Prominent vegetation greening and its correlation with climatic variables in northern China.
Global vegetation has been reported to be turning greener, especially in China and India. The Yellow River Basin is one of the most prominent greening areas in China. While some studies have attributed vegetation greening to large-scale ecological restoration efforts, our study focuses on the role of climate change in vegetation greening. We selected a time series of annual vegetation net primary productivity (NPP) and vegetation coverage from satellite data to quantify the vegetation greening trend. Annual temperature and precipitation were selected to examine the climate trend from 2000 to 2019. The results showed that the Yellow River Basin experienced a rapid increase in temperature and precipitation during this period. Annual temperature increased with an average speed of 0.905 °C per decade, approximately 4.5 times larger than that of global warming. Annual precipitation increased by 82.8%, with an average speed of 9.17 mm per year. There was widespread vegetation greening in the Yellow River Basin during 2000-2019. This was demonstrated by an increase in vegetation NPP and vegetation coverage in the Yellow River Basin. The increase of annual NPP and coverage from 2000 to 1019 was 26.6% and 30.8%, respectively. Even while considering the effects of conservation and restoration efforts, the rapid increases in temperature and precipitation allowed vegetation to flourish, as evidenced by significant positive correlations between climate variables and vegetation variables. Therefore, climate change played an important positive role in vegetation greening, rather than an undesirable disturbance.


Transformations and antioxidative activities of lignans and stilbenes at high temperatures.
Thermal transformations of polyphenols from the lignan and stilbene families were investigated at temperatures ranging from 200 °C to 250 °C, in polyethylene glycol (PEG-400), dimethylformamide (DMF) and in sunflower oil (SO). The polyphenols showed varying degrees of thermal stabilities and in some cases intramolecular transformations were observed. The formed products were isolated and characterized. Oligomerization of the polyphenols at thermo-oxidative conditions was also investigated. Finally, the antioxidative activity of the polyphenols against thermo-oxidative degradation α-linoleic acid was investigated at 200 °C. The results suggested that the studied substrates retained their antioxidative properties at elevated temperatures, with stilbenes showing most efficient protection against thermo-oxidative degradation of polyunsaturated fatty acids.


Corrigendum: Multi-Omics and miRNA Interaction Joint Analysis Highlight New Insights Into Anthocyanin Biosynthesis in Peanuts (Arachis hypogaea L.).
[This corrects the article DOI: 10.3389/fpls.2022.818345.].


Two decades' experience with aortic valve replacement with pulmonary autograft.
Aortic valve replacement with a pulmonary autograft was performed on 241 patients between June 1967 and October 1986 at National Heart Hospital, Guy's Hospital, Middlesex Hospital, Harley Street Clinic, and Italian Hospital in London by one of the authors (D.N.R.). The longest follow-up is 18 years 7 months, and the cumulative total follow-up is 1130 patient-years (pt-yr). The overall 30-day mortality rate is 6.6% (16 patients), with no deaths after 1976, and the late mortality rate is 1.7%/pt-yr (19 patients). The actuarial survival rate is 57.3% +/- 9.6% at 19 years. No anticoagulation has been used and there have been no thromboembolic episodes. The incidence of bacterial endocarditis is 1.2%/pt-yr (14 patients), and its actuarial event-free rate is 74.2% +/- 8.1% at 19 years. Reoperation because of failure of the pulmonary autograft was performed on 36 patients, 27 of whom needed valve replacement. The incidence of pulmonary autograft replacement is 2.5%/pt-yr, and its actuarial event-free rate is 48.5% +/- 13.7% at 19 years. For reconstruction of the right ventricular outflow tract, 186 aortic homografts, 26 pulmonary homografts, 16 autologous fascia lata valved conduits, 7 autologous pericardial conduits with or without a valve, and 6 xenograft valved Dacron conduits were used. Thirty-one patients were reoperated on, mostly because of degeneration of this material. Pulmonary rather than aortic homografts are now favored for reconstruction of the right ventricular outflow tract Because of its satisfactory long-term result without the need for anticoagulation, as well as its safety as an established surgical procedure, this operation can be recommended to a wider range of patients.


Microglia in the hypendyma of the rat subcommissural organ following brain lesion with serotonin neurotoxin.
The population of microglial cells in the subependymal layer of the subcommissural organ is sparse in normal adult rats. The number of microglial cells was substantially increased in this area following intraventricular injection of the serotonin neurotoxin 5,6-dihydroxytryptamine (5,6-DHT). In sections of plastic embedded material, 1 micron thick, the majority of phagocytic cells scattered in the subependymal layer had an appearance similar to that described in classical studies of microglial cells. At the electron microscopic level microglial cells exhibited the characteristic elongate nucleus with peripheral chromatin condensation. The perikaryon was scanty, containing strands of rough endoplasmic reticulum. The abundant organelles in the processes included Golgi complexes, mitochondria, rough and smooth endoplasmic reticulum as well as dense and multivesicular bodies. In addition, the processes contained phagocytosed axon terminals originating from the dense serotoninergic input to the subcommissural organ, which had degenerated on accumulating the serotonin neurotoxin. A fraction of the phagocytosed material was contained in subependymal subcommissural organ cells, astrocytes and oligodendrocytes. At the light microscopic level the phagocytosed terminals were visualized histochemically with Schmorl's reaction, which resulted in Prussian Blue precipitates. This allowed screening of microglial cells in complete series of sections through the well-defined subependymal layer of the subcommissural organ.


The Global Alliance for iPSC Therapies (GAiT).
The Global Alliance for iPSC Therapies (GAiT) is a new initiative to support the implementation and clinical application of therapies derived from pluripotent stem cells to the benefit of patients globally. GAiT's mission is to serve as a central, international resource for those organisations developing therapies from clinical-grade induced pluripotent stem cells, and to support the expansion of this nascent field. With the support of its international partners, GAiT already has an early position on manufacturing, regulatory and quality standards. This article details GAiT's development, its mission and structure, as well as how, and by whom, it is funded. The article ends with brief overview of current and upcoming activities.


The short-term dynamics of posttraumatic stress disorder symptoms during the acute posttrauma period.
The manner in which posttraumatic stress disorder (PTSD) develops remains largely unknown. PTSD is comprised of 20 symptoms across 4 clusters. These clusters were hypothesized to reflect a failure of recovery model in which intrusive symptoms appear first. Intrusive symptoms led to avoidance of trauma-related stimuli, which resulted in sustained arousal. The sustained arousal ultimately led to dysphoria. This hypothesized symptom progression was evaluated during the acute posttrauma period (the first 30 days postevent). Participants (N = 80) reported their PTSD symptoms for 30 days via mobile devices. Using a short-term dynamic modeling framework, a temporal and contemporaneous model of PTSD symptoms was obtained. In the temporal network, a fear-conditioning component was identified that supported the hypothesized set of relations among symptom clusters. The contemporaneous network was classified by two subnetworks. The first corresponded to a fear-conditioning model that included symptoms of intrusions and avoidance. The second included symptoms of dysphoria and arousal. These findings suggest that, after a trauma, there may be a fear-conditioning process that involves intrusions, avoidance, and arousal symptoms. Dysphoric symptoms were also present but developed as a partially distinct component.


Heart rate variability in individuals with autism spectrum disorders: A meta-analysis.
Heart rate variability (HRV) in individuals with autism spectrum disorders (ASD) has been investigated in some studies but the procedures and results vary. We conducted a systematic review and meta-analysis to compare HRV in individuals with and without ASD; the influence of different conditions and HRV indices is considered. Baseline HRV and HRV reactivity were analyzed in several ways: parasympathetic indices in hierarchical order (main analysis), total variability, specific parasympathetic indices and respiratory sinus arrhythmia (RSA), etc. The review covered 34 studies for quantitative analysis. Individuals with ASD had a significantly lower baseline HRV for parasympathetic indices in hierarchical order (Hedges'g=-0.5168, p < 0.0001) and RSA (g=-0.5860, p=0.0010). The reactivity of HRV in situations of social stress (g=-0.4647, p = 0.0033) and social debriefing (g=-0.5001, p = 0.0007) was also significantly lower in subjects with ASD. RSA reactivity was significantly lower in ASD group for all situations, with the largest effect size for social stress (g=-0.7246, p < 0.0001). The results support low HRV to be a potential biomarker of ASD, especially RSA reactivity under social stress.


Molecular cloning of the ets proto-oncogene of the sea urchin and analysis of its developmental expression.
The locus SU(Lv)-ets-2 of the sea urchin Lytechinas variegatus related to the oncogene v-ets of avian erythroblastosis virus E26 has been molecularly cloned. The cloned DNA was found to contain a region with a high degree of homology to E26 v-ets. The sea urchin homology with v-ets starts at a consensus splice acceptor sequence and stops at the point where homology between v-ets and human c-ets ends. This region corresponds to the Hu-ets-2 homologous sequences defined by Watson et al. (1985, Proc. Natl. Acad. Sci, USA 82, 7294-7298). Ninety-one out of 97 (or 94%) predicted amino acids are identical between sea urchin c-ets and E26 v-ets over the region of homology. This degree of homology exceeds the maximum homology previously found between any oncogene and an invertebrate homolog. A somewhat weaker homology with the Hu-ets-2 sequences continues beyond, for 13 codons, ending at a common termination codon. Northern blot analysis of mature unfertilized eggs and early embryos from sea urchins of the species Strongylocentrotus purpuratus revealed a single 6.8-kb ets-related RNA that is expressed at a maximum level during the early stages of embryonic development. This RNA species is polyadenylated indicating that it is the message for the sea urchin ets-2 gene.


Twenty years of Prevention of Mother to Child HIV Transmission: research to implementation at a national referral hospital in Uganda.
Over 90% of new paediatric HIV infections are acquired through mother to child transmission. Prevention of mother to child HIV transmission (PMTCT) research in sub-Saharan Africa informed WHO guidelines which enabled implementation of PMTCT programs globally. To describe Makerere University-Johns Hopkins University (MU-JHU) perinatal HIV prevention research and implementation of the Mulago National Referral Hospital (MNRH) PMTCT program. Perinatal HIV prevention studies conducted at MU-JHU between 1997-2016 were summarized. Program aggregated data was extracted and analyzed using STATA 15. In 1999, the HIVNET 012 study demonstrated that single-dose nevirapine (sdNVP) to the mother at onset of labor and to her newborn, reduced MTCT by nearly 50%. In 2016, the PROMISE study documented the safety and efficacy of ART during pregnancy and breastfeeding period. Program implementation at MNRH started in 2000. Uptake of HIV testing increased from 70% to 99% from 2006 onwards. sd NVP was the initial ARV regimen but by 2012, MOH recommended Option B+(triple therapy). MTCT rates reduced from 16.9% in 2001 to 2.3% in 2020. Perinatal HIV prevention clinical trials conducted at MU-JHU provided evidence to inform WHO PMTCT guidelines. MNRH program evaluation demonstrated the significant decline in MTCT rates over the last two decades.


