Clevidipine for the treatment of severe hypertension in adults.
Intravenous antihypertensive agents are used when immediate control of blood pressure (BP) is required, including during the perioperative cardiac surgery period. Controlling postoperative BP is challenging because of the need to adequately reduce BP while maintaining appropriate end-organ perfusion. Clevidipine is an intravenous, ultra-short-acting, third-generation dihydropyridine calcium channel antagonist with selectivity for arteriolar vasodilatation. It is approved by the US Food and Drug Administration for the treatment of severe hypertension. This paper reviews the clinical pharmacology, pharmacokinetic and pharmacodynamic properties, tolerability, and clinical efficacy of clevidipine. To minimize selection bias, each author conducted an independent search for English-language publications indexed on MEDLINE and International Pharmaceutical Abstracts through January 2010 using the term clevidipine. All identified prospective, randomized and nonrandomized Phase III trials were included in the review. Seven Phase III trials were identified in which clevidipine was compared with baseline, placebo, or other intravenous antihypertensive agents in the settings of severe hypertension (1 study), preoperative cardiac surgery (1), perioperative cardiac surgery (1), and postoperative cardiac surgery (4). In a multicenter, randomized, double-blind, placebo-controlled study of the efficacy of clevidipine in treating preoperative hypertension, the mean reduction from baseline in mean arterial pressure was 31.2% with clevidipine and 11.2% with placebo (P < 0.001). In a randomized, open-label, prospective study involving separate comparisons of clevidipine with nitroglycerin, sodium nitroprusside, and nicardipine, the median total AUC for digression in systolic BP from the predetermined target range differed significantly between clevidipine and nitroglycerin (4.14 vs 8.87 mm Hg . min/h; respectively, P < 0.001) and between clevidipine and sodium nitroprusside (4.37 vs 10.5 mm Hg . min/h; P = 0.003), but not between clevidipine and nicardipine (1.76 and 1.69 mm Hg . min/h). Another study found no significant difference in efficacy in controlling BP during the 3-hour study period between clevidipine and sodium nitroprusside (AUC for mean [SD] arterial pressure, 106 [25] and 101 [28] mm Hg . min/h, respectively). Adverse events in these studies included atrial fibrillation (13.0%-36.1% clevidipine vs 12.0% placebo), nausea (5.0%-21.0% vs 12.0%, respectively), fever (19.0% vs 13.7%), insomnia (12.0% vs 6.1%), and acute renal failure (9.0% vs 2.0%). In the studies reviewed, only 1 case of chest discomfort in the setting of severe hypertension was considered a serious adverse event related to clevidipine therapy. In the Phase III trials reviewed, clevidipine was effective in controlling BP in the settings of perioperative cardiac surgery and severe hypertension and was associated with minimal adverse effects.


Smoking and quitting among Irish teenage males.
Nicotine addiction in adulthood is usually preceded by exposure to cigarettes in adolescence. A minimal exposure may be sufficient to produce addiction. Strategies to reduce adult smoking must address those factors, which influence teenage smoking. In this study we aimed to establish the prevalence of smoking in male secondary schools, to measure the association between student's smoking status and parental, peer and sibling smoking and to describe attempted quitting. An anonymous questionnaire was given to 1070 male secondary school pupils in two schools in County Louth. Twenty-seven percent of respondents smoked every day or on most days. Having a best friend who smoked was associated with personal smoking (O.R. 11.75, C.I. 8.6-16.08) as was sibling smoking (O.R. 3.49, C.I. 2.67-4.57.) Seventy percent of smokers stated that they wanted to stop and 75% that they had tried to stop. Only five smokers (1.2%) had been advised to quit by their general practitioner. We conclude that smoking is as prevalent among teenage boys in Ireland as it has been shown to be elsewhere and that most teenagers are unable rather than unwilling to stop.


Printing cancer cells into intact microvascular networks: a model for investigating cancer cell dynamics during angiogenesis.
While cancer cell invasion and metastasis are dependent on cancer cell-stroma, cancer cell-blood vessel, and cancer cell-lymphatic vessel interactions, our understanding of these interactions remain largely unknown. A need exists for physiologically-relevant models that more closely mimic the complexity of cancer cell dynamics in a real tissue environment. The objective of this study was to combine laser-based cell printing and tissue culture methods to create a novel ex vivo model in which cancer cell dynamics can be tracked during angiogenesis in an intact microvascular network. Laser direct-write (LDW) was utilized to reproducibly deposit breast cancer cells (MDA-MB-231 and MCF-7) and fibroblasts into spatially-defined patterns on cultured rat mesenteric tissues. In addition, heterogeneous patterns containing co-printed MDA-MB-231/fibroblasts or MDA-MB-231/MCF-7 cells were generated for fibroblast-directed and collective cell invasion models. Printed cells remained viable and the cells retained the ability to proliferate in serum-rich media conditions. Over a culture period of five days, time-lapse imaging confirmed fibroblast and MDA-MB-231 cell migration within the microvascular networks. Confocal microscopy indicated that printed MDA-MB-231 cells infiltrated the tissue thickness and were capable of interacting with endothelial cells. Angiogenic network growth in tissue areas containing printed cancer cells was characterized by significantly increased capillary sprouting compared to control tissue areas containing no printed cells. Our results establish an innovative ex vivo experimental platform that enables time-lapse evaluation of cancer cell dynamics during angiogenesis within a real microvascular network scenario.


Prostaglandin-E2 enhances EPO-mediated STAT5 transcriptional activity by serine phosphorylation of CREB.
Erythroid colony formation in response to erythropoietin (EPO) stimulation is enhanced by costimulating the cells with prostaglandin-E2 (PGE2). The present study further analyzed the underlying mechanisms and demonstrated that EPO-mediated STAT5 transactivation in the erythroid AS-E2 cell line was enhanced 6-fold by PGE2 (10 microM), without affecting the STAT5 tyrosine phosphorylation or STAT5-DNA binding. Moreover, the PGE2-enhancing effect was independent of STAT5 serine phosphorylation. In AS-E2 cells STAT5 is constitutively phosphorylated on Ser780 (STAT5A) and EPO-dependently phosphorylated on Ser726/731 (STAT5A/STAT5B), but overexpression of STAT5 serine mutants did not affect STAT5 transactivation. In addition, PGE2 did not affect STAT5 serine phosphorylation. Instead, the stimulatory effect of PGE2 on STAT5 signaling could be mimicked by dibutyryl-cyclic adenosine monophosphate (cAMP) and the phosphodiesterase inhibitor IBMX, suggesting that the effect was mediated by cAMP. Activation of the cAMP pathway resulted in cAMP-response element binding protein (CREB) phosphorylation, which was sustained in the presence of EPO plus PGE2 and transient on EPO stimulation alone. The costimulatory effect of PGE2 on EPO-mediated STAT5 transactivation was inhibited by overexpression of serine-dead CREB or protein kinase A (PKA) inhibitor (PKI), in contrast to EPO-mediated transactivation, which was PKA independent. Furthermore, CREB-binding protein (CBP)/p300 was shown to be involved in EPO-mediated STAT5 transactivation, and a CBP mutant with increased affinity for CREB resulted in an additional enhancement of the PGE2 effect. Finally, we demonstrated that the STAT5 target genes Bcl-X, SOCS2, and SOCS3 were up-regulated by costimulation with PGE2. In summary, these studies demonstrate that PGE2 enhancement of EPO-induced STAT5 transactivation is mediated by the cAMP/PKA/CREB pathway.


A twin study of the genetics of fear conditioning.
Fear conditioning is a traditional model for the acquisition of fears and phobias. Studies of the genetic architecture of fear conditioning may inform gene-finding strategies for anxiety disorders. The objective of this study was to determine the genetic and environmental sources of individual differences in fear conditioning by means of a twin sample. Classic fear conditioning data were experimentally obtained from 173 same-sex twin pairs (90 monozygotic and 83 dizygotic). Sequences of evolutionary fear-relevant (snakes and spiders) and fear-irrelevant (circles and triangles) pictorial stimuli served as conditioned stimuli paired with a mild electric shock serving as the unconditioned stimulus. The outcome measure was the electrodermal skin conductance response. We applied structural equation modeling methods to the 3 conditioning phases of habituation, acquisition, and extinction to determine the extent to which genetic and environmental factors underlie individual variation in associative and nonassociative learning. All components of the fear conditioning process in humans demonstrated moderate heritability, in the range of 35% to 45%. Best-fitting multivariate models suggest that 2 sets of genes may underlie the trait of fear conditioning: one that most strongly affects nonassociative processes of habituation that also is shared with acquisition and extinction, and a second that appears related to associative fear conditioning processes. In addition, these data provide tentative evidence of differences in heritability based on the fear relevance of the stimuli. Genes represent a significant source of individual variation in the habituation, acquisition, and extinction of fears, and genetic effects specific to fear conditioning are involved.


Urinary desmosine excretion as a marker of lung injury in the adult respiratory distress syndrome.
Desmosine, the intermolecular and intramolecular cross link between the chains of elastin polypeptide, may be useful as a marker of a lung injury in adult respiratory distress syndrome (ARDS). A radioimmunoassay for rabbit antibody developed against desmosine, conjugated to bovine serum albumin, can detect as little as 100 pg of desmosine in plasma or urine. Desmosine is not metabolically absorbed, reused, or catabolized by the body, but rather eliminated unchanged in the urine as low molecular weight peptides. The lung is relatively rich in elastin, and we reasoned that a timed collection could be used as an index of elastin degradation in vivo. A 2-h collection of urine for desmosine assay was obtained at the time of Swan-Ganz catheter insertion in 41 consecutive patients. On the basis of clinical and initial Swan-Ganz catheter data, the patients were assigned to one of three groups: an ARDS group (n = 12); a cardiogenic pulmonary edema (CPE) group (n = 12); and a critically ill, nonpulmonary edema group (NPE, n = 17). The mean urine desmosine concentration (mg/L) for the ARDS group (0.728 +/- 0.22 SE) differed from the CPE group (0.149 +/- 0.07; p less than 0.001). The total excretion (microgram/2 h) was 64.95 +/- 24.7 in the ARDS group and 24.71 +/- 11.7 in the CPE group (p less than 0.05). Urine desmosine concentration/serum creatinine index for the ARDS group (0.78 +/- 0.28) was greater than in the CPE group (0.07 +/- 0.04; p = 0.019). Desmosine excretion was increased in the NPE group compared with CPE and ARDS groups, possibly reflecting heterogeneity in this group. In the differentiation of ARDS from CPE, we conclude that substantial increases in urinary desmosine excretion favor a diagnosis of ARDS.


