MUC1 Predicts Colorectal Cancer Metastasis: A Systematic Review and Meta-Analysis of Case Controlled Studies.
To evaluate the predicting value of MUC1 expression in lymph node and distant metastasis of colorectal cancer (CRC). Pubmed/ MEDLINE and EMBASE were searched to identify eligible studies that evaluated the correlation between MUC1 and CRC. A meta-analysis was conducted to evaluate the impact of MUC1 expression on CRC metastasis. A total of 18 studies (n = 3271) met inclusion criteria and the mean Newcastle-Ottawa Scale (NOS) score was 6.3 with a range from 4 to 8. The pooled OR in the meta-analysis of 15 studies indicated that positive MUC1 expression correlated with more CRC node metastasis (OR = 2.32, 95% CI = 1.63-3.29). The data synthesis of 6 studies suggested that MUC1 expression predicted more possibility of CRC distant metastasis (OR = 2.22, 95% CI = 1.23-4.00). In addition, the combined OR of 7 studies showed that MUC1 expression indicated higher Duke's stage (OR = 3.02, 95% CI = 2.11-4.33). No publication bias was found in the mate-analysis by Begg's test or Egger's test with the exception of the meta-analysis of MUC1 with CRC node metastasis (Begg's test p = 0.729, Egger's test p = 0.000). Despite of some modest bias, the pooled evidence suggested that MUC1 expression was significantly correlated with CRC metastasis.


Mechanisms of phenylalanine-induced pressor effects in conscious rats.
Phenylalanine and tyrosine reportedly decrease blood pressure in conscious restrained rats. However, tyrosine has recently been found to increase blood pressure in anesthetized animals, questioning the generality of findings obtained in restrained animals. The present study therefore evaluated the effects of phenylalanine on mean arterial pressure (MAP) and heart rate (HR) in unrestrained, conscious rats. Phenylalanine (0.32-1.33 mmol/kg i.p.) increased MAP and decreased HR, effects that were antagonized by carbidopa and prazosin but not by desipramine. In addition, both DOPA and tyrosine (1.33 mmol/kg) increased MAP. In contrast, phenylalanine-induced increases in plasma concentrations of its indirectly acting sympathomimetic amine metabolite, phenethylamine, were small and temporally unrelated to the phenylalanine-induced MAP elevation, and desipramine inhibited MAP increases produced by exogenous phenethylamine. These observations indicate that phenylalanine increases MAP in conscious, unrestrained animals by augmenting peripheral catecholamine synthesis and release rather than by affecting phenethylamine bioavailability.


Severe Left Main Coronary Stenosis Due to Aortic Bioprosthesis Implantation: A Case Report.
Coronary artery ostial stenosis is a common but life-threatening complication that usually presents right after valve implantation, especially in transcatheter aortic valve implantation (TAVI) procedure. However, as reported in our case, it may also have a late delayed presentation in valve replacement through median sternotomy. Here, we present a rare case of one patient who underwent percutaneous coronary intervention (PCI) for severe stenosis of the left main (LM) coronary artery six months after Mosaic aortic bioprosthesis implantation.


Detection and evaluation of intracranial aneurysms with 16-row multislice CT angiography: comparison with conventional angiography.
The aim of our study was to compare multidetector row computed tomography (CT) angiography (MDCTA) with digital subtraction angiography (DSA) in the detection and characterization of intracranial aneurysms. Between September 2005 and May 2007, 55 consecutive patients with suspected intracranial aneurysms underwent conventional DSA and MDCTA. Thirty-two women and 23 men were enrolled in the study. The mean patient age was 54 (range = 26-79 years). All MDCTA and DSA images were independently evaluated on a workstation by two radiologists, who had 8 and 6 years of experience in CT vascular imaging and angiography. Using DSA as the gold standard, the sensitivity and specificity of CT angiography was calculated for each reader with 95% confidence intervals. The sensitivity was also calculated for aneurysms smaller than 3 mm with 95% confidence intervals. The agreement between the readers for detecting aneurysms was calculated using kappa statistics. A kappa statistic greater than 0.75 was considered an excellent agreement beyond chance, a kappa statistic of 0.4-0.75, fair to good agreement, and a kappa statistic less than 0.4, poor agreement. At DSA, 64 aneurysms were present in 50 patients involved in the study; seven patients had two aneurysms each, and four patients had three aneurysms each. In five patients, no aneurysm was detected by using MDCTA and DSA, and evaluations were considered as true negative by MDCTA. These five patients also had negative findings at repeat DSA. For readers 1 and 2, the sensitivity of MDCT in detecting aneursyms were 96.9% (95% CI = 89.3-99.1%; 62 of 64) and 98.4 % (95% CI = 91.7-99.7%; 63 of 64), respectively. The spescificity was100% (95% CI = 99.7-100%; 1,256 of 1,256) for both readers. The kappa value indicating interobserver agreement was in the category of excellent (kappa = 0.99 (95% CI = 0.97-1). Regarding the aneurysms smaller than 3 mm, for readers 1 and 2, the sensitivities were 84.6% (95% CI = 57.8-95.7%; 11 of 13) and 92.3% (95% CI = 66.7-98.6; 12 of 13), respectively. MDCTA is accurate in the detection and characterization of intracranial aneurysms and can be used as a reliable alternative imaging technique to DSA. A strategy of using CT angiography as the primary method, with DSA reserved for any cases of uncertainty, appears safe and reliable.


Ambivalence over emotional expression in patients with gastrointestinal cancer and their caregivers: associations with patient pain and quality of life.
This study examined the role of patient and caregiver ambivalence over emotional expression (AEE) in pain and quality of life (QOL) in a sample of 78 patients with gastrointestinal (GI) cancer. Measures of ambivalence over emotional expression as well as ratings of patient pain and pain behavior were collected from patients and caregivers. Measures of pain catastrophizing, perceptions of social support, and QOL were obtained from patients. Data analyses revealed that patients high in AEE engaged in more catastrophizing and reported higher levels of pain behaviors and poorer QOL. In addition, patients whose caregivers were high in AEE engaged in more catastrophizing, had higher levels of pain and pain behavior, and reported lower emotional well-being. Patient catastrophizing mediated the effects of both patient and caregiver AEE on some patient outcomes. Taken together, these findings suggest that emotional regulation in both patients and their caregivers may be an important factor in understanding cancer patients' experience of and coping with symptoms such as pain.


What moves patients to participate in prehabilitation before major surgery? A mixed methods systematic review.
Prehabilitation offers patients the opportunity to actively participate in their perioperative care by preparing themselves for their upcoming surgery. Experiencing barriers may lead to non-participation, which can result in a reduced functional capacity, delayed post-operative recovery and higher healthcare costs. Insight in the barriers and facilitators to participation in prehabilitation can inform further development and implementation of prehabilitation. The aim of this review was to identify patient-experienced barriers and facilitators for participation in prehabilitation. For this mixed methods systematic review, articles were searched in PubMed, EMBASE and CINAHL. Articles were eligible for inclusion if they contained data on patient-reported barriers and facilitators to participation in prehabilitation in adults undergoing major surgery. Following database search, and title and abstract screening, full text articles were screened for eligibility and quality was assessed using the Mixed Method Appraisal Tool. Relevant data from the included studies were extracted, coded and categorized into themes, using an inductive approach. Based on these themes, the Capability, Opportunity, Motivation, Behaviour (COM-B) model was chosen to classify the identified themes. Three quantitative, 14 qualitative and 6 mixed methods studies, published between 2007 and 2022, were included in this review. A multitude of factors were identified across the different COM-B components. Barriers included lack of knowledge of the benefits of prehabilitation and not prioritizing prehabilitation over other commitments (psychological capability), physical symptoms and comorbidities (physical capability), lack of time and limited financial capacity (physical opportunity), lack of social support (social opportunity), anxiety and stress (automatic motivation) and previous experiences and feeling too fit for prehabilitation (reflective motivation). Facilitators included knowledge of the benefits of prehabilitation (psychological capability), having access to resources (physical opportunity), social support and encouragement by a health care professional (social support), feeling a sense of control (automatic motivation) and beliefs in own abilities (reflective motivation). A large number of barriers and facilitators, influencing participation in prehabilitation, were found across all six COM-B components. To reach all patients and to tailor prehabilitation to the patient's needs and preferences, it is important to take into account patients' capability, opportunity and motivation. Registered in PROSPERO (CRD42021250273) on May 18th, 2021.


An innovative model based on N7-methylguanosine-related lncRNAs for forecasting prognosis and tumor immune landscape in bladder cancer.
As a novel type of the prevalent post-transcriptional modifications, N7-methylguanosine (m7G) modification is essential in the tumorigenesis, progression, and invasion of many cancers, including bladder cancer (BCa). However, the integrated roles of m7G-related lncRNAs in BCa remain undiscovered. This study aims to develop a prognostic model based on the m7G-related lncRNAs and explore its predictive value of the prognosis and anti-cancer treatment sensitivity. We obtained RNA-seq data and corresponding clinicopathological information from the TCGA database and collected m7G-related genes from previous studies and GSEA. Based on LASSO and Cox regression analysis, we developed a m7G prognostic model. The Kaplan-Meier (K-M) survival analysis and ROC curves were performed to evaluate the predictive power of the model. Gene set enrichment analysis (GSEA) was conducted to explore the molecular mechanisms behind apparent discrepancies between the low- and high-risk groups. We also investigated immune cell infiltration, TIDE score, TMB, the sensitivity of common chemotherapy drugs, and the response to immunotherapy between the two risk groups. Finally, we validated the expression levels of these ten m7G-related lncRNAs in BCa cell lines by qRT-PCR. We developed a m7G prognostic model (risk score) composed of 10 m7G-related lncRNAs that are significantly associated with the OS of BCa patients. The K-M survival curves revealed that the high-risk group patients had significantly worse OS than those in the low-risk group. The Cox regression analysis confirmed that the risk score was a significant independent prognostic factor for BCa patients. We found that the high-risk group had higher the immune scores and immune cell infiltration. Furthermore, the results of the sensitivity of common anti-BCa drugs showed that the high-risk group was more sensitive to neoadjuvant cisplatin-based chemotherapy and anti-PD1 immunotherapy. Finally, qRT-PCR revealed that AC006058.1, AC073133.2, LINC00677, and LINC01338 were significantly downregulated in BCa cell lines, while the expression levels of AC124312.2 and AL158209.1 were significantly upregulated in BCa cell lines compared with normal cell lines. The m7G prognostic model can be applied to accurately predict the prognosis and provide robust directions for clinicians to develop better individual-based and precise treatment strategies for BCa patients.