Transcatheter arterial embolization of spontaneous rectus sheath haematoma in a Chinese woman.
Spontaneous extraperitoneal haemorrhage is a rare but well-described complication of anticoagulation therapy. We report a case of spontaneous rectus sheath haematoma in a 69-year-old Chinese woman who had received low-molecular-weight heparin for pulmonary embolism. She presented with sudden onset of lower abdominal pain, hypotension and a tender lower abdominal mass after 1 week of anticoagulation therapy. Computed tomography revealed a huge right rectus sheath haematoma extending into the pelvis, and angiography demonstrated active contrast extravasation from the right inferior epigastric artery. Arterial embolization with Gelfoam was performed and succeeded in stopping the bleeding. Transcatheter arterial embolization can be an effective and safe modality to localize and treat the bleeder in spontaneous extraperitoneal haematoma for high-risk patients.


Transforming growth factor-beta stimulates parathyroid hormone-related protein and osteolytic metastases via Smad and mitogen-activated protein kinase signaling pathways.
Transforming growth factor (TGF)-beta promotes breast cancer metastasis to bone. To determine whether the osteolytic factor parathyroid hormone-related protein (PTHrP) is the primary mediator of the tumor response to TGF-beta, mice were inoculated with MDA-MB-231 breast cancer cells expressing a constitutively active TGF-beta type I receptor. Treatment of the mice with a PTHrP-neutralizing antibody greatly decreased osteolytic bone metastases. There were fewer osteoclasts and significantly decreased tumor area in the antibody-treated mice. TGF-beta can signal through both Smad and mitogen-activated protein (MAP) kinase pathways. Stable transfection of wild-type Smad2, Smad3, or Smad4 increased TGF-beta-stimulated PTHrP secretion, whereas dominant-negative Smad2, Smad3, or Smad4 only partially reduced TGF-beta-stimulated PTHrP secretion. When the cells were treated with a variety of protein kinases inhibitors, only specific inhibitors of the p38 MAP kinase pathway significantly reduced both basal and TGF-beta-stimulated PTHrP production. The combination of Smad dominant-negative blockade and p38 MAP kinase inhibition resulted in complete inhibition of TGF-beta-stimulated PTHrP production. Furthermore, TGF-beta treatment of MDA-MB-231 cells resulted in a rapid phosphorylation of p38 MAP kinase. Thus, the p38 MAP kinase pathway appears to be a major component of Smad-independent signaling by TGF-beta and may provide a new molecular target for anti-osteolytic therapy.


The curious cases of nanoparticle induced amyloidosis during protein corona formation and anti-amyloidogenic nanomaterials: Paradox or prejudice?
Protein corona (PC) formation remains a major hurdle in the successful delivery of nanomedicines to the target sites. Interacting proteins have been reported to undergo structural changes on the nanoparticle (NP) surface which invariably impacts their biological activities. Such structural changes are the result of opening of more binding sites of proteins to adsorb on the NP surface. The process of conversion of α-helix proteins to their β-sheet enriched counterpart is termed as amyloidosis and in case of PC formation, NPs apparently play the crucial role of being the nucleation centres where this process takes place. Conversely, increasing numbers of artificial nano-chaperones are being used to treat the protein misfolding disorders. Anti-amyloidogenic nanomaterials (NM) have been gaining utmost importance in inhibiting Aβ42 (hallmark peptide for Alzheimer's disease) and Hen egg white lysozyme (HEWL, model protein for systemic amyloidosis) aggregation. Interestingly, in this process, NPs inhibit protein β-sheet enrichment. These two seemingly opposite roles of NPs, propelling confirmatory change onto the smorgasbord of adsorbed native proteins and the ability of NPs in inhibiting amyloidosis creates a paradox, which has not been discussed earlier. Here, we highlight the key points from both the facets of the NP behaviour with respect to their physicochemical properties and the nature of proteins they adsorb onto them to unravel the mystery. BRIEF: Protein corona formation remains a major hurdle in achieving the desired efficacy of nanomedicine. Proteins when interact with nanoparticle (NP) surface, undergo both structural and biological changes. Again, NPs are known to exhibit anti-amyloidogenic behaviour where these play the crucial role of preventing any change in their native structure. Such seemingly different roles of NPs need sincere inquisition.


Remedial operations for failed endovascular therapy of 32 renal artery stenoses in 24 children.
Percutaneous transluminal angioplasty (PTA) for the treatment of pediatric renovascular hypertension (RVH) in contemporary practice is accompanied with ill-defined complications. This study examines the mode of pediatric renal PTA failures and the results of their surgical management. Twenty-four children underwent remedial operations at the University of Michigan from 1996 to 2014 for failures of renal PTA. Their clinical courses were retrospectively reviewed and results analyzed. Renal PTA of 32 arteries, including 13 with stenting, was performed for severe RVH in 12 boys and 12 girls, having a mean age of 9.3 years. Developmental ostial stenoses affected 22 children. PTA failures included: 27 restenoses and five thromboses. Remedial operations included: 13 renal artery-aortic reimplantations, one segmental renal artery-main renal artery reimplantation, ten aortorenal bypasses, one arterioplasty, one iliorenal bypass, and six nephrectomies for unreconstructable arteries; the latter all in children younger than 10 years. Follow-up averaged 2.1 years. Postoperatively, hypertension was cured, improved, or unchanged in 25, 54, and 21 %, respectively. There was no perioperative renal failure or mortality. Renal PTA for the treatment of pediatric RVH due to ostial disease may be complicated by failures requiring complex remedial operations or nephrectomy, the latter usually affecting younger children.


Is coeliac disease a potentially treatable cause of liver failure?
Hypertransaminasaemia is a common abnormality found in up to 40% of untreated coeliac patients, which resolves with the institution of a gluten-free diet. A much rarer occurrence is the association of chronic liver disease with coeliac disease. Primary biliary cirrhosis, primary sclerosing cholangitis, and chronic autoimmune hepatitis have all been recognized in coeliac patients. More recently, the occurrence of coeliac disease in patients with chronic liver disease is found to be 10 times greater than that in the general population. Of particular note are the 13 patients reported to date with liver failure and coeliac disease. Among those patients commenced on a gluten-free diet an improvement in liver function was observed. The relationship between coeliac disease, a gluten-free diet, and the course of chronic liver disease needs to be clarified.


Bioinspired Luminescent HOF-Based Foam as Ultrafast and Ultrasensitive Pressure and Acoustic Bimodal Sensor for Human-Machine Interactive Object and Information Recognition.
Bionic sensors have extensively served smart robots, medical equipment, and flexible wearable devices. The luminescent pressure-acoustic bimodal sensor can be treated as a remarkable, multifunctional, integrated bionic device. Here, a blue-emitting hydrogen-bonded organic framework (HOF-TTA) as luminogen combines with melamine foam (MF), generating the flexible and elastic HOF-TTA@MF (1 and 2) as a pressure-auditory bimodal sensor. In the luminescent pressure sensing process, 1 has excellent maximum sensitivity (132.02 kPa-1 ), low minimum detection limit (0.0 1333 Pa), fast response time (20 ms), high precision and great recyclability. 2 as a luminescent auditory sensor exhibits the highest response to the 520 Hz sound at 255-1453 Hz. In the process of sensing sound at 520 Hz, 2 possesses high sensitivity (1 648 441.3 cps Pa-1 cm-2 ), low detection limit (0.36 dB) and ultrafast response time (10 ms) within 11.47-91.77 dB. The sensing mechanisms toward pressure and auditory are analyzed in detail by finite element simulation. Furthermore, 1 and 2, as a human-machine interactive bimodal sensor, can recognize nine different objects and word information of "Health", "Phone", and "TongJi" with high accuracy and strong robustness. This work provides a facile fabricated method of luminescent HOF-based pressure-auditory bimodal sensors and endows them with new recognition functions and dimensions.


Alignment Risk Factors for Proximal Junctional Kyphosis and the Effect of Lower Thoracic Junctional Tethers for Adult Spinal Deformity.
The aims of this retrospective cohort study were to 1) identify new alignment risk factors for proximal junctional kyphosis (PJK) in adult spinal deformity (ASD) patients with lower thoracic upper instrumented vertebra (UIV) and 2) determine the effect of junctional tethers on PJK and UIV alignment. We analyzed consecutive ASD patients who underwent posterior instrumented fusion with lower thoracic UIV (T9-T11). Posteriorly anchored junctional tethers were used more recently for ligamentous augmentation to prevent PJK. In addition to regional and global parameters, upper segmental lumbar lordosis (ULL) versus lower segmental lumbar lordosis and UIV angle (measured from UIV inferior endplate to horizontal) were assessed. Primary outcome of PJK was defined as proximal junctional angle >10° and >10° greater than the corresponding preoperative measurement. Univariable and multivariable analyses were performed. The study cohort comprised 120 ASD patients (mean age, 67 years) with minimum 1-year follow-up. Preoperative ULL (P = 0.034) and UIV angle (P = 0.026) were associated with PJK. No independent preoperative alignment risk factors of PJK were identified in multivariable analysis. Tether use was protective against PJK (odds ratio, 0.063 [0.016-0.247]; P < 0.001). PJK in tethered patients was more common with greater postoperative ULL (P = 0.047) and UIV angle (P = 0.026). Junctional tethers significantly reduced PJK in ASD patients with lower thoracic UIV. In tethered patients, PJK was more common with greater postoperative lordosis of the upper lumbar spine and greater UIV angle. This finding suggests potential benefit of tethers to mitigate effects of segmental lumbar and focal UIV malalignment that may occur after deformity surgery.


Environmental triggers of Parkinson's disease - Implications of the Braak and dual-hit hypotheses.
Idiopathic Parkinson's disease (PD) may take decades to develop, during which many risk or protective factors may come into play to initiate the pathogenesis or modify its progression to clinical PD. The lack of understanding of this prodromal phase of PD and the factors involved has been a major hurdle in the study of PD etiology and preventive strategies. Although still controversial, the Braak and dual-hit hypotheses that PD may start peripherally in the olfactory structures and/or the gut provides a theoretical platform to identify the triggers and modifiers of PD prodromal development and progression. This is particularly true for the search of environmental causes of PD as the olfactory structures and gut are the major human mucosal interfaces with the environment. In this review, we lay out our personal views about how the Braak and dual-hit hypotheses may help us search for the environmental triggers and modifiers for PD, summarize available experimental and epidemiological evidence, and discuss research gaps and strategies.


