Merging pathways: music therapy in neurosurgical rehabilitation.
Relatively few departments of Music Therapy are found within neurosurgical rehabilitation clinics. In institutions where these departments exist, music therapy has become an integral part of multi-professional treatment and research activities (Gilbertson 1999). The diverse intervention strategies in Music Therapy focus upon auditory, motor, visual, cognitive and affective processing which are all involved in receptive and expressive musical behaviour and which affect related non-musical behaviour. A clear differentiation is made between primary and adjunct therapy roles. The related fields of neuromusicology, neuroanatomy, neuropsychology, music psychology and humanistic psychology are primary sources in the development of models of clinical application (Hodges 1996). Our main interests are focussed on the following issues and areas of clinical application: The initialisation of contact with patients in vegetative status Communicative interaction with patients who can not (initially) use verbal communication (aphasic disorders) Temporal motor organisation with patients with sensomotor disorders Cognitive organisation and mnemonic framework with patients with neuropsychological functional disorders (concentration, memory, perception) Treatment of spatial perception disorders (neglect) Enhancing personal and social integration following individual isolation, social withdrawal. These topics will be discussed and highlighted with clinical examples.


Lower household income is associated with an increased risk of hospital readmission in patients with decompensated cirrhosis.
The impact of household income, a surrogate of socioeconomic status, on hospital readmission rates for patients with decompensated cirrhosis has not been well characterized. The Nationwide Readmission Database from 2012 to 2014 was used to study the association of lower median household income on 30-, 90-, and 180-day hospital readmission rates for patients with decompensated cirrhosis. From the 42 679 001 hospital admissions contained in the sample, there were 82 598 patients with decompensated cirrhosis who survived a hospital admission in the first 6 months of the year. During a uniform 6-month follow-up period, 25 914 (31.4%), 39 928 (48.3%), and 47 496 (57.5%) patients were readmitted at 30, 90, and 180 days, respectively. After controlling for demographic and clinical confounders, patients residing in the three lowest income quartiles were significantly more likely to be readmitted at 30 days than those in the fourth quartile (first quartile, odds ratio [OR] 1.32 [95% confidence interval, CI, 1.17-1.47, P < 0.01]; second quartile, OR 1.25 [95% CI 1.13-1.38, P < 0.01]; and third quartile, OR 1.08 [95% CI 0.97-1.20, P = 0.07]). The association between lower socioeconomic status and the higher risk of readmissions persisted at 90 days (first quartile, OR 1.21 [95% CI 1.14-1.30, P < 0.01]) and 180 days (first quartile, OR 1.32 [95% CI 1.20-1.44, P < 0.01]). Patients with decompensated cirrhosis residing in the lowest income quartile had a 32% higher odds of hospital readmissions at 30, 90, and 180 days compared with those in the highest income quartile.


Hydrazine-mediated cyclization of Ugi products to synthesize novel 3-hydroxypyrazoles.
This report discloses a novel concise synthesis of a series of 3-hydroxypyrazoles 5 via a tandem Ugi/debenzylation /hydrazine-mediated cyclization sequence. Herein, n-butyl isocyanide 4b was utilized as an alternative to classical convertible isocyanides enabling high yielding hydrazine-mediated cyclization. Taken together, a novel class of 3-hydroxypyrazoles 5a-5i was synthesized with potential to be of interest in future library enrichment strategies.


The incidence of candidiasis amongst the asymptomatic female students of the University of Jos, Nigeria.
A survey was carried out on the incidence of candidiasis amongst the asymptomatic female students of University of Jos. One hundred and three students were selected at guided random. Their first stream urine samples were collected with the aid of sterile McCarthney bottles. The deposits of the centrifuged urine samples were plated out on sabouraud's dextrose agar (SDA) fortified with antibiotics (penicillin G and streptomycin). A total number of 42 positive Candida cases were obtained. This represented 40.78% of the total samples (103) examined. The Candida species isolated included C. albicans, C. glabrata, C. guilliermondi, C. parapsilosis, C. pseudotropicalis, C. stellatoidea, C. tropicalis and C. viswanathii. C. albicans and C. tropicalis were more predominant than the other species. C. albicans had 38.10% frequency of occurrence while C. tropicalis had 21.43% occurrence. The least percentage occurrence was recorded for C. viswanathii which had 2.38%. There were significant relationships between the incidence of candidiasis and the predisposing factors like drug administration (antibiotics and contraceptive pills), cases of pregnancy and previous cases of urinogenital tract infection. Neither the marital status nor the age groups of the test female students had significant effects on the incidence of this disease. The pH values of the infected urine samples had a significant effect on the incidence of the disease.


Determination of histamine in biological fluids by capillary isotachophoresis and fluorescence.
Analytical isotachophoresis was used for the determination of histamine in biological fluids. For biological fluids with a very low content of histamine a method was developed that combines the fluorescing condensation product of histamine and o-phthaldialdehyde with the high concentration effect of isotachophoresis. This method permits the determination of histamine in serum and other biological fluids down to less than 3 ng/ml.


Abnormalities of glucose and lipid metabolism in myocardial ischemia-reperfusion injury.
Myocardial ischemia-reperfusion injury is a common condition in cardiovascular diseases, and the mechanism of its occurrence involves multiple complex metabolic pathways and signaling pathways. Among these pathways, glucose metabolism and lipid metabolism play important roles in regulating myocardial energy metabolism. Therefore, this article focuses on the roles of glucose metabolism and lipid metabolism in myocardial ischemia-reperfusion injury, including glycolysis, glucose uptake and transport, glycogen metabolism and the pentose phosphate pathway; and triglyceride metabolism, fatty acid uptake and transport, phospholipid metabolism, lipoprotein metabolism, and cholesterol metabolism. Finally, due to the different alterations and development of glucose metabolism and lipid metabolism in myocardial ischemia-reperfusion, there are also complex interregulatory relationships between them. In the future, modulating the equilibrium between glucose metabolism and lipid metabolism in cardiomyocytes and ameliorating aberrations in myocardial energy metabolism represent highly promising novel strategies for addressing myocardial ischemia-reperfusion injury. Therefore, a comprehensive exploration of glycolipid metabolism can offer novel theoretical and clinical insights into the prevention and treatment of myocardial ischemia-reperfusion injury.


Prenatal diagnosis of a fetus with a de novo trisomy 12p by array-comparative genomic hybridization (array-CGH).
Trisomy 12p syndrome is a rare chromosomal abnormality, which presents with facial dysmorphism, moderate to severe psychomotor retardation and generalized hypotonia. Here we present the prenatal sonographic findings investigated of a fetus in prenatal diagnosis with a de novo trisomy of 12p identified by array-comparative genomic hybridization (aCGH).


Bi-allelic variants in human TCTE1/DRC5 cause asthenospermia and male infertility.
Asthenozoospermia (AZS) is a common male infertility phenotype, accounting for 18% of infertile patients. The N-DRC (Nexin-dynein Regulatory Complex) complex is the motor regulating device in the flagellum, which is found in most eukaryotic organisms with flagellum. The deletion of TCTE1 (T-Complex-Associated Testis-Expressed 1), a component of the N-DRC complex also known as DRC5 (Dynein regulatory complex subunit 5), has been shown to cause asthenospermia in mice. This study mainly introduces a clinical case of male infertility with normal sperm count, normal morphological structure, but low motility and weak forward movement. By whole-exome sequencing, we found that TCTE1 became a frameshift mutant, ENST00000371505.5: c.396_397insTC (p.Arg133Serfs*33), resulting in the rapid degradation of TCTE1 protein and male infertility. This phenotype is similar to the Tcte1-/- (Tcte1 knockout) mice, which showed structural integrity but reduced motility. Further, different from mice, in vitro Fertilization (IVF) could successfully solve the patient's problem of infertility. Our data provides a better understanding of the biological functions of TCTE1 in human flagellum assembly and male fertility.


Effects of media portrayal on perceived cruise risk, image, and intentions.
This research examines how news media portrayal of Covid-19 cases on cruise ships can produce decision biases. Two experiments were conducted in which news stories were varied according to format, base rate, framing and number size. The results demonstrate that prior cruise experience increases travel intentions and cruise image and lowers perceptions of cruise risk. Perceived risk is higher when the number of cases is presented in concrete numbers versus abstract percentages. Negative framing increases perceptions of cruise risk versus positive framing, especially when expressed in small numbers. The results extend beyond Covid-19 by demonstrating that sensationalism in the news media can result in decision biases that over- emphasize negative outcomes and increases risk perceptions in the minds of consumers. The findings suggest travel companies should work together with news media outlets when crisis situations arise to shift away from sensationalism and provide concrete information that is useful for consumers.


CircTCF25 serves as a sponge for miR-206 to support proliferation, migration, and invasion of glioma via the Jak2/p-Stat3/CypB axis.
Glioma is the most common primary malignant intracranial tumor in humans, and glioblastoma (GBM) has been associated with a more aggressive histology and poorer prognosis. There is growing evidence that circular RNAs (circRNAs) are involved in the progression of various malignancies; however, the role and molecular mechanism of circRNAs in glioma remain elusive. In the present study, we screened for differentially expressed circRNAs in gliomas by using a bioinformatics method. Significant upregulation in glioma tissues was verified by quantitative real-time polymerase chain reaction (qRT-PCR), and the prognostic value was evaluated. The potential oncogenic role of circular RNA TCF25 (circTCF25) in glioma was assessed both in vivo and in vitro. Bioinformatics analysis and luciferase reporter assays confirmed the interaction among circTCF25, microRNA-206 (miR-206), and its target gene Cyclophilin B (CypB). circTCF25 was predominantly located in the cytoplasm; the combination of mir-206 and circTCF25 reverses the effects of knockdown of circTCF25 on the proliferation, migration, invasion, and tumorigenesis of glioma cells. Competitive binding between circTCF25 and miR-206 mainly upregulates target gene CypB expression by preventing its inhibition of the Jak2/p-stat3 pathway. In addition, knockdown of circTCF25 reduced CypB expression by inhibiting JAK2/p-stat3, which was rescued by treatment with a miR-206 inhibitor. In summary, our findings demonstrate that the circTCF25/miR-206/CypB axis plays a vital role in glioma progression, migration, invasion, and tumorigenesis.