Synthesizing biochar-based slow-releasing fertilizers using vermicompost leachate, cow dung, and plant weed biomass.
Biochar-based slow-releasing fertilizers (BSRF) have been recommended widely for efficient soil nutrient management and crop production. In this study, we examined the N, P, and K release behaviour of pyrolysed (at 350 °C) cow dung (CDB), vermicompost (VCB), and Lantana (LB) weed and impregnated LB (LBVW) and CDB (CDBVW) with vermicompost leachate (1:1 v/v) under a lab-scale trial. BSRFs (CDB, VCB, LBVW and VCBVW) characterization (FT-IR, SEM-EDX and surface area analysis) was done and then tested for its suitability for soil-plant applications. Soil incubation study indicated the slow-releasing behaviour of BSRFs and overall P, N, and K release was found to be in the ranges of 72.3-84.5%, 73.1-79.0%, and 43.1-85.3%, respectively in different BSRFs setups. Furthermore, lab trials suggested the highest P (64.5%), N (75.3%), and K (86.8%) uptakes by the plant (Vigna radiata) in CDBVW and LBVW setups. Moreover, pot trails with moong bean (Vigna radiata) suggested a high growth in shoot and root and plant yield as well in seedlings cultivated with BSRFs. This study indicates that animal manure, vermicompost and terrestrial weed Lantana biochar can be used effectively to prepare BSRFs for efficient soil-plant nutrient management with multiple environmental benefits.


Bridging Innovation and Outreach to Overcome Global Gaps in Radiation Oncology Through Information and Communication Tools, Trainee Advancement, Engaging Industry, Attention to Ethical Challenges, and Political Advocacy.
An evolving paradigm in global outreach in radiation oncology has been the implementation of a more region-specific, needs-based approach to help close the gap in radiation services to low- and middle-income countries through the use of innovative tools in information and communication technology. This report highlights 4 information and communication technology tools in action today: (1) the NCCN Framework for Resource Stratification of NCCN guidelines, (2) ASTRO e-Contouring, (3) i.treatsafely.org, and (4) ChartRounds.com. We also render special consideration to matters related to global outreach that we believe require distinct attention to help us meet the goals established by the 2011 United Nations׳ Declaration on noncommunicable diseases: (1) trainee advancement toward careers in global health, (2) ethical challenges of international outreach, (3) critical importance of political advocacy, and (4) collaboration with Industry.


Longitudinal antibody response kinetics following SARS-CoV-2 messenger RNA vaccination in pregnant and nonpregnant persons.
For some vaccine-preventable diseases, the immunologic response to vaccination is altered by a pregnant state. The effect of pregnancy on SARS-CoV-2 vaccine response remains unclear. We sought to characterize the peak and longitudinal anti-S immunoglobulin G, immunoglobulin M, and immunoglobulin A responses to messenger RNA-based SARS-CoV-2 vaccination in pregnant persons and compare them with those in nonpregnant, reproductive-aged persons. We conducted 2 parallel prospective cohort studies among pregnant and nonpregnant persons who received SARS-CoV-2 messenger RNA vaccinations. Blood was collected at the time of first and second vaccine doses, 2 weeks post second dosage, and with serial longitudinal follow-up up to 41.7 weeks post vaccination initiation. Anti-S immunoglobulin M, immunoglobulin G, and immunoglobulin A were analyzed by enzyme-linked immunosorbent assay. We excluded those with previous evidence of SARS-CoV-2 infection by history or presence of antinucleocapsid antibodies. In addition, for this study, we did not include individuals who received a third or booster vaccine dosage during the study period. We also excluded pregnant persons who were not fully vaccinated (14 days post receipt of the second vaccine dosage) by time of delivery and nonpregnant persons who became pregnant through the course of the study. We studied the effect of gestational age at vaccination on the anti-S response using Spearman correlation. We compared the peak anti-S antibody responses between pregnant and nonpregnant persons using a Mann-Whitney U test. We visualized and studied the longitudinal anti-S antibody response using locally weighted scatterplot smoothing, Mann-Whitney U test, and mixed analysis of variance test. Data from 53 pregnant and 21 nonpregnant persons were included in this analysis. The median (interquartile range) age of the pregnant and nonpregnant participants was 35.0 (33.3-37.8) years and 36.0 (33.0-41.0) years, respectively. Six (11.3%) participants initiated vaccination in the first trimester, 23 (43.3%) in the second trimester, and 24 (45.3%) in the third trimester, with a median gestational age at delivery of 39.6 (39.0-40.0) weeks. The median (interquartile range) follow-up time from vaccine initiation to the last blood sample collected was 25.9 (11.9) weeks and 28.9 (12.9) weeks in the pregnant and nonpregnant cohort, respectively. Among pregnant persons, anti-S immunoglobulin G, immunoglobulin A, and immunoglobulin M responses were not associated with gestational age at vaccine initiation (all P>.05). The anti-S immunoglobulin G response at 2 weeks post second dosage was not statistically different between pregnant and nonpregnant persons (P>.05). However, the anti-S immunoglobulin M and immunoglobulin A responses at 2 weeks post second dosage were significantly higher in nonpregnant persons (P<.001 for both). The anti-S immunoglobulin G and immunoglobulin M levels 6 to 8 months after vaccine initiation fell to comparable proportions of the peak 2 weeks post second dosage antibody levels between pregnant and nonpregnant persons (immunoglobulin G P=.77; immunoglobulin M P=.51). In contrast, immunoglobulin A levels 6 to 8 months after vaccine initiation fell to statistically significantly higher proportions of peak 2 weeks post second dosage antibody levels in pregnant compared with nonpregnant persons (P=.002). Maternal anti-S immunoglobulin G levels were strongly correlated with umbilical cord anti-S immunoglobulin G levels (R=0.8, P<.001). The anti-S immunoglobulin A, immunoglobulin M, and immunoglobulin G response to SARS-CoV-2 vaccination in pregnancy is independent of gestational age of vaccine initiation. Maintenance of the immunoglobulin G response is comparable between pregnant and nonpregnant persons. The differential peak response of immunoglobulin M and immunoglobulin A and the differential decline of anti-S immunoglobulin A between pregnant and nonpregnant persons requires further investigation.


Effects of nitric oxide synthase-3 overexpression on post-translational modifications and cell survival in HepG2 cells.
Hepatocarcinoma is the fifth most common neoplasm and the third cause of cancer-related death. The development of genetic- and/or molecular-based therapies is urgently required. The administration of high doses of nitric oxide (NO) promotes cell death in hepatocytes. NO contributes to cell signaling by inducing oxidative/nitrosative-dependent post-translational modifications. The aim of the present study was to investigate protein modifications and its relation with alteration of cell proliferation and death in hepatoma cells. Increased intracellular NO production was achieved by stable nitric oxide synthase-3 (NOS-3) overexpression in HepG2 cells. We assessed the pattern of nitration, nitrosylation and carbonylation of proteins by proteomic analysis. The results showed that NOS-3 cell overexpression increased oxidative stress, which affected proteins mainly involved in cell protein folding. Carbonylation also altered metabolism, as well as immune and antioxidant responses. The interaction of nitrosative and oxidative stress generated tyrosine nitration, which affected the tumor marker Serpin B3, ATP synthesis and cytoskeleton. All these effects were associated with a decrease in chaperone activity, a reduction in cell proliferation and an increased cell death. Our study showed that alteration of nitration, nitrosylation and carbonylation pattern of proteins by NO-dependent oxidative/nitrosative stress was related to a reduction of cell survival in a hepatoma cell line.


Thoracic computed tomographic interpretation for clinicians to aid in the diagnosis of dogs and cats with respiratory disease.
In humans, high-resolution computed tomography (CT) is a key diagnostic modality for pulmonary disorders. Its success likely lies in excellent correlation of lung diseases with associated subgross anatomic changes, as assessed by histopathology, and because of a multidisciplinary approach between clinicians, radiologists and pathologists. Although thoracic CT studies have been performed in dogs and cats for nearly three decades, there is a lack of uniformity in both protocols for acquisition and in terminology used to describe lesions. Importantly, terms such as a bronchial, interstitial, and alveolar patterns are inappropriate descriptors for canine and feline thoracic CT imaging changes; instead, lung patterns should be classified as increased or decreased attenuation, nodular patterns, and linear patterns, with specific vocabulary to describe subtypes of lesions. In this manuscript, the authors provide an overview of basic CT principles, strategies to optimize and acquire high-quality diagnostic studies (inclusive of paired inspiratory and expiratory series, contrast and triphasic angiography) and provide a roadmap for systematic interpretation of thoracic CT images.


Metastable structures and isotope exchange reactions in polyoxometalate ions provide a molecular view of oxide dissolution.
Reactions involving minerals and glasses in water are slow and difficult to probe spectroscopically but are fundamental to the performance of oxide materials in green technologies such as automotive thermoelectric power generation, CO2 capture and storage and water-oxidation catalysis; these must be made from geochemically common elements and operate in hydrous environments. Polyoxometalate ions (POMs) have structures similar to condensed oxide phases and can be used as molecular models of the oxide/water interface. Oxygen atoms in POM exchange isotopes at different rates, but, at present, there is no basis for predicting how the coordination environment and metal substitution influences rates and mechanisms. Here we identify low-energy metastable configurations that form from the breaking of weak bonds between metals and underlying highly coordinated oxygen atoms, followed by facile hydroxide, hydronium or water addition. The mediation of oxygen exchange by these stuffed structures suggests a new view of the relationship between structure and reactivity at the oxide/solution interface.


Rad9/53BP1 promotes DNA repair via crossover recombination by limiting the Sgs1 and Mph1 helicases.
The DNA damage checkpoint (DDC) is often robustly activated during the homologous recombination (HR) repair of DNA double strand breaks (DSBs). DDC activation controls several HR repair factors by phosphorylation, preventing premature segregation of entangled chromosomes formed during HR repair. The DDC mediator 53BP1/Rad9 limits the nucleolytic processing (resection) of a DSB, controlling the formation of the 3' single-stranded DNA (ssDNA) filament needed for recombination, from yeast to human. Here we show that Rad9 promotes stable annealing between the recombinogenic filament and the donor template in yeast, limiting strand rejection by the Sgs1 and Mph1 helicases. This regulation allows repair by long tract gene conversion, crossover recombination and break-induced replication (BIR), only after DDC activation. These findings shed light on how cells couple DDC with the choice and effectiveness of HR sub-pathways, with implications for genome instability and cancer.


