A novel human STE20-related protein kinase, HGK, that specifically activates the c-Jun N-terminal kinase signaling pathway.
The yeast serine/threonine kinase STE20 activates a signaling cascade that includes STE11 (mitogen-activated protein kinase kinase kinase), STE7 (mitogen-activated protein kinase kinase), and FUS3/KSS1 (mitogen-activated protein kinase) in response to signals from both Cdc42 and the heterotrimeric G proteins associated with transmembrane pheromone receptors. Using degenerate polymerase chain reaction, we have isolated a human cDNA encoding a protein kinase homologous to STE20. This protein kinase, designated HPK/GCK-like kinase (HGK), has nucleotide sequences that encode an open reading frame of 1165 amino acids with 11 kinase subdomains. HGK was a serine/threonine protein kinase that specifically activated the c-Jun N-terminal kinase (JNK) signaling pathway when transfected into 293T cells, but it did not stimulate either the extracellular signal-regulated kinase or p38 kinase pathway. HGK also increased AP-1-mediated transcriptional activity in vivo. HGK-induced JNK activation was inhibited by the dominant-negative MKK4 and MKK7 mutants. The dominant-negative mutant of TAK1, but not MEKK1 or MAPK upstream kinase (MUK), strongly inhibited HGK-induced JNK activation. TNF-alpha activated HGK in 293T cells, as well as the dominant-negative HGK mutants, inhibited TNF-alpha-induced JNK activation. These results indicate that HGK, a novel activator of the JNK pathway, may function through TAK1, and that the HGK --> TAK1 --> MKK4, MKK7 --> JNK kinase cascade may mediate the TNF-alpha signaling pathway.


Interim fluorine-18 fluorodeoxyglucose PET-computed tomography and cell of origin by immunohistochemistry predicts progression-free and overall survival in diffuse large B-cell lymphoma patients in the rituximab era.
The aim of this study was to analyze the prognostic value of the interim PET (iPET)-computed tomography (CT) (iPET-CT) after two cycles of immunochemotherapy with the R-CHOP protocol in patients with diffuse large B-cell non-Hodgkin lymphoma (DLBCL) treated with a curative intent in combination with the neoplastic cell origin defined by Hans's immunohistochemstry algorithm followed in a reference center for cancer treatment in Brazil. We prospectively evaluated 147 DLBCL patients treated with R-CHOP-21 to assess the value of the International Prognostic Index, iPET-CT, and cell of origin by immunohistochemistry as prognostic markers in the rituximab era. Fluorine-18 fluorodeoxyglucose PET-CT was performed after two cycles (iPET-CT) and at the end of treatment in 111 patients. Lymphoma cases were categorized into germinal center (GC) and nongerminal center subtypes by immunohistochemistry according to Hans's algorithm. The median age of GC-DLBCL patients (52.7 years) was lower than that of nongerminal center-DLBCL patients (59.4 years) (P=0.021); in addition, it was lower in patients with negative iPET-CT findings (52.7 years) versus positive findings (59.4 years) (P=0.031). The overall survival at 48 months was 100% for iPET-CT-negative GC-DLBCL patients and 61.2% for iPET-CT-positive GC-DLBCL patients (P=0.002). Progression-free survival at 30 months was 100% for iPET-CT-negative GC-DLBCL patients and 60.3% for iPET-CT-positive GC-DLBCL patients (P=0.001). We conclude that iPET-CT associated with cell origin identified a very good prognostic group in DLBCL patients treated with R-CHOP. Video Abstract: http://links.lww.com/NMC/A59.


Constant false alarm rate detection of pipeline leakage based on acoustic sensors.
During the transportation of oil and gas pipelines, there are many potential factors that can lead to pipeline leakage with serious consequences, making automatic and real-time pipeline leakage detection urgent. In response to the inconvenience of manual detection, constant false alarm rate (CFAR) detection technique in radar target detection theory is introduced for pipeline leakage detection based on acoustic signals. In this paper, an automatic pipeline leakage detection algorithm based on an improved CFAR detector is proposed. The improved CFAR detection is executed after pre-processing the acoustic signals so as to adaptively set the detection threshold to achieve the purpose of automatic detection of pipeline leakage incidents. A simulated leakage test of a real pipeline is used for validation, and the proposed method achieves detection accuracies of 84.6%, 97.7%, and 98% for different leakage diameter settings, i.e., 5 mm, 7 mm, and 10 mm leak hole diameters, respectively, with an overall accuracy of 94.1%, while the false alarm rates are 3.3%, 0.7%, and 0, respectively, as well as an overall of 1.2%. The results of experimental data based on real scenarios demonstrate the effectiveness of the proposed method.


Nutrient transport between ryegrass plants differeing in nutrient status.
It is known that nitrogen and phosphorus can be transferred from one living plant to another, but it is not known whether the amounts transferred are large enough to influence the growth of the species in the field. Two Lolium perenne plants were grown per pot of unfertilized soil. During 25 weeks one plant (the 'donor') in each pot was fed nutrients through leaves; donors in control pots received only water. The 'receiver' plants which shared a pot with the nutrient-fed donors increased significantly, compared with the controls, in leaf number and concentration of phosphorus, though not in concentration of nitrogen, potassium, calcium or magnesium. The rate of phosphorus transfer agreed well with previous results using 32P. The results are compared with rates of phosphorus uptake in the field. It is concluded that nutrient transfer could have an influence on the balance between coexisting species in the field, but probably the influence will be small.


Kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon: successful treatment with embolization and vincristine in two newborns.
Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor and has a high mortality in newborns when associated with Kasabach-Merritt syndrome (KMS). In two newborns with KHE and severe KMS refractory to medical treatment, emergency embolization led to clinical improvement in the acute neonatal setting by reducing tumor volume, increasing the platelet count, and improving other clotting parameters. Systemic vincristine treatment was added for further tumor control. Both patients remained symptom-free at long-term follow-up.


Toxicity, repellency, and horizontal transmission of fipronil in the formosan subterranean termite (Isoptera: Rhinotermitidae).
Toxicity of fipronil was evaluated against field-collected Coptoteres formosanus Shiraki. In topical application assays, fipronil was highly effective against both workers and soldiers at very low doses. Acute toxicity after 24 h was significantly greater in workers than in soldiers. The LD50s were 2.59- and 2.91-fold greater with soldiers than with workers from the two tested colonies. The LD50s of fipronil at 72 h after treatment were <2.0 ng/insect, with no significant differences regarding the tested workers/soldiers or colonies. Treated soldiers placed with untreated workers significantly increased worker mortality. However, there was no significant horizontal transmission of fipronil from treated workers to untreated soldiers. Fipronil at rates of 0.063% or less showed no repellency, whereas sand treatments of 0.125% fipronil were repellent to termite workers.


Comparison of an elemental and two polymeric diets in colectomized patients with or without intestinal resection.
The absorption of nutrients and minerals from the small bowel on enteral diets of different composition has been studied in seven ileostomy patients without or with only minor (< 100 cm) distal small bowel resection (group A) and in nine patients with major (> 100 cm) resections, i.e. jejunostomies (group B). In group A, a moderate-fat polymeric diet (MF) was compared to a peptide-based low-fat elemental diet (PD). Nitrogen and potassium absorption was higher on the MF, while the absorption of other nutrients and minerals studied did not differ. In group B a low-fat polymeric diet (LF) was also tested. Jejunostomy volumes were higher on the PD diet compared to the polymeric diets, as were losses of sodium and potassium. Nitrogen absorption was lower on the PD diet. Comparison of the MF and LF polymeric diets showed equal energy losses, while jejunostomy volumes and sodium losses were higher on the MF diet. Calcium absorption was higher and balance better on the LF diet. We conclude, that (a) elemental diets offer no nutritional advantages in enteral feeding of patients with intact or impaired small bowel function, and (b) we suggest that a low-fat polymeric diet could replace elemental diets in patients with malabsorption.


Physicians' and nurses' satisfaction with the clinical laboratory service of Gondar University Hospital, northwest Ethiopia.
To assess physicians' and nurses' satisfaction with the service provided by the laboratory at Gondar University Hospital. We conducted a cross-sectional study involving 196 nurses and physicians. Overall level of satisfaction was 51.1% for nurses and 51.5% for physicians. Lack of consistency in the quality of laboratory work, absence of a timely report of critical values, test turnaround time, acceptability of results released, and reporting of reference ranges with test results were areas mentioned as sources of dissatisfaction. The study showed wide room for improvement. In addition to taking intervention, root causes of dissatisfaction need to be investigated and means of improving the satisfaction level should be designed and implemented.


Promising toxicological biomarkers for the diagnosis of liver injury types: Bile acid metabolic profiles and oxidative stress marker as screening tools in drug development.
Promising biomarkers were identified in adult male Crl:CD (SD) rats for the screening of new chemical entities for their potential to cause liver injury. We examined the serum biochemistry, liver histopathology, and bile acid profiles by LC-MS/MS, and the mRNA expression of transporters and CYPs by an RT-PCR after the following treatments to male Crl:CD (SD) rats: (a) bile duct ligation (BDL); (b) a single oral dose of 150 mg/kg α-naphthylisothiocyanate (ANIT); and (c) repeated oral doses of a novel pyrrolidinecarboxylic acid derivative (abbreviated as PCA) at 30, 300, and 1000 mg/kg. The serum total bile acid levels and bilirubin concentrations were found to be elevated in all of the groups. However, the bile acid component profiles of the PCA group differed significantly from BDL and ANIT models: deoxycholic acid, lithocholic acid, and sulfated bile acids were upregulated in a dose-dependent manner only in the PCA group. In addition, the PCA group demonstrated high levels of hepatic heme oxygenase-1 expression, whereas the profiles of the mRNA levels of the hepatic transporters and CYPs of all groups were found to be similar. The histopathological findings, for both the BDL and ANIT groups, were of bile duct hyperplasia, hepatocyte degeneration and necrosis. In contrast, only bile duct hyperplasia and hepatocyte degeneration were observed in the PCA group, even at a lethal dose. These results indicated that PCA induced a cholestatic condition and the increase of oxidative stress markers implies that this will also lead hepatocellular injury. In conclusion, the serum bile acid components and sulfated bile acid levels, and the expression of oxidative stress markers could provide information that aids in the diagnosis of liver injury type and helps to elucidate the mechanisms of hepatotoxicity. These findings can be extrapolated into our clinical investigation. The analysis of these crucial biomarkers is likely to be a useful screening tool in the lead optimization phase of drug discovery.