Enantiospecific effect of pulegone and pulegone-derived lactones on Myzus persicae (Sulz.) settling and feeding.
The effect of pulegone chiral center configuration on its antifeedant activity to Myzus persicae was examined. Biological consequences of structural modifications of (R)-(+)- and (S)-(-)-pulegone, the lactonization, iodolactonization, and incorporation of hydroxyl and carbonyl groups were studied, as well. The most active compounds were (R)-(+)-pulegone (1a) and delta-hydroxy-gamma-spirolactones (5S,6R,8S)-(-)-6-hydroxy-4,4,8-trimethyl-1-oxaspiro[4.5]decan-2-one (5b) and (5R,6S,8S)-6-hydroxy-4,4,8-trimethyl-1-oxaspiro[4.5]decan-2-one (6b) derived from (S)-(-)-pulegone (1b). The compounds deterred aphid probing and feeding at preingestional, ingestional, and postingestional phases of feeding. The preingestional effect of (R)-(+)-pulegone (1a) was manifested as difficulty in finding and reaching the phloem (i.e., prolonged time preceding the first contact with phloem vessels), a high proportion of probes not reaching beyond the mesophyll layer before first phloem phase, and/or failure to find sieve elements by 20% of aphids during the 8-hr experiment. The ingestional activity of (R)-(+)-pulegone (1a) and hydroxylactones 5b and 6b resulted in a decrease in duration of phloem sap ingestion, a decrease in the proportion of aphids with sustained sap ingestion, and an increase in the proportion of aphid salivation in phloem. delta-Keto-gamma-spirolactone (5R,8S)-(-)-4,4,8-trimethyl-1-oxaspiro[4.5]decan-2,6-dione (8b) produced a weak ingestional effect (shortened phloem phase). The postingestional deterrence of (R)-(+)-pulegone (1a) and delta-hydroxy-gamma-spirolactones (5R,6S,8R)-(+)-6-hydroxy-4,4,8-trimethyl-1-oxaspiro[4.5]-decan-2-one (5a), 5b, (5S,6R,8R)-6-hydroxy-4,4,8-trimethyl-1-oxaspiro[4.5]decan-2-one (6a), 6b, and delta-keto-gamma-spirolactone 8b prevented aphids from settling on treated leaves. The trans position of methyl group CH3-8 and the bond C5-O1 in lactone 6b appeared to weaken the deterrent activity in relation to the cis diastereoisomer (5b).


Prevalence of body dysmorphic disorder in a German college student sample.
The prevalence of body dysmorphic disorder (BDD) was investigated in a non-clinical sample. German college students (n=133; 73.7% female) completed self-report questionnaires assessing BDD, self-esteem, symptoms of depression, obsessive-compulsive disorder and skin picking. Based on our data, seven participants (5.3%) satisfied DSM-IV BDD criteria. Significant differences were found between students with and without BDD in the number of endorsed obsessive-compulsive disorder symptoms. Poor body image was associated with poor self-esteem, symptoms of depression and obsessive-compulsive disorder. One student with BDD also reported severe skin picking. In conclusion, BDD is a common psychiatric disorder in college students.


Toll-like receptors in urothelial cells--targets for cancer immunotherapy.
Toll-like receptors (TLRs) have an important role in the activation of both innate and adaptive immunity in response to pathogens and danger signals. These receptors are expressed in immune cells and in some epithelia. They are expressed in the epithelium of the urinary bladder, where they actively participate in the fight against infection by uropathogens. TLR expression is decreased (although still evident) in bladder tumours, especially in non-muscle-invasive tumours. Intravesical immunotherapy with BCG to prevent recurrence of these tumours has been shown to involve the participation of three different TLRs (TLR2, TLR4, and TLR9). However, alternative therapies are needed as BCG fails in some patients and can sometimes cause severe adverse effects that are difficult to tolerate. In recent years, TLR2, TLR4, TLR7, and TLR9 agonists have been tested in vitro and in vivo for their ability to activate an antitumour immune response against bladder cancer. Promising results from these studies have led to the testing of TLR7 and TLR9 agonists in clinical trials.


[Immunodepressive action of vaccinia virus].
The hemolytic plaque test in mice was used to demonstrate that live vaccinia virus has marked immunosuppressant action. Inactivated vaccinia virus produces no such an effect and even stimulates the output of the antibody-forming cells. The experimental data were found to be statistically significant.


Induction of cell-cycle arrest and apoptosis in glioblastoma stem-like cells by WP1193, a novel small molecule inhibitor of the JAK2/STAT3 pathway.
Glioma stem-like cells (GSCs) may be the initiating cells in glioblastoma (GBM) and contribute to the resistance of these tumors to conventional therapies. Development of novel chemotherapeutic agents and treatment approaches against GBM, especially those specifically targeting GSCs are thus necessary. In the present study, we found that a novel Janus kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway inhibitor (WP1193) significantly decreased the proliferation of established glioma cell lines in vitro and inhibit the growth of glioma in vivo. To test the efficacy of WP1193 against GSCs, we then administrated WP1193 to GSCs isolated and expanded from multiple human GBM tumors. We revealed that WP1193 suppressed phosphorylation of JAK2 and STAT3 with high potency and demonstrated a dose-dependent inhibition of proliferation and neurosphere formation of GSCs. These effects were at least due in part to G1 arrest associated with down-regulation of cyclin D1 and up-regulation of p21( Cip1/Waf-1 ). Furthermore, WP1193 exposure decreased expression of stem cell markers including CD133 and c-myc, and induced cell death in GSCs through apoptosis. Taken together, our data indicate that WP1193 is a potent small molecule inhibitor of the JAK2/STAT3 pathway that shows promise as a therapeutic agent against GBM by targeting GSCs.


A ward-based procedure for assessment of fluid status in peritoneal dialysis patients using bioimpedance spectroscopy.
This study was carried out to evaluate a procedure for converting bioimpedance spectroscopy (BIS) data to a clinically useful measure of fluid status that is easily interpreted by nursing staff and patients. The ratio of extracellular water (ECW) to total body water (TBW) in a cohort of peritoneal dialysis (PD) patients was compared with the distribution for normal control subjects. The result was expressed as the difference between the measured ECW/TBW ratio and the mean ratio for age- and sex-matched controls divided by the standard deviation for the controls (the "hydration score"). Where possible, interventions were made to reduce the target weight in patients with a hydration score greater than +2.0. This clinical study was carried out in the nurse-led outpatient PD unit at St. James's University Hospital. BIS measurements were carried out during routine clinic visits. The data for the control subjects were obtained in a range of settings in the UK and the Czech Republic. 31 PD patients (21 M, 10 F; aged 19 - 78 years) who came to the PD unit for routine procedures during the study participated. The mean hydration score for PD patients was significantly higher than for the control subjects (+1.3 vs 0.0, p < 0.0001). 11 (35%) patients had a hydration score greater than +2.0, compared with only 2.5% of the controls; systolic blood pressure was greater than 130 mmHg in only two of these patients. After a 3-month follow-up, a weight reduction of 3.6 +/- 2.3 kg had been achieved in 7 patients through modality change and implementation of prescription changes, with no adverse effects. Although this was a small study, all the data collected indicated that the hydration score provides a reliable indication of fluid status in PD patients. BIS measurements are now carried out at 6-month intervals and are used to monitor the effect of interventions.


Hemopoietic stem cells in the liver of mice with Friend leukemia.
Hemopoietic stem cells were studied in the marrow, spleen and liver of individual, FV-P infected DBA/2 mice. At more than 17 days after infection there was a tendency for CFU-EI numbers in the spleen to be reduced compared to earlier intervals after virus infection; CFU-EI numbers in the marrow were low. At the same time all hemopoietic stem cells (CFU-S, CFU-C, BFU-E and CFU-EI) could be found in the enlarged liver. The migration of stem cells from the marrow to the spleen and further to the liver is discussed.


Deficient Radiation Transcription Response in COVID-19 Patients.
The ongoing SARS-CoV-2 pandemic has resulted in over 6.3 million deaths and 560 million COVID-19 cases worldwide. Clinical management of hospitalized patients is complex due to the heterogeneous course of COVID-19. Low-dose radiation therapy is known to dampen localized chronic inflammation and has been suggested to be used to reduce lung inflammation in patients with COVID-19. However, it is unknown whether SARS-CoV-2 alters the radiation response and associated radiation exposure related risk. We generated gene expression profiles from circulating leukocytes of hospitalized patients with COVID-19 and healthy donors. The p53 signaling pathway was found to be dysregulated, with mRNA levels of p53, ATM, and CHK2 being lower in patients with COVID-19. Several key p53 target genes involved in cell cycle arrest, apoptosis, and p53 feedback inhibition were upregulated in patients with COVID-19 while other p53 target genes were downregulated. This dysregulation has functional consequences as the transcription of p53-dependant genes (CCNG1, GADD45A, DDB2, SESN1, FDXR, APOBEC) was reduced 24 hours after x-ray exposure ex vivo to both low (100 mGy) or high (2 Gy) doses. SARS-CoV-2 infection affects a DNA damage response that may modify radiation-induced health risks in exposed patients with COVID-19.


Correction to: The Association Between Depression, Suicidal Ideation and Psychological Strains in College Students: A Cross-National Study.
The original version of the article unfortunately contained an error in acknowledgement section. The corrected acknowledgement is: This research was supported by a grant of Beijing Natural Science Foundation (9174046), for which the first author is PI.


Synthesis and characterization of a new class of stabilized apatite nanoparticles and applying the particles to in situ Pb immobilization in a fire-range soil.
Phosphate compounds and the related materials are effective agents for in situ immobilization of heavy metals in contaminated soils. Problems associated with using these phosphate materials include difficulties in delivering the solid phosphate minerals to the deep contaminated zones or risks of eutrophication with applying soluble phosphates. Therefore, a new class of apatite nanoparticles was synthesized using carboxymethyl cellulose as a stabilizer in order to increase the dispersion rate of phosphate in soils but without introducing significant amount of soluble phosphate into the environment. The product was confirmed by XRD as chlorapatite (Ca5(PO4)3Cl) with poor crystallinity. TEM and SEM revealed that the particles were spherical or irregular in shape with sizes spanning from a few nm to around 200 nm. FTIR spectra suggested that Ca(II) cations formed outer-sphere bonds with carboxyl and hydroxyl groups in cellulose molecules, thus inhibiting further agglomeration of the particles. Dry combustion data supported a formula of [C6H7O2(OH)2OCH2COOCa5(PO4)3Cl]n for the nano-apatite composite. Laboratory tests showed that the nanoparticles could effectively decrease the TCLP-leachable Pb fraction in a Pb-contaminated soil from 66% to 10% after one-month amendment with a ratio of 2 mL solution to 1g soil and the resultant Pb content in the TCLP solution was reduced to 12 from 94 mg L(-1). When the amendment ratio was increased by 5 times, the leachable Pb was further reduced to 3.8 mg L(-1) with only about 3% of the soil Pb leachable. The soil sample, containing an average of 2.7×10(3)mg Pb kg(-1), was taken from a shooting-range in Southern USA.