The Ludloff osteotomy: a review of current concepts.
The Ludloff osteotomy is a technique option to address hallux valgus in patients with a moderately to significantly increased first-second intermetatarsal angle. The Ludloff osteotomy is an oblique osteotomy of the first metatarsal extending dorsal-proximal to plantar-distal when viewed in the sagittal plane. The dorsal-proximal portion of the metatarsal is cut with the saw while maintaining the plantar-distal surface intact. A screw is inserted across the proximal aspect of the osteotomy, then the osteotomy is extended across the plantar surface distally. The metatarsal is rotated around the axis of the screw to the desired correction. In order to perform the osteotomy correctly, the surgeon must not only effectively complete the nuances of the technique, but also understand the limitations and contraindications of the Ludloff osteotomy. This review of current concepts for the Ludloff osteotomy reviews recent literature as well as technique pearls and pitfalls in the application of this powerful osteotomy.


Correlations between severity of anterior vaginal wall prolapse and parameters of urethral pressure profile.
Previous studies have shown that anterior vaginal wall prolapse (AVWP) results in reduction of pressure in the proximal urethra. However, the effect of severity of AVWP on urethral pressure is controversial. This study aimed to evaluate parameters of the urethral pressure profile in different stages of AVWP. From 2016 to 2017, 286 consecutive patients with urogynecologic complaints who were referred to our urodynamic unit were enrolled in this study to analyze their urethral pressure profiles. Stages of AVWP were regrouped into three groups ranging from mild to severe stages (groups 1-3). Maximal urethral pressure, urethral closure pressure, functional urethral length, length of continence zone, as well as area of continence zone were compared among these three groups. Distribution of age, parity, and menopausal women were significantly different among these three groups. Maximal urethral pressure (pressures for groups 1, 2, and 3 were 74.6∼75.9cmH2O, 69.7∼73.4cmH2O, and 58.3∼60.5cmH2O, respectively; all P<.05) and stress urethral closure pressure (pressures for groups 1, 2, and 3 were 69.3cmH2O, 62.3cmH2O, and 52.2cmH2O, respectively; all P<.05) gradually and significantly decreased, consistent with the severity of AVWP. However, the attenuated maximal urethral pressure and stress urethral closure pressure in accordance with severity did not show any significant difference after controlling for age, body mass index, parity, menopause, and stress urinary incontinence symptoms. Our results showed that AVWP significantly attenuated urethral pressure. However, patient age, menopausal status, and number of parities seem to be more influential in compromising urethral function than just AVWP alone.


Expression of the extracellular region of the human interleukin-4 receptor alpha chain and interleukin-13 receptor alpha1 chain by a silkworm-baculovirus system.
The receptor binding to interleukin (IL)-13 is composed of the IL-13 receptor alpha1 chain (IL-13Ralpha1) and the IL-4 receptor alpha chain (IL-4Ralpha). In order to investigate the interaction of IL-13 with IL-13Ralpha1 and IL-4Ralpha, the DNA fragments coding the extracellular regions of human IL-13Ralpha1 and the IL-4Ralpha (containing a cytokine receptor homologous region) were fused with mouse Fc and expressed by a silkworm-baculovirus system. The expressed receptors were successfully purified by affinity chromatography using protein A, and the Fc region was removed by thrombin digestion. After further purification with anion-exchange chromatography, these receptors were used to investigate the ligand-receptor interaction. Size exclusion chromatography and SPR analysis revealed that mixture of IL-13 and IL-13Ralpha1 showed predominant affinity to IL-4Ralpha, although neither detectable affinity of IL-13 nor IL-13Ralpha1 was observed against IL-4Ralpha. Combining these data with the moderate affinity of IL-13 to IL-13Ralpha1, this indicates that IL-13 first binds to IL-13Ralpha1 and recruits consequently to IL-4R.


Reliability of the assessment of preventable adverse drug events in daily clinical practice.
To determine the reliability of the assessment of preventable adverse drug events (ADEs) in daily practice and to explore the impact of the assessors' professional background and the case characteristics on reliability. We used a combination of the simplified Yale algorithm and the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) scheme to assess on the one hand the causal relationship between medication errors (MEs) and adverse events in hospitalised patients and on the other hand the severity of the clinical consequence of MEs. Five pharmacists and five physicians applied this algorithm to 30 potential MEs. After individual assessment, the pharmacists reached consensus and so did the physicians. Outcome was both MEs' severity (ordinal scale, NCC MERP categories A-I) and the occurrence of preventable harm (binary outcome, NCC MERP categories A-D vs. E-I). Kappa statistics was used to assess agreement. The overall agreement on MEs' severity was fair for the pharmacists (kappa = 0.34) as well as for the physicians (kappa = 0.25). Overall agreement for the 10 raters was fair (kappa = 0.25) as well as the agreement between both consensus outcomes (kappa = 0.30). Agreement on the occurrence of preventable harm was higher, ranging from kappa = 0.36 for the physicians through kappa = 0.49 for the pharmacists. Overall agreement for the 10 raters was fair (kappa = 0.36). The agreement between both consensus outcomes was moderate (kappa = 0.47). None of the included case characteristics had a significant impact on agreement. Individual assessment of preventable ADEs in real patients is difficult, possibly because of the difficult assessment of contextual information. Best approach seems to be a consensus method including both pharmacists and physicians.


High-resolution magnetic resonance angiography of the internal carotid artery: 2D vs 3D TOF in stenotic disease.
The aim of this study was to compare high-resolution 2D TOF with high-resolution 3D TOF in the study of internal carotid artery disease. Sixty-four patients with clinical signs of cerebrovascular insufficiency were studied with a superconductive 1.5 T magnet using two techniques: 2D and 3D TOF. Digital subtraction angiography (DSA) was the gold standard. The 2D TOF technique was performed using the following parameters: TR/TE/FA/MA 49 ms/9 ms/60 degrees/512 x 256; the 3D TOF was performed with the following parameters: TR/TE/FA/MA 50 ms/8 ms/20 degrees/512 x 256. The 2D TOF agreed with DSA in 116 of 128 diagnostic judgments (90%) and overestimated seven times. The 3D TOF technique agreed with DSA in 125 of 128 diagnostic judgments (97%) with one overestimation and two underestimations. There was no statistically significant difference (P < 0.05) between the two different techniques. Our study confirms the high reliability of the methodology carried out with the high-resolution 2D and 3D technique.


Physical training modulates proinflammatory cytokines and the soluble Fas/soluble Fas ligand system in patients with chronic heart failure.
We sought to investigate the effects of physical training on circulating proinflammatory cytokines and the soluble apoptosis mediators Fas (sFas) and Fas ligand (sFasL) in patients with chronic heart failure (CHF). Recent investigations have shown an overexpression of circulating proinflammatory cytokines and soluble apoptosis mediators in patients with CHF, which may be related to their exercise intolerance and clinical deterioration. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptors I and II (sTNF-RI and sTNF-RII, respectively), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), sFas and sFasL were measured in 24 patients with stable CHF (New York Heart Association functional class II/III; left ventricular ejection fraction 23.2 +/- 1.3%) and in 20 normal control subjects before and after a 12-week program of physical training in a randomized, crossover design. Functional status of patients with CHF was evaluated by using a cardiorespiratory exercise test to measure peak oxygen consumption (VO2max). Physical training produced a significant reduction in plasma levels of TNF-alpha (7.5 +/- 1.0 pg/ml vs. 4.6 +/- 0.7 pg/ml, p < 0.001), sTNF-RI (3.3 +/- 0.2 ng/ml vs. 2.7 +/- 0.2 ng/ml, p < 0.005), sTNF-RII (2.6 +/- 0.2 ng/ml vs. 2.3 +/- 0.2 ng/ml, p = 0.06), IL-6 (8.3 +/- 1.2 pg/ml vs. 5.9 +/- 0.8 pg/ml, p < 0.005), sIL-6R (34.0 +/- 3.0 ng/ml vs. 29.2 +/- 3.0 ng/ml, p < 0.01), sFas (5.5 +/- 0.7 ng/ml vs. 4.5 +/- 0.8 ng/ml, p = 0.05) and sFasL (34.9 +/- 5.0 pg/ml vs. 25.2 +/- 4.0 pg/ml, p < 0.05), as well as a significant increase in VO2max (16.3 +/- 0.7 ml/kg per min vs. 18.7 +/- 0.8 ml/kg per min, p < 0.001). Good correlations were found between a training-induced increase in VO2max and a training-induced reduction in levels of the proinflammatory cytokine TNF-alpha (r = -0.54, p < 0.01) and the apoptosis inducer sFasL (r = -0.57, p < 0.005) in patients with CHF. In contrast, no significant difference in circulating cytokines and apoptotic markers was found with physical training in normal subjects. Physical training reduces plasma levels of proinflammatory cytokines and the sFas/sFasL system in patients with CHF. These immunomodulatory effects may be related to the training-induced improvement in functional status of patients with CHF.


Circular RNA circRara promote the innate immune responses in miiuy croaker, Miichthys miiuy.
With the in-depth study of circRNA, more and more biological studies have shown that circRNAs play an important role in mammals, such as cell proliferation, apoptosis, invasion, development and disease state. However, the regulatory mechanism of circRNA in lower vertebrates remains unclear. Here, we found a new circular RNA and named it circRara. We carried out the experimental study on its antiviral and antibacterial response, cell proliferation and activity. The results showed that circRara had a positive regulatory effect on the antiviral and antibacterial response, cell proliferation and activity in miiuy croaker. First, we found that the expression of circRara could be up-regulated under the stimulation of LPS and poly (I: C), but not the expression of linear Rara. In addition, the increase of circRara can increase the production of inflammatory factors and antiviral genes, which was confirmed by double luciferase reporter gene experiment and qPCR. These results will help to further understand the immunomodulatory mechanism of circRNA in teleost fish.


Three-dimensional power Doppler sonography of tumor vascularity.
To assess the clinical value of three-dimensional (3D) power Doppler imaging of intratumoral blood flow. Two hepatocellular carcinomas (HCC), one renal cell carcinoma, one hepatic focal nodular hyperplasia (FNH), and one iliac bone metastasis of HCC were used. Images were collected by power mode using the GE-Yokogawa LOGIQ 700. Power Doppler images were recorded on S-VHS videotape and fed into a workstation. Flow information was then extracted, and 3D images were constructed by surface rendering. Preparation of 3D images could be accomplished in one minute after feeding flow information into the workstation. Intratumoral vascular structure could be easily evaluated. This 3D imaging was useful for the differential diagnosis of hepatic tumors, especially HCC and FNH, which were confirmed in 3D imaging to have distinctly different intratumoral vascular structures. 3D imaging of intratumoral blood flow was possible by 3D processing of the power Doppler images. 3D power Doppler imaging is expected to be helpful for the differential diagnosis of tumors.