[Effect of unilateral trauma of the sciatic nerve on characteristics of motor and reflex responses of paired gastrocnemius muscles].
The influence of unilateral n. ischiadicus lesion of conductivity on the electromyographic characteristics of the rat gastrocnemius muscles was investigated. The lesion was made by n. ischiadicus crashing. Motor and reflex gastrocnemius muscles' responses caused by n. ischiadicus stimulation (single impulses of various intensity and 0.3 ms duration) were estimated on broken and symmetric hind-limb before and 1, 5, 10, 20 and 30 days after the nerve crashing. Considerable changes of threshold and amplitude of the registered gastrocnemius muscle responses were observed ipsi- and contralaterally. It is suggested that the central dependence of processes arising in the motor centres of symmetric gastrocnemius muscles, follows unilateral n. ischiadicus lesion.


Somatic Embryogenesis and Plant Regeneration of Brachiaria brizantha.
The genus Brachiaria (Trin.) Griseb. belongs to the family Poaceae, order Poales, class Monocotyledonae. In Brachiaria brizantha (Hochst. ex A. Rich.) Stapf., embryogenic callus can be induced from seeds from apomictic plants, which results in high frequency somatic embryo development and plant regeneration. We report here a detailed protocol for callus induction from apomictic seed; followed by in vitro morphogenesis (somatic embryo and bud differentiation), plant regeneration, and acclimatization in the greenhouse. Important details regarding the positioning of seeds for callus induction and precautions to avoid endophytic contamination and the occurrence of albino plants are presented.


Transplantation of immature murine brain tissue into the anterior eye-chamber of adult rats.
Embryonic mouse hippocampi (E17) were placed in the anterior eye chamber of young adult rats. The transplants were photographed twice a week. Initially the transplants increased in size, thereafter focal bleeding occurred and later regression of the transplants was seen. Regression continued until the transplants were no longer macroscopically visible. At this time the eyes were prepared for histological examination. Comparison of these transplants with immature rat hippocampi transplanted to the anterior eye chamber of rats, and with mouse-rat in vitro co-cultures suggests that the regression is a result of an immunological response.


Selective metal leaching from technosols based on synthetic root exudate composition.
This study focused on metal release from technosols induced by synthetic root exudate (SRE). The effect of SRE composition on metal release was studied using six technosols. This was done by treating the technosols with SRE solutions having varying concentrations of low molecular weight organic acids (LMWOAs), namely oxalic, citric, and malic acids. Consequently, the physico-chemical parameters (pH and electric conductivity), Ca, Mg, Fe, Zn, and Cu release (by atomic absorption spectroscopy, AAS), chemical changes (by Fourier transform infrared, FT-IR), and organic parameters (by fluorescence) were investigated. Metal release showed to be dependent on the SRE composition and technosol characteristics. Citric acid selectively released Ca, Mg, Zn, and Cu from technosols in a concentration-dependent manner; oxalic acid showed a significant role in the release of Mg and Fe. Under relatively high LMWOA concentrations, particulate organo-mineral complexes precipitated. Additionally, technosol weathering was seen by the dissolution of humic substances and ferriallophanes, which in turn caused metal release. However, re-precipitation of these phases showed to re-sorb metals, thus underestimating the role of LMWOAs in metal release. Therefore, the selective metal leaching was highly dependent on the SRE composition and LMWOA concentrations on one hand, and on the mineral, organic, and organo-mineral components of the technosols on the other. The understanding of such processes is crucial for proposing and implementing environmental management strategies to reduce metal leaching or for the beneficial re-usage of metals (e.g., for agromining) from technosols.


A cell type-specific enhancer drives expression of the chick muscle acetylcholine receptor alpha-subunit gene.
The regulation of acetylcholine receptor alpha-subunit gene expression was analyzed by transient expression assays. Using rabbit beta-globin cDNA as a reporter gene, we have confirmed that the 5'-flanking sequence of the chicken acetylcholine receptor alpha-subunit gene directs specific expression in differentiated C2C12 cells, a mouse muscle cell line, but not in undifferentiated C2C12 cells and mouse 3T3 fibroblasts. Testing chimeric plasmids containing Bal31 deletion mutants of the alpha-subunit gene upstream sequence, we found the -116 to -81 region of the alpha-subunit to be responsible for tissue- and stage-specific expression. This 36 bp fragment stimulates the activity of both alpha-subunit and SV40 promoters in a distance- and orientation-independent manner, thus fulfilling the criteria of an enhancer.


Endotyping pediatric obesity-related asthma: Contribution of anthropometrics, metabolism, nutrients, and CD4+ lymphocytes to pulmonary function.
Obesity-related complications including visceral fat, metabolic abnormalities, nutrient deficiencies, and immune perturbations are interdependent but have been individually associated with childhood asthma. We sought to endotype childhood obesity-related asthma by quantifying contributions of obesity-related complications to symptoms and pulmonary function. Multiomics analysis using Similarity Network Fusion followed by mediation analysis were performed to quantify prediction of obese asthma phenotype by different combinations of anthropometric, metabolic, nutrient, and TH-cell transcriptome and DNA methylome data sets. Two clusters (n = 28 and 26) distinct in their anthropometric (neck and midarm circumference, waist to hip ratio [WHR], and body mass index [BMI] z score), metabolic, nutrient, and TH-cell transcriptome and DNA methylome footprint predicted 5 or more pulmonary function indices across 7 different data set combinations. Metabolic measures attenuated the association of neck, WHR, and BMI z score with FEV1/forced vital capacity (FVC) ratio and expiratory reserve volume (ERV), of neck, midarm, and BMI z score with functional residual capacity, but only of WHR with inspiratory capacity. Nutrient levels attenuated the association of neck, midarm circumference, and BMI z score with functional residual capacity, and of WHR with FEV1/FVC ratio, ERV, and inspiratory capacity. TH-cell transcriptome attenuated the association of all 4 anthropometric measures with FEV1/FVC ratio, but only of WHR with ERV and inspiratory capacity. The DNA methylome attenuated the association of all 4 anthropometric measures with FEV1/FVC ratio and ERV, but only of WHR with inspiratory capacity. Anthropometric, metabolic, nutrient, and immune perturbations have individual but interdependent contributions to obese asthma phenotype, with the most consistent effect of WHR, highlighting the role of truncal adiposity in endotyping childhood obesity-related asthma.


Factors of Good Collaboration in Home-Based End-of-Life Care: A Questionnaire Survey of Japanese Home Care Nurses, Home Helpers, and Care Managers.
Good interprofessional work (IPW) is essential to provide quality home-based end-of-life (EOL) care. The purpose of this study was to explore the factors of "good collaboration," as evaluated separately by home care nurses (HNs), home helpers (HHs), and care managers (CMs). The relationship was examined between their evaluation of good collaboration and their recent actual experience of interprofessional collaborative work for a home-based EOL case. The questionnaire was returned nationwide by 378 HNs, 305 HHs, and 476 CMs, and data were collected on 177 EOL cases from HNs, 84 cases from HHs, and 123 cases from CMs. Evaluation of good collaboration by HNs was associated with working with a CM with whom they had multiple collaborative experiences, the client being independent for their toileting until just before dying, and sharing information regarding the client's EOL decision with an HH 1 month before dying. Evaluation of good collaboration by HHs was associated with working at an agency that collaborated with fewer CM agencies and working at an agency that allowed staff to visit dying clients. Evaluation of good collaboration by CMs was associated only with the client being dependent for toileting. Our results highlighted the characteristics of how each professional seeks to collaborate depending on their preparedness, contexts, and resultant expectations toward other professionals when entering the IPW for home-based EOL care. To promote good IPW for home-based EOL care further, professionals need to understand these differences among ourselves and try to meet others' expectations.


Homogeneous Polymerization of Self-standing Covalent Organic Framework Films with High Performance in Molecular Separation.
Covalent organic frameworks (COFs) are typically isolated as microcrystalline powders. It remains fundamentally challenging to fabricate COFs into high-quality self-standing films to take full advantage of their ordered pore channels for molecular separation. Here, we report a new strategy for fabricating self-standing imine-linked COF films via homogeneous polymerization where films emerge from clear solutions without forming amorphous precipitates. The abundant basic nitrogen atoms of the monomers acted as a reaction controller to realize the homogeneous polymerization and also promoted the tight self-aggregation of COF crystallites to form compact films via H-bonding. The chemically supported self-standing COF films on nylon membranes were also developed via an in situ growth method. The resulting films showed an unprecedentedly ultrafast permeance of 2822 L m-2 h-1 MPa-1 with a high rejection rate (99.8%) in the filtration of a congo red (CR) solution, demonstrating the advantage of this new strategy in fabricating high-quality self-standing COF films.


Prognostic value of serum levels of immunoglobulins (IgG, IgA, IgM and IgE) in breast cancer: a preliminary study.
One hundred and sixty women admitted for breast tumour biopsy to the King's College Hospital group have been followed sequentially for 2 years. Sixty-nine women had early operable breast cancer and 91 had benign breast disease. All these women had serum immunoglobulin IgG, IgA, IgM and IgE levels measured preoperatively and postoperatively at 3 months, 1 year and 2 years. No differences were found in any of the serum immunoglobulin levels between the two groups at any time. There was, however, a positive correlation between the extent of metastatic breast cancer and the serum level of various immunoglobulins, particularly IgA. There was no evidence that routine postoperative radiotherapy influenced the levels of serum immunoglobulins. The findings suggest a secondary defence reaction against increasing tumour load, and do not support the theory of an early immune defect in immunoglobulin metabolism which could play a part in the pathogenesis of breast cancer. Although there is no diagnostic value in measuring the levels of serum immunoglobulins in patients with breast tumours, there may be some value in following the levels in cancer patients, as a guide to subclinical spread of the disease.


Effect of pinealectomy, eye enucleation, and melatonin treatment on ovarian activity and vitellogenin levels in the catfish exposed to short photoperiod or long photoperiod.
To investigate the relative importance of pineal, and eyes, and melatonin treatment on ovarian activity, catfish. Heteropneustes fossilis subjected to pinealectomy, eye enucleation, or both were exposed to short (LD 9:15) or long (LD 14:10) photoperiod during the different stages of the annual reproductive cycle. During the preparatory period, pinealectomy accelerated ovarian recrudescence under long photoperiod, but no effects of pinealectomy were observed under short photoperiod. Pineal has no influence on ovarian activity during the prespawning and spawning periods of the reproductive cycle. In the late postspawning period, ovarian recrudescence is accelerated after pinealectomy in catfish maintained under short photoperiod (LD 9:15 at 25 degrees C). But under long photoperiod (LD 14:10 at 25 degrees C), pinealectomy delayed ovarian recrudescence. An investigation into the role of the eyes revealed that eye enucleation nullifies the inhibitory effects of LD 9:15 and represses the stimulatory effects of LD 14:10. Combined surgery inhibited ovarian development under both the regimes. It is significant that pinealectomy and/or blinding neither counteracted nor delayed the postspawning ovarian regression. The findings suggest that the role of the pineal in catfish reproduction is variable and depends upon the photoperiod to which they are exposed as well as on the time of the year and the stage of the reproductive cycle. It is concluded that extraretinal and extrapineal photoreceptors also are involved in influencing seasonal reproduction. Further, no effects of melatonin treatment on ovarian activity or on vitellogenin levels during the preparatory or prespawning periods were observed, indicating that the pineal effects on gonadal activity in catfish may not be mediated through the secretion of melatonin.