Seroprevalence of bovine vaccinia in cows and its correlation with the productive profile of affected farms in Distrito Federal, Brazil.
Bovine vaccinia (BV) is an infectious disease caused by Vaccinia virus (VACV) characterized by vesicular and exanthematic lesions, mainly in cattle. Although BV has been described in some Brazilian regions in the last decades, official information regarding the current prevalence in bovine herds of Midwestern Brazil is lacking. Thus, the current study aimed to estimate the seroprevalence and risk factors associated with BV in cattle in the Distrito Federal (DF), Brazil. Sera of 312 cows of 64 herds were tested by virus-neutralizing test for VACV antibodies. Herd and animal seroprevalence were estimated to be 33.3% (CI 95%: 18.2-48.3%) and 10.6% (CI 95%: 1.0-20.2%), respectively. Seropositive cows were detected in dairy, beef, and mixed-purpose farms. The results of an epidemiological questionnaire showed that no risk factor analyzed was positively associated with seropositivity to VACV. There was no significant association between type of milking (manual/mechanic) and seropositivity to VACV; however, most seropositive cows were present in farms with high daily milk production and high number of lactating and adult cows. Our results indicate that VACV circulates in many regions of DF with considerable prevalence in dairy cows. Control measures to restrict VACV circulation and consequences of the infection may be advisable.


Inhibition of dendritic cell migration by transforming growth factor-β1 increases tumor-draining lymph node metastasis.
Transforming growth factor (TGF)-β is known to be produced by progressor tumors and to immobilize dendritic cells (DCs) within those tumors. Moreover, although TGF-β1 has been shown to promote tumor progression, there is still no direct, in vivo evidence as to whether TGF-β1 is able to directly induce distant metastasis. To address that issue and investigate the mechanism by which TGF-β1 suppresses DC activity, we subdermally inoculated mouse ears with squamous cell carcinoma cells stably expressing TGF-β1 or empty vector (mock). The numbers of DCs within lymph nodes draining the resultant TGF-β1-expressing tumors was significantly lower than within nodes draining tumors not expressing TGF-β1. We then injected fluorescently labeled bone marrow-derived dendritic cells into the tumors, and subsequent analysis confirmed that the tumors were the source of the DCs within the tumor-draining lymph nodes, and that there were significantly fewer immature DCs within the nodes draining TGF-β1-expressing tumors than within nodes draining tumors not expressing TGF-β1. In addition, 14 days after tumor cell inoculation, lymph node metastasis occurred more frequently in mice inoculated with TGF-β1 transfectants than in those inoculated with the mock transfectants. These findings provide new evidence that tumor-derived TGF-β1 inhibits migration of DCs from tumors to their draining lymph nodes, and this immunosuppressive effect of TGF-β1 increases the likelihood of metastasis in the affected nodes.


Distinct roles of the preparatory and payoff phases of glycolysis in hematopoietic stem cells.
In physiological conditions, most adult hematopoietic stem cells (HSCs) maintain a quiescent state. Glycolysis is a metabolic process that can be divided into preparatory and payoff phases. Although the payoff phase maintains HSC function and properties, the role of the preparatory phase remains unknown. In this study, we aimed to investigate whether the preparatory or payoff phases of glycolysis were required for maintenance of quiescent and proliferative HSCs. We used glucose-6-phosphate isomerase (Gpi1) as a representative gene for the preparatory phase and glyceraldehyde-3-phosphate dehydrogenase (Gapdh) as a representative gene for the payoff phase of glycolysis. First, we identified that stem cell function and survival were impaired in Gapdh-edited proliferative HSCs. Contrastingly, cell survival was maintained in quiescent Gapdh- and Gpi1-edited HSCs. Gapdh- and Gpi1-defective quiescent HSCs maintained adenosine-triphosphate (ATP) levels by increasing mitochondrial oxidative phosphorylation (OXPHOS), whereas ATP levels were decreased in Gapdh-edited proliferative HSCs. Interestingly, Gpi1-edited proliferative HSCs maintained ATP levels independent of increased OXPHOS. Oxythiamine, a transketolase inhibitor, impaired proliferation of Gpi1-edited HSCs, suggesting that the nonoxidative pentose phosphate pathway (PPP) is an alternative means to maintain glycolytic flux in Gpi1-defective HSCs. Our findings suggest that OXPHOS compensated for glycolytic deficiencies in quiescent HSCs, and that in proliferative HSCs, nonoxidative PPP compensated for defects in the preparatory phase of glycolysis but not for defects in the payoff phase. These findings provide new insights into regulation of HSC metabolism, which could have implications for development of novel therapies for hematologic disorders.


The effects of cystine and theanine mixture on the chronic survival rate and tumor incidence of rats after total body X-ray irradiation†.
Cystine and theanine (CT), an amino acid mixture, provides the substrates cysteine and glutamic acid that promote glutathione synthesis. We previously reported that CT pre-treatment significantly improved the acute survival rate and reduced acute radiation injury of the small intestine and bone marrow of rats after 5 Gy of total body X-ray irradiation. To examine the long-term effects of CT administration after irradiation, we investigated the effects of CT pre-treatment and pre- and post-treatment on the chronic survival rate and solid tumor (spleen, skin and subcutis, and thyroid) incidence after irradiation using 7-week-old male Wistar rats. CT pre-treatment of 280 mg/kg was administered orally for 5 days before 5 Gy irradiation, and CT pre- and post-treatment was administered 5 days before and 5 days after irradiation. A 0.5% carboxymethyl cellulose solution was administered as a control. The chronic survival rate of the pre-treated rats was higher than that of the control rats at 441 days after irradiation (40 vs 8.1%, P = 0.011). However, the survival rate did not significantly differ between the pre- and post-treatment and control rats at 467 days after irradiation (33.8 vs 30.2%, P = 0.792). In addition, more solid tumors, especially subcutis sarcomas, were observed in the pre-treatment rats (26.1%, 6/23) than in the control rats (4.5%, 1/22) after irradiation. Therefore, pre-administration of CT improves the chronic survival rate after irradiation; however, the occurrence of solid tumors was not suppressed.


Efficacy and safety of endoscopic submucosal dissection for submucosal tumors of the colon and rectum.
Endoscopic submucosal dissection (ESD) of colorectal submucosal tumors (SMTs) is becoming increasingly common; however, there have been few large consecutive studies analyzing its therapeutic efficacy and safety. The aim of this study was to evaluate the efficacy, safety, and long-term outcomes of ESD for colorectal SMTs. This retrospective study included 412 consecutive patients with colorectal SMTs who underwent ESD at the Zhongshan Hospital of Fudan University from January 2008 to July 2014. Tumor histopathology, completeness of resection, adverse events, tumor recurrence, and distant metastasis were analyzed. Complete resection was achieved for 358 lesions (86.9%). Thirteen patients had serious adverse events (3.2%) including bleeding and perforation, and 28 patients (6.8%) had post-ESD electrocoagulation syndrome (PEECS). Because more ESDs for colorectal SMTs were performed by endoscopists, the rate of complete resection increased (78.5% vs 88.5%), and the rate of serious adverse events decreased (9.2% vs 2.0%). SMTs in the colon increased the risk of incomplete resection (19.6% vs 11.3%), serious adverse events (8.7% vs 1.6%), and PEECS (16.3% vs 4.1%). SMTs originating from the muscularis propria and sized ≥20 mm increased the rate of PEECS (22.7% vs 5.9% and 31.3% vs 5.8%, respectively). ESD is effective for resection of colorectal SMTs and rarely causes serious adverse events. Tumor location and the experience of endoscopists influence the complete resection rate and the development of serious adverse events. ESD is feasible for large tumors and tumors in the muscularis propria, but this is associated with relatively high risks of adverse events.


Implant retained prosthesis on a free fibula flap: A challenging procedure for prosthetic and soft tissue management.
A 39-year-old woman who had undergone fibular flap reconstruction and simultaneous implant placement after the surgical removal of a cemento-ossifying fibroma was experiencing mild discomfort 3 years later and requested an implant-supported prosthesis to restore her edentulous left maxillary quadrant. Initially, an interim removable partial denture was provided and later duplicated with clear resin. The interim prosthesis identified the excessive thickness of the grafted cutaneous soft tissue and the inadequate emergence angle of the nonfunctioning implants. By using the interim prosthesis as a surgical guide, vestibuloplasty was performed to thin the peri-implant soft tissue and the excessive skin graft from the initial maxillofacial surgery. Concurrently, the emergence angle of the implant was corrected with angled multi-unit abutments. A tissue compression stent was then made and attached to the abutments to guide the soft tissue healing process. When the peri-implant soft tissue had stabilized, a definitive implant-supported prosthesis was provided.


Relationship Between Poverty and Mortality in Systemic Lupus Erythematosus.
A prior study established that concurrent poverty, persistent poverty, and exiting poverty were associated with the subsequent extent of damage accumulation in systemic lupus erythematosus (SLE). In this study, we examined whether concurrent poverty affects mortality after taking extent of damage accumulation into account. Analyses were conducted on 807 persons with SLE participating in the University of California-San Francisco Lupus Outcomes Study in 2009, stratified by whether they lived in households with incomes ≤125% of the federal poverty level in that year. We used Cox proportional hazards regression to estimate the risk of mortality as a function of poverty status, with and without adjustment for demographics; lupus status, including extent of disease damage; overall health status; health behaviors; and health care characteristics. Among 807 individuals interviewed in 2009, 71 (8.8%) had died by 2015, 57 (8.3%) among the nonpoor and 14 (12.1%) among the poor (P = 0.18). With adjustment only for age, poverty in 2009 was associated with an increased risk of mortality (hazard ratio [HR] 2.14 [95% confidence interval (95% CI) 1.18-3.88]) through 2015. However, after adjustment for extent of damage and age, poverty was no longer associated with an increased risk of mortality (HR 1.68 [95% CI 0.91-3.10]). Among those who died, those who were poor lived 13.9 fewer years (95% CI 6.9-20.8; P < 0.0001). The principal way that poverty results in higher mortality in SLE is by increasing the extent of damage accumulation.


Oxysterols in stored powders as potential health hazards.
Cholesterol oxidation products (COPs) have greater biological activity than cholesterol itself. Oxysterols reduce the nutritional value of foods and exhibit a wide range of biological activity, including pro-oxidant, carcinogenic, and cytotoxic properties. The most commonly detected oxysterols in foods are 7α-HC, 7β-HC, a product of their dehydrogenation 7-KC and α-CE, β-CE. The main dietary sources of oxysterols are eggs and egg-derived products, thermally processed milk and milk-based products, fried meat. This study aimed to measure the amount of cholesterol oxidation products in milk powder, egg powder and milk-egg powder during 24 months of storage. The changes in the selected oxysterols (determined by gas chromatography) were recorded. In milk powder, after the production process, the amount of cholesterol was 0.2 g 100 g-1 fat and in egg powder it was 3.4 g 100 g-1. After 6 months of storage, the dominant oxysterol in milk and egg powder was 7α-HC and in milk-egg powder it was 7-KC. After the storage period, oxysterols in powdered milk reached 1.81% of total cholesterol. The most stable cholesterol was in the milk-egg mixture and its oxidation was the slowest. This study showed the presence of COPs in milk powder, egg powder and milk-egg powder and the effect of storage on cholesterol oxidation.