Cobalt-iron selenides embedded in porous carbon nanofibers for simultaneous electrochemical detection of trace of hydroquinone, catechol and resorcinol.
In this study, cobalt-iron selenides embedded in porous carbon nanofibers (CoFe2Se4/PCF), derived from Prussian blue analogues, was prepared as a novel phenolic sensor. The obtained CoFe2Se4/PCF nanocomposites show three-dimensional (3D) networks nanostructures that can supply a desirable conductive network to accelerate electron transfer and avoid the aggregation of CoFe2Se4 nanoparticles. Electrochemical detection of hydroquinone (HQ), catechol (CC) and resorcinol (RS), at CoFe2Se4/PCF modified glassy carbon electrode (GCE) were researched. The results show the obtained 3D CoFe2Se4/PCF/GCE exhibits excellent electrochemical properties towards the simultaneous testing trace of HQ, CC and RS. The obtained electrode provides wide linear ranges of 0.5-200, 0.5-190 and 5-350 μM and low detection limit of 0.13, 0.15 and 1.36 μM for HQ, CC and RS, respectively. The as-prepared phenolic sensor displays satisfied selectivity and long-term storage stability. In addition, the constructed sensor can be used to determine HQ, CC and RS in actual samples.


Localization of calcitonin gene-related peptide (CGRP) at a neuronal nicotinic synapse.
The localization of calcitonin gene-related peptide (CGRP) in the parasympathetic cardiac ganglion of the frog was investigated with an immunofluorescence method. By doubly staining the whole ganglion with antibodies against a synaptic-vesicle antigen and anti-CGRP antibodies, we found that all of the boutons at the nicotinic synapses on the postganglionic neurons contained immunoreactivity against this peptide. In contrast, neither the muscarinic nor the adrenergic terminals of the postganglionic fibers on the cardiac muscle contained CGRP immunoreactivity. This suggests that CGRP is involved in the functions of the neuronal nicotinic synapses.


Differences between the photocycles of halorhodopsin and the acid purple form of bacteriorhodopsin analyzed with millisecond time-resolved FTIR spectroscopy.
At pH 1, bacteriorhodopsin (bR) is thought to function as a halide ion pump, in contrast to its biological function as a proton pump at neutral pH. Despite the apparent similarity in function between this 'acid purple' form of bR and the native form of halorhodopsin (hR), their FTIR difference spectra measured ca. 5 ms after photolysis are significantly different. The most striking difference is the appearance of a positive band at 1753 cm-1 and a negative band at 1732 cm-1 in the bRacid purple difference spectrum. These and other spectral features are similar, but not identical, to those of the bR-->O difference spectrum measured at neutral pH. The structure of the bRacid purple longest-lived product therefore corresponds more closely to the O photoproduct of the bR proton-pumping photocycle, rather than the hL photoproduct seen on a similar time scale in the hR photocycle. The 1753- and 1732-cm-1 bands are largely unaffected by the D212N mutation, but both appear to lose a portion of their intensities with either the D85N or D96N mutation. Thus Asp-85 and -96 likely undergo substantial changes in hydrogen-bonding environment during the halide-pumping cycle of bRacid purple. Our FTIR results deepen the distinctions between the hR and bR photocycles. The mechanism of chloride pumping in hR has been thought not to involve protonation or hydrogen bonding changes of carboxylic acid groups. In bRacid purple, however, it seems likely that at least one carboxylic acid might play an important role in the mechanism of chloride pumping, leading to an increase in thermodynamic or kinetic stabilization of the O intermediate.


Comparison of surgically induced astigmatism between horizontal and X-pattern sutures in the scleral tunnel incisions for manual small incision cataract surgery.
Two types of popular scleral tunnel sutures in the manual small incision cataract surgery (MSICS) are horizontal and X-pattern sutures. Surgically induced corneal astigmatism (SIA) is a useful indicator of the suturing effect. To compare SIA between horizontal and X-pattern sutures in the scleral tunnel incisions for MSICS. Prospective, nonrandomized comparative trial. After superior scleral tunnel incision and capsulorhexis, the nucleus was prolapsed into the anterior chamber and delivered. The wound was sutured with either horizontal or X-pattern suture. The simulated keratometry values were derived from the corneal topography preoperatively and 1.5 and 3 months postoperatively. The SIA was calculated by Cartesian coordinates based analysis. Sixty-four patients (32 patients in each group) were included in the study. In the horizontal suture group, the SIA centroid values at 1.5 and 3 months after the surgery were 0.87 × 1° and 1.11 × 180°, respectively, showing induction of against-the-rule astigmatism. In the X-pattern suture group, the SIA centroid values at 1.5 and 3 months after the surgery were 0.61 × 97° and 0.66 × 92°, respectively, showing induction of mild with-the-rule astigmatism. The difference between the amount of SIA at 1.5 and 3 months after surgery was small. In the MSICS, the X-pattern sutures were preferred to the horizontal sutures in the patients without significant preoperative steepening in line with the central meridian of the incision. In the cases with significant preoperative steepening, sutureless surgery or horizontal sutures were preferred. Corneal astigmatism in the patients undergoing MSICS was stable at 1.5 months after the surgery.


Implementing evidence-based medicine in general practice: a focus group based study.
Over the past years concerns are rising about the use of Evidence-Based Medicine (EBM) in health care. The calls for an increase in the practice of EBM, seem to be obstructed by many barriers preventing the implementation of evidence-based thinking and acting in general practice. This study aims to explore the barriers of Flemish GPs (General Practitioners) to the implementation of EBM in routine clinical work and to identify possible strategies for integrating EBM in daily work. We used a qualitative research strategy to gather and analyse data. We organised focus groups between September 2002 and April 2003. The focus group data were analysed using a combined strategy of 'between-case' analysis and 'grounded theory approach'. Thirty-one general practitioners participated in four focus groups. Purposeful sampling was used to recruit participants. A basic classification model documents the influencing factors and actors on a micro-, meso- as well as macro-level. Patients, colleagues, competences, logistics and time were identified on the micro-level (the GPs' individual practice), commercial and consumer organisations on the meso-level (institutions, organisations) and health care policy, media and specific characteristics of evidence on the macro-level (policy level and international scientific community). Existing barriers and possible strategies to overcome these barriers were described. In order to implement EBM in routine general practice, an integrated approach on different levels needs to be developed.


Clinical efficacy and safety of atezolizumab plus bevacizumab versus lenvatinib in the treatment of advanced hepatocellular carcinoma: A systematic review and meta-analysis.
Assess the effectiveness and safety of treatment options atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib in clinical practice for patients with advanced hepatocellular carcinoma (HCC) patients. To compare the effectiveness of Atez/Bev and lenvatinib in treating advanced HCC, we systematically searched the PubMed, EMBASE, and Web of Science databases. We utilized Review Manager 5.3 to extract and analyze the data. The present systematic review included 8 nonrandomized studies comprising a total of 6628 cases. There was no significant difference in 0.5-, 1-, 1.5-year OS rates and 0.5-, 1-year PFS rates between the 2 groups. However, patients with HCC caused by viral hepatitis would benefit more from the Atez/Bev therapy (hazard ratio = 0.75, 95% confidence interval: 0.63-0.89) but patients with a Child-Pugh class B liver function would benefit more from lenvatinib (hazard ratio = 1.70, 95% confidence interval: 1.07-2.70). At the same time, there are no major differences in safety between the 2 treatment options. Our study did not find any significant difference in effectiveness and safety between Atez/Bev and lenvatinib. However, Additional verification is required to determine whether these 2 therapeutic approaches have varying effects on distinct populations.


Unfolding of the tertiary structure of specific tRNA and ribosomal 5S RNA from plants as studied with hydroxyl radicals.
Ribosomal 5S RNA is present in all eubacterial and eukaryotic ribosomes. Despite a large amount of experimental data on the primary and secondary structures of these types of molecules, details of their tertiary structure and their precise function in protein biosynthesis are still not known. Recently we have proposed a new model for the tertiary structure of plant 5S rRNA. In this study we applied the Fe(II)-mediated cleavage reaction to test the model. The data presented here provide experimental evidence that in the 5S rRNA molecule only a few nucleotides are buried in the tertiary structure. Similar experiments performed with methionine initiator tRNA gave results which imply the difference in its structure when compared with the X-ray structure of yeast tRNAPhe.


Effects of TCP on spatial memory: comparison with MK-801.
TCP (N-[1-(2-thienyl)cyclohexyl]piperidine), A PCP (phencyclidine) derivative, has been shown to possess antiepileptic and neuroprotective efficacy against chemically induced seizures. However, it is known that other antagonists of the NMDA receptor impair spatial learning. This study was thus undertaken to explore the eventual effects of TCP on memory. The same study was done with MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine ), one of the most studied NMDA receptor antagonists, which can be considered as a reference molecule. Three doses of each drug were chosen: 0.05, 0.1, and 0.2 mg/kg for MK-801 and 0.5, 1, and 2 mg/kg for TCP, the second dosage corresponding to the minimal required for antiseizure activity. The drugs were injected IP 30 min each day before a classical procedure of acquisition in a Morris water maze test. At the highest dose of each drug, the animals did not learn the position of the platform. At 0.1 mg/kg MK-801, the rats used a praxis strategy to find the platform but they did not known where the platform was. Contrary to MK-801, TCP at 1 mg/kg did not induce any memory impairment. At the lowest doses used, no memory impairment was found. It thus appears that, at the minimal therapeutic dose effective against chemically induced seizures (0.1 mg/kg for MK-801 and 1 mg/kg for TCP), TCP, contrary to MK-801, does not induce any memory impairment. Furthermore, at all the doses used, TCP presents the particularity that its locomotor side effects are not long lasting, being no longer observed from 30 min after the injection.


Quercetin Impedes Th17 Cell Differentiation to Mitigate Arthritis Involving PPARγ-Driven Transactivation of SOCS3 and Redistribution Corepressor SMRT from PPARγ to STAT3.
Quercetin (QU) is one of the most abundant flavonoids in plants and has attracted the attention of researchers because of its remarkable antirheumatoid arthritis (RA) effects and extremely low adverse reactions. However, the underlying mechanism needs further study. Flow cytometry, immunofluorescence, enzyme linked immunosorbent assay (ELISA), and quantitative real-time polymerase chain reaction (qRT-PCR) reveal the obvious inhibitory effects of QU on Th17 cell differentiation in arthritic mice. More importantly, QU markedly limits the development of Th17 cell polarization, which is virtually compromised by the treatment with peroxisome proliferator activated receptor γ (PPARγ) inhibitor GW9662 and knockdown of PPARγ. Additionally, molecular dynamics simulation and immunofluorescence exhibit QU directly binds to PPARγ and increases PPARγ nuclear translocation. Besides, QU confers its moderation effect on suppressor of cytokine signaling protein (SOCS3)/signal transducer and activator of transcription 3 (STAT3) axis partially depending on PPARγ. Furthermore, coimmunoprecipitation shows QU redistributes the corepressor silencing mediator for retinoid and thyroid-hormone receptors (SMRT) from PPARγ to STAT3. Finally, the inhibition of Th17 response and the antiarthritic effect of QU are nullified by GW9662 treatment in arthritic mice. QU targets PPARγ and consequently inhibits Th17 cell differentiation by dual inhibitory activity of STAT3 to exert antiarthritic effect. The findings facilitate its development and put forth a stage for uncovering the mechanism of other naturally occurring compounds with chemical structures similar to QU.