Transgastric endoscopic rendezvous technique for removal of eroded Molina gastric band.
The application of the nonadjustable gastric band (NAGB) for the treatment of morbid obesity was common in the 1980s. However, it was associated with an unacceptable reoperative rate and numerous postoperative complications such as gastric erosion. Removing an eroded NAGB is fraught with difficulty secondary to the extensive inflammatory response around the proximal stomach and left lobe of the liver. To circumvent these difficulties, we have devised a transgastric endoscopic rendezvous (TGER) technique for the removal of eroded Molina NAGBs. A case series of 2 patients who had undergone the TGER technique for removal of an eroded Molina NAGB was undertaken. The outcomes assessed included preoperative morbidity, a description of the surgical procedure, and the postoperative course. Both patients presented with symptoms consistent with proximal gastric outlet obstruction. The TGER technique was effectively applied in removing the eroded NAGB in both patients with no intraoperative, perioperative, or postoperative complications at 6 months of follow-up. One patient requested additional treatment for morbid obesity and subsequently underwent successful placement of an adjustable gastric band. Our small series has demonstrated that the TGER technique is a safe and effective procedure applicable to the complicated case of an eroded NAGB. The use of a combined endoscopic/transgastric approach facilitates complete avoidance of the thick adhesion surrounding the previously banded stomach with the capability of securing a gastrotomy in virgin tissue rather than opening and then closing the dense perigastric pseudocapsule. Nevertheless, the true utility of the TGER technique is soundly dependent on the availability of adequate resources and experienced surgical assistance and needs to be explored further.


Particle swarm optimization based fusion of ultrasound echographic and elastographic texture features for improved breast cancer detection.
Breast cancer remains the main cause of cancer deaths among women in the world. As per the statistics, it is the most common killer disease of the new era. Since 2008, breast cancer incidences have increased by more than 20%, while mortality has increased by 14%. The statistics of breast cancer incidences as per GLOBOCAN project for the years 2008 and 2012 show an increase from 22.2 to 27% globally. In India, breast cancer accounts for 25% to 31% of all cancers in women. Mammography and Sonography are the two common imaging techniques used for the diagnosis and detection of breast cancer. Since Mammography fails to spot many cancers in the dense breast tissue of young patients, Sonography is preferred as an adjunct to Mammography to identify, characterize and localize breast lesions. This work aims to improve the performance of breast cancer detection by fusing the texture features from ultrasound elastographic and echographic images through Particle Swarm Optimization. The mean classification accuracy of Optimum Path Forest Classifier is used as an objective function in PSO. Seven performance metrics were computed to study the performance of the proposed technique using GLCM, GLDM, LAWs and LBP texture features through Support Vector Machine classifier. LBP feature provides accuracy, sensitivity, specificity, precision, F1 score, Mathews Correlation Coefficient and Balanced Classification Rate as 96.2%, 94.4%, 97.4%, 96.2%, 95.29%, 0.921, 95.88% respectively. The obtained performance using LBP feature is better compared to the other three features. An improvement of 6.18% in accuracy and 11.19% in specificity were achieved when compared to those obtained with previous works.


Coexistent pulmonary granulomatosis with polyangiitis (Wegener granulomatosis) and Crohn disease.
Crohn disease (CD) may be associated with various extraintestinal manifestations, including, rarely, respiratory tract involvement. When necrobiotic pulmonary nodules are present, the differential diagnosis includes granulomatosis with polyangiitis (Wegener granulomatosis) (GPA). The respiratory tract manifestations of CD and GPA may mimic each other, complicating the diagnosis and suggesting the possible coexistence of these 2 conditions. The aim of this study was to describe the clinical, radiographic, and pathologic features of patients in whom CD and GPA coexist. We reviewed the teaching files of the authors and searched the Mayo Clinic medical records for coexistent inflammatory bowel diseases and antineutrophilic cytoplasmic antibodies (ANCA)-associated vasculitides. We reviewed in detail 97 patient charts and excluded cases of ulcerative colitis and those in whom only one of the diagnoses was present. Pulmonary and gastrointestinal biopsies were reviewed when available. We also searched the medical literature for previously published cases. We found 6 cases of coexistent CD and pulmonary GPA and 4 cases with extrapulmonary GPA; 3 cases (all with extrapulmonary GPA) have been published previously. The diagnosis of CD preceded that of GPA in 11 cases. Proteinase 3-ANCA was positive in 6 cases, negative in 2, and not reported in 5 cases. Myeloperoxidase-ANCA was negative in 6 cases and unavailable in the remainder of patients. Pathology revealed features diagnostic of GPA in all cases with necrotizing granulomatous inflammation and segmental vasculitis. Pulmonary findings in patients with CD or the presence of granulomatous colitis in patients with GPA should prompt the inclusion in the differential diagnosis of a possible coexistence of CD and GPA.


Low daily oral PrEP adherence and low validity of self-report in a randomized trial among PWID in Ukraine.
The efficacy of daily oral pre-exposure prophylaxis (PrEP) in preventing HIV transmission among people who inject drugs (PWID) was demonstrated over a decade ago. However, only a few studies among PWID have since measured PrEP adherence using laboratory markers. In this trial, we randomized recently injecting PWID in Kyiv, Ukraine, to receive daily oral TDF/FTC with or without SMS reminders. Enrollment and PrEP initiation took place at an HIV clinic. Subsequent visits at months 1, 3, and 6 were conducted at a community harm reduction center and included a structured interview, adherence counseling, PrEP dispensing, and dried blood spot collection. PrEP adherence was assessed using standard self-reported measures and TDF/FTC biomarkers. A total of 199 PWID (99 SMS, 100 No-SMS) were enrolled, of whom 24 % were women, with a median age of 37. At month 6, 79.4 % (158/199) of participants were retained, with 84 % (133/158) reporting opioid injection and 20 % (31/158) reporting stimulant injection in the past 30 days. 77 % (122/158) reported taking >95 % of PrEP doses in the past month, and 87 % reported taking the last dose within 2 days. Tenofovir diphosphate was detected in 17 % (28/158) of participants, and emtricitabine triphosphate was detected in 25 % (40/158). Only 3 % (5/158) had metabolite levels indicative of consistent PrEP uptake at 4+ doses per week. There was no association between the SMS intervention and TDF/FTC metabolite detection. Adherence to daily oral PrEP among actively injecting PWID, without daily supervision or incentives, was extremely low, despite supportive counseling and SMS reminders. We also observed a high rate of discordance between self-report and classification by a validated biomarker of adherence. Given the scarcity of evidence and emerging data suggesting low oral PrEP adherence among PWID, additional implementation studies with TDF/FTC biomarkers are needed to study whether a sufficient level of adherence to daily PrEP is attainable among PWID, especially as long-acting injectable PrEP offers a promising alternative.


Risk factors for recurrent urinary tract infection in preschool children.
Children with urinary tract infections (UTI) are at risk of renal scarring which may lead to impaired renal function and hypertension. This study examines the risk factors that predispose to recurrent UTI in children and the role of recurrent UTI in renal scarring. A group of 290 children under 5 years of age with a first symptomatic UTI were studied. Micturating cystourethrogram and dimercaptosuccinic acid (DMSA) renal scintigraphy were performed at entry, and DMSA was repeated 1 year later. Two hundred and sixty-one children (90%) were followed up at 1 year. There were 46 confirmed recurrent infections in 34 children, a recurrence rate of 12%. Multiple recurrence occurred in 14/34 (34%) children. Age of less than 6 months on entry independently predicted for recurrent UTI (odds ratio (OR): 2.9)). Compliance with prophylactic antibiotics fell throughout the year of follow up. Vesicoureteric reflux (VUR) was present in 14/34 (34%) of the group with recurrent UTI, 69/256 (27%) without recurrence. Urinary tract infection was significantly associated with bilateral and intrarenal reflux; grade 3-5 reflux independently predicted for recurrent UTI (OR: 3.5). Recurrent UTI was significantly associated with high grade DMSA defects on entry, renal parenchymal defects at 1 year follow up, and new defects at 1 year. The independent risk factors for recurrent UTI identified by this study were an age of less than 6 months at the index UTI and grade 3-5 VUR. These findings suggest more selective targeting may minimize problems associated with prophylaxis and improve outcomes for children with urine infection.


Development of a questionnaire specifically for patients with Ileal Orthotopic Neobladder (IONB).
The ileal orthotopic neobladder (IONB) is often used in patients undergoing radical cystectomy. The IONB allows to void avoiding the disadvantages of the external urinary diversion.In IONB patients the quality of life (QoL) appears compromised by the need to urinate voluntarily. The patients need to wake up at night interrupting the sleep-wake rhythm with consequences on social and emotional life.At present the QoL in IONB patients is evaluated by generic questionnaires. These are useful when IONB patients are compared with patients with different urinary diversions but they are less effective when only IONB patients are evaluated. To address this problem a specific questionnaire-the IONB-PRO-was developed. A) Based on a conceptual framework, narrative-based interviews were conducted on 35 IONB patients. A basic pool of 43 items was produced and organized throughout two clinical and four QoL dimensions. An additional 15 IONB patients were interviewed for face validity testing.B) Psychometric testing was conducted on 145 IONB patients. Both classic test strategy and Rasch analysis were applied. Psychometric properties of the resulting scales were comparatively tested against other QoL-validated scales. The IONB-PRO questionnaire includes two sections: one on the QoL and a second section on the capability of the patient to manage the IONB. For evaluation of the QoL, three versions were delivered: 1) a basic 23-item QoL version (3 domains 23-items; alpha 0.86÷ 9.69), 2) a short-form 12-item QoL scale (alpha = 0.947), and 3) a short-form 15-item Rasch QoL scale (alpha = 0.967). Correlations of the long version scales with the corresponding dimensions of the EORTC-QLQ C30 and the EORTC-BLM30 were significant. The short forms exhibited significant correlations with the global health dimension of the EORTC-QLQ and with the urinary subscales of the EORTC-BLM30. The effect size was approximately 1.00 between patients at the 1-year follow-up period and those with 3, 5, and > 5-year follow-up periods for all scales. No relevant differences were observed between the 12-item short-form and the Rasch scale. The IONB-PRO long and short-forms demonstrated a high level of internal consistency and reliability with an excellent discriminanting validity.


