent to Phe-508 in CFTR) inhibited cross-linking between the NBDs. Deletion of Phe-508 in the P-gp/CFTR chimera also inhibited cross-linking between the NBDs. Cross-linking was restored, however, when the mutants were expressed in the presence of the chemical chaperone cyclosporin A. The "rescued" mutants exhibited drug-stimulated ATPase activity, and cross-linking between the NBDs was inhibited by vanadate trapping of nucleotide. These results together with our previous findings (Loo, T. W., Bartlett, M. C., and Clarke, D. M. (2002) J. Biol. Chem. 277, 27585-27588) indicate that processing mutations disrupt interactions among all four domains. It appears that cross-talk between the cytoplasmic and the transmembrane domains is required for establishment of proper domain-domain interactions that occur during folding of ATP-binding cassette protein transporters.


Microbial translocation and impairment of mucosal immunity induced by an elemental diet in rats is prevented by selective decontamination of the digestive tract.
To assess the effect of selective decontamination of the digestive tract (SDD) on intestinal secretory immunoglobulin A (sIgA) concentrations in a model of intestinal bacterial overgrowth and bacterial translocation induced by an elemental diet in rats. Laboratory study. University hospital, Germany. 45 specific pathogen free female Crl:CD(R) BR rats. For 7 days, 3 groups of rats were fed orally with standard chow (n = 15), total parenteral nutrition solution (ORAL-TPN, n = 15), or ORAL-TPN plus tobramycin (20 mg/L) and polymyxin E (25 mg/L) (ORAL-TPN + SDD). Bacterial translocation to mesenteric lymph nodes (MLN), numbers of gram negative enterobacteria and total aerobic bacteria in the caecum, and intestinal concentrations of sIgA. The incidence of bacterial translocation was significantly increased in the group given ORAL-TPN (8/15, 53%) compared with the group given chow (1/15, 7%, p < 0.01). Supplementation of ORAL-TPN with SDD reduced translocation to 0/15. The ORAL-TPN group had a pronounced overgrowth of aerobic bacteria in the caecum, mainly by gram negative enterobacteria, which was prevented by the SDD. The concentrations of intestinal sIgA were significantly reduced in the ORAL-TPN group. SDD resulted in both the soluble and insoluble sIgA fractions in the gut being within the reference ranges. SDD prevents gram negative caecal overgrowth and translocation to MLN in rodents fed on ORAL-TPN. The significantly reduced mucosal immunity caused by ORAL-TPN alone is restored by SDD, although one might have expected a further reduction in sIgA concentrations with lower microbial populations than in the ORAL-TPN group. Not only does SDD not seem to affect the mucosa associated immune system adversely, but also depressed mucosal immunity was restored.


Uncovering Important Drivers of the Increase in the Use of Virtual Care Technologies in Nursing Care: Quantitative Analysis From the 2020 National Survey of Canadian Nurses.
Canadian nurses are at the forefront of patient care delivery. Although the use of digital health technologies for care delivery is gaining momentum in Canada, nurses are encouraged to integrate virtual care into their practice. In early 2020, more Canadian nurses delivered care virtually compared with 3 years ago. This study seeks to uncover the professional characteristics of Canadian nurses accessing virtual care in 2020, understand how these characteristics differ across types of technologies, investigate whether the nurses accessing virtual care possess the skills and knowledge needed to use these technologies, and determine the important drivers of the uptake of virtual care observed in 2020. We used data from the 2017 and 2020 National Survey of Canadian Nurses. This survey collected data on the use of digital health technologies in nursing practice. It concerned regulated nursing professionals working in different health care settings and from different domains of nursing practice. We combined the chi-square independence test and logistic regression analysis to uncover the most relevant drivers of virtual care uptake by nurses in 2020. In early 2020, before the declaration of the COVID-19 pandemic, nurses who delivered care virtually were predominantly nurse practitioners (135/159, 84.9%) and more likely to work in a primary or community care setting (202/367, 55%) and in an urban setting (194/313, 61.9%). Factors such as nursing designation (P<.001), perceived quality of care at the health facility where the nurses practiced (P<.001), and the type of patient record-keeping system they had access to (P=.04) had a statistically significant effect on the probability of nurses to deliver care virtually in early 2020. Furthermore, nurses' perception of the quality of care they delivered through virtual technologies was statistically associated with their perception of the skills (χ24=308.7; P<.001) and knowledge (χ24=283.4; P<.001) to use these technologies. This study emphasizes the critical importance of nursing designation, geographic location, and type of patient record-keeping system in predicting virtual care integration in nursing practice. The findings related to geographic location can be used by decision-makers for better allocation of digital health resources among care settings in rural and urban areas. Similarly, the disparities observed across nursing designations have some implications for the digital training of nurses at all levels of practice. Finally, the association between electronic medical record use and uptake of virtual care could accelerate the implementation of more modernized record-keeping systems in care settings. Hence, this could advance interoperability and improve health care delivery.