A novel approach for automatic segmentation of prostate and its lesion regions on magnetic resonance imaging.
To develop an accurate and automatic segmentation model based on convolution neural network to segment the prostate and its lesion regions. Of all 180 subjects, 122 healthy individuals and 58 patients with prostate cancer were included. For each subject, all slices of the prostate were comprised in the DWIs. A novel DCNN is proposed to automatically segment the prostate and its lesion regions. This model is inspired by the U-Net model with the encoding-decoding path as the backbone, importing dense block, attention mechanism techniques, and group norm-Atrous Spatial Pyramidal Pooling. Data augmentation was used to avoid overfitting in training. In the experimental phase, the data set was randomly divided into a training (70%), testing set (30%). four-fold cross-validation methods were used to obtain results for each metric. The proposed model achieved in terms of Iou, Dice score, accuracy, sensitivity, 95% Hausdorff Distance, 86.82%,93.90%, 94.11%, 93.8%,7.84 for the prostate, 79.2%, 89.51%, 88.43%,89.31%,8.39 for lesion region in segmentation. Compared to the state-of-the-art models, FCN, U-Net, U-Net++, and ResU-Net, the segmentation model achieved more promising results. The proposed model yielded excellent performance in accurate and automatic segmentation of the prostate and lesion regions, revealing that the novel deep convolutional neural network could be used in clinical disease treatment and diagnosis.


Radiation inactivation analysis of the A1 adenosine receptor of rat brain. Decrease in radiation inactivation size in the presence of guanine nucleotide.
Radiation inactivation analysis of the binding of the A1 adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine to rat brain membranes yielded a radiation inactivation size of 58 kDa. In the presence of GTP gamma S this was reduced to 33 kDa, in good agreement with the size of the ligand-binding subunit detected after photoaffinity labelling. The data indicate that the structural association of A1 adenosine receptors with G-protein components is altered in situ in the presence of guanine nucleotides.


Multicentre study of thyroid nodules in patients with Graves' disease.
The association of Graves' disease with thyroid nodules and thyroid carcinoma is rarely reported. The incidence seems to be increasing according to recent literature. The aim of this multicentre study was to review patients who had surgery for Graves' disease associated with thyroid nodules, and to evaluate the risk of thyroid carcinoma. A retrospective study was made of 557 consecutive patients who underwent operation for Graves' disease between 1991 and 1997 in five endocrine surgery departments. Each patient underwent clinical, biochemical, ultrasonographic and scintigraphic evaluation. None of the patients had had previous radioactive iodine therapy or external irradiation. Surgery consisted of either a subtotal or total thyroidectomy. Nodules were observed before operation in 140 patients (25.1 per cent). Thyroid carcinoma was diagnosed in 21 patients (15.0 per cent), always inside a nodule. The incidence of thyroid carcinoma associated with Graves' disease was 3.8 per cent (21 of 557 patients): 20 papillary and one follicular carcinoma. The carcinoma was multifocal in two patients. Tumour diameter ranged from 2 to 25 mm. A nodule was palpable in four patients. This multicentre study of patients having thyroidectomy for Graves' disease showed that 3.8 per cent had a carcinoma; the rate of carcinoma in cold nodules was 15.0 per cent. Surgery should be advised in any patient with Graves' disease and a thyroid nodule; the operation should be total thyroidectomy.


Aggravated pulmonary injury after subarachnoid hemorrhage in PDGF-Bret/ret mice.
Recent advances in surgical and neuroprotective strategies could effectively manage the pathophysiological progression of subarachnoid hemorrhage (SAH). However, pulmonary dysfunction frequently occurs in SAH patients with an increased risk of unsatisfactory outcomes. Based on the similar microvascular structures in the blood-air barrier and blood-brain barrier and possible brain-lung crosstalks, we believe that pericytes may be involved in both neurological and pulmonary dysfunction after SAH. In our experiments, platelet-derived growth factor B (PDGF-B) retention motif knockout (PDGF-Bret/ret) mice and adeno-associated virus PDGF-B were employed to show the involvement of pericyte deficiency and PDGF-B expression. Neurological score, SAH grade, hematoxylin-eosin staining, and PaO2/FiO2 ratio analysis were performed to evaluate the neurological deficits and pulmonary functions in endovascular perforation SAH models at 24 h after surgery, as well as western blotting and immunofluorescence staining for underlying molecular expressions. We found that neonatal PDGF-Bret/ret mice exhibited pulmonary atelectasis 12 h after birth. Further investigation showed a decrease in PaO2/FiO2 and lung-specific surfactant proteins in adult PDGF-Bret/ret mice. These dysfunctions were much worse than those in wild-type mice at 24 h after SAH. PDGF-B overexpression alleviated pulmonary dysfunction after SAH. These results suggested pulmonary dysfunction after SAH and the pivotal role of PDGF-B signaling for the pathophysiological process and future therapeutic targets of pulmonary injury treatment after SAH. Further studies are needed for pathophysiological investigations and translational studies on pulmonary injuries after SAH.


Equivalence of a single saline nebulised dose of formoterol powder vs three doses of nebulised Albuterol every twenty minutes in acute asthma in children: a suitable cost effective approach for developing nations.
An increase in asthma prevalence is reported from developed as well as developing nations, with rising costs from acute asthma and great expenditures to health care systems. Venezuela's Ministry of Health ambulatory facilities care for 80 % or more of a mostly urban and impoverished population of 26 million inhabitants, registering close to a million acute asthma visits per year; a nebulised fixed fenoterol-ipratropium bromide combination (Bero-dual, Boehringer-Ingelheim) in repeated dosing is the standard treatment. to simplify acute asthma care and management in a cost effective manner employing Formoterol Fumarate powder, a long acting beta agonist with immediate bronchodilator effects. Fifty acute asthmatic children (5-12 years old) were randomly assigned (25 patients in each group) to receive either a nebulised single dose (US $1.35) of two 12 microg Formoterol Fumarate capsules (Foradil 12 microg/cap, Novartis Pharma AG, Basel, Switzerland) diluted in 2.5 ml of sterile saline solution; or 3 doses of Albuterol (US $ 6.73) every twenty minutes for one hour (Glaxo Smith Kline Albuterol ampoules, 2.5 mg/2.5 ml, at a dose of 0.15 mg/kg/dose, maximum dose 2.5 mg). Symptoms score, oxygen saturation and lung function testing were recorded before and one hour after commencing treatments. Both groups improved significantly on all parameters, except for FEV(1) in the Albuterol group. Single dose nebulised Formoterol Fumarate (dry powder) in sterile saline solution, as depicted in this trial, is equivalent to three doses of Albuterol every twenty minutes for one hour in acute asthma in children, simplifying acute care management and at one fifth of medication costs. A pursuit of simpler and more cost effective approaches is found wanting in developing nations with depressed economies and unique cultural and socio-medical contexts; also, in countries where pharmaco-economics orients quality of health policies, novel approaches like this are worth exploring.


Accuracy of Implant Analogs in 3D Printed Resin Models.
To study the effect of implant analog system, print orientation, and analog holder radial offset on 3D linear and absolute angular distortions of implant analogs in 3D printed resin models. A sectional master model simulating a 2-implant, 3-unit fixed prosthesis in a partially edentulous jaw was fabricated. Three implant analog systems for 3D printed resin models-Straumann (ST), Core3DCentres (CD) and Medentika (MD)-were tested. The corresponding scan bodies were secured onto the implants and scanned using an intraoral scanner. Models were obtained with a Digital Light Processing printer. Each implant analog system had 2 print orientations (transverse [X] and perpendicular [Y] to the printer door) and 2 analog holder radial offsets (0.04 mm and 0.06 mm), for a total of 60 models. The physical positions of the implants in the master model and the analogs in the printed resin models were directly measured with a Coordinate Measuring Machine (CMM). 3D linear distortion (ΔR) and absolute angular distortion (Absdθ) defined the 3D accuracy of the analogs in the printed models. Univariate ANOVA was used to analyse data followed by post hoc tests (Tukey HSD, α = 0.05). Mean ΔR for ST (-155.7 ± 60.6 µm), CD (124.9 ± 65.0 µm) and MD (-92.9 ± 48.0 µm) were significantly different (p < 0.01). Mean Absdθ was not significantly different between ST (0.57 ± 0.48°) and CD (0.41 ± 0.27°), but both were significantly different from MD (2.11 ± 1.14°) (p < 0.01). Print orientation had a significant effect on ΔR only but no discernible trend could be found. Analog holder radial offset had no significant effect on ΔR and Absdθ. Implant analog system had a significant effect on ΔR and Absdθ. Compared to the master model, CD produced greater mean interanalog distances, while ST and MD produced smaller mean interanalog distances. MD exhibited the greatest mean angular distortion which was significantly greater than ST and CD.


Temporal changes in bile acid levels and 12α-hydroxylation after Roux-en-Y gastric bypass surgery in type 2 diabetes.
Since the publication of the above article it has been noted that the author S O'Brien should have been listed as CS O'Brien. The authors should therefore appear as follows: R Dutia, M Embrey, CS O'Brien, RA Haeusler, KK Agénor, P Homel, J McGinty, RP Vincent, J Alaghband-Zadeh, B Staels, CW le Roux, J Yu and B Laferrère The corrected article html and online pdf versions have been amended. The authors wish to apologise for any inconvenience caused.


Machine learning to predict early TNF inhibitor users in patients with ankylosing spondylitis.
We aim to generate an artificial neural network (ANN) model to predict early TNF inhibitor users in patients with ankylosing spondylitis. The baseline demographic and laboratory data of patients who visited Samsung Medical Center rheumatology clinic from Dec. 2003 to Sep. 2018 were analyzed. Patients were divided into two groups: early-TNF and non-early-TNF users. Machine learning models were formulated to predict the early-TNF users using the baseline data. Feature importance analysis was performed to delineate significant baseline characteristics. The numbers of early-TNF and non-early-TNF users were 90 and 505, respectively. The performance of the ANN model, based on the area under curve (AUC) for a receiver operating characteristic curve (ROC) of 0.783, was superior to logistic regression, support vector machine, random forest, and XGBoost models (for an ROC curve of 0.719, 0.699, 0.761, and 0.713, respectively) in predicting early-TNF users. Feature importance analysis revealed CRP and ESR as the top significant baseline characteristics for predicting early-TNF users. Our model displayed superior performance in predicting early-TNF users compared with logistic regression and other machine learning models. Machine learning can be a vital tool in predicting treatment response in various rheumatologic diseases.