Granular clustering: a granular signature of data.
The study is devoted to a granular analysis of data. We develop a new clustering algorithm that organizes findings about data in the form of a collection of information granules-hyperboxes. The clustering carried out here is an example of a granulation mechanism. We discuss a compatibility measure guiding a construction (growth) of the clusters and explain a rationale behind their development. The clustering promotes a data mining way of problem solving by emphasizing the transparency of the results (hyperboxes). We discuss a number of indexes describing hyperboxes and expressing relationships between such information granules. It is also shown how the resulting family of the information granules is a concise descriptor of the structure of the data-a granular signature of the data. We examine the properties of features (variables) occurring of the problem as they manifest in the setting of the information granules. Numerical experiments are carried out based on two-dimensional (2-D) synthetic data as well as multivariable Boston data available on the WWW.


Does prey availability influence the detection of Dinophysis spp. by the imaging FlowCytobot?
The Imaging FlowCytobot (IFCB) is a field-deployable imaging-in-flow cytometer that is increasingly being used to monitor harmful algae. The IFCB acquires images of suspended particles based on their chlorophyll-a fluorescence and/or the amount of light they scatter (side scattering). The present study hypothesized that fluorescence-based image acquisition would undercount Dinophysis spp., a genus of non-constitutive mixotrophs, when prey is limited. This is because Dinophysis spp. acquire plastids via ingestion of their ciliate prey Mesodinium spp., and lose photosynthetic capacity and autofluorescence in the absence of prey. Even small blooms of Dinophysis spp. can be highly toxic and result in diarrhetic shellfish poisoning (DSP), highlighting the importance of accurately detecting low abundances. To explore this, laboratory experiments were conducted to determine optimal IFCB settings for a fed culture of Dinophysis acuminata, and an existing time series of IFCB observations collected in Puget Sound (Washington, U.S.A) was used to compare Dinophysis spp. abundance estimates from samples triggered via side scattering versus fluorescence in relation to Mesodinium spp. abundance. This study introduces a quantitative approach for optimizing the detection of target harmful algae which can be repeated across multiple IFCBs and demonstrates the effects of IFCB calibration on Dinophysis spp. detection. The laboratory experiments showed that IFCB settings for fluorescence-based image acquisition need to be fairly sensitive to accurately detect D. acuminata cells. A poorly calibrated IFCB can miss a significant proportion of D. acuminata abundance whatever the method used to trigger the image acquisition. Field results demonstrated that the physiological status of Dinophysis spp. can influence their detection by the IFCB when triggering on fluorescence. This was observed during a 7-day period when the IFCB failed to detect Dinophysis spp. cells when triggering on fluorescence while cells were still detected using the side scattering triggering method as well as observed by microscopy. During this period, Mesodinium spp. was not detected, IFCB-derived autofluorescence level of individual cells of Dinophysis spp. was low, and less than 50 % of Dinophysis spp. cells exhibited autofluorescence under the microscope. Together, this indicates that the unique feeding ecology of Dinophysis spp. may affect their detection by the IFCB when cells are starved.


On the complexity of supervisory control design in the RW framework.
The time complexity of supervisory control design for a general class of problems is studied. It is shown to be very unlikely that a polynomial-time algorithm can be found when either (1) the plant is composed of m components running concurrently or (2) the set of legal behaviors is given by the intersection of n legal specifications. That is to say, in general, there is no way to avoid constructing a state space which has size exponential in m+n. It is suggested that, rather than discouraging future work in the field, this result should point researchers to more fruitful directions, namely, studying special cases of the problem, where certain structural properties possessed by the plant or specification lend themselves to more efficient algorithms for designing supervisory controls. As no background on the subject of computational complexity is assumed, we have tried to explain all the borrowed material in basic terms, so that this paper may serve as a tutorial for a system engineer not familiar with the subject.


Systematic recovery and analysis of full-ORF human cDNA clones.
The Mammalian Gene Collection (MGC) consortium (http://mgc.nci.nih.gov) seeks to establish publicly available collections of full-ORF cDNAs for several organisms of significance to biomedical research, including human. To date over 15,200 human cDNA clones containing full-length open reading frames (ORFs) have been identified via systematic expressed sequence tag (EST) analysis of a diverse set of cDNA libraries; however, further systematic EST analysis is no longer an efficient method for identifying new cDNAs. As part of our involvement in the MGC program, we have developed a scalable method for targeted recovery of cDNA clones to facilitate recovery of genes absent from the MGC collection. First, cDNA is synthesized from various RNAs, followed by polymerase chain reaction (PCR) amplification of transcripts in 96-well plates using gene-specific primer pairs flanking the ORFs. Amplicons are cloned into a sequencing vector, and full-length sequences are obtained. Sequences are processed and assembled using Phred and Phrap, and analyzed using Consed and a number of bioinformatics methods we have developed. Sequences are compared with the Reference Sequence (RefSeq) database, and validation of sequence discrepancies is attempted using other sequence databases including dbEST and dbSNP. Clones with identical sequence to RefSeq or containing only validated changes will become part of the MGC human gene collection. Clones containing novel splice variants or polymorphisms have also been identified. Our approach to clone recovery, applied at large scale, has the potential to recover many and possibly most of the genes absent from the MGC collection.


Clinical outcome of percutaneous endoscopic lumbar decompression in treatment of elderly patients with lumbar spinal stenosis: a matched retrospective study.
This retrospective cohort study aimed to evaluate the efficacy and safety of percutaneous endoscopic lumbar decompression (PELD) in elderly patients with lumbar spinal stenosis (LSS). A matched retrospective study. The research was conducted in Beijing Chaoyang Hospital, Capital Medical University, China. This study included patients treated with PELD for LSS from September 2016 to September 2020. Patients with LSS aged ≥ 80 years were screened according to the inclusion and exclusion criteria as the study group, and then the same number of patients with LSS aged 50-80 years were matched according to gender, stenosis type, and surgical segment as the control group. Preoperative patient status was assessed using the Charlson comorbidity index (CCI) and the American Society of Anesthesiologists (ASA) physical status classification score. Clinical outcomes were assessed using the visual analog scale (VAS), Oswestry Disability Index (ODI) scores, modified Macnab criteria, radiological parameters and complication rates. A total of 624 LSS patients met the screening criteria between September 2016 and September 2020, with 47 LSS patients ≥ 80 years old serving as the study group. Forty-seven LSS patients aged 50-80 years were matched to the study group according to gender, stenosis type, and stenosis segment. The CCI score (1.77 ± 1.67) and ASA classification (2.62 ± 0.74) of the study group were significantly higher than the CCI score (0.66 ± 0.96) and ASA classification (1.28 ± 0.54) of the control group, and the difference was statistically significant. Compared with preoperative data, postoperative ODI, leg pain VAS scores and back pain VAS scores were significantly improved in both groups (p < 0.05). However, no significant difference was found between two groups in preoperative and postoperative ODI, leg pain VAS scores and back pain VAS scores (p > 0.05). The operation time and postoperative hospital stay in control group were significantly lower than those in study (p < 0.05), but there was no significant difference in blood loss between the two groups (p > 0.05). Besides, overall radiological parameters were comparable in elder and younger patients (p > 0.05), and disc height (DH), lumbar lordosis and segmental lordosis decreased after two year follow-up in both groups (p < 0.05). In addition, complication rates were similar between the two groups (p > 0.05), and no serious complications and deaths were found. Single-centre retrospective design, non-randomized sample, small sample size. Although elderly LSS patients (≥ 80 years old) are less fit and have more comorbidities, satisfactory outcomes can be achieved with PELD, comparable to those of LSS patients < 80 years old, and without increased complications.


Demonstration of a founder effect and fine mapping of dominant optic atrophy locus on 3q28-qter by linkage disequilibrium method: a study of 38 British Isles pedigrees.
Dominant optic atrophy, a hereditary optic neuropathy causing decreased visual acuity, colour vision deficits, a centro-caecal scotoma and optic nerve pallor, has been mapped to a genetic interval of 1.4 cM between loci D3S3669 and D3S3562 on chromosome 3q28-qter. In order to further refine the critical disease interval, and to test the power of haplotype analysis and linkage disequilibrium mapping, we identified a total of 38 families with dominant optic atrophy, unrelated on the basis of genealogy, from a data base of genetic eye disease families originating from the British Isles. They were studied with 12 highly polymorphic microsatellite markers spanning a region of 12 cM around the dominant optic atrophy locus (OPA1). Allelic frequency analysis [chi-squared test, likelihood ratio test (LRT) and P values] and haplotype parsimony analysis showed evidence of a founder effect in 36 of the 38 pedigrees. Six markers (D3S3669, D3S1523, D3S3642, D3S2305, D3S3590 and D3S3562), spanning 1.4 cM across the disease-associated region, demonstrated significant linkage disequilibrium by LRT (P < 0.05). A peak LRT value of 10.86 (P < 0.0005, lambda = 0.4) occurred at D3S3669. On linkage disequilibrium multipoint analysis the maximum lod score of 8.01 is achieved at D3S1523, and 95% confidence intervals suggest that OPA1 lies within ca. 400 kb of D3S1523.


Distance learning--an educational tool for developing countries.
Many anaesthetists in small hospitals and developing countries have poor access to educational materials. The use of electronic means of publication and distribution, combined with the concepts of distance learning, can lead to better levels of knowledge and clinical practice. A project based on these principles has been set up in Zimbabwe, and is proving helpful to both trainers and trainees. All District Hospitals have been visited, and trainees in them identified. A survey has been completed to identify the subject areas in which training is most necessary. Trainees have been provided with reference materials on CD-ROM which they can access by computer (each hospital has a computer). Specialist anaesthesiologists in the country are producing interactive tutorials which can be sent out by e-mail to every hospital, and these are backed up by a programme of regular visits, seminars and clinical teaching. The programme is proving helpful to both trainees and tutors, and has the potential to be used in the future in other developing countries.