Towards real-time metabolic profiling of a biopsy specimen during a surgical operation by 1H high resolution magic angle spinning nuclear magnetic resonance: a case report.
Providing information on cancerous tissue samples during a surgical operation can help surgeons delineate the limits of a tumoral invasion more reliably. Here, we describe the use of metabolic profiling of a colon biopsy specimen by high resolution magic angle spinning nuclear magnetic resonance spectroscopy to evaluate tumoral invasion during a simulated surgical operation. Biopsy specimens (n = 9) originating from the excised right colon of a 66-year-old Caucasian women with an adenocarcinoma were automatically analyzed using a previously built statistical model. Metabolic profiling results were in full agreement with those of a histopathological analysis. The time-response of the technique is sufficiently fast for it to be used effectively during a real operation (17 min/sample). Metabolic profiling has the potential to become a method to rapidly characterize cancerous biopsies in the operation theater.


Gait analysis of spastic walking in patients with cervical compressive myelopathy.
To assess neurological status and to evaluate the effect of surgical decompression in patients with cervical myelopathy, we performed computerized gait analysis in 24 patients with cervical compressive myelopathy who showed spastic walking. Gait analysis was repeated during neurological follow-up that averaged 32.4 months. The gait pattern in patients with severe myelopathy was characterized by hyperextension of the knee in the stance phase without plantar flexion of the ankle in the swing phase, significantly reduced walking speed and step length, prolonged stance phase duration and decreased single-stance phase duration, and increased step width. The angle of flexion of the knee joint in the stance phase was significantly correlated with the Japanese Orthopaedic Association (JOA) score. Postoperative neurological improvement was associated with increased walking speed and decreased extension angle of the knee joint (single-stance phase and swing phase). Postoperatively, 12 patients had normalized extension of the knee in stance phase and their walking speed, cadence, stance phase duration, and single-stance phase duration, as well as step length and width, showed nonsignificant differences from these parameters in healthy controls. Our results show that kinesiological gait analysis is clinically useful for the functional assessment of the severity of spastic walking in cervical myelopathy.


New Predictive Resting Metabolic Rate Equations for High-Level Athletes: A Cross-validation Study.
The present study aims a) to assess the agreement between the measured resting metabolic rate (RMR) using indirect calorimetry and different predictive equations (predicted RMR), and b) to propose and cross-validate two new predictive equations for estimating the RMR in high-level athletes. The RMR of 102 athletes (44 women) was assessed using indirect calorimetry, while the body composition was assessed using skinfolds. Comparisons between measured and predicted RMR values were performed using one-way ANOVA. Mean difference, Root Mean Square Error, Simple Linear Regression, and Bland-Altman plots were used to evaluate the agreement between measured and predicted RMR. The accuracy of predictive equations was analyzed using narrower and wider accuracy limits (±5% and ± 10%, respectively) of measured RMR. Multiple linear regressions models were employed to develop the new predictive equations based on traditional predictors (Equation 1) and the stepwise method (Equation 2). The new Equations 1 and 2 presented good agreement based on the mean difference (3 and -15 kcal.d-1), RMSE (200 and 192 kcal.d-1), and R2 (0.71 and 0.74), respectively, and accuracy (61% of subjects between the limit of ±10% of measured RMR). Cunningham's equation provided the best performance for males and females among the existing equations, whereas Harris & Benedict's equation showed the worst performance for males (mean difference = 406 kcal.d-1; RMSE = 473 kcal.d-1). Compared to measured RMR, most predictive equations showed heteroscedastic distribution (linear regression's intercept and slope significantly different from zero; p ≤ 0.05), mainly in males. The new proposed equations can estimate the RMR in high-level athletes accurately. Cunningham's equation is a good option from existing equations, and Harris & Benedict's equation should not be used in high-level male athletes.


The turnover of radiolabeled nuclear proteins in rats exposed to environmental and chemical stress.
Exposure to a 12 h light/12 h dark (L/D) cycle for 1 month, followed by reversal to a 12 h D/12 h L (D/L) cycle stimulated within 18 h the incorporation of [3H]leucine and [32P]orthophosphoric acid into new proteins (130-25 kDa) in the G0 phase of the cell cycle of the non-regenerating and regenerating rat liver as observed in two-dimensional gel autoradiograms. Six additional proteins from the rat submaxillary gland (130-20 kDa) revealed labeling with 32P within 3 h following combined administration of isoproterenol and sodium arsenite. Labeling disappeared within 7 days for all stressed proteins.


Functional photostability and cutaneous compatibility of bioactive UVA sun care products.
Sunscreens are the most-established approach for photoprotection. The strategy of providing antioxidant properties to sun care products by addition of natural and potent anti-free radical compounds has led to the development of bioactive sunscreens, able to neutralize the harmful effects of ultraviolet (UV) radiation. UVA filters, such as benzophenone-3 (BP) and butyl methoxydibenzoylmethane (BMDBM), can exhibit photodegradation which limits the development of broad spectrum sunscreens. Previous research verified that rutin interacts with filters incorporated in sunscreens. In this work, we focused on the development and evaluation of the efficacy of the sunscreens containing either BP or BMDBM with and without rutin. The addition of rutin to the UVA filters afforded antioxidant properties to the formulations and they were considered safe for human use. Additionally, rutin in combination with either BP or BMDBM increased the antioxidant activity about 40 times when compared with the UVA filters alone. Remarkably, the addition of rutin 0.1% (w/w) to BP 6.0% (w/w) raised the SPF from 24.3±1.53 to 33.3±2.89. In conclusion, these findings demonstrated that the addition of rutin into sunscreens can markedly improve the antioxidant properties of the formulation as well as photostabilize some of the UVA filters.


Open Preservation Rhinoplasty Using the Piezo Electric Instrument.
Preservation rhinoplasty represents a growing shift in rhinoplasty philosophy toward preserving structurally sound anatomy and reshaping existing nasal structures into esthetic and functional ideals. It is fast gaining popularity owing to the theoretic functional and esthetic benefits of preserving the dorsal keystone area and dorsal esthetic lines. The preservation technique is made more accessible by the open approach, which provides an opportunity for the deformity to be clearly visualized from the tip of the nose to the dorsum, as well as enables greater ease of powered instrument access. The addition of the Piezo-electric device, with its range of rhinoplasty inserts, enables more precise and accurate management of the osseocartilaginous vault, reduces the risk of surface irregularities, and hence optimizes the overall surgical outcome.


Islet-activating protein, pertussis toxin, inhibits Ca2+-induced and guanine nucleotide-dependent releases of histamine and arachidonic acid from rat mast cells.
Islet-activating protein (IAP) suppressed Ca2+-induced histamine release and phospholipase A2 activation in Gpp(NH)p-loaded mast cells. Since the guanine nucleotide-binding protein involved in adenylate cyclase inhibition is known to lose its function upon being ADP-ribosylated by IAP, the nucleotide-binding protein is likely to mediate Ca2+-linked biosignalling leading to histamine secretion.


Interleukin-1 beta is an irradiation-induced stromal growth factor.
Gamma irradiation of tissues and organs leads to many pathological consequences due to the formation of reactive oxygen species, DNA damage and the subsequent massive death of cells. The therapeutic use of gamma irradiation in the treatment of cancer is based on its penetrating power and damaging effects on tumor cells. Other effects from the irradiation are unnoticeable in comparison. Moreover, the long-term consequences of gamma irradiation are still poorly understood. When a donor bone marrow plug is implanted under the renal capsule of a syngeneic animal, а hematopoietic ectopic focus is formed. The size of the focus is increased in mice that received irradiation compared to non-irradiated ones, regardless of the amount of time between irradiation and bone marrow plug implantation. Long-term repetitive injections of blood serum from irradiated mice given to syngeneic non-irradiated recipients of bone marrow plugs also lead to the formation of enlarged foci. Hence, the blood of irradiated animals must contain an activity that induces the growth of a hematopoietic microenvironment. It was previously shown that the bones of irradiated animals secrete a growth factor required to create stromal microenvironments. The identity of this factor has, until now, been difficult to obtain. We demonstrated that interleukin 1 beta (IL-1) stimulates the growth of murine bone marrow stromal cells in vitro and in vivo. It was shown that the expression of the Il1b gene and the secretion of its product, IL-1, were activated in bone cells long after total body gamma irradiation. Hence, IL-1, or proteins regulated by this cytokine, appears to be the same stromal growth factor previously observed in the serum of irradiated animals. Our data demonstrate several non-canonical functions of IL-1. In addition, the presence of up-regulated levels of IL-1 long after irradiation points to an unknown mechanism governing its gene expression.


Intracranial arteriovenous malformations in infancy and adolescence.
Fifteen children and adolescents with intracranial arteriovenous malformations are reviewed and their data analyzed; their ages varied between 1 day and 15 years and there was a slight predominance of males (9 male and 6 female patients). In this series, the arteriovenous malformations appeared clinically as cerebral hemorrhage in 9 cases, epilepsy in 3, mental retardation with epilepsy in 1, subarachnoid hemorrhage in 1, and cardiac insufficiency at birth in the other. The diagnostic procedures used were computerized transmission tomography (CTT) of the cerebrum in 14 cases, cerebral panarteriography in 15, and EEG in 4 cases. Treatment took the form of surgery, radiation therapy, or medication. The last was administered to patients with epilepsy, either as a complement to other modes of treatment or as the only treatment. In all, 4 cases died, 2 for reasons to do with their operations, 1 from a lesion of the brain stem in a hematoma of the cerebellum that had not been surgically treated, and the other from an intraventricular hemorrhage 4 months after surgery. In the last patient, necropsy revealed remnants of the arteriovenous malformation. The overall mortality was thus 26% and the surgical mortality, 12.6%. Of the 11 surviving patients only 3 received anticonvulsant drugs; each of them had a good I.Q. and good marks at school, as did the other 8 survivors.


Photodynamic induction of an oncogenic virus in vitro.
Infectious simian virus 40 (SV40) was induced from SV40-transformed hamster kidney cells by treatment with proflavine and visible fluorescent light. The optimum levels of SV40 induced were about three orders of magnitude above spontaneous background levels observed with untreated cells. No virus induction above background levels was found by treatment of cells with either proflavine or light alone.