Mortality and severe neurological morbidity in extremely preterm growth-restricted fetuses.
To develop a model for the prediction of adverse perinatal outcome in growth-restricted fetuses requiring delivery before 28 weeks in order to provide individualized patient counseling. This was a retrospective multicenter cohort study of singleton pregnancies with antenatal suspicion of fetal growth restriction requiring delivery before 28 weeks' gestation between January 2010 and January 2020 in six tertiary public hospitals in the Barcelona area, Spain. Separate predictive models for mortality only and mortality or severe neurological morbidity were created using logistic regression from variables available antenatally. For each model, predictive performance was evaluated using receiver-operating-characteristics (ROC)-curve analysis. Predictive models were validated externally in an additional cohort of growth-restricted fetuses from another public tertiary hospital with the same inclusion and exclusion criteria. A total of 110 cases were included. The neonatal mortality rate was 37.3% and, among the survivors, the rate of severe neurological morbidity was 21.7%. The following factors were retained in the multivariate analysis as significant predictors of mortality: magnesium sulfate neuroprotection, gestational age at birth, estimated fetal weight, male sex and Doppler stage. This model had a significantly higher area under the ROC curve (AUC) compared with a model including only gestational age at birth (0.810 (95% CI, 0.730-0.889) vs 0.695 (95% CI, 0.594-0.795); P = 0.016). At a 20% false-positive rate, the model showed a sensitivity, negative predictive value and positive predictive value of 66%, 80% and 66%, respectively. For the prediction of the composite adverse outcome (mortality or severe neurological morbidity), the model included: gestational age at birth, male sex and Doppler stage. This model had a significantly higher AUC compared with a model including only gestational age at birth (0.810 (95% CI, 0.731-0.892) vs 0.689 (95% CI, 0.588-0.799); P = 0.017). At a 20% false-positive rate, the model showed a sensitivity, negative predictive value and positive predictive value of 55%, 63% and 74%, respectively. External validation of both models yielded similar AUCs that did not differ significantly from those obtained in the original sample. Estimated fetal weight, fetal sex and Doppler stage can be combined with gestational age to improve the prediction of death or severe neurological sequelae in growth-restricted fetuses requiring delivery before 28 weeks. This approach may be useful for parental counseling and decision-making. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.


Phylogenetic position of Dictyostelium inferred from multiple protein data sets.
The phylogenetic position of Dictyostelium inferred from 18S rRNA data contradicts that from protein data. Protein trees always show the close affinity of Dictyostelium with animals, fungi, and plants, whereas in 18S rRNA trees the branching of Dictyostelium is placed at a position before the massive radiation of protist groups including the divergence of the three kingdoms. To settle this controversial issue and to determine the correct position of Dictyostelium, we inferred the phylogenetic relationship among Dictyostelium and the three kingdoms Animalia, Fungi, and Plantae by a maximum-likelihood method using 19 different protein data sets. It was shown at the significance level of 1 SE that the branching of Dictyostelium antedates the divergence of Animalia and Fungi, and Plantae is an outgroup of the Animalia-Fungi-Dictyostelium clade.


Acute renal failure due to focal necrotizing glomerulonephritis in a patient with non-Hodgkin's lymphoma. Resolution with treatment of lymphoma.
Renal disease in association with lymphoma is more prevalent than generally recognized. Glomerulonephritis may occur as a paraneoplastic phenomenon. We report a patient who presented with acute renal failure due to focal necrotizing glomerulonephritis in association with non-Hodgkin's lymphoma in whom the acute renal failure and glomerulonephritis resolved on clinical, biochemical and histological grounds with treatment of the lymphoma. Focal necrotizing glomerulonephritis is extremely uncommon in association with lymphoma and, to our knowledge, this association with follow-up and histological resolution of glomerulonephritis has not previously been reported.


A bimetallic nanoplatform for STING activation and CRISPR/Cas mediated depletion of the methionine transporter in cancer cells restores anti-tumor immune responses.
Lack of sufficient cytotoxic T lymphocytes (CD8+ T cells) infiltration and dysfunctional state of CD8+ T cells are considered enormous obstacles to antitumor immunity. Herein, we construct a synergistic nanoplatform to promote CD8+ T cell infiltration in tumors while restoring T cell function by regulating methionine metabolism and activating the STING innate immune pathway. The CRISPR/Cas9 system down-regulates the methionine transporter SLC43A2 and restricts the methionine uptake by tumor cells, thereby relieving the methionine competition pressure of T cells; simultaneously, the released nutrition metal ions activate the cGAS/STING pathway. In this work, the described nanoplatform can enhance the effect of immunotherapy in preclinical cancer models in female mice, enhancing STING pathway mediated immunity and facilitating the development of amino acid metabolic intervention-based cancer therapy.


A rule-based automatic sleep staging method.
In this paper, a rule-based automatic sleep staging method was proposed. Twelve features including temporal and spectrum analyses of the EEG, EOG, and EMG signals were utilized. Normalization was applied to each feature to eliminating individual differences. A hierarchical decision tree with fourteen rules was constructed for sleep stage classification. Finally, a smoothing process considering the temporal contextual information was applied for the continuity. The overall agreement and kappa coefficient of the proposed method applied to the all night polysomnography (PSG) of seventeen healthy subjects compared with the manual scorings by R&K rules can reach 86.68% and 0.79, respectively. This method can integrate with portable PSG system for sleep evaluation at-home in the near future.


High-sensitive cardiac troponin T as a marker of hemorrhagic complications in elderly patients anticoagulated for non-massive pulmonary embolism.
Recent data have raised concerns about the risk/benefit ratio of thrombolysis in non-high risk pulmonary embolism patients due to increased serious bleeding events. Whether cardiac biomarkers could be of help for bleeding risk stratification in this setting remains elusive. To determine the prognostic accuracy of hs-cTnT, NT-proBNP, RIETE and PESI score for the occurrence of clinically relevant bleeding (CRB) in elderly patients under conventional anticoagulation therapy for non-massive pulmonary embolism (NMPE). We evaluated 230 elderly patients with available blood sample taken within one day from diagnosis. The primary study endpoint was CRB at 1, 3 and 24 months. Prognostic accuracies and associations were determined using C-statistics and subhazard ratios (SHR), respectively. hs-cTnT displayed the highest discriminatory power at 1 month (C-statistics: 0.77, 95% CI: 0.68-0.88) which remained stable over time. Although C-statistics comparison indicated that hs-cTnT was not statistically superior to RIETE score (0.77 vs 0.67, p = 0.11), adding hs-cTnT to RIETE score significantly improved the C-statistics from 0.67 to 0.78 (p = 0.02). SHRs indicated that for each hs-cTnT log-unit increase, there was a 58% increase in the risk of CRB independently of the RIETE score (adjusted SHR: 1.58, 95% CI: 1.31-1.92). At the pre-specified cut-off of 14 ng/l, the negative predictive value of hs-cTnT was 96.9% (95% CI: 91.4-99.0) and 94.9 (95%CI: 88.6-97.8) at 1 and 3 months, respectively. In elderly, hs-cTnT provides incremental prognostic information over the RIETE score and could represent a valuable tool to identify NMPE patients at low risk of bleeding.


Hand hygiene beliefs and behaviours about alcohol-based hand rub use: Questionnaire development, piloting and validation.
Behavioural theories are crucial to the development and success of effective hand hygiene interventions. Research demonstrates that hand hygiene behaviours can also be influenced by religious and cultural beliefs. In this paper we detail the processes undertaken to develop a valid and reliable questionnaire to examine healthcare workers' beliefs and behaviours related to the use of alcoholbased hand rub (ABHR), with particular emphasis on associated religious and cultural factors. Using the Theory of Planned Behaviour, an existing questionnaire was modified and pilot-tested on 35 staff in the Quality Department. Cronbach's alpha values and mean inter-item correlations of the scale items were the main outcome measures. A Pearson correlation was conducted to assess for social desirability response bias. The questionnaire demonstrated high content and face validity and satisfactory internal consistency in most scales, except for the religious beliefs, cultural beliefs and perceived behavioural control scales, where the inter-item correlations were 0.10, 0.13, and 0.14, respectively. There was a significant correlation between scores on the social desirability scale and the attitude scale. Partial correlation should be used to control the effect of social desirability responding when analysing data from the attitudes scale. A validation process allowed the introduction and subsequent modification of religious and cultural belief scales to an existing questionnaire examining behavioural and attitudinal influences on hand hygiene using ABHR. Such processes should be considered for questionnaire development and modification when considering religious and cultural factors as drivers of behaviour.


The effect of preoperative ureteral stenting in retrograde Intrarenal surgery: a multicenter, propensity score-matched study.
Stent placement before retrograde intrarenal surgery (RIRS) can theoretically expand the ureter to improve access and remove stones. The purpose of this study was to investigate the effect of preoperative ureteral stenting on access and surgery. We retrospectively analyzed patients who underwent RIRS between January 2010 and December 2016 at multiple centers. The patients were divided into two groups based on whether or not a ureteral stent was inserted preoperatively. The characteristics of the stone (size, number, density, and location), the success rate of the access sheath placement, perioperative complications, operative times, hospitalization periods, the period for which the stents remained, postoperative urinary tract infection rates, stone-free rates, and additional treatment rates were analyzed. Overall, 727 patients were included in the study (113 were pre-stented and 614 were non-stented). The median stone size was 12.2 mm. The overall stone-free rate (SFR) was 85.8% for the pre-stented group and 83.2% for the non-stented group, showing no significant (p = 0.498) difference between the two groups. Preoperative ureteral stenting improved the success rate of sheath placement (93.8% vs. 85.3%, p = 0.023) during surgery. The access sheath size in participants in the pre-stented group showed a tendency to be larger than that in participants in the non-stented group. However, there were no differences in perioperative complications, operative times, additional treatment rates, and stone-free rates. Although preoperative ureteral stenting did not affect operative outcomes, it increased the success rate of access sheath placement. Depending on the patient's characteristics, preoperative ureteral stenting can be considered as an adjunctive option when access sheath insertion is considered during RIRS.