Conductivities of three-layer live human skull.
Electrical conductivities of compact, spongiosum, and bulk layers of the live human skull were determined at varying frequencies and electric fields at room temperature using the four-electrode method. Current, at higher densities that occur in human cranium, was applied and withdrawn over the top and bottom surfaces of each sample and potential drop across different layers was measured. We used a model that considers variations in skull thicknesses to determine the conductivity of the tri-layer skull and its individual anatomical structures. The results indicate that the conductivities of the spongiform (16.2-41.1 milliS/m), the top compact (5.4-7.2 milliS/m) and lower compact (2.8-10.2 milliS/m) layers of the skull have significantly different and inhomogeneous conductivities. The conductivities of the skull layers are frequency dependent in the 10-90 Hz region and are non-ohmic in the 0.45-2.07 A/m2 region. These current densities are much higher than those occurring in human brain.


Group therapy for excoriation disorder: Psychodrama versus support therapy.
Excoriation disorder (ED) is characterized by recurring excoriation of the skin resulting in tissue damage, usually associated with emotional deregulation. Psychotherapy is a valuable treatment; however, no studies emphasize the patients' interactional aspect, nor the potential benefit of group treatment. We recruited a convenience sample of 38 individuals with ED according to DSM-5 criteria, in which 19 individuals proceeded to treatment, 10 with psychodrama group therapy (PGT), and 9 with support group therapy (SGT) in an open pilot study. The entire sample presented improvement of skin excoriation on both self-report and clinician rating and improvement of social adjustment; however, there was no difference between groups (ie, time × group interaction). Also, there was no relevant change for anxiety, depression, or emotional regulation throughout treatment. Emotional deregulation was associated with excoriation severity as well as depression, anxiety, and social maladjustment, both at the beginning and end of treatment. Although both groups showed improvement of skin picking, the results contradict our primary hypothesis that PGT would have a superior efficacy to SGT for patients with ED. The findings encourage future studies of group interventions for ED in larger samples with a focus on emotional regulation enhancement.


Tubulointerstitial and glomerular nephritis associated with rifampin. Report of a case.
In a patient with tuberculosis and acute renal failure related to administration of therapeutic rifampin, treatment was discontinued for five weeks. It was reinstituted three weeks later. Unlike other patients previously described, the expected adverse renal reaction occurred only gradually and without symptoms, although tubular and glomerular disease developed. Also unique was a striking deposition of immunoglobulin about the tubules. This finding, in association with interstitial nephritis and tubular glycosuria, is similar to an experimental autologous renal disease mediated by antibody to tubular basement membrane.


[Tandem mass tag-based quantitative proteomics analysis of plasma and plasma exosomes in Parkinson's disease].
The cardinal clinical features of Parkinson's disease (PD), a common neurodegenerative disease, include the irreversible impairment of movement coordination, such as tremors, gait rigidity, bradykinesia, and hypokinesia. Although various factors are associated with the pathological changes in PD, such as oxidative stress, mitochondrial dysfunction, and neuroinflammation, the availability of treatments to retard PD progression is limited. Therefore, novel biomarkers for PD diagnosis and therapeutic targets are urgently needed. The diagnosis of PD mainly depends on its clinical manifestations and has an error rate of approximately 20%. Studies have shown that α-synuclein (α-syn) levels are significantly increased in the cerebrospinal fluid of patients with PD; however, the invasive nature of lumbar puncture restricts further studies on its clinical applications. Hence, the development of novel peripheral blood markers would be helpful for the early diagnosis of PD. Exosomes are extracellular vesicles (EVs) released by various cell types under physiological and pathophysiological conditions. Because exosomes carry a variety of bioactive molecules, they play a key role in biological processes such as intercellular communication and the immune response. Central nervous system (CNS)-derived exosomes can be detected in the cerebrospinal and peripheral body fluids of patients with PD, and their contents are altered during the disease process, rendering them an attractive biomarker resource. Therefore, a comprehensive and high-throughput investigation of the plasma and its exosomes may enhance our understanding of PD. In this study, we isolated exosomes from plasma using standard differential centrifugation and performed tandem mass tag (TMT)-labeled quantitative proteomic analysis of plasma and plasma exosome samples from healthy individuals and patients with PD using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 724 proteins were quantified in the plasma samples, and 611 proteins were screened from the exosome samples. Among these 611 proteins, 413 were found in the Exosomal Protein Database (Exocarta). Using |log2FC|>0.26 and P-value (P)<0.05 as the cutoff, five upregulated and six downregulated proteins were identified in the plasma samples of the PD group compared with the healthy group. In the plasma exosome samples, compared with the healthy group, the PD group showed six upregulated and seven downregulated proteins. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted based on gene set enrichment analysis (GSEA). GO-cellular component (CC) analysis revealed that plasma-enriched proteins were mainly located in the nucleus whereas plasma exosome-enriched proteins were mainly located in the cytoplasm. According to the GO-molecular function (MF) analysis, the MFs of differentially expressed proteins in the plasma were mainly enriched in RNA, DNA binding, and complement binding. By contrast, the molecular functions of differentially expressed proteins derived from plasma exosomes were enriched in antioxidant activity, oxidoreductase activity, and peroxide acceptor activity. We then analyzed the enriched KEGG pathways of differentially expressed proteins derived from the plasma and plasma exosome samples. The enrichment pathways of differentially expressed proteins in the plasma samples included the lysosome pathway, cellular senescence, and protein processing in the endoplasmic reticulum. By contrast, the enrichment pathways of differentially expressed proteins in the plasma exosome samples included chemokine signaling and cytokine receptor interactions. Finally, we assessed the functions of some exosomal proteins in PD to elucidate their potential for PD diagnosis and treatment. Significant differences were observed between the plasma and plasma exosome protein profiles, and the functions of differentially expressed proteins in plasma exosomes were strongly related to the pathology of PD. Our study provides a reference for identifying the potential biomarkers and therapeutic targets of PD.


[Determination of trace platinum, palladium and gold in smples by ICP-AES and fire assay preconcentration].
A method of elemental determination is put forward in this paper. Namely, Pt, Pd, Au in 10-20 g samples were preconcentrated in milligram microgranular silver alloy by using fire assay. When compounded in solution, trace platinum, palladium, and gold in the solution were determined by ICP-AES. The detection limits of this method were 0.01, 0.005, and 0.01 microg x mL(-1) for Pt, Pd and Au, respectively. Recoveries of standard were more than 97% with precision of 0.1%, 0.12%, and 0.09% of RSD (n=10), respectively. It has proven that this analysis method is quick, simple and accurate. The method has been applied to the determination of contents of Pt, Pd and Au in samples.


Synthesis, Characterization and Computational Studies of Two Triazaspiro Tetracycles.
Two new triazaspiro tetracycles have been synthesized, the compounds have been characterized using spectroscopy, microanalysis and single crystal X-ray diffractometry. The single crystal X-ray crystallography of 4-methyl-8I,10I,17I-triazaspiro[cyclohexane-1,9I-teracyclo[8.7.02,7.011,16]heptadecane]-1I(17),2I(7I),3I,5I,11I,13I,15I-heptaene (compound I) has been discussed. The DFT computed bond angles have been obtained for both compounds and contrasted with experimental results for compound I. The atoms that make up the frontier orbitals which contribute to the reactivity of the compounds have been discussed.


Cell-mediated immune response to Shope fibroma virus-induced tumors in adult rabbits.
The parameters of cell-mediated immune responses of adult rabbits infected with Shope fibroma virus (SFV) were characterized by measurement of the size of local draining nodes, number of cells per lymph node, mitogen responses of lymphocytes, and kinetics of virus-specific cell-mediated lymphocytotoxicity (CML). In addition, the cytolytic effector population was characterized. After intradermal injections, tumors appeared within 3-4 days, reached maximum size in 10-12 days, and then regressed completely with 24 days. The size of local popliteal lymph nodes, in particular the diffuse cortex (paracortex), and the number of cells per node increased during tumor growth but then declined as the tumor regressed. Maximum specific CML to SFV-infected kidney cell monolayers (RK-13) occurred 10 days after inoculation of SFV and correlated with the initiation of tumor regression. Adult cytotoxic lymphocytes passed through nylon wool, and most of their activity was removed by treatment with antithymocyte globulin plus complement. Cytotoxic T-cells from SFV tumor-bearing rabbits killed only targets infected with SFV and not targets uninfected or infected with vaccinia virus. Therefore, T-cell-mediated virus-specific CML appeared as a major immune effector mechanism that correlated with tumor regression. However, antibody-dependent cell-mediated and NK cytotoxicity were also demonstrable. The presence of different cell-mediated cytotoxic mechanisms suggested a heterogeneity of effector mechanism.


Soccer-related Facial Trauma: Multicenter Experience in 2 Brazilian University Hospitals.
Soccer is the most popular sport in Brazil and a high incidence of related trauma is reported. Maxillofacial trauma can be quite common, sometimes requiring prolonged hospitalization and invasive procedures. To characterize soccer-related facial fractures needing surgery in 2 major Brazilian Centers. A retrospective review of trauma medical records from the Plastic Surgery Divisions at the Universidade Federal de São Paulo-Escola Paulista de Medicina and the Hospital das Clinicas-Universidade de São Paulo was carried out to identify patients who underwent invasive surgical procedures due to acute soccer-related facial fractures. Data points reviewed included gender, date of injury, type of fracture, date of surgery, and procedure performed. A total of 45 patients (31 from Escola Paulista de Medicina and 14 from Universidade de São Paulo) underwent surgical procedures to address facial fractures between March 2000 and September 2013. Forty-four patients were men, and mean age was 28 years. The fracture patterns seen were nasal bones (16 patients, 35%), orbitozygomatic (16 patients, 35%), mandibular (7 patients, 16%), orbital (6 patients, 13%), frontal (1 patient, 2%), and naso-orbito-ethmoid (1 patient, 2%). Mechanisms of injury included collisions with another player (n = 39) and being struck by the ball (n = 6). Although it is less common than orthopedic injuries, soccer players do sustain maxillofacial trauma. Knowledge of its frequency is important to first responders, nurses, and physicians who have initial contact with patients. Missed diagnosis or delayed treatment can lead to facial deformities and functional problems in the physiological actions of breathing, vision, and chewing.


[Hydrogen and carboxide bacteria belonging to the microflora of degradation].
The following bacteria oxidizing hydrogen and/or carbon monoxide were shown by cultivating in the concentration gradient of acetate, lactate, and glucose, to belong to the microflora of dispersal: Hydrogenomonas eutropha Z-1, H. pantotropha Z-11, Pseudomonas carboxydoflava Z-1107, Achromobacter carboxydus Z-1171, Paracoccus denitrificans, and Alcaligenes paradoxus.