Patch formation by herbivorous fish in a temperate Australian kelp forest.
The odacid fish Odax cyanomelas feeds on the kelp Ecklonia radiata, an important component of subtidal reef habitats on the central coast of New South Wales, Australia. Herbivory by Odax has a major impact on the structure and dynamics of discrete patches within larger stands of kelp at Cape Banks. This three-year study showed that each year, between August and October, approximately the same patches of kelp were denuded by preferential feeding on the meristem and primary laminae. This coincided with a variable pulse of Ecklonia recruits to the cleared patches, thereby generating patches of a single age-class of plants. Neighbouring areas of Ecklonia forest, non cleared by Odax, consisted of larger, perennial plants, which exhibited more gradual changes in abundance. The seasonal impact of Odax appeared to be due to a change in the behaviour of female Odax during their spawning period. Observations suggested that females aggregate at traditional sites prior to spawning with territorial males in adjacent areas of kelp forest. An alternative hypothesis, that Odax preferentially attacked stands of one-year old Ecklonia plants, was rejected by a field experiment; the establishment of experimental stands of one-year old plants did not lead to increased damage due to Odax or any change in the use of space by the fish. The generality of this effect of fish herbivory is unknown, but this and other Odax species are widely distributed throughout temperate Australia, where Ecklonia is the dominant laminarian alga. The effects of pulsed herbivory by Odax is contrasted to the more continuous grazing by sea urchins in the same system. The latter herbivore has been shown to maintain areas free of Ecklonia, the long-term effects of herbivory by Odax remain unclear.


Synthesis of the urinary glucuronic acid conjugate of N-hydroxy-4-aminobiphenyl.
The glucuronic acid conjugate of N-hydroxy-4-aminobiphenyl believed to be the carrier form responsible for transporting the active N-hydroxy compound from its site of formation in the liver to its site of carcinogenic action in the bladder has been prepared synthetically. The synthetic conjugate is identical by infrared and chromatographic analyses with the conjugate isolated from urine, thus unequivocally establishing its structure as an N--C conjugate, sodium (N,4-biphenyl-N-hydroxy-D-glucuronosylamine).


Increased response of cytochrome P-450 dependent biotransformation reactions in rat liver to repeated administration of inducers.
A single intraperitoneal administration of 3-methylcholanthrene (3MC) or beta-naphthoflavone (BNF) increased aryl hydrocarbon hydroxylase (AHH) and 7-ethoxyresorufin 0-deethylase (EROD) activities. Following a second administration of both inducers 3-4 weeks later, the extent of induction was considerably greater. Such a "booster"-phenomenon was also observed with different cytochrome P-450 (P-450)-dependent N-demethylation reactions after repeated phenobarbital (PB) administrations. Again the P-450 content was higher than after a single PB administration.


Are spliced ncRNA host genes distinct classes of lncRNAs?
Many small nucleolar RNAs and many of the hairpin precursors of miRNAs are processed from long non-protein-coding host genes. In contrast to their highly conserved and heavily structured payload, the host genes feature poorly conserved sequences. Nevertheless, there is mounting evidence that the host genes have biological functions beyond their primary task of carrying a ncRNA as payload. So far, no connections between the function of the host genes and the function of their payloads have been reported. Here we investigate whether there is evidence for an association of host gene function or mechanisms with the type of payload. To assess this hypothesis we test whether the miRNA host genes (MIRHGs), snoRNA host genes (SNHGs), and other lncRNA host genes can be distinguished based on sequence and/or structure features unrelated to their payload. A positive answer would imply a functional and mechanistic correlation between host genes and their payload, provided the classification does not depend on the presence and type of the payload. A negative answer would indicate that to the extent that secondary functions are acquired, they are not strongly constrained by the prior, primary function of the payload. We find that the three classes can be distinguished reliably when the classifier is allowed to extract features from the payloads. They become virtually indistinguishable, however, as soon as only sequence and structure of parts of the host gene distal from the snoRNAs or miRNA payload is used for classification. This indicates that the functions of MIRHGs and SNHGs are largely independent of the functions of their payloads. Furthermore, there is no evidence that the MIRHGs and SNHGs form coherent classes of long non-coding RNAs distinguished by features other than their payloads.


High concentrations of soluble tumor necrosis factor receptors in ascites.
Ascites and plasma concentrations of soluble tumor necrosis factor receptors p55 and p75 were measured in a prospective study in 34 patients (35 occasions of ascites) with hepatic (5 infected and 21 uninfected) and malignancy-related (9) ascites. All patients had high concentrations of both soluble tumor necrosis factor receptors in ascites and plasma; these were about 500 times higher than the corresponding tumor necrosis factor-alpha concentrations. Ascites levels of soluble tumor necrosis factor receptors p55 and soluble tumor necrosis factor receptors p75 were significantly elevated in patients with malignancy-related (p55: 26.0 +/- 8.6 ng/ml; p75: 20.5 +/- 17.4 ng/ml; mean +/- S.D.) and infected ascites (p55: 25.1 +/- 10.9 ng/ml, p75: 22.6 +/- 11.0 ng/ml) compared with patients with uncomplicated hepatic ascites (p55: 10.1 +/- 4.4 ng/ml; p75: 6.0 +/- 2.6 ng/ml). Patients with infected or malignancy-related ascites also showed higher soluble tumor necrosis factor receptor concentrations in plasma than did patients with plain hepatic ascites. Successful antibiotic treatment of peritonitis reduced soluble tumor necrosis factor receptor p55 and p75 ascites levels in three patients from 24.2 +/- 15.2 ng/ml to 10.7 +/- 1.9 ng/ml and from 20.2 +/- 14.4 ng/ml to 7.5 +/- 1.8 ng/ml, respectively. Soluble tumor necrosis factor receptors p55 and p75 at cutoff levels of 16.5 ng/ml and 9.5 ng/ml, respectively, differentiated between infected or malignant and plain hepatic ascites with diagnostic accuracies of 94% and 89%, respectively. They did not differentiate between infected and malignant ascites. The concentrations of soluble tumor necrosis factor receptor p55 were usually higher in ascites than in plasma in all subgroups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Defensive burying: effects of diazepam and oxprenolol measured in extinction.
When a rat is shocked via a prod in a chamber with sawdust on the floor it will typically push the flooring material with snout and forepaws towards and over the prod. We administered diazepam (.5 and 1.0 mg/kg) and oxprenolol (10 and 20 mg/kg) the day following shock exposure, and observed the complete suppression of burying by diazepam, and some suppression with oxprenolol. These effects are independent of interference with initial association of shock and prod, and of changes in general activity.


Identification of Essential Genes Using Sequential CRISPR and siRNA Screens.
Genome-wide CRISPR and siRNA screening methodologies are powerful tools that are aptly suited to the discovery of essential genes. In this chapter, we outline our methods to conduct sequential CRISPR and siRNA screens to quickly and efficiently identify essential genes within a collection of cell lines. The utilization of both screening methodologies provides a pipeline that minimizes costs and time while enabling the robust detection of candidate genes.


Association of Surgical Approach and Urinary Diversion in Radical Cystectomy for Bladder Cancer With Costs and Readmission: Results From a Large Private Health Insurance Cohort.
We sought to assess the comparative hospital outcomes and costs among a population-based cohort of bladder cancer patients by surgical approach and diversion. From a privately insured national database, we identified all bladder cancer patients who underwent open or robotic radical cystectomy and ileal conduit or neobladder from 2010 to 2015. The primary outcomes were length of stay, readmissions, and total health care costs at 90 days from surgery. We used multivariable logistic regression and generalized estimating equations to assess for 90-day readmission and health care costs, respectively. Most patients underwent open radical cystectomy with ileal conduit (56.7%; n = 1,680) followed by open radical cystectomy with neobladder (22.7%; n = 672), robotic radical cystectomy with ileal conduit (17.4%; n = 516), and robotic radical cystectomy with neobladder (3.1%; n = 93). On multivariable analysis, patients had higher odds of 90-day readmissions for open radical cystectomy and neobladder (OR: 1.36; P = .002) and robotic radical cystectomy with neobladder (OR 1.60; P = .03) relative to open radical cystectomy with ileal conduit. After adjusting for patient covariates, we also found lower adjusted total 90-day health care costs for open radical cystectomy with ileal conduit ($67,915) and open radical cystectomy with neobladder ($67,371) compared to robotic radical cystectomy with ileal conduit ($70,677) and neobladder ($70,818; P < .05). In our study, neobladder diversion was associated with higher odds of 90-day readmission, while robotic surgery increased total 90-day health care costs.


Eradication of Helicobacter pylori with lansoprazole, roxithromycin and metronidazole--an open pilot study.
The most extensively studied Helicobacter pylori eradication regimen comprises omeprazole, clarithromycin and metronidazole. Macrolide antibiotics other than clarithromycin should achieve similar efficacy, but they have not yet been thoroughly tested. To determine the efficacy and safety of a triple therapy regimen using lansoprazole, roxithromycin, and metronidazole on the basis of multicentre outpatient care in an open pilot study. 163 patients with duodenal ulcer and proven H. pylori infection received lansoprazole 30 mg b.d., roxithromycin 300 mg b.d. and metronidazole 500 mg b.d. for 7 days followed by another 7 days of lansoprazole 30 mg once daily. H. pylori status was determined by urease quick test, histology, microbiology and 13C-urea breath test before starting and at least 4 weeks after completing treatment. 150 patients were available for evaluation; H. pylori was successfully eradicated in 84.7% (127/ 150) as determined by urease quick test, 78.0% (117/150) by histology, 81.3% (109/134) by 13C-urea breath test; and in 75.3% (113/150), at least two tests were negative. Side-effects were reported in 34 patients (most commonly diarrhoea and changes in liver function tests), in two cases the study medication was interrupted. Prior to treatment, 23% of the H. pylori isolates were resistant against metronidazole and 3.4% against roxithromycin. After unsuccessful treatment, 84% of the isolates were resistant against metronidazole and 21% against roxithromycin. Primary resistance to metronidazole increased the chance of treatment failure approximately sevenfold (7% vs. 53%). For H. pylori eradication, the combination of lansoprazole, roxithromycin and metronidazole proved to be as safe as other current triple therapy regimens, while a comparison of efficacy rates yet remains to be assessed in prospective controlled trials. The metronidazole-resistant H. pylori is not rare in Germany and, in the present study, has strongly influenced treatment success.