Treatment of anaerobic digested effluent in biochar-packed vertical flow constructed wetland columns: Role of media and tidal operation.
Three types of vertical flow constructed wetland columns (VFCWs), packed with corn cob biochar (CB-CW), wood biochar (WB-CW) and gravel (G-CW) under tidal flow operations, were comparatively evaluated to investigate anaerobic digested effluent treatment performance and mechanisms. It was demonstrated that CB-CW and WB-CW provide significantly higher removal efficiencies for organic matter (>59%), NH4+-N (>76%), TN (>37%) and phosphorus (>71%), compared with G-CW (22%-49%). The higher pollutants removal ability of biochar-packed VFCWs was mainly attribute to the higher adsorption ability and microbial cultivation in the porous biochar media. Moreover, increasing the flooded/drained ratio from 4/8h to 8/4h of the tidal operation further improved around 10% of the removal of both organics and NH4+-N for biochar-packed VFCWs. The phosphorus removal was dependent on the media adsorption capacities through the whole experiment. However, the NH4+-N biodegradation by microbial communities was demonstrated to become the dominant removal mechanism in the long term treatment, which compensated the decreased adsorption capacities of the media. The study supported that the use of biochar would increase the treatment performance and elongate the lifespan of CWs under tidal operation.


The eighth version of American Joint Committee on Cancer nodal classification for high grade pancreatic neuroendocrine tumor should be generalized for the whole population with this disease.
Several indexes evaluating the lymph node metastasis of pancreatic neuroendocrine tumor (pNET) have been raised. We aimed to compare the prognostic value of the indexes via the analysis of Surveillance, Epidemiology, and End Results (SEER) database.We identified pNETs patients from SEER database (2004-2015). The prognostic value of N classification which adopted the 8th American Joint Committee on Cancer (AJCC) N classification for well differentiated pNET, revised N classification (rN) which adopted the AJCC 8th N classification for exocrine pancreatic cancer (EPC) and high grade pNET, lymph node ratio and log odds of positive nodes were analyzed.A total of 1791 eligible patients in the SEER cohort were included in this study. The indexes N, rN, lymph node ratio, and log odds of positive nodes were all significant independent prognostic factors for the overall survival. Specifically, the rN had the lowest akaike information criterion of 4050.19, the highest likelihood ratio test (χ) of 48.87, and the highest C-index of 0.6094. The rN was significantly associated with age, tumor location, tumor differentiation, T classification and M classification (P < .05 for all).The 8th version of AJCC N classification for high grade pNET could be generalized for the pNET population.


Family-size and birth-order in obsessional neurosis.
Family size and birth-order of 156 British-born patients diagnosed as having obsessive-compulsive neurosis were determined from case-notes; these were compared with matched controls. Separate consideration was given to male and female patients. Mean family size of obsessionals was found to be smaller than that of controls. An excess of first-born was found among male obsessional patients.


Evaluation of tumour extension by whole body scanner.
Fifteen patients with urinary bladder carcinoma were examined by computerised tomography parallel with conventional urography before, during and after radiation therapy. Computer tomography gave better diagnostic information in the cases in which the tumour had encroached upon, or was growing outside the bladder wall, and was equally as valuable as urography when it was located wholly within the bladder. The scans were of great value as a guide in the planning of computer-aided radiation therapy.


Accessing Bioactive Hydrazones by the Hydrohydrazination of Terminal Alkynes Catalyzed by Gold(I) Acyclic Aminooxy Carbene Complexes and Their Gold(I) Arylthiolato and Gold(III) Tribromo Derivatives: A Combined Experimental and Computational Study.
Hydrohydrazination of terminal alkynes with hydrazides yielding hydrazones 5-14 were successfully catalyzed by a series of gold(I) acyclic aminooxy carbene complexes of the type [{(4-R2-2,6-t-Bu2-C6H2O)(N(R1)2)}methylidene]AuCl, where R2 = H, R1 = Me (1b); R2 = H, R1 = Cy (2b); R2 = t-Bu, R1 = Me (3b); R2 = t-Bu, R1 = Cy (4b). The mass spectrometric evidence corroborated the existence of the catalytically active solvent-coordinated [(AAOC)Au(CH3CN)]SbF6 (1-4)A species and the acetylene-bound [(AAOC)Au(HC≡CPhMe)]SbF6 (3B) species of the proposed catalysis cycle. The hydrohydrazination reaction was successfully employed in synthesizing several bioactive hydrazone compounds (15-18) with anticonvulsant properties using a representative precatalyst (2b). The DFT studies favored the 4-ethynyltoluene (HC≡CPhMe) coordination pathway over the p-toluenesulfonyl hydrazide (NH2NHSO2C6H4CH3) coordination pathway, and that proceeded by a crucial intermolecular hydrazide-assisted proton transfer step. The gold(I) complexes (1-4)b were synthesized from the {[(4-R2-2,6-t-Bu2-C6H2O)(N(R1)2)]CH}+OTf- (1-4)a by treatment with (Me2S)AuCl in the presence of NaH as a base. The reactivity studies of (1-4)b yielded the gold(III) [{(4-R2-2,6-t-Bu2-C6H2O)(N(R1)2)}methylidene]AuBr3 (1-4)c complexes upon reaction with molecular bromine and the gold(I) perfluorophenylthiolato derivatives, [{(4-R2-2,6-t-Bu2-C6H2O)(N(R1)2)}methylidene]AuSC6F5 (1-4)d, upon treatment with C6F5SH.


Block nursing. Practicing autonomous professional nursing in the community.
One of the most interesting settings for nursing is on the block where you live. Jamieson describes a thriving program of block nursing that is reminiscent of earlier eras when a nurse was involved with a total community and all its citizens. Cost-effective, this community program provides nursing in a humanistic way that enables many people to remain in their own homes and in their own community.


Robust design of a multirotor aerial vehicle.
This paper introduces the methodology of systematic robust design of a multirotor vehicle as an example of how to carry out the robust design of a physical system. Robustness in aerial vehicles is highly desirable as it guarantees a desired level of performance even under environmental uncertainties. Thus far, robustness has been considered in terms of active control in the space of multirotor vehicles, but exploration of the design space itself is lacking. In this work, a conceptual design followed by a robust design is performed to come up with the specifications that lead to least uncertain performance of the multirotor vehicle with respect to stochastic wind disturbances.


Doctor-patient discussions of alternative medicine for back pain.
To document the frequency of conversations about alternative medicine during primary care consultations for back pain in diverse settings. "Exit interview" type patient survey. General practices in Seattle, Washington; rural Israel; and Birmingham, England. A convenience sample of 218 adults completing a doctor visit for back pain. Frequencies of doctor-patient discussions of alternative medicine. Alternative medicine was discussed in a minority of visits (US site 40%, Israel site 37%, UK site 14%, p < 0.05). At each site, patients initiated at least half of the discussions. Users were five to six times more likely to discuss alternative medicine with their doctor than non-users (p < 0.05 for comparison at each site). The percentage of patients who used alternative medicine but left the consultation without discussing it was similar at all sites (US site 17%, Israel site 23%, UK site 15%). Discussions of alternative medicine occurred in a minority of consultations for back pain although the rate varied considerably by site. Discussions were initiated primarily by patients who use it.


Maximal Lactate Steady State Versus the 20-Minute Functional Threshold Power Test in Well-Trained Individuals: "Watts" the Big Deal?
To (1) compare the power output (PO) for both the 20-minute functional threshold power (FTP20) field test and the calculated 95% (FTP95%) with PO at maximal lactate steady state (MLSS) and (2) evaluate the sensitivity of FTP95% and MLSS to training-induced changes. Eighteen participants (12 males: 37 [6] y and 6 females: 28 [6] y) performed a ramp-incremental cycling test to exhaustion, 2 to 3 constant-load MLSS trials, and an FTP20 test. A total of 10 participants returned to repeat the test series after 7 months of training. The PO at FTP20 and FTP95% was greater than that at MLSS (P = .00), with the PO at MLSS representing 88.5% (4.8%) and 93.1% (5.1%) of FTP and FTP95%, respectively. MLSS was greater at POST compared with PRE training (12 [8] W) (P = .002). No increase was observed in mean PO at FTP20 and FTP95% (P = .75). The results indicate that the PO at FTP95% is different to MLSS, and that changes in the PO at MLSS after training were not reflected by FTP95%. Even when using an adjusted percentage (ie, 88% rather than 95% of FTP20), the large variability in the data is such that it would not be advisable to use this as a representation of MLSS.


Impact of body mass index on in-hospital mortality for six acute cardiovascular diseases in Japan.
Body mass index (BMI) distribution and its impact on cardiovascular disease (CVD) vary between Asian and western populations. The study aimed to reveal time-related trends in the prevalence of obesity and underweight and safe ranges of BMI in Japanese patients with CVD. We analyzed 5,020,464 records from the national Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination dataset over time (2012-2019) and evaluated BMI trends and the impact on in-hospital mortality for six acute CVDs: acute heart failure (AHF), acute myocardial infarction (AMI), acute aortic dissection (AAD), ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). Patients were categorized into five groups using the WHO Asian-BMI criteria: underweight (< 18.5 kg/m2), normal (18.5-22.9 kg/m2), overweight at risk (23.0-24.9 kg/m2), obese I (25.0-29.9 kg/m2), and obese II (≥ 30.0 kg/m2). Age was significantly and inversely related to high BMI for all diseases (P < 0.001). The proportion of BMI categories significantly altered over time; annual BMI trends showed a significant and gradual increase, except AAD. In adjusted mixed models, underweight was significantly associated with a high risk of in-hospital mortality in all CVD patients (AHF, OR 1.41, 95% CI 1.35-1.48, P < 0.001; AMI, OR 1.27, 95% CI 1.20-1.35, P < 0.001; AAD, OR 1.23, 95% CI 1.16-1.32, P < 0.001; IS, OR 1.45, 95% CI 1.41-1.50, P < 0.001; ICH, OR 1.18, 95% CI 1.13-1.22, P < 0.001; SAH, OR 1.17, 95% CI 1.10-1.26, P < 0.001). Moreover, obese I and II groups were significantly associated with a higher incidence of in-hospital mortality, except AHF and IS. Age was associated with in-hospital mortality for all BMI categories in six CVD patients. BMI increased annually in patients with six types of CVDs. Although underweight BMI was associated with high mortality rates, the impact of obesity on in-hospital mortality differs among CVD types.


A case of vagal palsy due to dissecting aneurysm of the carotid artery.
A case of unilateral vagus palsy due to spontaneous painless dissection of the left internal carotid artery is reported. The anatomy of the extracranial course of the vagus nerve and the differential diagnosis of unilateral vagal palsy are discussed.