Gene expression profiling of reactive oxygen species (ROS) and antioxidant defense system following Sugarcane mosaic virus (SCMV) infection.
Viruses are infectious pathogens, and plant virus epidemics can have devastating consequences to crop yield and quality. Sugarcane mosaic virus (SCMV, belonging to family Potyviridae) is one of the leading pathogens that affect the sugarcane crop every year. To combat the pathogens' attack, plants generate reactive oxygen species (ROS) as the first line of defense whose sophisticated balance is achieved through well-organized antioxidant scavenging pathways. In this study, we investigated the changes occurring at the transcriptomic level of ROS associated and ROS detoxification pathways of SCMV resistant (B-48) and susceptible (Badila) sugarcane genotypes, using Saccharum spontaneum L. genome assembly as a reference genome. Transcriptomic data highlighted the significant upregulation of ROS producing genes such as NADH oxidase, malate dehydrogenase and flavin-binding monooxygenase, in Badila genotype after SCMV pathogenicity. To scavenge the ROS, the Badila genotype illustrated a substantial enhancement of antioxidants i.e. glutathione s-transferase (GST), as compared to its resistant counterpart. GST is supposed to be a key indicator of pathogen attacks on the plant. A remarkably lower GST expression in B-48, as compared to Badila, indicated the development of resistance in this genotype. Additionally, we characterized the critical transcription factors (TFs) involved in endowing resistance to B-48. Among these, WRKY, AP2, NAC, bZIP, and bHLH showed enhanced expression in the B-48 genotype. Our results also confirmed the linkage of transcriptomic data with the enzymatic and qPCR data. The estimation of enzymatic activities for superoxide dismutase, catalase, ascorbate peroxidase, and phenylalanine ammonia-lyase supported the transcriptomic data and evinced higher resistance in B-48 genotype. The current study supported the efficiency of the B-48 genotype under SCMV infection. Moreover, comparative transcriptomic data has been presented to highlight the role of significant transcription factors conferring resistance to this genotype. This study provides an in-depth knowledge of the expression profiling of defense mechanisms in sugarcane.


When is somebody just some body? Ethics as first philosophy and the brain death debate.
I, along with others, have been critical of the social construction of brain death and the various social factors that led to redefining death from cardiopulmonary failure to irreversible loss of brain functioning, or brain death. Yet this does not mean that brain death is not the best threshold to permit organ harvesting-or, as people today prefer to call it, organ procurement. Here I defend whole-brain death as a morally legitimate line that, once crossed, is grounds for families to give permission for organ donation. I do so in five moves. First, I make the case that whole-brain death is a social construction that transformed one thing, coma dépassé, into another thing, brain death, as a result of social pressures. Second, I explore the way that the 1981 President's Commission tried to establish the epistemological certainty of brain death, hoping to avoid making arcane metaphysical claims and yet still utilizing metaphysical claims about human beings. Third, I explore the moral meaning of the social construction of a definition that cannot offer metaphysical certainty about the point at which somebody becomes just some body. Fourth, I describe how two moral communities-Jewish and Catholic-actually ground their metaphysical positions with regard to brain death in the normativity of prior social relations. Finally, I conclude with a reflection on the aesthetic-moral enterprise of the metaphysical-epistemological apparatus of brain death, concluding that only such an aesthetic-moral approach is sufficiently strong to stave off the utility-maximizing tendencies of late-modern Western cultures.


Effect of potential HONO sources on peroxyacetyl nitrate (PAN) formation in eastern China in winter.
As an important secondary photochemical pollutant, peroxyacetyl nitrate (PAN) has been studied over decades, yet its simulations usually underestimate the corresponding observations, especially in polluted areas. Recent observations in north China found unusually high concentrations of PAN during wintertime heavy haze events, but the current model still cannot reproduce the observations, and researchers speculated that nitrous acid (HONO) played a key role in PAN formation. For the first time we systematically assessed the impact of potential HONO sources on PAN formation mechanisms in eastern China using the Weather Research and Forecasting/Chemistry (WRF-Chem) model in February of 2017. The results showed that the potential HONO sources significantly improved the PAN simulations, remarkably accelerated the ROx (sum of hydroxyl, hydroperoxyl, and organic peroxy radicals) cycles, and resulted in 80%-150% enhancements of PAN near the ground in the coastal areas of eastern China and 10%-50% enhancements in the areas around 35-40°N within 3 km during a heavy haze period. The direct precursors of PAN were aldehyde and methylglyoxal, and the primary precursors of PAN were alkenes with C > 3, xylenes, propene and toluene. The above results suggest that the potential HONO sources should be considered in regional and global chemical transport models when conducting PAN studies.


Increased urinary beta-thromboglobulin excretion in diabetes assayed with a modified RIA kit-technique.
A modification of the commercial radioimmunoassay (RIA) kit adapting to the assay of beta-thromboglobulin (beta-TG) in the urine, is described. The urine was concentrated by dialysis against dry Sepharose G 200. 131I-albumin was used as marker. Experiments in which 125I-beta-TG and 131I-albumin were added simultaneously showed a parallel recovery of both markers in the final sample. The sensitivity of the RIA was enhanced by incubation overnight of the urine sample with the antiserum. Increased urinary beta TG values were found in 20 patients with diabetes mellitus as compared to 20 young healthy normals. Increased urinary beta-TG values correlated with decreased creatinine clearance, but the difference between diabetics and normals was still observed when patients with a creatinine clearance of less than 100 ml/min were excluded. The urine beta TG level was correlated with the presence of neovascularization within the diabetic group.


Continual naringin treatment benefits the recovery of traumatic brain injury in rats through reducing oxidative and inflammatory alterations.
Naringin is neuroprotective in ischemia and other disease models. However, the effects of naringin are unknown after traumatic brain injury (TBI). The present study explored the role of naringin for neuroprotection in TBI rats. TBI was performed with the weight drop technique, and naringin was given orally at a dose of 100 mg/kg/day. The neurological scores, tissue edema, and oxidative stress/inflammation parameters [malondialdehyde (MDA), superoxide dismutase, nitric oxide, inducible nitric oxide synthase (iNOS), as well as interleukin-1β (IL-1β)] were measured. Compared to sham controls, TBI rats displayed obvious sensorimotor dysfunction, significant brain edema, and elevated oxidative and inflammatory molecules. Although a 7-day pre-treatment of naringin was unable to reverse these pathological changes, a 14-day continual treatment (7 days before and 7 days after the TBI) attenuated the increases in MDA and nitric oxide; enhanced the activation of superoxide dismutase; depressed the over-activation of iNOS; down-regulated the over-expression of IL-1β; and reduced the cortex edema. Additionally, the TBI-induced behavioral dysfunction was reduced. These results suggest that naringin treatment can attenuate cellular and histopathological alterations and improve the sensorimotor dysfunction of TBI rats, which may be partly due to the attenuation of oxidative and inflammatory damages.


Myocardial infarction in young vs old male rats: pathophysiologic changes.
Young (90 days) and old (15 months) male, Sprague-Dawley rats were subjected to an acute and massive myocardial infarct by giving them two injections of a large dose of isoproterenol. The animals were autopsied at sequential time intervals to ascertain the similarities or dissimilarities in the pathophysiologic events which attend acute myocardial infarction and repair in young vs old rats. Although the signs and severity of hypotensive shock appeared to be equal, mortality was higher in the old rats, especially during the acute necrosis phase. The older rats also manifested more severe and persistent congestive heart failure, i.e., hydrothorax. Serum enzymes (CPK, SGOT, SGPT, and LDH), lipids (triglycerides, free fatty acids, and cholesterol), glucose, and BUN levels manifested a dynamic rise and fall concomitant with the induced myocardial necrosis and repair phases with distinct differences in these metabolic changes between young and old rats. Despite initially higher circulating levels of corticosterone in the old vs young rats, the older animals manifested little or no increase in circulating corticosterone levels during the acute stress of myocardial infarction. This apparent lack of adrenocortical responsiveness was accentuated by the concomitant finding of greatly hypertrophied, hemorrhagic, and lipid-depleted adrenal glands in the old rats vs a dynamic increase in circulating corticosterone levels and alterations in the weight of adrenal and thymus glands of the young rats. During the myocardial repair phase, the young rats manifested extensive endocardial fibrosis whereas the old rats displayed little or no endocardial fibrosis but copous and persistent myocardial edema and ground substance in keeping with their higher concentration of cardiac hexosamine. The pathophysiologic course of events which attends myocardial necrosis and repair is quite different in young vs old rats and may be related to the degree of responsiveness of the pituitary-adrenal axis which changes with age.


Hepatic involvement in graft-versus-host disease associated with blood transfusion.
A 73-year-old man developed graft-versus-host disease (GVHD) after blood transfusion; he developed hepatitis, fever, rash, and pancytopenia. Although similar cases have been previously reported, the spectra of their liver injury was not clarified. The clinical and pathological findings of this case and a review of earlier reports suggest a possible predominance of hepatocellular injury in cases of GVHD after blood transfusion, which is in contrast to the prevalence of cholestatic liver disease in GVHD following bone marrow transplantation.


The B6.SW bilineal congenic sucrose octaacetate (SOA)-taster mice.
SWR/J inbred mice (Tasters) reliably avoid, whereas C57BL/6J inbred mice (Nontasters) are indifferent to, sucrose octaacetate (SOA) at certain concentrations. From these strains we have developed a set of bilineal congenic Taster mice. Approximately 4000 mice, from 2 isogenic and 12 segregating generations, were tested in a program designed to evaluate genetic models for SOA tasting during development of congenic strains. The criterion phenotype was avoidance or nonavoidance in preference tests of the bitter tastant SOA at concentrations of 10(-4) and 10(-5) M. Across the 12 segregating generations, the results were consistent with Mendelian expectations for a single autosomal locus with complete dominance of the Taster phenotype. The breeding program produced 12 replicate B6.SW lines containing the taster allele on the B6-Nontaster genomic background. The congenic Taster mice may facilitate a functional analysis of the sense of taste.


Correlation between autotomy-behavior and current theories of neuropathic pain.
The past 10 years have brought several new experimental models with which to study chronic neuropathic pain in animals. Consequently, our knowledge about the mechanisms subserving neuropathic pain in humans has improved. However, the first animal model that was used for studying this type of chronic pain was the autotomy-model which can still be considered as a useful tool for pain studies. The present review assesses some of the similarities and differences between autotomy-model and more recent models of experimental traumatic mononeuropathy. In addition, it considers some of the similarities between the results obtained in clinical studies and in autotomy studies.


A high-throughput fluorescence-based glycosyltransferase screen and its application in directed evolution.
This protocol details the application of a high-throughput fluorescence-based screen, in conjunction with error-prone PCR/saturation mutagenesis, for altering the proficiency and/or promiscuity of a secondary metabolite glycosyltransferase (GT) via directed evolution. Given the structural and mechanistic similarities among secondary metabolite-associated GTs, this approach may provide a template for engineering other members of the GT-B superfamily.