Lactobacillus plantarum in black soldier fly (Hermetica illucens) meal modulates gut health and immunity of freshwater crayfish (Cherax cainii).
Probiotic supplements are being used to improve the growth and immune performance of aquaculture species over the last couple of decades. In recent times, black soldier fly (BSF) is considered as one of the promising sources of alternative protein to fishmeal protein in aqua-diets. Since the freshwater crayfish, marron (Cherax cainii), a Western Australian's native and iconic freshwater crayfish species, grows fairly slow under commercial farming environment, this study was aimed to investigate the supplemental effect of BSF and BSF with probiotic bacteria Lactobacillus plantarum (BSFLP) on overall health and immune performance of marron after 56 days of feeding under laboratory conditions. The post-trial data revealed insignificant influences of any diets on growth performance, however, both BSF and BSFLP based diets significantly improved some haemolymph parameters and gut health of marron. High throughput sequence data revealed that both BSF and BSFLP diets significantly improved the diversity of microbial communities including some beneficial bacteria for crustaceans in the hindgut of marron. Further analysis showed that both BSF and BSFLP diets upregulated the expression of some genes in the gut tissue and haemocytes associated with the innate immune response of marron at 48 h post injection. The up-regulation of some immune genes in BSFLP diet group was found significantly linked to OTU abundance for Lactobacillus. The findings of this study could be helpful for improving overall health status of marron.


Carbon catabolite repression involves physical interaction of the transcription factor CRE1/CreA and the Tup1-Cyc8 complex in Penicillium oxalicum and Trichoderma reesei.
Cellulolytic enzyme production in filamentous fungi requires a release from carbon catabolite repression (CCR). The protein CRE1/CreA (CRE = catabolite responsive element) is a key transcription factor (TF) that is involved in CCR and represses cellulolytic gene expression. CRE1/CreA represents the functional equivalent of Mig1p, an important Saccharomyces cerevisiae TF in CCR that exerts its repressive effect by recruiting a corepressor complex Tup1p-Cyc8p. Although it is known from S. cerevisiae that CRE1/CreA might repress gene expression via interacting with the corepressor complex Tup1-Cyc8, this mechanism is unconfirmed in other filamentous fungi, since the physical interaction has not yet been verified in these organisms. The precise mechanism on how CRE1/CreA achieves transcriptional repression after DNA binding remains unknown. The results from tandem affinity purification and bimolecular fluorescence complementation revealed a direct physical interaction between the TF CRE1/CreA and the complex Tup1-Cyc8 in the nucleus of cellulolytic fungus Trichoderma reesei and Penicillium oxalicum. Both fungi have the ability to secrete a complex arsenal of enzymes to synergistically degrade lignocellulosic materials. In P. oxalicum, the protein PoCyc8, a subunit of complex Tup1-Cyc8, interacts directly with TF PoCreA and histone H3 lysine 36 (H3K36) methyltransferase PoSet2 in the nucleus. The di-methylation level of H3K36 in the promoter of prominent cellulolytic genes (cellobiohydrolase-encoding gene Pocbh1/cel7A and endoglucanase-encoding gene Poegl1/cel7B) is positively correlated with the expression levels of TF PoCreA. Since the methylation of H3K36 was also demonstrated to be a repression marker of cellulolytic gene expression, it appears feasible that the cellulolytic genes are repressed via PoCreA-Tup1-Cyc8-Set2-mediated transcriptional repression. This study verifies the long-standing conjecture that the TF CRE1/CreA represses gene expression by interacting with the corepressor complex Tup1-Cyc8 in filamentous fungi. A reasonable explanation is proposed that PoCreA represses gene expression by recruiting complex PoTup1-Cyc8. Histone methyltransferase Set2, which methylates H3K36, is also involved in the regulatory network by interacting with PoCyc8. The findings contribute to the understanding of CCR mechanism in filamentous fungi and could aid in biotechnologically relevant enzyme production.


Congenital tracheobronchial stenosis in monozygotic twins.
A pair of monozygotic twins suffering from noisy respirations and recurrent wheezes since early infancy were referred for evaluation. Using direct coronal CT and 3-dimensional reconstruction of the airway, congenital tracheobronchial stenosis was found in both twin babies, later confirmed by fibre optic bronchoscopy. The cause of congenital tracheobronchial stenosis remains obscure, but even in monozygotic twins an unidentified environmental factor cannot be excluded and may be responsible for discordant bronchopulmonary abnormalities. This case report shows that tracheobronchial stenosis may present in monozygotic twins. The pattern of malformation in twins differs from cases described previously.


Photodynamic diagnosis in respiratory tract malignancy using an excimer dye laser system.
Equipment has been developed for the early-stage diagnosis and treatment of cancer using an excimer dye laser. The excimer laser beam is obtained by exciting XeCl. A 405 nm beam tuned by DPS dye is used for tumour localization and a 630 nm beam obtained with a rhodamine B dye is used for treatment. The equipment was applied clinically on the basis of extensive experimental research. Effectiveness for cancer localization was examined in 11 cases: four were early stage (three lung cancer and one vocal cord cancer), four were stage I, two were stage III and one was stage IV. All cases were squamous cell carcinoma except for one case of adenocarcinoma. Fluorescence was recognized in all lesions and the equipment was effective for localization.


The career aspirations of women doctors who qualified in 1974 and 1977 from a United Kingdom medical school.
The career aspirations of doctors who qualified from a UK medical school were examined in relation to firmness of career choice and marital and family circumstances 1 year and 7 years after qualification. Although there was greater certainty of career choice amongst all doctors, the women were consistently less likely to be certain than the men. The men were more likely than the women to be married (and more likely to have children). The main differences in patterns of career choice were the greater popularity of medicine and surgery among the men and of general practice and community medicine among the women. The most plausible explanation for these differences is the different marital and family pressures experienced by men and women.


Pharmacokinetics, tissue distribution, and plasma protein binding study of platinum originating from dicycloplatin, a novel antitumor supramolecule, in rats and dogs by ICP-MS.
Dicycloplatin, as a new antitumor supramolecule, was considered to have higher solubility and higher stability compared with carboplatin. The aim of the present study was to evaluate the pharmacokinetic characteristics of platinum originating from dicycloplatin. A rapid, sensitive, and specific method with inductively coupled plasma mass spectrometry (ICP-MS) has been developed for the determination of platinum in bio-samples. The study was performed in male rats and dogs at a single dose of 10 and 5 mg kg(-1) separately by intravenous injection. Pharmacokinetic parameters were calculated by non-compartmental method, and the dose of platinum was used in the calculation of these parameters. Results showed that plasma concentrations of platinum began to decrease rapidly initially but decline slowly with a long terminal phase. The mean half-life was 27.39 and 100.98 and clearance was 0.77 and 0.08 L/h/kg for rats and dogs separately. Tissue distribution showed that platinum originating from dicycloplatin had a certain distribution in testis and prostate. Plasma protein binding proportion of platinum was increased with time. In conclusion, this research investigated the pharmacokinetic characteristics including plasma kinetics, tissue distribution, and plasma protein binding of platinum originating from dicycloplatin in rats and dogs in detail for the first time by ICP-MS.


Ambient intelligence-based multimodal human action recognition for autonomous systems.
Human activity recognition can deduce the behaviour of one or more people from a set of sensor measurements. Despite its widespread applications in monitoring activities, robotics, and visual surveillance, accurate, meticulous, precise and efficient human action recognition remains a challenging research area. As human beings are moving towards the establishment of a smarter planet, human action recognition using ambient intelligence has become an area of huge potential. This work presents a method based on Bi-Convolutional Recurrent Neural Network (Bi-CRNN) -based Feature Extraction and then Random Forest classification for achieving outcomes utilizing Ambient Intelligence that are at the cutting edge of human action recognition for Autonomous Robots. The auto fusion technique used has improved fusion for utilizing and processing data from various sensors. This paper has drawn comparisons with already existing algorithms for Human Action Recognition (HAR) and tried to propose a heuristic and constructive hybrid deep learning-based algorithm with an accuracy of 94.7%.


Lactobacillus acidophilus attenuates Salmonella-induced intestinal inflammation via TGF-β signaling.
Salmonella is a common intestinal pathogen that causes acute and chronic inflammatory response. Probiotics reduce inflammatory cytokine production and serve as beneficial commensal microorganisms in the human gastrointestinal tract. TGF-β (transforming growth factor β)/SMAD and NF-κB signaling play important roles in inflammation in intestinal cells. However, the involvement of the signaling in regulating inflammation between Salmonella and probiotics is not fully understood. L. acidophilus and prebiotic inulin were used to treat human intestinal Caco-2 cells prior to infection with Salmonella. The cells were harvested to examine the cytokines and MIR21 expression with immunoblotting and real-time PCR. NF-κB and SMAD3/4 reporter vectors were transfected into cells to monitor inflammation and TGF-β1 signaling, respectively. In this study, we showed that the probiotic L. acidophilus decreased Salmonella-induced NF-κB activation in human intestinal Caco-2 cells. Expression of the inflammatory cytokines, TNF-α and IL-8, in L. acidophilus-pretreated cells was also significantly lower than that in cells infected with Salmonella alone. Moreover, TGF-β1 and MIR21 expression was elevated in cells pretreated with L. acidophilus or synbiotic, a combination of inulin and L. acidophilus, compared to that in untreated cells or cells infected with S. typhimurium alone. By contrast, expression of SMAD7, a target of MIR21, was accordingly reduced in cells treated with L. acidophilus or synbiotics. Consistent with TGF-β1/MIR21 and SMAD7 expression, SMAD3/4 transcriptional activity was significantly higher in the cells treated with L. acidophilus or synbiotics. Furthermore, TGF-β1 antibody antagonized the SMAD3/4 and NF-κB transcriptional activity modulated by L. acidophilus in intestinal cells. Our results suggest that the TGF-β1/MIR21 signaling pathway may be involved in the suppressive effects of L. acidophilus on inflammation caused by S. typhimurium in intestinal Caco-2 cells.


Is binge eating experienced as an addiction?
To ascertain to what degree binge eating is experienced as an addiction, this study examined the proportion of women with binge-eating disorder (BED) whose symptoms met criteria for an addiction. Women (N = 79) with current BED completed a structured telephone interview to assess for symptoms of a modified version of DSM-IV substance dependence and Goodman's [(1990). Addiction: Definition and implications. British Journal of Addiction, 85, 1403-1408] proposed diagnosis of 'addictive disorder'. Most binge eaters (92.4%) met modified DSM-IV criteria for substance dependence, whereas many fewer (40.5%) met Goodman's more restrictive criteria for addictive disorder. Women meeting criteria for addictive disorder had more frequent eating binges than those who did not. Despite certain observed similarities between binge eating and addictions, we argue that BED should remain classified as an eating disorder.


Unusual nasal foreign body in a dog.
A metallic hunting arrowhead was found in the nasal sinuses of a dog with chronic nasal discharge. The arrowhead was removed via rhinotomy. Nasal discharge ceased after the foreign body's removal.