The Identification and Treatment of Common Skin Infections.
Skin conditions are a common problem addressed by medical providers. Up to 25% of individuals in the United States will seek attention for these conditions each year. The same problem occurs in the athletic training room, where athletes with infectious skin conditions can be seen. Most conditions are simple and can be treated without concern for spread to susceptible athletes. However, others can be quite serious and spread rapidly through a team and opponents during competition. Knowledge of the different types of skin infections is necessary to help treat these athletes and prevent spread to others. With proper diagnosis and treatment, certified athletic trainers can keep the athlete off the field of play for a minimum period and prevent transmission.


iBET: Immersive visualization of biological electron-transfer dynamics.
Recently, we presented a computational framework named VizBET to simulate and visualize biological electron-transfer (ET) dynamics. The visualization process was encapsulated as a plugin to the Visual Molecular Dynamics (VMD) software. However, the user's ability to understand complex, multidimensional ET pathways was severely limited when visualized in 2D on traditional computer monitors. To provide a more accurate representation with enhanced depth perception, we here present an extension of VizBET named iBET to render the VMD model of ET dynamics in a commodity virtual reality (VR) platform. The paper describes detailed procedures to export VMD models into the Unity game engine and render it in an Oculus Rift head mounted display. With the increasing availability of low-cost VR systems like the Rift and rich programmability of game engines, the iBET framework provides a powerful means to explore and understand not only biological ET processes but also a unique experiential tool for broad scientific communities.


Wanting and Getting Help for Substance Problems on Both Sides of the US-Mexico Border.
The US-Mexico border presents potential cultural and logistic barriers to obtaining substance abuse treatment. We compare the prevalence and correlates of wanting and getting help between border and non-border residents in both the US and Mexico. Data come from the 2011 to 2012 US-Mexico Study on Alcohol and Related Conditions which surveyed 3214 border and 1582 non-border residents in the US and Mexico. Multivariate logistic regressions estimate the effect of border residence on desire for and receipt of help. In both countries, border substance users were about half as likely as nonborder substance users to have wanted or obtained any kind of help, independent of predisposing, need and enabling factors, including migration status. Among those desiring help, however, about half had obtained it, both on and off the border in both countries. While substantial proportions of those who need help do not get it either on or off the border, lower motivation for treatment may be more important than access in explaining border/non-border differences. Future research should investigate whether there are border-specific barriers to wanting help, and how to minimize them.


Exposure to Particulate Matter Is Associated With Elevated Blood Pressure and Incident Hypertension in Urban India.
Ambient air pollution, specifically particulate matter of diameter <2.5 μm, is reportedly associated with cardiovascular disease risk. However, evidence linking particulate matter of diameter <2.5 μm and blood pressure (BP) is largely from cross-sectional studies and from settings with lower concentrations of particulate matter of diameter <2.5 μm, with exposures not accounting for myriad time-varying and other factors such as built environment. This study aimed to study the association between long- and short-term ambient particulate matter of diameter <2.5 μm exposure from a hybrid spatiotemporal model at 1-km×1-km spatial resolution with longitudinally measured systolic and diastolic BP and incident hypertension in 5342 participants from urban Delhi, India, within an ongoing representative urban adult cohort study. Median annual and monthly exposure at baseline was 92.1 μg/m3 (interquartile range, 87.6-95.7) and 82.4 μg/m3 (interquartile range, 68.4-107.0), respectively. We observed higher average systolic BP (1.77 mm Hg [95% CI, 0.97-2.56] and 3.33 mm Hg [95% CI, 1.12-5.52]) per interquartile range differences in monthly and annual exposures, respectively, after adjusting for covariates. Additionally, interquartile range differences in long-term exposures of 1, 1.5, and 2 years increased the risk of incident hypertension by 1.53× (95% CI, 1.19-1.96), 1.59× (95% CI, 1.31-1.92), and 1.16× (95% CI, 0.95-1.43), respectively. Observed effects were larger in individuals with higher waist-hip ratios. Our data strongly support a temporal association between high levels of ambient air pollution, higher systolic BP, and incident hypertension. Given that high BP is an important risk factor of cardiovascular disease, reducing ambient air pollution is likely to have meaningful clinical and public health benefits.


Building mammalian signalling pathways with RNAi screens.
Technological advances in mammalian systems are providing new tools to identify the molecular components of signalling pathways. Foremost among these tools is the ability to knock down gene function through the use of RNA interference (RNAi). The fact that RNAi can be scaled up for use in high-throughput techniques has motivated the creation of genome-wide RNAi reagents. We are now at the brink of being able to harness the power of RNAi for large-scale functional discovery in mammalian cells.


Intracranial cysts: incidental or neurodevelopmental?
Intracranial cysts are fluid-filled sacs within the brain. There is a diversity of intracranial cysts with different incidences in addition to the growing awareness about comorbidities and the consequences. The present study aimed to evaluate cystic findings in children who were admitted to the department of pediatric neurology. Children who were admitted to the Clinic of Pediatric Neurology and who had an MRI between 2016 and 2021 were evaluated. The MRI examination was performed with the pediatric epilepsy protocol. Children with primary intracranial cysts were enrolled in the study. Demographic and clinical findings were evaluated from the hospital's database and patients' files. Among the 78 patients, 36 (46.2%) were male and 42 (53.8%) were female. The mean age was 7 ± 5.4 years. The most frequent presenting complaint was a seizure (47.4%). Approximately one-quarter (28.2%) had mental and/or motor retardation. Nine (11.5%) of the children had a neuropsychiatric diagnosis. Most of the cysts were located at the midline (41%) with the majority located extra-axial (71.8%) and supratentorial (78.2%). Arachnoid cysts were observed most frequently with a percentage of 64.1%, followed by pineal cysts (15.4%). The history of seizure, epilepsy, presence of mental retardation, and neuropsychiatric problems were evaluated according to the population ratios based on z approximation in which significantly higher rates were observed among cases with intracranial cysts. Intracranial cysts should be taken into consideration for comorbid pathologies, especially in the childhood period. Early evaluation in patients with intracranial cysts for developmental delay and neuropsychiatric problems is important.


Pediatric acute myeloid leukemia: Insight into genetic landscape and novel targeted approaches.
Acute myeloid leukemia (AML) is a very heterogeneous hematological malignancy that accounts for approximately 20% of all pediatric leukemia cases. The outcome of pediatric AML has improved over the last decades, with overall survival rates reaching up to 70%. Still, AML is among the leading types of pediatric cancers by its high mortality rate. Modulation of standard therapy, like chemotherapy intensification, hematopoietic stem cell transplantation and optimized supportive care, could only get this far, but for the significant improvement of the outcome in pediatric AML, development of novel targeted therapy approaches is necessary. In recent years the advances in genomic techniques have greatly expanded our knowledge of the AML biology, revealing molecular landscape and complexity of the disease, which in turn have led to the identification of novel therapeutic targets. This review provides a brief overview of the genetic landscape of pediatric AML, and how it's used for precise molecular characterization and risk stratification of the patients, and also for the development of effective targeted therapy. Furthermore, this review presents recent advances in molecular targeted therapy and immunotherapy with an emphasis on the therapeutic approaches with significant clinical benefits for pediatric AML.


Primary oligodendroglioma of the lateral ventricle with computed tomographic and positron emission tomographic evaluations.
Two cases of primary intraventricular oligodendrogliomas are presented. Total excisions of well-demarcated large tumors in the lateral ventricle were successfully performed in young women by means of a frontal transventricular approach. An evaluation by computed tomography and positron emission tomography was attempted to obtain definite diagnosis of not only the location of the tumor but also the histologic grade of malignancy.


How to protect school children from the neurodevelopmental harms of air pollution by interventions in the school environment in the urban context.
Recently, there has been a flurry of publications assessing the effect of air pollution on neurodevelopment. Here we present a summary of the results obtained within the BRain dEvelopment and Air polluTion ultrafine particles in scHool childrEn (BREATHE) Project, which aimed to evaluate the effects of the exposure to traffic related air pollutants in schoolchildren in Barcelona. To this end, we comprehensively characterised air quality in 39 urban schools from Barcelona and identified the main determinants of children's increased exposure. We propose a series of measures to be implemented to improve air quality in schools within the urban context and, consequently, minimise the negative effects on children's neurodevelopment that we found to be associated with the exposure to air pollution. We also aimed to list some of the actions pushed by governments and the society (including school managers, parents, and children) that have been taking place around Europe for promoting better high quality in the school and its surroundings.


Clinical efficacy of a novel radiofrequency toothbrush for tooth stain reduction and tooth whitening: A randomized controlled trial.
The authors aimed to evaluate the effect of a novel radiofrequency (RF) toothbrush on tooth stains and shades compared with a sonic vibrating toothbrush (CVS Health SmileSonic Pro Advanced Clean Sonic Toothbrush, Ranir) that earned the American Dental Association Seal of Acceptance. The authors conducted a single-blind prospective study over 6 weeks. Participants were randomized to 1 of 2 study groups to receive either an RF toothbrush (ToothWave, Home Skinovations [test]) or a sonic vibrating toothbrush (SmileSonic powered toothbrush, Ranir [control]) and performed twice-daily toothbrushing with fluoridated toothpaste (Crest Cavity Protection, Procter & Gamble) for 6 weeks. Tooth stains and shades were assessed using the Lobene Stain Index and VITA Bleachedguide 3D-MASTER shade guide (VITA North America) at baseline and after 4 and 6 weeks of toothbrushing. In addition, the VITA Easyshade Advance 4.0 spectrophotometer (VITA North America) was used for shade evaluation. Safety was evaluated by means of oral soft-tissue examinations at each visit. Percentage reduction from baseline was compared between the groups. Statistical analyses were conducted using Mann-Whitney nonparametric model. Eighty-six participants (43 in each group) completed the study with fully evaluable data. At baseline, the groups did not differ significantly in mean measurement scores. Percentage reductions of the measured scores were significantly greater (more extrinsic stain removal and whitening) in the test group than in the control group (P < .001). Both toothbrushes were well-tolerated, and no device-related adverse events were reported during the study. The RF toothbrush produced substantial benefits in the reduction of tooth stains and whitening of tooth shade compared with a powered toothbrush (CVS Health SmileSonic Pro Advanced Clean Sonic Toothbrush, Ranir) that earned the American Dental Association Seal of Acceptance. The novel RF toothbrush is a safe and effective tool for stain removal and tooth whitening and can serve as an alternative to other whitening agents. This clinical trial was registered at ClinicalTrials.gov. The registration number is NCT03885609.