Continuous negative extrathoracic pressure or continuous positive airway pressure for acute hypoxemic respiratory failure in children.
Acute hypoxemic respiratory failure (AHRF) is an important cause of mortality and morbidity in the pediatric age group. Positive pressure ventilation is currently the standard of care, though is known to be associated with complications. Continuous negative extrathoracic pressure ventilation (CNEP) or continuous positive airway pressure ventilation delivered via non-invasive approaches (Ni-CPAP) have shown certain beneficial effects in animal and uncontrolled human studies. The primary objective of this review was to assess the effectiveness of CNEP and Ni-CPAP in pediatric patients with AHRF due to non-cardiogenic causes. We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005); MEDLINE (January 1966 to March 2005); EMBASE (1980 to March 2005); CINAHL (1982 to March 2005); published abstracts from the meetings of the American Thoracic Society and Pediatric Critical Care Meetings (1992 to 2005); and bibliographies of identified articles and asking the experts in the field. Randomized or quasi-randomized clinical trials of either CNEP or Ni-CPAP versus standard therapy (positive pressure ventilation) involving children (at least 1 month old and less than 18 years of age at the time of randomization) who met the criteria for diagnosis of AHRF with at least one of the outcomes reported were included. The methodological quality of included study was assessed using the following criteria: concealment of randomization, blinding of intervention, completeness of follow up and blinding of outcome measurements. Data on relevant outcomes were abstracted and the effect size was estimated by calculating relative risk (RR) with 95% confidence intervals (CI) and risk difference (95% CI). One eligible study was identified which was published in abstract format. Thirty-three infants (18 in the control group and 15 in the CNEP group) with a clinical diagnosis of bronchiolitis and fraction of inspired oxygen (FiO(2))()greater than 40% were studied. There was reduction in the FiO(2) (less than 30% within one hour of initiation of therapy) in four patients in the CNEP group compared to none in the control group (RR 10.7, 95% CI 0.6 to 183.9). One infant required positive pressure ventilation and one infant required nasal CPAP in the control group while all infants in the CNEP group were managed without intubation (RR for both outcomes 0.40, 95% CI 0.02 to 9.06). There is a lack of well designed, controlled experiments of noninvasive modes of respiratory support in children with AHRF. Implication for research: Reduction of in-hospital mortality is an important outcome and even a small reduction could be beneficial. Studies assessing other outcomes such as avoidance of intubation and its associated complications, reduction in hospital stay and improvement in patient comfort are also valuable in gauging the overall impact of these strategies.


Non-Invasive Liver Ablation Using Histotripsy: Preclinical Safety Study in an In Vivo Porcine Model.
This study investigates the safety profile for use of histotripsy, a non-invasive ultrasonic ablation method currently being developed for the treatment of liver cancer, for liver ablation in an in vivo porcine model. Histotripsy treatments were applied to the liver and hepatic veins of 22 porcine subjects, with half of the subjects receiving systemic heparinization. Vital signs (heart rate, blood pressure, temperature, electrocardiogram and SpO2) were monitored throughout the procedure and for 1 h post-treatment. Blood was drawn at six points during the experiment to analyze blood gases, liver function and free hemoglobin levels. All treatments were guided and monitored by real-time ultrasound imaging. After treatment, the tissue was harvested for histological analysis. Results indicated that histotripsy generated well-defined lesions inside the liver and around the treated hepatic veins of all subjects in both treatment groups. Vital signs and blood analysis revealed that animals responded well to histotripsy, with all animals surviving the treatment. One animal in the non-heparinized group had a transient increase in pH and decreases in blood pressure, heart rate and PCO2 during the 15-min vessel treatment, with these changes returning to baseline levels soon after the treatment. Overall, the results indicate that histotripsy can safely be performed on the liver without the need for systemic heparinization, even in regions containing large hepatic vessels, supporting its future use for the treatment of liver cancer.


Machine Learning Assessment of Left Ventricular Diastolic Function Based on Electrocardiographic Features.
Left ventricular (LV) diastolic dysfunction is recognized as playing a major role in the pathophysiology of heart failure; however, clinical tools for identifying diastolic dysfunction before echocardiography remain imprecise. This study sought to develop machine-learning models that quantitatively estimate myocardial relaxation using clinical and electrocardiography (ECG) variables as a first step in the detection of LV diastolic dysfunction. A multicenter prospective study was conducted at 4 institutions in North America enrolling a total of 1,202 subjects. Patients from 3 institutions (n = 814) formed an internal cohort and were randomly divided into training and internal test sets (80:20). Machine-learning models were developed using signal-processed ECG, traditional ECG, and clinical features and were tested using the test set. Data from the fourth institution was reserved as an external test set (n = 388) to evaluate the model generalizability. Despite diversity in subjects, the machine-learning model predicted the quantitative values of the LV relaxation velocities (e') measured by echocardiography in both internal and external test sets (mean absolute error: 1.46 and 1.93 cm/s; adjusted R2 = 0.57 and 0.46, respectively). Analysis of the area under the receiver operating characteristic curve (AUC) revealed that the estimated e' discriminated the guideline-recommended thresholds for abnormal myocardial relaxation and diastolic and systolic dysfunction (LV ejection fraction) the internal (area under the curve [AUC]: 0.83, 0.76, and 0.75) and external test sets (0.84, 0.80, and 0.81), respectively. Moreover, the estimated e' allowed prediction of LV diastolic dysfunction based on multiple age- and sex-adjusted reference limits (AUC: 0.88 and 0.94 in the internal and external sets, respectively). A quantitative prediction of myocardial relaxation can be performed using easily obtained clinical and ECG features. This cost-effective strategy may be a valuable first clinical step for assessing the presence of LV dysfunction and may potentially aid in the early diagnosis and management of heart failure patients.


Alterations of CDKN2 (MTS1/p16INK4A) gene in paraffin-embedded tumor tissues of human stomach, lung, cervix and liver cancers.
The CDKN2 (MTS1/p16INK4A) gene, encoding cyclin dependent kinase inhibitor, was found to be homozygously deleted at a high frequency in cell lines from many different types of cancer and some primary cancers. To determine the frequency of CDKN2 mutations in most common human cancers in Korea, PCR and PCR-SSCP analyses for the exon 2 of CDKN2 were performed on each set of 20 formalin-fixed and paraffin-embedded tumor tissues of stomach adenocarcinomas, lung cancers, cervix cancers and hepatocellular carcinomas. No mutations in exon 2 of CDKN2 were found in 20 stomach adenocarcinomas. In contrast to rare mutations in stomach adenocarcinomas, a high frequency of CDKN2 mutations was identified in other 3 cancers, 11 of 20 (55%) lung cancers (7 of 10 NSCLCs and 4 of 10 SCLCs), 14 of 20 (70%) cervix cancers and 11 of 20 (55%) hepatocellular carcinomas. These results suggest that mutations of the CDKN2 gene might be an important genetic change in NSCLCs, cervix cancers and hepatocellular carcinomas.


Color perception and deafness: college-level comparisons.
The performance of three groups of college-level subjects, deaf students, normal-hearing students, and Art students, were compared on nine tests involving color perception and color-verbal materials including (a) Color-Form Sorting, (b) Color-Form Pointing, (c) Color-Word Meaning, (d) Color-Pair Preferences (N=3), and (e) Color-Word Interference (N=3). Color perception differences between the deaf and the hearing groups were not substantiated: deaf and hearing groups differed only on tests involving verbal materials. The Deaf differed more from the Art students than from the Hearing.


Effects of Ca2+ channel blockers on Ca2+ loading induced by metabolic inhibition and hyperkalemia in cardiomyocytes.
The effects of the L-type (nifedipine and verapamil) and the T-type (mibefradil) Ca2+ channel blockers on the increase in intracellular Ca2+ concentration ([Ca2+]i) induced by NaCN metabolic inhibition and hyperkalemia were examined in chicken cardiomyocytes using fluorescence imaging with Fura-2. NaCN induced a slow and sustained rise in [Ca2+]i, which was not affected by pretreating the cells for 5 min with nifedipine, verapamil, or mibefradil at 100 nM or 10 microM. Pretreatment of the cells with 10 microM nifedipine, verapamil, or mibefradil for 5 min remarkably inhibited the K+-induced increase in [Ca2+]i. These inhibitory effects diminished after 48-h pretreatment with nifedipine or verapamil but not with mibefradil. Ryanodine also induces an increase in [Ca2+]i, and this effect was enhanced by 48-h pretreatment of the cells with 10 microM verapamil but not with 10 microM mibefradil. We conclude that the NaCN-induced increase in [Ca2+]i is independent of the Ca2+ influx though the L-type or T-type Ca2+ channels. Chronic inhibition of the L-type Ca2+ channels but not T-type channels may enhance the ryanodine receptor-mediated Ca2+ release, which may be responsible for the development of tolerance to their inhibitory effects on K+-induced increase in [Ca2+]i.


Synergetic inhibition of thermochemical formation of chlorinated aromatics by sulfur and nitrogen derived from thiourea: Multielement characterizations.
Nitrogen and sulfur (N/S)-containing compounds inhibit the formation of polychlorinated dibenzo-p-dioxins (PCDDs) and furans (PCDFs) in thermal processes. However, few studies have examined the inhibition mechanisms of N/S-containing compounds. In the present study, we focused on thiourea [(NH2)2CS] as such a compound and investigated its inhibition effects and mechanisms. The production of PCDD/Fs, polychlorinated biphenyls (PCBs), and chlorobenzenes (CBzs) were inhibited by >99% in the model fly ash in the presence of 1.0% thiourea after heating at 300 °C. Experimental results using real fly ash series were indicative of the thermal destruction of these chlorinated aromatics by thiourea. Multielement characterization using K-edge X-ray absorption fine structures of copper, chlorine, sulfur, nitrogen, and carbon revealed three possible inhibition paths, namely, (a) sulfidization of the copper catalyst to CuS, Cu2S, and CuSO4; (b) blocking the chlorination of carbon via the reaction of chlorine with N-containing compounds to generate ammonium chloride and other minor compounds; and (c) changing the carbon frame involved in attacking the carbon matrix by sulfur and nitrogen. Thus, thiourea plays a role as a sulfur and nitrogen donor to achieve multiple and synergistic inhibition of chlorinated aromatics. Our results suggest that other N/S-containing inhibitors function based on similar mechanisms.