Synthetic analogs of natural prenylated and chromene chalcones.
A number of synthetic analogs of the prenylated and chromene chalcones isolated from lonchocarpus neuroscapha (Leguminosae) were obtained by condensation of prenylated acetophenones with substituted benzaldehydes. The antibacterial activity of these products was studied and correlated with their structure.


Bladder and urethral dynamics in multiple sclerosis-like animal model.
Multiple sclerosis-like disease was induced in 18 rabbits by immunization with guinea pig spinal cord. The urodynamic studies conducted in the immunized rabbits showed a significantly lower maximal urethral pressure and a lower bladder capacity than those in the control group. We compared the urodynamic, clinical and histopathological parameters in the immunized rabbits. We conclude that the rabbit is an acceptable model for studying the bladder and urethral dynamics during various phases of experimental allergic encephalomyelitis (multiple sclerosis-like disease).


Photochromic oligothienoacene derivatives with photo-switchable luminescence properties and computational studies.
Photochromic thieno[3,2-b]thiophenes and dithieno[3,2-b:2',3'-d]thiophene with photo-switchable luminescence properties have been synthesized using a Suzuki cross-coupling reaction; their electronic structures, and photochromic and luminescence behaviour have also been studied.


Effect of different intensity exercises on cardiopulmonary function and quality of life of patients with chronic heart failure : A systematic review and meta-analysis.
Exercise-based cardiac rehabilitation has positive benefits for patients with chronic heart failure (CHF), but the choice of exercise intensity has been controversial. The aim of this systematic review and meta-analysis was to investigate the effects of different exercise intensities on cardiopulmonary function and quality of life (QoL) of patients with CHF. Randomized controlled trials (RCTs) of different exercise intensities applied to patients with CHF were searched in PubMed, Web of Science, the Cochrane Library, and Embase databases from inception to December 2021. Study selection and data extraction were performed simultaneously by two independent reviewers, using the Physiotherapy Evidence Database Scale (PEDro) for quality assessment of the included literature. The weighted mean differences (WMD) or standardized mean difference (SMD) were calculated by employing a fixed or random effects model. Other statistical analyses included subgroup analysis and sensitivity analysis. Quality of evidence was evaluated by the Grade of Recommendation, Assessment, Development, and Evaluation (GRADE) method. Eight RCTs were included. Analyses reported no significant improvement in left ventricular ejection fractions (LVEF; WMD = 0.47, 95% CI [-4.10, 5.03], p = 0.841), peak oxygen uptake (peak VO2) (SMD = 0.38, 95% CI [-0.03, 0.80], p = 0.069) and 6‑min walking distance (6MWD) (WMD = 14.10, 95% CI [-9.51, 37.72], p = 0.242). Exercise interventions of varying intensity produced small-to-moderate beneficial effects on QoL (WMD = -4.99, 95% CI [-8.29, -1.68], p = 0.003), which appeared to be attenuated at long-term follow-up (WMD = 2.12, 95% CI [-2.91, 7.16], p = 0.409). High-intensity exercise does not have a significant advantage over moderate-intensity exercise in improving cardiopulmonary function and aerobic capacity in patients with CHF. Beneficial changes in QoL from high-intensity exercise also appeared to decrease during long-term follow-up, indicating a cumulative effect of the efficacy of high-intensity exercise.


Time-course studies of the distribution of [1-14C]acrylonitrile in rats after intravenous administration.
Intravenous injection of acrylonitrile (ACN) causes adrenal hemorrhagic necrosis. ACN and its metabolites react with glutathione and bind covalently with macromolecules. Hence the purpose of this investigation was to measure the distribution and covalent binding of radiolabel derived from [1-14C]ACN in order to determine whether binding of ACN or its metabolites may be implicated in the pathogenesis of ACN-induced adrenal injury. Following intravenous injections of ACN, concentrations of total radiolabel were highest in the blood, liver, duodenum, kidneys, and adrenals. Except for blood, there was a time-dependent decrease in total radiolabel in these tissues. Compared with other major organ systems, the levels of covalently bound radiolabel were lower in the adrenal glands. These results do not support a role of covalent binding of ACN or its metabolites in the adrenal toxicity of ACN, but suggest that the initial high concentrations of total radiolabelled compounds derived from ACN could play a role in the action of ACN on the adrenal glands.


Malignant melanoma of the penis and male urethra: 4 case reports and literature review.
Malignant melanomas of the penis and male urethra are uncommon lesions. We report 3 new cases of male urethral melanoma and 1 case of penile melanoma, bringing the total numbers of reported cases to 26 and 57, respectively. The literature is reviewed, and biological, histopathological and therapeutic considerations are analyzed.


Symmetric and antisymmetric soliton states in two-dimensional photonic lattices.
We study the dynamics of off-site excitation in an optically induced waveguide lattice. A single beam centered between two waveguides leads to an asymmetric beam profile as the nonlinearity reaches a threshold. When two probe beams are launched in parallel into two nearby off-site locations, they form symmetric or antisymmetric (twisted) soliton states, depending on their relative phase. A transition of intensity pattern from on-site to off-site locations is also observed as the lattice is excited by a quasi-one-dimensional plane wave.


Pharmacological characterization of recombinant N-type calcium channel (Cav2.2) mediated calcium mobilization using FLIPR.
The N-type voltage-gated calcium channel (Ca(v)2.2) functions in neurons to regulate neurotransmitter release. It comprises a clinically relevant target for chronic pain. We have validated a calcium mobilization approach to assessing Ca(v)2.2 pharmacology in two stable Ca(v)2.2 cell lines: alpha1(B), alpha2delta, beta(3)-HEK-293 and alpha1(B), beta(3)-HEK-293. Ca(v)2.2 channels were opened by addition of KCl and Ca(2+) mobilization was measured by Fluo-4 fluorescence on a fluorescence imaging plate reader (FLIPR(96)). Ca(v)2.2 expression and biophysics were confirmed by patch-clamp electrophysiology (EP). Both cell lines responded to KCl with adequate signal-to-background. Signals from both cell lines were inhibited by omega-conotoxin (ctx)-MVIIa and omega-conotoxin (ctx)-GVIa with IC(50) values of 1.8 and 1nM, respectively, for the three-subunit stable, and 0.9 and 0.6nM, respectively, for the two-subunit stable. Other known Ca(v)2.2 blockers were characterized including cadmium, flunarizine, fluspirilene, and mibefradil. IC(50) values correlated with literature EP-derived values. Novel Ca(v)2.2 pharmacology was identified in classes of compounds with other primary pharmacological activities, including Na(+) channel inhibitors and antidepressants. Novel Na(+) channel compounds with high potency at Ca(v)2.2 were identified in the phenoxyphenyl pyridine, phenoxyphenyl pyrazole, and other classes. The highest potency at Ca(v)2.2 tricyclic antidepressant identified was desipramine.


Microsome-mediated clastogenicity of butylated hydroxyanisole (BHA) in cultured Chinese hamster ovary cells: the possible role of reactive oxygen species.
Butylated hydroxyanisole (BHA) was found to induce chromosome aberrations in Chinese hamster ovary (CHO) cells in the presence of Aroclor-induced rat-liver S9. The effects were more marked when washed microsomes were employed and chromosome damage was considerably reduced in the presence of catalase, suggesting that hydrogen peroxide was involved. Stimulation of H2O2 production by BHA in S9 or microsome incubation mixtures was demonstrated using the catalase-mediated production of formaldehyde from methanol. One of the major microsomal metabolites of BHA, tert.-butyl hydroquinone (t-BHQ), which autoxidises in solution producing H2O2 also induced extensive catalase-sensitive chromosome damage in the absence of metabolic activation. These observations suggest that extracellular generation of reactive oxygen species may be implicated in the mechanism of BHA clastogenicity in vitro. However, chromosome damage was not completely abolished by catalase and the end product of t-BHQ oxidation, tert.-butyl quinone, was also weakly clastogenic, suggesting that intracellular effects of quinone metabolites may also be involved in the clastogenicity of BHA.


Mimicking 3D breast tumor-stromal interactions to screen novel cancer therapeutics.
Most of the 3D breast tumor models used in drug screening studies only comprise tumor cells, keeping out other essential cell players of the tumor microenvironment. Tumor-associated macrophages and fibroblasts are frequently correlated with tumor progression and therapy resistance, and targeting these cells at the tumor site has been appointed as a promising therapeutic strategy. However, the translation of new therapies to the clinic has been hampered by the absence of cellular models that more closely mimic the features of in vivo breast tumor microenvironment. Therefore, the development of innovative 3D models able to provide consistent and predictive responses about the in vivo efficacy of novel therapeutics is still an unmet preclinical need. Herein, we have established an in vitro 3D heterotypic spheroid model including MCF-7 breast tumor cells, human mammary fibroblasts and human macrophages. To establish this model, different cell densities have been combined and characterized through the evaluation of the spheroid size and metabolic activity, as well as histological and immunohistochemistry analysis of the 3D multicellular structures. The final optimized 3D model consisted in a multicellular spheroid seeded at the initial density of 5000 cells and cell ratio of 1:2:1 (MCF-7:monocytes:fibroblasts). Our model recapitulates several features of the breast tumor microenvironment, including the formation of a necrotic core, spatial organization, and extracellular matrix production. Further, it was validated as a platform for drug screening studies, using paclitaxel, a currently approved drug for breast cancer treatment, and Gefitinib, a chemotherapeutic approved for lung cancer and in preclinical evaluation for breast cancer. Generally, the impact on the cell viability of the 3D model was less evident than in 2D model, reinforcing the relevance of such complex 3D models in addressing novel treatment approaches. Overall, the use of a 3D heterotypic spheroid of breast cancer could be a valuable tool to predict the therapeutic effect of new treatments for breast cancer patients, by recapitulating key features of the breast cancer microenvironment.


Chronic diazinon exposure: pathologies of spleen, thymus, blood cells, and lymph nodes are modulated by dietary protein or lipid in the mouse.
Little is known about the immunotoxicity of the organophosphate pesticide, diazinon. This study aims at detailing the pathologies in the thymus, spleen, blood cells, and lymph nodes (brachial, mesenteric, and hind quarter gluteal nodes) during chronic oral exposure (300 mg diazinonkg-1 food for 45 days), and explore the combined toxicity with excess dietary protein (40%) or lipid (20% corn oil). Animals were allowed to recover on normal food for 2 weeks. All experimental treatments caused organ pathologies, including necrotic degeneration of the trabeculae (spleen and thymus), hyperplasia of the cortex and medulla (thymus and lymph nodes), hyperplasia of white and red pulp (spleen), and sometimes haemorrhage (all tissues). Blood smears often showed crenated/hypochromic red cells and vacuolated white cells with abnormal nuclei. The severity of lesions during exposure was generally in the following order: lipid<protein<diazinon alone<protein plus diazinon<lipid plus diazinon. Post-exposure recovery was limited, especially in the thymus and for lipid treatments. Quantitative image analysis revealed treatment and organ-specific changes in the proportions of fixed lymphocytes, PAS-positive carbohydrates, DNA, and protein staining. Histochemical changes were greatest after exposure. We conclude that the immunotoxicity of diazinon is exacerbated by excess dietary protein or lipid. The limited recovery and post-exposure histochemical changes imply deleterious effects on metabolism with oxidative stress after exposure.