Single Institution trial of anthracycline- and taxane-based chemotherapy for operable breast cancer: The ASTER study.
The efficacy of anthracycline- and taxane-based chemotherapy for perioperative treatment of breast cancer (BC) has been established. No superiority of a cytotoxic regimen has been demonstrated, provided that administration of an anthracycline and a taxane is warranted. The ASTER study was designed to investigate the safety of 6 months of perioperative chemotherapy with Doxorubicin and Paclitaxel, followed by Cyclophosphamide, Methotrexate, and 5-Fluorouracil. ASTER enrolled patients with cT2-3 N0-1 or pT1-2 N1-3 BC, from November 2008 to August 2011. Treatment consisted of Doxorubicin 60 mg/sm, Paclitaxel 200 mg/sm q21 (AT) for three cycles followed by Cyclophosphamide 600 mg/sm, Methotrexate 40 mg/sm, 5-Fluorouracil 600 mg/sm d1,8 q28 (CMF) for three cycles, in either neo-adjuvant or adjuvant setting. All HER-positive patients received targeted therapy with Trastuzumab for 1 year. Disease-free and overall survival (DFS and OS, respectively) were estimated according to Kaplan-Meier method. Three hundred and thirty patients were enrolled, where 77.9% of cases were treated in an adjuvant setting; 65.5% received breast conservative surgery, 72.4% axillary dissection. 75.5% of cases presented estrogen receptor positivity, 66.7% progesterone receptor positivity; 18.5% of patients presented HER2-positive BC, 16.1% triple negative disease. Twenty-eight (8.5%) developed grade III-IV hematologic toxicity; nine patients (2.7%) developed grade III neurological toxicity. Loco-regional DFS was 99.6% at 1 year, 97.1% at 5 years, 95.9% at 7 years. Corresponding distant DFS was 98.4%, 90.2%, and 88.8%. One, 5, and 7-year OS was 99.6%, 94.9%, and 91.2%, respectively. Chemotherapy with ATx3→CMFx3 is confirmed safe and effective at 6.7 years follow-up. These results appear comparable to those reported in regulatory trials of most commonly prescribed anthracycline and taxane-based regimens.


Diagnosis and treatment of amebic "empyema": report of eighty-eight cases.
To prevent pleural soilage, early diagnosis and adequate treatment of amebic abscess of the liver are mandatory. Therapy includes administration of amebicidal drugs, drainage of the chest cavity, and treatment of associated respiratory, circulatory, and systemic derangements.


The detail of the en bloc technique and prognosis of spleen-preserving laparoscopic distal pancreatectomy for pancreatic cancer.
Although laparoscopic spleen-preserving distal pancreatectomy surgery is more and more popular, the reports about the en bloc technique used for pancreatic cancer were still rare. The aim of our study was to illustrate the detail of the spleen-preserving en bloc technique as well as the short-term and long-term outcomes. The detail of the en bloc technique with pictures was described. The prognosis of the successive 23 cases that underwent the laparoscopic distal pancreatectomy (LDP) surgery was evaluated. There were 17 cases that underwent spleen-preserving LDP while six cases underwent spleen-resecting LDP. The average surgery time was 203 ± 54 min, and the average blood loss volume was 208 ± 264 ml; one case transferred to open surgery because of severe adhesion. The complication rate was 47 % (n = 8) shortly after surgery. Pancreatic fistula rate was 41 % (n = 7). No lethal case occurred. The average diameter of the tumor was 32 ± 12 mm. The average number of the lymph nodes obtained was 19.8 ± 9.3. All the cutting edges were negative. Survival rates of the patient after 1, 3, and 5 years are 64.7, 52.9, and 41.2 %, respectively. These records showed no statistical significance compared with spleen-resecting LDP and open distal pancreatectomy (ODP) surgeries. The en bloc spleen-preserving LDP can be performed by experienced surgeons. This surgery has good short-term and long-term outcomes.


B and T cell epitope mapping and study the humoral and cell mediated immune response to B-T constructs of YscF antigen of Yersinia pestis.
YscF antigen, a type III secretion protein has recently been shown partial protection in murine model. Five peptides of YscF antigen were predicted using DNASTAR and T-cell prediction software. Peptides were synthesised and authenticated using competitive, direct binding immunoassay with anti YscF/peptide sera raised in mice. Peptide P1 and P2 were found to be B cell epitope while P3 was minor B cell epitope. P4 peptide was a pure T cell epitope based on lymphoproliferative response, cytokines profile and T-bet expression. Furthermore, with an intention to enhance immunogenicity, three B-T constructs were designed between the above epitopes. Conjugate B1T1 and B2T1 showed higher serum IgG/IgA titre, respectively, as well as high secretory IgA plus secretory component (Sc) both in lung and intestinal washes. Also, these conjugates showed high T-cell proliferation in addition to higher Th1 type cytokines (IFN-γ and IL-2) in cells obtained from spleen, lamina propria and Peyer's patches. B3T1 stimulated cells showed moderate levels of IFN-γ and IL-2 but higher levels of IL-4. This study demonstrates superior immunogen of B1T1 and B2T1 of YscF antigen to be exploited as vaccine candidate for plague.


Plates with angular stability: our personal experience in surgical treatment of fractures of the proximal extremity of the humerus.
We here report our experience in the use of locking proximal humerus plates that, compared to the old-generation ones, have shown a reduced incidence of complications, more manageability and higher preservation of soft tissues. Thirty-two patients underwent surgical treatment with plates with angular stability: 20 women and 12 men, with an average age of 52 years; in 6 cases they were fractures with 2 fragments, in 20 cases they were with 3 fragments and in 6 cases with 4 fragments. Results, evaluated according to the Constant Score, with a minimum follow-up of 6 months and the longest of 2 years, have revealed a 79-point Constant Score one year after surgery (min 42, max 94). In 2 cases we have observed necrosis of the epiphysis while there have not been any cases of secondary mobilisation of the synthesis equipment. Our findings, if we consider the low necrosis percentage, show the good adaptability and the preservation of the soft tissues as guaranteed by the synthesis equipment and by the surgery performed.


Nathalie Jurisch-Yaksi and Emre Yaksi.
Interview with Nathalie Jurisch-Yaksi and Emre Yaksi, who seek to understand the role of cilia in brain development and function, the neural mechanisms underlying neurological diseases, and how the sensory world is presented in the brain, at the Kavli Institute for Systems Neuroscience.


Electron-beam CT in the noninvasive assessment of coronary stent patency.
Coronary artery stents reduce the rate of restenosis in patients who have undergone balloon angioplasty; therefore, the implantation of coronary stents represents an important method in the treatment of coronary stenoses. The authors' purpose was to investigate the usefulness of electron-beam computed tomography (CT) as a noninvasive means of assessing the patency of coronary artery stents in patients who had undergone balloon angioplasty and stent placement. Electron-beam CT was used to assess stent patency in 177 patients with 285 stents. Contrast material-enhanced multisection flow studies were performed, and the images were evaluated by three investigators and compared with the findings of coronary angiography. Cine loop evaluations and time-attenuation curve analysis led to the correct diagnosis in 167 (94.3%) patients, as confirmed with coronary angiography. Stenoses had occurred in 18 of the 194 vessels with stents, and 14 of these were detected with electron-beam CT. Electron-beam CT appears to be a valuable imaging modality in the noninvasive assessment of stent patency in coronary arteries.


Enhanced optical properties of yttrium aluminum garnet with the yttrium vanadate impurity phase.
Yttrium aluminum garnet doped with europium with an additional impurity phase of yttrium vanadate doped europium has been prepared in different ways: synthesized by a sol-gel route and mechanically mixed in a mortar. The obtained samples were characterized by X-ray diffraction analysis, and scanning electron microscopy. Photoluminescence spectra were recorded to understand the role of the impurity phase in the garnet's optical properties. The impurity phase showed a significant contribution to the optical properties of Y3Al5O12:1%Eu.


Efficacy of laser treatment of tattoos using lasers emitting wavelengths of 532 nm, 755 nm and 1064 nm.
Multifunctional laser devices can be used to treat tattoos successfully. To report the efficacy of laser treatment in professional, amateur, accidental and permanent make-up tattoos from our own experience and to compare it with the literature. We retrospectively studied 74 consecutive patients with professional, amateur, make-up and accidental tattoos between June 1998 and November 2000. Patients were treated with a Q-switched Nd:YAG laser (wavelengths of 532 nm and 1064 nm), a Q-switched alexandrite laser (755 nm) and a variable pulse Nd:YAG laser (532 nm). Fourteen patients (19%) achieved a complete response (>95% lightening of treated tattoos), 23 (31%) an excellent response (76-95% lightening) and 21 (28%) a good response (51-75% lightening). Sixteen patients (22%) showed only a slight improvement (< or =50% lightening). Make-up tattoos and blue-black professional tattoos were most successfully treated. Multicoloured professional tattoos needed more treatments (mean +/- SD 5.7 +/- 5.4) in comparison with single-colour tattoos (3.5 +/- 2.0). The amateur tattoos needed fewer treatments (2.8 +/- 1.1) in comparison with professional tattoos. With accidental tattoos the results depended on the particles which had penetrated the skin. In contrast to literature reports, newer tattoos showed a trend to better treatment results than older tattoos. Using modern Q-switched lasers, tattoos are removed successfully with minimal risk of scarring and permanent pigmentary alterations. Even multicoloured tattoos can be treated successfully and with a low rate of side-effects.


Chitosan and silver nanoparticles as pudding with raisins with antimicrobial properties.
Chitosan nanoparticles (CS-NP) containing small silver nanoparticles are reported (Ag@CS-NP). CS-NP was synthesized using tripolyphosphate (TPP) as a polyanionic template. TPP also served to electrostatically attract Ag(+) inside CS-NP, where it was reduced by the terminal glucosamine units of the biopolymer. This procedure is environmental friendly, inexpensive, and permits the synthesis of very small AgNP (0.93-1.7 nm), with only a discrete dependence from the amount of silver nitrate used (5-200mg). The obtained hybrid nanocomposites Ag@CS-NP were characterized by DLS, HRTEM, and HAADF-STEM presenting a mean hydrodynamic diameter of 78 nm. The antimicrobial activity of Ag@CS-NP against Candida glabrata, Sacharomyces cerevisiae, Escherichia coli, Klebsiella pneumoniae, Salmonella, Staphylococcus aureus, and Bacillus cereus corresponded to MIC values lower than for AgNO(3).