Feeding glycerol-enriched yeast culture improves lactation performance, energy status, and hepatic gluconeogenic enzyme expression of dairy cows during the transition period.
This study aimed to evaluate the effects of feeding glycerol-enriched yeast culture (GY) on feed intake, lactation performance, blood metabolites, and expression of some key hepatic gluconeogenic enzymes in dairy cows during the transition period. Forty-four multiparous transition Holstein cows were blocked by parity, previous 305-d mature equivalent milk yield, and expected calving date and randomly allocated to 4 dietary treatments: Control (no additive), 2 L/d of GY (75.8 g/L glycerol and 15.3 g/L yeast), 150 g/d of glycerol (G; 0.998 g/g glycerol), and 1 L/d of yeast culture (Y; 31.1 g/L yeast). All additives were top-dressed and hand mixed into the upper one-third of the total mixed ration in the morning from -14 to +28 d relative to calving. Results indicated that the DMI, NE intake, change of BCS, and milk yields were not affected by the treatments ( > 0.05). Supplementation of GY or Y increased milk fat percentages, milk protein percentages, and milk protein yields relative to the Control or G group ( < 0.05). Cows fed GY or G had higher glucose levels and lower β-hydroxybutyric acid (BHBA) and NEFA levels in plasma than cows fed the Control ( < 0.05) and had lower NEFA levels than cows fed Y ( < 0.05). On 14 d postpartum, cows fed GY or G had higher enzyme activities, mRNA, and protein expression of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C; < 0.05); higher enzyme activities ( < 0.05) and a tendency toward higher mRNA expression ( < 0.10) of glycerol kinase (GK); and a tendency toward higher enzyme activities of pyruvate carboxylase (PC) in the liver ( < 0.10) when compared with cows fed Control or Y. The enzyme activities, mRNA, and protein expression of PEPCK-C, PC, and GK did not differ between cows fed GY and G ( > 0.10). In conclusion, dietary GY or Y supplementation increased the milk fat and protein content of the cows in early lactation and GY or G supplementation improved the energy status as indicated by greater plasma glucose and lower plasma BHBA and NEFA concentrations and upregulated the hepatic gluconeogenic enzymes of dairy cows during the transition period. Feeding cows with a GY mixture in the peripartum period combined the effects of yeast on lactation performance and the effects of glycerol on energy status in dairy cows.


Exploring PANoptosis in breast cancer based on scRNA-seq and bulk-seq.
PANoptosis, a cell death pathway involving pyroptosis, apoptosis, and necroptosis, is pivotal in the development of malignancy. However, in the field of breast cancer, the interaction between PANoptosis and tumor cells has not been thoroughly explored. We downloaded breast cancer data and GSE176078 single-cell sequencing dataset from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases to obtain PANoptosis-associated genes. To construct prognostic models, COX and LASSO regression was used to identify PANoptosis-associated genes with prognostic value. Finally, immune infiltration analysis and differential analysis of biological functions were performed. Risk grouping was performed according to the prognostic model constructed by COX regression and LASSO regression. The low-risk group showed a better prognosis (P < 0.05) and possessed higher levels of immune infiltration and expression of immune checkpoint-related genes. In addition, the lower the risk score, the higher the degree of microsatellite instability (MSI). Meanwhile, radixin (RDX), the gene with the highest hazard ratio (HR) value among PANoptosis prognosis-related genes, was explicitly expressed in artery Iendothelial cells (ECs) and was widely involved in signaling pathways such as immune response and cell proliferation, possessing rich biological functions. We demonstrated the potential of PANoptosis-based molecular clustering and prognostic features in predicting the survival of breast cancer patients. Furthermore, this study has led to a deeper understanding of the role of PANoptosis in breast cancer and has the potential to provide new directions for immunotherapy of breast cancer.