Spatial information and uncertainty in anisometropic amblyopia.
Anisometropic amblyopes were found to have a reduced sensitivity for shape discrimination. The introduction of positional jitter in the elements of the display had a profound effect on the performance of the normal eye, but not on that of the amblyopic eye. On the other hand the introduction of gaussian blur affects the performance of both eyes to the same degree. We conclude that raised spatial uncertainty due to metrical scrambling is a suitable model for anisometropic amblyopia.


Efficient protein production method for NMR using soluble protein tags with cold shock expression vector.
The E. coli protein expression system is one of the most useful methods employed for NMR sample preparation. However, the production of some recombinant proteins in E. coli is often hampered by difficulties such as low expression level and low solubility. To address these problems, a modified cold-shock expression system containing a glutathione S-transferase (GST) tag, the pCold-GST system, was investigated. The pCold-GST system successfully expressed 9 out of 10 proteins that otherwise could not be expressed using a conventional E. coli expression system. Here, we applied the pCold-GST system to 84 proteins and 78 proteins were successfully expressed in the soluble fraction. Three other cold-shock expression systems containing a maltose binding protein tag (pCold-MBP), protein G B1 domain tag (pCold-GB1) or thioredoxin tag (pCold-Trx) were also developed to improve the yield. Additionally, we show that a C-terminal proline tag, which is invisible in ¹H-¹⁵N HSQC spectra, inhibits protein degradation and increases the final yield of unstable proteins. The purified proteins were amenable to NMR analyses. These data suggest that pCold expression systems combined with soluble protein tags can be utilized to improve the expression and purification of various proteins for NMR analysis.


Treatment of Seizure Clusters in Epilepsy: A Narrative Review on Rescue Therapies.
Epilepsy is a common neurological disorder in the United States, affecting approximately 1.2% of the population. Some people with epilepsy may experience seizure clusters, which are acute repetitive seizures that differ from the person's usual seizure pattern. Seizure clusters are unpredictable, are emotionally burdensome to patients and caregivers (including care partners), and require prompt treatment to prevent progression to serious outcomes, including status epilepticus and associated morbidity (e.g., lacerations, fractures due to falls) and mortality. Rescue medications for community use can be administered to terminate a seizure cluster, and benzodiazepines are the cornerstone of rescue treatment. Despite the effectiveness of benzodiazepines and the importance of a rapid treatment approach, as many as 80% of adult patients do not use rescue medication to treat seizure clusters. This narrative review provides an update on rescue medications used for treatment of seizure clusters, with an emphasis on clinical development and study programs for diazepam rectal gel, midazolam nasal spray, and diazepam nasal spray. Results from long-term clinical trials have shown that treatments for seizure clusters are effective. Intranasal benzodiazepines provide ease of use and patient and caregiver satisfaction in pediatric and adult patients. Adverse events attributed to acute rescue treatments have been characterized as mild to moderate, and no reports of respiratory depression have been attributed to treatment in long-term safety studies. The implementation of an acute seizure action plan to facilitate optimal use of rescue medications provides an opportunity for improved management of seizure clusters, allowing those affected to resume normal daily activities more quickly.


Human mesenchymal stromal cells as cellular drug-delivery vectors for glioblastoma therapy: a good deal?
Glioblastoma (GB) is the most malignant brain tumor in adults. It is characterized by angiogenesis and a high proliferative and invasive capacity. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) is of limited efficacy. Innovative anticancer drugs targeting both tumor cells and angiogenesis are urgently required, together with effective systems for their delivery to the brain. We assessed the ability of human mesenchymal stromal cells (MSCs) to uptake the multikinase inhibitor, sorafenib (SFN), and to carry this drug to a brain tumor following intranasal administration. MSCs were primed with SFN and drug content and release were quantified by analytical chemistry techniques. The ability of SFN-primed MSCs to inhibit the survival of the human U87MG GB cell line and endothelial cells was assessed in in vitro assays. These cells were then administered intranasally to nude mice bearing intracerebral U87MG xenografts. Their effect on tumor growth and angiogenesis was evaluated by magnetic resonance imaging and immunofluorescence analyses, and was compared with the intranasal administration of unprimed MSCs or SFN alone. MSCs took up about 9 pg SFN per cell, with no effect on viability, and were able to release 60% of the primed drug. The cytostatic activity of the released SFN was entirely conserved, resulting in a significant inhibition of U87MG and endothelial cell survival in vitro. Two intranasal administrations of SFN-primed MSCs in U87MG-bearing mice resulted in lower levels of tumor angiogenesis than the injection of unprimed MSCs or SFN alone, but had no effect on tumor volume. We also observed an increase in the proportion of small intratumoral vessels in animals treated with unprimed MSCs; this effect being abolished if the MSCs were primed with SFN. We show the potential of MSCs to carry SFN to brain tumors following an intranasal administration. However, the therapeutic effect is modest probably due to the pro-tumorigenic properties of MSCs, which may limit the action of the released SFN. This calls into question the suitability of MSCs for use in GB therapy and renders it necessary to find methods guaranteeing the safety of this cellular vector after drug delivery.


Goldmann tonometer calibration: a national survey.
Recent studies suggest that Goldmann tonometers can rapidly develop calibration errors (CEs) in clinical use and routine checks are necessary to ensure accuracy. To determine current practice regarding CE checks in the United Kingdom and assess the views of senior nursing staff in charge of running ophthalmology outpatient clinics as to whom they feel to be responsible for CE checks. Every ophthalmology unit with training recognition in England, Northern Ireland, Scotland, and Wales was contacted. Senior nurses responded to a structured telephone questionnaire regarding local tonometer calibration practice and their views regarding who is responsible for CE checks. A total of 155 eye units were identified and contacted. The response rate was 100%. CEs were checked for daily in 8 units (5.2%), weekly in 20 units (12.9%), fortnightly in 1 unit (0.6%), monthly in 12 units (7.7%), trimonthly in 5 units (3.2%), biannually in 27 units (17.4%), and annually in 21 units (13.5%). CEs were either never checked or checked in a very random manner (no identifiable pattern) in 61 units (39.4%). Sixty-three (40.6%) of the respondents felt CE checks were a departmental responsibility, 48 (31.0%) felt it to be the doctor's responsibility, and 44 (28.4%) felt CE checks should be performed by the nursing staff. Our national survey suggests that very few units check their tonometers for CEs at intervals which ensure their accuracy. Our previous survey of doctors suggests that they believe nurses should check for CE, whereas the nursing staff believe CE checks are not their responsibility. This lack of communication between health-care professionals may lead to inaccurate tonometers being used in clinical practice. We suggest that every eye unit should have a protocol, which clearly identifies individuals responsible for checking for CEs at least on a monthly basis.


Remdesivir: A beacon of hope from Ebola virus disease to COVID-19.
Since the emergence of coronavirus disease 2019 (Covid-19), many studies have been performed to characterize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and find the optimum way to combat this virus. After suggestions and assessments of several therapeutic options, remdesivir (GS-5734), a direct-acting antiviral drug previously tested against Ebola virus disease, was found to be moderately effective and probably safe for inhibiting SARS-CoV-2 replication. Finally, on 1 May 2020, remdesivir (GS-5734) was granted emergency use authorization as an investigational drug for the treatment of Covid-19 by the Food and Drug Administration. However, without a doubt, there are challenging days ahead. Here, we provide a review of the latest findings (based on preprints, post-prints, and news releases in scientific websites) related to remdesivir efficacy and safety for the treatment of Covid-19, along with covering remdesivir history from bench-to-bedside, as well as an overview of its mechanism of action. In addition, active clinical trials, as well as challenging issues related to the future of remdesivir in Covid-19, are covered. Up to the date of writing this review (19 May 2020), there is one finished randomized clinical trial and two completed non-randomized studies, in addition to some ongoing studies, including three observational studies, two expanded access studies, and seven active clinical trials registered on the clinicaltrials.gov and isrctn.com websites. Based on these studies, it seems that remdesivir could be an effective and probably safe treatment option for Covid-19. However, more randomized controlled studies are required.


Adipose tissue macrophages exert systemic metabolic control by manipulating local iron concentrations.
Iron is essential to many fundamental biological processes, but its cellular compartmentalization and concentration must be tightly controlled. Although iron overload can contribute to obesity-associated metabolic deterioration, the subcellular localization and accumulation of iron in adipose tissue macrophages is largely unknown. Here, we show that macrophage mitochondrial iron levels control systemic metabolism in male mice by altering adipocyte iron concentrations. Using various transgenic mouse models to manipulate the macrophage mitochondrial matrix iron content in an inducible fashion, we demonstrate that lowering macrophage mitochondrial matrix iron increases numbers of M2-like macrophages in adipose tissue, lowers iron levels in adipocytes, attenuates inflammation and protects from high-fat-diet-induced metabolic deterioration. Conversely, elevating macrophage mitochondrial matrix iron increases M1-like macrophages and iron levels in adipocytes, exacerbates inflammation and worsens high-fat-diet-induced metabolic dysfunction. These phenotypes are robustly reproduced by transplantation of a small amount of fat from transgenic to wild-type mice. Taken together, we identify macrophage mitochondrial iron levels as a crucial determinant of systemic metabolic homeostasis in mice.


Admissions to the Western Australian state forensic hospital from court on hospital orders over a 10-year period from 2007 to 2016.
To investigate trends in admissions to the state forensic hospital (Western Australia (WA)) from court on hospital orders from 2007 to 2016. A retrospective survey was undertaken. Demographic, clinical and legal data were obtained from hospital records. Hospital orders referred on less serious charges or without a primary diagnosis of major mental illness were identified as 'non-forensic'. There were 890 hospital orders representing 40% of total admissions. Eighty-one per cent were male and 50% had a diagnosis of schizophrenia; 22% were Indigenous; 421 (47%) were admitted on less serious (non-Schedule 1) charges; 199 (22%) did not have a primary diagnosis of a major mental illness recorded on the discharge summary; 82 (9%) had neither major mental illness nor serious charges. Overall, 539 hospital orders (60%) were identified as non-forensic; 243 (45%) of these were made with no input from the Court Liaison Service (CLS). Hospital orders make up a significant proportion of admissions to the forensic unit in WA. Many do not require secure forensic care. Developing alternative diversion pathways is essential.