Heterologous expression implicates a GATA factor in regulation of nitrogen metabolic genes and ion homeostasis in the halotolerant yeast Debaryomyces hansenii.
The yeast Debaryomyces hansenii has a remarkable capacity to proliferate in salty and alkaline environments such as seawater. A screen for D. hansenii genes able to confer increased tolerance to high pH when overexpressed in Saccharomyces cerevisiae yielded a single gene, named here DhGZF3, encoding a putative negative GATA transcription factor related to S. cerevisiae Dal80 and Gzf3. Overexpression of this gene in wild-type S. cerevisiae increased caffeine and rapamycin tolerance, blocked growth in low glucose concentrations and nonfermentable carbon sources, and resulted in lithium- and sodium-sensitive cells. Sensitivity to salt could be attributed to a reduced cation efflux, most likely because of a decrease in expression of the ENA1 Na(+)-ATPase gene. Overexpression of DhGZF3 did not affect cell growth in a gat1 mutant but was lethal in the absence of Gln3. These are positive factors that oppose both Gzf3 and Dal80. Genome-wide transcriptional profiling of wild-type cells overexpressing DhGZF3 shows decreased expression of a number of genes that are usually induced in poor nitrogen sources. In addition, the entire pathway leading to Lys biosynthesis was repressed, probably as a result of a decrease in the expression of the specific Lys14 transcription factor. In conclusion, our results demonstrate that DhGzf3 can play a role as a negative GATA transcription factor when expressed in S. cerevisiae and that it most probably represents the only member of this family in D. hansenii. These findings also point to the GATA transcription factors as relevant elements for alkaline-pH tolerance.


Co2+, low Ca2+, and verapamil reduce mechanical activity in rat skeletal muscles.
We have studied the effects of Co2+ (5 mM), low-Ca2+ solution [0 added CaCl2, 5 mM ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid, 3 mM MgCl2 Ringer], and verapamil (0.1 mM) on mechanical and electrical properties of rat soleus muscle in vitro at 34 degrees C. Muscle fibers had normal resting potentials in Co2+ and verapamil solutions. Low-Ca2+ solution produces a depolarization of approximately 4 mV. The action potentials are smaller and have a slower time course when exposed to test solutions. Iterative generation of action potentials in the presence of Co2+ and low-Ca2+ solution is not modified. In the presence of Co2+ or low-Ca2+ solution, the mechanical output, twitch and tetanus tensions, and caffeine contracture are reduced significantly. Verapamil produces a decrease in the twitch and tetanic tensions but does not modify the caffeine contracture tension. The effect of verapamil on the twitch becomes more manifest when the muscle is stimulated at 3-5 Hz. We suggest that changes in the action potential characteristics or the inhibition of a Ca2+ current are responsible for the mechanical changes observed in the presence of the drugs.


Patient capacity and constraints in the experience of chronic disease: a qualitative systematic review and thematic synthesis.
Life and healthcare demand work from patients, more so from patients living with multimorbidity. Patients must respond by mobilizing available abilities and resources, their so-called capacity. We sought to summarize accounts of challenges that reduce patient capacity to access or use healthcare or to enact self-care while carrying out their lives. We conducted a systematic review and synthesis of the qualitative literature published since 2000 identifying from MEDLINE, EMBASE, Psychinfo, and CINAHL and retrieving selected abstracts for full text assessment for inclusion. After assessing their methodological rigor, we coded their results using a thematic synthesis approach. The 110 reports selected, when synthesized, showed that patient capacity is an accomplishment of interaction with (1) the process of rewriting their biographies and making meaningful lives in the face of chronic condition(s); (2) the mobilization of resources; (3) healthcare and self-care tasks, particularly, the cognitive, emotional, and experiential results of accomplishing these tasks despite competing priorities; (4) their social networks; and (5) their environment, particularly when they encountered kindness or empathy about their condition and a feasible treatment plan. Patient capacity is a complex and dynamic construct that exceeds "resources" alone. Additional work needs to translate this emerging theory into useful practice for which we propose a clinical mnemonic (BREWS) and the ICAN Discussion Aid.


Evaluation of selected new drugs: 1990.
1. The new drugs approved by the Food and Drug Administration during 1990 are presented. 2. The pharmacologic actions, indications, dosages, precautions, and adverse reactions of selected new medications are considered. 3. The occupational health nurse can use this information to help clients understand and follow drug treatment plans.


[Indicator volume spirometers].
Pointer volume-spirometers are shown to be of great importance in mass health screening. Considerations are given to design and operational parameters of some state-of-the-art models.


[Fibromyalgia and its diagnosis].
Fibromyalgia or fibromyalgic syndrome (FMS) is a clinical picture of unknown origin that is characterized by generalized, incapacitating and chronic pain together with the demonstration in the physical examination of previously defined points in which moderate pressure causes pain, called fibromyalgia tender points (FTP). FMS lacks objective, analytic imaging or pathological data, so that its diagnosis is based exclusively on subjective data, such as that the pain reported by the patient and the pain caused by the FTP pressure. Although the fibromyalgia classification criteria of the American College of Rheumatology are not diagnostic criteria, they have been extensively used to diagnose FMS in patients with chronic diffuse arthromyalgias. Fibromyalgia diagnosis reduces the patient's anxiety, avoiding complementary expensive and unnecessary tests and it allows the patient to share his/her fears, illnesses and expectations with other human beings who suffer the same problem.


Methods for evaluating the pollution impact of urban wet weather discharges on biocenosis: A review.
Rainwater becomes loaded with a large number of pollutants when in contact with the atmosphere and urban surfaces. These pollutants (such as metals, pesticides, PAHs, PCBs) reduce the quality of water bodies. As it is now acknowledged that physico-chemical analyses alone are insufficient for identifying an ecological impact, these analyses are frequently completed or replaced by impact studies communities living in freshwater ecosystems (requiring biological indices), ecotoxicological studies, etc. Thus, different monitoring strategies have been developed over recent decades aimed at evaluating the impact of the pollution brought by urban wet weather discharges on the biocenosis of receiving aquatic ecosystems. The purpose of this review is to establish a synthetic and critical view of these different methods used, to define their advantages and disadvantages, and to provide recommendations for futures researches. Although studies on aquatic communities are used efficiently, notably on benthic macroinvertebrates, they are difficult to interpret. In addition, despite the fact that certain bioassays lack representativeness, the literature at present appears meagre regarding ecotoxicological studies conducted in situ. However, new tools for studying urban wet weather discharges have emerged, namely biosensors. The advantages of biosensors are that they allow monitoring the impact of discharges in situ and continuously. However, only one study on this subject has been identified so far, making it necessary to perform further research in this direction.


Introduction of Subcutaneous Infliximab CT-P13 and Vedolizumab in Clinical Practice: A Multi-Stakeholder Position Statement Highlighting the Need for Post-Marketing Studies.
Although subcutaneous formulations of infliximab CT-P13 and vedolizumab are registered for treating moderate-to-severe inflammatory bowel disease [IBD], many questions on their use remain unanswered. We set up a multi-stakeholder initiative resulting in a position statement. Based on publicly available data, statements on subcutaneous infliximab and vedolizumab were developed and reviewed by 45 Belgian IBD physicians in a three-round modified Delphi process. During a consensus meeting, input from 16 IBD patients, nine IBD nurses and two clinical pharmacologists was provided and statements were further discussed, modified and scored. Statements achieving agreement by at least 70% of the IBD physicians were accepted. The Delphi process resulted in 79 agreed statements. In patients initiating intravenous therapy, IBD physicians would only consider switching to subcutaneous formulations in patients achieving both clinical and biological response [for Crohn's disease] or both clinical and endoscopic response [for ulcerative colitis]. For patients under maintenance therapy, switching to subcutaneous formulations was only considered in those achieving both clinical and endoscopic response while receiving standard dosing of infliximab or vedolizumab. While awaiting more scientific data, IBD physicians should consider weekly subcutaneous injections or switching back to an intravenous formulation in case of loss of response. Finally, switching to a subcutaneous formulation should always be a shared decision. All stakeholders welcomed subcutaneous infliximab and vedolizumab. However, more scientific data are needed to select the right patients and timing for switching to these newer formulations, and to explore the optimal strategy in case of loss of response.


Paeonol pretreatment attenuates cerebral ischemic injury via upregulating expression of pAkt, Nrf2, HO-1 and ameliorating BBB permeability in mice.
Oxidative damage plays a pivotal role in the pathogenesis of cerebral ischemic stroke and may represent a target for treatment. Our previous studies have proved that nuclear factor E2-related factor 2 (Nrf2) and its downstream genes served as a key mechanism for protection against oxidative stress. Paeonol (PN) is reputed to possess a broad range of therapeutic properties probably by virtue of its antioxidative ability. However little is elucidated regarding the underlying mechanisms in ischemic stroke. The aim of this study was to explore PNs effect in ischemic injury and the role of the pAkt, Nrf2 and hemeoxygenase-1 (HO-1) in the mice brains of permanent middle cerebral artery occlusion (pMCAO). Male CD-1 mice were subjected to pMCAO and randomly divided into five groups: Sham (sham-operated+0.9% saline), pMCAO (pMCAO+0.9% saline), Vehicle (pMCAO+vehicle), PN-L (pMCAO+PN 30 mg/kg) and PN-H (pMCAO+PN 60 mg/kg) groups. PN was pre-administered intragastrically once daily for 3 days and with the last administration at 30 min before the operation in the fourth day. Neurological deficit scores, brain water content and infarct volume were measured at 24h after pMCAO. Western blot and qRT-PCR were employed to determine the expressions of pAkt, Nrf2, HO-1 and claudin-5. Superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by spectrophotometer. Compared with Vehicle group, PN significantly alleviated neurological deficit, infarct volume and brain edema (P<0.05), upregulated the expression of pAkt, Nrf2, HO-1 and SOD (P<0.05), decreased the level of MDA (P<0.05). Meanwhile, the expression of claudin-5 was also enhanced. PN reduced ischemic brain injury after pMCAO; this effect may be accompanied with upregulation of pAkt, Nrf2, HO-1 and ameliorating BBB permeability.