Impact of Extending the Timing of Maternal Pertussis Vaccination on Hospitalized Infant Pertussis in England, 2014-2018.
In October 2012, a maternal pertussis vaccination program was introduced in England for women between 28 and 32 weeks of pregnancy. In April 2016, the recommended optimal window was extended to 20-32 weeks to improve vaccine coverage and protect preterm infants. This study assesses the impact of offering maternal pertussis vaccination earlier in pregnancy on hospitalized infant pertussis cases. Hospitalized pertussis cases ≤60 days old in England were extracted from Hospital Episode Statistics pre- and post-policy change. Data were linked to laboratory-confirmed cases, and clinical records were reviewed where cases were not matched. Maternal vaccine status of identified cases was established. Median hospital duration was calculated, and a competing risk survival analysis was undertaken to assess multiple factors. A total of 201 cases were included in the analysis. Of the 151 cases with reported gestational age, the number of hospitalizations among full-term infants was 60 cases pre-policy and 62 cases post-policy, respectively, while preterm cases declined from 20 to 9 (P = .06). Length of hospital stay did not differ significantly after the policy change. Significantly longer hospital stays were seen in cases aged 0-4 weeks (median of 3 more days than infants aged 5-8 weeks), premature infants (median of 4 more days than term infants), and cases with coinfections (median of 1 more day than those without coinfection). The number of preterm infants hospitalized with pertussis in England was halved after the policy change and preterm infants were no longer overrepresented among hospitalized cases.


New-onset cutaneous kaposi's sarcoma following SARS-CoV-2 infection.
COVID-19 is associated with several cutaneous manifestations, including chilbain-like lesions, urticaria, erythema multiforme, and maculopapular lesions. Dermatoses may be directly linked to the viral infection or also represent a consequence of systemic therapies administrated for COVID-19. A potential role of SARS-CoV-2 in triggering the reactivation of other viruses, such as HHV-6, HHV-7 and Epstein-Barr virus has been hypothesized. To better understand and hypothesize possible pathogenetic correlations of COVID-19 with other dermatological conditions. We report the case of an 83-year-old woman hospitalized in a nursing home for several years. On November 2020, the patient had been diagnosed with SARS-CoV-2 infection, with repeated positive swabs until January 2021. After a month, new-onset asymptomatic cutaneous purplish macular lesions and violaceous patches occurred bilaterally on the feet. An incisional cutaneous biopsy and the histological examination of the plantar lesion revealed the diagnosis of Kaposi Sarcoma. We report a unique case of new-onset bilateral Kaposi's sarcoma following COVID-19, speculating on a possible role of SARS-CoV-2 in the reactivation of human herpes virus-8 (HHV-8) infection.


Innervation of the intrapulmonary bronchi of the female Funambulus pennanti.
Ganglia of various shapes (rounded, oval and irregular) and of large, medium and small size were recorded on, or near, the bronchial wall either in free form or arranged in chain-like fashion. Most of the ganglia were AChE-positive and connected with the myelinated nerve fibres.


A comparison of carbon black with soot.
Carbon black is frequently confused with soot. In order to clarify the distinction between these materials, we have examined 6 carbon blacks and 18 samples of soot. Carbon black is composed of turbostratic colloidal aggregates which we call aciniform carbon (AC). Chimney soots from domestic wood or coal fires contain very little AC, while in diesel soots the solid particulates are essentially all AC. All soots examined contain much more extractable organic material and/or ash than does carbon black. Ames Salmonella assays were carried out on solvent extracts. The results were calculated as net revertants per mg of the original soot or carbon black. On this basis, the majority of the soot extracts assayed were at a much higher level of mutagenicity than any of the carbon black extracts. For several reasons, even greater differences in mutagen availability would be expected if the unextracted materials were compared in vivo.


Who can get the next Nobel Prize in infectious diseases?
The aim of this paper is to deliver a perspective on future Nobel prizes by reviewing the features of Nobel prizes awarded in the infectious diseases-related (IDR) field over the last 115 years. Thirty-three out of 106 Nobel prizes (31%) in Physiology or Medicine have been awarded for IDR topics. Out of 58 Nobel laureates for IDR topics, two have been female; 67% have been medical doctors. The median age of Nobel laureates in Physiology or Medicine was found to be lower than the median age of laureates in Literature (p<0.001). Since the Second World War, US-affiliated scientists have dominated the Nobel prizes (53%); however before 1945, German scientists did so (p=0.005). The new antimicrobials received Nobel prizes until 1960; however no treatment study was awarded the Prize until the discovery of artemisinin and ivermectin, for which the Nobel Prize was awarded in 2015. Collaborative works have increasingly been appreciated. In the future, more female laureates would be expected in the IDR field. Medical graduates and scientists involved in multi-institutional and multidisciplinary collaborative efforts seem to have an advantage.


Evaluation of in-vitro dissolution and in-vivo absorption for two different film-coated pellets of clarithromycin.
The aim of this study was to compare two formulations of film-coated pellets containing clarithromycin after single oral dose study in healthy male volunteers. Two formulations with different coating polymers were prepared: formulation-1 (F-1) was prepared by incorporating three kinds of pH-dependent gradient-release coated pellets into capsules and formulation-2 (F-2) was prepared by coated with an insoluble semiosmotic film. Release profiles of film-coated pellets were evaluated using paddle method under different conditions. Pharmacokinetic profiles of these formulations were obtained in three healthy male volunteers and compared to commercially available immediate release (IR) tablets. The relative bioavailability based on the AUC0-24h was found to be 96.2% and 58.7% for F-1 and F-2 compared with IR, and the Tmax was delayed.


Completely nonfluoroscopic catheter ablation of left atrial arrhythmias and ventricular tachycardia.
Fluoroscopy use during catheter ablation procedures increases the cumulative lifetime radiation exposure of patients and operators, potentially leading to a higher risk of cancer and radiation-related injuries. Nonfluoroscopic ablation (NFA) has been described for supraventricular tachycardia, typical atrial flutter, paroxysmal atrial fibrillation (AF), and outflow-tract ventricular tachycardia (VT). Complete transition to NFA of more complex arrhythmias, including persistent AF, left atrial (LA) flutter, and structural VT, has not been previously described. We describe the transition to completely NFA of complex arrhythmias, including LA flutter and structural VT. The techniques, challenges, limitations, and results are described. Complex ablation procedures were performed using intracardiac echocardiography (ICE) and a three-dimensional mapping system without fluoroscopy or lead protection. Eighty consecutive patients underwent NFA (mean age, 60.1 ± 9.9 years, 70 with LA arrhythmias, 10 with VT). All cases were performed without the need for rescue fluoroscopy. There was an initial increase in procedural time for ablation of LA arrhythmias upon transitioning to NFA. However, after excluding the first 20 NFA cases to allow for operator learning, the transition to NFA was not associated with an increase in mean procedural time (229 ± 38 vs 225 ± 32 minutes; P = 0.002 for noninferiority). All procedures were completed successfully with no complications. NFA of most complex arrhythmias (persistent AF, LA flutter, and structural VT) is feasible, with a modest learning curve and no increase in procedural times.


Hypothesis: Urbanization and exposure to urban heat islands contribute to increasing prevalence of kidney stones.
The prevalence of kidney stones is increasing worldwide. Various etiologies may in part explain this observation including increased prevalence of diabetes, obesity and the metabolic syndrome, increased dietary protein and salt content, and decreased dietary dairy products. We hypothesize an additional and novel potential contributor to increasing kidney stone prevalence: migration to urban settings, or urbanization, and resultant exposure of the population to the higher temperatures of urban heat islands (UHIs). Both urbanization and exposure to UHIs are worldwide, continuous trends. Because the difference in temperature between rural and urban settings is greater than the increase in temperature caused by global warming, the potential effect of urbanization on stone prevalence may be of greater magnitude. However, demonstration of a convincing link between urbanization and kidney stones is confounded by many variables simultaneously affected by migration to cities, such as changes in occupation, income, and diet. No data have yet been published supporting this proposed association. We explore the plausibility and limitations of this possible etiology of increasing kidney stone prevalence.


Critical Southern Ocean climate model biases traced to atmospheric model cloud errors.
The Southern Ocean is a pivotal component of the global climate system yet it is poorly represented in climate models, with significant biases in upper-ocean temperatures, clouds and winds. Combining Atmospheric and Coupled Model Inter-comparison Project (AMIP5/CMIP5) simulations, with observations and equilibrium heat budget theory, we show that across the CMIP5 ensemble variations in sea surface temperature biases in the 40-60°S Southern Ocean are primarily caused by AMIP5 atmospheric model net surface flux bias variations, linked to cloud-related short-wave errors. Equilibration of the biases involves local coupled sea surface temperature bias feedbacks onto the surface heat flux components. In combination with wind feedbacks, these biases adversely modify upper-ocean thermal structure. Most AMIP5 atmospheric models that exhibit small net heat flux biases appear to achieve this through compensating errors. We demonstrate that targeted developments to cloud-related parameterisations provide a route to better represent the Southern Ocean in climate models and projections.


The experiences of school-age children with a tracheostomy.
The purpose of this study was to explore the school-age child's perspective about living with a tracheostomy. A qualitative design using phenomenological methods was used to describe and interpret the lived experiences of school-age children with a tracheostomy. The perceptions of five children were explored, and three themes emerged: "I'm the only one," "friends are helpful," and "just tell them." Data indicated that encouraging friendships with other children enhances the well-being of the child with a tracheostomy. In addition, data suggested that when schoolmates understand the experiences of children with tracheostomies, they are supportive of the child. Nurse practitioners are in a unique position to assist the child with a tracheostomy in the development of peer networks.


Machine learning algorithm to predict anterior cruciate ligament revision demonstrates external validity.
External validation of machine learning predictive models is achieved through evaluation of model performance on different groups of patients than were used for algorithm development. This important step is uncommonly performed, inhibiting clinical translation of newly developed models. Machine learning analysis of the Norwegian Knee Ligament Register (NKLR) recently led to the development of a tool capable of estimating the risk of anterior cruciate ligament (ACL) revision ( https://swastvedt.shinyapps.io/calculator_rev/ ). The purpose of this study was to determine the external validity of the NKLR model by assessing algorithm performance when applied to patients from the Danish Knee Ligament Registry (DKLR). The primary outcome measure of the NKLR model was probability of revision ACL reconstruction within 1, 2, and/or 5 years. For external validation, all DKLR patients with complete data for the five variables required for NKLR prediction were included. The five variables included graft choice, femur fixation device, KOOS QOL score at surgery, years from injury to surgery, and age at surgery. Predicted revision probabilities were calculated for all DKLR patients. The model performance was assessed using the same metrics as the NKLR study: concordance and calibration. In total, 10,922 DKLR patients were included for analysis. Average follow-up time or time-to-revision was 8.4 (± 4.3) years and overall revision rate was 6.9%. Surgical technique trends (i.e., graft choice and fixation devices) and injury characteristics (i.e., concomitant meniscus and cartilage pathology) were dissimilar between registries. The model produced similar concordance when applied to the DKLR population compared to the original NKLR test data (DKLR: 0.68; NKLR: 0.68-0.69). Calibration was poorer for the DKLR population at one and five years post primary surgery but similar to the NKLR at two years. The NKLR machine learning algorithm demonstrated similar performance when applied to patients from the DKLR, suggesting that it is valid for application outside of the initial patient population. This represents the first machine learning model for predicting revision ACL reconstruction that has been externally validated. Clinicians can use this in-clinic calculator to estimate revision risk at a patient specific level when discussing outcome expectations pre-operatively. While encouraging, it should be noted that the performance of the model on patients undergoing ACL reconstruction outside of Scandinavia remains unknown. III.