GB virus C/hepatitis G virus and intravenous immunoglobulins.
Different intravenous immunoglobulins (IVIGs) were found to be GB virus C/hepatitis G virus polymerase chain reaction (GBV-C/HGV-PCR)-positive. The potential transmission of this virus to recipients by a PCR-positive IVIG batch was investigated. Polyclonal IVIGs of different manufacturers and with different virus inactivation procedures were analyzed by GBV-C/HGV-PCR and anti-E2-ELISA. Follow-up sera of 13 participants of a clinical trial performed with a GBV-C/HGV-PCR-positive batch were retrospectively investigated for GBV-C/HGV seroconversion (specific antibodies, viral RNA). Four out of ten IVIGs analysed by GBV-C/HGV-PCR were - at least for some batches - virus genome-positive. Virus inactivation by solvent/detergent treatment resulted in GBV-C/HGV-PCR-negative products. GBV-C/HGV-specific antibodies were detectable in all IVIGs analyzed. There was no transmission of GBV-C/HGV observed when recipients of a large amount of a GBV-C/HGV-PCR-positive batch were analyzed by an antibody test and specific PCR. Despite PCR positivity of an IVIG preparation no transmission of GBV-C/HGV to recipients was observed. Possible explanations are a sufficient virus inactivation procedure and/or presence of specific antibodies in the final products.


Development of luminescence procedures to evaluate permeation of multi-ring polyaromatic compounds through protective materials.
This study describes two practical and simple luminescence techniques developed to evaluate the efficacy of protective clothing materials against permeation of multi-ring polyaromatic compounds contained in heavy oil and petroleum products. The procedures use a rapid and simple technique based on room temperature phosphorimetry and fluorescence detection in which a portable fiberoptics luminoscope was used.


DYNAMIC cohort study evaluating metabolic predictors of influenza vaccine immune response in older adults.
Immunosenescence (age-related immune dysfunction) and inflamm-aging contribute to suboptimal immune responses in older adults to standard-dose influenza vaccines, which may be exacerbated in those with metabolic co-morbidities. We sought to investigate metabolic factors/predictors of influenza vaccine immune response in an older adult (age ≥65 years) cohort in Singapore, where influenza typically circulates year-round. The primary outcome for the DYNAMIC prospective cohort study was haemagglutination-inhibition titer (HAI) response to each of the trivalent inactivated influenza vaccine strains at day 28 (D28) compared to baseline (D0), as assessed by seroconversion and D28/D0 log2 HAI fold rise. Baseline blood samples were tested for total Vitamin D (25-(OH) D) levels. We enrolled 234 participants in June-Dec 2017. Two hundred twenty completed all study visits. The median age was 71 [IQR 68-75] years, 67 (30.5%) had diabetes mellitus (DM), and the median BMI was 24.9 [IQR 22.2-27.8] kg/m2. Median baseline totals 25-(OH) D was 29 [IQR: 21-29] ng/ml. Age, DM, obesity, and baseline 25-(OH) D were not associated with HAI fold rise in multivariable analysis. More recent prior influenza vaccination and higher baseline HAI titers were associated with lower HAI fold rise for influenza A/HK/H3N2. Physical activity was associated with a higher HAI fold rise for influenza A/HK/H3N2 in a dose-response relationship (p-test for trend = 0.015). Older adults with well-controlled metabolic co-morbidities retain HAI response to the influenza vaccine, and physical activity had a beneficial effect on immune response, particularly for influenza A/HK/H3N2.


Sand flies: Basic information on the vectors of leishmaniasis and their interactions with Leishmania parasites.
Blood-sucking arthropods transmit a variety of human pathogens acting as disseminators of the so-called vector-borne diseases. Leishmaniasis is a spectrum of diseases caused by different Leishmania species, transmitted quasi worldwide by sand flies. However, whereas many laboratories focus on the disease(s) and etiological agents, considerably less study the respective vectors. In fact, information on sand flies is neither abundant nor easy to find; aspects including basic biology, ecology, and sand-fly-Leishmania interactions are usually reported separately. Here, we compile elemental information on sand flies, in the context of leishmaniasis. We discuss the biology, distribution, and life cycle, the blood-feeding process, and the Leishmania-sand fly interactions that govern parasite transmission. Additionally, we highlight some outstanding questions that need to be answered for the complete understanding of parasite-vector-host interactions in leishmaniasis.


Localized surface plasmon resonance sensor for simultaneous kinetic determination of peroxyacetic acid and hydrogen peroxide.
A new sensor for simultaneous determination of peroxyacetic acid and hydrogen peroxide using silver nanoparticles (Ag-NPs) as a chromogenic reagent is introduced. The silver nanoparticles have the catalytic ability for the decomposition of peroxyacetic acid and hydrogen peroxide; then the decomposition of them induces the degradation of silver nanoparticles. Hence, a remarkable change in the localized surface plasmon resonance absorbance strength could be observed. Spectra-kinetic approach and artificial neural network was applied for the simultaneous determination of peroxyacetic acid and hydrogen peroxide. Linear calibration graphs were obtained in the concentration range of (8.20×10(-5) to 2.00×10(-3) mol L(-1)) for peroxyacetic acid and (2.00×10(-5) to 4.80×10(-3) mol L(-1)) for hydrogen peroxide. The analytical performance of this sensor has been evaluated for the detection of simultaneous determination of peroxyacetic acid and hydrogen peroxide in real samples.


The influence of modified pluronic F127 copolymers with higher phase transition temperature on arsenic trioxide-releasing properties and toxicity in a subcutaneous model of rats.
Pluronic F127 (PF-127) shows thermoreversible property, which is of the utmost interest in optimizing drug formulation and delivery. However, its hitherto unresolved drawback of a low phase transition temperature (T (tr)) has limited its application in injectable drug delivery systems. We have recently synthesized a new type of PF-127 copolymers with higher T (tr) using a simple oxidative method. Here, we have investigated the drug-releasing feature of oxidized PF-127 and oxidized PF-127-containing silver nanoparticles (SNPs), carrying arsenic trioxide (ATO), in a subcutaneous model of rats. Injectable hydrogels prepared with oxidized PF-127s were less viscous and easier to inject, at the same concentration, than their precursor. Addition of SNPs further elevated T (tr), resulting in even lower viscosity of the injectable hydrogel prepared from SNP-containing oxidized PF-127. The oxidized PF-127 copolymers did not differ significantly in ATO-releasing ability, compared with parental PF-127, but the addition of SNPs altered the ATO-releasing feature of oxidized PF-127 to some extent. ATO-carrying oxidized PF-127s had similar toxicity, but the addition of SNPs enhanced the hepatotoxicity of ATO, as evidenced by elevated serum levels of alanine aminotransferase and aspartate aminotransferase and histological alterations, compared to parental PF-127. The results presented herein warrant further investigation of the modified PF-127 copolymers to deliver ATO or other drugs in the form of injectable hydrogels.


APICAL INTRUSIVE GROWTH OF FIBRES FROM THE FLOWERING STEM OF LOLIUM TEMULENTUM L.
Extension of the internode below the point of insertion of the flag leaf of Lolium temulentum L. takes place in the lower 10 to 15 mm. Extension of the long epidermal cells also takes place in this region. However, fibre cells show little extension in the lower 10 mm and maximum extension occurs at about 30 mm above the node. Thus, there is extension of fibre cells within that portion of the internode which has ceased extension and is bounded by an epidermis, the cells of which have also ceased elongation. This suggests the occurrence of intrusive growth of the fibres and evidence for this is shown from the measurement of macerated fibres and from electron micrographs. The walls of fibre cells measured in internodes of different lengths and ages thicken only very slightly in the lower 30 mm and most cell wall thickening occurs between 45 and 90 mm above the node. Thus most cell wall thickening occurs after the fibre cells have ceased to elongate.


Benign course of juvenile laryngeal papillomata.
A 17 month-old child with laryngeal papillomata is presented. The symptoms were stridor and gradually developing dyspnea. He underwent two surgical procedures within 4 months, using microsurgical techniques, and eventually recovered. The etiological factors of this rare entity are discussed. The relatively benign course in our patient is stressed, in view of the usual protracted course which is reflected in the literature.


Radiotherapy-related quality of life in patients with head and neck cancers: a meta-analysis.
To compare effects of intensity-modulated radiotherapy (IMRT) with those of conventional radiotherapy on quality of life (QoL) and severity of xerostomia in patients with head and neck cancer. PubMed, Cochrane, and Embase databases were searched to July 1, 2019, to identify relevant studies, using the following terms: radiotherapy, head and neck cancer, quality of life, cognition, xerostomia, two-/three-dimensional conformal radiation therapy, IMRT, conformal proton beam radiation therapy, stereotactic radiosurgery, and volumetric modulated arc therapy. The outcomes of interest were QoL measured by global health status; emotional, social, and cognitive function; and severity of xerostomia. Seven studies with a total of 761 patients (n = 369 with IMRT; n = 392 with conventional RT) were included in this study. Median patient age was 18-65 years. IMRT group patients had better global health status (pooled standardized mean difference [SMD] = 0.80, 95% CI 0.26 to 1.35, P = 0.004) and cognitive function (pooled SMD = 0.30, 95% CI 0.06 to 0.54, P = 0.013) than the conventional RT group. Patients receiving IMRT also had significantly lower scores for xerostomia than those receiving conventional RT (pooled SMD = - 0.60, 95% CI - 0.97 to - 0.24, P = 0.001). No differences were found in emotional function (P = 0.531) and social function (P = 0.348) between the two groups. IMRT significantly improves QoL and reduces the severity of xerostomia in patients with head and neck cancer. Results of this study provide clinicians with guidelines for decisions on the use of IMRT versus conventional RT.


Disruption of RCI2A leads to over-accumulation of Na+ and increased salt sensitivity in Arabidopsis thaliana plants.
For plant salt tolerance, it is important to regulate the uptake and accumulation of Na+ ions. The yeast pmp3 mutant which lacks PMP3 gene accumulates excess Na+ ions in the cell and shows increased Na+ sensitivity. Although the function of PMP3 is not fully understood, it is proposed that PMP3 contributes to the restriction of Na+ uptake and consequently salt tolerance in yeasts. In this paper, we have investigated whether the lack of RCI2A gene, homologous to PMP3 gene, causes a salt sensitive phenotype in Arabidopsis (Arabidopsis thaliana (L.) Heynh.) plants; and to thereby indicate the physiological role of RCI2A in higher plants. Two T-DNA insertional mutants of RCI2A were identified. Although the growth of rci2a mutants was comparable with that of wild type under normal conditions, high NaCl treatment caused increased accumulation of Na+ and more reduction of the growth of roots and shoots of rci2a mutants than that of wild type. Undifferentiated callus cultures regenerated from rci2a mutants also accumulated more Na+ than that from wild type under high NaCl treatment. Furthermore, when wild-type and rci2a plants were treated with NaCl, NaNO3, Na2SO4, KCl, KNO3, K2SO4 or LiCl, the rci2a mutants showed more reduction of shoot growth than wild type. Under treatments of tetramethylammonium chloride, CaCl2, MgCl2, mannitol or sorbitol, the growth reduction was comparable between wild-type and rci2a plants. These results suggested that RCI2A plays a role directly or indirectly for avoiding over-accumulation of excess Na+ and K+ ions in plants, and contributes to salt tolerance.