Real-time TaqMan PCR for rapid detection and typing of genes encoding CTX-M extended-spectrum beta-lactamases.
The prevalence of CTX-M-producing members of the Enterobacteriaceae is increasing worldwide. A novel, multiplex, real-time TaqMan PCR assay to detect and type bla(CTX-M) genes is described which is an improvement on previously described techniques with respect to reduced assay time, elimination of the need for protracted post-PCR processing and the convenience of a single reaction vessel. Based on beta-lactam antibiogram and MIC data, 478 of 1279 Enterobacteriaceae isolates from clinical blood and urine culture specimens were selected and tested for extended-spectrum beta-lactamase (ESBL) production using phenotypic methods. The new TaqMan assay detected and typed bla(CTX-M) genes in 21 of 28 ESBL-producing isolates.


Presenting symptoms of COVID-19 and clinical outcomes in hospitalised older adults.
In July 2020, a COVID-19 outbreak was recognised in the geriatric wards at a subacute campus of the Royal Melbourne Hospital affecting patients and staff. Patients were also admitted to this site after diagnosis in residential care. To describe the early symptoms and the outcomes of COVID-19 in older adults. Patients diagnosed with COVID-19 at the facility in July or August 2020 were identified and their medical records were examined to identify symptoms present before and after their diagnosis and to determine their outcomes. Overall, 106 patients were identified as having COVID-19, with median age of 84.3 years (range 41-104 years); 64 were diagnosed as hospital inpatients after a median length of stay of 49 days, 31 were transferred from residential aged care facilities with a known diagnosis and 11 were diagnosed after discharge. There were 95 patients included in an analysis of symptom type and timing onset. Overall, 61 (64.2%) were asymptomatic at the time of diagnosis of COVID-19, having been diagnosed through screening initiated on site. Of these, 88.6% developed symptoms of COVID-19 within 14 days. The most common initial symptom type was respiratory, but there was wide variation in presentation, including fever, gastrointestinal and neurological symptoms, many initially not recognised as being due to COVID-19. Of 104 patients, 32 died within 30 days of diagnosis. COVID-19 diagnosis is challenging due to the variance in symptoms. In the context of an outbreak, asymptomatic screening can identify affected patients early in the disease course.


Sinoatrial node remodels in chronic sleep-restricted rats.
Chronic Sleep Restriction (CSR) is known as a risk factor for cardiovascular diseases. However, the structural changes of Sinoatrial (SA) node cells have received less attention. This study aimed to evaluate the effects of CSR on SA node in an animal model using stereological methods. Adult male Sprague-Dawley rats were randomly divided into CSR, grid-floor, and control groups. The CSR procedure was designed such a way that the animals had a full cycle of sleep (6 hours) per day, while they were unable to have a Rapid Eye Movement (REM) sleep during the remaining 18 hours. This was induced by a multiplatform box containing water. The grid-floor animals were placed in the same multiplatform box with a grid-floor covering to prevent falling in water. After 21 days, the right atria were dissected out. Then, the location of the SA node was determined and evaluated by stereological techniques. The total volume of the SA node, the total volume of the main node cells, the volume of the connective tissue, and mean volume of the node cells were respectively enlarged by 60%, 47%, 68%, and 51% in the CSR animals compared to the grid-floor rats (p < 0.05). However, no significant changes were detected in these parameters in the control and grid-floor animals. The population of the main node cells remained constant in all animal groups. In addition, the three-dimensional reconstruction of the SA node in the CSR group showed a hypertrophied appearance. In conclusion, CSR induced hypertrophic changes in the rats' SA node structures without alteration in the number of main node cells.