Polylysine-modified polyethylenimine polymer can generate genetically engineered mesenchymal stem cells for combinational suicidal gene therapy in glioblastoma.
Glioblastoma remains the most resistant malignant brain tumor owing to the lack of an efficient delivery system for therapeutic genes or drugs, especially in outgrowing tumor islands. Cell-based delivery systems such as mesenchymal stem cells (MSCs) are a potential candidate in this regard. Conventionally, MSCs have been genetically modified for cancer therapy by using viral vectors that can illicit oncogenicity and limit their use in clinical trials. In this study, we have used nonviral agents such as the polylysine-modified polyethylenimine (PEI-PLL) copolymer to generate genetically engineered MSCs with suicidal genes, namely, HSV-TK and TRAIL. Our results demonstrated that an intratumoral injection of polymer-double-transfected MSCs along with prodrug ganciclovir injections can induce a significant synergistic therapeutic response both in vitro and in vivo compared to single plasmid transfections or untransfected MSCs. The proliferation marker Ki67 and the angiogenesis marker VEGF were also significantly reduced in treatment groups, whereas the TUNEL assay demonstrated that apoptosis is significantly increased after treatment. Our findings suggest that the PEI-PLL copolymer can successfully modify MSCs with therapeutic genes and can produce a pronounced impact during glioblastoma therapy. This study proposes a potential nonviral approach to develop a cell-based therapy for the treatment of glioma. STATEMENT OF SIGNIFICANCE: In this study, we have used a polylysine-modified polyethylenimine polymer (PEI-PLL) copolymer, a non viral transfection agent, for gene delivery in mesenchymal stem cells. These PEI-PLL-transfected mesenchymal stem cells with HSV-TK and TRAIL genes have the potential to treat glioma both in vitro and in vivo. This combinational therapy through PEI-PLL-transfected mesenchymal stem cells can provide cost-effective, low immunogenic, and tumor-targeted delivery of suicideal genes (HSV-TK and TRAIL) for promising glioblastoma treatment.


Optimized sample preparation for isotopic analyses of CO2 in air: systematic study of precision and accuracy dependence on driving variables during CO2 purification process.
A systematic analysis of efficiency, reproducibility and accuracy of cryogenic purification of CO(2) from air samples for isotopic analyses is presented. The technical characteristics of the cryogenic line are given in detail. To study the cryogenic process, three different operating parameters are considered: flow rate of the gas entering the line, pressure of the gas in the line, and CO(2)-trap shape. Experimental results demonstrate that efficiency, reproducibility and accuracy strongly depend on the CO(2)trap shape. Moreover, a dependence of reproducibility and accuracy on the flow rate of the gas is found, but not on its pressure. High precision (< or =0.02 per thousand for delta(13)C and < or =0.05 per thousand for delta(18)O) and good accuracy (<0.09 per thousand for delta(13)C and <0.14 per thousand for delta(18)O) is achieved after applying the N(2)O correction.


Increased prevalence of pediatric pneumococcal serotypes in elderly adults.
Pneumococcal disease is most prevalent among young children and elderly adults. We explored whether similarities exist in the serotypes that cause disease in these 2 high-risk groups. With use of US population-based data from 1998-1999 (before the introduction of the 7-valent pneumococcal conjugate vaccine [PCV7] as routine immunization for infants) from the Centers for Disease Control and Prevention's Active Bacterial Core surveillance, we evaluated whether the rate of invasive pneumococcal disease caused by the pediatric serotypes (6B, 9V, 14, 19F, and 23F) increased among elderly persons. We adjusted for potential confounders in multivariable logistic regression. We analyzed 2987 pneumococcal isolates recovered from adults. The risk of infection with pediatric serotypes increased from 32.5% in 35-49-year-old persons to 51.2% in > or = 85-year-old persons (P < .001). Compared with 35-49-year-old persons, the risk of infection with pediatric serotypes was significantly elevated among 65-74-year-old persons (relative risk [RR], 1.68; 95% confidence interval [CI], 1.29-2.20) and increased progressively among persons aged 75-84 years (RR, 1.82; 95% CI, 1.41-2.36) and > or = 85 years (RR, 2.29; 95% CI, 1.72-3.05), with adjustment for sex, race, geographic location, underlying illness, and penicillin resistance. The rate of penicillin resistance was also elevated in the elderly population but was not significant after adjustment for serotype and race. The increased proportion of severe pneumococcal disease caused by pediatric serotypes in the elderly population might indicate opportunities for prevention with use of PCV7.


Household slow sand filter to treat groundwater with microbiological risks in rural communities.
Household slow sand filters (HSSFs) improve the quality of life in rural communities as they provide safe water. However, HSSFs require time for the growth of the biological layer (schmutzdecke) to achieve maximum performance, especially when groundwater is used as it normally has few nutrients. In this ripening period, pathogenic microorganisms can pass through the filter. In this context, this study reports the performance of two HSSF settings, intermittent (I-HSSF) and continuous (C-HSSF) flows followed by disinfection with sodium hypochlorite to treat groundwater with Escherichia coli, Giardia muris cysts and Cryptosporidium parvum oocysts. The weekly introduction of river water was tested as a filter-ripening agent and this procedure reduced the ripening time in approximately 80 days. Filtered water disinfection improved the water quality and inactivated protozoa. The costs and operational challenges addressed in this study can provide support to HSSF technology transfer in rural communities worldwide.


Cost containment interventions introduced on the community drugs schemes in Ireland-evaluation of expenditure trends using a national prescription claims database.
The majority of pharmaceutical expenditure in Ireland occurs in the community for services provided by general practitioners and pharmacists. In the current national and international economic climate, it is anticipated that demand on these services will continue to grow. The aim of this article was to examine trends in expenditure of pharmaceuticals on the Community Drugs Schemes from 2005 to 2010, and to examine the impact of cost-containment interventions on expenditures that were introduced at this time and affected the pricing mechanism for pharmaceuticals in Ireland. Prescription data were analyzed using an Irish national prescription claims database according to drug category, that is, generic, patent, and off patent for the 2 largest schemes; the publicly funded General Medical Services (GMS) Scheme and copayment Drugs Payment (DP) Scheme. Segmented regression analysis of interrupted time series was used to analyze the effects of the interventions on expenditure. An increase in expenditure was noted across all schemes up to 2009 and declined thereafter to the end of the study period (October 2010). Significant reductions in expenditure were noted after introduction of a 20% price cut to patent-expired products (off patents) (P < 0.001). In July 2009, pharmacy and wholesale margins were reduced, resulting in significant reductions in expenditure for patented (GMS Scheme: P < 0.05 and DP Scheme: P < 0.001) and generic (DP Scheme only: P < 0.01) products. Significant reductions in expenditure were noted for off-patent products on the GMS Scheme at this time (P < 0.01). No significant reductions in expenditure were noted for off patents after a 15% price reduction in January 2009. An additional 40% price reduction in February 2010 resulted in significant reductions in expenditure for off-patent products on both the GMS (P < 0.01) and DP Scheme (P < 0.05). Results from this study, based on a section of the total population of Ireland during a 6-year period, indicate that reductions in the wholesale margin and pharmacy markup had the largest impact on reducing pharmaceutical expenditure during the study period.


Mechanical ventilation in the prone position for acute respiratory failure after cardiac surgery.
Ten patients with acute respiratory failure (ARF) after coronary artery bypass grafting were studied during conventional mechanical ventilation in the supine and in the prone position. Impaired gas exchange was defined as an inspired oxygen fraction (FIO2) greater than 0.5 to maintain an arterial oxygen tension (PaO2) > or = 70 mmHg, an alveolar-arterial PaO2 gradient (PA-aO2) > 200 mmHg and a venous admixture (QVA/QT) > 15% during mechanical ventilation with a tidal volume (VT) = 10 to 12 mL/kg, frequency (f) = 10 to 15 VT/min, inspiratory-expiratory (I:E) ratio = 0.5, and positive end-expiratory pressure (PEEP) of 5 to 7.5 cm H2O. In the supine position, systemic and pulmonary hemodynamics were in the normal range, but oxygenation was severely impaired. In all patients thoracic computed tomography scans were obtained and revealed crest-shaped bilateral densities in the dependent lung regions. FIO2 of 0.67 +/- 0.22 was required to maintain a PaO2 greater than 70 mmHg during mechanical ventilation in the supine position. Under these conditions PA-aO2 and QVA/QT were 362 +/- 153 mmHg and 32.5 +/- 8.3%, respectively. CO2 elimination was not severely affected. The patients were turned into the prone position after an average of 30.6 +/- 5.4 hours postoperatively and ventilated with unchanged VT, f, PEEP, and inspiratory-expiratory ratio for 26.7 +/- 11.7 hours (range, 10 to 42 hours). A second cardiopulmonary status was obtained within 2 to 5 hours of ventilation in the prone position.(ABSTRACT TRUNCATED AT 250 WORDS)


Nimodipine does not affect cerebral lactate levels following complete ischemia in dogs.
Nimodipine is known to improve postischemic cerebral blood flow (CBF) and neurologic outcome in experimental animals. Whether or not the two observations are related is unknown. This study searched for a possible improved rate of brain metabolic recovery in animals treated with nimodipine postischemia. Complete cerebral ischemia was produced for 11 min in 16 dogs, followed by reperfusion for 70 min. Prior to ischemia, glucose was administered (0.75 g X kg-1) in 12 dogs. Half of the glucose-treated dogs were given i.v. nimodipine, beginning 5 min postischemia (10 micrograms X kg-1 bolus followed by 1 microgram X kg-1 X min-1). The other half were given only saline postischemia. The remaining four dogs were given no glucose and received saline only postischemia. In all dogs, serial brain biopsies were taken at 2, 20, 40, and 70 min postischemia. In 5 dogs, the integrity of the blood-brain barrier (BBB) was tested by injection of Evans blue dye and postmortem examination of the brains. Brain biopsies were assayed for concentrations of phosphocreatine, ATP, ADP, AMP, glucose, lactate, and pyruvate. In all dogs, there was rapid restoration of a normal brain energy state following reperfusion. Brain lactate had returned to near normal in all dogs by 70 min postischemia, and the rate of lactate depletion was not different between groups. The integrity of the BBB was only minimally affected. A portion of the brain lactate was converted to pyruvate rather than crossing the BBB.(ABSTRACT TRUNCATED AT 250 WORDS)