Temporal trend of cardiorespiratory endurance in urban Catalan high school students over a 20 year period.
Physical fitness is considered an important indicator of health in adolescents. However, in recent years several studies in the scientific literature have shown a considerable lower trend and an alarming worsening of the current adolescents' physical condition when comparing with previous decades, especially in urban populations. The aim of the current study was to analyse the temporal trend in cardiorespiratory endurance (CRE) in urban Catalan adolescents over a 20-year period (1999-2019). A cross-sectional analysis study considering the 20-m Shuttle Run test (SRT) results obtained in the last 20 years was carried out. 1,701 adolescents between 15 and 16 years old (914 boys and 787 girls) were divided into four groups, corresponding to consecutive periods of five years (Group 1: 1999-2004; Group 2: 2005-2009; Group 3: 2010-2014 and Group 4: 2015-2019). ANOVA was used to test the period effect on CRE and post hoc Bonferroni analysis was performed to test pairwise differences between groups (p < 0.05). Results showed a significantly lower performance in CRE in both sexes. The percentual negative difference was 0.67%, 9.6% and 7% for boys and 5.06%, 14.97% and 9.41% for girls, when comparing the performance in 20-m Shuttle Run test for the first period, respectively. Results suggest that the physical fitness of Catalan urban adolescents is lower in both sexes when comparing the different analysed periods of time. Therefore, CRE adolescents should be improved in order to help to protect against cardiovascular disease and other health risks in adulthood.


A method of increasing EA positive cells in mouse spleen lymphocytes.
Treatment of mouse spleen lymphocytes with a high concentration of trypsin (1 mg/ml) increases the number of EA positive cells to include nearly all the B lymphocytes. It seems that all B lymphocytes express Fc receptors but in some cells these are hidden by other proteins present on the cell surfaces.


Clinical utility of a near patient care microarray based diagnostic test for influenza and respiratory syncytial virus infections.
In primary care medicine, establishing a diagnosis of influenza and respiratory syncytial virus (RSV) infections is usually based on clinical history and physical examination as well as a consideration of time of the year and circulating respiratory viruses in the community. We tested the potential clinical samples using the automated molecular assay which included rapid influenza diagnostic test, Rapid Immunochromatographic Antigen Test, Verigene Respiratory Virus Plus Nucleic Acid Test, BD Veritor(TM) System for Rapid Detection of RSV in the paediatric setting for diagnosis of influenza and respiratory syntactical virus infections when testing was done by the paediatrician seeing the patient. Principally, with respect influenza virus specificity and sensitivity for RIAT were 100% and 68.8%; compared to 100% and 100%, respectively for RV(+). The specificity and sensitivity for 92.23% and 98% for BD Veritor(TM) System for Rapid Detection of RSV as compared to 96.6% and 98.42% for RIDT. Therefore, this study confirms the clinical utility of RV(+) in the pediatric setting.


RNA sequencing reveals region-specific molecular mechanisms associated with epileptogenesis in a model of classical hippocampal sclerosis.
We report here the first complete transcriptome analysis of the dorsal (dDG) and ventral dentate gyrus (vDG) of a rat epilepsy model presenting a hippocampal lesion with a strict resemblance to classical hippocampal sclerosis (HS). We collected the dDG and vDG by laser microdissection 15 days after electrical stimulation and performed high-throughput RNA-sequencing. There were many differentially regulated genes, some of which were specific to either of the two sub-regions in stimulated animals. Gene ontology analysis indicated an enrichment of inflammation-related processes in both sub-regions and of axonal guidance and calcium signaling processes exclusively in the vDG. There was also a differential regulation of genes encoding molecules involved in synaptic function, neural electrical activity and neuropeptides in stimulated rats. The data presented here suggests, in the time point analyzed, a remarkable interaction among several molecular components which takes place in the damaged hippocampi. Furthermore, even though similar mechanisms may function in different regions of the DG, the molecular components involved seem to be region specific.


Enhancing oral bioavailability of insulin through bilosomes: Implication of charge and chain length on apical sodium-dependent bile acid transporter (ASBT) uptake.
This study investigates the impact of charge and chain length of bile salts in the bilosomes on the oral bioavailability of insulin (IN) by examining their uptake via the apical sodium-dependent bile acid transporter (ASBT). Deoxycholic acid bile salt was conjugated with different amino acids to create conjugates with varying charge and chain length, which were then embedded in liposomes. The resulting bilosomes had a particle size <400 nm, a PDI of 0.121 ± 0.03, and an entrapment efficiency of ∼70 %, while maintaining the chemical and conformational integrity of the loaded IN. Bilosomes also provided superior protection in biological fluids without compromising their biophysical attributes. Quantitative studies using the Caco-2 cell line demonstrated that anionic bilosomes were taken up more efficiently through ASBT than cationic bilosomes with 4- and 1.3-fold increase, respectively. Ex-vivo permeability studies corroborated these findings. In-vivo efficacy studies revealed a 1.6-fold increase in the AUC of IN with bilosomes compared to subcutaneous IN. The developed bilosomes were able to reduce blood glucose levels by ∼65 % at 6 h, with a cumulative hypoglycemic value of 35 % and a BAR of ∼30 %. These results suggest that ASBT can be a suitable target for improving the oral bioavailability of bilosomes containing IN.


Quantitation of day to day variability in mode of induction of ventricular tachyarrhythmias by programmed stimulation.
Spontaneous day to day variability in the mode of induction of ventricular tachycardia at programmed stimulation in the drug-free state has been described but not quantitated. To quantitate this variability, this study employed a new protocol of programmed stimulation in which the number of extrastimuli required for tachycardia induction was the only major stimulation variable. This protocol was applied to 18 consecutive patients with previously documented sustained ventricular tachyarrhythmia due to coronary artery disease. One to seven extrastimuli were available for arrhythmia induction if required. Each patient underwent programmed stimulation in the absence of antiarrhythmic drugs on 3 separate days with a mean interval of 5 +/- 2.7 days between studies. A sustained ventricular tachyarrhythmia was inducible in all studies with less than or equal to 4 extrastimuli; the mean number of extrastimuli required was 2.4 +/- 0.8. Day to day variability in the number of extrastimuli required for tachycardia induction was observed in the majority of patients (72%). Eleven patients (61%) varied by one extrastimulus over the three control studies, and two patients (11%) varied by two extrastimuli. At analysis of variance, the 95% confidence interval for the degree of day to day variability was +/- 1 extrastimulus from the mean number required in the three studies. Multiple configurations of induced ventricular tachycardia were frequently observed at repeat studies and occurred in 15 patients (83%). In conclusion, spontaneous day to day variability in mode of induction of ventricular tachycardia in the absence of drugs is common.(ABSTRACT TRUNCATED AT 250 WORDS)


Identification of non-coding RNA related prognosis biomarkers based on ceRNA network in thyroid cancer.
Introduction: Thyroid cancer (THCA) has become a serious malignant tumor worldwide. Identification of non-coding RNA related regulators is very necessary to improve the knowledge of THCA treatment. The aim of this study was to identify novel therapeutic targets and prognosis biomarkers for predicting pathological characteristics and subsequently treating THCA. Methods: We investigated the alterations of miRNAs, mRNAs and lncRNAs in THCA. Functional enrichment and clustering analysis were conducted for these aberrantly expressed RNAs. Multiple interaction networks among miRNAs, mRNAs and lncRNAs were constructed and the functional modules associated with THCA patients' prognosis were identified. Furthermore, we evaluated the prognostic roles of the important miRNAs, mRNAs and lncRNAs in THCA and investigated the regulatory potential of non-coding RNAs on immune cell infiltration. Results: We firstly identified that miR-4709-3p and miR-146b-3p could significantly classify patients into high/low risk groups, which may be potential prognosis biomarkers of THCA. Secondly, we constructed a THCA-related miRNA-mRNA network, which displayed small world network topological characters. Two THCA-related functional modules were identified from the miRNA-mRNA network by MCODE. Results showed that two modules could implicate in known cancer pathways, such as apoptosis and focal adhesion. Thirdly, a THCA-related miRNA-lncRNA network was constructed. A subnetwork of miRNA-lncRNA network showed strong prognosis effect in THCA. Fourthly, we constructed a THCA-related mRNA-lncRNA network and detected several typical lncRNA-miRNA-mRNA crosstalk, such as AC068138, BCL2, miR-21 and miR-146b, which had good prognosis effect in THCA. Immune infiltration results showed that lncRNAs LA16c-329F2, RP11-395N3, RP11-423H2, RP11-399B17 and RP11-1036E20 were high related to neutrophil and dendritic cell infiltration. Discussion: Non-coding RNA-mediated gene regulatory network has the strong regulatory potential in pathological processes of THCA. All these results could help us uncover the non-coding RNA-mediated regulatory mechanism in THCA.


Chemical organization of projection neurons in the rat accumbens nucleus and olfactory tubercle.
Projection neurons in the ventral striatum, the accumbens nucleus and olfactory tubercle, were examined by combining the retrograde tracing method and immunocytochemistry with antibodies against C-terminals of the preprodynorphin (PPD), preproenkephalin (PPE), preprotachykinin A (PPTA) and preprotachykinin B (PPTB). When the retrograde tracer was injected into the ventral pallidum, about 60% and 40% of retrogradely labeled neurons in the accumbens nucleus were immunoreactive for PPD and PPE, respectively. In contrast, all accumbens nucleus neurons projecting to the ventral mesencephalic regions including the substantia nigra and ventral tegmental area were immunopositive for PPD but not for PPE. Although no olfactory tubercle neurons projected fibers to the mesencephalic regions, 60% and 40% of olfactory tubercle neurons projecting to the ventrolateral portion of the ventral pallidum were immunoreactive for PPD and PPE, respectively, as were the accumbens nucleus neurons. About 70% of accumbens nucleus and olfactory tubercle neurons projecting to the ventral pallidum and all accumbens nucleus neurons projecting to the ventral mesencephalic regions showed PPTA immunoreactivity. A small population (2-12%) of accumbens neurons projecting to the ventral pallidum and mesencephalic regions displayed immunoreactivity for PPTB. Compared with the dorsal striatopallidal projection neurons that were reported to mostly express PPE, it was characteristic of the ventral striatum that only the smaller population (about 40%) of ventral striatopallidal projection neurons expressed PPE. This suggests that the ventral striatopallidal projection system is less specialized than the dorsal striatopallidal system in terms of peptide production, or that the ventral pallidum should be compared with a combined region of the globus pallidus and entopeduncular nucleus in the dorsal system.