The safety effect of open-median management on one-side widened freeways: A driving simulation evaluation.
Highway expansions and upgrades are often required to increase road network capacity. The widening of one side of a highway, referred to as 'one-side widening,' is sometimes implemented in these highway expansion projects. During one-side widening, to save costs, openings can be configured on existing medians (as opposed to removing the existing medians altogether). The median openings allow vehicles in the outer lanes to enter the inner lanes, but they also raise safety concerns and may require alternate open-median management strategies for traffic authorities. There is little existing research that has evaluated the safety effect of these open-median management strategies. To bridge this gap, this study proposes a procedure that evaluates the safety of open-median management strategies for one-side widened highways. The proposed procedure was implemented through driving simulation experiments on a section of Binlai Freeway in Shandong, China. First, the minimum location requirements for median openings were determined by calculating the short length of the weaving segment. Then, simulation tests were carried out to observe driving performance and workload measures. The results indicate that the procedure successfully evaluates the safety effect of open-median management strategies for one-side widened freeways. It was also found that driving performance and workload are sensitive to the opening length and traffic flow. Therefore, median opening placement should be carefully selected in consideration of not only driving performance and workload but also traffic volume predictions. Practical Applications: The findings in this study can guide open-median management strategies for traffic safety one-side widened highways.


A novel proline rich bombesin-related peptide (PR-bombesin) from toad Bombina maxima.
A novel bombesin-related peptide was isolated from skin secretions of Chinese red belly toad Bombina maxima. Its primary structure was established as pGlu-Lys-Lys-Pro-Pro-Arg-Pro-Pro-Gln-Trp-Ala-Val-Gly-His-Phe-Met-NH(2.) The amino-terminal (N-terminal) 8-residue segment comprising four prolines and three basic residues is extensively different from bombesins from other Bombina species. The peptide was thus named proline rich bombesin (PR-bombesin). PR-bombesin was found to elicit concentration-dependent contractile effects in the rat stomach strip, with both increased potency and intrinsic activity as compared with those of [Leu(13)]bombesin. Analysis of different bombesin cDNA structures revealed that an 8 to 14- nucleotide fragment replacement in the peptide coding region (TGGGGAAT in the cDNAs of multiple bombesin forms from Bombina orientalis and CACCCCGGCCACCC in the cDNA of PR-bombesin) resulted in an unusual Pro-Pro-Arg-Pro-Pro motif in the N-terminal part of PR-bombesin.


Membrane-active amino acid-coupled polyetheramine derivatives with high selectivity and broad-spectrum antibacterial activity.
Membrane active antimicrobial peptide mimics have been considered as promising alternatives to antibiotics, which interact with bacterial cell membranes to combat bacteria and avoid the emergence of multidrug-resistant bacteria. Herein, a series of star-shaped and membrane-active cationic polyetheramides derived from amino acids, were synthesized via condensation of amino acids and polyetheamine (T403). The antibacterial and anti-biofilm activitives as well as the biocompatibility of these amino acids derived polyetheramides (AAPEAs) were investigated in detail. The star-shaped AAPEAs showed high-efficient and broad-spectrum antibacterial activity against the Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) pathogens. In addition, the antibacterial activity was significantly affected by the type of amino acid. L-Trp-T403, which was obtained from L-tryptophan and polyetheramine, exhibited the best antibacterial activity with the minimum inhibitory concentration (MIC) of 1 µg/mL against methicillin-resistant S. aureus (MRSA). Time-kill kinetics and multi-passage resistance tests experiments indicated that L-Trp-T403 could rapidly kill bacteria within 1 h. This compound also showed potent antibacterial activity against bacteria over many passages. Moreover, the AAPEAs exhibited outstanding stability and long-term antibacterial activity in complex mammalian body fluids, as well as good biocompatibility, low hemolytic activity, slight toxicity for mammalian cell (L929) and low in vivo toxicity. The antibacterial activity of L-Trp-T403 was found to be based on the disruption of bacterial membranes, which leads to the leakage of the internal cytoplasm. The AAPEAs possessed high antibacterial and anti-biofilm activity, thus, they are promising to be used as long-term and biofilm-disrupting antimicrobial agents. STATEMENT OF SIGNIFICANCE: The growing epidemic of MDR-bacteria is becoming a severe public health threat. Here, a series of amino acids derived polyetheramides (AAPEAs) with a star-shaped polyether amide scaffold was synthesized. The star-shaped AAPEAs displayed broad-spectrum antibacterial activity against Gram-positive, Gram-negative bacteria and drug-resistant bacteria MRSA. Notably, the star-shaped AAPEAs were stable under plasma conditions and showed outstanding stability and long-term antibacterial activity in various complex mammalian fluids. Moreover, these star-shaped AAPEAs not only inhibited the formation of biofilms but also disrupted the established biofilms. Furthermore, the membrane-active AAPEAs eradicated bacteria via the fast membrane lytic mechanism, thus plausibly overcoming the MDR effect. These results demonstrate that membrane-active AAPEAs can serve as emerging long-term and biofilm-disrupting antimicrobial agents to treat biofilm-related infections.


Perspectives of health care workers and village health volunteers on community-based Integrated Management of Childhood Illness in Madagascar.
The Ministry of Health and Family Planning of Madagascar introduced Integrated Management of Childhood Illness (IMCI) strategy in 2006, and community-based IMCI (c-IMCI), in Mahajanga II District in 2007. Following the 2009 political crisis, foreign organisations' suspension of development aid until 2012 significantly affected the implementation of c-IMCI. This study aimed to elucidate the perspectives of village health volunteers (VHVs) and public health officers (PHO) on c-IMCI. Semi-structured in-depth interviews with all VHVs working in three communes and PHOs working at central, district, and health centre levels were conducted in 2013. Textual data, created from transcripts, were translated into English and French. Data management involved analysis of sections of translated transcripts, which were marked, coded, and linked with similar experiences, challenges, and opinions; these were categorised into words and phrases to discover meaningful relationships between emerging themes. From all interviews of 30 VHV in three Mahajanga II communes and 4 PHOs, 3 themes emerged: 1) benefits of c-IMCI to the community and for VHVs, 2) challenges to continue c-IMCI, and 3) motivation to continue c-IMCI. Although all respondents considered c-IMCI as beneficial, they stated it was difficult to continue. The health system and implementation of c-IMCI should be strengthened to enable programme survival beyond the initial phase, especially during times of political instability.


Identifying polymorphism in enamelin gene in amelogenesis imperfecta (AI).
Amelogenesis imperfecta (AI) is a developmental defect of dental enamel formation. This enamel defect can be caused by mutation in ENAM gene. Hence this study investigated the molecular defect in the enamelin gene in a patient with the clinical features of AI. The genomic DNA was extracted from patient's whole blood samples and the DNA was subjected to the polymerase chain reaction (PCR) in the presence of 16 pairs of oligonucleotide primers specifically designed to amplify all the 10 exons, g2382, g6395 and g8344 of the enamelin (ENAM) gene in the long arm of the chromosome 4. The PCR products were gel purified and sequenced to identify any mutation. The ENAM gene sequences from the patient were aligned with the reference sequence (GenBank accession no. AY167999) using VectorNTI software. We identified a single base difference at location g359 A-->G on exon 1 between the reference sequence and patient's sequence. We successfully ruled out any possible mutation on exon 2, exon 3, exon 4, exon 5, exon 6, exon 7, exon 8, exon 9, exon 10, g2382, g6395 and g8344.


An exploratory randomised controlled trial of a support programme for carers of patients with a psychosis.
Despite an acknowledgement of the impact of serious mental disorders on informal caregivers, we still know little about how to best help them. The aim of the study was to evaluate the effectiveness of a two-phased carers' intervention comprising family sessions followed by relatives' groups. This intervention was designed to be of 'intermediate' intensity, that is,one lying between brief educational programmes and long-term family psychoeducational treatments. An exploratory randomised controlled trial was conducted comparing the experimental support programme with 'standard' care. All carers of patients with a psychotic disorder from a defined population were approached. Outcome measures were based on a 'stress-appraisal-coping' model of caregiving. Despite concerted attempts to engage carers, only 42% participated in the study. The carers' programme did not offer any significant advantage on any of the outcome measures: psychological morbidity, negative appraisal, coping or social support. The severity of caregiving difficulties decreased over the study period for the group as a whole. There is still uncertainty about the most effective interventions for carers. Meeting 'needs' may not improve caregiver distress.


The effect of amphotericin B-deoxycholate on proliferation and protein synthesis in human skin fibroblast cultures.
Cultures of adult human skin fibroblasts were grown in the presence of the recommended antifungal dose (3 microgram per ml) of amphotericin B-deoxycholate. A reduction in cell culture growth, measured as DNA content and protein content per culture, was observed. However, radioisotope incorporation into noncollagen protein and, to a lesser extent, collagen protein was enhanced. These effects were due to amphotericin B, not to deoxycholate. These observations were made under several growth conditions and indicate that cell proliferation or isotope-labeling studies in fibroblasts in the presence of amphotericin B-deoxycholate are susceptible to errors in interpretation.


Oncogenic Targets Regulated by Tumor-Suppressive miR-30c-1-3p and miR-30c-2-3p: TRIP13 Facilitates Cancer Cell Aggressiveness in Breast Cancer.
Accumulating evidence suggests that the miR-30 family act as critical players (tumor-suppressor or oncogenic) in a wide range of human cancers. Analysis of microRNA (miRNA) expression signatures and The Cancer Genome Atlas (TCGA) database revealed that that two passenger strand miRNAs, miR-30c-1-3p and miR-30c-2-3p, were downregulated in cancer tissues, and their low expression was closely associated with worse prognosis in patients with BrCa. Functional assays showed that miR-30c-1-3p and miR-30c-2-3p overexpression significantly inhibited cancer cell aggressiveness, suggesting these two miRNAs acted as tumor-suppressors in BrCa cells. Notably, involvement of passenger strands of miRNAs is a new concept of cancer research. Further analyses showed that seven genes (TRIP13, CCNB1, RAD51, PSPH, CENPN, KPNA2, and MXRA5) were putative targets of miR-30c-1-3p and miR-30c-2-3p in BrCa cells. Expression of seven genes were upregulated in BrCa tissues and predicted a worse prognosis of the patients. Among these genes, we focused on TRIP13 and investigated the functional significance of this gene in BrCa cells. Luciferase reporter assays showed that TRIP13 was directly regulated by these two miRNAs. TRIP13 knockdown using siRNA attenuated BrCa cell aggressiveness. Inactivation of TRIP13 using a specific inhibitor prevented the malignant transformation of BrCa cells. Exploring the molecular networks controlled by miRNAs, including passenger strands, will facilitate the identification of diagnostic markers and therapeutic target molecules in BrCa.