The heterogeneity of rat-liver mitochondrial DNA.
Two types of mitochondrial DNA (mtDNA) can be distinquished in an inbred strain of rats of the Wistar type. The population of DNA molecules of the liver of one single rat is homogeneous. This was shown for a number of 100 animals and confirms the data of other investigators. The two types of mitochondrial DNA, designated A and B, differ in their number of cleavage sites for the restriction endonucleases Eco RI (2sites), Hind II (1 site) and Hha I (1 site). No differences were found for the restriction enzymes Bam HI, Hap II, Hind III and Hpa I. The degree of sequence divergence of the two types of DNA is calculated to be roughly 5% on the basis of these observations. From 20 rats part of the liver was taken and the mtDNA was characterized. Heterologous and homologous crosses between type A and type B rats were made. Analysis of the offspring revealed strictly maternal inheritance of the A and B mtDNA traits. For purposes of base-sequence analysis and RNA.DNA hybridization the strain could easily be "purified" genetically.


Effects of fasting on tissue glucose utilization in conscious resting rats. Major glucose-sparing effect in working muscles.
The effects of fasting on glucose metabolism in the conscious resting rat were studied. Fasting decreased whole-body glucose utilization by 40%. The fast induced a decrease in glucose utilization in muscles which are constantly working even in the resting state, i.e. heart, diaphragm and postural muscles. No modification was observed in other tissues.


Phortica variegata as an intermediate host of Thelazia callipaeda under natural conditions: evidence for pathogen transmission by a male arthropod vector.
Knowledge about Phortica variegata (Drosophilidae, Steganinae), the intermediate host of the eyeworm Thelazia callipaeda (Spirurida, Thelaziidae), is confined to experimental studies. To investigate the role P. variegata plays in the transmission of T. callipaeda under natural conditions, the population dynamics of these flies in the natural environment and their feeding preferences (on vegetables and/or animal lachrymal secretions) were examined. From April to November 2005, a total number of 969 (557 males and 412 females) P. variegata flies were collected weekly in a region of southern Italy with a history of canine thelaziosis. The flies were identified and dissected or subjected to a PCR assay specific for a region within the ribosomal ITS-1 DNA of T. callipaeda. The zoophilic preferences of P. variegata were assessed by collecting flies around the eyes of a person or around a fruit bait. Seven hundred and twenty flies (398 males and 322 females) were dissected under a stereomicroscope; 249 flies (158 males and 91 females) that died prior to the dissection were subjected to molecular investigation. Only P. variegata males were infected with larval T. callipaeda both at dissection (six, 0.83%) and with the specific PCR (seven, 2.81%), representing a total percentage of 1.34% flies infected. Interestingly, only males were collected around the eyes, compared with a male/female ratio of 1:4 around the fruit. This survey indicated that P. variegata males act as intermediate hosts of T. callipaeda under natural conditions in Europe. Both the zoophilic behaviour of P. variegata males on lachrymal secretions and their role as vector of T. callipaeda have been discussed as they represent a peculiarity in medical and veterinary entomology. The synchrony between the fly population dynamics and the biology of the nematode in the definitive host provides an interesting model for exploring the co-evolution of Thelazia spp. with their hosts.


Elevated serum CK-BB levels in patients with cerebral transtentorial herniation after ischemic stroke.
We examined the time course of CK and its isoenzymes in 15 patients with severe ischemic stroke. Patients with cerebral transtentorial herniation (n = 7) had the highest CK-BB activity during herniation (1.54 +/- 0.6 U/L, mean +/- SD; range: 1.0-2.6 U/L). These values were distinctly above the values of a control group of 20 patients with non-neurological diseases (0.39 +/- 0.2 U/L, mean +/- SD). In patients with smaller lesions without herniation (n = 8) the maximum CK-BB increase was lower (0.56 +/- 0.26 U/L, mean +/- SD).


Practice guidelines for the therapy of essential thrombocythemia. A statement from the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation.
The Italian Society of Hematology (SIE) and the two affiliated Societies (SIES and GITMO) commissioned a project to develop guidelines for the therapy of essential thrombocythemia (ET) using evidence-based knowledge and consensus formation techniques. Key questions on the optimal management of ET patients were formulated by an Advisory Council (AC) and approved by an Expert Panel (EP) composed of 7 senior hematologists. The AC systematically reviewed the published literature from 1980 to August 2002, and articles were graded according to their internal validity and quality. Using the Delphi technique, the EP was asked to answer the key questions according to the available evidence. From September 2002 to March 2003, four Consensus Conferences were held in accordance with the Nominal Group Technique with the goal of solving residual disagreement on recommendations. The EP provided recommendations on when to start platelet-lowering therapy, the most appropriate platelet-lowering agent, the use of anti-platelet therapy, and the management of women in childbearing age and of pregnant women. By using evidence and consensus, recommendations for the treatment of key problems in ET have been issued. Statements are graded according to the strength of the supporting evidence and uncertainty is explicitly declared.


The relationship between mode of female masturbation and achievement of orgasm in coitus.
To determine the relationship between masturbatory and coital behavior, 117 middle-class female volunteers were classified into three styles of masturbatory behavior--direct, indirect, and nonmasturbators. Direct masturbation was defined as the direct digital manipulation of the clitoris or use of a vibrator. Indirect masturbation included all other methods of masturbation not defined as direct. The classification was done on the basis of responses to a questionnaire. Of the masturbators 70% reported no change in their masturbatory style from initial masturbatory experiences. No relationship was found between either ability to masturbate or masturbatory style and coital orgasmic capacity. It was also found that (a) nonmasturbators achieved orgasm in coitus via additional clitoral stimulation significantly less frequently than either direct or indirect masturbators and (b) direct masturbators have a significantly greater preference for clitoral, as opposed to vaginal, stimulation as a means of achieving orgasm. The results are interpreted within the context of possible deficiencies in the questionnaire and confounding between the ongoing psychological and biological processes occurring in sexual activity. Within these constraints, the findings support current methods of treatment for primary and secondary anorgasmia.


The dynamics of drug resistance: a mathematical perspective.
Resistance to chemotherapy is a key impediment to successful cancer treatment that has been intensively studied for the last three decades. Several central mechanisms have been identified as contributing to the resistance. In the case of multidrug resistance (MDR), the cell becomes resistant to a variety of structurally and mechanistically unrelated drugs in addition to the drug initially administered. Mathematical models of drug resistance have dealt with many of the known aspects of this field, such as pharmacologic sanctuary and location/diffusion resistance, intrinsic resistance, induced resistance and acquired resistance. In addition, there are mathematical models that take into account the kinetic/phase resistance, and models that investigate intracellular mechanisms based on specific biological functions (such as ABC transporters, apoptosis and repair mechanisms). This review covers aspects of MDR that have been mathematically studied, and explains how, from a methodological perspective, mathematics can be used to study drug resistance. We discuss quantitative approaches of mathematical analysis, and demonstrate how mathematics can be used in combination with other experimental and clinical tools. We emphasize the potential benefits of integrating analytical and mathematical methods into future clinical and experimental studies of drug resistance.


Effects of nitrogen limitation on species replacement dynamics during early secondary succession on a semiarid sagebrush site.
A soil nitrogen (N) availability gradient was induced on a disturbed sagebrush site in northwestern Colorado by fertilizing with nitrogen (high available N), applying sucrose (low available N), and applying neither nitrogen nor sucrose (control). Species composition was studied for 3 years. At the end of the study, N concentration of aboveground tissue of 3 major species was determined. The rate of species replacement was most rapid on plots receiving the sucrose treatment and was slowest on plots receiving the N treatment. Early-seral dominats had greater tissue N concentrations when availability of the resource was high but lower tissue N concentrations when available soil N became limited. Midseral dominants displayed the opposite pattern. These results suggest that the supply of available soil N, and therefore the dynamics of N incorporation in perennial plant tissue, is a primary mechanism in controlling the rate of secondary succession within this semiarid ecosystem.


Reliability and accuracy in reporting CIN in 14 laboratories. Developing new indices of diagnostic variability in an interlaboratory study. The Working Group for External Quality Control in Cervical Cytopathology.
To report the results of the second phase of a pilot study of an Italian national external quality evaluation program (EQA) aimed at assessing whether participation in the first phase had increased the reliability and accuracy of diagnoses and to what extent. In the second phase, two sets of cervical smears (similar to the ones examined in the first phase) were circulated among the 14 participating cytologic laboratories throughout Italy. Responses were recorded on a standardized form. Participants were asked to judge the adequacy of each smear and to formulate a diagnosis. They were also asked to recommend management of the patient on the basis of the smear report and to evaluate the degree of diagnostic difficulty of each slide. The results were discussed in workshops, and it was possible to reach a consensus diagnosis on 37 of 40 smears. In the statistical analysis, new indices of diagnostic variability were developed and calculated; a gross index of agreement, unweighted and weighted kappas, analysis of exchangeability, sensitivity and specificity were also estimated. The results of the second phase are similar to those of the first phase and no substantial improvement in accuracy and little reduction in variability were observed. The interventions carried out in this study (discussion between representatives of laboratories of diagnostic differences and reassessment of the most controversial slides) were aimed at increasing consensus among the participating pathologists but were insufficient to change the diagnostic routines in their laboratories. It may be advisable to promote two kinds of interlaboratory quality programs with two separate but integrated components: (1) a core component with slides having clear-cut diagnoses, and (2) a continuing education component.


Acute cellular rejection occurring on the first day after living-related renal transplantation: a case report.
The patient was a 52-year-old man who received an ABO-compatible but non-identical living-related renal graft from his wife. The graft started to function immediately and the urine output rate was over 100 mL/h. However, this was gradually decreased within 12 h after transplantation. On day 2 post-transplant, the urine output almost stopped. A biopsy specimen revealed lymphocyte dominant cellular infiltration in the interstitium with mild tubulitis (according to Banff's schema grade Ia) and no C4d deposition in peritubular capillaries. Immunohistochemistry disclosed T-cell infiltration. The patient responded to a course of steroid pulse therapy (five days of 500 mg of methylprednisolone). The urine output gradually increased and the level of serum creatinine gradually decreased to 1.0 mg/dL. These clinical and histological findings strongly suggested acute cellular rejection. Acute cellular rejection occurring within 24 h post-transplant is extremely rare. In the present case acute cellular rejection occurred within the first day after living-related renal transplantation and was strongly suspected from histopathological findings in the allograft biopsy specimen.


[Correlation of the changes in the calorimetric indices of energy metabolism and of the morphofunctional changes in the thyroid gland of rats with various forms of experimental obesity].
Changes in heat exchange were compared with the morphofunctional changes of the thyroid gland in rats with various forms of experimental adiposity. Reduction of the hormone-forming function of the thyroid gland proved to correlate with the changes in heat formation and thermoregulation, and corresponded to the degree of adiposity observed.