Immunoreactive endothelin in the human kidney: comparison with natriuretic peptides.
The presence of immunoreactive endothelin (IR-ET) was studied by radioimmunoassay in human kidney with and without clinical renal failure, and the levels were compared with those of three natriuretic peptides: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Kidney tissues were obtained at autopsy from three subjects with renal disorders (diabetic nephropathy, renal tubular necrosis, and end-stage kidney disease). Normal renal tissue was obtained at surgery from two patients with renal cell carcinoma. IR-ET was detected in three diseased kidneys obtained at autopsy (0.101 +/- 0.043 pmol/g wet weight, mean +/- SD) but not in tissues of two normal kidneys obtained at surgery (< 0.015 pmol/g wet weight). Reverse-phase HPLC showed that most of the IR-ET in the kidney (> 90%) was eluted in the position of ET-1. IR-ANP (0.23 +/- 0.06 pmol/g wet weight), IR-BNP (1.15 +/- 0.94 pmol/g wet weight), and IR-CNP (0.44 +/- 0.16 pmol/g wet weight) were detected in all samples examined. Higher concentrations of IR-BNP were found in three diseased kidneys obtained at autopsy (1.70 +/- 0.83 pmol/g wet weight vs. mean in two normal kidney tissues, 0.32 pmol/g wet weight). Such increases were not observed in IR-ANP or IR-CNP. These findings indicate that IR-ET is present in the human diseased kidney even in end-stage disease, with high concentrations comparable to those of natriuretic peptides. This raises the possibility that the production of ET-1 and BNP is increased in kidneys of patients with renal disorders.


Total shoulder arthroplasty in France: An analysis of trends between 2009 and 2019 and projections to the year 2070.
Over the past decades, total shoulder arthroplasty (TSA) procedures have steadily increased in the United States and Europe. In France, the number of shoulder surgeries rose by 24.5% between 2012 and 2018, but no study has yet analyzed TSA trends based on patient characteristics. Therefore, the aim of our study was to use the French healthcare database to (1) analyze growth trends based on the patient's sex, age, and comorbidity profile and (2) estimate the most appropriate incidence rate (IR) projections to the year 2070. We hypothesize that in France, the upward trends are different for each sex and age group. This study was conducted in France from 2009 to 2019 based on the French healthcare database (SNDS), which contains all nationwide procedures. Patients were analyzed by sex, age group (< 65 years, 65-74 years, ≥ 75 years), and comorbidity profile (4 levels). IR trends per 100,000 population were inferred by patient age, sex, and comorbidity using data from the French hospital discharge database (PMSI) and population forecasts and censuses from the French National Institute of Statistics and Economic Studies (INSEE). Linear, Poisson, logistic, and Gompertz projection models were created to forecast IRs to the year 2070. Between 2009 and 2019, there was a sharper increase in IR in males (+155%; from 6.0 to 15.3) than in females (+118%; from 16.2 to 35.3) across all age groups. This increase was most significant in those younger than 65 years (+112%; from 2.3 to 4.9), in both males (+129%; from 2.1 to 4.8) and females (+99%; from 2.5 to 5.0). From 2012 to 2019, the proportion of patients with mild comorbidities increased by +92% (from 5,435 to 10,410 TSAs, i.e., from 56% to 61% of total procedures), unlike the other comorbidity profiles. All the projections modeled the data from 2009 to 2019 with minor deviations. However, the logistic projection was the most likely, with a 45% increase in the IR for the overall population by 2070 (from 17,175 to 25,338 TSAs), which will start to plateau in 2050. The IR has risen sharply in the overall population, as in all age, sex, and comorbidity categories, with the most significant growth seen in the < 65 and 65-74 age groups and a shift toward patients with milder comorbidities. According to our projections, the IR will continue to be more significant in older patients, except for males, for whom the IR for those 65 to 74 years old will exceed that of those 75 and older around 2030. In the longer term, the IRs follow a logistic trend, reaching a plateau around 2050. Therefore, an increase in healthcare burden is to be expected to meet the growing demand for TSAs. IV; Descriptive epidemiological study.


Diet Traps during Eating Disorders among Dentate Patients at an Oral Health Glance.
Persons suffering from eating disorders (ED) may often experience a recurrence/persistence symptoms despite the completion of psychiatric therapy. In most cases, their general health status is linked to current nutritional behaviors. Medical professionals, general practitioners (GPs), dieticians, and dentists may see those patients in their practices. At the same time, due to low sense of illness, some patients may delay or never seek professional medical care. The aim of this article is to analyze the main ED types according to dietary behaviors causing oral health problems and discuss oral health complications in affected dentate patients. The second objective is to update oral preventive measures and technological innovations together with active agents for oral hygiene care that might effectively support oral health maintenance during the presence of long-term symptoms. The research method involved a review of clinical reports as a synthesis of the electronic research in the Pubmed, Web of Science, and Google Scholar databases. Based on the research, ED patients were found to present related incidences of oral complications. Studies have reported that the possible course of an ED and comorbidities may be an imbalance in the oral environment. The results showed an association between biological (malnutrition, etc.), behavioral (binge eating episodes, vomiting, acidic diet, poor oral hygiene), and pharmacotherapeutic (addiction, hyposalivation) factors that may threaten oral health. Early diagnosis of the past and present symptoms is essential to eliminate and take control of destructive behaviors. Oral changes need to be tackled with medical insight, and additionally, the perception of dietary interactions is recommended.


Ethnobotanical study of indigenous knowledge on medicinal plant use by traditional healers in Oshikoto region, Namibia.
The objective of this study was to establish a regional profile of the indigenous knowledge system (IKS) for medicinal plant use and cultural practices associated with the healing process of these plants by traditional healers in the Oshikoto region, Namibia. An ethnobotanical survey was undertaken to collect information from traditional healers during September and October 2008. Data was collected through the use of questionnaires and personal interviews during field trips in the ten constituencies of the Oshikoto region. A total of 47 respondents were interviewed with most of them aged 66 and above. The traditional healers in Oshikoto region use 61 medicinal plant species that belong to 25 families for the treatment of various diseases and disorders with the highest number of species being used for mental diseases followed by skin infection and external injuries. Trees (28 species) were found to be the most used plants followed by herbs (15 species), shrubs (10 species) and climbers (4 species). The average of the informant consensus factor (F IC) value for all ailment categories was 0.75. High F IC values were obtained for Pergularia daemia, and Tragia okanyua, which were reported to treat weakness and dizziness problems, snake bite, swelling and cardiovascular problems indicating that these species traditionally used to treat these ailments are worth examining for bioactive compounds. The traditional healers in Oshikoto possess rich ethno-pharmacological knowledge. This study allows for identifying many high value medicinal plant species, indicating high potential for economic development through sustainable collection of these medicinal plants.


Extracellular Vesicles Generated Using Bioreactors and their Therapeutic Effect on the Acute Kidney Injury Model.
Extracellular vesicles (EVs) are nano-sized vesicles secreted by cells, having beneficial effects for various types of regenerative processes. Although EVs have shown promising effects as therapeutic agents, these effects are difficult to research due to the limitations of EV production. In this study, an EV production method based on a flat-plate bioreactor is introduced. The bioreactor produces approximately seven times more mesenchymal stem cell-derived EVs than static culture conditions. The mechanism underlying the increased production of EVs in a flat-plate bioreactor and its application to acute kidney injury is investigated. This study describes the mechanism of EV production by demonstrating the link between EV biogenesis and increased calcium ion concentration under flow conditions. EVs secreted by cells cultured in the bioreactor have therapeutic efficacy in terms of improving kidney damage, resulting in tissue regeneration in a cisplatin-induced acute kidney injury model. This method will help overcome the limitations of EV production, and the analysis of the application of EVs will increase their reliability as well as the understanding of the use of bioreactor-derived EVs as therapeutic agents.


Methicillin-Resistant Staphylococcus aureus ST80 Clone: A Systematic Review.
This review assessed the molecular characterization of the methicillin-resistant Staphylococcus aureus (MRSA)-ST80 clone with an emphasis on its proportion of total MRSA strains isolated, PVL production, spa-typing, antibiotic resistance, and virulence. A systematic review of the literature was conducted on MRSA-ST80 clone published between 1 January 2000 and 31 August 2019. Citations were chosen for a review of the full text if we found evidence that MRSA-ST80 clone was reported in the study. For each isolate, the country of isolation, the sampling period, the source of isolation (the type of infection, nasal swabs, or extra-human), the total number of MRSA strains isolated, number of MRSA-ST80 strains, antibiotic resistance patterns, PVL production, virulence genes, and spa type were recorded. The data from 103 articles were abstracted into an Excel database. Analysis of the data showed that the overall proportion of MRSA-ST80 has been decreasing in many countries in recent years. The majority of MRSA-ST80 were PVL positive with spa-type t044. Only six reports of MRSA-ST80 in extra-human niches were found. This review summarizes the rise of MRSA-ST80 and the evidence that suggests that it could be in decline in many countries.


Cyclooxygenase-2 in rat nephron development.
The inducible second isoform of cyclooxygenase (COX-2) that mediates inflammation also is expressed at low levels in normal adult rat kidneys and is upregulated in response to noninflammatory stimuli (R. C. Harris, J. A. McKanna, Y. Akai, H. R. Jacobson, R. N. DuBois, and M. D. Breyer, J. Clin. Invest. 94: 2504-2510, 1994). Roles in morphogenesis are indicated by reported teratogenicity of COX inhibitors and renal dysgenesis in COX-2 knockout mice (J. E. Dinchuk, B. D. Car, R. J. Focht, J. J. Johnston, B. D. Jaffee, M. B. Covington, N. R. Contel, V. M. Eng, R. J. Collins, P. M. Czerniak, A. G. Stewart, and J. M. Trzaskos, Nature 378: 406-409, 1995; S. G. Morham, R. Lagenbach, C. D. Loftin, H. F. Tiano, N. Vouloumanos, J. C. Jennette, J. F. Mahler, K. D. Kluckman, A. Ledford, C. A. Lee, and O. Smithies. Cell 83: 473-482, 1995). Blots from developing rat kidneys demonstrated that COX-2 mRNA and immunoreactive protein were present in neonates, peaked in the 2nd and 3rd postnatal weeks and declined to adult levels by the 3rd month. Immunolocalization and in situ hybridization detected intense COX-2 immunoreactivity and mRNA in a subset of thick ascending limb epithelial cells near the macula densa in each developing nephron; after 2 wk the COX-2 gradually waned. These data demonstrate that COX-2 expression is subject to normal developmental regulation and can be sustained over extended periods; they also support the conclusion that metabolites of COX-2 play important roles in the differentiation and early functions of mammalian nephrons.