A method for localized and longlasting microapplication of drugs into nervous tissue of freely moving animals.
A method is described for localized microapplication of drugs into nervous tissue of freely moving rats. Fairly constant release of material was observed over a period of more than three weeks. The amount of substance released was small because the rate of release was determined largely by diffusion rather than by mass movement of solution.


Voltage dependence of membrane charge movement and calcium release in frog skeletal muscle fibres.
Voltage dependent membrane charge movement (gating current) and the release of Ca2+ from intracellular stores have been measured simultaneously in intact frog skeletal muscle fibres. Charge movement was measured using the three microelectrode voltage clamp technique. Ca2+ release was measured using the metallochromic indicator dye arsenazo III. Fibres were bathed in 2.3 X hypertonic solutions to prevent contraction. Rb+, tetraethylammonium and tetrodotoxin (TTX) were used to eliminate voltage-dependent ionic currents. The maximum rate of Ca2+ release from the sarcoplasmic reticulum in response to voltage-clamp step depolarizations to 0 mV was calculated using the dye-related parameters of model 2 of Baylor et al. (1983) and a method described in the Appendix for calculating a scaling factor (1 + p) that accounts for the additional Ca2+ buffering power of the indicator dye. The estimates of the maximum rate of Ca2+ release at 5-6 degrees C ranged from 3 to 19 microM ms-1 in the 17 fibres examined. The mean value was 8.9 +/- 1.1 microM ms-1 (S.E.M.) The maximum rate of Ca2+ release was linearly related to the magnitude of the nonlinear membrane change moved during suprathreshold depolarizing steps. The voltage dependence of charge movement and the maximum rate of Ca2+ releases were nearly identical at 6 degrees C. The voltage-dependence of the delay between the test step and the onset of Ca2+ release could be adequately described by an equation having the same functional form as the voltage dependence of nonlinear charge movement. The relationship between the test pulse voltage and the delay was shifted to more negative voltages and to shorter delays as the temperature was raised from 6 degrees C to 15 degrees C. The inactivation of Ca2+ release was found to occur at more negative holding voltages and to be more steeply voltage dependent than the immobilization of nonlinear membrane charge movement. The above data are discussed using the 'hypothetical coupler' model of excitation-contraction coupling (Miledi et al., 1983b) applied to the specific case in which each mobile charge group controls the gating of one Ca2+ release site in the sarcoplasmic reticulum.


Comparative host-pathogen protein-protein interaction analysis of recent coronavirus outbreaks and important host targets identification.
Last two decades have witnessed several global infectious outbreaks. Among these, coronavirus is identified as a prime culprit ranging from its involvement in severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) to COVID-19. These infections involved in huge healthcare and economic cost incurred globally. Every time, coronavirus improved its infection ability and surprised the medical practitioners and researchers. Currently, COVID-19 is also causing numerous infections and stalled global activities. Global efforts are underway to identify potential viral targets for management of these outbreaks, but significant progress in prevention of these outbreaks is not yet achieved. We explored host-pathogen protein-protein interactions of MERS, SARS and COVID-19, and identified host targets common among all recent coronavirus outbreaks. Further, we tried to understand their potential for management of coronavirus. The common proteins involved in coronavirus host-pathogen interactions indicate their indispensable role in the pathogenesis and therefore targeting these proteins can give strategies to prevent current and future coronavirus outbreaks. Viral variability necessitates development of new therapeutic modalities for every outbreak, in contrast targeting necessary human proteins required by all coronaviruses can provide us a clue to prevent current and future coronavirus outbreaks. We found that targeting FURIN and TMPRSS2 can provide good results due to their common involvement in current and previous outbreaks. We also listed some known molecules against these two targets for their potential drug repurposing evaluation. Although, several recent studies undergoing with targeting these proteins for management of coronavirus, but safety evaluation and risk assessment must be given prime importance while targeting human proteins.


Activin a plasma levels at birth: an index of fetal hypoxia in preterm newborn.
Activin-A is a growth factor involved in cell growth and differentiation, neuronal survival, early embryonic development and erythropoiesis. Hypoxemia is a specific trigger for increasing activin-A in fetal lamb circulation. We tested the hypothesis that fetal hypoxia induces activin-A secretion in preterm newborn infants. Fifty newborn infants with gestational ages ranging from 26 to 36 wk were enrolled in a prospective study performed at the Pediatrics, Obstetrics and Reproductive Medicine Department, University of Siena, Italy. Heparinized blood samples were obtained from the umbilical vein after cord clamping, immediately after delivery. Activin A, hypoxanthine (Hx), xanthine (Xa) plasma levels and absolute nucleated red blood cell (NRBC) count were measured. Activin-A levels (p < 0.0001) and NRBC (p < 0.0001) were significantly higher in hypoxic than in non hypoxic preterm newborns. Cord activin A levels were significantly related with Hx (taua=0.64, taub=0.64, p < 0.0001) and Xa (taua=0.56, taub=0.57, p < 0.0001) levels, NRBC ((taua=-0.45, taub=-0.46, p < 0.0001) count; pH (taua=-0.47, taub=-0.48, p < 0.0001) and base deficit (taua=-0.36, taub=0.-0.36, p = 0.0002). Preterm newborns with signs of perinatal hypoxia at birth have increased activin-A levels, suggesting that activin-A may reflect indirectly intrauterine hypoxia.


[Effect of vinblastine and cyclophosphamide on the formation of antigen-induced B-suppressors].
Seven days after administration of sheep red blood cells (SRBC) to CBA and (CBA X C57BL/6) F1 mice antigen-induced B-suppressors are formed in the spleen. These suppressors are capable of inhibiting the unirradiated syngeneic recipients' response to SRBC. Administration to donors to vinblastine (1.5 mg/kg) concurrently with SRBC did not affect and partially reversed, 5 days after SRBC, the formation of antigen-induced suppressors. On the contrary, administration to donors of cyclophosphamide (20 mg/kg) 24 h prior to SRBC or in a dose of 250 mg/kg concurrently with SRBC or 5 days after SRBC completely reversed the formation of antigen-induced suppressors.


How can veterinarians base their medical decisions on the best available scientific evidence?
With the advent of a One World-One Health concept, veterinarians will play a central role, at the level of trading zones (such as the European Union), countries, food production farms, and individual animals. They will be mandated to produce, interpret, communicate, and apply scientific information in the best possible way to make informed decisions and take adequate actions. The principles of evidence-based medicine will help the accomplishment of this mission. However, for the moment, we may still have the impression of two separate worlds, the academic research on one side and the reality of practice on the other side, and there is a need to join them.


Diazepam in the prevention of seizures and death in cocaine-intoxicated rats.
Rats were exposed to high-dose intraperitoneal cocaine. Pretreatment with diazepam was found to be highly effective in reducing observed seizures from 90% to 0% and reducing the incidence of death from 85% to 10%. Furthermore, diazepam treatment after cocaine exposure was also effective in decreasing deaths, from 80% to 21%, even when given after the onset of seizures. Although diazepam pretreatment was shown to prevent clinically overt seizures, cortical EEGs in these rats demonstrated a continuum of convulsantlike electrical activity. Our study points to the protective effects of diazepam when given before or after cocaine exposure. Together, these data suggest that diazepam has significant efficacy against cocaine intoxication even though it does not totally suppress cocaine-induced cortical EEG seizure activity.


Comparative study of two different modes of noninvasive home mechanical ventilation in chronic respiratory failure.
Two modes of noninvasive home mechanical ventilation (NIHMV) with volumetric ventilators were compared in patients with chronic respiratory failure. Retrospective, parallel-group, comparative study. Third-level teaching Hospital in Barcelona (Spain). We studied 110 patients with chronic hypercapnic respiratory failure secondary to neuromuscular disease, kyphoscoliosis or post-tuberculosis sequelae, starting NIHMV with volumetric ventilators. The assist/control (A/C) ventilation mode was used in 45 patients and the control (C) mode in 65 patients. Clinical characteristics, pulmonary function results and arterial blood gas findings were assessed in each patient before establishing ventilation and at 6 and 12 months after. The patient's satisfaction with ventilation, the time required for adaptation, and compliance with the prescription were also assessed. Significant improvements in PaO(2) and PaCO(2) (P<0.001) were found at 6 and 12 months with both modes of mechanical ventilation. There were no significant differences between the two modes for pulmonary function or blood gas parameters with the exception of maximum inspiratory pressure (MIP) in patients receiving the C mode, which was significantly different as compared to the baseline value after 12 months of use (mean+/-sd: 36.6+/-14.8 and 44.7+/-24.2 cmH(2)O, respectively; P=0.010). No significant differences were found in adaptation, compliance with ventilation or patient satisfaction between the two modes studied. According to several factors analysed, results with the A/C or C mode used with volumetric ventilators appear to be comparable in patients with chronic respiratory disease receiving NIHMV. Choice of mode will depend on the acquired experience of the prescribing physicians in each centre.


A novel prognostic model for hepatocellular carcinoma based on pyruvate metabolism-related genes.
Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer, accounting for over 90% of cases. As pyruvate metabolic pathways are often dysregulated in cancer cells, investigating pyruvate metabolism-related genes may help identify prognostic gene signature and develop potential strategies for the management of patients with HCC. The mRNA expression profile, gene mutation data, and clinical information of HCC were obtained from open-source databases. A list of pyruvate metabolism-related genes was downloaded from the MSigDB dataset. Our findings revealed that certain pyruvate metabolism-related genes had copy number variations and single nucleotide variations in patients with liver cancer. Based on pyruvate metabolism-related genes, we stratified patients with HCC into three subtypes with different prognoses, clinical features, mutation profiles, functional annotation, and immune infiltration status. Next, we identified 13 key pyruvate metabolism-related genes significantly correlated with the prognosis of HCC using six machine learning algorithms and constructed a risk model. We also observed that the risk score was positively associated with a worse prognosis and increased immune infiltration. In summary, our study established a prognostic risk model for HCC based on pyruvate metabolism-related genes, which may contribute to the identification of potential prognostic targets and the development of new clinical management strategies for HCC.