Improvement of phencyclidine-induced social behaviour deficits in rats: involvement of 5-HT1A receptors.
We have recently shown that sub-chronic phencyclidine (PCP) treatment produces social behaviour deficits in female rats which are reversed by ziprasidone but not haloperidol or clozapine. This investigation was designed to extend the previous findings and identify the role of 5-HT(1A) receptors in mediating the effects of these drugs in this model. Female hooded-Lister rats received vehicle (n=36; intraperitoneal (i.p.)) or PCP (n=22; 2mg/kg, i.p.) twice daily for 7 days, followed by a 7-day washout period. On test days, PCP-treated rats were treated acutely with aripiprazole (5mg/kg, s.c.) or WAY100635 (0.5mg/kg, i.p.) alone and in combination. In a second experiment, PCP-treated rats were treated acutely with either fluoxetine (2.5mg/kg, i.p.) or chlordiazepoxide (CDP) (2.5mg/kg, i.p.) all 30 min prior to testing. For the test, pairs of unfamiliar rats receiving acute doses of drugs described above were placed in the test arena and social behaviours (following, sniffing, climbing over and under, exploration of inanimate object and avoiding) were recorded on video for subsequent blind scoring. The results showed that PCP-induced deficits in social behaviours were reversed by acute treatment with both aripiprazole and fluoxetine but not CDP or WAY100635. Furthermore, pre-treatment with WAY100635 prevented the reversal of social behaviour deficits observed with aripiprazole. These findings suggest that the beneficial effects of drugs such as aripiprazole and fluoxetine on PCP-induced social behaviour deficits, a potential model of negative symptoms of schizophrenia, may be a consequence of modifications of the serotonergic system, in particular through an interaction with 5-HT(1A) receptors.


Intensive adsorption of tetracycline by cobalt oxide quantum dots-loaded mineral carbon.
Spent bleaching earth (SBE), a waste by-product produced from the bleaching step of edible oil by montmorillonite clays (bleaching earth), causes serious public health and environmental problems. Accordingly, in this study, SBE was pyrolyzed to yield mineral carbon materials (SBE@C) and cobalt oxide (Co3O4) was loaded to improve the active site of those materials. Due to the carrier function of SBE@C, ultra-fine Co3O4 quantum dots (QDs) (2-6 nm) were homogeneously and robustly immobilized onto SBE@C. The obtained adsorbent exhibited high regeneration performance and an outstanding adsorption capacity (253.36 mg/g). It can be attributed to the surface complexation of cobalt with TC being the dominant process contributing to adsorption behavior. Further, Co3O4 QDs-SBE@C still maintained adequate sorption capacity at a broad range of pH values and in the presence of co-occurring ions. These results suggested the significant application potential of SBE and demonstrated the efficiency of using Co3O4 QDs-SBE@C for wastewater remediation.


Separation of membrane currents using a Paramecium mutant.
The net membrane current of the electrically excitable membrane of Paramecium during step depolarisations was measured using voltage-clamp techniques. The mutant, pawn B, lacks a functional Ca channel. Thus the difference between the total current measured in the wild type and the leakage and rectification currents measured in the pawn mutant is the Ca current. These findings were confirmed by ion substitution experiments. The possibility that inactivation may be apparent only, and caused by a hypothetical, superposed, Ca-induced, rectifying K+ current was eliminated.


Puerarin protects mouse liver against nickel-induced oxidative stress and inflammation associated with the TLR4/p38/CREB pathway.
Nickel (Ni), one of hazardous environmental chemicals, is known to cause liver injury. Accumulating evidence showed that puerarin (PU) possessed comprehensive biological effects. The purpose of the current study was to test the hypothesis that the puerarin protects against enhanced liver injury caused by Ni in mice. ICR mice received intraperitoneally nickel sulfate (20 mg/kg/body weight, daily) for 20 days, and puerarin (200 and 400 mg/kg/body weight) was applied before Ni exposure. The results indicated that puerarin markedly inhibited Ni-induced liver injury, which was characterized by decreased aminotransferase activities and inflammation. Puerarin also inhibited the oxidative stress and decreased the metallothionein (MT) levels. Puerarin decreased the level of pro-inflammatory cytokines TNF-α and IL-6 in livers. Puerarin significantly inhibited the TLR4 activation and p38 MAPK phosphorylation, which in turn inhibited NF-κB activity. Likewise, Ni-induced inflammatory responses were diminished by puerarin as observed by a remarkable reduction in the levels of phosphorylated CREB. Furthermore, puerarin also reduced inflammatory mediators such as cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) levels in livers. Data from this study suggested that the inhibition of Ni-induced oxidative stress and inflammatory responses by puerarin is due to its ability to modulate the TLR4/p38/CREB signaling pathway.


Effect of percutaneous coronary intervention on coronary blood flow at rest in myocardial sites remote from the intervention site in patients with stable angina pectoris.
Little is known about changes in myocardial perfusion of myocardial regions supplied by angiographically normal or near-normal coronary arteries after percutaneous coronary intervention (PCI) of the target lesion. The purpose of this study was to assess the effect of PCI on coronary blood flow at rest in sites remote from the PCI. We studied 85 patients who underwent successful elective PCI for stable angina. We used the Thrombolysis In Myocardial Infarction frame count to provide a simple continuous index of coronary flow and myocardial perfusion in the target and nontarget arteries. Coronary artery diameters of nontarget vessels did not significantly differ before and after PCI and at 6 months' follow-up. At baseline, the greater the percent diameter stenosis in the target artery, the slower the flow in the target (r = 0.22, p <0.01) and nontarget arteries (r = 0.28, p <0.01). Relief of stenosis using PCI did not account for simultaneous changes in epicardial coronary blood flow of the nontarget artery. After 6 months, coronary blood flow improved in both the target (p <0.05) and nontarget arteries (p = 0.007). In conclusion, this study provided evidence of a functional link between coronary blood flow in diseased and nondiseased arteries. Relief of a significant stenosis using PCI globally improved regional and global myocardial blood flow at rest in patients with stable angina. Flow improvement was not apparent at the time of revascularization, but at 6 months' follow-up. Late upturn of the microcirculation may account for delayed recovery of myocardial perfusion.


[State policy of development of resort business in Russia: legal and organizational aspects, including those in an emergency].
To analyze the normative and regulatory support of the state policy of development of health resort business in Russia and organizational and methodological aspects of its implementation, including those in emergency and coronavirus pandemic. The following current methods of community hygienic and medical-organizational research were applied: analytical, statistical, best practice study, monographic, etc. Data from state and departmental official sources, statistical books, scientific publications, and other sources were studied. The main normative, regulatory, organizational and methodological aspects of the strategy implementation, developed in accordance with the order of the Government of the Russian Federation «On approval of the development strategy of the health-resort complex of the Russian Federation» dated 26.11.18 №2581-p were analyzed. Some discrepancies in the state and departmental statistics of health-resort organizations were found. The nomenclature of the health-resort area was reviewed, and the used term «health-resort treatment» was criticized, which does not correspond to the parts of this type of daily practice medical care, unlike the concepts «health-resort care» or «health-resort business». The article presents the author's vision of the issue of normative and organizational support of health-resort organizations in an emergency such as COVID-19 pandemic since 2020. It is shown that the national and local experience of coronavirus infection control contributed to the development of a considerable number of federal regulatory documents in a short time frame. The publication describes an analysis and systematic review of the most important documents, including those related to the spa resorts. Addressing the demanding challenges of further development of the country's health-resort complex largely relies on the state of its facilities and resources. However, its objective analysis is hindered by the identified significant discrepancies in the state and departmental statistic data concerning the number of functioning health-resort organizations and its change over time. As opposed to the concept of «health-resort treatment», the term «health-resort care» most accurately describes its complexity.


Organorhodium(III)- and Iridium(III)-Substituted 20-Tungstobismuthates(III) and -Antimonates(III), [(MCp*)2X2W20O70]10- (M = RhIII and IrIII; X = BiIII and SbIII).
The synthesis of four organometallic RhCp*- and IrCp*-containing heteropoly-20-tungstates, [{RhCp*}2Bi2W20O70]10- (1), [{IrCp*}2Bi2W20O70]10- (2), [{RhCp*}2Sb2W20O70]10- (3), and [{IrCp*}2Sb2W20O70]10- (4) has been accomplished by reaction of (MCp*Cl2)2 with [X2W22O74(OH)2]12- in aqueous solution at pH 6 and 70 °C. The four polyanions 1-4 were structurally characterized in the solid state by single-crystal XRD, FTIR, and TGA and in solution by 183W and 13C NMR. For the Rh derivatives 1 and 3 the 183W-103Rh coupling (2 J W-Rh 3.0 Hz) could be identified by 183W NMR.


The activity of milk leukocytes in response to a water-soluble fraction of Mycobacterium phlei in bovine subclinical mastitis.
The effect of a water-soluble fraction (WSF) of a non-pathogenic strain of Mycobacterium phlei was studied in bovine subclinical mastitis (SCM) by measuring the myeloperoxidase and acid phosphatase enzyme levels in the milk leukocytes. Forty-five cows were divided into three equal groups. Group I, consisting of 15 healthy cows, served as the control, whereas groups II and III each contained 15 cows with subclinical mastitis on the basis of a positive reaction in the California mastitis test (CMT). The cows in group II received 100 microg of WSF in 5 ml sterile phosphate-buffered saline, pH 7.4 (PBS) once only, while those in group III received 5 ml sterile PBS daily for 7 days, both treatments being given by the intramammary route. Observations were made up to 30 days after treatment (AT). The CMT of the healthy milk was negative (0), whereas it ranged between 1 and 2 points in SCM. The somatic cell count (SCC) increased significantly (p < 0.05) on day 3, then fell steeply from day 7 up to day 30 AT in the cows in group II. A steady decrease in the total bacterial count (TBC) was observed in the group treated with WSF but the bacterial counts remained high in the groups treated with PBS. The mean acid phosphatase level was enhanced by 119% on day 3 AT in group II but only by 18.7% in the cows in group III. The mean myeloperoxidase level was enhanced by 100% in the cows in group II but only by 18% in those in group III on day 3 AT. This significant reduction in the bacterial load in infected cows caused by intramammary infusion of WSF may be due to activation of the microbicidal activity of the neutrophils, but this requires confirmation.