New mitochondrial primers for metabarcoding of insects, designed and evaluated using in silico methods.
Insect metabarcoding has been mainly based on PCR amplification of short fragments within the "barcoding region" of the gene cytochrome oxidase I (COI). However, because of the variability of this gene, it has been difficult to design good universal PCR primers. Most primers used today are associated with gaps in the taxonomic coverage or amplification biases that make the results less reliable and impede the detection of species that are present in the sample. We identify new primers for insect metabarcoding using computational approaches (ecoprimers and degeprime) applied to the most comprehensive reference databases of mitochondrial genomes of Hexapoda assembled to date. New primers are evaluated in silico against previously published primers in terms of taxonomic coverage and resolution of the corresponding amplicons. For the latter criterion, we propose a new index, exclusive taxonomic resolution, which is a more biologically meaningful measure than the standard index used today. Our results show that the best markers are found in the ribosomal RNA genes (12S and 16S); they resolve about 90% of the genetically distinct species in the reference database. Some markers in protein-coding genes provide similar performance but only at much higher levels of primer degeneracy. Combining two of the best individual markers improves the effective taxonomic resolution with up to 10%. The resolution is strongly dependent on insect taxon: COI primers detect 40% of Hymenoptera, while 12S primers detect 12% of Collembola. Our results indicate that amplicon-based metabarcoding of insect samples can be improved by choosing other primers than those commonly used today.


China's success in increasing per capita food production.
China has to feed 20% of the global population with only about 5% of the planet's water resources and 7% of its arable land. With such limited natural conditions, however, China's grain production has increased from about 200 kg per capita in 1949 to about 400 kg in the early 1990s. Hunger as a social problem has largely disappeared after being prevalent in China for several thousand years with the rise and decline of dynasties. This achievement has been accompanied by a 2.5-fold increase in the population and a 4.5-fold increase in total grain production. Although total cropped land has increased slightly in some areas, land used for cropping has decreased from 0.18 hectare per capita in the 1950s to less than 0.1 hectare per capita today. Apparently, yield increase or improved land productivity is the major contributor to the increase of food production per capita. What are the major reasons for the unprecedented achievement in China's food production? Political decisions, good or bad, on land distribution and ownership changes, have caused unusual fluctuation in grain production. Technical progress, however, has maintained a long-term increasing trend. The semi-dwarf cultivars of rice and wheat, the use of heterosis in rice and maize, and the alleviation of salinized soil stress in the major grain-producing areas have all played significant roles in increasing China's food production capability.


Artificial intelligence-based predictive models in vascular diseases.
Cardiovascular disease represents a source of major health problems worldwide, and although medical and technical advances have been achieved, they are still associated with high morbidity and mortality rates. Personalized medicine would benefit from novel tools to better predict individual prognosis and outcomes after intervention. Artificial intelligence (AI) has brought new insights to cardiovascular medicine, especially with the use of machine learning techniques that allow the identification of hidden patterns and complex associations in health data without any a priori assumptions. This review provides an overview on the use of artificial intelligence-based prediction models in vascular diseases, specifically focusing on aortic aneurysm, lower extremity arterial disease, and carotid stenosis. Potential benefits include the development of precision medicine in patients with vascular diseases. In addition, the main challenges that remain to be overcome to integrate artificial intelligence-based predictive models in clinical practice are discussed.


Phase transitions and optimal transport in stochastic roundabout traffic.
We study traffic in a roundabout model, where the dynamics along the interior lane of the roundabout are described by the totally asymmetric simple exclusion process (TASEP). Vehicles can enter the interior lane or exit from it via S intersecting streets with given rates, and locally modified dynamics at the junctions take into account that collisions of entering vehicles with vehicles approaching the entrance point from the interior lane should be avoided. A route matrix specifies the probabilities for vehicles to arrive from and to exit to certain intersecting streets. By subdividing the interior lane into segments between consecutive intersecting streets with effective entrance and exit rates, a classification of the stationary roundabout traffic in terms of TASEP multiphases is given, where each segment can be in either the low-density, high-density, or maximum current TASEP phase. A general methodology is developed, which allows one to calculate the multiphases and optimal throughput conditions based on a mean-field treatment. Explicit analytical results from this treatment are derived for equivalent interesting streets. The results are shown to be in good agreement with kinetic Monte Carlo simulations.


Role of wire-guided breast biopsy for diagnosis of malignant nonpalpable mammographic lesions.
Biopsies of mammographically detected nonpalpable lesions have resulted in increased numbers of diagnosed early breast malignancies. From June 1992 to September 1996 a total of 433 consecutive patients underwent 438 biopsies. The mean age was 55.7 years (range 30-82 years); 150 patients were younger than 50 years. Mammographic findings were classified as microcalcifications (C), masses (M), masses with microcalcifications (MC), architectural distortions (A), and stellate lesions (S). In 30 women two needles were placed to localize a lesion in the ipsilateral side and in 5 on the contralateral side. There were 182 (41.6%) biopsies performed for M, 144 (32.9%) for C, 78 (17.8%) for A, 25 (5.7%) for MC, and 9 (2.1%) for S. The overall malignancy rate was 34% (149/438). Thirty-four women (23%) who presented malignancy were younger than 50 years of age. From year to year, it increased from 27% during the first year to 51% during the fourth year. Altogether 100 (67%) patients had invasive carcinoma, 40 (27%) ductal carcinoma in situ (DCIS), 6 (4%) lobular carcinoma in situ, and 3 (2%) tubular carcinoma. Four patients had simultaneous bilateral palpable and nonpalpable carcinoma. Among the patients, 9 of 20 with previously operated breast carcinoma and 9 of 19 with other previous malignancies were found to have early breast carcinoma. The mammographic finding with high rates of malignancy were S 67%, MC 40%, M 34%, C 33%, and A 28%. A group of 11 of 110 (10%) patients had histologically proven axillary lymph node metastasis. Results from this large retrospective study of wire-guided localization biopsies showed a relatively high rate of malignancy (34%) and DCIS (27%).


Insulin Sensitivity Is Retained in Mice with Endothelial Loss of Carcinoembryonic Antigen Cell Adhesion Molecule 1.
CEACAM1 regulates endothelial barrier integrity. Because insulin signaling in extrahepatic target tissues is regulated by insulin transport through the endothelium, we aimed at investigating the metabolic role of endothelial CEACAM1. To this end, we generated endothelial cell-specific Ceacam1 null mice (VECadCre+Cc1fl/fl) and carried out their metabolic phenotyping and mechanistic analysis by comparison to littermate controls. Hyperinsulinemic-euglycemic clamp analysis showed intact insulin sensitivity in VECadCre+Cc1fl/fl mice. This was associated with the absence of visceral obesity and lipolysis and normal levels of circulating non-esterified fatty acids, leptin, and adiponectin. Whereas the loss of endothelial Ceacam1 did not affect insulin-stimulated receptor phosphorylation, it reduced IRS-1/Akt/eNOS activation to lower nitric oxide production resulting from limited SHP2 sequestration. It also reduced Shc sequestration to activate NF-κB and increase the transcription of matrix metalloproteases, ultimately inducing plasma IL-6 and TNFα levels. Loss of endothelial Ceacam1 also induced the expression of the anti-inflammatory CEACAM1-4L variant in M2 macrophages in white adipose tissue. Together, this could cause endothelial barrier dysfunction and facilitate insulin transport, sustaining normal glucose homeostasis and retaining fat accumulation in adipocytes. The data assign a significant role for endothelial cell CEACAM1 in maintaining insulin sensitivity in peripheral extrahepatic target tissues.


A Pro-resolving Role for Galectin-1 in Acute Inflammation.
Galectin-1 (Gal-1) exerts immune-regulatory and anti-inflammatory actions in animal models of acute and chronic inflammation. Its release into the extracellular milieu often correlates with the peak of inflammation suggesting that it may serve a pro-resolving function. Gal-1 is reported to inhibit neutrophil recruitment and induce surface exposure of phosphatidylserine (PS), an "eat me" signal on the surface of neutrophils, yet its role in resolution remains to be fully elucidated. We hypothesized that the anti-inflammatory and pro-resolving properties of Gal-1 are mediated through its ability to inhibit neutrophil recruitment and potentiate neutrophil clearance. To investigate this, a murine model of self-resolving inflammation was utilized to uncover the role of both the endogenous and exogenous protein using Gal-1 null mice and recombinant protein, respectively. We found that peritoneal macrophages express increased Gal-1 during the resolution phase and enhanced neutrophil recruitment occurs in the early phases of zymosan peritonitis in Gal-1 null mice compared to their wild-type (WT) counterparts. Administration of recombinant Gal-1 following the peak of inflammation led to reduced neutrophil numbers at 24 and 48 h, shortening the resolution interval from 39 to 14 h. Gal-1 treatment also enhanced neutrophil apoptosis, indicating a pro-resolving action. Together these results indicate an important role for Gal-1 in the timely resolution of acute inflammation.


[Ischemia-Reperfusion Injury: Molecular Mechanisms of Pathogenesis and Methods of Their Correction].
Ischemia-reperfusion is a cascade of complex and interrelated pathological processes underlying many human diseases, including such socially significant diseases as stroke, myocardial infarction, acute renal failure, etc. The present review considers modern ideas about the main biochemical and signal-regulatory processes in the cell under conditions of ischemia-reperfusion. Both generally accepted and newly developed ways of ischemia-reperfusion lesion correction aimed at different chains of this pathological process are considered.


FolamiRs: Ligand-targeted, vehicle-free delivery of microRNAs for the treatment of cancer.
MicroRNAs are small RNAs that negatively regulate gene expression posttranscriptionally. Because changes in microRNA expression can promote or maintain disease states, microRNA-based therapeutics are being evaluated extensively. Unfortunately, the therapeutic potential of microRNA replacement is limited by deficient delivery vehicles. In this work, microRNAs are delivered in the absence of a protective vehicle. The method relies on direct attachment of microRNAs to folate (FolamiR), which mediates delivery of the conjugated microRNA into cells that overexpress the folate receptor. We show that the tumor-suppressive FolamiR, FolamiR-34a, is quickly taken up both by triple-negative breast cancer cells in vitro and in vivo and by tumors in an autochthonous model of lung cancer and slows their progression. This method delivers microRNAs directly to tumors in vivo without the use of toxic vehicles, representing an advance in the development of nontoxic, cancer-targeted therapeutics.