[Constant-frequency trans-esophageal electric atrial stimulation for evaluation of the severity of illness in patients with stenocardia and the anti-angina effect of erinit].
Constant-frequency transesophageal atrial pacing was used in 87 patients with coronary heart disease concurrent with stable angina pectoris of various functional classes (I-IV). This technique, as a bicycle ergometric test, allows one to assess the functional class of patients with angina and to ascertain the antianginal effect of agents, which was exemplified by erinit given in doses of 80 and 120 mg.


The role of ERK-RSK signaling in the proliferation of intrahepatic biliary epithelial cells exposed to microcystin-leucine arginine.
Microcystin-leucine arginine (MC-LR) is a potent specific hepatotoxin produced by cyanobacteria in diverse water systems, and it has been documented to induce liver injury and hepatocarcinogenesis. However, its toxic effects on intrahepatic biliary epithelial cells have not been invested in detail. In this study, we aimed to investigate the effects of MC-LR exposure on the intrahepatic biliary epithelial cells in the liver. MC-LR was orally administered to mice at 1 μg/L, 7.5 μg/L, 15 μg/L, or 30 μg/L for 180 consecutive days for histopathological and immunoblot analysis. We observed that MC-LR can enter intrahepatic bile duct tissue and induce hyperplasia of mice. Human primary intrahepatic biliary epithelial cells (HiBECs) were cultured with various concentrations of MC-LR for 24 h, meanwhile the cell viability and proteins level were detected. Western blotting analysis revealed that MC-LR increased RSK phosphorylation via ERK signaling. RSK participated in cell proliferation and cell cycle progression. Taken together, after chronic exposure, MC-LR-treated mice exhibited abnormal bile duct hyperplasia and thickened bile duct morphology through activating the ERK-RSK signaling. These data support the potential toxic effects of MC-LR on bile duct tissue of the liver.


[Markers for early detection of alterations in carbohydrate metabolism after acute myocardial infarction].
Undiagnosed abnormal glucose metabolism is often seen in patients admitted with acute myocardial infarction, although there is no consensus on which patients should be studied with a view to establishing an early diagnosis. The present study examines the potential of certain variables obtained upon admission to diagnose abnormal glucose metabolism. A prospective cohort study was carried out. The Intensive Care Unit of Arrixaca University Hospital (Murcia), Spain. A total of 138 patients admitted to the Intensive Care Unit with acute myocardial infarction and without known or de novo diabetes mellitus. After one year, oral glucose tolerance testing was performed. Clinical and laboratory test parameters were recorded upon admission and one year after discharge. Additionally, after one year, oral glucose tolerance tests were made, and a study was made of the capacity of the variables obtained at admission to diagnose diabetes, based on the ROC curves and multivariate analysis. Of the 138 patients, 112 (72.5%) had glucose metabolic alteration, including 16.7% with diabetes. HbA1c was independently associated with a diagnosis of diabetes (RR: 7.28, 95%CI 1.65 to 32.05, P = .009), and showed the largest area under the ROC curve for diabetes (0.81, 95%CI 0.69 to 0.92, P = .001). In patients with acute myocardial infarction, HbA1c helps identify those individuals with abnormal glucose metabolism after one year. Thus, its determination in this group of patients could be used to identify those subjects requiring a more exhaustive study in order to establish an early diagnosis.


Ca10(PO4)6(OH)2-modified carbon-paste electrode for the determination of trace lead(II) by square-wave voltammetry.
The analytical performance of hydroxyapatite Ca10(PO4)6(OH)2(HAp) screen-printed sensors designed for the detection of metals was evaluated. The hydroxyapatite plays an important role in modern analytical electrochemistry due to their usefulness for the preparation of sensors giving rise to improved responses from metals. The suitable HAp-modified carbon-paste electrode (HAp-CPE) for the electrochemical determination of lead is illustrated in this work using cyclic and square-wave voltammetry in the potential range between -0.3 and -0.8V. Perchlorate acid solution (1.0molL(-1)) was employed as the supporting electrolyte. The voltammetric measurements were carried out using as working electrode HAp-CPE, and a platinum electrode and an SCE electrode as auxiliary and reference electrodes, respectively. Under the optimized working conditions, calibration graph is linear for 5min of preconcentration time with the detection limit 7.68x10(-10)molL(-1). This detection limit is remarkably lower than those reported previously using other modified electrodes or amperometric detection. The results indicate that this electrode is sensitive and effective for the determination of Pb2+.


Isolation of alpha- and beta-subunits of peak-I hCG and generation of highly specific polyclonal antisera.
Development of polyclonal antisera is still a choice in some hard-pressed budget laboratories. In the present study, an attempt was made to isolate alpha- and beta-subunits from peak-I hCG, generation of polyclonal antisera and their characterization. The anti-hCG-a antisera showed titres of 1: 8000 and anti-hCG-beta antisera 1: 16,000 at 50% binding to radiolabelled hCG in RIA. Studies on specificity using anti hCG-beta antiserum demonstrated no cross-reaction with several hormones tested in the present study, except for hCG-beta and hCG, thus eliciting a highly specific hCG-beta antiserum.


The vitamin D receptor Taq I polymorphism is associated with reduced VDR and increased PDIA3 protein levels in human intestinal fibroblasts.
The synonymous single nucleotide polymorphism (SNP) rs731236, located in the vitamin D receptor (VDR) gene (Taq I) has been associated with both decreased levels of the protein in peripheral blood mononuclear cells and a fibrosis-related complication in Crohn´s disease (CD). Interactions between VDR and a protein-disulfide isomerase-associated 3 (PDIA3) in the regulation of extracellular matrix have been reported and we aim to analyze the relevance of the VDR genotypes and the effects of Vitamin D (VD) in the expression of VDR, PDIA3 and proliferation of intestinal fibroblasts. Human intestinal fibroblasts were isolated from the non-affected surgical resections of colorectal patients and classified according to the VDR genotype. In some cases, cells were transfected with specific PDIA3 siRNA. Basal and VD-stimulated expression of VDR, PDIA3 and Collagen 1A1 (COL1A1) as well as fibroblast migration/proliferation were analyzed. Our data show that intestinal fibroblasts homozygous for the C allele in the VDR gene exhibited lower VDR protein levels and higher proliferation than cells homozygous for the T allele. VD increased VDR and attenuated the accelerated proliferation of CC fibroblasts. The diminished VDR level detected in CC cells was associated with increased levels of both PDIA3 and COL1A1 expression and the transient silencing of PDIA3 significantly reduced COL1A1 expression. We conclude that intestinal fibroblasts homozygous for the C allele in the VDR gene exhibited: reduced VDR protein levels, increased proliferation and increased PDIA3/COL1A1 expression. Treatment with VD increased VDR and attenuated proliferation of these cells.


Use of spreadsheets to manipulate field scanning data.
Computerized field scanning systems are now standard tools in most radiotherapy departments. These systems can easily measure central axis depth dose curves and beam profiles. Data acquired from these systems forms the basis of what is used for machine calibrations and patient dosimetry. Unfortunately, the data is often not in the best format for these applications. Each data point is often acquired in a fraction of a second with a small volume ionization chamber resulting in "noisy" data. Many dosimetric applications require tissue maximum ratio data which is technically difficult to directly measure with these scanning systems. And finally, it is desirable to have the data clearly organized in tables according to the specific needs of the department. Commercial spreadsheets can be used to solve these problems. We have used Lotus 1-2-3 to smooth the central axis data, calculate additional data points, calculate tissue maximum ratios, and clearly present this data in neatly organized tables.


Human papillomavirus is an important risk factor for esophageal carcinoma in a Chinese population.
Different types of HPV have been associated with cancer in humans, but the role of HPV in esophageal cancer (EC) is controversial. The purpose of this study was to evaluate the correlation between HPV infection and EC in the Chinese population and to provide the scientific basis for the future prevention, control, early diagnosis, and treatment strategies of EC in China. PCR detected HPV infection in 1112 esophageal cancer tissue samples, and 89 HPV-positive samples were detected by genotyping. Proximity ligation assays (PLAs) and immunohistochemistry were used to detect the expression of HPV E6 and E7 proteins. Real-time fluorescent quantitative PCR was used to detect the integration of HPV16 E6. The level of HPV-specific antibody IgG in serum was detected by ELISA and PLA. The positive rates of HPV L1, HPV16, HPV18, hpv16 + 18 E6 and hpv16/18 E6 in 1,112 EC tissue samples were 77.6%, 41.4%, 27.2%, 14.2% and 55.4% respectively. Multiple HPV subtypes were detected in HPV-positive EC samples. PLA showed that E6 and E7 were expressed in EC109 and formed complexes with p53 and pRb, respectively. Immunohistochemistry showed that the positive rates of hpv16 + 18 E6 and E7 in HPV-positive EC samples were 56.4% and 37.0%, respectively. HPV-DNA integration rate in HPV-positive EC tissues (88.79%) was higher than that in adjacent tissues (54.17%). HPV antibody was found in the serum of EC patients by a serological test. The study suggests that HPV, especially HPV16 and HPV18, the infection may be a risk factor for EC in the Chinese population and that the E6 protein may play a key role in HPV-associated malignancies. These results may be important for the prevention and treatment of HPV-positive EC in China.


Regional disparity on patient characteristics and perceptions after implantable cardioverter-defibrillator implantation: results from an EHRA patient survey.
The aim of this study was to identify potential regional disparities in characteristics of implantable cardioverter-defibrillator (ICD) recipients, patient perceptions and perspectives after implantation and level of information provided to patients. The prospective, multicentre, and multinational European Heart Rhythm Association patient Survey 'Living with an ICD' included patients already implanted with an ICD (median ICD dwell time - 5 years, interquartile range 2-10). An online questionnaire was filled-in by patients invited from 10 European countries. A total of 1809 patients (the majority in their 40s to 70s, 65.5% men) were enrolled, with 877 (48.5%) from Western Europe (group 1), followed by 563 from Central/Eastern Europe (group 2, 31.1%), and 369 from Southern Europe (group 3, 20.4%). A total of 52.9% of Central/Eastern Europe patients reported increased satisfaction after ICD placement compared with 46.6% from Western and 33.1% from Southern Europe (1 vs. 2 P = 0.047, 1 vs. 3 P < 0.001, 2 vs. 3 P < 0.001). About 79.2% of Central/Eastern and 76.0% of Southern Europe patients felt optimally informed at the time of device implantation compared with just 64.6% from Western Europe (1 vs. 2 P < 0.001, 1 vs. 3 P < 0.001, 2 vs. 3 P = ns). While physicians in Southern Europe should address the patients' concerns about the impact of the ICD on quality of life, physicians from Western Europe should focus on improving the quality of information provided to their prospective ICD patients. Novel strategies to address regional differences in patients' quality of life and provision of information are warranted.