Vaginal discharge: The diagnostic enigma.
Vaginal discharge is a common clinical problem with varied etiologies, most common being bacterial vaginosis which presents as homogenous gray discharge caused by overgrowth of facultative and anaerobic bacterial species, next common is vulvovaginal candidiasis characterized by pruritus and cottage cheese like discharge followed by vaginal trichomoniasis associated with copious yellow or green and frothy discharge. This necessitates the need to identify the specific cause of vaginal discharge. To determine the etiology of pathological vaginal discharges in women attending tertiary care hospital. 698 sexually active females in age group of 15 to 65 years with complaints of vaginal discharge attending Department of Dermatology Venereology and Leprosy at a Tertiary care hospital from June 2017 to May 2018 participated in the study. After presumptive clinical diagnosis vaginal discharge was collected. Wet mounts and 10% KOH preparations were examined immediately. Identification of pathogens was done by Gram stain and culture. 18.33% of 698 patients showed vulvovaginal candidiasis, 13.75% had bacterial vaginosis, 1.86% showed trichomoniasis. Gold standard was considered to be culture for candidiasis & trichomoniasis whereas for bacterial vaginosis it was Nugent's score. Vaginal discharge is of multiple yet specific etiologies hence simple and minimal tests like microscopy available in most laboratories (supported by culture wherever possible) would help in accurate diagnosis without over or under treatment of patient due to the empirical therapy. Syndromic management of STIs (WHO guidelines) should be used only in non-specific cases.


Development of liquid-lithium film jet-flow for the target of (7)Li(p,n)(7)Be reactions for BNCT.
A feasibility study on liquid lithium target in the form of a flowing film was performed to evaluate its potential use as a neutron generation target of (7)Li(p,n)(7)Be reaction in BNCT. The target is a windowless-type flowing film on a concave wall. Its configuration was adapted for a proton beam which is 30mm in diameter and with energy and current of up to 3MeV and 20mA, respectively. The flowing film of liquid lithium was 0.6mm in thickness, 50mm in width and 50mm in length. The shapes of the nozzle and concave back wall, which create a stable flowing film jet, were decided based on water experiments. A lithium hydrodynamic experiment was performed to observe the stability of liquid lithium flow behavior. The flowing film of liquid lithium was found to be feasible at temperatures below the liquid lithium boiling saturation of 342°C at the surface pressure of 1×10(-3)Pa. Using a proto-type liquid lithium-circulating loop for BNCT, the stability of the film flow was confirmed for velocities up to 30m/s at 220°C and 250°C in vacuum at a pressure lower than 10(-3) Pa. It is expected that for practical use, a flowing liquid lithium target of a windowless type can solve the problem of radiation damage and target cooling.


Techniques for understanding the customer.
Who are the customers and what do they want? Every health care employee sometimes serves as a supplier providing input to an activity and sometimes as the recipient of the activity. This article explains the Kano model, which distinguishes between expected quality, one-dimensional, quality, and exciting quality. It also introduces Quality Function Deployment and the Customer Window, two tools for understanding and prioritizing customer demands.


Solid-liquid interface free energies of pure bcc metals and B2 phases.
The solid-liquid interface (SLI) free energy was determined from molecular dynamics (MD) simulation for several body centered cubic (bcc) metals and B2 metallic compounds (space group: Pm3̄m; prototype: CsCl). In order to include a bcc metal with a low melting temperature in our study, a semi-empirical potential was developed for Na. Two additional synthetic "Na" potentials were also developed to explore the effect of liquid structure and latent heat on the SLI free energy. The obtained MD data were compared with the empirical Turnbull, Laird, and Ewing relations. All three relations are found to predict the general trend observed in the MD data for bcc metals obtained within the present study. However, only the Laird and Ewing relations are able to predict the trend obtained within the sequence of "Na" potentials. The Laird relation provides the best prediction for our MD data and other MD data for bcc metals taken from the literature. Overall, the Laird relation also agrees well with our B2 data but requires a proportionality constant that is substantially different from the bcc case. It also fails to explain a considerable difference between the SLI free energies of some B2 phases which have nearly the same melting temperature. In contrast, this difference is satisfactorily described by the Ewing relation. Moreover, the Ewing relation obtained from the bcc dataset also provides a reasonable description of the B2 data.


Undergraduate nursing students' attitudes towards organ donation: a survey in an Italian university.
To examine undergraduate nursing students' attitudes towards organ donation and to determine whether or not attitudes were related to the students' education and training. Nurses' knowledge and personal opinion can influence patient's willingness to donate organs or to hold an organ donor card. It is unclear how Italy's future nurses view organ donation. The study's source population consisted of third-year undergraduate nursing students enrolled in seven nursing schools from an Italian university during 2008. Respondents completed self-administered quantitative questionnaire with 61 questions, including the Organ Donation Attitude Scale. Of the 378 students contacted, 183 (48%) completed all survey questions; 140 were females (76.5%) and the mean age of students was 25. The median score of students' attitude scores towards organ donation was 151 (the attitude is positive when the score is higher than 161). No significant correlations were found to exist between organ-donation attitude and sex, age, clinical practice in hospitals with a transplant unit, nursing care to patients waiting for a transplant or dialysis patients. Only 16% of the students had previously signed a donor card consenting to their own organ donation. The study revealed that doubts about transplantable organs still exist within the student body. This study highlighted that students' awareness of organ donation was not adequate and that attitude levels were lower than in other countries. If these future workers would receive adequate training, they could promote organ donation to the general public and to other hospital personnel.


Anti-Ma2-associated limbic encephalitis with coexisting chronic inflammatory demyelinating polyneuropathy in a patient with non-Hodgkin lymphoma: A case report.
We report the rare case of a 74-year-old man with anti-Ma2-associated paraneoplastic neurologic syndrome (PNS), and review and analyze the clinical manifestations, diagnosis, and treatment of the disease. The patient presented with a 5-month history of muscle weakness, progressive body aches, and weakness and numbness in both lower extremities. Before his hospitalization, he had experienced cognitive function decline; ptosis, inward gaze, and vertical gaze palsy in the right eye; and occasional visual hallucinations. Brain and spinal cord magnetic resonance imaging (MRI) yielded normal results. Anti-Ma2 antibodies were detected in both serum and cerebrospinal fluid. A 4-hour electroencephalogram showed irregular sharp slow waves and δ waves in the temporal region. Electromyography showed peripheral nerve demyelination. Positron-emission tomography/computed tomography (PET-CT) examination revealed hypermetabolism in the lymph nodes of the whole body. Biopsy of the lymph nodes showed non-Hodgkin lymphoma. A clinical diagnosis of lymphoma and PNS was made. The patient was treated with intravenous dexamethasone (15 mg/day) for 3 days. We have presented a rare case of a PNS involving both the central and peripheral nervous systems. The clinical features of this case indicated anti-Ma2-associated encephalitis and chronic inflammatory demyelinating polyneuropathy. PET-CT played a critical role in enabling early diagnosis and prompt treatment in this case.


Long-term loss of color vision after exposure to mercury vapor.
We evaluated the color vision of 24 subjects (41.6 +/- 6.5 years; 6 females) who worked in fluorescent lamp industries. They had been occupationally exposed to mercury vapor (10.6 +/- 5.2 years) and had been away from the source of exposure for 6.4 +/- 4.04 years. Mean urinary concentration of mercury was 40.6 +/- 36.4 microg/g creatinine during or up to 1 year after exposure and 2.71 +/- 1.19 microg/g creatinine at the time of color vision testing or up to 1 year thereafter. All patients were diagnosed with chronic mercury intoxication, characterized by clinical symptoms and neuropsychological alterations. A control group (N = 36, 48.6 +/- 11.9 years, 10 females, 1.5 +/- 0.47 microg mercury/g creatinine) was subjected to the same tests. Inclusion criteria for both groups were Snellen VA 20/30 or better and absence of known ophthalmologic pathologies. Color discrimination was assessed with the Farnsworth D-15 test (D-15) and with the Lanthony D-15d test (D-15d). Significant differences were found between the two eyes of the patients (P < 0.001) in both tests. Results for the worst eye were also different from controls for both tests: P = 0.014 for D-15 and P < 0.001 for D-15d. As shown in previous studies, the D-15d proved to be more sensitive than the D-15 for the screening and diagnosis of the color discrimination losses. Since color discrimination losses were still present many years after the end of exposure, they may be considered to be irreversible, at least under the conditions of the present study.


Treatment of recurrent sustained ventricular tachycardia with mexiletine and disopyramide. Control by programmed ventricular stimulation.
Oral antiarrhythmic treatment with mexiletine and disopyramide was evaluated in 34 patients with recurrent sustained ventricular tachycardias by programmed ventricular stimulation, except in a few instances where spontaneous attacks occurred under therapy. Coronary heart disease was present in 17 patients, cardiomyopathy in 11, myocarditis in five, and mitral valve prolapse in one. Complete suppression of ventricular tachycardia was observed in three of 30 patients under mexiletine and in one of 25 patients under disopyramide. Disopyramide slowed the rate of the ventricular tachycardia considerably, while mexiletine had no such influence. For a mean of 24 months, 19 patients were maintained on either substance. Complete suppression of ventricular tachycardia during programmed stimulation predicted freedom from recurrences. Ventricular tachycardias recurred less frequently and at a slower rate in the other patients, but 31% have died. This study shows that complete suppression of ventricular tachycardia by mexiletine or disopyramide can be achieved only in a minority of patients with previously drug-resistant tachycardias.


Income-Related Inequalities in Informal Care: Evidence From the Longitudinal Healthy Longevity Survey in China.
This report aims to examine income-related inequalities in informal care among older people with functional limitations in China. Data are drawn from the 2005, 2008, 2011, and 2014 waves of the Chinese Longitudinal Healthy Longevity Survey. Erreygers concentration index, concentration index, and horizontal inequity index are used to examine inequalities in informal care. A random effects model is then used to investigate the relationship between household income and informal care. There is no significant association between household income and the probability of receiving informal care. However, we observed a significant positive association between household income and hours of informal care received, indicating that those with higher household income receive more hours of informal care compared to those with lower household income. The degree of this inequality increases as the number of functional limitations increases. Lower household income is associated with lower intensity of informal care received, particularly for older people with more functional limitations. Policies are required to support low-income older people with more functional limitations.